M. R. Mahmoud, M. M. El-Shahawi, F. S. Abu El-Azm, and M. Abdeen
Vol 000
70e.V. Elemental analysis was performed by Vario EL-III
elemental analysis.
1H, NH, exchangeable with D2O), 8.50 (s, 1H, C4-H
coumarin), 7.87–7.37 (m, 9Harom.), 6.92 (d, 1H, PhCH=,
J = 15.4 Hz), 6.54 (d, 1H,PhCH = CH, J = 15.4 Hz).
IR (KBr) ν(cmÀ1): 3190 (NH), 1712, 1689 (C=O), 1636
(C=N) MS m/z (%): 375 (M.+; 10), 245 (100), 172 (79),
146 (71), 131 (90), 103 (98), 77 (78). Anal. Calcd. for
C20H13N3O3S (375.392): C, 63.99; H, 3.49; N, 11.19; S,
8.54. Found: C, 63.92; H, 3.52; N, 11.10; S, 8.58.
Synthesis of (3) and (4). Ammonium thiocyanate (1 g,
0.01 mol) was added to a solution of cinnamoyl chloride
(1.66 g, 0.01 mol) in dioxane (10 mL), and then the
reaction mixture was stirred for 10 min. The reaction
mixture was filtrated off, and the filtrate was added to a
solution of cyanoacetohydrazide (1 g, 0.01 mol) in
dioxane (10 mL), and then the reaction mixture was
heated under reflux for 15 min. The formed solid (two
spots on TLC) was collected by filtration, dried, and
fractionally crystallized from methanol to give 4 (63%),
while the residue was crystallized from dioxane to afford
the 3 (17%).
4-Cinnamoyl-1-(2-cyanoacetyl)thiosemicarbazide (3). White
crystals, Yield: 17%, mp: 235–236°C; 1H–NMR (DMSO-d6)
δ (ppm): 12.50 (s, 1H, NH, exchangeable with D2O), 11.71 (s,
1H, NH, exchangeable with D2O), 11.21 (s, 1H, NH,
exchangeable with D2O), 7.78–7.46 (m, 5Harom.), 7.03 (d, H,
PhCH=, J = 15.4 Hz), 6.98 (d, 1H, PhCH = CH, J = 15.4 Hz),
3.86 (s, 2H, CH2CN); IR (KBr) ν(cmÀ1): 3297, 3221 (NH),
2267 (CN), 1680, 1666 (C = O); MS m/z (%): 288 (M.+; 74),
270 (21), 204 (24), 131 (100), 103 (90), 77 (89); Anal. Calcd.
for C13H12N4O2S (288.315): C, 54.16; H, 4.19; N, 19.43; S,
11.12. Found: C, 54.10; H, 4.08; N, 19.39; S, 11.08.
5-Cinnamoylamino-2-cyanomethyl-1,3,4-thiadiazole (4). White
crystals, Yield: 63%, mp: 218–220°C; 1H–NMR (DMSO-d6) δ
(ppm): 11.72 (s, 1H, NH, exchangeable with D2O), 7.78–7.45
(m, 5Harom.), 7.03(d, 1H, PhCH=, J = 15.7 Hz), 6.98 (d, 1H,
PhCH = CH, J = 15.7 Hz), 3.86 (s, 2H, CH2CN); IR (KBr)
ν(cmÀ1): 3158 (NH), 2252 (CN), 1691 (C = O), 1634 (C = N);
MS m/z (%): 270 (M.+; 21), 202 (20), 131 (6), 76 (46), 69
(100). Anal. Calcd. for C13H10N4OS (270.302): C, 57.77; H,
3.73; N, 20.73; S, 11.86. Found: C, 57.80; H, 3.70; N, 20.68;
S, 11.80.
4-Cinnamoyl-1-(2-imino-2H-chromene-3-carbonyl)thiosemica-
rbazide (6). To a solution of compound 3 (2.88 g, 0.01 mol)
in dioxane (20 mL), salicylaldehyde (1.23 mL, 0.01 mol) was
added with piperidine (0.2 mL), and then the reaction mixture
was refluxed for 3 h. After evaporation of excess solvent and
acidification with dilute cold hydrochloric acid, the solid
separated was collected by filtration, washed with water,
dried, and then recrystallized from dioxane to give 6,
yellowish-white crystals, Yield: 43%, mp: 208–210°C; IR
(KBr) ν(cmÀ1): 3254, 3158 (NH), 1691 (C = O), 1634
(C = N); MS m/z (%): 392 (M.+; 14), 245 (79), 206 (40),
173 (41), 146 (92), 131 (100), 103 (89), 77 (99). Anal.
Calcd. for C20H16N4O3S (392.419): C, 61.22; H, 4.11; N,
14.28; S, 8.17. Found: 61.18; H, 4.17; N, 14.32; S, 8.10.
Cyclization of (6). Thiosemicarbazide derivative 6 (1 g),
acetic anhydride (10 mL), and glacial acetic acid (10 mL)
were heated under reflux for 2 h. The reaction mixture was
concentrated and then poured into ice/cold water. The
yielded solid was collected by filtration, washed with
water, dried, and recrystallized from dioxane to give 5
(identity M.p., mixed M.p., IR, and TLC comparison).
2-[1-Cyano-2-(3,4-dimethoxyphenyl)vinyl]-5-cinnamoylamino-
1,3,4-thiadiazole (7).
A mixture of thiadiazole 4 (2.7 g,
0.01 mol), 3,4-dimethoxybenzaldehyde (1.66 g, 0.01 mol)
and piperidine (0.5 mL) in ethanol (20 mL) was refluxed
for 1 h. The produced solid on hot was separated by
filtration, dried, and recrystallized from dioxane to give 7
1
as yellow crystals, Yield: 48%, mp:160–162°C; H–NMR
Cyclization of (3).
Thiosemicarbazide derivative 3
(DMSO-d6) δ (ppm): 11.68 (s, 1H, NH, exchangeable with
D2O), 8.20 (s, 1H, CH=), 7.78–7.73 (m,3Harom.), 7.71–7.47
(m,5Harom.), 7.20 (d, 1H, PhCH=, J = 15.2 Hz), 7.04 (d,
1H, PhCH = CH, J = 15.2 Hz), 3.88(s, 3H,OCH3), 3.83
(s, 3H,OCH3); IR (KBr) ν(cmÀ1): 3189 (NH), 2201
(C≡N), 1670 (C=O), 1618 (C=N); MS m/z (%): 418 (M.+;
23.9), 288 (23), 151 (54), 131 (100), 103 (99), 77 (55).
Anal. Calcd. for C22H18N4O3S (418.455): C, 63.15; H,
4.33; N, 13.39; S,7.66. Found: C, 63.20; H, 4.29; N,
13.35; S, 7.70.
(1 g), freshly distilled acetic anhydride (10 mL) and
glacial acetic acid (10 mL) was heated under reflux for
2 h. The reaction mixture was concentrated and then
poured into ice/cold water. The yielded solid was
separated by filtration, washed with water, dried, and
recrystallized from methanol to give 4 (identity M.P.,
mixed M.P., IR, and TLC comparison).
2-(2-Oxo-2H-chromen-3-yl)-5-cinnamoylamino-1,3,4-thiadiazole
(5).
A mixture of thiadiazole 4 (2.7 g, 0.01 mol),
salicylaldehyde (1.23 mL, 0.01 mol), and piperidine
(0.5 mL) in dioxane (20 mL) was refluxed for 2 h. The
reaction mixture was concentrated and then poured into
ice/cold water and acidified with concentrated hydrochloric
acid. The yielded solid was separated by filtration, washed
with water, dried, and recrystallized from ethanol/dioxane
mixture (7:3) to give 5 as yellow crystals, Yield: 51%,
2-[2-(3,4-Dimethoxyphenyl)-1-(4-oxo-4,5-dihydrothiazol-
2-yl)vinyl]-5-cinnamoylamino-1,3,4-thiadiazole (8). A mixture
of arylidene derivative 7 (2.1 g, 0.005 mol) and
mercaptoacetic acid (0.46 g, 0.005 mol) and in pyridine
(15 mL) was heated under reflux for 7 h. The reaction
mixture was concentrated and then poured into ice/cold
water and acidified with concentrated hydrochloric acid.
1
mp: 228–230°C; H–NMR (DMSO-d6) δ (ppm): 10.92 (s,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet