Medicinal Chemistry Research
10a as light yellow crystals (0.62 g, 72%). FT-IRνmax
(KBr): 3257.78, 3059.98, 2961.91, 2857.91, 1542.57,
1424.52 (C = S stretch and C–N stretch, aromatic ring,
C=C stretch), 1224.34, 1109.02, 1024.29 (C=S stretch)
after completion was repeatedly washed with anhydrous
ether. The solid thus obtained was filtered, dried and
recrystallised from ethanol to afford 13a as white crystals
(0.70 g, 62%). FT-IRνmax (KBr): 3419.88, 3153.52,
3003.91, 2918.40, 1548.18 (C=S stretch and C–N stretch,
aromatic ring, C=C stretch), 1447.39, 1381.33, 1233.28
1
and 762.71 cm−1. H NMR (CDCl3): δ 14.10 (br s, 1H, >
NH), 7.85 (m, 2H, ArH), 7.50 (m, 3H, ArH), 4.10 (s, 4H, O
(CH2)2, morpholine), 3.67 (s, 4H, –N(CH2)2, morpholine) p.
p.m. 13CNMR (CDCl3): δ 184.56, 168.70, 153.14, 130.81,
129.97, 129.38, 126.23, 65.91, 52.91 p.p.m. ESI-MS: m/z
307.15 [M + 1]+. Anal. Calculated for C13H14N4OS2: C,
50.96; H, 4.61; N, 18.29. Found: C, 50.89; H, 4.58; N,
18.20%. m.p. 286–288 °C. Solid is crystalline.
(monofluorinated aromatic ring stretch) and 735.90 cm−1
.
1H NMR (CDCl3+DMSO-d6): δ 12.49 (br s, 1H, >NH),
7.87 (m, 1H, ArH), 7.51 (m, 4H, ArH), 7.09 (m, 3H, ArH),
7.01 (m, 1H, ArH), 3.77 (s, 4H, –NHC=SN(CH2)2, piper-
azine), 3.03 (t, 4H, J = 4.86 Hz, –N(CH2)2, piperazine) p.p.
m. 13CNMR (CDCl3+DMSO-d6): δ 186.83, 163.81,
154.10, 152.86, 137.40, 130.33, 129.27, 126.44, 126.23,
124.81, 119.54, 116.03, 115.72, 57.54, 50.07 p.p.m. ESI-
MS: m/z 400.24 [M + 1]+. Anal. Calculated for
C19H18FN5S2: C, 57.12; H, 4.54; N, 17.53. Found: C, 57.08;
H, 4.48; N, 17.46%. m.p. 288–290 °C. Solid is crystalline.
4-Ethyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)piperazine-1-car-
bothioamide (11a) On completion of the reaction, the
contents were cooled and poured into ice-cold water. The
precipitates formed were filtered, dried and recrystallised
from ethanol to afford 11a as light yellow crystals (0.75 g,
80%). FT-IRνmax (KBr): 2972.08.74, 2931.7, 2823.31,
1532.67, 1433.05 (C=S stretch and C–N stretch, aromatic
ring C=C stretch), 1360.90, 1220.69, 1145.12 (C=S
stretch) and 757.31 cm−1. 1H NMR (DMSO-d6): δ 13.94 (br
s, 1H, > NH), 7.84 (m, 2H, ArH), 7.49 (m, 3H, ArH), 4.12
(s, 4H, –NHC=SN(CH2)2, piperazine), 2.45 (m, 6H, N
(CH2)2CH2CH3), 1.08 (t, 3H, J = 7.16 Hz, -CH2CH3.) p.p.
m. 13CNMR (DMSO-d6): δ 184.53, 168.71, 152.91, 130.41,
130.18, 128.89, 126.05, 52.10, 51.41, 47.06, 11.72 p.p.m.
ESI-MS: m/z 334.20 [M + 1]+. Anal. Calculated for
C15H19N5S2: C, 54.03; H, 5.74; N, 21.00. Found: C, 54.00;
H, 5.68; N, 20.92%. m.p. 258–260 °C. Solid is crystalline.
General procedure for the synthesis of 5-(2-chlorophenyl-
1,3,4-thiadiazol-2-yl) carbothioamide derivatives (9b–11b)
A mixture of 5-(2-chlorophenyl)-1,3,4-thiadiazol-2-amine
(4b) (0.5 g, 2.36 mmol), 1-(2-fluorophenyl)piperazine
(0.5 mL, 2.82 mmol) and carbon disulphide (0.2 mL) in an
alkaline isopropyl alcohol (30 mL) solution was refluxed at
90 °C for 20 h with continuous stirring. The progress of the
reaction was monitored by TLC. On completion of the
reaction, the contents were cooled and poured into ice-cold
water. The precipitates thus formed were filtered, dried and
recrystallised from ethanol to afford 9b in appreciable yield.
The same procedure was repeated with phenylpiperazine
(0.4 mL, 2.82 mmol) and N-ethyl piperazine (0.4 mL,
2.82 mmol) to afford final carbothioamide derivatives, 10b
and 11b, respectively in appreciable yields.
4-Phenyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)piperazine-1-car-
bothioamide (12a) On completion of the reaction, the
contents were cooled and poured into ice-cold water. The
precipitates thus formed were filtered, dried and recrys-
tallised from ethanol to afford 12a as light yellow crystals
(0.88 g, 81.76%). FT-IRvmax (KBr): 3141.42, 2890.97,
2827.88, 1571.72, 1475.41 (C=S stretch and C–N stretch,
aromatic ring, C=C stretch), 1222.89, 1180.31 (C=S
stretch) and 748.46 cm−1. 1H NMR (DMSO-d6): δ 14.36 (br
s, 1H, >NH), 7.87 (m, 2H, ArH), 7.54 (m, 3H, ArH), 7.24 (t,
2 H, J = 8.00 Hz, ArH), 6.99 (d, 2H, J = 8.00 Hz, ArH),
6.82 (t, 1H, J = 7.24 Hz, ArH), 4.23 (s, 4H, –NHC=SN
(CH2)2, piperazine), 3.22 (s, 4H, N(CH2)2C6H5, piperazine)
p.p.m. 13CNMR (DMSO-d6): δ 184.52, 168.66, 152.96,
150.60, 130.71, 130.16, 129.33, 128.96, 126.28, 119.21,
115.73, 59.10, 48.17 p.p.m. ESI-MS: m/z 382.23 [M + 1]+.
Anal. Calculated for C19H19N5S2: C, 59.81; H, 5.02; N,
18.36. Found: C, 59.75; H, 4.99; N, 18.32%. m.p.
320–322 °C. Solid is crystalline.
N-(5-(2-Chlorophenyl)-1,3,4-thiadiazol-2-yl)-4-(2-fluorophe-
nyl)piperazine-1-carbothioamide (9b) The precipitates
formed were filtered, dried and recrystallised from ethanol
to afford 9b as creamy crystalline solid (0.60 g, 58.53%).
FT-IRνmax (KBr): 3362.14, 2922.55, 2849.67, 1550.66
(C=S stretch and C–N stretch, aromatic ring, C=C stretch),
1452.32, 1380.41, 1236.05 (monofluorinated aromatic ring
stretch) and 737.49 cm−1. 1H NMR (DMSO-d6): δ 12.30 (br
s, 1H, > NH), 7.86 (m, 1H, ArH), 7.48 (m, 3H, ArH), 7.02
(m, 4H, ArH), 3.79 (s, 4H, –NHC=SN(CH2)2, piperazine),
3.07 (t, 4H, J = 4.86 Hz, –N(CH2)2, piperazine) p.p.m.
13CNMR (DMSO-d6): δ 181.39, 168.71, 157.13, 150.84,
138.24, 136.76, 130.32, 128.87, 127.41, 122.54, 116.03,
115.26, 56.38, 54.74 p.p.m. ESI-MS: m/z 434.13 [M + 1]+.
Anal. Calculated for C19H17ClFN5S2: C, 52.59; H, 3.95; N,
16.14. Found: C, 52.47; H, 3.72; N, 15.98%. m.p.
254–258 °C. Solid is crystalline.
4-(2-Fluorophenyl)-N-(5-phenyl-1,3,4-thiadiazol-2-yl)pipera-
zine-1-carbothioamide (13a) The sticky mass obtained