Page 215 - Academic Press Encyclopedia of Physical Science and Technology 3rd Organic Chemistry

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Organic Chemistry, Synthesis 501

conditions required for direct amination; therefore, func- Acids may be converted to amides through reaction of
tional group transformations are employed. the acid chloride with an amine:
O
1. Displacement of Halides
R NHCH 2 R
RCOCl R CH 2 NH 2
Thereactionofanalkylhalidewithammoniaoftenleadsto
a mixture of primary, secondary, and tertiary amines where O (24)
more than one alkyl halide molecule has reacted with a
LiAlH 4
single ammonia. Selective formation of the primary amine R NHCH 2 R R CH 2 NHCH 2 R
maybepossibleifthealkylhalideissolubleinthepresence
of a large excess of ammonia. On a laboratory scale, the
Reduction of the acid amide to a new amine is possible
Gabriel synthesis or one of its modifications may be a
by catalytic hydrogenation using a metal catalyst (such
more practical approach. The alkyl halide is treated with
as platinum oxide, palladium oxide, palladium on barium
phthalimide or an alkali metal salt of phthalimide. The
sulfate, or Raney nickel). Metal hydrides such as lithium
product alkylated phthalimide is hydrolyzed to selectively
aluminum hydride, aluminum trihydride(alane), or dibo-
form the primary amine:
rane will also conveniently reduce amides to amines.
The direct conversion of acids to amines via an acyl
O O
nitrene intermediate is also possible by the Hofmann,
N Na CH 3 CH 2 CH 2 Br N CH 2 CH 2 CH 3 NaBr
Schmidt, or Curtius rearrangement:
O O O
O
NaOH ONa
ONa H 2 NCH 2 CH 2 CH 3 (21) H 2 O
R N 3 RN C O N 2 RNH 2 CO 2
O
(25)
Selective formation of secondary or tertiary amines by
reaction of an alkyl or dialkyl amine is generally ineffec-
tive for the same reason that the reaction of ammonia is 3. Allylic Amination
not selective. However, direct reaction of an amine with
Allylic amination of alkenes via sulfur and selenium
an excess of an alkyl halide can be a useful method to the
reagents is also possible. In the latter case, the reagent
preparation of quaternary ammonium salts.
is prepared by treatment of selenium with chloramine
T, in the former, by reaction of thionyl chloride with
2. Derivatization of Carbonyl Compounds p-toluenesufonamide:
An especially useful way to prepare secondary and ter- 2CH 3 SO 2 NH 2 SOCl 2 CH 3 SO 2 N S NSO 2 CH 2
tiary amines is via an intermediate imine or iminium ion.
R CH CH CH 2
For example, reaction of formaldehyde with a secondary RCH 2 CH CH 2
NH (26)
amine in the presence of formic acid leads directly to a
SO 2 CH 3
new tertiary amine:
R R
4. Mannich Reaction
NH HCHO N CH 2 HCO 2 H
R R Condensation of formaldehyde with an amine forms an
iminum ion which can act as an electrophile in further syn-
R
thetic transformations. One result is the addition of a car-

N CH 3 CO 2 H (22)
bon bearing an amine to the nucleophile. Commonly the
R
reaction is effected with enolizable carbonyl compounds;
however, the reaction will work with any compound with
Dimethyl amines are conveniently prepared by reaction
an activated hydrogen:
of formaldehyde with a primary amine in the presence of
formic acid: OH O
CH 3 CH 3 CH 3
HCHO NH N CH 2 CH 2 CH 3 N CH 2 CH 2 CH 3
HCHO HCO 2 H
CH 3 CH 2 CH 2 NH 2 CH 3 CH 3 CH 3
(23) (27)
CH 3 CH 2 CH 2 N(CH 3 ) 2