Igor N. Tarabara

Comprehensive DFT and MP2 Level Investigations of Reaction of 2,3-Dihydro-1,5-benzodiazepine-2-thiones with Hydrazine

Density functional theory approach was used for the 4-phenyl-2,3-dihydro-1,5-benzodiazepine-2-thione compound to determine the mechanism of hydrazinolysis of 4-substituted 2,3-dihydro-1,5-benzodiazepine-2-thiones. Single-point calculations at the MP2/6-311+G(d,p)//B3LYP/6-311+G(d,p) level were performed for the more accurate energy prediction. The solvent effect was taken into account by carrying out single-point calculations using the PCM methodology. The obtained results show that in the investigating mechanism the first step consists of the hydrazine molecule addition to the thiocarbonyl bond of the 4-phenyl-2,3-dihydro-1,5-benzodiazepine-2-thione following removal of H(2)S. Further addition of another hydrazine molecule to the azomethyne bond and cyclization with pyrazole ring formation occur, and then the diazepine ring-opening and the removal of hydrazine molecule proceed. Finally, imine-enamine tautomerization leads to 5-N-(2-aminophenyl-1-amino)-3-phenylpyrazole as a main product that is in agreement with the experimental observation. The cyclization step is a rate-determining step of this reaction.

exo-2,3-Epoxybicyclo[2.2.1]heptan-endo-5,6-dicarboximides: versatile starting materials for the preparation of oxazaheterocyclic cage compounds

A convenient method is reported for the synthesis of N-substituted exo-2-hydroxy-6-aza-4-oxatetracyclo[5.2.1.13,508,9]undecan-7-ones, exo-2-hydroxy-6-aza-4-oxatetracyclo[5.2.1.13,508,9]undecanes, and endo-8,exo-9-dihydroxy-4-azatricyclo[5.2.1.02,6]decanes in high to moderate yields. The method involves treatment of easily available exo-2,3-epoxybicyclo[2.2.1]heptan-endo-5,6-dicarboximides with LiAlH4.Graphical abstract

Theoretical Study of Mechanism of 2,3-Dihydro-1,5-benzodiazepin-2-ones Hydrazinolysis

Density functional theory approach was used for the 4-methyl-2,3-dihydro-1,5-benzodiazepin-2-one compound to determine the mechanism of hydrazinolysis of 4-substituted 2,3-dihydro-1,5-benzodiazepin-2-ones. Single point computations at the MP2/6-311+G(d,p)//B3LYP/6-31G(d) level were performed for the more precise energy prediction. The solvent effect was taken into account by carrying out single point calculations using the PCM methodology. The obtained results show that in the investigating mechanism the first step consists of the hydrazine molecule addition to the azomethine bond of the 4-methyl-2,3-dihydro-1,5-benzodiazepin-2-one. Further cyclization occurs with pyrazole ring formation, and then the diazepine ring opening is revealed. Finally, removal of o-phenylendiamine leads to 3-methylpyrazolone-5 as a main product that is in agreement with the experimental observation. The final step is a rate-determining step of this reaction.

Azabrendanes V. Synthesis and reactions of stereoisomeric exo- and endo-5-aminomethylbicyclo[2.2.1]hept-2-ene-based ureas

A number of stereoisomeric ureas (N-[aryl(benzyl, or cycloalkyl)carbamoyl]-exo(endo)-5-aminomethylbicyclo[2.2.1]hept-2-enes) have been synthesized from bicyclo[2.2.1]hept-2-en-exo(endo)-5-carbonitrile by reduction with lithium aluminum hydride and subsequent reaction of the resulting amines with aryl (benzyl, or cycloalkyl) isocyanates. Regioselective alkylation of stereoisomeric ureas has been performed with benzyl chloride under liquid/solid phase-transfer catalysis. The outcome of the reactions of ureas with peroxy acids is dependent upon the orientation of substituents in the bicyclic fragment. Exo-isomeric ureas are transformed into corresponding epoxy-derivatives, while reactions of the endo-isomers are accompanied by intramolecular cyclization, resulting in the formation of azatricyclononane derivatives. Quantum-chemical calculations have established a decisive role for additional hydrogen bonding in the stabilization of transition states in these heterocyclization reactions of ureas. The structures and stereochemical homogeneity of the products have been confirmed by the analysis of 1H and 13C NMR spectra and correlation spectroscopy. The mechanism of the intramolecular heterocyclization reaction of ureas and carboxamide of endo-5-aminomethyl-exo-2,3-epoxybicyclo[2.2.1]heptane series has been studied at the BHandHLYP/6-31G(d) level of theory.

Synthesis and some reactions of 2-(3,5-dioxo-4-azatricyclo[5.2.2.02,6]undec-8-ene-4-yl)propanoic acid

Novel 2-(3,5-dioxo-4-azatricyclo[5.2.2.0 2,6 ]undec-8-ene-4-yl)propanoic acid was synthesized from easily accessible starting material, 4-oxatricyclo[5.2.2.0 2,6 ]undec-8-ene-3,5-dione. Chemical reactivity of the title was investigated. In particular, it was converted into the corresponding acyl chloride and simple amides. Curtius rearrangement of the acyl azide delivered an isocyanate, which was then transformed into a series of polycyclic ureas. Noteworthy, the thermal rearrangement of the azide underwent without interference from the strained double bond present in the parent compound.

Interaction of 2,3-dihydro-1H-benzodiazepinone-2 with epichlorhydrine

Derivatives of 1,5-benzodiazepines show various pharmacological activity. The presence of several reactive centers predetermines the possibility of reactions of 1,5-benzodiazepines both with electrophilic and nucleophilic reagents of various types. In addition, these compounds are suitable objects for the synthesis of new tricyclic systems containing a diazepinic cycle. In the article, the interaction of 4-phenyl- and 4-methyl-2,3-dihydro-1Н-1,5-benzodiazepine-2-ones with epichlorhydrin under various conditions is reported. It has been shown that under strongly basic conditions the reactions proceed at the nitrogen atom N 1 and N 1 -glycidyl-1,5- benzodiazepine-2-ones are obtained. The yields of products were 71-79%. Under soft basic conditions the reactions either did not proceed at all or were accompanied by the formation of side-products.

Research of the molecular regrouping of endo-2-aminobicyclo- [2.2.1]hept-5-ene by spectral and theoretical methods

The bicyclic fragment of norbornene (and norbornane) occurs in vegetative therpenoids and defines various biological activity of these compounds, in particular, amines and their derivatives. Some of them, viz., the derivatives of stereoisomeric amines (la, Ib) — sulfonamides and ureas, possessing various biological activity, have been widely investigated in recent years. However, derivatives of other amines, for example, amine (II) are almost not investigated. The highly important factor of an association of biological activity with deleting amino-group from a bicyclic frame is not investigated.