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

Abstract

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.

Crystal structure of 5-chloro-N 1-(5-phenyl-1H-pyrazol-3-yl)benzene-1,2-diamine

“…The synthesis and reactions of benzodiazepin-2-ones and thiones have been studied in detail by our group (Gaponov et al, 2016;Okovytyy et al, 2009). The mechanism of ethanolassisted hydrazinolysis of 1,3-dihydro-2H-benzo [b][1,4]diazepine-2-thiones ( Fig.…”

“…The mechanism of ethanolassisted hydrazinolysis of 1,3-dihydro-2H-benzo [b][1,4]diazepine-2-thiones ( Fig. 1) has been modelled by quantumchemical calculations (Okovytyy et al, 2009). However, instead of obtaining the previously suggested products (IIIa) and (IIIb), compounds N 1 -(5-phenyl-1H-pyrazol-3-yl)benzene-1,2-diamine (Ia) and its 5-chloro-derivative (Ib) were prepared from 4-phenyl-1,3-dihydro-2H-benzo [b][1,4]diazepine-2-thiones (IIa) and (IIb) and hydrazine hydrate ( Fig.…”

Mechanism for the reaction of 2‐naphthol with N‐methyl‐N‐phenyl‐hydrazine suggested by the density functional theory investigations

“…Full gas-phase geometry optimizations were performed using the density functional theory with the Beck's three-parameter nonlocal exchange functional and the gradient-corrected functional of Lee et al (B3LYP), [72][73][74] due to its successful application in a number of hydrazinolysis [75,76] and analogous substituted hydrazine systems, [9,11,12] obtaining reasonable molecular structures, vibrational frequencies, and bond energies. Basis set of double-f split valence plus polarization and diffusion quality (6-31þG(d,p)) [77] was employed in all optimization calculations.…”

Hydrazinolysis of 3-R-[1,2,4]Triazino[2,3-c]quinazolin-2-ones. Synthetic and Theoretical Aspects

“…Despite the abundance of data based on experimental results, only a few studies − have dealt with the overall mechanism of nucleophile addition reactions. Okovytyy and co-workers described the hyrazinolysis mechanism of 2,3-dihidro-1,5-benzodiazipine-2-thiones and the 2,3-dihidro-1,5-benzodiazipin-2-ones . They have examined in detail the possible mechanisms of the initial step of the reactions and concluded that the benzodiazipine systems were attacked by a hydrazine molecule toward the azomethine bond.…”

“…Despite the abundance of data based on experimental results, only a few studies − have dealt with the overall mechanism of nucleophile addition reactions. Okovytyy and co-workers described the hyrazinolysis mechanism of 2,3-dihidro-1,5-benzodiazipine-2-thiones and the 2,3-dihidro-1,5-benzodiazipin-2-ones .…”