A novel method for the synthesis of 2-ketomethylquinolines under solvent-free conditions using microwave irradiation

Article abstract of DOI:10.1016/S0040-4039(01)00710-9

Several 2-ketomethylquinolines are synthesized by heating 2-methylquinolines with acyl chlorides, in a conventional microwave oven.

Full text of DOI:10.1016/S0040-4039(01)00710-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4363–4364
A novel method for the synthesis of 2-ketomethylquinolines under
solvent-free conditions using microwave irradiation†
Hossein Loghmani-Khouzani,* Majid M. Sadeghi, Javad Safari and Alireza Minaeifar
Department of Chemistry, Faculty of Sciences, University of Isfahan, Isfahan 81744, IR Iran
Received 2 October 2000; accepted 27 April 2001
Abstract—Several 2-ketomethylquinolines are synthesized by heating 2-methylquinolines with acyl chlorides, in a conventional
microwave oven. © 2001 Published by Elsevier Science Ltd.
The synthesis of 2-ketomethylquinolines is an impor-
tant reaction in organic chemistry because of the appli-
cations of these compounds in heterocyclic synthesis
and chemical transformations.1–6 The ability of 2-
ketomethylquinolines to act as polydentate ligands to
form stable complexes with different cations is well
known.7 Although the synthesis of 2-ketomethylquino-
lines has been extensively documented with a variety of
methods being available, many of these have limitations
in their general application.8–19 Microwave irradiation
has opened up new perspectives in synthetic organic
chemistry, not only in terms of yield and selectivity, but
Methylquinoline and 2,3-dimethylquinoline (1) were
reacted with several acyl chlorides (2) affording the
desired 2-ketomethylquinolines (3) (Scheme 1).
In order to evaluate the synergy between the solvent-
free medium and microwave irradiation in this reaction,
several experiments were carried out, as shown in Table
1. The reaction of 2-methylquinoline and benzoyl chlo-
ride without irradiation at room temperature and at
200°C was unsuccessful and the 2-methylquinoline was
recovered unchanged (entry 1, 2). Similarly the use of
irradiation in the absence of silica gel for 4 min was
unsuccessful (entry 3). Only under solvent-free condi-
tions coupled with microwave irradiation, taking
advantage of the synergy between both methodologies,
20–23
also in ease of the reaction conditions.
We report here that silica gel is a useful catalyst for the
preparation of 2-ketomethylquinolines under solvent-
free conditions using microwave irradiation. 2-
Scheme 1.
Table 1. Reaction of 2-methylquinoline with benzoyl chloride
Run
Catalyst
Temp. or MW Power
Time (min)
2-Ketomethylquinoline (%)
1
2
3
4
Silica gel
Silica gel
None
rt
60
60
4
0
0
0
200°C
900 W
400 W
Silica gel
4
91
Keywords: 2-ketomethylquinolines; silica gel; microwave irradiation; 2-methylquinoline.
* Corresponding author.
†
Dedicated to Professor J. V. Greenhill for his invaluable help.
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00710-9

4364
H. Loghmani-Khouzani et al. / Tetrahedron Letters 42 (2001) 4363–4364
were the 2-ketomethylquinolines produced in excellent
yields (entry 4). The reaction product is formed by loss
of hydrogen chloride after 4 min. Next, we studied the
reaction of 2-methylquinoline and benzoic acid or
methyl benzoate in the presence of silica gel. No special
reaction occurred.
as a broad singlet2,3 and in the IR spectra the CꢀO/CꢀC
groups in CHCl3 were observed around 1610–1640
cm−1.
In conclusion, the reported method is an interesting,
easy and novel method for the preparation of 2-
ketomethylquinolines. In addition, high yields of the
products, short reaction times, ease of work-up condi-
tions and low cost make the above method preferable
to other existing methods.
The present procedure provides a useful and convenient
method for the preparation of 2-ketomethylquinolines
in the presence of silica gel.
General experimental procedure: The preparation of 1-
phenyl-2-(quinol-2-yl)-ethan-1-one 3a (Table 2) is repre-
sentative of the general procedure employed. To an
equimolar (1 mmol) mixture of 2-methylquinoline (143
mg) and benzoyl chloride; (140 mg) placed in an open
glass container, silica gel (silica gel 60, 230–240 mesh,
Merck) (300 mg) was added and the reaction mixture
was irradiated in a microwave oven at 400 W power for
4 min. Upon completion of the reaction, as followed by
TLC examination, the product is extracted into
dichloromethane (3×10 ml). The solvent was evapo-
rated and the resulting crude material was purified on a
silica gel plate (eluent; CCl4/Et2O) affording the 1-
phenyl-2-(quinol-2-yl)-ethane-1-one (3a) in 91% yield
(Table 2).
Acknowledgements
We are grateful to the University of Isfahan Research
Council for the partial support of this work.
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