A simple and convenient procedure for the conversion of esters to secondary amides

Article abstract of DOI:10.1081/SCC-120015715

An improved procedure has been developed for the direct conversion of carboxylic esters to secondary amides by simple treatment with primary amines in presence of indium triiodide.

Full text of DOI:10.1081/SCC-120015715

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A Simple and Convenient Procedure for the Conversion
of Esters to Secondary Amides
Brindaban C. Ranu a b & Pinak Dutta a
a Department of Organic Chemistry , Indian Association for the Cultivation of Science ,
Jadavpur, Calcutta, India
b Department of Organic Chemistry , Indian Association for the Cultivation of Science ,
Jadavpur, Calcutta, 700 032, India
Published online: 21 Aug 2006.
To cite this article: Brindaban C. Ranu & Pinak Dutta (2003) A Simple and Convenient Procedure for the Conversion of Esters
to Secondary Amides, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 33:2, 297-301, DOI: 10.1081/SCC-120015715
To link to this article: http://dx.doi.org/10.1081/SCC-120015715
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 2, pp. 297–301, 2003
A Simple and Convenient Procedure for the
Conversion of Esters to Secondary Amides
*
Brindaban C. Ranu and Pinak Dutta
Department of Organic Chemistry, Indian Association for the
Cultivation of Science, Jadavpur, Calcutta, India
ABSTRACT
An improved procedure has been developed for the direct conversion
of carboxylic esters to secondary amides by simple treatment with
primary amines in presence of indium triiodide.
Key Words: Esters; Secondary amides; Indium triiodide; Amines.
The preparation of amides from the corresponding carboxylic acids
and their derivatives is a very useful process in organic synthesis.[1] As
reactions of carboxylic acids themselves with ammonia or amines to
provide the corresponding amides are of not much preparative value,[2]
*Correspondence: Brindaban C. Ranu, Department of Organic Chemistry,
Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032,
India. Fax: þ91-33-473-2805; E-mail: ocbcr@mahendra.iacs.res.in.
297
DOI: 10.1081/SCC-120015715
Copyright & 2003 by Marcel Dekker, Inc.
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Ranu and Dutta
other derivatives of acids particularly acyl halides, acid anhydrides, and
esters are most commonly used. However, limitations are associated with
the use of acyl halides and acid anhydrides and thus esters are preferred.
Usually, reactions with esters require strongly basic or acidic catalysts.
Although, quite a number of methods are reported for the conversion of
esters to amides,[3] most of these have serious drawbacks with regard to
toxicity of the reagent particularly those involving tin compounds,[3b,3c]
operational simplicity and efficiency. Thus, in recent times other
approaches involving N-acylimidazoles[4a,4b] and N-acylbenzotriazoles[4c]
have been demonstrated which also are not very simple and cost effective.
Hence, there is a scope for further improvement of this procedure.
Recently, we have reported very useful applications of indiumtriiodide
in transesterification,[5a] acylation,[5b] hydrolysis of esters,[5c] and direct
conversion of THP ether to acetate[5d] and we wish to disclose here its
another successful use in the conversion of ester to secondary amide.
The experimental procedure is very simple. A carboxylic ester was
heated (roomtemperature stirring did not lead to any reaction) with a
primary amine in presence of a catalytic amount of indium triiodide for a
certain period of time (TLC). Usual workup and purification furnished
pure amide.
Several structurally varied carboxylic esters are converted to the corre-
sponding amides by treatment with primary amines by this procedure.
The results are reported in Table 1. The yields are very high. Both aro-
matic and non-aromatic amines such as aniline and benzyl amine have
been used. This procedure is quite compatible with several sensitive
functionalities such as, chloro, methoxy, and C¼C bond.
The reaction is catalytic and proceeds even with 5 mol% of indium
triiodide although the reaction is relatively slow. The reaction does not
proceed at all in the absence of indiumtriiodide. It was also observed that
indiumalone is not capable to catalyze the process whereas, iodine
pushes the conversion to the extent of 5–10% under similar conditions.
Indiumtriiodide is thus essential for an efficient reaction. However, this
procedure is not very effective for the preparation of primary and tertiary
amides using ammonia and secondary amine, respectively.

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Conversion of Esters to Secondary Amides
299
Table 1. Conversion of carboxylic esters to secondary amides.
Entry
R
R1
Me
PhCH2
Menthyl
i-Pr
R2
Time (h)
Yield (%)a
1
2
3
4
PhCH2
Ph
PhCH2
PhCH2
PhCH2
PhCH2
PhCH2
PhCH2
7
7.5
8
92
90
93
92
8
5
Me
PhCH2
5.5
87
6
7
Ph2CH
CH3(CH2)14
Me
Et
PhCH2
PhCH2
7.5
8.5
90
91
8
Me
PhCH2
7.5
83
9
10
11
12
13
PhCH2
Ph2CH
CH3(CH2)16
Ph
Me
Me
Et
CH2Ph
CH2Ph
Ph
Ph
Ph
Ph
Ph
8.5
9
8
9
8.5
90
85
91
93
91
CH3
aYields refer to those of pure isolated products fully characterized by comparison
of their spectral (IR and NMR) data and melting point of those reported.
In conclusion, the present procedure provides an efficient methodol-
ogy for the conversion of a carboxylic ester to a secondary amide. The
operational simplicity, no involvement of toxic reagents and high yield
make this procedure a practical alternative to the existing methods.[3,4]
GENERAL EXPERIMENTAL PROCEDURE
A carboxylic ester (1 mmol) was heated at an oil bath temperature of
110–120ꢀC in a primary amine (2 cm3) in presence of catalytic amount of
indiumtriiodide (20 mol%), freshly prepared by stirring indiumand iodine
in THF.[6] After the reaction was over (TLC), the reaction mixture was

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Ranu and Dutta
extracted with ether and the ether extract was washed successively with
aqueous hydrochloric acid (1N) to remove excess amine, brine, and dried
over Na2SO4. Evaporation of solvent left a crude solidꢀwhich was purified
by recrystallization fromether–petroleumether (60–80 C) solvent mixture
to furnish pure amide. The same procedure is followed for the conversion
of all carboxylic esters to the corresponding amides listed in Table 1. Most
of these amides are known compounds and are easily identified by their
melting points and spectral data. New compounds are also in good agree-
ment with their spectral and analytical data.
ACKNOWLEDGMENTS
This investigation has enjoyed financial support fromCSIR,
New Delhi. P.D. also thanks CSIR for his fellowship.
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Received in the UK September 11, 2001

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