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MedChemComm
Page 6 of 9
DOI: 10.1039/C7MD00311K
ARTICLE
Journal Name
multiplicities are given as s (singlet), d (doublet), t (triplet) and m
(multiplet). Mass spectrometry was carried out with a Kratos MSꢀ50
or a Varian MATꢀ711 spectrometer. Elemental analyses were
performed by a PerkinꢀElmer 240B microanalyzer and were within ±
0.4% of calculated values in all cases. The analytical results were ≥
95% purity for all compounds. Flash Chromatography (FC) was
performed on silica gel (Merck 60, 230–400 mesh); analytical TLC
was performed on precoated silica gel plates (Merck 60 F254).
Organic solutions were dried over anhydrous sodium sulfate.
Concentration and evaporation of the solvent after reaction or
extraction were carried out on a rotary evaporator (Büchi Rotavapor)
operating at reduced pressure.
2-(4’-bromophenyl)-7-methylbenzofuran (3): yield: 50%; mp:
66ꢀ67 °C; H NMR (500 MHz, CDCl3): δ = 2.61 (s, 3H, CH3), 7.04
1
(s, 1H, Hꢀ3), 7.11ꢀ7.19 (m, 2H, Hꢀ5, Hꢀ6), 7.44 (d, 1H, Hꢀ4, J = 7.5),
7.58ꢀ7.62 (m, 2H, Hꢀ2, Hꢀ6), 7.77 ppm (d, 2H, Hꢀ3’, Hꢀ5’, J = 8.5);
13C NMR (125 MHz, CDCl3): δ = 15.58, 102.75, 122.22, 122.63,
123.35, 124.46, 127.23, 127.50, 129.39, 129.98, 132.10, 154.32,
158.30 ppm; MS (EI, 70eV): m/z (%): 288 (100) [M+2]+, 286 (98)
[M]+, 206 (10), 178 (15); Anal. calcd for C15H11BrO: C 62.74; H
3.86, found: C 62.78; H 3.89.
7-methyl-2-phenylbenzofuran (4)30: yield: 45%; mp: colorless
1
liquid; H NMR (500 MHz, CDCl3): δ = 2.62 (s, 3H, CH3), 7.04 (s,
1H, Hꢀ3), 7.11 (d, 1H, Hꢀ6, J = 7.2,), 7.16 (t, 1H, Hꢀ5, J = 7.5), 7.37
(t, 1H, Hꢀ4’, J = 7.4), 7.42ꢀ7.51 (m, 3H, Hꢀ4, Hꢀ3’, Hꢀ5’), 7.91 (d,
2H, Hꢀ2’, Hꢀ6’, J = 7.4 ); 13C NMR (125 MHz, CDCl3): δ = 15.10,
101.16, 118.30, 121.40, 122.9, 124.90, 125.20, 128.40, 128.65,
128.70, 130.70, 153.85, 155.50 ppm; MS (EI, 70eV): m/z (%): 208
(100) [M]+, 193 (15), 165 (5); Anal. calcd for C15H12O: C 86.51; H
5.81, found: C 86.54; H 5.84.
Synthesis
General procedure for
the
preparation of
2-
hydroxybenzylalcohols: Sodium borohydride (6.60 mmol) was
added to a stirring solution of 2ꢀhydroxybenzaldehyde (6.60 mmol),
in ethanol (20 mL), in an ice bath. The reaction mixture was stirred
at room temperature for 1 h. After that, the solvent was removed, 1
N aqueous HCl solution (40 mL) was added to the residue and
extracted with diethyl ether. The solvent was evaporated under
vacuum to give the desired compounds Ia-Ic.24ꢀ26
2-(2’-bromophenyl)-5-methylbenzofuran (5): yield: 22%; mp:
1
49ꢀ51 °C; H NMR (500 MHz, CDCl3): δ = 2.49 (s, 3H, CH3), 7.16
(dd, 1H, Hꢀ6, J = 8.4, 1.4), 7.19ꢀ7.25 (m, 1H, Hꢀ4’), 7.42 (s, 1H, Hꢀ
3), 7.43ꢀ7.46 (m, 2H, Hꢀ4, Hꢀ5’), 7.49 (d, 1H, Hꢀ7, J = 0.7), 7.73
(dd, 1H, Hꢀ6’, J = 8.1, 1.1), 7.98 ppm (dd, 1H, Hꢀ3’, J = 7.9, 1.7);
13C NMR (125 MHz, CDCl3): δ = 21.30, 101.39, 112.92, 121.20,
123.69, 126.12, 126.93, 127.99, 129.10, 130.33, 132.00, 133.02,
135.26, 155.71, 157.59 ppm; MS (EI, 70eV): m/z (%): 288 (100)
[M+2]+, 286 (97) [M]+, 207 (12), 178 (23); Anal. calcd for
C15H11BrO: C 62.74; H 3.86, found: C 62.75; H 3.89.
General
procedure
for
the
preparation
of
2-
hydroxybenzyltriphenylphosphonium bromide: A mixture of 2ꢀ
hydroxybenzylalcohol (16.27 mmol) and PPh3·HBr (16.27 mmol) in
CH3CN (40 mL) was stirred under reflux for 2 h. The solid formed
was filtered and washed with CH3CN to give the desired compounds
IIa–IIc.20,24,27
2-(3’-bromophenyl)-5-methylbenzofuran (6): yield: 22%; mp:
90ꢀ94 °C; H NMR (500 MHz, CDCl3): δ = 2.47 (s, 3H, CH3), 7.00
General procedure for the preparation of 2-phenylbenzofuran
1-12: A mixture of 2ꢀhydroxybenzyltriphenylphosphonium bromide
(1.11 mmol) and benzoyl chloride (1.11 mmol) in a mixed solvent
(toluene 20 mL and Et3N 0.5 mL) was stirred under reflux for 2 h.
The precipitate was removed by filtration. The filtrate was
concentrated, and the residue was purified by silica gel
1
(s, 1H, Hꢀ3), 7.14 (d, 1H, Hꢀ6, J = 8.3), 7.33 (d, 1H, Hꢀ5’, J = 4.1),
7.38ꢀ7.44 (m, 2H, Hꢀ4, Hꢀ7), 7.48 (d, 1H, Hꢀ4’, J = 8.9), 7.79 (d, 1H,
Hꢀ6’, J = 7.8), 8.02 ppm (s, 1H, Hꢀ2’); 13C NMR (125 MHz, CDCl3):
δ = 21.25, 101.83, 112.93, 122.16, 123.75, 125.53, 126.15, 128.10,
129.52, 130.73, 131.42, 131.99, 132.83, 155.69, 159.47 ppm; MS
(EI, 70eV): m/z (%): 288 (100) [M+2]+, 286 (97) [M]+, 206 (10), 178
(26), 152 (10); Anal. calcd for C15H11BrO: C 62.74; H 3.86, found:
C 62.74; H 3.88.
chromatography (hexane/EtOAc 9:1) to give the desired compounds.
27ꢀ29
2-(2‘-bromophenyl)-7-methylbenzofuran (1): yield: 32%; mp: 65ꢀ67
1
°C; H NMR (500 MHz, CDCl3): δ = 2.61 (s, 3H, CH3), 7.10ꢀ7.23 (m,
2-(4’-bromophenyl)-5-methylbenzofuran (7): yield: 35%; mp:
195ꢀ197 °C; H NMR (500 MHz, CDCl3): δ = 2.47 (s, 3H, CH3),
2H, Hꢀ3, Hꢀ6), 7.27ꢀ7.40 (m, 1H, Hꢀ5), 7.46 (t, 1H, Hꢀ4’, J = 7.6), 7.50
(d, 1H, Hꢀ5’, J = 7.4), 7.54 (d, 1H, Hꢀ4, J = 1.9), 7.74 (d, 1H, Hꢀ6’, J =
8.0), 8.01 ppm (dd, 1H, Hꢀ3’, J = 7.9, 1.6); 13C NMR (125 MHz,
CDCl3): δ = 15.58, 103.92, 121.19, 122.22, 122.60, 123.33, 126.85,
127.21, 129.10, 129.38, 130.32, 132.92, 135.25, 154.29, 156.32 ppm;
MS (EI, 70eV): m/z (%): 288 (100) [M+2]+, 286 (97) [M]+, 207 (12), 178
(24); Anal. calcd for C15H11BrO: C 62.74; H 3.86, found: C 62.75; H
3.88.
1
6.98 (s, 1H, Hꢀ3), 7.13 (d, 1H, Hꢀ6, J = 8.4), 7.37ꢀ7.43 (m, 2H, Hꢀ4,
Hꢀ7), 7.59 (d, 2H, Hꢀ2’, Hꢀ6’, J = 8.6), 7.74 ppm (d, 2H, Hꢀ3’, Hꢀ5’,
J = 8.6); 13C NMR (125 MHz, CDCl3): δ = 21.25, 100.46, 112.92,
123.69, 124.46, 126.14, 127.52, 127.99, 129.99, 131.82, 132.07,
155.72, 159.83 ppm; MS (EI, 70eV): m/z (%): 288 (100) [M+2]+,
286 (98) [M]+, 206 (10), 178 (15); Anal. calcd for C15H11BrO: C
62.74; H 3.86, found: C 62.76; H 3.88.
5-methyl-2-phenylbenzofuran (8)30: yield: 55%; mp: 128ꢀ130 °C;
1H NMR (500 MHz, CDCl3): δ = 2.47 (s, 3H, CH3), 6.97 (s, 1H, Hꢀ
3), 7.11 (d, 1H, Hꢀ6, J = 8.3), 7.37 (d, 2H, Hꢀ3’, Hꢀ5’, J = 7.5), 7.40ꢀ
7.49 (m, 3H, Hꢀ4, Hꢀ7, Hꢀ4’), 7.84ꢀ7.90 ppm (m, 2H, Hꢀ2’, Hꢀ6’);
13C NMR (125 MHz, CDCl3): δ = 21.28, 101.00, 110.58, 120.64,
124.77, 125.46, 128.33, 128.68, 129.22, 130.53, 132.26, 153.24,
155.89 ppm; MS (EI, 70eV): m/z (%):MS (EI, 70eV): m/z (%): 208
(100) [M]+, 193 (25), 165 (10); Anal. calcd for C15H12O: C 86.51; H
5.81, found: C 86.53; H 5.85.
2-(3’-bromophenyl)-7-methylbenzofuran (2): yield: 72%; mp:
1
44ꢀ45 °C; H NMR (500 MHz, CDCl3): δ = 2.63 (s, 3H, CH3), 7.05
(s, 1H, Hꢀ3), 7.12ꢀ7.20 (m, 2H, Hꢀ5, Hꢀ6), 7.33 (dd, 1H, Hꢀ4, J =
9.9, 5.9), 7.45 (dd, 1H, Hꢀ6’, J = 7.6, 0.4), 7.50 (ddd, 1H, Hꢀ5’, J =
7.9, 1.9. 0.9), 7.79ꢀ7.83 (m, 1H, Hꢀ4’), 8.05 ppm (t, 1H, Hꢀ2’, J =
1.7); 13C NMR (125 MHz, CDCl3): δ = 15.63, 104.18, 122.02,
122.20, 122.63, 123.35, 125.52, 127.24, 129.30, 129.42, 130.72,
131.42, 132.84, 154.29, 158.12 ppm; MS (EI, 70eV): m/z (%): 288
(100) [M+2] +, 286 (97) [M]+, 207 (5), 178 (15), 152 (5); Anal. calcd
for C15H11BrO: C 62.74; H 3.86, found: C 62.76; H 3.90.
6 | J. Name., 2012, 00, 1-3
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