Synthesis and physical-chemical properties of 8-aminoderivatives of 7-m-bromobenzyl-3-methylxanthine
DOI:
https://doi.org/10.14739/2409-2932.2020.2.207111Keywords:
xanthine, organic synthesis, NMR-spectroscopyAbstract
The current stage of scientific and technological progress in pharmaceutical science is associated with the development of the targeted synthesis of biologically active compounds and the creation of new highly effective and low-toxic drugs on their basis that could compete with expensive imported drugs. A wide range of biological activity of natural xanthines stimulated the search for biologically active compounds among their synthetic analogs, which led to the creation of a row of drugs (Aminophylline, Diprophyllinum, Pentoxiphyllinum, Complamin, etc.) that are used successfully to nowadays. It is known that derivatives of 1- and 7-benzylxanthines exhibit versatile pharmacological effects. It should be noted that 8-bromoxanthines containing benzyl substituents at positions 1 or 7 are convenient synthons for further structural modification of the xanthine molecule.
The aim of this work is to study the reaction conditions of 8-bromo-7-m-bromobenzyl-3-methylxanthine with primary and secondary aliphatic amines and to study their physical-chemical properties.
Materials and methods. The melting point has been determined with the open capillary method using the PTP-M device. Elemental analysis has been performed with the Elementar Vario L cube, NMR-spectra has been taken on a spectrometer Bruker SF-400 (operating frequency – 400 MHz, solvent – DMSO, internal standard – TMS).
Results. The reaction of 7-m-bromobenzyl-8-bromo-3-methylxanthine with amines was carried out in a steel autoclave in methanol at 170 °C. It should be noted that despite the excess of the primary or secondary amine, only the Bromine atom in position 8 of the xanthine molecule was replaced with the formation corresponding 8-amino-7-m-bromobenzyl-3-methylxanthines. The obtained 8-aminoxanthines were white crystalline compounds with high melting points in virtue of their existence in the form of associates due to hydrogen bonds. The structure of the synthesized compounds was unambiguously proved by the method of NMR-spectroscopy.
Conclusions. Simply implemented methods for the synthesis of 8-amino-7-m-bromobenzyl-3-methylxanthines were developed. NMR-spectroscopic study of the obtained compounds, which clearly confirms their structure, was conducted. The prospective of the synthesized compounds for subsequent modification of their structure was demonstrated.
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