Cryst. Res. Technol. 37 2002 2-3 309–317
© WILEY-VCH Verlag Berlin GmbH, 13086 Berlin, 2002 0232-1300/02/2-303-0309 $ 17.50+.50/0
The crystal structure and molecular conformation of solvated 1-(4-methoxybenzenesulfonyl)-5-oxo-
pyrrolidine-2-carboxamide (C
12
H
14
O
5
N
2
S.H
2
O), synthesized and biologically evaluated as a possible
antineoplastic agent, have been studied by X-ray analysis and AM1 molecular orbital methods. The
compound crystallizes in the monoclinic space group P2
1
, with a = 9.661(4), b = 7.246(3), c =
11.378(5)Å, β = 113.42(2)°, Z= 2. The structure has been solved by direct methods and refined to R =
0.0438 for 1721 observed reflections. The crystal structure consists of an essentially planar
methoxyphenyl ring linked to a 2- carboxamide substituted oxo-pyrrolidine moiety via sulfonyl group
and a lattice water molecule. The conformational analysis of the title compound investigated by semi-
empirical quantum mechanical AM1 calculations shows a good agreement with the X-ray structure
except a rotation of the carboxamide moiety about the C (oxo-pyrrolidine) - C (carboxamide) bond. In
the solid state, the molecules translated in the b-direction are linked by intermolecular N-H⋅⋅⋅O
hydrogen bonds to form infinite one-dimensional chain.
Keywords: X-ray crystal structure, conformation, AM1 molecular mechanics, oxo-pyrrolidine
derivative
(Received October 12, 2001; Accepted November 19, 2001)
1.Introduction
The oxopyrrolidine-2-carboxylic acid, an important heterocyclic system in medicinal
chemistry, can be viewed as the cyclized version of glutamic acid. Several structural variants
of glutamic acid such as glutarimides, glutaramides, glutamines, isoglutamines,
oxopyrrolidines etc., display useful biological activity as possible antineoplastic and
therapeutic agents (GOSWAMI et al., 2001; P URKAYASTHA et al., 1994; CHOI et al., 1988;
BANDOLI et al., 1987). As a part of an ongoing program on the synthesis and characterization
of novel biologically active systems containing an oxopyrrolidine moiety, the title compound
1-(4-methoxybenzenesulfonyl)-5-oxo-pyrrolidine-2-carboxamide ( 1) was synthesized. The
compound (1) showed encouraging antineoplastic activity against Ehrlich Ascites Carcinoma
(EAC) in Swiss albino mice (inhibition of EAC cells: 75.70%; inhibition of EAC fluid
weight: 66.67%). In the present paper we report the structural characterization and molecular
conformation of (1) .H
2
O by X-ray analysis and semi-empirical AM1 molecular orbital
calculations.
S. BANERJEE, A. K. MUKHERJEE , D. GOSWAMI*, A. U. DE* , M. HELLIWELL **
Department of Physics, Jadavpur University, Calcutta, India
*Division of Medicinal & Pharmaceutical Chemistry, Department of Pharmaceutical Technology,
Jadavpur University, Calcutta, India
**Department of Chemistry, University of Manchester, England
Structure and Conformation of Solvated 1-(4-
methoxybenzenesulfonyl)-5-oxo-pyrrolidine-2-
carboxamide