Chemistry of Heterocyclic Compounds 2015, 51(5), 447–456
1H NMR spectrum, δ, ppm (J, Hz): 11.40 (1H, s, NH, D2O
(3H, t, J = 7.4, CH3). Found, %: C 50.28; H 4.89;
N 18.07. C13H15ClN4O3. Calculated, %: C 50.25;
H 4.87; N 18.03.
exchangeable); 7.47 (2H, d, J = 6.0, H Ar); 7.20 (2H, d,
J = 6.0, H Ar); 5.12 (2H, s, NH2, D2O exchangeable); 3.81
(2H, s, CH2). 13C NMR, δ, ppm: 155.0 (C=O); 147.8
(C=N); 136.2; 131.7 (2C); 131.5 (2C); 120.2; 30.5 (CH2).
Mass spectrum, m/z: 291 [M(Br79)+Na]+, 293
[M(Br81)+Na]+. Found, %: C 40.22; H 3.41; N 20.86.
C9H9BrN4O. Calculated, %: C 40.17; H 3.37; N 20.82.
4-Amino-5-(3-bromobenzyl)-2,4-dihydro-3H-1,2,4-triazol-
3-one (3d). Yield 2.01 g (63%). Mp 171–172°C (EtOAc).
1H NMR spectrum, δ, ppm (J, Hz): 11.42 (1H, s, NH); 7.44
(1H, s, H Ar), 7.42–7.35 (1H, d, J = 8.0, H Ar); 7.25 (2H,
d, J = 8.0, H Ar); 5.15 (2H, s, NH2); 3.85 (2H, s, CH2).
13C NMR spectrum, δ, ppm: 155.0 (C=O); 147.7 (C=N);
139.4; 131.9; 131.0; 130.0; 128.4; 122.0; 30.5 (CH2). Mass
spectrum, m/z: 269 [M(Br79)+H]+, 271 [M(Br81)+H]+, 291
[M(Br79)+Na]+, 293 [M(Br81)+Na]+. Found, %: C 40.21;
H 3.42; N 20.89. C9H9BrN4O. Calculated, %: C 40.17; H 3.37;
N 20.82.
Ethyl [4-amino-3-(4-bromobenzyl)-5-oxo-4,5-dihydro-
1H-1,2,4-triazol-1-yl]acetate (4c). Yield 3.05 g (86%).
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Mp 164–165°C. H NMR spectrum, δ, ppm (J, Hz): 7.49
(2H, d, J = 8.0, H Ar); 7.22 (2H, d, J = 8.0, H Ar); 5.33
(2H, s, NH2, D2O exchangeable); 4.49 (2H, s, NCH2); 4.11
(2H, q, J = 7.6, OCH2); 3.86 (2H, s, CH2); 1.18 (3H, t,
J = 7.6, CH3). 13C NMR spectrum, δ, ppm: 168.3 (C=O);
153.7 (C=O); 147.4 (C=N); 135.7; 131.7 (2C); 131.5 (2C);
120.3; 61.5; 47.0; 30.2; 14.5 (CH3). Mass spectrum, m/z:
355 [M(Br79)+H]+, 357 [M(Br81)+H]+, 377 [M(Br79)+Na]+,
379 [M(Br81)+H]+, 393 [M(Br79)+K]+, 395 [M(Br81)+K]+.
Found, %: C 43.91; H 4.20; N 15.73. C13H15BrN4O3.
Calculated, %: C 43.96; H 4.26; N 15.77.
Ethyl [4-amino-3-(3-bromobenzyl)-5-oxo-4,5-dihydro-
1H-1,2,4-triazol-1-yl]acetate (4d). Yield 2.80 g (79%).
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Mp 161–162°C. H NMR spectrum, δ, ppm (J, Hz):7.45
4-Amino-5-(2-bromobenzyl)-2,4-dihydro-3H-1,2,4-triazol-
3-one (3e). Yield 1.45 g (54%). Mp 179–180°C (EtOAc).
1H NMR spectrum, δ, ppm (J, Hz): 11.43 (1H, s, NH); 7.59
(1H, d, J = 8.0, H Ar); 7.33–7.26 (2H, m, H Ar); 7.16 (1H,
t, J = 8.0, H Ar); 5.20 (2H, s, NH2); 3.96 (2H, s, CH2).
13C NMR spectrum, δ, ppm: 165.5 (C=O); 156.2 (C=N);
144.2; 141.9; 139.8; 137.5; 136.3; 132.2; 33.9 (CH2). Mass
spectrum, m/z: 269 [M(Br79)+H]+, 271 [M(Br81)+H]+, 291
[M(Br79)+Na]+, 293 [M(Br81)+Na]+. Found, %: C 40.20;
H 3.40; N 20.88. C9H9BrN4O. Calculated, %: C 40.17; H 3.37;
N 20.82.
(1H, s, H Ar), 7.42 (2H, d, J = 7.8, H Ar); 7.26–7.15 (1H,
m, H Ar); 5.35 (2H, s, NH2); 4.51 (2H, s, NCH2); 4.13 (2H,
q, J = 7.6, OCH2); 3.90 (2H, s, CH2); 1.17 (3H, t, J = 7.2,
CH3). 13C NMR spectrum, δ, ppm: 168.3 (C=O); 153.7
(C=O); 147.3 (C=N); 139.0; 131.9; 131.0; 130.1; 128.4;
122.1; 61.5; 47.1; 30.3; 14.5 (CH3). Mass spectrum, m/z:
355 [M(Br79)+H]+, 357 [M(Br81)+H]+, 377 [M(Br79)+Na]+,
379 [M(Br81)+Na]+, 393 [M(Br79)+K]+, 395 [M(Br81)+K]+.
Found, %: C 43.90; H 4.19; N 15.71. C13H15BrN4O3.
Calculated, %: C 43.96; H 4.26; N 15.77.
Ethyl [4-amino-3-(2-bromobenzyl)-5-oxo-4,5-dihydro-
1H-1,2,4-triazol-1-yl]acetate (4e). Yield 2.63 g (74%).
4-Amino-5-(3,4-dichlorobenzyl)-2,4-dihydro-3H-1,2,4-
triazol-3-one (3f). Yield 2.02 g (78%). Mp 169–170°C
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Mp 169–170°C. H NMR spectrum, δ, ppm (J, Hz): 7.61
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(mp 171–172°C)55. H NMR spectrum, δ, ppm (J, Hz):
(1H, d, J = 8.0, H Ar); 7.34–7.21 (2H, m, H Ar); 7.20–7.15
(1H, m, H Ar); 5.38 (2H, s, NH2); 4.49 (2H, s, NCH2); 4.08
(2H, q, J = 6.8, OCH2); 4.00 (2H, s, CH2); 1.16 (3H, s,
CH3). 13C NMR spectrum, δ, ppm: 168.3 (C=O); 153.7
(C=O); 146.7 (C=N); 135.5; 133.0; 131.5; 129.4; 128.2;
124.5 (C Ar); 61.5 (OCH2); 47.1 (NCH2); 31.4 (CH2); 14.4
(CH3). Mass spectrum, m/z: 355 [M(Br79)+H]+, 357
[M(Br81)+H]+, 377 [M(Br79)+Na]+, 379 [M(Br81)+Na]+.
Found, %: C 43.91; H 4.22; N 15.73. C13H15BrN4O3.
Calculated, %: C 43.96; H 4.26; N 15.77.
11.49 (1H, s, NH); 7.48 (1H, s, H Ar); 7.20 (1H, d,
J = 6.2, H Ar); 7.12 (1H, d, J = 6.2, H Ar); 5.16 (2H, s,
NH2); 3.86 (2H, s, CH2). Found, %: C 41.76; H 3.15;
N 21.66. C9H8Cl2N4O. Calculated, %: C 41.72; H 3.11;
N 21.62.
Synthesis of compounds 4a–f. Compound 3a–f (0.01 mol)
was refluxed with sodium ethoxide (0.68 g, 0.01 mol) in
EtOH (50 ml) for 2 h. Then ethyl bromoacetate (1.84 g,
0.011 mol) was added and the mixture was refluxed for 6 h.
After the reaction was complete (monitored by TLC, eluent
EtOAc–hexane, 3:1), the solvent was evaporated under
reduced pressure. The obtained solid was washed with H2O
and recrystallized from EtOH.
Ethyl [4-amino-3-(3,4-dichlorobenzyl)-5-oxo-4,5-dihydro-
1H-1,2,4-triazol-1-yl]acetate (4f). Yield 3.11 g (90%). Mp
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156–157°C. H NMR spectrum, δ, ppm (J, Hz): 7.56 (1H,
d, J = 8.0, H Ar); 7.51 (1H, d, J = 2.0, H Ar); 7.25 (1H, dd,
J = 8.0, J = 2.0, H Ar); 5.37 (2H, s, NH2); 4.45 (2H, s,
NCH2); 4.11 (2H, q, J = 6.8, OCH2); 3.92 (2H, s, CH2);
1.64 (3H, t, J = 6.8, CH3). 13C NMR spectrum, δ, ppm:
168.3 (C=O); 153.7 (C=O); 147.1 (C=N); 137.4; 131.4;
131.2; 130.9; 129.9; 129.7; 61.5; 47.0; 29.8; 14.4 (CH3).
Mass spectrum, m/z: 367 [M(Cl35)+Na]+, 369
[M(Cl37)+Na]+, 383 [M(Cl35)+K]+, 385 [M(Cl37)+K]+. Found,
%: C 45.28; H 4.14; N 16.28. C13H14Cl2N4O3. Calculated,
%: C 45.23; H 4.09; N 16.23.
Ethyl (4-amino-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-
triazol-1-yl)acetate (4a). Yield 1.68 g (84%). Mp 117–
1
118°C (mp 116°C)56. H NMR spectrum, δ, ppm (J, Hz):
5.39 (2H, s, NH2); 4.45 (2H, s, NCH2); 4.17 (2H, q, J = 7.6,
OCH2); 3.83 (2H, s, CH2); 2.15 (3H, s, CH3), 1.12 (3H, t,
J = 7.6, CH3). Found, %: C 41.96; H 6.01; N 27.92.
C7H12N4O3. Calculated, %: C 42.00; H 6.04; N 27.99.
Ethyl [4-amino-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-
1H-1,2,4-triazol-1-yl]acetate (4b). Yield 2.48 g (80%).
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Mp 159–160°C (mp 156–157°C)54. H NMR spectrum,
Synthesis of compounds 5a–f. Hydrazine monohydrate
(1.25 ml, 0.025 mol) was added to a solution of compound
4a–f (0.01 mol) in n-butanol (15 ml). The mixture was then
refluxed for 3 h. After the mixture was cooled, a white
δ, ppm (J, Hz): 7.56 (2H, d, J = 8.2, H Ar); 7.28 (2H, d,
J = 8.2, H Ar); 5.36 (2H, s, NH2); 4.40 (2H, s, NCH2);
4.12 (2H, q, J = 7.4, OCH2); 3.80 (2H, s, CH2); 1.10
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