Synthesis and crystal structure of 4-(2-chlorophenylamino)-6-methoxy-2- phenylquinazoline

Article abstract of DOI:10.1007/s10593-011-0805-1

4-(2-Chlorophenylamino)-6-methoxy-2-phenylquinazoline was synthesized from substituted thiourea by the photochemical method. The structure of the title compound was confirmed by IR, ¹H NMR, mass spectrometry, and X-ray crystallography.

Full text of DOI:10.1007/s10593-011-0805-1

Chemistry of Heterocyclic Compounds, Vol. 47, No. 5, August 2011 (Russian original Vol. 47, No. 5, May, 2011)
SYNTHESIS AND CRYSTAL STRUCTURE
OF 4-(2-CHLOROPHENYLAMINO)-
6-METHOXY-2-PHENYLQUINAZOLINE
Z.-Y. Xing1, Q. Zhao1, Y. Fu1, F. Ye1*
4-(2-Chlorophenylamino)-6-methoxy-2-phenylquinazoline was synthesized from substituted thiourea by
1
the photochemical method. The structure of the title compound was confirmed by IR, H NMR, mass
spectrometry, and X-ray crystallography.
Keywords: quinazoline, X-ray crystallography, synthesis.
The synthesis of halogen-containing N,N'-substituted thioureas and 1,2,4-triazole-3-thiones, which un-
der 254 nm ultraviolet irradiation for several hours in alcohol or a mixed solution of MeCN and aqueous NaOH
undergo photocyclization to give benzothiazoles and triazolobenzothiazines, respectively, was reported
previously [1–3]. It was shown that the ortho-halo substituent at the N-phenyl group is necessary for the
photochemical transformation of N,N'-disubstituted thioureas to benzothiazole. The objective of the present
work includes the study of the photoreaction of N,N'-disubstituted thiourea 1 with the aim to obtain new
benzothiazole derivatives 2.
Cl
h(365 nm)
NaOH
Cl
S
N
N
HN
S
N
NH
MeCN/H2O
N2
NH
NH
N
N
OMe
OMe
OMe
1
3
2
However, the irradiation of compound 1 with a high-pressure mercury lamp in a H2O–MeCN solution of
NaOH at room temperature did not lead to the expected product 2, but a novel product, 4-(2-chlo-
rophenylamino)-6-methoxy-2-phenylquinazoline (3), was obtained in 45% yield. It is probable that the presence
_______________
* To whom correspondence should be addressed, e-mail: yefei@neau.edu.cn.
1 College of Science Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 727–731, May, 2011. Original
article submitted December 8, 2010, in revised form March 25, 2011.
0009-3122/11/4705-0607©2011 Springer Science+Business Media, Inc.
607

of the o-chlorine atom at the phenyl ring of the N,N'-disubstituted thiourea 1, which increases the population of
the triplet state, influences the desulfurization by enhancing the intersystem crossing effect (heavy atom effect)
1
[3]. The novel compound 3 was confirmed by IR, H NMR, mass spectrometry, and single crystal X-ray
structure determination.
Fig.1 The X-ray structure of compound 3
According to X-ray analysis the structure contains a quinazoline molecule with phenyl, 2-chlorophenyl-
amino, and methoxy substitutuents. The distances N(1)–C(9) (1.314(3) Å) and N(2)–C(8) (1.309(3) Å) are signi-
ficantly shorter than N(1)–C(5) (1.369(3) Å) and N(2)–C(9) (1.364(3) Å), respectively, indicating the existence
of a double bond between N(1) and C(9), as well as between N(2) and C(8). In the quinazoline moiety, the phe-
nyl ring (mean deviation 0.0026 Å) and the pyrimidine ring (mean deviation 0.0038 Å) are almost coplanar, and
the dihedral angle between the two fused rings is 0.7(2)°. Otherwise, all the bond lengths and angles are in their
normal range (Table 1 and 2).
TABLE 1. Bond Lengths (d) in the Structure of Compound 3
Bond
d, Å
Bond
d, Å
Bond
d, Å
Cl(1)–C(21)
O(1)–C(2)
O(1)–C(1)
N(1)–C(9)
N(1)–C(5)
N(2)–C(8)
N(2)–C(9)
N(3)–C(8)
N(3)–C(16)
C(2)–C(7)
1.737(3)
1.360(3)
1.419(3)
1.314(3)
1.369(3)
1.309(3)
1.364(3)
1.374(3)
1.404(2)
1.359(3)
C(2)–C(3)
C(3)–C(4)
C(4)–C(5)
C(5)–C(6)
C(6)–C(7)
C(6)–C(8)
C(9)–C(10)
C(10)–C(15)
C(10)–C(11)
C(11)–C(12)
1.410(3)
1.353(3)
1.407(3)
1.409(3)
1.407(3)
1.431(3)
1.486(3)
1.379(3)
1.387(3)
1.370(3)
C(12)–C(13)
C(13)–C(14)
C(14)–C(15)
C(16)–C(21)
C(16)–C(17)
C(17)–C(18)
C(18)–C(19)
C(19)–C(20)
C(20)–C(21)
1.363(4)
1.383(4)
1.382(3)
1.383(3)
1.389(3)
1.378(3)
1.371(4)
1.371(4)
1.381(3)
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TABLE 2. Valence Angles (ω) in the Structure of Compound 3
Angle
ω, deg
Angle
ω, deg
C(2)–O(1)–C(1)
C(9)–N(1)–C(5)
C(8)–N(2)–C(9)
C(8)–N(3)–C(16)
C(7)–C(2)–O(1)
C(7)–C(2)–C(3)
O(1)–C(2)–C(3)
C(4)–C(3)–C(2)
C(3)–C(4)–C(5)
N(1)–C(5)–C(4)
N(1)–C(5)–C(6)
C(4)–C(5)–C(6)
C(7)–C(6)–C(5)
C(7)–C(6)–C(8)
C(5)–C(6)–C(8)
C(2)–C(7)–C(6)
N(2)–C(8)–N(3)
N(2)–C(8)–C(6)
N(3)–C(8)–C(6)
N(1)–C(9)–N(2)
117.53(19)
116.3(2)
117.1(2)
127.7(2)
125.8(2)
119.6(2)
114.6(2)
120.9(2)
121.0(2)
119.4(2)
122.3(2)
118.2(2)
119.9(2)
125.3(2)
114.8(2)
120.5(2)
118.7(2)
122.8(2)
118.5(2)
126.6(2)
N(1)–C(9)–C(10)
N(2)–C(9)–C(10)
117.9(2)
115.4(2)
118.6(3)
121.2(2)
120.2(2)
120.9(3)
120.2(3)
120.1(3)
119.7(3)
120.5(3)
118.0(2)
119.4(2)
122.4(2)
120.5(2)
120.4(3)
120.1(3)
119.5(3)
121.4(3)
118.9(2)
119.6(2)
C(15)–C(10)–C(11)
C(15)–C(10)–C(9)
C(11)–C(10)–C(9)
C(12)–C(11)–C(10)
C(13)–C(12)–C(11)
C(12)–C(13)–C(14)
C(15)–C(14)–C(13)
C(10)–C(15)–C(14)
C(21)–C(16)–C(17)
C(21)–C(16)–N(3)
C(17)–C(16)–N(3)
C(18)–C(17)–C(16)
C(19)–C(18)–C(17)
C(18)–C(19)–C(20)
C(19)–C(20)–C(21)
C(20)–C(21)–C(16)
C(20)–C(21)–Cl(1)
C(16)–C(21)–Cl(1)
EXPERIMENTAL
The melting point was measured on a Yanagimoto MP-500 apparatus (uncorrected). The IR spectrum
was recorded on a Bio-Rad FTS 3000 spectrometer using KBr discs. The 1H NMR spectrum was recorded on a
Bruker AV-500 spectrometer in CDCl3, internal standard TMS. The mass spectrum was recorded on a Shimadzu
GCMS-QP2010 spectrometer. The elemental analysis was performed on a Flash EA 1112 elemental analyzer.
Compound 1 was prepared using a literature procedure [4].
4-(2-Chlorophenylamino)-6-methoxy-2-phenylquinazoline (3). To compound 1 (0.2 g, 0.5 mmol) in a
quartz tube, MeCN (300 ml) and aqueous 2 M NaOH (20 ml) were added. The mixture, deoxygenated by
purging with N2 for 0.5 h, was stirred and irradiated with a high-pressure mercury lamp for 7 h. TLC analysis
showed that the photolysis was carried to 100% conversion. After removal of the organic solvent under reduced
pressure, the product 3 was isolated from the precipitated solid by column chromatography with chloroform as
eluent. White block solid (0.08 g, 45%); mp 159–161°C. IR spectrum, ν, cm–1: 3434 (NH), 1557 (C=N), 1358
1
(C–N). H NMR spectrum, δ, ppm (J, Hz): 3.53 (3H, s, OCH3); 7.07–7.11 (1H, m, H Ar); 7.14 (1H, d, J = 2.5,
H Ar); 7.44–7.53 (6H, m, H Ar); 7.94 (1H, s, H-5); 7.96 (1H, s, NH); 8.51–8.53 (2H, m, H Ar); 9.02 (1H, d,
J = 8.5, H Ar). Mass spectrum, m/z (Irel, %): 361 [M]+ (27), 326 [M–Cl]+ (100), 311 [M–Cl–CH3]+ (5). Found,
%: C 69.79; H 4.52; N 11.58. C21H16ClN3O. Calculated, %: C 69.71; H 4.46; N 11.61.
X-Ray Structural Analysis of Compound 3. A crystal suitable for X-ray structure determination was
obtained by slow evaporation of an acetonitrile solution of compound 3. Cell parameters and the intensities of
9709 independent reflections for compound 3 were measured at 21°C on a Bruker Smart-1000 automatic
diffractometer with a graphite monochromator using MoKα radiation. The monoclinic crystals of compound 3
have space group P21/c. The unit cell parameters: a = 12.536(3), b = 6.9533(17), c = 20.576(5) Å,
β = 95.094(5)°, V = 1786.5(7) Å3, dcalc = 1.345 g·cm–3, Z = 4, Mr = 361.82. In the calculations 1506 reflections
with intensities I > 2σ(I) were used. The structure was solved by direct methods using the SHELXS-97 program
[5] and refined by full matrix least squares on F2 using the SHELXL-97 program [6]. All non-hydrogen atoms
were refined anisotropically, and hydrogen atoms were added according to theoretical modes. The final
609

divergence factors were R = 0.0472 and wR2 = 0.0861. Plots were produced with the XP program. Crystallo-
graphic data have been deposited at the Cambridge Crystallographic Data Center (deponent CCDC 630620).
This work was supported by the Research Science Foundation in Technology Innovation of Harbin
(No. 2010RFQXS070), Heilongjiang Province Postdoctoral Science Foundation funded project (No. LBH-
Z10241), and Northeast Agricultural University Doctor Foundation funded project (No. 2009RC22).
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