The reactions of 8 chlorotetrazolo [1,5 a]pyrazine with N , O , and S nucleophiles in volve the ipso substitution of the chlorine atom. Heating of this compound with benzotriazole or phenyltetrazole results in elimination of the nitrogen molecule from one of the tetrazole rings to form new annelated azapentalenes.In spite of extensive progress in the chemistry of azolo[a]pyrazines, which have attracted interest because of their numerous useful properties, such as luminescence and complexation properties and bronchospasmolytic, cardiotonic, anti inflammatory, and antibacterial activi ties, 1-3 tetrazolo[1,5 a]pyrazines are a poorly studied class of heterocycles. The published studies on the chemistry of these compounds were concerned mostly with the azido tetrazole tautomerism. 4-6 The aim of the present study was to perform the reactions of 8 chlorotetrazolo[1,5 a]pyr azine (1) with N , O , and S nucleophiles and investigate the properties of 8 substituted tetrazolo[1,5 a]pyrazines.According to the modern concepts of nucleophilic substitution in aromatic moieties, nucleophiles can attack unsubstituted positions of heterocycles even in the pres ence of good leaving groups. 7 In particular, this is mani fested in the competitive ipso and tele substitution of halo gen in triazolo[4,3 a]pyrazines, positions 5 and 8 being most prone to the nucleophilic attack (Scheme 1). 8
Scheme 1The reactions of 8 chlorotetrazolo[1,5 a]pyrazine (1) with nucleophiles can involve not only the competitive ipso and tele substitution but also the azido tetrazole tau tomerism, due to which the course of nucleophilic substi tution becomes even less predictable.In the present study, we investigated the reactions of 8 chlorotetrazolo[1,5 a]pyrazine (1) with N , S , and O nucleophiles. The reactions were performed at room temperature (with secondary amines, hydrazine, and thiolates) or under reflux in various solvents (with alcohols and aniline). All the reactions under study were demon strated to involve the ipso substitution of the chlorine atom giving rise to the corresponding 8 substituted tetrazolo[1,5 a]pyrazines 2a-l (Scheme 2).
Scheme 2Nu = H 2 C=CHCH 2 NH (a), PhCH 2 NH (b), PhNH (c), piperidin 1 yl (d), morpholin 4 yl (e), NH 2 NH (f), MeO (g),The structures of the resulting compounds were estab lished by IR and 1 H NMR spectroscopy. The 1 H NMR spectra of compounds 2a-l show signals for the H(5) and H(6) protons of the pyrazine ring as doublets with the spin spin coupling constants J H(5),H(6) = 4.2-4.6 Hz. In the IR spectra, an N 3 vibration band is absent, which indicates that the products exist in the tetrazole rather than azide form. This approach to the synthesis of 8 substituted tetrazolo[1,5 a]pyrazines might be useful taking into account that the synthesis of such compounds by an alternative way, viz., by the reaction of the corre sponding 2 substituted 3 chloropyrazine with NaN 3 , pre
