14.6 Synthesis of Alcohols Using Grignard Reagents

1
14.6Synthesis of Alcohols Using Grignard
Reagents
2
Grignard reagents act as nucleophilestoward the
carbonyl group
d
d
C

MgX
O



H3O

• two-step sequence gives an alcohol as the
  isolated product

3
Grignard reagents react with

• formaldehyde to give primary alcohols
• aldehydes to give secondary alcohols
• ketones to give tertiary alcohols
• esters to give tertiary alcohols

4
Grignard reagents react with

• formaldehyde to give primary alcohols

5
Grignard reagents react with formaldehyde
H
H
H
d
d
H
C
O



H3O
H
H

• product is a primary alcohol

6
Example
Mg
diethylether
H3O
(64-69)
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Grignard reagents react with

• formaldehyde to give primary alcohols
• aldehydes to give secondary alcohols

8
Grignard reagents react with aldehydes
H
H
R'
d
d
R'
C
O



H3O
H
R'

• product is a secondary alcohol

9
Example
Mg
CH3(CH2)4CH2Br
CH3(CH2)4CH2MgBr
diethylether
H3O
(84)
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Grignard reagents react with

• formaldehyde to give primary alcohols
• aldehydes to give secondary alcohols
• ketones to give tertiary alcohols

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Grignard reagents react with ketones
R"
R"
R'
d
d
R'
C
O



H3O
R"
R'

• product is a tertiary alcohol

12
Example
Mg
CH3Cl
CH3MgCl
diethylether
O
H3O
(62)
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14.7Synthesis of AlcoholsUsing Organolithium
Reagents

• Organolithium reagents react with aldehydes and
  ketones in the same way that Grignard reagents
  do.

14
Example

1. diethyl ether 2. H3O
(76)
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14.8Synthesis of Acetylenic Alcohols
16
Using Sodium Salts of Acetylenes
NaNH2
NH3
1. NH3

2. H3O
(65-75)
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Using Acetylenic Grignard Reagents

CH3CH2MgBr
diethyl ether

CH3CH3
2. H3O
(82)
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14.9Retrosynthetic Analysis

• Retrosynthetic analysis is the process by which
  we plan a synthesis by reasoning backward from
  the desired product (the "target molecule").

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Retrosynthetic Analysis of Alcohols

• Step 1 Locate the carbon that bears the
  hydroxyl group.

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Retrosynthetic Analysis of Alcohols

• Step 2 Disconnect one of the groups attached to
  this carbon.

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Retrosynthetic Analysis of Alcohols
OH
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Retrosynthetic Analysis of Alcohols

• What remains is the combination of Grignard
  reagent and carbonyl compound that can be used to
  prepare the alcohol.

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Example

• There are two other possibilities. Can you see
  them?

CH3MgX
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Synthesis
Mg, diethyl ether
CH3Br
CH3MgBr
1.
2. H3O
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14.10Preparation of Tertiary AlcoholsFrom
Esters and Grignard Reagents
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Grignard reagents react with esters
R'
R'
d
d
C

MgX
O

• but species formed is unstable and dissociates
  under the reaction conditions to form a ketone

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Grignard reagents react with esters
R'
R'
d
d
C

MgX
O



CH3OMgX

• this ketone then goes on to react with a second
  mole of the Grignard reagent to give a tertiary
  alcohol

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Example

2 CH3MgBr
1. diethyl ether 2. H3O

• Two of the groups attached to the tertiary
  carbon come from the Grignard reagent

OH
(CH3)2CHCCH3
CH3
(73)