Organic Reactions Volume 4 - Sciencemadness Dot Org

PREPARATION OF AMINES BY REDUCTIVE ALKYLATION 187
Since many aromatic primary amines are prepared by reduction, it
often is possible to combine the preparation and alkylation of such an
amine into a single operation. Secondary amines are obtained in 60-
95% yields by the reduction of a mixture of an aromatic nitro compound
and an aldehyde over Raney nickel catalyst in the presence of
sodium acetate. 43 If the nitro compound contains an amino, hydroxyl,
alkoxyl, or alkyl group in the para position, the amount of tertiary
amine formed as a by-product is increased (see Table X). 43 ' 44 ' 45 Acidic
reducing agents can be used in the reductive alkylation of nitro compounds
by aldehydes other than formaldehyde; 46 evidently the concentration
of the primary amine remains so low that the condensations to
give quinoline derivatives and resins (p. 186) occur only very slowly.
In the preparation of secondary amines by the reductive alkylation of
nitrobenzene with aliphatic aldehydes, hydrogen, and Raney nickel
catalyst with ethanol as the solvent, the yields pass through a maximum
with n-butyraldehyde; methylaniline is obtained in yields of about 50%;
ethylaniline, about 60%; n-butylaniline, about 95%; n-amylaniline,
about 85%; and n-heptylaniline, about 40%. 43 n-Propylaniline has not
been prepared under comparable experimental conditions.
A few reductive alkylations of aromatic nitroso compounds to secondary
amines have been reported, but the yields are low. 47 Azobenzene
yields 50-75% of secondary amines in reactions with aliphatic aldehydes
and hydrogen over Raney nickel catalyst, but the readily available azo
compounds produced by coupling give mixtures of secondary and tertiary
amines. 48 For example, the reaction of p-phenylazodimethylaniline,
butyraldehyde, and hydrogen yields almost equal quantities of nbutylaniline
and N;N-di-n-butyl-N ; ;N'-dimethyl-p-phenylenediamine.
(CHs)2NC6H6 - ^ ^ (CHa)2NC6H1N=NC6H6 -*5£%
(«•2)
(CH3)2NC6H4N(C4H9)2 + C6H5NHC4H9
(73%) (76%)
A comparison of the various reductive alkylation procedures with
other methods for the synthesis of n-butylaniline is shown in Table IV,
p. 205.
The only aromatic aldehydes that have been used in direct reductive
alkylations of primary aromatic amines are benzaldehyde, anisaldehyde,
43 Emerson and Mohrman, J. Am. Chem. Soc, 62, 69 (1940).
44 Major, /. Am. Chem. Soc, 53, 4373 (1931).
45 Fitch, U. S. pat. 2,249,352 [C. A., 35, 6602 (1941)].
48 Emerson and Uraneck, unpublished work.
47 Girhard, Thesis, University of Illinois, 1940.
48 Emerson, Reed, and Merner, /. Am. Chem. Soc, 63, 751 (1941).