JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 603
OCTOBER, 603–605
Green and efficient method for the acylation of amines and phenols in
the presence of hydrotalcite in water
Ahmad Reza Massah*, Mitra Toghyani and Batool Hojati Najafabadi
Department of Chemistry, Shahreza Branch, Islamic Azad University, 311-86145, Shahreza, Isfahan, Iran
In this study a mild, efficient and environmentally friendly method has been developed for the synthesis of amides
and esters in the presence of hydrotalcite in water at room temperature. Different types of amines and phenols have
been used and in all cases the products were obtained in moderate to high yields after an easy work-up. This method
follows the principles of green chemistry.
Keywords: hydrotalcite, water, acylation, amines, phenols, green synthesis
The acylation of phenols and amines is very important in vari-
ous organic transformations.1 Acylation is usually carried out
by treating phenols or amines with carboxylic acid chlorides or
anhydrides in the presence of acid or base catalyst in a suitable
organic solvent. Recently, N,N,N′,N′-tetramethylethylenedi-
amine (TMEDA) was used as base catalyst for acylation of
alcohols and thiols.2 On the other hand, Lewis acids such as
metal halides and oxide,3 metal triflates,4 and metal perchlo-
rates,5 and several solid acids such as zeolite6 have also
been utilised to achieve the acylation of phenols and amines.
However, these methods have some disadvantages such as
exothermic reaction, the formation of by products, compli-
cated conditions, excess acylating agents and toxic organic
solvents. The main drawbacks of homogeneous process include
lack of reusability of the catalyst, hazardous nature of liquid
base like pyridine or DMAP (highly toxic e.g., intravenous
LD50 in the rat: 56 mg kg−1) and post-reaction work-up of
spent liquid bases. However, despite the efficiency of the latter
protocols, the development of less expensive and environmen-
tally benign reaction conditions is a major goal for organic
synthesis.
In recent years, organic reactions that can proceed in water
have attracted great interest because of significant environ-
mental and economic advantages over those occurring in
organic solvents.10 As a part of our ongoing research project to
develop newer synthetic methodologies, particularly in acyla-
tion reactions,11 we now report our results on the hydrotalcite
catalysed acylation of amines and phenols, with some carbox-
ylic acid anhydrides and chlorides in water (Scheme 1). Due to
its operational simplicity, generality and efficacy, this method
may have wider applicability for the acylation reaction of
amines and phenols and it represents a better, eco-friendly
alternative to many existing procedures.
Results and discussions
In order to optimise the reaction conditions, we chose the
reaction of 4-methoxyaniline, and 4-nitrobenzoyl chloride as
a reaction model. To start with, the reaction was screened in
different solvents. Water provided excellent yields and proved
to be the solvent of choice as a green solvent. Next this conver-
sion was carried out at room temperature using different
amount of water including 3 mL (70%), 2 mL (78%), and
1 mL (83%). However the best yield of product (89%) was
obtained when 0.5 mL of water was used as solvent. The effect
of the amount of catalyst on the reaction was also investigated.
The yield of amide increased with increasing the amounts of
the hydrotalcite from 0.05 to 0.2 g. No improvement in the
yield was found with a further increase of the catalyst. Hence,
the optimal amount of hydrotalcite was chosen as 0.2 g based
on 1.0 mmol of 4-methoxyaniline and 1.2 mmol of 4-nitroben-
zoylchloride (1.0 mmol of benzoic anhydride, 4.0 mmol of
acetic anhydride) for further study.
To demonstrate the scope of these reaction conditions, a
variety of phenols and amines were acylated to form the
corresponding ester and amide in good to high yields and
high purity at ambient temperature in water. Several examples
illustrating the usefulness of this efficient and rapid acylation
procedure are summarised in Table 1. Various functional
groups such as Me, Cl, OMe, NO2, and Br were tolerated under
these conditions. In spite of the fact that the presences of the
chloro and nitro group(s) in the aromatic amines and phenols
make the amino and hydroxy group of these substrates poor
nucleophiles, good to excellent yields of the corresponding
Therefore, it was desirable to develop a solid base catalyst
which would overcome these disadvantages and provide a
commercial process involving easy handling of the catalyst,
separation of products, decreased corrosion of the reactor, and
possible regeneration and re-use of the catalyst.
Hydrotalcite (HT) or hydrotalcite-like compounds (HTlc)
are layered double hydroxides belonging to the class of anionic
clays. The structure of these compounds are very similar to
that of brucite, Mg(OH)2, where some of Mg2+ represented
as [M(II)] are isomorphously replaced by Al3+ represented
as [M(III)] and the net positive charge is compensated by an
inter-layered exchangeable anion (An−). The general formula
of these compounds can be represented as: [M(II)1−x M(III)x
(OH)2] An−x/n·mH2O. Hydrotalcite has recently received much
attention as a solid base catalyst. The basicity of the hydro-
talcite could be modified either by changing the divalent to
trivalent cations molar ratio [M(II)/M(III)] or by intercalation
of a suitable anion in the interlayer space. These catalysts
can be used for different purposes in organic chemistry,
such as condensations reactions,7 alkylation of phenol,8 and
N-arylation of amines.9
Scheme 1 Acylation of phenols and amines in water.
* Correspondent. E-mail: massah@iaush.ac.ir