R. Lesyk et al. / Bioorg. Med. Chem. 14 (2006) 5230–5240
5237
300 MHz and 13C NMR spectra on Varian Gemini
75 Hz in DMSO-d6 using tetramethylsilane (TMS) as
an internal standard (chemical shifts values are reported
in parts per million units, coupling constants (J) are in
hertz). Abbreviations are as follows: s, singlet; d,
doublet; dd, double doublet; t, triplet; m, multiplet;
and br, broad. The elemental analyses (C, H, and N)
were performed at the Perkin-Elmer 2400 CHN and
Carlo-Erba 1106 CHN analyzer and were within
0.4% of the theoretical values. LC/MS were obtained
on Agilent 1100 instrument.
54.99, 57.25, 113.99, 114.58, 120.98, 129.61, 133.19,
158.43, 170.69 (C@O). IR (KBr) : 3449, 3151 (N–H),
2956 (C@C), 2870, 2831 (CH2), 1659 (C@O), 1580,
1512 (Ar), 1437, 1301, 1253, 1206, 1176, 1036, 923,
832, 697, 609, 581 cmꢁ1. EI-MS: m/z 346 (100%,
M++1). Anal. (C18H19NO2S2) C, H, N.
9.2.4.
9-(40-Methylphenyl)-3,7-dithia-5-azatetracyclo-
[9.2.1.02,10.04,8]tetradecen-4(8)-one-6 (16). Yield 73%,
1
mp 240–242 ꢁC. H NMR (DMSO-d6) d: 1.10m, 1.21d,
1.31t, 1.45m, 1.64m, 1.98d, 2.16m, 2.22m (9H, norborn-
ane fragment), 3.32 (d, 1H, J = 10.4 Hz, SCH), 3.38 (d,
1H, J = 7.9 Hz, ArCH), 2.33 (s, 3H, CH3), 7.12d, 7.17d
(4H, J = 8.8 Hz, 4-Me–C6H4), 11.29 (s, 1H, NH). 13C
NMR (DMSO-d6) d: 20.61, 28.38, 29.01, 34.07, 41.16,
43.02, 45.46, 51.35, 57.15, 114.24, 121.14, 128.45,
129.24, 136.57, 138.25, 170.66 (C@O). IR (KBr) :
3424, 3122 (N–H), 2945 (C@C), 2870 (CH2), 1649
(C@O), 1579, 1512 (Ar), 1446, 1300, 1206, 1113, 1039,
922, 821, 699, 606, 585 cmꢁ1. EI-MS: m/z 330 (98.2%,
M++1). Anal. (C18H19NOS2) C, H, N.
The starting compounds: 2,4-thiazolidinedione (1),43 4-
thioxo-2-thiazolidone (2)13 were obtained according to
methods described previously. 5-Ylidene-4-thioxo-2-
thiazolidones (3–13) were prepared by treating 4-thioxo-
thiazolidine-2-one with corresponding aldehydes R1-
CHO in glacial acetic acid at water bath (100 ꢁC)
20 min, as described.13,14
9.2. Chemistry
9.2.1. General procedure for the preparation of 9-R-3,7-
dithia-5-azatetracyclo[9.2.1.02,10.04,8]tetradecen-4(8)-ones-
6 (14–24). A mixture of appropriate 5-R-methylidene-4-
thioxo-2-thiazolidone (10 mmol) and norbornene-2
(11 mmol) was refluxed for 1 h with catalytic amount
of hydroquinone (2–3 mg) for preventing of polymeriza-
tion processes in 10 ml of glacial acetic acid, then left
overnight at room temperature. The precipitated crys-
tals were filtered off, washed with methanol
(5–10 ml), and recrystallized from butanol (10–15 ml).
9.2.5. 9-(40-Hydroxyphenyl)-3,7-dithia-5-azatetracyclo-
[9.2.1.02,10.04,8]tetradecen-4(8)-one-6 (17). Yield 69%,
mp >260 ꢁC. 1H NMR (DMSO-d6) d: 1.11m, 1.18d,
1.31m, 1.47m, 1.64m, 2.04m, 2.13m, 2.21m (9H, nor-
bornane fragment), 3.22 (d, 1H, J = 7.7 Hz, SCH),
3.35 (d, 1H, J = 10 Hz, ArCH), 6.70d, 7.03d (4H,
J = 8.8 Hz, 4-HO–C6H4), 9.08 (s, 1H, OH), 11.29 (s,
1H, NH). 13C NMR (DMSO-d6) d: 28.37, 29.01,
34.02, 41.14, 43.00, 45.04, 51.36, 57.20, 114.90, 115.33,
120.79, 129.50, 131.46, 156.50, 170.73 (C@O). IR
(KBr) : 3420, 3129 (N–H, O–H), 2961 (C@C), 2873
(CH2), 1636 (C@O), 1513 (Ar), 1447, 1369, 1304, 1249,
1228, 1110, 924, 834, 700, 646, 610 cmꢁ1. EI-MS: m/z
332 (100%, M++1). Anal. (C17H17NO2S2) C, H, N.
Substances 14–24 were isolated as white or yellowish
powders. The NMR spectra show multiplets from the
norbornane fragments in the 1.10–1.30 ppm region, sig-
nal from the CH group connected with the aromatic ring
shows up as a doublet in the 3.36–3.98 region, which of-
ten overlays signals from the norbornane fragment.
9.2.6.
9-(20-Chlorophenyl)-3,7-dithia-5-azatetracyclo-
[9.2.1.02,10.04,8]tetradecen-4(8)-one-6 (18). Yield 72%,
1
mp 259–261 ꢁC. H NMR (DMSO-d6) d: 1.14m, 1.23d,
9.2.2.
9-(40-Chlorophenyl)-3,7-dithia-5-azatetracyclo-
1.35m, 1.45m, 1.62m, 1.95m, 2.10m, 2.24m (9H, nor-
bornane fragment), 3.39 (m, 1H, SCH), 4.00 (d, 2H,
J = 10.5 Hz, ArCH), 7.36m, 7.46d (4H, J = 8.6 Hz, 2-
Cl–C6H4), 11.41 (s, 1H, NH). 13C NMR (DMSO-d6)
d: 28.25, 28.82, 34.19, 41.10, 41.69, 43.00, 51.21, 56.51,
112.54, 121.76, 127.78, 129.12, 129.48, 129.62, 133.39,
138.18, 170.30 (C@O). IR (KBr) : 3423, 3118 (N–H),
2961 (C@C), 2870 (CH2), 1647 (C@O), 1577 (Ar),
1473, 1441, 1306, 1253, 1211, 1124, 1036, 951, 927,
759, 739, 690, 571 cmꢁ1. EI-MS: m/z 350 (100%,
M++1). Anal. (C17H16ClNOS2) C, H, N.
[9.2.1.02,10.04,8]tetradecen-4(8)-one-6 (14). Yield 89%,
mp 222–224 ꢁC. 1H NMR (DMSO-d6 + CCl4) d:
1.12m, 1.23m, 1.33m, 1.47m, 1.65m, 2.01m, 2.14m,
2.23m (9H, norbornane fragment), 3.37–3.43 (m, 2H,
ArCH, SCH), 7.30d, 7.34d (4H, J = 8.6 Hz, 4-Cl-
C6H4), 11.24 (s, 1H, NH). 13C NMR (DMSO-d6) d:
28.29, 28.81, 34.03, 41.09, 42.97, 44.97, 51.15, 56.82,
113.23, 121.33, 128.50, 130.39, 132.00, 140.16, 170.34
(C@O). IR (KBr): 3446, 3126 (N–H), 2957(C@C),
2871 (CH2), 1653 (C@O), 1579 (Ar), 1491, 1449, 1304,
1208, 1091, 1014, 922, 831, 681, 592 cmꢁ1. EI-MS: m/z
350 (97.5%, M++1). Anal. (C17H16ClNOS2) C, H, N.
9.2.7.
9-(Thiophen-2-yl)-3,7-dithia-5-azatetracyclo-
[9.2.1.02,10.04,8]tetradecen-4(8)-one-6 (19). Yield 80%,
mp 243–241 ꢁC. 1H NMR (DMSO-d6) d: 1.17m,
1.33m, 1.46m, 1.61m, 2.06m, 2.20m (10H, norbornane
fragment), 3.43 (d, 1H, J = 7.2 Hz, SCH), 3.85 (d, 2H,
J = 10.4 Hz, ArCH), 7.04m, 7.13d (J = 3.5 Hz), 7.48d
(J = 5.5 Hz) (3H, thiophene), 11.49 (s, 1H, NH). 13C
NMR (DMSO-d6) d: 28.31, 28.99, 34.14, 40.79, 41.68,
43.00, 51.36, 58.24, 114.03, 121.17, 125.22, 127.04,
143.95, 170.56 (C@O). IR (KBr) : 3423, 3114 (N–H),
2947 (C@C), 2866 (CH2), 1644 (C@O), 1584 (C@C,
9.2.3. 9-(40-Methoxyphenyl)-3,7-dithia-5-azatetracyclo-
[9.2.1.02,10.04,8]tetradecen-4(8)-one-6 (15). Yield 68%,
mp 216–218 ꢁC. 1H NMR (DMSO-d6 + CCl4) d:
1.12m, 1.22d, 1.33t, 1.47m, 1.65m, 2.02m, 2.12m,
2.23m, (9H, norbornane fragment), 3.29 (d, 1H,
J = 10.7 Hz, SCH), 3.38 (d, 1H, J = 7.2 Hz, ArCH),
3.80 (s, 3H, OCH3), 6.85d, 7.16d (4H, J = 8.8 Hz, 4-
MeO–C6H4), 11.16 (s, 1H, NH). 13C NMR (DMSO-
d6) d: 28.40, 29.02, 34.07, 41.17, 43.02, 44.99, 51.36,