UNIT 17 ORGANIC COMPOUNDS CONTAINING OXYGEN ...

UNIT 17 ORGANIC COMPOUNDS CONTAINING OXYGEN AND NITROGEN ATOMS

Structure 17.1 Introd~~ction

Ob-jective 17.2 . Aldehydes and Ketones

Structure and Reactivity Reactions of Carbonyl Compounds Reaction with Water Reaction with Alcol~ol Wittig Reaction Aldol Condensation Cannizzaro Reaction Michael Addition

17.3 Carboxylic Acids Preparation of Carboxylic Acids From Alcohols From Aldehydes and Ketones From Alky l Benzene Reaction of Carbo~iylic acids Reaction at 0 - H Bond Acidity and Basicity of Carboxylic acid Reactions at the carbonyl carbon of Carboxylic Acid becarboxy lation IColbe's Electrolytic Method Substitution on Carbon Chain Hell-Volhard-Zeli~lsky Reaction

17.4 Amines Preparation ofAmines Reaction of Anlines Reaction of primary arnines with Carboxyl Compound Reaction of Secondary A~nines with Carbonyl Compounds

17.5 Summary 17.6 Terminal Questions

-

17.1 INTRODUCTION

In tliis unit we will study the compounds containing oxygen and nitrogen atoms. As you know nulneroils c o ~ n p o u ~ l d s are know11 which collie under this category, like alcoliols, plie~iols, aldehydes, ketones, acids, amides, a ~ n i n e s etc. It is quite impossible to take all these classes in just one unit. Therefore in tliis ~111it w e will clisci~ss only some important methods o f the preparatioli and reactions of aldehydes, ketones, carboxylic acids and amines. Here we will not discu'ss the reactiolis of . alcohols separately, but w e will discuss sollle o f them under different headings.

Objectives

After studying tliis nit, you should be able to :

describe tlie str~lcture of carbonyl group, and explain its polarity,

explain tlie relative reactivity C = 0 group,

discuss the different reactions of aldehydes and ketones, carboxylic acids an$ amines,

discuss the general mechanisms of different reactions of carbonyl compounds, carboxylic acid and amines.

17.2 ALDEHYDES AND KETONES

Organic Compounds containing Oxygen and

Nitrogen Atoms

Both aldehydes and ketones have a carbonyl group, ) C = 0 . An aldehyde has at

least one hydrogen atom attached to carbonyl carbon atom and the other may bk alkyl or aryl group. Only in case of methanal, two hydrogen atoms are attached to the carbonyl group. A ketone has two alkyl or aryl or both the groups attached to

, carbonyl carbon atom.

0 0 I I I I

H-C-R . R-C-R Aldehyde Ketone

Aliphatic aldehydes form a homologous series with the general formula RCHO and ketons with general formula RCOR'. Aldehydes and ketones have the same general formula CnH,"O. Since carbonyl group is present in both aldehydes and ketones, many of their properties are common. But in aldehyde, there is also a reactive hydrogen atom, which confers reducing properties upon the molecule.

You have already studied in the previous units (or will study in coming sections) several methods that can be used for the preparation of aldehyde and ketones under different headings. Therefore here we will not discuss the preparation of aldehyde and ketones separately.

17.2.1 Structure and Reactivity - A carbonyl group consists of a carbon doubly bonded to an oxygen atom. The carbonyl double bond is similar in many respects to the carbon-carbon double bond of an alkene. The carbonyl carbon atom is sp2 hybridised and an unhybridised p orbital is left on the carbon atom. Of the three o bonds formed by the carbonyl carbon atom, one is with the oxygen atom. AlSo the unhybridisedg orbital of the carbon atoms is used in forming the n-bond with oxygen atom. Thus the carbon- oxygen double bond of a carbonyl compound consists of the o bond and the n bond. Carbonyl compounds are planar and have bond angles of approximately 120" at the carbonyl carbon atom.

' H (1 s) - C(2sp2) bond formed by 0 bond overlap of 2p orbitals

of carbon and oxygen

6 bond *

Fig. 17.1 : Bonding in carbonyl compound.

Unlike carbon-carbon double bond, carbon-oxygen double bond is polar. This is because of the higher electronegativity of oxygen atom relative to carbon atom. The n electrons of the carbon-oxygen double bond are pulled towaids the oxygen atom and the bond is polarised. This electron imbalance in the n bond makes the carbon

Chemistry of Ci~rbon at0111 electron-deficient, as a result, the carbonyl group as a whole has an electroll Compounds withdrawing effect. Thus, the carbonyl group has t h o active centres, viz.,

The carbon atom carrying partial positiv'e charge, called electrophilic or cationic centre; This can be attacked by nucleophilic reagents.

The oxygen atom carrying partial negative charge, called nucleopl~ i 1 ic or an ionic centre. This can be attacked by electrophilic reagents.

As you know, ni~cleopliilicaddition reaction involves addition of a nucleopliile to the partially positively charged carbon atom of tlie carbonyl group. Tlie relative reactivities of carbonyl group in ni~cleophilic addition reactions may be attributed partly to the extent of polarisatiou of tlie carbonyl carbon. The rate determining step involves tlie attack of ~iucleopl~ile at the positively charged carbon atonl. Therefore, tlie reactivity of tlie carbonyl group depends up011 the magnitude of the positive cliarge on tlie carbonyl carbon atom. Thus, a greater positive charge means higher reactivity. Iftliis partial positive charge is dispersed throughoi~t the molecule, then tlie carbonyl co~npoi~~id is less reactive. Electroll withdrawing substituents at tlie carbonyl carbon, which increase its positive character, increase its reactivity towards nucleophilic addition reaction. Similarly, electron donating substituents decrease its positive character and hence decrease tlie reactivity towards nucleophilic add ition reaction.

You know that alkyl groups have electron releasing effect. Therefore, ketones, which contain two alkyl groups, are less reactive than aldehydes. Further cliloroetlianal, which contains tlie electron withdrawing chlorine atonl, is more reactive tlian etlianal. Similarly, nitroetlianal, where -NO, group has stronger electron withdrawing character than clilorine, is more reactive than cliloroethanal. Tlius tlie order of reactivity is :

0 0 0 0 I I I1 I1 I1

CH3CH2 t t C H < CH3 t C H < C l t C H 2 - C H < 0 2 N + C H 2 - C H I

Aromatic aldeliydes or ketones are less reactive than aliphatic aldehydes and ketones; this can be attributed to resonance interaction between the carbonyl group and the, aromatic ring. Tlie result of this interactio~i is a weakening of tlie positive charge on the carbonyl carbon atom through dispersal of tlie cliarge within the ring.

+

Steric factor also plays an important role in tlie relative reactivity ofaldehydes and ketones. A bulky group in tlie viciriity of the carbo~iyl carbon presents greater steric hindrance than tlie smaller hydrogen atom to tlie approaching ~iucleophi le.

With the above general ideas, it will be easier to study tlie reactions of aldehydes and ketones, wliicli we will take up in the next section.

SAQ 1

Considering the steric factor, arrange the following compounds in the order of their reactivity :

17.2.2 Reactions of Carbonyl Compounds

Theoretically, a carbonyl compound may be attacked either by a nucleophile or by an electrophile. Addition of the negative nucleophilic part of the reagent to the carbon atom or addition of the positive electrophilic part to the oxygen atom would Qve the same product ultimately.

The addition reactions of carbonyl compounds, therefore, can theoretically proceed by the following two mechanism.

Mechanism I : In the first mechanism, the proton adds to the carbonyl oxygen in the first step (slow step). This further increases the electrophilic nature of the carbonyl carbon atom. In the next step (fast step) the nucleophile attacks the carbocation.

t Fast 4. 1 <-OH + N U - - C -OH

I I Nu

Mechanism I1 : In the second type of mechanism, nucleophile attacks the polarised carbonyl carbon in the first step and forms an anionic intermediate.

This intermediate can undergo either protonation to form an alcohol, or it might expel oxygen as water to form a new double bond between carbon and the nucleophile.

NuH .L I

An acid catalysed reaction should follow mechanism I and the base catalysed mechanism IT.

,Organic Compounds mn&g Oxygen and

Nltrogen Atoms

Now let us study some important reactions of aldehydes or ketones.

Reaction with Water . . . Cheqistry of Carbon Compounds

Aldehydes and ketones react with water to form 1, ldiols, (geminaldiols) or hydmtes. Hydrogen atom becomes bonded to the negatively polarised carbonyl oxygen and hydroxyl group to the positively polarised carbon. This reaction is niversible and the hidrate formed is generally too unstable to be isolated.

OH I

-C=O+H20 -C-OH 1

Oeminal diol

The rate of reaction depends on the nature of the carbonyl group and is influenced by the combination of electronic and steric effects.

With increase of al kyl substitution on the carbonyl group, the reactivity of carbonyl compounds decreases, when treated with water under similar conditions. For example,

Methanal has no alkyl substituents to stabilise its carbonyl group and is converted almost compktely to the corresponding diol(99.%%). The carbonyl group of ethanal is stabilised by one alkyl substituent and the carbonyl of propanone by two. Ethanal gives 50% while propanone gives only 0.14% of diols.

Reactivity of carbonyl comwunds increases when electron-withdrawing p u p s are attached to the carbonyl carbon. For example, in contrast to the almost negligible hydration of propanone, the hexafluoropmpanone is completely hydrated.

loo %

Now let us consider the steric effw on the rate of reactions. Let us examine the abova reaction. Thepubon atom that bears two hydroxyl group is s# hybridised. Its substituents are kre.crowded thap they are in the starting aldehyde or ketone. -. . b:

x - b

Increased crowding can be better tolerated when the substituents are hydrogen than when they are alkyl groups. Diol of methanal is least crowded and hence formed in large amount. Diol of propanone on the other hand is more crowded, therefore, fonned in a lesser amount. Finally, the amount of diol of ethanal is formed between the above two limits.

As the electronic and steric effects combine hydration of aldehydes becomes mare favourable than that of ketones.

SAQ 2

Which of the following compougds do you predict would form stable hydrates and why? * .

Reaction with Alcohol

Like water, an alcohol can undergo addition reactions with carbonyl group in the presence of an acid catalyst. It is also a reversible reaction. In most cases, the equilibrium lies to the aldehyde or ketone side. Addition of one molecule of an . alcohol to an aldehyde or ketone give hemiacetal or hemiketal, respectively. On the other hand, addition of two molecules of alcohol to an aldehyde or a ketone, with the loss of water, gives acetal or ketal, respectively. Unlike hydrates, acetals and ketals are quite stable and can be isolated.

0 OR OR !I KOHIH. 1 ROHIII' 1 RCH+ RCH , L R C H + H , O

I I

&I I

OR Aldehyde Hemlaceta1 Aceial

(OH and OR on C) (hw OR'S on C)

Mechanism : The mechanism of formation of hemiacetal is analogous to that of the acid catalysed hydration of an aldehyde.


~itroien toms

Oxoniurn ion

In the mechanism for acetalfO&tian from the hemiacetal, protonation of miacetal takes place followed by dehydration to give a carbocation.

Chemistry ofcarbon Compounds :OH i ) ~ ,

I H+ 1 H,O +

-C-OR -' -C-OR \-' -C-OR+H20 I I I

The carbocation is stabilised by electron release from its oxygen substituent to yield oxonium ion.

Oxonium Ion .

Reaction of a second molecule of alcohol forms the protonated acetal which on deprotonation gives acetal.

' H Acetal

An acetal can be hydrolysed back into parent aldehyde and alcohol on treatment with aqueous mineral acid even at room temperature.

. is just the reverse of that for the formation of the acetal.

Now you will see how acetal formation and hydrolysis have been applied to synthetic organic chemistry as a means of carbonyl group protection. In some chemical reactions one functional group may interfere with intended reaction elsewhere in a complex molecule. We can often circumvent the problem in such cases by first protecting the interfering functional group, carrying out the des'ired reaction, and then removing the protecting group. For example, if we wish to oxidise propenal to 2,3-dihydroxypropanal, there is an interference of the carbonyl group, ' since both the double bond (C=C and C=O) would be oxidised. But after converting the carbonyl group to an acetal, we can oxidise a carbon-carbon double bond

; without oxidising the carbonyl group.

I I cannot bp I I II CH2 =CHCH CH2CH-CH

done directly

Since acetal formation is a reversifle reaction, it can be cleaved by hydrolysis to regenerate the carbonyl group. Thus, 2,3-di hydroxypropanal is obtained. Similarly take another example; conversion of ethyl 4-,oxopentanoate to 5-dydroxypentan-2-

one. We cannot reduce the ester group directly by LiAIH, as both the carbonyl OrganicCompounds groups would be reduced simultaneously. If we first protect the ketone by forming a containing Oxygen and ketal, however subseque~it ester reduction proceed nor~nally and acetal can be Nitrogen Atoms cleaved to get back ketone. _. _

0 0 0 I I I I I I

CH,CCH2CH2COCH2CH3 Ca'lnOt be >CH3CCH2CH2CH20H done d~rectly

I:th> l 4-o\opentanoate 5-Hydroxypentan-2-one

H' HOCH2CH20H I CH2-Ci12 CH2-CH2

I I 0 0 0

I I 0 0

I.+ \/ 1 1 LtAIH4 \/

CH3CCH2CH2COCH2CH3 >CH3CCH2CH2CH20H Ether

Reaction with ammonia derivatives

Aldehydes and ketones react with a number of ammonia derivatives such as hydroxy- lamine, hydrazine, cer~nicarbazide etc. in weak acidic medium. In general these derivatives [nay be represented as H2N4 and their reaction with aldehydes and ketones can represented as follows :

The reaction of aldehydes or ketones with ammonia derivatives is catalysed by acids. In acidic medium, the carbonyl oxygen gets protonated. Due to the presence of positive charge, the carbon of carbonyl group undergoes nucleophilic attack very easily.

It is necessary to adjust the reaction medium to right pH. This reaction involves nucleophilic attack by the basic nitrogen. Protonation ofcarbonyl oxygen makes it more susceptible to nucleophilic attack so, as far carbonyl group is concerned, the reaction is favoured by high acidity. But under highly acidic conditions the ammonia derivative can also undergo protenation to for H,N-G ion which is no longer a nucleophile. So as far ammonia derivative is concerned, the addition is favoured by low acidity. That is why is

Clkemistry of Carbon Co'mpollnds

In 1954. George Wittig reported a ~netliod of synthesising alkenes from carbonyl co~npounds.

these reactions the pH is carefully coatrolled. The optimum pH is 3.5 although the dxa~t coi~ditions also depend upon the basicity of the reagent.

SAQ 3

Consider the acid-catalysed reaction of ethanal with methanol. Write structural 'formulae for,s

a) the he~niacetal intermediate

.b) the cacbbcation intermediate

c) the acetal product.

--------------------------------------.----.-----*---------------------------------------------- .................................................................................................

Wittig Reaction

In this reaction, carbnyl oxygen is replaced by the group = CRR' (where R and R' are lrydrogen or alkyl group).

I ' Wittig reaction + .-+c=o 1 I -c =c-

There are'two,main steps in Wigig reaction. In the first step, the nucleophilic reqgent tripllenylphasphine reacts with only a primary or secondary alkyl halide to give aplrosphonium salt. The alkyhalide can also contain double bond or alkenyl group.

/

R ' R ' Ph,P: + RAHX - P ~ ~ P + - AHRX-

Triphenyl *lky' Phosphonium phosphine 'Iaiide salt

This plwqplionium salt further reacts with a strong base, which abstracts a weakly acidic a-hydrogen to give alkylidene triphenylphosphorane (a phosphorus ylide) commonly known as the Wittig reagent.

R' R' I I .

P ~ * ~ P + - C HR X' + C6H3Li -3 Ph3P = C R + C6H6 + LiX (ylide)

The rqsultingphosphorus ylide attacks the carbonyl carbon to form a dipolar interniediGecal led a betahe, which often undergoes elimination spontaneously to yield an alkene.

~ e c b a n i s m i~ebhanisrn of Wittig reaction.'has been'the subject of much .discussi&, btit ~~~~~~~e is now strongly in favour of the formation of an intermediatgbetajne. This betaine intermediate is unstable and rapidly fragments, prdbab~y by Way of a second inteimedia~4 containing a fauf-membered ring, to an alkene qlid triphenyl-phosphine oxide.

Betaine

'I'riphenyl Alkene pliosphinc

oxlde

The great value of Wittig reaction is that pure alkenes o f known structures can be prepared. The position at wliich the double bond is introduced is never in~dqubt. The

. double bond is formed betweed the carbonyl carbon o f the aldehyde or ketone and the negatively charged carbon oftlie ylide.

I

Aldol Condensation

In the presence o f a dilute base, such as aqueous NaOH, h o or more molecules o f an aldehyde or a ketone, containing an a-hydrogen may combine to form a P- hydroxyaldehyde or P-hydroxyketone, a compound containing alcoholic and aldehydic or ketonic groups, respectively. This reaction is called aldol condensation. The product results from addition o f one molecule of the carbonyl co~npounds to a second n~olecule in such ti way that the a-carbon'of the first is attached to the carbo~iyl carbon o f the second. For example, consider reaction between the two ethanal molecules. rf

H ' H OH H 0 I I I I II

CH3C = O + CH3C = O ---+ CH3CHCH2 C =O di'HC1 bCH3CH = CHCH Elhi~nill Ethanal 3-Hydroxybutand Z-Elutenal

'The condensation product loses a water molecule to give unsaturated aldehyde or ketone (conjugated enones). For an aldol condensation aldehyde or ketone must contain an a-hydrogen. If the aldehyde or ketone does not contain an u-hydrogen, a simple aldol condensation cannot take place.

AI-CHO

.. di'ute.h ,NO reaction

* ArCOAr ArCOCR,

C'OII~OU~U~S' ui~ltuinil) no tr-,iyjrDgen

Mlcbambm : Aldol condensation is s t yo step process. I n fhe.fwst step. the .dm:' abstracts a protocl. f m a-c& sf-the d&hyde fa form "ehdate' ion.


Nitrogen Atoms

cnolatc ion

In tlie next step, the enolate ion attacks the carbonyl carbon of another aldehyde molecule to form an alkoxide ion, which abstracts a proton from water to yik~d the

Crossed aldol condensation : As ~lientioned above, an aldeliyde without a- hydrogen does not undergo aldol condensation. However, if such an aldeliyde is mixed with an aldehyde that does have an a-hydrogen, aldol condensation can occul-. Aldol condensation between the two different carbonyl compounds is called crossed aldol condensation which is oftwo types :

c? 0

CHI CH + CH, !H- u- -

In type one, both the carbonyl compounds have a-hydrogen atoms. In these cases a mixture of four possible products may be formed. Because of the formation of such a mixture, h i s type of reaction is corn~nercially of no use.

In type two, one of the carbonyl compound does not have an a-hydrogen, e.g.,

0 0 I I1

CHI CH - CH2 CH

13znzaldchyde IJthanol (No a-hydrogen)

H 0 I I I OH 0

2 CH,CHCH~CH +OH

Methyl ketones can be used successfully in crossed aldol condensation with aldehydes that contain no a-hydrogen.

There are a large number of reactions that are closely related to aldol condensation. At first glance each of these reactions may seem quite different from others. But a close examination of these reactions shows; that like aldol condensation, each of these involves an attack by a carbanion formed from one molecule on the carbonyl group of another:

Michael Addition

Nucleophiles and carbanions generally do not add to isolated carbon-carbon double bonds. However, when an electron withdrawing group like C=O is present in co~ijugation with a carbon-carbon double bond, carbanions add to the conjugated system at the site of electron deficiency, i.e., the P-carbon atom. Such addition reactions are known as Mkhael addition. In other words, addition of active methylene compounds to carbon-carbon double bond of a , P-unsaturated carbonyl co~npounds in the presence of basic catalyst is known as Michael addition. The following exa~nples are illustrative :

Mechanism : We take here the condensation of ethyl ~nalonate with propenal as an example. In the first step of Michael reaction, the base removes an a-hydrogen atom from ethyl malonate to generate the corresponding carbanion (enolate anion).

6 ~ 2 ~ 5 - CH(COOC~H, )~ + C2H,0H CH2(COOC2H5)2 - Enolate ion

In the next step, the carbanion attacks at the P-carbon atom of propenal to give the more stable enolate which abstracts a proto11 from the solvent to yield the final product.

HC-CH =CH, + CH(COOC,H,)~ +HC=CH - CH2 L/ I

CH(COOC2H5)2

In general the colnpound from which carbanion is generated must have an acidic hydrogen, so that the carbanion call be obtained easily. Such a compound is usually one that contain a -CH,- or >CH- group flanked by two electron withdrawing . groups on either side.

Michael addition is a general reaction and is not limited to conjugated carbonyl compounds. Conjugated esters, n itriles, amides and nitro compounds can also undergo Michael addition. For example :

N = CCH = CH2 +CH2(COOC2H5)2 -N I CCH2CH2CH(COOC2HS)2

SAQ 4

How can the following colnpounds be prepared using Michael reaction?

OrganicCompounds containing Oxygen and

Nitrogen Atoms

Chemistry of Carbon 0 0 Compounds II 11

b' CH, CCH2CH2CH2 CCH,

17.3 CARBOXYLIC ACIDS *

All the organic acids contain carboxyl group as their functional group, attached to al kyl group (RCOOH) or an aryl group (ArCOOH) except formic acid (HCOOH) : Those which contain one carboxyl group in each molecule are called the monocarboxylic acids. These compounds form a homologous series of general formula C,H,,+,.COOH. The lowest members are formic acid (HCOOH) and acetic acid (CH,COOH).

17.3.1 Preparation of Carboxylic Acid

There am number of methods for the preparation of carboxylic acids. But in this unit we will discuss only few important methods for the preparation of carboxylic acids.

From Alkenes : Oxidation of alkene (in which at least one carbon atom of the carbon-carbon double bond contains a hydrogen atom) with permanganate gives an aldehyde which is further oxidised to carboxylic acid.

Since th& carboxylic acids are formed as salt, the acidification (using mineral acids) is needed to isolate the product as prboxylic acid.

In the oxidation of te~mina-1 alkene, tbe terminal (2% group is completely oxidised to carbon dioxide arid water.

From Alcohols

An impolrtant reaction of alcohols is their oxidation to yield carbonyl compounds. Alcohols with a-hydrogen atom (s) undergo oxidation readily. Oxidation of an alcohol involves the loss of one or more a-hydrogens. The nature of the product formed depends upon the number of a-hydrogens present in the alcohol, that is, whether the atcohol is primary, secondary or tertiary. Primary alcohols first give aldehydes by losing two hydrogens. The aldehyde formed tends to undergo further oxidation to give a carboxylic acid. In aqueous solution, aldehydes are &ore easily oxidised than alcohols. Therefore, oxidation usually continues until the carboxylic

J acid is formed. , <

I I I RCOH lo' , R C - 0 [01 , R C = O

I H

Alcohol aldehyde carboxylic acid

, Oxidisi~ig agents co~nmo~ily used for the oxidation o f primary alcohols to carboxylic

I I. acids are, chromium trioxide (CrO,) in aqueous sulphuric acid (Jone's reagent),

, potassiuni permariganate or potassium dichromate. For example,

1 I CH3(CH2) CH20H Jone's reagent ,cH,(cH~), 6 =O

I-1)ccrnol X h n o i c acid

If tlie reaction mixture is kept in between the boiling points o f the aldehyde and the - alcohol, tlie aldehyde distils offas soon as it is formecl and further oxidation is avoided. Yield o f aldehydes by this method is usually low.

4 From Aldehydes and Ketones

As~mentioned above, aldehydes are very readily oxidised to acid, Aldehydes can be oxidised by the same reagents that oxidise alcohols. Permanganate or dichromate salts are the most commoli oxidising agents.

Aldehydes are so easy to oxidise that even a mild reagent like silver diammonia complex (Tollens' reagent) can be used for oxidation. For example:

H

Tollens' reagent oxidises aldehydes in high yield without attacking carbon-carbon double bond o i othersfunctio~;al groups.

I RCH =CHC=O Tollen's . . ,RCH=CHCOOH

u,P-iniseturatod reFgent . a,$-unsaturated' ntdtliyde acid

In this reactibn, a shining coat o f silvbr metal gets deposited on the glass suetace o f tlie reactib~i vessel. So it can be used as a test to detect the presence o f aldehydes. 'Mirrors are also prepared commercial l y'in this.way.

' Ketones.are not easily oxidised. Oxidation o f ketones occurs only when forced by - tlie use o f strong oxidising agents and perhaps involves the cleavage o f the molecule

through tlie corresponding enol to produce an acid.


Nitrogen Atoms

The reaction is only useful for sym~netrical ketones.

Chemistry of Carbon Compounds

By carbonation of Grignard Reagents

Carboxylic acids are obtained is good yield by carbonation ofGrignard reagents. In this Grignard reagents add on to carbon dioxides which on hydrolysis give carboxylic acid with one more carbon than those present in Grignard reagent. Grignard reagents are obtained from corresponding alkyl halides. So this makes a good method for obtaining carboxylic acids from alkyl halides and is used for ascending tile series in conversions.

From Alkyl Benzene :

Although benzene and alkanes are quite unreactive towards the usual oxidising agents (KMnO,, K2Cr20, etc.), the benzene ring renders an aliphatic side chain quite susceptible to oxidation. The side chain, irrespective df its length, is oxidised to a carboxylic group (XOOH). Tertiary alkyl substituted aromatic compound do not follow this reaction. For example toluene and propylebenzene (I -methyl ethyl) benzene are oxidised to benzoic acid in higher yields. p-Methyltoluene on oxidation gives tetraphthalic (benzene-1 ,4-dicarboxylic) acid but tertiary butylbenzene is not affected.

benzoic acid

' (1 -111ethylethy I) benzene

C(CH,), .

[OI No reaction

tert butylbenzene

The number and the position oftlle carboxylic groups produced indicate the number and positions of alkyl chain attached to the aromatic ring.

CH, HOOC J3c00H p-methyl toluene

This reaction is useful for two purposes : (1) synthesis of carboxylic acids (2) identification ofthe position ofthe side chain

SAQ 5

~ i v e the ofthe following :


Nitrogen Atoms

b) CH3CH2CH0 Tollen's

reagent

CH3CH20H Jone's C) .........................................

reagent

17.3.2 Reactions of carboxylic acids

0 . II As you know, the carboxylic acid has a functional group - C-OH. Most of the

reactions of carboxylic acid belong to any one of the following four categories.

0

.a. Reactions at 0 - H bond II

R-C-0-H

b. Reaction at carbonyl carbon

c. Decarboxylation

d. Substitution on carbon chain -CH,CH,-COOH

\ In this unit we will discuss some important reactions of carboxylic acids.

a) Reaction at 0-H Bond

Acidity and Basicity of Carboxylic acid

_ Carboxylic acids are very week acids. The acidity of carboxylic acid is due to polar nature of carbony1 group. Since it is an acid, it has a tendency of forming salt on treatment with base such as NaOH e.g.

0 0 II II - +

R - C-OH + NaOH---+R - C-ONa+ H 2 0 Salt

'This salt forming property of carboxylic acid helps us to separate water insoluble carboxylic acid from water insoluble nonacidic substances. To do so, first convert the acid into salt form, which is soluble in water, then separate the two and you can get the carboxylic acid by acidification of salt with mineral acids.

Although its name indicates that it is an acid, but it also acts as a weak base. Carbonyl oxygen contains two lone pair which gets protonated, which is characteristic of any base. -

Chemistry of Carbon colnpounds

This piotonation or basicity plays an important tole in the reactions of carboxylic acids.

Hydroxyl oxygen can also accepts proton ftom mineral acids but this possibility is very less. This type of ptotonation plays a tole in esterification when alkyl group is bulky and, in addition, has electron donating properties, thereby fhvouring ionisation to give an acyl carbocation. e.g.

b) Reactions at the carbonyl carbon of Carboxylic Acid

Most ofthe reactions of carboxylic acids involve addition of nucleophile to the partially positively charged carbon atom of the carbony1 group. These reactions generdly are catalyzed by acids because addition of H+ or formation of hydrogen bond to the carbonyl oxygen makes the carbonyl carbon more vulnerable to nucleophile attack. e.g.

C I1 < I1 I

R-C-OH + H+ R-C-OH = b R-C-OH A,

. . f i ~ + 0: E?" OH I1 I

R-C-OH + H+ R-C-OH R-C-OH I

Nu

This is a substitution reaction. Some important examples of this type of reaction are formation of esters, acyl chloride formation, amide formation etc. Let us take the - case of esterification.

Esterification :- Reaction of alcohol with carboxylic acid in the presence of acid give ester. Thi9 reaction is known as Fischer ester1j7cation.

Since this is a reversible reaction, the yield of ester is very poor. The yield can , increase by using one of the reactants in excess (Le Chatelier's principle).

The yield can also be increased by removing water, a product responsible for reversibility of the reaction,

Mechanism : In the first step, tIie carboxylic acid gets protonakd.

The second and the key step of the reaction is the attack of alcohol at carbonyl carbon which gives tetrahedral intermediate.

OH OH - . I

H - Q - ~ e R - L - ~ H R R - C - O R

AH AH Tetrahedral Intermediate

, In the third step, the tetrahedral intermediate eliminates water and yield the required product i.e. ester.

OH + BH +OH 0 I +H -H,O II -Hi H

R-C-OR R-C-OR .; R - C - O R R-C-OR I I +H@ +H ester

OH (;OH2

Reduction of Carboxylic Acids :

Generally carboxylic acids do not react towards most of the reducing agents. But LiAlH, reduces the acid to primary alcohol. e.g.

R - COOH . b ,RCH20H 2.H20, H+

Kolbets Electrolytic Method

When a concentrated solution of sodium or potassium salt of a carboxylic acid is . electrolysed, an alkane is formed. The method is known as Kolbe's electrolytic method. In this method, carboxylate radicals are formed by transfer of electron h n carboxylate ion. Decarboxylation may take place simultaneously or subsequent to, the formation of carboxylate radicals, leading to alkyLradicals, which combines to give alkane.

1

RCOOK+ R'COOK + H20--+RR1+2C02+ H2 + 2KOH at anode at cathode

The following mechanistic pathway illustrates this method :

Isotope spbstitution studies have proved that the oxygen of the water comes from acid and, alcohol oxygen is incorporated into the ester.

II I\ CH,C-6 -' PCH,C-6

acetoxy radical

Chemistry of Carbon compounds.

0 II

CH, C- d----td~,+ C O ~

In case a mixture of salts of two carboxylic acids is electrolysed, a mixtureof alkanes is formed:

R'R'

R'COOK + RUCOOK - i ( '~" + C02 + HI + KOH + R"R"

This reaction has limited synthetic application, because of the formation of many side products as a result of other reasons of the free radicals formed.

d) Substitution on Carbon chain

Hell - volhard - zelinsky (HVZ) reactions

This reactions involves the halogenation at a-carbon of aliphatic acid. The reaction involves the treatment of carboxylic acids with C1, or Br, is presence of red phosphorus. If the number of a-hydrogens are more then the reaction does not stop after monohalogenation. It continues till all the a-hydrogens are replaced by chlorine or bromine. For example

CH3CH,COOH Bb'P ) CH, CHCOOH Br2'P ) CH3CBr2COOH

8 r

The function of the phosphorus is to convert a little of acid into acid halide. These are more reactive than the parent acid k d undergo a-halogenation easily. Such as in case of propanoic acid the reaction proceeds as follows

0 I1

3CH3CH,COOH + PBr, - CH, C H,CBr + H3P03

. 1.

The Hell-Volhard-Zelinsky reaction is an important reaction as a number of ' derivatives of carboxylic acid can be obtained from halo acids. The halogen of an a- halo acid is replaced readily by nucleopbilic reagents such as,

2. l1+, H 2 0 I OH

2-hydroxy acid

ji) R - C HCOOH + 2NH3 --+R -CHCOOH I I

N H ~ 2-a mino acid

iii) R - C HCOOH + KCN '. +R -CHCOOH "O ,R C HCOOH \ ~ M + , H ~ O I b

X CN 2-Cyano-

COOH Dicarboxylic acid

carboxyl~c a c ~ d

SAQ 6

Give the mechanism Hell-Volhard-Zelinsky reaction.

17.4 AMINES

Aliphatic amines are the derivatives of ammonia formed by replacing one or more hydrogen by alkyl group. Amines are classified as primary, secondary or tertiary, according to the number of alkyl group attached to the nitrogen atom. It is unlike alcohols or alkyl halides, where classification is based on the number of alkyl groups .attached to halogen or hydroxyl group bearing carbon atom.

Organic Cornpol~nds containing Oxygen and

Nitrogen Atonls

Pnmary amine ' 7

Sccoilllaty 'lkriinry ami~lcs arniocs

Aniines form a honiologous series with general formula C,H,,+IN <; Methyl amine

(CH,NH,) is the lowest member of amine. Since alkyl group is relatively inert it is amino group which determines the reactions.

When one of the substituent attached to the nitrogen atom is an aryl group the amine is called aryl amine.

17.4.1 Preparation of Amines

There are number of methods for the preparation of amines. Some important methods for their preparation are given below:

~ l k ~ i a t i o n of Ammonia : Reaction of alkyl halide with ammonia it gives amine. Ammonia is a very good nucleophile. Therefore this reaction follows S,2 mechanism. Alkylation of ammonia, primary arnines,and secondary amines gives primary. secondary and tertiary amines respectively.

Chemistry of Carbon Con~poutlds

Alkyl azidc is very explosive so it should bc kept in solution only.

Sicg~~~und Gabriel (J 851-1 924) b. Bcrlin; Ph. D-University of Berlh~ (1874).

f

- OH i R2NH RNH2 + R - X + K 2 N H 2 X . Primary ammne Secondary amine

+ - R2NH +R-x'-----+R~NHX----+R~-N

Secondary amine

Linlitation of this reaction is that it does not stop after single alkylation and mixture of products are formed i.e.

R - X + N H 3 j R - N l 1 2 + R 2 N H + R 3 -N 45% 43% Trace

Multiple alkylation can be minimized by using a large excess of anmlonia. Even then this method is not good enough to get good yield and better methods of preparation are needed. In order to overcome thc limitations of this method two other methods are oftcn used i.e. azide synthesis and Gabriel synthesis. L

Azide Synthesis : It is a very good method for preparing primary amine froin alkylhalide. First convert the alkyl halid to alkyl azide by the following reaction.

- + - + -

R - X + N = N = N - - - - R - - N = N = N H21Pd-C + R -NH2 +.N2 Azide ion Alkyl azide

Since alkyl azide is a good nucleophile over alkylation can not take place. The alkyl azide formed can be reducedto primary amine by catalytic hydrogenation over palladium or by LiAlH,.

Gobriel Synthesis : This is also a good method for preparing primary amine from alkyl halide. Pure primary amines can be prepared conveniently if the nitrogen atom is protected so that alkylation can take place only once, i.e., multiple alkylation can be avoided. Such a protected nitrogen is present In phthalimide. phthalimide is quite acidic, due to two carbonyl groups. It can be converted to potassium phthalimide on treatment with base.

0

I'hthal~nl~dt:

ill11011

phthalimide anion is a strong nucleophile and it reacts with an alkyl hal~de by S,2 mechanism to give N-alkyl phthalimide. Basic hydrolys~s of N-alkyl phthalimide yields prinlary amine.

, This reaction is useful forprimary and unbranched secondary alkylhalide.

Reduction of Imine :

Organic Compounds' cotitaining Osygcn and

Nitrogen Atoms

Reduction of imine gives amine The carbon nitrogen double bond of imine can be reduced to primary or secondary amines by simple catalytic hydrogenation.

5 R2C = NH H 2 / P t , R ,CHNH2

lmine primary amine

H /Pt R2C = N R ' A - 4 R2CHNHR1 Imine secondary aminc

Hofmann Rearrangement of Amides

Primary amide react with bromine or chlorine in basic solution to give arnine. This reaction is known as Hofmann rearrangement.

In this reaction one carbon atom of the amide is lost and alkyl group of amide gets attached to nitrogen of the amine. An example of this reaction is :

Mechanism : In the first step 0 H abstract proton from amide and amidate

intermediate is formed. The electron-withdrawing nature of acyl group of the amide , make the amido hydrogen much more acidic than amine.

i -- o n 0 I1 - X-X I I

K - C - N H , + OH-K-C-NFI ,R -C-NHX i Amidate N-haloainidc

In the next step halogenation take place and N-haloamide is formed, which react - with hydroxide ion to give N-haloamidate. This anion spontaneously rearrange with

loss of bromide ion to give an isocynate. In the rearrangement the alkyl group migrate from carbon to electron-deficient nitrogen. The isocynate formed reaction with water to give carbamic acids which spontaniously loses CO, to yield the amine.

Cllenlistry of Carbon Co~npounds I I

R - N = C = O + H 2 0 - - - + ~ - N H ' - C - O ~ ---+ R - N H 2 + C 0 2 Carbanic acid

Curtius Rearrangement :

Curtius rearrangement is similar to Hofmann rearrangement. In this reaction acyl halide react with sodium azide (NaN,) to give amine.

., i! llc- A A

NaNi-N-a=N: ---- .-N = C = O R -. (1 -- X -- Acyl halide -NaC:l Acyl azidc - N 2

There is an other similar type of rearrangement called Schmidt rearrangement. In this case the starting material is a carboxylic acid. Reaction of carboxylic acid with sodium azide in the presence of catalyst gives an alkhnoyl azide which after similar rearrangement gives amine.

R - COOH 1. N ~ N ~ , H + ,C6H6 >R-NH, 2. NaOH, H 2 0

SAQ 7

Give the mechanism of Schmidt rearrangement?

17.4.2 Reaction of Amines

We have discussed some reactions of arnines earlier in this unit. Here we will discuss some other important reactions of amines and their mechanism.

Oxidation of Amines : All types of amines are easily oxidized. Oxidation of primary and secondary amines do not give useful product but gives some complex mixtures. Oxidation of tertiary arninhs'm presence of hydrogen peroxide or peroxy acids give corresponding amine oxide.

+ - H202 or RCOOOH R3 N-

Tertiary amine Oxide

Tertiary arnine oxide on heating undergoes elimination to give dialkylhydroxylalnine and alkene. This type of elimination is known as cope elimination.

I I R - CH2CH2 - N +- CH3 lsOOc

) RCH = CH, + : N - CH3 I I

CH3 CH3

I Mechanism :

OH I

CII, - R - - C F I = C I I + N - - C H , I

CH,


Nitrogen Atoms '

Reaction with aldehydes and Ketones :

Reactions of amine with carbonyl compounds can be classified into the following two categories.

Reaction of primary amines with carbonyl compounds

Reaction of secondary amines with carbonyl compounds

' Reaction of primary amines with Carbonyl Compounds '

In the presence of an acid catalyst a primary amine adds to carbonyl compounds to I give an imine (compounds with C=N group). In this reaction the initial addition of

H+ is followed by an attack of H,NG. Subsequent dehydration forms a carbon- nitrogen double bond. The net result is substitution of oxygen by another group. Primary amines react with aldehydes or ketones to form corresponding N-alkyl or N-aryl substituted imines.

The unsubstituted imines, obtained by reaction of carbonyl compounds with NH,, are very unstable; while substituted imines, formed form RNH,, are more stable. Substituted imines are also called Schiff bases.

- Mechanism : Formation of a Schiff base is a two step reaction. In the first- step, the nucleophile (RNH,) adds to the partially positive carbonyl carbon. This step is followed by the loss of a proton from nitrogen k d the gain of proton by oxygen to give an intermediate called carbinolarnine;

I 0'': CH3NH2 d

I 0 TcH3 - H 2 0 , a CH = NCH,

Chemistry of Carbon Compounds D 0- OF1

R\ I C = O + RN112 ,L R C R RCR

R'\ - . . I I RNI-I RNI I

I C:nrbinoIamine

In the second step, the carbinolamine eliminates water and gives the imine,

OH I -H+

p H 2 1 - H 2 0 + '4 R2C- NHR' KL R 2 C- N HR' \-' R2C =NHR - R2C = NR'

t Both the addition and the elimination steps of the reaction are sensitive to acid catalysis. Hence careful control of pH is essential. The rate of reaction is increased by an increase in acidity but beyond a certain limit, the rate decreases with further increase of acidity.

This is because, these reactions are catalysed by acids, thus, protonation of the carbonyl compound as well as the reagent can take place.

The first step of the reaction is the addition of the amine to the carbonyl group. In strongly acid medium, the concentration of the amine becomes very low because we get GNH, in excess amounts. In other words, the rate of the first step decreases

with increase in acidity. As G&H, is a poor nucleophile than GNH,.

The second step involves the elimination of water. In acidic medium concentration of the protonated carbinolamine increases with the increasing acid concentration.

(Remember - 0 H, is a better leaving group than -OH).

An increase in acidity causes step 2 to go faster, but step 1 to go slower, while decreasing acidity causes step 1 to go faster but step 2 to go slower. Between these two extremes is the optimum pH (-34), at which the rate of the over all reaction is greatest. At this pH, some of the amine is protonated, but some are free to initiate the nucleophilic addition. At this pH, too, enough acid is present so that elimination of water in the second step can proceed at a reasonable rate.

Reaction of Secondary Amines with Carbonyl compounds

Aldehydes and ketones with an a-hydrogen react with secondary amines to yield iminium ions, which undergo further reaction to give enamines (vinylamines).

L,

I I - 0 1 I=+ I [rnrn~n~urn )on I * + CH, C H + (CH,),NH ,2 CH2 -CH = N ( C H 3 ) ~ CH2 =CHN(CH3)2 D~cthylamine T,nilm~ne

Since there is no proton remaining on nitrogen of this intermediate iminium ion, the imine formation cannot occur. Instead an enamine is formed by loss of a proton from a carbon atom p to the nitrogen-This results in the formation of a double bond between a and p carbon atoms.

'Like imine formation, enamine formation is reversible, and enamines can be converted back to the corresponding carbonyl compounds.

You must have noticed from the above that the mechanism of enamine formation is similar to the mechanism of imine formation. Reaction of aldehydes or ketones with primary and secondary amine may appear different but they are quite similar. Both are typical examples of nucleophilic addition reaction in which the initially formed tetrahedral intermediate is not stable. Instead, the carbonyl oxygen is eliminated and a new carbon-nucleophile double bond is formed.

Coupling Reaction

Aromatic diazonium salts react with highly activated aromatic compounds like phenols to give azo compounds. Azo compounds are coloured and many of these are used as dyes and indicators. The reaction with phenols take place in slightly alkaline medium. The reaction is also used for the detection of aromatic primary amines and is called as dye test.

The reaction with diazonium salts is basically electrophilic substitution reaction. The positiyely charged nitrogen of diazonium group acts as an electrophile and the reaction proceeds as following.

I

SAQ 8

Write the mechanism of the following reaction.

H,C \ H,C\ / ( 3 3

/ CHCHO + CH3NHPh ----+

I1,C I-1,C / C=CHN \ ~ h


Nitrogen Atoms

Chemistry of Carbon Comp0un.d~

, r

In this unit you have studied that

The cabonylcutmn of sp2 hybridized and for three o bonds. The unhybridizedp orbital for one 7c bond with oxygen atom.

Carbonyl compounds can be classified in two groups : i.e. i) aldehyde and ketones ii) carboxylic acid and its derivatives.

Due to higher electronegativity difference between carbon and oxygen, the carbon-oxygen double bond is polarised, and hence it cin undergo electrophilic attack at oxygen or nucleophilic attack at carbon.

Electron withdrawing substituents increase the reactivity while electron donating substituents decrease the reactivity of carbonyl con~pounds towards nucleophilic addition reactions.

The importance and mechanism of Wittig reaction aldol condensation, Parkin condensation, Claisen condensation, Cannizzaro reaction and Michael addition reaction.

Carboxylic acid can be prepared by oxidation of alkenes, alcohols ahd aldehydes.

Carboxylic.acids act as an acid as well as a base.

Using appropriate reagents carboxylic acids can be converted into esters, 2- halo acids, alcohols and alkanes.

Amines can be prepared by alkylation of ammonia, by reduction nf imines and by Hofmann and curtius rearrangements of amides.

UNIT 17 ORGANIC COMPOUNDS CONTAINING OXYGEN ...

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