Car Banion Si

8/13/2019 Car Banion Si

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Carbanions

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C:

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The conjugate bases of weak acids,

strong bases, excellent

nucleophiles.


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1. Alpha-halogenation of ketones

CC

H

O

+ X2

OH-or H+

CC

X

O

+ HX

X2= Cl2, Br2, I2

-haloketone

H3C C CH3

O

+ Br2, NaOH H3C C CH2Br

O

+ NaBr

acetone -bromoacetone


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O

+ Cl2, H+

O

Cl

+ HCl

2-chlorocyclohexanone

C CH3

O

+ Br2, NaOH C CH2Br + NaBr

O

-bromoacetophenone

cyclohexanone

acetophenone


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Alpha-hydrogens: 1o> 2o> 3o

CH3CH2CH2CCH3O

2-pentanone

+ Br2, NaOH CH3CH2CH2CCH2Br + NaBrO

1-bromo-2-pentanone

Hydrogens that are alpha to a carbonyl group are weakly acidic:

H3CC

CH3

O

H3CC

CH2

O

+ OH + H2O


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R C CH2

O

RC

CH2

O

"enolate" anion

Hydrogens that are alpha to a carbonyl are weaklyacidic due to resonance stabilization of the carbanion.

The enolate anion is a strong base and a good nucleophile


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Mechanismfor base promoted alpha-bromination of acetone:

H3CC

CH3

O

H3CC

CH2

O

+ OH + H2ORDS

H3CC

CH2

O

+ Br Br

H3CC

CH2Br

O

+ Br

1)

2)

Rate = k [acetone] [base]


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Mechanismfor acid catalyzed halogenation of ketones. Enolization.

H3CC CH3

O

H3CC

CH3

OH

+ H+

H3C

C

CH3

OH+ :B

H3C

C

CH2

OH

+ H:B

H3CC

CH2

OH

+ Br Br H3C

CCH2Br

OH+ :Br

H3CC

CH2Br

OH

H3CC

CH2Br

O+ H

enol1)

2)

3)

4)


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RC

CH3

O

Oxidation of "methyl" ketones. Iodoform test.

+ (xs) OI R C

O

O

+ CHI3

NaOH + I2

RC

CH2I

O

RC

CHI2

O

RC

CI3

O

+ OH

R C CI3

O

OH

goodleavinggroup


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Carbanions. The conjugate bases of weak acids;

strong bases, good nucleophiles.

1. enolate anions

2. organometallic compounds

3. ylides

4. cyanide

5. acetylides


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Aldehydes and ketones: nucleophilic addition

Esters and acid chlorides: nucleophilic acyl substitution

Alkyl halides: SN2

C

O

+ YZ C

OY

Z

C

W

O + Z C

Z

O + W

R X + Z R Z + X

Carbanions as the nucleophiles in the above reactions.


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2. Carbanions as the nucleophiles in nucleophilicaddition to aldehydes and ketones:

a) aldol condensation

crossed aldol condensation

b) aldol related reactions (see problem 21.18

on page 811)

c) addition of Grignard reagents

d) Wittig reaction


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Carbanions as the nucleophiles in nucleophilic addition to

aldehydes and ketones:c) addition of Grignard reagents

Grignard reagents are examples of organo metallic

carbanions.

C

O

+ RMgXC

OMgX

R


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a) Aldol condensation. The reaction of an aldehyde or ketone

with dilute base or acid to form a beta-hydroxycarbonyl product.

CH3CH=Odil. NaOH

CH3CHCH2CH O

OH

acetaldehyde3-hydroxybutanal

CH3CCH3

Odil. NaOH

CH3CCH2CCH3

OOH

CH3acetone

4-hydroxy-4-methyl-2-pentanone


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CH3CH=O

dil. NaOH

CH3CHCH2CH O

OH

acetaldehyde 3-hydroxybutanal

OH

CH2CH=O CH3CH+ OCH3CHCH2CH O

O

+ H2O

+ H2O

nucleophilic addition by enolate ion.


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H3C C CH3

O

OH

H3CC

CH2

O

H3CC

CH3

O

H3CC

O

C

H2

C

O

CH3

CH3

+ H2O

+ H2O

H3C C

O

CH2

C

OH

CH3

CH3dil. NaOH


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CH3CH2CH=O + dil. NaOH CH3CH2CHCH2CH2CH

OH

O

CH3CHCH O

alpha!

CH3CH2CH CH3CH2CHCHCH

OH

CH3OO


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O

dil. OH-

O

OH

OH

O

O

O

O + HOH


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dil. H+

O

+ H2O

O

With dilute acid the final product is the ,-unsaturated carbonyl compound!


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CH2CH O

phenylacetaldehyde

dil NaOHCH2 C

H

CH

OH

CH=O

dilute H+

CH2 CH

C CH=O

note: double bond is conjugatedwith the carbonyl group!

+ H2O


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NB: An aldehyde without alpha-hydrogens

undergoes the Cannizzaro reaction with conc. base.

CHO

benzaldehyde

conc. NaOH

COO- CH2OH

+


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Crossed aldol condensation:

If you react two aldehydes or ketones together in analdol condensation, you will get four products. However, if

one of the reactants doesnt have any alpha hydrogens it can be

condensed with another compound that does have alpha

hydrogens to give only one organic product in a crossedaldol.

CH3CH2CH + H2C OO CH3CHCH2 OH

CH ONaOH


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N.B. If the product of the aldol condensation under basic

conditions is a benzyl alcohol, then it will spontaneouslydehydrate to the ,-unsaturated carbonyl.

CH=O + CH3CH2CH2CH=Odil OH-

CH=CCH=O

CH2

CH3

CHCHCH=O

OH

CH2

CH3

-H2O


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A crossed aldol can also be done between an aldehyde and a

ketone to yield one product. The enolate carbanion from theketone adds to the more reactive aldehyde.

C CH3

O

acetophenone

+ CH3CH=O

acetaldehyde

dil OH-CCH2

O

CH

OH

CH3


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b) Aldol related reactions: (see problem 21.18 page 811

of your textbook).

CH=O + CH3NO2KOH

CH=CHNO2 + H2O

CH2NO2

CH=O + CH2C N

NaOEt

CH=C CN

CHC N

+ H2O


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Perkin condensation

CH=O + (CH3CO)2OCH3COONa

CH=CHCOOH

H2C C

O

O

CCH3O

CH

OH

CH2 C

O

O

CCH3O

+ H2O

H

C CH C

O

O

CCH3O

hydrolysis ofanhydride

+ CH3COOH


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d) Wittig reaction (synthesis of alkenes)

1975 Nobel Prize in Chemistry to Georg Wittig

C O + Ph3P=C R'

R

ylide

C

O

C R'

R

PPh3

C C

R

R' + Ph3PO

CH2CH=O + Ph3P=CH2 CH2CH=CH2 + Ph3PO

Ph = phenyl


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CO

C R'R

PPh3

C CR

R' + Ph3PO

PPh

Ph

Ph

CR

R' CO

ylide

nuclephilic addition by ylide carbanion, followed by loss of

Ph3PO (triphenylphosphine oxide)


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O + Ph3PCHCH=CH2 CHCH CH2 + Ph3P


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3. Carbanions as the nucleophiles in nucleophilic acyl

substitution of esters and acid chlorides.

a) Claisen condensation

a reaction of esters that have alpha-hydrogens in basic

solution to condense into beta-keto esters

CH3COOEt

ethyl acetate

NaOEtCH3CCH2COOEt

O

+ EtOH

ethyl acetoacetate


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CH3COOEtNaOEt

CH3CCH2COOEtO

+ EtOH

CH3 C

OEt

O

CH3 C OEt

O

CH2COOEt

nucleophilic acyl substitution by enolate anion

OEt

CH2COOEt

Mechanism for the Claisen condensation:


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ethyl propionate

CH3CH2CCHCOOEt

CH3

O

ethyl 2-methyl-3-oxopentanoate

OEtCH3CH2COOEt

OEt

CH3CHCOOEt CH3CH2C

O

OEtCH3CH2C

O

OEt

CHCOOEtCH3


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CH2COOEt

NaOEt

CH2C

O

CHCOOEt

ethyl phenylacetate

CHCOOEt CH2CO

OEtCH2C

O

CHCOOEt

OEt

OEt


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Crossed Claisen condensation:

COOEt + CH3COOEtNaOEt

C

O

CH2COOEt

ethyl benzoate

HCOOEt + CH3CH2COOEt

ethyl formate

H C

O

CHCOOEt

CH3

OEt


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COOEt

COOEtCH3CH2COOEt

OC2H5

+ C

O

C

O

OEt

CHCOOEt

CH3

COOEt

COOEt2CH3CH2COOEt

NaOC2H5+ C

O

C

O

CHCOOEt

CH3

CHCOOEt

CH3

ethyl oxalate


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EtOCOEt

ethyl carbonate

+COOEtCH2

COOEt

ethyl malonate

NaOEtC CH

O COOEt

COOEt

EtO

CH3CH2COOEt

ethyl propionate

+

O

cyclohexanone

NaOEtCH3CH2C

OO

enolate from ketone in nucleophilic acyl substitution on ester

O


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b) Coupling of lithium dialkyl cuprate with acid chloride

R C

Cl

O+ R'2CuLi R C

R'

O

nucleophile = R'


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4. Carbanions as nucleophiles in SN2 reactions with RX:

a) Corey-House synthesis of alkanes

R2CuLi + RX R-R

b) metal acetylide synthesis of alkynes

RC

C

-

M

+

+ RX RC

CRc) Malonate synthesis of carboxylic acids

d) Acetoacetate synthesis of ketones

5. Michael Addition to ,-unsaturated carbonyl

compounds


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Carbanions are the conjugate bases of weak acids and

are therefore strong bases and excellent nucleophiles

that can react with aldehydes/ketones (nucleophilic

addition), esters/acid chlorides (nucleophilic acyl

substitution), and alkyl halides (SN2), etc.


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Reactions involving carbanions as nucleophiles:

1. Alpha-halogenation of ketones

2. Nucleophilic addition to aldehydes/ketones

a) aldol and crossed aldol

b) aldol related reactions

c) Grignard synthesis of alcohols

d) Wittig synthesis of alkenes

3. Nucleophilic acyl substitution with esters and acid

chlorides

a) Claisen and crossed Claisen

b) R2CuLi + RCOCl

(next slide)


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4. SN2 with alkyl halidesa) Corey-House

b) metal acetylide

c) Malonate synthesisd) Acetoacetate synthesis

5. Michael Addition to ,-unsaturated carbonyl

compounds

Car Banion Si

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