September 2015
Applications of Azoalkenes in the Synthesis of Fused Ring Pyridazine Derivatives
1347
Scheme 1
12%), 227, 209, 118, 95, 91, 77 (100%). Anal. Calcd for C21H24N2:
C, 82.85; H, 7.95; N, 9.20%. Found: C, 82.80; H, 8.04; N, 9.16%.
2-Phenyl-2,3,4,4a,5,6,7,8-octahydrocinnoline-3-carbonitrile (5c).
This compound was obtained from 1(1.0g, 5.3 mmol), 4c (0.30 g,
5.66 mmol), chloramine-T trihydrate (1.52 g, 5.40 mmol) and
1
triethylamine as a pale yellow oil to yield 0.91 g (72%); H-NMR
CDCl3: δ 1.30–1.40 (m, 8H, CH2), 1.60–164 (m, 1H, CH2), 1.92
(t, 2H, CH2), 4.22 (dd, 1H, J = 9.8 and 2.9 Hz, CH), 6.63–6.75
(m, 3H, ArH), 7.10 (t, 2H, ArH); 13C-NMR CDCl3: δ 27.4, 28.9,
30.6, 30.9, 31.3, 33.4, 56.5, 113.0, 116.5, 119.9, 143.4, 157.2; MS
(relative abundance) m/z: 239 (M+ 20%), 212, 144, 95 (100%), 91,
77, 53. Anal. Calcd for C15H17N3: C, 75.28; H, 7.16; N, 17.56%.
Found: C, 75.35; H, 7.14; N, 17.51%.
2-Phenyl-2,3,4,4a,5,6,7,8-octahydrocinnoline-3-carboxylic
acid ethyl ester (5d).
This compound was obtained from 1
(1.0 g, 5.3 mmol), 4d (0.54g, 5.40mmol), chloramine-T trihydrate
(1.52 g, 5.40 mmol), and triethylamine as a pale yellow oil to yield
1.08 g (71%); 1H-NMR CDCl3: δ 1.28 (t, 3H, CH3), 1.33–1.44
(m, 8H, CH2), 1.58–162 (m, 1H, CH2), 1.93 (t, 2H, CH2), 4.21
(dd, 1H, J = 9.7 and 2.8 Hz, CH), 4.65 (q, 2H, CH2), 6.68–6.76
(m, 3H, ArH), 7.09 (t, 2H, ArH); 13C-NMR CDCl3: δ 12.9, 27.4,
29.7, 30.5, 31.0, 31.3, 61.2, 68.3, 113.3, 116.4, 130.2, 144.4,
157.2, 176.3; MS (relative abundance) m/z: 286 (M+), 241
(100%), 213, 191, 146, 95, 91, 77. Anal. Calcd for C17H22N2O2:
C, 71.30; H, 7.74; N, 9.78%. Found: C, 71.37; H, 7.70; N, 9.70%.
2,3-Diphenyl-3,4,4a,5,6,7-hexahydro-2H-cyclopenta[c]
EXPERIMENTAL
1H-NMR spectra were recorded on a Bruker Avance 400 MHz
spectrometer (MIT, India) using CDCl3 as solvent and
tetramethylsilane as internal standard. 13C-NMR spectra were
measured on Bruker Avance (100 MHz) instrument. The chemi-
cal shifts are expressed in δ and following abbreviations were
used. s = singlet, d = doublet, t = triplet, and m = multiplet. Mass
spectra were obtained on a Finnigan 4021 mass spectrometer at
an ionizing energy of 35 eV. Elemental analyses were obtained
on a Vario-EL instrument. TLC was done with pre-coated silica
gel G plates using chloroform-acetone (9:1) as eluent.
Typical procedure for the preparation of 2,3-diphenyl-2,3-
,4,4a,5,6,7,8-octahydrocinnoline (5a). A mixture of 1 (1.0 g,
5.3 mmol) and chloramine-T trihydrate (1.52 g, 5.40mmol) in
ethanol (10 mL) were refluxed for 2 h. The mixture was cooled to
room temperature, triethylamine (2 mL) was added and stirred at
room temperature for 30 min. A solution of 4a (0.56 g, 5.38 mmol)
in ethanol (5 mL) was then added and the mixture was refluxed for
3 h. It was then concentrated under reduced pressure, and the residue
was extracted with CH2Cl2 (25 mL). This extract was then washed
with water (15 mL), with 1N aq. NaOH (2 × 15 mL) and dried
(Na2SO4). The solvent was evaporated, and the remaining residue
was purified by column chromatography (chloroform/ethyl acetate,
7:3) to give 5a as yellow oil to yield 1.06 g (69%); 1H-NMR CDCl3:
δ 1.26–1.36 (m, 8H, CH2), 1.61–163 (m, 1H, CH2), 1.92 (t, 2H,
CH2), 3.95 (dd, 1H, J= 9.8 and 2.9 Hz, CH), 6.6–6.7 (m, 3H, ArH),
7.10–7.25 (m, 7H, ArH); 13C-NMR CDCl3: δ 27.1, 29.7, 30.8, 31.2,
31.9, 38.4, 66.3, 113.3, 118.2, 126.2, 128.6, 129.2, 130.8, 139.0,
144.4, 158.3; MS (relative abundance) m/z: 290 (M+, 15%), 213,
195, 104, 95, 91, 77 (100%). Anal. Calcd for C20H22N2: C, 82.72;
H, 7.64; N, 9.65%. Found: C, 82.77; H, 7.70; N, 9.53%.
pyridazine (9a).
This compound was obtained from 6 (1.0g,
5.74mmol), 4a (0.60 g, 5.76mmol), chloramine-T trihydrate
(1.64 g, 5.83 mmol), and triethylamine as a pale yellow oil to
1
yield 1.10 g (70%); H-NMR CDCl3: δ 1.30–1.40 (m, 6H, CH2),
1.60–164 (m, 1H, CH2), 1.92 (t, 2H, CH2), 4.12 (dd, 1H, J = 9.8
and 2.9 Hz, CH), 6.60–6.72 (m, 3H, ArH), 7.02 (t, 2H, ArH),
7.15–7.25 (m, 5H, ArH); 13C-NMR CDCl3: δ 27.0, 32.9, 33.7,
36.9, 37.2, 66.5, 113.6, 117.0, 125.2, 128.6, 128.9, 130.7, 140.8,
144.4, 157.1; MS (relative abundance) m/z: 276 (M+, 14%), 199,
195, 91, 81, 77 (100%). Anal. Calcd for C19H20N2: C, 82.57; H,
7.29; N, 10.14%. Found: C, 82.62; H, 7.20; N, 10.18%.
3-Methyl-2,3-Diphenyl-3,4,4a,5,6,7-hexahydro-2H-cyclopenta
[c]pyridazine (9b). This compound was obtained from 6 (1.0g,
5.74mmol), 4b (0.69 g, 5.84 mmol), chloramine-T trihydrate
(1.64 g, 5.83 mmol), and triethylamine as a pale yellow oil to
1
yield 1.21 g (73%); H-NMR CDCl3: δ 1.32–1.41 (m, 6H, CH2),
1.58 (s, 3H, CH3), 1.62–166 (m, 1H, CH2), 1.92 (d, 2H, CH2),
6.65–6.75 (m, 3H, ArH), 7.05 (t, 2H, ArH), 7.10–7.20 (m, 5H,
ArH),; 13C-NMR CDCl3: δ 24.8, 27.3, 33.7, 34.6, 35.3, 39.9,
65.5, 113.3, 117.4, 125.9, 128.7, 128.9, 130.7, 140.5, 144.8,
157.4; MS (relative abundance) m/z: 290 (M+, 14%), 213, 209,
118, 91, 81, 77 (100%). Anal. Calcd for C20H22N2: C, 82.72; H,
7.64; N, 9.65%. Found: C, 82.79; H, 7.60; N, 9.61%.
2-Phenyl-3,4,4a,5,6,7-hexahydro-2H-cyclopenta[c]pyridazine-3-
carbonitrile (9c). This compound was obtained from 6 (1.0g,
5.74mmol), 4c (0.32 g, 6.0 mmol), chloramine-T trihydrate
(1.64 g, 5.83 mmol), and triethylamine as a pale yellow oil to
1
3-Methyl-2,3-diphenyl-2,3,4,4a,5,6,7,8-octahydrocinnoline (5b).
This compound was obtained from 1 (1.0 g, 5.3 mmol), 4b
(0.64 g, 5.42 mmol), chloramine-T trihydrate (1.52 g, 5.40 mmol),
and triethylamine as a pale yellow oil to yield 1.14 g (71%);
1H-NMR CDCl3: δ 1.29–1.41 (m, 8H, CH2), 1.59–164 (m, 1H,
CH2), 1.71 (s, 3H, CH3), 1.92 (d, 2H, CH2), 6.65–6.74 (m, 3H,
ArH), 7.10–7.25 (m, 7H, ArH); 13C-NMR CDCl3: δ 23.8, 27.5,
28.2, 30.7, 31.1, 32.0, 41.2, 67.5, 112.7, 117.6, 126.1, 128.6, 128.9,
130.6, 139.0, 144.6, 158.6; MS (relative abundance) m/z: 304 (M+,
yield 0.93 g (72%); H-NMR CDCl3: δ 1.34–1.43 (m, 6H, CH2),
1.60–164 (m, 1H, CH2), 1.94 (t, 2H, CH2), 4.59 (dd, 1H, J = 9.9
and 2.9 Hz, CH), 6.72–6.83 (m, 3H, ArH), 7.12 (t, 2H, ArH); 13C-
NMR CDCl3: δ 27.8, 30.1, 32.6, 33.4, 36.6, 55.5, 113.1, 116.8,
119.3, 144.2, 157.5; MS (relative abundance) m/z: 225 (M+,10%),
224, 198, 144, 91, 81 (100%), 77. Anal. Calcd for C14H15N3: C,
74.64; H, 6.71; N, 18.65%. Found: C, 74.70; H, 6.70; N, 18.60%.
2-Phenyl-3,4,4a,5,6,7-hexahydro-2H-cyclopenta[c]pyridazine-3-
carboxylic acid ethyl ester (9d).
This compound was obtained
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet