Helvetica Chimica Acta – Vol. 91 (2008)
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in acetone. After cooling, solid impurities were filtered off to give 1.85 g (70%, Method B) of pure 5i as a
colorless, hygroscopic solid. [a]2D0 ¼ À26.0 (c ¼ 0.20, CH2Cl2). IR (KBr): 3350 – 3600vs (br.), 1747vs
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(C¼O), 1438m, 1409m, 1383m, 1348m, 1320m, 1266m, 1203m, 1181m. H-NMR (CDCl3): 8.73 (br. s,
NH); 8.05 (s, HÀC(2’)); 7.39 (d, J ¼ 1.6, 1 H); 6.56 (s, 1 H); 5.22 (q, J ¼ 4.8, 1 H); 3.81 (s, MeO); 3.42 –
3.24 (m, 2 H); 2.07, 2.02 (2s, 2 Me). 13C-NMR (CDCl3): 169.0 (s, C¼O); 135.8, 125.53, 125.47 (3d,
3 CH(imidazole)); 131.7, 122.6, 116.5 (3s, 3 Cq(imidazole)); 57.9 (d, CH); 53.1 (q, MeO); 29.9 (t, CH2);
8.5, 6.9 (2q, 2 Me). EI-HR-MS: 264.12182 (Mþ, C12H16N4O3þ ; calc. 264.12224).
Methyl (S)-2-(4,5-Dimethyl-3-oxido-1H-imidazol-1-yl)-3-(4-hydroxyphenyl)propanoate (5j). Yield
after two CC (SiO2; acetone, then AcOEt/MeOH 1:1): 2.17 g (63%, Method A), 2.35 g (81%, Method
B). Colorless solid. M.p. 164 – 1698 (CHCl3/Et2O). [a]2D0 ¼ À99.5 (c ¼ 0.20, CHCl3). IR (KBr): 3550 –
3300vs, 3200 – 2450vs (br.), 1744vs (C¼O), 1613m, 1518s, 1448m, 1260s, 1174m. 1H-NMR (CDCl3):
8.09 (s, HÀC(2’)); 6.72, 6.68 (2 br. s, 4 arom. H); 4.87 – 4.74 (m, 1 H); 3.78 (s, MeO); 3.53 – 2.98 (m, CH2);
2.08, 1.79 (2s, 2 Me). 13C-NMR (CDCl3): 168.6 (s, C¼O); 157.9, 125.8, 123.6, 122.1 (4s, 2 arom. Cq, C(4’),
C(5’)); 129.5, 124.0, 116.2 (3d, 5 arom. C); 59.8 (d, CH); 53.1 (q, MeO); 38.4 (t, CH2); 8.4, 6.9 (2q, 2 Me).
EI-HR-MS: 290.12646 (Mþ, C15H18N2O4þ ; calc. 290.12666).
4. Aminolysis of N-Oxides 5. To a sat. soln. of N-oxide 5 (3 mmol) in benzene (for 8b – 8d) or CHCl3
(for 8a and 8e – 8g) (ca. 1.0 ml), the corresponding amine (3.5 mmol, i.e., 375 mg of PhCH2NH2, 200 mg
of cyclopropylamine, 347 mg of cyclohexylamine, and 424 mg of (1-phenylethyl)amine, resp.) was added,
and the resulting mixture was occasionally shaken. The mixture was left for 48 h at r.t. (usually, after 2 h a
little precipitate was observed). The soln. was concentrated, the resulting solid was treated with Et2O,
triturated with a small portion of cold acetone, and left in the refrigerator for 30 min. The pure crystalline
product was filtered and dried under reduced pressure for 2 h. The synthesis of amides 8b, 8c, 8e, 8f, and
8h – 8i was also performed without solvent in very good yields: to the N-oxide 5 (1 mmol), an excess of
amine (2 – 2.5 mmol) was added, and the mixture left at r.t. for the required time (usually ca. 2 – 3 d) with
occasional stirring. The resulting suspension was treated with Et2O, washed with cold acetone, filtered,
and purified by crystallization from the appropriate solvent.
N-Benzyl-2-(4,5-dimethyl-3-oxido-1H-imidazol-1-yl)acetamide (8a). Yield: 528 mg (68%), 2 d.
Colorless crystals. M.p. 190 – 1918 (CH2Cl2/acetone). IR (KBr): 3450 – 2700vs (br.), 1683vs (C¼O),
1605s, 1453m, 1403s, 1378m, 1338m, 1275m, 1237m, 1193m, 1174m, 702m, 656m. 1H-NMR (CD3OD): 8.19
(s, HÀC(2’)); 7.28 (s, 5 arom. H); 4.72, 4.38 (2s, 2 CH2); 2.12, 2.10 (2s, 2 Me). 13C-NMR (CD3OD): 168.0
(s, C¼O); 139.8, 128.4, 127.2 (3s, arom. Cq, C(4’), C(5’)); 129.8, 128.9, 128.6, 124.8 (4d, 5 arom. C, C(2’));
48.8, 44.4 (2t, 2 CH2); 8.3, 7.0 (2q, 2 Me). EI-MS: 259 (3, Mþ), 241 (100, [M À H2O]þ), 150 (44), 109 (28),
91 (88). Anal. calc. for C14H17N3O2 (259.31): C 64.85, H 6.61, N16.20; found: C 64.69, H 6.59, N16.07.
N-Benzyl-2-(5-methyl-3-oxido-4-phenyl-1H-imidazol-1-yl)acetamide (8b). Yield: 570 mg (59%),
2 d. Colorless crystals. M.p. 205 – 2068 (MeOH/H2O). IR (KBr): 3450 – 2750vs (br.), 1689vs (C¼O),
1585m, 1497m, 1436m, 1401m, 1346m, 1263m, 1214m, 1016m, 764m, 738m, 698s, 608m. 1H-NMR
(CD3OD): 8.03 (s, HÀC(2’)); 7.57 – 7.21 (m, 5 arom. H); 7.28 (s, 5 arom. H); 4.58, 4.39 (2s, 2 CH2); 2.21 (s,
Me). 13C-NMR (CD3OD): 166.2 (s, C¼O); 138.3, 130.5, 127.0, 124.8 (4s, 2 arom. Cq, C(4’), C(5’)); 130.4,
129.4, 129.2, 129.0, 128.4, 128.1, 128.0 (7d, 10 arom. C, C(2’)); 48.8, 44.2 (2t, 2 CH2); 9.6 (q, Me). EI-MS:
321 (2, Mþ), 303 (100, [M À H2O]þ), 212 (36), 158 (13), 109 (27), 91 (54). Anal. calc. for C19H19N3O2
(321.38): C 71.01, H 5.96, N13.07; found: C 71.07, H 5.80, N13.03.
N-Benzyl-2-(4-methyl-3-oxido-5-phenyl-1H-imidazol-1-yl)acetamide (8c). Yield: 480 mg (51%),
2 d. Colorless crystals. M.p. 220 – 2228 (MeOH/H2O). IR (KBr): 3450 – 2600vs (br.), 1663vs (C¼O),
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1608m, 1454m, 1395m, 1369m, 1336m, 1284m, 1227m, 1165m, 757m, 702m, 656m. H-NMR (CD3OD):
8.10 (s, HÀC(2’)); 7.52 – 7.17 (m, 10 arom. H); 4.51, 4.35 (2s, 2 CH2); 2.16 (s, Me). 13C-NMR (CD3OD):
166.2 (s, C¼O); 138.0, 135.7, 127.1, 126.5 (4s, 2 arom. Cq, C(4’), C(5’)); 130.5, 130.1, 129.4, 128.9, 128.1,
128.0, 127.8 (7d, 10 arom. C, C(2’)); 48.5, 43.8 (2t, 2 CH2); 7.6 (q, Me). EI-MS: 321 (2, Mþ), 303 (61, [M À
H2O]þ), 212 (28), 177 (33), 144 (20), 106 (18), 91 (100). Anal. calc. for C19H19N3O2 (321.38): C 71.01, H
5.96, N13.07; found: C 69.90, H 5.87, N12.99.
N-Benzyl-2-(3-oxido-4,5-diphenyl-1H-imidazol-1-yl)acetamide (8d). Yield: 970 mg (84%), 2 d.
Colorless crystals. M.p. 112 – 1168 (MeOH/H2O). IR (KBr): 3450 – 2800vs (br.), 1675vs (C¼O),
1603m, 1590m, 1577m, 1452m, 1404m, 1351m, 1272m, 1203m, 757s, 697vs, 657m. 1H-NMR (CD3OD): 8.43
(s, HÀC(2’)); 7.60 – 6.98 (m, 15 arom. H); 4.67, 4.29 (2s, 2 CH2). 13C-NMR (CD3OD): 165.8 (s, C¼O);