COMMUNICATION
The synthesis of amines by the homogeneous hydrogenation of
secondary and primary amides
Angel A. Nu´n˜ez Magro,a Graham R. Easthamb and David J. Cole-Hamilton*a
Received (in Cambridge, UK) 2nd May 2007, Accepted 8th June 2007
First published as an Advance Article on the web 6th July 2007
DOI: 10.1039/b706635j
N-phenylnonamide was used as substrate, in the absence of
ruthenium precatalyst, no conversion was obtained (Table 1,
entries 1 and 3). The use of [Ru(acac)3] gave a moderate yield of
61% (Table 1, entry 2) while the combination of [Ru(acac)3] and
triphos gave full conversion and high selectivity (93%) to amine (3)
(Table 1, entry 4). The corresponding alcohol, 6, was obtained as a
secondary product (7%). The origin of this alcohol (Fig. 3) is either
from the hydrolysis of amide (1) to obtain the acid (4), or of imine
(2) to obtain the aldehyde (5) followed by hydrogenation. In the
absence of additional water, full conversion was obtained with
only traces (1%) of alcohol (Table 1, entry 5). However, the
catalyst was not stable under these conditions, so water was
included in subsequent reactions.
Amides can be hydrogenated to amines using a catalyst
prepared in situ from [Ru(acac)3] and 1,1,1-tris(diphenylpho-
sphinomethyl)ethane; water is required to stabilize the catalyst
and primary amines can only be formed (selectivity up to 85%)
if ammonia is also present.
With a production of 100,000 t/a, amines are an important class of
compounds in bulk chemistry, but they also high-value inter-
mediates in organic synthesis. They are used in the manufacture of
plastics, surfactants, textiles, dyes, drugs, agrochemicals and in the
paper industry.1 Hydrogenation of amides (which are available via
aminocarbonylation)2 would be a very attractive method for the
synthesis of these high-value compounds. Hydrogenation of
carboxylic acids and their derivatives is normally a difficult process
which generally requires drastic conditions, e.g. heterogenous
copper chromite at 250 uC and 300 bar of hydrogen.3 In the
particular case of amides a mixture of primary, secondary and
tertiary amines has been obtained using copper chromite or Pd/Re/
zeolite.4 Ruthenium complexes of triphos (1,1,1-tris(diphenylpho-
sphinomethyl)ethane) are excellent homogeneous systems5 that
catalyse the hydrogenation of esters under mild conditions (40 bar,
164 uC).6 Recently some other homogeneous catalysts for the
hydrogenation of carboxylic acids have been described.7
The hydrogenation of amides could be carried out at 140 uC
without any apparent difference from reactions at 164 uC (Table 1,
entry 6) but reducing the temperature to 120 uC resulted in a loss
of selectivity, giving more alcohol from the acid (4) or aldehyde (5),
which is easier to reduce (Table 1, entry 7). Only alcohol (no
amine) was produced at 100 uC (Table 1, entry 8). The addition of
aniline reduced the stability of the catalyst, resulting in a loss of
both yield and selectivity (Table 1, entry 9).
As indicated above,8 a complex mixture of products (alcohol,
secondary amine (9), secondary amide and ester but not the
desired primary amine) was obtained by homogenous hydrogena-
tion of propanamide (Fig. 1). According to the hypothetical
mechanism proposed here (Fig. 3), primary amine (3) may react
with the substrate, primary amide (1) giving secondary amide (8),
or with the aldehyde (5) to generate imine (7). Both compounds (8)
and (7) can then lead to the secondary amine (9) by hydrogenation
Under the conditions described but using butanamide as
substrate,8 we also observed no primary amine, but the main
products were secondary and tertiary amines with traces of alcohol
(Table 2, entry 1). The tertiary amine, 10, presumably arises from
reaction of 9 with 1 followed by hydrogenation. Reducing the
concentration of water in the medium did not lead to significant
changes (Table 2, entry 2).
There has only been one report, of the homogeneous hydro-
genation of an amide.8 This also used ruthenium triphos and
produced a mixture of alcohol, secondary amine, ester and amide
from propanamide (see Fig. 1). None of the desired primary amine
was formed.8
We now report the selective hydrogenation of amides to
primary or secondary amines under relatively mild conditions
catalysed by the ruthenium–triphos catalyst (Fig. 2).6,8{ When
Fig. 1 Hydrogenation of a primary amide.8
aEaStCHEM, School of Chemistry, University of St. Andrews, St.
Andrews, Fife, Scotland, UK KY16 9ST. E-mail: djc@st-and.ac.uk;
Fax: +44 (0)1334463808; Tel: +44(0)1334463805
bLucite International, Technology Centre, PO Box 90, Wilton,
Middlesbrough, Cleveland, England, UK TS6 8JE.
Fig. 2 Hydrogenation of the N-phenylnonamide catalysed by
E-mail: graham.eastham@lucite.com; Fax: +44 (0)1642 447119;
Tel: +44 (0)1642 447109
Ru/triphos.
3154 | Chem. Commun., 2007, 3154–3156
This journal is ß The Royal Society of Chemistry 2007
Nú?ez Magro, Angel A.
