Ethanolysis of N-substituted norbornane epoxyimides: discovery of diverse pathways depending on substituent's character.

Combined experimental and theoretical studies have been carried out to investigate the transformations of the epoxyimides of norbornane into heterocyclic compounds. We established that interaction of the aryl-substituted epoxyimides of norbornane with sodium ethoxide results in the formation of new heterocyclic compounds in preparatively useful yields and with complete regioselectivity. The reactions of epoxyimides, containing aryl electron-donor substituents, result in the formation of endo-9-carbamoyl-exo-2-hydroxy-5-oxo-4-oxatricyclo[4.2.1.0(3,7)]nonanes, while in the case of the absence of an aryl electron-donor group or the presence of aryl electron-withdrawing group in the epoxyimide, exo-2-hydroxy-5-oxo-4-azatricyclo[4.2.1.0(3,7)]nonan-endo-9-carboxylic acids were obtained as products of the ethanolysis reaction. Unexpectedly, the ethanolysis of alkyl-substituted epoxyimides leads to dihydroxyimide formation as the major product. In order to understand the vital role of the imide substituent, a systematic theoretical DFT study at the PCM/B3LYP/6-31+G(d) level was carried out. We found that substituents at the nitrogen atom of epoxyimides exerted remarkable effects on the regioselectivity in the ethanolysis reaction, based on the solvent effects and intramolecular electronic interactions. Particularly, the preference for the formation of dihydroxyimides over heterocyclic systems for alkyl derivatives might be explained by kinetic stability of the formed acetal intermediate over the competitive epoxyamido acid intermediate. The above results provide a convenient and efficient method for predicting the structures of heterocyclic systems formed under basic ethanol conditions depending on the substituent on the nitrogen atom of the norbornane epoxyimides.

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.

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.