ꢁꢀꢀꢀ
H.M. Refat and K.S. Mohamed: Fused benzothiazole derivativesꢂ
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Synthesis of (E)-2-(benzo[d]thiazol-2-yl)-3-(pyridin-4-yl)acry- Synthesis of 2,4-diamino-5-(pyridin-4-yl)-5H-[1,3]benzothiazolo
lonitrile (6)ꢁA solution of compound 1 (1.74 g, 0.01 mol) and isoni- [3,2-a][1,8]naphthyridine-3,6-dicarbonitrile (10)ꢁA mixture of
cotinaldehyde (1.07 g, 0.01 mol) in THF (10 mL) containing three compound 7 (3.29 g, 0.01 mol) and malononitrile (0.66 g, 0.01 mL)
drops of Et3N was heated under reflux for approximately 4 h, with in DMF (10 mL) containing a few drops of Et3N was heated under
progress monitored by TLC. The solid product 6 formed upon cooling reflux for 8 h and then allowed to cool. The precipitate that formed
was filtered off, dried, and crystallized from EtOH: Yellow crystals; was filtered off and crystallized from DMF to give compound 10:
yield 88%; mp 195–196°C; IR: ν 2215 cm-1 (CN); 1H NMR: δ 7.41 (d, 2H, Black crystals; yield 29%; mpꢀ>ꢀ350°C; IR ν cm-1: 3405–3313 (2 NH2)
J ꢀ=ꢀ 7.60 Hz, C3-H, C5-H of pyridine), 7.55 (m, 2H, C5-H and C6-H of ben- and 2205, 2199 cm-1 (2 CN); 1H NMR: δ 4.73 (s, 1H, C5-H), 6.52 (s, 2H,
zothiazole), 7.95 (dd, 1H, J ꢀ=ꢀ 7.40 Hz and 1.50 Hz, C7-H of benzothia- NH2), 7.18 (dd, 1H, J ꢀ=ꢀ 7.50 Hz and 1.50 Hz, C11-H), 7.23 (d, 2H, J ꢀ=ꢀ 7.70
zole), 8.20 (s, 1H, vinylic H), 8.23 (dd, 1H, J ꢀ=ꢀ 7.50 Hz and 1.50 Hz, C4-H Hz, C3-H, C5-H of pyridine), 7.35–7.48 (m, 2H, C9-H and C10-H), 7.89
of benzothiazole), 8.66 (d, 2H, J ꢀ=ꢀ 7.80 Hz, C2-H, C6-H of pyridine); (dd, 1H, J ꢀ=ꢀ 7.50 Hz and 1.50 Hz, C8-H), 8.25 (s, 2H, NH2), 8.59 (d, 2H,
13C NMR: δ 113.2, 117.8, 121.4, 122.0, 123.7 (3C), 126.1, 133.3, 144.9 (3C), J ꢀ=ꢀ 7.70 Hz, C2-H, C6-H of pyridine); 13C NMR: δ 27.0, 58.4, 61.6, 101.4,
+
152.6, 153.8, 162.2; MS: m/z 263 (M , 52%). Anal. Calcd for C15H9N3S 115.3, 117.5, 120.3, 121.7, 122.5, 124.4 (3C), 126.5, 145.2, 146.1, 148.4
+
(263.32): C, 68.42; H, 3.45; N, 15.96. Found C, 68.40; H, 3.49; N, 16.01.
(2C), 153.9, 162.2 (2C), 163.5; MS: m/z 395 (M , 100%). Anal. Calcd
for C21H13N7S (395.44): C, 63.78; H, 3.31; N, 24.79. Found C, 63.85; H,
Synthesis of 1-amino-3-(pyridin-4-yl)-3H-pyrido[2,1-b][1,3]ben- 3.40; N, 24.70.
zothiazole-2,4-dicarbonitrile (7)ꢁA mixture of compound 6 (2.62 g,
0.01 mol) and malononitrile (0.66 g, 0.01 mol) in absolute EtOH (10 mL) Synthesis of 4-amino-2-oxo-5-(pyridin-4-yl)-1,5-dihydro-2H-[1,3]
containing Et3N (3 drops) was heated under reflux for 4 h and then benzothiazolo[3,2-a][1,8]naphthyridine-3,6-dicarbonitrile
allowed to cool. The precipitated product was filtered off, washed with (15)ꢁA solution of compound 7 (3.29 g, 0.01 mol) in DMF (10 mL) con-
EtOH, and crystallized from EtOH to afford compound 7: Yellow crys- taining ethyl cyanoacetate (1.13 g, 0.01 mL) and Et3N (4 drops) was
tals; yield 95%; mp 263–264°C; IR: ν 3363, 3243 (NH2), 2208 and 2191 heated under reflux for 8 h and then allowed to cool. The precipitate
1
(two CN), 1618, 1490 cm-1, aromatic; H NMR: δ 4.71 (s, 1H, C3-H), 6.52 that formed was filtered off and crystallized from DMF to give com-
(s, 2H, NH2), 7.12 (dd, 1H, J ꢀ=ꢀ 7.70 Hz and 1.50 Hz, C4-H of benzothiazole), pound 15: Black crystals; yield 29%; mp 195–197°C; IR: ν 3430, 3329
7.27 (d, 2H, J ꢀ=ꢀ 7.70 Hz, C3-H, C5-H of pyridine), 7.38 (m, 2H, C5-H and (NH2), 3298 (NH), 2202, 2193 (2CN), and 1644 cm-1 (Cꢀ=ꢀO); 1H NMR: δ
C6-H of benzothiazole), 7.70 (dd, 1H, J ꢀ=ꢀ 7.50 and 1.50 Hz, C7-H of ben- 4.73 (s, 1H, CH), 6.42 (s, 2H, NH2), 7.09 (dd, 1H, J ꢀ=ꢀ 7.50 Hz and 1.5 Hz,
zothiazole), 8.59 (d, 2H, J ꢀ=ꢀ 7.80 Hz, C2-H, C6-H of pyridine); 13C NMR: C11-H), 7.25 (d, 2H, J ꢀ=ꢀ 7.7 Hz, C3-H, C5-H of pyridine), 7.30–7.40 (m, 2H,
δ 30.9, 62.5, 67.8, 117.5 (2C), 120.3, 121.0, 122.8 (3C), 124.4, 126.6, 145.7, 148.5 C9-H and C10-H), 7.80 (dd, 1H, J ꢀ=ꢀ 7.50 Hz and 1.50 Hz, C8-H), 8.55 (d,
+
(2C), 151.2, 162.5, 164.5; MS: m/z 329 (M , 49%). Anal. Calcd for C18H11N5S 2H, J ꢀ=ꢀ 7.7 Hz, C2-H, C6-H of pyridine), 11.45 (s, 1H, NH); 13C NMR: δ
(329.38): C, 65.64; H, 3.37; N, 21.26. Found C, 65.69; H, 3.45; N, 21.35.
28.3, 58.9, 61.2, 102.1, 115.5, 117.6, 120.1, 121.4, 122.6, 123.5 (3C), 126.4,
+
136.8, 145.5, 146.7, 148.3 (2C), 162.3, 163.4, 165.4; MS: m/z 396 (M ,
Synthesis of 4-amino-5-(pyridin-4-yl)-5H-pyrimido[5′,4′:5,6] 100%). Anal. Calcd for C21H12N6OS (396.43): C, 63.63; H, 3.05; N, 21.20.
pyrido[2,1-b][1,3]benzothiazole-6-carbonitrile (8)ꢁA solution of Found: C, 63.55; H, 3.13; N, 21.28.
compound 7 (3.29 g, 0.01 mol) in (5 mL) of formamide (0.45 g, 0.01 mol)
was refluxed for 12 h, and then allowed to cool. The precipitate that
Acknowledgments: The authors are very grateful to
formed was filtered off and crystallized from DMF to give compound
8: Black crystals; yield 29%; mpꢀ>ꢀ350°C; IR: ν 3398, 3312 (NH2) and Dr. A.A. Fadda, professor of Organic Chemistry, Chemistry
1
2198 cm-1 (CN); H NMR: δ 4.76 (s, 1H, C5-H), 6.56 (s, 2H, NH2), 7.15
Department, Faculty of Science, Mansoura University, for
guidance, precious advice, and support.
(dd, 1H, J ꢀ=ꢀ 7.40 Hz and 1.50 Hz, C11-H), 7.21 (d, 2H, J ꢀ=ꢀ 7.60 Hz, C3-H,
C5-H of pyridine), 7.30–7.40 (m, 2H, C9-H and C10-H), 7.81 (dd, 1H, J ꢀ=ꢀ
7.50 Hz and 1.50 Hz, C8-H), 7.92 (s, 1H, C2-H), 8.56 (d, 2H, J ꢀ=ꢀ 7.80 Hz,
C2-H, C6-H of pyridine); 13C NMR: δ 27.2, 61.4, 106.0, 117.8, 120.3, 121.7,
References
122.8, 124.4 (3C), 126.5, 145.6 (2C), 148.6 (2C), 155.4, 156.5, 162.2, 163.6;
+
MS: m/z 356 (M , 25%). Anal. Calcd for C19H12N6S (356.41): C, 64.03; H,
3.39; N, 23.58. Found C, 64.12; H, 3.47; N, 23.50.
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Synthesis of 4-oxo-5-(pyridin-4-yl)-3,5-dihydro-pyrimido[5′,4′:
5,6]pyrido[2,1-b][1,3]benzothiazole-6-carbonitrile (9)ꢁA mixture
of compound 7 (3.29 g, 0.01 mol) and formic acid (15 mL, 88%) was
heated under reflux for 16 h and then allowed to cool. The precipi-
tate that formed was filtered off and crystallized from DMF to give
compound 9: Pink crystals; yield 35%; mp 320–322°C; IR: ν 3284
(NH), 2195 (CN), and 1645 cm-1 (Cꢀ=ꢀO);1H NMR: δ 4.71 (s, 1H, C5-H), 7.15
(dd, 1H, J ꢀ=ꢀ 7.40 Hz and 1.50 Hz, C11-H), 7.21 (d, 2H, J ꢀ=ꢀ 7.70 Hz, C3-H,
C5-H of pyridine), 7.30–7.40 (m, 2H, C9-H and C10-H), 7.78 (dd, 1H, J ꢀ=ꢀ
7.60 Hz and 1.40 Hz, C8-H), 8.56 (d, 2H, J ꢀ=ꢀ 7.80 Hz, C2-H, C6-H of pyri-
dine), 8.68 (s, 1H, C2-H), 11.23 (s, 1H, NH); 13C NMR: δ 29.5, 61.7, 102.7,
117.4, 120.2, 121.3, 122.6, 123.6 (3C), 126.5, 145.6, 146.7, 148.5 (2C), 150.4,
+
153.8, 162.3, 165.3; MS: m/z 357 (M , 25%). Anal. Calcd for C19H11N5OS
(357.39): C, 63.85; H, 3.10; N, 19.60. Found C, 63.80; H, 3.18; N, 19.68.
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