10.1002/ejoc.201700833
European Journal of Organic Chemistry
FULL PAPER
2 H), 1.43-1.52 (m, 2H). 13C-NMR (101 MHz, CDCl3) δ/ppm: 137.9 (CH),
133.5 (C), 131.3 (C), 127.6 (CH), 124.5 (CH), 53.8 (CH2), 43.9 (CH2), 39.2
(CH2), 28.3 (CH2), 25.2 (CH2), 22.8 (CH2), 22.2 (CH2). IR (neat, ν/cm-1):
3110 (broad, 2925 (m), 2835 (m), 1501 (m), 1437 (m), 1361 (m), 1110 (m),
1019 (s), 919 (m), 820 (m), 728 (s), 661 (s). HR-MS (TQF+) calculated for
C12H19N2O 207.1497, found 207.1474.
2,2,2-Trifluoroethyl
carboxylate 7e
1-(2,6-difluorobenzyl)-1H-imidazole-5-
Off-white solid. Yield: 77%. 1H-NMR (400 MHz, CDCl3) δ/ppm: 7.83 (d, J
= 1.0 Hz, 1 H), 7.58 (s, 1H), 7.35 (app tt, J = 8.5, 6.5 Hz, 1H), 6.95 (dd, J
= 8.5, 6.5 Hz, 2H), 5.61 (s, 2H), 4.65 (q, J = 8.3 Hz, 2H). 13C-NMR (101
MHz, CDCl3) δ/ppm: 161.4 (2CF, dd, J = 252, 7 Hz), 158.3 (C), 142.8 (CH),
139.2 (CH), 131.2 (CH, t, J = 10 Hz), 122.9 (CF3, q, J = 277 Hz), 121.1 (C),
111.7 (2CH, m), 111.3 (C, t, J = 19 Hz), 60.0 (CH2, q, J = 37 Hz), 38.1
(CH2, t, J = 4 Hz). 19F-NMR (376 MHz, CDCl3) δ/ppm: -73.7, -114.0. IR
(neat, ν/cm-1): 1728 (s), 1628 (m), 1537 (m), 1472 (m), 1365 (m), 1273 (m),
1219 (m), 1164 (s), 1102 (s), 1028 (m), 971 (m), 840 (m), 791 (m), 757
(m), 651 (s). HR-MS (TQF+) calculated for C13H10N2O2F5 321.0662, found
321.0665.
General procedure for batch oxidation:
To a solution of alcohol 6 in the desired alcohol solvent (0.3 M) was added
MnO2 (40 equiv.), NaCN (0.5 equiv.) and acetic acid (2 drops). This mixture
was heated at 80 °C until t.l.c. and 1H-NMR indicated complete conversion
of the substrate into the desired ester species (typically 12 h). The reaction
mixture was cooled to 25 °C and filtered over a pad of celite yielding the
crude product after evaporation of the solvents. Final purification was
accomplished by silica column chromatography using EtOAc/hexanes (10-
30% EtOAc) as eluent.
Ethyl 1-(2,4-dichlorobenzyl)-1H-imidazole-5-carboxylate 7f
Off-white solid. Melting range: 90.5-91.6 °C. Yield: 87%. 1H-NMR (400
MHz, CDCl3) δ/ppm: 7.76 (d, J = 1.0 Hz, 1H), 7.61 (d, J = 1.0 Hz, 1H), 7.37
(d, J = 2.1 Hz, 1H), 7.12 (dd, J = 8.4, 2.1 Hz, 1H), 6.70 (dd, J = 8.4, 0.8 Hz,
1H), 5.53 (s, 2H), 4.22 (q, J = 7.1 Hz, 2H), 1.26 (t, J = 7.1 Hz, 3H). 13C-
NMR (101 MHz, CDCl3) δ/ppm: 160.0 (C), 142.4 (CH), 138.0 (CH), 134.9
(C), 133.3 (C), 133.0 (C), 129.5 (CH), 129.0 (CH), 127.6 (CH), 122.7 (C),
60.7 (CH2), 47.2 (CH2), 14.2 (CH3). IR (neat, ν/cm-1): 3097 (w), 2993 (w),
1698 (s), 1541 (m), 1470 (m), 1373 (s), 1347 (m), 1295 (m), 1264 (m),
1234 (s), 1194 (m), 1121 (s), 1101 (s), 1047 (m), 1022 (m), 864 (m), 834
(m), 817 (m), 766 (s), 658 (m). HR-MS (TQF+) calculated for
C13H13N2O2Cl2 299.0354, found 299.0352.
Methyl 1-benzyl-1H-imidazole-5-carboxylate 7a
Off-white solid. Yield: 78%. 1H-NMR (400 MHz, CDCl3) δ/ppm: 7.76 (d, J
= 1.0 Hz, 1H), 7.61 (s, 1H), 7.28-7.35 (m, 3H), 7.13-7.18 (m, 2H), 5.50 (s,
2H), 3.80 (s, 3H). 13C-NMR (101 MHz, CDCl3) δ/ppm: 160.6 (C), 142.2
(CH), 138.0 (CH), 136.2 (C), 128.9 (2CH), 128.1 (CH), 127.3 (2CH), 122.5
(C), 51.5 (CH3), 50.0 (CH2). IR (neat, ν/cm-1): 1709 (s), 1541 (m), 1436
(m), 1363 (s), 1295 (m), 1222 (s), 1200 (m), 1107 (s), 918 (w), 809 (m),
765 (m), 711 (s), 657 (s). HR-MS (TQF+) calculated for C12H13N2O2
217.0977, found 217.0980.
Methyl 1-(2,4-dichlorobenzyl)-1H-imidazole-5-carboxylate 7g
Ethyl 1-benzyl-1H-imidazole-5-carboxylate 7b
Off-white solid. Melting range: 102.4-105.0 °C. Yield: 81%. 1H-NMR (400
MHz, CDCl3) δ/ppm: 7.72 (d, J = 1.1 Hz, 1H), 7.60 (d, J = 1.1 Hz, 1H), 7.33
(d, J = 2.1 Hz, 1H), 7.09 (dd, J = 8.3, 2.1 Hz, 1H), 6.69 (d, J = 8.3 Hz, 1H),
5.51 (s, 2H), 3.73 (s, 3H). 13C-NMR (101 MHz, CDCl3) δ/ppm: 160.4 (C),
142.5 (CH), 138.1 (CH), 134.5 (C), 133.3 (C), 132.9 (C), 129.5 (CH), 129.0
(CH), 127.6 (CH), 122.4 (C), 51.6 (CH3), 47.1 (CH2). IR (neat, ν/cm-1): 3024
(w), 2963 (w), 1698 (s), 1532 (m), 1473 (m), 1426 (m), 1365 (s), 1298 (m),
1262 (m), 1225 (s), 1196 (s), 1115 (s), 1047 (m), 953 (m), 831 (s), 771 (s),
655 (s). HR-MS (TQF+) calculated for C12H11N2O2Cl2 285.0198, found
285.0189.
Off-white solid. Melting range: 53.0-54.9 °C. Yield: 85%. 1H-NMR (400
MHz, CDCl3) δ/ppm: 7.76 (d, J = 1.0 Hz, 1H), 7.60 (s, 1H), 7.25-7.33 (m,
3H), 7.13-7.16 (m, 2H), 5.49 (s, 2H), 4.24 (q, J = 7.1 Hz, 2H), 1.29 (t, J =
7.1 Hz, 3H). 13C-NMR (101 MHz, CDCl3) δ/ppm: 160.2 (C), 142.2 (CH),
137.9 (CH), 136.3 (C), 128.9 (2CH), 128.1 (CH), 127.2 (2CH), 122.8 (C),
60.5 (CH2), 50.0 (CH2), 14.2 (CH3). IR (neat, ν/cm-1): 2983 (w), 1708 (s),
1539 (w), 1373 (m), 1293 (m), 1221 (s), 1124 (s), 1103 (s), 1019 (w), 921
(w), 840 (w), 765 (m), 713 (s), 658 (m). HR-MS (TQF+) calculated for
C13H15N2O2 231.1134, found 231.1132.
Isopropyl 1-benzyl-1H-imidazole-5-carboxylate 7c
Ethyl 1-(3,5-bis(trifluoromethyl)benzyl)-1H-imidazole-5-carboxylate
7h
Off-white solid. Yield: 81%. 1H-NMR (400 MHz, CDCl3) δ/ppm: 7.76 (d, J
= 1.0 Hz, 1H), 7.59 (s, 1H), 7.27-7.39 (m, 3H), 7.14-7.18 (m, 2H), 5.51 (s,
2H), 5.14 (sept, J = 6.3 Hz, 1H), 1.28 (d, J = 6.3 Hz, 6H). 13C-NMR (101
MHz, CDCl3) δ/ppm: 159.8 (C), 142.0 (CH), 137.8 (CH), 136.3 (C), 128.9
(2CH), 128.1 (CH), 127.2 (2CH), 123.2 (C), 68.2 (CH), 50.1 (CH2), 21.9
(2CH3). IR (neat, ν/cm-1): 2983 (w), 1708 (s), 1543 (w), 1459 (w), 1374 (s),
1294 (w), 1225 (s), 1124 (m), 1100 (s), 715 (m), 657 (w). HR-MS (TQF+)
calculated for C14H17N2O2 245.1290, found 245.1262.
Off-white solid. Melting range: 63.8-65.0 °C. Yield: 75%. 1H-NMR (400
MHz, CDCl3) δ/ppm: 7.78 (m, 2H), 7.73 (s, 1H), 7.59 (s, 2H), 5.62 (s, 2H),
4.24 (q, J = 7.1 Hz, 2H), 1.28 (t, J = 7.1 Hz, 3H). 13C-NMR (101 MHz,
CDCl3) δ/ppm: 160.1 (C), 142.1 (CH), 139.1 (C), 138.3 (CH), 132.2 (2C, q,
J = 34 Hz), 127.3 (2CH, m), 123.0 (2CF3, q, J = 274 Hz), 122.6 (C), 122.1
(CH, dt, J = 8, 4 Hz), 60.8 (CH2), 49.0 (CH2), 14.1 (CH3). 19F-NMR (376
MHz, CDCl3) δ/ppm: -63.0. IR (neat, ν/cm-1): 1711 (m), 1543 (w), 1477 (w),
1376 (m), 1353 (m), 1276 (s), 1170 (s), 1123 (s), 905 (m), 843 (m), 704
(m), 682 (m), 659 (m). HR-MS (TQF+) calculated for C15H13N2O2F6
367.0881, found 367.0876.
Ethyl 1-(2,6-difluorobenzyl)-1H-imidazole-5-carboxylate 7d
Off-white solid. Yield: 80%. 1H-NMR (400 MHz, CDCl3) δ/ppm: 7.72 (d, J
= 1.0 Hz, 1H), 7.50 (s, 1H), 7.32 (app tt, J = 8.4, 6.5 Hz, 1H), 6.93 (dd, 8.4,
J = 7.6 Hz, 2H), 5.63 (s, 2H), 4.33 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz,
3H). 13C-NMR (101 MHz, CDCl3) δ/ppm: 161.4 (2CF, dd, J = 252, 7 Hz),
160.3 (C), 141.7 (CH), 137.5 (CH), 131.1 (CH, t, J = 10 Hz), 122.9 (C),
111.7 (2CH, m), 111.5 (C, m), 60.6 (CH2), 38.0 (CH2), 14.3 (CH3). 19F-NMR
(376 MHz, CDCl3) δ/ppm: -114.0. IR (neat, ν/cm-1): 2984 (w), 1710 (s),
1627 (m), 1471 (s), 1374 (m), 1351 (m), 1220 (s), 1101 (s), 1025 (s), 902
(w), 834 (m), 792 (s), 763 (m), 655 (s). HR-MS (TQF+) calculated for
C13H13N2O2F2 267.0945, found 267.0949.
Ethyl 1-(4-bromobenzyl)-1H-imidazole-5-carboxylate 7i
Off-white solid. Melting range: 66.5-68.9 °C. Yield: 84%. 1H-NMR (400
MHz, CDCl3) δ/ppm: 7.74 (d, J = 1.0 Hz, 1H), 7.61 (s, 1H), 7.41 (d, J = 8.4
Hz, 2H), 6.99 (d, J = 8.4 Hz, 2H), 5.43 (s, 2H), 4.23 (q, J = 7.1 Hz, 2H),
1.28 (t, J = 7.1 Hz, 3H). 13C-NMR (101 MHz, CDCl3) δ/ppm: 160.1 (C),
142.1 (CH), 138.0 (CH), 135.4 (C), 132.0 (2CH), 128.8 (2CH), 122.6 (C),
122.0 (C), 60.6 (CH2), 49.4 (CH2), 14.2 (CH3). IR (neat, ν/cm-1): 3096 (w),
2983 (w), 1700 (s), 1540 (m), 1487 (m), 1368 (m), 1343 (s), 1260 (m), 1227
This article is protected by copyright. All rights reserved.