Two approaches to a new heterocyclic system of pyrazolo[4,3-e ][1,2,4]triazolo[1,5-c ]pyrimidine

Derivatives of a new heterocyclic system, viz . pyrazolo[4,3-e ][1,2,4]triazolo[1,5-c ]pyrimidine 5 , have been synthesized by coupling imidoesters of 1-substituted-5-aminocarbonitriles 2 with acylhydrazides. The thermal recyclization of 1-substituted-4-(2-acylhydrazin-1-yl)pyrazolo[3,4-d ]-pyrimidines 7 is found to be an alternative approach to the heterocyclic system 5 . Keywords: 2,7-Disubstituted pyrazolo[4,3-e ][1,2,4]triazolo[1,5-c ]pyrimidines, bis-heterocycli-zation, carboxylic acids hydrazides


Introduction
][9][10][11] We have presumed that by employing hydrazides as the amine components of this reaction, the cascade heterocyclization 2→3→4→5 may occur to afford derivatives of a new heterocyclic system of pyrazolo [4,3-e] [1,2,4]triazolo [1,5-c]pyrimidine 5. 1 Indeed, it has been shown that the imidoesters 2 react with hydrazides under prolonged reflux in bromobenzene to give compounds 5 in about 50% yield.The reaction mechanism illustrated in Scheme 1 has been confirmed by isolation of the intermediates 3a and 4a in the reaction of imidoester 2 (R = H) with 4-methoxybenzoic acid hydrazide under milder conditions.Subsequent heating of a bromobenzene solution of pyrazolopyrimidine 4a smoothly converts it to the final product 5a.

Results and Discussion
The amidrazone 3a is obtained by short-term reflux of an ethanolic solution of the imidoester 2 (R = H) and 4-methoxybenzoylhydrazine taken in equimolar amounts.The IR-spectrum of 3a contains the bands characteristic of the stretching vibrations of nitrile (2200 cm -1 ), carbonyl (1675 cm -1 ), amidine (1650 cm -1 ) and imino (3060, 3330, 3355 cm -1 ) groups.Both the initial molecular ion peak M 1 + (284) and that of the ion M 2 + (266) related to the pyrazolotriazolopyrimidine 5a formed by elimination of a molecule of water from 3a in the gas phase appear in the mass spectrum of the amidrazone 3a.Heating a dimethylformamide solution of the amidrazone 3a gives rise to 4-iminopyrazolopyrimidine 4a, the IR-spectrum of which does not contain a ν CN vibration band, whereas ν CO and ν NH vibration bands appear at 1650 and 3115, 3200 cm -1 , respectively.The cyclization of 4a to 5a, via elimination of a molecule of water, proceeds upon reflux in bromobenzene for 3-4 hours.The structure of pyrazolotriazolopyrimidine 5a was supported by its  With the goal of the synthesis of derivatives of another heterocyclic system of pyrazolo [4,3-e] [1,2,4]triazolo [4,3-c]pyrimidine 8 isomeric to 5 we have prepared a series of 4acylhydrazinopyrazolo [3,4-d]pyrimidines 7 by coupling 6-chloropyrazolo [3,4-d]pyrimidines 6 3,4 with acylhydrazines and studying their cyclization reactions.The energy preference of the amino form of the acylhydrazines 7 over the possible imino tautomer is confirmed by their 1

Scheme 2
The decisive evidence for the pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine structure 5 of the compounds prepared by dehydration of the acylhydrazines 7 is provided by an X-ray determination of the molecular and crystal structure of compound 5g obtained from 7g (Figure 1).Of certain interest is the mode of crystal packing for compound 5g.Due to the formation of a network of C-HN bonds, the molecules of 5g are assembled in the crystal in almost planar layers.The attractive π-π stacking interaction between the neighboring layers of the tricyclic aromatic systems of 5g is manifested by their almost parallel (the dihedral angle between the planes is 5.5 o ) orientation (Figures 2 and 3).

Conclusions
Two new routes to the preparation of derivatives of a new fused heterocyclic system of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine 5 have been elaborated.The heterocyclization of the acylhydrazines 7 involves a rearrangement 7→5, the direction of which is opposite to that of the base-catalyzed Dimroth rearrangement. 1 It is suggested here that the initial step of the 7→5 rearrangement involves tandem migration of hydride and an acyl group (B→C).The 1-acyl-1hetarylhydrazine (C) undergoes cleavage of the N-N bond with the intermediate formation of the tight ionic pair (D) of the resonance-stabilized anion and the aminium cation, which then quenches to the N-amine E. The mechanism of the last stage is similar to that operating in the Namination of nitrogen heterocycles with hydroxylaminosulfuric acid 14 .

Figure 1 .
Figure 1.Perspective view and atom labeling of the X-ray crystal structure of 5g.

Figure 3 .
Figure 3.A fragment of the crystal structure of compound 5g.The shortest distance between the nearly parallel layers of the molecules is that between the N(5) and C(6) atoms of the fivemembered heterocyclic moiety.

Issue in Honor of Prof. Alexander T. Balaban ARKIVOC 2005 (x) 9-17 ISSN 1424-6376 Page 14 © ARKAT USA, Inc Experimental Section General Procedures
13NMR spectra were recorded on a Varian Unity-300 spectrometer (300 MHz) using DMSO and CDCl 3 as solvents.IR spectra were recorded on a Specord 71 spectrophotometer in nujol or KBr tablets.Mass spectra were obtained on a Kratos instrument using an ionization energy of 71 eV and a directing voltage of 1.75 kV.Single-crystal X-ray diffraction experiments were carried out with a Bruker SMART 1000 CCD area detector using graphite monochromated Mo-Kα radiation (λ = 0.71073 Å), ω-scans with a 0.3 o step in w and 10s per frame exposure, 2θ <58 o ) at 120 K.A total of 12416 reflections were measured, 4436 (R int = 0.0531).The structures were solved by direct method and refined by the full-matrix leastsquares against F 2 in anisotropic (for no-hydrogen atoms) approximation.The hydrogen atom positions were calculated and were refined isotropically in riding model approximation.The final refinements were converged to R1 = 0.0576 (from 3549 unique reflections with I > 2σ(I)) and wR2 = 0.1693 (from all 4436 unique reflections; the number of the refined parameters is 244.All calculations were performed on an IBM PC/AT using the SHELXTL software13.Crystal data for 5g.Colorless plate C 19 H 13 ClN 6 O (M = 376.80),monoclinic, space group P2 1 /c (no.14), a = 19.047(7)Å,b = 12.206(5)Å, c = 7.226(3)Å, β = 93.292(8)o , V = 1677(1)Å 3 , Z = 4, d calc = 1.492 g cm