2006
M. M. Suni et al. / Tetrahedron 57 (2001) 2003±2009
(90 MHz, DMSO-d6) 2.4 (s, 3H, ArMe), 5.85 (s, 1H, NH),
6.04 (s, 1H, NH), 6.05±6.81 (br s, 2H, NH2), 7.0 (s, 1H,
NH), 7.15 (d, J8.7 Hz, 2H, Ph), 7.25 (d, J8.7 Hz, 2H,
Ph); dC (90 MHz, DMSO-d6) 30.9, 126.6, 129.5, 130.1,
139.3, 154.8, 162.3; m/z 224 (M1, 100), 165 (18), 149
(21), 105 (88).
DMSO-d6) 27.3, 157.8, 160.1; m/z 148 (M1, 100), 132
(21), 89 (14), 73 (6).
The other 1-alkyl-2-thiobiureas 3(g±i) similarly prepared by
the condensation of corresponding isothiocyanates with
semicarbazides are listed below.
2.2.2. 1-Ethyl-2-thiobiurea (3g). White needles, mp 2028C;
(Found: C, 29.48; H, 6.02; N, 34.52; S, 19.70. C4H10N4OS
requires C, 29.63; H, 6.17; N, 34.57; S, 19.75%); Rf (CHCl3)
0.48; nmax (KBr, pellet) 3480, 3450, 3300, 3220, 2890,
1670, 1320 cm21; dH (90 MHz, DMSO-d6) 1.27 (t,
J7.3 Hz, 3H, Me), 3.65 (q, J7.3 Hz, 2H, CH2), 5.48 (s,
1H, NH), 5.61 (s, 1H, NH), 5.9 (s, 1H, NH), 6.03±6.08 (br s,
2H, NH2); dC (90 MHz, DMSO-d6) 14.1, 36.5, 157.6, 160.1;
m/z 162 (M1, 100), 146 (18), 118 (13), 88 (3).
2.1.3. 1-p-Anisyl-2-thiobiurea (3c). White solid, mp
2048C; (Found: C, 45.08; H, 5.10; N, 23.28; S, 13.53.
C9H12N4O2S requires C, 45.0; H, 5.0; N, 23.33; S,
13.33%); Rf (15% CHCl3/isopropanol) 0.49; nmax (KBr,
pellet) 3510, 3500, 3460, 3340, 3000, 2930, 1690, 1520,
1320 cm21; dH (90 MHz, DMSO-d6) 3.8 (s, 3H, ArOMe),
5.69 (s, 1H, NH), 6.01 (s, 1H, NH), 6.05±6.74 (br s, 2H,
NH2), 6.9 (s, 1H, NH), 7.08 (d, J8.9 Hz, 2H, Ph), 7.3 (d,
J8.9 Hz, 2H, Ph); dC (90 MHz, DMSO-d6) 55.5, 114.8,
124.8, 128.2, 155.1, 160.0, 161.8; m/z 240 (M1, 100), 167
(20), 165 (41), 121 (82).
2.2.3. 1-Propyl-2-thiobiurea (3h). White needles, mp
2128C; (Found: C, 34.0; H, 6.72; N, 31.86; S, 18.21.
C5H12N4OS requires C, 34.09; H, 6.82; N, 31.82; S,
18.18%); Rf (CHCl3) 0.47; nmax (KBr, pellet) 3460, 3450,
3300, 3280, 2980, 1690, 1320 cm21; dH (90 MHz, DMSO-
d6) 0.88 (t, J7.1 Hz, 3H, Me), 1.64 (m, 2H, CH2Me), 3.46
(t, J6.9 Hz, 2H, NCH2), 5.48 (s, 1H, NH), 5.62 (s, 1H,
NH), 5.7 (s, 1H, NH), 6.01±6.08 (br s, 2H, NH2); dC
(90 MHz, DMSO-d6) 10.9, 22.1, 38.5, 157.2, 159.8; m/z
176 (M1, 100), 160 (12), 132 (31), 117 (24), 102 (11).
2.1.4. 1-p-Phenetyl-2-thiobiurea (3d). White solid, mp
2108C; (Found: C, 47.36; H, 5.62; N, 22.0; S, 12.67.
C10H14N4O2S requires C, 47.24; H, 5.51; N, 22.05; S,
12.60%); Rf (20% CHCl3/isopropanol) 0.51; nmax (KBr,
pellet) 3520, 3480, 3460, 3340, 3010, 2950, 1680,
1320 cm21; dH (90 MHz, DMSO-d6) 1.33 (t, J7.3 Hz,
3H, Me), 4.1 (q, J7.3 Hz, 2H, ArOCH2), 5.5 (s, 1H,
NH), 5.85 (s, 1H, NH), 6.01±6.8 (br s, 2H, NH2), 6.9 (s,
1H, NH), 7.0 (d, J9.0 Hz, 2H, Ph), 7.3 (d, J9.0 Hz, 2H,
Ph); dC (90 MHz, DMSO-d6) 14.7, 63.8, 115.3, 124.6,
128.2, 154.7, 159.4, 160.4; m/z 254 (M1, 35), 181 (29),
179 (18), 135 (100).
2.2.4. 1-Butyl-2-thiobiurea (3i). White needles, mp 1988C;
(Found: C, 37.78; H, 7.3; N, 29.28; S, 16.91. C6H14N4OS
requires C, 37.89; H, 7.37; N, 29.47; S, 16.84%); Rf (CHCl3)
0.44; nmax (KBr, pellet) 3460, 3450, 3320, 3280, 2950,
1700, 1320 cm21
; dH (90 MHz, DMSO-d6) 0.9 (t,
2.1.5. 1-p-Chlorophenyl-2-thiobiurea (3e). White solid,
mp 1888C; (Found: C, 39.32; H, 3.85; N, 22.96; S, 13.15.
C8H9N4OSCl requires C, 39.26; H, 3.68; N, 22.9; S,
13.09%); Rf (30% CHCl3/isopropanol) 0.45; nmax (KBr,
J7.1 Hz, 3H, Me), 1.31 (m, 2H, CH2CH2Me), 1.52, (m,
2H, CH2CH2Me), 3.48 (t, J6.9 Hz, 2H, NCH2), 5.9 (s, 1H,
NH), 6.01 (s, 1H, NH), 6.04 (s, 1H, NH), 6.06±6.1 (brs, 2H,
NH2); dC (90 MHz, DMSO-d6) 13.5, 19.7, 30.7, 40.1, 157.3,
160.2; m/z 190 (M1, 100), 131 (18), 119 (11).
pellet) 3520, 3480, 3460, 3340, 3080, 1680, 1340 cm21
;
dH (90 MHz, DMSO-d6) 5.73 (s, 1H, NH), 5.92 (s, 1H,
NH), 6.01 (s, 1H, NH), 6.06±7.1 (br s, 2H, NH2), 7.37 (d,
J8.6 Hz, 2H, Ph), 7.5 (d, J8.6 Hz, 2H, Ph); dC (90 MHz,
DMSO-d6) 127.3, 129.1, 130.5, 133.9, 154.8, 160.8; m/z
244.5 (M1, absent), 172 (11), 170 (44), 126 (100).
2.3. General procedure for compounds 4(a±e).
To a solution of 1-phenyl-2-thiobiurea 3a (2.10 g, 0.01 mol)
in minimum quantity of NaOH (2 M, 8 ml) in ethanol
(20 ml), butyl iodide (1.2 ml, 0.01 mol) was added dropwise
and the mixture kept stirred at 208C for 11 h. The white solid
which got precipitated was collected and washed with dilute
alkali, to free it from any thiobiurea present, and ®nally with
cold water. Crystallization from DMF/H2O mixture (1:1) in
the cold condition afforded 4a. The S-benzyl derivatives
were formed when an alkaline solution of the 1-aryl-2-thio-
biureas were stirred with equivalent quantity of benzyl
chloride 4(b±c). The S-methylisothiobiurea was obtained
by the reaction of an alkaline solution of 1-aryl-2-thiobiurea
with equivalent quantity of dimethyl sulfate 4(d±e).
2.2. General procedure for compounds 3(f±i)
A solution of semicarbazide hydrochloride (11.15 g,
0.1 mol) in minimum amount of water was warmed with
an ethanolic solution of methyl isothiocyanate (7.3 ml,
0.1 mol) in the presence of sodium carbonate (5.3 g,
0.05 mol) for 10 min. The white solid obtained was puri®ed
by dissolution in NaOH (2 M, 15 ml). The alkaline solution
was decolourised with charcoal and the clear solution was
neutralized with HCl (4 ml) to obtain 3f. It was collected
and crystallized from hot ethanol.
2.3.1. 1-Phenyl-2-S-butyl-isothiobiurea (4a). White
needles, mp 1628C; (Found: C, 54.11; H, 6.67; N, 18.10;
S, 12.08. C12H18N4OS requires C, 54.13; H, 6.77; N, 21.05;
S, 12.03%); Rf (30% Petroleum ether/ethylacetate) 0.51;
nmax (KBr, pellet) 3400, 3200, 3150, 3050, 2950, 1670,
2.2.1. 1-Methyl-2-thiobiurea (3f). White needles, mp
2128C; (Found: C, 24.54; H, 5.56; N, 37.86; S, 21.68.
C3H8N4OS requires C, 24.32; H, 5.41; N, 37.84; S,
21.62%); Rf (CHCl3) 0.54; nmax (KBr, pellet) 3480, 3450,
3300, 3220, 2950, 1690, 1340 cm21; dH (90 MHz, DMSO-
d6) 3.2 (s, 3H, Me), 5.62 (s, 1H, NH), 5.7 (s, 1H, NH), 6.01
(s, 1H, NH), 6.04±6.09 (br s, 2H, NH2); dC (90 MHz,
1540, 740 cm21
;
dH (90 MHz, DMSO-d6) 0.9 (t,
J7.4 Hz, 3H, Me), 1.4 (m, 2H, CH2CH2Me), 1.6 (m, 2H,
CH2CH2Me), 3.2 (t, J7.2 Hz, 2H, SCH2), 5.8±6.1 (br s,