Synthesis of 3,5-diaryl-4-benzylidene-amino-1,2,4-triazoles and 4-amino-3,5-diaryl-1,2,4-triazoles

Article abstract of DOI:10.1023/A:1013227632521

A one-pot reaction leading to 3,5-diaryl-4-benzylideneamino-1,2,4-triazoles is described, the key step of which is the reaction of arenecarbohydrazonoyl chloride with benzylidenehydrazide. Compounds obtained in this way were hydrolyzed to 4-amino-3,5-diaryl-1,2,4-triazoles.

Full text of DOI:10.1023/A:1013227632521

Chemistry of Heterocyclic Compounds, Vol. 37, No. 9, 2001
SYNTHESIS OF 3,5-DIARYL-4-BENZYLIDENE-
AMINO-1,2,4-TRIAZOLES AND 4-AMINO-
3,5-DIARYL-1,2,4-TRIAZOLES
W. Zielinski, W. Czardybon
A one-pot reaction leading to 3,5-diaryl-4-benzylideneamino-1,2,4-triazoles is described, the key step of
which is the reaction of arenecarbohydrazonoyl chloride with benzylidenehydrazide. Compounds
obtained in this way were hydrolyzed to 4-amino-3,5-diaryl-1,2,4-triazoles.
Keywords: 4-amino-3,5-diaryl-1,2,4-triazole, 3,5-diaryl-4-benzylideneamino-1,2,4-triazole, benzylidene-
hydrazide, cyclization.
Methods for the synthesis of heterocyclic compounds containing a nitrogen–nitrogen bond often start
from hydrazonyl compounds. For instance, tetrazoles have been prepared by the reaction of 1-chloro-2,3-
diazabutadienes with the azide anion [1, 2]. Similarly 1,2,4-triazoles were obtained by the reaction of 1-chloro-
2,3-diazabutadienes with ammonia or amines [3].
Recently we have described the reaction of 1-chloro-2,3-diazabutadienes with titanium tetrachloride
which gives dihydro-1,2,4,5-tetrazines [4].
1-Chloro-2,3-diazabutadienes are readily synthesized in three steps. Interac-tion of carboxylic esters and
hydrazine hydrate yields hydrazides, which react with aromatic aldehydes to afford arylidenehydrazides 1 [5].
Transformation of the latter with chlorinating agents, e.g., PCl5, SOCl2 or POCl3, finally gives the target
chlorides [6].
Results and Discussion
In this work we studied the synthesis of 1,2,4-triazole derivatives from 1,3-chloro-2,3-diazabutadienes.
Starting hydrazonyl chlorides were synthesized in situ from arylidenehydrazides 1 and POCl3. 1-Chloro-2,3-
diazabutadienes 2 were found to undergo condensation in situ with unreacted hydrazides 1 to 4-arylideneamino-
1,2,4-triazoles 3 in boiling toluene in the presence of acetonitrile (Scheme and Table 1).
Acetonitrile facilitates the formation of carbocation by increasing the polarity of the reaction media.
4-Arylideneamino-1,2,4-triazoles 3 were hydrolyzed in boiling aqueous methanol in the presence of
hydrochloric acid to yield 4-amino-1,2,4-triazoles 4 (Scheme and Table 1).
__________________________________________________________________________________________
Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland; e-mail:
wojtekcz@zeus.polsl.gliwice.pl. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1207-1210,
September, 2001. Original article submitted August 28, 2000.
0009-3122/01/3709-1107$25.00©2001 Plenum Publishing Corporation
1107

TABLE 1. Characteristics of 4-Arylideneamino-1,2,4-triazoles 3 and
4-Amino-1,2,4-triazoles 4
Compounds
3, 4
3
4
R
R'
Yield, %
mp, °C
Yield, %
mp, °C
Ph
Ph
Ph
Ph
Ph
Ph
83
92
78
90
71
81
145-147*
152-153
165-166
143-145
189-190
172-174
93
91
88
90
86
—
268-269*2
242-244*3
210-212
245-246*4
>250
a
b
c
d
e
f
3- MeC6H4
3-ClC6H4
3-MeOC6H4
3-NO2C6H4
Ph
2-MeC6H4
—
_______
* Isolated as a trihydrate (microanalysis).
*2 Ref. [7] mp 269°C.
*3 Ref. [8] mp 176-177°C.
*4 Ref. [9] mp 244°C.
Scheme
Cl
H O
POCl3
POCl3
MeCN
R'–CH=N–N=C–R
R'–CH=N–N–C–R
2
1
H
O
O
H
N
N
+
+
1
+
R'
R'–CH=N–N–C–R
R
R'–CH:N–N=C–R
R
R'–CH=N–N
C
+
O
N
N
R
NH
N
R
N
N
R
R'
R'
R'
1. HCl, H2O
2. NaOH
N
N
+
N
N
–H
R
R
N
NH2
R
R
N
N
–R'CHO
–R'CHO
R'
4
3
EXPERIMENTAL
1
Toluene was distilled from sodium prior to use and stored over sodium. POCl3 was distilled. H NMR
spectra were recorded on a Varian Unity-Nova 300 spectrometer (300 MHz) as solutions in methanol-d4. Mass
spectra were recorded on the GC-MS QP-2000 Schimadzu spectrometer.
1108

3,5-Diaryl-4-arylideneamino-1,2,4-triazoles
(3a–f).
General
procedure:
Arylidene
arenecarbohydrazide (1) (0.018 mol), acetonitrile 3 ml, and POCl3 (0.018 mol) in 50 ml of toluene were refluxed
for 14 hours with exclusion of moisture. The mixture was cooled and poured on 50 g of ice. The gluey
precipitate was separated. After its crystallization from CHCl3 3,5-diaryl-4-arylideneamino-1,2,4-triazole (3)
was obtained.
4-Amino-3,5-diaryl-1,2,4-triazoles (4a–e). General procedure: 3,5-Diaryl-4-benzylidene- amino-1,2,4-
triazole (3) (1.0 mmol) was dissolved in 20 ml of ethanol, then 20 ml of 10% hydrochloric acid was added. The
mixture was refluxed for 2 hours, diluted with 20 ml of water and filtered. The filtrate was alkalyzed with 10%
NaOH and then the precipitate was collected. After crystallization from ethanol 4-amino-3,5-diaryl-1,2,4-
triazole (4) was obtained.
4-Benzylideneamino-3,5-diphenyl-1,2,4-triazole (3a·3H2O). 1H NMR spectrum, ppm: 7.70-7.41 (13H,
m, Ph); 8.02 (2H, m, H-2, H-6 in PhCH=N); 8.58 (1H, s, N=C–H). Mass spectrum (m/z, Irel, %): 324
(M+ - 3H2O), 221. Found, %: C 66.52; H 5.53; N 14.43. C21H16N4·3H2O. Calculated, %: C 66.67; H 5.82;
N 14.81.
1
4-Benzylideneamino-3,5-bis(3-methylphenyl)-1,2,4-triazole (3b). H NMR spectrum, ppm: 2.36 (3H,
s, CH3); 2.43 (3H, s, CH3); 7.45-7.65 (11H, m, Ar); 8.01 (2H, m, H-2, H-6 in N=CH–Ph); 8.59 (1H, s, N=C–H).
Mass spectrum (m/z, Irel, %): 352 (M+), 249. Found, %: C 78.13; H 5.55; N 15.69. C23H20N4. Calculated, %:
C 78.41; H 5.68; N 15.91.
1
4-Benzylideneamino-3,5-bis(3-chlorophenyl)-1,2,4-triazole (3c). H NMR spectrum, ppm: 7.50-7.56
(6H, m, Ar); 7.65 (1H, t, J = 7.8 Hz, H-4 in N=CH–Ph); 7.79-7.84 (4H, m, Ar); 7.94 (2H, s, Ar); 8.50 (1H, s,
N=C–H). Mass spectrum (m/z, Irel, %): 392 (M+), 289, 255. Found, %: C 63.83; H 3.35; N 14.20. C21H14Cl2N4.
Calculated, %: C 64.14; H 3.56; N 14.25.
1
4-Benzylideneamino-3,5-bis(3-methoxyphenyl)-1,2,4-triazole (3d). H NMR spectrum, ppm: 3.81
(3H, s, OCH3); 3.84 (3H, s, OCH3); 7.21-7.61 (9H, m, Ar); 7.17 (2H, m, Ar); 8.01 (2H, m, H-2, H-6 in
PhCH=N); 8.58 (1H, s, N=C–H). Mass spectrum (m/z, Irel, %): 384 (M+), 281. Found, %: C 71.53; H 5.04;
N 14.25. C23H20N4O2. Calculated, %: C 71.88; H 5.21; N 14.58.
1
4-Benzylideneamino-3,5-bis(3-nitrophenyl)-1,2,4-triazole (3e). H NMR spectrum, ppm: 7.54 (2H,
dd, J = 7.8, J' = 7.2 Hz, H-3, H-5 in N=CH–Ph); 7.65 (1H, t, J = 7.8 Hz, H-4 in N=CH–Ph); 7.70 (2H, dd,
J = 8.4, J' = 7.8 Hz, H-5 in 3-NO2C6H4); 7.82 (2H, d, J = 8.4 Hz, H-4 in 3-NO2C6H4); 8.24 (1H, s, N=C–H); 8.33
(2H, m, H-2, in N=CH–Ph); 8.36 (2H, d, J = 7.8 Hz, H-6 in 3-NO2C6H4); 8.94 (2H, s, H-2 in 3-NO2C6H4). Mass
spectrum (m/z, Irel, %): 414 (M+), 311. Found, %: C 60.71; H 3.45; N 20.10. C21H14N6O4. Calculated, %:
C 60.87; H 3.38; N 20.29.
4-(2-Methylbenzylideneamino)-3,5-diphenyl-1,2,4-triazole (3f). 1H NMR spectrum, ppm: 2.03 (3H, s,
CH3); 7.18 (1H, d, J = 7.8 Hz, H-3 in ArCH=N); 7.31 (1H, dd, J = 7.2, J' = 7.5 Hz, H-5 in ArCH=N); 7.41 (1H,
d, J = 7.5 Hz, H-6 in ArCH=N); 7.45-7.51 (6H, m, Ar); 7.91-7.96 (5H, m, Ar); 8.43 (1H, s, N=C–H). Mass
spectrum (m/z, Irel, %): 338 (M+), 221. Found, %: C 77.78; H 5.19; N 16.47. C22H18N14. Calculated, %: C 78.11;
H 5.33; N 16.57.
4-Amino-3,5-diphenyl-1,2,4-triazole (4a). 1H NMR spectrum, ppm: 4.89 (2H, s, NH2); 7.56-7.54 (6H,
m, H-2, H-4, H-6; Ph); 7.99 (4H, dd, J = 6.0, J' = 7.2 Hz, H-3, H-5, Ph). Mass spectrum (m/z, Irel, %): 236 (M+),
133. Found, %: C 71.31; H 5.21; N 23.51. C14H12N4. Calculated, %: C 71.19; H 5.08; N 23.73.
1
4-Amino-3,5-bis(3-methylphenyl)-1,2,4-triazole (4b). H NMR spectrum, ppm: 2.44 (6H, s, CH3);
4.82 (2H, s, NH2); 7.33 (2H, d, J = 7.5 Hz, H-4, Ar); 7.42 (2H, dd, J = 7.8, J' = 7.5 Hz, H-5, Ar); 7.73 (2H, d,
J = 7.5 Hz, H-6, Ar); 7.77 (2H, s, H-2, Ar). Mass spectrum (m/z, Irel, %): 264 (M+), 147. Found, %: C 72.96;
H 5.87; N 21.02. C16H16N4. Calculated, %: C 72.73; H 6.06; N 21.21.
e
1H NMR spectrum, ppm: 4.88 (2H, s, NH2);
4-Amino-3,5-bis(3-chlorophenyl)-1,2,4-triazol (4c).
7.52-7.60 (4H, m, H-4, H-5, Ar); 7.97 (2H, d, J = 7.9 Hz, H-6, Ar); 8.08 (2H, s, H-2, Ar). Mass spectrum (m/z,
Irel, %): 304 (M+), 167. Found, %: C 55.41; H 3.41; N 18.19. C14H10Cl2N4. Calculated, %: C 55.10; H 3.28;
N 18.37.
1109

4-Amino-3,5-bis(3-methoxyphenyl)-1,2,4-triazole (4d). 1H NMR spectrum, ppm: 3.88 (6H, s, OCH3);
4.88 (2H, s, NH2); 7.12 (2H, d, J = 8.1 Hz, H-4, Ar); 7.47 (2H, dd, J = 8.1, J' = 8.1 Hz, H-5, Ar); 7.57 (2H, d,
J = 8.1 Hz, H-6, Ar); 7.90 (2H, s, H-2, Ar). Mass spectrum (m/z, Irel, %): 296 (M+), 163. Found, %: C 64.98;
H 5.37; N 18.70. C16H16N4O2. Calculated, %: C 64.86; H 5.41; N 18.92.
1
4-Amino-3,5-bis(3-nitrophenyl)-1,2,4-triazole (4e). H NMR spectrum, ppm: 4.80 (2H, s, NH2);
7.82-7.93 (4H, m, H-4, H-5, Ar); 8.42 (2H, d, J = 7.8 Hz, H-6, Ar); 9.01 (2H, s, H-2; Ar). Mass spectrum (m/z,
Irel, %): 326 (M+), 178. Found, %: C 51.71; H 3.18; N 25.65. C14H10N6O4. Calcuted, %: C 51.53; H 3.07;
N 25.77.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
P. A. Cashell, A. F. Hegarty, and F. L. Scott, Tetrah. Lett., 4767 (1971).
A. F. Hegarty, K. Brady, and M. J. Mullane, J. Chem. Soc. Chem. Commun., 871 (1978).
J. T. A. Boyle, M. F. Grundon, and M. D. Scott, J. Chem. Soc. Perkin Trans. 1, 207 (1976).
W. Zielinski and W. Czardybon, Pol. J. Appl. Chem., No. 1, 37 (2000).
L. Horner and H. Fernekess, Chem. Ber., 94, 712 (1961)
W. T. Flowers, D. R. Taylor, A. E. Tipping, and C. N. Wright, J. Chem. Soc. (C), 1986 (1971).
R. A. Bowie, M. D. Gardner, D. G. Nellson, K. M. Watson, S. Mahmood, and V. Ridd, J. Chem. Soc.
Perkin Trans. 1, 2395 (1972)
8.
9.
E. Müller and L. Herrdegen, J. prakt. Chem., 102, 113 (1921)
C. R. Grammaticakis, Compt. Rend. Seances Acad. Sci. Fr., 258, 1262 (1964).
1110