Organic Reactions Volume 4 - Sciencemadness Dot Org

PREPARATION OF AMINES BY REDUCTIVE ALKYLATION 177
tion of secondary amines consists in the isolation and subsequent reduction
of the Schiff's base (see p. 189).
RCHO + R'NH2 -> RCH=NR 7 -^5> RCH2NHR'
Certain tertiary amines containing three identical groups attached
to the nitrogen atom can be prepared from ammonia and a carbonyl
compound. Those containing two identical groups can be prepared
either from a secondary amine and one mole of an aldehyde or a ketone,
or from a primary amine and two moles of an aldehyde or a ketone.
T&tiary amines containing three dissimilar alkyl groups can be prepared
only from a secondary amine and a carbonyl compound.
3R'C0R + NH3 + 6(H) -» I \cH ) N
2R'C0R + R"NH2 + 4(H) \^ /R\
RV }[ XHjNR'
R'COR + V)HNHR" + 2(H) ' \ R A
R R'
R'COR + R"R'"NH + 2(H) -» NcHNR'R'"
R /
(R = hydrogen or alkyl)
If an amine to be used in a reductive alkylation is one which itself is
prepared by a process of reduction it may be possible to employ the
precursor instead of the amine (see p. 183). For example, di-n-butylaniline
is prepared conveniently by hydrogenation of a mixture of
nitrobenzene and w-butyraldehyde. 2
C6H5NO2 + 2W-C3H7CHO + 5H2 -» C6H6N(C4Hg)2 -f 4H2O
The usefulness of each of the various reactions formulated above is
modified by the structural features of the carbonyl compound and of
the amine employed or formed. A carbonyl compound which has little
tendency to undergo addition of ammonia or an amine may be reduced
largely to the carbinol, with the result that the reductive alkylation
fails. Similarly, structural features of the particular reactants may favor
the formation of an amine or amines of a degree of alkylation different
from that desired. Such effects of structure are considered in detail in
the next section. It may be said at the outset that in a great many
preparations it has been found possible to obtain high yields of amines
of the desired degree of alkylation by proper choice of the conditions.
2 Emerson and Uraneck, J. Awi. Chem. Soc, 63, 749 (1941).