Synthesis and investigation of the physical-chemical properties of 2-(5-((theophylline-7’-yl)methyl)-4-methyl-4H-1,2,4-triazole-3-ylthio) acetic acid salts

At this stage of modern science development scientists get a lot of questions in the field of medicine and pharmacy. The study and search of new ways for synthesis of high-performance and low-toxic substances is one of the most important questions among them. Special attention is paid to 1,2,4-triazole and xanthine. On their basis some medical drugs have been previously made and are widely used in nowadays medicine. The aim of this work was the synthesis of salts of 2-(5-((theophylline-7'-yl)methyl)-4-methyl-4 H -1,2,4-triazole-3-ylthio)acetic acid and the study of their properties. Methods and results . Theophylline has been selected as starting material. Through a number of stages 7'-((3-thio-4-methyl-4 H -1,2,4-triazole-5-yl)methyl)theophylline has been obtained. Salts with organic and inorganic bases have been obtained by the neutralization reaction in aqueous medium. The structure of the compounds has been confirmed with elemental analysis on Elemental Vario EL cube (Elementar Analysensysteme, Germany), IR spectra (4000–400 cm -1 ) have been taken off the module ALPHA-T of Bruker ALPHA FT-IR spectrometer (Bruker optics, Germany). Gear Liquid Chromatography System with Mass spectrometric detector (Agilent Technologies, USA): Agilent 1260 Infinity HPLC System; single quadrupole mass spectrometer Agilent 6120 with electrospray ionization (ESI); Open LAB CDS Software. The formation of salts has been confirmed by the signals corresponding to protonated amines. Conclusions. The optimal conditions of obtaining salts of 2-(5-((theophylline-7'-yl)methyl)-4-methyl-4 H -1,2,4-triazole-3-ylthio)acetic acid with inorganic and organic bases have been determined. Corresponding carboxylic acid has been obtained by interaction of the resulting thiol with monochloroacetic acid in aqueous solution with double quantity of alkali and subsequent neutralization by hydrochloric acid. It has been confirmed that the greatest outputs of the reaction products were observed while using water as the solvent and its further replacement of propan-1-ol or acetone.  The general physical-chemical properties of the obtained compounds have been studied and a preliminary study of biological activity has been done.

At this stage of modern science development scientists get a lot of questions in the fi eld of medicine and pharmacy.The study and search of new ways for synthesis of highperformance and low-toxic substances is one of the most important questions among them.Special attention is paid to 1,2,4-triazole and xanthine.On their basis some medical drugs have been previously made and are widely used in nowadays medicine.
Salts with organic and inorganic bases have been obtained by the neutralization reaction in aqueous medium.The structure of the compounds has been confi rmed with elemental analysis on Elemental Vario EL cube (Elementar Analysensysteme, Germany), IR spectra (4000-400 cm -1 ) have been taken off the module ALPHA-T of Bruker ALPHA FT-IR spectrometer (Bruker optics, Germany).Gear Liquid Chromatography System with Mass spectrometric detector (Agilent Technologies, USA): Agilent 1260 Infi nity HPLC System; single quadrupole mass spectrometer Agilent 6120 with electrospray ionization (ESI); Open LAB CDS Software.The formation of salts has been confi rmed by the signals corresponding to protonated amines.

Conclusion.
The optimal conditions of obtaining salts of 2-(5-((theophylline-7'-yl) methyl)-4-methyl-4H-1,2,4-triazole-3-ylthio)acetic acid with inorganic and organic bases have been determined.Corresponding carboxylic acid has been obtained by interaction of the resulting thiol with monochloroacetic acid in aqueous solution with double quantity of alkali and subsequent neutralization by hydrochloric acid.
A t this stage of modern science development scientists get a lot of questions in the fi eld of medicine and pharmacy.The study and search of new ways for synthesis of high-performance and low-toxic substances is one of the most important questions among them.Derivatives of 1,2,4-triazole and xanthine are of special interest [2][3][4][5][6][7][8][9][10].Established drugs on their basis are widely used in medicine.Despite the achievements of modern pharmacy in the sphere of this group of heterocyclic compounds the search for new biologically active compounds remains timely and important.
The study of physical-chemical properties of the obtained compounds was carried out using methods listed in the State Pharmacopoeia of Ukraine (Table 1).
The melting point was determined using capillary method on Stanford Research Systems Melting Point Apparatus 100, America.The structure of the compounds was confi rmed with elemental analysis on Elemental Vario EL cube (Elementar Analysensysteme, Germany), IR spectra (4000-400 cm -1 ) were taken off the module ALPHA T of Bruker ALPHA FT-IR spectrometer (Bruker optics, Germany).Chromate-mass-spectral studies were carried out on Agilent 1100 Series LC/MSD System, method of ionization -chemical ionization at atmospheric pressure (APCI).

Results and their discussion
1 H NMR spectrum of the synthesized acid is characterized by the signals of the protons of -CH 3 groups of xanthine fragment and 1,2,4-triazole in the form of singlets at 3.25 ppm, 3.38 ppm and 3.45 ppm, the signals of protons of -CH 2 -groups in the form of the singlet at 4.05 ppm and 5.12 ppm.=CH-group is defi ned by singlet signal, which is fi xed with at 8.36 ppm.Proton of a -COOH group resonate in the form of widening the singlet at 11.2 ppm.
The IR spectrum of the obtained acid includes the bands of stretching vibrations of associated OH-links at 2880 cm -1 and at 2937 cm -1 , -CH 2 -group at 2820 cm -1 , -COOH group at 1706 cm -1 .There are also absorption bands of C=O, C=N and C=C xanthine fragment apparent in the area 1503-1658 cm -1 .Fragment C-S is recorded in the form of bands of stretching vibrations at 745 cm -1 .
The formation of salts was confi rmed by the signals corresponding protonated amines.For example, in the spectrum diethylammonium salt is observed triplet and quadruplet   Morpholinium salt is characterized by a set of signals of the protonated morpholine in the form of two multiplets at 3.25, 3.89 ppm and singlet at 8.95 ppm.Piperazinium cation is described by the presence of singlets of protons at 2.80 ppm and 3.40 ppm.Piperidinium salt is characterized by the signals of the protons of the organic bases in the form of multiplet when of 1.51 ppm and 2.60 ppm and singlet at 7.03 ppm.
In the IR spectra of salts of 2-((5-((theophylline-7'-yl) methyl)-4-methyl-4H-1,2,4-triazole-3-yl)thio)acetic acid the absence of absorption bands of stretching vibrations of OH-bond and the presence of three bands of stretching vibrations in the region of 1740-1660 cm -1 is observed.For salts of organic bases broad absorption bands of primary and secondary amines in the region 3050-2900 cm -1 and 2710-2250 cm -1 and deformation vibrations in the region of 1610-1565 cm -1 is observed.

Conclusions
The optimal conditions of obtaining salts of 2-(5-((theophylline-7'-yl)methyl)-4-methyl-4H-1,2,4-triazole-3-ylthio) acetic acid with inorganic and organic bases have been determined.It has been confi rmed that the greatest outputs of the reaction products were observed while using water as the solvent and its further replacement of propan-1-ol or acetone.
The general physical-chemical properties of the obtained compounds have been studied and a preliminary study of biological activity has been done.
Confl icts of Interest: аuthors have no confl ict of interest to declare.

Table 1 Physicochemical properties of the synthesized compounds
centers at 1.35 and 2.95 ppm and singlet at 7.10 ppm, in the spectrum diethylmonoethanolammonium salt -quartets at 3.18 ppm and a triplet at 1.46 ppm and a singlet at 7.05 ppm, and the signal of OН-group in the form of a triplet at 3.48 ppm. 1 H NMR spectrum benzylammonium salt is characterized by a singlet NCH 2 group at 3.82 ppm and multiplet С 6 Н 5 -group at 7.15-7.72ppm. with