J Chem Crystallogr
DOI 10.1007/s10870-012-0386-6
ORIGINAL PAPER
Unusual C–Hꢀꢀꢀp Interactions in the Structure
of 3,4,5-Trimethoxy-N-p-tolylbenzamide
•
Aamer Saeed Jim Simpson
Received: 16 June 2012 / Accepted: 6 November 2012
ꢀ Springer Science+Business Media New York 2012
Abstract 3,4,5-trimethoxy-N-p-tolylbenzamide, C17H19NO4,
(1), is a benzanilide derivative derived from p-toluidine and
3,4,5-trimethoxybenzoyl chloride. The structure was identified
from spectroscopic and elemental analysis data and unambigu-
ously confirmed by the single crystal X-ray diffraction studies in
Introduction
N-substituted benzamides are an important class of struc-
turally simple compounds with a wide range of medicinal,
commercial and synthetic applications. For example declo-
pramide (3-chloroprocainamide) is a well known anticancer
compound [1]. The cytotoxic effects of N-(3-chloro-1,
4-dioxo, 4-dihydro-naphthalen-2-yl)-benzamide on andro-
gen-dependent and independent prostate cancer cell lines
have also been reported [2]. 2-Oxy-6-fluoro-N-((S)-1-
hydroxy-3-phenylpropan-2-yl)-benzamides are inhibitors of
hepatitis C virus polymerase [3] while alo-nitrobenzamides
find potential applications against human African trypano-
somiasis [4] and aminopiperidine benzamides have been
identified as MCHr1 antagonists [5].
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space group P21, with a = 5.1065(7) A; b = 13.9148(18) A;
˚
c = 11.2054(14) A; b = 103.118(7)ꢁ; Z = 2. In the X-ray
structure packing is predictably influenced by strong N–HꢀꢀꢀO
hydrogen bonds, augmented by C–HꢀꢀꢀO contacts generating
R21(6) ring motifs and forming chains of molecules along the
b axis. Chains are also linked in a head-to-tail fashion by an
additional weak Ar–C–HꢀꢀꢀO contact involving the tolyl methyl
group. A particularly unusual feature of the packing in this
structure however, is the extensive contribution of C–Hꢀꢀꢀp
interactions, involving two hydrogen atoms from each of the
methyl groups of the 3- and 5-methoxy substituents. These link
the chains into a three-dimensional network. A CSD investiga-
tion of intermolecular interactions involving both phenyl-bound
and methoxy methyl groups is also presented.
A diversity of benzamides can be prepared by systemati-
cally changing the substituents on either of the benzene rings.
Introduction of various electron-donating or withdrawing
substituents affects the hydrogen-bonding ability of the amide
carbonyl which depends, inter alia upon the acidity of the
-NH proton [6, 7]. While derivatives of 1,2,3-trimethoxy-
benzene abound, 535 entries in the Cambridge Structural
Database, CSD, [8] only 32 of these have C(O)–NH substitu-
ents, with hydrazine derivatives predominating, [9–11]. Fur-
thermore only eight of the compounds whose structures have
been reported have aromatic substituents on the amide N atom
forming phenyl-3,4,5-trimethoxybenzamides such as [12–16].
Interest in the potential medical applications of these com-
pounds prompted us to continue our investigations of these
derivatives with the preparation and structure determination of
3,4,5-trimethoxy-N-p-tolylbenzamide (1), Scheme 1. Crystal
packing in this structure is shown to be influenced particularly
by intermolecular interactions involving the methyl groups of
the tolyl and tri-methoxy benzene rings. These and related
contacts are therefore examined in some detail in what follows.
Keywords Benzamides ꢀ Tri-methoxy benzene
derivatives ꢀ Spectroscopic characterisation ꢀ Crystal
structure ꢀ Hydrogen bonding ꢀ C–Hꢀꢀꢀp interactions
A. Saeed
Department of Chemistry, Quaid-I-Azam University,
Islamabad 45320, Pakistan
J. Simpson (&)
Department of Chemistry, University of Otago,
P.O. Box 56, Dunedin 9054, New Zealand
e-mail: jsimpson@alkali.otago.ac.nz
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