Download Alcohols I - ChemConnections

Sources of Alcohols
Reactions discussed earlier:
Catalytic Reduction
Hydration of alkenes
Alcohols
Hydroboration-oxidation of alkenes
Hydrolysis of alkyl halides
Syntheses using
Grignard reagents
Organolithium reagents
Question
• The reaction between propanal and
ethylmagnesium chloride followed by
H3O+ will produce
•
A)
B)
•
C)
D)
Sources of Alcohols
New methods or reagents:
Reduction of aldehydes and ketones
Reduction of carboxylic acids
Reduction of esters
Reaction of Grignard reagents with epoxides
Diols by hydroxylation of alkenes
Reduction of Aldehydes and Ketones
Example: Catalytic Hydrogenation
Reduction of Aldehydes Gives Primary Alcohols
O
CH3O
R
R
C
H
O
OH
C
H
CH
+
H2
Pt, ethanol
H
CH3O
CH2OH
(92%)
Example: Catalytic Hydrogenation
Reduction of Ketones Gives Secondary Alcohols
C
H
O
OH
C
R'
H
O
R
R
+
R'
H2
OH
Pt
ethanol
(93-95%)
Retrosynthetic Analysis
R
H
C
R
OH
R'
O
H
R
C
C
H :–
H
H
Question
• Which isomer of C4H10O can be
prepared by hydrogenation of a ketone?
•
A)
B)
•
C)
D)
R
OH
H :–
C
R'
O
Examples: Sodium Borohydride
Metal Hydride Reducing Agents
Aldehyde
O 2N
H
+
Na
H
B
–
O
H
O 2N
NaBH4
CH2OH
CH
methanol
H
(82%)
Ketone
-
Act as hydride donors (H )
The analagous deuterated agents
NaBD 4 and LiAlD 4 produce (D )
and work in the same way
O
NaBH4
ethanol
H OH
(84%)
Lithium Aluminum Hydride
Question
• Reduction of acetaldehyde (CH3CH=O)
with NaBD4 in H2O produces:
More reactive than sodium borohydride.
Cannot use protic solvents:
water, ethanol, methanol, etc..
•
A)
B)
•
C)
D)
Diethyl ether is most commonly used solvent.
Examples: Lithium Aluminum Hydride
Aldehyde
O
CH3(CH2)5CH
1. LiAlH4
diethyl ether
2. H2O
CH3(CH2)5CH2OH
(86%)
Ketone
O
(C6H5)2CHCCH 3
1. LiAlH4
diethyl ether
2. H2O
OH
(C6H5)2CHCHCH 3
(84%)
Question
• Which one of the isomeric alcohols of
formula C5H12O can be prepared by
LiAlH4 reduction
•
of a ketone?
•
A) 1-pentanol
•
B) 2-methyl-2-butanol
•
C) 3-methyl-2-butanol
•
D) 2,2-dimethyl-1-propanol
Selectivity
Neither NaBH4 or LiAlH 4
reduces carbon-carbon
double bonds.
Preparation of Alcohols By Reduction
of Carboxylic Acids and Esters
O
1. LiAlH4
diethyl ether
2. H2O
(90%)
H
OH
Example: Reduction of a Carboxylic Acid
Reduction of Carboxylic Acids
Gives Primary Alcohols
R
R
C
HO
O
H
C
OH
O
1. LiAlH4
diethyl ether
COH
2. H2O
H
CH2OH
(78%)
lithium aluminum hydride is only
effective reducing agent; not sodium borohydride
Reduction of Esters
Gives Primary Alcohols
Example: Reduction of an Ester
O
COCH2CH3
Lithium aluminum hydride is overwhelmingly
preferred for reductions of esters.
Sodium borohydride reduction is too slow.
1. LiAlH4
diethyl ether
Catalytic hydrogenation is used in industry,
but requires a special catalyst, high
temperature, and high pressure.
2. H2O
CH2OH +
(90%)
CH3CH2OH
Question
• Which of the esters shown, after
reduction with LiAlH4 and aqueous
workup, will yield two
•
molecules of only a single alcohol?
•
A) CH3CH2CO2CH2CH3
•
B) C6H5CO2CH2C6H5
•
C) C6H5CO2C6H5
•
D) none of these
Reaction of Grignard Reagents
with Epoxides
R
MgX
MgX
CH2
H 2C
Example
CH2
CH3(CH2)4CH2MgBr
MgBr + H2C
R
CH2
Preparation of Alcohols From Epoxides
O
CH2
O
OMgX
MgX
H3O+
RCH2CH2OH
1. diethyl ether
2. H3O+
CH3(CH2)4CH2CH2CH2OH
(71%)
Question
• Select the best combination of reagents to prepare
2-phenylethanol from bromobenzene.
•
A)
1. Mg, diethyl ether; 2. ethylene oxide; 3.
H3O+
•
B)
1. Mg, diethyl ether; 2. acetaldehyde
(CH3CH=O); 3. H3O+
•
C)
1. Mg, diethyl ether; 2. 2-chloroethanol;
3. H3O+
•
D)
1. Mg, diethyl ether; 2. CH3CH2OCH2CH3;
3. H3O+
Preparation of Diols
Example: Reduction of a Dialdehyde
Reactions used to prepare alcohols
O
O
Reduction of dicarbonyl compounds
HCCH
HCCH2CHCH 2CH
Hydroxylation of alkenes
H2 (100 atm)
Ni, 125°
125°C
CH3
HOCH2CH2CHCH 2CH2OH
CH3
3-Methyl-1,5-pentanediol
(81-83%)
Hydroxylation of Alkenes
→ Vicinal Diols
Vicinal diols have hydroxyl groups on adjacent
carbons.
Ethylene glycol (HOCH2CH2OH) is most familiar
example.
Osmium Tetraoxide is Key Reagent
Stereospecific syn addition of (2) —OH groups:
C
C
C
HO
OsO4
C
C
OH
C
O
O
Os
O
O
Intermediate is a cyclic osmate ester
Example
Example
CH3(CH2)7CH
CH2
(CH3)3COOH
OsO
OsO4 (cat)
terttert-Butyl alcohol
HO–
CH3(CH2)7CHCH 2OH
OH
(73%)
Stereospecific syn addition produces cis
1,2 product (axial-equatorial
configuration)
H
(CH3)3COOH
OsO
OsO4 (cat)
H
terttert-Butyl alcohol
HO–
H
H
HO
(62%)
OH
Question
• Which compound is produced when
cyclohexene reacts with OsO4, (CH3)3COOH,
tert-butyl alcohol, HO-?
•
A)
B)
•
C)
D)