Diverse confirmations in the crystal structures of 2,3-dihydro-2,2- dimethylquinazolin-4(1H)-one derivatives

Article abstract of DOI:10.1007/s10870-012-0303-z

The 3-(propan-2-ylideneamino)-2,3-dihydro- 2,2-dimethylquinazolin-4(1H)-one and 3-(3-nitrobenzylideneamino)- 2,3-dihydro-2,2-dimethylquinazolin-4(1H)- one were synthesized and characterized by IR, ¹H NMR and HRMS. The molecular structures were further confirmed by X-ray diffraction analysis. The former 1, C₁₃H₁₇N₃O, is monoclinic, space group P2(1)/c, a = 9.056(2), b = 9.439(2), c = 14.872(3) A, β = 133.121(12)°, Z = 4, V = 1270.9(5) A³. The latter 2, C ₁₇H₁₆N₄O₃, is also monoclinic, space group P2(1)/c, a = 10.0006(2), b = 12.2298(3), c = 13.3255(3) A, β = 96.602(2)°, Z = 4, V = 1618.97(6) A³. It is very interesting that the pyrimidine ring in the 1 adopts a half-chair confirmation, while adapting a skew-boat one in the structure of 2. Springer Science+Business Media, LLC 2012.

Full text of DOI:10.1007/s10870-012-0303-z

J Chem Crystallogr (2012) 42:701–705
DOI 10.1007/s10870-012-0303-z
ORIGINAL PAPER
Diverse Confirmations in the Crystal Structures
of 2,3-Dihydro-2,2-dimethylquinazolin-4(1H)-one Derivatives
•
•
•
Jie Sheng Mei-Mei Zhang Lian Lu
Xiang-Shan Wang
Received: 21 July 2011 / Accepted: 30 March 2012 / Published online: 13 April 2012
Ó Springer Science+Business Media, LLC 2012
Abstracts The 3-(propan-2-ylideneamino)-2,3-dihydro-
2,2-dimethylquinazolin-4(1H)-one and 3-(3-nitrobenzy-
lideneamino)-2,3-dihydro-2,2-dimethylquinazolin-4(1H)-
utility [1–3]. Especially for the 4(3H)-quinazolinone core,
is well-known as a ‘‘privileged structure’’ [4, 5] for drug
design, which is defined as a class of molecules that are
capable of binding to multiple receptors with high affinity
[6, 7]. These include anti-inflammatory [8], antihyperten-
sive [9], anticancer [10], antitumor [11] and antibacterial
activity [12]. They have recently also been evaluated as
antagonists of various biological receptors, such as 5-HT5A
related diseases [13], calcitonin gene-related peptide [14]
and vasopressin V3 receptors [15]. In this paper, we would
like to report the crystal structures of 3-(propan-2-ylide-
neamino)-2,3-dihydro-2,2-dimethylquinazolin-4(1H)-one
(1) and 3-(3-nitrobenzylideneamino)-2,3-dihydro-2,
2-dimethyl quinazolin-4(1H)-one (2), with entirely
different confirmations in their pyrimidine cores, this
may be indicate different potential activities in bio-
active screening.
1
one were synthesized and characterized by IR, H NMR
and HRMS. The molecular structures were further con-
firmed by X-ray diffraction analysis. The former 1, C13H17
N3O, is monoclinic, space group P2(1)/c, a = 9.056(2),
˚
b = 9.439(2), c = 14.872(3) A, b = 133.121(12)°, Z = 4,
3
V = 1270.9(5) A . The latter 2, C17H16N4O3, is also
˚
monoclinic, space group P2(1)/c, a = 10.0006(2), b =
˚
12.2298(3), c = 13.3255(3) A, b = 96.602(2)°, Z = 4,
3
V = 1618.97(6) A . It is very interesting that the pyrimi-
˚
dine ring in the 1 adopts a half-chair confirmation, while
adapting a skew-boat one in the structure of 2.
Keywords Quinazoline Á Confirmation Á Hydrogen bond Á
Infrared Á Nmr
Introduction
Experimental
Quinazolinone derivatives are an important class of mole-
cules with physiological significance and pharmaceutical
Synthesis of 1 and 2
A dry 50 mL flask was charged with 2-aminobenzohyd-
razide (0.151 g, 1.0 mmol), acetone (0.232 g, 4.0 mmol)
and ionic liquid of [BMIm]Br (BMIm is the abbreviation of
1-butyl-3-methylimidazolium, 2 mL). The reaction mix-
ture was stirred at 50 °C for 10 h, and then 5 mL water was
added to the mixture, and the generated yellow solid was
filtered off. The crude yellow products were washed with
water and purified by recrystallization from 95 % EtOH to
give 1 as colorless crystals in 95 % yield, mp 249–251 °C.
1H NMR (DMSO-d6, 400 MHz): dH 1.37–1.50 (m, 6H,
29CH3), 1.75 (s, 3H, CH3), 2.08 (s, 3H, CH3), 6.66–6.71
(m, 2H, ArH), 6.91 (s, 1H, NH), 7.25–7.29 (m, 1H, ArH),
J. Sheng Á M.-M. Zhang Á L. Lu Á X.-S. Wang (&)
School of Chemistry and Chemical Engineering, Jiangsu Key
Laboratory of Green Synthetic Chemistry for Functional
Materials, Jiangsu Normal University, Xuzhou 221116, Jiangsu,
People’s Republic of China
e-mail: xswang1974@yahoo.com
J. Sheng Á M.-M. Zhang Á L. Lu Á X.-S. Wang
The Key Laboratory of Biotechnology on Medical Plant of
Jiangsu Province, Jiangsu Normal University, Xuzhou 221116,
Jiangsu, People’s Republic of China
123

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J Chem Crystallogr (2012) 42:701–705
7.61 (d, J = 7.6 Hz, 1H, ArH). IR (KBr): m 3262, 2998,
2981, 2972, 1629, 1586, 1518, 1488, 1464, 1438, 1382,
1350, 1327, 1285, 1268, 1214, 1181, 1155, 1091, 974, 943,
828, 752, 734, 693 cm-1. HRMS (ESI, m/z): Calcd for
C17H16N4O3 [M ? Na] ? 347.1120, found, 347.1144.
1349, 1264, 1189, 1165, 950, 747, 693 cm-1. HRMS (ESI,
?
m/z): Calcd for C26H34N6O2Na [2M ? Na]
found 485.2639.
485.2635,
X-ray Analysis
A dry 50 mL flask was charged with 2-aminobe-
nzohydrazide (0.151 g, 1.0 mmol), 3-nitrobenzaldehyde
(0.151 g, 1 mmol), and ionic liquid of [BMIm]Br (2 mL).
After the reaction mixture was stirred at 0 °C for 2 h, the
acetone (0.116 g, 2.0 mmol) was added to the mixture for
6 h at 50 °C. And then a small amount of water (5 mL) was
added to the mixture, and the generated yellow solid was
filtered off. The crude yellow products were washed with
water and purified by recrystallization from 95 % EtOH to
give 2 as yellow crystals in 92 % yield, mp 186–188 °C. 1H
NMR (DMSO-d6, 400 MHz): dH 1.61 (s, 6H, 2CH3),
6.73–6.77 (m, 2H, ArH), 7.13(s, 1H, NH), 7.32–7.36 (m, 1H,
ArH), 7.70 (d, J = 7.6 Hz, 1H, ArH), 7.77–7.81 (m, 1H,
ArH), 8.25 (d, J = 8.0 Hz, 1H, ArH), 8.31–8.34 (m, 1H,
ArH), 8.60 (s, 1H, ArH), 9.13 (s, 1H, CH). IR(KBr): m 3449,
3103, 3017, 2976, 2936, 1632, 1526, 1489, 1461, 1434, 1385,
A summary of the crystallographic data was given in Table 1.
The structure was solved by direct method using SHELXTL
[16] program and expanded using Fourier technique. The non-
hydrogen atoms were refined anisotropically, the hydrogen
atoms were positioned geometrically and refined as riding
˚
[C–H = 0.93–0.96 A except for H(1) in 1 and 2, respec-
tively, and Uiso(H) = 1.2Ueq(C)]. A full-matrix least-squares
refinement gave final R = 0.0406 and xR = 0.0993
(R = 0.0362 and xR = 0.0876 for 2) with x = 1/[r2
(F2o) ? (0.0507P)2 ? 0.2209 P](x = 1/[r2(F2o) ? (0.0418P)2 ?
0.2894P] for 2), where P = (F2o ? 2Fc2)/3.
Analysis
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on a TENSOR 27
Table 1 Crystallographic data for 1 and 2
Compounds
1
2
Empirical formula
CCDC deposit no.
Color/shape
C13H17N3O
832529
C17H16N4O3
832530
Colorless/block
231.30
Yellow/block
324.34
Formula weight
Temperature
296(2) K
Monoclinic
P2(1)/c
296(2) K
Monoclinic
P2(1)/c
Crystal system
Space group
˚
˚
Unit cell dimensions
a = 9.056(2) A, a = 908
a = 10.0006(2) A, a = 908
˚
˚
b = 9.439(2) A, b = 133.121(12)8
b = 12.2298(3) A, b = 96.602(2)8
˚
˚
c = 14.872(3) A, c = 908
˚
1270.9(5) A
c = 13.3255(3) A, c = 908
˚
1618.97(6) A
3
3
Volume
Z
4
4
Density (calculated), Mg/m3
Absorption coefficient, mm-1
Diffractometer/scan
F(000)
1.209
1.331
0.079
0.094
CCD area detector/u and x
496
CCD area detector/u and x
680
Crystal size
0.293 9 0.257 9 0.116 mm
2.56–25.20 8
0.271 9 0.195 9 0.116 mm
2.05–25.20 8
Theta range for data collection
Limiting indices
-10 B h B 10, -17 B k B 17, -15 B l B 15
15381
-11 B h B 11, -14 B k B 14, -15 B l B 15
12422
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I [ 2r (I)]
R indices (all data)
Largest diff. peak and hole
2279 [R(int) = 0.0304]
2279/1/162
2900 [R(int) = 0.0278]
2900/1/224
1.044
1.025
R1 = 0.0406, wR2 = 0.0993
R1 = 0.0571, wR2 = 0.1076
0.137 and -0.167 e A-3
R1 = 0.0362, wR2 = 0.0876
R1 = 0.0532, wR2 = 0.0979
0.141 and -0.130 e A-3
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J Chem Crystallogr (2012) 42:701–705
703
˚
Table 2 Selected bond lengths (A) and selected bond angles (°) for 1 and 2
Selected Bond Lengths for 1
Selected Bond Lengths for 2
O(1)–C(1)
N(1)–C(3)
N(1)–C(2)
N(1)–H(1)
N(2)–C(1)
N(2)–N(3)
N(2)–C(2)
1.234(2)
1.381(2)
1.455(2)
0.86(1)
N(3)–C(11)
C(1)–C(4)
1.272(2)
1.465(2)
1.517(2)
1.522(3)
1.483(3)
1.496(2)
N(3)–C(11)
N(3)–N(2)
N(2)–C(1)
N(2)–C(2)
C(4)–C(1)
C(1)–O(1)
N(1)–C(3)
N(1)–C(2)
1.266(2)
1.381(2)
1.373(2)
1.497(2)
1.471(2)
1.230(2)
1.369(2)
1.449(2)
N(1)–H(1)
C(12)–C(1)
C(2)–C(10)
C(2)–C(9)
C(16)–N(4)
O(2)–N(4)
N(4)–O(3)
0.86(1)
1.464(2)
1.518(2)
1.524(2)
1.471(2)
1.214(2)
1.221(2)
C(2)–C(10)
C(2)–C(9)
1.371(2)
1.429(2)
1.486(2)
C(11)–C(12)
C(11)–C(13)
Selected Bond Angles for 1
Selected Bond Angles for 2
124.0(1)
C(3)–N(1)–C(2)
C(3)–N(1)–H(1)
C(2)–N(1)–H(1)
C(1)–N(2)–N(3)
C(1)–N(2)–C(2)
N(3)–N(2)–C(2)
C(11)–N(3)–N(2)
O(1)–C(1)–N(2)
O(1)–C(1)–C(4)
N(2)–C(1)–C(4)
N(1)–C(2)–N(2)
N(1)–C(2)–C(10)
119.3(1)
N(2)–C(2)–C(10)
N(1)–C(2)–C(9)
N(2)–C(2)–C(9)
C(10)–C(2)–C(9)
N(1)–C(3)–C(4)
N(1)–C(3)–C(8)
C(5)–C(4)–C(1)
C(3)–C(4)–C(1)
N(3)–C(11)–C(12)
N(3)–C(11)–C(13)
C(12)–C(11)–C(13)
109.6(1)
112.4(1)
109.9(1)
110.8(2)
118.8(1)
122.5(1)
120.3(1)
119.8(1)
127.3(1)
115.4(2)
117.3(2)
C(11)–N(3)–N(2)
C(1)–N(2)–N(3)
C(1)–N(2)–C(2)
N(3)–N(2)–C(2)
C(5)–C(4)–C(1)
C(3)–C(4)–C(1)
O(1)–C(1)–N(2)
O(1)–C(1)–C(4)
N(2)–C(1)–C(4)
C(3)–N(1)–C(2)
C(3)–N(1)–H(1)
C(2)–N(1)–H(1)
N(1)–C(3)–C(4)
N(1)–C(3)–C(8)
C(17)–C(12)–C(11)
C(13)–C(12)–C(11)
N(1)–C(2)–N(2)
N(1)–C(2)–C(10)
N(2)–C(2)–C(10)
N(1)–C(2)–C(9)
N(2)–C(2)–C(9)
C(10)–C(2)–C(9)
C(17)–C(16)–N(4)
C(15)–C(16)–N(4)
N(3)–C(11)–C(12)
O(2)–N(4)–O(3)
O(2)–N(4)–C(16)
O(3)–N(4)–C(16)
121.6(1)
119.4(1)
106.6(1)
107.8(1)
110.5(1)
111.9(1)
108.6(1)
111.4(1)
118.3(2)
119.4(2)
118.9(1)
123.5(2)
119.0(2)
117.6(2)
118.2(1)
111.3(1)
117.7(1)
120.7(1)
111.2(1)
114.8(1)
121.7(1)
122.4(1)
115.8(1)
105.5(1)
108.6(1)
125.5(1)
121.5(1)
110.9(1)
120.2(1)
119.7(1)
121.8(1)
122.0(1)
116.2(1)
118.8(1)
116.4(1)
112.8(1)
118.3(1)
122.8(1)
Fig. 1 The molecular structures of 1 (a) and 2 (b) showing 30% probability displacement ellipsoids
spectrometer in KBr pellet. 1H NMR spectra were obtained
from solution in DMSO-d6 with Me4Si as internal standard
using an Inova-400 spectrometer. HRMS analyses were
carried out using a Bruker-micro-TOF-Q-MS analyzer.
X-ray diffraction was performed on a Bruker APEX-II area
detector diffractometer.
Results and Discussion
In the infrared spectrography of 1, it was observed a sharp
band at 3262 cm-1 (3449 cm-1 for 2) for the amino group.
The carbonyl groups in 1 and 2 exhibit strong bands at
1629 and 1632 cm-1, respectively. In the 1H NMR
123

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J Chem Crystallogr (2012) 42:701–705
Fig. 2 The packing arrangement in a unit cell of 1 (a) and 2 (b)
molecules forming one-dimensional chain structures along
Table 3 Classical hydrogen bonds geometry for 1 and 2
b and c, respectively (Fig. 2).
˚
(D–HÁÁÁA)
D–H
˚
(A)
HÁÁÁA (A) DÁÁÁA
D–HÁÁÁA
(°)
˚
(A)
N(1)–H(1)ÁÁÁO(1)#1 (1) 0.86(1) 2.08(1)
N(1)–H(1)ÁÁÁO(1)#2 (2) 0.86(1) 2.06(2)
#1: x-1, 1/2-y, z-1/2
2.934 (2) 168(2)
Supplementary Material
2.914(2)
172(2)
Crystallographic data for the structures reported in this
paper have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication no.
CCDC-832529 and CCDC-832530. Copies of available
material can be obtained, free of charge, on application to
the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK (Fax: ?44-(0)-1223-336033 or e-mail: deposit@ccdc.
cam.ac.uk).
#2: x,-y ? 3/2, z ? 1/2
spectrum of 1, a singlet is identified as hydrogen on the
amino group at 6.91 ppm (7.13 ppm for 2). The other data
1
in IR, H NMR and HRMS are in good agreement with
their structures.
The selected bond lengths and bond angles of 1 and 2
are given in Table 2. The structures of 1 and 2, packing
arrangement in a unit cell of 1 and 2 are shown in
Figs. 1a,b, and Fig. 2a, b respectively. In 1. The atoms
N(1)/N(2)/C(1)–C(4) form a new pyrimidine ring, among
these atoms, N(1)/N(2)/C(1)/C(3) and C(4) are coplanar,
while the atom C(2) deviating from the defined plane by
Acknowledgments We are grateful to the National Natural Science
foundation of China (20802061), a project Funded by the Priority
Academic Program Development of Jiangsu Higher Education Insti-
tutions and Qing Lan Project (08QLT001, 10QLD008) of Jiangsu
Education Committee for financial support.
˚
0.581(2) A. These data indicate that the above-mentioned
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