10.1002/ejoc.202000014
European Journal of Organic Chemistry
FULL PAPER
phase was dried (MgSO4), filtered and concentrated in vacuo. Purification
by flash column chromatography (petroleum ether/ethyl acetate 7:3) gave
2-phenyl-5,6-dimethoxy-1,3-benzoxazole (2a) (0.0286 g, 57%) as a white
solid. Mp 109–112 °C (lit.[19] 114–115 °C). 1H NMR (400 MHz, CDCl3): d =
3.95 (s, 3H, OCH3), 3.96 (s, 3H, OCH3), 7.13 (s, 1H, 7-H), 7.25 (s, 1H, 4-
H), 7.48–7.52 (m, 3H, 3′-H, 4′-H and 5′-H), 8.16–8.20 (m, 2H, 2′-H and 6′-
H). 13C NMR (101 MHz, CDCl3): d = 56.5 (CH3), 56.5 (CH3), 94.4 (CH),
101.8 (CH), 127.0 (2 × CH), 127.5 (C), 128.9 (2 × CH), 130.9 (CH), 135.0
(C), 145.2 (C), 147.8 (C), 148.4 (C), 162.3 (C). MS (ESI) m/z (%): 278
(100) [M + Na]+.
2-Phenyl-5,6-methylenedioxy-1,3-benzoxazole (2e):[20] 2-Phenyl-5,6-
methylenedioxy-1,3-benzoxazole (2e) was synthesized as described for 2-
phenyl-5,6-dimethoxy-1,3-benzoxazole
(2a)
using
N-(3,4-
methylenedioxyphenyl)benzamide (1e) (0.0513 g, 0.213 mmol) in toluene
(1.6 mL) and tetrahydrofuran (0.4 mL). The bromination step was carried
out at 40 °C for 3 h and the O-arylation step at 130 °C for 20 h. Purification
by flash column chromatography (hexane/diethyl ether, 19:1) gave 2-
phenyl-5,6-methylenedioxy-1,3-benzoxazole (2e) (0.0351 g, 69%) as a
white solid. Mp 142–143 °C (lit.[20] 147–148 °C). 1H NMR (500 MHz,
CDCl3): d = 6.03 (s, 2H, OCH2O), 7.06 (s, 1H, 7-H), 7.17 (s, 1H, 4-H), 7.46–
7.52 (m, 3H, 3′-H, 4′-H and 5′-H), 8.12–8.18 (m, 2H, 2′-H and 6′-H). 13C
NMR (126 MHz, CDCl3): d = 92.6 (CH), 99.5 (CH), 101.7 (CH2), 126.9 (2
× CH), 127.4 (C), 128.9 (2 × CH), 130.9 (CH), 136.1 (C), 145.7 (C), 145.8
(C), 146.4 (C), 162.6 (C). MS (ESI) m/z (%): 262 (100) [M + Na]+.
2-(4′-Methoxyphenyl)-5,6-dimethoxy-1,3-benzoxazole
(2b):
2-(4′-
Methoxyphenyl)-5,6-dimethoxy-1,3-benzoxazole (2b) was synthesized as
described for 2-phenyl-5,6-dimethoxy-1,3-benzoxazole (2a) using 4′-
methoxy-N-(3,4-dimethoxyphenyl)benzamide (1b) (0.057 g, 0.20 mmol) in
toluene (1.0 mL) and acetonitrile (0.4 mL). The bromination step was
carried out at 40 °C for 4 h and the O-arylation step at 130 °C for 48 h.
Purification by flash column chromatography (hexane/ethyl acetate 4:1)
gave 2-(4′-methoxyphenyl)-5,6-dimethoxy-1,3-benzoxazole (2b) (0.030 g,
52%) as a light yellow solid. Mp 118–120 °C. IR (neat): νmax = 2928, 1605,
1481, 1250, 1219, 1128, 1057, 1018, 837. 1H NMR (500 MHz, CDCl3): d =
3.88 (s, 3H, OCH3), 3.94 (s, 3H, OCH3), 3.95 (s, 3H, OCH3), 7.01 (d, J =
8.9 Hz, 2H, 3′-H and 5′-H), 7.11 (s, 1H, 7-H), 7.23 (s, 1H, 4-H), 8.11 (d, J
= 8.9 Hz, 2H, 2′-H and 6′-H). 13C NMR (101 MHz, CDCl3): d = 55.4 (CH3),
56.4 (CH3), 56.5 (CH3), 94.3 (CH), 101.6 (CH), 114.3 (2 × CH), 120.1 (C),
128.7 (2 × CH), 135.0 (C), 145.0 (C), 147.6 (C), 148.0 (C), 161.8 (C), 162.4
(C). HRMS (ESI) m/z [M + Na]+ calcd. for C16H15NNaO4 308.0893, found
308.0883.
2-(4′-Chlorophenyl)-5,6-methylenedioxy-1,3-benzoxazole (2f):[14] 2-(4′-
Chlorophenyl)-5,6-methylenedioxy-1,3-benzoxazole (2f) was synthesized
as described for 2-phenyl-5,6-dimethoxy-1,3-benzoxazole (2a) using 4′-
chloro-N-(3,4-methylenedioxyphenyl)benzamide (1f) (0.055 g, 0.20 mmol)
in toluene (1.0 mL) and acetonitrile (1.0 mL). The bromination step was
carried out at 40 °C for 3 h and the O-arylation step at 130 °C for 24 h.
Purification by flash column chromatography (dichloromethane/hexane,
7:3) gave 2-(4′-chlorophenyl)-5,6-methylenedioxy-1,3-benzoxazole (2f)
(0.0412 g, 75%) as a white solid. Spectroscopic data were consistent with
the literature.[14] Mp 252–254 °C. 1H NMR (500 MHz, DMSO-d6): d = 6.13
(s, 2H, OCH2O), 7.36 (s, 1H, 7-H), 7.49 (s, 1H, 4-H), 7.65 (d, J = 8.6 Hz,
2H, 3′-H and 5′-H), 8.10 (d, J = 8.6 Hz, 2H, 2′-H and 6′-H). 13C NMR (126
MHz, DMSO-d6): d = 93.5 (CH2), 99.7 (CH), 102.4 (CH), 126.0 (C), 128.7
(2 × CH), 129.9 (2 × CH), 135.8 (C), 136.4 (C), 145.9 (C), 146.1 (C), 146.9
(C), 161.2 (C). MS (EI) m/z (%): 273 (100) [M]+.
2-(4′-Chlorophenyl)-5,6-dimethoxy-1,3-benzoxazole
(2c):
2-(4′-
Chlorophenyl)-5,6-dimethoxy-1,3-benzoxazole (2c) was synthesized as
described for 2-phenyl-5,6-dimethoxy-1,3-benzoxazole (2a) using 4′-
chloro-N-(3,4-dimethoxyphenyl)benzamide (1c) (0.058 g, 0.20 mmol) in
toluene (1.0 mL) and acetonitrile (0.2 mL). The bromination step was
carried out at 40 °C for 4 h and the O-arylation step at 130 °C for 48 h.
Purification by flash column chromatography (hexane/ethyl acetate 7:3)
gave 2-(4′-chlorophenyl)-5,6-dimethoxy-1,3-benzoxazole (2c) (0.038 g,
66%) as a light yellow solid. Mp 160–161 °C. IR (neat): νmax = 2928, 1481,
1159, 1134, 1007, 883, 824. 1H NMR (500 MHz, CDCl3): d = 3.95 (s, 3H,
OCH3), 3.96 (s, 3H, OCH3), 7.11 (s, 1H, 7-H), 7.23 (s, 1H, 4-H), 7.46 (d, J
= 8.7 Hz, 2H, 3′-H and 5′-H), 8.09 (d, J = 8.7 Hz, 2H, 2′-H and 6′-H). 13C
NMR (101 MHz, CDCl3): d = 56.4 (CH3), 56.5 (CH3), 94.2 (CH), 101.7 (CH),
126.0 (C), 128.2 (2 × CH), 129.2 (2 × CH), 134.8 (C), 137.0 (C), 145.2 (C),
147.9 (C), 148.6 (C), 161.2 (C). HRMS (ESI) m/z [M + Na]+ calcd. for
C15H1235ClNNaO3 312.0398, found 312.0391.
2-Phenyl-5,6,7-trimethoxy-1,3-benzoxazole
trimethoxy-1,3-benzoxazole (2g) was synthesized as described for 2-
phenyl-5,6-dimethoxy-1,3-benzoxazole (2a) using N-(3,4,5-
(2g):
2-Phenyl-5,6,7-
trimethoxyphenyl)benzamide (1g) (0.072 g, 0.25 mmol). The bromination
step was carried out at 40 °C for 3 h and the O-arylation step at 130 °C for
16 h. Purification by flash column chromatography (hexane/ethyl acetate,
7:3) gave 2-phenyl-5,6,7-trimethoxy-1,3-benzoxazole (2g) (0.030 g, 42%)
as a brown solid. Mp 56–57 °C. IR (neat): νmax = 2947, 1601, 1557, 1487,
1458, 1421, 1123, 1038, 685. 1H NMR (400 MHz, CDCl3): d = 3.92 (s, 3H,
OCH3), 3.92 (s, 3H, OCH3), 4.31 (s, 3H, OCH3), 6.98 (s, 1H, 4-H), 7.49–
7.55 (m, 3H, 3’-H, 4’-H and 5’-H), 8.17–8.23 (m, 2H, 2’-H and 6’-H). 13C
NMR (101 MHz, CDCl3): d = 56.5 (CH3), 60.5 (CH3), 61.6 (CH3), 96.0 (CH),
127.1 (C), 127.3 (2 × CH), 128.9 (2 × CH), 131.3 (CH), 136.2 (C), 138.4
(C), 138.7 (C), 138.7 (C), 152.0 (C), 162.9 (C). HRMS (ESI) m/z [M + Na]+
calcd. for C16H15NNaO4 308.0893, found 308.0886.
2-(4′-Cyanophenyl)-5,6-dimethoxy-1,3-benzoxazole
(2d):
2-(4′-
Cyanophenyl)-5,6-dimethoxy-1,3-benzoxazole (2d) was synthesized as
described for 2-phenyl-5,6-dimethoxy-1,3-benzoxazole (2a) using 4′-
cyano-N-(3,4-dimethoxyphenyl)benzamide (1d) (0.0565 g, 0.20 mmol) in
toluene (1.0 mL) and acetonitrile (1.0 mL). The bromination step was
carried out at 40 °C for 4 h and the O-arylation step at 130 °C for 48 h.
Purification by flash column chromatography (dichloromethane/ethyl
acetate 19:1) gave 2-(4′-cyanophenyl)-5,6-dimethoxy-1,3-benzoxazole
2-(4’-Fluorophenyl)-5,6,7-trimethoxy-1,3-benzoxazole (2h): 2-(4’-
Fluorophenyl)-5,6,7-trimethoxy-1,3-benzoxazole (2h) was synthesized as
described for 2-phenyl-5,6-dimethoxy-1,3-benzoxazole (2a) starting from
4’-fluoro-N-(3,4,5-trimethoxyphenyl)benzamide (1h) (0.076 g, 0.25 mmol).
The bromination step was carried out at 40 °C for 3 h and the O-arylation
step at 130 °C for 16 h. Purification by flash column chromatography
(hexane/ethyl acetate, 7:3) gave 2-(4’-fluorophenyl)-5,6,7-trimethoxy-1,3-
benzoxazole (2h) (0.034 g, 45%) as a white solid. Mp 89–90 °C. IR (neat):
νmax = 2940, 1601, 1498, 1462, 1423, 1192, 1138, 1040, 1011, 849, 791.
1H NMR (400 MHz, CDCl3): d = 3.92 (s, 3H, OCH3), 3.92 (s, 3H, OCH3),
4.29 (s, 3H, OCH3), 6.96 (s, 1H, 4-H), 7.20 (t, J = 8.8 Hz, 2H, 3’-H, and 5’-
H), 8.16–8.23 (m, 2H, 2’-H and 6’-H). 13C NMR (101 MHz, CDCl3): d = 56.5
(CH3), 60.5 (CH3), 61.6 (CH3), 96.0 (CH), 116.2 (d, 2JCF = 22.3 Hz, 2 × CH),
(2d) (0.028 g, 51%) as a white solid. Mp 247–248 °C. IR (neat): νmax
=
2968, 2220, 1481, 1329, 1273, 1192, 1161, 1134, 1003, 887, 839. 1H NMR
(400 MHz, CDCl3): d = 3.96 (s, 3H, OCH3), 3.98 (s, 3H, OCH3), 7.14 (s, 1H,
7-H), 7.26 (s, 1H, 4-H), 7.78 (d, J = 8.4 Hz, 2H, 3′-H and 5′-H), 8.26 (d, J =
8.4 Hz, 2H, 2′-H and 6′-H). 13C NMR (101 MHz, CDCl3): d = 56.5 (CH3),
56.5 (CH3), 94.2 (CH), 101.8 (CH), 113.9 (C), 118.3 (C), 127.2 (2 × CH),
131.4 (C), 132.7 (2 × CH), 134.9 (C), 145.5 (C), 148.3 (C), 149.4 (C), 160.1
(C). HRMS (EI) m/z [M]+ calcd. for C16H12N2O3 280.0848, found 280.0860.
4
3
123.5 (d, JCF = 3.2 Hz, C), 129.5 (d, JCF = 8.9 Hz, 2 × CH), 136.3 (C),
138.5 (C), 138.7 (C), 138.8 (C), 152.1 (C), 162.1 (C), 164.7 (d, 1JCF = 254.0
Hz, C). HRMS (ESI) m/z [M + Na]+ calcd. for C16H14FNNaO4 326.0799,
found 326.0793.
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