REACTION OF FUNCTIONALIZED XANTHINEPYRIMIDINES WITH BENZYL(β-OXYETHYL)HYDRAZINES

• Main Authors: T. A. Yuyrova, A. A. Krysko, V. M. Povstyanoy
• Format: Article
• Language: English
• Published: Odessa I. I. Mechnikov National University 2019-12-01
• Series: Vìsnik Odesʹkogo Nacìonalʹnogo Unìversitetu: Hìmìâ
• Subjects: дигідропіримідини; ксантини; реакційноздатні ксантинопіримідини; гідразиноліз
• Online Access: http://heraldchem.onu.edu.ua/article/view/185569

Xanthine and pyrimidine derivatives that show various types of biological activity, present valuable building blocks for design of novel biologically active compounds. These compounds are also important building blocks for designing novel bioactive compounds. We have previously synthesized intermediates, which contained fragments of functionalized derivatives of dihydropyrimidine. These compounds were connected with halogensubstituted derivatives of theophylline and imidazole via a methylene bridge. The ability of these compounds to participate in reactions with N-nucleophiles, which leads to the formation of various products with one substituted functional groups, along with intramolecular heterocyclization with the formation of polyazaheterosystems. In this work, novel dihidropyrimidine-based bicyclic synthons have been studied. The initial bromomethylsubstituted pyrimidines were reacted with the potassium salt of 8-bromo-3-methylxanthine in DMF. This reaction led to the formation of new intermediates – reactive xanthinopyrimidines and allowed their functionalization in regards to substituted N-hydrazines as N-nucleophiles. Reaction product yields for xanthinopyrimidine intermediates reached up to 80%. These compounds contain bromine at C8 of xanthine and carbethoxy group at C5 of pyrimidine fragment. In spite of a wide spectrum for theoretically possible products for the above-described reaction, the reaction was straightforward and led to the substitution of the bromine atom in the xanthine for hydrazide residue. These reactions were studied using different solvents such as methanol, butanol, dimethylformamide and excess of the liquid reagent. Triethylamine was used as catalysts and running reaction in lower alcohols using autocalve for 24 hours at temperatures between 120 – 220 oC, which leads to substitution ofbromine in xanthine moiety for hydrazine. It should be notes, that we were unable to achieve intramolecular cyclization with the formation of the 7-membered cycle, largely due to the sterical hindrance of the second nitrogen atom of hydrazine.