8432
S.S. Michaelidou, P.A. Koutentis / Tetrahedron 65 (2009) 8428–8433
59.9; H, 3.35; N, 10.35%); lmax (DCM)/nm 221 (log
3
4.07), 225
(Ph CH), 19.5 (CH3); m/z (EI) 171 (Mþ, 100%), 156 (7), 143 (16), 116
(3.81), 264 (3.40), 272 (3.39), 300 (3.51), 365 inf (2.93); vmax/cmꢁ1
3330w (NH), 2923w, 2847w, 2199m (C^N), 1607w, 1570w, 1533s,
1483m, 1449w, 1445w, 1436m, 1421w, 1325s, 1271s, 1236m, 1209m,
1188w, 1112s, 1074m, 1010w, 1000w, 909w, 887w, 873w, 846w,
742s, 719s; dH (300 MHz; DMSO-d6) 11.99 (1H, br s, NH), 8.19 (1H, d,
J 2.1, indole H-4 or 6), 8.04 (1H, d, J 2.1, indole H-4 or 6), 7.81–7.74
(6H, m, Ph3P H), 7.70–7.56 (9H, m, Ph3P H); dC (75 MHz; DMSO-d6)
143.0, 139.8, 136.65, 132.5 (d, JPC 3.0, Ph3P C-4), 132.1 (d, JPC 10.5,
Ph3P C-3), 130.1 (d, JPC 100.5, Ph3P C-1), 129.1 (d, JPC 12.0, Ph3P C-2),
123.7 (d, JPC 12.1, indole C-3), 122.0 (Ph CH), 117.5 (Ph CH), 115.4 (d,
JPC 2.3, C^N), 104.7, 98.7 (d, JPC 14.3, indole C-2, CC^N); dC
(75 MHz; DEPT-135, DMSO-d6) 132.5 (d, JPC 3.0, Ph3P C-4), 132.1 (d,
JPC 10.5, Ph3P C-3), 129.1 (d, JPC 12.0, Ph3P C-2), 122.0 (Ph CH), 117.5
(Ph CH); dP(121.5 MHz; DMSO-d6) 7.24; m/z (EI) 542 (Mþþ2, 100%),
540 (Mþ, 100), 515 (8), 495 (9), 494 (8), 493 (8), 462 (9), 415 (4), 389
(2), 336 (2), 311 (3), 282 (3), 278 (7), 277 (17), 262 (10), 247 (4), 234
(3), 207 (5), 201(7), 185 (15), 184 (15), 183 (88), 152 (13), 132 (7), 108
(14), 77 (12).
(15), 89 (15), 76 (3), 63 (6), 51 (3).
4.3.9. 3-Amino-6-methoxyindole-2-carbonitrile 3g. (2.6 mg, 7%) red
crystals, mp 179–180 ꢀC (from cyclohexane–EtOH); (Found: C, 64.2;
H, 4.7; N, 22.4. C10H9N3O requires C, 64.2; H, 4.85; N, 22.5%); lmax
(DCM)/nm 230 inf (log 3 4.18), 254 (4.37), 305 inf (4.12), 312 (4.16);
vmax/cmꢁ1 3440w (NH2), 3378w and 3348w (NH), 3234w, 2971w,
2936w, 2843w, 2207s (C^N), 1623s, 1586s, 1556m, 1506m, 1455s,
1441w, 1338m, 1315s, 1251w, 1225s, 1207w, 1185w, 1167s, 1103s,
1021s, 951w, 941w, 823s, 808s; dH (300 MHz; DMSO-d6) 10.46 (1H,
br s, NH), 7.60 (1H, d, J 8.7, Ph H-4), 6.61–6.57 (2H, m, Ph H-5 and 7),
5.64 (2H, br s, NH2), 3.76 (3H, s, CH3O); dC (75 MHz; DMSO-d6) 159.1,
139.4, 137.9, 121.0 (Ph CH), 116.55, 112.5, 109.3 (Ph CH), 93.3 (Ph CH),
85.3 (CC^N), 55.0 (CH3O); dC (75 MHz; DEPT-135, DMSO-d6) 121.0
(Ph CH),109.35 (Ph CH), 93.3 (Ph CH), 55.0 (CH3O); m/z (EI) 187 (Mþ,
100%),186 (7),172 (72),159 (8),144 (42),129 (3),117 (18), 90 (11), 76
(4), 63 (13), 52 (3).
4.3.10. 6,7-Dimethoxyquinazoline-2-carbonitrile 5. (5.2 mg, 15%)
yellow cotton, mp 170–171 ꢀC (from cyclohexane); (Found: C, 61.35;
H, 4.2; N, 19.5. C11H9N3O2 requires C, 61.4; H, 4.2; N, 19.5%); lmax
4.3.6. 3-Amino-6-chloroindole-2-carbonitrile 3d. (27.1 mg, 71%) red
powder, mp 210–211 ꢀC (from EtOH); (Found: C, 56.4; H, 3.04; N,
21.8. C9H6ClN3 requires C, 56.4; H, 3.2; N, 21.9%); lmax (DCM)/nm
(DCM)/nm 228 (log
3 3.02), 235 (3.21), 261 (3.35), 285 inf (2.88),
253 (log
3
3.64), 298 (3.17), 309 inf (3.08), 336 (2.88); vmax/cmꢁ1
363 (3.02); vmax/cmꢁ1 2974w, 2920w, 2851w, 2230m (C^N),
1597m, 1547w, 1537w, 1516s, 1464m, 1441w, 1396w, 1368m, 1339w,
1287s, 1231s, 1198w, 1109s, 1026w, 993s, 908w, 876m, 837m; dH
(300 MHz; DMSO-d6) 8.17 (1H, s, Ph H-4), 7.51 (1H, s, Ph H-5), 7.31
(1H, s, Ph H-8) 3.87 (3H, s, CH3O), 3.86 (3H, s, CH3O); dC (75 MHz;
DMSO-d6) 152.9, 150.2, 143.85, 137.4 (Ph CH), 116.8, 116.0, 114.5 (Ph
CH), 102.2, 101.8 (Ph CH), 56.3 (CH3O), 56.25 (CH3O); dC (75 MHz;
DEPT-135, DMSO) 137.4 (Ph CH), 114.5 (Ph CH), 101.8 (Ph CH), 56.3
(CH3O), 56.25 (CH3O); m/z (EI) 215 (Mþ, 100%), 200 (72), 188 (2), 172
(33), 157 (5), 145 (74), 129 (11), 117 (25), 115 (12), 106 (8), 104 (29),
102 (49), 90 (39), 88 (23), 78 (57), 76 (58), 64 (33), 53 (30).
3411w, 3386w, 3354w (NH), 3335w, 3298w, 3228w, 2221s and
2212s (C^N), 1617m, 1581m, 1551m, 1507w, 1490w, 1465w, 1458w,
1444w, 1338s, 1290w, 1245w, 1221w, 1188m, 1113w, 1061s, 922m,
859w, 843m, 799s; dH (300 MHz; DMSO-d6) 10.88 (1H, br s, NH),
7.75 (1H, d. J 8.7, Ph H-4), 7.23 (1H, d, J 1.8, Ph H-7), 6.97 (1H, dd, J
1.8, 8.7, Ph H-5) 5.83 (2H, br s, NH2); dC (75 MHz; DMSO-d6) 139.0,
136.8, 131.0, 121.8 (Ph CH), 118.5 (Ph CH), 117.0, 115.7 (C^N), 111.05
(Ph CH), 87.3 (CC^N); dC (75 MHz; DEPT-135, DMSO-d6) 121.80 (Ph
CH), 118.5 (Ph CH), 111.05 (Ph CH); m/z (EI) 193 (Mþþ2, 32%), 191
(Mþ, 100), 165 (7), 163 (15), 156 (MþꢁCl, 19), 137 (19), 129 (11), 110
(3), 102 (12), 100 (9), 95 (5), 75 (12), 63 (2), 50 (4).
4.4. 3-Amino-1H-indole-2-carbonitrile 3a from
4.3.7. 3-Amino-5-chloroindole-2-carbonitrile 3e. (12.2 mg, 32%)
light red powder, mp 190–191 ꢀC (from EtOH); (Found: C, 56.4; H,
3.2; N, 21.9. C9H6ClN3 requires C, 56.4; H, 3.2; N, 21.9%); lmax (DCM)/
(2-cyanoindol-3-yl)iminotriphenylphosphorane 4a
4.4.1. Using HCl (0.5 M). To a stirred solution of (2-cyanoindol-3-
yl)iminotriphenylphosphorane 4a (20 mg, 0.05 mmol) in MeOH
(1 mL) at ca. 20 ꢀC and protected with a CaCl2 drying tube, was
added 0.5 M HCl (1 mL) and the mixture was then heated to ca.
80 ꢀC for 32 h, until no starting material remained (TLC). The re-
action mixture was then extracted (DCM), dried (Na2SO4) and
adsorbed onto silica. Chromatography (DCM, 100%) gave the title
compound 3a (7.3 mg, 93%) as light yellow cotton fibres, mp 172–
173 ꢀC (from cyclohexane–EtOH), identical to that described above.
nm 221 (log 3 3.65), 223 (3.56), 253 (3.46), 256 (3.43), 299 (3.03),
307 inf (2.98), 341 (2.80); vmax/cmꢁ1 3458w (NH2), 3371w and
3329m (NH), 2202s (C^N), 1627m, 1581w, 1554m, 1473m, 1447w,
1374w, 1321m, 1292s, 1235w, 1188w, 1140m, 1123m, 1055m, 1025w,
1000w, 924w, 847m, 800s, 782w; dH (300 MHz; DMSO-d6) 10.92
(1H, br s, NH), 7.85 (1H, s, Ph H), 7.22–7.21 (2H, m, Ph H), 5.76 (2H, br
s, NH2); dC (75 MHz; DMSO-d6) 138.3, 135.0, 126.1 (Ph CH), 122.4,
119.45 (Ph CH), 119.0, 115.6 (C^N), 113.4 (Ph CH), 88.1 (CC^N); dC
(75 MHz; DEPT-135, DMSO-d6) 126.1 (Ph CH), 119.45 (Ph CH), 113.4
(Ph CH); m/z (EI) 193 (Mþþ2, 32%), 191 (Mþ, 100), 165 (6), 163 (15),
156 (MþꢁCl, 33), 138 (17), 137 (16), 136 (11), 129 (14), 112 (2), 102
(14), 100 (11), 95 (4), 75 (13), 62 (2), 50 (6).
4.4.2. Using AcOH (80%). To a stirred solution of 80% acetic acid
(2 mL) at ca. 20 ꢀC and protected with a CaCl2 drying tube, was
added (2-cyanoindol-3-yl)iminotriphenylphosphorane 4a (20 mg,
0.05 mmol) and the mixture was heated to ca. 80 ꢀC for 6.5 h, until
no starting material remained (TLC). The reaction mixture was then
extracted (DCM), dried (Na2SO4) and adsorbed onto silica. Chro-
matography (DCM, 100%) gave the title compound 3a (7.2 mg, 92%)
as light yellow cotton fibres, mp 172–173 ꢀC (from cyclohexane–
EtOH), identical to that described above.
4.3.8. 3-Amino-4-methylindole-2-carbonitrile 3f. (2.1 mg, 6%) yel-
low cotton fibres, mp 156–157 ꢀC (from cyclohexane–EtOH);
(Found: C, 70.3; H, 5.3; N, 24.55. C10H9N3 requires C, 70.2; H, 5.3; N,
24.5%); lmax (DCM)/nm 230 inf (log 3 3.35), 242 (3.41), 273 (1.95),
297 (2.85), 331 (2.87); vmax/cmꢁ1 3423w and 3330s (NH2), 3049w
and 3018w (Ar CH), 2977w, 2927w, 2202s, (C^N), 1615m, 1586m,
1546m, 1516w, 1470w, 1439w, 1419w, 1376w, 1358m, 1318m,
1262m, 1245m, 1185m, 1165w, 1133w, 1077w, 1050w, 1030w, 967w,
948w, 864w, 789w, 772s; dH (300 MHz; DMSO-d6) 10.81 (1H, br s,
NH), 7.07 (1H, dd, J 7.5, 7.5, Ph H-5), 6.99 (1H, d, J 8.1, Ph H-7), 6.64
(1H, d, J 6.6, Ph H-6), 5.16 (2H, br s, NH2), 3.39 (3H, s, CH3); dC
(75 MHz; DMSO-d6) 139.6, 137.3, 132.1, 126.1 (Ph CH), 119.6 (Ph CH),
117.3 (C-7), 115.95 (C^N), 109.7 (Ph CH), 88.3 (CC^N),19.5 (CH3); dC
(75 MHz; DEPT-135, DMSO-d6) 126.1 (Ph CH), 119.6 (Ph CH), 109.7
4.5. (2-Cyanoindol-3-yl)iminotriphenylphosphorane 4a from
3-amino-1H-indole-2-carbonitrile 3a
To a stirred solution of 3-aminoindole-2-carbonitrile 3a (20 mg,
0.13 mmol) in distilled benzene (2 mL) at ca. 20 ꢀC and protected
with a CaCl2 drying tube, were added triethylamine (72.1 mL,
0.52 mmol, 4 equiv), triphenylphosphine (68.2 mg, 0.26 mmol,
2 equiv) and then hexachloroethane (61.6 mg, 0.26 mmol, 2 equiv).