328
Vol. 58, No. 3
pound 5 with halogenated hydrocarbon in ethanol with K2CO3.
(NH), 1667 (CꢁO), 1462 (C–O–C), 1069 (C–O–C); MS m/z: 306 (Mꢃ1);
Anal. Calcd for C15H12ClNO2S: C, 58.92; H, 3.96; N, 4.58. Found: C, 58.68;
H, 3.79; N, 4.76.
7-Methoxy-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazine (4a) mp
203—205 °C; yield 96%; 1H-NMR (CDCl3, 300 MHz) d: 3.85 (s, 3H,
–OCH3), 4.19 (s, 2H, –S–CH2–), 6.88 (dd, 1H, J1ꢁ 2.6 Hz, J2ꢁ6.7 Hz, Ar-
H), 7.02 (d, 1H, Jꢁ2.6 Hz, Ar-H), 7.37 (s, 1H, Ar-H), 8.56 (s, 1H,
N–CHꢁN–); IR (KBr) cmꢂ1: 1596 (CꢁN), 1301 (C–N), 1245, 1216
(C–O–C), 1032 (N–N). MS m/z: 220 (Mꢃ1); Anal. Calcd for C10H9N3OS:
C, 54.78; H, 4.14; N, 19.16. Found: C, 54.80; H, 4.17; N, 19.13.
7-Ethoxy-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazine (4b) mp
157—159 °C; yield 68%; 1H-NMR (CDCl3, 300 MHz) d: 1.45 (t, 3H,
Jꢁ7.0 Hz, –CH3), 4.06 (t, 2H, Jꢁ7.1 Hz, –O–CH2–), 4.19 (s, 2H, –S–CH2–),
6.88 (dd, 1H, J1ꢁ2.6 Hz, J2ꢁ7.0 Hz, Ar-H), 7.02 (s, 1H, Ar-H), 7.37 (d, 1H,
Jꢁ8.9 Hz, Ar-H), 8.56 (s, 1H, N–CHꢁN–); IR (KBr) cmꢂ1: 1595 (CꢁN),
1305 (C–N), 1243, 1212 (C–O–C), 1030 (N–N). MS m/z: 234 (Mꢃ1); Anal.
Calcd for C11H11N3OS: C, 56.63; H, 4.75; N, 18.01. Found: C, 56.82; H,
4.64; N, 18.23.
7-Propoxy-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazine (4c) mp
116—118 °C; yield 70%; 1H-NMR (CDCl3, 300 MHz) d: 1.05 (t, 3H,
Jꢁ7.4 Hz, –CH3), 1.82 (m, 2H, –CH2–), 3.94 (t, 2H, Jꢁ6.5 Hz, –OCH2–),
4.06 (s, 2H, –S–CH2–), 6.86 (dd, 1H, J1ꢁ 2.7 Hz, J2ꢁ 8.8 Hz, Ar-H), 7.01
(s, 1H, Ar-H), 7.34 (d, 1H, Jꢁ8.8 Hz, Ar-H), 8.54 (s, 1H, N–CHꢁN–); IR
(KBr) cmꢂ1: 1594 (CꢁN), 1306 (C–N), 1241, 1209 (C–O–C), 1039 (N–N).
MS m/z: 248 (Mꢃ1); Anal. Calcd for C12H13N3OS: C, 58.28; H, 5.30; N,
16.99. Found: C, 58.48; H, 5.19; N, 16.85.
7-(2,6-Dichloro-benzyloxy)-2H-benzo[b][1,4]thiazin-3(4H)-one (3q)
1
mp 184—186 °C; yield 31%; H-NMR (CDCl3, 300 MHz) d: 3.44 (s, 2H,
–S–CH2–), 5.13 (s, 2H, –OCH2–), 6.77—6.89 (m, 3H, Ar-H), 7.02—7.40
(m, 3H, H-3, H-4, H-5), 7.83 (s, 1H, –CONH); IR (KBr) cmꢂ1: 3457 (NH),
1648 (CꢁO), 1430 (C–O–C), 1054 (C–O–C); MS m/z: 340 (Mꢃ1); Anal.
Calcd for C15H11Cl2NO2S: C, 52.95; H, 3.26; N, 4.12. Found: C, 52.83; H,
3.44; N, 4.09.
7-(2-Bromo-benzyloxy)-2H-benzo[b][1,4]thiazin-3(4H)-one (3r) mp
226—228 °C; yield 32%; 1H-NMR (CDCl3, 300 MHz) d: 3.43 (s, 2H,
–S–CH2–), 5.11 (s, 2H, –OCH2–), 6.74—6.83 (m, 3H, Ar-H), 7.32—7.58
(m, 4H, H-2, H-3, H-4, H-5), 8.39 (s, 1H, –CONH); IR (KBr) cmꢂ1: 3479
(NH), 1659 (CꢁO), 1427 (C–O–C), 1048 (C–O–C); MS m/z: 350 (Mꢃ1);
Anal. Calcd for C15H12BrNO2S: C,51.44; H, 3.45; N, 4.00. Found: C, 51.56;
H, 3.26; N, 4.18.
7-(4-Bromo-benzyloxy)-2H-benzo[b][1,4]thiazin-3(4H)-one (3s) mp
211—213 °C; yield 31%; 1H-NMR (CDCl3, 300 MHz) d: 3.43 (s, 2H,
–S–CH2–), 4.99 (s, 2H, –OCH2–), 6.74—6.93 (m, 3H, Ar-H), 7.30—7.54
(m, 4H, H-2, H-3, H-5, H-6), 7.94 (s, 1H, –CONH); IR (KBr) cmꢂ1: 3424
(NH), 1690 (CꢁO), 1458 (C–O–C), 1017 (C–O–C); MS m/z: 350 (Mꢃ1);
Anal. Calcd for C15H12BrNO2S: C,51.44; H, 3.45; N, 4.00. Found: C, 51.65;
H, 3.38; N, 4.22.
7-Butoxy-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazine (4d) mp
113—115 °C; yield 62%; 1H-NMR (CDCl3, 300 MHz) d: 0.98 (t, 3H,
Jꢁ7.4 Hz, –CH3), 1.50 (m, 2H, –CH2–), 1.78 (m, 2H, –CH2–), 3.97 (t, 2H,
Jꢁ6.4 Hz, –OCH2–), 4.17 (s, 2H, –S–CH2–), 6.86 (dd, 1H, J1ꢁ2.6 Hz,
J2ꢁ8.8 Hz, Ar-H), 7.01 (s, 1H, Ar-H), 7.35 (d, 1H, Jꢁ8.9 Hz, Ar-H), 8.54 (s,
1H, N–CHꢁN–); IR (KBr) cmꢂ1: 1597 (CꢁN), 1309 (C–N), 1246, 1215
(C–O–C), 1033 (N–N). MS m/z: 262(Mꢃ1); Anal. Calcd for C13H15N3OS:
C, 59.74; H, 5.79; N, 16.08. Found: C, 59.89; H, 5.56; N, 16.19.
7-(Pentyloxy)-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazine (4e) mp
107—109 °C; yield 63%; 1H-NMR (CDCl3, 300 MHz) d: 0.94 (t, 3H,
Jꢁ6.9 Hz, –CH3), 1.41 (m, 4H, –CH2–CH2–), 1.80 (m, 2H, –CH2–), 3.97 (t,
2H, Jꢁ6.5 Hz, –OCH2–), 4.18 (s, 2H, –S–CH2–), 6.86 (dd, 1H, J1ꢁ2.7 Hz,
J2ꢁ8.9 Hz, Ar-H), 7.01 (s, 1H, Ar-H), 7.35 (d, 1H, Jꢁ8.9 Hz, Ar-H), 8.54 (s,
1H, N–CHꢁN–); IR (KBr) cmꢂ1: 1596 (CꢁN), 1304 (C–N), 1247, 1211
(C–O–C), 1033 (N–N). MS m/z: 276 (Mꢃ1); Anal. Calcd for C14H17N3OS:
C, 61.06; H, 6.22; N, 15.26. Found: C, 61.23; H, 6.19; N, 15.33.
7-(4-Methyl-benzyloxy)-2H-benzo[b][1,4]thiazin-3(4H)-one (3t) mp
179—181 °C; yield 38%; 1H-NMR (CDCl3, 300 MHz) d: 2.38 (s, 3H,
–CH3), 3.42 (s, 2H, –S–CH2–), 5.00 (s, 2H, –OCH2–), 6.77—6.95 (m, 3H,
Ar-H), 7.21 (d, 2H, Jꢁ8.0 Hz, Ar-H), 7.31 (d, 2H, Jꢁ8.0 Hz, Ar-H), 7.88 (s,
1H, –CONH); IR (KBr) cmꢂ1: 3409 (NH), 1668 (CꢁO), 1430 (C–O–C),
1036 (C–O–C); MS m/z: 286 (Mꢃ1); Anal. Calcd for C16H15NO2S: C,67.34;
H, 5.30; N, 4.91. Found: C, 67.46; H, 5.21; N, 4.86.
7-(4-Methoxy-benzyloxy)-2H-benzo[b][1,4]thiazin-3(4H)-one (3u)
1
mp 165—167 °C; yield 34%; H-NMR (CDCl3, 300 MHz) d: 3.42 (s, 2H,
–S–CH2–), 4.23 (s, 3H, –OCH3), 4.96 (s, 2H, –OCH2–), 6.74—6.95 (m, 3H,
Ar-H), 6.93 (d, 2H, Jꢁ8.7 Hz, Ar-H), 7.34 (d, 2H, Jꢁ8.7 Hz, Ar-H), 7.90 (s,
1H, –CONH); IR (KBr) cmꢂ1: 3445 (NH), 1696 (CꢁO), 1437 (C–O–C),
1030 (C–O–C); MS m/z: 302 (Mꢃ1); Anal. Calcd for C16H15NO3S: C,63.77;
H, 5.02; N, 4.65. Found: C, 63.57; H, 5.26; N, 4.74.
7-(3,4-Dimethoxy-benzyloxy)-2H-benzo[b][1,4]thiazin-3(4H)-one (3v)
1
mp 179—181 °C; yield 29%; H-NMR (CDCl3, 300 MHz) d: 3.43 (s, 2H,
7-(Hexyloxy)-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazine (4f) mp
86—88 °C; yield 79%; 1H-NMR (CDCl3, 300 MHz) d: 0.92 (t, 3H,
Jꢁ6.6 Hz, –CH3), 1.35 (m, 4H, –CH2-CH2–), 1.46—1.63 (m, 2H, –CH2–),
1.80 (m, 2H, –CH2–), 3.97 (t, 2H, Jꢁ6.5 Hz, –OCH2–), 4.18 (s, 2H,
–S–CH2–), 6.86 (dd, 1H, J1ꢁ2.6 Hz, J2ꢁ8.8 Hz, Ar-H), 7.01 (s, 1H, Ar-H),
–S–CH2–), 3.82 (s, 3H, –OCH3), 4.28 (s, 3H, –OCH3), 4.96 (s, 2H,
–OCH2–), 6.66—6.79 (m, 3H, Ar-H), 6.80—6.95 (m, 3H, H-2, H-5, H-6),
7.91 (s, 1H, –CONH); IR (KBr) cmꢂ1: 3450 (NH), 1618 (CꢁO), 1420
(C–O–C), 1073 (C–O–C); MS m/z: 332 (Mꢃ1); Anal. Calcd for
C17H17NO4S: C,62.41; H, 5.82; N, 4.04. Found: C, 62.66; H, 5.73; N, 4.28.
Target compounds 4a—u were synthesized according to Chart 2.
7.35 (d, 1H, Jꢁ8.8 Hz, Ar-H), 8.54 (s, 1H, N–CHꢁN–); IR (KBr) cmꢂ1
:
1595 (CꢁN), 1306 (C–N), 1239, 1220 (C–O–C), 1039 (N–N). MS m/z: 290
(Mꢃ1); Anal. Calcd for C15H19N3OS: C, 62.25; H, 6.62; N, 14.52. Found: C,
62.47; H, 6.54; N, 14.61.
To a stirring mixture of acetonitrile and triethylamine in a three-necked
round-bottomed flask in an ice bath, P2S5 (1.2 eq) was divided into multiple
portions and added one portion at a time after the previous portion had com-
pletely dissolved. Then, 3a was added, and the solution was refluxed for 3 h
under nitrogen. After removing the solvent under reduced pressure, the
residue was dissolved in dichloromethane (30 ml), washed with water
(30 mlꢄ3) and dried over anhydrous MgSO4. Evaporation of the solvents
gave a crude product, which was purified by silica gel column chromatogra-
phy with dichloromethane to a light yellow solid. (compound 6). The result-
ing compound 6 reacted further with formohydrazide in cyclohexanol to
produce compound 4a. 7-Hydroxy-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]
thiazine (5) was yielded by compound 4a by demethylation. Demethylation
was accomplished by treatment of the dichloromethane with boron tribro-
mide. Then compounds 4b—u were synthesized through reaction of com-
7-(Heptyloxy)-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazine (4g) mp
97—99 °C; yield 77%; 1H-NMR (CDCl3, 300 MHz) d: 0.89 (t, 3H,
Jꢁ6.7 Hz, –CH3), 1.36 (m, 6H, –CH2–CH2–CH2–), 1.58—1.61 (m, 2H,
–CH2–), 1.81 (m, 2H, –CH2–), 3.97 (t, 2H, Jꢁ6.5 Hz, –OCH2–), 4.18 (s, 2H,
–S–CH2–), 6.86 (dd, 1H, J1ꢁ2.6 Hz, J2ꢁ8.8 Hz, Ar-H), 7.01 (s, 1H, Ar-H),
7.35 (d, 1H, Jꢁ8.8 Hz, Ar-H), 8.54 (s, 1H, N–CHꢁN–); IR (KBr) cmꢂ1
:
1591 (CꢁN), 1308 (C–N), 1241, 1219 (C–O–C), 1035 (N–N). MS m/z: 304
(Mꢃ1); Anal. Calcd for C16H21N3OS: C, 63.33; H, 6.98; N, 13.85. Found: C,
63.46; H, 6.82; N,13.64.
7-(Octyloxy)-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazine (4h) mp
96—98 °C; yield 79%; 1H-NMR (CDCl3, 300 MHz) d: 0.88 (t, 3H,
Jꢁ6.8 Hz, –CH3), 1.30 (m, 8H, (–CH2)4), 1.46—1.67 (m, 2H, –CH2–), 1.78
(m, 2H, –CH2–), 3.97 (t, 2H, Jꢁ6.5 Hz, –OCH2–), 4.18 (s, 2H, –S–CH2–),
6.86 (dd, 1H, J1ꢁ2.6 Hz, J2ꢁ8.8 Hz, Ar-H), 7.01 (s, 1H, Ar-H), 7.35 (d, 1H,
Jꢁ8.8 Hz, Ar-H), 8.54 (s, 1H, N–CHꢁN–); IR (KBr) cmꢂ1: 1599 (CꢁN),
1304 (C–N), 1247, 1212 (C–O–C), 1037 (N–N). MS m/z: 318 (Mꢃ1); Anal.
Calcd for C17H23N3OS: C, 64.32; H, 7.30; N, 13.24. Found: C, 64.54; H,
7.16; N,13.50.
7-(Dodecyloxy)-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazine (4i)
mp 95—97 °C; yield 72%; 1H-NMR (CDCl3, 300 MHz) d: 0.87 (t, 3H,
Jꢁ6.8 Hz, –CH3), 1.27—1.46 (m, 16H, (–CH2–)8), 1.57 (m, 2H, –CH2–),
1.78 (m, 2H, –CH2–), 3.97 (t, 2H, Jꢁ6.4 Hz, –OCH2–), 4.18 (s, 2H,
–S–CH2–), 6.86 (dd, 1H, J1ꢁ2.6 Hz, J2ꢁ8.8 Hz, Ar-H), 7.01 (s, 1H, Ar-H),
7.35 (d, 1H, Jꢁ8.8 Hz, Ar-H), 8.54 (s, 1H, N–CHꢁN–); IR (KBr) cmꢂ1
:
Chart 2. The Synthesis Route of Target Compounds 4a—u
1600 (CꢁN), 1301 (C–N), 1251, 1219 (C–O–C), 1029 (N–N). MS m/z: 374