The Journal of Organic Chemistry
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residue was purified by flash chromatography on basic alumina
(petroleum ether/EtOAc) to give N-acetylbenzoxazine (2a′−j′ and
2a″−j″).
MHz, CDCl3): δ 6.84−6.76 (m, 3H, H−C-5, H−C-7 and H−C-8),
5.35 and 5.27 (s, 2H, H−C-2), 4.75 and 4.67 (s, 2H, H−C-4), 2.24 and
2.19 (s, 3H, H−COCH3); 13C{1H} NMR (75 MHz, CDCl3): δ 169.2
1
Analytical Data. 3,4-Dihydro-3-acetyl-6-methyl-2H-1,3-benzox-
azine (2a). It was purified by flash column chromatography (petroleum
ether/EtOAc = 8:1). White solid, mp = 101−102 °C, 879 mg, 92%
yield. 1H NMR (300 MHz, CDCl3): δ 6.99−6.74 (m, 3H, H−C-5, H−
C-7 and H−C-8), 5.37 and 5.26 (s, 2H, H−C-2), 4.75 and 4.65 (s, 2H,
H−C-4), 2.27 (s, 3H, H−CH3), 2.24 and 2.19 (s, 3H, H−COCH3);
13C{1H} NMR (75 MHz, CDCl3): δ 169.4 (CO), 151.7 and 151.4
(CO), 158.9 and 158.7 (C−F, JC−F = 240.0 Hz, C-6), 155.7 and
155.5 (C−F, 1JC−F = 240.0 Hz, C-6), 149.8 and 149.4 (C−F, 4JC−F = 1.5
3
Hz, C-8a), 121.4 and 120.0 (C−F, JC−F = 7.5 Hz, C-4a), 121.3 and
119.9 (C−F, 3JC−F = 7.5 Hz, C-4a), 118.5 and 118.0 (C−F, 3JC−F = 8.3
Hz, C-8), 118.3 and 117.9 (C−F, 3JC−F = 8.3 Hz, C-8), 115.0 and 114.6
(C−F, 2JC−F = 22.5 Hz, C-7), 114.7 and 114.3 (C−F, 2JC−F = 22.5 Hz,
C-7), 113.1 and 112.6 (C−F, 2JC−F = 22.5 Hz, C-5), 112.8 and 112.3
(C−F, 2JC−F = 22.5 Hz, C-5), 74.9 and 70.4 (C-2), 45.3 and 41.6 (C-4),
21.5 and 20.6 (−COCH3); HRMS (ESI-ICR) m/z: [M + Na]+ calcd
for C10H10FNNaO2, 218.0588; found, 218.0589.
(C-8a), 131.3 and 131.0 (C-5), 128.9 and 128.4 (C-6), 127.4 and 126.7
(C-7), 120.1 and 118.8 (C-4a), 117.3 and 116.8 (C-8), 75.1 and 70.7
(C-2), 45.7 and 42.0 (C-4), 21.8 and 20.9 (−COCH3), 20.5 (C6−
CH3); HRMS (ESI-ICR) m/z: [M + H]+ calcd for C11H14NO2,
192.1019; found, 192.1019.
3,4-Dihydro-3-acetyl-6-chloro-2H-1,3-benzoxazine (2g). It was
purified by flash column chromatography (petroleum ether/EtOAc =
8:1). White solid, mp = 122−124 °C, 749 mg, 71% yield. 1H NMR (300
MHz, CDCl3): δ 7.10−7.02 (m, 2H, H−C-5 and H−C-7), 6.82 and
6.75 (d, J = 9.0 Hz, 1H, H−C-8), 5.35 and 5.25 (s, 2H, H−C-2), 4.73
and 4.63 (s, 2H, H−C-4), 2.22 and 2.17 (s, 3H, H−COCH3); 13C{1H}
NMR (75 MHz, CDCl3): δ 169.5 (CO), 152.6 and 152.2 (C-8a),
128.4 and 127.9 (C-7), 126.9 and 126.8 (C-5), 126.5 and 126.3 (C-6),
122.0 and 120.6 (C-4a), 119.0 and 118.5 (C-8), 75.2 and 70.7 (C-2),
45.4 and 41.7 (C-4), 21.8 and 21.9 (−COCH3); HRMS (ESI-ICR) m/
z: [M + Na]+ calcd for C10H10ClNNaO2, 234.0292; found, 234.0294.
3,4-Dihydro-3-acetyl-6-bromo-2H-1,3-benzoxazine (2h). It was
purified by flash column chromatography (petroleum ether/EtOAc =
3,4-Dihydro-3-acetyl-6,8-dimethyl-2H-1,3-benzoxazine (2b). It
was purified by flash column chromatography (petroleum ether/
EtOAc = 8:1). Colorless viscous oil, 820 mg, 80% yield. 1H NMR (300
MHz, CDCl3): δ 6.80 and 6.77 (s, 1H, H−C-7), 6.66 (s, 1H, H−C-5),
5.34 and 5.23 (s, 2H, H−C-2), 4.68 and 4.58 (s, 2H, H−C-4), 2.22 and
2.20 (s, 3H, C−CH3−C-6), 2.20 and 2.13 (s, 3H, H−COCH3), 2.13 (s,
3H, C−CH3−C-8); 13C{1H} NMR (75 MHz, CDCl3): δ 169.0 and
168.8 (CO), 149.6 and 149.2 (C-8a), 130.1 and 129.8 (C-6), 129.7
and 129.3 (C-7), 126.0 and 125.5 (C-8), 124.4 and 123.8 (C-5), 119.2
and 118.0 (C-4a), 74.6 and 70.1 (C-2), 45.2 and 41.6 (C-4), 21.3 and
20.4 (−COCH3), 20.1 (C6−CH3), 15.0 (C8−CH3); HRMS (ESI-
ICR) m/z: [M + Na]+ calcd for C12H15NNaO2, 228.0995; found,
228.0995.
4-Dihydro-3-acetyl-6-t-butyl-2H-1,3-benzoxazine (2c). It was
purified by flash column chromatography (petroleum ether/EtOAc =
8:1). Light-yellow waxy solid, 885 mg, 76% yield. 1H NMR (300 MHz,
CDCl3): δ 7.21−7.14 (m, 1H, H−C-7), 7.06 (s, 1H, H−C-5), 6.83 and
6.79 (d, J = 9.0 Hz, 1H, H−C-8), 5.36 and 5.26 (s, 2H, H−C-2), 4.78
and 4.68 (s, 2H, H−C-4), 2.23 and 2.19 (s, 3H, H−CH3CO), 1.29 and
1.27 (s, 9H, H−C(CH3)3); 13C{1H} NMR (75 MHz, CDCl3): δ 169.3
(CO), 151.6 and 151.1 (C-8a), 144.6 and 144.4 (C-6), 125.2 and
124.7 (C-7), 123.6 and 123.0 (C-5), 119.5 and 118.2 (C-4a), 116.9 and
116.4 (C-8), 75.0 and 70.4 (C-2), 45.8 and 42.1 (C-4), 34.0
(−C(CH3)3), 31.3 (−C(CH3)3), 21.7 and 20.8 (−COCH3); HRMS
(EI-TOF) m/z: [M]+ calcd for C14H19NO2, 233.1416; found,
233.1418.
3,4-Dihydro-3-acetyl-6-methoxy-2H-1,3-benzoxazine (2d). It was
purified by flash column chromatography (petroleum ether/EtOAc =
8:1). Yellow solid, mp = 56−57 °C, 849 mg, 82% yield. 1H NMR (300
MHz, CDCl3): δ 6.81−6.65 (m, 2H, H−C-7 and H−C-8), δ 6.56 (d, J =
3 Hz, 1H, H−C-5), 5.31 and 5.20 (s, 2H, H−C-2), 4.72 and 4.62 (s, 2H,
H−C-4), 3.71 (s, 3H, H−OCH3), 2.20 and 2.15 (s, 3H, H−COCH3);
13C{1H} NMR (75 MHz, CDCl3): δ 169.3 (CO), 154.3 and 154.2
(C-6), 147.8 and 147.3 (C-8a), 120.8 and 119.5 (C-4a), 118.1 and
117.6 (C-7 or C-8), 114.1 and 113.9 (C-8 or C-7), 111.2 and 110.8 (C-
5), 75.0 and 70.5 (C-2), 55.5 (−OCH3), 45.6 and 42.0 (C-4), 21.7 and
20.8 (−COCH3); HRMS (EI-TOF) m/z: [M]+ calcd for C11H13NO3,
207.0895; found, 207.0894.
3,4-Dihydro-3-acetyl-6-phenyl-2H-1,3-benzoxazine (2e). It was
purified by flash column chromatography (petroleum ether/EtOAc =
8:1). White solid, mp = 99−102 °C, 974 mg, 77% yield. 1H NMR (300
MHz, CDCl3): δ 7.51−7.49 (m, 2H, H−o-phenyl), 7.42−7.32 (m, 4H,
H−m-phenyl and H−p-phenyl, H−C-7), 7.30−7.27 (m, 1H, H−C-5),
6.97 and 6.92 (d, J = 8.7 Hz, 1H, H−C-8), 5.41 and 5.29 (s, 2H, H−C-
2), 4.84 and 4.72 (s, 2H, H−C-4), 2.25 and 2.20 (s, 3H, H−CH3);
13C{1H} NMR (75 MHz, CDCl3): δ 169.4 (CO), 153.4 and 153.0
(C-8a), 140.2 and 140.2 (C1−phenyl), 135.1 and 134.8 (C-6), 128.7
(C−m-phenyl), 126.9 (C-7), 126.6 (C−o-phenyl), 126.6 and 126.6 (C-
5), 125.6 and 125.0 (C−p-phenyl), 120.6 and 119.3 (C-4a), 117.8 and
117.3 (C-8), 75.1 and 70.6 (C-2), 45.7 and 42.0 (C-4), 21.7 and 20.8
(−COCH3); HRMS (EI-TOF) m/z: [M]+ calcd for C16H15NO2,
253.1103; found, 253.1100.
1
8:1). White solid, mp = 135−136 °C, 1024 mg, 80% yield. H NMR
(300 MHz, CDCl3): δ 7.28−7.21 (m, 2H, H−C-5 and H−C-7), 6.81
and 6.73 (d, J = 9.0 Hz, 1H, H−C-8), 5.39 and 5.28 (s, 2H, H−C-2),
4.77 and 4.67 (s, 2H, H−C-4), 2.25 and 2.21 (s, 3H, H−COCH3);
13C{1H} NMR (75 MHz, CDCl3): δ 169.4 (CO), 153.2 and 152.6
(C-8a), 131.3 and 130.8 (C-7), 129.8 and 129.2 (C-5), 122.4 and 121.0
(C-4a), 119.4 and 118.9 (C-8), 114.1 and 113.7 (C-6), 75.1 and 70.7
(C-2), 45.3 and 41.6 (C-4), 21.8 and 20.9 (−COCH3); HRMS (EI-
TOF) m/z: [M]+ calcd for C10H10BrNO2, 254.9895; found, 254.9890.
3,4-Dihydro-3-acetyl-2H-1,3-benzoxazine (2i). It was purified by
flash column chromatography (petroleum ether/EtOAc = 8:1). Yellow
1
solid, mp = 55−57 °C, 531 mg, 60% yield. H NMR (300 MHz,
CDCl3): δ 7.18−7.05 (m, 2H, H−C-6 and H−C-7), 6.99−6.85 (m, 2H,
H−C-5 and H−C-8), 5.40 and 5.30 (s, 2H, H−C-2), 4.80 and 4.70 (s,
2H, H−C-4), 2.26 and 2.21 (s, 3H, H−COCH3); 13C{1H} NMR (75
MHz, CDCl3): δ 169.5 and 169.5 (CO), 154.0 and 153.5 (C-8a),
128.3 and 127.8 (C-5), 127.2 and 126.5 (C-7), 121.9 and 121.6 (C-6),
120.4 and 119.1 (C-4a), 117.6 and 117.0 (C-8), 75.0 and 70.6 (C-2),
45.7 and 42.0 (C-4), 21.8 and 20.9 (−COCH3); HRMS (ESI-ICR) m/
z: [M + H]+ calcd for C10H12NO2, 178.0863; found, 178.0860.
2,3-Dihydro-2-acetyl-1H-naphth[1,2-e][1,3]oxazine (2j). It was
purified by flash column chromatography (petroleum ether/EtOAc =
8:1). Yellow solid, mp = 60−64 °C, 874 mg, 77% yield. 1H NMR (300
MHz, CDCl3): δ 7.71−7.66 (m, 1H, H−C-8), 7.61−7.45 (m, 2H, H−
C-5 and H−C-4), 7.44−7.31 (m, 2H, H−C-6 and H−C-7), 7.03 and
6.96 (d, J = 9.0 Hz, 1H, H−C-3), 5.38 and 5.20 (s, 2H, H−OCH2N),
4.98 and 4.79 (s, 2H, H−CH2N), 2.18 and 2.15 (s, 3H, H−COCH3);
13C{1H} NMR (75 MHz, CDCl3): δ 169.3 and 169.0 (CO), 151.5
and 150.9 (C-2), 130.6 and 130.3 (C-4a), 128.8 and 128.7 (C-8a),
128.5 and 128.2 (C-4 or C-5), 128.4 and 128.1 (C-5 or C-4), 126.7 and
126.6 (C-7), 123.8 and 123.8 (C-6), 120.9 and 120.2 (C-8), 118.3 and
117.8 (C-3), 112.1 and 110.6 (C-1), 74.5 and 70.0 (−OCH2N), 43.4
and 39.9 (−CH2N), 21.6 and 20.6 (−COCH3); HRMS (EI-TOF) m/
z: [M]+ calcd for C14H13NO2, 227.0946; found, 227.0942.
2,3-Dihydro-2-acetyl-8-cyano-1H-naphth[1,2-e][1,3]oxazine
(2k). It was purified by flash column chromatography (petroleum
ether/EtOAc = 8:1). White solid, mp = 179−180 °C, 1109 mg, 88%
yield. 1H NMR (300 MHz, CDCl3): δ 8.18 and 8.15 (s, 1H, H−C-1),
7.81−7.64 (m, 3H, H−C-4, H−C-8 and H−C-3), 7.23 and 7.18 (d, J =
9.0 Hz, 1H, H−C-7), 5.54 and 5.44 (s, 2H, H−OCH2N), 5.13 and 5.01
(s, 2H, H−CH2N), 2.33 and 2.31 (s, 3H, H−COCH3); 13C{1H} NMR
(75 MHz, CDCl3): δ 169.4 (CO), 154.4 and 153.6 (C-6), 134.4 and
134.2 (C-1), 132.6 and 132.3 (C-4a), 129.2 and 128.8 (C-8), 128.0 (C-
8a), 127.6 and 127.5 (C-3), 122.4 and 121.7 (C-4), 120.7 and 120.1 (C-
3,4-Dihydro-3-acetyl-6-fluoro-2H-1,3-benzoxazine (2f). It was
purified by flash column chromatography (petroleum ether/EtOAc =
8:1). White solid, mp = 85−86 °C, 868 mg, 89% yield. 1H NMR (300
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J. Org. Chem. 2021, 86, 4932−4943