8.0 Gugus Karbonil

8/7/2019 8.0 Gugus Karbonil

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SENYAWA GUGUS KARBONIL


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Aldehydes and Ketones


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The Carbonyl Group

In the remainder of the course, we will studythe physical and chemical properties of classesof compounds containing the carbonyl C=O group.

aldehydes and ketones (Chapter 16) carboxylic acids

acid halides, acid anhydrides, esters, amides


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The Carbonyl Group

The carbonyl group consists of one sigmabond formed by the overlap of sp2 hybridorbitals and one pi bond formed by the

overlap of parallel 2p orbitals pi bonding and pi antibonding MOs forformaldehyde


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Structure

The functional group of an aldehyde is acarbonyl group bonded to an H atom and acarbon atom.

The functional group of a ketone is a carbonyl

group bonded to two carbon atoms.

Propanone

(Acetone)

Ethanal

(Acetaldehyde)

Methanal

(Formaldehyde)

O O O

CH3 CHHCH CH3 CCH3


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Nomenclature

IUPAC names: The parent chain is the longest chain thatcontains the carbonyl group.

For an aldehyde, change the suffix from --ee

to --alal. For an unsaturated aldehyde, change the

infix from --anan-- to --enen--; the location ofthe suffix determines the numberingpattern.

For a cyclic molecule in which -CHO isbonded to the ring, add the suffix -carbaldehydecarbaldehyde.


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Nomenclature: Aldehydes

H

O

3-Meth ylb utanal 2-Propen al(Acrolein)

(2E)-3,7-Dimethyl-2,6-octadienal(Geranial)

1

2

3

4

5

6

7

8H

O

H

O

CHO HO CHO

Cycl p n t n -carbald hyde

trans- -Hydroxycyclo-

hexanecarbaldehyde

14

CHOC6 H5CHO

t ra s-3-Phe yl-2-prope alCi amal ehyde)Be zaldehyde

The IUPAC naming uses the common namesbenzaldehyde, cinnamaldehyde, formaldehydeand acetaldehyde.


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Nomenclature: Ketones

IUPAC names The parent alkane is the longest chain that

contains the carbonyl group.

For a ketone, change the suffix--ee to --oneone.

Number the chain to give C=O the smallernumber.

IUPAC uses the common names acetone,

acetophenone, and benzophenone.

Propanone(Acetone) Benzophenone 1-Phenyl-1-pentanoneAcetophenone

O O OO


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Order of PrecedenceFor compounds containing more than onefunctional group usually indicated by a suffix:


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Common Names For an aldehyde, the common name is derived

from the common name of the correspondingcarboxylic acid.

For a ketone, name the two alkyl or aryl groups

bonded to the carbonyl carbon and add theword ketone.

HCH

O

HCOH

O

CH3 CH

O

CH3 COH

O

Formaldehyde Formic acid Acetaldehyde Acetic acid

Ethyl isopropyl ketone Diethyl ketone Dicyclohexyl ketone

OO

O


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Physical Properties Oxygen is more electronegative than

carbon (3.5 vs 2.5) and, therefore, a C=Ogroup is polar.

C C H-H+ +

More importantcontributing

structure

C C C

Polarity ofa carbonyl

group

+C

Aldehydes and ketones are polar compounds andinteract in the pure state by dipole-dipole interaction.

They have higher boiling points and are moresoluble in water than nonpolar compounds of

comparable molecular weight.


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Reaction Themes

One of the most common reactionthemes of a carbonyl group is additionof a nucleophile to form a tetrahedralcarbonyl addition compound.

Tetrahedral carbonyladdition compound

+ C

R

R

CNu

RR

Nu


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Reaction Themes

A second common theme is reaction with aproton or other Lewis acid to form aresonance-stabilized cation.

Protonation increases the electron

deficiency of the carbonyl carbon and makesit more reactive toward nucleophiles.

B

C OR

R

H N

H B

C O

R

R

H

B C O

R

RH

CN

O H

RR

C O

R

RH

H B

+

fas ++

+

+slow

Tetredr r

+

+ +


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Reaction Themes

Often the addition to a carbonyl group willproduce a new stereocenter.

If none of the starting materials is chiral andthe reaction takes place in an achiral

environment, a racemic mixture will be formed.

N u- C ORR'

N u

OR'

R

N u

OR

R' + 3 O+

N u

OR

R'

N u

OR'

R

+

A racemic mixt reA new chiralcenteris created

Approach from

the bottom face

Approach from

the top face


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Addition of C NucleophilesAddition of carbon nucleophiles is one of themost important types of nucleophilic additionsto a C=O group.

A new carbon-carbon bond is formed in the

process. Four common types of carbon nucleophiles are:

RMgX RLi - CRC C - N

A Grig arreage t

An organolit iumreagent

An al ynean ion

Cyan i e ion


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Grignard Reagents

Given the difference in electronegativitybetween carbon and magnesium (2.5 - 1.3),the C-Mg bond is polar covalent, with C- andMg +.

A Grignard reagent behaves as acarbanion.

Carbanion:Carbanion: An anion in which carbon has anunshared pair of electrons and bears a

negative charge. A carbanion is a good nucleophile and adds

readily to the carbonyl group of aldehydesand ketones.


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Grignard Reagents

Addition of a Grignard reagent toformaldehyde followed by treatment withH3O

+ gives a 1r alcohol.

CH CH2 -MgBr

O

H-C-H

O-[MgBr]

+

CH CH2 -CH2HCl

H2 O

OH

CH CH2 -CH2 Mg2+

ether

1-Propanol(a1alcohol)

Formaldehyde

+

+

Amagnesiumalkoxide


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Grignard Reagents

Addition to any other RCHO gives a2r alcohol.

MgBr

-[MgBr]

+

ClH2 O

OH

Mg2+

+et er

Acetal e y e

(analdehyde)

+

A magne ium

al o i e

1-Cyclo e ylet anol

(a 2 alco ol;

(racemic)


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Grignard Reagents

Addition to a ketone gives a 3r

alcohol.

Ph-MgBrO

Ph

O-[MgBr]

+HCl

H2 O Ph

OH

Mg2+

+

Acetone(a ketone)

ether

+

Amagnesiumalkoxide

2-Phenyl-2-propanol(a 3 alcohol)

Phenyl-magnesiumbromide


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Grignard Reagents

Problem:Problem: 2-Phenyl-2-butanol can besynthesized by three different combinationsof a Grignard reagent and a ketone. Show eachcombination.

C-CH2 CH3

CH3

OH


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Organolithium Compounds

Organolithium compounds are generallymore reactive in C=O addition reactionsthan RMgX, and typically give higheryields.

LiO

O-

Li

HCl

H2 O

OH

3,3- imethyl-2-b ta o e

3,3- imethyl-2-phe yl-2-b ta ol(racemic)

+

Phe yl-

lithi m

A lithi m al o ide

(racemic)


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Salts of Terminal Alkynes

Addition of an alkyne anion followed bytreatment with H3O+ gives an -acetylenic alcohol.

C:-

N a+

HC

OC O-N a+HC

HCl

H2 O

C OHHC

1- t ynyl-cyclo e anol

A o iumal o i e

+

Cyclo e anoneSo ium

acetyli e


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Hydration of Terminal Alkynes

H2

H C CH H2 S 4 , H S 4

1. (sia)2 BH

2. H2 2 , Na H

H CCH3

H CH2

CH

AnE-h drox kon

AF-h drox deh de

E

F

E


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Addition of HCN

HCN adds to the C=O group of an aldehyde orketone to give a cyanohydrin.

Cyanohydrin:Cyanohydrin: A molecule containing an -OHgroup and a -CN group bonded to the same

carbon.

-H r r e itrile( cet l e e c ri )

+ HC N CH3

C-

C NCH3

CH

OH

H

O


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Addition of HCN Mechanism of cyanohydrin formation

Step 1: Nucleophilic addition of cyanide

-

+

H3 C

C

H3 C

O

O-

H3 C

H3

C

C

N

N

C

C

O-

H3

C

H3

C

C N

NH C C

C

H3

C

H3 C

O-H

N

C N++-

- Step 2: Proton transfer gives thecyanohydrin and regenerates cyanide ion

nucleophile.


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Cyanohydrins

Acid-catalyzed dehydration gives an alkene.

Prope e itrile

(Acrylo itrile)

+

acidcataly t

2- ydro ypropa e itrile

(Acetaldehyde cya ohydri )

CH3 CHC N NCH2 = CHC H2 O

OH

CHC

OH

N 2 H2Ni

OH

CHCH2 NH2

2-Am i o- -phe yletha ol(racem ic)

+

Be zaldehydecya ohydri

(racemic)

Catalytic reduction of the cyano group gives a 1ramine.


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Wittig Reaction

The Wittig reaction is a very versatilesynthetic method for the synthesis ofalkenes from aldehydes and ketones.

Tri enyl-o ine o i e

Met ylene-cyclo e ane

A o oniumyl i e

++-+

CH2 Ph3 P= OPh3 P-CH2

Cyclo e anone

O


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Phosphonium YlidesPhosphonium ylides are formed in two steps:

Step 1: Nucleophilic displacement of iodine bytriphenylphosphine.

Ph3P CH3-I Ph3P-CH3 I

Triphenylphosphine

++

2

Methyltriphenylphosphoniumiodide(analkyltriphenylphosphinesalt)

CH3CH2CH2CH2 Li + H-CH2 -PPh3 I

CH2 -PPh3CH3CH2CH2CH3 LiI

phosphoniumylide

Butane

Butyllithium

+++

++

Step 2: Treatment of the phosphonium salt witha very strong base, such as BuLi, NaH, or NaNH2


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Wittig Reaction Phosphonium ylides react with aldehydes and

ketones to give alkenes. Step 1: Nucleophilic addition of the ylide to

the electrophilic carbonyl carbon.CR2O

CH2Ph3 PCH2

-:O C

R2

Ph3 P

O CR2

Ph3 P CH2-+

An o a o etane

+

A etaine

CH2

O CR2

Ph 3 PPh 3 P= O R2 C= CH2

An al ene

+

Tri enyl o ine

o ide

- Step 2: Decomposition of the oxaphosphatane.


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Wittig ReactionExamples:Examples:

O Ph3

P + Ph3 P=O

2-Methyl-2-heptene

+

Acetone

HPh

O

Ph3P Ph Ph Ph3 P= O

Phenyl-

cet l ehy e

+ +

(Z)- -Phe l- -

b t e e

(87%)

(E)- -Phe l- -

b t e e

(1 %)

+

HPh

O

+ OEtPh3 P

O

PhOEt

O

Ph3 P= O

Ethyl (E)-4-phe yl-2-b te oate(only the E isomerisormed)

+

Phe yl-acetaldehyde


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Wittig Reaction Some Wittig reactions are Z selective, others

are E selective. Wittig reagents with an anion-stabilizing

group, such as a carbonyl group, adjacent tothe negative charge are generally E selective.

OEtPh3 P

O

OEtPh3 P

O

Resonan e cont ibutingst uctu es fo anylidestabili ed byanadjacent ca bonylg oup

Wittig reagents without an anion-stabilizinggroup are generally Z selective.


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Wittig Reaction

Horner-Emmons-Wadsworth modification Uses a phosphonoester.

Br-CH2 -C-OEt

O

(MeO)3PBr-CH2-C-R

O

(MeO) 2P-CH2-C-R

OO

(MeO)2P-CH2-C-OEt

OO

MeBr

MeBranE-bromoester

anE-bromoketone

+

+

AnE-phosphonoester

AnE-phosphonoketone

Trimethyl-phosphite


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Wittig Reaction

Phosphonoesters are prepared bysuccessive SN2 reactions.

( Me O) 3 P CH2 - C-OEO

Br

CH 3 -O- P-CH2 - C-OE

O

OMe

OMe

Br

( MeO ) 2 P-CH2 - C- OE

OO

MeBr

+

+

SN2

SN2

AnE-pho sph on oester


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Wittig Reaction Treatment of a phosphonoester with a strong

base followed by an aldehyde or ketone givesan alkene.

A particular value of using a phosphonoester-stabilized anion is that they are almostexclusively E selective.

( MeO) 2 P-C 2 -C- OEt

OO

O

H

OEt

O

MeO-P- O-

O

OMe

1. strongbas e

2 .O n ly th e Eiso m e r

is formed

+

D im ethy lpho sp hate

an ion


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Addition of H2O

Addition of water (hydration) to the carbonylgroup of an aldehyde or ketone gives a geminaldiol, commonly referred to a gem-diol. A gem-diol is also referred to as a hydrate.

C O + H2 O C

OH

OH

Carbonyl groupof an aldehyde

or ketone

A hydrate(a gem-diol)

acid orbase


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Addition of H2O

When formaldehyde is dissolved in water at 20rC,the carbonyl group is more than 99% hydrated.

H

H

O H2 O+

Formaldehyde

H

HOH

OH

Formaldehydehydrate(>99%)

O H2 O+

2,2-Propanediol

(0.1%)

Acetone(99.9%)

OH

OH

The equilibrium concentration of a hydratedketone is considerably smaller.


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Addition of Alcohols

Addition of one molecule of alcohol to theC=O group of an aldehyde or ketone givesa hemiacetal.

Hemiacetal:Hemiacetal: A molecule containing an -OHand an -OR or -OAr bonded to the samecarbon.

O H-O t OH

O t+

aci or

base

he iacetal


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Hemiacetals are only minor components of anequilibrium mixture, except where a five- orsix-membered ring can form.

(S)-4- y ro y entanal Cyclic emiacetal(majorformsresent at equilibrium)

OH

H

O

O OH O OH+

41 14 14

OH

OH

OH

HO

H

OOH

O

OH

HO

HO

H2 OH

OH

HO

H2 OH

O

OH

HO OH1

2

3

6

6

12

anomeric

carbon

FAnomerofD -glucose

cyclic hemiacetal

(pr domin t s

t quilibrium)

E Anomerof

D -glucose cyclic

hemiacetal

+

4

5

D-Glucose(op n h in form)

123

45

3

4 5

6


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At equilibrium, the b anomer of glucosepredominates because the -OH group on theanomeric carbon is equatorial.

OOH

HO

OH

HOO

OH

OH

HO

HO

CH2 OH

OHO

HO

HO

OH

O

OH

HO

HO

CH2 OH

OH

12

34 5

6

anomeric

car on

FAnomer

anomeric

car on

132

4 56

(eq atorial)

123

45

6

anomericcar on

Anomer

anomericcar on

13

2

4 56

(axial)

re rawasac air

conformation

re rawasac air

conformation

OH

OH


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Addition of Alcohols Formation of a hemiacetal is base catalyzed

Step 1: Proton transfer from HOR gives analkoxide.

B - H O B H - O+ +

fas tandreversible

H3 - - H3

O:O-

O:

H3 - - H3

O

+

Step 2: Attack of RO- on the carbonyl carbon.


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Step 3: Proton transfer from the alcohol toO- gives the hemiacetal and generates a newbase catalyst.

O:

CH3 -C-CH3

OR

H OR

OR

OH

CH3 -C-CH3-

OR++


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Formation of a hemiacetal is also acid catalyzed.Step 1: Proton transfer to the carbonyl oxygen.

O

CH3-C-CH3 H-A

O

CH3-C-CH3

H

A

-

+

+ +

fastandreversi le

O

CH3 -C-CH3

H

H-O- CH3 -C-CH3

O-H

O

H

++

+

Step 2: Attack of ROH on the carbonyl carbon.


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Step 3: Proton transfer from the oxonium ion toA- gives the hemiacetal and generates anew acid catalyst.

RH

CH3 -C-CH3

O

OH

OR

OH

CH3 -C-CH3 H-A

A-

+

+


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Hemiacetals react with alcohols toform acetals.

Acetal:Acetal: A molecule containing two -OR or -OAr groups bonded to the same carbon.

OH

OE

H OEH

+OE

OE

H2O

Ad iethyl acetal

+

Ahemiacetal

+


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Addition of AlcoholsStep 1: Proton transfer from HA givesoxonium ion.

HO

R-C-OCH3

H

H A

HHO

H

R-C-OCH3 A:-

+

Anoxoniumion

+

+

R-C OCH3

H

OHH

H

R-C OCH3 R-C

H

OCH3 H2 O+

A re onance- tabili cation

++

+

Step 2: Loss of water gives resonance-stabilized cation.


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Addition of AlcoholsStep 3: Reaction of the cation with methanol gives

the conjugate acid of the acetal.

CH3 -OH

H

R-C OCH3 R-C OCH3

H

OCH

3H

A rotonate acetal

++

+

A:-

R-C OCH3

H

OCH

3H OCH3

H

R-C-OCH3 H-A+(4)

Anacetal

+

+

Step 4: Proton transfer to A- gives the acetal and

generates a replacement acid catalyst.


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With ethylene glycol and other glycols, theproduct is a five-membered cyclic acetal.

+H+HO

OHOO

O

Cyclic acetal

+ H2 O


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Dean-Stark Trap


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Acetals as Protecting Groups

Suppose you want to run the Grignardreaction between these compounds.

5- ydroxy-5-phenylpentanal(racemic)

4- romobutanalenzaldehyde

??+

H

O

H

O

H

OH O

Br


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Acetals as Protecting Groups The Grignard reagent prepared from 4-

bromobutanal will self-destruct! To avoid this: First protect the -CHO group as an acetal.

HBr

A li et l

+H

+

H2H

H+

Br

Br1 . Mg ethe r

2 . C6 H CH

-Mg Br

+

Ahir l m gnesium lkoxide(producedasaracemicmixture)

Then do the Grignard reaction.

Hydrolysis (not shown) gives the target molecule.


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Acetals as Protecting Groups

Tetrahydropyranyl (THP) protecting group.

RCH 2 OH +

OO RCH2 O

Di ydro yran Atetra ydro yranylet er

H+

THPgro

The THP group is an acetal and,therefore, stable to neutral and basicsolutions, and to most oxidizing andreducing agents.

It is removed by acid-catalyzedhydrolysis.


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Addition of Nitrogen Nucleophiles

Ammonia, 1r aliphatic amines, and 1r aromaticamines react with the C=O group of aldehydesand ketones to give imines (Schiff bases).

CH3 CH H2 NH

+

CH3 C H =N H2 O+ +

Acet l e e Aniline Ani ine(a Schi base)

O

Ani ine(a Schi base)

AmmoniaC clohexanone

++ N H3 H2 OO N H

H+


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Formation of an imine occurs in two steps:Step 1: Carbonyl addition followed by protontransfer.

C

O

H2 N-R

H

H

C

O:-

N-R

OH

N-R

H

C+ +

O H

H

H H

C

OH

N-R N-R

H

C

OHH

OH

H

C N-R OH

H

HA i mi e

+

+

++

++ H2 O

Step 2: Loss of H2O and proton transfer


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A value of imines is that the carbon-nitrogendouble bond can be reduced to a carbon-nitrogen single bond.

+

Dicyclohexylamine

Cyclohexanone

(Animine)

Cyclohexylamine

O

N NH

-H2 O

H2 / N i

H+H 2N


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Rhodopsin (visual purple) is the imineformed in the eye between 11-cis-retinal

(vitamin A aldehyde) and the protein opsin.

1 1

1 2

11-cis-RetinalRhodopsin

(Visualpurple)

H2 N-op n

H N-op nH O

+


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Secondary amines react with the C=O group ofaldehydes and ketones to form enamines.

The mechanism of enamine formation involvesformation of a tetrahedral carbonyl additioncompound followed by its acid-catalyzeddehydration.

O H-NH

+

N H2

O

An enaminePi eri ine(aecondar amine)

++

C clohexanone


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The carbonyl groups of aldehydes and ketonesreact with hydrazine in a manner similar to their

reactions with 1r amines.

O H2 NNH2 NNH2 H2 O+

Hydrazine

+

A hydrazone

H2 N NHCNH2

H2 N OH

H2N NH

H2N NH NO2

O2 N

Reagen t,H2N-R

Hydro ylam ine O ime

Phenylhydrazine

2,4-D initrophenyl-hydrazine

S emicar azide

2,4-D initrop henylhydrazone

Semicar azone

NameofDeri ati e FormedNameofReagen t

Phenylhydrazone

O


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Acidity ofE-Hydrogens

Hydrogens alpha to a

carbonyl group are more

acidic than hydrogens ofalkanes, alkenes, and

alkynes but less acidic

than the hydroxyl

hydrogen of alcohols.

CH3

CH2 -H

CH3 CCH2 -H

CH2 = CH-H

CH3 CH2 - H

CH3 C C-H

TypeofBond pKa

16

20

25

44

51


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Acidity ofE-Hydrogens

E-Hydrogens are more acidic becausethe enolate anion is stabilized by:

1. Delocalization of its negative charge.

2. The electron-withdrawing inductive effectof the adjacent electronegative oxygen.

CH3 -C-CH2 -H

O

:A-

O

CH3 -C CH2

O-

CH3 -C= CH2 H-A

Re onance- ta ilize enolate anion

+ +


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Keto-Enol Tautomerism

Protonation of the enolate anion on oxygen gives

the enol form; protonation on carbon gives the keto

form.

Enolateanion

Enol formKeto form

-O

CH3 -C-CH2 CH3 -C=CH2

CH3 -C=CH2

H-A

CH3 -C-CH3 +A-

A- +

H-A OH

O-

O


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Acid-catalyzed equilibration of keto and enoltautomers occurs in two steps.

Step 1: Proton transfer to the carbonyl oxygen.

Step 2: Proton transfer to the base A-.

O

CH3 -C-CH3 H-A

O

CH3 -C-CH3

H

A-

+

+

+

Keto form

The conjugate aciofthe etone

fa t and

rever i le

O

CH3 -C-CH2 -H

H

:A-

OH

CH3 -C=CH2 H-A

nol form

+

+

low+


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Keto-enol

equilibria for

simple

aldehydes andketones lie far

toward the keto

form.

OH

O

O

CH 3 CH CH2 = CH

CH 3 CCH3

Keto form Enol form

% Enol at

Equilibrium

6 10-5

OH

CH3 C = C H2 6 10-7

O

O OH

OH

1 10-6

4 10-5


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For some molecules, the enol is the major form

present at equilibrium:

ForF-diketones, the enol is stabilized by conjugation of

the pi system of the carbon-carbon double bond and the

carbonyl group.

For acyclic F-diketones, the enol is further stabilized by

hydrogen bonding.

8.0 Gugus Karbonil

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