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J Chem Crystallogr (2012) 42:711–720
function of the complex processes of molecular genetics
depends on the covalent bonds and directed electrostatic
interactions. With the development of uracil based anti-
cancer and antiviral drugs (e.g. AZT, DDI, DDC, BVDU),
there is a renewed interest in the synthesis and design of
heteroaromatic species of uracil origin having biological
significances [9]. Several patents have been reported
describing the synthesis of such heterocycles, derivatives
of which are useful as vasodilators, bronchodilators [10],
antiallergic [10, 11], antihypertensive [12, 13], antiphyt-
oviral drugs [14] and anticancer [10] agents. Many drug
candidates have been modeled on these compounds, par-
ticularly for cancer and virus research. It is to be mentioned
that the 5-substituted uracils and their nucleosides are
widely used in the chemotherapy of cancer [15]. The
synthetic exploitation of nucleophilic double bond of uracil
is still an undeveloped field in view of great variety of
potential products [16]. There has been many reports for
the functionalisation of uracil though most of them suffer
from harsh reaction condition or longer synthetic pathway
[17]. Additionally in recent years, X-ray single crystal
diffraction of uracil derivatives [18] enormously increases
due to the uracil nucleobase and its derivatives which have
a fascination to researchers in the solid organic synthetic
chemistry [19] as well as biological chemistry [20].
structures are again reviewed in brief to make a rigorous
discussion between the motifs arising from different substi-
tuted uracil derivatives.
Experimental Section
All the reagents and solvents were obtained from standard
commercial sources (Sigma-Aldrich, Merck) and were
used without further purification. Elemental analysis and
mass measurements were carried on Perkin-Elmer (2400
series II) elemental analyzer, Waters Q-TOF Premier and
Aquity UPLC spectrometer respectively. IR spectra were
recorded as KBr pellets on a Nicolet (Impact 410) FT-IR
1
spectrometer in the range of 4000-400 cm-1 whereas H
NMR spectra were recorded on a JNM ECS 400 MHz
NMR spectrophotometer (JEOL) using CDCl3 and
DMSO-d6 as solvents and TMS as internal reference.
X-ray Crystallographic Studies
Suitable X-ray quality crystals of ligands are grown
directly from their corresponding solutions EtOH/H2O
media at room temperature and X-ray crystallographic data
are collected by mounting a single-crystal of the sample on
glass fibers. Bruker SMART CCD area detector diffrac-
tometer equipped with an LN-2 low-temperature attach-
ment was used for the determination of cell parameter and
intensity data collection. Appropriate empirical absorption
corrections using the programs multi-scan were applied.
The oxygen and nitrogen sites (O1, O2 and N3) in our
precursor compound 1,3-dimethyl-6-aminouracil are suit-
able for metal coordination and also N-H and C-O hydro-
gen bonded sites arranged with suitable geometry, making
them ideal for H-bond formation. This uracil precursor also
has sp3 ring carbon which motivated us to go for design
and control of these organic architectures by simple crystal
growth. Keeping these in mind, we have examined the
favourability of different hydrogen bonds and non-covalent
interacting motifs for the 5,6-substituted uracil, a system of
biological relevance [21] and a preliminary report is pre-
sented in this manuscript which deal with the synthesis,
spectroscopic characterization and X-ray crystallographic
structural analysis of 1,3-dimethyl-6-aminouracil (L1)
along with its 5-substituted derivatives viz. 6,6’-diamino-
1,1’,3,3’-tetramethyl-5,5’-(benzylidene)bis -[pyrimidine-2,
4(1H,3H)-dione] (L2), 6,6’-diamino-1,1’,3,3’-tetramethyl-5,
5’-(4-chloro-benzylidene)bis[pyrimidine-2,4(1H,3H)-dione]
(L3), 6,6’-diamino-1,1’,3,3’-tetramethyl-5,5’-(furayl)bis[pyr-
imidine-2,4(1H,3H)-dione] (L4), 6,6’-diamino-1,1’,3,3’-tet-
ramethyl-5,5’-(formyl)bis[pyrimidine-2,4(1H,3H)-dione] (L5)
and an amidine side chain derivative 6-[(dimethylamino)
methyleneamino]-1,3-dimethylpyrimidine-2,4(1H,3H)-dione
dihydrate (L6). These stabilised crystals could be further
processed for designing new drug molecules. It is also worth
to mention that Ferguson et al. reported the crystal structure
of L1 (1,3-dimethyl-6-aminouracil) [22] while that of L3 and
L6 have been reported by us [23] though these crystal
˚
Monochromated Mo Ka radiation (k = 0.71073 A) was
used for the measurements. The crystal structures were
solved by direct methods [24] and refined by full matrix
least squares SHELXL-97 [25]. Drawings were rendered
out using MERCURY [26], DIAMOND [27] and special
computations carried out with PLATON [28]. Crystallo-
graphic data and refinement details for the structural
analyses of the complexes are summarized in Table 1.
Selected bond lengths and bond angles with their estimated
standard deviations are presented in Table 2, while selected
parameters for weak interactions are listed in Table 3.
Preparation of 1,3-dimethyl-6-amino uracil (L1)
Ligand L1 is prepared by following a reported literature
method1 in which a mixture of 1,3-dimethylurea (0.1 mol),
cyanoacetic acid (0.1 mol) and acetic anhydride (12.5 ml)
were heated with exclusion of moisture under stirring at
60 ꢁC for 3 h. The excess of acetic anhydride and acetic acid
formed during the reaction were removed under reduced
pressure. A 5% cold sodium hydroxide solution (50 ml) was
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Saikia, Binoy K.
