P. Rey et al.
that was stirred at ambient temperature for 12 h. During that time the
color of the suspension changed to yellow/green. Most of the solvent was
removed and diethyl ether (300 mL) was added. Ice-cold water was
added carefully dropwise with vigorous stirring, until the effervescence
had stopped (30 mL). Solid Na2CO3 (20 g) and NaCl (10 g) were added
and extraction with diethyl ether (3ꢃ100 mL) gave a pale-yellow solu-
tion, which was then dried over Na2SO4. Evaporation gave 2 as a pale-
yellow solid (7.60 g, 94%, 24.4 mmol, m.p. 184–1858C, lit.=1778C),[13]
which was used without further purification. 1H NMR (CDCl3,
200 MHz): d=6.64 (s, 1H; benzyl), 7.32–7.59 (m, 11H; aromatic), 8.04–
8.07 ppm (m, 4H; aromatic).
(1.07 G); UV/Vis (CHCl3): l (e): 567 (562), 389 nm (2485 mꢀ1cmꢀ1); el-
emental analysis calcd (%) for C22H18N3O: C 77.65, H 5.29, N 12.35;
found: C 77.58, H 5.26, N 12.46.
2,2,4,6-Tetraphenyl-1,2-dihydro-1,3,5-triazinyl-1-oxy (6b): From 5b
(100 mg) by following the same procedure as for 5a, a solution was ob-
tained the dark-green color of which faded rapidly. EPR spectra did
show the presence of a free radical the features of which (aN1 (7.05 G),
aN5 (3.21 G), aN3 (1.16 G)) are in agreement with the proposed structure.
The instability of the compound in the reaction medium precluded
workup and purification of the free radical.
2-Methyl-4,6-diphenyl-1,2-dihydro-1,3,5-triazine (8): Benzamidine hydro-
chloride (8.0 g 51.1 mmol) was suspended in CH2Cl2 (100 mL). A solution
of sodium hydroxide (8 g) in H2O (20 mL) was carefully added and stir-
ring was continued for 10 min. The organic phase was separated and
dried over Na2SO4. Acetaldehyde (2.3 g, 52.2 mol) was dissolved in
CH2Cl2 (7 mL) and added to the benzamidine solution in seven portions
over 7 h. After 12 h at room temperature, concentration of the solution
gave 5.4 g of yellow oil, which was purified on alumina (diethyl ether)
giving product 8 as an off-white solid (1.20 g, 4.8 mmol, 9.5%, m.p. 166–
1678C). MS (CH3OH): 250 [M+H]+; 1H NMR (CDCl3, 200 MHz): d=
1.55–1.58 (d, 3H, J=7 Hz), 5.24–5.33 (q, 1H, J=7 Hz), 7.38–7.45 (m,
6H; aromatic), 7.95–7.98 ppm (brm; aromatic); UV/Vis (CHCl3): l (e):
253 (12635), 341 nm (1315 mꢀ1cmꢀ1); IR (KBr): n˜ =3197 (w, broad;
NH), 3052 (w, sharp, CH), 1612 (s, sharp, phenyl), 1489 (s, sharp, phenyl),
1342 (s, sharp), 1267 cmꢀ1 (s, sharp); elemental analysis calcd (%) for
C16H15N3: C 77.10, H 6.03, N 16.87; found: C 77.21, H 6.15, N 16.78; the
structure of 8 was confirmed by a X-ray analysis.
2,4,6-Triphenyl-1,3,5-triazine-1-oxide (4): mCPBA (8.0 g, 46.4 mmol) in
chloroform (50 mL) was added dropwise to a solution of 2 (4.80 g,
15.43 mmol) in chloroform (100 mL). The bright-yellow solution was re-
fluxed gently for 2 h and then extracted with NaOH (3ꢃ50 mL, 2n).
Drying of the organic phase over Na2SO4 and evaporation gave a crude
yellow solid (7.50 g). Chromatography on silica (CH2Cl2) gave two major
products, 4 (5.25 g, 65%) and 2,4,6-triphenyl-1,3,5-triazine (1) (1.9 g,
25%). An analytical sample and single crystals of 4 were obtained by
slow evaporation of a CH2Cl2 solution (m.p. 2308C, dec.); MS (CH2Cl2):
326 [M+H]+; 1H NMR (CDCl3, 200 MHz): d=7.52 (m, 9H; aromatic),
8.54–8.59 (m, 2H; aromatic); 8.77–8.79 (m, 4H; aromatic); UV/Vis
(CHCl3): l (e)=331 (10656), 396 nm (4439 mꢀ1cmꢀ1); IR (KBr): n˜ =
1610 (s, sharp), 1544 (s, sharp), 1480 (s, sharp), 1442 (s, sharp), 1404 (s,
sharp), 1326 (ms sharp), 1270 (s, sharp), 1175 cmꢀ1 (s, sharp); elemental
analysis: calcd (%) for C21H15N3O: C 77.54, H 4.62, N 12.92; found: C
77.20, H 4.42, N 12.99.
2-Methyl-2,4,6-triphenyl-1,2-dihydro-1,3,5-triazine-1-oxide (5a): Methyl-
magnesium iodide (40 mmole) in diethyl ether (100 mL) was added to a
suspension of 4 (3 g, 9.2 mmol) in dry diethyl ether (50 mL) under argon
with rapid stirring. Progress of the reaction was monitored by TLC analy-
sis and, once 4 had been consumed, the suspension was filtered under
argon and the white solid washed with diethylether (2ꢃ50 mL). The solid
was removed and suspended in CH2Cl2 (200 mL) and cold water (20 mL)
carefully added giving immediately a bright-yellow solution. The water
was basified with Na2CO3, saturated with NaCl, and extracted with
CH2Cl2 (3ꢃ50 mL). Drying over Na2SO4 and evaporation gave a crude
yellow solid (3.2 g). Chromatography on alumina (ethyl acetate/CH2Cl2
2:1) gave 5a as a yellow powder-like solid (2.5 g, 80%, m.p. 225–2268C);
2-Methyl-4,6-diphenyl-1,3,5-triazine-1-oxide (10): mCPBA (4.0 g, 23
mmol) in chloroform (30 mL) was added dropwise to a solution of 8
(2.40 g, 9.6 mmol) in chloroform (50 mL). The bright-yellow solution was
refluxed gently for 2 h and then extracted with NaOH (3ꢃ25 mL, 2n).
Drying of the organic phase over Na2SO4 and evaporation gave a crude
yellow solid (2.50 g). Chromatography on silica gave two major products,
2-methyl-4,6-diphenyl-1,3,5-triazine (9) (650 mg, 27%, m.p. 1128C)[22]
1
and 10 (1.6 g, 63%, m.p. 97–988C). MS (CH2Cl2): 264 [M+H]+; H NMR
(CDCl3, 200 MHz): d=7.47–7.60 (m, 6H; aromatic), 8.45–8.50 (m, 2H;
ꢀ
aromatic), 8.81–8.85 (m, 2H; aromatic), 2.86 ppm (s, 3H; CH3); IR
(KBr): 1564 (m, sharp), 1484 (s, sharp), 1406 (s, sharp), 1329 (s, sharp),
1285 (s, sharp), 1178 cmꢀ1 (m, sharp); elemental analysis calcd (%) for
C16H13N3O: C 73.00, H 4.94, N 15.97; found: C 72.88, H 5.14, N 15.74.
1
MS (CH2Cl2): 342 [M+H]+; H NMR (CDCl3, 200 MHz): d=2.11 (s, 3H;
methyl), 7.38–7.56 (m, 10H; aromatic), 8.25–8.28 (m, 3H; aromatic),
2,2-(2,6)-Dimethyl-4,6-(2,4)-diphenyl-1,2-dihydro-1,3,5-triazine-1-oxide
(11) and compound 12: Freshly prepared CH3MgI (40 mmol) in diethyl
ether (50 mL) was added dropwise to compound 10 (1 g, 3.8 mmol) sus-
pended in diethyl ether (50 mL). When TLC showed that the starting
compound had been consumed, the flask was cooled in an ice bath and
H2O (20 mL) was carefully added. The organic phase was separated; the
residue was extracted with CH2Cl2, and the organic phases dried and con-
centrated to give a semi-solid yellow compound (1.2 g). Chromatography
on alumina (ethyl acetate/CH2Cl2) gave two compounds: 12 was eluted
first (448 mg, 43%, m.p. 191–1928C); MS (MeOH): 280 [M+H]+;
1H NMR (CDCl3, 200 MHz): d=2.04 (s, 3H; methyl), 2.28 (s, 3H;
methyl), 7.27–7.51 (m, 6H; aromatic), 8.00–8.04 ppm (d, 2H; aromatic);
UV/Vis (CHCl3): l (e): 242 (10220), 378 nm (2664 mꢀ1cmꢀ1); elemental
analysis calcd (%) for C17H17N3O: C 73.12, H 6.10, N 15.05; found: C
73.04, H 6.29, N 15.18; the second compound eluted was 11 (388 mg,
37%, m.p. 2358C); MS (MeOH) 280 [M+H]+; 1H NMR (CDCl3,
200 MHz): d=1.72 (s, 6H; methyl), 7.36–7.53 (m, 6H; aromatic), 7.98–
8.03 (m, 2H; aromatic), 8.54–8.58 ppm (brm, 2H; aromatic); UV/Vis
(CHCl3): l (e): 273 (10742) 385 nm (5980 mꢀ1cmꢀ1); elemental analysis
calcd (%) for C17H17N3O: C 73.12, H 6.10, N 15.05; found: C 72.98, H
6.21, N 14.97.
8.48–8.49 ppm (m, 2H; aromatic); UV/Vis (CHCl3):
l (e)=276
(10566 mꢀ1cmꢀ1), 390 nm (4979); IR (KBr): n˜ =3154 (w, br), 2983 (w,
br), 1590 (m, sharp), 1532 (s, sharp), 1492 (m, sharp), 1439 (s, sharp),
1361 (m, sharp), 1189 (s, sharp), 1131 (s, sharp), 1070 cmꢀ1 (m, sharp); el-
emental analysis: calcd (%) for C22H19N3O: C 77.42, H 5.57, N 12.32;
found: C 77.21, H 5.74, N 12.44.
2,2,4,6-Tetraphenyl-1,2-dihydro-1,3,5-triazine-1-oxide (5b): This com-
pound was prepared by using the same procedure as that described for
5a, except that C6H5MgBr (Aldrich, 3m in diethyl ether) replaced
CH3MgI. Thus 5b was obtained in 73% yield (m.p. 1408C); MS
(CH2Cl2): 404 [M+H]+; 1H NMR (CDCl3, 200 MHz): d=7.29–7.56 (m,
16H; aromatic), 8.03–8.08 (m, 2H; aromatic), 8.69 (brm, 2H; aromatic),
8.00–8.04 ppm (d, 2H; aromatic); UV/Vis (CHCl3):
l
(e)=276
(15113 mꢀ1cmꢀ1) 394 nm (5711 mꢀ1cmꢀ1); IR (KBr): n˜ =1590 (s,
sharp), 1547 (s, sharp), 1529 (s, sharp), 1489 (s, sharp), 1439 (s, sharp),
1366 (m, sharp), 1201 (s, sharp), 1134 cmꢀ1 (m, sharp); elemental analy-
sis: calcd (%) for C27H21N3O: C 80.40, H 5.01, N 10.42; found: C 80.62,
H 4.86, N 10.36.
2-Methyl-2,4,6-triphenyl-1,2-dihydro-1,3,5-triazinyl-1-oxy (6a): MnO2
(100 mg) was added to 5a (100 mg) in CH2Cl2 (5 mL) at room tempera-
ture. The black suspension was stirred for 3 min and then filtered.
Hexane (5 mL) was added and CH2Cl2 removed with an argon stream.
Flash chromatography (SiO2, hexane/diethyl ether 9:1) afforded a dark-
black solution, which was concentrated to 2 mL by using an argon stream
and allowed to stand in the dark at ꢀ158C. Crystallization occurred in
2 days giving 6a as dark-green single crystals (53 mg, 53%, m.p. 1078C).
EPR (CHCl3, deoxygenated): g=2.0076, aN1 (7.18), aN5 (3.23), aN3
2,2-Dimethyl-2,4-diphenyl-1,2-dihydro-1,3,5-triazinyl-1-oxy (13): Nitrone
11 (100 mg) was dissolved in CH2Cl2 (5 mL) and MnO2 (50 mg) was
added at room temperature. The black suspension was stirred for 3 min
and then filtered. Hexane (5 mL) was added and CH2Cl2 removed with
an argon stream. Flash chromatography (silica, hexane/diethyl ether 9:1)
afforded a black solution, which was concentrated to 2 mL by using an
argon stream and placed in the dark at ꢀ158C. Crystallization occurred
11256
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 11250 – 11257