L.-Y. Zhang et al. / Bioorg. Med. Chem. Lett. 21 (2011) 5722–5725
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J = 11.2 Hz, 1H), 8.06 (s, 1H), 8.28 (d, J = 2.0 Hz, 1H). N-(2,4-Dimethoxyphenyl)-
5-isopropyl-3,8-dimethylazulene-1-sulfonamide (3b). 1H NMR (400 MHz,
CDCl3) d 1.36 (d, J = 6.8 Hz, 6H), 2.50 (s, 3H), 3.10 (q, J = 6.4 Hz, 1H), 3.42 (s,
3H), 3.72 (s, 6H, 2 ꢁ OCH3), 6.31–6.37 (m, 2H, PhH), 7.00 (s, 1H, PhH), 7.37 (d,
J = 10.8 Hz, 1H), 7.56 (d, J = 11.2 Hz, 1H), 8.02 (s, 1H), 8.22 (d, J = 2.0 Hz, 1H).
N,5-Diisopropyl-3,8-dimethylazulene-1-sulfonamide (3c). 1H NMR(400 MHz,
CDCl3) d 1.15 (d, J = 7 Hz, 6H, 2 ꢁ CH3), 1.38 (d, J = 7.2 Hz, 6H), 2.58 (s, 3H), 3.12
(q, J = 6.8 Hz, 1H), 3.37 (s, 3H), 3.53 (m, 1H, CH), 4.28 (br, 1H, NH), 7.37 (d,
J = 11.2 Hz, 1H), 7.57 (d, J = 11.2 Hz, 1H), 8.16 (s, 1H), 8.26 (d, J = 2.0 Hz, 1H). N-
(Naphthalen-1-yl)-5-isopropyl-3,8-dimethylazulene-1-sulfonamide (3d). 1H
2H, PhH), 6.78 (d, J = 8.0 Hz, 2H, PhH), 7.44 (d, J = 10.8 Hz, 1H), 7.73 (d,
J = 10.4 Hz, 1H), 7.92 (s, 1H), 8.30 (s, 1H).
General Procedure for schiff base and sulfonyl hydrazone of guaiazulene: A
mixture of an arylaldehyde (1 mmol) and
4 (1 mmol) or 5 (1 mmol) in
anhydrous ethanol (10 mL) was stirred at room temperature for 1 h. After
checking for product formation via TLC in petroleum ether-ethyl acetate (4:1),
the mixture was concentrated with reduced pressure. The products were
collected by neutral alumina column chromatography and silica gel column
chromatography to give compounds 6a–6c and compounds 7a–7d,
respectively.
NMR (400 MHz, CDCl3)
d
1.37 (d, J = 7.6 Hz, 6H), 2.49 (s, 3H), 3.12 (q,
N-[4-(Benzylideneamino)phenyl]-5-isopropyl-3,8-dimethylazulene-1-
sulfonamide (6a). 1H NMR (400 MHz, DMSO-d6) d 1.31 (d, J = 7.2 Hz, 6H), 2.52
(s, 3H), 3.16 (q, J = 7.2 Hz, 1H), 3.33 (s, 3H), 7.14–7.19 (m, 4H, PhH), 7.46–7.48
(m, 3H, PhH), 7.49 (d, J = 10.4 Hz, 1H), 7.75 (d, J = 11.2 Hz, 1H), 7.86 (m, 2H,
PhH), 8.02 (s, 1H), 8.33 (d, J = 2.0 Hz, 1H), 8.54 (s, 1H,N@CH). N-[4-(2-
Hydroxybenzylideneamino)phenyl]-5-isopropyl-3,8-dimethylazulene-1-
sulfonamide (6b). 1H NMR (400 MHz, CDCl3) d 1.37 (d, J = 6.8 Hz, 6H), 2.51 (s,
3H), 3.11 (q, J = 6.8 Hz, 1H), 3.43 (s, 3H), 4.12 (br, 1H, NH), 6.85–7.34 (m, 8H,
PhH), 7.40 (d, J = 11.2 Hz, 1H), 7.60 (d, J = 11.2 Hz, 1H), 8.08 (s, 1H), 8.26 (d,
J = 2.0 Hz, 1H), 8.51 (s, 1H, N@CH). N-[4-(2-Thienylmethyleneamino)phenyl]-
5-isopropyl-3,8-dimethylazulene-1-sulfonamide (6c). 1H NMR (400 MHz,
DMSO-d6) d 1.31 (d, J = 7.2 Hz, 6H), 2.51 (s, 3H), 3.16 (q, J = 7.2 Hz, 1H), 3.32
(s, 3H), 7.12–7.20 (m, 5H, ArH), 7.49 (d, J = 11.2 Hz, 1H), 7.59 (d, J = 11.2 Hz,
1H), 7.76 (d, J = 7.2 Hz, 2H, PhH), 8.00 (s, 1H), 8.32 (d, J = 2.0 Hz, 1H), 8.69 (s,
1H,N = CH). N0-(4-Methoxy-benzylidene)-5-isopropyl-3,8-dimethylazulene-1-
sulfonohydrazide (7a). 1HNMR (400 MHz, CDCl3) d 1.37 (d, J = 7.2 Hz, 6H), 2.57
(s, 3H), 3.12 (q, J = 6.8 Hz, 1H), 3.40 (s, 3H), 3.80 (s, 3H, PhOCH3), 6.83 (d,
J = 8.0 Hz, 2H, PhH), 7.41 (d, J = 11.2 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H, PhH), 7.59
(d, J = 10.8 Hz, 1H), 7.88 (s, 1H), 8.16 (s, 1H, N@CH), 8.28 (d, J = 2.0 Hz, 1H). N0-
J = 7.2 Hz, 1H), 3.45 (s, 3H), 7.17–7.60 (m, 5H, PhH), 7.39 (d, J = 11.2 Hz, 1H),
7.58 (d, J = 10.8 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 8.08 (s,
1H), 8.26 (d, J = 2.0 Hz, 1H). N-Isobutyl-5-isopropyl-3,8-dimethylazulene-1-
sulfonamide (3e). 1H NMR (400 MHz, CDCl3) d 0.90 (d, J = 6.8 Hz, 6H, 2 ꢁ CH3),
1.38 (d, J = 6.8 Hz, 6H), 1.79 (m, 1H, CH), 2.58 (s, 3H), 2.89 (t, J = 6.4 Hz, 2H,
CH2), 3.12 (q, J = 7.2 Hz, 1H), 3.37 (s, 3H), 4.53 (br, 1H, NH), 7.37 (d, J = 10.4 Hz,
1H), 7.57 (d, J = 11.2 Hz, 1H), 8.07 (s, 1H), 8.27 (s, 1H). N-Propyl-5-isopropyl-
3,8-dimethylazulene-1-sulfonamide (3f). 1H NMR (400 MHz, CDCl3) d 0.90 (t,
J = 7.2 Hz, 3H, CH3), 1.38 (d, J = 6.8 Hz, 6H), 1.56 (m, 2H, CH2), 2.57 (s, 3H), 3.06
(m, 2H, CH2), 3.12 (q, J = 7.2 Hz, 1H), 3.36 (s, 3H), 4.48 (br, 1H, NH), 7.37 (d,
J = 11.2 Hz, 1H), 7.57 (d, J = 11.2 Hz, 1H), 8.08 (s, 1H), 8.27 (s, 1H). N-(P-toly)-5-
isopropyl-3,8-dimethylazulene-1-sulfonamide (3g). 1H NMR (400 MHz, CDCl3)
d 1.37 (d, J = 6.8 Hz, 6H), 2.23 (s, 3H, PhCH3), 2.51 (s, 3H), 3.12 (q, J = 7.2 Hz, 1H),
3.41 (s, 3H), 6.94 (d, J = 8.4 Hz, 2H, PhH), 7.00 (d, J = 8.4 Hz, 2H, PhH), 7.38 (d,
J = 11.2 Hz, 1H), 7.57 (d, J = 11.2 Hz, 1H), 8.06 (s, 1H), 8.25 (d, J = 2.0 Hz, 1H). N-
Ethyl-5-isopropyl-3,8-dimethylazulene-1-sulfonamide
(3h).
1H
NMR
(400 MHz, CDCl3) d 1.17 (t, J = 7.2 Hz, 3H, CH3), 1.37 (d, J = 6.8 Hz, 6H), 2.58
(s, 3H), 3.09 (m, 2H, CH2), 3.16 (q, J = 7.2 Hz, 1H), 3.37 (s, 3H), 4.42 (br, 1H, NH),
7.37 (d, J = 10.8 Hz, 1H), 7.58 (d, J = 11.2 Hz, 1H), 8.09 (s, 1H), 8.27 (d, J = 2.0 Hz,
1H). N-Cyclohexyl-5-isopropyl-3,8-dimethylazulene-1-sulfonamide (3i). 1H
NMR (400 MHz, CDCl3) d 1.38 (d, J = 7.2 Hz, 6H), 1.91–1.50 (m, 10H), 2.58 (s,
3H), 3.12 (q, J = 7.2 Hz, 1H), 3.27 (m, 1H, CH), 3.37 (s, 3H), 4.37 (br, 1H, NH),
7.36 (d, J = 10.4 Hz, 1H), 7.57 (d, J = 10.4 Hz, 1H), 8.15 (s, 1H), 8.26 (d, J = 2.0 Hz,
1H). N-Benzyl-5-isopropyl-3,8-dimethylazulene-1-sulfonamide (3j). 1H NMR
(400 MHz, CDCl3) d 1.39 (d, J = 6.8 Hz, 6H), 2.58 (s, 3H), 3.14 (q, J = 7.2 Hz, 1H),
3.37 (s, 3H), 4.23 (d, J = 6.0 Hz, 2H, CH2), 4.74 (br, 1H, NH), 7.22–7.24 (m, 5H,
PhH), 7.38 (d, J = 10.8 Hz, 1H), 7.57 (d, J = 10.8 Hz, 1H), 8.13 (s, 1H), 8.28 (d,
(4-Trifluoromethylbenzylidene)-5-isopropyl-3,8-
dimethylazulene-1-
sulfonohydrazide (7b). 1H NMR (400 MHz, DMSO-d6) d 1.32 (d, J = 7.2 Hz,
6H), 2.54 (s, 3H), 3.18 (q, J = 7.2 Hz, 1H), 3.33 (s, 3H), 7.72–7.79 (m, 4H, PhH),
7.50 (d, J = 11.2 Hz, 1H), 7.78 (d, J = 10.8 Hz, 1H), 7.95 (s, 1H), 8.12 (s, 1H,
N@CH),
8.36
(s,
1H).
N0-(2-Hydroxybenzylidene)-5-isopropyl-3,8-
dimethylazulene-1-sulfonohydrazide (7c). 1H NMR (400 MHz, DMSO-d6)
d
1.30 (d, J = 6.8 Hz, 6H), 2.51 (s, 3H), 3.18 (q, J = 7.2 Hz, 1H), 3.29 (s, 3H), 6.79–
6.84 (m, 2H, PhH), 7.20 (t, J = 7.6 Hz, 1H, PhH), 7.41 (d, J = 8.4 Hz, 1H, PhH), 7.51
(d, J = 11.2 Hz, 1H), 7.77(d, J = 10.4 Hz, 1H), 7.93 (s, 1H), 8.29 (s, 1H, N@CH),
8.36 (s, 1H), 10.25(br, 1H, OH). N0-(2-Thienylmethylene)-5-isopropyl-3,8-
dimethylazulene-1-sulfonohydrazide (7d). 1H NMR (400 MHz, DMSO-d6) d
1.31 (d, J = 6.4 Hz, 6H), 2.54 (s, 3H), 3.17 (q, J = 7.2 Hz, 1H), 3.30 (s, 3H), 7.06–
7.55 (m, 3H, ArH), 7.50 (d, J = 11.2 Hz, 1H), 7.77 (d, J = 11.2 Hz, 1H), 7.90 (s, 1H),
8.22 (s, 1H, N@CH), 8.35 (s, 1H).
J = 2.0 Hz,
1H).
N-(4-Chlorophenyl)-5-isopropyl-3,8-dimethylazulene-1-
sulfonamide (3k). 1H NMR (400 MHz, CDCl3) d 1.37 (d, J = 6.8 Hz, 6H), 2.51 (s,
3H), 3.13 (q, J = 7.2 Hz, 1H), 3.39 (s, 3H), 6.99 (d, J = 8 Hz, 2H, PhH), 7.15 (d,
J = 8 Hz, 2H, PhH), 7.40 (d, J = 11.2 Hz, 1H), 7.61 (d, J = 10.8 Hz, 1H), 8.02 (s, 1H),
8.27 (d, J = 2.0 Hz, 1H). N-(4-Aminophenyl)-5-isopropyl-3,8-dimethylazulene-
1-sulfonamide (4). 1H NMR (400 MHz, DMSO-d6) d 1.31 (d, J = 6.4 Hz, 6H), 2.49
(s, 3H), 3.17 (q, J = 6.8 Hz, 1H), 3.30 (s, 3H), 4.84 (s, 2H, NH2), 6.37 (d, J = 8.0 Hz,
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