612
L. Hed6ati et al. / European Journal of Medicinal Chemistry 37 (2002) 607–616
(C-4), 167.4 (CO2); MS (DCI, CH4) m/z 417 ([MH]+,
100), 371 ([MH]+ꢀMeCH2OH, 11), 193 ([MH]+
ꢀC16H33, 12); HRMS (DCI, CH4) Calc. for C27H45O3
([MH]+): 417.3369. Found: 417.3410.
(C-4), 172.16 (CO2); MS (DCI, CH4) m/z 221 ([MH]+,
100), 203 ([MH]+ꢀH2O, 30), 165 ([MH]+ꢀC4H8, 12);
HRMS (DCI, CH4) Calc. for C13H17O3 ([MH]+):
221.1178. Found: 221.1140.
5.1.8. Ethyl 4-octadecyloxycinnamate (15%w)
M.p. 63 °C; H-NMR (CDCl3) l 0.88 (t, 3H, J=7
5.1.12. 4-Octyloxycinnamic acid (10t)
M.p. 150 °C; H-NMR (CDCl3) l 0.88 (br t, 3H,
1
1
Hz, Me(CH2)17), 1.21–1.54 (m, 30H, Me(CH2)15), 1.34
(t, 2H, J=7 Hz, CO2CH2Me), 1.78 (sextet, 2H, J=7
Hz, OCH2CH2), 3.98 (t, 2H, J=7 Hz, OCH2), 4.26 (q,
2H, J=7 Hz, CO2CH2Me), 6.30 (d, 1H, J=16 Hz,
CHCO2), 6.89 and 7.47 (AA%XX% system, 4H, J=8 Hz,
ArH), 7.65 (d, 1H, J=16 Hz, ArCH); 13C-NMR
(CDCl3) l 14.0 and 14.3 (two Me), 22.6 (C17), 25.9 and
29.1–29.8 (C2ꢀC15), 31.8 (C16), 60.2 (CO2CH2Me), 68.0
(CH2O), 114.7 (C-3 and C-3%), 115.4 (CHCO2), 126.8
(C-1), 129.6 (C-2 and C-2%), 144.3 (ArCH), 160.9 (C-4),
167.24 (CO2); MS (DCI, CH4) m/z 445 ([MH]+, 100),
399 ([MH]+, MeCH2OH, 18), 193 ([MH]+C18H35, 28);
HRMS (DCI)CH4) Calc. for C29H49O3 ([MH]+):
445.3682. Found: 445.3690.
J=6 Hz, Me), 1.2-1.65 (m, 10H, Me(CH2)5), 1.79
(quintet, 2H, J=6 Hz, OCH2CH2), 3.99 (t, 2H, J=6
Hz, OCH2), 6.31 (d, 1H, J=16 Hz, CHCO2), 6.90 and
7.50 (AA%XX% system, 4H, J=8 Hz, ArH), 7.40 (d, 1H,
J=16 Hz, ArCH); 13C-NMR (CDCl3)
l 14.08
(MeCH2), 22.64, 25.98, 29.12, 29.21, 29.34 (Me(CH2)5),
31.79 (CH2CH2O), 68.79 (CH2O), 114.38 (CHCO2),
114.88 (C-3 and C-3%), 126.55 (C-1), 130.07 (C-2 and
C-2%), 146.74 (ArCH), 161.37 (C-4), 172.11 (CO2); MS
(DCI, CH4) m/z 277 ([MH]+, 100), 259 ([MH]+ꢀH2O,
26), 165 ([MH]+ꢀC8H16, 12); HRMS (DCI, CH4) Calc.
for C17H25O3 ([MH]+): 277.1804. Found: 277.1800.
5.1.13. 4-Dodecyloxycinnamic acid (10u)
1
M.p. 128 °C; H-NMR (CDCl3) l 0.88 (t, 3H, J=7
5.1.9. Hydrolysis of methyl 4-alkoxycinnamates (15) to
4-alkoxycinnamic acids 10
Hz, Me(CH2)11), 1.85–1.91 (m, 18H, Me(CH2)9), 1.79
(sextet, 2H, J=7 Hz, OCH2CH2), 3.99 (t, 2H, J=7
Hz, OCH2), 4.25 (q, 2H, J=7 Hz, CO2CH2Me), 6.31
(d, 1H, J=16 Hz, CHCO2), 6.90 and 7.49 (AA%XX%
system, 4H, J=8 Hz, ArH), 7.74 (d, 1H, J=16 Hz,
ArCH); 13C-NMR (CDCl3) l 14.13 (Me), 22.70 (C11),
26.00 and 29.1–29.7 (C2ꢀC9), 31.93 (C10), 68.22
(CH2O), 114.39 (CHCO2H), 114.91 (C-3 and C-3%),
126.58 (C-1), 130.10 (C-2 and C-2%), 146.80 (ArCH),
161.41 (C-4), 172.18 (CO2H); MS (DCI, CH4) m/z 333
([MH]+, 100), 315 ([MH]+ꢀH2O, 24), 193 ([MH]+
ꢀC11H23, 7); HRMS (DCI, CH4) Calc. for C21H33O3
([MH]+): 333.2430. Found: 333.2420.
5.1.9.1. General procedure. A methyl 4-alkoxycinnamate
(10 mmol) in EtOH (10 mL) was added to NaOH (5 M,
20 mL, 100 mmol). The solution was refluxed for 4 h
during which the salt precipitated. The mixture was
cooled, acidified (conc. HCl), extracted (EtOAc–H2O),
dried (MgSO4), and evaporated to dryness. The acids
were obtained as solids in quantitative yield.
5.1.10. 4-Propoxycinnamic acid (10r)
1
M.p. 155 °C; H-NMR (CDCl3) l 1.03 (t, 3H, J=8
Hz, Me), 1.82 (sextet, 2H, J=8 Hz, CH2CH2Me), 3.93
(t, 2H, J=8 Hz, OCH2), 6.42 (d, 1H, J=16 Hz,
CHCO2), 6.87 and 7.47 (AA%XX% system, 4H, J=8 Hz,
ArH), 7.66 (d, 1H, J=16 Hz, ArCH); 13C-NMR
(CDCl3) l 10.4 (Me), 22.5 (CH2CH2O), 69.7 (CH2O),
114.8 (C-3 and C-3%), 116.2 (CHCO2), 129.8 (C-2 and
C-2%), 145.2 (ArCH), 161.0 (C-4), 171.8 (CO2); MS
(DCI, CH4) m/z 207 ([MH]+, 100), 189 ([MH]+ꢀH2O,
36), 165 ([MH]+ꢀC3H6, 9); HRMS (DCI, CH4) Calc.
for C12H15O3 ([MH]+): 207.1021. Found: 207.1020.
5.1.14. 4-Hexadecyloxycinnamic acid (107)
M.p. 125 °C; H-NMR (CDCl3) l 0.88 (t, 3H, J=7
1
Hz, Me(CH2)15), 1.30–1.58 (m, 26H, Me(CH2)13), 1.85
(sextet, 2H, J=7 Hz, OCH2CH2), 3.99 (t, 2H, J=7
Hz, OCH2), 6.31 (d, 1H, J=16 Hz, CHCO2), 6.90 and
7.49 (AA%XX% system, 4H, J=8 Hz, ArH), 7.74 (d, 1H,
J=16 Hz, ArCH); 13C-NMR (CDCl3) l 14.10 (Me),
22.68 (C15), 26.01 and 29.2–29.7 (C2ꢀC13), 31.93 (C14),
68.25 (CH2O), 114.30 (CHCO2H), 114.96 (C-3 and
C-3%), 126.65 (C-1), 130.07 (C-2 and C-2%), 146.77
(ArCH), 161.43 (C-4), 171.53 (CO2H); MS (DCI, CH4)
m/z 389 ([MH]+, 100), 371 ([MH]+ꢀH2O, 18), 193
([MH]+ꢀC16H33, 13); HRMS (DCI, CH4) Calc. for
C25H41O3 ([MH]+): 389.3056. Found: 389.3060.
5.1.11. 4-Butoxycinnamic acid (10s)
1
M.p. 152 °C; H-NMR (CDCl3) l 0.98 (t, 3H, J=7
Hz, Me), 1.50 (sextet, 2H, J=7 Hz, CH2CH2Me), 1.79
(quintet, 2H, J=16 Hz, CH2CH2CH2), 4.00 (t, 2H,
J=7 Hz, OCH2), 6.31 (d, 1H, J=16 Hz, CHCO2),
6.91 and 7.50 (AA%XX% system, 4H, J=8 Hz, ArH),
7.74 (d, 1H, J=16 Hz, ArCH); 13C-NMR (CDCl3) l
13.82 (Me), 19.20 (MeCH2), 31.25 (CH2CH2O), 67.89
(CH2O), 114.38 (C-3 and C-3%) 114.91 (CHCO2), 126.64
(C-1) 130.10 (C-2 and C-2%), 146.82 (ArCH), 161.66
5.1.15. 4-Octadecyloxycinnamic acid (10w)
1
M.p. 119 °C; H-NMR (CDCl3) l 0.88 (t, 3H, J=7
Hz, Me(CH2)17), 1.20–1.62 (m, 30H, Me(CH2)15), 1.78
(sextet, 2H, J=7 Hz, OCH2CH2), 3.99 (t, 2H, J=7
Hz, OCH2), 6.31 (d, 1H, J=16 Hz, CHCO2), 6.90 and