Transcript nucleophilic addition

REACTIONS OF ALDEHYDES AND
KETONES
BY
HARJEET GUJRAL
ASSOCIATE PROFESSOR
GOVT. COLLEGE ROPAR
Reactions of aldehydes and ketones:
oxidation
reduction
nucleophilic addition
1) Aldehydes are easily oxidized, ketones are not.
2) Aldehydes are more reactive in nucleophilic additions than
ketones.
alkane
alcohol
reduction
reduction
aldehyde
ketone
oxidation
carboxylic acid
addition
product
nucleophilic
addition
nucleophilic addition to carbonyl:

O
C

+
Y Z
OY
C
Z
Mechanism: nucleophilic addition to carbonyl
1)
O
C
2)
O
C
Z
Z
O
C
Z
Y
OY
C
Z
RDS
+
+
Mechanism: nucleophilic addition to carbonyl, acid catalyzed
1)
O
C
2)
OH
C
3)
OH
C
ZH
+
OH
C
H
OH
C
ZH
RDS
+
HZ
OH
C
Z
+
H
Aldehydes & ketones, reactions:
1) Oxidation
2) Reduction
3) Addition of cyanide
4) Addition of derivatives of ammonia
5) Addition of alcohols
6) Cannizzaro reaction
7) Addition of Grignard reagents
8) (Alpha-halogenation of ketones)
9) (Addition of carbanions)
1) Oxidation
a) Aldehydes (very easily oxidized!)
CH3CH2CH2CH=O
+ KMnO4, etc. 
CH3CH2CH2COOH
carboxylic acid
CH3CH2CH2CH=O + Ag+  CH3CH2CH2COO- + Ag
Silver mirror
Tollen’s test for easily oxidized compounds like aldehydes.
(AgNO3, NH4OH(aq))
Ketones only oxidize under vigorous conditions via the enol.
O
+
KMnO4
NR
Cyclohexanone
O
+ KMnO4, heat
HOOCCH2CH2CH2CH2COOH
adipic acid
OH
enol
b) Methyl ketones:
R
O
C
CH3
+
OI-
R
O
C
O-
+
CHI3
iodoform
Yellow ppt
test for methyl ketones
O
CH3CH2CH2CCH3
2-pentanone
+ (xs) NaOI
CH3CH2CH2CO2- + CHI3
2) Reduction:
a) To alcohols
O
C
H2, Ni
NaBH4 or LiAlH4
then H+
OH
C
H
H2, Pt
H
O
OH
cyclopentanol
cyclopentanone
O
C CH3
acetophenone
1. NaBH4
2. H+
OH
CHCH3
1-phenylethanol
O
H2, Pt
C
H
CH2OH
benzaldehyde
CH3
CH3CHCH=O
isobutyraldehyde
benzyl alcohol
LiAlH4
H+
CH3
CH3CHCH2OH
isobutyl alcohol
hydride reduction
mechanism: nucleophilic addition; nucleophile = hydride
1)
2)
O
C
O
C
H
RDS
H: Al
+
+
Al
O
C
H
+
Al
H C O Al
Then + H+  alcohol
Reduction
b) To hydrocarbons
O
C
NH2NH2, OH-
O
C
Zn(Hg), HCl
CH2
Wolff-Kishner
Clemmensen
CH2
O
Cl
+
O
AlCl3
Zn(Hg), HCl
n-pentylbenzene
cannot be made by Friedel-Crafts alkylation
due to rearrangement of carbocation
3) Addition of cyanide
O
C
1. CN-
OH
C
CN
cyanohydrin
2. H+
+
O + NaCN; then H
OH
CN
mechanism for addition of cyanide
nucleophilic addition
1)
2)
O
C
O
C
C
N
RDS
+
C N
+ Na+
O
C
C
N
ONa
C
C
N
then + H+
Cyanohydrins have two functional groups plus one additional
carbon. Nitriles can be hydrolyzed to carboxylic acids in
acid or base:
OH
CH2CH C N
H2O, OH-
OH
CH2CH C N
H2O, H+
heat
heat
OH
CH2CH COO-
C C COOH
H H
4) Addition of derivatives of ammonia
O
+ H2N G
(H+)
+ H2O
N G
O
H2N NH2
H2N OH
hydrazine
hydroxylamine
NH2
H2N N
H
semicarbazide
O2N
H2N HN
H2N HN
NO2
phenylhydrazine
2,4-dinitrophenylhydrazine
acid catalyzed nucleophilic addition mechanism followed by dehydration
1)
2)
3)
O
C
OH
C
OH
C
NH2 G
+
OH
C
+
H
OH
C
NH2 G
+ H2N G
C
N
+
G
RDS
H2O + H+
CH2 CHO
+ H2NOH
CH2 CH NOH
hydroxylamine
an oxime
phenylacetaldehyde
H+
O
O
+
H2NHNCNH2
O
NHNCNH2
semicarbazide
cyclohexanone
CH3CH2CH2CH2CHO
pentanal
a semicarbazone
+ NH2 NH
phenylhydrazine
CH3CH2CH2CH2CH N NH
a phenylhydrazone
5) Addition of alcohols
O
C
+ ROH, H+
OH
C
OR
OR
C
OR
hemiacetal
acetal
Mechanism = nucleophilic addition, acid catalyzed
1)
O
C
+
OH
C
H
RDS
2)
3)
OH2
C
OH
C
HOR
+
ROH
OH
C
OR
OH
C
HOR
+ H
(xs) EtOH, H+
CH2CHO
OEt
CH2 CH
OEt
acetal
O
(xs) CH3OH, dry HCl
OCH3
OCH3
ketal
6) Cannizzaro reaction. (self oxidation/reduction)
a reaction of aldehydes without α-hydrogens
COO-
CH2OH
CHO
conc. NaOH
+
Br
Br
conc. NaOH
H2C=O
CH3OH + HCOO-
Br
Formaldehyde is the most easily oxidized aldehyde. When
mixed with another aldehyde that doesn’t have any alphahydrogens and conc. NaOH, all of the formaldehyde is
oxidized and all of the other aldehyde is reduced.
Crossed Cannizzaro:
CH=O
CH2OH
+ H2C=O
conc. NaOH
+ HCOO-
OCH3
OH
vanillin
OCH3
OH
7) Addition of Grignard reagents.
O
C
+ RMgX
O MgBr
+ H2O
C
R
O MgBr
C
R
OH
+ Mg(OH)Br
C
R
larger alcohol
mechanism = nucleophilic addition
1)
O
C
2)
O
C
R
RDS
+ RMgBr
+ MgBr
O
C
R
+ MgBr
OMgBr
C
R
#3 synthesis of alcohols. Used to build larger molecules
from smaller organic compounds.
RMgX +
O
C
H
H
formaldehyde
RMgX +
O
C
R'
H
other aldehydes
RCH2OMgX
R'CHOMgX
R
H+
RCH2OH
1o alcohol + 1 C
H+
R'CHOH
R
2o alcohol + X C's
O
R-MgX + C
R'
R"
R'
R-COMgX
R"
ketone
O
RMgX +
H2C CH2
ethylene oxide
R'
H+
R-COH
R"
3o alcohol + X C's
H+
RCH2CH2OMgX
RCH2CH2OH
1o alcohol + 2 C's
Planning a Grignard synthesis of an alcohol:
a) The alcohol carbon comes from the carbonyl
compound.
b) The new carbon-carbon bond is to the alcohol carbon.
O
C
+ RMgX
H+
New carbon-carbon bond
OH
C
R
“The Grignard Song” (sung to the tune of “America the Beautiful”)
Harry Wasserman
The carbonyl is polarized,
the carbon end is plus.
A nucleophile will thus attack
the carbon nucleus.
The Grignard yields an alcohol
of types there are but three.
It makes a bond that corresponds
from “C” to shining “C.”