C.M.Duarte et al./ European Journal of Pharmaceutical Sciences 23 (2004) 363–369
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cooling to ambient temperature, the reaction mixture was
neutralized with 1N hydrochloric acid under ice bath, ob-
serving crystallization of a white solid, which was filtered in a
(3 × 30 mL). The organic layers were dried under anhydrous
sodium sulfate and the solvent was totally removed under
reduced pressure. The resulting yellow oil was purified by
column chromatography using hexane:ethyl acetate (7:3) as
eluent.
¨
␣,-unsaturated acids in 94–95% yield.
3-Phenyl-1-propanol (16). Yellow oil, yield 94%, 0.94
1
3-Phenyl-2(E)-propenoic acid (14). White solid, yield
95%, 1.23 mmol; mp 134 ◦C (lit. 131–136 ◦C; Heilbron and
Bunbury, 1953); 1H NMR (CDCl3) δ: 6.47 (d, 1H, J =
16.1 Hz), 7.2–7.4 (m, 5H), 7.81 (d, 1H, J = 16.1 Hz), 11.02
(s, 1H). 13C NMR (CDCl3) δ: 117.4 (C-2); 128.4 (C-2ꢀ,6ꢀ);
128.9 (C-3ꢀ,5ꢀ); 130.7 (C-4ꢀ); 134.1(C-1ꢀ); 147,1(C-3); 172.8
(C O). IR νmax (KBr disk) (cm−1): 3027, 2696, 1686, 1631,
1224, 982, 769, 712.
mmol; H NMR (CDCl3) δ: 1.92 (quintet, 2H, J = 4.7 Hz),
2.73 (t, 2H, J = 4.7 Hz), 3.68 (t, 2H, J = 4.7 Hz), 7.2–7.4 (m,
5H). 13C NMR (CDCl3) δ: 32.2 (C-2), 34.3 (C-3), 62.2 (C-1),
126.0 (C-4ꢀ), 128.5 (C-3ꢀ,5ꢀ), 128.6 (C-2ꢀ,6ꢀ), 141.3 (C-1ꢀ).
IR νmax (film) (cm−1): 3458, 2929, 1738, 1036, 701.
3-(4ꢀ-Methoxyphenyl)-1-propanol (17). Yellow oil, yield
96%, 0.96 mmol; 1H NMR (CDCl3) δ: 1.87 (quintet, 2H, J =
3.5 Hz), 2.65 (t, 2H, J = 3.5 Hz), 3.67 (t, 2H, J = 3.5 Hz), 3.80
3-(4ꢀ-Methoxyphenyl)-2(E)-propenoic acid (15). White
solid, yield 94%, 1.22 mmol; mp 173–175 ◦C (lit.
170–173 ◦C; Heilbron and Bunbury, 1953); 1H NMR
(CDCl3) δ: 3.81 (s, 3H), 6.41 (d, 1H, J = 16.0 Hz), 6.98 (d,
2H, J = 8.5 Hz), 7.58 (d, 1H, J = 16.0 Hz), 7.65 (d, 2H, J =
8.5 Hz), 12.01 (s, 1H). 13C NMR (CDCl3) δ: 55.2 (OCH3);
114.3 (C-3ꢀ,5ꢀ); 116.5 (C-2); 126.8 (C-1ꢀ); 129.9 (C-2ꢀ,6ꢀ);
143.7 (C-1ꢀ); 160.9 (C-4ꢀ); 167.8 (C O). IR νmax (KBr disk)
(cm−1): 3031, 2589, 1689, 1601, 1514, 1259, 1176, 826.
5-Phenyl-2(E)-pentenoic acid (20). White solid, yield
94%, 1.22 mmol; mp 105 ◦C (lit. 104 ◦C; Cristau and Taille-
fer, 1998); 1H NMR (CDCl3) δ: 2.42 (q, 2H, J = 7.2 Hz), 2.72
(t, 2H, J = 7.2 Hz), 5.84 (d, 1H, J = 15.3 Hz), 7.06 (d, 1H, J =
15.3 Hz), 7.1–7.3 (m, 5H), 11.03 (s, 1H). 13C NMR (CDCl3)
δ: 30.8 (C-4); 33.6 (C-5); 121.4 (C-2); 126.3 (C-4ꢀ); 128.4
(C-2ꢀ,6ꢀ); 141.1 (C-1ꢀ); 149.9 (C-3); 171.7 (C O). IR νmax
(KBr disk) (cm−1): 3029, 2695, 1684, 1632, 1225, 984, 771,
710.
(s, 3H), 6.84 (d, 2H, J = 8.6 Hz), 7.13 (d, 2H, J = 8.6 Hz). 13
C
NMR (CDCl3) δ: 31.3 (C-2), 34.6 (C-3), 55.5 (OCH3), 62.5
(C-1), 114.0 (C-3ꢀ,5ꢀ), 129.5 (C-2ꢀ,6ꢀ), 134.1 (C-1ꢀ), 158.0
(C-4ꢀ). IR νmax (film) (cm−1): 3364, 2936, 1513, 1037, 832.
2.2.3. General procedure for the preparation of
To a mixture of pyridinium chlorochromate (PCC)
(0.323 g, 1.5 mmol) and dichloromethane (50 mL), 1.0 mmol
of the corresponding alcohol was added. The resulting mix-
ture was stirred for 1 h under ambient temperature, when TLC
analyses indicated the disappearance of the starting material.
The mixture was filtered over silica gel and magnesium sul-
fate, under vacuum, washing with dichloromethane. The sol-
vent was totally removed under reduced pressure, resulting in
a yellow oil, which was purified by column chromatography
using hexane:ethyl acetate (8:2) as eluent.
3-Phenyl-1-propanaldehyde (18). Yellow oil, yield 93%,
1
5-(4ꢀ-Methoxyphenyl)-2(E)-pentenoic acid (21). White
solid, yield 95%, 1.23 mmol; mp 137 ◦C; 1H NMR (CDCl3)
δ: 2.44 (q, 2H, J = 7.3 Hz), 2.75 (t, 2H, J = 7.3 Hz), 3.77
(s, 3H), 6.02 (d, 1H, J = 15.6 Hz), 6.91 (d, 2H, J = 8.7 Hz),
6.98 (d, 1H, J = 8.7 Hz), 7.07 (d, 2H, J = 15.6 Hz), 12.03
(s, 1H). 13C NMR (CDCl3) δ: 28.3 (C-4); 33.2 (C-5); 55.1
(OCH3); 113.3 (C-3ꢀ,5ꢀ); 116.5 (C-2); 121.6 (C-1); 129.9 (C-
2ꢀ,6ꢀ); 133.5 (C-1ꢀ); 149.9 (C-2); 158.2 (C-4ꢀ); 171.2 (C O).
IR νmax (KBr disk) (cm−1): 3030, 2586, 1685, 1603, 1618,
1257, 1174, 825.
0.93 mmol; H NMR (CDCl3) δ: 2.82 (t, 2H, J = 5.9 Hz),
2.99 (t, 2H, J = 5.9 Hz), 7.2–7.4 (m, 5H), 9.8 (s, 1H). 13C
NMR (CDCl3) δ: 27.5 (C-2), 44.7 (C-3), 126.4 (C-4ꢀ), 128.4
(C-3ꢀ,5ꢀ), 128.7 (C-2ꢀ,6ꢀ), 139.7 (C-1ꢀ), 201.2 (C O). IR νmax
(film) (cm−1): 2928, 1739, 1032, 701.
3-(4ꢀ-Methoxyphenyl)-1-propanaldehyde(19). Yellowoil,
yield 96%, 0.96 mmol; 1H NMR (CDCl3) δ: 2.67 (t, 2H, J =
6.0 Hz), 2.85 (t, 2H, J = 6.0 Hz), 3.73 (s, 3H), 6.77 (d, 2H,
J = 10.0 Hz), 7.07 (d, 2H, J = 10.0 Hz), 9.75 (s, 1H). 13C
NMR (CDCl3) δ: 27.4 (C-3), 45.6 (C-2), 55.4 (OCH3), 114.4
(C-3ꢀ,5ꢀ), 129.3 (C-2ꢀ,6ꢀ), 132.5 (C-1ꢀ), 158.2 (C-4ꢀ), 201.9
(C O). IR νmax (film) (cm−1): 2933, 1513, 1036, 831.
2.2.2. General procedure for the preparation of
compounds 16 and 17
To a suspension of lithium aluminum hydride (0.114 g,
3 mmol) in THF (10 mL), under nitrogen atmosphere, a so-
lution of the corresponding acid (1.0 mmol) in THF (10 mL)
was gently added, under ice bath. The resulting mixture was
stirred until it reached ambient temperature and then it was
submitted to reflux for 4 h, when TLC analyses indicated the
disappearance of the starting material. After cooling to ambi-
ent temperature, 10 mL of methanol and then 10 mL of water
were added to the reaction mixture, which was concentrated
under reduced pressure. The crude mixture was neutralized
with 1N hydrochloric acid and extracted with ethyl acetate
2.2.4. General procedure for the preparation of
compounds 10 and 11
To the corresponding acid (1.0 mmol), thionyl chloride
(7.2 mL, 100 mmol) was added, under inert atmosphere. The
resulting mixture was refluxed for 1 h. The solvent was com-
pletely removed under vacuum and the crude material was
dissolved in dichloromethane (8 mL). Then, thiomorpho-
line (0.289 g, 2.8 mmol) was added, and the resulting react-
ing mixture was stirred at ambient temperature for 30 min,
when TLC analyses indicated the disappearance of the start-
ing material. Water (30 mL) was added and the mixture