M. S. Aleksanyan

Synthesis and structure of 3-oxopyrano[3,4-c]pyridines

Acylation of the enamine of 2,2-dimethyltetrahydropyran-4-one with acid chlorides produced α-acylpyran-4-ones which give 3-oxopyrano[3,4-c]pyridines when treated with cyanoacetamide.

Connection between the structure and the antibacterial activity of the N-oxides of quinoxalines. Molecular structure of dioxidine and quinoxidine

The di-N-oxides of quinoxaline derivatives describe a specific class of chemotherapeutic agents [7]. The highly effective antibacterial preparation dioxidine [2,3-bis(hydroxymethyl)quinoxaline-l,4-di-N-oxide (I)] and quinoxidine [2,3-bis-(acetoxymethyl)quinoxaline-l,4-di-N-oxide (II)], which were developed at the VNIKhFI, appertain to compounds of this type; they are produced industrially and are successfully applied in medical practice for the treatment of purulent, wound, and burn infections [5, 8, 113]. Dioxidine and quinoxidine are preparations having a broad spectrum of antibacterial action and exhibit activity toward bacterial strains which are resistant to other chemotherapeutic medicinal agents including antibiotics. The peculiarity of the spectrum of antibacterial activity is evidently associated with features of the molecular structure and reactivity of the di-N-oxides of a-hydroxymethyl derivatives of quinoxaline. It was previously found that (II) is metabolized rapidly in the intestines, plasma, and liver, being converted to the main metabolite (I) via an intermediate product [1]. On the basis of these data and the comparison of the activity of (I) and (II), it was concluded that the antibacterial effect of (II) is determined by the activity of its main metabolite (I). The investigation of the characteristic functional conversions of the biologically important quinoxaline-N-oxides showed that the presence of the hydroxymethyl group containing available protons in the a-position to the readily polarized N-*O function is the main structural factor determining the capacity of dioxidine and its analogs to undergo a certain type of oxidation-reduction and photochemical reactions [3, 6, 9, 11-14]. It was established on the basis of the study of the EPR spectra of the anion-radicals formed by the electrochemical reduction of quinoxaline-di-N-oxides in DMF that a stepped reduction reaction with the sequential deoxidation of the nitrogen atoms is characteristic of the compounds containing the methyl or formyl groups in the pyrazine ring. Under the same conditions, the anion-radicals of the a-hydroxymethyl derivatives of quinoxaline undergo the intramolecular oxidative-reduction deoxidation reaction with the simultaneous conversion of the hydroxymethyl groups to aldehyde groups [9]. The ability of the N-oxides of the a-hydroxymethyl derivatives of quinoxaline to undergo the analogous conversion in the presence of alkaline reagents was found previously [6]. Our investigations showed that, in the acid media, (I) undergoes the same oxidation-reduction reaction proceeding in two sequential kinetically controlled stages as follows: the formation of the cyclic hemiacetal of 2-hydroxymethyl-3-formylquinoxaline-l-N-oxide and its conversion to the cyclic bishemiacetal of 2,3-diformylquinoxaline [11, 14]. When hydroxymethyl groups are substituted by the methyl or acetoxymethyl groups, the quinoxaline-N-oxides lose the ability to undergo this reaction. It was shown that the main process in the conversion of quinoxidine in both the alkaline and acidic media is the solvolysis reaction with the formation of dioxidine [14]. Features of the molecular structure are also shown by the high selectivity of the photochemical conversions of the biologically active quinoxaline-N-oxides [3, 4, 12, 13]. It was established that, depending on the character of the substituent at the pyrazine ring of the quinoxaline-di-N-oxides, they can undergo one of two types of photochemical rearrangements with the transfer of the oxygen of the N~O group to the pyrazine ring procee.ding by different mechanisms: the isomerization with the migration of the substituent to the nitrogen of the heterocycle, and the rearrangement with the elimination of the substituent. Dioxidine and quinoxidine, for which the main structural difference is the presence and absence correspondingly of the available hydroxyl protons in the molecule, undergo different types of rearrangements, and one determined photo-reaction is characteristic of each preparation. The conception according to which the possibility of the formation of six-membered rings on account of the intramolecular hydrogen bonds in the molecules of dioxidine and its analogs determines the features of the photorarrangement mechanism with the elimination of the substituent was considered in [3, 4]. In connection with this, the principal interest is

Synthesis of 4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrospiro(benzo[h]quinazoline-5,1′-cyclohexane and its reaction with dibromoalkanes

Abstract4-(N′-Benzoylthioureido)-3-ethoxycarbonyl-1,2-dihydrospiro(naphthalene-2,1′-cyclohexane), which was synthesized from 4-amino-3-ethoxycarbonyl-1,2-dihydrospiro(naphthalene-2,1′-cyclohexane) and benzoyl isothiocyanate, cyclized to give 4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrospiro(benzo[h]quinazoline-5,1′-cyclohexane). Reaction of the latter with 1,2-dibromoethane or 1,3-dibromopropane gave products of intramolecular dialkylation at the S and N(3) atoms.

Synthesis and structure of diethyl 2-oxo-1-oxaspiro[4,5]decane-3,4-dicarboxylate

Ethyl 1-oxaspiro[2,5]octane-2-carboxylate reacts with diethyl sodiomalonate in toluene to give diethyl 2-oxo-1-oxaspiro[4,5]decane-3,4-dicarboxylate, which on distillation under goes partial de-ethoxycarbonylation to give ethyl 2-oxo-1-oxaspiro[4,5]decane-4-carboxylate.