K. Bhandari et al. / Bioorg. Med. Chem. 12 (2004) 4189–4196
4193
þ
(
(
1
C
m, 5H, ArH); MS (FAB) m=z: 401 (M , 2%), 403
ArH), 7.17–7.36 (m, 4H, ArH); MS (FAB) m=z: 386
((M+1) , 100%); IR (KBr, cm ): 3755, 3457, 2371,
1634, 1512, 1220, 1030. Anal. Calcd for
þ
ꢁ1
þ
ꢁ1
(M+2) , 18%); IR (KBr, cm ): 3387, 3298, 2835, 1597,
551, 1423, 1349, 1218, 1028. Anal. Calcd for
OSÆ1.25H O: C, 59.43; H, 6.25; N, 9.91.
Found: C, 59.26; H, 6.29; N, 9.82.
21
H
24ClN
3
2
C
21
H
24FN
Found: C, 58.89; H, 4.36; N, 8.47.
3
2
OSÆ1.15CS : C, 58.81; H, 4.45; N, 8.89.
4
(
.1.10. 2-Hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl-2-
4-methylpiperazine)-1-carbothioamide (12). With 5 and
4.1.14. 2-Hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl-2-
(3-a,a,a-trifluoromethylphenyl piperazine)-1-carbothio-
amide (16). With 5 and 1-(3-a,a,a-trifluorotolyl)piper-
1
2
-methylpiperazine (6f). Yield: 88%, mp ¼ 160 ꢁC, H
NMR (CDCl , 200 MHz): d 1.96–2.16 (m, 2H, H-3),
.34 (s, 3H, N-Me), 2.47–2.52 (t, 4H, J ¼ 5 Hz, CH –
1
3
azine (6j). Yield: 50%, mp ¼ 180–2 ꢁC, H NMR
2
(CDCl , 200 MHz): d 1.9–2.26 (m, 2H, H-3), 2.89–2.99
2
3
N(Me)–CH ), 2.87–2.89 (m, 2H, H-4), 3.8–3.89 (m, 4H,
(m, 2H, H-4), 3.39–3.44 (t, 4H, J ¼ 5:3 Hz, piperazinyl
H’s adjacent to phenyl ring), 4.06–4.08 (m, 5H, piper-
azinyl H’s adjacent to thiourea group, H-2), 5.89–5.92
(d, 1H, J ¼ 7:4 Hz, H-1), 7.00–7.42 (m, 8H, ArH); MS
2
CH
1
2 2
–N–CH ), 3.91–4.04 (m, 1H, H-2), 5.89–5.93 (d,
H, J ¼ 7:4 Hz, H-1), 7.14–7.26 (m, 4H, ArH); MS
þ
ꢁ1
(
3
FAB) m=z: 306 ((M+1) , 27%); IR (KBr, cm ): 3754,
418, 3251, 2933, 2367, 1627, 1558, 1422, 1038, 848.
Anal. Calcd for C16 OSÆ3.5H O: C, 52.17; H, 8.15;
N, 11.41. Found: C, 52.38; H, 7.92; N, 10.95.
þ
ꢁ1
(FAB) m=z: 436 ((M+1) , 34%); IR (KBr, cm ): 3752,
3438, 2931, 2374, 1617, 1369, 1122, 698. Anal. Calcd for
C H F N OSÆ0.4CS : C, 57.76; H, 5.16; N, 9.02.
H
23
N
3
2
22
24
3
3
2
Found: C, 57.61; H, 4.83; N, 9.37.
4
(
.1.11. 2-Hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl-2-
4-(2-pyridyl)piperazine)-1-carbothioamide (13). With 5
4.1.15. 1,2,3,4-Tetrahydronaphthalen-1-yl-2-(4-fluoro-
phenylpiperazine)-1-carbothioamide (17). With 4 and
and 1-(2-pyridyl)piperazine (6g). Yield: 73%, mp ¼ 163–
1
5
ꢁC, H NMR (CDCl , 200 MHz): d 1.97–2.17 (m, 2H,
1-[(4-fluoro)phenyl]piperazine (6i). Yield: 48%, mp ¼
3
1
H-3), 2.86–2.93 (m, 2H, H-4), 3.73–3.79 (m, 4H, piper-
azinyl H’s adjacent to pyridine ring), 3.97–4.06 (m, 5H,
piperazinyl H’s adjacent to thiourea group, H-2), 5.91–
115–20 ꢁC, H NMR (CDCl , 200 MHz): d 1.84–1.98
3
(m, 3H, H-2, H-3), 2.17 (m, 1H, H-3), 2.80 (m, 2H, H-4),
3.16–3.18 (m, 4H, piperazinyl H’s adjacent to phenyl
ring), 3.95–3.97 (m, 4H, piperazinyl H’s adjacent to
thiourea group), 5.85 (m, 1H, H-1), 6.81–7.01 (m, 4H,
ArH), 7.15–7.24 (m, 3H, ArH), 7.32 (m, 1H, ArH); MS
5
.95 (d, 1H, J ¼ 7:7 Hz, H-1), 6.57–6.70 (m, 2H, pyrid-
inyl H’s adjacent to piperazine), 7.15–7.29 (m, 4H,
ArH), 7.49–7.57 (m, 1H, pyridinyl H adjacent to N),
þ
ꢁ1
8
.17–8.19 (m, 1H, pyridinyl H adjacent to N); MS
þ
(FAB) m=z: 370 ((M+1) , 60%); IR (KBr, cm ): 3413,
3248, 2932, 2835, 1508, 1415, 1347, 1221, 1153, 1020,
ꢁ1
(
FAB) m=z: 369 ((M+1) , 28%); IR (KBr, cm ): 3757,
3
1
410, 3224, 3062, 2923, 2371, 1597, 1550, 1489, 1429,
230, 1037, 760. Anal. Calcd for C H N OSÆ0.25CS :
819. Anal. Calcd for C21
H
6.75; N, 10.78. Found: C, 64.52; H, 6.98; N, 10.92.
24FN
3
2
SÆ1.15H O: C,64.67; H,
20
33
4
2
C, 62.09; H, 6.20; N, 14.47. Found: C, 62.31; H, 5.88; N,
4.56.
1
0
4.1.16. N-Benzyl-N-methyl-N -(1,2,3,4-tetrahydronaphth-
alen-1-yl)-thiourea (18). With 4 and benzylmethylamine
1
4
.1.12. 2-Hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl-2-
3
(6d). Yield: 72%, oil, H NMR (CDCl , 200 MHz): d
(
[
4-tolylpiperazine)-1-carbothioamide (14). With 5 and 1-
(4-methyl)phenyl]piperazine (6h). Yield: 65%,
, 200 MHz): d 1.98–
.17 (m, 2H, H-3), 2.28 (s, 3H, Ar-CH ), 2.86–2.91 (m,
H, H-4), 3.17–3.29 (m, 4H, piperazinyl H’s adjacent to
1.67–1.90 (m, 3H, H-2, H-3), 2.13–2.20 (m, 1H, H-3),
2.74–2.79 (m, 2H, H-4), 3.18 (s, 3H, N-Me), 5.03–5.06
1
mp ¼ 205–7 ꢁC, H NMR (CDCl
3
(d, 2H, J ¼ 5:98 Hz, N–CH
2
), 5.81 (m, 1H, H-1), 7.08–
7.17 (m, 3H, ArH), 7.24–7.38 (m, 6H, ArH); MS (FAB)
ꢁ1
2
2
3
þ
m=z: 311 ((M+1) , 100%); IR (neat, cm ): 3406, 3315,
2929, 1523, 1351, 1211, 1081, 746. Anal. Calcd for
phenyl ring), 3.93–4.06 (m, 5H, piperazinyl H’s adjacent
to thiourea group, H-2), 5.91–5.95 (d, 1H, J ¼ 7:9 Hz,
C
69.62; H, 7.30; N, 8.74.
19
H
22
N
2
2
SÆH O: C, 69.51; H, 7.01; N, 8.54. Found: C,
H-1), 6.80–6.85 (d, 2H, J ¼ 8:5 Hz, ArH), 7.08–7.36 (m,
þ
6
H, ArH); MS (FAB) m=z: 382 ((M+1) , 45%); IR
ꢁ
1
(
KBr, cm ): 3753, 3420, 3237, 2931, 2371, 1620, 1549,
425, 1351, 1223, 1037. Anal. Calcd for
C H N OSÆ0.75H O: C, 66.92; H, 7.22; N, 10.65.
1
4.1.17. General procedure for preparation of compounds
0
(19–23). A mixture of N-ethyl-N -(3-dimethylamino-
propyl)-carbodiimidehydrochloride (EDCI) (117.5 mg,
22
27
3
2
Found: C, 67.31; H, 7.13; N, 10.47.
0.613 mmol) and carbondisulfide (466 mg, 6.13 mmol) in
acetonitrile (1.5 mL) was cooled to )10 ꢁC in an ice-salt
bath and treated dropwise with a solution of compound
4/5 (0.613 mmol) in acetonitrile (1.5 mL). The reaction
mixture was allowed to attain the rt and was stirred for
3 h. Reaction was monitored by TLC. Removal of the
solvent under reduced pressure afforded a white solid.
Water (15 mL) was added to it and the compound was
extracted with dichloromethane (10 mL · 3). Combined
4
(
5
.1.13. 2-Hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl-2-
4-fluorophenylpiperazine)-1-carbothioamide (15). With
and 1-[(4-fluoro)phenyl]piperazine (6i). Yield: 89%,
1
mp ¼ 188–90 ꢁC, H NMR (CDCl
.25 (m, 2H, H-3), 2.91 (m, 2H, H-4), 3.20–3.25 (m, 4H,
piperazinyl H’s adjacent to phenyl ring), 4.02–4.11 (m,
3
, 200 MHz): d 1.95–
2
5
5
H, piperazinyl H’s adjacent to thiourea group, H-2),
.91–5.95 (d, 1H, J ¼ 7:2 Hz, H-1), 6.88–7.04 (m, 4H,
2 4
dichloromethane extracts were dried (anhyd Na SO )