Acylation of amines with 5-phenyltetrazol-2-ylacetyl chloride

Article abstract of DOI:10.1023/B:COHC.0000044567.39872.b0

The acylation of primary and secondary amines by 5-phenyltetrazol-2- ylacetyl chloride leads to the corresponding tetrazolylacetamides irrespective of the nature of the substituent in the structure of the amine.

Full text of DOI:10.1023/B:COHC.0000044567.39872.b0

Chemistry of Heterocyclic Compounds, Vol. 40, No. 7, 2004
ACYLATION OF AMINES WITH
5-PHENYLTETRAZOL-2-YLACETYL CHLORIDE
S. M. Putis, V. Yu. Zubarev, V. S. Poplavskii, and V. A. Ostrovskii
The acylation of primary and secondary amines by 5-phenyltetrazol-2-ylacetyl chloride leads to the
corresponding tetrazolylacetamides irrespective of the nature of the substituent in the structure of the
amine.
Keywords: 5-phenyltetrazol-2-ylacetamide, 5-phenyltetrazol-2-ylacetyl chloride, acylation.
Tetrazolylacetic acids and their derivatives are regarded as potential biologically active compounds. A
special position is occupied by the amides of tetrazolylacetic acids, which are intermediate products for the
synthesis of biologically active compounds. For example, antibiotics of the cephalosporin series (kefzol,
ceftezol), which contain a tetrazolylacetic acid fragment in their chemical structure, have found widespread use
in clinical practise [1]. These drugs form a group of semisynthetic cephalosporin antibiotics that are highly
effective and have extended therapeutic activity. The search for analogous compounds having improved
characteristics and also investigation of the reactivity of the key reagents in the synthesis of compounds of
diverse practical significance present an urgent task in modern medical chemistry [2, 3].
The esters of tetrazolylacetic acids play a special role in the synthesis of antibiotics containing a tetrazole
fragment [4]. In previous work we showed for the case of ethyl 5-phenyltetrazol-2-ylacetate that such esters can
be regarded as key reagents in the synthesis of certain tetrazolylacetamides [5]. However, the aminolysis of
tetrazolylacetic esters does not make it possible to obtain the corresponding amides from amines with branched
structures and aromatic or heterocyclic substituents [5].
An alternative to aminolysis of the esters may be acylation of the amines by carboxylic acid chlorides.
Unfortunately, there are no published data that would characterize the ability of tetrazolylacetyl chlorides to
enter into the acylation of nitrogen compounds. Exceptions are the reactions with 7-aminocephalosporanic acid
and its derivatives and also the transacylation of tetrazoles [4, 6, 7].
In the present work we studied the acylation of various amines by 5-phenyltetrazol-2-ylacetyl chloride.
In order to produce the respective acetamides we used amines with low basicity (aniline and its derivatives) and
with branched aliphatic and bulky substituents containing several reactive amino groups and also some weakly
nucleophilic heterocyclic amines.
The acylation was conducted in ether, chloroform, or THF depending on the solubility of the amine [7].
Triethylamine was used as base to combine with the released hydrogen chloride. The amides of 5-phenyltetrazol-
2-ylacetamides were synthesized from the respective acid chlorides according to the following scheme:
__________________________________________________________________________________________
St. Petersburg State Technological Institute (Technical University), St. Petersburg, Russia; e-mail:
ostrovskii@mail.convey.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 997-1005,
July, 2004. Original article submitted April 8, 2004.
854
0009-3122/04/4007-0854©2004 Springer Science+Business Media, Inc.

Ph
Ph
O
O
Et3N
N
N
+
R1R2NH
N
N
.
N
N
–Et3N HCl
NR1R2
Cl
N
N
2–14
1
2 R1 = R2 = Et; 3 R1 = R2 = CH2CH2CN; 4 R1R2 = (CH2)5; 5 R1R2 = (CH2)2O(CH2)2;
6 R1R2 = (CH2)2N(CO2Et)(CH2)2; 7-14 R1 = H; R2 = Ph, 8 R2 = 4-O2NC6H4, 9 R2 = 3-NO2C6H4,
10 R2 = 2-O2NC6H4, 11 R2 = 3,5-(NO2)2C6H3, 12 R2 = MeCHPh,
13 R2 = (1,2,4-triazol-4-yl), 14 R2 = (4-methylfurazan-3-yl)
By the effective acylation of sterically blocked and low-basicity amines with 5-phenyltetrazol-2-ylacetyl
chloride it was possible the extend this strategy to the synthesis of the amides from bifunctional amines. As
model bifunctional amines we used diazo-18-crown-6 (having sterically blocked amino groups) and
3,4-diaminofurazan, which contains amino groups with reduced nucleophilicity [8]. The above-mentioned
amines were acylated with a twofold molar excess of the acid chloride 1. In both cases we obtained the products
from exhaustive substitution, i.e., N,N'-bis(5-phenyltetrazol-2-ylacetyl)-1,4,10,13-tetraoxa-7,16-diazacyclo-
octadecane (15) and N,N'-bis(5-phenyltetrazol-2-ylmethylcarbonyl)-3,4-diaminofurazan (16).
Ph
Ph
N
N
O
O
O
O
N
N
N
N
N
N
N
N
O
diazo-18-crown-6
O
Ph
N
15
Ph
Ph
O
N
N
2
N
N
N
O
N
N
O
N
N
Cl
N
N
H
N
N
NH
N
3,4-diaminofurazan
16
O
While continuing this direction of investigation, we attempted the exhaustive acylation of hydrazine.
However, during the reaction in THF we only isolated the monosubstitution product. For this reason it was
necessary to use more rigorous conditions and to use boiling toluene, in which the monosubstitution product
formed at the first stage of acylation is readily soluble. Under these conditions exhaustive acylation is complete
in 10 h (monitored by TLC) with the formation of N,N'-bis(5-phenyltetrazol-2-ylmethylcarbonyl)-1,2-hydrazine
(17).
Ph
N
Ph
O
O
Et3N
N
N
N
2 1
NH2NH2
+
N
N
N
N
toluene
H
H
N
N
17
Unfortunately, we were unable to obtain the amide 13 by this method. Analysis of the published data
showed that quaternary 1,2,4-triazolium salts are formed during the acylation of 4-amino-1,2,4-triazole with
carboxylic acid chlorides used in equimolar amounts. With the addition of a base (such as triethylamine) these
salts undergo cleavage of the triazole ring [9].
855

O
R
+
N
N
N N
O
_
R
Cl
+
N
N
Cl
NH2
NH2
Et3N
O
R
N
NH
CHO
O
H2O
HCO2H + R
NH2NH2
+
NH–NH2
N
NH2
We used 4-amino-1,2,4-triazole itself as base for the acylation of 4-amino-1,2,4-triazole at the amino
group. N-(1,2,4-Triazol-2-yl)-5-phenyltriazol-2-ylacetamide (13) was isolated as a result of the reaction.
Ph
O
N
N
N
N
N
N
2
1
H2N
N
+
N
N
N
N
H
13
Thus, acylation with 5-phenyltetrazol-2-ylacetyl chloride takes place readily both with highly basic
amines containing branched substituents and with low-basicity amines. At the same time it was not possible to
acylate N,N-diphenylamine with the acid chloride (1). Steric hindrances probably play a significant role in this
case [10].
The tetrazolylacetamides, which have become accessible as a result of the present investigation, in turn
open up the way to further functionalization with the production of polynuclear tetrazoles. Thus, the
corresponding tritetrazole 18 was obtained from the amide 3 containing two cyanoethyl groups.
Ph
O
N
N
N
N
N
N
NH
N
N
N
NH
N
N
18
It is interesting that an attempt at the production of the tritetrazole 18 using the cycloaddition [11] of
dimethylammonium azide to the dinitrile 3 in DMF did not lead to the desired result. We therefore used the
recently proposed conditions [12] (azidization with triethylammonium azide in toluene) for the preparation of the
tritetrazole 18. By optimizing these conditions it was possible to reduce the temperature of the process from 110
to 95°C and to shorten the reaction time from 24 to 6 h (monitored by TLC).
856

TABLE 1. The 1H NMR Spectra of the Amides 2-18
Chemical shifts of signals, δ, ppm (J, Hz)
Com-
pound
C
(5)–C6H5
(m)
N(2)–CH2 (s)
Other signals
[NH (s)]
2
3
4
5
6
7
8.09-8.07 (2Н),
7.60-7.54 (3Н)
5.91
6.10
5.95
5.99
6.01
3.43 (2Н, q, J = 7.0, СН2); 3.31 (2Н, q, J = 7.0, СН2);
1.20 (3Н, t, J = 6.9, СН3); 1.05 (3Н, t, J = 6.9, СН3)
8.09-8.07 (2Н),
7.60-7.55 (3Н)
3.83 (2Н, t, J = 6.9, СН2); 3.63 (2Н, t, J = 6.9, СН2);
3.03 (2Н, t, J = 6.9, СН2); 2.78 (2Н, t, J = 6.9, СН2)
8.09-8.06 (2Н),
7.60-7.56 (3Н)
3.48-3.43 (4Н, m, СН2); 1.61 (4Н, s, СН2);
1.48 (2Н, s, СН2)
8.09-8.06 (2Н),
7.61-7.53 (3Н)
3.69 (2Н, t, J = 4.4, СН2); 3.61 (2Н, t, J = 4.4, СН2);
3.54 (2Н, t, J = 4.4, СН2); 3.47 (2Н, t, J = 4.4, СН2)
8.08-8.06 (2Н),
7.60-7.55 (3Н)
4.08 (2Н, q, J = 7.2, СН2); 3.54-3.47 (6Н, m, СН2);
3.42-3.40 (2Н, m, СН2); 1.20 (3Н, t, J =7.0, СН3)
8.10-8.08 (2Н),
7.61-7.55 (3Н)
5.77
[10.64]
7.61-7.55 (2Н, m, CONH-C6H5);
7.35 (2Н, t, J = 7.1 Hz, CONH-C6H5);
7.11 (1Н, t, J = 7.0 Hz, CONH-C6H5)
8
8.11-8.07 (2Н),
7.60-7.52 (3Н)
5.87
[11.25]
8.25 (2Н, d, J = 9.5, СН); 7.84 (2Н, d, J = 8.7, СН)
9
8.11-8.07 (2Н),
7.60-7.53 (3Н)
5.84
[11.11]
8.58 (1Н, s, CH); 7.98-7.90 (2Н, m, CH);
7.65 (1Н, t, J = 8.4, CH)
10
11
12
8.11-8.09 (2Н),
7.60-7.55 (3Н)
5.90
[10.92]
8.01 (1Н, d, J = 7.0, СН); 7.76 (2Н, d, J = 7.0, СН);
7.45 (1Н, J = 5, СН)
8.11-8.08 (2Н),
7.61-7.55 (3Н)
8.10-8.01 (2Н),
7.61-7.51 (3Н)
5.92
[11.57]
5.57
[9.01]
8.82 (2Н, d, J = 2.2, CH); 8.56 (1Н, t, J = 2.0, CH)
7.40-7.31 (4H, m, CH-C6H5);
7.30-7.22 (1H, m, CH-C6H5); 4.94 (1H, q, J = 7.2, CH);
1.41 (3Н, d, J = 7.2, CH3)
13
8.13-8.03 (2Н),
7.63-7.52 (3Н)
5.86
[12.30]
8.76 (2Н, s, in triazole)
14
15
16
17
18
*
8.18-8.11 (2Н),
7.59-7.50 (3Н)
5.95
[10.40]
2.39 (3Н, s, СН3)
8.09-8.04 (4Н),
7.58-7.52 (6Н)
5.95 (4Н)
3.80-3.54 (24Н, m, CH2)
8.16-8.03 (4Н),
5.89 (4Н)
—
—
7.65-7.49 (6Н) [11.24 (2H)]
8.12-8.03 (4Н), 5.68 (4Н)
7.61-7.51 (6Н) [10.92 (2Н)]
8.12-8.03 (2Н),
7.60 7.53 (3Н)
5.99
17.1-12.8 (2Н, br. s, CN4H); 3.87 (2Н, t, J = 6.9, СН2);
3.69 (2Н, t, J=6.9, СН2); 3.37 (2Н, t, J = 6.9, СН2);
3.16 (2Н, t, J = 6.9, СН2)
_______
1
* The H NMR spectrum of compound 14 was recorded in acetone-d6, and
the spectra of the other compounds were recorded in DMSO-d6.
EXPERIMENTAL
The 1H and 13C NMR spectra of the synthesized amides were recorded on a Bruker DPX-300 instrument
1
(300 MHz for H and 75 MHz for 13C) with DMSO-d6 as internal standard. The IR spectra were obtained on a
Perkin-Elmer Spectrum 1000 instrument for tablets with potassium bromide. Elemental analysis was performed
on a semiautomatic Hewlett-Packard 185 C,H,N analyzer. The melting points were determined on a PTP
instrument at 1 deg/min in the melting range. The reaction was monitored by TLC on Merck Kieselgel 60F245
plates with development in UV light.
857

TABLE 2. The 13C NMR Spectra of the Amides 2-18
Com-
pound
Chemical shifts, δ, ppm
N(2)–CH2
CH2–С=O
CN4
C6H5
Other signals
2
163.9
165.2
163.9
164.0
164.0
164.2
164.3
164.3
164.3
164.5
164.1
164.6
165.9
164.9
164.3
165.1
164.8
163.4
164.1
162.6
163.3
163.4
162.9
164.1
163.8
163.7
163.7
163.2
164.4
164.9
163.9
164.1
163.9
164.1
130.5, 129.3, 126.9, 126.3
130.6, 129.3, 126.8, 126.3
130.5, 129.3, 126.9, 126.2
130.5, 129.3, 126.9, 126.2
130.6, 129.3, 126.9, 127.3
130.6, 139.3, 126.8, 126.3
130.7, 129.3, 126.7, 126.4
130.6, 129.3, 126.7, 126.3
130.6, 129.3, 126.7, 126.4
130.7, 130.2, 126.7, 126.4
130.6, 129.3, 126.9, 126.3
130.8, 129.4, 126.6, 126.4
131.3, 129.9, 128.3, 127.4
130.5, 129.2, 126.9, 126.3
130.7, 129.4, 126.7, 126.4
131.6, 130.2, 127.6, 127.2
130.6, 129.3, 126.9, 126.3
53.9
53.9
54.0
53.9
54.0
55.3
55.5
55.3
55.0
55.4
54.8
53.4
55.6
54.1
54.8
54.2
54.0
13.9 (СН2), 12.7 (СН3)
3
118.8 (С≡N), 42.4 (СON–СН2), 41.5 (СON–СН2), 16.6 (СН2–CN), 15.2 (СН2–CN)
45.3, 42.5, 25.7, 25.1, 23.7 (СН2)
65.8 (СН2–O–СН2), 44.8, 41.9 (СН2)
4
5
6
154.6 (СО–О), 61.0 (СН2), 44.1, 43.1, 42.9, 41.3 (СН2), 14.5 (СН3)
138.2, 128.9, 124.0, 119.3 (NH–C6H5)
7
8
144.2 (С–NO2), 142.8 (СONН–C), 125.1 (CH–C–NO2), 119.2 (СONН–C–CH)
139.2, 130.2, 125.3, 118.5, 113.5 (C in the substituent)
142.5, 134.1, 130.1, 126.1, 125.7, 125.1 (C in the substituent)
155.8, 151.5, 148.3, 140.1, 118.8, 113.2 (C in the substituent)
143.9, 128.3, 126.0 (CH–C6H5), 48.5 (CH), 22.4 (CH3)
143.4 (C(3) and С(5 in tetrazole)
9
10
11
12
13
14
15
16
17
18
*
151.2, 149.2 (C(3) and С(4) in furazan), 8.9 (CH3)
70.1, 70.0, 69.4, 69.3, 68.4, 68.3, 49.5, 48.1 (C in the substituent)
152.2 (C(3) and С(4) and furazan)
—
153.7 (С(5) in tetrazole), 43.6 (СON–СН2), 42.4 (СON–СН2), 22.4 (СН2–C(5)), 21.2 (СН2–C(5)
)
_______
*The NMR spectra of compound 14 were recorded in acetone-d6, and the others in DMSO- d6.

5-Phenyltetrazol-2-ylacetyl Chloride (1). A mixture of 5-phenyltetrazol-2-ylacetic acid (6 g, 30 mmol)
and phosphorus pentachloride (6.75 g, 32 mmol) was heated at 100°C until homogeneous with the formation of a
colorless solution. To the hot solution we added 75 ml of boiling hexane. As the solution cooled colorless
crystals were formed. The suspension was filtered, and the acid chloride was crystallized from hexane. We
1
obtained 6.43 g (96%) of compound 1; mp 103-104°C. H NMR spectrum, δ, ppm: 8.17-8.14 (2H, m, C6H5);
7.53-7.49 (3H, m, C6H5); 5.84 (2H, s, N(2)–CH2). 13C NMR spectrum, δ, ppm: 166.5 (С=О), 166.2 (CN4),
131.0, 129.2, 127.2, 126.6 (С6Н5), 60.7 (N(2)–CH2). IR spectrum, ν, cm-1: 1777 (C=O), 2985, 2945 (С–Н), 1450,
1278, 1148, 1073, 1022, 933 (vibration of the tetrazole ring), 729, 688 (C6H5). Found, %: C 48.31; H 3.20;
N 25.60. C9H7СlN4O. Calculated, %: C 48.55; H 3.17; N 25.17.
Preparation of Tetrazolylacetamides 2-12. (General Procedure). To a solution of the substrate 1
(10 mmol) in ether (chloroform or THF) (50 ml) at 0-2°C with stirring we added the amine (10 mmol) in ether
(chloroform or THF) (20 ml) and triethylamine (10 mmol) in the same solvent (10 ml). An exothermic effect
was observed during the reaction. After 1-2 h at room temperature the solvent was evaporated under vacuum,
and the residue was washed with distilled water (3×20 ml) and crystallized from the respective solvent or
solvent system.
Diethylamide of 5-Phenyltetrazol-2-ylacetic Acid (2). By crystallization from 50% ethanol we
obtained 1.25 g (48%) of the amide 2; mp 98-99°C. Rf 0.74 (9:1 chloroform–methanol). IR spectrum, ν, cm-1:
1658 (C=O), 2982, 2936 (С–Н), 1425, 1269, 1205, 1144, 1100, 1073, 1023 (vibration of the tetrazole ring), 730,
690 (C6H5). Found, %: C 60.57; H 6.97; N 27.34. C13H17N5O. Calculated, %: C 60.21; H 6.61; N 27.01.
Bis(2-cyanoethyl)amide of 5-Phenyltetrazol-2-ylacetic Acid (3). By crystallization from 2-propanol
we obtained 2.25 g (73%) of the amide 3; mp 162-163°C. Rf 0.54 (95:5 chloroform–methanol). IR spectrum,
ν, cm-1: 1672 (C=O), 2999 (С–Н), 1435, 1261, 1203, 1177, 1072, 1027 (vibration of the tetrazole ring), 729, 692
(C6H5), 2252 (C≡N). Found, %: C 58.28; H 4.59; N 32.03. C15H15N7O. Calculated, %: C 58.24; H 4.89; N 31.70.
Piperidide of 5-Phenyltetrazol-2-ylacetic Acid (4). By crystallization from ethanol we obtained 1.32 g
(42%) of the amide 4; mp 178-179°C. Rf 0.76 (95:5 chloroform–methanol). IR spectrum, ν, cm-1: 1662, 1649
(C=O), 2987, 2939, 2857 (С–Н), 1425, 1254, 1230, 1138, 1097, 1030 (vibration of the tetrazole ring), 728, 691
(C6H5). Found, %: C 62.25; H 5.67; N 25.47. C14H17N5O. Calculated, %: C 61.98; H 6.32; N 25.81.
Morpholide of 5-Phenyltetrazol-2-ylacetic Acid (5). By crystallization from 25% ethanol we obtained
0.71 g (26%) of the amide 5; mp 178-179°C. Rf 0.62 (9:1 chloroform–methanol). IR spectrum, ν, cm-1: 1667,
1651 (C=O), 2986, 2944, 2851 (С–Н), 1426, 1241, 1200, 1157, 1120, 1072, 1020 (vibration of the tetrazole
ring),729, 691 (C6H5), 1273 (C–O–C). Found, %: C 57.27; H 5.23; N 25.93. C13H15N5O2. Calculated, %:
C 57.13; H 5.53; N 25.63.
N'-Ethoxycarbonylpiperazide of 5-Phenyltetrazol-2-ylacetic Acid (6). By crystallization from 50% 2-
propanol we obtained 1.24 g (40%) of the amide 6; mp 132-133°C. Rf 0.72 (9:1 chloroform–methanol).
IR spectrum, ν, cm-1: 1672, 1665 (N–C=O), 1730 (O–C=O), 2993, 2932, 2874 (С–Н), 1421, 1254, 1210, 1154,
1090, 1071, 1027 (vibration of the tetrazole ring), 732, 694 (C6H5). Found, %: C 56.70; H 5.41; N 25.03.
C16H20N6O3. Calculated, %: C 55.80; H 5.85; N 24.40
Anilide of 5-Phenyltetrazol-2-ylacetic Acid (7). By crystallization from 60% 2-propanol we obtained
2.95 g (70%) of the amide 7; mp 189-190°C. Rf 0.28 (chloroform). IR spectrum, ν, cm-1: 1672 (C=O), 2998,
2954, 2851 (С–Н), 3440, 3275 (NH), 1447, 1255, 1204, 1140, 1072, 1027 (vibration of the tetrazole ring), 730,
692 (C6H5). Found, %: C 65.03; H 5.18; N 25.17. C15H13N5O. Calculated, %: C 64.51; H 4.61; N 25.07.
p-Nitroanilide of 5-phenyltetrazol-2-ylacetic Acid (8). By crystallization from 50% ethanol we
obtained 2.14 g (66%) of the amide 8; mp 211-212°C. Rf 0.8 (95:5 chloroform–methanol). IR spectrum, ν, cm-1:
1694 (C=O), 3336 (NH), 2990, 2930, 2845 (С–Н), 1555, 1512, 1345 (NO2), 1448, 1252, 1192, 1150, 1109,
1069, 1023 (vibration of the tetrazole ring), 729, 688 (C6H5), 844 (1,4-disubstituted benzene). Found, %:
C 55.77; H 3.58; N 26.10. C15H12N6O3. Calculated, %: C 55.56; H 3.73; N 25.91.
859

m-Nitroanilide of 5-Phenyltetrazol-2-ylacetic Acid (9). By crystallization from 50% ethanol we
obtained 2.53 g (78%) of the amide 9; mp 217-218°C. Rf 0.70 (95:5 chloroform–methanol). IR spectrum, ν, cm-1:
1686 (C=O), 3330 (NH), 3000, 2943, 2840 (С–Н), 1551, 1529, 1355 (NO2), 1450, 1255, 1207, 1150, 1104,
1072, 1021 (vibration of the tetrazole ring), 729, 689 (C6H5), 801 (1,3-disubstituted benzene). Found, %: C
55.32; H 4.00; N 26.28. C15H12N6O3. Calculated, %: C 55.56; H 3.73; N 25.91.
o-Nitroanilide of 5-Phenyltetrazol-2-ylacetic Acid (10). By crystallization from 50% ethanol we
obtained 2.31 g (71%) of the amide 10; mp 196-197°C. Rf 0.85 (95:5 chloroform–methanol). IR spectrum,
ν, cm-1: 1718 (C=O), 3293 (NH), 2995, 2950, 2860 (С–Н), 1560, 1520, 1353 (NO2), 1450, 1269, 1203, 1149,
1098, 1073, 1020 (vibration of the tetrazole ring), 730, 689 (C6H5), 743 (1,2-disubstituted benzene). Found, %:
C 55.21; H 4.06; N 25.80. C15H12N6O3. Calculated, %: C 55.56; H 3.73; N 25.91.
3,4-Dinitroanilide of 5-Phenylthiazol-2-ylacetic Acid (11). By crystallization from 50% ethanol we
obtained 2.52 g (68%) of the amide 11; mp 218-219°C. Rf 0.40 (95:5 chloroform–ethanol). IR spectrum, ν, cm-1:
1713 (C=O), 3361 (NH), 2994, 2948, 2843 (С–Н), 1550, 1536, 1346 (NO2), 1452, 1261, 1199, 1147, 1109,
1076, 1025 (vibration of the tetrazole ring), 727, 685 (C6H5), 828, 787 (1,3,5-trisubstituted benzene). Found, %:
C 48.27; H 2.91; N 26.34. C15H11N7O5. Calculated, %: C 48.79; H 3.00; N 26.55.
N-(1-Phenylethyl)amide of 5-Phenyltetrazol-2-ylacetic Acid (12). By crystallization from 70%
2-propanol we obtained 2.0 g (65%) of the amide 12; mp 169-170°C. Rf 0.63 (9:1 chloroform–methanol).
IR spectrum, ν, cm-1: 1657 (C=O), 3270 (NH), 2990, 2947 (С–Н), 1448, 1247, 1205, 1100, 1043, 1026
(vibration of the tetrazole ring), 1385 (C–N), 731, 692 (C6H5). Found, %: C 66.64; H 5.73; N 22.55. C17H17N5O.
Calculated, %: C 66.43; H 5.57; N 22.79.
N-(1,2,4-Triazol-4-yl)amide of 5-Phenyltetrazol-2-ylacetic Acid (13). During the synthesis of this
amide 4-amino-1,2,4-triazole, taken in a 2:1 molar ratio in relation to the acid chloride 1, was used instead of
triethylamine. By crystallization from 50% ethanol we obtained 1.83 g (68%) of the amide 13; mp 216-217°C.
IR spectrum, ν, cm-1: 1722 (C=O), 3120 (NH), 2994, 2950 (С–Н), 1451, 1260, 1200, 1173, 1071, 1044
(vibration of the tetrazole ring), 1359 (C–N), 734, 694 (C6H5). Found, %: C 48.93; H 4.09; N 41.46. C11H10N8O.
Calculated, %: C 48.89; H 3.73; N 41.46.
N-(4-Methylfurazan-3-yl)amide of 5-Phenyltetrazol-2-ylacetic Acid (14). By crystallization from
50% 2-propanol we obtained 2.02 g (71%) of the amide 14; mp 190-191°C. Rf 0.36 (9:1 chloroform–methanol).
IR spectrum, ν, cm-1: 1704 (C=O), 3273 (NH), 2996, 2953 (С–Н), 1448, 1252, 1200, 1155, 1100, 1043, 1024
(vibration of the tetrazole ring), 1388 (C–N), 727, 686 (C6H5). Found, %: C 50.27; H 3.64; N 34.64. C12H11N7O2.
Calculated, %: C 50.53; H 3.89; N 34.37.
N,N'-Bis(5-phenyltetrazol-2-ylacetyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadodecane (15). During
the synthesis of this amide we used compound 1 (20 mmol) in chloroform (100 ml) and triethylamine (20 mmol)
in chloroform (20 ml). By crystallization from ethanol we obtained 3.0 g (47%) of the diamide 15;
mp 183-184°C. Rf 0.68 (9:1 chloroform–methanol). IR spectrum, ν, cm-1: 1665 (C=O), 3004, 2959, 2856 (С–Н),
1450, 1249, 1203, 1140, 1110 1090, 1029 (vibration of the tetrazole ring), 1296, 1050 (C–O–C), 1336, 1029
(C–N), 730, 696 (C6H5). Found, %: C 57.42; H 6.01; N 22.27. C30H38N10O6. Calculated, %: C 56.77; H 6.03;
N 22.07.
N,N'-Bis(5-phenyltetrazol-2-ylmethylcarbonyl)-3,4-diaminofurazan (16). During the synthesis of
this amide we used compound 1 (20 mmol) in THF (100 ml) and triethylamine (20 mmol) in THF (20 ml). By
crystallization from 50% ethanol we obtained 5.34 g (62%) of the amide 16; mp 196°C (decomp.). Rf 0.46 (9:1
chloroform–methanol). IR spectrum, ν, cm-1: 1698 (C=O), 3000, 2948 (С–Н), 1449, 1246, 1200, 1142, 1104,
1046, 1026 (vibration of the tetrazole ring), 1353 (C–N), 730, 690 (C6H5). Found, %: C 50.21; H 3.83; N 36.06.
C20H16N12O3. Calculated, %: C 50.85; H 3.41; N 35.58.
N,N'-Bis(5-phenyltetrazol-2-ylmethylcarbonyl)-1,2-hydrazine (17). To a solution of the acid chloride
1 (4.7 g, 21 mmol) in toluene (100 ml) at 0-2°C with stirring we added hydrazine hydrate (0.5 g, 10 mmol) in
toluene (10 ml) and triethylamine (2.02 g, 20 mmol) in toluene (10 ml). The reaction mixture was boiled for 10 h
on a salt bath, the solvent was evaporated under vacuum, and the residue was washed with
860

distilled water (3×20 ml) and crystallized from aqueous DMF. We obtained 1.66 g (41%) of the hydrazine 17;
mp 246-248°C. IR spectrum, ν, cm-1: 1629 (C=O), 3217 (NH), 3001, 2994 (С–Н), 1449, 1232, 1140, 1060, 1029
(vibration of the tetrazole ring), 1399 (C–N), 729, 689 (C6H5). Found, %: C 52.83; H 4.48; N 34.24.
C18H16N10O2. Calculated, %: C 53.46; H 3.99; N 34.64.
N,N'-Bis[2-(tetrazol-5-yl)ethyl]amide of 5-Phenyltetrazol-2-ylacetic Acid (18). To a suspension of
compound 3 (1 g, 3.2 mmol) in toluene (100 ml) we added triethylamine hydrochloride (2.67 g, 19.2 mmol) and
sodium azide (1.26 g, 19.2 mmol). The mixture was stirred at 98-100°C for 5 h, cooled to room temperature, and
washed with water (3×70 ml). The aqueous layer was separated and acidified to pH 1-2 with concentrated
hydrochloric acid. The precipitate was filtered off and crystallized from ethanol. We obtained 0.9 g (70%) of the
tetrazole 18; mp 124-126°C. IR spectrum, ν, cm-1: 1631 (C=O), 1453, 1238, 1100, 1066 (vibration of the
tetrazole ring), 3428 (NH-tetrazole), 1379 (C–N), 731, 693 (C6H5). Found, %: C 45.12; H 4.65; N 45.65.
C15H17N13O. Calculated, %: C 45.57; H 4.33; N 46.05.
The work was carried out with financial support from the Ministry of Education of the Russian
Federation (grant T02-09.3-3222) and the Federal Special-Purpose Program of State Support and Integration of
Education and Fundamental Science (grant No. I0667).
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