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Y.-G. Chang, K. Kim
LETTER
mL) was added TiCl4 (0.55–0.64 mmol) by using a
(5) (a) Armarego, W. L. F. Advances in Heterocyclic Chemistry,
Vol. 1; Katritzky, A. R., Ed.; Academic Press: New York,
1963, 253. (b) Armarego, W. L. F. Advances in Heterocyclic
Chemistry, Vol. 24; Katritzky, A. R., Ed.; Academic Press:
New York, 1979, 1. (c) Brown, D. J. Comprehensive
Heterocyclic Chemistry, Vol. 3; Katritzky, A. R.; Rees, C.
W., Eds.; Pergamon: Oxford, 1984, 57. (d) Undheim, K.
Comprehensive Heterocyclic Chemistry II; Katritzky, A. R.;
Rees, C. W.; Scriven, E. F., Eds.; Pergamon: Oxford, 1996,
93.
(6) Weinstein, L.; Chang, T. W.; Hudson, J. B. Antibiot.
Chemother. 1957, 7, 443.
(7) Perlman, D.; Barrett, J. M. Can. J. Microbiol. 1958, 4, 9.
(8) Ishikawa, F.; Kosasayama, A.; Higashi, K. Chem. Pharm.
Bull. 1980, 28, 2024.
(9) (a) Meguro, K.; Tawada, H.; Kuwada, Y. Chem. Pharm.
Bull. 1973, 21, 1619. (b) Derieg, M. E.; Fryer, R. J.; Hillery,
S. S.; Metlesics, W.; Silverman, G. J. Org. Chem. 1971, 36,
782. (c) Hirai, K.; Fujishita, T.; Ishiba, T.; Sugimoto, H.;
Matsutani, S.; Tsukinoki, Y.; Hirose, K. J. Med. Chem.
1982, 25, 1466.
(10) Bahr, F.; Dietz, G. Pharmazie 1980, 35, 256.
(11) Hirai, K.; Ishiba, T.; Sugimoto, H.; Fujishita, T. J. Org.
Chem. 1981, 46, 4489.
hypodermic syringe under nitrogen atmosphere.
Subsequently arylamines were added. When p-toluidine was
added, the reaction mixture showed a yellow spot (Rf = 0.7,
EtOAc–n-hexane = 1:3), assignable to be 3,4-dihydro-4-
methylene-3-(4-tolyl)quinazoline-2-carbonitrile (9a). IR
(neat): 2240, 1635, 1603, 1581, 1555, 1504, 1469, 1344,
1322, 1226, 1206, 1110, 816, 762 cm–1. 1H NMR (CDCl3,
300 MHz): = 2.47 (s, 3 H, CH3), 3.61 (d, 1 H, J = 2.5 Hz,
=CH), 4.65 (d, 1 H, J = 2.5 Hz, =CH), 7.26–7.32 (m, 3 H,
ArH), 7.36–7.52 (m, 4 H, ArH), 7.53 (d, 1 H, J = 7.8 Hz,
ArH). 13C NMR (CDCl3, 75 MHz): = 21.8, 85.0, 112.1,
123.4, 123.7, 128.2, 128.9, 129.4, 131.1, 131.9, 133.1,
135.9, 140.8, 141.0, 142.8. Anal. Calcd for C17H13N3: C,
78.74; H, 5.05; N, 16.20. Found: C, 78.62; H, 5.09; N, 16.35.
Compound 9a gradually faded out during chromatography
to give a new spot (Rf = 0.5, EtOAc–n-hexane = 1: 3),
corresponding to 2-cyano-3-(4-tolyl)quinazolin-4(3H)-one
(2b), which was eluted with a mixture of EtOAc and n-
hexane (1:5) as an eluent to give 2b, which was
recrystallized from EtOH. Mp 175-176 °C. IR (KBr): 1677,
1581, 1501, 1456, 1328, 1312, 1274, 1104, 1082, 810, 774
cm–1. 1H NMR (CDCl3, 300 MHz): = 2.49 (s, 3 H, CH3),
7.31 (d, 2 H, J = 8.3 Hz, ArH), 7.43 (d, 2 H, J = 8.3 Hz, ArH),
7.67–7.73 (m, 1 H, ArH), 7.82–7.92 (m, 2 H, ArH), 8.38 (d,
1 H, J = 7.6 Hz, ArH). 13C NMR (CDCl3, 75 MHz): = 21.9,
111.6, 123.4, 127.9, 128.3, 129.1, 130.7, 131.2, 132.1,
132.9, 135.8, 141.5, 146.9, 160.6. Anal. Calcd for
(12) Hara, T.; Kayama, Y.; Sunami, T. J. Org. Chem. 1978, 43,
4865.
(13) (a) Zimaity, T.; Anwar, M.; Abdel-Hay, F. I.; Abdel-
Megeid, F. M. E. Acta Chim. Acad. Sci. Hung. 1975, 87,
251. (b) Elkaschef, M. A.-F.; Abdel-Megeid, F. M. E.;
Abdel-Kader, A. Collect. Czech. Chem. Commun. 1974, 39,
287. (c) Abdel-Megeid, F. M. E.; Elkaschef, M. A.-F.;
Mokhtar, K.-E. M.; Zaki, K.-E. M. J. Chem. Soc. C 1971,
1055.
(14) Yamagishi, M.; Ozaki, K.-I.; Yamada, Y.; Da-te, T.;
Okamura, K.; Suzuki, M. Chem. Pham. Bull. 1991, 39, 1694.
(15) Burlaka, B. M. Khim. Geterotsikl. Soedin. 1980, 708.
(16) Kim, K. Sulfur Reports 1998, 21, 147.
C16H11N3O: C, 73.55; H, 4.24; N, 16.08. Found: C, 73.50; H,
4.22; N, 16.21.
(20) General Procedure for the Synthesis of 3-Aryl-3,4-
dihydro-4-hydroxy-4-phenylquinazoline-4-carbonitriles
6. To a solution of 2-[N-(4-chloro-5H-1,2,3-dithiazol-5-
ylidene)]benzophenone (5a) (0.29–0.41 mmol) in CH2Cl2
(15 mL) was added TiCl4 (0.46–0.91 mmol) by using a
hypodermic syringe under nitrogen atmosphere, followed by
addition of arylamines (0.61–1.03 mmol). The mixture was
worked up as described in the general procedure for the
synthesis of 2. Elution with a mixture of n-hexane and
EtOAc (3:1) gave 6a,b and 6f. 4-Hydroxy-3-(4-
methoxyphenyl)-4-phenylquinazoline-2-carbonitrile (6a),
which was recrystallized from a mixture of CH2Cl2 and n-
hexane. Mp 179–182 °C (dec.). IR (KBr): 3168, 2224, 1597,
1578, 1454, 1467, 1446, 1354, 1290, 1248, 1168, 1030, 995,
819, 765, 733 cm–1. 1H NMR (CDCl3, 300 MHz): = 3.73
(s, 3 H, OCH3 of major), 3.84 (s, 3 H, OCH3 of minor), 5.99
(s, br, 1 H, OH of major), 6.60–6.66 (m, 2 H, ArH of major),
6.80–6.82 (m, 1 H ArH of major), 6.89 (d, 1 H, J = 7.4 Hz,
ArH of major), 7.12–7.26 (m, 6 H, ArH of major), 7.39–7.53
(m, 2 H, ArH of major), 7.74–7.76 (m, 1 H, ArH of major).
13C NMR (CDCl3, 75 MHz): = 55.3, 87.6, 112.0, 113.7,
124.7, 127.6, 128.1, 128.1, 128.2, 128.3, 129.7, 129.8,
131.1, 133.1, 134.3, 139.0, 141.8, 159.7. The aromatic
proton signals of minor compound are envisaged to overlap
with those of major. Anal. Calcd for C22H17N3O2: C, 74.35;
H, 4.82; N, 11.82. Found: C, 74.49; H, 4.80; N, 11.71.
(21) Okabayashi, I.; Fujiwara, H. J. Heterocycl. Chem. 1984, 21,
1401.
(17) Lee, H.-S.; Chang, Y.-G.; Kim, K. J. Heterocycl. Chem.
1998, 35, 659.
(18) Appel, R.; Janssen, H.; Siray, M.; Knoch, G. Chem. Ber.
1985, 118, 1632.
(19) General Procedure for the Synthesis of 3-Aryl-2-
cyanoquinazolin-4(3H)-ones 2. (A) To a solution of methyl
N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)anthranilate (1)
(0.42–0.94 mmol) in CH2Cl2 (20 mL) was added TiCl4
(0.82–1.37 mmol) by using a hypodermic syringe under
nitrogen atmosphere. The solution turned immediately dark
red. Arylamines (1.86–3.78 mmol) were added to the dark
red solution, which was stirred until no spot corresponding
to 1 was observed on TLC (silica gel, Rf = 0.6, EtOAc–
hexane = 1:3). Water (30 mL) was added and the mixture
was extracted with CH2Cl2 (25 mL 3). The combined
extracts were dried over MgSO4, followed by evaporation of
the solvent. The residue was chromatographed on a silica gel
(70–230 mesh, 2 10 cm). Elution with n-hexane gave
sulfur. Subsequent elution with a mixture of n-hexane and
EtOAc (5:1) gave unknown mixtures and 2. (B) To a
solution of 2-[N-(4-chloro-5H-1,2,3-dithiazol-5-
ylidene)]acetophenone (5c) (0.36–0.59 mmol) in CH2Cl2 (15
Synlett 2002, No. 9, 1423–1426 ISSN 0936-5214 © Thieme Stuttgart · New York