Martic et al.
73
tions were washed with NaHCO3, H2O, NaCl, and brine and
dried over MgSO4. Column chromatography was performed
with hexane : ethyl acetate (60:40 v/v) to remove residual
allylamine and isolate the pure product as a white powder
(yield: 1.0648 g, 34.3 %; mp 103 °C).
4.58 (2H, d, J = 4.8 Hz), 4.59 (2H, d, J = 5.1 Hz), 5.23 (1H,
d, J = 1.5, 10.5 Hz), 5.28 (1H, d, J = 1.5, 10.4 Hz), 5.38
(1H, d, J = 1.5, 17.3 Hz), 5.47 (1H, d, J = 1.5, 17.4 Hz),
6.03 (1H, m, J = 5.2, 10.5 Hz), 6.04 (1H, m, J = 5.2,
18.3 Hz), 7.02 (1H, dd, J = 2.5, 8.2 Hz), 7.38 (1H, d, J =
2.0 Hz), 7.43 (1H, dd, J = 2.4, 8.2 Hz), 9.74 (1H, d, J =
2.5 Hz). 13C NMR (CDCl3, 200 MHz) δ: 69.8, 111.6, 112.4,
118.2, 118.4, 126.7, 130.2, 132.4, 132.7, 148.9, 153.9,
190.9. CI-MS m/z (%): 218 [M+] (100), 177 (23), 149 (20),
121 (9). ESI-MS m/z (%): 363 (18), 331 [M + TFA]– (100),
249 (63), 217 [M – H]– (23), 176 (13). LC–MS: rt = 17.0
min.
λmax = 324 nm, ⑀337nm = 4691.03 M–1 cm–1, λex = 340 nm,
λem = 399, 441, 494 nm. FTIR (neat) ν (cm–1): 3399, 3334,
1576, 1546, 1226, 993, 947. 1H NMR (MeOH-d4, 200 MHz)
δ: 3.99 (2H, d, J = 5.2 Hz), 5.17 (1H, dd, J = 1.2, 10.3 Hz),
5.23 (1H, dd, J = 1.2, 17.2 Hz), 5.92 (1H, m, J = 5.2, 10.3,
19.4 Hz), 6.74 (1H, d, J = 8.8 Hz), 6.85 (1H, dd, J = 2.8,
8.8 Hz), 7.22 (1H, d, J = 2.8 Hz). 13C NMR (MeOH-d4,
200 MHz) δ: 42.8, 114.8, 116.2, 117.7, 118.9, 122.3, 135.5,
150.9, 153.5, 170.1. CI-MS m/z (%): 193 [M+] (100), 175
(14), 164 (18), 136 (44), 108 (11). ESI-MS m/z (%): 306 [M +
TFA]– (74), 238 [M + 45]– (97), 192 [M – H] (100), 138
(12), 112 (22). ESI-MS m/z (%): 194 [M + H]+ (100), 65
(68), 216 [M + Na]+ (12). CI-MS m/z (%): 193 (M+). LC–
MS: rt= 8.18 min.
Methyl 4-hydroxy-3-methoxybenzoate (10)
After 3-methoxy-4-hydroxy benzoic acid (1.14 g,
6.7 mmol) was dissolved in methanol (50 mL) and cooled to
0 °C, thionyl chloride (2.44 mL, 33.8 mmol) was added
dropwise through a rubber septum. The reaction mixture was
stirred at room temperature for 20 h. The solvent was evapo-
rated, and the mixture was extracted with diethyl ether,
washed with sodium bicarbonate, water, sodium chloride,
and brine. Organic fractions were evaporated to recover an
ester as a white solid (yield: 0.974 g, 85.4%; mp. 59 °C).
3-Allyloxy-4-hydroxybenzaldehyde + 4-allyloxy-3-
hydroxybenzaldehyde (7); 3,4-diallyloxybenzaldehyde (8)
To 3,5-dihydroxybenzaldehyde (4.0234 g, 29.1 mmol),
dissolved in 150 mL of absolute methanol, was added previ-
ously oven dried potassium carbonate (4.0273 g,
29.1 mmol). The mixture was heated to 50 °C, and allyl bro-
mide (3.04 mL, 1.39 g/mL, 34.9 mmol) was added to the
flask dropwise through a septum. The mixture was further
heated to 60 °C and then refluxed overnight (16 h). After the
solvent was evaporated, the brown liquid was dissolved in
ethyl acetate and washed with 1 mol/L HCl until an acidic
pH was obtained (pH = 6.2). After the separation and extrac-
tion with ethyl acetate, the organic fractions were washed
with brine and dried with anhyd. MgSO4. The organic sol-
vent was evaporated, and the brown liquid was then sepa-
rated using silica gel column chromatography with 3%
methanol in dichloromethane as the solvent. Three different
fractions were recovered: (i) monoallyloxy derivative
(0.970 g, 24.5%; brown gel), (ii) diallyloxy derivative
(0.8501 g, 21%; brown liquid), and (iii) mono/diallyloxy de-
rivative mixture (yield: 1.8256 g, 45%; approximate
mono/diallyloxy ratio in the mixture was 3.1:1 (from LC–
MS intensity ratio)). Each fraction was separately character-
ized.
λ
max= 292 nm, ⑀337nm = 1054. 94 M–1 cm–1, λex = 340 nm,
λem = 392 and 432 nm. FTIR (neat) ν (cm–1): 3537, 3100,
3050, 2940, 1697, 1602, 1512, 1462, 1297, 1217, 1155, 777.
1H NMR (MeOH-d4, 200 MHz) δ: 3.84 (OCH3, 3H), 3.88
(OCH3, 3H), 6.82 (1H, d, J = 8.7 Hz), 7.51 (1H, s), 7.54
(1H, s). 13C NMR (MeOH-d4, 200 MHz) δ: 52.4, 56.4,
113.4, 115.9, 122.5, 124.9, 148.9, 152.8, 168.6. CI-MS m/z
(%): 182 [M]+ (85), 151 [M – OMe]+ (100).
Ethyl 4-allyloxy-3-methoxybenzoate (11)
To a solution of 3-methoxy-4-hydroxy-ethyl benzoate
(0.974 g, 5.35 mmol) in absolute ethanol (20 mL) was added
previously oven dried potassium carbonate (0.739 g,
5.35 mmol). When the reaction mixture was heated to 50 °C,
allyl bromide (0.539 g, 0.377 mL, 4.45 mmol) was added
dropwise through a septum. The mixture was refluxed over
night (16–18 h). After the solvent was evaporated, the brown
liquid was dissolved in ethyl acetate and washed with
1 mol/L HCl until an acidic pH was obtained (pH = 6.2). Af-
ter the separation of the organic fractions and extraction with
ethyl acetate, the organic fractions were washed with brine
and dried with anhyd. MgSO4. The organic solvent was
evaporated, and the brown liquid was then purified using sil-
ica gel column chromatography with hexane : ethyl acetate
(60:40 v/v) mixture as the solvent. The yellow liquid was re-
covered in 42.5% yield (0.409 g).
Monoallyl derivatives
λ
max= 322 nm, ⑀337nm = 2411.54 M–1 cm–1, λex = 340 nm,
λem = 395 and 433 nm. FTIR (neat) ν (cm–1): 3420, 3090,
1
2980, 2860, 1681, 1548, 1508, 1271, 1125, 993. H NMR
(CDCl3, 200 MHz) δ: 4.68 (2H, d, J = 5.4 Hz), 5.34 (1H, d,
J = 19.5 Hz), 5.41 (1H, dd, J = 1.0, 17.3 Hz), 6.04 (1H, m),
6.94 (1H, d, J = 8.2 Hz), 7.38 (1H, dd, J = 1.8, 8.1 Hz), 7.48
(1H, d, J = 1.9 Hz), 9.80 (1H, s). 13C NMR (CDCl3,
200 MHz) δ: 69.9, 111.5, 114.4, 119.3, 124.5, 130.7, 131.9,
146.4, 150.9, 191.2. CI-MS m/z (%): 178.06 [M+] (100), 149
(8), 137 (9). ESI-MS: 355 [2M – H]– (11), 291 [M + TFA]–
(92), 177 [M – H]– (100), 136 (14). LC–MS: rt = 15.11 min.
λmax = 294 nm, ⑀337nm = 1076.60 M–1 cm–1, λex = 340 nm,
λem = 392 and 433 nm. FTIR (neat) ν (cm–1): 3084, 2981,
1
2930, 1708, 1599, 1511, 1267, 1214, 1018, 761. H NMR
(MeOH-d4, 200 MHz) δ: 1.38 (3H, t, J = 7.2 Hz), 3.86
(OCH3, 3H, s), 4.31 (2H, q, J = 7.2, 14.2 Hz), 4.62 (2H, d,
J = 5.1 Hz), 5.26 (1H, d, J = 10.5 Hz), 5.41 (1H, dd, J = 1.4,
17.3 Hz), 6.05 (1H, m, J = 1.4, 16.7, 10.6 Hz), 6.96 (1H, d,
J = 8.4 Hz), 7.54 (1H, d, J = 1.5 Hz), 7.60 (1H, q, J = 1.6,
8.4 Hz). 13C NMR (MeOH-d4, 200 MHz) δ: 14.6, 56.4, 61.9,
70.6, 113.4, 113.5, 118.1, 124.1, 124.6, 134.3, 150.5, 153.7,
167.9. CI-MS m/z (%): 237 [M+] (100), 195 (28), 151 (9).
Diallyloxy derivative
λ
max= 304 nm; ⑀337nm = 1500.00 M–1 cm–1; λex= 340 nm;
λ
em= 394 and 434 nm. FTIR (neat) ν (cm–1): 3050, 2931,
1
2750, 1695, 1684, 993. H NMR (MeOH-d4, 200 MHz) δ:
© 2007 NRC Canada