718
Design, Synthesis, Biological Evaluation and Molecular Modeling Studies of Novel Eugenol Esters
J. Braz. Chem. Soc.
d 8.09-8.06 (m, 2H, H3, H5), 7.67-7.64 (m, 2H, H2,
H6), 6.78 (s, 2H, H10, H12), 6.04-5.92 (m, 1H, H21,
JH21-H20 6.72 Hz, JH21-H22cis 10.14 Hz, JH21-H22trans 16.88 Hz),
5.15-5.09 (m, 2H, H22), 3.80 (s, 3H, H14), 3.40-3.38 (m,
8H, H15, H17, H18, H20, JH20-H21 6.72 Hz), 2.29 (m, 4H,
H16, H19); 13C NMR (75 MHz, CDCl3) d 40.14 (C20),
53.40 (C16, C19), 55.99 (C14), 58.70 (C15), 66.71 (C17,
C18), 111.87 (C12), 116.23 (C22), 122.55 (C10), 128.38
(C1), 128.89 (C4), 130.86 (C8), 131.66 (C2, C6), 131.86
(C3, C5), 137.06 (C21), 137.24 (C9), 138.45 (C11), 151.65
(C13), 163.90 (C7); MS MALDI-TOF (m/z): calcd. for
C22H24NO4Br [M + H]+: 446.10, found: 446.33.
4-Allyl-2-methoxy-6-(morpholin-4-ylmethyl)phenyl
4-fluorobenzoate (4h)
From 4-fluorobutilmetilbenzoyl chloride. White solid;
yield 80%; mp 95-98 °C; IR (ATR) max / cm-1 2955, 2921,
2850, 2812, 1738, 1596, 1505, 1263, 1197, 1110, 1068,
1
1010; H NMR (300 MHz, CDCl3) d 8.26-8.21 (m, 2H,
H3, H5), 7.26-7.15 (m, 2H, H2, H6), 6.79 (s, 1H, H10),
6.78 (s, 1H, H12), 6.05-5.92 (m, 1H, H21, JH21-H20 6.75 Hz,
JH21-H22cis 10.11 Hz, JH21-H22trans 16.88 Hz), 5.16-5.09 (m, 2H,
H22), 3.80 (s, 3H, H14), 3.44-3.38 (m, 8H, H15, H17, H18,
H20, JH20-H21 6.72 Hz), 2.30 (m, 4H, H16, H19); 13C NMR
(75 MHz, CDCl3) d 40.1 (C20), 53.4 (C16, C19), 56.0
(C14), 58.6 (C15), 66.7 (C17, C18), 111.9 (C12), 115.5
and 115.8 (C2, C6, J 22.5 Hz), 116.2 (C22), 122.5 (C10),
126.2 (C4), 130.86 (C8), 132.7 (C3, C5), 137.1 (C21),
137.3 (C9), 138.6 (C11), 151.7 (C13), 163.5 and 167.6 (C1,
J 307.5 Hz), 164.3 (C7); MS MALDI-TOF (m/z): calcd. for
C22H24NO4F [M + H]+: 386.18, found: 386.44.
4-Allyl-2-methoxy-6-(morpholin-4-ylmethyl)phenyl
4-(trifluoromethyl)benzoate (4f)
From 4-(trifluoromethyl)benzoyl chloride. White solid;
yield 82%; mp 82-87 °C; IR (ATR) max / cm-1 3078, 2969,
2855, 1743, 1598, 1491, 1456, 1351, 1263, 1166, 1115,
1063, 1015, 911; 1H NMR (300 MHz, CDCl3) d 8.35-8.32
(d, 2H, H3, H5, J 8.07 Hz), 7.79-7.76 (d, 2H, H2, H6,
J 8.16 Hz), 6.79 (s, 2H, H10, H12), 6.05-5.91 (m, 1H, H21,
JH21-H20 6.72 Hz, JH21-H22cis 10.17 Hz, JH21-H22trans 16.85 Hz),
5.16-5.10 (m, 2H, H22), 3.81 (s, 3H, H14), 3.41-3.39
(m, 8H, H15, H17, H18, H20), 2.29 (m, 4H, H16, H19);
13C NMR (75 MHz, CDCl3) d 40.13 (C20), 53.40 (C16,
C19), 55.97 (C14), 58.78 (C15), 66.66 (C17, C18), 111.91
(C12), 116.26 (C22), 121.83 (C4), 122.59 (C10), 125.56
(C2, C6), 127.02, 130.77, 134.91 and 138.62 (C23,
J 290.07 Hz), 130.52 (C3, C5), 133.26 (C8), 134.48 (C9),
137.00 (C21), 137.15 (C11), 151.59 (C13), 163.25 (C7);
MS MALDI-TOF (m/z): calcd. for C23H24NO4F3 [M + H]+:
436.17, found: 436.43.
4-Allyl-2-methoxy-6-(morpholin-4-ylmethyl)phenyl
4-aminobenzoate (4i)
Reduction of the nitro group to the amine for the
synthesis of the 4-allyl-2-methoxy-6-(morpholin-
4-ylmethyl)phenyl-4-aminobenzoate was based on the
methods described by Gamble et al.18 and Bellamy and
Ou.19
Into a round bottom flask containing 0.223 g of
compound 4b (0.54 mmol), 5 mL of absolute ethanol
and 1.22 g of SnCl2·2H2O (5.41 mmol) were added. The
reaction was conducted in an ultrasonic bath under periodic
stirring at room temperature and in an atmosphere of argon
for 16 min.
The reaction was monitored by TLC (hexane/ethyl
acetate 6:4, v/v). After completion of the reaction, the
medium was neutralized to approximately pH 7 with
saturated sodium bicarbonate solution over crushed ice,
and an extraction was then performed with ethyl acetate.
The organic phase was dried with anhydrous Na2SO4 and
filtered. The filtrate was then concentrated using a rotary
evaporator. The product was purified by CC (ethyl acetate/
hexane 3:7, v/v).
4-Allyl-2-methoxy-6-(morpholin-4-ylmethyl)phenyl
4-tert-butylbenzoate (4g)
From 4-tert-butylbenzoyl chloride. White solid; yield
53%; mp 79-85 °C; IR (ATR) max / cm-1 2959, 2865, 2804,
1736, 1608, 1489, 1454, 1351, 1265, 1183, 1110, 1065,
1012, 910; 1H NMR (300 MHz, CDCl3) d 8.15-8.13 (d, 2H,
H3, H5, J 7.14 Hz), 7.53-7.50 (m, 2H, H2, H6, J 7.02 Hz),
6.82 (s, 1H, H10), 6.76 (s, 1H, H12), 6.02-5.94 (m, 1H,
H21), 5.15-5.08 (m, 2H, H22), 3.79 (s, 3H, H14), 3.47-3.39
(m, 8H, H15, H17, H18, H20), 2.33 (m, 4H, H16, H19),
1.37 (s, 9H, H24, H25, H26); 13C NMR (75 MHz, CDCl3)
d 31.15 (C24, C25, C26), 35.18 (C23), 40.16 (C20), 53.41
(C16, C19), 55.98 (C14), 58.21 (C15), 66.71 (C17, C18),
111.77 (C12), 116.11 (C22), 122.42 (C10), 125.47 (C2,
C6), 127.02 (C4), 130.09 (C3, C5), 130.93 (C8), 137.18
(C21), 137.47 (C9), 138.17 (C11), 151.71 (C13), 157.01
(C1), 164.41 (C7); MS MALDI-TOF (m/z): calcd. for
C26H33NO4 [M + H]+: 424.25, found: 424.55.
Yellow oil; yield 49%; IR (ATR)
/ cm-1 3465,
max
3362, 3227, 2958, 2806, 1712, 1625, 1598, 1517, 1489,
1454, 1351, 1264, 1167, 1111, 1065, 1008, 908; 1H NMR
(300 MHz, CDCl3) d 8.02-7.99 (m, 2H, H3, H5), 6.81 (s,
1H, H10), 6.75 (s, 1H, H12), 6.69-6.67 (m, 2H, H2, H6),
6.04-5.92 (m, 1H, H21, JH21-H20 6.72 Hz, JH21-H22cis 10.11 Hz,
JH21-H22trans 16.94 Hz), 5.14-5.08 (m, 2H, H22), 4.14 (s, 2H,
NH2), 3.79 (s, 3H, H14), 3.51 (m, 6H, H15, H17, H18),
3.39-3.37 (d, 2H, H20, J 6.69 Hz), 2.35 (m, 4H, H16, H19);
13C NMR (75 MHz, CDCl3) d 40.16 (C20), 53.37 (C16,