Crystal structure of ethyl (2Z, 5R)-2-benzylidene-7-methyl-3-oxo-5-phenyl- 2,3-dihydro-5H-[1,3] thiazolo [3,2-a] pyrimidine-6-carboxylate

Article abstract of DOI:10.1007/s10870-009-9587-z

The title compound, C₂₃H₂₀N₂O ₃S, (I), crystallizes in the orthorhombic space group, Pna 2 ₁, with cell parameters a = 18.7975(6), b = 12.5173(4), c = 8.4804(3) A, Z = 4. The molecular structure consi

Full text of DOI:10.1007/s10870-009-9587-z

J Chem Crystallogr (2009) 39:898–901
DOI 10.1007/s10870-009-9587-z
ORIGINAL PAPER
Crystal Structure of Ethyl (2Z, 5R)-2-benzylidene-7-methyl-3-oxo-
5-phenyl-2,3-dihydro-5H-[1,3] Thiazolo [3,2-a] Pyrimidine-6-
carboxylate
Mukesh M. Jotani Æ Bharat B. Baldaniya Æ
Jerry P. Jasinski
Received: 30 December 2008 / Accepted: 7 June 2009 / Published online: 24 June 2009
Ó Springer Science+Business Media, LLC 2009
Abstract The title compound, C23H20N2O3S, (I), crys-
tallizes in the orthorhombic space group, Pna 21, with cell
Introduction
˚
parameters a = 18.7975(6), b = 12.5173(4), c = 8.4804(3) A,
The remarkable biological activities of fused pyrimidines
which give rise to antiviral, anticancer, anti-inflammatory
and antihypertensive actions [1, 2], continue to bring this
class of heterocyclic compounds to the forefront of interest
and study. The title thiazolo[3,2-a]pyrimidine compound,
(I), exhibits both anticancer and anti-inflammatory activity.
In support of these observations, an anticancer drug screen
has been carried out using a diverse panel of cultured
human tumor cell lines [3]. Anti-inflammatory activity has
been determined by examination of inhibition by the
Carageena-induced rat paw edema method [4]. In view of
these observations and in the continuation of our recent
studies on thiazolo[3,2-a]pyrimidine compounds [5–8],
we have been investigating the influence of different
substituent’s on the structural parameters of these com-
pounds as well as crystal packing when relating these
properties to the biological effects of these compounds.
We report herethe crystal structure of the title compound,
C23H20N2O3S, (I).
Z = 4. The molecular structure consists of a central
pyrimidine ring which is significantly puckered to assume a
screw-boat conformation fused to a thiazole ring with
benzyl, carboxylate, methyl, phenyl and oxy groups bon-
ded around this fused-ring moiety. The dihedral angle
between the mean planes of the thiazole, benzyl and phenyl
groups and the mean plane of the pyrimidine ring is
6.1(4)°, 83.8(7)° and 6.8(4)°, respectively. The dihedral
angle between the mean planes of the benzyl and phenyl
rings is 88.3(5)° while between the mean planes of
the phenyl and thiazole groups measures 12.6(6)°. In the
absence of expected hydrogen bonding interactions, the
crystal packing is influenced by a collective action of
strong intramolecular C–HÁÁÁS hydrogen bond interactions,
close C–HÁÁÁO intramolecular contacts and O–Cg p-ring
interactions. A DFT molecular orbital calculation gives
support to these observations.
Keywords Thiazole Á Pyrimidine Á Ring puckering Á
Benzene Á DFT calculations
Synthesis of Ethyl (2Z, 5R)-2-benzylidene-7-methyl-3-
oxo-5-phenyl-2,3-dihydro-5H-[1,3] thiazolo [3,2-a]
pyrimidine-6-carboxylate
M. M. Jotani
Department of Physics, Bhavan’s Sheth R.A. College of Science,
Khanpur, Ahmedabad, Gujarat 380 001, India
A mixture of ethyl 6-methyl-4-phenyl-2-thioxo-1,2,3,4-
tetrahydropyrimidine-5-carboxylate (0.01 mol), chloroace-
tic acid (0.01 mol), fused sodium acetate (6 g) in glacial
acetic acid (25 mL), acetic anhydride (10 mL) and benz-
aldehyde (0.01 mol) was refluxed for 3 h. The reaction
mixture was cooled and poured into cold water. The
resulting solid was collected and crystallized from metha-
nol to obtain the final product (86% yield, mp 443 K). The
compound was recrystallized by slow evaporation of a
B. B. Baldaniya
Department of Chemistry, M.G. Science Institute, Navrangpura,
Ahmedabad, Gujarat 380 009, India
J. P. Jasinski (&)
Department of Chemistry, Keene State College, 229 Main Street,
Keene, NH 03435-2001, USA
e-mail: jjasinski@keene.edu
123

J Chem Crystallogr (2009) 39:898–901
899
Table 1 Crystal and experimental data for (I)
Formula
C23H20N2O3S
Formula weight
Crystal color, habit
Crystal size (mm)
Crystal system
Space group, Z
Temperature (K)
404.47
O
Yellow, plate
0.45 9 0.3 9 0.2
Orthorhombic
Pna 21, 4
293(2)
EtOOC
Me
N
S
N
˚
a (A)
18.7975(6)
12.5173(4)
8.4804(3)
1,995.39(11)
1.346
˚
b (A)
Fig. 1 Chemical scheme for of Ethyl (2Z, 5R)-2-benzylidene-7-
methyl-3-oxo-5-phenyl-2,3-dihydro-5H-[1,3] thiazolo [3,2-a] pyrim-
idine-6-carboxylate, (I)
˚
c (A)
3
V (A )
˚
Dcalc (g cm-3
)
benzene-ethanol solution (8:2) yielding yellow plate-like
single crystals suitable for X-ray diffraction. A scheme for
the molecular structure of (I) is shown in Fig. 1.
No. of reflections [I [ 2r(I)]
2hlan (°) with Mo Ka
R, Rw [I [ 2r(I)]
(Dr)max
2,923
49.98
0.0347/0.0864
0.002
-3
˚
(Dq)max (e A
)
0.160
Structure Determination and Refinement
-3
˚
(Dq)min (e A
)
-0.165
Measurement
APEX2, [11]
APEX2/SAINT
SIR92
X-ray data were collected with a Bruker AXS Kappa AP-
EXII CCD diffractometer using APEXII software and
Program system
Structure determination
Refinement
˚
graphite-monochromated Mo-Ka (k = 0.71073 A) radia-
Full-matrix least-squares on
F2 (SHELXL97)
tion at 293(2) K. The structure was solved by direct
methods using SIR92 [9]. All of the non-hydrogen atoms
were refined anisotropically by full-matrix least-squares on
F2 using SHELXL97 [10]. All H atoms were allowed to
ride on the parent atom in the model during refinement. An
absorption correction was performed using SADABS [11]
and all calculations were performed using PLATON [12].
Crystal and experimental data for (I) are listed in Table 1.
structures. The corresponding average values in the Cam-
bridge Structural Data Base (Version 5.30 and November
2008 updates) [14] for these bonds differ slightly, viz 1.31
˚
and 1.39 A, respectively, from that seen here. The fused
thiazole ring has similar geometry as observed in other
fused thiazolopyrimidine compounds [1–4, 15, 16]. The
˚
short C(9)–C(10) distance [1.404(5) A] may be due to a
Results and Discussion
collective interaction of C10 with the nearby ethoxy group,
an intramolecular close contact interaction with the nearby
carbonyl oxygen atom (C9–H9BÁÁÁO3; see Table 2), and/or
an O3–Cg1 p-ring interaction (C8–O3ÁÁÁCg1; x, y, -1 ? z;
The molecular structure of C23H20N2O3S, (I), consists of a
central pyrimidine ring which is significantly puckered to
assume a screw-boat conformation fused to a thiazole ring
with benzyl, carboxylate, methyl, phenyl and oxy groups
bonded at the C2, C3, C4, C6 and C5 positions, respec-
tively, around this fused-ring moiety. The dihedral angle
between the mean planes of the thiazole, phenyl and benzyl
groups and the mean plane of the pyrimidine ring is
6.1(4)°, 6.8(4)°, and 83.8(7)°, respectively. The dihedral
angle between the mean planes of the benzyl and phenyl
rings is 88.3(5)° while between the mean planes of the
phenyl and thiazole groups measures 12.6(6)°. The ring
puckering parameters [13] for the pyrimidine ring are
h = 68.1(1)° and / = 163.3(6)°; the idealized values are
h = 67.5° and / = (60k ? 30)o, where k is an integer. All
the bond lengths and angles in the pyrimidine ring have
o
˚
C8ÁÁÁCg1 = 3.912(7) A; O3–C8ÁÁÁCg1 = 111 ; O3ÁÁÁCg1 =
˚
4.48(1) A) that may influence the bond strength of the C9–
C10. The ethoxy group lies in a trans configuration about
the O(2)–C(9) bond (torsion angles C(3)–C(8)–O(2)–
C(9) = 0.8(4)° and C(8)–O(2)–C(9)–C(10) = 115.1(4)°,
respectively).
˚
Table 2 Intramolecular hydrogen bond interactions for I (A and °)
D–HÁÁÁA
d(D–H)
d(HÁÁÁA)
d(DÁÁÁA)
\(DHA)
C(9)–H(9B)ÁÁÁO(3)
C(17)–H(17)ÁÁÁO(1)
C(19)–H(19)ÁÁÁS(1)
0.97
0.93
0.93
2.25
2.57
2.47
2.680(3)
2.907(6)
3.163(3)
106
106
132
˚
normal values except C(1)–N(1) [1.276(3) A] and N(1)–
˚
C(4) [1.398(4) A] which are similar to earlier reported
123

900
J Chem Crystallogr (2009) 39:898–901
Fig. 4 The molecular packing for (I) viewed down the a axis
compound here crystallizes in the orthorhombic space
group.
Fig. 2 ORTEP drawing of C23H20N2O3S, (I), showing the atom
numbering scheme and 50% probability displacement ellipsoids
A Density Functional Theory (DFT) geometry optimi-
zation molecular orbital calculation (WebMO Pro [18])
with the GAUSSIAN-03 program package [19] employing
the B3LYP (Becke three parameter Lee-Yang-Parr)
exchange correlation functional, which combines the
hybrid exchange functional of Becke [20, 21] with the
gradient-correlation functional of Lee, Yang and Parr [22]
and the 3-21G basis set [23] was performed on the title
molecule, (I). Starting geometries were taken from X-ray
refinement data. The N–C, C–C and C–O bond distances
involving atoms involved in the intramolecular hydrogen
bond interactions and close intermolecular contacts in the
DFT calculated model are all slightly longer that those
determined experimentally (Table 3). The largest discrep-
ancies of 0.025(6), 0.125(5), 0.054(7), 0.033(6), and
˚
0.051(7) A are for N(1)–C(4), C(9)–C(10), C(8)–O(2),
C(9)–O(2), and C(8)–O(3), respectively, with the C(9)–
C(10) bond difference being the largest. The differences
Table 3 Selected geometric parameters for (I) and DFT calculation
˚
(A, °)
X-ray
1.276(3)
DFT
1.280
N(1)–C(1)
Fig. 3 The molecular packing for (I) viewed down the c axis
N(1)–C(4)
1.398(4)
1.364(3)
1.404(5)
1.332(3)
1.451(4)
1.184(3)
116.65(19)
123.33(17)
108.29(17)
126.9(2)
179.7(3)
115.0(4)
-173.50(17)
2.3(4)
1.424
1.374
N(2)–C(1)
C(9)–C(10)
1.530
The molecules pack in a stacking like mode, arranged in
an alternating pattern diagonally across the bc plane of the
unit cell (Figs. 2, 3, 4). Strong intramolecular C–HÁÁÁS
hydrogen bond interactions (Table 2) exist with C19–
H19ÁÁÁS1 forming a pseudo-six-membered ring of S(6)
graph-set motif [17]. Weak C–HÁÁÁO intramolecular con-
tacts with C9–H19BÁÁÁO3 and C17–H17ÁÁÁO1 forming a
second pseudo-5-membered ring of O(5) graph-set motif
[17] also influence crystal packing. [12]. There are no
hydrogen bond, C–HÁÁÁp or p–p stacking interactions
present in the structure of (I), which is in contrast to the
presence of such interactions in similar structures reported
earlier [1–4]. It is noted that these structures all crystallize
in the monoclinic or triclinic space group while the title
C(8)–O(2)
1.387
C(9)–O(2)
1.485
C(8)–O(3)
1.236
C(1)–N(2)–C(5)
C(5)–N(2)–C(2)
N(2)–C(2)–C(3)
N(1)–C(2)–N(2)
C(9)–O(2)–C(8)–C(3)
C(8)–O(2)–C(9)–C(1)0
C(4)–N(1)–C(1)–S(1)
S(1)–C(6)–C(17)–C(18)
C(11)–C(2)–C(3)–C4
C(4)–C(3)–C(8)–O(3)
118.42
121.72
108.48
126.55
178.46
78.57
-171.23
-0.13
-100.19
3.01
-104.4(3)
11.4(4)
123

J Chem Crystallogr (2009) 39:898–901
901
Acknowledgments The authors are thankful to Department of
Science and Technology (DST), and SAIF, I.I.T. Madras, Chennai,
India for the X-ray data collection. MMJ thanks the University Grant
Commission (Western Regional Office), India for their support of
Minor Research Project F. no. 47-254/07.
between the calculated and observed geometry could be
related to the crystal packing in the molecules. However,
the observation of a collection of strong C–HÁÁÁS intra-
molecular hydrogen bond interactions, close C–HÁÁÁO
intramolecular contacts and weak O–Cg p-ring interactions
provide evidence of a collective effect of all of these
interactions on crystal packing in the unit cell.
References
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the mean plane of the pyrimidine ring became 1.34°,
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Supporting Information Available
X-ray crystallographic files, in Cif format, for the structure
determinationsof(I) (CCDC 714517) has beendeposited with
the Cambridge Crystallographic Date Center, CCDC: 26091.
Copies of this information may be obtained free of charge
from the Director, CCDC, 12 Union Road, Cambridge, CB2
1EZ (fax: ?44-1223-336033; email:deposit@ccdc.cam.uk or
at http://www.ccdc.cam.ac.uk.
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