Synthesis, X-Ray crystal structure and spectroscopic properties of 1,2,3,4-tetrahydro-2-(thenyl)-3-(N-thenylidine)-4-oxoquinazoline

Article abstract of DOI:10.1007/s10870-011-0030-x

The Schiff base formed between anthraniloyl hydrazide and thiophen-2-aldehyde is synthesized. Reaction of this Schiff base with VOSO ₄ in methanol at room temperature does not yield the expected vanadium complex; instead, the Schiff base is transformed to 1,2,3,4-tetrahydro-2-(thenyl)-3-(N-thenylidine)-4-oxoquinazoline, which has been characterized by elemental analyses and by LC-MS, i.r., n.m.r. and electronic spectroscopies. The X-ray crystal structure of the quinazoline product is reported. The compound crystallizes with monoclinic (P2₁/n) space group, and the cell parameters are: a = 5.9442(7) A, b = 13.6357(15) A, c = 19.455(2) A, β = 90.499(2)°. The oxo-quinazoline product is found to be luminescent when excited at its lowest energy transition.

Full text of DOI:10.1007/s10870-011-0030-x

J Chem Crystallogr (2011) 41:986–990
DOI 10.1007/s10870-011-0030-x
ORIGINAL PAPER
Synthesis, X-Ray Crystal Structure and Spectroscopic Properties
of 1,2,3,4-Tetrahydro-2-(thenyl)-3-(N-thenylidine)-4-
oxoquinazoline
•
Sumita Naskar Subhendu Naskar
•
•
•
Alexander J. Blake Haregewine Tadesse
Shyamal Kumar Chattopadhyay
Received: 4 February 2010 / Accepted: 10 February 2011 / Published online: 25 February 2011
Ó Springer Science+Business Media, LLC 2011
Abstract The Schiff base formed between anthraniloyl
hydrazide and thiophen-2-aldehyde is synthesized. Reac-
tion of this Schiff base with VOSO4 in methanol at room
temperature does not yield the expected vanadium complex;
instead, the Schiff base is transformed to 1,2,3,4-tetrahydro-
2-(thenyl)-3-(N-thenylidine)-4-oxoquinazoline, which has
been characterized by elemental analyses and by LC–MS,
i.r., n.m.r. and electronic spectroscopies. The X-ray
crystal structure of the quinazoline product is reported.
The compound crystallizes with monoclinic (P21/n) space
and Doxazosin [1–3]. They are also known to have tumor-
inhibiting properties [1, 2]. Recently 4-oxo quinazoline
derivatives have been investigated for their fluorescent
behavior, non-linear optical properties and applications in
electroluminescent devices [4–6]. The 4-oxoquinazolines are
often synthesized by the Niementowski reaction (Scheme 1)
which involves reaction of anthranilic acid with a carboxy-
amide, when 4-oxo-3,4-dihydroquinazolines are obtained
[7]. The present paper reports the synthesis, characterization
and X-ray crystal structure of 1,2,3,4-tetrahydro-2-(thenyl)-
3-(N-thenylidine)-4-oxoquinazoline (Scheme 2).
˚
group, and the cell parameters are: a = 5.9442(7) A,
˚
˚
b = 13.6357(15) A, c = 19.455(2) A, b = 90.499(2)°.
The oxo-quinazoline product is found to be luminescent
when excited at its lowest energy transition.
Experimental
Keywords Oxo-quinazoline Á X-ray crystal structure Á
n.m.r. Á Schiff base Á Thiophen-2-aldehyde Á Hydrazone Á
Anthraniloyl hydrazide
All chemicals for syntheses were of reagent grade, obtained
from commercial sources, and used without further purifi-
cation. The solvents for spectroscopic measurements were
of Spectral grade. Anthraniloyl hydrazide was prepared by
refluxing methyl anthranilate and hydrazine hydrate, fol-
lowing a procedure described in the literature [8]. C,H,N
analyses were done on a Perkin Elmer 2400 instrument.
Infrared spectra were recorded of the KBr pellets of the
compounds using a JASCO FT-IR 460 PLUS spectrometer.
Electronic spectra were recorded on an Ocean Optics
USB2000 spectrophotometer, while the luminescence
spectral data were acquired using a PTI made modular
spectrofluorimeter consisting of Xe-arc lamp and a model
814 photomultiplier detection system, at 90° configuration.
Introduction
Quinazoline and its derivatives are known to be intermediates
for the synthesis of important drugs like Prazosin, Bunazosin
S. Naskar Á S. K. Chattopadhyay (&)
Department of Chemistry, Bengal Engineering and Science
University, Shibpur 711 103, Howrah, India
e-mail: shch20@hotmail.com
S. Naskar
Department of Applied Chemistry, Birla Institute of Technology,
Mesra 835 215, Ranchi, India
Synthesis of the Schiff Base Between Anthraniloyl
Hydrazide and Thiophen-2-aldehyde
A. J. Blake Á H. Tadesse
The Schiff base was prepared by the condensation
of anthraniloyl hydrazide with thiophen-2-aldehyde in
School of Chemistry, The University of Nottingham, University
Park, Nottingham NG7 2RD, UK
123

J Chem Crystallogr (2011) 41:986–990
987
O
bs), 7.39–7.34 (H7,d;H6,t; 2H), 7.17 (H5; 1H, bs), 7.06 (H2;
1H, bs), 6.93 (H15; 1H, bs), 6.89 (H17; 1H, d), 6.79 (H16;
1H, t), 6.57 (H16n; 1H, s) [bs = broad singlet]. 13C NMR(d6-
dmso, 500 MHz): 161.07 (C3), 148.41 (C8), 146.44 (C9),
143.98 (C12), 139.83 (C14), 134.66 (C11), 132.44 (C13),
130.12 (C10), 128.46 (C4,C7), 126.85 (C5), 126.64
(C6),126.59 (C1), 118.75 (C15), 115.65 (C16), 115.29 (C17),
70.12 (C2) [Carbon numbers refer to those given in Fig. 1].
O
O
R2
R1
R2
OH
NH2
R1
NH
N
N
Scheme 1 Nimentowski reaction for the synthesis of 4-oxoquinaz-
olines (R1 and R2 may be alkyl/aryl/alkoxy etc.; R2 may also be alkyl
or aryl carboxylic acid/ester)
H
H
H
H
H
O
H
X-ray Crystallography
S
O
H
H
H
H
N
H
H
H
,
Et3N
N
VOSO4
MeOH
H
H
N
S
N
H
NH2
H
S
H
Diffraction data were collected on a Bruker SMART CCD
area detector diffractometer at 150(2) K, using a graphite
monochromated Mo-Ka radiation. The structure was
solved by direct methods using SHELXS97 [9] and refined
by least squares using SHELXL-97 [9]. The non-hydrogen
atoms were refined with anisotropic displacement param-
eters. All hydrogen atoms except N–H hydrogens were
H
N
H
H
H
Scheme 2 Transformation of thiophen-2-aldehyde anthraniloyl hydra-
zone to 1,2,3,4-tetrahydro-2-(thenyl)-3-(N-thenylidine)-4-oxoquinaz-
oline
1:1 mol ratio in methanol at room temperature. The com-
pound was purified by column chromatography using a
silica gel (100–200 mesh) column. The pale yellow band
eluted with chloroform-hexane (3:1) was collected, which
on evaporation on a rotary evaporator gave a pale yellow
solid. Yield: 66%. M.P.: 164 °C.
Table 1 Crystal data and structure refinement for C17H13N3OS2 (1)
Empirical formula
Formula weight
Temperature
C17 H13 N3 O S2
339.42
150(2)K
˚
0.71073 A
Anal. calc. for C12H11N3SO (Found): C 58.77(58.39), H
Wavelength
4.48 (4.41), N 17.14 (16.82)%.
Crystal system
Space group
Monoclinic
P 21/n
1
LC MS, m/z: 246(100%) (M??1). H NMR (d6-dmso,
500 MHz): 11.56 (N–H; 1H,s), 8.59 (N=C–H; 1H, s), 7.66
(Ph-H(3); 1H, d), 7.54 (Ph-H(6); 1H, d), 7.44 (thiophen-H;
1H, d), 7.22 (Ph-H(4); 1H, t), 7.15 (Ph-H(5);1H, t), 6.76
(thiophen-H; 1H, d), 6.59 (thiophen-H; 1H, t), 6.35 (–NH2;
2H, d).
˚
Unit cell dimensions
a = 5.9442(7) A, a = 90°
˚
b = 13.6357(15) A, b = 90.499(2)°
˚
c = 19.455(2) A, c = 90°
3
˚
Volume
1576.8 (5) A
Z
4
Density (calculated)
Absorption coefficient
F(000)
1.430 g/cm3
0.345 mm-1
704
Synthesis of 1,2,3,4-tetrahydro-2-(thenyl)-3-(N-
thenylidine)-4-oxoquinazoline (1)
Crystal size
0.18 9 0.18 9 0.08 mm3
This compound was obtained during an attempt to prepare the
vanadium complex of the Schiff base described above. The
Schiff base ligand (0.246 g, 1 mmol) was dissolved in
methanol (15 mL) and to it VOSO4ÁH2O (0.182 g, 1 mmol)
dissolved in methanol (10 mL) was added with stirring at
room temperature. Et3N (0.101 g, 1 mmol) was added and
the mixture was stirred for 4 h. The reaction mixture was then
filtered and single crystals suitable for X-ray diffraction were
obtained by evaporation from the brown filtrate. M.P.:
162 °C. Anal. calc. for C17H13N3S2O (Found): C 60.17
(60.41), H 6.37 (6.33), N 12.38 (11.95)%. Electronic spec-
trum in MeOH solution, k/nm (e/dm3 mol-1 cm-1): 249 nm
(1300), 256 (sh) nm (1247), 315 nm (sh) (1159), 327 nm
(1210) nm, 359 nm (894); LC–MS, m/z: 339/340(100%)
(M??1). 1H NMR (d6-dmso, 500 MHz): 9.32 (= C–H; 1H,
s), 7.89 (H14; 1H, s), 7.70(H12,H13; 2H, t), 7.53 (H11; 1H,
h range for data collection
Index ranges
2.09–25°
-7 B h B 7, -16 B k B 16,
-23 B l B 13
Reflections collected
8028
Independent reflections
Observed data [I [ 2.0 r(I)]
Absorption correction
2751 [R(int) = 0.041]
2229
Semi-empirical from equivalents
0.8560 and 0.7277
Full-matrix least-squares on F2
2751/0/208
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
1.07
Final R indices [I [ 2r(I)]
R indices (all data)
R1 = 0.0551, wR2 = 0.136
R1 = 0.0690, wR2 = 0.145
-3
˚
Largest diff. peak and hole
CCDC deposition number
0.40 and -0.22 e A
762751
123

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J Chem Crystallogr (2011) 41:986–990
placed at calculated positions and refined as riding atoms
using isotropic displacement. The N–H hydrogens were
located from DF syntheses and refined freely with a dis-
tance restraint. Crystallographic data are given in Table 1.
electrophilic character of the aldimine carbon atom.
Besides, VO2? may also act as a template for the reaction.
It is found that in the absence of the vanadium salt, when
the Schiff base is reacted with excess thiophen-2-carbal-
dehyde in presence of Et3N, the tetrahydro-4-oxo-quina-
zoline product is not formed, even on prolonged reflux,
clearly showing VO2? is essential for the reaction.
Results and Discussion
The ORTEP diagram for the compound is shown in
Fig. 1 and important bond distances and angles are col-
lected in Table 2. The C–C distances within the benzene
The title compound was obtained during an attempt to
prepare the vanadium complex of the Schiff base between
anthraniloyl hydrazide and thiophen-2-aldehyde. The
compound was adequately characterized using elemental
analyses, infrared and NMR spectroscopy and mass spec-
tra. We have reported earlier [10] that the ring –NH2 group
of anthraniloyl hydrazide does not participate in Schiff
base formation, only the hydrazinic –NH2 can form Schiff
base. It was found, that at PM3 [11] level of calculation,
the nitrogen atom of the ring –NH2 group carries a positive
charge of ?0.029, while the nitrogen atom of hydrazinic
–NH2 carries a negative charge of -0.079, explaining the
lack of nucleophilic character of the ring –NH2 group. The
same level of calculation shows that after deprotonation, in
the enolate form of anthraniloyl hydrazide, both the ring
–NH2 and the hydrazinic –NH2 carries negative charges of
-0.012 and -0.0414 respectively, and thus both of them
are expected show nucleophilic reactivity, though the
hydrazinic –NH2 is expected to be more reactive. Thus one
of the roles of the VO2? may be to stabilize the enolate
form of the Schiff base by chelation, which enhances the
nucleophilic character of ring –NH2, as well as the
˚
ring are in the range 1.374(4)–1.403(4) A, which is con-
sistent with a delocalized aromatic system [12, 13]. The
lack of aromaticity of the tetrahydro-pyrimidine ring
fused to the benzene ring is reflected in the C8–C9 dis-
˚
tance of 1.472(4) A and C2–N3 and C2–N1 distances
˚
of 1.445(4) and 1.491(4) A respectively. However the
˚
C8–N1 and C10–N3 distances are 1.383(4) and 1.378(3) A
respectively and they are shorter than the C2–N3 and
C2–N1 distances, because first two involve C(sp2)–N(sp3)
bonds, while the last two bonds are C(sp3)–N(sp3) in
nature. The tetrahydro-pyrimidine ring is in a envelope
conformation in the crystal lattice, with the C2 atom
˚
deviating by -0.626(3) A from the nine membered plane
consisting of N1, N3, C8, C9, C10, C11, C12, C13 and
C14. The two thiophene rings are twisted by 82.66° (12)
(ring containing S1) and 80.02° (12) (ring containing S2)
from the nine membered ring discussed above. The
˚
C8–O1 distance is 1.230(3) A, while C3–N2 distance is
˚
1.279(4) A, which are consistent with the double bond
characters of these two bonds. The N1–N2 distance is
Fig. 1 ORTEP diagram (50%
probability level) of 1 showing
atom numbering scheme
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J Chem Crystallogr (2011) 41:986–990
989
˚
Table 2 Selected bond lengths (A) and bond angles (°) for C17 H13
N3 O S2 (1)
˚
Bond lengths (A)
O1–C8
1.230(3)
1.383(4)
1.422(3)
1.491(4)
1.496(4)
1.279(4)
1.445(4)
1.378(3)
1.472(4)
1.392(4)
1.402(4)
1.403(4)
1.374(4)
1.392(4)
1.374(4)
N1–C8
N1–N2
N1–C2
Fig. 2 View along the a axis showing the interconnected one
dimensional chains of 1
C1–C2
N2–C3
C2–N3
Table 3 Hydrogen bonds for C17 H13 N3 O S2 (1)
N3–C10
C8–C9
D–HÁÁÁÁA
d(D–H)
d(HÁÁÁA)
d(DÁÁÁA)
\(D–HÁÁÁA)
C9–C14
N3–H16nÁÁÁO1i
C11–H11ÁÁÁ O1i
C13–H13ÁÁÁS2ii
C7–H7ÁÁÁO1iii
0.87
0.95
0.95
0.95
2.12
2.66
3.17
2.61
2.980(3)
3.390(3)
3.415(3)
3.531(4)
168
134
127
164
C9–C10
C10–C11
C11–C12
C12 C13
Symmetry codes: (i) 3/2-x, -1/2 ? y, 1/2-z; (ii) -1/2 ? x, 1/2-y,
1/2 ? z; (iii) 1 ? x, y, z
C13–C14
Bond angles (°)
C8–N1–N2
C8–N1–C2
N2–N1–C2
C3–N2–N1
N3–C2–N1
N3–C2–C1
N1–C2–C1
C10–N3–C2
O1–C8–N1
O1–C8–C9
N1–C8–C9
C14–C9–C10
C14–C9–C8
C10–C9–C8
N3–C10–C9
N3–C10–C11
C9–C10–C11
C12–C11–C10
C11–C12–C13
C13–C14–C9
117.0(2)
119.5(2)
110.2(2)
113.7(2)
106.6(2)
110.0(2)
110.4(2)
117.1(2)
121.6(3)
123.2(3)
115.2(2)
119.9(3)
119.9(2)
120.1(2)
118.9(2)
122.0(2)
119.0(3)
120.0(3)
120.9(3)
120.5(3)
1.4
tetrahydrooxoquinazoline
Schiff base
1.2
1.0
0.8
0.6
0.4
0.2
0.0
300
400
500
600
Wavelength (nm)
Fig. 3 Electronic spectra of 1 and the Schiff base in MeOH
Infrared, Electronic and Luminescence Spectra
For 1 a sharp band at 3306 cm-1 is assigned to mN–H
stretching vibration. The mC=O vibration is observed at
1632 cm-1, while the mC=N vibration is assigned to a band
˚
1.422(3) A, which is close to the N–N single bond dis-
tance [14].
at 1611 cm-1
.
The molecules are linked together by strong hydrogen
bonds [N3–H16nÁÁÁO1i] (symmetry code for i = 3/2-x,
-1/2 ? y, 1/2-z) and weak hydrogen bonds [C11–
H11ÁÁÁO1i], forming one dimensional chains that lie along
the crystallographic b axis. The chains are further linked
via weak C13–H13ÁÁÁS2ii (symmetry code for ii = -1/2 ? x,
1/2-y, 1/2 ? z) [15–18] and H7–C7ÁÁÁO1iii (symmetry code
for iii = 1 ? x, y, z) interactions, to form a three dimensional
network (Fig. 2, Table 3).
The electronic spectra of the tetrahydrooxoquinazoline
along with that of the parent Schiff base are shown in
Fig. 3. The two compounds have very similar spectral
features in the 250–400 nm region; in the higher energy
region there is an additional band at 216 nm for the parent
Schiff base, which is absent in the tetrahydrooxoquinazo-
line compound. There are strong absorptions at 249, 327
and 359 nm, with shoulders at 260 and 315 nm for the
tetrahydrooxoquinazoline compound; the bands above
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J Chem Crystallogr (2011) 41:986–990
1.2
1.0
0.8
0.6
0.4
0.2
0.0
electronic absorption and emission spectra of the newly
formed compound is very similar to that of the parent
Schiff base. The X-ray crystal structure of the compound
shows that in the solid state there is strong N–HÁÁÁO
intermolecular hydrogen bonding along with weak C–HÁÁÁO
and C–HÁÁS hydrogen bonds, leading to the formation of a
three dimensional network.
tetrahydrooxoquinazoline
Schiff base
Supplementary Material
CCDC-762751 for 1 contains the supplementary crystal-
lographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/datarequest/cif, by
e-mailing data request@ccdc.cam.ac.uk or by contacting
The Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK; fax: ?44(0)1223-336033.
350
400
450
500
550
600
650
700
Wavelength (nm)
Fig. 4 Normalized emission spectra of 1 and the Schiff base in
MeOH
Acknowledgments This study is supported by CSIR and AICTE,
India. We also thank DST (FIST), UGC (SAP) and MHRD grants to
our department for purchase of different sophisticated equipments.
300 nm are red shifted with respect to the parent Schiff
base, while the band below 300 nm is blue shifted com-
pared to that of the Schiff base. PM3 calculations [11],
which include configuration interactions from states arising
from 10 highest occupied orbitals and 10 lowest unoccu-
pied orbitals, predict two bands at 351 nm (HOMO ?
LUMO ? 1, LUMO ? 2) and 322 nm (HOMO-1 ?
LUMO), which is in good agreement with the experimental
observation. The HOMO is mainly a p orbital on the
benzene ring, HOMO-1 is a p orbital on the thiophene ring
attached to C3, LUMO is a p* orbital on the thiophene ring
attached to C3, LUMO ? 1 is a p*-orbital on the thiophene
ring attached to C2 and LUMO ? 2 is p* orbital on the
benzene ring. As the transitions involve p and p* orbitals
of benzene and thiophene rings, so the similarity between
the electronic spectra of the Schiff base and the tetra-
hydrooxoquinazoline compound is expected.
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Conclusions
It is shown that the anthraniloyl hydrazone of thiophen-2-
aldehyde is transformed to a fluorescent 4-oxo tetrahy-
droquinazoline derivative in presence of VOSO4. The
123