DOI: 10.1002/cctc.201500601
Full Papers
A Heterogeneous Niobium(V) Oxide Catalyst for the Direct
Amidation of Esters
[a]
[b]
[a]
[a, b]
Md. Ayub Ali, S. M. A. Hakim Siddiki, Kenichi Kon, and Ken-ichi Shimizu*
5
+
This study reports the first example of a heterogeneous cata-
lytic system for the direct amidation of various esters with
amines. Of 25 types of catalyst, Nb O shows the highest activi-
between the Nb Lewis acid site and carbonyl oxygen, which
can result in high reactivity of the ester with a nucleophile
(amine) and, thus, high activity of Nb O . Kinetic results show
2
5
2
5
ty in the amidation of methyl benzoate with aniline. Nb O5
that the activity of Nb O does not markedly decrease with in-
2 5
2
gives high yields in the amidation of various esters and amines
under solvent-free conditions, is reusable, and shows higher
turnover numbers than previously reported homogeneous cat-
creasing aniline concentration, in contrast to reference cata-
lysts TiO and La(OTf) . The relatively low negative impact of
2
3
basic molecules on the Lewis acid catalysis of Nb O also ena-
2
5
alysts such as La(OTf) . IR spectroscopic studies of ethyl acetate
bles its high activity.
3
adsorbed on the catalysts show a strong acid–base interaction
Introduction
[
4a]
[4b]
Amides are ubiquitous and important functional groups in nat-
ural and synthetic organic compounds, such as pharmaceuti-
methods with N-heterocyclic carbenes, K PO , and organo-
3 4
[
4c,d]
base
tolerate only amino alcohols as amines. Although
[1]
[5a]
[5b]
[5c]
cally and biologically important molecules. Amides can be
Sb(OEt)3, Zr(OtBu)4, and triazabicyclo[4.4.0]dec-5-ene are
effective homogeneous catalysts for the amidation of esters
with various amines, these systems require high catalyst load-
[
2]
prepared from the reaction of amines with carboxylic acids,
[
3–9]
[10]
esters,
or amides (transamidation). Conventionally, the re-
[
6]
[7]
action of carboxylic acids with amines is performed via activat-
ed carboxylic acid derivatives, such as carboxylic acid anhy-
drides or acyl chlorides, or by using stoichiometric amounts of
ing (10–30 mol%). Recently, sodium methoxide, La(OTf)3,
[
5d]
and Lewis acids supported on ionic liquids have been re-
ported as more effective catalysts for the amidation of esters
with various amines, though these methods are not effective
[1c]
condensation reagents, which generates a large amount of
unwanted co-products. Recently, atom-efficient catalytic meth-
ods for the direct amidation of carboxylic acids with amines
[
8a]
for amidations with less reactive amines such as aniline. Ru
[
8b,c]
and Ir complexes
catalyze direct amidation from esters and
[2,5]
have been developed.
amines driven by a hydrogen transfer-type mechanism with
Direct amidation of esters with amines is a promising alter-
native synthetic method for amides. Several non-catalytic
methods have been reported for the direct amidation of esters
with amines that involve a large amount of promoters and
suffer from low atom efficiency due to the generation of stoi-
liberation of H . These excellent homogeneous catalytic sys-
2
tems suffer from the necessity of solvent and difficulties in cat-
alyst reuse and catalyst–product separation (except for Lewis
[
5d]
acid/ionic liquids ). A few heterogeneous catalysts (montmor-
[
9a,b]
[9b]
illonite clay
and Al O3 ) catalyze the reaction of methyl
2
[3]
chiometric amounts of unwanted co-products. To overcome
benzoate with NH to give a mixture of benzamide and benzo-
3
[4–8]
these problems, homogeneous catalytic methods
have also
nitrile. However, the yields of the amide are low and the sub-
strate scopes of various esters and amines are not reported.
Thus, it is desirable to develop a reusable heterogeneous cata-
lytic method for direct amidation from various esters and
amines.
been developed for the amidation of esters with amines but
the reported methods suffer from drawbacks, including limited
substrate scope, high catalyst loading (>10 mol% with respect
to substrate), and the need for additives. For example, catalytic
Our group has studied direct amide bond formation from
amines and amides with heterogeneous Lewis acidic cata-
[
a] M. A. Ali, Dr. K. Kon, Prof. K.-i. Shimizu
Catalysis Research Center
Hokkaido University
N-21, W-10, Sapporo 001-0021 (Japan)
E-mail: kshimizu@cat.hokudai.ac.jp
[10]
lysts. Recently, we reported the first example of the direct
synthesis of cyclic imides from dicarboxylic acids and amines
[
11]
by using Nb O5 as a reusable Lewis acid catalyst. In the
2
course of our continuous efforts on Lewis acid catalysis by
metal oxides, we have found that Nb O is an effective and re-
[
b] Dr. S. M. A. H. Siddiki, Prof. K.-i. Shimizu
Elements Strategy Initiative for Catalysts and Batteries
Kyoto University
2
5
usable catalyst for the direct amidation of esters with amines.
Herein, we report the first successful example of a heterogene-
ous and reusable catalyst for the direct synthesis of amides
from various esters and amines under solvent-free conditions.
Katsura, Kyoto 615-8520 (Japan)
ChemCatChem 2015, 7, 2705 – 2710
2705
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim