Carbanions
|
— C: –
|
The conjugate bases of weak acids,
strong bases, excellent
nucleophiles.
1. Alpha-halogenation of ketones
OH- or H+
O
C C
H
+ X2
O
C C
X
+ HX
 -haloketone
X2 = Cl2, Br2, I2
H3C
O
C
CH3
acetone
+ Br2, NaOH
H3C
O
C
CH2Br
 -bromoacetone
+
NaBr
O
O
Cl
+
+ Cl2, H
cyclohexanone
O
C CH3
acetophenone
+ HCl
2-chlorocyclohexanone
+ Br2, NaOH
O
C CH2Br + NaBr
 -bromoacetophenone
Alpha-hydrogens: 1o > 2o > 3o
O
CH3CH2CH2CCH3 + Br2, NaOH
O
CH3CH2CH2CCH2Br + NaBr
1-bromo-2-pentanone
2-pentanone
Hydrogens that are alpha to a carbonyl group are weakly acidic:
H3C
O
C
CH3
+ OH
H3C
O
C
CH2
+ H2O
Hydrogens that are alpha to a carbonyl are weakly
acidic due to resonance stabilization of the carbanion.
R
O
C
CH2
R
O
C
CH2
"enolate" anion
The enolate anion is a strong base and a good nucleophile
Mechanism for base promoted alpha-bromination of acetone:
1)
H3C
2)
H3C
O
C
O
C
CH3
CH2
+ OH
+
RDS
H3C
Br Br
Rate = k [acetone] [base]
H3C
O
C
O
C
CH2
CH2Br
+ H2O
+ Br
Mechanism for acid catalyzed halogenation of ketones. Enolization.
1)
H3C
O
C
CH3
+
H+
2)
OH
+ :B
C
H3C
CH3
3)
OH
+ Br Br
C
H3C
CH2
4)
OH
C
H3C
CH2Br
OH
C
H3C
CH3
“enol”
OH
+ H:B
C
H3C
CH2
OH
+ :Br
C
H3C
CH2Br
H3C
O
C
+ H
CH2Br
Oxidation of "methyl" ketones. Iodoform test.
R
O
C
CH3
O
R C
O
+ (xs) OI
+
CHI3
NaOH + I2
R
R
O
C
O
C
O
R C CI3
OH
CH2I
CHI2
R
O
C
CI3
+ OH
good
leaving
group
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
O
C
+ YZ
OY
C
Z
Esters and acid chlorides: nucleophilic acyl substitution
O
C
W
+ Z
O
C
Z
+ W
Alkyl halides: SN2
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.
O
C
+ RMgX
OMgX
C
R
a) Aldol condensation. The reaction of an aldehyde or ketone
with dilute base or acid to form a beta-hydroxycarbonyl product.
CH3CH=O
acetaldehyde
OH
CH3CHCH2CH O
3-hydroxybutanal
O
CH3CCH3
acetone
OH O
CH3CCH2CCH3
CH3
dil. NaOH
dil. NaOH
4-hydroxy-4-methyl-2-pentanone
dil. NaOH
CH3CH=O
acetaldehyde
OH
CH3CHCH2CH O
3-hydroxybutanal
+ H2O
OH
CH2CH=O + CH3CH O
O
CH3CHCH2CH O
+ H2O
nucleophilic addition by enolate ion.
H3C
O
C
dil. NaOH
CH3
H3C
O
C
OH
H3C
O
C
CH2
+ H2O
OH
CH3
C
C
CH3
H2
+ H2O
H3C
O
C
CH3
H3C
O
C
O
CH3
C
C
CH3
H2
CH3CH2CH=O + dil. NaOH
CH3CHCH O
alpha!
CH3CH2CH O
OH
CH3CH2CHCH2CH2CHO
OH
CH3CH2CHCHCHO
CH3
O
O
dil. OHOH
OH
O
O
O
O
+
HOH
O
O
dil. H+
+ H2O
With dilute acid the final product is the α,βunsaturated carbonyl compound!
dil NaOH
CH2CH O
OH
CH2 C CH CH=O
H
phenylacetaldehyde
dilute H+
CH2 C C CH=O
H
+ H2O
note: double bond is conjugated
with the carbonyl group!
NB: An aldehyde without alpha-hydrogens
undergoes the Cannizzaro reaction with conc. base.
CHO
benzaldehyde
conc. NaOH
COO+
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.
NaOH
CH3CH2CH O + H2C O
CH O
CH3CHCH2 OH
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=O
OH
CHCHCH=O
CH2
CH3
dil OH-
-H2O
CH=CCH=O
CH2
CH3
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.
O
C CH3
acetophenone
+ CH3CH=O
acetaldehyde
dil
OH-
O
OH
C CH2 C CH3
H
b) Aldol related reactions: (see problem 21.18 page 811
of your textbook).
KOH
CH=O + CH3NO2
CH=CHNO2
+ H2O
CH2NO2
NaOEt
CH=O +
CH2C N
CHC
N
CH=C CN
+ H2O
Perkin condensation
CH=O
+ (CH3CO)2O
CH3COONa
CH=CHCOOH
+ CH3COOH
O
H2C C
O
CH3 C
O
OH
O
CHCH2 C
O
CH3 C
O
hydrolysis of
anhydride
O
H
C C C
H O
CH3 C
O
+ H2O
d) Wittig reaction (synthesis of alkenes)
1975 Nobel Prize in Chemistry to Georg Wittig
R
C O + Ph3P=C R'
ylide
CH2CH=O
Ph = phenyl
O R
C C R'
PPh3
+ Ph3P=CH2
R
C C R'
+ Ph3PO
CH2CH=CH2 + Ph3PO
Ph R
Ph P C R'
Ph
ylide
O
C
O R
C C R'
PPh3
R
C C R'
+ Ph3PO
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
NaOEt
O
CH3CCH2COOEt + EtOH
ethyl acetoacetate
Mechanism for the Claisen condensation:
CH3COOEt
NaOEt
O
CH3CCH2COOEt + EtOH
OEt
CH2COOEt
CH3
O
C
OEt
CH3
O
C OEt
CH2COOEt
nucleophilic acyl substitution by enolate anion
ethyl propionate
CH3CH2COOEt
ethyl 2-methyl-3-oxopentanoate
OEt
O
CH3CH2CCHCOOEt
CH3
OEt
CH3CHCOOEt
O
CH3CH2C
OEt
O
CH3CH2C OEt
CHCOOEt
CH3
ethyl phenylacetate
NaOEt
CH2COOEt
O
CH2C CHCOOEt
OEt
CHCOOEt
O
CH2C
OEt
O
CH2C OEt
CHCOOEt
Crossed Claisen condensation:
NaOEt
COOEt + CH3COOEt
O
C CH2COOEt
ethyl benzoate
OEt
HCOOEt + CH3CH2COOEt
ethyl formate
O
H C CHCOOEt
CH3
COOEt
OC2H5
+
COOEt
ethyl oxalate
COOEt
COOEt
CH3CH2COOEt
NaOC2H5
+ 2 CH3CH2COOEt
O CH3
C CHCOOEt
C OEt
O
O
C
C
O
CH3
CHCOOEt
CHCOOEt
CH3
COOEt
O
+
EtOCOEt
ethyl carbonate
CH2
COOEt
O COOEt
EtO C CH
COOEt
NaOEt
ethyl malonate
O
CH3CH2COOEt
ethyl propionate
+
NaOEt
O
CH3CH2C
O
cyclohexanone
enolate from ketone in nucleophilic acyl substitution on ester
b) Coupling of lithium dialkyl cuprate with acid chloride
O
R C
Cl
+ R'2CuLi
nucleophile = R'
O
R C
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
RCC-M+ + R’X  RCCR’
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