Page 213 - Academic Press Encyclopedia of Physical Science and Technology 3rd Organic Chemistry

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Organic Chemistry, Synthesis 499

2. Reactions of Alcohols O O
Alcohols are easily converted to halides by displacement HF CH 2 F
CHN 2 N 2
reactions. It is necessary to improve the leaving group
ability of the hydroxyl by protonation or by conversion to
(9)
a sulfonate or phosphate ester for successful displacement:
Dihalomethylation may also be effected by reaction of
CH 3
O dihalocarbanionswithcarbonylcompoundsorbythealky-
CH 3 CH 2 CH 2 CH 2 OH CH 3 CH 2 CH 2 CH 2 OS CH 3 lation of a carbanion with chloroform:
O O
SO 2 Cl
R OH
CH 3 R R LiCHCl 2 (10)
O R CHCl 2
NaBr
CH 3 CH 2 CH 2 CH 2 OS CH 3 CH 3 CH 2 CH 2 CH 2 Br
Halomethylenation is possible by reaction of an appro-
O
SO 3 Na priately halogenated Wittig reagent with an aldehyde or
ketone.
(6)
In reactions of primary and secondary alcohols with hy- B. Hydroxylation
drogen fluoride, hydrogen chloride, or hydrogen bromide,
The selective direct hydroxylation of alkanes is not a
competing rearrangements of the cationic intermediate
practical general laboratory transformation although en-
may lessen the selectivity of the reaction:
zymatic hydroxylation of unactivated carbons is a major
CH 3 OH CH 3 metabolic reaction in animals. Preparatively hydroxyla-
tion is more easily accomplished by hydrolysis of a halide.
CH CH HBr CBr CH 2 CH 3
The ease of hydrolysis, iodide > bromide > chloride, par-
CH 3 CH 3 CH 3 allels the synthetic utility of the reaction:
(7) H 2 O
CH 3 CH 2 CH 2 CH 2 I CH 3 CH 2 CH 2 CH 2 OH (11)
Treatment of an alcohol with thionyl chloride, sulfur
tetrafluoride, phosphorous tribromide, or phosphorous
Hydrolysis of fluorides is of little consequene. In order to
pentachloride can yield the unrearranged halide regios-
minimize side reactions, such as elimination to an alkene
electively.
or rearrangement, S N 2 reaction conditions are desirable.
However,undersomeconditionseliminationreactionscan
be useful or desired. The synthesis of phenol from treat-
3. Haloalkylation Reactions
ment of chlorobenzene with hydroxide ion first proceeds
Halogenation can also be effected simultaneously with by elimination to form benzyne followed in a second step
carbon carbon bond forming reactions employing halo- by the addition of water to form phenol.
genated reactants. The chloromethylation reaction of aro-
matics with chloromethyl methyl ether and a Lewis acid is
1. Addition of Water to Alkenes
probably the best known example of such a reaction. It is
possible to avoid the use of the toxic chloromethyl methyl The direct hydroxylation of alkenes with aqueous acid
ether by in situ formation of the reagent with formalde- results in the Markovnikov addition of water. Under these
hyde and hydrogen chloride: conditions, rearrangements of the intermediate cation are
possible with a corresponding loss of regiospecificity.
CH 2 Cl
HCl/ZnCl 2
HCHO (8) CH 3 CH 3

/
H H 2 O
C CH 2 C CH 3 (CH 3 ) 3 COH
Alpha haloketones may be prepared by the reaction of
CH 3 CH 3
carboxylic acid halides with diazomethane. Direct treat-
(12)
ment of a diazoketone with a hydrogen halide, in a related
reaction, also yields alpha haloketones or, under modi- Regiospecific addition of water in an anti-Markovnikov
fied conditions, dihaloketones substituted with different sense is readily possible via hydroboration of an olefin.
halogens: The addition of borane or alkylborohydrides can be highly