17.8 Acetal Formation

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17.8Acetal Formation
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Some reactions of aldehydes and ketones
progressbeyond the nucleophilic addition stage

• Acetal formation
• Imine formation
• Enamine formation
• Compounds related to imines
• The Wittig reaction

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Recall Hydration of Aldehydes and Ketones
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Alcohols Under Analogous Reactionwith Aldehydes
and Ketones

• Product is called a hemiacetal.

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Hemiacetal reacts further in acid to yield an
acetal

• Product is called an acetal.

ROH, H
Product is called a hemiacetal.
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Example

2CH3CH2OH
HCl
H2O
Benzaldehyde diethyl acetal (66)
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Diols Form Cyclic Acetals

CH3(CH2)5CH
HOCH2CH2OH
benzene
p-toluenesulfonic acid

H2O
(81)
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In general

• Position of equilibrium is usually
  unfavorablefor acetal formation from ketones.
• Important exception Cyclic acetals can be
  prepared from ketones.

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Example
C6H5CH2CCH3

HOCH2CH2OH
benzene
p-toluenesulfonic acid
H2C
CH2

O
O
H2O
(78)
C
CH3
C6H5CH2
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Mechanism of Acetal Formation

• First stage is analogous to hydration andleads
  to hemiacetal
• acid-catalyzed nucleophilic addition of
  alcohol to CO

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Mechanism
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Mechanism
H


O
O
C


H
R
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Mechanism


O
C
H
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Mechanism
R


O
O
C


H
H
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Mechanism
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Mechanism of Acetal Formation

• Second stage is hemiacetal-to-acetal conversion
• involves carbocation chemistry

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Hemiacetal-to-acetal Stage
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Hemiacetal-to-acetal Stage
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Hemiacetal-to-acetal Stage
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Hemiacetal-to-acetal Stage
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Hemiacetal-to-acetal Stage
Carbocation is stabilized by delocalizationof
unshared electron pair of oxygen
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Hemiacetal-to-acetal Stage
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Hemiacetal-to-acetal Stage
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Hemiacetal-to-acetal Stage
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Hydrolysis of Acetals

• mechanism
• reverse of acetal formationhemiacetal is
  intermediate
• application
• aldehydes and ketones can be "protected" as
  acetals.

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17.9Acetals as Protecting Groups
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Example

• The conversion shown cannot be carried
  outdirectly...

1. NaNH22. CH3I
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because the carbonyl group and thecarbanion are
incompatible functionalgroups.

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Strategy

• 1) protect CO
• 2) alkylate
• 3) restore CO

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Example Protect

HOCH2CH2OH
CH3CCH2CH2C
benzene
p-toluenesulfonic acid
CH2CH2C
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Example Alkylate
1. NaNH22. CH3I
CH2CH2C
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Example Deprotect
H2O
HCl

HOCH2CH2OH
(96)
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17.10Reaction with Primary AminesImines
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Some reactions of aldehydes and ketones
progressbeyond the nucleophilic addition stage

• Acetal formation
• Imine formation
• Compounds related to imines
• Enamines
• The Wittig reaction

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Some reactions of aldehydes and ketones
progressbeyond the nucleophilic addition stage

• Acetal formation
• Imine formation
• Compounds related to imines
• Enamines
• The Wittig reaction

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Imine (Schiff's Base) Formation
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Example

CH3NH2
CHNCH3
H2O
N-Benzylidenemethylamine (70)
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Example

CH3NH2
CHNCH3
H2O
N-Benzylidenemethylamine (70)
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Example
(CH3)2CHCH2NH2

O
NCH2CH(CH3)2
H2O
N-Cyclohexylideneisobutylamine (79)
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Example
(CH3)2CHCH2NH2

O
OH
NHCH2CH(CH3)2
NCH2CH(CH3)2
H2O
N-Cyclohexylideneisobutylamine (79)
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Some reactions of aldehydes and ketones
progressbeyond the nucleophilic addition stage

• Acetal formation
• Imine formation
• Compounds related to imines
• Enamines
• The Wittig reaction

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Some reactions of aldehydes and ketones
progressbeyond the nucleophilic addition stage

• Acetal formation
• Imine formation
• Compounds related to imines
• Enamines
• The Wittig reaction

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Reaction with Derivatives of Ammonia
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Example
(81-93)
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Reaction with Derivatives of Ammonia
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Example
H2NNH2
H2O
(73)
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Example
CCH3
phenylhydrazine
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Example
O

CH3(CH2)9CCH3
H2NNHCNH2
semicarbazide
a semicarbazone (93)
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17.11Reaction with Secondary AminesEnamines
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Some reactions of aldehydes and ketones
progressbeyond the nucleophilic addition stage

• Acetal formation
• Imine formation
• Compounds related to imines
• Enamines
• The Wittig reaction

51
Some reactions of aldehydes and ketones
progressbeyond the nucleophilic addition stage

• Acetal formation
• Imine formation
• Compounds related to imines
• Enamines
• The Wittig reaction

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Enamine Formation
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Example


(heat in benzene)

NH