M. Zia-ur-Rehman et al. / European Journal of Medicinal Chemistry 44 (2009) 1311–1316
1315
TLC), solvent was removed under vacuum and the residue obtained
was treated with cold hydrochloric acid (5%) followed by washing
1174, 1128, 1037 cm 1; 1H NMR (DMSO-d
ꢀ
) d: 3.81 (s, 3H, OCH ),
6 3
7.03 (d, J ¼ 8.7 Hz, 2H, ArH), 7.66 (d, J ¼ 8.7 Hz, 2H, ArH), 7.81–
7.88 (m, 3H, ArH), 8.02 (d, J ¼ 7.7 Hz, 1H, ArH), 8.58 (s, 1H, NCH),
9.54 (br s, 1H, NH), 11.71 (br s, 1H, NH), 14.06 (s, 1H, OH enolic);
ꢁ
with water to get the product (4.89 g; 96.4%); m.p. 292 C decomp;
ꢀ
1 1
IR (KBr) 3409, 3266, 1674,1326,1128,1030 cm ; H NMR (CDCl
.49 (br s, 2H, NH ), 7.55–7.87 (m, 4H, ArH), 9.61 (br s,1H, NH),10.28
br s, 1H, NH), 12.64 (s, 1H, OHenolic); HRMS/EI (g mol ) calcd for
3
) d:
þ
2
(
2
MS m/z (%): 373 (100) [M ].
ꢀ1
0
N -(2,4-Dimethoxybenzylidene)-4-hydroxy-2H-benzo[e][1,2]-
CHNOS 255.2505, found 255.2511.
thiazine-3-carbohydrazide 1,1-dioxide (5g): Light orange powder
ꢁ
(
0.73 g; 90.9%); m.p. 240 C decomp; IR (KBr) 3285, 3168, 1669,
0
ꢀ1
1
6
.1.4. 4-Hydroxy-N -(benzylidene)-2H-benzo[e][1,2]
1604, 1327, 1177, 1132, 1034 cm
; H NMR (DMSO-d ) d: 3.82 (s,
6
thiazine-3-carbohydrazide 1,1-dioxides 5a–o
.1.4.1. Using methanol as solvent. A mixture of 4-hydroxy-2H-1,2-
benzothiazine-3-carbohydrazide 1,1-dioxide (4) (2.0 mmol), alde-
3H, OCH
3
), 3.87 (s, 3H, OCH
3
), 6.61 (d, J ¼ 6.7 Hz, 1H, ArH), 6.64
6
(d, J ¼ 6.7 Hz, 1H, ArH), 7.78–7.89 (m, 4H, ArH), 8.01 (d, J ¼ 6.6 Hz,
1H, ArH), 8.90 (s, 1H, NCH), 9.48 (br s, 1H, NH), 11.78 (br s, 1H,
þ
hyde (2.0 mmol), ortho phosphoric acid (2 drops) and methanol
NH), 14.08 (s, 1H, OH enolic); MS m/z (%): 403 (100) [M ].
0
(
50 ml) was refluxed till completion of the reaction (for yields,
N -(2,3-Dimethoxybenzylidene)4-hydroxy-2H-benzo[e][1,2]-
reaction conditions and reaction times, see Table 1). The contents
were cooled to 5 C in an ice bath, filtered and the solids were
washed with cold methanol to get the pure compound.
thiazine-3-carbohydrazide 1,1-dioxide (5h): Pale yellow powder
(0.74 g; 92.3%); m.p. 248–249 C; IR (KBr) 3299, 3101, 1668, 1589,
ꢁ
ꢁ
ꢀ
1
1
1322, 1171, 1128, 1071 cm
OCH ), 3.83 (s, 3H, OCH
;
H NMR (DMSO-d
6
)
d: 3.81 (s, 3H,
3
3
), 7.04 (d, J ¼ 6.4 Hz, 1H, ArH), 7.60–8.03 (m,
6.1.4.2. Using ultrasonic waves. A mixture of 4-hydroxy-2H-1,2-
6H, ArH), 8.62 (s, 1H, NCH), 9.64 (br s, 1H, NH), 11.71 (br s, 1H, NH),
þ
benzothiazine-3-carbohydrazide 1,1-dioxide (4) (0.51 g; 2.0 mmol),
aldehyde (2.0 mmol), ortho phosphoric acid (1 drop) and methanol
14.05 (s, 1H, OH enolic); MS m/z (%): 403 (100) [M ].
0
4-Hydroxy-N -(2,3,4-trimethoxybenzylidene)-2H-benzo[e][1,2]
(
2.5 ml) taken in a loosely screw capped test tube was immersed in
thiazine-3-carbohydrazide 1,1-dioxide (5i): Light yellow crystals
ꢁ
an ultrasonic reaction bath (for yields, reaction conditions and
reaction times, see Table 1). Contents were cooled to 10 C and
(0.80 g; 93.2%); m.p. 254–257 C decomp; IR (KBr) 3288, 2987,
ꢁ
ꢀ1
1
1648, 1560, 1320, 1165, 1124, 1055 cm
; H NMR (DMSO-d ) d:
6
washed with cold methanol to get the pure compound.
3.71 (s, 3H, OCH3 (para)), 3.84 (s, 6H, OCH3 (meta)), 7.0 (s, 2H, ArH),
7.81–8.04 (m, 4H, ArH), 8.56 (s, 1H, NCH), 9.56 (br s, 1H, NH), 11.81
(br s, 1H, NH), 13.99 (s, 1H, OH enolic); MS m/z (%): 433 (41.17)
0
4
-Hydroxy-N -(benzylidene)-2H-benzo[e][1,2]thiazine-3-car-
bohydrazide 1,1-dioxide (5a): Light yellow crystals (0.59 g; 93.2%).
ꢁ
þ
m.p. 251 C decomp; IR (KBr) 3395, 3055, 1631, 1543, 1175,
[M ], 73 (100).
ꢀ1
1
0
1
071 cm ; H NMR (DMSO-d
6
)
d: 7.61–8.03 (m, 9H, ArH), 8.57 (s,
N -(2-Chlorobenzylidene)-4-hydroxy-2H-benzo[e][1,2]thiazine-
1
H, NCH), 9.51 (br s, 1H, NH), 11.78 (br s, 1H, NH), 13.12 (s, 1H, OH
3-carbohydrazide 1,1-dioxide (5j): Bright yellow crystals (0.71 g;
þ
ꢁ
enolic); MS m/z (%): 359 (57.9) [M ].
95.4%). m.p. 245 C decomp; IR (KBr): 3390, 3078, 1678, 1545, 1340,
0
ꢀ1
1
4
-Hydroxy-N -(2-hydroxybenzylidene)-2H-benzo[e][1,2]thia-
1173, 1067 cm ; H NMR (DMSO-d
6
)
d
: 7.52 (s, 1H, ArH), 7.55 (s, 1H,
zine-3-carbohydrazide 1,1-dioxide (5b): Yellow crystals (0.68 g;
ArH), 7.73–8.04 (m, 6H, ArH), 8.65 (s, 1H, NCH), 9.56 (br s, 1H, NH),
11.91 (br s, 1H, NH), 13.95 (s, 1H, OH enolic); MS m/z (%): 377 (100)
ꢁ
9
4.6%); m.p. 262–263 C; IR (KBr) 3390, 2937, 1647,1544,1341,1172,
ꢀ1
1
þ
þ
1071 cm ; H NMR (DMSO-d
6
)
d
: 6.91 (d, J ¼ 6.6 Hz, 1H, ArH), 6.95
[M ], 379 (34.5) [M þ 2].
0
(
7
m, 1H, ArH), 7.32 (t, J ¼ 6.6 Hz, 1H, ArH), 7.54 (d, J ¼ 6.8, 1H, ArH),
N -(3-Chlorobenzylidene)-4-hydroxy-2H-benzo[e][1,2]thiazine-
.85 (m, 3H, ArH), 8.03 (dd, J ¼ 6.4, 1.2 Hz, 1H, ArH), 8.87 (s, 1H,
3-carbohydrazide 1,1-dioxide (5k): Yellow powder (0.69 g; 92.8%);
ꢁ
NCH), 9.59 (br s, 1H, NH), 11.02 (s, 1H, ArOH), 12.14 (br s, 1H, NH),
m.p. 253–254 C; IR (KBr) 3391, 3074, 1674, 1540, 1339, 1172,
þ
ꢀ1
1
13.77 (s, 1H, OH enolic); MS m/z (%): 359 (100) [M ].
1067 cm ; H NMR (DMSO-d
6
)
d: 7.55 (s, 1H, ArH), 7.77–8.01 (m,
0
N -(2,4-Dihydroxybenzylidene)-4-hydroxy-2H-benzo[e][1,2]-
7H, ArH), 8.63 (s, 1H, NCH), 9.58 (br s, 1H, NH), 11.90 (br s, 1H, NH),
þ
thiazine-3-carbohydrazide 1,1-dioxide (5c): Orange crystals
13.91 (s, 1H, OH enolic); MS m/z (%): 377 (100) [M ], 379 (34.6)
ꢁ
þ
(
1
0.68 g; 91.1%); m.p. 270–272 C; IR (KBr) 3392, 3284, 3052, 1633,
[M þ 2].
ꢀ1
1
0
541, 1320, 1170, 1069 cm
;
H NMR (DMSO-d
6
)
d
: 6.31 (d,
N -(4-Chlorobenzylidene)-4-hydroxy-2H-benzo[e][1,2]thiazine-
J ¼ 6.2 Hz, 1H, ArH), 6.35 (d, J ¼ 6.2, 1H, ArH), 7.31 (d, J ¼ 8.4 Hz, 1H,
3-carbohydrazide 1,1-dioxide (5l): Dirty yellow powder (0.68 g;
90.7%); m.p. 255–256 C; IR (KBr) 3388, 3076, 1675, 1544, 1342,
ꢁ
ArH), 7.78–8.03 (m, 4H, ArH), 8.71 (s, 1H, NCH), 9.55 (br s, 1H, NH),
ꢀ
1 1
1
0.01 (s, 1H, ArOH), 11.20 (s, 1H, ArOH), 11.96 (br s, 1H, NH), 13.84 (s,
1175, 1063 cm ; H NMR (DMSO-d
6
)
d
: 7.07 (d, J ¼ 8.7 Hz, 2H, ArH),
þ
1
H, OH enolic); MS m/z (%): 375 (82.8) [M ], 137 (100).
7.69 (d, J ¼ 8.7 Hz, 2H, ArH), 7.84–7.87 (m, 3H, ArH), 8.01 (d,
0
4
-Hydroxy-N -(3-hydroxy-4-methoxybenzylidene)-2H-ben-
J ¼ 7.7 Hz, 1H, ArH), 8.61 (s, 1H, NCH), 9.56 (br s, 1H, NH), 11.68 (br s,
þ
zo[e][1,2]thiazine-3-carbohydrazide 1,1-dioxide (5d): Pale yellow
1H, NH), 13.89 (s, 1H, OH enolic); MS m/z (%): 377 (100) [M ], 379
ꢁ
þ
crystals (0.70 g; 92.0%); m.p. 255 C decomp; IR (KBr) 3389, 3280,
(35.1) [M þ 2].
ꢀ1
1
0
3
049, 1637, 1544, 1326, 1174, 1073 cm ; H NMR (DMSO-d
6
)
d
: 3.80
N -(2,4-Dichloro benzylidene)-4-hydroxy-2H-benzo[e][1,2]thia-
(
s, 3H, OCH
3
), 6.82 (d, J ¼ 8.1 Hz, 1H, ArH), 7.09 (s, 1H, ArH), 7.19 (dd,
zine-3-carbohydrazide 1,1-dioxide (5m): Light yellow powder
ꢁ
J ¼ 8.1, 1.5 Hz, 1H, ArH), 7.81–7.88 (m, 3H, ArH), 8.02 (d, J ¼ 7.5 Hz,
(0.77 g; 93.9%); m.p. 262 C decomp; IR (KBr) 3395, 2944, 1684,
ꢀ1 1
1
1
H, ArH), 8.50 (s, 1H, NCH), 9.53 (br s, 1H, NH), 9.59 (br s, 1H, NH),
4.11 (s, 1H, OH enolic); MS m/z (%): 389 (100) [M ].
1564, 1347, 1181, 1073 cm
; H NMR (DMSO-d ) d: 7.52 (dd, 1H,
6
þ
J ¼ 6.6, 1.2 Hz, 1H, ArH), 7.54–8.04 (m, 6H, ArH), 9.05 (s, 1H, NCH),
0
4
-Hydroxy-N -(4-hydroxy-3-methoxybenzylidene)-2H-benzo[e]
9.62 (br s, 1H, NH), 12.19 (br s, 1H, NH), 13.85 (s, 1H, OH enolic); MS
þ
þ
þ
[1,2]thiazine-3-carbohydrazide 1,1-dioxide (5e): Dark yellow
m/z (%): 412 (100) [M ], 414 (61.4) [M þ 2], 416 (15.0) [M þ 4].
ꢁ
0
crystals (0.72 g; 93.4%); m.p. 262–263 C; IR (KBr) 3379, 3272, 3054,
1
3
4-Hydroxy-N -(2-nitrobenzylidene)-2H-benzo[e][1,2]thiazine-
ꢀ1 1
631, 1595, 1332, 1176, 1031 cm ; H NMR (DMSO-d
6
)
d
: 3.83 (s,
3-carbohydrazide 1,1-dioxide (5n): Yellow powder (0.69 g;
0
H, OCH
3
), 6.85 (d, J ¼ 8.1 Hz, 1H, ArH), 7.07 (dd, J ¼ 8.1, 1.5 Hz, 1H,
92.6%); m.p. 280 C decomp; IR (KBr) 3404, 3034, 1668, 1544,
ꢀ
1
1
ArH), 7.29 (s,1H, ArH), 7.78–7.89 (m, 3H, ArH), 8.02 (d, J ¼ 7.6 Hz,1H,
1340, 1156, 1049 cm
; H NMR (DMSO-d ) d: 7.68–8.11 (m, 8H,
6
ArH), 8.52 (s, 1H, NCH), 9.53 (br s, 1H, NH), 9.61 (br s, 1H, NH), 14.08
ArH), 9.07 (s, 1H, NCH), 9.60 (br s, 1H, NH), 12.24 (br s, 1H, NH),
þ
þ
(
s, 1H, OH enolic); MS m/z (%): 389 (100) [M ].
13.84 (s, 1H, OH enolic); MS m/z (%): 388 (56.1) [M ].
0
0
4
-Hydroxy-N -(4-methoxybenzylidene)-2H-benzo[e][1,2]thia-
4-Hydroxy-N -(3-nitrobenzylidene)-2H-benzo[e][1,2]thiazine-
zine-3-carbohydrazide 1,1-dioxide (5f): Yellow crystals (0.50 g;
3-carbohydrazide 1,1-dioxide (5o): Light yellow powder (0.71 g;
92.7%); m.p. 255–256 C; IR (KBr) 3385, 3074, 1671, 1543, 1340,
ꢁ
ꢁ
9
6.6%); m.p. 250–251 C; IR (KBr) 3281, 3170, 1651, 1590, 1330,