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L. Rubio-Perez et al. / Tetrahedron 68 (2012) 2342e2348
2347
ArH), 6.74 (s, 2H, ArH), 4.58 (d, J¼6.0 Hz, 2H, CH2), 3.82 (s, 6H, OMe),
3.72 (s, 3H, OMe). 13C NMR (75 MHz, acetone-d6)
171.0 (CO), 163.2,
154.4, 138.4, 134.8, 128.3, 127.5, 119.3, 118.7, 115.4, 106.1, 60.5 (OMe),
56.4 (OMe), 43.9 (CH2). HRMS (EI): m/z [M]þ calcd for C17H19NO5,
317.1263; found, 317.1262.
ArH), 7.29e7.26 (m, 1H, ArH), 7.11e7.06 (m, 2H, ArH), 7.01e6.98
(m, 1H, ArH), 6.44 (br, 1H, NH), 4.81 (d, J¼5.4 Hz, 2H, CH2). 13C
d
NMR (75 MHz, CDCl3) d 161.5 (CO), 140.5, 138.4, 130.2, 128.3, 127.6,
127.0, 126.4, 125.4, 38.7 (CH2). HRMS (EI): m/z [M]þ calcd for
C10H9NOS2, 223.0126; found, 223.0131.
4.2.13. 2-Hydroxy-N-(thiophen-2-ylmethyl)benzamide (3jd). Color-
less crystals, yield: 51%, mp 151e154 ꢀC. IR (KBr) 3358, 1640, 1543.
4.2.20. N-(3-Methylbenzyl)propionamide (3qj). Light yellow oil,
yield: 86%. IR (sol CHCl3) 3447, 1666, 1514. 1H NMR (300 MHz,
1H NMR (300 MHz, acetone-d6)
d
12.68 (br, 1H, OH), 8.76 (br, 1H,
CDCl3) d 7.29e7.18 (m, 1H, ArH), 7.08e7.04 (m, 3H, ArH), 6.50 (br,
NH), 7.82 (dd, J¼8.1, 1.5 Hz, 1H ArH), 7.44 (td, J¼8.1, 1.5 Hz, 1H ArH),
7.36 (dd, J¼8.1, 1.2 Hz, 1H ArH), 7.10e7.09 (m, 1H, ArH), 6.99e6.85
(m, 3H, ArH), 4.81 (d, J¼5.7 Hz, 2H, CH2). 13C NMR (75 MHz, ace-
1H, NH), 4.34 (d, J¼5.7 Hz, 2H, CH2), 2.33 (s, 3H, Me), 2.23 (q, 2H,
J¼7.5 Hz, CH2), 1.15 (t, 3H, J¼7.5 Hz, CH3). 13C NMR (75 MHz, CDCl3)
d
174.0 (CO), 138.4, 138.2, 128.52, 128.50, 128.0, 124.7, 43.4 (CH2),
tone-d6)
d
170.9 (CO), 162.7, 142.4, 134.9, 127.5, 126.9, 126.0, 119.4,
29.5 (CH2), 21.3 (Me), 9.9 (CH3). HRMS (EI): m/z [M]þ calcd for
119.3, 118.7, 115.2, 38.2 (CH2). HRMS (EI): m/z [M]þ calcd for
C11H15NO, 177.1154; found, 177.1155.
C12H11NO2S, 233.0511; found, 233.0509.
4.2.21. N-(4-tert-Butylbenzyl)-2-cyanoacetamide (3ek). White solid,
yield: 90%; mp 128e131 ꢀC. IR (sol CHCl3) 3515, 2245(CN),1705,1593,
1515. 1H NMR (300 MHz, CDCl3) 7.39 (d, J¼8.4 Hz, 2H, ArH), 7.25 (d,
J¼8.4 Hz, 2H, ArH), 6.17 (br, 1H, NH), 3.66 (d, J¼5.7 Hz, 2H, CH2), 3.28
(d, J¼5.1 Hz,1H, CH2), 3.21 (d, J¼5.1 Hz,1H, CH2),1.34 [s, 9H, C(CH3)3].
4.2.14. 4-tert-Butyl-N-(4-tert-butylbenzyl)benzamide (3ee). White
solid, yield: 92%, mp 108e111 ꢀC. IR (sol CHCl3) 3451, 1655, 1525. 1H
NMR (300 MHz, CDCl3)
d
7.81 (d, J¼8.4 Hz, 2H, ArH), 7.45 (d,
J¼8.4 Hz, 2H, ArH), 7.40 (d, J¼8.4 Hz, 2H, ArH), 7.35 (d, J¼8.2 Hz, 2H,
ArH), 7.05 (br, 1H, NH), 4.62 (d, J¼5.4 Hz, 2H, CH2), 1.38 [s, 9H,
13C NMR (75 MHz, CDCl3)
d 166.4 (CO),150.7, 132.4, 128.8, 125.8, 117.9
C(CH3)3], 1.37 [s, 9H, C(CH3)3]. 13C NMR (75 MHz, CDCl3)
d
167.3
(eCN), 40.4 (CH2), 35.2 (CH2), 34.5 [C(CH3)3], 31.3 [C(CH3)3]. HRMS
(CO), 155.0, 150.5, 135.3, 131.5, 127.7, 126.9, 125.6, 125.5, 43.7 (CH2),
34.9 [C(CH3)3], 34.5 [C(CH3)3], 31.3 [C(CH3)3], 31.2 [C(CH3)3]. HRMS
(EI): m/z [M]þ calcd for C22H29NO, 323.2249; found, 323.2255.
(EI): m/z [M]þ calcd for C14H18N2O, 230.1419; found, 230.1425.
4.2.22. N-Hexyl-4-pyridinecarboxamide (3kh). Colorless needles,
yield: 57%, mp 58e61 ꢀC IR (sol CHCl3) 3448, 1670, 1523. 1H NMR
4.2.15. N-(4-tert-Butylbenzyl)-4-chlorobenzamide (3ef). White solid,
yield: 94%, mp 138e141 ꢀC. IR (sol CHCl3) 3450, 1660, 1596, 1516. 1H
(400 MHz, CDCl3)
d
8.77 (d, J¼5.2 Hz, 2H, ArH), 7.81 (d, J¼5.2 Hz, 2H,
ArH), 6.69 (br, 1H, NH), 3.50e3.45 (m, 2H, CH2), 1.68e1.60 (m, 2H,
CH2), 1.40e1.25 (m, 6H, CH2), 0.89 (t, J¼6.8 Hz, 3H, CH3). 13C NMR
NMR (300 MHz, CDCl3)
d
7.74 (d, J¼8.7 Hz, 2H, ArH), 7.40 (d, J¼8.4 Hz,
2H, ArH), 7.38 (d, J¼8.7 Hz, 2H, ArH), 7.30 (d, J¼8.4 Hz, 2H, ArH), 6.68
(100 MHz, CDCl3) d 164.6 (CO), 148.4, 144.0, 121.9, 40.4 (CH2NH),
(br,1H, NH), 4.60 (d, J¼5.4 Hz, 2H, CH2),1.35 [s, 9H, C(CH3)3].13C NMR
31.4, 29.4, 26.6, 22.5 (CH2), 13.9 (Me). HRMS (EI): m/z [M]þ calcd for
(75 MHz, CDCl3)
d
166.3 (CO), 150.7, 137.7, 134.9, 132.8, 128.8, 128.4,
C12H18N2O, 206.1419; found, 206.1420.
127.7, 125.7, 43.9 (CH2), 34.5 [C(CH3)3], 31.3 [C(CH3)3]. HRMS (EI): m/z
[M]þ calcd for C18H20ClNO, 301.1233; found, 301.1228.
4.2.23. N-(Hexen-1-yl)-4-pyridinecarboxamide (3kh0). White solid,
yield: 19%, mp 56e59 ꢀC. IR (sol CHCl3) 3452, 2933, 2855, 1665,
4.2.16. 4-Chloro-N-[(4-dimethylamino)benzyl]benzamide (3pf). Co-
lorless crystals, yield: 80%, mp 148e151 ꢀC. IR (sol CHCl3) 3450,1659,
1505, 1483. 1H NMR (500 MHz, CDCl3)
d
8.76 (d, J¼5.5 Hz, 2H, ArH),
8.15 (d, J¼10.0 Hz, 1H, NH), 7.56 (d, J¼5.5 Hz, 2H, ArH), 6.95e6.89
(m, 1H, CH]CHNH), 5.48e5.43 (m, 1H, CH]CHNH), 2.12e2.07 (m,
2H, CH2),1.41e1.30 (m, 4H, CH2), 0.91 (t, J¼7.2 Hz, 3H, CH3). 13C NMR
1596, 1521. 1H NMR (300 MHz, CDCl3)
d
7.72 (d, J¼8.7 Hz, 2H, ArH),
7.38 (d, J¼8.7 Hz, 2H, ArH), 7.24 (d, J¼8.7 Hz, 2H, ArH), 6.74 (d,
J¼8.4 Hz, 2H, ArH), 6.53 (br,1H, NH), 4.52 (d, J¼5.4 Hz, 2H, CH2), 2.91
(125 MHz, CDCl3)
d 161.8 (CO), 149.6, 140.8, 122.2 (CH]CHNH),
[s, 6H, NMe2]. 13C NMR (75 MHz, CDCl3)
d
166.1 (CO), 150.1, 137.5,
121.4, 116.4 (CH]CHNH), 31.8, 29.4, 22.0 (CH2), 13.8 (CH3). HRMS
132.9,129.2,128.7,128.4,125.7,112.8, 43.9 (CH2), 40.7 (NMe2). HRMS
(EI): m/z [M]þ calcd for C12H16N2O, 204.1263; found, 204.1459.
(EI): m/z [M]þ calcd for C16H17ClN2O, 288.1029; found, 288.1034.
4.2.24. N-Cyclohexylmethyl-4-pyridinecarboxamide
solid, yield: 49%, mp 106e108 ꢀC. IR (sol CHCl3) 3453, 1667, 1522. 1H
NMR (400 MHz, CDCl3)
(3rh). White
4.2.17. N-(4-tert-Butylbenzyl)-3,4,5-trimethoxybenzamide (3eg). Color-
less oil, yield: 83%. IR (sol CHCl3) 3449, 1656, 1586, 1522. 1H NMR
d
8.69 (d, J¼5.0 Hz, 2H, ArH), 7.59 (dd, J¼5.0,
(300 MHz, CDCl3)
d
7.39 (d, J¼8.4 Hz, 2H, ArH), 7.30 (d, J¼8.4 Hz, 2H,
1.6 Hz, 2H, ArH), 6.54 (br, 1H, NH), 3.28 (t, J¼6.2 Hz, 2H, CH2),
ArH), 7.06 (s, 2H, ArH), 6.72 (br, 1H, NH), 4.60 (d, J¼5.4 Hz, 2H, CH2),
2.07e1.80 (m, 1H, CHCH2), 1.79e1.52 (m, 7H, CH2), 1.28e1.12 (m,
3.88 (s, 3H, OMe), 3.87 (s, 6H, OMe), 1.33 [s, 9H, C(CH3)3]. 13C NMR
3H, CH2). 13C NMR (100 MHz, CDCl3)
d 165.6 (CO),150.3, 141.9,120.9,
(75 MHz, CDCl3)
d
167.1 (CO), 153.1, 150.6, 140.8, 135.2, 129.8, 127.7,
46.3 (CHCH2), 37.8, 30.8, 26.2, 25.7 (CH2). HRMS (EI): m/z [M]þ calcd
125.6, 104.4, 60.9 (OMe), 56.2 (OMe), 43.9 (CH2), 34.5 [C(CH3)3], 31.3
[C(CH3)3]. HRMS (EI): m/z [M]þ calcd for C21H27NO4, 357.1940; found,
357.1939.
for C13H18N2O, 218.1419; found, 218.1423.
4.2.25. N-(Cyclohexylidenemethyl)-4-pyridinecarboxamide (3kh0).
White solid, yield: 28%. IR (sol CHCl3) 3453, 2934, 2857, 1667, 1506,
4.2.18. N-(4-Methylbenzyl)-4-pyridinecarboxamide (3ch). White
solid, yield: 83%, mp 128e130 ꢀC. IR (sol CHCl3) 3447, 1669, 1518.
1483. 1H NMR (400 MHz, CDCl3)
d
8.73 (d, J¼5.6 Hz, 2H, ArH),
7.63e7.61 (m, 3H, NHþArH), 6.69 (d, J¼10.1 Hz, 1H, CH]CHNH),
1H NMR (400 MHz, CDCl3)
d
8.68 (d, J¼5.6 Hz, 2H, ArH), 7.60 (d,
2.17e2.14 (m, 4H, CH2), 1.59e1.57 (m, 6H, CH2). 13C NMR (100 MHz,
J¼5.6 Hz, 2H, ArH), 7.22 (d, J¼8.0 Hz, 2H, ArH), 7.15 (d, J¼8.0 Hz, 2H,
CDCl3) d 162.3 (CO), 150.6, 141.3, 126.2 (CH]CHNH), 120.7, 113.7
ArH), 6.77 (br, 1H, NH), 4.57 (d, J¼5.6 Hz, 2H, CH2), 2.34 (s, 3H, Me).
(CH]CHNH), 27.9, 27.7, 26.9, 26.4 (CH2). HRMS (EI): m/z [M]þ calcd
13C NMR (100 MHz, CDCl3)
d
165.2 (CO), 150.3, 141.5, 137.6, 134.4,
for C13H16N2O, 216.1263; found, 216.1266.
129.5, 127.9, 120.9, 44.0 (CH2), 21.0 (Me). HRMS (FABþ): m/z
[MþH]þ calcd for C14H15N2O, 227.1184; found, 227.1188.
4.3. General procedure for N-alkylation of acetamide with
ketones (Table 4)
4.2.19. N-(Thiophen-2-ylmethyl)-2-thiophenecarboxamide (3ji).
Colorless needles, yield: 79%; mp 111e114 ꢀC. IR (sol CHCl3) 3447,
The procedure was the same for N-alkylation of primary amides
with aldehydes. The crude product was purified by column
1650, 1532, 1501. 1H NMR (300 MHz, CDCl3)
d
7.55e7.50 (m, 2H,