Synthesis of condensed [1,2,3]triazolo-[5,1-b][1,3,4]thiadiazepine systems

Full text of DOI:10.1007/s10593-013-1255-8

Chemistry of Heterocyclic Compounds, Vol. 49, No. 2, May, 2013 (Russian Original Vol. 49, No. 2, February, 2013)
SYNTHESIS OF CONDENSED [1,2,3]TRIAZOLO-
[5,1-b][1,3,4]THIADIAZEPINE SYSTEMS
T. A. Kalinina1, D. V. Shatunova1, T. V. Glukhareva1, and Yu. Yu. Morzherin1*
Keywords: pyrazoles, quinolines, 1,3,4-thiadiazepines, 1,2,3-thiadiazoles, 1,2,3-triazoles, Dimroth
rearrangement.
In contemporary organic chemistry, rearrangements and transformations of one type of heterocycle to
another are promising and convenient methods for the preparation of heterocyclic structures difficult to obtain
by other means. However, these reactions are rarely used as a planned method for preparing heterocyclic
systems. 1,2,3-Thiadiazoles are convenient starting materials for carrying out various rearrangements. Several
rearrangements of 1,2,3-thiadiazoles involving a substituent in the ring position 5 are known [1-3], but only a
few of these lead to the preparation of condensed 1,2,3-triazoles. Thus, for example, methods are known for the
synthesis of [1,2,3]triazolo[5,1-b][1,3,4]thiadiazines using the Dimroth rearrangement [4, 5].
CO2Et
N
N
S
NHNH
1
2  HCl
Et3N
EtOH, 
Ph
Cl
N
N
CHO
Cl
CO2Et
S
CO2Et
S
Me
N
N
CO2Et
S–
N
CHO
N
N
N
3
4
N
N
Ph
N
N
N
N
N
N
+
N
Et3NH
NH2
Me
2
5
6
We propose a method for the preparation of novel condensed [1,2,3]triazolo[5,1-b][1,3,4]thiadiazepines
from the 5-hydrazino-1,2,3-thiadiazole 1. The first stage of this process is a Dimroth rearrangement of the
5-hydrazino-1,2,3-thiadiazole 1 [4] in ethanol in the presence of triethylamine. The subsequent stage is a cyclo-
condensation of the intermediate 5-mercapto-1,2,3-triazoles 2 (without their separation from the reaction
mixture) with the quinoline 3 [6] or pyrazole 4 [7] derivatives, which contain chlorine and formyl groups at the
ortho position.
_______
*To whom correspondence should be addressed, e-mail: yu.yu.morzherin@ustu.ru.
1Ural Federal University named after the First President of Russia B. N. Yeltsin, 19 Mira St., Yekaterinburg
620002, Russia.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 375-377, February, 2013. Original
article submitted February 8, 2013.
350
0009-3122/13/4902-0350©2013 Springer Science+Business Media New York

The resultant [1,2,3]triazolo[5',1':2,3][1,3,4]thiadiazepino[7,6-b]quinoline 5 and 7-methyl-5-phenyl-
5H-pyrazolo[4,3-f][1,2,3]triazolo[5,1-b][1,3,4]thiadiazepine 6 have not been reported before in the literature.
Similar condensed quinolino- [8-10] and pyrazolothiadiazepines [11] were prepared from 1-amino-5-mercapto-
1,3,4-triazole.
Thus, we have proposed a one-pot method for the synthesis of tri- and tetracyclic triazolothiadiazepines.
1
The H and 13C NMR spectra were recorded on a Bruker Avance-II 400 spectrometer (400 and 100
MHz, respectively) using DMSO-d6 with TMS as internal standard. Mass spectra were recorded on a Finnigan
MAT 8200 spectrometer at an ionization potential of 70 eV and with direct introduction of the sample into the
source. Elemental analysis was performed on a PE 2400 Series II CHNS-analyzer. Melting points were
determined using a Stuart SMP3 heating apparatus. Monitoring of the reaction course and the purity of the
synthesized materials was performed by TLC on Silufol UV-254 plates with ethyl acetate–hexane (1:2) mobile
phase.
Condensed Ethyl [1,2,3]Triazolo[5,1-b][1,3,4]thiadiazepine-3-carboxylates 5, 6 (General Method).
Et3N (0.45 ml, 4.46 mmol) was added to a suspension of ethyl 5-hydrazino-1,2,3-thiadiazole-4-carboxylate
hydrochloride 1 (0.5 g, 2.23 mmol) in ethanol (20 ml) and heated to dissolution. The aldehyde 3 or 4 (2.23
mmol) was then added; the reaction mixture was refluxed for 3 h, cooled, and the precipitate formed was filtered
off. The product was recrystallized from ethanol.
Ethyl [1,2,3]Triazolo[5',1':2,3][1,3,4]thiadiazepino[7,6-b]quinoline-3-carboxylate (5). Yield 0.42 g
(58%). Mp 236-238°C. 1H NMR spectrum, , ppm (J, Hz): 1.16 (3Н, t, J = 7.0, OCH2CH3); 4.16 (2H, q, J = 7.0,
OCH2CH3); 7.55-7.61 (2H, m, Н Ar); 7.74 (1Н, dd, J = 7.2, J = 8.8, Н Ar); 8.01 (1H, d, J = 8.0, Н Ar); 8.88
13
(1H, s, Н-11); 9.19 (1H, s, Н Ar). C NMR spectrum, , ppm: 13.6; 60.2; 124.9; 125.2; 127.0; 127.7; 128.6;
129.8; 132.2; 140.0; 142.0; 142.1; 146.9; 153.9; 160.0. Mass spectrum, m/z (Irel, %): 325 [М]+ (7), 281
[М-OEt]+ (30), 224 (54), 153 (100), 140 (54), 126 (49), 113 (33), 101 (52), 76 (17), 69 (49). Found, %: С 54.98;
H 3.46; N 21.51; S 9.69. C15H11N5O2S. Calculated, %: C 55.38; H 3.41; N 21.53; S 9.86.
Ethyl
7-Methyl-5-phenyl-5H-pyrazolo[4,3-f][1,2,3]triazolo[5,1-b][1,3,4]thiadiazepine-3-carboxylate
1
(6). Yield 0.15 g (66%). Mp 210-212°C. H NMR spectrum, , ppm (J, Hz): 1.26 (3Н, t, J = 7.0, OCH2CH3);
2.39 (3H, s, СH3); 4.28 (2H, q, J = 7.0, OCH2CH3); 7.56-7.86 (5H, m, H Ph); 8.54 (1H, s, H-8). 13C NMR
spectrum, , ppm: 12.2; 14.3; 61.6; 115.9; 125.1; 125.5; 129.7; 129.9; 134.8; 136.2; 137.4; 151.8; 153.0; 159.5.
Mass spectrum, m/z (Irel, %): 354 [М]+ (6), 281 [М-OEt]+ (1), 253 (90), 225 (45), 215 (22), 185 (28), 159 (24),
128 (27), 77 [Ph]+ (100), 69 (33). Found, %: С 54.17; H 4.04; N 23.51; S 9.03. C16H14N6O2S. Calculated, %:
C 54.23; H 3.98; N 23.71; S 9.05.
This work was carried out with the financial support of the Russian Foundation for Basic Research
(grant 13-03-00137).
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