Nov-Dec 2007
Synthesis of Novel Coumarin and Benzocoumarin Derivatives
1299
anhydrous aluminum chloride was combined in 50 mL round
bottom flask, 20 mL of dry nitrobenzene was then added. The
reaction mixture was refluxed at 130-40 °C for 4 hours. The
nitrobenzene was evaporated by steam bath, the residual solid
was then treated with ethanol, filtered, washed and dried (yield
1.85 g, 70 %).
1-(Chloromethyl)-3H-benzo[f]chromen-3-one (36a). Creamy
(4.5g, 93%) m.p. 160°C; IR (KBr disc): 1734.42 (C=O); PMR
(DMSO-d6): ꢀ 5.41 (s, 2H, -CH2), 6.87 (s, 1H, H-2), 7.58-7.75
(m, 3H, Ar-H), 8.07, 8.11 (d, 1H, Ar-H), 8.23, 8.27 (d, 1H, Ar-
H), 8.52, 8.57 (d, 1H, Ar-H); C14H9O2Cl (244.68); Cal.: C,
68.72; H, 3.71; Found: C, 68.64; H, 3.65.
CH), 131.26 (Ar-C), 136.77 (Ar-C), 150.97 (Ar-C), 151.77 (Ar-
C), 158.26 (4-CH), 159.80 (CO); C14H9O3Cl (260.68); Cal.: C,
64.51; H, 3.48; Found: C, 64.78; H, 3.47.
6-Chloro-4-(chloromethyl)-2H-benzo[h]chromen-2-one
(40). Off-white (2.68g, 48.00%) m.p. 185°C; IR (KBr disc):
1735 (C=O); PMR (DMSO-d6) ꢀ 5.06 (s, 2H, -CH2), 6.75 (s, 1H,
H-3), 7.69-7.81 (m, 2H, H-8, 9), 7.90 (s, 1H, H-5), 8.07, 8.10 (d,
1H, H-10), 8.24, 8.27 (d, 1H, H-7); CMR (DMSO-d6) ꢀ = 45.98
(CH2), 115.63, 121.04, 122.45, 123.79, 124.21, 125.124, 125.27,
126.34, 128.55, 130.39, 130.81, 150.68, 152.76 (Ar-C, Ar-CH),
159.07 (CO); C14H8O2Cl2 (279.12); Cal.: C, 60.24; H, 2.89;
Found: C, 60.22; H, 2.80.
1-(Chloromethyl)-8-hydroxy-3H-benzo[f]chromen-3-one
(36b). Green (5.10g, 98%) m.p. 240°C; IR (KBr disc): 3286.55
(OH), 1688.2 (C=O); PMR (DMSO-d6): ꢀ 5.29 (s, 2H, -CH2), 6.76
(s, 1H, H-2), 7.13, 7.18 (d, 1H, H-5), 7.89, 7.94 (d, 1H, H-6), 8.06,
8.11 (d, 1H, H-7), 10.19 (s, 1H, OH; cancelled by D2O); 13C NMR
(APT) (DMSO-d6) ꢀ = 46.09 (CH2), 108.58 (C-10), 110.59 (C-
10b), 113.81 (C-2), 115.66 (C-5), 117.17 (C-8), 125.15 (C-6a),
130.23 (C-10a), 131.25 (C-6), 134.22 (C-7), 152.11 (C-4a),
155.25 (C-9), 157.74 (C-1), 159.30 (C=O); C14H9O3Cl (260.68);
Cal.: C, 64.51; H, 3.48; Found: C, 64.54; H, 3.50.
3-(Chloromethyl)-2H-benzo[h]chromen-2-one (42). Yellowish-
white (3.62g, 69.00%) m.p. >300°C; IR (KBr disc): 1729, 1765
(C=O); PMR (DMSO-d6) ꢀ 4.24 (s, 2H, -CH2), 6.02 (s, 1H, H-
3), 7.34-7.53 (m, 2H, H-8,9), 7.61-8.01 (m, 2H, H-7,10); CMR
(DMSO-d6) ꢀ 29.30 (CH2), 112.82 (C-4a), 116.19 (C-3), 116.59
(C-10a), 123.44 (C-7), 123.77 (C-9), 125.15 (C-10), 132.15 (C-
8), 152.58 (C-6a), 156.53 (C-10b), 157.80 (C-1), 162.40 (C-5),
162.72 (C-2); C13H7O4Cl (262.65); Cal.: C, 59.45; H, 2.69;
Found: C, 59.67; H, 2.76.
Synthesis of 2-(Naphtho[2,1-b]furan-1-yl)acetic acid (43).
A mixture of 36a (1.22 g, 5 mmol) and KCN (0.326 g, 5 mmol)
was refluxed in 20 mL of EtOH/H2O mixture (1:1) for four
hours. The ethanol was then evaporated and the clear yellow
aqueous solution was acidified by 2 mL of concentrated HCl to
give a white precipitate. The precipitate was collected by
filtration, washed with water and dried under reduced pressure.
2-(Naphtho[2,1-b]furan-1-yl)acetic acid (43). Grey (0.90g,
79.00%) m.p.145°C; IR (KBr disc): 1707 (CO), 3421 (br. OH).;
PMR (DMSO-d6) ꢀ 4.06 (2H, s, CH2), 7.50, 7.53 (1H, d, Ar-H),
7.58, 7.60 (1H, d, Ar-H), 7.75-7.85 (2H, m, Ar-H), 8.02, 8.05
(2H, d, Ar-H + H-furan), 8.18, 8.21 (1H, d, Ar-H), 12.62 (1H,
hump, COOH, cancelled by D2O).; CMR (DMSO-d6) ꢀ 31.38
(CH2), 116.16 (furan-C), 113.32, 121.54, 123.44, 125.08,
126.34, 127.14, 128.39, 129.63, 130.89 (Ar-C and Ar-CH),
144.19 (furan-CH), 153.26 (Ar-C), 173.00 (CO).; Ms (%): m/z
226 ([M+], 100), 45 ([M+ - H, CO2], 81), 152 ([M+ - H, CO2,
CHO], 60), 126 ([M+ - H, CO2, CHO, C2H2], 6), 76 ([M+ - H,
CO2, CHO, C2H2, C4H2], 9); C14H10O3 (226.23); Cal.: C, 74.33;
H,, 4.45; Found: C, 74.53; H, 4.57.
Synthesis of 2-(benzo[f]coumarin-1-yl)acetic acid, 2-
(benzo[f]coumarin-1-yl)acetonitrile and 2-naphthol (44 and
45). To a stirred solution of 36a (1.22 g, 5 mmol) in DMSO (10
mL), KCN (0.326 g, 5 mmol) was added and the stirring was
continued for 1 hour under nitrogen at room temperature. The
reaction mixture was poured into 100 mL of water. The solid
formed was collected by filtration, washed with water and dried,
it has characterized as 45 (yield, 0.25 g, 70.95%). The yellowish
filtrate was treated with 3 mL of concentrated hydrochloric acid
to produce 44 and 34a. The solid was collected by filtration and
washed with cooled water and ether to give 44 (yield, 0.07 g,
19.86 %), the ether layer was evaporated and the solid formed
was characterized as 2-naphthol (34a) (yield, 0.03 g, 8.51 %).
Crossover experiments for (44). Compound 44 was prepared
independently according to procedure in literature [45].
1-(Chloromethyl)-9-hydroxy-3H-benzo[f]chromen-3-one
(36c). Yellow (3.54g, 68%) m.p. 220°C; IR (KBr disc): 1737
(C=O); PMR (DMSO-d6): ꢀ 5.34 (s, 2H, -CH2), 6.81 (s, 1H, H-
2), 7.27, 7.28 (d, 1H, H-5), 7.30 (s, 1H, H-7), 7.45, 7.48 (d, 1H,
H-6), 8.01, 8.04 (d, 1H, H-9), 8.36, 8.39 (d, 1H, H-10), 10.09
(brs, 1H, OH; cancelled by D2O); CMR (DMSO-d6) ꢀ = 46.34
(CH2), 111.29 (Ar-CH), 112.06 (Ar-C), 116.77 (2-CH), 117.58
(Ar-CH), 119.96 (Ar-CH), 121.88 (Ar-C), 127.08 (Ar-CH),
132.92 (Ar-C), 132.97 (Ar-CH), 151.70 (Ar-C), 152.88 (Ar-C),
154.99 (1-C), 159.39 (CO); C14H9O3Cl (260.68); Cal.: C, 64.51;
H, 3.48; Found: C, 64.70; H, 3.57.
9-Bromo-1-(chloromethyl)-3H-benzo[f]chromen-3-one
(36d). Off-white (5.36g, 83%) m.p. 210°C; IR (KBr disc): 1736
(C=O); PMR (DMSO-d6) ꢀ 5.34 (s, 2H, -CH2), 6.85 (s, 1H, H-2),
7.60, 7.63 (d, 1H, H-5), 7.81, 7.84 (d, 1H, H-6), 8.18, 8.21 (d, 1H,
H-9), 8.36 (s, 1H, H-7), 8.52, 8.55 (d, 1H, H-10). CMR (DMSO-
d6) ꢀ = 46.14 (CH2), 112.11 (2-CH), 117.51 (Ar-C), 118.89 (Ar-
CH), 127.04 (Ar-CH), 127.95 (Ar-CH), 128.86 (Ar-C), 129.34
(Ar-CH), 130.89 (Ar-CH), 131.18 (Ar-CH), 132.43 (Ar-C),
151.48 (Ar-C), 154.80 (2-CH), 159.02 (CO); C14H8O2BrCl
(323.57); Cal.: C, 51.97; H, 2.49; Found: C, 52.04; H, 2.58
4-(Chloromethyl)-7-hydroxy-2H-benzo[h]chromen-2-one
(38a). Deep green (4.06g, 78%) m.p. 205°C; IR (KBr disc):
1728 (C=O), 3412 (OH); PMR (DMSO-d6) ꢀ 5.12 (s, 2H, -CH2),
6.72 (s, 1H, H-3), 7.06, 7.09 (d, 1H, H-8), 7.45 (t, 1H, H-9),
7.70, 7.73 (d, 1H, H-5), 7.74,7.77 (d, 1H, H-6), 8.01, 8.04 (d,
1H, H-10), 5.95 (brs, 1H, OH; cancelled by D2O); CMR
(DMSO-d6) ꢀ = 41.76 (CH2), 108.36 (Ar-CH), 112.72 (3-CH),
114.84 (Ar-CH), 118.45 (Ar-CH), 123.75 (Ar-C), 124.90 (Ar-
CH), 125.62 (Ar-C), 126.06 (Ar-C), 128.30 (Ar-CH), 151.51
(Ar-C), 153.07 (Ar-C), 153.54 (4-CH), 159.74 (CO); C14H9O3Cl
(260.68); Cal.: C, 64.51; H, 3.48; Found: C, 64.59; H, 3.58.
4-(Chloromethyl)-8-hydroxy-2H-benzo[h]chromen-2-one
(38b). Yellow (3.80g, 73.00%) m.p. 170°C; IR (KBr disc): 1711
(C=O), 3382 (OH); PMR (DMSO-d6) ꢀ 5.06 (s, 2H, -CH2), 6.65
(s, 1H, H-3), 7.23 (s, 1H, H-7), 7.26, 7.27 (d, 1H, H-9), 7.66,
7.70 (d, 1H, H-6), 7.73, 7.74 (d, 1H, H-5), 8.28, 8.31 (d, 1H, H-
10), 10.05 (brs, 1H, OH; cancelled by D2O); CMR (DMSO-d6) ꢀ
= 41.74 (CH2), 109.55 (Ar-CH), 112.92, (3-CH), 116.29 (Ar-C),
119.68 (Ar-CH), 121.00 (Ar-CH), 122.67 (Ar-CH), 123.75 (Ar-
2-(3-Oxo-3H-benzo[f]chromen-1-yl)acetic acid (44). Off-
white (0.07g, 19.86%) m.p. 200°C;IR (KBr disc): 1664, 1719
(2CO), 3425 (br. OH).; PMR (DMSO-d6) ꢀ 4.35 (2H, s, CH2),
6.61 (1H, s, H-2), 7.54-7.70 (3H, m , Ar-H), 8.04, 8.07 (1H, d,
Ar-H), 8.17, 8.20 (1H, d, Ar-H), 8.36, 8.39 (1H, d, Ar-H).; CMR
(DMSO-d6) ꢀ 42.91 (CH2), 113.68 (C-2), 117.75, 118.35,