carbanions | — c: – | the conjugate bases of weak acids, strong bases, excellent nucleophiles
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Carbanions
| — C: –
|
The conjugate bases of weak acids,strong bases, excellent nucleophiles.
1. Alpha-halogenation of ketones
CC
H
O
+ X2
OH- or H+
CC
X
O+ HX
X2 = Cl2, Br2, I2
-haloketone
H3CC
CH3
O
+ Br2, NaOH H3CC
CH2Br
O+ NaBr
acetone -bromoacetone
O
+ Cl2, H+
O
Cl+ HCl
2-chlorocyclohexanone
C CH3
O
+ Br2, NaOH C CH2Br + NaBr
O
-bromoacetophenone
cyclohexanone
acetophenone
Alpha-hydrogens: 1o > 2o > 3o
CH3CH2CH2CCH3
O
2-pentanone
+ Br2, NaOH CH3CH2CH2CCH2Br + NaBr
O
1-bromo-2-pentanone
Hydrogens that are alpha to a carbonyl group are weakly acidic:
H3CC
CH3
O
H3CC
CH2
O+ OH + H2O
RC
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
Mechanism for base promoted alpha-bromination of acetone:
H3CC
CH3
O
H3CC
CH2
O+ OH + H2O
RDS
H3CC
CH2
O+ Br Br
H3CC
CH2Br
O+ Br
1)
2)
Rate = k [acetone] [base]
Mechanism for acid catalyzed halogenation of ketones. Enolization.
H3CC
CH3
O
H3CC
CH3
OH+ H+
H3CC
CH3
OH+ :B
H3CC
CH2
OH+ H:B
H3CC
CH2
OH+ Br Br
H3CC
CH2Br
OH+ :Br
H3CC
CH2Br
OH
H3CC
CH2Br
O+ H
“enol”
1)
2)
3)
4)
RC
CH3
O
Oxidation of "methyl" ketones. Iodoform test.
+ (xs) OI R CO
O+ CHI3
NaOH + I2
RC
CH2I
O
RC
CHI2
O
RC
CI3
O+ OH
R C CI3
O
OH
goodleavinggroup
Carbanions. The conjugate bases of weak acids; strong bases, good nucleophiles.
1. enolate anions
2. organometallic compounds
3. ylides
4. cyanide
5. acetylides
Aldehydes and ketones: nucleophilic addition
Esters and acid chlorides: nucleophilic acyl substitution
Alkyl halides: SN2
C
O+ YZ C
OY
Z
CW
O+ Z C
Z
O+ W
R X + Z R Z + X
Carbanions as the nucleophiles in the above reactions.
2. Carbanions as the nucleophiles in nucleophilic addition 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
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+ RMgX C
OMgX
R
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
acetaldehyde 3-hydroxybutanal
CH3CCH3
Odil. NaOH
CH3CCH2CCH3
OOH
CH3acetone
4-hydroxy-4-methyl-2-pentanone
CH3CH=Odil. NaOH
CH3CHCH2CH O
OH
acetaldehyde 3-hydroxybutanal
OH
CH2CH=O CH3CH+ O CH3CHCH2CH O
O
+ H2O
+ H2O
nucleophilic addition by enolate ion.
H3CC
CH3
O
OH
H3CC
CH2
O
H3CC
CH3
O
H3CC
O
CH2
C
O
CH3
CH3
+ H2O
+ H2O
H3CC
O
CH2
C
OH
CH3
CH3dil. NaOH
CH3CH2CH=O + dil. NaOH CH3CH2CHCH2CH2CH
OH
O
CH3CHCH O
alpha!
CH3CH2CH CH3CH2CHCHCH
OH
CH3
OO
O
dil. OH-
O
OH
OH
O
O
O
O + HOH
dil. H+
O
+ H2O
O
With dilute acid the final product is the α,β-unsaturated carbonyl compound!
CH2CH O
phenylacetaldehyde
dil NaOHCH2 C
HCH
OH
CH=O
dilute H+
CH2 CH
C CH=O
note: double bond is conjugatedwith the carbonyl group!
+ H2O
NB: An aldehyde without alpha-hydrogens undergoes the Cannizzaro reaction with conc. base.
CHO
benzaldehyde
conc. NaOHCOO- CH2OH
+
Crossed aldol condensation:
If you react two aldehydes or ketones together in an aldol condensation, you will get four products. However, if one of the reactants doesn’t have any alpha hydrogens it can be condensed with another compound that does have alpha hydrogens to give only one organic product in a “crossed” aldol.
CH3CH2CH + H2C OO CH3CHCH2 OH
CH ONaOH
N.B. If the product of the aldol condensation under basic conditions is a “benzyl” alcohol, then it will spontaneously dehydrate to the α,β-unsaturated carbonyl.
CH=O + CH3CH2CH2CH=Odil OH-
CH=CCH=O
CH2
CH3
CHCHCH=O
OH
CH2
CH3
-H2O
A crossed aldol can also be done between an aldehyde and a ketone to yield one product. The enolate carbanion from the ketone adds to the more reactive aldehyde.
C CH3
O
acetophenone
+ CH3CH=O
acetaldehyde
dil OH-
CCH2
O
CH
OH
CH3
b) Aldol related reactions: (see problem 21.18 page 811 of your textbook).
CH=O + CH3NO2KOH
CH=CHNO2 + H2O
CH2NO2
CH=O + CH2C NNaOEt
CH=C CN
CHC N
+ H2O
Perkin condensation
CH=O + (CH3CO)2OCH3COONa
CH=CHCOOH
H2C CO
OCCH3
O
CH
OH
CH2 CO
OCCH3
O
+ H2OHC C
HC
O
OCCH3
O
hydrolysis ofanhydride
+ CH3COOH
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
C
O
C R'
R
PPh3
C C
R
R' + Ph3PO
P
Ph
Ph
Ph
C
R
R' C
O
ylide
nuclephilic addition by ylide carbanion, followed by loss of Ph3PO (triphenylphosphine oxide)
O + Ph3PCHCH=CH2 CHCH CH2 + Ph3PO
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
+ EtOHethyl acetoacetate
CH3COOEtNaOEt
CH3CCH2COOEt
O
+ EtOH
CH3 COEt
OCH3 C OEt
O
CH2COOEt
nucleophilic acyl substitution by enolate anion
OEt
CH2COOEt
Mechanism for the Claisen condensation:
ethyl propionate
CH3CH2CCHCOOEt
CH3
O
ethyl 2-methyl-3-oxopentanoate
OEtCH3CH2COOEt
OEt
CH3CHCOOEt CH3CH2CO
OEtCH3CH2C
O
OEt
CHCOOEt
CH3
CH2COOEt
NaOEtCH2C
O
CHCOOEt
ethyl phenylacetate
CHCOOEt CH2CO
OEtCH2C
O
CHCOOEt
OEt
OEt
Crossed Claisen condensation:
COOEt + CH3COOEtNaOEt
C
O
CH2COOEt
ethyl benzoate
HCOOEt + CH3CH2COOEt
ethyl formate
H C
O
CHCOOEt
CH3
OEt
COOEt
COOEtCH3CH2COOEt
OC2H5
+ C
O
C
O
OEt
CHCOOEt
CH3
COOEt
COOEt2 CH3CH2COOEt
NaOC2H5
+ C
O
C
O
CHCOOEt
CH3
CHCOOEt
CH3
ethyl oxalate
EtOCOEtethyl carbonate
+
COOEt
CH2
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
b) Coupling of lithium dialkyl cuprate with acid chloride
R CCl
O+ R'2CuLi R C
R'
O
nucleophile = R'
4. Carbanions as nucleophiles in SN2 reactions with R’X:
a) Corey-House synthesis of alkanes
R2CuLi + R’X R-R’
b) metal acetylide synthesis of alkynes
RCC-M+ + R’X RCCR’
c) Malonate synthesis of carboxylic acids
d) Acetoacetate synthesis of ketones
5. Michael Addition to α,β-unsaturated carbonyl compounds
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.
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)
4. SN2 with alkyl halides
a) Corey-House
b) metal acetylide
c) Malonate synthesis
d) Acetoacetate synthesis
5. Michael Addition to α,β-unsaturated carbonyl compounds
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