KINETICS AND MECHANISM OF OXIDATION OF

4-OXOACIDS BY N-BROMO COMPOUNDS

A thesis submitted to the

Bharathidasan University, Tiruchirappalli

for the award of the degree of

DOCTOR OF PHILOSOPHY IN CHEMISTRY

By

A. AFROOS BANU, M.Sc.,M.Phil.,B.Ed., (Ref No.42426/Ph.D.1/Chemistry/Full-Time/January-2012)

Under the guidance of Dr. N.A.Mohamed Farook, M.Sc., M.Phil., P.G.D.E-Com., Ph.D.,

Research Advisor & Associate Professor P.G & Research Department of Chemistry

Khadir Mohideen College Adirampattinam-614 701

P.G. and Research Department of Chemistry

KHADIR MOHIDEEN COLLEGE

(Nationally Reaccredited with B by NAAC)

ADIRAMPATTINAM-614 701

INDIA

September - 2015

Declaration

This is to declare that the thesis entitled “Kinetics and Mechanism of

Oxidation of 4-Oxoacids by N-Bromo Compounds” submitted by

me to the Bharathidasan University, Tiruchirappalli for the award of

the degree of Doctor of Philosophy in Chemistry is a bonafide record

of the research work carried out by me under the guidance of

Dr. N.A.Mohamed Farook, Associate Professor, Khadir Mohideen

College, Adirampattinam. The contents of the thesis have not been

submitted and will not be submitted to any other University or

Institute for the award of any degree or diploma.

Signature of the Research Scholar

Adirampattinam

Date:

Forwarded

Research Advisor

(Dr. N.A.Mohamed Farook)

Phone No. 242236

KHADIR MOHIDEEN COLLEGE ADIRAMPATTINAM Thanjavur- District

Date___________

Dr. N. A. Mohamed Farook, Ph.D., Research Supervisor

CERTIFICATE This is to certify that the thesis entitled “KINETICS AND

MECHANISM OF OXIDATION OF 4–OXOACIDS BY N–

BROMO COMPOUNDS” submitted to the Bharathidasan University

for the award of the degree of DOCTOR OF PHILOSOPHY, is a

bonafide record of the research work carried out by A. AFROOS

BANU, M.Sc., M. Phil., B.Ed., (Ref No.42426/Ph.D.1/Chemistry/Full-

Time/January-2012) in the Department of Chemistry, Khadir

Mohideen College, Adirampattinam, during the period 2012– 2015

under my guidance and supervision. The work is original and has not

previously formed the basis for the award of any Diploma, Degree,

Associateship or Fellowship in this or any other university.

N.A.MOHAMED FAROOK

ACKNOWLEDGEMENT

I express my deep sense of gratitude and heartfelt thanks to my

research supervisor Dr. N. A. Mohamed Farook, Associate Professor

of Chemistry, Khadir Mohideen College, Adirampattinam for his

inspiring guidance, ingenious suggestions and valuable discussions. I

am very indebted to him for his constant encouragement.

I wish to record my respectful thanks to Dr. A. Jalal, Principal,

Khadir Mohideen College, Adirampattinam for his encouragement to

complete this work.

I express my heartfelt thanks to Dr. A. M. Uduman Mohideen,

Head of the Department of Chemistry, Khadir Mohideen College,

Adirampattinam for his kind gesture.

My sincere thanks are due to my learned colleagues and the non-

teaching staff of the department for their co-operation and support.

Finally, I want to place on record the sustained encouragement

offered by my husband Mr. G. Basul Khan, family members, friends

and students.

Above all, my thanks are due to the Almighty for the successful

completion of this work.

A. Afroos Banu

List of Abbreviations

NBA - N-Bromoacetamide

NBB - N-Bromobenzamide

NBBS - N-Bromobenzenesulphonamide

NBP -N-Bromophthalimide

NBS -N-Bromosuccinimide

NBSac -N-Bromosaccharin

NCSA -N-Chlorosaccharin

NCS -N-Chlorosuccinimide

NCA -N-Chloroacetamide

PTA -Phosphotungstic acid

KA -Keto acid

TA - Tartaric acid

MA - Malic acid

CAB -Chloramine - B

CAT -Chloramine - T

TMG - Trimethylene glycol

AcOH -Acetic Acid

CTAB - Cetyltrimethylammonium bromide

LFER - Linear Free Energy Relationship

r - Regression Coefficient

CONTENTS

Chapter 1 Page No.

Introduction 1.1 Chemical Kinetics 1

1.2 Significance of N-Halo compounds 2

1.3 Review of Literature 4

1.3.1 N-Halo compounds as oxidizing agents 4

1.3.2 N- Halo compounds in acid medium 5

1.3.3 Studies with N-Bromo Compounds

1.3.3.1 N-Bromophthalimide 6

1.3.3.2 N-Bromoacetamide 10

1.3.3.3 N-Bromobenzamide 13

1.3.3.4 N-Bromosaccharin 15

1.3.3.5 N-Bromosuccinimide 21

1.3.3.6 N-Bromobenzene-sulphonamide 25

1.3.3.7 N-Bromoanisamide 26

1.4 Glimpses of Oxoacids

1.4.1 General features 28

1.4.2 Reported methods of preparation of 4-oxoacids 29

1.4.3 Biological importance of oxoacids 31

1.5 Oxidation Studies with Oxoacids 32

1.6 Structure-Reactivity Relationships 36

1.7 Scope of the Present Investigation 39

Chapter 2

Experimental Methods

2.1 Materials 42

2.1.1 Preparation of N-Bromobenzamide 42

2.1.2 Chemicals 42

2.1.3 Preparation of 4-Oxoacids 42

2.1.3.1 4-Oxo-4-phenylbutanoic acid 43

2.1.3.2 4- Oxo-4-biphenylbutanoic acid 44

2.1.3.3 4- Oxo-4- (4’-bromophenyl)butanoic acid 44

2.1.3.4 4- Oxo-4-(3’-nitrophenyl)butanoic acid 44

2.1.4 Melting points of 4-oxoacids 44

2.1.5 Purification of solvents 45

2.2 Instrumentation 46

2.3 Methods 46

2.3.1 Oxidation of 4-oxoacids by NBB 46

2.3.1.1 Rate measurements 46

2.3.1.2 Product analysis 47

2.3.1.3 Stoichiometry 48

2.3.2 Oxidation of 4-oxoacids by NBSac 49

2.3.2.1 Rate measurements 49

2.3.2.2 Product analysis 49

2.3.2.3 Stoichiometry of oxidation 50

Chapter 3

Results and Discussion

4-Oxoacids and N-Bromobenzamide System

3.1 Structure of 4-oxoacid and N-Bromobenzamide 51

3.2 List of Substituted 4-oxoacids 51

3.3 Kinetics of oxidation of 4-oxo-4-phenylbutanoic acid

by N-bromobenzamide 52

3.3.1 Effect of varying [S1]0 53

3.3.2 Effect of varying [NBB]0 57

3.3.3 Effect of varying [H+]0 58

3.3.4 Comparison of rates in presence and

absence of H+ ion 61

3.3.5 Effect of varying ionic strength on reaction rate 62

3.3.6 Effect of added benzamide 64

3.3.7 Effect of added acrylonitrile 66

3.3.8 Effect of solvent polarity on reaction rate 67

3.3.9 Rate of enolization by bromination method 70

3.4 Studies with Substituted Oxoacids 71

3.5 Effect of Substituents and Applicability of LFER 83

3.6 Mechanism of Oxidation 88

3.7 Derivation of Rate Law 91

3.8 Structure-Reactivity Correlations 94

3.9 Activation Parameters 95

3.10 Isokinetic Relationship 99

Chapter 4

4-Oxoacids and N-Bromosaccharin System

4.1 Kinetics of Oxidation of 4-Oxo-4-Phenylbutanoic acid

by N-Bromosaccharin 104

4.1.1 Effect of varying [reactants]0 105

4.1.2 Effect of varying [H+] 109

4.1.3 Effect of varying ionic strength 112

4.1.4 Effect of added Saccharin 112

4.1.5 Effect of free-radical inhibitor 115

4.1.6 Effect of solvent composition 117

4.1.7 Rate of enolization of substrate 119

4.2 Studies with Substituted Oxoacids 119

4.3 Effect of Substituents and Applicability of LFER 129

4.4 Mechanism of Oxidation 135

4.5 Derivation of Rate Law 137

4.6 Structure-Reactivity Correlations 140

4.7 Activation Parameters 142

4.8 Isokinetic Relationship 145

4.9 Comparative Study of NBB / 4-Oxoacids and

NBSac / 4-Oxoacids Systems 148

SUMMARY 151

REFERENCES 155

CHAPTER 1

INTRODUCTION

1 

 

CHAPTER 1

INTRODUCTION

1.1 Chemical Kinetics

Chemical kinetics, also known as reaction kinetics, is the study

of rates of chemical processes. Chemical kinetics includes

investigations of how different experimental conditions can influence

the speed of a chemical reaction and yield information about

the reaction's mechanism and transition states, as well as the

construction of mathematical models that can describe the

characteristics of a chemical reaction.

The processes of oxidation and reduction are common in

chemistry. The knowledge of oxidative path way may be very useful in

understanding the phenomena in nature and synthetic situations. The

oxidation processes are many, varied and are manifested in a variety of

net effects. The rate of chemical processes and their dependence on

different experimental parameters have been studied for many years.

These studies are useful for understanding the behavior of different

reaction mechanisms.

There is no limit to the number of possible organic reactions and

mechanisms1,2. However, certain general patterns are observed that

can be used to describe many common or useful reactions. Each

reaction has a stepwise reaction mechanism that explains how it

2 

 

happens, although this detailed description of steps is not always clear

from a list of reactants alone. Organic reactions can be organized into

several basic types3-9. Some reactions fit into more than one category.

For example, some substitution reactions follow an addition-elimination

pathway. This overview isn't intended to include every single organic

reaction. Rather, it is intended to cover the basic reactions.

1.2 Significance of N-Halo Compounds

The N-haloamides or imides are generally named by putting the prefix,

e.g., N-bromo, before the name of the parent amide or imide. The

halogen when linked to oxygen or nitrogen acquires a positive oxidation

state. The electro-negativity of nitrogen is further enhanced by linking it to

a certain electron-withdrawing groups, e.g., acyl groups. Thus N-

Substituted haloimides are referred to as “positive halgen compounds”. A

large number of N-halo compounds have been prepared and tested as

reagents for allylic halogeneation and oxidation of organic compounds.

Some of the commonly used ones are listed it the table below10.

Some N-Halo imides and amides

Name and formula Active halogen %

N-Bromoacetamide (NBA)

CH3CONHBr 58

N-Bromobenzamide (NBB)

C6H5CONHBr 40

3 

 

These organic “positive” halogen compounds have been used in

the oxidation of a variety of organic compounds. The oxidation reactions

of N-halo compounds generally involve the abstraction of hydrogen from

C-H, O-H or S-H bonds, thought the reactions involving addition of

N-Bromobenzenesuphonamide (NBBS)

C6H2SO2NHBr 33.9

N-Bromophthalimide (NBP)

35.4

N-Bromosuccinimide (NBS)

44.9

N-Chlorosuccinimide (NCS)

(H2CCO)2NCl 26.4

N-Chloroacetamide (NCA)

CH3CONHCl 38

Sodium N-chloro-p-toluenesulphonamide

(chloramine-T) CAT

p-CH3C6H4SO2NCl.Na.3H2O

17.2

Sodium N-chlorobenzenesulphonamide

(chlormine-B) CAB

C6H5SO2NCl.Na

18.5

4 

 

oxygen have also been observed. These reactions have found extensive

applications in the estimation of a variety of organic compounds.

Though hypohalite solutions have frequently been used to

bring about oxidations, N-halo compounds have been found to

possess certain specific advantages as they are available in a high

state of purity, they can, therefore, be used as primary standards and

the solid reagents are fairly stable.

A variety of reactions conditions have been employed to affect

such oxidations and the ease of reactions and the selectivity is often

dependent on the solvent and pH of the medium. Under suitable

conditions, these N-halo compounds also react with defines to add

halogen to the double bond or act as a source of hypohalous acid in

aqueous solution. These compounds have been used successfully not

only as halogenating agents for oxidation and dehydrogenation.

1.3 Review of Literature

1.3.1 N-Halo Compounds as Oxidizing Agents

N-Halo compound forms a separate branch in chemistry, which is of

great synthetic importance11-48. N-Halo amides have been extensively

employed as oxidizing agents for organic substrates49-91. In the

recent development, N-halo amides are the sources of positive halogen

and have been exploited as oxidant for a variety of substrates in both

the acidic and alkaline media. The nature of active oxidizing species

5 

 

and mechanism depends on the nature of the halogen atom, the groups

attached to the nitrogen and the reaction conditions.

The various N-halo compounds extensively used as reagents in

organic chemistry are N-bromophthalimide92,93, N-bromoacetamide94-113,

N-chloroacetamide114, N-chlorobenzenesulphonamide115, N-bromo-

benzenesulphonamide116-117, N-chlorobenzamide118-121, N-bromobenz-

amide122-125, N-chloro-p-toluensulphonamide126, N-chloronicotin-

amide127,128, N-chlorosuccinimide129-149, N-bromosaccharin150-158,

N-bromo-3,5-dinitrobenzamide159, N-chlorosaccharin160-175, N-bromo-

succinimide176-211 and N-bromoanisamide212,213.

1.3.2 N-Halo compounds in acid medium

It has been reported earlier in the case of N-halo compounds that in the

absence of mineral acids, HOX is the reactive oxidant species87,102. In

the oxidation with N-bromo compounds such as N-bromoacetamide,

“positive” bromine is the effective oxidant90,201. Further Mukerji and

Banerji96 have proposed HOBr as oxidizing species in the study of

oxidation of primary alcohol by N-bromoacetamide in the absence of

mineral acid.

The probable reactive species74 of N-halo amides in acid solution

are >NX, HOX, >N+HX or H2O

+X and the reactive species in alkaline

solution are >NX, HOX and OX- For example, in the case of N-bromo-

benzamide the actual reacting species in acid medium are as follows.

6 

 

NBB + H2O HOBr + Benzamide (1)

HOBr + H+ H2O

+Br (2)

NBB + H+ NBBH

+ (3)

NBBH+ + H2O H2O

+Br + Benzamide (4)

The protonation of HOBr results in a hypobromous acidium ion

H2O+Br, a prime cationic and remote profile of the choice.

Some of the mechanisms that have been reported for the

oxidation of a number of organic substrates by N-bromo compounds

are outlined in the following pages to get a broad view on the subject.

1.3.3 Studies with N-Bromo Compounds

1.3.3.1 N-Bromophthalimide

The kinetics of oxidation of glycine by N-bromophthalimide (NBP)

were studied92a in the presence of an anionic surfactant, sodium

dodecyl sulfate, in acidic medium at 308 K. The rate of reaction was

found to have first-order dependence on [NBP] and fractional-order

dependence on [glycine] and [H+]. The addition of reduced product of

the oxidant had no significant effect on the rate of reaction. Increasing

[Hg(OAc)2] and [Br−] increased the rate of reaction, whereas a change

in ionic strength (μ) of the medium had no effect on oxidation velocity.

The rate of reaction decreased with a decrease in dielectric constant of

the medium. HCN was identified as the main oxidation product of the

reactions. The various activation parameters have been computed. A

7 

 

suitable mechanism consistent with the experimental findings has been

proposed. The index of cooperativity and the micelle binding constant

have been calculated.

The kinetics and mechanism of the oxidation of lactose by N-

bromophthalimide in the absence and presence of cetyltrimethyl-

ammonium bromide and sodium dodecyl sulfate micelles was

investigated by Katre et al.92b in the presence of sulfuric acid medium.

Under pseudo-first-order conditions reaction rate agreed with a first-,

fractional- and negative fractional-order kinetics in N-

bromophthalimide, lactose and sulfuric acid, respectively. In the

presence of additives, the critical micellar concentration values were

lower than those given in the literature. The catalytic role of cationic

micelles was explained by the Berezin model. The anionic micelles

showed slightly inhibitory effect. The influence of salts, phthalimide and

mercuric acetate on the reaction rate was also studied. Using the kinetic

data, the rate constant, binding constants, and corresponding activation

parameters were evaluated. A possible reaction mechanism, which is

based on the kinetic results and the product analysis, is proposed.

Kinetics of oxidation of aniline by N-bromophthalimide (NBP) in

acetonitrile-water solvent mixture at 303 K in the presence of perchloric

acid has been studied92c. The reaction is first order with respect to both

aniline and NBP and is catalyzed by H+ ion and the order of the reaction

8 

 

with respect to [H+] is also one. It has been found that the reaction rate is

not affected by changes in ionic strength of the reaction medium or by

the addition of acrylonitrile and potassium bromide. However, addition

of phthalimide causes a decrease in the rate of reaction. An increase in

the water content of the solvent mixture decreases the rate of reaction.

Thermodynamic and activation parameters have also been evaluated.

NBr

O

O

H+ H2OK1

H2O+BrNH

O

O

H2O+Br

NH2 NH+

HBr H2O

NH2NH+

NH HN

+

slow

k

+ +

+ + +

+fast

H++

N N 2H++NH HNoxidation

 

The rate law was given as

Rate = [NHP]

]ine][H[NBP][Anil1kK

This rate law explains the first-order dependence of the reaction on

[aniline], [NBP] and [H+] and the retarding effect of phthalimide.

kobs = [NHP]

]H[Aniline][1kK

k2 = [NHP]

][H1kK

(5)

(6)

(7)

(8)

(9)

(10)

(11)

9 

 

Kinetic investigations in Keggin-type phosphotungstic acid

catalyzed oxidation of benzhydrol and p-substituted benzhydrols by N-

bromophthalimide (NBP) in aqueous acetic acid medium in presence of

mercuric(II) acetate as a scavenger have been studied by Jagdish et

al.,92d. In absence of mineral acids, the oxidation kinetics of benzhydrols

by NBP in presence of PTA (Phosphotungstic acid) shows a first order

dependence on NBP and fractional order on benzhydrols and PTA. The

variation of ionic strength, Hg(OAC)2, H+ and phthalimide (reaction

product) have insignificant effect on reaction rate. Activation parameters

for the reaction have been evaluated from Arrhenius plot by studying the

reaction at different temperature. A mechanism involving transfer of

hydride ion in rate determining step is suggested.

The kinetics of oxidation of some α-hydroxy acids viz. Tartaric acid

(TA) and Malic acid (MA) by N-bromophthalimide (NBP) were studied

by Sangeeta et al.92f in the presence of a cationic surfactant,

cetyltrimethylammonium bromide (CTAB), in perchloric acid medium at

313 K. The oxidation of TA and MA by N-bromophthalimide in the

presence of CTAB is faster than in the absence of surfactant. The rate of

oxidation of hydroxy acids was found to be in the order: TA > MA. First

order kinetics with respect to NBP was observed in the oxidation of both

hydroxy acids. The kinetics results indicate that the first order kinetics in

hydroxy acids at lower concentrations tends towards a zero order at its

10 

 

higher concentrations. Inverse fractional order in [H+] and [phthalimide]

were noted throughout its tenfold variation. With a progressive increase

in [CTAB], the rate of reaction increased, reaches a maximum value and

then constancy in k Ψ was observed. Variation of [Hg(OAc)2] and ionic

strength (μ) of the medium did not bring about any significant change in

the rate of reaction. The applicability of different kinetic models viz. the

Piszkiewicz cooperative model, the Raghvan and Srinivasan model, and

the Menger–Portnoy model were tested to explain the observed micellar

effects. The effect of [CTAB] on the activation parameters was explored

to rationalize the micellar effect. The values of rate constants observed at

four different temperatures were utilized to calculate the activation

parameters. A suitable mechanism consistent with the experimental

findings has been proposed. The index of cooperativity and the micelle

binding constant have been calculated.

1.3.3.2 N-Bromoacetamide

The kinetics of oxidation of 3-benzoylpropionic acid (KA) with N-

bromoacetamide (NBA) have been studied by Farook et al.94a

potentiometrically in 50:50 (v/v) aqueous acetic acid medium at 298 K

The reaction was first order each with respect to [KA], [NBA] and

[H+]. The main product of the oxidation is the corresponding

carboxylic acid. The rate decreases with the addition of acetamide, one

of the products of the reaction. Variation in ionic strength of the

11 

 

reaction medium has no significant effect on the rate of oxidation. But

the rate of the reaction is enhanced by lowering the dielectric constant

of the reaction medium. A mechanism consistent with observed results

have been proposed and the related rate law was deduced.

The oxidation of 2-ketoglutaric acid in the presence of N-

bromoacetamide have been studied by singh et al.94b in alkaline

medium in temperature range 30-40 oC shows first order kinetics with

respect to N-bromoacetamide (NBA) and zero order kinetics with

respect to 2-ketoglutaric acid. Hydroxide ions variations show negative

effect while acetamide and sodium perchlorate additions show

insignificant effect on oxidation rate. Addition of mercuric acetate

(used as Br- scavenger) increases the rate which shows that probably

Hg(II) acts as catalyst. NBA as such is the reactive species. Products

identified are oxalic and malonic acids. Various activation parameters

have been calculated and recorded on the basis of the experimental

findings, and a suitable mechanism has been proposed.

The kinetics of oxidation of the sugars d(+)Melibiose (mel) and

Cellobiose (cel) by N-bromoacetamide (NBA) in the presence of

Rh(III) chloride as homogeneous catalyst in acidic medium at 45o C

have been investigated by Srivastava et al.95a. The reactions are first-

order with respect to [NBA], [Rh(III)] and [substrate]. The rate is

proportional to [H+]. No effects of [Hg(II)], [NHA] or [Cl-] on the rates

12 

 

were observed. Ionic strength and dielectric constant also have little

effect. The observed kinetic data, available literature and spectroscopic

evidence lead us to conclude that NBAH+ and [RhCl5(H2O)]2- are the

reactive species of NBA and Rh(III) chloride, respectively. The rate-

determining step of the proposed reaction path common for both sugars

gives an activated complex by the interaction of a charged complex

species and neutral sugar molecule, which in the subsequent steps

disproportionates into the reaction products with the regeneration of

catalyst. The reactions have been studied at four different temperatures

and with the help of first-order rate constant values, various activation

parameters have been calculated. The main oxidation products of the

reactions were identified as arabinonic acid, formic acid and lyxonic

acid in the case of mel and arabinonic acid and formic acid in the

case of cel.

The kinetic oxidation of trimethylene glycol (TMG) with Os(VIII)

in alkaline N-bromoacetamide (NBA) in the presence of mercuric

acetate as Br- ions scavenger has been studied by Singh et al.99a. The

reaction is first order in NBA, Os(VIII) and OH- while zero order

dependence of the reaction on trimethylene glycol was observed. The

rate of reaction was independent on addition of acetamide and sodium

perchlorate. A solvent isotope effect (K-0(D2O)/K-0(H2O)=2.3-2.7 and

2.4-2.8 for trimethylene glycol) has been observed at 35 oC. Various

13 

 

thermodynamic parameters have been computed and the corresponding

trimethylene glycol was found to be product. A mechanism consistent

with the kinetic data has been proposed.

1.3.3.3 N-Bromobenzamide

Kinetics Studies of the oxidation of ethanol by p-methoxy-N-

bromobenzamide in aqueous acetic acid medium in the presence of

mercuric acetate have been investigated by Badole et al.122c. The reaction

was first order with respect to both, the oxidant and near about are with

respect to the substrates. The order with respect to perchloric acid was

fractional or first order depending upon the substrate concentration. The

reaction was retarded by the initial addition of benzamide and was

enhanced by the added potassium bromide. The activation parameters

have been calculated and a suitable mechanism has been proposed.

Kinetics of oxidation of ethylene glycol (EG) by NBB (N-

bromobenzamide) has been studied122d in aq. HClO4 with PdCl2 as

catalyst and in the presence of Hg (OAc)2 to ensure oxidation by pure

NBB. The order of reaction with respect to NBB was unity. However

the rate decreased with the increasing concentration of [NBB]0. The

rate was directly proportional to Pd(II) for EG. The retarding effects of

HClO4 benzamide, Cl- and AcOH on the rate of oxidation were

observed. A mechanism consistent with the observed kinetic data in

proposed.

14 

 

The kinetics of the oxidation of twelve ortho-substituted

benzaldehydes by N-bromobenzamide (NBB) to the corresponding

benzoic acids have been studied123c. The reaction was first order with

respect to NBB, the aldehyde and hydrogen ions. The addition of

benzamide has no effect on the reaction rate. (PhCONH2Br)+ has been

postulated as the reactive oxidising species. The correlation of rates with

the single substituent-parameter equations is poor. The correlation with

Charton’s equation of inductive, resonance and steric parameters was

satisfactory. However, excellent correlations were obtained, when

Charton’s steric parameter was used along with Taft’s σ1; and σR+

substituent constants. The polar reaction constants have negative values.

The reaction is subject to steric hindrance by the ortho-substituents.

The oxidation of six aliphatic aldehydes by N-bromobenzamide

(NBB) in 1:1 (v/v) acetic acid-water leads to the formation of the

corresponding carboxylic acids have been investigated by Banerji

et al.,123d. The reaction was first order with respect to both NBB and

aldehyde and was catalysed by hydrogen ions. The observed hydrogen

ion dependence indicates that both NBB and its protonated form are

reactive oxidizing species. The oxidation of MeCDO exhibits a

substantial kinetic isotope effect. With an increase in the proportion of

acetic acid in the solvent mixture of acetic acid and water, the rate

decreases. Addition of benzamide has no effect on the rate. The

15 

 

reaction fails to induce the polymerization of acrylonitrile. The role of

aldehyde hydrate in the oxidation process is discussed. The rates

correlate well with Taft's sigma substituent constants, with negative

reaction constant. A mechanism involving transfer of a hydride ion to

the oxidant in the rate determining step has been proposed.

1.3.3.4 N-Bromosaccharin

N-Bromosaccharin (NBSac) is a strong oxidizing and chlorinating

agent. It is a white powder, easy to handle, with its melting point at 160-

170 °C. It is soluble in organic solvents, for example in acetic acid,

alcohols, acetonitrile, tetrachloromethane, ethyl acetate, trichloro-

methane, acetone, and 1,4-dioxane. N-Bromosaccharin has been

proven to be a useful and alternative reagent for diverse organic

transformations, such as halogenation of aromatic compounds, co-

halogenation of alkenes, oxidation of alcohols, halogenation of

benzylic and carbonylic positions, etc. N-Bromosaccharin150a can

easily be prepared by bromination of the sodium salt of saccharin

which is commonly available, non-corrosive, and non-toxic.

The kinetics of bromination of some substituted 4-piperidones

and 4-selenanones by N-bromosaccharin in the presence of perchloric

acid in aqueous acetic acid have been investigated150b. The bromination

is first order in both substrate and H3O+ and zero order in NBSA.

A plausible mechanism based on these observations is proposed.

16 

 

The effects of the various substituents on the rates of bromination have

been rationalized on the basis of their inductive and steric effects. The

effect of solvent polarity on the rate has also been studied.

N-Bromo and N-iodosaccharins in the presence of triphenyl-

phosphine convert alcohols into the corresponding bromides and

iodides in good to excellent yields at room temperature under neutral

conditions151a.

ROH RX (12)

X = Br.I

Chemoselective oxidation of thiols to their corresponding

disulfides with N-bromosaccharin in a very short time and with high

yields in dichloromathane under microwave irradiation conditions are

described by Khazaei et al.151c.

Mechanism 1

NXSac/PPh3

CH2Cl2 / r.t.

(13)

(14)

(15)

(16)

17 

 

Mechanism 2

N-Chloro- and N-bromosaccharins react with electron rich

aromatic compounds (anisole, acetanilide, N,N-dimethylaniline)

producing halogenated compounds152a. The reaction with N-bromo-

saccharin gives para- substituted compounds only, whereas N-chloro-

saccharin produces ortho and para mixtures (para isomer

predominantly, ca. 4-5 : 1). The reactions of the N-halosaccharins with

alkenes (cyclohexene, styrene, α-methylstyrene, and 1-hexene) give the

corresponding halohydrins.

A new method for the direct conversion of various oximes into

aldehydes and ketones by treatment with N-bromosaccharin is

described153a. N-Bromosaccharin was used for an effective, selective

and mild oxidizing agent for the regeneration of carbonyl compounds

from oximes in good yield.

The kinetics of oxidation of acetophenone and substituted

acetophenones by N-bromosaccharin has been investigated158 in

aqueous acetic acid medium in the temperature range 308–323 K. The

reaction is found to be first order with respect to acetophenone and

(17)

(18)

18 

 

zero order with respect to the reaction does not induce polymerisation

of added acrylonitrile. A positive catalytic effect has been noticed on

the addition of A-cyclodextrin. Thermodynamic parameters such as

ΔS#, ΔH# and ΔG# have been evaluated and presented.

The oxidation of -hydroxy acids by N-bromosaccharin has been

studied by Vijaya Mohan et al.158b. On the basis of observed first order

with respect to [substrate], [oxidant] and [H+] and the inverse effect of

[saccharin] on the reaction rate, they proposed a mechanism involving

protonated hydroxyl acid and HOBr in the rate-determining step. 

The kinetics of oxidation of benzaldehyde by N-bromosaccharin

and N-bromophthalimide has been investigated158c in aqueous acetic acid

medium in the presence of mercuric acetate over a temperature range of

308-328 K. The rate was first order with respect to both the substrate and

oxidants. The stoichiometry of the process is 1 : 1, substrate : oxidant.

(19)

(20)

(21)

(22)

19 

 

The effect of ionic strength on the rate was negligible, but the dielectric

constant of the medium has a positive influence. The thermodynamic

parameters were calculated. Saccharin and H+ were found to inhibit the

rate, whereas, phthalimide did not inhibit the rate.

The kinetics of oxidation of acetophenone and substituted

acetophenones by N-bromosaccharin has been investigated158d in

aqueous acetic acid medium in the temperature range 308–323 K. The

reaction is found to be first order with respect to acetophenone and

zero order with respect to the reaction does not induce polymerisation

of added acrylonitrile. A positive catalytic effect has been noticed on

the addition of -cyclodextrin. Thermodynamic parameters such as

ΔS#, ΔH#, and ΔG# have been evaluated and presented.

Kinetics of oxidation of some aldoses viz. D- ribose, D-xylose,

L– arabinose and D- glucose by N-bromosaccharin in aqueous acetic

medium have been studied158e in the presence of mercuric acetate as a

scavenger for Br-, exhibits first order dependence in [NBSA] and

[HC1O4]. The order with respect to aldose varies from 1 to 0. The

reaction rate is retarded by the addition of saccharin. Effect of variation

of composition of acetic acid-water binary mixture was also studied.

Various activation parameters have been computed. These results

points to a polar mechanism involving the formation of hypobromite

20 

 

ester in pre- equilibrium step which disproportionates into products via

rate limiting attack of water molecule.

The effect of sodium lauryl sulphate on the oxidation of glycolic

and tactic acid by N-bromosaccharin in aqueous-acetic acid in the

presence of Hg(II) acetate has been investigated158f. The reactions are

first order with respect to oxidant in the presence as well as in absence

of sodium lauryl sulphate (NaLS). The Michaelis-Menten kinetics is

observed in the substrate. The reactions exhibit complex kinetics in H+.

Change in polarity of the medium, effect of addition of saccharin and

Hg(II) acetate have also been investigated, Sodium lauryl sulphate

exhibits an inhibition effect. These effects are discussed on the basis of

interactions of hydroxy acids with the micelle. Binding parameters

have been calculated by analyzing the data using the model suggested

by Piszkiewicz. Influence of surfactant on the activation parameters of

the reaction has also been discussed.

The rates of oxidation of benzilic acid by N-bromosaccharin were

measured158g in aqueous acetic acid medium in the absence and in

presence of cationic surfactant, cetyl trimethylammonium bromide

(CTAB) and anionic surfactant, sodium lauryl sulphate (NaLS). Kinetic

observations indicate first order in [NBSA] and fractional to [BA]. The

reaction rate is retarded in the presence of perchloric acid and by addition

of the reaction product, saccharin. Addition of NaClO4 and Hg(II) acetate

21 

 

has no effect. The rates were also found to be sensitive to solvent

polarity. Formation of an intermediate complex between NBSA and BA

in pre-equilibrium step and subsequent decomposition in a slow step has

been proposed as probable mechanism. The inhibitory effect of CTAB

and NaLS is analyzed on the basis of Piszkiewicz model.

1.3.3.5 N-Bromosuccinimide

Dipeptides (DP), namely valyl–glycine (Val–Gly), alanyl–proline (Ala–

Pro), and valyl–proline (Val–Pro) were synthesized by classical solution

phase methods and characterized. The kinetics of oxidation of amino acids

(AA) and DP by N-bromosuccinimide (NBS) was studied by Gowda et

al.188a in the presence of perchlorate ions in acidic medium at 28°C. The

reaction was followed spectrophoto-metrically at λmax = 240 nm. The

reactions follow identical kinetics, being first order each in [NBS], [AA],

and [DP]. No effect on [H+], reduction product [succinimide], and ionic

strength was observed. Effects of varying dielectric constant of the

medium and addition of anions such as chloride and perchlorate were

studied. Activation parameters have been computed. The oxidation

products of the reaction were isolated and characterized. The proposed

mechanism is consistent with the experimental results. An apparent

correlation was noted between the rate of oxidation of AA and DP.

The kinetics of oxidation of gabapentin (GBP) by N-

bromosuccinimide (NBS) in an alkaline medium has been investigated

22 

 

by Alaa Eldin et al.,189a. The oxidation reaction showed unique kinetics

that greatly differed on going from acid to base medium. In an acid

medium (pH=2.52), the reaction rate showed first order dependence on

[NBS], fractional order dependence on both [GBP] and [H+] and

increased with temperature over (303–321oK) range. In an alkaline

medium, the rate showed first order dependence on [GBP], fractional

order on [H+] over (1.99-39.80) x10-9 range and zero order dependence

on [NBS]. It is noteworthy that the reaction rate decreased with

temperature over the range studied. An inner- sphere mechanism for the

oxidation pathway supported by free radicals intervention was proposed.

Kinetics and mechanism of micellar catalyzed N-

bromosuccinimide oxidation of dextrose in H2SO4 medium was

investigated by Minu Singh195a under pseudo-first-order condition

temperature of 40 °C. The results of the reactions studied over a wide

range of experimental conditions show that NBS shows a first order

dependence, fractional order, on dextrose and negative fractional order

dependence on sulfuric acid. The determined stoichiometric ratio was

1 : 1 (dextrose : N-bromosuccinimide). The variation of Hg(OAC)2 and

succinimide (reaction product) has insignificant effect on reaction rate.

Effects of surfactants, added acrylonitrile, added salts, and solvent

composition variation have been studied. The Arrhenius activation

energy and other thermodynamic activation parameters are evaluated.

23 

 

The rate law has been derived on the basis of obtained data. A plausible

mechanism has been proposed from the results of kinetic studies,

reaction stoichiometry, and product analysis. The role of anionic and

nonionic micelle was best explained by the Berezin’s model.

The oxidation of diazepam (DZ) by N-Bromosuccinimide (NBS)

have been studied by Nanda et al.,196a in aqueous acid medium follows a

first-order kinetics in [NBS] and a fractional-order each on [HCl] and

[DZ]. The reaction stoichiometry involves one mol NBS consumed by

one mol DZ. The rate of the reaction increases with the decrease in

dielectric constant of the medium. Added products and the variation of

ionic strength have no significant effect on the rate of the reaction. The

oxidation products were identified by spectral analysis. A mechanism

involving the formation of an intermediate NBS-DZ complex has been

proposed. The solvent effect is consistent with the charge dispersion

going into the transition state. The activation parameters for the

reaction have been determined. The negative entropy of activation

suggests the formation of a rigid, associative transition state involving

loss of degrees of freedom.

Kinetics of oxidation of glycine (gly) and valine (val) by N-

bromosuccinimide (NBS) using chloro complex of Rh(III) in its nano-

concentration range as homogeneous catalyst have been investigated by

Singh et al.,197a at 35 oC . The reaction shows first order kinetics with

24 

 

respect to NBS and Rh(III) in the oxidation of both the amino acids. The

first order kinetics with respect to amino acid obtained at its lower

concentration changes to zero order at its higher concentration. Inverse

fractional order with respect to [H+] was obtained in Rh(III)-catalysed

oxidation of gly and val. Variation in [Hg(II)], [NHS], [Cl-], ionic

strength and dielectric constant of the medium has no effect on the rate of

oxidation of both the amino acids. NBS itself and [RhCl5(H2O)]2- have

been postulated as the reactive species of NBS and Rh(III) chloride in

acidic medium, respectively. Various activation parameters have been

calculated with the pseudo-first-order rate constant values observed at

four different temperatures. The main oxidation products of the reactions

have been identified as formaldehyde and ammonia in the case of gly

and isobutaldehyde and ammonia in the case of val. The proposed

reaction mechanism is well supported by kinetic data, spectrophoto-

metric evidence and positive entropy of activation.

A kinetic study of oxidation of 2-phenylethylamine (PEA), a

bioactive compound, with potent oxidant, N-bromosuccinimide (NBS)

has been investigated by Mohana et al.198a in HCl and NaOH media at

313 K. The experimental rate laws obtained are:

-d[NBS] = k[NBS][PEA][H+] dt

in hydrochloric acid medium and

-d[NBS] = k[NBS][PEA]x [OH-]y dt

(23)

(24)

25 

 

in alkaline medium where x and y are less than unity. Accelerating effect

of [Cl-], and retardation of the added succinimide on the reaction rate

have been observed in acid medium. Variation of ionic strength of the

medium shows negligible effect on rate of reaction in both media.

Decrease in dielectric permittivity of the medium decreased the rate in

both media. The stoichiometry of the reaction was found to be 1:1 in acid

medium and 1:2 in the case of alkaline medium. The oxidation products

of PEA were identified as the corresponding aldehyde and nitrile in acid

and alkaline medium, respectively. The reactions were studied at different

temperatures and the activation parameters have been evaluated. The

reaction constants involved in the proposed mechanisms were computed.

The reaction was found to be faster in alkaline medium in comparison

with the acid medium, which is attributed to the involvement of different

oxidizing species. The proposed mechanisms and the derived rate laws

are consistent with the observed experimental results.

1.3.3.6 N-Bromobenzene-sulphonamide

The kinetics of oxidation of 2-propanol, 2-butanol, 2-pentanol, 2-hexanol

and 2-heptanol to the respective ketones by sodium N-bromobenzene-

sulphonamide (bromamine-B) in presence of HCl was studied by Mohan

et al.116a at 40°C. The rate shows a first-order dependence on both

[oxidant]0 and [alcohol]0 and is fractional in [H+] and [Cl−]. The proposed

mechanism assumes the formation of a hypobromite in the rate-limiting

26 

 

step followed by a fast reaction to form products. The magnitude of the

solvent isotope effect, k′H2O/k′D2O is 0–90. The rates do not correlate

satisfactorily with Taft’s substituent constants. An isokinetic relation is

observed with β=331 K indicating enthalpy as a controlling factor.

Kinetics of oxidation of cysteine in the presence of H2SO4 and

HClO4 by sodium N-bromobenzene sulfonamide (Bromamine-B or BAB)

has been investigated by Rangaswamy et al.117a at 30 °C. The reactions

follow identical kinetics, and obeys the rate law, rate = k [BAB] [S]

[H+]x- where x is less than unity. Addtion of [SO42-] and [ClO4-] in the

form of Na2SO4 and NaClO4 had no effect on the reaction rate. The

reaction product, benzene sulfonamide had no effect on the reaction rate.

Variation of ionic strength and dielectric constant of the medium on the

rate of reaction has been studied. Thermodynamic parameters have been

evaluated by studying the kinetics at various temperatures. The

protonation constant of monobromamine-B is found to be 36.50 in H2SO4

medium and 65.06 in HClO4 medium. Suitable mechanism has been

proposed in consistency with the kinetic results.

1.3.3.7 N-Bromoanisamide

The kinetics of the oxidation of the mandelic by N-bromoanisamide has

been studied by Siriah et al211. in 40% acetic acid medium in the

presence HC1O4 and of [Hg(OAc)2]. The reactions exhibit a first order

rate dependence with respect to oxidant and fractional order with respect

27 

 

to substrate. The reaction rate decreases slightly with increasing the

concentration of [H+] and retarded by the addition of anisamide, (as one

of the oxidation product of oxidant). The decrease in dielectric constant

of the medium decreases rate of the reaction. Increase in ionic strength,

by the addition of sodium perchlorate has no effect on the rate constant.

The effect of temperature on the reaction has been investigated in the

temperature range 308-323 K. The activation parameters were

calculated and a possible operative mechanism was proposed.

From the mechanisms, the following rate equation was derived.

The kinetics of the oxidation of the malic and by N-bromo-

anisamide in HC1O4 and in the presence of Hg(OAc)2 have been studied

by Malviya et al.212. The reactions exhibit a first order rate dependence

with respect to the oxidant and substrate. The reactions are acid catalyzed

and retarded by the addition of anisamide, a byproduct of reaction. The

rate of oxidation decreases with decrease in dielectric constant of the

(25)

(26)

(27)

(29)

(28)

28 

 

medium. The effect of temperature on the reaction has been investigated

in the temperature range 313-328 K. The stoichiometric studies revealed

1:1 mole ratio. Various thermodynamic parameters have been computed

and a possible operative mechanism is proposed.

1.4 Glimpses of Oxoacids

1.4.1 General features

In 2-oxoacids (R-CO-COOH), due to the interaction of the pi electron

clouds of the carbonyl and carboxyl groups in the 2 and 1 position

respectively, each group influences the characteristics of the other

group. The studies of the 2-oxoacids are found widely in the

literature214-217. For instance, 2-oxopropionic acid commonly called

pyruvic acid (CH3-CO-COOH) is involved in the biochemical

processes like respiration. Among 3-oxoacids, the well known is the

ester of 3-oxobutanoic acid, namely acetoacetic ester which is most

useful in the synthesis of various organic compounds218.

In 4-oxoacids, the carbonyl and the carboxyl groups are

separated by two carbon atoms and so they possess the characteristics

of both compounds without the direct influence of the other group.

However, intramolecular catalysis (carboxylic acid group can catalyze

the reactions of oxo group) has been reported in the halogenation of

4-oxoacids219. Among the 4-oxoacids, the reaction of levulinic acid

(CH3-CO-CH2-CH2-COOH) has been studied extensively220,221.

29 

 

1.4.2 Reported methods of preparation of 4-oxoacids

The preparation of 4-oxo-4-phenylbutanoic acid, commonly known as β-

benzoylpropionic acid, by the Friedel-Craft’s reaction between benzene

and succinic anhydride in the presence of anhydrous aluminium chloride

was reported222 as early as 1882. Haworth synthesized naphthalene from

4-oxo-4-phenylbutanoic acid.223 The Friedel-Craft’s reaction of succinic

anhydride with toluene, xylenes, mesitylene and a number of

alkylated benzenes were reported to give the corresponding phenyl

substituted 4-oxo-4-phenylbutanoic acids224,225. Phenanthrene

derivatives226,227 were obtained from 4-oxo-4-phenylbutanoic acids

which were synthesized by the condensation between succinic

anhydride and naphthalene derivatives. Tetralin, p-cymene,

phenanthrene and anthracene were reacted with succinic anhydride

to get the corresponding 4-oxoacids228-230. 4-Oxo-4-(4’-bromo-

phenyl)butanoic acid was prepared from bromobenzene and succinic

anhydride under drastic conditions231. The structure of the oxoacid

was established by heating it with alkaline potassium permanganate

and identifying the resulting 4-bromobenzoic acid. 4-Oxo-4-(3’-nitro-

phenyl)butanoic acid was prepared232 by the nitration of 4-oxo-4-

phenylbutanoic acid. Aromatic ethers like anisole, phenetole, p-

methylanisole, o-methylanisole, p-chloroanisole and veratrole were

condensed with succinic anhydride to get the corresponding 4-oxoacids233.

30 

 

Methyl ethers of dihydric phenols were also condensed with succinic

anhydride234. The Friedel-Craft’s succinolylation of 1,2-dichlorobenzene

yielded 4-oxo-4-(3’,4’-dichlorophenyl)butanoic acid235.

The following mechanism has been proposed for the

condensation between succinic anhydride and aromatic compounds in

the presence of anhydrous aluminium chloride236. For the complete

reaction, one molecule of succinic anhydride (I) requires two

molecules of anhydrous aluminium chloride. It is suggested that one

molecule of aluminium chloride is used to open the anhydride ring

with the formation of the carboxylic acid salt from one half of the

anhydride group and the other half is converted into a carbonyl

chloride group (II). This reacts in the usual manner with the second

molecule of aluminium chloride to give the complex (III) which then

reacts with the nucleophilic component to form the 4-oxoacid (VI) via

the intermediates IV and V.

I II III

IV V

(30)

(31)

31 

 

VI

4-Oxo-4-phenylbutanoic acid (4-oxoacid)

1.4.3 Biological importance of oxoacids

Many of the 4-oxoacids and their esters possess fungicidal,

antibacterial, microbial237 and anti-inflammatory activities238.

For example, 4-oxo-4-phenylbutanoic acid is involved in human

metabolism239. The 4-oxoacids are also used for protecting the

hydroxyl functions in nucleosides. The esters and salts of the 4-

oxoacids are also utilized widely in the industrial preparation of insect

repellents and plastics240.

The 4-oxoacids are very useful in the synthesis of several

carboxylic acid and heterocyclic compounds. For instance241, the

bromo oxoacids are used for preparing imidazothiazoles and

pyridazinones. They are the starting compounds in the preparation of

β-benzoylacrylic esters.

Structure-activity studies242 of 3-benzoylpropionic acid

derivatives establish the fact that these acids possess immunodulative

activity and suppress adjuvant arthritis.

3-Benzoylpropionic acid (4-oxoacid) and its derivatives play an

important role in the pharmaceutical chemistry243-251. 3-Benzoyl-

(32)

32 

 

propionic acid derivatives are used as antirheumatic agents243. A study

with three types of 3-benzoylpropionic acid derivatives having a

mercapto moiety in their structures shows that substitution on the

phenyl ring contributes to the antirheumatic activity.

1.5 Oxidation Studies with Oxoacids

Although a lot of work has been reported on the -ketoesters, hydroxyl

acids, aldehyde and aromatic ketones, a very little work has been

reported so far on the oxidation of oxoacids252-260.

Kinetics of oxidation of 4-oxoacids by permanganate in buffer

media have been reported253. Oxidation of 4-oxo-4-phenylbutanoic

acid and its phenyl substituted compounds by permanganate in

different buffer media is first order each in [oxoacid] and [MnO4-].

The reactions undergo general acid catalysis. Addition of

electrolytes has no significant effect on the reaction rate. Electron

releasing substituents in aromatic ring enhance the reaction rates,

while electron withdrawing substituents retard the rate. The

reaction constant is – 1.08 at 303 KThe oxidation products have

been identified and activation parameters are computed. A mechanism

consistent with the kinetic results has been proposed.

The oxidation of substituted and unsubstituted 4-oxoacids by

alkaline hexacyanoferrate(III) in sodium carbonate-bicarbonate buffer

33 

 

has been studied254. The reaction is zero order in oxidant, first order

with respect to Os(VIII), first order at higher concentrations with

respect to both substrate and alkali. The reaction products are identified

as benzoic acid and malonic acid by comparing the Rf values with that

of the authentic samples. The presence of electron releasing groups in

the benzene ring decreases the rate of oxidation and the presence of

electron withdrawing groups enhances the rate. The observed rate

constants increase with temperature for all the compounds. The

reaction constants are positive and decrease with increasing

temperature. Based on the kinetic results and observations, an

oxidation mechanism is formulated as given in eqs. (33) – (39).

(33)

(34)

(35)

I

34 

 

+ H2O (36)

C1 C2

(37) C3

(38)

(39)

Kinetics of oxidation of unsubstituted and substituted

oxoacids by acid permanganate in aqueous acetic acid medium have

been studied255 at high and low [H3O+]. At high [H3O

+], the reaction is

first order each in [H3O+] and the [oxoacid]. Variation in ionic strength

of the reaction medium has no significant effect on the rate of the

reaction. But the rate of the reaction is enhanced by lowering the

dielectric constant of the reaction medium. Electron releasing

substituents in the aromatic ring accelerate the reaction rates and

electron withdrawing substituents retard them. The value of the at

303 K (at [H3O+] = 1 M) obtained from the Hammett’s plot is -1.49. A

mechanism involving the attack of permanganic acid on the enol form

of the substrate in the rate determining step has been proposed. The

protonation of permanganate ion leads to the formation of permanganic

acid. The enolization is proposed to be the necessary step prior to the

35 

 

oxidation of the substrate. The above two processes are assumed

following the mechanism suggested for acid catalyzed permanganate

oxidation of ketones260-263. The mechanism is given (eqs. 40-45).

(40)

(41)

(42)

(43)

(44)

(45)

36 

 

The kinetics of oxidative decarboxylation of benzoylpropionic

acid by manganese(III) acetate in aqueous acetic acid medium have been

studied259. The reaction is first order each in [substrate], [oxidant] and

[H+] ion. The effects of solvent polarity and temperature on the rate of

oxidation have been studied. A suitable mechanism consistent with the

experimental results has been proposed.

1.6 Structure-Reactivity Relationships

For justifying and generalizing a particular reaction mechanism for

similar reactions, almost all the kinetic studies invoke structure-

reactivity relationships which depend on the empirical and qualitative

rule that like substances react similarly and that similar change in

structure produce similar changes in reactivity264. The most successful

quantitative correlation between structure and reactivity is given by the

Hammett equation265, a linear free- energy relationship.

log k = log k0 +

loglog K0

where k or K is the rate or equilibrium constant respectively, for a side-

chain reaction of meta- or para- substituted benzene derivatives. The k0

or K0 denotes the corresponding quantity for the parent compound. The

substituents constant is independent of the nature of the reaction and

gives a measure of the polar effect of replacing H by a given substituents

37 

 

(in the m- or p- position). The reaction constant depends on the nature

of the reaction and its conditions (reagent, catalyst or temperature) and

is independent of substituents. For evaluating for a given substituents

the ionization of benzoic acid in water at 25o C is chosen as the standard

process for which was arbitrarily defined as 1.00.

Hammett equation is applied to a given reaction by getting a best

straight line, by the method of least squares, between log k or log K and

and the slope of that line gives the value of the reaction constant .

The success of the Hammett equation is commonly assessed266-270 in

terms of correlation coefficient (r) and the standard deviation (s).

To account for the failure of Hammett equation in reactions

where the conjugation involving substituents and reaction center is

substantially more marked than in the ionization of benzoic acids

(cross-conjugation)271,272 ‘exalted’ constants (and) are

introduced. The values are used for +R substituents (e.g. NO2, CN,

COOH, COOMe, and SO2Me) and are based on the ionization of

anilinium ions or of phenols in water. The values, introduced by

Brown and Okamato273 based on the solvolysis of t-cumyl chloride in

90% acetone-water at 250C, are used for –R substituents (e.g. OMe,

Me, OH, NH2, SMe, and Hal ). The differences (and

(give a measure of conjugative ability of a given acceptor and

38 

 

donor respectively. Both and

values are sometimes used in the

same correlation for a reaction in which an electron-deficient /

electron-rich reaction centre can directly conjugate with electron-

donating / electron-withdrawing substituents.

On the view that the contribution of the resonance effect of a

substituents must vary continuously as the electron-demanding quality

of the reaction centre is varied, Wepster274, 275 introduced a ‘sliding

scale’ of (unexalted) values, called n. Taft276 also evaluated similar

set of unexalted constants, called , on the basis of ionization of

phenylacetic and phenylpropionic acids.

To deal with the influence of –R and +R substituents respectively

on reactions that are more or less electron-demanding than the ionization

of benzoic acid, Yukawa and Tsuno277 and Yasioka278 formulated the

following eqs. (48) and (49) known as Yukawa-Tsuno equations.

log k = log k0 + r

R

log K = log K0 + r

R

where

R = and

R =

r ±

gives a measure of the

extent to which cross-conjugation of substituents with reaction centers

stabilizes the transition state or product relative to the initial state. The

r+ in eq. (48) can have values varying from 0 to unity and values

greater than one is also possible for r- in eq. (49).

39 

 

A quantitative separation of substituents effect into inductive

and resonance contributions by Taft279, 280 led to the possibility

of a ‘dual substituents parameters’ (DSP) treatment of reaction

series, where simple correlations based on Hammett equation fail,

in the form of eq. (50)

log ( k / k0 ) = R (50)

where and R are the inductive and resonance substituent constants,

and I and R are the corresponding reaction constants.

1.7 Scope of the Present Investigation

A thorough literature survey reveals that only few works on the

oxidation of 4-oxoacids have been reported so far252-259. Although the

N-bromo compounds oxidation of a large variety of organic

compounds have been studied, there seems to be no report on a

systematic kinetic study of the oxidation of 4-oxoacids by N-

bromobenzamide and N-bromosaccharin.

The present investigation employs N-bromo compounds such as

N-bromobenzamide and N-bromosaccharin as oxidants, perchloric acid

as catalyst and 4-oxoacids as substrates. The choice of this system may

be rationalized on the following aspects.

40 

 

Of the many efficient oxidation systems known, those involving

positive halogen species as an oxidant are among the most numerous

and well studied. The 4-oxoacid has much biological significance

associated with it and plays an essential role in the pharmaceutical

chemistry. Few examples are; the 4-oxoacids and its derivatives act as

antirheumatic agents for human being242. It plays an important role in

suppressing adjuvant arthritis243.

Mutations in components of the extraordinarily large -ketoacid

dehydrogenase multienzyme complexes can lead to serious and often

fatal disorders in humans, including maple syrup urine disease246.

In view of these facts, 4-oxoacid is a suitable substrate to be

employed in the oxidation studies. This study makes interesting and

useful findings in elucidating the mechanism of the 4-oxoacid

oxidation process.

A detailed study of the oxidation of 4-oxoacids by N-bromo

compounds is undertaken with a view to propose the mechanism for

the oxidation. The experiments have been focused to explore the

following aspects:

i) To determine the order of the reaction with respect to the

reactants namely, the oxoacids and N-bromo compounds.

41 

 

ii) To determine the catalytic activity of hydrogen ions in the

oxidation.

iii) To determine whether the reaction is general acid

catalyzed.

iv) To determine the rate of enolization by bromination

method.

v) To determine the effect of dielectric constant of the

reaction medium on the rate of reaction.

vi) To determine the effect of ionic strength on the reaction

rate.

vii) To determine whether the reaction involves the formation

of polar (or) free radical intermediates.

viii) To determine the stoichiometry of the reaction and to

study the product analysis.

ix) To determine the effect of substituents on the reaction

rate and to apply the linear free energy relationship.

x) To determine the reaction constant and isokinetic

temperature.

xi) To determine the activation parameters for the oxidation

and finally and

xii) To propose a suitable mechanism.

CHAPTER 2

EXPERIMENTAL

42

CHAPTER 2

Experimental Methods 2.1 Materials

2.1.1 Preparation of N-Bromobenzamide281

690 mg of solid sodium bromide (6.7mmol) was slowly added to a stirred

solution of benzamide (1.21g, 10 mmol), sodium bromate (760 mg, 5

mmol), and conc. H2SO4 (740 mg, 7.5 mmol) in 70% aqueous acetic acid

(7 ml), and the mixture was stirred for 20 min at room temperature. The

resulting precipitate was collected by filtration, washed with cold H2O

and dried to give colorless solid, yield 1.55 g (mp. 124-126 oC).

2.1.2 Chemicals

All the chemicals used were of AR grade. Acetic acid (BDH) was

first refluxed over chromic acid for 6 h and then distilled. Solutions

of sodium perchlorate, perchloric acid were prepared in double

distilled water. Double distilled water (conductivity <10 S.cm-1) was

employed in all kinetic runs.

2.1.3 Preparation of 4-Oxoacids

The 4-oxo-4-(4'-methoxyphenyl)butanoic acid (S2), 4-oxo-4-(4'-

methyl-phenyl)-butanoic acid (S3) and 4-oxo-4-(4'-chlorophenyl)-

butanoic acid (S5) were obtained from Sigma-Aldrich Chemical

Co. The remaining 4-oxoacids (S1, S4, S6 and S7) were prepared by

43

Friedel-Crafts acylation of the substituted benzene with succinic

anhydride282.

All the 4-oxo acids used in this study were crystallized twice

from water and their purity was checked by their melting points.

2.1.3.1 4-Oxo-4-phenylbuatnoic acid (S1)

Succinic anhydride, 9 g was mixed with sodium dried benzene, 45 ml in

a round bottomed flask fitted with a reflux condenser protected by a

drying tube containing calcium chloride. The mixture was added with

anhydrous aluminium chloride, 25 g all at once. The mixture was

refluxed on a water bath with continued stirring for an hour. After

cooling, it was added with 50 ml of water and 20 ml of ice cold con.

HCl. The contents were then steam distilled to separate the

unreacted benzene and cooled in freezing mixture. The colorless

crystals of 4-oxo-4-phenylbutanoic acid separated from the solution

were filtered and washed with a cold dilute solution of HCl and

then with cold water. The crude product was dissolved in sodium

carbonate solution, boiled for 10 minutes and filtered. The hot filtrate

was treated with decolorizing carbon, 1 g, stirred and filtered. The

filtrate was cooled, acidified with con. HCl, 30 ml and further cooled in

a freezing mixture. The oxoacid obtained was filtered, washed

thoroughly with cold water and dried. Finally, the oxoacid was

recrystallised in boiling water and dried for 12 h at 45-500 C.

44

2.1.3.2 4-Oxo-4-biphenylbutanoic acid (S4)

Biphenyl, 40 g was mixed with succinic anhydride, 18 g and nitro

benzene, 50 ml in a round bottomed flask. Anhydrous aluminium

chloride, 50 g, was added in several portions and the mixture was

refluxed in a water bath for two hours. The contents after cooling

were added with ice cold HCl, 50 ml. then the reaction mixture was

steam distilled and cooled. The crude product obtained was purified

and recrystallised from alcohol.

2.1.3.3 4-Oxo-4-(4’-bromophenyl)butanoic acid (S6)

Bromobenzene was condensed with succinic anhydride. About 10 ml

of nitrobenzene was also added to the reaction mixture and refluxed

for a long time. The oxoacid was recrystallised from hot water.

2.1.3.4 4-Oxo-4-(3’-nitrophenyl)butanoic acid (S7)

4-Oxo-4-phenylbutanoic acid, 5 g was added in small quantities to a

ice cooled (< 50 C) mixture of fuming nitric acid, 10 ml and Con.

H2SO4, 2 ml with constant stirring for about 30 minutes. The

temperature of the reaction mixture was allowed to rise to 15 0C,

during the addition of the oxoacid. A clear solution was obtained and it

was added slowly to crushed ice, with constant stirring. The product

was formed as a precipitate. It was filtered and washed thoroughly with

cold water. The oxoacid was purified and recrystallised in water.

45

2.1.4 Melting points of 4-Oxoacids The melting points of all the 4-oxoacids synthesized correspond to the

values reported in the literature. These values along with their

percentage yield are presented in following Table

S.No 4-oxoacids Lit. [Ref]

Melting Point 0C

Observed Reported

S1 4-Oxo-4-phenylbutanoic acid 282 116 116

S2 4-Oxo-4-(4’-methoxyphenyl)butanoic acid

283 146 147

S3 4-Oxo-4-(4’-methylphenyl)butanoic acid

224 128 129

S4 4-Oxo-4-biphenylbutanoic acid 284 184 185

S5 4-Oxo-4-(4’-chlorophenyl)butanoic acid

231 132 133

S6 4-Oxo-4-(4’-bromophenyl)butanoic acid

231 148 149

S7 4-Oxo-4-(3’-nitrophenyl)butanoic acid

232 163 164

2.1.5 Purification of solvents Analar acetic acid (BDH) was refluxed for three hours with chromic

acid. The acid was then distilled in a glass distillation apparatus and the

fraction distilling at 117-118 0C was collected. The fraction collected

has a boiling point of 118 0C.

Water purified, by a permutit ion exchanger, was distilled with a

few crystals of potassium permanganate in a glass distillation apparatus.

The distillate collected was used for preparing all the reagents and

solutions. Fresh solutions were used for each kinetic runs

46

2.2 Instrumentation The reaction was followed potentiometrically by setting up a cell made

up of the reaction mixture into which a platinum electrode and a

standard calomel electrode were dipped. The emf of the cell was

measured periodically using an Equip-Tronics potentiometer, while the

reaction mixture was continuously stirred using a magnetic stirrer. An

electrically operated thermostat was used to maintain the desired

temperature with an accuracy of ±0.10 C. A double walled 100 ml

beaker with inlet-outlet water circulation facility, specially designed

for this experiment, was used as reaction vessel.

2.3 Methods

2.3.1 Oxidation of 4-oxoacids by N-Bromobenzamide

N-Bromobenzamide (NBB) was employed as oxidant for the oxidation

of unsubstituted and substituted 4-oxoacids. The kinetics of oxidation

of 4-oxoacids by NBB was studied by potentiometric method.

2.3.1.1 Rate measurements

The reactions were carried out in binary mixtures of acetic acid and

water. Requisite amounts (appropriate volume of known concentration)

of separately thermostated oxoacid, NBB, acetic acid, sodium

perchlorate, perchloric acid solutions and water were pipetted out into

the reaction vessel. The total volume of the reaction mixture being 50 ml,

47

after the addition of all the solutions. The vessel was kept at the desired

temperature (30 0C). The emf values of the reaction mixture were

determined at definite intervals of time. The pseudo-first order rate

constants were computed from the plots of ln (Et - E∞) versus time.

The following precautions were taken:

i) When the reaction was followed potentiometrically and

iodometrically both the methods gave the same values.

ii) Duplicate experiments were conducted in an atmosphere of

nitrogen and without nitrogen. But there was no difference in the

results obtained. All experiments reported in this thesis were

done in air.

iii) All reactions were carried out under pseudo-first order

conditions with substrate concentration in large excess. The rate

constants were computed from linear plots of log(Et-E) versus

time by least square method using linear regression

method(r>0.98).

All experiment was carried out in duplicate and the velocity constants

were reproducible within ±2% error. All pseudo first order rate

constant (kobs) are expressed in s-1.

2.3.1.2 Product analysis A typical product analysis was carried out as follows: 4-Oxo-4-

phenylbutanoic acid (0.1 M), perchloric acid (1.0 M) and N-

48

bromobenzamide (0.5 M) were mixed together in 50 percent aqueous

acetic acid so that the total volume of the mixture was 100 ml. The

reaction mixture was allowed to stand for about 24 h to ensure the

completion of the reaction. The gas evolved during the reaction was

found out to be carbon dioxide. The solution was then shaken well with

ether and aqueous layer was discarded. The ether layer was washed with

distilled water several times, dried over anhydrous sodium sulphate and

evaporated. The products were extracted with ether, dried and analyzed.

Benzoic acid was identified by its m.pt. (121 oC) and estimated

quantitatively with a standard curve at λmax = 235 nm and also tested

with its characteristic spot test. Identification of the products,

namely, benzoic acid, were also made by comparing the Rf values of the

authentic samples.

2.3.1.3 Stoichiometry

Different sets of reaction mixtures containing different quantities of

NBB and 4-oxoacids at constant concentration of perchloric acid and

sodium perchlorate were allowed to react for 24 h at 30o C and then

analyzed. The remaining NBB was estimated. The results show that

one mole of oxoacid consumes one mole of NBB.

C6H5COCH2CH2COOH + C6H5CONHBr + 5H2OH

+

C6H5COOH C6H5CONH2 3CO2 6H2 HBr+ + + +

49

2.3.2 Oxidation of 4-Oxoacids by N-Bromosaccharin

N-Bromosaccharin (NBSac) was purchased from Sigma Aldrich

Chemical Co. and employed as oxidant for the oxidation of

unsubstituted and substituted 4-oxoacids. The kinetics of oxidation of

4-oxoacids by NBSac was studied by potentiometric method.

2.3.2.1 Rate measurements

The reactions were carried out in binary mixtures of acetic acid and water.

Requisite amounts (appropriate volume of known concentration) of

separately thermostated oxoacid, NBSac, acetic acid, sodium perchlorate,

perchloric acid solutions and water were pipette out into the reaction

vessel. The total volume of the reaction mixture being 50 ml, after the

addition of all the solutions. The vessel was kept at the desired

temperature (300 C). The emf values of the reaction mixture were

determined at definite intervals of time. The pseudo-first order rate

constants were computed from the plots of ln (Et - E∞) versus time.

2.3.2.2 Product analysis

A typical product analysis was carried out as follows: 4-Oxo-4-

phenylbutanoic acid (0.1 M), perchloric acid (1.0 M) and NBSac (0.5 M)

were mixed together in 50 percent aqueous acetic acid so that the total

volume of the mixture was 100 ml. The reaction mixture was allowed

to stand for about 24 h to ensure the completion of the reaction.

50

The gas evolved during the reaction was found out to be carbon

dioxide. The solution was then shaken well with ether and aqueous

layer was discarded. The ether layer was washed with distilled water

several times, dried over anhydrous sodium sulphate and evaporated.

The products were extracted with ether, dried and analyzed. Benzoic

acid was identified by its m.pt. (121 oC) and estimated quantitatively

with a standard curve at λmax = 235 nm and also tested with its

characteristic spot test. Identification of the products, namely,

benzoic acid, was also made by comparing the Rf values of the

authentic samples285.

2.3.2.3 Stoichiometry of oxidation

The stoichiometry of the reaction was determined by equilibrating

reaction mixture of various [NBSac]/[4-oxoacid] ratios at 30 oC for 12 h,

keeping all other reagent concentrations constant. Estimation of

unconsumed NBSac revealed that one mole of 4-oxoacid consumed

one mole of NBSac.

C6H5COCH2CH2COOH C6H4SO2CONBr 5H2O

C6H5COOH C6H4SO2CONH 3CO2 6H2 HBr

+ +

+ ++

H+

+

CHAPTER 3

RESULTS AND DISCUSSION

4-Oxoacids and N-Bromobenzamide system

51

CHAPTER 3

Results and Discussion

4-Oxoacids and N-Bromobenzamide System

Unsubstituted and substituted 4-oxoacids were taken as substrates and N-

bromobenzamide (NBB) as oxidant. The oxidation was carried out in the

presence of perchloric acid. The results obtained on the oxidation of 4-

oxoacids with N-bromobenzamide in aqueous acetic acid medium are

presented and discussed here.

3.1 Structure of 4-Oxoacid and N-Bromobenzamide

4-Oxo-4-phenylbutanoic acid (S1)

Br

O NH

N-Bromobenzamide (NBB)

3.2 List of Substituted 4-Oxoacids The various substituted 4-oxoacids employed in the present study are

listed below (Table 1).

52

Table 1. Name of the unsubstituted and substituted 4-oxoacids used in

this study

Compound Code Name

S1 4-Oxo-4-phenylbutanoic acid

S2 4-Oxo-4-(4’-methoxyphenyl)butanoic acid

S3 4-Oxo-4-(4’-methylphenyl)butanoic acid

S4 4-Oxo-4-biphenylbutanoic acid

S5 4-Oxo-4-(4’-chlorophenyl)butanoic acid

S6 4-Oxo-4-(4’-bromophenyl)butanoic acid

S7 4-Oxo-4-(3’-nitrophenyl)butanoic acid

3.3 Kinetics of Oxidation of 4-Oxo-4-phenylbutanoic Acid

(S1) by N-Bromobenzamide

All the experiments were carried out in aqueous acetic acid medium. The

kinetic runs were conducted under pseudo-first order conditions keeping

the concentration of oxoacid at least ten times greater than that of NBB.

The reaction was followed potentiometrically by setting up a cell made up

of the reaction mixture into which a platinum electrode and a standard

calomel electrode were dipped. The emf of the cell was measured

periodically using an Equip-Tronics potentiometer, while the reaction

mixture was continuously stirred.

The kinetics of oxidation of 4-oxoacids by N-bromobenzamide

has been studied potentiometrically in aqueous acetic acid medium

53

in the presence of perchloric acid at constant ionic strength. The ionic

strength of the medium was maintained by the addition of NaClO4. The

reaction was carried out in the absence of perchloric acid or other

mineral acids, it was found that the reaction proceeded extremely slow

(Table 3). The same trend was observed in the earlier reports285-288.

Hence the reaction was carried out in the presence of perchloric acid.

The pseudo-first order rate constants k1 computed from the plots of

ln(Et-E) against time were reproducible within 3%. Experiments

were carried out at 30o C

3.3.1 Effect of varying [S1]0

The order of the reaction with respect to the concentration of 4-

oxoacid was determined by studying the rate of the reaction at different

initial concentrations of the oxoacid. The rate constants were

determined at various initial concentrations of 4-oxo-4-phenylbutanoic

acid (0.02-0.08 M) at constant concentration of N-bromobenzamide

(0.002 M), perchloric acid (0.5 M) and sodium perchlorate (0.5 M) in

50% (v/v) aqueous acetic acid medium. The values are given in

Table 2. The plots of ln(Et - E∞) versus time (sec) for the various

concentrations of the oxoacid are linear (Figure 1). The second order

rate constants k2, were calculated by dividing the observed pseudo first

order rate constants with the initial concentrations of the oxoacids.

54

The values are found to be constant. These results indicate the first

order dependence of the oxoacid on the rate of the reaction. This is

further supported by the fact that the plot log k1 against log [S1] is

linear (r2 = 0.989) with a slope value of 0.996 (Figure 2) and the plot

of k1 versus [S1] gives a straight line passing through the origin

(Figure 3).

55

Table 2. Rate constants for the oxidation of 4-oxo-4-phenylbutanoic

acid (S1) by NBB in aqueous acetic acid medium at 30 0Ca

aAs determined by a potentiometric technique following the

disappearance of oxidant; the error quoted in k values is the 95%

confidence limit of 'Student t' test287. bEstimated from pseudo-first order plots over 70% reaction. cIndividual k2 values estimated as k1 / [S1].

102 [S] M

103 [NBB]

M

[H+] M

104 k1b

s-1 103 k2

c M-1 s-1

2.0 2.0 0.5 1.62 ± 0.15 8.08 ± 0.75

3.0 2.0 0.5 2.42 ± 0.12 8.07 ± 0.40

4.0 2.0 0.5 3.22 ± 0.25 8.06 ± 0.63

6.0 2.0 0.5 4.85 ± 0.24 8.09 ± 0.40

8.0 2.0 0.5 6.44 ± 0.35 8.05 ± 0.44

2.0 2.0 0.8 2.56 ± 0.21 0.32 ± 0.03

2.0 2.0 1.2 3.84 ± 0.21 0.32 ± 0.02

2.0 2.0 1.4 4.48 ± 0.28 0.32 ± 0.02

2.0 2.0 1.6 5.12 ± 0.22 0.32 ± 0.01

2.0 1.6 0.5 1.62 ± 0.31 -

2.0 1.2 0.5 1.61 ± 0.22 -

2.0 1.0 0.5 1.62 ± 0.41 -

2.0 0.8 0.5 1.62 ± 0.34 -

56

Figure 1. Dependence of rate on [S1]

Figure 2. Order with respect to S1

4+lo

g k 1

3 + log[S1]

2+ln

(E

t - E

)

r2

57

Figure 3. Direct plot for the oxidation of S1 by NBB

3.3.2 Effect of varying [NBB]0

The reaction was studied at various concentrations of the NBB

keeping the concentration of other reagents. The concentrations of

N-bromobenzamide were varied from 2.0-0.8 X 10-3 M at constant

concentration of 4-oxoacid, perchloric acid and sodium perchlorate

in 50% (v/v) aqueous acetic acid medium. For the various

concentrations of N-bromobenzamide, the plots of ln(Et - E∞) versus

time (sec) are linear (Figure 4). The rate constants are found to be

nearly constant for the different concentrations of the N-

bromobenzmide as shown in the Table 2. This indicates clearly that

the reaction is first order with respect to N-bromobenzamide.

r2

58

Figure 4. Dependence of rate on [NBB]

3.3.3 Effect of varying [H+]0

The reaction was studied in the presence and absence of hydrogen ions.

In the absence of mineral acid, the reaction occurs very slowly and the

half life period of the reaction is more than 20 h. However, the reaction

is enhanced remarkably when mineral acid is used as catalyst.

The dependence of the reaction rate on the hydrogen ion

concentration has been studied. The rate of the reaction increases

linearly with increase in concentration of hydrogen ions when the

a = 0.002 M b = 0.0016 M c = 0.0012 M d = 0.001 M e = 0.0008 M

59

concentration of perchloric acid is varied in the range of 0.5 M to 1.6 M at

constant ionic strength. The extent of increase in the reaction rate with

[H+] is shown in the Table 2 and in Figure 5. The plot of log k1 against

log [H+] is linear (r2 = 0.993) with a slope of 0.927 (Figure 6).

Figure 5. Dependence of rate on [H+]

60

Figure 6. Order with respect to [H+]

The k1 versus [H+] plot is linear passing through the origin

(Figure 7) showing that the reaction proceeds completely through the

acid-catalyzed pathway114 and the order with respect to [H+] is one. It

has been reported earlier in the case of N-halo amides that in the

absence of mineral acids, HOBr is the reactive oxidizing

species87,94,102. The linear increase in the oxidation rate with an

increase in [H+] in the present investigation indicates the protonation of

HOBr to give a cationic chlorine species which is a stronger

electrophile and oxidant (eq.51).

HOBr + H3O+ H2O

+Br + H2O (51)

The participation of hypobromous acidium ions in many

electrophilic substitution and oxidation reactions is well documented49.

r2

61

Figure 7. Plot of k1 versus [H+]

It has been reported earlier, in the case of N-halo amides, that the

probable reactive species74 in acid solution are >NX, >N+HX, HOX,

and H2O+X. In the case of N-bromobenzamide the actual reacting

species173 in acid medium are HOBr and H2O+Br. The formation of

benzamide as one of the products in the present study indicates that

N+XH and >NX may not be the reactive species. Thus, the most probable

oxidizing species is hypobromous acidium ion H2O+Br.

3.3.4 Comparison of rates in presence and absence of H+ ion

The relative rates for the oxidation of 4-oxoacids by N-

bromobenzamide in the presence and absence of perchloric acid are

given in the Table 3.

r2

62

Table 3. Comparative rates in the presence and absence of H+ iona.

S 104 k1b, s-1

In the absence of HClO4 In the presence of 0.5 M HClO4

S1 0.14 ± 0.03 1.62 ± 0.15

S2 0.28 ± 0.06 4.55 ± 0.32

S3 0.24 ± 0.08 3.22 ± 0.26

S4 0.23 ± 0.04 1.88 ± 0.17

S5 0.18 ± 0.06 1.24 ± 0.23

S6 0.15 ± 0.04 0.89 ± 0.12

S7 0.11 ± 0.03 0.23 ± 0.09

a General conditions: [S] = 0.02 M, [NBB] = 0.002 M, Temp: 30 0C,

Solvent composition : 50% Acetic acid – 50% Water (v/v). b Estimated from pseudo-first order plots.

3.3.5 Effect of varying ionic strength on reaction rate

The ionic strength of the reaction medium was changed by the addition

of anhydrous sodium perchlorate and the influence of ionic strength on

the reaction rate has been studied. The values of the rate constants at

different ionic strengths are given for several 4-oxoacids in Table 4. It

is found that the ionic strength of the reaction medium has no

significant effect on the reaction rate. Similar result was obtained by

Harihar et al.,176 in the oxidation of L-arginine by N-bromosuccinimide

in aqueous acetic acid medium.

63

Table 4. Effect of ionic strength for the oxidation of 4-oxoacids by

NBB in aqueous acetic acid medium at 30 0Ca

S [NaClO4], M 104 k1b, s-1

S1 0.5 1.62 ± 0.15

1.0 1.60 ± 0.13

1.5 1.61 ± 0.22

2.0 1.61 ± 0.12

S2 0.5 4.55 ± 0.32

1.0 4.65 ± 0.34

1.5 4.45 ± 0.31

2.0 4.54 ± 0.44

S7 0.5 0.23 ± 0.09

1.0 0.23 ± 0.14

1.5 0.23 ± 0.17

2.0 0.23 ± 0.13

Thimme Gowda and Ishwara Bhat178 have reported that the

increase in ionic strength of the medium slightly decreased the rates for

both N-chlorosuccinimide and N-bromosuccinimide oxidation of

thiosemicarbazide (TSC) in the absence of mercuric acetate in aqueous

medium. The effect of ionic strength was considerable in NCS

oxidation in 1:1 (v/v) aqueous acetic acid medium. In the case of NBS

oxidation the rate increased with increase in ionic strength of the

medium. In the present study, it is observed that the rate of the reaction

is independent of ionic strength of the medium.

64

3.3.6 Effect of added benzamide

The reversibility or otherwise of the electron transfer step is usually

tested by the effect of adding one of the products. As benzamide is

one of the products of oxidation in the present study, the oxidation

reaction is carried out in the presence of benzamide. The addition of

benzamide reduced the rate of oxidation of oxoacids (Table 5).

Thus the retardation of reaction rate on the addition of

benzamide suggests128 a pre-equilibrium step involving a process in

which benzamide is one of the products.

NBB + H3O+ H2O

+Br + Benzamide (52)

If this equilibrium is involved in the oxidation process, the

rate should be an inverse function of benzamide concentration,

which is borne out by the observation that the inverse of the rate

constant gives a linear (r2 = 0.984) plot against [benzamide] (Figure 8).

Similar conclusions have been arrived at in the N-chloronicotinamide

oxidation of amino acids128, and N-bromoacetamide oxidation of some

hydroxy acids93.

65

Table 5. Effect of added benzamide on the rate of the reaction a

102 [Benzamide], M 104 k1, s-1

Nil 1.62 ± 0.15

2.0 1.57 ± 0.22

4.0 1.47± 0.14

6.0 1.38 ± 0.16

8.0 1.31 ± 0.24

10.0 1.27 ± 0.13

aGeneral conditions: Solvent composition : 50% Acetic acid - 50% Water(v/v).

[S] = 0.02 M, [NBB] = 0.002 M, [NaClO4] = 0.5M, [H+] = 0.5 M, Temp: 30 0C

Figure 8. Effect of added benzamide

r2

66

3.3.7 Effect of adding acrylonitrile

Vinyl monomers like acrylonitrile are added to the reaction mixture

under nitrogen atmosphere to find out whether the reaction under

investigation involves the formation of free radicals as the

reaction intermediates.92

In the present study, freshly distilled acrylonitrile freed from

inhibitor is added to the deaerated reaction mixture containing 0.2 M

perchloric acid, since the presence of high concentration of

perchloric acid may prevent precipitation of the polymer. After the

completion of the reaction, the reaction mixture is diluted with

methanol to observe the formation of polymer. It is observed that the

oxidation reaction does not induce the polymerization. Similarly, the

polymer formation is not obtained when ethyl acrylate is added to the

reaction mixture. It reveals the absence of any free radical intermediate

during the oxidation of 4-oxoacid by N-bromobenzamide. Further it is

confirmed by carrying out the oxidation of S1 at different initial

concentrations of acrylonitrile. The results are tabulated (Table 6). It

shows that the rate of the reaction has not been affected by the addition

of acrylonitrile.

67

Table 6. Effect of added acrylonitrile on the rate of the reactiona

103 [Acrylonitrile], M 104 k1, s-1

Nil 1.62 ± 0.15

2.0 1.61 ± 0.28

4.0 1.61 ± 0.23

6.0 1.61 ± 0.11

8.0 1.61 ± 0.25

a General conditions: Solvent composition: 50% Acetic acid - 50% Water (v/v).

[S] = 0.02 M, [NBB] = 0.002 M, [NaClO4] = 0.5M, [H+] = 0.5 M, Temp: 300 C.

3.3.8 Effect of solvent polarity on reaction rate

The oxidation of 4-oxoacids by N-bromobenzamide has been studied in

the binary mixture of acetic acid and water as the solvent medium. For

the oxidation of all the 4-oxoacids, the reaction rate increased

remarkably with the increase in the proportion of acetic acid in the

solvent medium. These results are presented in Table 7.

The enhancement of the reaction rate with an increase in the

amount of acetic acid may generally be attributed to two factors, viz, (i)

increase in acidity at constant [perchloric acid] and (ii) decrease in

dielectric constant with increase in acetic acid content. The plots of log

k1 against the inverse of the dielectric constant are linear with positive

slopes (Figure 9), indicating an interaction between a positive ion and

dipolar molecule287-290 .This supports the postulation of H2O+Br as the

reactive species.

68

Similar results and conclusions are arrived at in the oxidation

of primary alcohols by N-bromo-3,5-dinitrobenz-amide159. Sikkandar

and Basheer Ahamed have observed255 that as acetic acid

percentage is increased three times, the reaction rate also

increases three times and have attributed this trend i) to the

lowering of dielectric constant of the medium which favors reactions

involving protonation and ii) to the enolization of the oxoacid which

may be catalyzed by acetic acid.

In the present study, the significant rate enhancement with

the lowering of dielectric constant of the solvent medium may

be attributed to the enolization of the ketoacid group in the 4-

oxoacid. This trend is observed for all the substituted 4-oxoacids taken

for investigation. The enolization of the keto group of the oxoacid

is facilitated by the increase in percentage of acetic acid in the

solvent medium and this may also favors the rate enhancement. This

is in agreement with the observation made by Banerji et al. during the

oxidation of cyclohexanone and several methyl ketones291.

69

Table 7. Effect of solvent polarity on the rate of reactiona

S 104 k1

b, s-1 r2 CH3 COOH - H2O (v/v) %

50-50 60-40 70-30 80-20

S1 1.620.15 1.850.15 2.010.13 2.350.15 0.982

S2 4.550.32 4.820.37 4.950.35 5.450.51 0.994

S3 3.220.31 3.450.23 3.550.54 4.050.53 0.995

S4 1.880.14 2.150.12 2.250.14 2.650.18 0.983

S5 1.240.13 1.280.12 1.380.12 1.620.01 0.997

S6 0.890.04 1.020.05 1.110.15 1.370.14 0.983

S7 0.230.05 0.420.06 0.540.07 0.820.18 0.983 aGeneral conditions : [S] = 0.02 M, [NBB] = 0.002 M, [H+] = 0.5 M,

[NaClO4] = 0.5 M, Temperature = 300 C; bEstimated from pseudo-first order plots; cThe values obtained from the plots drawn between 4+log k1 and 1/D

Figure 9. Effect of solvent polarity

5+lo

g k 1

S2

S3

S4S1

S5S6

S7

70

3.3.9 Rate of enolization by bromination method

It has been reported earlier in the case of oxidation of keto compounds

that the oxidation proceeds via enolization of the keto compounds291-295,298.

The rate of enolization of keto compound is found to be faster than

the rate of oxidation. The reactive species of the substrate may be

determined by enolization, which is an acid as well as base

catalyzed reaction and proceeds by a concerted or push-pull

mechanism. The rate of enolization was determined by bromination

method299 for the system under investigation.

The order for the bromination reaction with respect to the 4-

oxoacid, bromine and H+ has been determined. The experimental

results are presented in Table 8. These data indicate that the

bromination of the oxoacid is first order each with respect to the

oxoacid and H+ ion but zero order with respect to bromine.

From the values, it is obvious that the rate of enolization

is faster than the rate of oxidation of the oxoacid. It is interesting

to note that similar trend has been reported by Marigangaiah and

Banerji in the oxidation of methyl aryl ketones288. Hence enol form

of the substrate is probably participating in the rate determining step.

Enol as a reactive species of the substrate has also been reported

in oxidation by Tl(III)300,301.

71

Table 8. Rate of enolizationa

102 [S1] 103 [Br2] [H+] 104 k1 103 k2

M M M s-1 M-1 s-1

2.0 2.0 0.5 1.62 ± 0.15 -

2.0 3.0 0.5 1.61 ± 0.23 -

2.0 4.0 0.5 1.62 ± 0.14 -

2.0 5.0 0.5 1.63 ± 0.13 -

2.0 6.0 0.5 1.61 ± 0.13 -

3.0 2.0 0.5 2.42 ± 0.12 8.07 ± 0.40

4.0 2.0 0.5 3.22 ± 0.25 8.06 ± 0.63

6.0 2.0 0.5 4.85 ± 0.24 8.09 ± 0.40

8.0 2.0 0.5 6.44 ± 0.35 8.05 ± 0.44

2.0 2.0 0.8 2.56 ± 0.21 0.32 ± 0.03

2.0 2.0 1.2 3.83± 0.21 0.32 ± 0.02

2.0 2.0 1.4 4.48 ± 0.28 0.32 ± 0.02

2.0 2.0 1.6 5.12 ± 0.22 0.32 ± 0.01

a General conditions: Solvent composition : 50% Acetic acid - 50% Water (v/v),

Temp: 30 0 C

3.4 Studies with Substituted Oxoacids

The oxidation of substituted 4-oxoacids, S2-S7 by N-bromobenzamide in

aqueous acetic acid medium was studied in the presence of perchloric

acid in order to assess the effect of substituents in the phenyl ring of the

72

oxoacid on reaction rate. The pseudo first order rate constants were

measured at different initial concentrations of oxoacids. The second

order rate constants k2 were found to be constant. The values are given in

the Tables 9-14. The plots of log k1 against log [S] are linear (Figure 10).

These results indicate the first order dependence of the oxoacids

on the rate of the reaction. This is further supported by the fact that

the plot of k1 versus [S] gives a straight line passing through the origin

(Figure 11).

The oxidation was carried out at different initial concentrations of

N-bromobenzamide. The rate constants are found to be nearly constant

(Tables 9-14). This shows that the reaction is first order with respect to N-

bromobenzamide.

The dependence of the reaction rate on the hydrogen ion

concentration has been studied for the various oxoacids (S2-

S7). The rate of the reaction increases linearly with increase in the

concentration of hydrogen ion. The plots of log k1 against log [H+] is

linear with slope values equal to one (Figure 12). This establishes that

the reaction is first order with respect to hydrogen ion concentration.

Also the plots of k1 versus [H+] for the oxidation of various oxoacids

are linear passing through the origin (Figure 13) showing that the

reaction proceeds completely through the acid catalyzed pathway and

the order is one.

73

Table 9. Rate constants for the oxidation of methoxy substituted 4-

oxoacid (S2) by NBB in aqueous acetic acid medium at 300 Ca

102 [S2] M

103 [NBB] M

[H+] M

104 k1b

s-1 103 k2

c M-1 s-1

2.0 2.0 0.5 4.55 ± 0.45 22.8 ± 2.3

4.0 2.0 0.5 9.07 ± 0.5 22.7 ± 1.4

6.0 2.0 0.5 13.52 ± 0.8 22.5 ± 1.4

8.0 2.0 0.5 18.22 ± 1.2 22.8 ± 1.5

2.0 2.0 0.8 7.28 ± 0.40 0.91 ± 0.05

2.0 2.0 1.2 10.92 ± 0.6 0.91 ± 0.05

2.0 2.0 1.4 12.74 ± 0.1 0.91 ± 0.01

2.0 1.5 0.5 4.53 ± 0.43 -

2.0 1.0 0.5 4.57 ± 0.41 -

2.0 0.5 0.5 4.56 ± 0.35 -

a General conditions : [NaClO4] = 0.5 M, Solvent composition : 50%-

Acetic acid - 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S2].

74

Table 10. Rate constants for the oxidation of methyl substituted 4-

oxoacid (S3) by NBB in aqueous acetic acid medium at 300 Ca

102 [S3] M

103 [NBB] M

[H+] M

104 k1b

s-1 103 k2

c M-1 s-1

2.0 2.0 0.5 3.22 ±0.26 16.1 ±0.54

4.0 2.0 0.5 6.44 ±0.28 16.1 ±0.42

6.0 2.0 0.5 9.72 ±0.32 16.2 ±0.35

8.0 2.0 0.5 13.04 ±0.42 16.3 ±0.28

2.0 2.0 0.8 5.16 ±0.32 0.64 ±0.22

2.0 2.0 1.2 7.68 ±0.23 0.64 ±0.11

2.0 2.0 1.4 8.96 ±0.33 0.64 ±0.12

2.0 1.5 0.5 3.25 ±0.24 -

2.0 1.0 0.5 3.24 ±0.18 -

2.0 0.5 0.5 3.28 ±0.16 -

a General conditions : [NaClO4] = 0.5 M, Solvent composition : 50%-

Acetic acid - 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S2].

75

Table 11. Rate constants for the oxidation of phenyl substituted 4-

oxoacid (S4) by NBB in aqueous acetic acid medium at 300 Ca

102 [S4] M

103 [NBB]

M

[H+] M

104 k1b

s-1 103 k2

c M-1 s-1

2.0 2.0 0.5 1.88 ± 0.11 9.40 ± 0.54

4.0 2.0 0.5 3.71 ± 0.13 9.28 ± 0.33

6.0 2.0 0.5 5.56 ± 0.18 9.27 ± 0.30

8.0 2.0 0.5 7.41 ± 0.33 9.26 ± 0.54

2.0 2.0 0.8 3.04 ± 0.12 0.38 ± 0.01

2.0 2.0 1.2 4.56 ± 0.26 0.38 ± 0.02

2.0 2.0 1.4 5.32 ± 0.26 0.38 ± 0.02

2.0 1.5 0.5 1.82 ± 0.15 -

2.0 1.0 0.5 1.87 ± 0.15 -

2.0 0.5 0.5 1.88 ± 0.08 -

a General conditions : [NaClO4] = 0.5 M, Solvent composition : 50%-

Acetic acid - 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S2].

76

Table 12. Rate constants for the oxidation of chloro substituted 4-

oxoacid (S5) by NBB in aqueous acetic acid medium at 300 Ca

102

[S5] M 103 [NBB]

M [H+]

M 104 k1

b s-1

103 k2c

M-1 s-1

2.0 2.0 0.5 1.24 ±0.17 6.20 ± 0.85

4.0 2.0 0.5 2.10 ±0.20 5.25 ± 0.50

6.0 2.0 0.5 3.13 ±0.17 5.21 ± 0.28

8.0 2.0 0.5 4.19 ±0.22 5.24 ± 0.28

2.0 2.0 0.8 2.04 ±0.09 0.25 ± 0.01

2.0 2.0 1.2 2.83 ±0.07 0.24 ± 0.02

2.0 2.0 1.4 3.35 ±0.12 0.24 ± 0.01

2.0 1.5 0.5 1.05 ±0.07 -

2.0 1.0 0.5 1.03 ±0.13 -

2.0 0.5 0.5 1.06 ±0.14 -

a General conditions : [NaClO4] = 0.5 M, Solvent composition : 50%-

Acetic acid - 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S2].

77

Table 13. Rate constants for the oxidation of bromo substituted 4-

oxoacid (S6) by NBB in aqueous acetic acid medium at 30 0Ca

102 [S6] M

103

[NBB] M

[H+] M

104 k1b

s-1 103 k2

c M-1 s-1

2.0 2.0 0.5 0.89 ± 0.04 4.45 ± 0.20

4.0 2.0 0.5 1.77 ± 0.10 4.44 ± 0.25

6.0 2.0 0.5 2.67 ± 0.12 4.45 ± 0.20

8.0 2.0 0.5 3.57 ± 0.23 4.46 ± 0.29

2.0 2.0 0.8 1.43 ± 0.10 0.18 ± 0.01

2.0 2.0 1.2 2.14 ± 0.13 0.18 ± 0.01

2.0 2.0 1.4 2.49 ± 0.12 0.18 ± 0.01

2.0 1.5 0.5 0.88 ± 0.11 -

2.0 1.0 0.5 0.87 ± 0.11 -

2.0 0.5 0.5 0.89 ± 0.10 -

a General conditions : [NaClO4] = 0.5 M, Solvent composition : 50%-

Acetic acid - 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S2].

78

Table 14. Rate constants for the oxidation of nitro substituted 4-

oxoacid (S7) by NBB in aqueous acetic acid medium at 30 0Ca

102 [S7] M

103 [NBB] M

[H+] M

104 k1b

s-1 103 k2

c M-1 s-1

2.0 2.0 0.5 0.23 ± 0.05 1.15 ± 0.15

4.0 2.0 0.5 0.45 ± 0.06 1.13 ± 0.15

6.0 2.0 0.5 0.68 ± 0.06 1.13 ± 0.10

8.0 2.0 0.5 0.91 ± 0.09 1.14 ± 0.11

2.0 2.0 0.8 0.36 ± 0.05 0.04 ± 0.01

2.0 2.0 1.2 0.54 ± 0.06 0.04 ± 0.01

2.0 2.0 1.4 0.63 ± 0.11 0.05 ± 0.01

2.0 3.0 0.5 0.24 ± 0.02 -

2.0 5.0 0.5 0.23 ± 0.01 -

2.0 7.0 0.5 0.25 ± 0.02 -

a General conditions : [NaClO4] = 0.5 M, Solvent composition : 50%-

Acetic acid - 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S2].

79

Figure 10. Double logarithmic plots for the reaction between

(a) S2 and NBB, (b) S3 and NBB, (c) S4 and NBB,

(d) S5 and NBB, (e) S6 and NBB, (f) S7 and NBB,

3+log [S]

3+lo

g k 1

a

b

c

d e

f

80

Figure 11. Plots of k1 versus [S] for the reaction between

(a) S2 and NBB, (b) S3 and NBB, (c) S4 and NBB,

(d) S5 and NBB, (e) S6 and NBB, (f) S7 and NBB

81

Figure 12. Double logarithmic plots for the reaction between

(a) S2 and NBB, (b) S3 and NBB, (c) S4 and NBB,

(d) S5 and NBB, (e) S6 and NBB, (f) S7 and NBB

2+log [H+]

5+lo

g k 1

a

b

c

d

e

f

82

Figure 13. Plots of k1 versus [H+] for the reaction between

(a) S2 and NBB, (b) S3 and NBB, (c) S4 and NBB,

(d) S5 and NBB, (e) S4 and NBB, (f) S7 and NBB

[H+], M

104 k

1, s

-1

83

3.5 Effect of Substituents and Applicability of LFER

All the seven 4-oxoacids with mono substituents in the phenyl ring

are subjected to oxidation by NBB in 50% aqueous acetic acid

medium in the presence of 0.5 M perchloric acid at four different

temperatures from 303 K to 323 K.

It has been observed that the presence of electron-releasing

groups in the phenyl ring enhances the reaction rate while the electron

withdrawing groups retard the rate. The second order rate constants

for the oxidation of all of the substituted 4-oxoacids are presented

in Table 15.

The reactivity decreases for substituents in the order 4-Methoxy >

4-Methyl > 4-Phenyl > 4- H > 4-Cl > 4-Br > 3-NO2

To correlate the effect of the substituents on the reaction rate

and to find out the validity of linear free energy relationship in the

present series, Hammett’s equation

log k = log k0 +

is applied. The Hammett’s plot for the oxidation of 4-oxoacids by NBB

at various temperatures is found to be linear. The Hammett’s plots are

shown in Figures 14-17. The reaction constant values obtained

from the plots are negative and are presented in Table 16.

84

Table 15. Second order rate constants for the oxidation of 4-

oxoacidsa

S 10 2 k2

b, M-1 s-1

303 K 308 K 313 K 323 K

S1 0.81 ± 0.04 1.13 ± 0.85 1.26 ± 0.11 1.71 ± 0.32

S2 2.27 ± 0.30 2.60 ± 0.30 2.94 ± 0.41 3.45 ± 0.29

S3 1.61 ± 0.29 1.78 ± 0.03 1.92 ± 0.20 2.17 ± 0.25

S4 0.94 ± 0.06 1.14 ± 0.05 1.32 ± 0.01 1.71 ± 0.08

S5 0.62 ± 0.28 0.78 ± 0.54 0.93 ± 0.08 1.22 ± 0.11

S6 0.44 ± 0.02 0.57 ± 0.01 0.74 ± 0.01 0.99 ± 0.01

S7 0.12 ± 0.02 0.23 ± 0.01 0.31 ± 0.08 0.51 ± 0.04

a General conditions : [S] = 0.02 M, [NBB] = 0.002 M, [H+] = 0.5 M,

[NaClO4] = 0.5 M, Solvent composition is 50%-Acetic acid - 50%

Water (v/v); b Individual k2 values estimated as k1 / [S].

85

Figure 14. Hammett (303 K) plot for the oxidation of oxoacids by NBB

The points are referred as: (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

Figure 15. Hammett (308 K) plot for the oxidation of oxoacids by NBB

The points are referred as: (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

r2

r2

86

Figure 16. Hammett (313 K) plot for the oxidation of oxoacids by NBB

The points are referred as: (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

Figure 17. Hammett (323 K) plot for the oxidation of oxoacids by NBB

The points are referred as: (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

r2

r2

87

Table 16. Reaction constant values at different temperatures a

Temperature

K

Reaction constant b

Correlation

coefficient

303 -1.28 0.982

308 -1.04 0.987

313 -0.95 0.984

323 -0.80 0.983 a values were taken from reported works302-304.

b The values were obtained by correlating log (k2 / k20) with p for the reactions

of S1-S7 with NBB.

The values indicate the sensitivity of a reaction to the effects

of electronic perturbation. It also provides information about the nature

of the transition state involved during the reaction. A reaction

involving a development of positive charge in the transition state is

aided by electron-releasing substituents and the valueis negative305-307.

In the present investigation, the acceleration of reaction rate

with the electron-releasing substituents and the negative value of the

reaction constant, indicate explicitly that the mechanism of oxidation

involves the development of positive charge in the transition state.

The Hammett correlations were also made for the rate constants

obtained at different solvent compositions (c.f. Table 7) and the

values are reported in the following Table 17 .

88

Table 17. Reaction constant values at different solvent compositionsa

Solvent

CH3COOH-H2O (v/v) %

Reaction constant b

Correlation

coefficient

50-50 -1.28 0.982

60-40 -1.06 0.986

70-30 -0.97 0.988

80-20 -0.84 0.987 a values were taken from reported works302-304.

b The values were obtained by correlating log (k2 / k20) with p for the reactions

of S1-S7 with NBB.

The data reveal that the selectivity of the oxidant towards

oxoacids decreases with increase in the acetic acid content in the

solvent mixture.

3.6 Mechanism of Oxidation

A probable mechanism for the oxidation of 4-oxoacids by N-

bromobenzamide has been proposed based on the experimental results

and in analogy with the oxidation of oxo compounds with other

oxidants. The results obtained in the kinetic study are briefly

summarized below.

i) The reaction is first order each with respect to the 4-

oxoacid, NBB, and H+ ion.

ii) The linear increase in the reaction rate with the increase

in [H+] ion is attributed to the formation of hypobromous

89

acidium ion (H2O+Br) and to the enolization of the 4-

oxoacid.

iii) The formation of hypobromous acidium ion and the

enolization of the 4-oxoacid is facilitated at lower

dielectric constant of the medium.

iv) The rate of enolization is found to be greater than the rate

of oxidation.

v) The course of the oxidation does not involve any free

radical intermediate.

vi) The retarding effect of the addition of benzamide

suggests that the pre-equilibrium step involves a process

in which benzamide is one of the products.

vii) The reaction rate is enhanced by electron-releasing

substituents in the phenyl ring while the rate is retarded

by electron-withdrawing substituents.

viii) The reaction constant is negative which indicates the

electron deficient transition state.

Considering these facts and findings a suitable mechanism

has been proposed for the oxidation (scheme 1).

90

NBB + H3O+ H2O

+Br Benzamide+

k1

k-1

(55)

(56)

(57)

(58)

Scheme-1

The proposed scheme is formulated to fit in the following

features.

a) The enolization of the 4-oxoacid (eqs. 55 and 56) is

necessary step prior to the oxidation of the substrate. This

is predicted from the experimental finding that under

k -1

(54)

91

identical conditions, the rate of enolization is greater than

the rate of oxidation. Similar conclusions have been

arrived at in the oxidation of several ketones291,292,294 by

acid permanganate.

b) The interaction of oxidizing species H2O+Br with the

enol form of the 4-oxoacid in the rate determining step

(eq.57) leads to the formation of intermediate (F). A

similar type of intermediate has been proposed in the

oxidation of many organic and inorganic compounds308-310.

The intermediate then undergoes further oxidative

cleavage to give the products.

3.7 Derivation of Rate Law

Based on kinetic observations and the mechanism proposed, the

following rate expression can be derived applying steady-state

approximation,

The rate of the reaction is given by

-d [NBB] = k4 [E] [H2O+Br] (59)

dt Applying steady state approximation for [E] k -3 [H3O

+] [E] + k4 [H2O+Br] [E] = k3 [S

+] [H2O] k3 [S

+] [H2O] Therefore, [E] = (60) k-3 [H3O

+] + k4 [H2O+Br]

92

Applying steady state approximation for [S+] k -2 [H2O] [S+] + k 3 [H2O] [S+] = k 2 [H3O

+] [S] + k -3 [H3O+] [E]

k 2 [H3O

+] [S] + k -3 [H3O+] [E]

Therefore, [S+] = k -2 [H2O] + k 3 [H2O]

[H3O

+] { k 2 [S] + k -3 [E]} i.e. [S+] = (61) [H2O] (k -2 + k 3 ) Using the value of [S+] in eq. (60). k 3 [H3O

+] { k 2 [S] + k -3 [E] } [E] = ( k -2 + k 3 ) { k -3 [H3O

+] + k 4 [H2O+Br] }

[E] (k -2 + k 3 ) {k -3 [H3O

+] + k 4 [H2O+Br] } = k 3 [H3O

+] { k 2 [S] + k -3 [E] }

[E](k -2 + k 3 ){ k -3 [H3O+]+k 4[H2O

+Br]}= k 3 k 2 [H3O

+][S]+k3 k -3 [H3O+][E]

[E]{(k -2 +k 3 ) k -3 [H3O

+] + k 4 [H2O+Br] – k 3 k -3 [H3O

+]}= k 3 k2 [H3O+] [S]

k 3 k 2 [H3O

+] [S] [E] = { (k -2 +k 3 ) k -3 [H3O

+] + k 4 [H2O+Br]} – k 3 k -3 [H3O

+] k 3 k 2 [H3O

+] [S] [E] =

k -2 k -3 [H3O+] + k -2 k 4 [H2O

+Br] + k 3 k 4 [H2O

+Br]

k 3 k 2 [H3O

+] [S] [E] = (62)

k -2 k -3 [H3O+] + k 4 (k -2 + k 3) [H2O

+Br]

93

Substituting the value of [E] in eq. (59)

-d [NBB] k 2 k 3 k 4 [H3O+] [S] [H2O

+Br]

= (63) dt k -2 k -3 [H3O

+] + k 4 (k -2 + k 3) [H2O+Br]

At high concentration of [H3O+] = 0.5 M

k -2 k -3 [H3O

+] > > k 4 (k -2 + k 3) [H2O+Br]

So the eq. (63) simplifies to the form

-d [NBB] k 2 k 3 k 4 [H3O+] [S] [H2O

+Br]

= dt k -2 k -3 [H3O

+] k 2 k 3 k 4 [S] [H2O

+Br]

= (64)

k -2 k -3

The value of [H2O+Br] can be obtained from eq. (54) in

the scheme of mechanism

k -1 [NBB] [H3O+]

K a = = k 1 [H2O

+Br] [Benz]

[NBB] [H3O+]

Therefore, [H2O+Br] =

Ka [Benz] Using the value of [H2O

+Br] in eq. (64) -d [NBB] k 2 k 3 k 4 [S] [H3O

+] [NBB] = (65) dt k -2 k -3 Ka [Benz]

94

Hence, at higher concentration of mineral acid, the

reaction is first order each with respect to the oxoacid (S), [NBB]

and [H3O+].

The observed rate constant at high [H3O+] is

k 2 k 3 k 4 kobs = (66)

k -2 k -3 K a

3.8 Structure –Reactivity Correlations

The effect of the substituents present in the phenyl ring of the 4-

oxoacids (S1-S7), on the rates of oxidation has been correlated

quantitatively by the application of Hammett equation. Plots of

log (k2 / k20) versus p are excellently linear with negative slopes

(Figures 14-17). The ρ values for the oxidation range between -1.28 and

-0.80 at different temperatures.

It is generally recognized that oxidations lead to electron

deficient species which are either radical cations, radicals or

carbocations. These reactions normally have a negative ρ value and the

magnitude of values depends on the extent of electron deficiency.

Oxidation reactions involving free radical formation in the rate

controlling step usually have a small negative ρ value and the

oxidations involving the formation of carbocation have a large negative

ρ values. Based on these arguments we expect a large value but the

95

measured ρ value is in the range -1.28 to -0.84. The low value may

be attributed to the nature of observed rate constant. The observed rate

constant is composite of several terms and is shown in eq.(66).

The terms shown in eq.(66) deserve comment. The rate constant

k3 depends on the concentration of the protonated substrate (S+) and

the electron donating substituents tend to delocalize the positive charge

on S+ and hence favors the formation of this positive species. The

value for the enolization of the 4-oxoacids, determined by bromination

method has been reported to be -0.75311. In the rate limiting step

(eq.57) of the scheme, the formation of the carbocation is facilitated by

electron releasing substituents.

Thus we get a slightly low negative value of -1.28 (at 303 K)

because kobs is composite of the enolization as well as the oxidation of the

4-oxoacids. Hence in the present investigation the measured value and

other findings fit in with the formulation of mechanism outlined in the

scheme 1.

3.9 Activation Parameters

The dependence of reaction rate on the structure of the reacting

molecule is related to activation parameters. The decisive term

concerning the dependence on the structure is neither free energy nor

96

enthalpy but potential energy which is experimentally not accessible.

Many authors support the opinion that the activation energy at a certain

temperature is a better approximation towards the unknown potential

energy312. The activation parameters for the oxidation of 4-oxoacid by

NBB have been evaluated from the slope values of the Arrhenius plots

(Figures 18 & 19). A close look at activation parameters presented in

Table 18 shows that the activation energies for the oxoacids with

electron-releasing substituents are relatively lower than that with

electron-withdrawing substituents. The entropy of activation is

negative for all the 4-oxoacids ranging from -119.5 to -248.4 J K-1 mol-1.

Figure 18. Arrhenius plot for the oxidation of S1, S2, S3 & S4 by NCB

1/T X 103

4+lo

g k 2

97

Figure 19. Arrhenius plot for the oxidation of S5, S6 & S7 by NCB

The large negative entropy of activation in conjunction with

other experimental data supports the mechanism outlined in the

scheme. The formation of an activated complex from reactant

molecules is accompanied by the conversion of translation-like and

rotational-like degree of freedom of the reactants to vibrational degree

of freedom of the transition state species. The more widely spaced

energy level for the latter type of molecular motion imply a small

entropy and thus a negative value of S#313. As the charge separation

begins in the transition state, each end of the dipole becomes solvated

by a sheath of solvent molecules, which must, however be suitably

98

oriented. This increase in orientation means restricted freedom and

results in a decrease in entropy310. A careful analysis of the activation

parameters in Table 18 reveals that the present series is neither

isoentropic nor isoenthalpic314.

Table 18. Activation parameters for the oxidation of 4-oxoacids by

NBB in aqueous acetic acid mediuma

S Ea

kJ mol-1 ∆H#

kJ mol-1 −∆S#

JK-1 mol-1∆G#

kJ mol-1

S1 30.71 28.19 -192.09 86.40

S2 16.83 14.31 -229.32 83.79

S3 11.91 9.39 -248.43 84.67

S4 24.03 21.51 -212.91 86.02

S5 27.07 24.55 -206.32 87.07

S6 32.40 29.88 -191.51 87.91

S7 57.63 55.11 -119.48 91.31

a General conditions : [S] = 0.02 M, [NBB] = 0.002 M, [H+] = 0.5 M,

[NaClO4] = 0.5 M, Solvent composition is 50%-Acetic acid - 50% Water (v/v);

99

3.10 Isokinetic Relationships

Leffler’s isokinetic equations

Ea = E0 + 2.303 R log A (67)

H# = H0 + S# (68)

hold good in a series of related reactions. The validity of the isokinetic

relation can be tested graphically by plotting either H# versus S# or

Ea versus log A. This linear relationship between activation enthalpies

and activation entropies or activation energies and frequency factors in

a series of related reactions is known as isokinetic relationship315,316.

The validity of the isokinetic plot is questionable317,318 because

the quantities H# and S# are mutually dependent, both being derived

from the same experimental rate constants. An alternative graphical

method for finding out the isokinetic temperature is suggested by

Exner. A plot of the rate constants measured at two different

temperatures [log k2 (T2) versus log k2 (T1)] is known as Exner plot.

From the slope b, of the Exner plot, the isokinetic temperature , can

be calculated using the equation.

= T1 T2 (1- b) (69)

T1 – b T2

Based on the values of b, the reaction series (Table 19) have been

characterized as follows317.

100

Table 19. b values of the reaction series

Series b

Isoentropic ∞ T2 / T1

Isoenthalpic 0 1

Compensation > Texp <1

The Exner plots drawn for the reaction by choosing k2 values at

any two different temperatures are shown in Figures 20-22 . The values

of b are less than unity in all the plots. This indicates that the present

reaction series is neither isoentropic nor isoenthalpic but involves

compensation. The lsokinetic temperature evaluated from the Exner

plots is found to be 347 K. As the experiment has been carried at a

temperature far away from the isokinetic temperature the application of

Hammett equation to the observed kinetic data is valid. The validity

of isokinetic relationship in the present study implies that all the 4-

oxoacids undergo oxidation by the same mechanism310, 319, 320.

101

Figure 20. Exner plot for the oxidation of oxoacids by NBB

The points referred as; (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

K

K

r2

102

Figure 21. Exner plot for the oxidation of oxoacids by NBB

The points referred as; (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

K

K

r2

103

Figure 22. Exner plot for the oxidation of oxoacids by NBB

The points referred as; (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

K

K

r2

CHAPTER 4

4-Oxoacids and N-Bromosaccharin system

104

CHAPTER 4

4-Oxoacids and N-Bromosaccharin System

Studies of oxidation of various organic compounds by N-halo amides

in the presence of perchloric acid have attracted considerable

attention176-213. N-Bromosaccharin (NBSac) is a source of positive

halogen and have been exploited as oxidant for a variety of substrates

in both the acidic and alkaline media.

Moreover with the same 4-oxoacids no detailed kinetic study on

oxidation with N-bromosaccharin (NBSac) has been attempted so far.

It is also interesting to know whether the oxidation of unsubstituted and

substituted 4-oxoacids by NBSac follow similar type of mechanism or

not. In this chapter the results obtained from a detailed kinetic study on

the oxidation of 4-oxoacids with NBSac in the presence of perchloric

acid in aqueous acetic acid medium are analyzed.

4.1 Kinetics of Oxidation of 4-Oxo-4-phenylbutanoic

Acid (S1) by N-Bromosaccharin

The kinetics of oxidation of 4-oxoacids by N- bromosaccharin (NBSac)

has been studied potentiometrically in aqueous acetic acid medium in the

presence of perchloric acid at constant ionic strength. The ionic strength

of the medium was maintained by the addition of NaClO4. Using 10 – 50

fold excess of oxoacid over oxidant, excellent ln (Et - E∞) versus time

105

plots were obtained; from these, the pseudo first order rate constants k1,

and hence k2 were determined. (cf. chapter 3).

4.1.1 Effect of varying [reactants]0

The pseudo first order rate constants (k1) obtained at different initial

concentrations of one reactant, keeping the concentration of other

reactant constant for the oxidation of 4-oxo-4-phenylbutanoic acid

with NBSac in the presence of perchloric acid are listed in Table 20.

The plots of ln(Et - E∞) versus time (sec) for the various concentrations

of the oxoacids are linear (Figure 23).

106

Table 20. Rate constants for the oxidation of 4-oxo-4-

phenylbutanoic acid (S1) by NBSac in aqueous acetic acid

medium at 30 0Ca

102 [S1] M

103 [NBSac]

M

[H+] M

104 k1b

s-1 103 k2

c M-1 s-1

2.0 2.0 0.5 1.44 ± 0.12 7.20 ± 0.31

4.0 2.0 0.5 2.84 ± 0.17 7.10 ± 0.24

6.0 2.0 0.5 4.32 ± 0.02 7.20 ± 0.23

8.0 2.0 0.5 5.62 ± 0.25 7.01 ± 0.33

2.0 2.0 1.0 2.84 ± 0.12 0.28 ± 0.21

2.0 2.0 1.2 3.43 ± 0.16 0.29 ± 0.22

2.0 2.0 1.4 4.04 ± 0.29 0.29 ± 0.13

2.0 0.8 0.5 1.42 ± 0.06 -

2.0 0.4 0.5 1.46 ± 0.03 -

2.0 0.2 0.5 1.48± 0.03 -

a General conditions: [NaClO4] = 0.5 M,

Solvent composition : 50% Acetic acid – 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S1]

107

Figure 23. Dependence of rate on [S1]

The second order rate constants k2, obtained by dividing the

observed pseudo first order rate constants with initial concentrations of

the oxoacid are found to be constant. These results indicate the first

order dependence of the oxoacid on the rate of the reaction.

This is further supported by the fact that the plot of log k1 against

log [S1] is linear (r2 = 0.998) with a unit slope (slope = 0.987) (Figure

24 and Table 20) and the plot of k1 versus [S1] gives a straight line

passing through the origin (Figure 25). The k1 values obtained at

different initial concentrations of NBSac (Table 20) reveal that the rates

are almost independent of initial concentration of NBSac (Figure 26).

108

Figure 24. Order with respect to [S1]

Figure 25. Plot of k1 versus [S1]

r2

109

Figure 26. Dependence of rate on [NBSac]

4.1.2 Effect of varying [H+]

The dependence of the reaction rate on the hydrogen ion concentration

has been investigated at different initial concentrations of perchloric acid,

keeping the concentrations of the other reactants constant. The time

dependent plots of ln (Et – E∞) versus time at different [H+] are shown in

Figure 27. The observed k1 values are presented in the Table 20. It may be

seen that the rate of the reaction increases linearly with increase in

concentration of hydrogen ion.

110

Figure 27. Dependence of rate on [H+]

The plot of log k1 against log [H+] is linear (r2 = 0.997) with a

slope value of 0.996 (Table 20 and Figure 28). This establishes that the

reaction is first order with respect to hydrogen ion concentration. A

plot of k1 versus [H+] is also linear passing through the origin

(Figure 29) showing that the reaction proceeds completely through the

acid-catalyzed pathway114.

It has been reported earlier in the case of N-halo oxidants that in

the absence of mineral acids, HOBr is the reactive oxidant species87,102.

Bishnoi and Banerji have observed93 in the oxidation of some -

hydroxy acids by NBA that linear increase in the oxidation rate with an

increase in [H+] indicates the protonation of HOBr to give a cationic

111

bromine species (see eq.70), which is a stronger electrophile and

oxidant.

HOBr + H3O+ H2O

+Br + H2O (70)

Thus the most probable oxidizing species is hypobromous

acidium ion, (H2O+Br). The participation of hypohalous acidium ions

in many electrophilic substitution and oxidation reactions is well

documented49. Similar results have been arrived at in the case of N-

halo compound oxidation of ketones173.

Figure 28. Order with respect to [H+]

r2

112

Figure 29. Plot of k1 versus [H+]

4.1.3 Effect of varying ionic strength

The ionic strength of the reaction medium was changed by the addition

of anhydrous sodium perchlorate and the influence of ionic strength on

the reaction rate was studied. The values of the rate constants at

different ionic strengths are given for several 4-oxoacids (Table 21). It

is found that the ionic strength of the reaction medium has no

significant effect on the reaction rate.

4.1.4 Effect of added Saccharin

The effect of added saccharin was studied by the addition of saccharin

in the concentration range 0.02 – 0.08 M and the data are presented in

Table 22. The addition of saccharin decreases the rate of oxidation

reaction.

113

Thus the retardation of reaction rate on the addition of saccharin

suggests128 a pre-equilibrium step involving a process in which

saccharin is one of the products.

NBSac + H3O+ H2O

+Br + Saccharin (71)

Table 21. Effect of ionic strength for the oxidation of 4-oxoacids by

NBSac in aqueous acetic acid medium at 30 0C a

S [NaClO4]

M

104 k1b

s-1

S1 0.5 1.44 ± 0.12

1.0 1.41 ± 0.16

1.5 1.43 ± 0.17

2.0 1.42 ± 0.21

S2 0.5 5.25 ± 0.42

1.0 5.22 ± 0.33

1.5 5.21 ± 0.24

2.0 5.20 ± 0.21

S7 0.5 0.18 ± 0.03

1.0 0.19 ± 0.13

1.5 0.17 ± 0.12

2.0 0.20 ± 0.12

a General conditions: [S1] = 0.02 M, [NBSac] = 0.002M, [H+] = 0.5 M,

Solvent composition: 50% Acetic acid-50% Water (v/v). Temp:30 0C. b Estimated from pseudo-first order plots.

114

Table 22. Effect of added saccharin on the rate of the reactiona

S 102 [Saccharin] 104 k1b

M s-1

S1 Nil 1.44 ± 0.12

2.0 1.28 ± 0.11

4.0 1.07 ± 0.12

6.0 1.01 ± 0.13

8.0 0.87 ± 0.12

a General conditions: [S1] = 0.02 M, [NBSac] = 0.002M, [H+] = 0.5 M,

Solvent composition: 50% Acetic acid-50% Water (v/v). Temp:30 0C. b Estimated from pseudo-first order plots.

If this equilibrium is involved in the oxidation process, the

rate should be an inverse function of saccharin concentration, which

is borne out by the observation that the inverse of the rate constant

(Figure 30) gives a linear (r2 = 0.982) plot against [Saccharin].

Similar conclusions have been arrived at in the N-

chloronicotinamide oxidation of amino acids128, and N-

bromoacetamide oxidation of some - hydroxy acids93.

115

Figure 30. Effect of added saccharin

4.1.5 Effect of free radical inhibitor

In the previous reports of oxidation of organic compounds with N-halo

amide free radical inhibitors such as acrylamide114, acrylonitrile94,179,255

have been used for detecting the involvement of free radical oxidizing

species. Vinyl monomers like acrylonitrile are added to the reaction

mixture under nitrogen atmosphere to find out whether the reaction

under investigation involves the formation of free radicals as the

reaction intermediates.

In the present study freshly distilled acrylonitrile freed from

inhibitor is added to the deaerated reaction mixture containing 0.2 M

perchloric acid. After the completion of the reaction, the reaction

mixture is diluted with methanol to observe the formation of polymer.

s-1

r2

116

It is observed that the oxidation reaction does not induce the

polymerization.

Further it is confirmed by carrying out the oxidation reaction at

different initial concentrations of the inhibitor for the reaction of S1

with NBSac catalyzed by perchloric acid and the data are collected in

the Table 23. These data illustrate that the rate of the reaction is almost

unaffected in the presence of inhibitor. Consequently it may be inferred

that free radicals are not involved in the rate controlling step of the

present reaction.

Table 23. Effect of added acrylonitrile on the rate of the reaction a

S 103 [Acrylonitrile] 104 k1b

M s-1

S1 Nil 1.44 ± 0.12

3.0 1.45 ± 0.13

4.0 1.44 ± 0.11

6.0 1.43 ± 0.13

8.0 1.45 ± 0.12

a General conditions: [S1] = 0.02 M, [NBSac] = 0.002M, [H+] = 0.5 M,

Solvent composition: 50% Acetic acid-50% Water (v/v). Temp:300 C. b Estimated from pseudo-first order plots.

117

4.1.6 Effect of solvent composition

The effect of changing solvent composition on the reaction rate was

studied by varying the concentration of acetic acid from 50% - 80%.

The pseudo first-order rate constants for the oxidation reactions of all

oxoacids, S1-S7 with NBSac were estimated in the presence of

perchloric acid at constant ionic strength. The rate constants listed in

Table 24 suggest that the rate of the reaction increases with increase in

acetic acid content of the solvent mixture. A plot of log k1 versus 1/D

is linear with positive slope.

Table 24. Effect of solvent polarity on the rate of reactiona

S 104 k1b, s-1

rc CH3 COOH - H2O (v/v) % 50-50 60-40 70-30 80-20

S1 1.440.12 2.240.24 3.120.14 5.280.29 0.998

S2 5.250.42 6.830.34 7.850.48 9.350.60 0.983

S3 3.820.41 4.910.22 6.310.24 7.520.34 0.985

S4 1.560.11 2.110.07 2.920.14 4.230.18 0.998

S5 0.980.14 1.320.06 2.320.11 3.010.01 0.998

S6 0.910.02 1.070.05 1.680.12 2.360.15 0.994

S7 0.180.03 0.310.03 0.610.07 0.920.08 0.998

a General conditions: [S1] = 0.02 M, [NBSac] = 0.002M, [H+] = 0.5 M, b Estimated from pseudo-first order plots. c The values obtained from the plots drawn between 4+log k1 and 1/D

118

The observed effect is similar to those reported in the oxidation

of other organic compounds by NBA110. In the solution containing

acetic acid, one can not exclude the possibility of (AcO+HBr) acting as

a reactive oxidizing species.

The enhancement of the reaction rate with an increase in the

amount of acetic acid may generally be attributed to two factors, viz

(i) increase in acidity at constant [perchloric acid] and (ii) decrease in

dielectric constant with increase in HOAc content. The plots of log k1

against the inverse of dielectric constant are linear with positive slopes,

indicating an interaction between a positive ion and a dipole

molecule287-290. This supports the postulation of H2O+Br as the reactive

species.

But, in the oxidation of some amino acids by NBSac in aqueous

acetic acid medium, variation of solvent composition shows negligible

effect on the rate of the reaction110. The negligible effect of changing

the dielectric constant of the medium might be due to the involvement

of neutral species in the reaction.

In the present system, the significant rate enhancement, with the

lowering of dielectric constant of the solvent medium may be

attributed to the enolization of the ketoacid group in the 4-oxoacid.

This trend is observed for all the substituted 4-oxoacids taken for

investigation. The enolization of the keto group of the oxoacid is

119

facilitated by the increase in percentage of acetic acid in the solvent

medium and this may also favor the rate enhancement. This is in

agreement with the observations made by Basheer Ahamed and

Sikkandar255 during the oxidation of 4-oxoacids by acid permanganate.

4.1.7 Rate of enolization of substrate

The rate of enolization was studied by bromination method and it has

been discussed in the chapter 3.3.9. It is known that the rate of

enolization was much faster than the rate of oxidation (cf. Table 8).

Hence in the present system also we can infer that the enol forms of the

substrate probably participate in the rate determining step.

4.2 Studies with Substituted Oxoacids

The oxidation of substituted oxoacids, S2-S7 by NBSac in aqueous acetic

acid medium was studied in the presence of perchloric acid in order to

assess the effect of substituents in the phenyl ring of the oxoacid on

reaction rate. The pseudo first order rate constants were measured at

different initial concentrations of oxoacids. The second order rate

constants k2 were found to be constant. The values are given in the Tables

25-30. The plots of log k1 against log [S] is linear and the slope is close to

unity. These results indicate the first order dependence of the

oxoacids on the rate of the reaction (Figure 31). This is further

supported by the fact that the plot of k1 versus [S] gives a straight line

passing through the origin (Figure 32).

120

The oxidation was carried out at different initial

concentrations of N-bromosaccharin. The rate constants are found to

be nearly constant (Table 25-30). This shows that the reaction is first

order with respect to N-bromosaccharin.

Table 25. Rate constants for the oxidation of methoxy substituted

4–oxoacid (S2) by NBSac in aqueous acetic acid medium at 30 0Ca

102 [S2] M

103 [NBSac]

M

[H+] M

104 k1b

s-1 103 k2

c M-1 s-1

2.0 2.0 0.5 5.25± 0.42 26.3 ± 1.5

4.0 2.0 0.5 10.41± 0.60 26.1 ± 1.7

6.0 2.0 0.5 15.7± 1.2 26.2 ± 1.8

8.0 2.0 0.5 20.70± 2.1 25.8 ± 1.6

2.0 2.0 1.0 10.5± 0.50 1.05 ± 0.02

2.0 2.0 1.2 12.4± 0.60 1.03 ± 0.04

2.0 2.0 1.4 14.2± 0.1 1.10 ± 0.06

2.0 0.8 0.5 5.21± 0.06 -

2.0 0.4 0.5 5.25± 0.07 -

2.0 0.2 0.5 5.23± 0.16 -

a General conditions: [NaClO4] = 0.5 M,

Solvent composition : 50% Acetic acid – 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S2]

121

Table 26. Rate constants for the oxidation of methyl substituted 4–

oxoacid (S3) by NBSac in aqueous acetic acid medium at 30 0Ca

102 [S3] M

103 [NBSac]

M

[H+] M

104 k1b

s-1

103 k2c

M-1 s-1

2.0 2.0 0.5 3.82 ± 0.41 19.25 ± 0.14

4.0 2.0 0.5 7.60 ± 0.86 19.00 ± 0.13

6.0 2.0 0.5 11.58 ± 0.80 19.30 ± 0.12

8.0 2.0 0.5 15.12 ± 0.20 18.90 ± 1.12

2.0 2.0 1.0 7.64 ± 0.25 0.76 ± 0.04

2.0 2.0 1.2 9.12 ± 0.26 0.76 ± 0.03

2.0 2.0 1.4 10.42 ± 0.60 0.74 ± 0.02

2.0 0.8 0.5 3.81 ± 0.10 -

2.0 0.4 0.5 3.85 ± 0.11 -

2.0 0.2 0.5 3.83 ± 0.10 -

a General conditions: [NaClO4] = 0.5 M,

Solvent composition : 50% Acetic acid – 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S2]

122

Table 27. Rate constants for the oxidation of phenyl substituted 4–

oxoacid (S4) by NBSac in aqueous acetic acid medium at 30 0Ca

102 [S4] M

103 [NBSac]

M

[H+] M

104 k1b

s-1 103 k2

c M-1 s-1

2.0 2.0 0.5 1.56 ± 0.11 7.80 ± 0.32

4.0 2.0 0.5 3.08 ± 0.13 7.70 ± 0.24

6.0 2.0 0.5 4.56 ± 0.18 7.60 ± 0.18

8.0 2.0 0.5 6.41 ± 0.43 8.01 ± 0.25

2.0 2.0 1.0 3.12 ± 0.26 0.31 ± 0.03

2.0 2.0 1.2 3.74 ± 0.22 0.31 ± 0.21

2.0 2.0 1.4 4.35 ± 0.19 0.31 ± 0.03

2.0 0.8 0.5 1.52 ± 0.05 -

2.0 0.4 0.5 1.53 ± 0.03 -

2.0 0.2 0.5 1.51 ± 0.08 -

a General conditions: [NaClO4] = 0.5 M,

Solvent composition : 50% Acetic acid – 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S2]

123

Table 28. Rate constants for the oxidation of chloro substituted 4–

oxoacid (S5) by NBSac in aqueous acetic acid medium at 30 0Ca

102 [S5] M

103 [NBSac]

M

[H+] M

104 k1b

s-1 103 k2

c M-1 s-1

2.0 2.0 0.5 0.98 ± 0.14 0.49 ± 0.32

4.0 2.0 0.5 1.88 ± 0.20 0.47 ± 0.41

6.0 2.0 0.5 2.88 ± 0.17 0.48 ± 0.22

8.0 2.0 0.5 4.01 ± 0.22 0.50 ± 0.41

2.0 2.0 1.0 1.96 ± 0.07 0.19 ± 0.03

2.0 2.0 1.2 2.34 ± 0.15 0.19 ± 0.04

2.0 2.0 1.4 2.72 ± 0.17 0.19 ± 0.04

2.0 0.8 0.5 0.97 ± 0.07 -

2.0 0.4 0.5 0.97 ± 0.13 -

2.0 0.2 0.5 0.98 ± 0.04 -

a General conditions: [NaClO4] = 0.5 M,

Solvent composition : 50% Acetic acid – 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S2].

124

Table 29. Rate constants for the oxidation of bromo substituted 4–

oxoacid (S6) by NBSac in aqueous acetic acid medium at 30 0Ca

102 [S6] M

103 [NBSac]

M

[H+] M

104 k1b

s-1 103 k2

c

M-1 s-1

2.0 2.0 0.5 0.91 ± 0.02 4.55 ± 0.32

4.0 2.0 0.5 1.82 ± 0.10 4.55 ± 0.26

6.0 2.0 0.5 2.65 ± 0.12 4.42 ± 0.22

8.0 2.0 0.5 3.62 ± 0.23 4.52 ± 0.28

2.0 2.0 1.0 1.81 ± 0.07 0.18 ± 0.04

2.0 2.0 1.2 2.18 ± 0.11 0.18 ± 0.02

2.0 2.0 1.4 2.52 ± 0.13 0.18 ± 0.03

2.0 0.8 0.5 0.92 ± 0.11 -

2.0 0.4 0.5 0.95 ± 0.10 -

2.0 0.2 0.5 0.96 ± 0.03 -

a General conditions: [NaClO4] = 0.5 M,

Solvent composition : 50% Acetic acid – 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S2]

125

Table 30. Rate constants for the oxidation of nitro substituted

4–oxoacid (S7) by NBSac in aqueous acetic acid medium at 30 0Ca

102 [S7] M

103 [NBSac]

M

[H+] M

104 k1b

s-1 103 k2

c

M-1 s-1

2.0 2.0 0.5 0.18 ± 0.03 0.90 ± 0.11

4.0 2.0 0.5 0.36 ± 0.06 0.90 ± 0.05

6.0 2.0 0.5 0.56 ± 0.06 0.93 ± 0.08

8.0 2.0 0.5 0.72 ± 0.09 0.90 ± 0.07

2.0 2.0 1.0 0.36 ± 0.04 0.04 ± 0.01

2.0 2.0 1.2 0.42 ± 0.03 0.04 ± 0.01

2.0 2.0 1.4 0.51 ± 0.01 0.04 ± 0.01

2.0 0.8 0.5 0.20 ± 0.02 -

2.0 0.4 0.5 0.21 ± 0.01 -

2.0 0.2 0.5 0.19 ± 0.01 -

a General conditions: [NaClO4] = 0.5 M,

Solvent composition : 50% Acetic acid – 50% Water (v/v). b Estimated from pseudo-first order plots over 70% reaction. c Individual k2 values estimated as k1 / [S2]

126

Figure 31. Double logarithmic plots for the reaction between (a) S2

and NBSac (b) S3 and NBSac (c) S4 and NBSac (d) S5 and NBSac (e)

S6 and NBSac (f) S7 and NBSac

3+log [S]

5+lo

g k 1

a b c d e f

127

Figure 32. Plots of k1 versus [S] for the reaction between (a) S2 and

NBSac (b) S3 and NBSac (c) S4 and NBSac (d) S5 and NBSac (e) S6

and NBSac (f) S7 and NBSac

The dependence of the reaction rate on the hydrogen ion

concentration has been studied for the various oxoacids (S2-S7).

The rate of the reaction increases linearly with increase in the

concentration of hydrogen ion. The plot of log k1 against log [H+]

is linear (shown in Figure 33) and the slope is unity. This establishes

that the reaction is first order with respect to hydrogen ion

concentration. Also the plots of k1 versus [H+] for the oxidation of

various oxoacids are linear passing through the origin (Figure 34)

showing that the reaction proceeds completely through the acid

catalyzed pathway and the order is one.

[S], M

104 , k

1, s

-1

a

b

c

d e

f

128

Figure 33. Double logarithmic plots for the reaction between (a) S2

and NBSac (b) S3 and NBSac (c) S4 and NBSac (d) S5 and NBSac (e)

S6 and NBSac (f) S7 and NBSac

3+log [H+]

5+lo

g k 1

a

b

c

d e

f

129

Figure 34. Plots of k1 versus [S] for the reaction between (a) S2 and

NBSac (b) S3 and NBSac (c) S4 and NBSac (d) S5 and NBSac (e) S6

and NBSac (f) S7 and NBSac

4.3 Effect of Substituents and Applicability of LFER

All the nine 4-oxoacids with mono and disubstituents in the phenyl

ring are subjected to oxidation by NBSac in 50% aqueous acetic acid

medium in the presence of 0.5 M perchloric acid at four different

temperatures from 303 K to 323 K.

It has been observed that the presence of electron-releasing

groups in the phenyl ring enhances the reaction rate while the electron

withdrawing groups retard the rate. The second order rate constants

for the oxidation of all of the substituted 4-oxoacids are presented

in Table 31.

a

b

c

d e

f

130

The reactivity decreases for substituents in the order

4-Methoxy > 4-Methyl > 4-Phenyl > 4- H > 4-Cl > 4-Br > 3-NO2.

Table 31. Second order rate constants for the oxidation of 4-

oxoacidsa

S 10 2 k2

b, M-1 s-1

303 K 308 K 313 K 323 K

S1 0.72 ± 0.11 0.93 ± 0.55 1.11 ±0.13 1.74 ± 0.22

S2 2.63 ± 0.12 2.86 ± 0.21 3.71 ±0.31 4.07 ± 0.24

S3 1.91 ± 0.24 2.08 ± 0.06 2.48 ±0.17 2.81 ± 0.22

S4 0.78 ± 0.04 1.14 ± 0.04 1.46 ±0.02 2.06 ± 0.11

S5 0.49 ± 0.18 0.56 ± 0.34 0.66 ±0.04 0.99 ± 0.10

S6 0.46 ± 0.02 0.51 ± 0.03 0.61 ±0.05 0.93 ± 0.04

S7 0.09 ± 0.05 0.16 ± 0.06 0.24 ±0.08 0.33 ± 0.04

a General conditions : [S] = 0.02 M, [NBSac] = 0.002 M, [H+] = 0.5 M,

[NaClO4] = 0.5 M, Solvent composition is 50%-Acetic acid - 50%

Water (v/v). b Individual k2 values estimated as k1 / [S].

To correlate the effect of the substituents on the reaction rate

and to find out the validity of linear free energy relationship in the

present series, Hammett’s equation (eq.68) is applied. The Hammett’s

plots for the oxidation of 4-oxoacids by NBSac at various temperatures

131

are found to be linear. The Hammett’s plots are shown in Figures 35- 38.

The reaction constant ( values obtained from the Hammett’s plots

are negative and are presented in Table 32.

Table 32. Reaction constant values at different temperatures a

Temperature

K

Reaction constant b

Correlation

coefficient

303 -1.41 0.983

308 -1.32 0.992

313 -1.20 0.988

323 -0.98 0.996 a values were taken from reported works302-304.

b The values were obtained by correlating log (k2 / k20) with p for the reactions

of oxidations S1-S7 with NBSac.

The value indicates the sensitivity of a reaction to the

effects of electronic perturbation. It also provides information about

the nature of the transition state involved during the reaction. A

reaction involving a development of positive charge in the transition

state is aided by electron-releasing substituents and the value is

negative305-307.

In the present investigation, the acceleration of reaction rate

with the electron-releasing substituents and the negative value of the

reaction constant, indicate explicitly that the mechanism of oxidation

involves the development of positive charge in the transition state.

132

The Hammett correlations were also made for the rate constants

obtained at different solvent compositions (c.f. Table 24) and the

values are reported in the following Table 33.

Table 33. Reaction constant values at different solvent compositions a

Solvent

CH3COOH-H2O (v/v) %

Reaction constant b

Correlation

coefficient

50-50 -1.41 0.982

60-40 -1.35 0.983

70-30 -1.12 0.978

80-20 -1.03 0.993 a values were taken from reported works302-304.

b The values were obtained by correlating log (k2 / k20) with p for the reactions

of S1-S7 with NBSac.

The data reveal that the selectivity of the oxidant towards oxoacids

decreases with increase in the acetic acid content in the solvent mixture.

133

Figure 35. Hammett plot (at 303 K) for the oxidation of oxoacids by NBSac

The points referred as (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

Figure 36. Hammett plot (at 308 K) for the oxidation of oxoacids by NBSac

The points referred as (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

Slope = -1.41 r2 = 0.983

Slope = -1.32 r2 = 0.992

134

Figure 37. Hammett plot (at 313 K) for the oxidation of oxoacids by NBSac

The points referred as (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

Figure 38. Hammett plot (at 323 K) for the oxidation of oxoacids by NBSac

The points referred as (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

Slope = -1.20 r2 = 0.988

Slope = -0.98 r2 = 0.996

135

4.4 Mechanism of Oxidation

A probable mechanism for the oxidation of 4-oxoacids by NBSac has

been proposed based on the experimental results and in analogy with

the oxidation of oxo compounds with other oxidants. The results

obtained in the kinetic study are briefly summarized below.

i) The reaction is first order each with respect to the 4-

oxoacid, NBSac, and H+ ion.

ii) The linear increase in the reaction rate with the increase

in [H+] ion is attributed to the formation of hypobromous

acidium ion (H2O+Br) and to the enolization of the 4-

oxoacid.

iii) The formation of hypobromous acidium ion and the

enolization of the 4-oxoacid is facilitated at lower

dielectric constant of the medium.

iv) The rate of enolization is found to be greater than the rate

of oxidation.

v) The course of the oxidation does not involve any free

radical intermediate.

vi) The retarding effect of the addition of saccharin suggests

that the pre-equilibrium step involves a process in which

saccharin is one of the products.

136

vii) The reaction rate is enhanced by electron-releasing

substituents in the phenyl ring while the rate is retarded

by electron-withdrawing substituents.

viii) The reaction constant is negative which indicates the

electron deficient transition state.

Considering these facts and findings a suitable mechanism has

been proposed for the oxidation (Scheme 2).

NBSac+ H3O+ H2O

+Br Saccharin+

k1

k-1 (72)

(73)

(74)

(75)

(76) Scheme- 2

k -1

137

The proposed scheme is formulated to fit in the following

features.

a) The enolization of the 4-oxoacid (eqs.73 and 74) is a

necessary step prior to the oxidation of the substrate. This

is predicted from the experimental finding that under

identical conditions, the rate of enolization is greater than

the rate of oxidation. Similar conclusions have been

arrived at in the oxidation of several ketones by acid

permanganate291, 292, 294.

b) The interaction of oxidizing species (H2O+Br) with the

enol form of the 4-oxoacid in the rate determining step

(eq.75) leads to the formation of intermediate (F). Similar

type of intermediate has been proposed in the oxidation

of many organic and inorganic compounds308-310. The

intermediate then undergoes further oxidative cleavage to

give the products.

4.5 Derivation of Rate Law

Based on kinetic observations and the mechanism proposed, the

following rate expression can be derived applying steady-state

approximation,

The rate of the reaction is given by

-d [NBSac] = k4 [E] [H2O+Br] (77)

dt

138

Applying steady state approximation for [E]

k -3 [H3O+] [E] + k4 [H2O

+Br] [E] = k3 [S

+] [H2O] k3 [S

+] [H2O] Therefore, [E] = (78)

k -3 [H3O+] + k4 [H2O

+Br]

Applying steady state approximation for [S+] k -2 [H2O] [S+] + k 3 [H2O] [S+] = k 2 [H3O

+] [S] + k -3 [H3O+] [E]

k 2 [H3O

+] [S] + k -3 [H3O+] [E]

Therefore, [S+] = k -2 [H2O] + k 3 [H2O]

[H3O

+] { k 2 [S] + k -3 [E]} i.e. [S+] = (79)

[H2O] (k -2 + k 3 ) Using the value of [S+] in eq. (78) k 3 [H3O

+] { k 2 [S] + k -3 [E] } [E] =

( k -2 + k 3 ) { k -3 [H3O+] + k 4 [H2O

+Br] }

[E] (k -2 + k 3 ) {k -3 [H3O+] + k 4 [H2O

+Br] } = k 3 [H3O

+] { k 2 [S] + k -3 [E] }

[E](k -2 + k 3 ){ k -3 [H3O+]+k 4[H2O

+Br]}= k 3 k 2 [H3O

+][S]+k3 k -3 [H3O+][E]

[E]{(k -2 +k 3 ) k -3 [H3O+] + k 4 [H2O

+Br] – k 3 k -3 [H3O

+]}= k 3 k2 [H3O+] [S]

k 3 k 2 [H3O

+] [S] [E] = { (k -2 +k 3 ) k -3 [H3O

+] + k 4 [H2O+Br]} – k 3 k -3 [H3O

+] k 3 k 2 [H3O

+] [S] [E] =

k -2 k -3 [H3O+] + k -2 k 4 [H2O

+Br] + k 3 k 4 [H2O

+Br]

139

k 3 k 2 [H3O+] [S]

[E] = (80)

k -2 k -3 [H3O+] + k 4 (k -2 + k 3) [H2O

+Br]

Substituting the value of [E] in eq. (77)

-d [NBSac] k 2 k 3 k 4 [H3O+] [S] [H2O

+Br]

= (81)

dt k -2 k -3 [H3O+] + k 4 (k -2 + k 3) [H2O

+Br]

At high concentration of [H3O+] = 0.5 M

k -2 k -3 [H3O+] > > k 4 (k -2 + k 3) [H2O

+Br]

So the eq. (81) simplifies to the form

-d [NBSac] k 2 k 3 k 4 [H3O+] [S] [H2O

+Br]

= dt k -2 k -3 [H3O

+]

k 2 k 3 k 4 [S] [H2O+Br]

= (82)

k -2 k -3

The value of [H2O+Br] can be obtained from eq. (72) given in

the Scheme 2 of mechanism

k -1 [NBSac] [H3O+]

K a = =

k 1 [H2O+Cl] [Saccharin]

[NBSac] [H3O+]

Therefore, [H2O+Br] =

Ka [Saccharin] Using the value of [H2O

+Br] in eq. (82)

-d[NBSac] k 2 k 3 k 4 [S] [H3O+] [NBSA]

= (83) dt k -2 k -3 K a [Saccharin]

140

Hence, at higher concentration of mineral acid, the reaction is

first order each with respect to the oxoacid (S), [NBSac] and [H3O+].

The observed rate constant at high [H3O+] is

k 2 k 3 k 4 kobs = (84)

k -2 k -3 K a

4.6 Structure –Reactivity Correlations

The effect of the substituents present in the phenyl ring of the 4-

oxoacids (S1-S7) on the rates of oxidation has been correlated

quantitatively by the application of Hammett equation. Plots of log

(k2/k20) versus P are excellently linear with negative slopes

(Figures 34-37). The reaction constant (ρ) for the oxidation ranges

between -1.41 and -0.98 at different temperatures.

It is generally recognized that oxidations lead to electron

deficient species which are either radical cations, radicals or

carbocations. These reactions normally have a negative ρ value and the

magnitude of value depends on the extent of electron deficiency.

Oxidation reactions involving free radical formation in the rate

controlling step usually have a small negative ρ value and the

oxidations involving the formation of carbocation have a large negative

ρ values. Based on the these arguments we expect a large ρ value but

the measured value is in the range -1.41 to -0.98. The low value

141

may be attributed to the nature of observed rate constant. The observed

rate constant is composite of several terms and is shown in eq.(85).

(85)

The terms shown in eq.(85) deserve comment. The rate constant

k3 depends on the concentration of the protonated substrate (S+) and

the electron donating substituents tend to delocalize the positive charge

on S+ and hence favors the formation of this positive species. The

value for the enolization of the title compounds, determined by

bromination method has been reported311 to be -0.75. In the rate

limiting step (eq.77) of the scheme, the formation of the carbocation is

facilitated by electron releasing substituents.

Thus we get a slightly low negative value of -1.41 (at 303 K)

because kobs is composite of the enolization as well as the oxidation of

the 4-oxoacids. Hence in the present investigation the measured

value and other findings fit in with the formulation of mechanism

outlined in the scheme 2.

4.7 Activation Parameters

The dependence of reaction rate on the structure of the reacting

molecule is related to activation parameters. The decisive term

concerning the dependence on the structure is neither free energy

142

nor enthalpy but potential energy which is experimentally not

accessible. Many authors support the opinion that the activation

energy at a certain temperature is a better approximation towards

the unknown potential energy312. The activation parameters for the

oxidation of 4-oxoacid by NBSac have been evaluated from the

slope values of the Arrhenius plots (Figures 39 & 40). A close look

at activation parameters presented in Table 34 shows that the

activation energies for the oxoacids with electron-releasing

substituents are relatively lower than that with electron-

withdrawing substituents. The entropy of activation is negative for

all the 4-oxoacids ranging from -126.2 to -232.6 J K-1 mol-1.

The large negative entropy of activation in conjunction with other

experimental data supports the mechanism outlined in the scheme 2. The

formation of an activated complex from reactant molecules is

accompanied by the conversion of translation-like and rotational-like

degree of freedom of the reactants to vibrational degree of freedom of the

transition state species. The more widely spaced energy level for the latter

type of molecular motion imply a small entropy and thus a negative

value313 of S#. As the charge separation begins in the transition state,

each end of the dipole becomes solvated by a sheath of solvent molecules,

which must, however be suitably oriented. This increase in orientation

means restricted freedom and results in a decrease in entropy310. A careful

143

analysis of the activation parameters in Table 34 reveals that the present

series is neither isoentropic nor isoenthalpic314.

Figure 39. Arrhenius plot for the oxidation of oxoacids by NBSac

The points referred as (a) S1 (b) S4 (c) S3 (d) S2

a b

c

d

144

Figure 40. Arrhenius plot for the oxidation of oxoacids by NBSac

The points referred as (a) S5 (b) S6 (c) S7

a

b

c

145

Table 34. Activation parameters for the oxidation of oxoacid by

NBSac in aqueous acetic acid medium a

S Ea

kJ mol-1 ∆H#

k J mol-1 ∆S#

J K-1 mol-1 ∆G#

k J mol-1

S1 34.8 32.3 -178.2 86.4

S2 15.9 13.4 -231.8 83.4

S3 16.6 14.1 -232.6 84.3

S4 36.2 33.7 -173.9 85.8

S5 32.4 29.9 -191.8 87.8

S6 34.7 32.2 -185.0 87.5

S7 55.8 53.3 -126.2 91.2

a General conditions : [S] = 0.02 M, [NBSac] = 0.002 M, [H+] = 0.5 M,

[NaClO4] = 0.5 M, Solvent composition : 50%-Acetic acid-50% Water (v/v).

4.8 Isokinetic Relationship

Leffler’s isokinetic eqs. (67) and (68) hold good in a series of related

reactions. The validity of the isokinetic relation can be tested

graphically by plotting either H# versus S# or Ea versus log A. This

linear relationship between activation enthalpies and activation

entropies or activation energies and frequency factors in a series of

related reactions is known as isokinetic relationship315, 316.

146

The validity of the isokinetic plot is questionable317, 318 because

the quantities H# and S# are mutually dependent, both being derived

from the same experimental rate constants. An alternative graphical

method for finding out the isokinetic temperature is suggested by

Exner. A plot of the rate constants measured at two different

temperatures [log k2 (T2) versus log k2 (T1)] is known as Exner plot.

From the slope b, of the Exner plot, the isokinetic temperature , can

be calculated using the eq.(84).

Based on the values of b, the reaction series have been

characterized as mentioned in the Table 19.

The Exner plots drawn for the reaction by choosing k2 values at

any two different temperatures are shown in Figures 41 - 43. The

value of b is less than unity for all the plots. This indicates that the

present reaction series is neither isoentropic nor isoenthalpic but

involves compensation. The lsokinetic temperature evaluated from the

Exner plots is found to be 333.3 K (from Figure 43). As the experiment

has been carried out at a temperature far away from the isokinetic

temperature the application of Hammett equation to the observed

kinetic data is valid. The validity of isokinetic relationship in the

present study implies that all the 4-oxoacids undergo oxidation by the

same mechanism310, 319, 320.

147

Figure 41. Exner plot for the oxidation of oxoacids by NBSac

The Points referred as (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

Figure 42. Exner plot for the oxidation of oxoacids by NBSac

The Points referred as (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

r2

r2

148

Figure 43. Exner plot for the oxidation of oxoacids by NBSac

The Points referred as (1) S2 (2) S3 (3) S4 (4) S1 (5) S5 (6) S6 and (7) S7

4.9 Comparative Study of NBB / 4-Oxoacids and NBSac /

4-Oxoacids Systems

The kinetic data obtained for the oxidation of several 4-oxoacids with

NBB and NBSac under similar conditions are collected in Table 35.

The excellent correlation (slope = 0.986 , r2 = 0.994) shown by log k2

of NBB oxidation with log k2 of NBSac oxidation (Figure 44 and

Table 35) suggests a similar mechanism for the oxidation of 4-

oxoacids by both the oxidants.

r2

149

Table 35. Comparison of oxidation of 4-oxoacids by NBB and NBSac a

S 10 3 k2, M

-1, s-1

NBB b NBSac c

S1 7.2 8.1

S2 26.1 22.8

S3 19.1 16.1

S4 7.8 9.4

S5 4.9 6.2

S6 4.6 4.5

S7 0.9 1.15

a General conditions:[H+] = 0.5 M, [S] = 0.02 M, Solvent composition: 50%

Acetic acid- 50% Water (v/v). b [NBB] = 0.002 M. c [NBSac] = 0.002 M.

150

Figure 44. Correlation plot for the oxidation of oxoacids by NBB and NBSac

The Points referred as (1) S2 (2) S9 (3) S3 (4) S8 (5) S4 (6) S1 (7) S5 (8) S6

and (9) S7

r2

SUMMARY

151

SUMMARY

4-Oxoacids / NBB – System

The hypobromous acidium ion (H2O+Br), a prime cationic bromine

species is responsible for the oxidation of 4-oxoacids in the present

system. The kinetics of oxidation of 4-oxoacids have been investigated

in aqueous acetic acid medium in the presence of perchloric acid

potentiometrically at 30 0C.

The oxidation of 4-oxoacids by N-bromobenzamide is first

order each with respect to the 4-oxoacid, NBB and hydrogen ion.

The oxidation is observed to be a general acid catalyzed reaction.

The linear increase in the reaction rate with the increase in [H+] ion

is attributed to the formation of hypobromous acidium ion and the

formation of enol form of the substrate.

The lowering of dielectric constant of reaction medium

enhances the reaction rate significantly. This favors the formation of

H2O+Br and the enolization of the 4-oxoacid has been studied by

bromination method. The enolization of the oxoacid is found to be first

order each with respect to the 4-oxoacid and hydrogen ion but zero

order with respect to bromine. The rate of enolization is greater than

the rate of oxidation of the 4-oxoacid. Hence the enolization of the

oxoacid is proposed to occur prior to the oxidation. The ionic strength

152

of the reaction medium does not affect the rate of the reaction. The

reaction does not induce the polymerization, which indicates the

absence of free radical intermediate in the oxidation.

The effect of substituents on the reaction rate has been studied

with all the 4-oxoacids. The electron-releasing group in the phenyl ring

accelerates the reaction rate while the electron-withdrawing group

retards the rate. The Hammett plot is linear (r = 0.987) and the value of

the reaction constant () is -1.279. The negative value indicates the

development of positive charge in the transition state.

The activation parameters for the oxidation reaction are

evaluated from the Arrhenius plot. The Exner plot is linear and the

isokinetic temperature ( = 347 K) is evaluated from the plot. The

validity of Exner plot indicates that the oxidation of all the 4-oxoacids

by NBB in aqueous acetic acid medium proceeds by the same

mechanism. A rate law consistent with the experimental results has

been derived. Based on the kinetic results, a suitable mechanism has

been proposed for the oxidative cleavage.

4-Oxoacids / NBSac – System

The kinetics of oxidation of 4-oxoacids (S1- S7) in aqueous acetic acid

medium have been followed potentiometrically at 30 0C. The reaction

153

is first order each in NBSac, 4-oxoacid and perchloric acid. The

hypobromous acidium ion, H2O+Br is the reactive oxidizing species,

which interacts with the enolic form of substrate.

The present reaction is observed to be a general acid catalyzed

reaction. The oxidation reaction does not induce the polymerization,

which indicates the absence of free radical intermediates in the

oxidation.

The effect of changes in the electronic nature of the substrate

has been studied with substituted oxoacids (S1-S7). The electron-

releasing group in the phenyl ring accelerates the reaction rate while

the electron-withdrawing group retards the rate. An excellent

correlation exists between log k2 and values ( = -1.41, r2 = 0.983).

The negative value of the reaction constant indicates the development

of positive charge in the transition state. The activation parameters for

the oxidation are evaluated from the Arrhenius plot. The Exner plot is

linear and the isokinetic temperature ( = 333 K) is evaluated from the

plot. The validity of Exner plot points out that all oxoacids follows

similar mechanism towards NBSac. A rate law consistent with the

experimental results has been derived. Based on the kinetic results, a

suitable mechanism has been proposed for the oxidation of 4-oxoacids

by NBSac.

154

A comparative study of NBB / 4-oxoacids and NBSac / 4-

oxoacids system have been made. In both the systems the

hypobromous acidium ion (H2O+Br) is the reactive oxidizing species,

which interacts with the enolic form of substrate. The excellent

correlation (slope = 0.986, r2 = 0.994) shown by log k2 of NBB

oxidation with log k2 of NBSac oxidation suggests a similar

mechanism for both the oxidants and for all the 4-oxoacids. The rate of

the oxidation reaction of oxoacids with NBS is slower compared to

NBB. The lower value measured in NBB oxidation is also in

consistent with the rate data for the two system, i.e., NBB has less

selectivity towards oxoacids than NBSac.

REFERENCES

155

References

1. Robert B. Grossman, The Art of Writing Reasonable Organic

Reaction Mechanisms, 2nd Edn., 2003, Springer, ISBN:

0-387-95468-6.

2. P.S. Kalsi, Organic Reactions and Their Mechanisms, New

Age International, 2009, ISBN: 8122425968,

9788122425963.

3. Micheal B. Smith and Jerry March, March’s Advanced

Organic Chemistry, Sixth Edn., Willey Interscience, 2007,

ISBN: 978-0-471-72091-7.

4. Adam Jacobs, Understanding Organic Reaction Mechanisms,

Cambridge University Press, 1997, ISBN: 0521467764,

9780521467766.

5. M. Gomez Gallego, M. A. Sierra, Organic Reaction

Mechanism, Springer, Berlin, 2004, ISBN: 3-540-00352-5.

6. Michael Edenborough, Organic reaction mechanisms: a step

by step approach, Taylor & Francis, 1999; ISBN:

0748406417, 9780748406418.

7. A. C. Knipe, Organic Reaction Mechanisms, 2009, Volume

141, John Wiley and Sons, 2011; ISBN: 1119972485,

9781119972488.

156

8. P. N. Mukherjee, Organic Reaction Mechanism, Dominant

Publishers & Distribuors, 2003; ISBN: 8178881101,

9788178881102.

9. B. Capon and C. W. Rees, Organic Reaction Mechanisms,

1967, Volume 105, John Wiley & Sons, 2008; ISBN:

0470067012, 9780470067017.

10. Kuldeep singh and A.K.Agrawal, kinetics and mechanism of

the oxidation of organic compounds, by N-

bromophthalimide, Ph.D Thesis, Ch. Charan Singh

University, Meerut, India

11. F. A. Patrocinio and J. S. Paulo Moran, J. Organomet.

Chem., 603, 220, 2000.

12. A. Graven, K. A. Joergensen, S. Dahl and A. Stanczak,

J. Org. Chem., 59, 3543, 1994.

13. S. Duan, J. Turk, J. Speigle, J. Corbin, J. Masnovi and

R.J. Baker, J. Org. Chem., 65, 3005, 2000.

14. P. S. Dhurn, N. U. Mohe and M. M. Salunkhe, Synth.

Commun., 31, 3653, 2001.

15. V. Canibano, J. F. Rodriguez, M. Santos, M. A. Sanz-

Tejedor, M. C. Carreno, G. Gonzalez and J. L. Garcia-

Ruano, Synthesis, 14, 2175, 2001.

157

16. B. P. Bandgar, L.S. Uppalla and V.S. Sadavarte, Syn. Lett.,

11, 1715, 2001.

17. M. K. Hossain, T. Kameyama, T. Shibata and K. Takagi,

Bull. Chem. Soc. Jpn., 74, 2415, 2001.

18. A. K. Tehrani, D. Borremans and N. De Kimpe,

Tetrahedron, 55, 4133, 1999.

19. C. Brindaban Ranu and U. Jana, J. Org. Chem., 64,

6380, 1999.

20. J. He and Jr. U. Charles Pittman, Synth. Commun., 29,

855, 1999.

21. R. Bartnik, D. Cal, P. Alan Marchand, S. Alihodzic and

A. Devasagayaraj, Synth. Commun., 28, 3949, 1998.

22. P. Maganus and D. Jennifer Kreisberg, Tetrahedron Lett.,

40, 451, 1999.

23. Pinho e Melo , M. V. D. Teresa, M. A. R Gonsloves, M. A.

Antonio, M. S. Sara Carrapato and M. O. M. P. Tabordo,

Molecules, 40, 217, 1999.

24. A. Olofson, K. Yakushijin and A. David Horne, J. Org.

Chem., 63, 1248, 1998.

25. A. Panayiotis Koutentis and W. Charles Rees, J. Chem. Soc.,

Perkin Trans. 1 , 2505, 1998.

158

26. R. P. Litrinovskaya, S.V. Drach and V. A. Kripach, Russ. J.

Org. Chem., 33, 172, 1997.

27. R. Adam Renslo and R. L. Danheiser, J. Org. Chem., 63,

7840, 1998.

28. B. Touaux, F. Texier-Boullet and J. Hamelin, Heteroat.

Chem., 9, 351, 1998.

29. M. Sergio Bones and R. Erra-Balsells, J. Heterocycl. Chem.,

34, 877, 1997.

30. M. Serge Ivono, J. Juston Rockwell, M. Susie Miller,

P. Oren Anderson, A. Konstantin Solntsev and H. Steven

Strauss, Inorg. Chem., 35, 7882, 1996.

31. K. John Gallos, V. Theoharis Koftis, I. Vassiliki Karamitrou

and C. Alexandros Koumbis, J. Chem. Soc., Perkin Trans. 1,

17, 2461, 1997.

32. M. Werner, S. David Stephenson and G. Szeimies, Liebigs

Ann., 11, 1705, 1996.

33. I. Janigova and J. Rychly, Chem. Pap., 45, 845, 1991.

34. (a) V. Ozola, N. Ramzaeva, Y. Maurinsh and M. Lidaks,

Nucleosides Nucleotides, 12, 479, 1993; (b) K. Ardeshir,

M. Tajbakhsh and S. Habibzadeh, Asian J. Chem.,12, 291,

2000.

159

35. Y. Msuyama, Y. Kobayashi and Y. Kurusu, J. Chem. Soc.

Chem. Commun., 9, 1123, 1994.

36. K. Takagi, H. Tkachi and N. Hayama, Chem. Lett., 3,

509, 1992.

37. J. M. Antelo, F. Arce, J. Florencio, L. Garcia, C. Maria,

M. Sanchez and A. Varela, Int. J. Chem. Kinet., 20, 397,

1988.

38. (a) A. Madjdabadi, R. Beugelmans and A. Lechvallier,

Synthesis, 826, 1986; (b) S. D. Bhatta Mishra and S. K.

Mishra, Oxid. Commun., 10, 235, 1987.

39. (a) B. M. Sasmal, D. P. Patnaik and P. S. N. Subudhi,

Acta. Cienc. Indica. Chem., 12, 55, 1986; (b) A. Khazaei,

E. Mehdipour and A. Roodpeima, Iran J. Chem., and Chem.

Eng., 2, 14, 1995.

40. (a) C. Tetzlaff, E. Vilsmaier and R. Wolf Schlag,

Tetrahedron, 6, 8117,1990. (b) A. Khazaei, E. Mehdipour

and M. Sadri, Iran Poly. J., 2, 5, 1996.

41. J. Garin, C. Guillen, E. Melendez, F. L. Merchand J. Orduna

and T. Tejero, Heterocycles, 26, 2371, 1987.

42. M. V. D. Terasa, M. A. Rocha Antonio, S. J. Glaudia Lopes

and L. Thomas Gilchrist, Tetrahedron Lett., 40, 789, 1999.

160

43. L. Eberson, P. Michael Hartshorn, F. Radner and O. Persson,

Perkin Trans. 2, 59, 1998.

44. R. Hyoung Kim, I. Seung Shin, Ju. H. Park, Ju. Dong Jeon

and K. Eung Ryn, Syn. lett., 7, 789, 1998.

45. M. Uma, R. Gurumurthy and C. S. Kalavathi, Acta. Cienc.

Inidca. Chem., 12, 88, 1989.

46. A. Deagostino, B. Paolo Tivola, C. Prandi and F. Venturello,

Syn.lett., 11, 1841, 1999.

47. M. M. Cambell and G. Jhonson, Chem. Rev., 78, 65,1978.

48. L. Horner and E. H. Winkelmann in Newer Methods of

Preparation of Organic Chemistry, edn. W. FOERSI

Academic , New York, 1964.

49. E. Berliner, J. Chem. Educ., 43, 124, 1966.

50. V. A. Morab and S. T. Nandibewoor, React. Kinet. Catal.

Lett., 53, 25, 1994.

51. S. V. Rao and V. Jagannadham, React. Kinet. Catal. Lett.,

27, 239, 1985.

52. S. C. Negi, I. Bhatia and K. K. Banerji, J. Chem. Res.,

360, 1981.

53. R. C. Gupta and S. P. Srivastava, Indian J. Chem., 10,

706, 1972.

161

54. S. P. Srivastava, R. C. Gupta and A. K. Shukla, Indian J.

Chem., 15A, 605, 1977.

55. E. Boyland and P. Sims, J. Chem. Soc., Part I, 980, 1954.

56. A. Lal and M. C. Agarwal, Indian J. Chem., 26A, 696,

1987.

57. G. P. Panigrahi and D. D. Mahapatro, Int. J. Chem. Kinet.,

14, 977, 1982.

58. P. S. Radhakrishnamoorthy and R. Panda, Indian J. Chem.,

9, 1247, 1971.

59. R. Vedavrath, B. Sethuram and T. Navaneeth Rao, Proc.

Natl. Acad. Sci. Inida, 51A, 443, 1981.

60. M. D. Prasada Rao and J. Padmanabha, Indian J. Chem.,

19A, 984, 1980.

61. Vijayalakshmi and E. V. Sundaram, Indian J. Chem., 17A,

495, 1979.

62. A. Lal and M. C. Agarwal, Indian J. Chem., 23A, 411,

1984.

63. C. Subas Pati, B. R. Dev, B. Narasingh and M. Minakshi,

Proc. Ind. Natl. Sci. Acad., 49A, 538, 1983.

64. M. Prasada Rao, B. Sethuram and T. Navaneeth Rao,

Indian J. Chem., 17A, 52, 1979.

162

65. P. V. Sreenivasulu, M. Adinarayana, B. Sethuram and

T. Navaneeth Rao, Oxid. Commun., 8, 199, 1985.

66. A. Lal and M. C. Agarwal, J. Indian Chem. Soc., 67, 164,

1990.

67. A. Agarwal, S. Mittal and K. K. Banerji, Indian J. Chem.,

26A, 339, 1987.

68. M. K. Reddy, C. H. S. Reddy and E. V. Sundaram,

Tetrahedron, 41, 307, 1985.

69. M. L. Bishnoi and K. K . Banerji, Tetrahedron., 41, 6047,

1985.

70. P. Manikyamba and E. V. Sundaram, Indian J. Chem., 19A,

1122, 1980.

71. P. S. Radhakrishnamoorthy and J. C. Panigrahi, Oxid.

Commun., 12, 25, 1989.

72. S. C. Hiremath, S. Mayanna and N. Venkatasubramanian,

J. Chem. Soc., Perkin Trans. 2, 1569, 1987.

73. S. Kandlikar, B. Sethuram and T. Navaneeth Rao, Indian J.

Chem., 17A, 264, 1979.

74. S. C. Negi and K. K. Banerji, Indian J. Chem., 21B, 946,

1982.

75. K. Vijayamohan, K. Rao and E.V. Sundaram, J. Indian

Chem. Soc., 61, 225, 1984.

163

76. B. Thimme Gowda and J. Iswara Bhat, Tetrahedron, 43,

2119, 1987.

77. (a) V. Thiagarajan and N. Venkatasubramanian, Indian J.

Chem., 6, 809, 1967; (b) B. Thimme Gowda and R. V.

Rao, J. Chem Soc., Perkin Trans. 2, 355, 1988.

78. (a) S. C. Negi and K. K. Banerji, Indian J. Chem., 21B, 846,

1982; (b) B. Thimme Gowda and B. S. Sherigara, Int. J.

Chem. Kinet., 21, 31, 1989.

79. B. Thimme Gowda and P. Ramachandra, J. Chem Soc.,

Perkin Trans. 2, 1067,1989.

80. F. Ruff and A. Kucsman, J. Chem. Soc., Perkin Trans. 2,

1075,1982.

81. D. M. Rosa, C. G. Nieto and F. F. Gago, J. Org. Chem., 54,

5437, 1989.

82. X . L. Armesto, M. Canle , M. V. Carcia and J. A.

Santaballa, Chem. Soc. Rev., 27, 453, 1998.

83. W. Stummn and J. J. Morgan, Aquatic Chemistry, Chemical

Equilibria and Rates in Natural Waters, John Wiley, New

York, 3rd edn., 1996.

84. R. L. Jolley, L. W. Condie, J. D. Johnson, S. Katz, R. A.

Minear, J. S. Matice and V. A. Jacobs, eds., Water

164

Chlorination: Chemistry, Environmental and Health Effects,

Lewis Publishers, Michigam, 6, 1990.

85. P. Kovacic, M. K. Lowery and K. W. Field, Chem. Rev., 70,

639, 1970.

86. J. Arotsky and M. C. R. Symons, Quart. Rev. Chem. Soc.,

16, 282, 1962.

87. P. S. Radhakrishnamurthi and M. D. Prasad Rao, Indian J.

Chem., 14B, 790, 1976.

88. N. S. Shrinivasan and N. Venkatasubramanian, Tetrahedron,

30, 419, 1974.

89. P. Saroja, K. B. Kishore and S. Kandlikar, Indian J. Chem.,

28A, 501, 1989.

90. M. Puttaswamy, T. M. Anuradha, R. Ramachandrappa, and

N. M. Made Gowda, Int. J. Chem. Kinet., 32, 221, 2000.

91. P. S. Radhakrishnamurti and L. D. Sarangi, Indian J. Chem.,

20A, 30, 1981.

92. (a) Ghanat K. Joshi, Y. R. Katre, and Ajaya K. Singh,

Journal of Surfactants and Detergents, 9(3), 231-235, 2006,

DOI:10.1007/s11743-006-5002-3; (b) Yokraj Katre ,

Minu Singh and Ajaya K. Singh, Colloid Journal, 74(3),

391-400, 2012, DOI:10.1134/S1061933X12030167; (c) N.

M. I. Alhaji, G. K. Ayyadurai and A. Shajahan, Chemical

165

Science Transactions , 2(2), 467-472, 2013,

DOI:10.7598/cst2013.409; (d) Jagdish V. Bharad, Balaji R.

Madje and Milind B. Ubale, International Journal of

ChemTech Research, 2(1), 346-353, 2010; (e) N.M.I.Alhaji

and Sowfiya Lawrence Mary, E-J Chem., 8(4),1472-1477,

2011.; (f) P. Sangeeta, K. Y Katre and Singh Ajaya,

Journal Surfactants and Detergents, 10(3), 175-184, 2007.

93. N.M.I.Alhaji and Sowfiya Lawrence Mary, E-J Chem.,

8(4),1728-1733, 2011.

94. (a) N. A. Mohamed Farook and G. A. Seyed Dameem, E-

Journal of Chemistry, 8(2), 479-482, 2011, DOI:

10.1155/2011/173749; (b) B. Singh, S. Sahai and D. Gupta,

Oxidation Communications, 34(4), 741-745, 2011; (c) P. R.

Sharadamani and V. Jagannadham, Indian J. Chem., 29A,

700, 1990.

95. (a) R. K. Singh, A.K. Singh, R. Srivastava, S. Srivastava, J.

Srivastava and Rahmani, Transition Metal Chemistry, 35(3),

349-355, 2010, DOI: 10.1007/s11243-010-9334-5; (b) M.

Komal Reddy, Ch. Sanjeeva Reddy and E.V. Sundaram,

Indian J. Chem., 23A, 197,1984.

96. S. Bajpai, M. Saxena, B. Singh and A. K. Singh, J Indian

Chem Soc., 68(9), 497-499, 1991.

166

97. (a) R. K. Singh, A.K. Singh, R. Srivastava, S. Srivastava, J.

Srivastava and Rahmani, Abstracts of Papers Of The

American Chemical Society, 238, Meeting Abstract: 608-

ORGN, Published: AUG 16 2009; (b) B. T. Gowda and P. J.

Rao, Proceedings of the Indian Academy of Sciences-

Chemical Sciences, 103(1), 55-68, 1991.

98. (a) A. K. Singh, S. Srivastava, J. Srivastava and Rahmani,

Chinese Journal of Chemistry, 26(6), 1057-1067, 2008,

DOI: 10.1002/cjoc.200890188; (b) N. Gupta, N. Chaurasia,

V. Singh and A. K. Singh, Oxid. Commun., 23(1), 42-49,

2000.

99. (a) R. A. Singh, V. Yadav, R. A. Singh, and K. Singh,

Oxidation Communications, 31(1), 160-166, 2008;

(b) S. Kabilan, S. Kirubasankar, and K. Krishnasamy,

Oxid. Commun., 29(2), 335-342, 2006.

100. A. Moondra, A. Mathur and K.K. Banerji, Int J Chem Kinet.,

23(8), 669-681, 1991.

101. M. S. Ramachandran, D. Easwaramoorthy and R. P. M.

Maniraj, Int J Chem Kinet., 28(7), 545-551, 1996.

102. B.B.L. Saxena, S. Trivedi, C. Waqar, A. Kumar and

B. Singh, J Indian Chem Soc., 67(3), 202-203, 1990.

167

103. M. Saxena, R. Gupta, A. Singh, B. Singh and A. K. Singh, J.

Mol. Catal., 65(3), 317-327. 1991.

104. P. R. Sharadamani and V. Jagannadham, Indian J Chem., A,

30(6), 518-521, 1991.

105. P. Shardamani and V. Jagannadham, National Academy

Science Letters-India, 14(8), 331-335, 1991.

106. A. K. Singh, A. Srivastava, A. Kumar and B. Singh,

Transition Metal Chemistry, 18(4), 427-430, 1993.

107. A. K. Singh, V. Singh, N. Gupta and B. Singh, Carbohydrate

Research, 334(4), 345-351, 2002.

108. A. K. Singh, V. Singh, S. Rahmani and Singh, J Mol Catal.,

A-Chemical, 197(1-2), 91-100, 2003.

109. A. K. Singh, S. Rahmani, B. Singh, R. K. Singh, and M.

Singh, J Phys Org Chem., 17(3), 249-256, 2004.

110. a) A. K. Singh, V. Singh and Ashish Srivastava, J Indian J

Chem., A, 45(3), 599-608, 2006; b) R. A. Singh, V. Yadav, A.

K. Singh, K. Singh, Oxid. Commun., 38(1), 160-166, 2008; c)

R.A.Singh, V. K. Srivastava, A. Srivastava and V. Yadav,

Oxid Commun., 27(3), 643-649, 2004; d) B. Singh, S. Sahai

and D. Gupta, Oxid. Commun., 33(2), 295-299, 2010;

e) B. Singh and S. Sahai, J Indian Chem Soc., 68(4), 208-209,

168

1991; f) B. Singh, D. Singh, S. Bajpai and A Kumar,

Transition Metal Chem., 16(6), 610-613, 1991.

111. P. K. Tandon, J. P. Singh and M.P. Singh, Oxid. Commun.,

22(3), 424-431, 1999.

112. S. Srivastava, V. Srivastava, V. Gupta and L. Chaudhary,

Oxid. Commun., 30, 553-560, 2007.

113. a) S. Srivastava and S. Singh, Oxid. Commun., 29(3), 708-

714, 2006; b) S. Srivastava, A. Awasthi and K. Singh, Int J

Chem Kinet., 37(5), 275-281, 2005: c) S. Srivastava,

A. Awasthi and V. Srivastava, Oxid. Commun., 26(3), 426-

431, 2003.; d) S. Srivastava, V. Srivastava, and A. Awasthi,

Oxid Commun., 26(3), 378-384, 2003.

114. S. Perumal and M. Ganesan, Indian J. Chem., 28A, 961,

1989.

115. (a) D. S. Mahadevappa, M. Sayeed Ahmed, N. M. Made

Gowda and B. Thimme Gowda, Int J of Chem Kinet.,

15(8), 775 – 793, 2004; (b) S. Meenakshisundaram and M.

Selvaraju, Int. J. Chem. Kinet., 34, 27, 2002; (c) H.

Ramachandra, K. S. Rangappa and D. S. Mahadevappa,

Chinese Journal of Chemistry, 26(3), 536 – 542, 2008; (d)

K. S. Rangappa, H. Ramachandra and D. S. Mahadevappa,

Int J Chem Kinet., 37 (9), 572 – 582, 2005; (e) Puttaswamy

169

and R. V. Jagadeesh, Central European Journal of

Chemistry, 3(3), 482-501, 2005.

116. (a) K. Mohan, Mahadevappa and Puttaswamy, Chemical

Science, 102(1), 65-72, 1990, DOI:10.1007/BF02861572; (b)

Puttaswamy, Nirmala Vaz and N. M. Made Gowda, Int J

Chem Kinet., 37(11), 700-709, 2005; (c) B. Thimme Gowda,

V. Pardhasarathi and P. Ramachandra, Indian J. Chem., 29A,

1192, 1990.

117. (a) M. Rangaswamy and Ananda, Journal of Indian Council

of Chemists, 18(2), 12-19, 2001; (b) Mallamma, S. Ananda,

Rangaswamy and N. M. Made Gowda, Synthesis and

Reactivity in Inorganic, Metal-Organic, and Nano-Metal

Chemistry, 33(9), 1555 – 1568, 2003; (b) M. Puttaswamy,

V. Nirmala and N. M. Made Gowda, Int. J. Chem. Kinet., 33

480, 2001.

118. (a) M.C.Agarwal and A. Lal, Journal of the Indian

Chemical Society, 62(2), 164-166, 1990; (b) A.N. Mohamed

Kassim and K.A. Basheer Ahamed, Indian J Chem., A 38(6),

533-540, 1999; (c) N.A. Mohamed Farook and G.A. Seyed

Dameem, Journal of Chemistry, 8(2), 561-564, 2011.

119. (a) Suresh P. Nayak and Thimme Gowda, Journal of

Physical Organic Chemistry, 5(11), 755-763, 2004,

170

DOI: 10.1002/poc.610051108; (b) S. P. Nayak and B.T.

Gowda, J Indian Chem Soc., 69(10), 637-641, 1992.

120. (a) D. Anjali, Indian Journal of Chemical Society, 67, 164-

166, 1990; (b) S. P. Nayak and B. T. Gowda, J Phys Org

Chem., 92, 755-763, 1992, DOI: 10.1002/poc.610051108.

121. (a) B. T. Gowda and P. J. M. Rao, Indian J Chem., A, 30(2),

148-153, 1991; (b) B. T. Gowda and P. J. M. Rao,

Zeitschrift Fur Physikalische Chemie Neue Folge, 68, 183-

192, 1990; c) K. A. B. Ahamed, Indian J Chem., A, 36(3),

222-224, 1997.

122. (a) K. Chowdhury and K. K. Banerji, J. Org. Chem., 55,

5391, 1990; (b) V. K. Siriah and N. Mohan Gupta, Asian J.

Chem., 12, 1071, 2000; c) M.K. Badole, L.N. Malviya, K.S.

Sariya and V.K. Siriah, Oriental Journal of Chemistry, 28,

1433-1436, 2012; d) Rachna Prakash and Shashi Agarwal,

Journal of Engineering, Science and Management

Education, 6(1), 2013;

123. (a) K. K. Banerji, J. Org. Chem., 51, 4764, 1986;

(b) P. Archana and V. K. Seeriya, Asian J. Chem., 4, 744,

1992; (c) Kalyan K Banerji, Indian Academy of Science

(Chem. Sci), 100(5), 397-403, 1988; (d) Vyas V.K, Kothari S

171

and Banerji K.K, Indian Journal of Chemistry, Section A,

35(2), 112-115, 1996.

124. V. K. Seeriya, V. R. Chourey, R. S Varmaa, S. K. Solankee

and Vi. Raa. Shaastry, J. Indian Chem. Soc., 63, 847,1986.

125. (a) V. K. Viyas, S. Kothari and K. K. Banerji, Indian J.

Chem., 35A, 112, 1996; (b) O. N. Choubey , V. K.

Seeriya and S. K. Aswathi, Asian J. Chem., 12, 302, 2000.

126. K. S. Rangappa, K. Manjunathaswamy, M. P. Ragahavendra

and N. M. Made Gowde, Int. J. Chem. Kinet., 34, 49, 2002.

127. K. Vivekanandan and K. Nambi, Indian J. Chem., 35B,

1117, 1996.

128. K. Vivekanandan and K. Nambi, J. Indian Chem. Soc., 76,

198, 1999.

129. G. F. Hambly and T. H. Chan, Tetrahedron Lett., 27, 2563,

1986.

130. K. K. Banerji, J. Chem. Soc., Perkin Trans. 2, 1015, 1988.

131. D. Thenraja, P. Subramaniam and C. Srinivasan, J. Chem.

Soc., Perkin Trans. 2, 2125, 2002.

132. T. Mukaiyama, J. Matsuo, D. Iida and H. Kitagawa, Chem.

Lett., 8, 846, 2001.

133. J. Einborn, C. Einborn, F. Ratajczak and J. Pierre, J. Org.

Chem., 61, 7452, 1996.

172

134. J. M. Antelo, F. Arce, J. O. Crugeiras and M. Parajo, J. Phys.

Org. Chem., 10, 631, 1997.

135. L. Fieser and S. Rajagopalan, J. Am. Chem. Soc., 71, 3935,

1979.

136. N. N. Hallingudi, S. M. Desai and S. T. Nandibewoor, Oxid.

Commun., 23, 117, 2000.

137. S. T. Nandibewoor, S. M .Desai and N. N. Hallingudi, Indian

J. Chem., 38A, 943, 1999.

138. M. S. Ramachandran, R. Santhanalakshmi and D. Easwara-

moorthy, Oxid. Commun., 21, 230, 1998.

139. K. Takaki, M. Ysumura and K. Negoro, J.Org. Chem., 48,

54, 1983.

140. M. S. Ramachandran, D. Easwaramoorthy, V. Rajasingh and

T. S. Venkatasundaram, Bull. Chem. Soc. Jpn., 63, 2397,

1990.

141. E. J. Barry, M. Finkelstein, W. M. Moore and D. S.

Ross, J. Org. Chem., 50, 528, 1985.

142. S. M. Farook, S. Sivakamasundari and S. Viswanathan,

Indian J. Chem., 23A, 239, 1984.

143. Y. Nagao and S. Katagiri , Bull. Chem. Soc., Jpn, 61, 1393,

1998.

173

144. K. S. Kim, I. H. Cho, K. B. Yoo, Y. H. Song and C. S.

Hahn, J. Chem. Soc., Chem. Commun., 12, 762, 1984.

145. (a) N. Mathiyalagan and R. Sridharan, Indian J Chem., A,

44(10), 2044-2047, 2005; (b) P. S. Radhakrishnamurthy and

B .M. Sasmal, Indian J. Chem., 19A, 880, 1980.

146. J. M. Antelo, F. Arce, J. Crugeiras, C. Pastoriza and R. A.

Cristina, J. Chem. Res. Synop., 1, 20, 2001.

147. T. Ikemoto and M. Wakimasu, Heterocycles, 55, 99, 2001.

148. B. Thimme Gowda and P. S. Krishna Kumar, Z. Phys. Chem.

(Munich) , 167, 151, 1990.

149. N. Venkatasubramanian and V. Thiagarajan, Can. J. Chem.,

47, 694, 1969.

150. (a) Pandey, K. L., Synlett., 947, 2008; (b) M. Jambulingam,

P. Nagarajan, P. Arulvani and K. Ramarajan, J. Chem. Soc.,

Perkin Trans., 2, 957-959, 1986,

DOI: 10.1039/P29860000957; (c) V. K. Sharma, K. Sharma,

H.D. Gupta and O. P. Gupta, O. P. Oxidation

Communications, 18(4), 395-406, 1995.

151. (a) H. Firouzabadi, N. Iranpoor and F. Ebrahimzadeh,

Tetrahedron Lett., 47, 1771, 2006, DOI:10.1016/

j.tetlet.2006.01.033; (b) U. Mishra, K. Sharma and V.K.

Sharma, Carbohydr. Res., 147, 155-159, 1986; (c) Khazaei

174

A, Rostami A and Aminimanesh A, J. Chin. Chem. Soc., 53,

437-441, 2006.

152. (a) S. P. L. De Souza, J. F.Da Silva and M.C.S De Mattos,

J. Braz., Chem. Soc., 14, 832, 2003, DOI:10.1590/S0103-

50532003000500021; (b) K. Mohan, R. Vijaya, P.

Rahgunath and E. V. Sundaram, J. Indian. Chem. Soc., 65,

91, 1988.

153. (a) A.Khazaei, A.Aminimanesh and A.Rostami, Phosphorus

Sulfur Relat. Elem., 179, 2483, 2004, DOI:10.1080/

10426500490485471; (c) C. M. Das and P. Indrasenan,

Indian J. Chem., 26A, 55, 1987, ibid., 26A, 717, 1987.

154. (a) E.I.Shchez and M.J.Fumarola, J. Org. Chem., 47, 1588,

1982; (b) S. Meenakshisundaram and M. Selvaraju, Int. J.

Chem. Kinet., 34, 1, 2002.

155. (a) D.Yang, Ye X Y, M. Xu, K.W.Pang and K.K.Cheung, J.

Am. Chem. Soc., 122, 1658, 2000; (b) U. Mishra, K. Sharma

and V. K. Sharma, J. Indian Chem. Soc., 63, 586, 1986.

156. (a) J.T.Tateiwa and A.Hosomi, Eur. J. Org. Chem., 1445,

2001; (b) D.Yang, Y.Yan and B.Lui, J. Org. Chem., 67,

7429, 2002; (c) V. Manoharan and N. Venkatasubramanian,

Indian J. Chem., 23A, 389, 1984.

175

157. (a) A. K. Tiwari, O.P. Gupta, K. Sharma and V.K.Sharma,

Oxidation Communications, 22, 591-598, 1999; (b)

K. Vijayamohan, R. Rao and E. V. Sundaram, J. Indian

Chem. Soc., 61, 225, 1984.

158. (a) B. Ramkumar, Asian J. Chem., 14, 463, 2002; (b)

K. Vijaya Mohan, P. Raghunatha Rao and E.V. Sundaram,

Proc. Nat. Acad. Sci. India, 58(A), I, 49, 1988; (c) Zachariah

A, Asian Journal of Chemistry, 15, 1567-1571, 2003; (d) T.

D. R. Nair, and A. Zachariah, Asian Journal of Chemistry,

14, 117-120, 2002; (e) P. C. Shukla, P. S. Tiwari and Deepa

Khare, International Journal of Pharmacy & Life Sciences,

3(1), 1380-1384, 2012; (f) V.K. Sharma, K. Sharma, A.

Pandey and P.F.Hashmi, Oxidation Communications, 23(1),

62-70, 2000; (g) V.K. Sharma, K. Sharma and P.F.Hashmi,

Oxidation Communications, 23(1), 71-77, 2000.

159. S. Kothari, A. Agrawal and K. K. Banerji, Indian J. Chem.,

25A, 722, 1986.

160. K. Nagarajan, V. Balasubramanian and N. Venkatasubra-

manian, Indian J. Chem., 19A, 576, 1980.

161. K. A. Basheer Ahamed, S. Sheik Dawood, B. Baskaran and

K. Nambi, J. Indian Chem. Soc., 73, 687, 1996.

176

162. (a) N. A. Mohamed Farook, G. A. Seyed Dameem,

A. Murugesan and M. Kanagaraj, E-J Chem., 1(2), 132-

136, 2004; (b) V. K. Mohan Rao, P. Ragunatha and E.

V. Sundaram, J. Indian Chem. Soc., 63, 698,1986.

163. J. M. Bacchawat and N. C. Mathur, Indian J. Chem., 9, 1335,

1993.

164. M. U. Khan, J. K. Verma, V. R. Singh and H. P. Dwivedi,

Oxid. Commun., 16, 235, 1993.

165. K. Vijayamohan, P. Raghunath Rao and E. V. Sundaram,

Proc. Indian Acad. Sci., 58A, 49, 1988.

166. (a) N. A. Mohamed Farook and N. M. I. Alhaji, Int. J. Chem.

Sci, 2(1), 76-80, 2004; (b) P. K. Tiwari, J. K. Verma and H.

D. Gupta, Oxid. Commun., 20, 117, 1997.

167. M. U. Khan, J. K. Verma, S. K. Nigam and S. S. Parihar,

Oxid. Commun., 21, 362, 1998.

168. M. U. Khan, S. K. Nigam, J. K. Verma and A. Nigam, Oxid.

Commun., 18, 304, 1995.

169. N. Jayasree and P. Indrasenen, Indian J. Chem., 26, 714,

1987.

170. V. P. Singh, M. U. Khan, D. B. S. Chauhen and J. K. Verma,

Oxid. Commun., 20 , 124, 1997.

177

171. (a) N. A. Mohamed Farook, G. A. Seyed Dameem, A.

Murugesan and M. Kanagaraj, E-J Chem., 2(1), 132-136,

2004; (b) M. U. Khan, S. K. Nigam, and O. P Gupta Oxid.

Commun., 22, 259, 1999.

172. (a) N. A. Mohamed Farook, R. Prabaharan, S. Rahini,

R. Senthil Kumar, G. Rajamahendran, and B. Gopala

krishnan , E-J Chem., 1(2), 127- 131, 2004; (b) M. U. Khan,

J. K. Verma, S. K. Nigam, S. S. Pariher and H. P. Dwivedi,

Oxid. Commun., 21, 362, 1998.

173. S. Khan, M. U. Khan, S. K. Singh, H. D. Gupta and P. K.

Singh, Asian J. Chem., 15, 595, 2003.

174. (a) N. A. Mohamed Farook, J Solution Chem., 36(3), 345-

356, 2007; (b) H. L. Riley, J. F. Moreley and N. A. Friend, J.

Chem. Soc., 1875, 1932.

175. S. Tiwari, M. U. Khan, B. M. L. Tiwari, K. S. Tiwari and

N. D. Valechha, Oxid. Commun., 22, 259-267, 1999.

176. (a) B. L. Hiran1, R. K. Malkani1 and N. Rathore, Kinetics

and Catalysis, 46(3), 334-339, 2005; (b) A. L. Harihar, M.

R. Kembhavi and S. T. Nandibewoor, J. Indian Chem.

Soc., 76, 128, 1999.

177. (a) Abdel-Hady, Alaa Eldin Mokhtar, Farag, Rabie S, Abu-

Khadra and Ahmad S. Transition Metal Chemistry,35(5),

178

571-576, 2010; (b) A. K. Singh, S. Rahmani, K. V. Singh, V

.Gupta, D. Kesarwani and B. Singh, Indian J. Chem., 40,

519, 2001.

178. (a) N. A. Mohamed Farook, J Iran Chem Soc., 3(4),378-386,

2006; (b) B. Thimme Gowda and J. Ishwara Bhat, Indian J.

Chem. 28A, 211, 1989.

179. (a) Katre Y, Singh M and A.K. Singh, Tenside Surfactants

Detergents, 47(2), 98-105, 2010; (b) C. Karunakaran and

K. Ganapathy, Indian J. Chem., 29A, 133, 1990.

180. (a) B. Thimme Gowda and J. Ishwara Bhat, Indian J.

Chem., 28A, 43, 1989; (b) R. Saxena, S. Gupta and K. S.

Upadhyay, Indian J. Chem., 29, 847,1990.

181. (a) M. N. Kumara, N.S. Gowda, Linge and Mantelingu K et

al., Journal of Molecular Catalysis A-Chemical, 309(1-

2), 172-177, 2009; (b) P. G. Reddy, T. Kistayya, J. A. Khan

and S. Kandlikar, Z. Phys. Chem. (Leipzig), 269, 1253,

1988.

182. (a) Abdel-Hady, Alaa Eldin M, Transition Metal Chemistry,

33(7), 887-892, 2008; (b) P. S. Radhakrishnamurti, B. M.

Sasmal and D. P. Patnaik, Indian J. Chem., 25A, 69, 1986.

179

183. (a) M. Alaa Eldin, Abdel-Hady, Transition Metal Chemistry,

33(7), 887-892, 2008; (b) P. Saroja and S. Kandlikar,

Indian J. Chem., 27A, 632, 1988.

184. (a) P. Shalini and U. Santosh, J Colloid and Interface

Science 285(2), 789-794, 2005; (b) A. Sukla and S. K.

Upadhyay, J. Indian Chem. Soc., 11, 745, 1992.

185. (a) Patil, B.Dilip, Chachere and D.Sunil, Asian Journal of

Chemistry, 20(2), 1539-1543, 2008; (b) B. Singh, V. K.

Singh, A. K. Singh and M. B. Singh, J. Indian Chem. Soc.,

63, 1049, 1986.

186. (a) A. Ewais Hassan, A. Nagdy Mohamed and A. Abdel-

Khalek Ahmed, Journal of Coordination Chemistry, 60(22-

24), 2471-2483, 2007; (b) R. Saxena and S. K. Upadhyay,

Indian J. Chem., 32A, 1060, 1993; (c) Ewais Hassan A,

Nagdy Mohamed A and Abdel-Khalek Ahmed A, Journal of

Coordination Chemistry, 60(22-24), 2471-2483, 2007.

187. (a) A. Ewais Hassan, E. Ahmed Ahmed and A. Abdel-

Khalek Ahmed, Int J Chem Kinet., 36(7), 394-400, 2004; (b)

B. Bhargava, B. Sethuram and T. N. Rao, Indian J. Chem.,

16A, 651, 1978.

188. (a) N.S. Linge Gowda, M.N.Kumara, D.C.Gowda and

Rangappa, International Journal of Chemical Kinetics,

180

38(6), 376-385, 2006; (b) G. S. Sundaram and N.

Venkatasubramanian, J. Chem. Soc., Perkin Trans. 2, 949,

1983.

189. (a) M.A.Alaa Eldin, International Research Journal of Pure

and Applied Chemistry, 4(1), 76-87, 2014; (b) R. T. De

Mattos, E. R. Lachter and A. C. Neto, Quim. Nova, 1, 17,

1985 (Chem. Abstr., 107, 1987).

190. (a) K. N. Mohana and K. R. Ramya, J Molr Catal A,

Chemical, 302(1/2), 80-85, 2009; (b) J. P. Sharma, R. N. P.

Singh, A. K. Singh and B. Singh, Tetrahedron, 42, 2739,

1986.

191. N. K. Mathu and C. K. Narang, The Determination of

Organic Compounds with N-Bromosuccinimide and Allied

Reagents. Academic Press, New York, 15, 1975.

192. (a) R. Ramachandrappa, Puttaswamy, S. M. Mayanna and N.

M. Made Gowda, Int J Chem Kinet., 36(7), 394-400, 2004;

(b) S. Perumal, K. Syed Abbas and R. Chandrasekaran,

Indian J. Chem., 28A, 592, 1989.

193. (a) S. Pandey and S. K. Upadhyay, Langmuir., 21(24),

10983-10991, 2005; (b) D. L. Kamble and S. T.

Nandibewoor, Pol. J. Chem., 71, 91, 1997.

181

194. R. B. Chougale, D. L . Kamble and S. T. Nandibewoor, Pol.

J. Chem., 71, 986, 1997.

195. (a) Minu Singh, International Journal of Carbohydrate

Chemistry, 2014, Article ID 783521, 9 pages,

DOI:10.1155/2014/783521; (b) D. L. Kamble, G.H.

Hugar and S. T. Nandibewoor, Indian J. Chem., 35, 144,

1996.

196. (a) N. Nanda, S. Malini, Puneeth Kumar and Netkal M.

Gowda, International Research Journal Pure and Applied

Chemistry, 4(6), 834-845, 2014; (b) K. Meenal and

D. Vimala Devi, J. Indian Chem. Soc., 73, 391, 1996.

197. (a) A. K. Singh, R. K. Singh, Srivastava, J. Rahmani and Y.

Sarita, Indian Journal of Chemistry, 51A, 681-689, 2012; (b)

D. L. Kamble, R. B. Chougale and S. T. Nandibewoor,

Indian J. Chem., 35, 865, 1996.

198. (a) K. N. Mohana and P. M. Ramdass, Journal of the

Chinese Chemical Society, 54, 1223-1232, 2007; (b)

R. Ramachandrappa, M. Puttaswamy, S. M. Mayanna and

N. M. Made Gowda, Int. J. Chem. Kinet., 30, 407, 1998.

199. A. A. Abdel-Khalek, M. El -Said Sayyah and S. H. E.

Khaled, Indian J. Chem., 37, 489, 1998.

182

200. A. K Singh, D. Chopra, S. Rahmani and B. Singh,

Carbohyd. Res., 314, 157, 1998.

201. (a) A. A. Abdel-Khalek, H. A. Ewais, E. S. H. Khaled and

A. Abdel-Hamied, Transition Metal Chemistry, 28(6), 635-

639, 2003; (b) V. Thiagarajan and N. Venkatasubramanian,

Tetrahedron Lett., 3349, 1967.

202. T. Kistayya, M. S. Reddy and S. Kandlikar, Indian J. Chem.,

25A, 905, 1986.

203. (a) B. Hiran, R. Malkani, and N. Rathore, Kinetics and

Catalysis, 46(3), 334-339, 2005; (b) G. Gopalakrishnan and

L. H. John, J. Org. Chem., 50, 1206, 1985.

204. S. Bharat, P. Lalji, J. Sharma and S. M. Pandey,

Tetrahedron, 38, 169, 1982.

205. K. Ganapathy and C. Karunakaran, Monatsh. Chem., 113,

1239, 1982.

206. S. P. Srinivasan and N. S. Gnanapragasam, J. Indian Chem.

Soc., 60, 953, 1983.

207. L. S. A. Dikshitulu, P. Vani and B. Vasantha Kumar, J.

Indian Chem. Soc., 61, 385, 1984.

208. M. Vijayasree, K. Srinivas and P.V. Subba Roa, Indian J.

Chem., 22A, 806, 1983.

183

209. S. M. Pandey, J. Sharma, O. Prakash and S. P. Mushran,

Indian J. Chem., 20A, 1021, 1981.

210. (a) S. P. Mushran, L. Pandey and S. Kameshwar, Monatsh.

Chem., 111, 1135, 1980; (b) G. Gopalakrishnan, B. R. Pai

and N. Venkatasubramanian, Indian J. Chem., 19B, 293,

1980; (c) P. S. Radhakrishnamurti and S. N. Sahu, Indian J.

Chem., 15A, 785, 1977.

211. (a) V. Siriah and M. K. Badole, International Journal of

Scientific Research Publications, 3(9), 1-5, 2013.

212. L. N. Malviah, V. K. Siriah and M.K.Badole, Oriental

Journal of Chemistry, 29(2), 767-770, 2013.

213. R. Natarajan and N. Venkatasubramanian, Indian J. Chem.,

13A, 261, 1975.

214. (a) A. Mamoru and K. Ohdan, Chem. Lett., 5, 405, 1995;

(b) F. V. Bagrov, G. P. Parlov and D. F. Bagrov, Russ. J.

Org. Chem., 36, 117, 2000.

215. (a) P. Ruoff and G. Nevda, J. Phys. Chem., 93, 7802, 1989;

(b) M. A. El-Maghraby and A. I. M. Koraiem, Indian J.

Chem., 20B, 73, 1981.

216. I. Tapia, V. Alcazar, J. R. Moran and M. Grande, Bull.

Chem. Soc. Jpn., 63, 2408, 1990.

184

217. P. C. Samal, B. B. Pattnaik, S. C. Dharma Rao and S. N.

Mahapatro, Tetrahedron, 39, 143, 1983.

218. (a) I. D. Komaritsa, Chem. Heterocycl. Compd., 25, 1297,

1988; (b) B. Zaleska and S. Lis, Synth. Commun., 31,

189,2001.

219. R. P. Bell and D. Covington, J. Chem. Soc., Perkin Trans. 2,

1343, 1975.

220. (a) S. Prasad and R. K. Prasad, Indian J. Chem., 17A, 491,

1979; (b) D. Vlaovic, G. Cetkovic, I. Juranic, J. Balaz,

S. Lajsic and D. Djokovic, Monatsh. Chem., 121, 931,

1990; (c) J. S. F. Pade and W. A. Waters, J. Chem. Soc.,

712, 1956; (d) E. B. Hughes, H. B. Watson and E. D. Yates.

J. Chem. Soc., 3318, 1931.

221. (a) B. Singh, B. B. Singh and S. Singh, J. Indian Chem. Soc.,

57, 662, 1980; (b) U. R. Joshi and P. A. Limaye, Indian J.

Chem., 21B, 1122, 1982; (c) P. L. Huang and P. Williams, J.

Chem. Soc., 2637, 1958.

222. E. Burcher, Ann. Chim., 26, 435, 1882.

223. R. D. Haworth, J. Chem. Soc., 1125, 1932.

224. E. Barnet, De Barry and F. G. Sanders, J. Chem. Soc., 434.

1933.

225. G. Levy, Ann. Chim., 9, 5, 1938.

185

226. L. F. Fieser and M.A. Peters, J. Am. Chem Soc., 54, 4347,

1937.

227. W. E. Bachman and W. S. Struve, J. Org. Chem., 4, 472,

1939.

228. J. D. Reinheimer and S. Taylor, J. Org. Chem., 19, 802,

1954.

229. F. Muhr, Ber., 28, 3215, 1895.

230. N. W. Fadnavis and G. Bagavant, Indian J. Chem., 17B, 518,

1979.

231. L. F. Fieser and A. M. Seligman, J. Am. Chem. Soc., 60, 170,

1938.

232. E. L. Martin, J. Am. Chem. Soc., 58, 1439, 1936.

233. J. D. Reinheimer and S. Taylor, J. Org. Chem., 17, 1505,

1952.

234. G. A. Dalal and K. S. Nargund, J. Indian Chem. Soc., 14,

406, 1937.

235. Syed Sheriff, Can. J. Chem., 39, 2563, 1961.

236. M. A. Saboor, J. Chem. Soc., 922, 1945.

237. C. Forzato, R. Gandolfi, F. Molinari, P. Nitti, G.Pittiaco and

E. Valentin, Tetrahedron, Asymmetry., 12, 1039, 2001.

238. F. Reisch, W. Spitzner and K. E. S. Arzneim, Forsch., 17,

816, 1967.

186

239. O. Helia, T. Autonin and M. Senionsky, Prange (Zech),

Neoplauma, 16, 597,1969.

240. H. Adolphi and G. Gerhard (BASF. A-G), Ger. Offen. 070,

2530, 1975.

241. G. Sikkandar, Ph. D. Thesis, Bharathidasan University,

Tiruchy, 58, 1992.

242. K. Kameo, K. Orgawa, K. Takeshita, S. Nakaike, K. Tomi-

sawa and K. Sota, Chem. Pharm. Bull., 36, 2050, 1988

243. Y. Kawashima, K. Kameo, M. Kato, M. Hasegawa, and

K. Tomisawa, Chem. Pharm. Bull., 40, 774, 1992.

244. F. V. Bagrov, Russ. J. Org. Chem., 37, 15, 2001.

245. T. N. Mandar, Yu-Chu Chang and Tai-huang Huang, FEBS

Lett., 530, 133, 2002.

246. A. Avarsson, J. L Chaung, R. Max Wynn, S. Turley, D. T

Chauang and W. G. J. Hol, FEBS Lett., 8, 277, 2000.

247. C. A. Aspiotis Renee, B. Cameron, G. Andre, L. Grimm

Erich and H. Yongxin, Merck Forsst Canada Inc. C.A.,

(Patent No. US 6525025), 2003.

248. D. Denoya Claudio and J. Stutzman-Engwall kim, Pfizer

Inc., (Patent No. US 6399324), 2002.

249. A. Renee, B. Christopher, B. Cameron, F. Sabastien, G.

Andre, G. Erich, H. Yongxin, M. Dan, P. Petpiboon and Z.

187

Robert, Merch Frosst-Canada Inc., C. A, ( Patent No. US

6225288), 2001.

250. J. Van Scott Eugene and J. Yu. Ruey, FEBS Lett., (Patent

No. US 6225288), 1996.

251. B. Zaleska and S. Lis, Synth. Commun., 31, 189, 2001.

252. G. Sikkandar, Asian J. Chem., 12, 1037, 2000; ibid., 12,

1337, 2000.

253. K. A. Basheer Ahamed, G. Sikkandar and S. Kannan, Indian

J. Chem., 38A, 183,1999.

254. D. Freeda Gnana Rani, F. J. Maria Pushparaj, I. Alphones

and K. S. Rangappa, Indian J. Chem., 41B, 2153, 2002.

255. G. Sikkandar and K. A. Basheer Ahamed, Indian J. Chem.,

31A, 845, 1992.

256. D. V. Hertzler, J. M. Berdahl and E. J. Eisenbraun, J. Org.

Chem., 33, 2008, 1968.

257. P. P. Sane, K. J. Divakar and A. S. Rao, Synthesis, 541,

1973.

258. M. Krishna Pillai and K. Banumathi, J. Chem. Research,

225, 1997.

259. M. V. Bhat, M. S. Ravindranathan and G. V. Rao, J. Org.

Chem., 49, 3170, 1984.

188

260. P. Nath and K. K. Banerji, Bull. Chem. Soc., Jpn, 42, 2038,

1969.

261. J. S. Littler, G. R. Quick and D. Woznik, J. Chem. Soc.,

Perkin Trans. 2, 657, 1980.

262. J. Shorter and C. N. Hinshelwood, J. Chem. Soc., 3425,

1962.

263. N. P. Marigangaiyah and K. K. Banerji, Indian J. Chem.,

14A, 85, 1976.

264. L. P. Hammett, Physical Organic Chemistry, II edn.

McGraw- Hill, Tokyo, chapter 11, 348, 1970.

265. L. P. Hammett, J. Am. Chem. Soc., 59, 96, 1937.

266. R. Dubois, M. Ruasse and A. Argile, J. Am. Chem. Soc., 106,

4840, 1984.

267. J. Shorter, Correlation Analysis of Organic Reactivity,

Research Studies Press, England, chapter 3 & 7, 1982.

268. R. P. Wells, Chem. Rev., 63, 171, 1963.

269. M. Charton, Progr. Phys. Org. Chem., 8, 235, 1971.

270. R. W. Taft, in Steric Effects in Organic Chemistry, edn.

M. S. Newman, John-Wiley and Sons, Inc., New York,

Chapter 13, 1956.

271. J. Shorter, Correlation Analysis in Organic Chemistry,

Clarendon Press, Oxford, Chapter 2, 1973.

189

272. C. D. Johnson, The Hammett Equation, Cambridge

University Press, Chapter 1 & 2, 1973.

273. H. C. Brown and Y. Okamoto, J. Am. Chem. Soc., 80, 4979,

1958.

274. H. Van Bekkum, P. E. Verkade and B. M. Wepster, Rect.

Trav. Chim., 78, 815, 1959.

275. B. M. Webster, J. Am. Chem. Soc., 95, 102, 1973.

276. R. W. Taft Jr, S. Ehrenson, I. C. Lewis and R. E. Glick, ibid.,

81, 5352, 1959.

277. Y. Yukawa and T. Tsuno, Bull. Chem. Soc., Jpn, 32, 971,

1959.

278. M. Yoshioka, K. Hamamoto and T. Kubota, ibid., 35, 1723,

1961.

279. R. W. Taft, J. Phys. Chem., 64, 1805, 1960.

280. S. Ehrenson, R.T.C. Brownlee and R. W. Taft, Progr. Phys.

Org. Chem., 10, 1, 1973.

281. (a) Weinreb S. M. J and Antoline, Science of Synthesis,

George Theime Verlag KG, Theime Newyork, p. 854, 2005,

ISBN: 3-13-118721-2; (b) Shizuo Fujisaki, Satoshi Hamura,

Hisao Eguchi and Akiko Nishida, Bulletin of Chemical

Society of Japan, 66(8), 2426-2428, 1993; DOI:

10.1246/bcsj.66.2426.

190

282. A. I. Vogel, A Text book of Practical Organic Chemistry,

Long mans Green, London, 737, 1962.

283. W. G. Douben, and R. E. Adams, J. Am. Chem. Soc., 70,

1559, 1948.

284. D. H. Hey and R. Wilkinson, J. Chem. Soc., 1030, 1940.

285. F. Feigl, Spot Tests in organic Analysis, Elsevier, New York,

1975.

286. G. P. Panigrahi and P. K Misro, Indian J. Chem., 15A,

1066, 1977.

287. S. B. Chapman, Advances in Linear Free Energy

Relationships, Shorter, J., Ed.; Plenum Press: New York,

1972.

288. K. B. Wiberg and R. Evans, J. Am. Chem. Soc., 80, 3019,

1958.

289. K. K. Banerji, Indian J. Chem., 16A, 595, 1978.

290. E. S. Amis, Solvent effects on reaction rates and

mechanisms, Academic Press, New York, 1967.

291. N. P. Marigangaiah and K. K. Banerji, Indian J. Chem., 14A,

660, 1976.

292. S. Rao and V. Pulugurtha, Z. Phys. Chem (Leipzig), 255,

382, 1974.

293. J. S. Littler, J. Chem. Soc., 827, 1962.

191

294. N. P. Marigangaiah, and K K. Banerji, Aust. J. Chem., 29,

1939, 1976.

295. J. Shorter and C. N. Hinshelwood, J. Chem. Soc., 3276,

1950.

296. P. S. Radhakrishnamurti and M. D. Prasad Rao, Indian J.

Chem., 15A, 524, 1977.

297. M. Krishnapillay and A. Thirunavukkarasu, Indian J. Chem.,

20B, 583, 1981.

298. J. Shorter, J. Chem. Soc., 1868, 1962.

299. W. S. Nathan and H. B. Waston, J. Chem. Soc., 217, 1933.

300. A. Meenakshi and M. Santhappa, Indian J. Chem., 11, 393,

1973.

301. K. B. Wiberg and H. Schaefer, J. Am. Chem. Soc., 91, 933,

1969.

302. H. H. Jaffe, Chem. Rev., 53, 191, 1953.

303. K. B. Wiberg, Physical Organic Chemistry, John Wiley,

New York, 416, 1964.

304. E. S. Gould, Mechanism and Structure in Organic

Chemistry, Holt Riehart and Winston, New York, 181, 1964.

305. A. Y. Richard Johnes, Physical and Mechanistic Organic

Chemistry, Cambridge Univ. Press, New York, II edn. 42,

1984.

192

306. F. Ruff and A. Kucsman, J. Chem. Soc., Perkin Trans. 2,

683, 1985.

307. F. Ruff, A. Komoto, N. Furukawa and S. Oae, Tetrahedron,

32, 2763, 1976.

308. F. A. Cotton and G. Wilkinson, Advanced Inorganic

Chemistry, John Wiley, 5th edn. 707, 1988.

309. N. N. Greenwood and A. Earnshaw, Chemistry of the

Elements, Pergamon Press, Oxford, 1222, 1984.

310. Freeman. Fillmore, Rev. React. Species. Chem. React., 1,

179, 1976.

311. K. Banumathi, M.Phil. Dissertation, Bharathidasan

University, 1987.

312. S Neil Issacs, Physical Organic Chemistry, Longman

Scientific & Technical, New York, 1987.

313. P. S. Radhakrishnamurti and B. V. Damoder Rao,, Indian J.

Chem., 20A, 473, 1981.

314. B. A. Blackaddar and C. Hinshelwood, J. Chem. Soc., 2720,

1978.

315. W. Good, D. B. Ingham and J. Stone, Tetrahedron, 31, 257,

1975.

316. J. E. Leffler, J. Chem. Phys., 27, 981, 1957.

193

317. O. Exner, Colln. Czech. Commun., 29, 1094, 1964 ; ibid., 37,

1425, 1972.

318. O. Exner, J. Chem. Soc., Perkin Trans. 2, 973, 1993.

319. J. E. Leffler and E. Grunwald, Rates and Equilibrium of

Organic Reactions, Wiley, New York, 1963.

320. J. E. Leffler, J. Org. Chem., 20, 1202, 1955.

321. D. G. Peters, J. M. Hayes and G. M. Hiefitje, Chemical

Separations and Measurements-Theory and Practice of

Analytical Chemistry, Saunders Golden Series, London,

32, 1974.

PUBLISHED PAPERS

http://www.e-journals.in Chemical Science Transactions DOI:10.7598/cst2015.1054 2015, 4(2), 638-641

Kinetics of Oxidation of 3-Benzoylpropionic Acid by N-Bromobenzamide in Aqueous Acetic Acid Medium

N. A. MOHAMED FAROOK* and A. AFROOS BANU

P. G & Research Department of Chemistry Khadir Mohideen College, Adirampattinam - 614 701, India nafarook@hotmail.com

Received 10 January 2015/ Accepted 15 February 2015

Abstract: The kinetics of the oxidation of 3-benzoylpropionic acid (KA) by N-bromobenzamide (NBB)to yield the corresponding carboxylic acid were studied potentiometrically in 50:50 (v/v) aqueous acetic acid medium at 298 K. The effects of temperature, composition of solvent medium and concentration of added mineral acid on the rate of reaction were also studied. The reaction was first order with respect to the [KA], [NBB] and hydrogen ions. There is no effect of added benzamide. Protonated NBB has been postulated as the reactive oxidizing species.

Keywords: Kinetics, Oxidation, N-Bromobenzamide, 4-Oxoacids, 3-Benzoylpropionic acid.

Introduction

The chemistry of reactions of N-halo compounds forms a separate branch, which is of great synthetic importance1-4. N-halo compounds have been extensively employed as oxidizing agents for organic substrates5,6. N-Halo compounds are the source of positive halogen and have been exploited as oxidant for a variety of substrates in both acidic and alkaline media. The species responsible for such oxidizing character may be different depending on the pH of the medium7,8. Although a lot of works have been reported on the oxidation of organic compounds by N-halo compounds9-12 it is to be noted that no systematic kinetic investigation on the oxidation of 3-benzoylpropionic acid by N-bromobenzamide has yet been reported in the literature. Here we report the results of the kinetics of the oxidation of 3-benzoylpropionic acid (KA) with N-bromobenzamide (NBB) in aqueous acetic acid medium in the presence of perchloric acid.

Experimental All the chemicals used were of p.a.grade. Their purity was checked by comparing their boiling or melting points with the literature values. Acetic acid was refluxed over chromic oxide for 6 h and then fractionated. Solutions of sodium perchlorate and perchloric acid were prepared in double-distilled water. Double-distilled water was employed in all kinetic runs.

RESEARCH ARTICLE

NBB H 3O H 2O Brk1

-1+

k Benzamide+

Chem Sci Trans., 2015, 4(2), 638-641 639

The reaction was followed potentiometrically by setting up a cell containing the reaction mixture, into which a platinum electrode and a standard calomel electrode were dipped. The emf of the cell was measured periodically using a Equip-Tronic potentiometer, while the reaction mixture was continuously stirred. The pseudo-first order rate constants computed from the plots of log (Et-E∞) against time were reproducible within ± 3%.

Results and Discussion Reaction order The reaction orders were determined from the slopes of log k1 versus log (concentration) plots by varying the concentration of substrate (KA) and perchloric acid in turn while keeping others constant. The plot log k1 against log [KA] is linear (r = 0.989) with a slope value of 0.988 and the plot log k1 against log [H+] is also linear (r = 0.996) with a unit slope. This is further supported by the fact that the plots of k1 versus [KA] and k1 versus [H+] gives a straight line passing through the origin, the linearity of the plots of log [NBB] versus time indicates the order in [NBB] as unity, this is also confirmed by constant values of k1 at varying [NBB] (Table 1). This indicates clearly that the reaction is first order with respect to [KA], [NBB] and [H+].

Table 1. Rate constant for the oxidation of 3-benzoylpropionic acid by NBB in aqueous acetic acid medium at 30 0Ca

102 [KA] mol dim-3 103 [NBB] mol dm-3 [H+]mol dm-3 104 k1b,s-1 103 k2

c dm3 mol-1 s-1

2.0 2.0 0.5 1.615 8.08 3.0 2.0 0.5 2.422 8.07

4.0 2.0 0.5 3.224 8.06

6.0 2.0 0.5 4.854 8.09

8.0 2.0 0.5 6.441 8.05 2.0 2.0 0.8 2.562 0.32

2.0 2.0 1.2 3.839 0.32

2.0 2.0 1.4 4.482 0.32

2.0 2.0 1.6 5.121 0.32

2.0 1.6 0.5 1.621 -

2.0 1.2 0.5 1.624 -

2.0 1.0 0.5 1.618 -

2.0 0.8 0.5 1.621 -

aGeneral conditions: [NaClO4] = 0.5 mol dm-3,Solvent composition: 50% Acetic acid - 50% Water (v/v). bEstimated from pseudo-first order plots, the error quoted in k1 values is the 95% confidential limit of ‘Student t’ test.13 cIndividual k2 values estimated as k1 / [KA] or k1 / [H+]

Effect of products The effect from adding benzamide was studied, which caused a decrease in the oxidation rate. Thus, retardation of the reaction rate upon addition of benzamide suggests that there is a pre-equilibrium step involving a process in which benzamide is a product. (1)

The effect of dielectric constant in the reaction medium was studied by adding acetic acid (40%-80%) in the reaction medium at constant concentrations of other reactants. The reaction rate increased remarkably with the increase in the proportion of acetic acid in the solvent medium. The effect of ionic strength was studied by varying the concentration of NaClO4 in the reaction medium. It was found that the rate of reaction is independent of ionic strength of the medium. The reaction mixture was kept for 24 h with acrylonitrile in an inert atmosphere. Test for free radical was negative.

NBB H3O H2O Brk1

-1+

k Benzamide+

C CH 2 CH 2 C OH

O O

+ H3O

C CH 2 CH 2 C OH

OH O

H2O+

k2

k -2

(S)

(S )

C CH CH2 C OH

OOH

H3O+H2O+(S )k3

k -3

(E)

C CH CH 2 C OH

OOHk4

slow

H2O Br

C CH CH 2 C OH

OOH

H2O Br

(F)

640 Chem Sci Trans., 2015, 4(2), 638-641

Effect of temperature The rate of reaction was measured at different temperatures. The activation parameters for the oxidation of keto acid by NBB have been evaluated from the slope of the Arrhenius plots.

Mechanism It is known that14 the probable reactive species of NCA in acid solution. H2O

+Br. The reaction is first order in [NBB], [KA] and [H+]. The reaction rate increases with increase in [H+] at constant ionic strength, showing that the reaction proceeds completely through the acid-catalyzed pathway. The change in the polarity of the medium has a marked effect on the reaction rate. The trend in the rate observed may be due to more than one factor. It may be attributed to the lowering of dielectric constant of the medium which favors reaction involving protonation. Further, the enolization of the keto acid may be catalyzed by acetic acid and this may also contribute to rate enhancement. The plot of log k1 versus 1/D is linear (r = 0.988) with positive slope, indicating an interaction between a positive ion and a dipole molecule. This supports the postulation of (H2O

+Br) as the reactive species. The retardation of reaction rate on the addition of saccharin suggests15 a pre-equilibrium step involves a process in which benzamide is one of the products.

If this equilibrium is involved in the oxidation process, the retardation should be an inverse function of benzamide concentration, which is borne out by observation that the inverse of the rate constant gives a linear (r = 0.987) plot against [benzamide].

A mechanism has been proposed involving the attack of H2O+Br on the enol form of the

substrate (E) in the rate determining step. It is known14 that the enolization is proposed to be the necessary step prior to the oxidation of the substrate

(2)

(3) .

(4)

(5)

(F)C

O

OHOther products+

fast

+ C6H5COCH2CH2COOH C6H5CONHBr 5 H2O

C6H5CONH2C6H5 COOH 6H23CO2 HBr

H+

+

+ + + +

Chem Sci Trans., 2015, 4(2), 638-641 641

(6)

Scheme 1

Scheme 1 leads to rate law (7)

][

]][][[][

32

23432

Benzamidekkk

BrOHOHSkkk

dt

NBBd

a

(7)

Equation (7) clearly points out the observed results i.e. first order in [KA], [NBB], [H+] and inverse order in [Benzamide] on the rate of the oxidation.

Stoichiometry and reaction products Different sets of reaction mixtures containing different quantities of NBB and KA at constant [H+] and ionic strength were reacted for 24 h at 30 0C and then analyzed. The remaining NBB was estimated. The oxidation products were identified as benzoic acid and benzamide. It was confirmed by noting the mixed melting point, chemical methods and TLC techniques. The results are in good agreement with 1:1 stoichiometry.

(8)

Reference 1. Amauri F Patrocino and Paulo J S Moran., Organomet Chem., 2000, 603, 220-224. 2. Sameer P Dhuru, Nikhil U Mohe and Manikrao M Salunkhe, Synth Commun., 2001,

31(23), 3653-3657. 3. Canibano V, Rodriguez J F, Santose M, Sanz-Tejedor M A, Carreno M C, Gonzalez

G and Garcia-Ruano J L, Synthesis, 2001, 14, 2175-2179. 4. Bandgar B P, Uppalla L S and Sadavarte V S, Syn Lett., 2001, 11, 1715-1718. 5. Duraisamy Thenraja, Perumal Subramaniam and Chockalingam Srinivasan, J Chem

Soc Perkin Trans 2, 2002, 2125-2129. 6. Teruaki Mukaiyama, Jun-ichi Matsuo, Daisuke Lida and Hideo Kitagawa, Chem

Lett., 2001, 8 846-847. 7. Thenraja D, Subramaniam P and Srinivasan C, J Chem Soc Perkin Trans 2, 2002, 2125. 8. Mukaiyama T, Mastsuo J I, Lida D and Kitagawa H, Chem Lett., 2001, 8, 846. 9. Hambly G F and Chan T H, Tetrahedron Lett., 1986, 27, 2563. 10. Antelo J M, Arce F, Crugeiras J O and Parajo M, J Phys Org Chem., 1997, 10, 631-636. 11. Karunakaran C and K Ganapathy K, Indian J Chem., 1990, 29A, 133. 12. Harihar A L, Kembhavi M R and Nandibewoor S T, J Indian Chem Soc., 1999, 76,

128-130. 13. Shorter J, Correlation Analysis in Organic Chemistry, Clarendon Press, Oxford,

Chapter 2, 1973. 14. Shahnaz Khan, Khan M U, Singh S K, Gupta H D and Singh P K, Asian J Chem.,

2003, 15, 595. 15. Vivekanandan K and Nambi K, J Indian Chem Soc., 1999, 76, 198-201.

1 23

Journal of Solution Chemistry ISSN 0095-9782Volume 42Number 1 J Solution Chem (2013) 42:239-250DOI 10.1007/s10953-012-9942-0

Kinetics and Mechanism of Oxidationof Substituted 4-Oxoacids by N-Bromosaccharin

N. A. Mohamed Farook, S. Manochitra &A. Afroos Banu

1 23

Your article is protected by copyright and all

rights are held exclusively by Springer Science

+Business Media New York. This e-offprint is

for personal use only and shall not be self-

archived in electronic repositories. If you

wish to self-archive your work, please use the

accepted author’s version for posting to your

own website or your institution’s repository.

You may further deposit the accepted author’s

version on a funder’s repository at a funder’s

request, provided it is not made publicly

available until 12 months after publication.

Kinetics and Mechanism of Oxidation of Substituted4-Oxoacids by N-Bromosaccharin

N. A. Mohamed Farook • S. Manochitra • A. Afroos Banu

Received: 29 November 2011 / Accepted: 11 March 2012 / Published online: 3 January 2013� Springer Science+Business Media New York 2012

Abstract The kinetics of the oxidation of substituted 4-oxoacids by N-bromosaccharin

(NBSac) has been studied in aqueous acetic acid medium at 30 �C. The reactions follow

first-order kinetics in the 4-oxoacids, NBSA and H?. Variation in the ionic strength has no

effect on the reaction rate. The order of reactivity among the studied 4-oxoacids is:

4-methoxy [ 4-methyl [ 4-phenyl [ 4-H [ 4-Cl [ 4-Br [ 3-NO2. The effect of changes

in the electronic nature of the substrate revealed that there is a development of positive

charge in the transition state. The activation parameters were computed from an Arrhenius

plot. Based on the kinetic results, a suitable mechanism has been proposed. The mechanism

involves the attack of the oxidizing species hypobromous acidium ion, (H2O?Br).

Keywords Kinetics � Oxidation � 4-Oxoacids � NBSac

1 Introduction

4-Oxoacid is an attractive substrate in terms of its enolization. In strong acid medium the

substrate undergoes enolization. The reactive species of the substrate has been reported in

the literature to be the enol form [1].

N-Bromosaccharin is a source of positive halogen and this reagent has been exploited as

oxidant for a variety of substrates in both acidic and alkaline medium [2]. The nature of

active oxidizing species and mechanism depends on the nature of halogen atom, the groups

attached to the nitrogen and the reaction condition. The species responsible for such

oxidizing character may be different depending on the pH of the medium. The probable

reactive species [3] of NBSac in acid solution are[ NX, HOX, [ N?HX, or H2OX? and

the reaction species in alkaline solutions are [ NH, HOX, and OX-.

In recent years, studies of the oxidation of various organic compounds by N-halo

compounds, in the presence of perchloric acid, have attracted considerable attention. A

through literature survey reveals that relatively little work on the oxidation of 4-oxoacid

N. A. Mohamed Farook (&) � S. Manochitra � A. Afroos BanuDepartment of Chemistry, Khadir Mohideen College, Adirampattinam 614 701, Indiae-mail: nafarook@hotmail.com

123

J Solution Chem (2013) 42:239–250DOI 10.1007/s10953-012-9942-0

Author's personal copy

have been reported so far [4–7]. Although the N-bromosaccharin oxidations of organic

compounds have been studied, there seems to be no report on a systematic kinetic study of

the oxidation of 4-oxoacids by N-bromosaccharin.

The main objectives of the present study are to ascertain the reactive species of the

substrate and oxidant, elucidate a plausible mechanism, deduce an appropriate rate law,

identify the oxidation products and evaluate the kinetic parameters.

2 Experimental

2.1 Materials

All the chemicals used were of AR grade. Acetic acid (BDH) was first refluxed over

chromic acid for 6 h and then distilled. Solutions of sodium perchlorate and perchloric acid

and were prepared in double distilled water. Double distilled water (conductivity \10 lS�cm-1) was employed in all kinetic runs. All the chemicals used were 99.8 % pure.

The 4-oxo-4-(40-methoxyphenyl)butanoic acid (S2), 4-oxo-4-(40-methylphenyl)-buta-

noic acid (S3), 4-oxo-4-(40-chlorophenyl)butanoic acid (S5) and N-bromosaccharin

(NBSac) were obtained from Sigma-Aldrich Chemical Co. The remaining 4-oxoacids (S1,S4, S6, S7) were prepared by Friedel–Crafts acylation of the substituted benzene with

succinic anhydride [5–12].

All the 4-oxo acids used in this study (Table 1) were crystallized twice from water and

their purity was checked by their melting points and UV, IR and NMR spectra. Solutions of

the reagents were prepared either in doubly distilled water or in purified acetic acid and

were standardized by iodometric methods [10] using standard potassium dichromate and

sodium thiosulfate solutions. Fresh solutions were used for each kinetic run.

2.2 Kinetic Studies

The reaction mixtures, containing 4-oxo acid, acetic acid and mercuric acetate solutions

were thermally equilibrated for an hour at the desired temperature. The reaction was

initiated by the addition of temperature-equilibrated NBSac solution of the requisite

concentration. The rate of the reaction was followed by estimating the amount of unreacted

NBSac iodometrically. All the reactions were carried out under pseudo-first order

Table 1 List of substituted 4-oxoacids

S.no. 4-oxoacids Code Melting point �C

Observed Reported5

1 4-Oxo-4-phenylbutanoic acid S1 116 116

2 4-Oxo-4-(40-methoxyphenyl)butanoic acid S2 146 147

3 4-Oxo-4-(40-methylphenyl)butanoic acid S3 128 129

4 4-Oxo-4-biphenylbutanoic acid S4 184 185

5 4-Oxo-4-(40-chlorophenyl)butanoic acid S5 132 133

6 4-Oxo-4-(40-bromophenyl)butanoic acid S6 148 149

7 4-Oxo-4-(30-nitrophenyl)butanoic acid S7 163 164

240 J Solution Chem (2013) 42:239–250

123

Author's personal copy

conditions by keeping an excess (910 or greater) of [4-oxo acid] over [NBSac]. The

pseudo-first order rate constants were computed from linear plots of log10 [NBSac]t against

time up to 90 % completion of the reaction, the rate constants (k) were reproducible within

5 %.

The precision of the rate constant values is given in terms of 95 % confidence limit of

the student’s t test [13]. Freshly prepared solutions of 4-oxo acids in purified acetic acid

were used. The stoichiometry of the reaction was determined by equilibrating reaction

mixture of various [NBSac]/[4-oxo acid] ratios at 30 �C for 12 h, keeping all other reagent

concentrations constant. Estimation of unconsumed NBSac revealed that one mole of

4-oxo acid consumed one mole of NBSac.

C6H5COCH2CH2COOHþ C6H4SO2CONBrþ 5H2O

! C6H5COOHþ C6H4SO2CONHþ 3CO2 þ 6H2 þ HBr ð1Þ

The products were extracted with ether, dried and analyzed. Benzoic acid was identified by

its melting point (121 �C). Then it was estimated quantitatively using UV–Vis spectro-

photometry with a standard curve at kmax = 235 nm and also tested with its characteristic

spot test. Identification of benzoic acid was also made by comparing the Rf values of

authentic samples.

3 Results and Discussion

3.1 Order of Reaction

The rate of oxidation was found to be first order each in [NBSac] and [S]. Linear plots of log10k1

versus log10 [S] with unit slope (S1: slope = 1.03 ± 0.02, r = 0.994; S2: slope = 1.01 ±

0.03, r = 0.996; S3: slope = 1.04 ± 0.01, r = 0.989; S4: slope = 1.04 ± 0.03, r = 0.999;

S5: slope = 0.995 ± 0.02, r = 0.991; S6: slope = 0.993 ± 0.07, r = 0.994; S7: slope =

1.10 ± 0.08, r = 0.992) show first order dependences of the rate on [S]. The k1 values at

different [S] are given in Table 2. The k1 values obtained at different initial concentrations of

NBSac reveal that the rates are almost independent of the initial concentration of NBSac (Table 2).

The dependence of the reaction rate on the hydrogen ion concentration has been

investigated at different initial concentrations of perchloric acid, keeping the concentra-

tions of the other reactants constant. The observed k1 values are presented in the Table 2. It

may be seen that the rate of the reaction increases linearly with increase in concentration of

hydrogen ion. This establishes that the reaction is first order with respect to hydrogen ion

concentration. A plot of k1 versus [H?] is linear, passing through the origin (Fig. 1),

showing that the reaction proceeds completely through the acid-catalyzed pathway [14].

It was reported earlier in the case of N-halo oxidants that in the absence of mineral

acids, HOBr is the reactive oxidant species. Farook et al. [14] have observed for the

oxidation of some a-hydroxy acids by NBSac that the linear increase in the oxidation rate

with an increase in [H?] indicates the protonation of HOBr to give a cationic bromine

species (Eq.2), which is a stronger electrophile and oxidant:

HOBrþ H3Oþ � H2OþBrþ H2O ð2Þ

Thus the most probable oxidizing species is the hypobromous acidium ion, (H2O?Br). The

participation of hypohalous acidium ions in many electrophilic substitution and oxidation

reactions is well documented [15].

J Solution Chem (2013) 42:239–250 241

123

Author's personal copy

Ta

ble

2E

ffec

to

fvar

yin

g[S

][N

BS

ac]

and

[H?

]o

nth

era

teof

reac

tion.a

Solv

ent:

50

%ac

etic

acid

–50

%w

ater

(v/v

),T

=3

03

K

10

2[S

]/m

ol�d

m-

31

03[N

BS

ac]/

mol�d

m-

3[H

?]/

mo

l�dm

-3

10

4k 1b

s-1

S1

S2

S3

S4

S5

S6

S7

2.0

2.0

0.5

1.4

4±

0.1

25

.25

±0

.42

3.8

2±

0.4

11

.56

±0

.11

0.9

8±

0.1

40

.91

±0

.02

0.1

8±

0.0

3

4.0

2.0

0.5

2.8

4±

0.1

71

0.4

1±

0.6

7.6

0±

0.8

63

.08

±0

.13

1.8

8±

0.2

01

.82

±0

.10

0.3

6±

0.0

6

6.0

2.0

0.5

4.3

2±

0.0

21

5.7

±1

.21

1.5

8±

0.8

4.5

6±

0.1

82

.88

±0

.17

2.6

5±

0.1

20

.56

±0

.06

8.0

2.0

0.5

5.6

2±

0.2

52

0.7

±2

.11

5.1

2±

0.2

6.4

1±

0.4

34

.01

±0

.22

3.6

2±

0.2

30

.72

±0

.09

2.0

0.8

0.5

1.4

2±

0.0

65

.21

±0

.06

3.8

1±

0.1

01

.52

±0

.05

0.7

9±

0.0

70

.92

±0

.11

0.2

0±

0.0

2

2.0

0.4

0.5

1.4

6±

0.0

35

.25

±0

.07

3.8

5±

0.1

11

.53

±0

.03

0.7

7±

0.1

30

.95

±0

.10

0.2

1±

0.0

1

2.0

0.2

0.5

1.4

8±

0.0

35

.23

±0

.16

3.8

3±

0.1

01

.51

±0

.08

0.7

8±

0.0

40

.96

±0

.03

0.1

9±

0.0

2

2.0

2.0

1.0

2.8

4±

0.1

21

0.5

±0

.57

.64

±0

.25

3.1

2±

0.2

61

.96

±0

.07

1.8

1±

0.0

70

.36

±0

.04

2.0

2.0

1.2

3.4

3±

0.1

61

2.4

±0

.69

.12

±0

.26

3.7

4±

0.2

22

.34

±0

.15

2.1

8±

0.1

10

.42

±0

.03

2.0

2.0

1.4

4.0

4±

0.2

91

4.2

±0

.11

0.4

2±

0.6

4.3

5±

0.1

92

.74

±0

.17

2.5

2±

0.1

30

.51

±0

.01

aA

sdet

erm

ined

by

iodom

etri

cte

chniq

ue

foll

ow

ing

the

dis

appea

rance

of

oxid

ant;

the

erro

rquote

din

kv

alu

esis

the

95

%co

nfi

den

celi

mit

of

‘stu

den

tt

test

[13]

bE

stim

ated

from

pse

udo-fi

rst

ord

erplo

tsover

70

%re

acti

on

242 J Solution Chem (2013) 42:239–250

123

Author's personal copy

3.2 Effect of Varying Ionic Strength

The ionic strength of the reaction medium was changed by the addition of anhydrous

sodium perchlorate and the influence of ionic strength on the reaction rate was studied. It is

found that the ionic strength of the reaction medium had no significant effect on the

reaction rate.

3.3 Effect of Products

The addition of saccharin decreased the rate of the oxidation reaction. Thus the retardation

of reaction rate on the addition of saccharin suggests a pre-equilibrium step involving a

process in which saccharin is one of the products:

NBSacþ H3Oþ � H2OþBrþ saccharin ð3Þ

If this equilibrium is involved in the oxidation process, the rate should be an inverse

function of the saccharin concentration, which is borne out by the observation that the

inverse of the rate constant gives a linear (r = 0.982) plot against [saccharin]. Similar

conclusions have been arrived at in the N-chloronicotinamide [16] oxidation of amino

acids.

3.4 Effect of Free Radical Inhibitor

The oxidation reactions of S1 with NBSac catalyzed by perchloric acid at different initial

concentrations of acrylonitrile have been investigated. The reaction neither induces

polymerization nor retards the reaction. Under the experimental conditions, there is no

reaction between NBSac and acrylonitrile. Consequently it may be inferred that free

radicals are not involved in the rate controlling step of the present reaction.

0

2

4

6

8

10

12

14

16

0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6

[H+], mol dm-3

104 k

1s-1

S1

S2

S3

S4

S5S6

S7

Fig. 1 Plots of k1 versus [H?]for the reaction between S andNBSac

J Solution Chem (2013) 42:239–250 243

123

Author's personal copy

3.5 Effect of Solvent Composition

The effect of changing solvent composition on the reaction rate was studied by varying

the concentration of acetic acid from 50 to 80 %. The pseudo first-order rate constants

for the oxidation reactions of all oxoacids, S1–S7 with NBSac, were estimated in the

presence of perchloric acid at constant ionic strength. The rate of the reaction increases

remarkably with increase in the proportion of acetic acid in the medium (Table 3).

When the acetic acid content increases in the medium, the acidity of the medium is

increased while the dielectric constant of the medium is decreased. These two effects

cause the rate of oxidation to increase remarkably. The observed effect is similar to

those reported in the oxidation of other organic compounds by N-chlorosaccharin [17].

When the acetic acid content of the medium is increased from 50 to 80 %, the pH of the

medium changes, leading to the increase in [H?] and hence catalysis by acetate ion is

untenable.

The enhancement of the reaction rate with an increase in the amount of acetic acid may

generally be attributed to two factors: (i) increase in acidity at constant [perchloric acid]

and (ii) decrease in dielectric constant with increase in HOAc content. The plots of log10 k1

against the inverse of dielectric constant are linear with positive slopes, indicating an

interaction between a positive ion and a dipole molecule [18, 19]. This supports the

postulation of H2O?Br as the reactive species.

3.6 Rate of Enolization by the Bromination Method

It has been reported, in the case of oxidation of keto compounds, that the oxidation

proceeds via enolization of the keto compounds [20]. The rate of enolization of keto

compound was found to be faster than the rate of oxidation. The reactive species of the

substrate may be determined by enolization, which is an acid as well as base catalyzed

reaction and proceeds by a concerted or push–pull mechanism. The rate of enolization was

determined by the bromination method for the system under investigation.

Table 3 Effect of solvent polarity on the rate of reaction, where [S] = 2.0 9 10-2 mol�dm-3,[NBSac] = 2.0 9 10-3 mol�dm-3, [H?] = 0.5 mol�dm-3, and T = 303 K

S 104 k1a/ s-1 ra

CH3COOH–H2O (v/v) %

50–50 60–40 70–30 80–20

S1 1.44 ± 0.12 2.24 ± 0.24 3.12 ± 0.14 5.28 ± 0.29 0.998

S2 5.25 ± 0.42 6.83 ± 0.34 7.85 ± 0.48 9.35 ± 0.60 0.983

S3 3.82 ± 0.41 4.91 ± 0.22 6.31 ± 0.24 7.52 ± 0.34 0.985

S4 1.56 ± 0.11 2.11 ± 0.07 2.92 ± 0.14 4.23 ± 0.18 0.998

S5 0.98 ± 0.14 1.32 ± 0.06 2.92 ± 0.11 3.01 ± 0.01 0.998

S6 0.91 ± 0.02 1.07 ± 0.05 1.68 ± 0.12 2.36 ± 0.15 0.994

S7 0.18 ± 0.03 0.31 ± 0.03 0.61 ± 0.07 0.92 ± 0.08 0.998

a Estimated from pseudo first-order plots

244 J Solution Chem (2013) 42:239–250

123

Author's personal copy

3.7 Effect of Substituents

The oxidation of 4-oxo-4-phenylbutanoic acid (S1) and substituted 4-oxoacids (S2–S7)

were carried out in the temperature range of 303–323 K. The observed rate constants

increase with temperature for all of the compounds. The activation parameters for the

oxidation of 4-oxoacid by NBSac have been evaluated from the slope values of the

Arrhenius plots.

A close look at activation parameters presented in Table 4 shows that the activation

energies for the oxoacids with electron-releasing substituents are relatively lower than

those with electron-withdrawing substituents. The entropy of activation is negative for all

the 4-oxoacids ranging from -126 to -232 J � K-1 � mol-1. The large negative entropy of

activation in conjunction with other experimental data supports the mechanism outlined in

Scheme-1. The formation of an activated complex from reactant molecules is accompanied

by the conversion of translation-like and rotational-like degrees of freedom of the reactants

to vibrational degrees of freedom of the transition state species. The more widely spaced

energy level for the latter type of molecular motion implies a small entropy and thus a

negative value of DS# [21].

It is interesting to note that the reactivity decreases for substituents in the order:

4-methoxy [ 4-methyl [ 4-phenyl [ 4-Cl [ 4-Br [ 3-NO2 ð4ÞThe Hammett’s plot for the oxidation of S by NBSac at various temperatures was found

to be linear. The Hammett’s plot is shown in Fig. 2. The values of reaction constants (q)

are shown in Table 5.

The points are referenced as (1) S2, (2) S3, (3) S4, (4) S1, (5) S5, (6) S6, (7) S7.

The q value indicates the sensitivity of a reaction to the effects of electronic pertur-

bation. It also provides information about the nature of the transition state involved in the

reaction. A reaction involving a development of positive charge in the transition state is

aided by electron-releasing substituents and the q coefficient is negative [21–26].

In the present investigation, the acceleration of reaction rate with the electron-releasing

substituents and the negative value of the reaction constant, q, indicates explicitly that the

mechanism of oxidation involves the development of positive charge in the transition state.

It is generally recognized that oxidations lead to electron deficient species which are

radical cations, radicals or carbocations. These reactions normally have a negative q value

and the magnitude of q depends on the extent of electron deficiency. Oxidation reactions

involving free radical formation in the rate controlling step usually have a small negative qvalue and the oxidations involving the formation of a carbocation have large negative qvalues. Based on these arguments we expect a large q value but the measured q value is in

the range -1. 41 to -0.98. The low q values may be attributed to the nature of observed

rate constant. The observed rate constant is a composite of several terms and is shown in

Eq. 12.

The terms shown in Eq. 12 deserve comment. The rate constant k3 depends on the

concentration of the protonated substrate (S?) and the electron donating substituents tend

to delocalize the positive charge on S? and hence favor the formation of this positive

species. In the rate limiting step (Eq. 6) of the Scheme-1, the formation of the carbocation

is facilitated by electron releasing substituents.

Thus we get a slightly low negative q value of -1.41 (at 303 K) because kobs is

composite of the enolization as well as the oxidation of the 4-oxoacids. Hence in the

present investigation the measured q value and other findings fit in with the formulation of

mechanism outlined in the Scheme-1.

J Solution Chem (2013) 42:239–250 245

123

Author's personal copy

Ta

ble

4A

ctiv

atio

np

aram

eter

san

dra

teco

nst

ants

for

the

ox

idat

ion

of

S1

–S

7b

yN

BS

acin

aqu

eous

acet

icac

idm

ediu

m

S1

04/k

1a,

s-1

Ea/k

J�mol-

1D

H#/k

J�mo

l-1

DS

#/J�K

-1�m

ol-

1D

G#/k

J�mo

l-1

30

3K

30

8K

31

3K

32

3K

S1

1.4

4±

0.1

21

.85

±0

.18

2.2

2±

0.2

63

.48

±0

.64

34

.8±

0.5

33

2.3

±0

.61

-1

78

.2±

0.7

28

6.4

±0

.32

S2

5.2

5±

0.4

25

.72

±0

.60

7.4

2±

0.6

28

.14

±0

.58

15

.9±

0.3

21

3.4

±0

.44

-2

31

.8±

1.0

88

3.4

±0

.16

S3

3.8

2±

0.4

14

.15

±0

.20

4.9

5±

0.4

05

.62

±0

.68

16

.6±

0.3

51

4.1

±0

.06

-2

32

.6±

0.9

68

4.3

±0

.87

S4

1.5

6±

0.1

12

.28

±0

.10

2.9

2±

0.0

24

.12

±0

.14

36

.2±

0.2

23

3.7

±0

.19

-1

73

.9±

1.0

58

5.8

±0

.19

S5

0.9

8±

0.1

41

.11

±0

.14

1.3

1±

0.0

81

.98

±0

.22

32

.4±

0.1

82

9.9

±0

.32

-1

91

.8±

1.1

48

7.8

±0

.58

S6

0.9

1±

0.0

21

.01

±0

.01

1.2

2±

0.0

11

.86

±0

.01

34

.7±

0.3

63

2.2

±0

.61

-1

85

.0±

0.6

28

7.5

±0

.78

S7

0.1

8±

0.0

30

.31

±0

.01

0.4

8±

0.0

10

.65

±0

.01

55

.8±

1.0

15

3.3

±0

.75

-1

26

.2±

0.2

49

1.2

±0

.44

No

te:

[S]

=2

.09

10

-2

mo

l�dm

-3,

[NB

Sac

]=

2.0

91

0-

3m

ol�d

m-

3,

[H?

]=

0.5

mol�d

m-

3;

solv

ent

com

po

siti

on

:5

0%

acet

icac

id–5

0%

wat

er(v

/v)

aE

stim

ated

from

pse

udo-fi

rst

ord

erplo

tsover

70

%re

acti

on

246 J Solution Chem (2013) 42:239–250

123

Author's personal copy

The dependence of the reaction rate on the structure of the reacting molecule is related

to activation parameters. The decisive term concerning the dependence on the structure is

neither Gibbs energy nor enthalpy but potential energy, which is experimentally not

accessible. Many authors support the opinion that the activation energy at a certain tem-

perature is a better approximation towards the unknown potential energy [27].

The validity of the isokinetic relation can be tested graphically by plotting with Exner

plots. The isokinetic temperature evaluated from the Exner plots is found to be 378 K. As

the experiment has been carried out at a temperature far away from the isokinetic tem-

perature, application of the Hammett equation to the observed kinetic data is valid. The

validity of isokinetic relationship in the present study implies that all the 4-oxoacids

undergo oxidation by the same mechanism [28].

NBSac H3O H2O Brk1

-1+

k Saccharin+

C CH2 CH2 C OH

O O

+ H3O

C CH2 CH2 C OH

OH O

H2O+

k2

k -2

(S)

(S )

C CH CH2 C OH

OOH

H3O+H2O+(S )k3

k -3

(E)

C CH CH2 C OH

OOHk4

slow

H2O Br

C CH CH2 C OH

OOH

H2O Br

(F)

(F)C

O

OHOther products+

fast

(5)

(3)

(4)

(7)

(6)

Scheme 1 Reaction mechanism

J Solution Chem (2013) 42:239–250 247

123

Author's personal copy

3.8 Mechanism

A probable mechanism for the oxidation of 4-oxoacids by NBSac is proposed based on the

experimental results and in analogy with the oxidation of oxo compounds with other oxidants.

3.9 Derivation of the Rate Law

Based on kinetic observations and the mechanism proposed, the following rate expression

can be derived applying the steady-state approximation.

The rate of the reaction is given by:

� d NBSac½ �dt

¼ k4 E½ � H2OþBr½ � ð5Þ

Applying the steady state approximation for [E]:

� d NBSac½ �dt

¼ k2k3k4 H3Oþ½ � S½ � H2OþBr½ �k�2k�3 H3O½ � þ k�4 k�2 þ k3ð Þ H2OþBr½ � ð6Þ

Table 5 Reaction constant values at different temperatures

Temperature K Reaction constanta q Correlation coefficient SD*

303 -1.41 ± 0.09 0.983 0.025

308 -1.32 ± 0.17 0.992 0.051

313 -1.20 ± 0.20 0.988 0.052

323 -0.98 ± 0.19 0.996 0.054

r values were taken from reported work [21, 22]

* Standard deviationa The values were obtained by correlating log10 (k2/k2

0) with rp for the reactions of oxidations S1–S7 withNBSac

ρ = -1.4473r = 0.9826

-1.20

-0.80

-0.40

0.00

0.40

0.80

-0.4 -0.2 0.0 0.2 0.4 0.6 0.8

Substituent constant,σp

log(

k2 /

k20)

1

2

3 4

5 6

7

Fig. 2 Hammett plot (at 303 K)for the oxidation of S by NBSac

248 J Solution Chem (2013) 42:239–250

123

Author's personal copy

At high concentration of [H3O?] = 0.5 mol�dm-3,

k�2k�3 H3Oþ½ �[ [ k4 k�2 þ k3ð Þ H2OþBr½ � ð7Þ

So Eq. 9 simplifies to the form:

� d NBSac½ �dt

¼ k2k3k4 H3Oþ½ � S½ � H2OþBr½ �k�2k�3 H3O½ �

¼ k2k3k4 S½ � H2OþBr½ �k�2k�3

ð8Þ

The value of [H2O?Br] can be obtained from Eq. 3 given in Scheme-1:

Ka ¼k�1

k1

¼ NBSac½ � H3Oþ½ �H2OþBr½ � saccharin½ � ð9Þ

Therefore,

H2OþBr½ � ¼ NBSac½ � H3Oþ½ �Ka saccharine½ � ð10Þ

Using the value of [H2O?Br] in Eq. 10:

� d NBSac½ �dt

¼ k2k3k4 S½ � NBSac½ �k�2k�3Ka saccharine½ � ð11Þ

Hence, at higher concentrations of mineral acid, the reaction is first order each with respect

to the oxoacid (S), [NBSac] and [H3O?].

The observed rate constant at high [H3O?] is:

kobs ¼k2k3k4

k�2k�3Ka

ð12Þ

4 Conclusion

The above study shows that oxidizing species is the hypobromous acidium ion, (H2O?Br),

which reacts with the enol form of 4-oxo acid in the rate determining step, giving the

product. This experimental protocol suggests that this reaction could find utility as a

regioselective route for the synthesis of benzoic acids. The order of reactivity among the

studied 4-oxoacids is: 4-methoxy [ 4-methyl [ 4-phenyl [ 4-H [ 4-Cl [ 4-Br [ 3-NO2.

References

1. Reddy, C.S., Manjari, P.S.: Kinetics and mechanism of acid bromate oxidation of substituted 4-oxo-acids. Indian J. Chem. 49A, 418–424 (2010)

2. Gupta, M.-K., Rekha, L., Sharma, P.-K., Sharma, K., Sharma, V.-K.: Oxidation of glycolic acid byN-bromosaccharin–A kinetic and mechanistic study in presence and absence of cationic surfactant.Asian J. Chem. 18, 1340–1346 (2006)

3. Mohamed Farook, N.A.: Kinetics of oxidation of 4-oxo acids by N-bromosuccinimide in aqueous aceticacid medium. J. Iranian Chem. Soc. 3, 378–386 (2006)

4. Mohamed Farook, N.-A.: Kinetics of oxidation of 4-oxo acids by N-chlorosaccharin in aqueous aceticacid. J. Solution Chem. 36, 345–356 (2007)

J Solution Chem (2013) 42:239–250 249

123

Author's personal copy

5. Mohamed Farook, N.-A., Seyed Dameem, G.-A.: Kinetics of oxidation of 3-benzoylpropionic acid byN-chlorobenzamide in aqueous acetic acid medium. J. Chem. 8, 561–564 (2011)

6. Freeda Gnana Rani, D., Maria Pushparaj, F.-J., Alphones, I., Rangappa, K.-S.: Kinetics and mechanismof oxidation of 4-oxoacids by hexacyanoferrate(III) catalysed by Os(VIII). Indian J. Chem. 41B,2153–2159 (2002)

7. Sikkandar, G.: Kinetics of oxidatative decarboxylation of b-benzoylpropionic acid by manganese(III)acetate. Asian J. Chem. 12, 1037–1040 (2000)

8. De Barry, E.B., Sanders, F.G.: The synthesis of some homologous naphthalenes. J. Chem. Soc. 434–437(1933)

9. Fieser, L.F., Seligman, A.M.: 10-Methyl- and 10,10-dimethyl-1,2-benzanthracene. J. Am. Chem. Soc. 60,170–176 (1938)

10. Vogel, A.I.: A Text Book of Practical Organic Chemistry. Longmans Green, London (1962)11. Russell, R.R., Van der Werf, C.A.: The malonic ester synthesis with styrene oxide and with butadiene

oxide. J. Am. Chem. Soc. 69, 11–13 (1947). doi:10.1021/ja01193a00312. Hey, D.H., Wilkinson, R.: The preparation of 2-phenylnapthalene from diphenyl. J. Chem. Soc. 1030

(1940)13. Chapman, N.B., Shorter, J.: Advances in linear free energy relationships. Plenum Press (1972)14. Mohamed Farook, N.-A., Dameem, S.: Kinetics of oxidation of 3-benzoylpropionic acid by N-bro-

moacetamide in aqueous acetic acid medium. J. Chem. 8, 479–482 (2011)15. Mohamed Farook, N.-A., Prabhkaran, R., Rahini, S., Senthil Kumar, R., Raja Mahendran, G., Gopala

Krishnan, G.: Kinetics of oxidation of some amino acids by N-chlorosaccharin in aqueous acetic acidmedium. J. Chem. 2, 127–131 (2004)

16. Vivekanandan, K., Nambi, K.: Kinetics and mechanistic study of amino acids by N-chloronicotinimidein acid medium. J. Indian Chem. Soc. 76, 198–202 (1999)

17. Mohamed Farook, N.-A., Alhaji, N.-M.-I.: Kinetics of oxidation of substituted c-ketoacid by N-chlo-rosaccharin in aqueous acetic acid medium. Int. J. Chem. Sci. 2, 76–80 (2004)

18. Mohamed Farook, N.-A., Seyed Dameem, G.-A., Murugesan, A., Kanagaraj, M.: Kinetics of oxidationof some essential amino acids by N-chlorosaccharin in aqueous acetic acid medium. J. Chem. 2,132–136 (2004)

19. Kothari, S., Agarwal, A., Banerji, K–.K.: Kinetics and mechanism of oxidation of primary alcohols byN-bromo-3-5-dinitrobenzamide. Indian J. Chem. 25A, 722–724 (1986)

20. Nath, M.-P., Banerji, K.-K.: Kinetics and mechanisms of the oxidation of methyl aryl ketones by acidpermanganate. Aust. J. Chem. 29, 1939–1945 (1976)

21. Vanangamudi, G., Srinivasan, S.: Kinetic studies on the oxidation of some para and meta-substitutedcinnamic acids by pyridinium bromochromate in the presence of oxalic acid (a co-oxidation study).J. Chem. 6, 920–927 (2009)

22. Gould, E.-S.: Mechanism and Structure in Organic Chemistry, pp. 181–185. Holt Riehart and Winston,New York (1964)

23. Richard Johnes, A.-Y.: Physical and Mechanistic Organic Chemistry. Cambridge University Press, NewYork (1984)

24. Ruff, F., Kucsman, A.: Mechanism of the oxidation of sulphides with sodium periodate. J. Chem. Soc.Perkin Trans. II, 683–688 (1985)

25. Cotton, F.-A., Wilkinson, G.: Advanced Inorganic Chemistry. John Wiley, 5th edn. (1988)26. Greenwood, N-.N., Earnshaw, A.: Chemistry of the Elements, p. 1222. Pergamon Press, Oxford (1984)27. Issacs, S.N.: Physical Organic Chemistry. Longman Scientific & Technical, New York (1987)28. Leffler, J.-F., Grunwald, E.: Rates and Equilibrium of Organic Reactions. Wiley, New York (1963)

250 J Solution Chem (2013) 42:239–250

123

Author's personal copy