Z. Hussain, H. Hopf, L. Pohl, T. Oeser, A. K. Fischer, P. G. Jones
FULL PAPER
5.45 (m, 2 H, 5-,7-H), 6.21 (2 d, J = 9.10 Hz, 2 H, 4-,8-H) ppm. C=O) ppm. IR (KBr): ν = 3023 cm–1 (w, C–H stretching), 2957,
3
˜
13C NMR (100.6 MHz, CDCl3): δ = 14.07 (q, C-14), 14.24 (q, C-
16), 22.66 (t, C-13), 26.02 (t, C-12), 33.01 (t, C-11), 35.92 (t, C-10),
37.32 (d, C-2), 42.80 (2 t, C-1,-3), 45.20 (d, C-6), 60.93 (t, C-15),
2923, 2870, 2853 (m, C–H stretching), 2699, 2595 (m), 1712 (s,
C=O), 1219 (m). UV (CH3CN): λmax (lg ε) = 206 nm (4.30), 268
(3.53). MS (EI = 70 eV): m/z (%) = 246 (12) [M+], 228 (5) [M+
–
115.97, 116.63 (2 d, C-5,-7), 125.30, 125.45 (2 d, C-4,-8), 141.81 (s, H2O], 201 (100) [M+ – CO2H], 129 (21) [201 – C5H12].
C-3a,-8a), 173.28 (s, C-9) ppm. IR (film): ν = 3023 cm–1 (w, C–H
˜
Ethyl 2-Propyl Perhydro-6-azulenecarboxylate (13/14): Ethyl 2-pro-
pyl-1,2,3,6-tetrahydro-6-azulenecarboxylate (12a, 3.29 g,
13.37 mmol) was dissolved in ethyl acetate (300 mL) in a 500-mL
flask and Pd/C (1.1 g) added to the mixture. A stream of H2 was
blown through the suspension after evacuation, and the flask was
shaken for 2 h under hydrogen. The mixture was filtered to remove
the catalyst and the solvent was evaporated to yield the product
(3.09 g, 92%) as a colourless liquid. The product was obtained in
the form of a mixture of isomers, which were later separated by
stretching), 2956, 2925 (s, C–H stretching aliphatic), 1737 (s, C=O),
1465, 1447, 1367, 1301 (w), 1256 (m), 1223 (w), 1192, 1175, 1161
(m). UV (CH3CN): λmax (lg ε) = 206 nm (4.14), 274 (3.64), 288
(3.64), 312 (3.50), 344 (3.30), 374 (2.98). MS (EI = 70 eV): m/z (%)
= 274 (5) [M+], 245 (5) [M+ – C2H5], 228 (2) [245 – OH], 201 (100)
[M+ – C3H5O2], 129 (10) [201 – C5H12].
2-Propyl-1,2,3,6-tetrahydroazulene-6-carboxylic Acid (24): From
12a (0.70 g, 2.85 mmol), 24 was prepared by the same route as de-
scribed above for 20. The acid was recrystallized from hexane/ column chromatography on silica gel with pentane. The cis-fused
dichloromethane mixture to yield colourless irregular crystals.
isomer (13, 2.6 g, 77%) eluted first followed by the trans isomer 14.
However, pure trans-fused material could not be separated as it
always contained traces of the cis-fused derivative. The spectro-
scopic data for 13 are given below. B.p. 135–140 °C/5 Torr. 1H
Yield: 0.5 g (81 %). M.p. 118–120 °C. 1H NMR (400.1 MHz,
3
CDCl3): δ = 0.96 (t, J = 7.1 Hz, 3 H, 12-H), 1.36–1.50 (m, 4 H,
side-chain protons), 2.29 (m, 1 H, 2-H), 2.39–2.44/2.82–2.88 (m, 4
3
3
3
H, 1-,3-H), 2.89–2.90 (m, 1 H, 6-H), 5.43–5.46 (dd, J5,4 = J7,8
=
NMR (400.1 MHz, CDCl3): δ = 0.90 (t, J = 6.94 Hz, 3 H, 12-H),
3
3
3
9.07Hz, J5,6 = J7,6 = 5.6 Hz, 2 H, 5-,7-H), 6.24–6.27 (2 d, J =
1.28 (t, 3J = 7.12 Hz, 3 H, 14-H), 1.30–1.33 (m, 4 H, side-chain
protons), 1.51–1.53 (m, 2 H, 3a-,8a-H), 1.55–1.60 (m, 4 H, 4-,8-H),
9.1 Hz, 2 H, 4-,8-H) ppm. 13C NMR (100.6 MHz, CDCl3): δ =
14.23 (q, C-12), 21.39 (t, C-11), 37.04 (d, C-2), 38.18 (t, C-10), 1.67–1.72 (m, 1 H, 2-H), 0.82/1.89 (m, 4 H, 1-,3-H), 2.10–2.14 (m,
3
42.75 (2 t, C-1,-3), 44.72 (d, C-6), 115.74 (2 d, C-5,-7), 125.81 (2 d,
4 H, 5-,7-H), 2.64–2.67 (m, 1 H, 6-H), 4.15 (q, J = 7.12 Hz, 2 H,
13-H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 14.26 (q, C-12),
14.38 (q, C-14), 21.78 (t, C-11), 28.75 (2 t, C-4,-8), 29.56 (2 t, C-
C-4,-8), 141.95 (2 s, C-3a,-8a), 178.20 (s, C=O) ppm. IR (KBr): ν
˜
= 3023 cm–1 (w, C–H stretching), 2964, 2950, 2924 (m, C–H
stretching), 2834, 2871, 2829 (w), 2700 (w), 2596 (w), 1713 (s, 5,-7), 37.79 (t, C-10), 39.94 (d, C-2), 41.63 (2 t, C-1,-3), 41.87 (2 d,
C=O), 1686 (w), 1655 (w), 1419 (w), 1312, 1298, 1220 (w). UV C-3a,-8a), 43.41 (d, C-6), 59.97 (t, C-13), 176.11 (s, C=O) ppm. IR
(CH3CN): λmax (lg ε) = 206 nm (4.31), 268 (3.57). MS (EI = 70 eV): (film): ν = 2932 cm–1(s, CH-stretching), 1732 (s, C=O), 1463, 1450
˜
m/z (%) = 218 (14) [M+], 200 (6) [M+ – H2O], 173 (100) [M+
–
(w), 1376, 1221 (w), 1183, 1143 (m), 1095, 1046, 1033 (w). UV
CO2H], 129 (17) [173 – C3H8]. C14H18O2 (218.30): calcd. C 77.02, (CH3CN): λmax (lg ε) = 204 nm (2.92), 216 (2.55), 234 (2.15), 284
H 8.32; found C 77.08, H 8.17.
(1.86), 312 (1.80), 342 (1.64), 374 (1.54). GC/MS (EI = 70 eV):
m/z (%) = 252 (95) [M+], 237 (5) [M+ – CH3], 223 (12) [M+ – C2H5],
209 (29) [M+ – C3H7], 206 (18) [223 – OH], 178 (15) [206 – CO],
163 (100) [206 – C3H7], 135 (57) [163 – CO], 109 (52) [135 – C2H2],
81 (49) [109 – C2H4]. HRMS (C16H28O2): calcd.252.2089; found
252.20856 Ϯ 0.5 ppm.
2-Butyl-1,2,3,6-tetrahydroazulene-6-carboxylic Acid (25): From 12b
(0.70 g, 2.69 mmol), 25 was prepared by the same route as de-
scribed above for 20. Yield: 0.49 g (78%). M.p. 78–81 °C (com-
1
pound was obtained as an off-white solid). H NMR (400.1 MHz,
3
CDCl3): δ = 0.94 (t, J = 6.86 Hz, 3 H, 13-H), 1.30–1.39 (m, 6 H,
side-chain protons), 1.40–1.55 (m, 4 H, 1-,3-H), 2.27–2.30 (m, 1 H,
2-H), 2.83–2.87 (m, 1 H, 6-H), 5.39–5.43 (dd, 3J5,4 = 3J7,8 = 9.0 Hz,
3J5,6 = 3J7,6 = 5.7 Hz, 2 H, 5-,7-H), 6.24–6.27 (d, 3J = 9.1 Hz, 2 H,
4-,8-H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 14.11 (q, C-13),
Ethyl 2-Butyl-perhydroazulene-6-carboxylate (15/16): From 12b
(1.07 g, 4.24 mmol), 15/16 was prepared by the same route as de-
scribed above for 13 (colourless liquid). The spectroscopic and ana-
lytical data for 15 are given below. Yield: 0.86 g (76%). B.p. 146 °C/
3
22.82 (t, C-12), 30.54 (t, C-11), 35.82 (t, C-10), 37.79 (d, C-2), 42.98 5 Torr. 1H NMR (400.1 MHz, CDCl3): δ = 0.90 (t, J = 6.74 Hz, 3
(2 t, C-1,-3), 44.71 (d, C-6), 115.73 (2 d, C-5,-7), 125.62 (2 d, C-4,-
H, 13-H), 1.28 (t, 3J = 7.12 Hz, 3 H, 15-H), 1.27–1.34 (m, 6 H,
side-chain protons), 1.49–1.53 (m, 2 H, 3a-,8a-H), 1.53–1.59 (m, 4
H, 4-,8-H), 1.70 (m, 1 H, 2-H), 0.82/1.89 (m, 4 H, 1-,3-H), 2.09–
8), 141.82 (2 s, C-3a,-8a), 179.20 (s, C-9) ppm. IR (KBr): ν =
˜
3024 cm–1 (w, C–H stretching), 2956, 2924, 2872, 2853 (s, C–H
3
stretching), 2695, 2596 (w), 1710 (s, C=O), 1612, 1466, 1455 (w),
2.16 (m, 4 H, 5-,7-H), 2.64–2.67 (m, 1 H, 6-H), 4.13–4.18 (q, J =
1420, 1298 (m), 1211 (w). UV (CH3CN): λmax (lg ε) = 206 nm 7.12 Hz, 2 H, 14-H) ppm. 13C NMR (100.6 MHz, CDCl3): δ =
(4.31), 248 (3.56), 268 (3.47), 300 (3.04). MS (EI = 70 eV): m/z (%) 14.09 (q, C-13), 14.25 (q, C-15), 22.96 (t, C-12), 28.75 (2 t, C-4,-8),
= 232 (15) [M+], 214 (8) [M+ – H2O], 187 (100) [M+ – CO2H], 129 29.56 (2 t, C-5,-7), 30.96 (t, C-11), 35.16 (t, C-10), 40.18 (d, C-2),
(21) [187 – C4H10].
41.67 (2 t, C-1,-3), 41.87 (2 d, C-3a,-8a), 43.41 (d, C-6), 59.96 (t,
C-14), 176.08 (s, C-9) ppm. IR (film): ν = 2928 cm–1 (s, CH-stretch-
˜
2-Pentyl-1,2,3,6-tetrahydroazulene-6-carboxylic Acid (26): From 12c
(0.68 g, 2.48 mmol), 26 was prepared by the same route as de-
scribed above for 20. Yield: 0.5 g (82%). M.p. 70–72 °C (from hex-
ane/dichloromethane off-white needles). H NMR (400.1 MHz,
CDCl3): δ = 0.92 (t, J = 5.9 Hz, 3 H, 14-H), 1.25–1.50 (m, 8 H,
ing), 1462, 1378 (w), 1732 (s, C=O), 1182, 1160 (s, C–O). UV
(CH3CN): λmax (lg ε) = 192 nm (3.95), 232 (2.60), 260 (2.37), 278
(2.30), 310 (2.18). MS (EI = 70 eV): m/z (%) = 266 (88) [M+], 237
(45) [M+ – C2H5], 220 (36) [237 – OH], 251 (19) [M+ – CH3], 209
(78) [M+ – C4H9], 163 (100) [220 – C4H9], 135 (55) [163 – CO].
HRMS (C17H30O2): calcd. 266.2246; found 266.22431 Ϯ 5 ppm.
1
3
side-chain protons), 2.27–2.30 (m, 1 H, 2-H), 2.32–2.84 (m, 4 H,
3
1-,3-H), 2.87–2.90 (m, 1 H, 6-H), 5.43–5.46 (dd, J5,4
= =
3J7,8
3
9.2 Hz, J5,6
=
3J7,6 = 5.7 Hz, 2 H, 5-,7-H), 6.25–6.28 (d, 3J =
Ethyl 2-Pentyl-perhydroazulene-6-carboxylate (17/18): From 12c
(0.8 g, 2.91 mmol), 17/18 was prepared by the same route as de-
8.9 Hz, 2 H, 4-,8-H) ppm. 13C NMR (100.6 MHz, CDCl3): δ =
14.07 (q, C-14), 22.67 (t, C-13), 27.98 (t, C-12), 32.0 (t, C-11), 35.90 scribed above for 13. In addition to 17/18 (colourless liquid) par-
(t, C-10), 37.30 (d, C-2), 42.98 (2 t, C-1,-3), 44.72 (d, C-6), 115.75
(2 d, C-5,-7), 125.81 (2 d, C-4,-8), 141.95 (2 s, C-3a,-8a), 178.17 (s,
tially reduced 19 was also isolated (164 mg, 20 %) and charac-
terized; on further hydrogenation it was quantitatively converted to
5566
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Eur. J. Org. Chem. 2006, 5555–5569