T. Shi et al. / Tetrahedron xxx (xxxx) xxx
7
13C NMR (101 MHz, CDCl3)
d
168.4, 133.1, 130.8, 127.8, 123.2, 65.8;
4.2.17. N,N-Diethylbenzamide (3af)
Colourless oil (237 mg, 67% yield); 1H NMR (400 MHz, CDCl3)
7.60e7.30 (m, 5H), 3.54 (s, 2H), 3.25 (s, 2H), 1.27e0.98 (m, 6H); 13
HRMS (ESI) m/z calcd for C11H12BrNO2 [MþH]þ 271.1260, found
271.1284.
d
C
NMR (101 MHz, CDCl3)
d 170.3, 136.2, 128.1, 127.4, 125.3, 42.3, 38.2,
4.2.8. N-(4-Chlorobenzoyl)morpholine (3ha)
30.5, 29.1, 13.2, 11.9; HRMS (ESI) m/z calcd for C11H15NO [MþH]þ
White solid (364 mg, 81% yield); 1H NMR (400 MHz, CDCl3)
178.1187, found 178.1183.
d
7.38 (q, J ¼ 8.5 Hz, 4H), 3.92e3.32 (m, 8H); 13C NMR (101 MHz,
CDCl3)
d
168.4, 135.0, 132.6, 127.9, 127.6, 99.9, 65.8; HRMS (ESI) m/z
4.2.18. N-methyl-N-phenylbenzamide (3 ag)
calcd for C11H12ClNO2 [MþH]þ 226.6720, found 226.6724.
Colourless oil (333 mg, 79% yield); 1H NMR (400 MHz, CDCl3)
d
7.20 (dd, J ¼ 7.9, 6.6 Hz, 2H), 7.16e7.02 (m, 6H), 6.95 (d, J ¼ 7.6 Hz,
4.2.9. N-(3-Chlorobenzoyl)morpholine (3ia)
2H), 3.42 (s, 3H); 13C NMR (101 MHz, CDCl3)
d
169.6, 143.9, 134.9,
Colourless oil (333 mg, 74% yield); 1H NMR (400 MHz, CDCl3)
128.6, 128.1, 127.7, 126.7, 125.9, 125.4, 37.4; HRMS (ESI) m/z calcd for
C
d
7.35e7.24 (m, 3H), 7.23e7.17 (m, 1H), 3.83e3.23 (m, 8H); 13C NMR
14H13NO [MþH]þ 212.1031, found 212.1048.
(101 MHz, CDCl3)
d 167.8, 136.0, 133.6, 129.00, 128.9, 126.3, 124.1,
65.8, 47.0, 41.4, 25.9; HRMS (ESI) m/z calcd for C11H12ClNO2 [MþH]þ
4.2.19. N-Benzyl-N-methylbenzamide (3ah)
226.6720, found 226.6735.
Colourless oil (391 mg, 87% yield); 1H NMR (400 MHz, CDCl3)
d
7.42e7.00 (m, 10H), 4.67 (s, 1H), 4.42 (s, 1H), 2.85 (d, J ¼ 69.0 Hz,
4.2.10. N-(2-Chlorobenzoyl)morpholine (3ja)
3H); 13C NMR (101 MHz, CDCl3)
d
170.9, 136.0, 135.6, 135.2, 128.6,
Light yellow solid (306 mg, 68% yield); 1H NMR (400 MHz,
127.7, 127.4, 127.1, 126.5, 125.9, 54.1, 49.8, 36.0, 32.1, 28.6; HRMS
CDCl3)
11.3, 5.6 Hz, 1H), 3.83e3.73 (m, 3H), 3.73e3.65 (m, 1H), 3.63e3.55
(m, 1H), 3.34e3.16 (m, 2H); 13C NMR (101 MHz, CDCl3)
165.9,
d
7.43e7.38 (m, 1H), 7.37e7.27 (m, 3H), 3.89 (ddd, J ¼ 16.6,
(ESI) m/z calcd for C15H15NO [MþH]þ 226.1187, found 226.1189.
d
4.2.20. N,N-Dibenzylbenzamide (3ai)
134.4, 129.4, 129.3, 128.7, 126.8, 126.3, 65.8, 65.7, 46.1, 41.0; HRMS
White solid (547 mg, 91% yield); 1H NMR (400 MHz, CDCl3)
(ESI) m/z calcd for C11H12ClNO2 [MþH]þ 226.6720, found 226.6753.
d
7.51e7.11 (m, 15H), 4.70 (s, 2H), 4.40 (s, 2H); 13C NMR (101 MHz,
CDCl3)
d 172.3, 137.0, 136.4, 136.2, 129.7, 128.8, 128.6, 128.4, 127.6,
4.2.11. 4-Morpholinyl-2-thienylmethanone (3ka)
127.0, 126.7, 51.6, 46.9; HRMS (ESI) m/z calcd for C21H19NO [MþH]þ
Light yellow oil (307 mg, 78% yield); 1H NMR (400 MHz, CDCl3)
302.1500, found 302.1509.
d
7.39 (dd, J ¼ 5.0, 1.0 Hz, 1H), 7.22 (dd, J ¼ 3.6, 1.0 Hz, 1H), 6.97 (dd,
J ¼ 5.0, 3.7 Hz, 1H), 3.71e3.63 (m, 8H); 13C NMR (101 MHz, CDCl3)
4.2.21. N-Ethylbenzamide (3aj)
d
162.63,135.57,127.9, 127.8, 125.7, 65.8, 59.4, 20.0,13.2; HRMS (ESI)
White solid (241 mg, 81% yield); 1H NMR (400 MHz, CDCl3)
m/z calcd for C9H11NO2S [MþH]þ 198.0544, found 198.0568.
d
7.77 (d, J ¼ 7.1 Hz, 2H), 7.55e7.29 (m, 3H), 6.41 (s, 1H), 3.57e3.17
(m, 2H), 1.29e0.98 (m, 3H); 13C NMR (101 MHz, CDCl3)
d
167.5,
4.2.12. 2-Furanyl-4-morpholinylmethanone (3la)
134.8, 131.3, 128.5, 126.9, 34.9, 14.9; HRMS (ESI) m/z calcd for
C9H11NO [MþH]þ 150.0874, found 150.0887.
Yellow oil (275 mg, 76% yield); 1H NMR (400 MHz, CDCl3)
d 7.48
(dd, J ¼ 1.7, 0.8 Hz,1H), 7.03 (dd, J ¼ 3.5, 0.7 Hz,1H), 6.49 (dd, J ¼ 3.5,
1.8 Hz, 1H), 3.82 (s, 4H), 3.77e3.72 (m, 4H); 13C NMR (101 MHz,
4.2.22. N-Butylbenzamide (3ak)
CDCl3)
d
158.1, 146.8, 142.8, 115.8, 110.4, 65.9, 29.3; HRMS (ESI) m/z
White solid (283 mg, 80% yield); 1H NMR (400 MHz, CDCl3)
calcd for C9H11NO3 [MþH]þ 182.0772, found 182.0783.
d
7.64 (dd, J ¼ 93.1, 13.0 Hz, 2H), 7.48e7.09 (m, 3H), 6.22 (d,
J ¼ 75.4 Hz, 1H), 3.53e3.11 (m, 2H), 1.58 (dt, J ¼ 14.0, 7.0 Hz, 2H),
4.2.13. Benzoylpiperidine (3 ab)
1.39 (dd, J ¼ 14.5, 7.2 Hz, 2H), 0.94 (dd, J ¼ 9.2, 5.4 Hz, 3H); 13C NMR
Colourless oil (298 mg, 79% yield); 1H NMR (400 MHz, CDCl3)
(101 MHz, CDCl3) d 167.6, 134.9, 131.2, 128.5, 126.8, 39.8, 31.7, 20.2,
d
7.31 (s, 5H), 3.63 (s, 2H), 3.27 (s, 2H), 1.70e1.35 (m, 6H); 13C NMR
13.8; HRMS (ESI) m/z calcd for C11H15NO [MþH]þ 178.1187, found
(101 MHz, CDCl3)
d
169.3, 135.5, 128.3, 127.4, 125.8, 47.8, 42.1, 25.4,
178.1189.
24.6, 23.6; HRMS (ESI) m/z calcd for C12H15NO [MþH]þ 190.1187,
found 190.1192.
4.2.23. N-Cyclopentylbenzamide (3am)
White solid (302 mg, 80% yield); 1H NMR (400 MHz, CDCl3)
4.2.14. 1-Benzoyl-4-methylpiperazine (3ac)
d 7.80e7.70 (m, 2H), 7.51e7.35 (m, 3H), 6.11 (s, 1H), 4.45e4.34 (m,
Yellow oil (342 mg, 84% yield); 1H NMR (400 MHz, CDCl3)
1H), 2.08 (td, J ¼ 11.4, 6.1 Hz, 2H), 1.78e1.59 (m, 4H), 1.49 (td,
d
7.40e7.28 (m, 5H), 3.74 (s, 2H), 3.34 (s, 2H), 2.55e2.27 (m, 4H),
J ¼ 12.5, 6.1 Hz, 2H); 13C NMR (101 MHz, CDCl3)
d 167.2, 135.0, 131.2,
128.5, 126.8, 51.7, 33.2, 23.8; HRMS (ESI) m/z calcd for C12H15NO
2.25 (s, 3H); 13C NMR (101 MHz, CDCl3)
d
173.4, 169.3, 134.7, 128.7,
127.5, 126.0, 54.2, 53.6, 46.5, 44.9, 40.9, 20.5; HRMS (ESI) m/z calcd
for C12H16N2O [MþH]þ 205.1296, found 205.1305.
[MþH]þ 190.1187, found 190.1192.
4.2.24. N-Phenylbenzamide (3an)
4.2.15. Benzoylpyrrolidine (3ad)
White solid (268 mg, 68% yield); 1H NMR (400 MHz, CDCl3)
Colourless oil (304 mg, 87% yield); 1H NMR (400 MHz, CDCl3)
d
7.87 (d, J ¼ 7.9 Hz, 3H), 7.65 (d, J ¼ 8.1 Hz, 2H), 7.58e7.52 (m, 1H),
d
7.43 (dt, J ¼ 8.5, 3.7 Hz, 2H), 7.35e7.28 (m, 3H), 3.46 (d, J ¼ 81.7 Hz,
7.48 (t, J ¼ 7.7 Hz, 2H), 7.37 (t, J ¼ 7.8 Hz, 2H), 7.16 (t, J ¼ 7.4 Hz, 1H);
4H), 1.84 (s, 4H); 13C NMR (101 MHz, CDCl3)
d
168.7, 136.2, 128.8,
13C NMR (101 MHz, CDCl3)
d 164.7, 136.9, 134.0, 130.8, 128.1, 127.8,
127.2, 126.0, 48.6, 45.2, 25.4, 23.5; HRMS (ESI) m/z calcd for
126.0, 123.6, 119.2; HRMS (ESI) m/z calcd for C13H11NO [MþH]þ
C
11H13NO [MþH]þ 176.1031, found 176.1045.
198.0874, found 198.0886.
4.2.16. N,N-Dimethylbenzamide (3ae)
4.2.25. N-Benzylbenzamide (3ao)
White solid (188 mg, 63% yield); 1H NMR (400 MHz, CDCl3)
White solid (320 mg, 76% yield); 1H NMR (400 MHz, CDCl3)
d
7.54e7.32 (m, 5H), 3.03 (s, 6H); 13C NMR (101 MHz, CDCl3)
d
171.6,
d
7.79 (d, J ¼ 7.2 Hz, 2H), 7.53e7.20 (m, 8H), 6.48 (s, 1H), 4.64 (d,
136.4, 129.5, 128.3, 127.0; HRMS (ESI) m/z calcd for C9H11NO
J ¼ 5.5 Hz, 2H); 13C NMR (101 MHz, CDCl3)
d 167.4, 138.2, 134.4,
[MþH]þ 150.0874, found 150.0889.
131.5, 128.8, 128.6, 127.9, 127.6, 127.0, 44.2; HRMS (ESI) m/z calcd for
Please cite this article as: T. Shi et al., Two-step continuous flow synthesis of amide via oxidative amidation of methylarene, Tetrahedron, https://
doi.org/10.1016/j.tet.2020.131044