Alan W. Douglas

The behavior of indene oxide in the ritter reaction: A simple route to cis-aminoindanol

Abstract A regio- and stereoselective synthesis of cis-1-aminoindan-2-ol via a Ritter reaction is described.

High resolution spectroscopic evidence and solution calorimetry studies on the polymorphs of enalapril maleate

Abstract Enalapril maleate, a potent angiotensin converting enzyme inhibitor, exists as polymorphs, Form I and Form II. X-Ray powder diffraction measurements have shown slightly different patterns. Differential scanning calorimetric thermograms failed to show any significant differences during melting. High resolution spectroscopic techniques, including solid state carbon-13 NMR, Fourier-transform IR and Raman, detect differences between Form I and Form II. Heats of solution data obtained also indicate measurable energy differences. It was concluded that these two polymorphic forms of enalapril maleate are energetically very similar. Virtual equivalence of in vitro dissolution rate was obtained from formulations of enalapril maleate made from either Form I, or Form II, or mixtures.

THE OXAZABOROLIDINE-BORANE REDUCTION OF KETONES : IDENTIFICATION AND REACTIVITY OF TRANSIENT INTERMEDIATES

Abstract An investigation of the reaction pathway for oxazaborolidine — borane reduction of ketones has revealed a transient intermediate which can competitively reduce ketones.

An improved method for chiral oxazaborolidine-catalyzed reduction of 4-chromanone analogs and MK-0499☆

Abstract Addition of isopropanol to the stoichiometric reduction of ketones 4 – 8 using oxazaborolidine-borane complex 3 or the oxazaborolidine-catalyzed reduction of 4-chromanone analogs ( 1 , 7 – 9 ) enhances the enantioselectivity of the reduction.

In situ NMR spectroscopic studies of aniline ortho acylation (“sugasawa reaction”): The nature of reaction intermediates and Lewis acid influence on yield

Abstract Ortho acylation of anilines by nitriles in the presence of BCl 3 and a second Lewis acid appear to proceed through an intermediate “supercomplex” including all four components. Yield improvements were obtained based on recognition that chloride affinity of the second Lewis acid governs supercomplex formation. Aniline protonation was found to be the cause of incomplete reaction.

Synthesis of a new generation reverse transcriptase inhibitor via the BCl3/GaCl3-induced condensation of anilines with nitriles (sugasawa reaction)

Abstract The synthesis of 1 was achieved in high overall yield through a mechanism-based improvement of the preparation of o-acyl anilines.

Autooxidation of simvastatin

Abstract Autooxidation of the cholesterol-lowering agent simvastatin in ethylene dichloride solution with an azo-type free-radical initiator was investigated in kinetic studies using HPLC. The primary products were oligomers, with peroxide groups within the backbone chain, and some monomeric epoxides. These and several secondary products were isolated chromatographically and identified spectroscopically. A reaction scheme was proposed in which the oligomers arise from competitive hydrogen abstraction and addition reactions of oligomeric free radicals with simvastatin while the epoxides arise from homolytic peroxide cleavage.

Intramolecular aromatic 1,5-hydrogen transfer in free radical reactions. II. Rearrangement of iodobenzophenones

Abstract Products derived from the homolysis of the aromatic CI bond of ortho -iodobenzophenones by photolysis or tributyltin radicals indicate 1,5-hydrogen migration. The reactions include iodine migration, hydrogen abstraction and arylation.

The mechanism of serine fluorodehydroxylation: 13C and 19F nmr studies

Abstract Competetive reaction pathwys responsible for the incomplete flourination of serine by SF 4 elucidated and inhibited.