Preparation of Alcohols

Alcohols can be formed from many, many different sources. More than 7
different functional groups can be converted to an alcohol.
Ketones
Ethers Epoxides
Aldehydes
O
R O O
R' R C
Alkenes R
R'
CH CH2
R C D
B E, F Carboxylic Acids
O
Alcohols G
R C
R—OH O H
A
Alkyl Halides Diols
R—X HO OH Esters
H
R2 C CR2 O
R C
O R'
Legend:
A: Substitution only. Hydroxide nucleophile; difficult reaction because of competing elimination (E2).
See Carey Chpt. 8.
B: Hydration can go in two ways to give different regioselectivities. Oxymercuration-demercuration gives
Markovnikov product, hydroboration/oxidation gives opposite. Generally clean and high-yielding.
Carey 6.10-11.
D i o l s ("vicinal" diols) also can be formed by two complementary sequences. Hydroxylation (KMnO4
or OsO4 with reductive cleavage) yields vicinal diols with syn addition (Carey 15.5). Epoxidation
followed by cleavage (peracid, then acid or basic cleavage) yields anti- or trans addition.
C: Benzyl ethers can be cleaved by hydrogenolysis (H2/Pt or Pd) to give the alcohol.
R O H2 R O H
CH2 + CH
H 2
Pt or Pd
D: Addition of hydride reagents (LiAlH4, or NaBH4) or organometallic reagents (RMgBr or R-Li) yield
alcohols. The process converts the carbonyl carbon to a carbinol carbon (1° from reduction of
aldehyde; 2° from reduction of ketone or alkylation of aldehyde; 3° from alkylation of ketone). Carey
15.2.
E: Addition of hydride reagents (LiAlH4, or NaBH4) or organometallic reagents (RMgBr or R-Li) yield
alcohols. Attack of the nucleophile is usually on the less hindered carbon, and trans geometry
usually is seen. Carey 15.4.
F: Hydroxide attacks the less hindered carbon to give the trans diol. Carey 16.12-13.
G: Alcohols are formed by the use of hydride reagents: LiAlH4, BH3. NaBH4 doesn't work (not
reactive enough), even though BH3 does. Go figure. Carey Table 15.3.
H: Two ways to do this, depending on which part of the R' H
ester should yield the alcohol. First, simple H2O
hydrolysis of an ester gives an alcohol and an acid. O O O O + HO
C C R'
+ -
R H or OH R
Second, reduction of an ester gives two alcohol
products. Often, with simple esters, one of the
alcohols is small, water soluble or volatile, and can O
be separated easily from the other (Carey Table R C R CH2 O H + HO R'
15.3.): O R'
Hydration of Alkenes

CH3 CH3
BH3 H H2 O2 H
THF BR2 NaOH OH
CH3 H H

H CH3 CH3
Hg(OAc)2 OH NaBH4 OH
H2 O H H
HgOAc H
Hydroxylation of Alkenes

H O
O Os
OsO4 NaHSO3
O O
Pyridine H2 O
CH3 H
H OH
Basic KMnO 4
OH
CH3
CH3

H H
RCO3 H NaOH OH
O
CH2 Cl2 H2 O OH
CH3 CH3
Reduction of Carbonyl Compounds

Aldehydes Ketones Esters Carboxylic Acids

O
O C O CH3 O
H3C H2
C O
CH C H3 C(H2 C)8 C
H
H3C OH
NaBH4 NaBH4 LiAlH4 LiAlH4
CH3 OH CH3 OH ether ether
H2
OH C OH
H3C H2 H3 C(H2 C)8 CH2
C OH
CH C + HO CH3 OH
H2
H3C