Arch. Pharm. Chem. Life Sci. 2011, 11, 255–263
Novel Benzimidazo[2,1-c][1,4]thiazinone Derivatives
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the extracts was dried over sodium sulfate and evaporated. The
resulting solid was recrystallized from ethanol.
1H-NMR (DMSO-d6, d ppm): 4.35 (s, 2H, CH2CO), 4.73 (s, 2H, CH2S),
7.85 (m, 2H, H-6 and H-7), 8.25 (s, 1H, H-8), 10.57 (br.,
OH, D2O exchangeable). 13C-NMR(DMSO-d6, d ppm): 52.2, 52.6,
115.1, 118.9, 125.2, 135.5, 138.3, 142.1, 166.7, 198.5. MS (m/z, %):
280 (Mþ, 20), 263 (Mþ – OH, 50), 91 (CH2SO2CH2 – 1, 100).
Calcd. C11H8N2O5S for (280.26): C, 47.14; H, 2.88; N, 10.00;
S, 11.44. Found: C, 47.20; H, 2.80; N, 10.04; S, 11.46.
Yield (48%), mp 195–1978C. IR (cmꢁ1): 3440 (NH), bonded (OH)
–
–
–
centered at 3200, 1705 (C O, ester), 1690 (C O, acid), 1622 (C N).
–
–
–
1H-NMR (DMSO-d6, d ppm): 1.32 (t, 3H, J ¼ 7 Hz, CH3), 3.42 (s, 2H,
CH2CO), 4.07 (s, 2H, CH2S), 4.29 (q, 2H, J ¼ 7 Hz, CH2), 7.63 (d, 1H,
J ¼ 8 Hz, H-7), 7.85 (d, 1H, J ¼ 8 Hz, H-6), 8.15 (s, 1H, H-4), 8.95 (bs,
NH, D2O exchangeable), 12.62 (OH, D2O exchangeable). 13C-NMR
(DMSO-d6, d ppm): 15.3, 48.4, 60.4, 115.3, 117.6, 123.6, 124.8,
133.2, 137.6, 143.6, 152.3, 165.6, 173.9. MS (m/z, %): 294
(Mþ, 20), 276 (Mþ – H2O, 40), 204 (Mþ – SCH2CO2, 100). Calcd.
for C13H14N2O4S (294.33): C, 53.05; H, 4.79; N, 9.52; S, 10.89.
Found: C, 53.23; H, 4.77; N, 9.54; S, 10.88.
Ethyl 2,2-dioxo-1,3-dihydro-4H-benzo[40,50]imidazo[2,1-c]-
[1,4]thiazine-4-one-8-carboxylate (8)
Yellow solid, yield (61%), mp. 295–2988C. IR (cmꢁ1): 1724 (C O,
–
–
–
–
–
–
ester), 1690 (C O, lactam), 1629 (C N), 1564 and 1461 (SO ).
2
1H-NMR (DMSO-d6, d ppm): 1.39 (t, 3H, J ¼ 7 Hz, CH3), 4.55
(s, 2H, CH2CO), 4.35 (q, 2H, J ¼ 7 Hz, CH2), 4.73 (s, 2H, CH2S),
7.87 (m, 2H, H-6 and H-7), 8.16 (s, 1H, H-8). 13C-NMR(DMSO-d6,
d ppm): 14.7, 43.5, 52.5, 60.3, 115.1, 117.9, 124.4, 134.6, 137.2,
140.7, 146.1, 165.6, 198.7. MS (m/z,%): 308 (Mþ, 50), 263
(Mþ – OC2H5, 100). Calcd. for C13H12N2O5S: C, 50.64; H, 3.92;
N, 9.09; S, 10.40. Found: C, 50.49; H, 3.87; N, 9.12; S, 10.49.
General procedure for the preparation of compounds 5
and 6
A mixture of compound 3 or 4 (19 mmol) in acetic anhydride
(10 mL) and pyridine (5 mL) was heated at 908C for 0.5 h. The
reaction mixture was evaporated under reduced pressure. The
resulting residue was column chromatographed from petroleum
ether (40–608C)/chloroform (2:1) and recrystallized from acetone
as buff crystals.
General procedure of the preparation of compounds 9–12
A mixture of compound 3 or 5 (1.9 mmol) in acetic anhydride
(10 mL), pyridine (5 mL), and pyridine-3-carbaldehyde,
benzo[1,3]-dioxole-5-carbaldehyde, 1H-Indole-3-carbaldehyde or
furan-2-carbaldehyde (4.0 mmol) was heated at 908C for 0.5–
1 h, allowed to cool and evaporated under reduced pressure.
The resulting residue was column chromatographed from ethyl
acetate/petroleum ether (40:60) (4:1) as an eluent to give the
corresponding products 9-12, respectively.
Preparation of 1,3-dihydro-4H-benzo[4‘,5‘]imidazo[2,1-c]-
[1,4]thiazine-4-one-8-carboxylic acid (5)
Yield (59%), mp 193–1958C. IR (cmꢁ1): 3500–3380 (OH), bonded
–
–
(OH) centered at 2800, 1697 (C O, acid and lactam), 1637 (C N).
–
–
1H-NMR (DMSO-d6, d ppm): 3.55 (s, 2H, CH2CO), 4.30 (s, 2H, CH2S),
7.87 (m, 2H, H-6 and H-7) 8.13 (s, 1H, H-9), 12.67 (br.,
OH, D2O exchangeable). 13C-NMR(DMSO-d6, d ppm): 33.2, 33.6,
115.3, 119.3, 125.0, 125.6, 135.3, 138.5, 141.7, 166.4, 198.5.
MS (m/z, %): 248 (Mþ, 100). Calcd. for C11H8N2O3S (248.26): C,
53.22; H, 3.25; N, 11.28; S, 12.92. Found: C, 53.42; H, 3.36; N,
11.39; S, 12.81.
1-(Pyridin-3-ylmethylene)-3-hydro-
4H-benzo[40,50]imidazo[2,1-c][1,4]thiazine-4-one-8-
carboxylic acid (9)
Buff solid. Rf ¼ 0.33. Yield (59%), mp >3008C. IR (cmꢁ1): 3480–
–
3320 (OH), bonded (OH) centered at 2800, 1700 (C O, acid), 1678
–
–
(C O, lactam), 1637 (C N). H-NMR (DMSO-d , d ppm): 3.75 (s, 2H,
1
Ethyl 1,3-dihydro-4H-benzo[4‘,5‘]imidazo[2,1-c]-
[1,4]thiazine-4-one-8-carboxylate (6)
–
–
–
6
–
CH2CO), 7.07 (s, 1H, CH),7.55 (m, 1H, H-5‘ pyridine ring), 7.87
–
Yield (55%), mp 183–1858C. IR (cmꢁ1): 1716 (C O, ester), 1700
–
(m, 2H, H-6 and H-7), 7.98 (m, 1H, H-40 pyridine ring), 8.19 (s, 1H,
H-9), 8.36 (m, 1H, H-60 pyridine ring), 8.90 (s, 1H, H-20 pyridine),
12.70 (br., D2O exchangeable OH). 13C-NMR (DMSO-d6, d ppm):
34.6, 115.5, 119.4, 123.4, 124.6, 125.3, 126.1, 127.1, 135.2, 137.8,
141.5, 146.4, 147.3, 148.1, 166.6, 198.4. MS (m/z, % of abundance):
337(Mþ, 18), 320(Mþ - OH, 48). 293 (Mþ – COOH, 100). Anal. calcd.
for C17H11N3O3S (337.36): C, 60.52; H, 3.29; N, 12.46; S, 9.50.
Found: C, 60.44; H, 3.44; N, 12.6 1; S, 43.
–
(C O, lactam), 1627 (C N). 1HNMR (DMSO-d6, d ppm): 1.39
–
–
–
–
(t, 3H, J ¼ 7 Hz, CH3), 3.43 (s, 2H, CH2CO), 4.20 (s, 2H, CH2S),
4.35 (q, 2H, J ¼ 7 Hz, CH2), 7.79 (m, 2H, H-6 and H-7), 8.14 (s, H,
H-9). 13C-NMR(DMSO-d6, d ppm): 14.5, 36.2, 36.5, 60.5, 115.1,
117.9, 124.7, 126.1, 134.4, 138.8, 141.7, 165.5, 198.7. MS
(m/z, %): 276 (Mþ, 20), 231 (Mþ – OC2H5, 45), 204 (Mþ
–
(OC2H5 þ CO), 100). Calcd. for C13H12N2O3S (276.32): C, 56.51; H,
4.38; N, 10.14; S, 11.66. Found: C, 56.47; H, 4.34; N, 10.20; S, 11.60.
1-(Benzo[1,3]dioxol-5-ylmethylene)-3-hydro-
4H-benzo[40,50]imidazo[2,1-c][1,4]thiazine-4-one-8-
carboxylic acid (10)
General procedure of the preparation of compounds 7
and 8
A mixture of compound 5 or 6 (3.8 mmol) in glacial acetic acid
(10 mL) and hydrogen peroxide (15 mL, 30%) was stirred for 24 h
at room temperature. The resulting solid of compounds 7 or 8
was separated, filtered, washed with acetone and recrystallized
from DMF.
Brown solid. Rf ¼ 0.26. Yield (66%), mp >3008C. IR (cmꢁ1): 3480–
–
–
–
–
3400 (OH), 1690 (C O, acid), 1672 (C O, lactam), 1635 (C N).
–
–
1H-NMR (DMSO-0d6, d ppm): 3.59 (s, 2H, CH2CO), 6.38 (s, 2H, CH2),
–
7.05 (m, 1H, H-7 benzo[1,3]dioxol), 7.17 (s, 1H, CH), 7.35 (m, 1H,
–
H-60 benzo[1,3]dioxol), 7.52 (s, 1H, H-40 benzo[1,3]dioxol), 7.92
(m, 2H, H-6 and H-7), 8.21 (s, 1H, H-9), 12.10 (br., OH, D2O exchange-
able). 13C-NMR (DMSO-d6, d ppm): 34.4, 102.1, 107.6, 110.5, 115.4,
121.7, 124.5, 125.1, 125.9, 128.1, 135.2, 137.8, 141.6, 142.8, 147.7,
148.2, 165.7, 198.5. Anal. calcd. for C19H12N2O5S: C, 59.99; H, 3.18;
N, 7.36; S, 8.43. Found: C, 59.78; H, 3.29; N, 7.46; S, 8.40.
2,2-Dioxo-1,3-dihydro-4H-benzo[40,50]imidazo[2,1-c]-
[1,4]thiazine-4-one-8-carboxylic acid (7)
Yellow solid, yield (66%), mp >3008C. IR (cmꢁ1): 3480 (OH), 1704
–
–
–
(C O, acid), 1690 (C O, lactam), 1629 (C N), 1560 and 1467 (SO ).
–
–
–
2
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