510
H. Foks, D. Pancechowska-Ksepko, and K. Gobis
Vol 51
2-(Furan-2-carbonyl)--(piperidin-1-yl)hydrazinecarbothioamide
C-C), 1111 (n C-O), 837 (g C-H) cm-1; 1H NMR (500 MHz,
DMSO-d6): d 2.77–2.87 (m, 4H, 2NCH2), 3.55–3.65 (m, 4H,
2OCH2), 7.23–7.29 (m, 2H, Ph), 7.76–7.83 (m, 2H, Ph), 9.32
(s, 1H, NH) ppm; Anal. Calcd. for C12H13FN4OS (mw
280.32): C, 51.42; H, 4.67; N, 19.99. Found: C, 51.52; H,
4.66; N, 19.95.
(13). The crude product was recrystallized from dioxane. Yield
95%, mp 240–242ꢀC; IR (KBr): 3247, 3149 (n N-H), 2945, 2853
(n C-H), 1698 (n C=O), 1568 (n C=C), 1545 (n N-H), 1513 (n
1
C=C), 1318 (n C-N), 1121 (n C-O), 871 (g C-H) cm-1; H NMR
(200MHz, DMSO-d6): d 1.15–1.92 (m, 6H, 3CH2), 2.48–2.97
(m, 4H, 2NCH2), 6.58–6.69 (m, 1H, furan-2-yl, H-4),7.22 (d,
1H, furan-2-yl, H-3, J = 3.5 Hz), 7.88 (d, 1H, furan-2-yl, H-5,
J = 1.7 Hz), 9.26 (s, 1H, NH), 9.53 (s, 1H, NH), 10.28 (s, 1H,
NH) ppm; Anal. Calcd. for C11H16N4O2S (mw 268.34): C, 49.24;
H, 6.01; N, 20.88. Found: C, 49.09; H, 6.02; N, 20.93.
N-(5-(4-Chlorophenyl)-1,3,4-thiadiazol-2-yl)morpholin-4-
amine (19).
The crude product was recrystallized from
ethanol. Yield 63%, mp 228–229ꢀC; IR (KBr): 3169 (n N-H),
3065, 2921, 2854, 2835 (n C-H), 1577, 1438 (n C=C), 1266
(n C-C), 1113 (n C-O), 1078 (d C-H), 871, 830 (g C-H) cm-1;
N0-(2,2)-dimethylhydrazinecarbonothioyl)benzohydrazide
(14). The crude product was recrystallized from ethanol. Yield
53%, mp 182–183ꢀC; IR (KBr): 3254, 3169 (n N-H), 2990,
2861 (n C-H), 1672 (n C=O), 1540 (d N-H), 1484 (n C=C),
1307 (n C-N), 1259 (n C=S), 714 (g N-H) cm-1; 1H NMR
(200 MHz, CDCl3): d 2.64 (s, 6H, 2NCH3), 7.48–7.55 (m, 3H,
Ph), 7.84–7.93 (m, 2H, Ph), 6.67 (s, 1H, NH), 9.57 (s, 1H,
NH), 9.88 (s, 1H, NH) ppm; Anal. Calcd. for C10H14N4OS
(mw 238.31): C, 50.40; H, 5.92; N, 23.51. Found: C, 50.29; H,
5.91; N, 23.45.
1H NMR (200 MHz, DMSO-d6):
d 2.77–2.87 (m, 4H,
2NCH2), 3.54–3.64 (m, 4H, 2OCH2), 7.46–7.52 (m, 2H, Ph),
7.75–7.81 (m, 2H, Ph), 9.38 (s, 1H, NH) ppm; Anal. Calcd.
for C12H13ClN4OS (mw 296.78): C, 48.56; H, 4.42; N, 18.88.
Found: C, 48.68; H, 4.41; N, 18.83.
N-(5-(4-Methoxyphenyl)-1,3,4-thiadiazol-2-yl)morpholin-
4-amine (20).
The crude product was recrystallized from
methanol. Yield 20%, mp 208–210ꢀC; IR (KBr): 3164 (n N-
H), 2918, 2857, 2830 (n C-H), 1609, 1579, 1522, 1428 (n
C=C), 1250 (d C-C), 1174, 1110 (g C-O), 1070 (d C-H), 873,
1
4-Chloro-N0-(2,2)-dimethylhydrazinecarbonothioyl)
843 (g C-H), 651 (g N-H) cm-1; H NMR (200 MHz, DMSO-
benzohydrazide (15).
The crude product was recrystallized
d6): 2.82–2.90 (m, 4H, 2NCH2), 3.63–3.72 (m, 4H, 2OCH2),
3.79 (s, 3H, OCH3), 7.01 (d, 2H, Ph, J = 8.7 Hz), 7.71 (d, 2H,
Ph, J = 8.7 Hz), 9.07 (s, 1H, NH) ppm; Anal. Calcd. for
C13H16N4O2S (mw 292.36): C, 53.41; H, 5.52; N, 19.16.
Found: C, 53.29; H, 5.53; N, 19.19.
from ethanol. Yield 84%, mp 210–212ꢀC; IR (KBr): 3289, 3148
(n N-H), 2964, 2861 (n C-H), 1678 (n C=O), 1541 (d N-H), 1495
(n C=C), 1313 (n C-N), 1091, 1011 (d C-H) cm-1; 1H NMR
(500MHz, DMSO-d6): d 2.50 (s, 6H, 2NCH3), 7.58 (d, 2H, Ph,
J = 7.9 Hz), 7.90 (d, 2H, Ph, J = 8.0 Hz), 9.22 (s, 1H, NH), 9.70
(s, 1H, NH), 10.51 (s, 1H, NH) ppm; Anal. Calcd. for
C10H13ClN4OS (mw 272.75): C, 44.03; H, 4.80; N, 20.54.
Found: C, 44.14; H, 4.78; N, 20.49.
5-(4-Chlorophenyl)-N-(piperidin-1-yl)-1,3,4-thiadiazol-2-
amine (21).
The crude product was recrystallized
from dimethylformamid-water mixture (1:1). Yield 77%,
mp 194–196ꢀC; IR (KBr): 3166 (n N-H), 3056, 2934, 2853
(n C-H), 1581, 1497, 1432 (n C=C), 1090, 1074 (d C-H),
982, 830 (g C-H) cm-1; 1H NMR (500 MHz, DMSO-d6):
1.31–1.36 (m, 2H, CH2), 1.50–1.59 (m, 4H, 2CH2), 2.72–
2.81 (m, 4H, 2NCH2), 7.52 (d, 2H, Ph, J = 8.1 Hz), 7.80 (d,
2H, Ph, J = 8.2 Hz), 9.29 (s, 1H, NH) ppm; Anal. Calcd. for
C13H15ClN4S (mw 294.80): C, 52.96; H, 5.13; N, 19.00.
Found: C, 52.83; H, 5.14; N, 19.04.
2-(2,2-Dimethylhydrazinyl)-5-phenyl-1,3,4-thiadiazole (22).
The crude product was recrystallized from ethanol-water mixture
(1:1). Yield 40%, mp 155–156ꢀC; IR (KBr): 3165 (n N-H), 3044,
2994, 2828 (n C-H), 1586, 1455, 1415 (n C=C), 1104, 879, 759
(g C-H), 688 (g N-H) cm-1; 1H NMR (200 MHz, DMSO-d6):
d 2.59 (s, 6H, 2NCH3); 7.36–7.43 (m, 3H, Ph); 7.70–7.77
(m, 2H, Ph); 9.12 (s, 1H, NH) ppm; Anal. Calcd. for C10H12N4S
(mw 220.29): C, 54.52; H, 5.49; N, 25.43. Found: C, 54.37; H,
5.49; N, 25.49.
N0-(2,2)-dimethylhydrazinecarbonothioyl)-4-fluorobenzo-
hydrazide (16).
The crude product was recrystallized from
water. Yield 98%, mp 236–237ꢀC; IR (KBr): 3288, 3152 (n
N-H), 2996, 2964, 2863 (n C-H), 1675 (n C=O), 1542 (d N-
H), 1487 (n C=C), 1234 (n C=S), 1160 (d C-H), 853 (g C-H)
1
cm-1; H NMR (500 MHz, DMSO-d6): d 2.50 (s, 6H, 2NCH3),
7.28–7.42 (m, 2H, Ph), 7.90–8.14 (m, 2H, Ph), 9.21 (s, 1H,
NH), 9.68 (s, 1H, NH), 10.45 (s, 1H, NH) ppm; Anal. Calcd.
for C10H13FN4OS (mw 256.30): C, 46.86; H, 5.11; N, 21.86.
Found: C, 47.00; H, 5.12; N, 21.91.
General method for the synthesis of 1,3,4-thiadiazoles
(17–24).
2-Benzoyl-N-aminohydrazincarbothioamide (7–9,
12, 14–16) (2 mmole) was dissolved in 4 mL of concentrated
H2SO4. The mixture was heated at 90ꢀC in an oil bath for 1 h.
Then, mixture was cooled, poured on 10 g of ice and
neutralized with concentrated NH4OH. The precipitate was
filtered off, dried, and recrystallized from suitable solvent.
N-(5-Phenyl-1,3,4-thiadiazol-2-yl)morpholin-4-amine (17).
This compound was recrystallized from methanol–water mixture
(1:1). Yield 53%, mp 211–212ꢀC; IR (KBr): 3141 (n N-H), 3045,
2964, 2852 (n C-H), 1558 (d N-H), 1424 (n C=C), 1264 (n C-C),
1118 (n C-O), 1066 (d C-H), 877 (g C-H) cm-1; 1H NMR
(200 MHz, CDCl3): 2.71–3.03 (m, 4H, 2NCH2), 3.49–3.80
(m, 4H, 2OCH2), 7.31–7.42 (m, 3H, Ph), 7.75–7.82 (m, 2H, Ph),
9.17 (brs, 1H, NH) ppm; Anal. Calcd. for C12H14N4OS
(mw 262.33): C, 54.94; H, 5.38; N, 21.36. Found: C, 54.79;
H, 5.37; N, 21.41.
2-(4-Chlorophenyl)-5-(2,2)-dimethylhydrazinyl)-1,3,4-thiadiazole
(23).
The crude product was recrystallized from ethanol-water
mixture (1:1). Yield 68%, mp 180–182ꢀC; IR (KBr): 3268, 3169 (n
N-H), 3070, 2927, 2864 (n C-H), 1574, 1455 (n C=C), 1090 (d C-
H), 826 (g C-H) cm-1; H NMR (500 MHz, DMSO-d6): d 2.60 (s,
1
6H, 2NCH3), 7.52 (d, 2H, Ph, J= 8.2 Hz), 7.90 (d, 2H, Ph,
J= 8.3 Hz), 9.20 (s, 1H, NH) ppm; Anal. Calcd. for C10H11ClN4S
(mw 254.74): C, 47.15; H, 4.35; N, 21.99. Found: C, 47.21; H,
4.33; N, 21.93.
2-(2,2-Dimethylhydrazinyl)-5-(4-fluorophenyl)-1,3,4-thiadiazole
(24).
This compound was recrystallized from ethanol-water
N-(5-(4-Fluorophenyl)-1,3,4-thiadiazol-2-yl)morpholin-4-
mixture (1:1). Yield 26%, mp 177–178ꢀC; IR (KBr): 3168 (n N-
H), 2999, 2961, 2834 (n C-H), 1597, 1518, 1456 (n C=C), 1221,
amine (18).
The crude product was recrystallized from
1
ethanol. Yield 31%, mp 206–207ꢀC; IR (KBr): 3171 (n N-H),
3031, 2922, 2832 (n C-H), 1596, 1512, 1440 (n C=C), 1222 (n
838 (g C-H) cm-1; H NMR (200 MHz, DMSO-d6): 2.59 (s, 6H,
2NCH3), 7.23–7.30 (m, 2H, Ph), 7.74–7.81 (m, 2H, Ph), 9.13 (s,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet