Transcript Document

Carbanions
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— C: –
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The conjugate bases of weak acids,
strong bases, excellent
nucleophiles.
1. Alpha-halogenation of ketones
O H - or H +
O
C C
+
X2
H
O
+ HX
C C
X
 -h a lo ke to n e
X 2 = C l2 , B r 2 , I 2
O
H 3C
C
O
CH3
a ce to n e
+
B r2 , N a O H
H 3C
C
C H 2B r
 -b ro m o a c e to n e
+
NaBr
O
O
Cl
+
C l2 , H
+
+
2 -c hlo roc yc lo h exa n o ne
c yc lo h exa no ne
O
C CH3
a ce to ph e non e
HCl
O
+
B r 2 , N aO H
C C H 2Br
 -bro m oa ce top h eno n e
+
N aBr
Alpha-hydrogens: 1o > 2o > 3o
O
O
C H 3C H 2C H 2C C H 3 +
B r 2 , N aO H
C H 3C H 2C H 2C C H 2B r
+
N aB r
1 -brom o-2-pen tan one
2-pe nta none
H ydro gens that are alph a to a ca rbonyl group are w eakly acid ic:
O
H 3C
C
O
CH3
+
OH
H 3C
C
CH2
+
H 2O
H yd rog e n s th a t a re a lp ha to a carbo nyl are w eakly
a cid ic du e to re son a n ce stab iliza tio n of th e carba n ion .
O
R
C
O
CH2
R
C
CH2
"e no la te " a n io n
Th e e n o la te an io n is a stron g ba se an d a go od nu cle oph ile
Mechanism for base promoted alpha-bromination of acetone:
O
1)
H 3C
C
O
RDS
CH3
+
OH
H 3C
O
2)
H 3C
C
C
+
CH2
H 2O
O
+
Br
CH2
Rate = k [acetone] [base]
Br
H 3C
C
+
C H 2B r
Br
M echanism for acid catalyzed h alogen a tion o f ketones. E n oliza tion .
O
1)
H 3C
C
OH
+
H
+
CH3
H 3C
C
OH
2)
H 3C
C
CH3
OH
+
:B
CH3
H 3C
C
OH
3)
H 3C
4)
H 3C
CH2
Br
H 3C
OH
O
C
C
C H 2B r
+
H :B
CH2
OH
+ Br
C
“enol”
H 3C
C
+
C H 2Br
+
C H 2Br
H
:B r
O xid atio n o f "m eth yl" ke to ne s. Io do fo rm test.
O
R
C
O
+ (xs) OI
R
CH3
+
C
CHI3
O
NaOH + I2
O
O
R
R
C
R
OH
CH2I
O
O
C
C
CHI2
C
R
+
CI3
OH
CI3
goo d
le a vin g
grou p
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
OY
O
+
C
C
YZ
Z
Esters and acid chlorides: nucleophilic acyl substitution
O
O
+
C
W
Z
+ W
C
Z
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
O M gX
+
R M gX
C
R
a) Aldol condensation. The reaction of an aldehyde or ketone
with dilute base or acid to form a beta-hydroxycarbonyl product.
OH
d il. N a O H
C H 3C H = O
C H 3C H C H 2C H
ac eta lde h yd e
3 -h yd ro xy bu ta n a l
O
C H 3C C H 3
a ce ton e
OH
d il. N a O H
O
O
C H 3C C H 2C C H 3
CH3
4 -h y d ro x y -4 -m e th yl-2 -p e n ta n o n e
OH
d il. N a O H
C H 3C H =O
C H 3C H C H 2C H
O
a ce ta ld e h y d e
3 -h yd ro xyb u ta n a l
+ H 2O
OH
O
C H 2C H =O +
+
C H 3C H O
C H 3C H C H 2C H O
H 2O
nucleophilic addition by enolate ion.
O
H 3C
C
dil. N aO H
CH3
O
OH
CH3
C
C
H 3C
C
CH3
H2
OH
+
O
H 3C
+
C
CH2
H 2O
H 3C
O
O
O
C
C
C
CH3
H 3C
C
H2
H 2O
CH3
CH3
OH
C H 3C H 2C H =O
+
dil. N aO H
C H 3C H 2C H C H 2C H 2C HO
C H 3C H C H O
a lph a!
OH
C H 3C H 2C H O
C H 3C H 2C H C H C HO
CH3
O
O
d il. O H OH
OH
O
O
O
O
+
HOH
O
O
dil. H +
+
H 2O
With dilute acid the final product is the α,βunsaturated carbonyl compound!
d il N a O H
C H 2C H O
OH
CH2 C CH CH=O
H
p h e n yla c e ta ld e h y d e
d ilu te H +
C H 2 C C C H =O
H
+
H 2O
n o te : d o u b le b o n d is c o n ju g a te d
w ith th e c a rb o n y l g ro u p !
NB: An aldehyde without alpha-hydrogens
undergoes the Cannizzaro reaction with conc. base.
CHO
co nc. N a O H
b enzald ehyde
COO+
C H 2O H
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
C H 3C H 2C H O +
H 2C
O
CH O
C H 3C H C H 2 O H
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.
dil O H CH=O
+ C H 3C H 2C H 2C H = O
C H =C C H = O
CH2
CH3
OH
-H 2 O
CHCHCH=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
dil O H
+
C H 3C H =O
a ce ta ld eh y de
ac e to ph e n o n e
-
O
OH
C CH2 C CH3
H
b) Aldol related reactions: (see problem 21.18 page 811
of your textbook).
KOH
CH=O
+
C H 3N O 2
CH=CHNO2
+
H 2O
C H 2N O 2
N aO E t
CH=O
+
C H 2C N
CHC
N
C H =C C N
+ H 2O
Perkin condensation
CH=O
+
(C H 3 C O ) 2 O
C H 3C O O N a
CH=CHCOOH
+
C H 3C O O H
O
H 2C C
O
CH3
hy d rolys is o f
an h yd rid e
C
O
OH
O
C HC H 2 C
O
CH3
C
O
O
H
C C C
H
O
CH3 C
O
+
H 2O
d) Wittig reaction (synthesis of alkenes)
1975 Nobel Prize in Chemistry to Georg Wittig
R
C O +
P h3P =C
O R
R'
C C R'
Ph = phenyl
C C R'
+
Ph3P O
PP h3
ylide
C H 2C H =O
R
+
Ph3P =C H 2
C H 2C H =C H 2 +
P h3P O
Ph
Ph R
O
P
C
C R'
Ph
ylid e
O R
C C R'
R
C C R'
+
P h3PO
PPh3
nuclephilic addition by ylide carbanion, followed by loss of
Ph3PO (triphenylphosphine oxide)
O
+
Ph3P C H C H =C H 2
CHCH CH2
+
Ph3P O
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
N aO E t
C H 3C O O E t
ethyl acetate
O
C H 3C C H 2C O O E t +
ethyl a ce toacetate
E tO H
Mechanism for the Claisen condensation:
O
NaOEt
C H 3C O O E t
C H 3C C H 2C O O Et +
E tO H
OEt
O
O
C H 2C O O Et
CH3
C
CH3
OEt
C OEt
C H 2C O O E t
n u cle op h ilic a cyl su bstitution by e no late an io n
ethyl pro pion ate
e th yl 2 -m e th yl-3-oxo pe n ta no ate
O
OEt
C H 3C H 2C O O Et
C H 3C H 2C C H C O O E t
CH3
OEt
O
C H 3C H C O O Et
C H 3C H 2C
OEt
O
C H 3C H 2C O E t
CHCOOEt
CH3
ethy l p h e ny la ce tate
N aO Et
O
C H 2C C H C O O E t
C H 2C O O E t
OEt
O
CHCOOEt
C H 2C
O
C H 2C O E t
OEt
CHCOOEt
Crossed Claisen condensation:
O
NaO Et
COOEt +
C H 3C O O Et
C
C H 2C O O E t
e th yl b e n zo a te
OEt
HCOOEt
+
e th yl fo rm ate
C H 3C H 2C O O Et
O
H C
CHCOOEt
CH3
O C 2H 5
COOEt
+
COOEt
C CHCOOEt
C H 3C H 2C O O E t
C OEt
ethyl o xala te
O
N aO C 2 H 5
COOEt
+
COOEt
O CH3
2 C H 3C H 2C O O E t
O CH3
C CHCOOEt
C CHCOOEt
O CH3
COOEt
O
E tO C O E t
+
e th yl ca rb o n a te
O COOEt
N aO Et
CH2
E tO C C H
COOEt
COOEt
e th y l m a lo n a te
O
C H 3C H 2C O O E t
e th yl p ro p io n a te
+
N aO E t
O
O
C H 3C H 2C
cy clo h e x a n o n e
e n o la te fro m ke to n e in n u cle o p h ilic a cyl su b stitu tio n o n e ste r
b) Coupling of lithium dialkyl cuprate with acid chloride
O
R
O
+
C
R '2 C u L i
Cl
n u c le o p h ile = R '
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