Hidetsura Cho

Regioselective Synthesis of Heterocycles Containing Nitrogen Neighboring an Aromatic Ring by Reductive Ring Expansion Using Diisobutylaluminum Hydride and Studies on the Reaction Mechanism

A systematic investigation of the reductive ring-expansion reaction of cyclic ketoximes fused to aromatic rings with diisobutylaluminum hydride (DIBALH) is described. This reaction regioselectively afforded a variety of five- to eight-membered bicyclic heterocycles or tricyclic heterocycles containing nitrogen neighboring an aromatic ring, including indoline, 1,2,3,4,5,6-hexahydrobenz[b]azocine, 3,4-dihydro-2H-benzo[b][1,4]oxazine, 2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine, 1,2,3,4,5,6-hexahydroazepino[3,2-b]indole, 2,3,4,5-tetrahydro-1H-benzothieno[2,3-b]azepine, 2,3,4,5-tetrahydro-1H-benzothieno[3,2-b]azepine, 5,6-dihydrophenanthridine, and 5,6,11,12-tetrahydrodibenz[b, f]azocine. The reaction mechanism leading to the rearrangement was investigated on the basis of the restricted Becke three-parameter plus Lee-Yang-Parr (B3LYP) density functional theory (DFT) with the 6-31G (d) basis set. It was found that the reaction proceeds through a three-centered transition state via a stepwise mechanism because the potential energy curve along the intrinsic reaction coordinate (IRC) had two maxima (saddle points; TS1 and TS2) and the partial phenonium cation intermediate C. In addition to cyclic ketoximes fused to aromatic rings, the reactions of various cyclic and acyclic ketoximes were examined to investigate preference of migrating group. It was found that the more electron-rich group migrated preferentially to give the corresponding secondary amines.

Novel benzthiodiazepinones as antiherpetic agents: SAR improvement of therapeutic index by alterations of the seven-membered ring.

A series of novel benzthiodiazepinones was studied as antiherpetic agents. Significant improvements in potency and therapeutic index in a viral replication assay were realized over the starting molecule. The role of stereospecific substitution on the diazepine ring and optimal nitrogen substitution were investigated.

X-ray crystallographic analysis of tautomeric dihydropyrimidine derivatives

Abstract X-ray crystallographic analysis of various dihydropyrimidine tautomers was carried out. 4-(2-Chlorophenyl)-5-ethoxycarbonyl-2,6-dimethyldihydropyrimidine 1 exists in an electron-localized 1,4-dihydro form with a flat boat conformation in the crystalline state. 6-Chloro-4-(2-chlorophenyl)-5-ethoxycarbonyl-2-methyldihydropyrimidine 2 synthesized as 1/2 HCl salt after extractive work-up under basic conditions consists of two different molecules with Cl atoms;the molecules of electron-localized 1,4-dihydro form 2a and electron-delocalized form 2b. Both forms are linked by hydrogen bonding around the center of symmetry in the unit cell. X-ray analysis of compound 2c prepared by the addition of excess HCl-Et2O to a solution of compound 2 exhibits an electrondelocalized structure of different molecular arrangement.