Chemistry of Heterocyclic Compounds

The reaction of 1,2,5,6-tetramethyl-3-nitropyridinium perchlorate with acetone and piperidine on a solid carrier has given the novel, relatively stable 3-nitropyridine anhydro-base, 1,2,5-trimethyl-3-nitro-6-methylene-1,6-dihydropyridine, which bears alkyl groups only. This anhydro-base has been shown not to be an intermediate in the synthesis of indoles from 3-nitropyridinium salts.

The configuration of 1-(2-R-1,3-dioxan-5-yl)uracils and the conformation of the dioxane ring in these compounds were investigated by 1H NMR spectroscopy with the aid of the Eu(fod)3 shift reagent. It is shown that the dioxane ring exists in the preferred chair conformation with an axial orientation of the pyrimidine ring; this is confirmed by the resonance of the 5′-Ha proton in the form of a broad singlet with υ1/2υ8.5 Hz. An analysis of the spectral peculiarities of the synthesized compounds made it possible to establish the orientation of the substituents attached to the second C2 steric center. The three-dimensional structure of 1-(2, 2-dimethyl-1,3-dioxan-5-yl)uracil was determined by an x-ray diffraction study, and the axial orientation of the pyrimidine ring was confirmed. It is shown that significant flattening of the carbon part of the ring (ψ = 46.6 °) is observed in this molecule. An intramolecular (C6...O1, = 3.05 Å) hydrogen bond was observed in the molecule of this compound.

The N-(2′-hydroxyethyl)-1, 2, 3, 4-tetrahydroquinoline, -isoquinoline, and -silaisoquinoline, and their trimethyland triethylsilyl derivatives and the corresponding methiodides were synthesized. The acute toxicity and psychotropic activity of the compounds synthesized were studied.

The acylation of benzimidazolin-2-one and its 5,6-disubstituted derivatives with aliphatic acid chlorides in the presence of anhydrous aluminum chloride was studied. The corresponding 5(6)-acyl-, 5-R-6-acyl-, and 5,6-dimethyl-4-acylbenzimidaz-olin-2-ones, the structures of which were confirmed by the results of elementary analysis and IR, PMR, and mass spectroscopy, were obtained. The yields of the acylation products depend on the electronic effects of the substituents in the benzene ring of the benzimidazolin-2-one and on steric factors.

We have investigated the molecular and crystal structure of 3, 7-di(2-propenyl)-1, 5-diphenyl-3, 7-diazabicyclo[3.3.1]nonan-9-one complexed with copper(II) chloride. We have shown for the first time that the reason for the distortion of the coordination polyhedron of the metal is the interaction of the substituents at the nitrogen atoms with the halogen atoms.

The kinetics of the reaction of chloroacetaldehyde with thiourea in water at the C=O and C-Cl bonds were studied. The first step of the formation of the 2-aminothiazole is the reaction of the NH2 group of thiourea with the C=O group of chloroacetaldehyde. Hydrogen chloride evolution and the formation of a thiazole ring are secondary processes that occur simultaneously.

3β-Acetoxy-2′-methyl-5′-cyanoandrost-5-eno[17,16-c]pyridine-6′(1′H)-thione was obtained by thiylation of 16α-dicyanomethyl-3β-hydroxypregn-5-en-20-one acetate, and its alkylation by chloroacetonitrile and phenacyl bromide was studied. The same thione was also synthesized by treating the corresponding 6′-bromo-2′-methyl-5′-cyanoandrost-5-eno[17,16-c]pyridine with urea.

The cis-trans isomerization in a number of enamines — 1-methyl-2-(2'-R-2'-R'-methylene)pyrrolidines,-piperidines, and -hexahydroazepines — depends substantially on the nature of the 2'-substituent and the ring size. The energy barrier to this process decreases as the ability of the substituents to delocalize the anionic center in the transition state increases. The free energy of activation of rotation about the C=C bond is appreciably lower for six-membered enamines than for the corresponding seven- and five-membered analogs.