Acyl and sulfonyl derivatives of 3,5-diamino-1-r-1,2,4-triazoles

Article abstract of DOI:10.1007/s10593-005-0293-2

3-Acylamino-5-amino-1-R-1,2,4-triazoles are formed regioselectively on acylating 3,5-diamino-1-R-1,2,4-triazoles with an equimolar amount of anhydrides, carboxylic acid chlorides, and sulfonyl chlorides. With an excess of anhydride and carboxylic acid chl

Full text of DOI:10.1007/s10593-005-0293-2

Chemistry of Heterocyclic Compounds, Vol. 41, No. 9, 2005
ACYL AND SULFONYL DERIVATIVES
OF 3,5-DIAMINO-1-R-1,2,4-TRIAZOLES
V. M. Chernyshev, V. A. Rakitov, V. A. Taranushich, and V. V. Blinov
3-Acylamino-5-amino-1-R-1,2,4-triazoles are formed regioselectively on acylating 3,5-diamino-1-R-
1,2,4-triazoles with an equimolar amount of anhydrides, carboxylic acid chlorides, and sulfonyl
chlorides. With an excess of anhydride and carboxylic acid chloride 3,5-diacylamino-1-R-1,2,4-triazoles
are formed. 3-Acylamino-5-amino-1-R-1,2,4-triazoles do not interact with sulfonyl chlorides. The higher
reactivity of the 3-amino group towards acylating agents is determined by electronic and not steric
factors.
Keywords: 3-acylamino-5-amino-1-R-1,2,4-triazoles, 5-amino-3-sulfonylamino-1-R-1,2,4-triazoles,
amino-, 3,5-diamino-1,2,4-triazole, 3,5-diacylamino-1,2,4-triazoles, 1,2,4-triazole, acylation,
regioselectivity, structure.
Depending on the reaction conditions, acylation of unsubstituted 3,5-diamino-1,2,4-triazole leads to the
formation of acylation products at both the ring N(1) atom and at the exocyclic amino groups [1-4]. The direction
of acylation of 3,5-diamino-1-R-1,2,4-triazole 1 has not been established precisely up to the present time. It has
been shown that brief heating of 3,5-diamino-1-phenyl-1,2,4-triazole (1a ) with acetic anhydride leads to the
formation of a monoacetyl derivative, but refluxing in an excess of anhydride leads to the formation of a diacetyl
derivative, the structures of which were not determined [5]. The product of the interaction of 1a with acetoacetic
ester was assigned the structure of 1-acetoacetyl-3,5-diimino-2-phenyl-1,2,4-triazole [6], but with cyanates and
thiocyanates the carbamoyl and thiocarbamoyl derivatives at one of the exocyclic amino groups were formed [7].
The problem of the reaction direction remained open.
The aim of the present work is the determination of the direction of acylation and sulfonation reactions
of 3,5-diamino-1-R-1,2,4-triazoles 1a,b.
It was established that the interaction of compounds 1a,b with an equimolar quantity of anhydrides 2a-c,
carboxylic acid chlorides 2d-f,i, and sulfonyl chlorides 2g,h proceeds regioselectively and gives 3-acylamino-5-
amino-1-R-1,2,4-triazoles 3a-f,i,j and 5-amino-3-sulfonylamino-1-R-1,2,4-triazoles 3g,h,k in good yield
(Scheme 1, Table 1).
According to the data of [8, 9] the 1H NMR spectra of 3,5-diamino-1-R-1,2,4-triazoles in DMSO-d6 have
broad discernible singlets for the protons of the 3-NH2 and 5-NH2 groups in the region of 5 and 6 ppm
respectively. The chemical shifts of 5.08 and 4.75 (3-NH2), 6.15 and 6.05 ppm (5-NH2) correspond to the
1
protons of the amino groups of compounds 1a,b. In the H NMR spectra of compounds 3a-k the 3-NH2 signal
has disappeared, but a signal for an amide proton appears at 9.8-12.5 ppm. The singlet of the 5-NH2 protons is
displaced a little towards low field and appears in the range 6.25-6.60 ppm (Table 2). These values of the
__________________________________________________________________________________________
South-Russian State Technical University, Novocherkassk 346428, Russia; e-mail: tnw@novoch.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1342-1350, September, 2005. Original
article submitted April 19, 2005.
0009-3122/05/4109-1139©2005 Springer Science+Business Media, Inc.
1139

Scheme 1
R1X
2a,b,d–i
R
R
O
O
N
N
N
N
R1
N
NH2
H2N
NH2
N
H
N
3a–k
1a,b
O
2c
R1
N
H
N
N
BnCl
MeONa
NH
NH2
3i–k
10a–c
1a, 3a-h R = Ph; 1b, 3i-k R = Bn; 2a, 3a,i, 10a R1 = Ac; 2b, 3b R1 = CF3CO;
3c R1 = HO2C(CH2)2CO; 2d, 3d R1 = PrCO; 2e, 3e, 10b R1 = p-MeC6H4CO;
2f, 3f R1 = p-O2NC6H4CO; 2g, 3g,k, 10c R1 = Ts; 2h, 3h R1 = MeSO2; 2i, 3j R1 = PhCO;
2a,b X = OR1; 2d-i X = Cl
chemical shifts are in good agreement with those of protons of the amino group of 5-amino-3-arylideneamino-1-
R-1,2,4-triazoles 4 [9], but are substantially different from the chemical shifts of the NH2 of compounds 5 [10],
which may be considered as structural analogs of the isomers of acyl derivatives 3a-f.i,j.
TABLE 1. Characteristics of Compounds 3a-k
Yield, %,
(method of
synthesis)
Found, %
Calculated, % N
Com-
pound
Empirical
formula
——————
mp, °С*
3a
C10H11N5O
32.2
32.2
25.9
25.8
25.2
25.4
239-241
213-214
90 (A)
61 (A)
63 (A)
3b
3c
C10H8F3N5O
C12H13N5O3
206
(dec.)
3d
3e
3f
C12H15N5O
C16H15N5O
C15H12N6O3
28.8
28.6
24.0
23.9
26.1
25.9
177-179
75
231-232
71 (A)
89 (A)
282
(dec.)
3g
C15H15N5O2S
21.3
21.3
256-257
73 (A),
96 (C)
3h
3i
C9H11N5O2S
C11H13N5O
27.7
27.8
30.5
30.3
262-263
224-225
81 (A)
75 (A),
70 (B)
3j
C16H15N5O
23.9
23.7
168-170
271-273
63 (A),
45 (B)
3k
C16H17N5O2S
20.4
20.4
65 (A)
_______
* Solvents: EtOH (compounds 3a-e,h-j) and DMF–EtOH (compounds 3f,g,k).
1140

Ar
R
Ar
N
N
δ = 5.27-5.43 ppm
H2N
δ = 6.40-6.70 ppm
N
N
N
N
N
NH2
N
H
O
4
5
The values of the absorption frequencies of the carbonyl group of compounds 3a-f,i,j (1650-1680 cm-1)
indicate that the acyl group is linked with one of the amino groups and not with the nitrogen of the triazole ring
[2, 3, 11]. Otherwise the frequency of the vibrations of the carbonyl group must have a higher value
(1700-1735 cm-1) [3, 11]. In the IR spectra of compounds 3a-k there are characteristic absorption bands for a
free amino group at 3370-3470 cm-1.
The UV spectra of the acyl derivatives having no additional chromophores in the acyl group, are
analogous to the spectra of acylamino-1,2,4-triazoles described in the literature [11].
Additional conformation of the position of the acyl group was obtained by the conversions shown on
Scheme 2.
On condensing compound 3a with benzaldehyde and hydrogenating the resulting benzylidene derivative
6 to compound 7 with subsequent hydrolysis, the benzyl derivative 8 is formed which proved to be isomeric with
the benzyl derivative 9, obtained by us by hydrogenation of 5-amino-3-benzylideneamino-1-phenyl-1,2,4-
triazole (4a), the structure of which was established in [9].
TABLE 2. Characteristics of Compounds 3a-k
IR spectrum,
UV spectrum,
λ
Com-
pound
1Н NMR spectrum, δ, ppm (J, Hz)
ν, cm-1
max,nm (ε·10-3)
3a
3b
3c
2.05 (3Н, s, CH3); 6.38 (2H, s, NH2);
7.30-7.55 (5Н, m, C6H5); 9.92 (1H, s, NH)
1670 (CO),
3430 (NH2)
246 (8.9)
6.40 (2H, s, NH2); 7.25-7.40 (3Н, m, arom.);
8.0 (2Н, m, arom.); 12.5 (1H, s, NH)
1680 (CO),
3430 (NH2)
288 (21.5)
2.45 (4Н, m, 2CH2); 6.47 (2H, s, NH2);
7.30-7.55 (5Н, m, C6H5); 10.12 (1H, s, NH);
12.10 (1Н, br. s, НО)
1700 (CO),
3470 (NH2)
244 (9.6)
246 (9.1)
3d
0.94 (3Н, t, J = 7.4, CH3), 1.60 (2Н, m, СН2);
2.25 (2Н, m, СН2); 6.38 (2H, s, NH2);
1650 (CO),
3360 (NH2)
7.28-7.56 (5Н, m, C6H5); 9.89 (1H, s, NH)
3e
3f
2.40 (3Н, s, CH3); 6.35 (2H, s, NH2);
7.21-7.88 (9H m, arom.); 10.27 (1H, s, NH)
1670 (CO),
3470 (NH2)
246 (18.2)
256 (15.1)
6.45 (2H, s, NH2); 7.35-7.50 (5Н, m, C6H5);
8.17 (2H, d, J = 8.9, arom.); 8.33 (2H, d,
J = 8.9, arom.); 10.80 (1H, s, NH)
1680 (CO),
3440 (NH2)
3g
3h
3i
2.38 (3Н, s, CH3); 6.40 (2H, s, NH2);
7.30-7.85 (9Н, m, arom.); 10.65 (1H, s, NH)
1160 (SO2),
3470 (NH2)
223 sh. (18.7),
248 sh. (8.3)
3.25 (3Н, s, CH3); 6.60 (2H, s, NH2);
7.32-7.50 (5Н, m, C6H5); 10.46 (1H, s, NH)
1150 (SO2),
3440 (NH2)
246 sh.
(5.5)
2.0 (3Н, s, CH3); 5.01 (2Н, s, СН2);
6.25 (2H, s, NH2); 7.15-7.38 (5Н, m, C6H5);
9.80 (1H, s, NH)
1660 (CO),
3370 (NH2)
227 sh.
(7.1)
3j
5.07 (2Н, s, СН2); 6.30 (2H, s, NH2);
7.25-7.50 (8Н, m, arom.); 7.92 (2Н, m, arom.);
10.15 (1H, s, NH)
1670 (CO),
3450 (NH2)
224 sh.
(13.6)
3k
2.41 (3Н, s, CH3); 4.93 (2Н, s, СН2);
6.27 (2H, s, NH2); 7.09-7.28 (7Н, m, arom.);
7.73 (2Н, m, arom.); 10.40 (1H, s, NH)
1150 (SO2),
3430 (NH2)
223 sh.
(14.4)
1141

Scheme 2
Ph
PhCHO
Ac
N
N
NaBH4
N
3a
N
H
N
Ph
6
Ph
Ph
N
N
Ac
N
N
H+
EtOH
N
N
H2N
N
H
Bn
Bn
N
H
N
H
7
8
Ph
Ph
N
N
Ph
NaBH4
Bn
N
N
N
N
N
H
NH2
N
9
NH2
4a
Compounds 3i-k were obtained by an alternate synthesis by the benzylation of compounds 10a-c, which
excludes structures in which the acyl or sulfonyl group is linked with the endocyclic nitrogen atom.
We propose that the higher nucleophilicity of the 3-amino group is caused by electronic and not by steric
factors since the benzyl group in compound 9 has no influence on the reaction direction. The interaction of
triazole 9 with acylating agents 2a,g occurs at the amino group in position 3 of the ring with the formation of
compounds 11a,b. Products of monoacylation at the amino group in position 5 were not detected. Compound 12,
which is a by-product, is probably formed as a result of the acylation of triazole 11a with an excess of anhydride
2a.
Bn
Bn
Ac
Bn
Ph
Ph
Ph
N
N
N
N
2a,g
N
N
N
N
N
N
N
N
H
Ac
Py
NH2
R1
N
H
NH2
11a,b
11 a R1 = Ac, b R1 = Ts
12
9
The reduction in the nucleophilicity of the 5-amino group in comparison with the amino group in
position 3 was also noted in [9, 12] and is probably connected with the fact that the 5-amino group is in linear
conjugation with the electron-withdrawing system of double bonds of the triazole ring, but the 3-amino group is
in cross conjugation. This difference is confirmed, according to data of X-ray structural analysis, by the
reduction of the C(5)–NH2 bond length compared with C(3)-NH2 in the molecules of 3,5-diamino-1,2,4-triazole
and the isomeric 1-R-3(5)-alkylthio-5(3)-amino-1,2,4-triazoles [13-15].
On interacting compound 1a with an excess of acylating agent, 3,5-diacylamino-1-phenyl-1,2,4-triazoles
13a,b were successfully obtained, in spite of the reduction in nucleophilicity of the 5-amino group.
Ph
Ph
O
O
N
N
N
N
LiAlH4
R1
R1
R1
13b
R1
N
N
N
N
N
N
H
H
H
H
13a,b
14
13a R1 = Me, 13b, 14 R1 = p-MeC6H4
1142

Signals for the protons of free amino groups were absent from the 1H NMR spectra of compounds 13a,b,
but there were signals for two amide protons at 10.48-11.05 ppm. The band for the free amino group vibrations
at 3370-3470 cm-1 disappears from the IR spectra (Table 2). The UV spectra were analogous to the spectra of the
two acylamino-1,2,4-triazoles described in [11]. The structure of compound 13b was confirmed by its
hydrogenation to the dialkyl derivative 14.
On acylating triazole 3g with acid chloride 2e in boiling acetonitrile in the presence of pyridine a
compound was obtained, which on the basis of spectral data and elemental analysis, was assigned the structure of
5-amino-1-phenyl-3-(N-p-toluenesulfonyl)amino-1,2,4-triazole (15). The 3-amino group therefore displays a
definite nucleophilicity even after sulfonation. Acylation of compound 3g in boiling pyridine or boiling
compound 15 in pyridine in the presence of catalytic amounts of acid chloride leads to the formation of the
thermodynamically more stable compound 16. Migration of the p-methylbenzoyl but not the tosyl group was
confirmed. This was demonstrated by acid hydrolysis of compound 16 to the initial 3g.
Ph
Ph
N
N
N
N
Py, 120 oC
2e
Ts
Ts
R
3g
N
N
N
NH2
MeCN + Py,
80 oC
N
N
H
H
R
15
Py, 120 oC
R = p-MeC6H4CO
16
2e,
A mixture of reaction products was formed during attempts to obtain diacyl derivatives of triazoles 1a,b,
uniting the different acyl groups in one molecule, by acylating compounds 3a-f,i,j. The reason for this is
probably the formation of intermediates analogous in structure to compound 15. As a result of lability and the
possibility of migration of any of the acyl groups, rearrangement of these intermediates leads to the formation of
a mixture of compounds. Acylation of the 5-amino group with sulfonyl chlorides 2g,h was unsuccessful,
probably due to the reduced reactivity of sulfonyl chlorides compared with carboxylic acid chlorides and
anhydrides. On interacting compounds 1a,b and 9 with an excess of the sulfonyl chlorides in pyridine only
monosulfonyl derivatives 3g,h,k and 11b were formed and on heating 3-acylamino-5-amino-1-R-1,2,4-triazoles
3a-f with sulfonyl chlorides under analogous conditions the starting materials were isolated.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Varian UNITY 300 (300 MHz) instrument in DMSO-d6,
internal standard was TMS, IR spectra were obtained on a Specord IR-75 instrument in nujol. The UV spectra
were obtained on a SF 26 spectrophotometer in water.
The starting materials were synthesized by known methods, viz. 1a [7], 1b, 4a [9], 10a,b [3], 10c [16].
3-Acylamino-5-amino-1-R-1,2,4-triazoles 3a-f,i,j and 5-Amino-3-sulfonylamino-1-R-1,2,4-triazoles
3g,h,k. A. A solution of anhydride (for compounds 3a-c,i) (6.6 mmol), acid chloride (for compounds 3d-f,j), or
sulfonyl chloride (for compounds 3g,h,k) in acetonitrile (3 ml) was added dropwise to a mixture of compound
1a or 1b (6 mmol), pyridine (0.5 ml), and acetonitrile (5 ml). The reaction mixture was boiled for 10 min, cooled
to 20°C, the precipitated solid was filtered off, and crystallized from ethanol. To isolate compound 3c the
reaction mixture was acidified with 2 N HCl solution to pH 3-4.
B. A solution of Na (0.2 g, 8.51 mmol) in MeOH (2 ml) was added to a mixture of compound 10a
(1.00 g, 7.09 mmol) and DMSO (10 ml), then benzyl bromide (1.33 g, 7.8 mmol) was added with stirring. The
reaction mixture was stirred for 10 h at 20°C and the solvent distilled off in vacuum. The residue was washed
1143

with water, and crystallized from ethanol. Compound 3i was obtained and was identical in physicochemical
properties to that obtained by method A.
Compound 3j was obtained analogously from benzoyl derivative 10b, and compound 3k analogously
from tosyl derivative 10c.
C. A mixture of compound 16 (0.3 g, 0.67 mmol), alcohol (3 ml), and conc. HCl (1 ml) was refluxed for
2 h, then neutralized with saturated NaOAc solution. The precipitated solid compound 3g was filtered off,
washed with water, and crystallized from a DMF–EtOH mixture. The compound was identical to that obtained
by method A.
3-Acetylamino-5-benzylideneamino-1-phenyl-1,2,4-triazole (6). A mixture of compound 3a (1 g,
4.6 mmol), benzaldehyde (0.59 g, 5.52 mmol), and DMF (1 ml) was refluxed for 1 h, diluted with water (10 ml),
and extracted with chloroform (3 × 10 ml). The extract was dried over CaCl2, the chloroform distilled off, the
residue was crystallized from CCl4, and compound 6 (0.8 g, 57%) was obtained; mp 148-149°C. UV spectrum
1
λ
max, nm (ε): 248 (16600), 320 sh (9900). IR spectrum, ν, cm-1: 1620 (C=N), 1670 (CO). H NMR spectrum,
δ, ppm: 2.09 (3H, s, CH3); 7.60-8.05 (10H, m, 2C6H5); 9.23 (1H, s, CH=N); 10.57 (1H, s, NH). Found, %:
N 22.8. C17H15N5O. Calculated, %: N 22.9.
3-Acetylamino-5-benzylamino-1-phenyl-1,2,4-triazole (7). Sodium borohydride (0.11 g, 2.9 mmol)
was added in portions during 10 min to a solution of compound 6 (0.6 g, 2 mmol) in ethanol (10 ml) at 50-60°C.
The mixture was then refluxed for 30 min and diluted with water (10 ml). The precipitated solid compound 7
was crystallized from alcohol. Yield 0.52 g (85%); mp 133-134°C. UV spectrum, λmax, nm (ε): 252 (8000).
1
IR spectrum, ν, cm-1: 1660 (CO). H NMR spectrum, δ, ppm (J, Hz): 2.00 (3H, s, CH3); 4.47 (2H, d, J = 5.9,
CH2); 7.08 (1H, t, J = 5.9, NH); 7.15-7.60 (10H, m, 2C6H5); 10.02 (1H, s, NH). Found, %: N 22.8. C17H17N5O).
Calculated, %: N 22.8.
3-Amino-5-benzylamino-1-phenyl-1,2,4-triazole (8). A mixture of compound 7 (0.5 g, 1.63 mmol),
conc. HCl (1 ml), and ethanol (3 ml) was refluxed for 2 h, then poured into 10% aqueous NaOAc solution (8
ml). The precipitated solid was crystallized from ethanol. Yield 0.36 g (60%); mp 127-128°C. UV spectrum,
1
λ
max, nm (ε): 264 (6500). IR spectrum, ν, cm-1: 3420 NH2. H NMR spectrum, δ, ppm (J, Hz): 4.40 (2H, d,
J = 5.8, CH2); 5.18 (2H, s, NH2); 6.97 (1H, t, J = 5.8, NH); 7.20-7.50 (10H, m, 2C6H5). Found, %: N 26.5.
C15H15N5. Calculated, %: N 26.4.
5-Amino-3-benzylamino-1-phenyl-1,2,4-triazole (9). Sodium borohydride (0.22 g, 5.7 mmol) was
added in portions during 10 min to a suspension of 5-amino-3-benzylideneamino-1,2,4-triazole 4a [9] in ethanol
(10 ml) at 50-60°C. The mixture was then refluxed for 30 min and poured into water (10 ml). The precipitated
solid was crystallized from ethanol. Yield 0.7 g (70%); mp 165-166°C. UV spectrum, λmax, nm (ε): 264 (6600).
1
IR spectrum, ν, cm-1: 3450 (NH2). H NMR spectrum, δ, ppm (J, Hz): 4.25 (2H, d, J = 6.0, CH2); 6.24 (2H, s,
NH2); 6.27 (1H, t, J = 6.0, NH); 7.15-7.50 (10H, m, 2C6H5). Found, %: N 26.2. C15H15N5. Calculated, %:
N 26.4.
3-(N-Acetyl-N-benzyl)amino-5-amino-1-phenyl-1,2,4-triazole (11a) and 5-Acetylamino-3-(N-acetyl-
N-benzyl)amino-1-phenyl-1,2-4-triazole (12). A mixture of compound 9 (0.8 g, 3 mmol), pyridine (0.5 ml),
Ac2O (0.37 g, 3.6 mmol), and acetonitrile (3 ml) was refluxed for 6 h, cooled, the precipitated solid compound
11a was filtered off, and crystallized from ethanol. Yield 0.54 g (59%); mp 194-196°C. UV spectrum, λmax, nm
1
(ε): 242 (7500). IR spectrum, ν, cm-1: 1670 (CO), 3470 (NH2). H NMR spectrum, δ, ppm: 2.26 (3H, s, CH3);
4.91 (2H, s, CH2); 6.66 (2H, s, NH2); 7.15-7.53 (10H, m, 2C6H5). Found, %: N 22.5. C17H17N5O. Calculated, %:
N 22.8.
Water (8 ml) was added to the reaction mixture after separating compound 11a, the precipitated solid
was filtered off, dissolved in chloroform, and passed through a column of aluminum oxide (4 × 3 cm). The
chloroform was distilled off, and compound 12 crystallized from ethanol. Yield 0.20 g (19%); mp 131-133°C.
1
UV spectrum, λmax, nm (ε): 238 sh (7800). IR spectrum, ν, cm-1: 1650 (CO), 1720 (CO). H NMR spectrum,
δ, ppm: 1.98 (3H, s, CH3); 2.38 (3H, s, CH3); 5.00 (2H, s, CH2); 7.15-7.55 (10H, m, 2C6H5); 10.58 (1H, s, NH).
Found, %: N 20.3. C19H19N5O2. Calculated, %: N 20.0.
1144

5-Amino-3-(N-benzyl-N-p-toluenesulfonyl)amino-1-phenyl-1,2,4-triazole (11b) was synthesized
analogously to compound 11a by the sulfonylation of compound 9 with p-toluenesulfonyl chloride. Yield 84%;
mp 170-172°C (ethanol). UV spectrum, λmax, nm (ε): 250 (10400). IR spectrum, ν, cm-1: 1160 (SO2), 3430 NH2).
1H NMR spectrum, δ, ppm: 2.41 (3H, s, CH3); 4.92 (2H, s, CH2); 6.38 (2H, s, NH2); 7.18-7.50 (12H, m, arom.);
7.78, (2H, m, arom.). Found, %: N 16.3. C22H21NO2S. Calculated, %: N 16.7.
3,5-Diacetylamino-1-phenyl-1,2,4-triazole (13a). A mixture of compound 1a (1.05 g, 6 mmol) in Ac2O
(5 ml) was refluxed for 6 h, the excess of anhydride was distilled off in vacuum, and the residue crystallized
from a DMF–EtOH, 1:2 mixture. Yield 1.28 g (82%); mp 210-212°C. UV spectrum, λmax, nm (ε): 218 sh
1
(18000). IR spectrum, ν, cm-1: 1680 (CO). H NMR spectrum, δ, ppm: 1.96 (3H, s, CH3); 2.04 (3H, s, CH3);
7.35-7.58 (5H, m, C6H5); 10.48 (1H, s, NH); 10.58 (1H, s, NH). Found, %: N 27.2. C12H13N5O2. Calculated, %:
N 27.0.
3,5-Di-p-methylbenzoylamino-1-phenyl-1,2,4-triazole (13b). A mixture of compound 1a (6 mmol),
p-methylbenzoyl chloride (2.78 g, 18 mmol), and pyridine (5 ml) was refluxed for 6 h, then poured into water
(20 ml). The precipitated oil was washed with water and dissolved in ethanol (5 ml). The resulting solid was
filtered off, and crystallized from ethanol. Yield 1.53 g (62%); mp 154-156°C. UV spectrum, λmax, nm (ε): 252
1
(37700). IR spectrum, ν, cm-1: 1680 (CO). H NMR spectrum, δ, ppm: 2.36 (3H, s, CH3); 2.38 (3H, s, CH3);
7.30-7.58 (9H, m, arom.); 7.78-7.91 (4H, m, arom.); 10.86 (1H, s, NH); 11.05 (1H, s, NH). Found, %: N 16.7.
C24H21N5O2. Calculated, %: N 17.0.
3,5-Di-p-methylbenzylamino-1-phenyl-1,2,5-triazole (14). Lithium aluminum hydride (0.37 g,
9.6 mmol) was added in portions to a suspension of compound 13b (1 g, 2.4 mmol) in THF (30 ml). The mixture
was refluxed for 3 h, water (2 ml) was added, and the solvent distilled off. The residue was extracted with
chloroform (3 × 20 ml), the chloroform distilled off, and the compound obtained was crystallized from ethanol.
Yield 0.63 g (68%); mp 105-106°C. IR spectrum, ν, cm-1: 3450 (NH2). 1H NMR spectrum, δ, ppm (J, Hz): 2.25
(6H, s, 2CH3); 4.18 (2H, d, J = 6.4, CH2); 4.36 (2H, d, J = 5.7, CH2); 6.25 (1H, t, J = 6.4, NH); 6.91 (1H, t,
J = 5.7, NH); 7.07-7.45 (13H, m, arom.). Found, %: N 18.3. C24H25N5. Calculated, %: N 18.3.
5-Amino-3-(N-p-methylbenzoyl-N-p-toluenesulfonyl)amino-1-phenyl-1,2,4-triazole (15). A mixture
of compound 3g (1 g, 3 mmol), pyridine (0.5 ml), p-methylbenzoyl chloride (0.7 g, 4.5 mmol), and acetonitrile
(3 ml) was refluxed for 6 h, cooled, and water (10 ml) added. The precipitated solid was filtered off, dissolved by
heating in chloroform (70 ml), and twice passed through a column (4 x 3 cm) of aluminum oxide. The
chloroform was distilled off and the residue crystallized from ethanol. Yield 0.31 g (23%); mp 187-188°C.
1
UV spectrum, λmax, nm (ε): 240 (25200). IR spectrum, ν, cm-1: 1170 (SO2), 1710 (CO), 3420 (NH2). H NMR
spectrum, δ, ppm: 2.42 (3H, s, CH3); 2.64 (3H, s, CH3); 6.78 (2H, s, NH2); 7.14-7.20 (2H, m, arom.); 7.36-7.52
(9H, m, arom.), 7.94 (2H, m, arom.). Found, %: N 16.0. C23H21N5O3S. Calculated, %: N 15.7.
5-p-Methylbenzoylamino-1-phenyl-3-p-toluenesulfonylamino-1,2,4-triazole (16). A. A mixture of
compound 3g (1 g, 3 mmol), pyridine (3 ml), and p-methylbenzoyl chloride 2e (0.7 g, 4.5 mmol) was refluxed
for 6 h, cooled, and ethanol (5 ml) added. The precipitated solid was crystallized from a DMF–EtOH, 1:2
1
mixture. Yield 0.82 g (61%); mp 276-278°C. IR spectrum, ν, cm-1: 1160 SO2, 1660 (CO). H NMR spectrum,
δ, ppm (J, Hz): 2.34 (3H, s, CH3); 2.37 (3H, s, CH3); 7.28-7.44 (9H, m, arom.); 7.73 (2H, d, J = 8.2, arom.); 7.85
(2H, d, J = 8.2, arom.); 10.97 (1H, s, NH); 11.38 (1H, s, NH). Found, %: N 15.8. C23H21N5O3S. Calculated, %: N
15.7.
B. A mixture of compound 15 (0.5 g, 1.1 mmol), pyridine (2 ml) and acid chloride 2e (catalytic amount)
was refluxed for 6 h. Compound 16 was isolated and purified in an analogous manner to method A. Yield 0.45 g
(90%), the compound was identical to that obtained by method A.
1145

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