Molecules 2016, 21, 1716
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H-30, H-50, H-60), 7.03–6.86 (m, 1H; H-6), 6.88–6.69 (m, 1H; H-5) ,4.47 (d, J = 5.8 Hz, 2H, H-70), 3.77
(s, 3H; Me), 2.27 (s, 3H; Me). 13C-NMR (CDCl3): 168.8 (O=C-O), 166.6 (O=C-N), 151.3 (C-3), 142.3
(C-4), 136.6 (C-10), 133.2 (C-1), 132.9 (C-40), 129.0 (C-20, C-60), 128.7 (C-30, C-50), 122.6 (C-5), 118.7 (C-6),
111.8 (C-2), 55.9 (OMe), 43.3 (C-70), 20.6 (Me) [19]. HRMS (MALDI) calculated for C17H16ClNNaO4
[M + Na]+: 356.0666; found 356.0664.
Procedure 4: Preparation of N-(4-chlorobenzyl)-3-methoxy-4-(4-methylphenetoxy)benzamide (28). In a 100 mL
flask equipped with magnetic stirring vanillic amide 15 (0.1000 g, 0.3400 mmol) was added to a solution
of acetone (4 mL) together with K2CO3 (0.1388 g, 1.0046 mmol) and 4-methylbenzyl bromide (0.08 mL,
◦
0.6011 mmol) under reflux (60 C) for 16 h. After the reaction, the solvent was removed under reduced
pressure. A solution of CH2Cl2:H2O was poured onto the product, placed in a separation funnel and
extracted with three portions of CH2Cl2 (10 mL each). The organic phase was washed 1 N NaOH
(3 × 10 mL) and dried with Na2SO4, filtered and concentrated by rotary evaporation. The product was
purified by silica gel column chromatography using EtOAc:Hex (65:35) as the mobile phase system to
give a white amorphous solid; yield: 30% (42 mg), m.p. 126–129 ◦C, IR
ν
(cm−1): 3290 (N-H), 3001
max
(C-H sp2), 1629 (C=O), 1600 and 1490 (aromatic C=C), 1029 (stretching C-Cl). H-NMR (CDCl3): 7.44
(s, 1H; H-2), 7.32–7.07 (m, 9H; H-6, H-20, H-30, H-50, H-60, H-2”, H-3”, H-5”, H-6”), 6.80 (d, J = 8.4 Hz,
1H; H-5), 6.49 (t, J = 5.2 Hz, 1H, NH), 4.56 (d, J = 5.8 Hz, 2H; H-70), 4.18 (t, J = 7.6 Hz, 2H; CH2-O),
1
3.88 (s, 3H; OCH3), 3.11 (t, J = 7.6 Hz, 2H; C
H
2-C6H5). 13C-NMR (CDCl3): 167.0 (O=C-N), 151.2 (C-3),
149.3 (C-4), 136.9 (C-10), 136.2 (C-4”), 134.3 (C-1”), 133.3 (C-40), 129.2 (C-20, C-60), 129.1 (C-3”, C-5”),
0
0
128.9 (C-3 , C-5 ), 128.8 (C-2”, C-6”), 126.7 (C-1), 119.3 (C-6), 111.6 (C-2), 111.1 (C-5), 69.9 (CH2-O), 56.1
(OMe), 43.3 (C-70), 35.1 (CH2-C6H5), 21.0 (Me) [23]. HRMS (MALDI) calculated for C24H24ClNNaO3
[M + Na]+: 432.1342; found 432.1328.
Procedure 5: Preparation of N-(4-chlorobenzyl)-4-(4-hydroxyphenoxy)-3-methoxybenzamide (29). In a 100 mL
flask equipped with magnetic stirring, vanillic amide 15 (0.1000 g, 0.3400 mmol) was added to
a solution of DMF (3.43 mL), K2CO3 (0.0711 g, 0.5142 mmol), and 4-hydroxyphenyl bromide
(0.0827 g, 0.4113 mmol), and left stirring for 24 h at room temperature. After the reaction, the product
was extracted in a separation funnel with CH2Cl2 (3
×
10 mL). The extraction solution was washed
with distilled water (3 10 mL), and then with 10% NaOH (10 mL). The solution was treated with
×
Na2SO4, filtered, and concentrated by rotary evaporation [24]. The product was purified by silica gel
column chromatography using EtOAc:Hex (65:35) as the mobile phase system to afford a colorless oil;
yield: 75% (106 mg), IR ν
max (cm−1): 3350 (OH) 3016 (CH sp2), 1645 (C=O), 1600 and 1489 (aromatic
C=C), 1014 (stretching C-Cl). 1H-NMR (CDCl3): 7.95 (s, 1H; NH), 7.44 (s, 1H; H-2), 7.30–6.94 (m,
8H; H-5, H-6, H-20, H-30, H-50, H-60, H-2”, H-6”), 6.79 (dd, J = 8.5, 2.6 Hz, 2H; H-3”, H-5”), 4.54
(d, J = 5.8 Hz, 2H; H-70), 4.14 (t, J = 7.6 Hz, 2H; CH2-O), 3.82 (s, 3H; OMe), 3.04 (t, J = 7.5 Hz, 2H;
0
CH
2-C6H5). 13C-NMR (CDCl3): 167.5 (O=C-N), 155.0 (C-4”), 151.3 (C-4), 149.2 (C-3), 136.7 (C-1 ), 133.3
(C-40), 130.0 (C-20, C-60), 129.1 (C-2”, C-6”), 128.8 (C-30, C-50), 128.9 (C-1”), 126.4 (C-1), 119.5 (C-6),
0
115.6 (C-3”, C-5”), 111.6 (C-2), 111.2 (C-5), 70.1 (CH2-O), 56.1 (OCH3), 43.4 (C-7 ), 34.8 (
HRMS (MALDI) calculated for C23H22ClNNaO4 [M + Na]+: 434.1135; found 434.1123.
C
Preparation of N-(4-chlorobenzyl)-3-methoxy-4-propoxybenzamide (30). This product was prepared
◦
according to procedure 4, using 1-propyl bromide (0.05 mL, 0.4102 mmol) under reflux (60 C),
for 16 h and finally extracted to give after◦the silica gel column chromatography a white amorphous
solid; yield: 54% (62 mg), m.p. 124–126 C.
(aromatic C=C), 1014 (C-Cl stretch). H-NMR (CDCl3): 7.40 (d, J = 1.8 Hz, 1H; H-2), 7.31–7.22 (m, 5H;
ν
IR (cm−1): 3296 (N-H), 1631 (C=O), 1581 to 1450
max
1
0
0
0
0
0
H-6, H-2 , H-3 , H-5 , H-6 ), 6.81 (d, J = 8.4 Hz, 1H; H-5), 6.74 (bs, 1H; NH), 4.55 (d, J = 5.8 Hz, 2H; H-7 ),
3.98 (t, J = 6.8 Hz, 2H; H-1”), 3.86 (s, 3H; OMe), 2.04–1.76 (m, 2H; H-2”), 1.03 (t, J = 7.4 Hz, 3H; H-3”).
13C-NMR (CDCl3): 167.0 (O= -N), 151.4 (C-4), 149.2 (C-3), 137.0 (C-10), 133.1 (C-40), 129.1 (C-20, C-60),
C
128.7 (C-30, C-50), 126.3 (C-1), 119.4 (C-6), 110.9 (C-2), 111.4 (C-5), 70.4 (C-1”), 56.0 (OCH3), 43.3 (C-70),