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8/13/2019 Car Banion Si
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Carbanions
|
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