Jul-Aug 2001
A Simple One Pot Synthesis of Condensed 1,2,4-Triazines
905
was stirred for 2 hours at 20 °C. The precipitate was isolated by
filtation and washed with CH Cl to yield 260 mg (70%) of com-
Anal. Calcd for C H N O •C H NO: C, 64.28; H, 4.79; N,
15 9 3 2 3 7
16.66. Found: C, 64.45; H, 4.73; N, 16.38.
2
2
1
pound 2, mp 148-149 °C (dec). H NMR (DMSO-d ): δ 4.38 (s,
6
6-(1-Aminothioureido)-5-methoxy-1-methyl-3-phenyl-1,4-dihy-
3H, OCH ), 4.52 (s, 3H, NCH ), 7.75-7.79 (m, 2H), 7.76-7.72 (m,
3
3
dro-1,2,4-triazine (7 x HBF ).
13
4
1H), 8.38-8.42 (m, 2H), 9.49 (s, 1H, C6-H); C NMR (DMSO-
d ): δ 52.3 (N1-CH ), 58.1 (5-OCH ), 131.5, 128.9, 130.0, 135.0,
Triethylamine (0.014 ml, 0.1 mmol) was added to a mixture of
2 (150 mg, 0.51 mmol), thiosemicarbazide (55.6 mg, 0.61 mmol)
and methanol (1.5 ml), and the reaction mixture was stirred for 24
hours at 20 °C followed by reflux for 1 hour. Solvent was
removed in vacuo. The residue was separated by column chro-
matography to give compound 1 (10 mg, 11%), compound 7 as
yellow solid with mp 228 °C (dec) (41 mg, 21%) and compound
6
3
3
165.8 (C3
), 168.5 (C5
), 139.2 (C6
).
triazine
triazine
triazine
Anal. Calcd for C H N O•BF : C, 45.71; H, 4.18; N, 14.54.
11 12
3
4
Found: C, 45.78; H, 4.30; N, 14.59.
7-Amino-1-methyl-3-phenyl-4,5-dihydro-1H[1,2,4]triazino-
[5,6-b]indole (4 x HBF ).
4
1
8 (9 mg, 5%). 7: H NMR (DMSO-d ): δ 3.54 (s, 3H), 4.13 (s,
A suspension of 2 (150 mg, 0.50 mmol) and m-phenylenedi-
amine (55.2 mg, 0.51 mmol) in methanol (4 ml) was stirred for 2
hours at 20 °C. After evaporation of solvent in vacuo, the residue
was separated by column chromatography to give 5-methoxy-3-
phenyl-1,2,4-triazine (1) (4.5 mg, 2%) and compound 4 (127 mg,
6
3H), 7.38-7.48 (m, 3H), 7.94-7.98 (m, 2H), 8.09 (bs, ~1H), 9.02
(bs, ~1H) (two NH protons are exchanged with the signal of
13
water); C NMR (DMSO-d ): δ 41.5, 55.1, 125.2, 128.47,
6
129.2, 130.3, 133.7, 141.9, 158.3, 174.9.
1
68%) as red crystals, mp 234-236 °C. H NMR (DMSO-d ): δ
6
7-Amino-1-methyl-3-phenyl-4,6,7,7a-tetrahydro-1H-imi-
4.56 (s, 3H, NCH ), 5.73 (bs, 2H, NH), 7.46 (bs, 2H, NH), 6.68
3
dazo[4,5-e][1,2,4]-triazin-6-thione (8•H[BF ]).
4
(d, J = 1.7 Hz, 1H), 6.77 (dd, J = 1.7 Hz, 9.0 Hz, 1H), 8.04 (d,
13
A mixture of 2 (200 mg, 0.68 mmol), thiosemicarbazide (74.4
mg, 0.82 mmol) and methanol (2 ml) was stirred at 20 °C for 24
hours. Then the reaction mixture was refluxed for 5 hours. Solvent
was removed in vacuo and the residue was purified by column
chromatography to give compound 8 as red crystals, mp 191-193
J = 9.0 Hz, 1H), 7.75-7.57 (m, 3H), 8.26-8.31 (m, 2H); C NMR
(DMSO-d , See Figure 9): δ 47.6 (C17), 95.7 (C9), 100.5 (C7),
6
113.5 (C11), 127.6 (C14), 129.1 (C12), 129.3 (C15), 131.6
(C16), 134.2 (C13), 151.7 (C10), 155.91 (C3), 157.12 (C5),
158.2 (C6), 158.2 (C8).
1
°C (40 mg, 14%). H NMR (DMSO-d ): δ 3.90 (d, J = 0.9 Hz,
Anal. Calcd for C H N •HBF : C, 52.63; H, 4.42; N, 19.18.
6
16 15
5
4
3H), 7.37 (bs, 2H) , 7.50-7.53 (m, 3H), 8.12-8.16 (m, 2H), 8.23 (d,
J = 0.9 Hz, 1H, C6-H), 9.55 (bs, 1H); H NMR (Acetone-d ): δ
4.04 (d, J = 0.9 Hz, 3H), 7.19 (bs, 2H), 7.40-7.70 (m, 3H), 8.09 (d,
Found: C, 52.14; H, 4.37; N, 18.98.
1
6
6-(2,4-Dihydroxyphenyl)-5-methoxy-3-phenyl-1,2,4-triazine (5).
13
J = 0.9 Hz, 1H, C6-H), 8.21-8.24 (m, 2H), 9.67 (bs, 1H);
C
A mixture of 2 (200 mg, 0.68 mmol), resorcinol (74.8 mg, 0.68
mmol) and dry methanol (5 ml) was refluxed for 24 hours. The
reaction mixture was subjected to column chromatography on sil-
ica gel to give compound 1 (8 mg, 6%) and compound 5 (50 mg,
NMR (DMSO-d ): δ 49.1(N1-CH ), 127.2, 128.4, 131.4, 134.3,
6
3
139.1 (C6
) 145.1 (C5
), 163.5 (C3
), 175.1 (C=S).
triazine
triazine
triazine
Anal. Calcd for C H N S•HBF : C, 37.95; H, 3.76; N,
11 12
6
4
1
24.14. Found: C, 37.82; H, 3.68; N, 24.25.
25%), mp 238-239 °C. H NMR (DMSO-d ): δ 3.97 (s, 3H), 6.41
6
(dd, J = 2.2 Hz, 8.5 Hz, 1H), 6.46 (d, J = 2.2 Hz, 1H), 7.23 (d,
J = 8.5 Hz, 1H), 7.48-7.56 (m, 3H), 8.21 (dd, J= 7.8 Hz, 1.6 Hz,
2H), 10.01 (bs, 1H), 10.41 (bs, 1H).
7-Amino-1-methyl-3-phenyl-4,6,7,7a-tetrahydro-1H-imi-
dazo[4,5-e][1,2,4]triazin-6-one tetrafluoroborate (9 x HBF ) and
4
5-Semicarbazido-3-phenyl-1,2,4-triazine (10).
Anal. Calcd for C H N O : C, 65.08; H, 4.44; N, 14.23.
16 13
3 3
Triethylamine (62 mg, 0.61 mmol) was added to a suspension of
2 (150 mg, 0.51 mmol) and semicarbazide hydrochloride (88.3 mg,
0.61 mmol) in methanol (2 ml), and the mixture was stirred for 24
hours at 20 °C and at which time it was refluxed for 2 hours. After
that the reaction mixture was separated by column chromatography
Found: C, 65.10; H,4.50; N,14.30.
6-(2,4-Dihydroxyphenyl)-5-methoxy-3-phenyl-1,2,4-triazine (5)
and 7-Hydroxy-3-phenylbenzo[4,5-e]furo[2,3-e][1,2,4]triazine (6).
A solution of 2 (150 mg, 0.50 mmol) and resorcinol (74.8 mg,
0.50 mmol) in DMF (1.5 ml) was stirred for 3 days. Solvent was
evaporated in vacuo and the residue was separated by column
chromatography to give compounds 1 (3 mg, 3 %), 5 (44 mg,
29%, mp 238-239 °C) and 6 as a complex 1:1 with DMF (10 mg,
6%, mp 208-209 °C).
to give triazine 10 as yellow solid with mp 154-156 °C (36 mg,
1
30%): H NMR (DMSO-d ): δ 6.13 (b.s), 6.22 (b.s), 7.47-7.63 (m,
6
3H), 8.10-8.13 (m, 2H), 8.13 (b.s), 8.33 (b.s), 8.80 (s, 1H, C6-H).
Anal. Calcd for C
H N O: C, 52.17; H, 4.38; N, 36.50.
10 10 6
Found: C, 52.20; H, 4.35; N, 36.41.
Compound 9 was obtained as dark red crystals, mp 210-214 °C
7-Hydroxy-3-phenyl-benzo[4,5-e]furo[2,3-e][1,2,4]triazine (6).
1
(80 mg, 48%); H NMR (DMSO-d ): δ 3.82 (d, J = 0.6 Hz, 3H),
6
6.18 (b.s, 2H), 7.42-7.54 (m, 3H), 8.10 (d, J = 0.6 Hz, 1H, C6-
H), 8.11-8.19 (m, 2H), 8.7 b.s (1H, NH); C NMR (DMSO-d ,
Boron trifluoride etherate (61 mg, 0.43 mmol) was added to a
solution of 1 (80 mg, 0.43 mmol) and resorcinol (47 mg, 0.43
mmol) in DMF (2 ml). The reaction mixture was stirred for 3
days at 20 °C with bubbling of air through the solution. Solvent
was evaporated in vacuo and the residue was purified by column
chromatography to give compound 6 as a complex with the DMF,
13
6
300 MHz): δ 49.1, 127.7, 128.5, 131.5, 135.2, 139.8 (C6
),
triazine
144.0 (C=O), 156.4 (C5
), 164.2 (C3
).
triazine
triazine
Anal. Calcd for C H N O•H[BF ]: C, 39.79; H, 3.95; N,
11 12
6
4
25.31. Found: C, 39.58; H, 3.84; N, 25.25.
1
mp 208 °C (decomp.) (38 mg, 26%). H NMR (DMSO-d ): δ
6
1-Acetyl-5-methoxy-3-phenyl-6-ureido-1,6-dihydro-1,2,4-tri-
azine (11a).
2.69 (s, 3H, DMF), 2.89 (s, 3H, DMF), 6.18 (d, J = 8.7 Hz, 1H),
6.33 (d, J = 2.4 Hz, 1H), 6.41 (dd, J = 2.4 Hz, 8.7 Hz, 1H),
7.57–7.68 (m, 3H), 7.96 (s, 1H, DMF), 8.09-8.14 (m, 2H), 9.97
(b.s, 1H).
A mixture of 1 (50 mg, 0.27 mmol) and urea (16 mg, 0.27 mmol)
in acetic anhydride (1.5 ml) was stirred for 48 hours at 20 °C. The