Synthesis and structure analysis of 2-(2′-propanonylthio)-3-(o-methyl phenyl) quinazol-4(3H)-one

Article abstract of DOI:10.1023/B:JOCC.0000047645.53340.5f

The three-dimensional molecular and crystal structure of 2-(2′-propanonylthio)3-(o-methyl phenyl)quinazol-4(3H)-one has been determined by X-ray crystallographic methods. This compound crystallizes in the orthorhombic space group P_bca with unit

Full text of DOI:10.1023/B:JOCC.0000047645.53340.5f

Journal of Chemical Crystallography, Vol. 34, No. 10, October 2004 (ꢀC 2004)
Synthesis and structure analysis of
2-(2ꢀ-propanonylthio)-3-(o-methyl phenyl)
quinazol-4(3H)-one
Rajnikant,(1)∗ Dinesh,(1) Mousmi,(1) M.B. Deshmukh,(2) S.S. Patil,(2) and Anshu Sawhney(1)
Received January 2, 2003
The three-dimensional molecular and crystal structure of 2-(2ꢁ-propanonylthio)3-(o-methyl
phenyl)quinazol-4(3H)-one has been determined by X-ray crystallographic methods. This
compound crystallizes in the orthorhombic space group Pbca with unit cell parameters:
˚
a = 9.649(5), b = 30.102(10), c = 11.403(9) A. It has been solved by direct methods and
refined to a residual index of 0.054. The magnitude of torsion along C16 C11 N3 C4
bond is 93.5(4)◦. The dihedral angle between the plane comprising all the ring atoms
of quinazoline moiety and the atoms of the methyl substituted phenyl ring is 94.12(1)◦.
The crystal structure is stabilized by one intramolecular C H· · ·O interaction and three
intermolecular C H· · ·N contacts.
KEY WORDS: Crystal structure; molecular interactions; X-ray diffraction; side chain descriptors.
Experimental
Introduction
Alkaloids containing a quinazoline moiety
Step I: Synthesis of 3-(o-methyl phenyl)2-
thioquinazolin-4(3H)-one
are known for their biological properties.1−4
Recent studies have shown some remarkable
properties exhibited by a variety of quinazoline
derivatives and most notable among these have
found place in analgesic, antiallergic, anti-
inflammatory, secretion inhibition, anticoagulant,
etc.5 The study being reported in this paper is a
part of our ongoing work on the synthesis and
structure analysis of a variety of quinazoline
molecules.6−9
Thiocarbonate salt of o-toludine was heated
with anthranilic acid in ethanol on a steam bath
for 6 h, cooled, and the excess of solvent removed
under reduced pressure. The semisolid mass was
dissolved in NaOH (10%) and filtered. The filtrate
on neutralization with HCl (1:1) yielded a solid
which was recrystallized from ethanol to get I,
(90%), mp 542 K.
(1) X-Ray Crystallography Laboratory, Post-Graduate Department of
Physics, University of Jammu, Jammu Tawi, India.
(2) Department of Chemistry, Shivaji University, Kolhapur,
Maharashtra, India.
∗ To whom correspondence should be addressed; e-mail:
rkantverma@rediffmail.com.
693
ꢀ
C
1074-1542/04/1000-0693/0 2004 Springer Science+Business Media, Inc.

694
Rajnikant et al.
Step II: Synthesis of 2-(2ꢁ-propanonylthio)-3-(o-
methylphenyl)quinazol- 4(3H)-one
A mixture of I (0.02 mole) and chloroace-
tone (0.02 mole) in acetone (10 mL), to which
anhydrous K2CO3 (0.5 g) was added and the re-
action mixture was refluxed for 18 h, cooled, and
the solvent removed under reduced pressure to
get a solid which was recrystallized from ethanol,
yield (80%), mp 373 K. The chemical structure
as shown above has been assigned on the basis
of IR, UV, NMR, and mass spectral data (M.B.
Deshmukh, Private communication, 2002, Shiv-
aji University, Kolhapur, India).
employed for data collection. The θ-range for the
entire data collection is 2.24–24.98◦. A total of
2861 reflections were found unique (0 ≤ h ≤ 11,
0 ≤ k ≤ 35, 0 ≤ l ≤ 13). Two standard reflec-
¯ ¯ ¯
tions (2 4 9) (0 2 16) measured every 100 reflec-
tions showed no significant variation in the inten-
sity data. The reflection data were corrected for
Lorentz and polarization effects. Absorption and
extinction corrections were not applied.
The structure has been elucidated by di-
rect methods using SHELXS program.10 All non-
hydrogenatomsofthemoleculewerelocatedfrom
Three-dimensional intensity data of
transparent rectangular plate single crystal of 2-
(2ꢁ-propanonylthio)-3-(o-methylphenyl)quinazol
-4(3H)-one were collected on an Enraf-Nonius
CAD-4 diffractometer using MoKα radiation
Table 2. Atomic Coordinates and Equivalent Isotropic Displace-
2
˚
ment Parameters (A ) with esd’s in Parentheses, for the Non-
Hydrogen Atoms
˚
(λ = 0.71073 A. The ω/2θ scan mode was
Atom
X
Y
Z
Ueaq.
S1
O1
O2
N1
N3
C2
C4
C5
C6
C7
C8
C9
C10
C11
C12
C13
C14
C15
C16
C17
C18
C19
C20
0.0266(1) 0.4394(0) 0.5275(1) 0.0582(3)
−0.3041(2) 0.3164(1) 0.4778(2) 0.0653(8)
−0.0613(2) 0.4886(1) 0.7502(2) 0.0731(8)
−0.0463(3) 0.3842(1) 0.6972(2) 0.0496(8)
−0.1439(2) 0.3705(1) 0.5099(2) 0.0442(8)
−0.0600(3) 0.3934(1) 0.5886(3) 0.0452(9)
−0.2279(3) 0.3351(1) 0.5476(3) 0.0495(1)
−0.2875(4) 0.2885(1) 0.7187(3) 0.0710(14)
−0.2719(4) 0.2776(1) 0.8334(4) 0.0809(17)
−0.1822(4) 0.3015(1) 0.9038(3) 0.0768(16)
−0.1077(3) 0.3365(1) 0.8583(3) 0.0614(12)
−0.1218(3) 0.3484(1) 0.7412(3) 0.0498(10)
−0.2125(1) 0.3237(1) 0.6697(3) 0.0505(11)
−0.1432(3) 0.3816(1) 0.3860(3) 0.0448(9)
−0.0580(3) 0.3579(1) 0.3115(3) 0.0514(10)
−0.0611(3) 0.3687(1) 0.1936(3) 0.0609(12)
−0.1491(4) 0.4012(1) 0.1525(3) 0.0644(13)
−0.2342(3) 0.4238(1) 0.2275(3) 0.0596(11)
−0.2318(3) 0.4138(1) 0.3448(3) 0.0527(11)
−0.0391(4) 0.3225(1) 0.3560(3) 0.0777(15)
−0.1288(3) 0.4541(1) 0.6533(3) 0.0565(10)
−0.0486(3) 0.4700(1) 0.7583(3) 0.0544(11)
−0.1171(4) 0.4617(2) 0.8739(3) 0.0774(15)
Table 1. Crystal Data and Structure Refinement Details
CCDC
203248
Crystal description
Empirical formula
Formula weight
Rectangular plates
C18 H16N2O2S
324.39
Temperature
293(2)K
Crystal system, space group
Radiation, Wavelength (λ)
Unit cell dimensions
Orthorhombic, Pbca
˚
MoKα, 0.71073 A
a = 9.649(5), b = 30.102(10),
˚
c = 11.403(9) A
3
3
˚
Z, Volume, Calculated density
F(000)
8, 3312(3) A , 1.301 Mg/m
1360
Crystal size
θ range for data collection
Index ranges
0.3 × 0.3 × 0.2 mm
2.24–24.98◦
0 ≤ h ≤ 11, 0 ≤ k ≤ 35,
0 ≤ l ≤ 13
No. of reflections collected/unique 2861/2861
−3
˚
Largest diff. Peak and hole
Refinement method
0.28 < ρ < −0.29 e A
Full-matrix least-square on F2
Data/restraints/parameters
Final R indices [F0 > 4(σF0)]
R indices (all data)
2857/0/208
R1 (0.054), wR2 (0.1325)
R1 = 0.0834, wR2 = 0.1499
1.093
ꢀ ꢀ
Goodness of Fit
aUe∗q = (1/3)
j Ui j ai∗a∗j (ai · aj ).
i

Structure analysis of 2-(2ꢀ-propanonylthio)-3-(o-methyl phenyl) quinazol-4(3H)-one
695
the E-map. Full-matrix least-squares refinement
of the structure has been carried out by using
SHELXL program.11 The positional and thermal
parameters of non-hydrogen atoms were refined
isotropically. Allhydrogenatomswerefixedstere-
ochemically. Further refinement with anisotropic
thermal parameters resulted into a final value of
Fig. 1. The chemical structure with atom numbering scheme.
the reliability index, R(0.054). The maximum and
minimum values for the−re3sidual electron density
˚
are 0.28 and −0.29 eA , respectively. Atomic
bridge Crystallographic Data Centre (CCDC), 12
Union Road, Cambridge CB2 1EZ, UK; fax:
+44(0)1223-336033; e-mail:deposit@ccdc.cam.
ac.uk].”
scattering factors were obtained from Interna-
tional Tables for Crystallography (1992, Vol. C,
Tables 4.2.6.8 and 6.1.1.4). The crystallographic
data are listed in Table 1.
“CCDC 203248 contains the supplementary
crystallographic data for this paper. These data can
be obtained free of charge at www.ccdc.cam.ac.
uk/uk/conts/retrieving.html [or from the Cam-
Results and discussion
The final atomic positions and equivalent
isotropic displacement parameters for all the non-
hydrogen atoms are listed in Table 2. Bond lengths
and bond angles for non-hydrogen atoms are given
in Table 3. A general view of the molecule indi-
cating atom numbering scheme (thermal ellipsoid
drawn at 50% probability) is shown in Fig. 2.12
The geometrical calculations were performed us-
ing PARST program.13
The bond lengths and bond angles of pyri-
dine ring and phenyl ring are quite close to the
values as obtained in case of some analogous
structures.14−17 The length of S1 C18 bond is
◦
˚
Table 3. Bond Distances (A) and Bond Angles ( ) for Non
-Hydrogen Atoms (esd’s Are Given in Parentheses)
S1 C2
S1 C18
O1 C4
O2 C19
N1 C2
N1 C9
N3 C11
N3 C2
C13 C14
C14 C15
C15 C16
C18 C19
C2 S1 C18
C2 N1 C9
C4 N3 C11
C2 N3 C11
C2 N3 C4
N1 C2 N3
S1 C2 N3
S1 C2 N1
O1 C4 N3
N3 C4 C10
O1 C4 C10
C5 C6 C7
C6 C5 C10
C5 C6 C7
C6 C7 C8
N1 C9 C10
C5 C10 C9
N1 C9 C8
C8 C9 C10
1.761(3)
1.796(4)
1.221(4)
1.202(4)
1.276(4)
1.394(4)
1.451(4)
1.391(5)
1.377(5)
1.366(5)
1.371(5)
1.503(5)
97.9(1)
117.6(3)
118.3(3)
120.7(3)
120.9(2)
125.4(3)
114.2(2)
120.4(3)
119.8(3)
114.6(3)
125.6(3)
120.2(4)
120.7(3)
120.2(4)
120.4(3)
119.6(3)
119.3(3)
119.6(3)
118.8(3)
C6 C7
C7 C8
C8 C9
C9 C10
C11 C12
C11 C16
C12 C13
C12 C17
C4 C10
C5 C6
C5 C10
C19 C20
C4 C10 C9
C4 C10 C5
N3 C11 C16
N3 C11 C12
C12 C11 C16
C11 C12 C13
C13 C12 C17
C12 C13 C14
C13 C14 C15
C14 C15 C16
C11 C16 C15
S1 C18 C19
O2 C19 C18
C18 C19 C20
C7 C8 C9
O2 C19 C20
C4 C10 C9
C11 C12 C17
1.382(5)
1.376(5)
1.389(5)
1.408(4)
1.387(5)
1.375(4)
1.383(5)
1.499(5)
1.441(5)
1.356(6)
1.399(4)
1.495(5)
119.8(3)
120.8(3)
119.5(3)
118.7(3)
121.8(3)
119.5(1)
120.9(3)
121.1(3)
120.7(3)
119.4(3)
119.9(3)
115.6(2)
122.7(3)
114.9(3)
120.6(3)
122.4(3)
119.8(3)
121.9(3)
˚
significantly long (1.796 A) than the standard
Fig. 2. A general view of the molecules (thermal ellipsoid
drawn at 50% probability).

696
Rajnikant et al.
18
New Delhi for the financial support under its
DRS Research Project No: F.530/3/DRS/2001
(SAP-I).
˚
value (1.70 A) and variation of this kind in the
bond length could be attributed to the hybridiza-
tion state of C18(sp3) and C2(sp2) atoms.19
A
comparison of some S C bond distances obtained
in the present case and those which exists in litera-
ture clearly indicates that the S1 C18 and S1 C2
bond lengths are significantly large.20−24 The
bond angle between S1 C2 and S1 C18 is well
within the expected value.19 Both the phenyl rings
i.e. B & C have normal bond distances and angles.
All the three rings are planar as depicted
References
1. Asano, K.; Asai, S. Yakugaku Zasshi. 1958, 78, 450.
2. Baker, B.R.; Koehler, R.; Goodman, L.; De Graw, J. Org. Chem.
1961, 26, 1156.
3. Desai, N.C.; Undavia, N.K.; Trivedi, P.B.; Dipika, D.; Vyas,
G.D. Indian J. Exp. Biol. 1998, 36, 1280.
4. Siegfield, L.; Karl, D.; Guenther, W.; Herwart, A.; Dieter, I. C.A.
1992, 116, 34567.
by the magnitude of the torsion angles present
in these rings. The oxygen atom O1 is deviated
below the plane of the ring A [deviation being
5. Babita, M. PhD Thesis; Regional Research Laboratory: Jammu
Tawi, India, 1994.
6. Thappa, R.K.; Agarwal, S.G.; Dhar, K.L.; Gupta, V.K.;
Goswami, K.N. Phytochemistry 1996, 42, 1485.
7. Magotra, D.K.; Gupta, V.K.; Rajnikant; Goswami, K.N.;
Thappa, R.K.; Aggarwal, S.G. Acta Crystallogr. 1996, C52,
521.
˚
(−0.041(2) A]. The magnitude of torsion present
in the bond C16 C11 N3 C4 [93.5(4)◦] is in-
dicative of the dihedral angle [94.1(1)◦] between
the quinazoline moiety and the methyl substituted
phenyl ring. The crystal structure is stabilized by
the following interactions:
8. Rajnikant; Gupta, V.K.; Singh, A. Crystallogr. Rep. 2000, 45,
611.
9. Rajnikant;Gupta, V.K.;Deshmukh, M.B.;Varghese, B.;Dinesh.
Cryst. Res. Technol. 2001, 36, 1456.
10. Sheldrick, G.M. SHELXS86, Program for the Solution
of Crystal Structures; University of Gottingen: Germany,
1986.
11. Sheldrick, G.M. SHELXS93, Program for the Refinement
of Crystal Structures; University of Gottingen: Germany,
1993.
H· · ·A(A) D· · ·A(A) D-H· · ·A(◦)
˚
˚
D-H· · ·A
12. Farrugia, L.J. Molecular Graphics—ORTEP-3 for Windows. J.
Appl. Cryst. 1997, 30, 565.
13. Nardelli, M. Comput. Chem. 1983, 7, 95.
14. Freer, A.A.; Robins, D.J.; Sheldrake, G.N. Acta Crystallogr.
1987, C43, 1119.
15. Johnson, A.T.; Kelszler, D.A.; Sakuma, K.; White, J.D. Acta
Crystallogr. 1989, C45, 1114.
16. Djinovic, K.; Golic, L.; Leban, I. Acta Crystallogr. 1990, C46,
281.
C17 H17A· · ·N3
C6 H6· · ·O1(i)
2.40(4)
2.49(5)
2.50(4)
2.61(4)
2.87(4)
3.29(5)
3.30(4)
3.53(4)
110.5(3)
144.5(3)
145.8(3)
168.8(3)
C15 H15· · ·O2(iii)
C13 H13· · ·O1(ii)
Equivalent position: (i) x, −y + 1/2 + 1, z + 1/2.
(ii) x + 1/2, y, −z + 1/2.
(iii) x + 1/2, (+y, −z − 1/2.
17. Pecorari, P.; Renaldi, M.; Antolini, L. Acta Crystallogr. 1992,
C48, 2027.
18. Sutton, L.E. Tables of Interatomic Distances and Configuration
in Molecules and Ions, Chemical Society Special Publication
No. 18; Chemical Society: London, 1965.
The conformational side chain designa-
tions across the single bonds S1 C18, S1 C2,
and C18 C19 are -synclinal, synperiplanar, and
synperiplanar, respectively.25
19. Form, G.R.; Raper, E.S. Acta Crystallogr. 1974, B30,
342.
20. Fehlmann, M. Acta Crystallogr. 1970, B26, 1736.
21. Stenson, P.E. Acta Chem. Scand. 1970, 24, 3729.
22. Kruger, G.J.; Gafner, G. Acta Crystallogr. 1971, B27, 326.
23. Amirthalingham, V.; Mauralidharan, K.V. Acta Crystallogr.
1972a, B28, 2417.
Acknowledgments
24. Amirthalingham, V.; Mauralidharan, K.V. Acta Crystallogr.
1972b, B28, 2421.
The corresponding author (Dr Rajnikant) is
25. Klyne, W.; Prelong, V. Experientia 1960, 16, 521.
thankful to the University Grants Commission,