The study of reactions of 7-substituted 8-hydrazino-3-methylxanthine with β-dicarbonyl compounds

C studies of chemical and biological properties of 7,8-disubstituted 3-methylxanthine [1–8], we investigated the reaction of 7-substituted 8-hydrazino-3methylxanthine with acetylacetone and acetoacetic ester to obtain 8-(1-pyrazolyl-1-)xanthines, which have not been studied previously in any chemical nor biological aspect. The aim of the research was to study the reactions of 7-substituted-8-hydrazino-3-methylxanthine with acetylacetone and acetoacetic ester.

The aim of the research was to study the reactions of 7-substituted-8-hydrazino-3-methylxanthine with acetylacetone and acetoacetic ester.
In the pyrazolylxantines 19-22 spectra, there is no signals of hydrazino protons, but two intensive singlets in 2.40-2.18ppm are clearly fi xed due to resonance absorption of the protons of the methyl group of the pyrazole nucleus.Aromatic protones at position 4 of pyrazole substituent were recorded as singlets with one proton intensity unit at 6.19-6.02ppm.The protons signals of the uracil part of molecules and substituents in the 7-position fully consists with their structure.
The peak of the molecular ion with m/z 318 has been registered in the mass spectrum of 8-(3,5-dimethylpyrazole-1-yl)-3-methyl-7-(2-methoxyethyl) xanthine (21), this peak corresponds to the calculated molecular weight and shows even number of nitrogen atoms in the molecule.Initial degradation processes of molecular ion are associated with partial and complete elimination of methoxyethyl substituent in position 7 of the molecule (F ion m/z 260) and subsequent decay of the uracil moiety.Ion m/z 43 (99.9%) is maximum in the spectrum and corresponds HNCO particle from the F ion.
Interaction of hydrazinoxantines 10-18 with the excess of acetoacetic ester in glacial acetic acid takes place with the formation of new derivatives of heterocyclic system, namely 8- (3,4-dimethyl-6-oxopyrano[2,3-c]pyrazole-1yl) xanthines (23-31) (Scheme 1) analogously to [11,12].The IR spectra of 23-31 pyranopyrazoles contain stretching vibrations band of carbonyl group of α-pyran nucleus, which is fi xed at 1780-1744 cm -1 .For the PMR spectra of pyranopyrazoles 23-31 (Table .1) the intense proton singlets of methyl groups are registered in the DMSO at 2.5-2.44 ppm and only for phenoxyethyl substituted 29 the doublet protons of two methyl groups with six proton intensity units at 2.35 ppm is registered.Proton signals at 5-position of the pyran ring is clearly captured in a relatively narrow range at 6.02-5.97ppm (1H).
As it is shown in Scheme 2, the initial fragmentation act M + of pyranopyrazole 28 is methyl vinyl ether-radical cleavage from position 7 and the formation of ions with m/z 328 (F), m/z 58 and m/z 59 (99.9%), besides the last one is the maximum one in the spectrum and corresponds to the structure of the protonated form of methyl vinyl ether.Later CO particle is cleaved from F ion and forms F 1 ion with m/z 300, which corresponds to the stable structure of furanopyrazole radical.Disintegration of F 1 ion leads to two ions with m/z 165 and m/z 135, confi rming the presence of both xanthine and pyranopyrazole parts in molecule.
Thus, the above mentioned infoprmation confi rms the astructure of the synthesized pyranopyrazoles 28-31.In our opinion, the reaction of 8-hydraazynoxantines with excess of ethyl acetoacetate is common for mono-substituted of hydrazine, thus it will be necessary to investigate its mechanism and stereochemical features of pyranopyrazoles.One can assume that classical circuit of pyrazole nucleus occurs at the beginning, and then a second molecule of acetoacetic ester acts as an acylating and electrophilic reagent, which leads to the closure of the pyran ring.
2. The structure of the synthesized compounds has been confi rmed by IR and PMR spectroscopy and mass spectrometry.