894
L. C. Hwang, C. H. Tu and J. H. Wang
Vol 43
mmoles) and a catalytic amount of 18-crown-6-ether (0.08 g, 0.3
mmoles). Then benzyl bromide (0.51 g, 3 mmoles) was added
and refluxed for 24 hours. The solvent was evaporated to afford
a crude product which was then applied to a silica gel (230-400
mesh) column. The column was eluted with a mixed solvent of
chloroform and methanol (60:1) and the proper fractions were
combined and evaporated. The residue thus obtained was
recrystallized from dichloromethane and ethanol (5:1) to give a
white crystal compound 0.46 g (55%) of 9, which was a material
identical in every respect with the corresponding compound in
our previous research [12].
N HCl): ꢁmax nm (log ꢁ) 205 (3.86); (H2O): ꢁmax nm (log ꢁ) 266
(3.73); (0.1 N NaOH): ꢁmax nm (log ꢁ) 218 (3.37), 266 (3.54) ;
1H nmr (200 MHz): ꢀ 4.43 (d, 1H, J = 13.1, CHH-C6H5), 5.03 (d,
1H, J = 13.1, CHH-C6H5), 5.98 (s, 2H, CONH2), 6.49 (s, 2H, 2-
NH2). 7.22 (s, 5H, C6H5), 7.41 (s, 1H, NHNHCO), 7.71 (s, 1H,
NHNHCO); 13C nmr (200 MHz): ꢀ 53.22 (CH2), 141.02 (C-6),
156.56 (C-3), 157.39 (C-5), 158.56 (CO), 128.00, 128.36,
130.12, 135.02 (C6H5); ms: m/z (EI) 275 (M+, 1), 149 (30), 127
(24), 106 (98), 91 (100), 77 (20), 71 (4), 65 (21); hrms: m/z
Calcd. for C11H13N7O2: 275.1131. Found: 275.1131.
Anal. Calcd. for C11H13N7O2: C, 48.00; H, 4.76; N, 35.62.
Found: C, 47.73; H, 4.78; N, 35.41.
3-Amino-2-benzyl-6-(2-formylhydrazino)-1,2,4-triazin-5(2H)-
one (11).
3-Amino-6-azido-2-benzyl-1,2,4-triazin-5(2H)-one (14).
A solution of compound 10 (0.70 g, 3 mmoles) in 99% formic
acid (15 mL) was refluxed for 12 hours. Cooling separated white
crystal 0.42 g. The filtrate was evaporated to 3 mL to give 0.13
g. The total crude compound was recrystallized from ethanol to
afford 11 (0.41 g, 53%). The product was a white crystal with a
conformer mixture in a ratio of about 2:1. The major conformer
was a material identical in every respect with the corresponding
compound in our previous research [12]; and the minor
To a solution of compound 10 (0.70 g, 3 mmoles) in 6 M
hydrochloric acid (6 mL) under stirring at 0 °C, a solution of
sodium nitrite (0.24 g, 3.5 mmoles) in water (6 mL) was added
drop by drop. After the addition was complete, stirring was
continued for an additional 10 minutes and the precipitate was
collected. The solid precipitate was suspended in 15 mL of water
and was stirred at room temperature overnight. Collection of the
precipitate and recrystallization from ethanol produced 14 (0.45
g, 62%), mp 170-171 °C (from EtOH); ir: (ꢀ, cm–1) 3380, 3113,
2122 (N3), 1642 (C=O), 1535, 1374, 1271, 1152, 1081; uv: (0.1
N HCl): ꢁmax nm (log ꢁ) 206 (3.68), 238 (3.31), 296 (3.02), 298
(3.15); (H2O): ꢁmax nm (log ꢁ) 206 (3.95), 234 (3.94), 236 (3.52),
1
conformer showed the following spectral data: H nmr (400
MHz): ꢀ 5.00 (s, 2H, CH2), 7.02 (s, 2H, NH2), 7.22-7.37 (m, 5H,
C6H5), 7.92 (d, 1H, J = 10.8, NHNHCO), 8.75 (s, 1H, CHO),
9.27 (d, 1H, J = 10.8, NHNHCO); 13C nmr (200 MHz): ꢀ 54.95
(CH2), 146.58 (C-6), 154.58 (C-3), 158.28 (C-5), 167.55 (CO).
1
294 (3.34); (0.1 N NaOH): ꢁmax nm (log ꢁ) 239 (3.49); H nmr
(200 MHz): ꢀ 5.08 (s, 2H, CH2), 7.27-7.39 (m, 5H, C6H5), 7.46
(s, 2H, NH2); 13C nmr (400 MHz): ꢀ 55.34 (CH2), 142.73 (C-6),
154.96 (C-3), 158.70 (C-5), 127.24, 127.78, 128.61, 135.21
(C6H5); ms: m/z 243 (M+, 1), 217 (4), 129 (2), 106 (9), 91 (100),
77 (12), 69 (16), 65 (49); hrms: m/z Calcd. for C10H9N7O:
243.0869. Found: 243.0872.
3-Amino-2-benzyl-6-(2-acetylhydrazino)-1,2,4-triazin-5(2H)-
one (12).
A solution of compound 10 (0.70 g, 3 mmoles) in glacial
acetic acid (15 mL) was refluxed for 12 hours. Cooling
separated white crystal 0.61 g. The filtrate was evaporated to 3
mL to give 0.11 g. The total crude compound was recrystallized
from ethanol to afford 12 (0.61 g, 74%). The product was a
white crystal with a conformer mixture in a ratio of about 10:1;
mp > 300 °C (from EtOH); ir: (ꢀ, cm–1) 3366, 3190, 1639
(C=O), 1508, 1267, 1077; uv: (0.1 N HCl): ꢁmax nm (log ꢁ) 207
(4.01), 240 (3.80), 294 (3.55); (H2O): ꢁmax nm (log ꢁ) 222 (3.88),
285 (3.35); (0.1 N NaOH): ꢁmax nm (log ꢁ) 229 (4.41), 268
Anal. Calcd. for C10H9N7O: C, 49.38; H, 3.73; N, 40.31.
Found: C, 49.65; H, 3.66; N, 40.38.
3-Amino-6-hydrazino-2-[(2-hydroxyethoxy)methyl]-1,2,4-triazin-
5(2H)-one (16).
A solution of compound 15 (0.53 g, 2 mmoles) and hydrazine
monohydrate (0.4 g, 8 mmoles) in ethanol (30 mL) was refluxed
for 16 hours. Evaporating the solvent to 5 mL in vacuo afforded
a crude solid which was recrystallised from methanol to give
white crystal compound 16 (0.32g, 74%), mp 214-215 °C (from
MeOH); ir: (ꢀ, cm–1) 3397, 3362, 1677 (C=O), 1618, 1561,
1511, 1109, 1054; uv: (0.1 N HCl): ꢁmax nm (log ꢁ) 221 (4.25),
272 (3.73); (H2O): ꢁmax nm (log ꢁ) 224 (4.19), 288 (3.51); (0.1 N
1
(4.11), 332 (3.98); the major conformer H nmr (400 MHz): ꢀ
1.81 (s, 3H, CH3), 4.96 (s, 2H, CH2), 6.96 (s, 2H, NH2), 7.23-
7.37 (m , 5H, C6H5), 8.04 (d, 1H, J = 2.2, NHNHCO), 9.60 (d,
1H, J = 2.2, NHNHCO); 13C nmr (400 MHz): ꢀ 20.51 (CH3),
54.88 (CH2), 145.16 (C-6), 154.11 (C-3), 158.04 (C-5), 168.02
(CO), 127.13, 127.50, 128.44, 135.85 (C6H5); the minor
1
1
conformer H nmr (400 MHz): ꢀ 1.73 (s, 3H, CH3), 5.00 (s, 2H,
NaOH): ꢁmax nm (log ꢁ) 225 (4.31); H nmr (200 MHz): ꢀ 3.52-
CH2), 7.01 (s, 2H, NH2), 7.23-7.37 (m, 5H, C6H5), 7.35 (d, 1H, J
= 15.6, NHNHCO), 8.73 (d, 1H, J = 15.6, NHNHCO); ms: m/z
(EI) 274 (M+, 14), 232 (13), 141 (35), 91 (100), 69 (8), 65 (19);
hrms: m/z Calcd. for C12H14N6O2: 274.1178. Found: 274.1180.
Anal. Calcd. for C12H14N6O2: C, 52.55; H, 5.14; N, 30.64.
Found: C, 52.53; H, 5.17; N, 30.40.
3.58 (m, 4H, OCH2CH2O), 3.92 (s, 2H, NHNH2), 4.72 (t, 1H, 4'-
OH), 5.17 (s, 2H, NCH2O), 6.90 (s, 2H, NH2), 7.30 (s, 1H,
NHNH2); 13C nmr (200 MHz): ꢀ 60.31 (C-4'), 70.52 (C-3'),
81.88 (C-1'), 146.96 (C-6),154.69 (C-3), 158.87 (C-5); ms: m/z
216 (M+, 31), 153 (32), 142 (100), 113 (7), 91 (30), 85 (27), 69
(69).
Anal. Calcd. for C6H12N6O3: C, 33.33; H, 5.59; N, 38.87.
Found: C, 33.43; H, 5.62; N, 38.91.
2-N-(2-Amino-1-benzyl-4-oxo-1,2,4-triazin-5-yl)semicarbazide (13).
A solution of compound 10 (0.70 g, 3 mmoles) with cyanogen
bromide (0.64 g, 6 mmoles) in water (20 mL) was refluxed for
24 hours. Cooling separated a white crystal compound, which
was washed with ice water and then recrystallized from ethanol
to give product 13 (0.48 g, 58%), mp 263-265 °C (from EtOH);
ir: (ꢀ, cm–1) 3330, 3215, 1679 (C=O), 1589, 1451, 1089; uv: (0.1
6-Amino-3-methyl-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one (3b).
Method A. A solution of compound 16 (0.43 g, 2 mmoles) in
glacial acetic acid (10 mL) was refluxed for 12 hours (monitored
by tlc). Removal of excess acid in vacuo followed by
recrystallization from water afforded a white crystal compound