Aromatization Reaction New Method Of Synthesis Of N-phenyl-substituted Amine Compound

N-phenyl amines are important organic pharmaceutical intermediates and usually prepared by Ullmann condensation of halogenated aromatic with amines catalyzed by heavy metals or their salts.A new synthetic method for the preparation of N-phenyl amines was developed. It is a new aromatization reaction involving in the application of 3-phenyl-2,4-dioxa-3-borabicyclo[3.3.1]nonan-7-one as the origin of phenyl group.In this paper, cyclohexane-1,3,5-triol was prepared from phloroglucinol by hydrog enation (66%), then converted to 3-phenyl-2,4-dioxa-3-borabicyclo[3.3.1]nonan-7-ol by esterification with phenylboronic acid (96.5%). The aromatization reagent 3-phenyl-2,4-dioxa-3-borabicyclo[3.3.1]nonan-7-one was then synthesized by oxidation of the alcohol with Al2O3 immobilized PCC in a yield of 65%.3-phenyl-2,4-dioxa-3-borabicyclo[3.3.1]nonan-7-one was used to introduce phenyl on the nitrogen of piperidine to afford N-phenyl of piperidine. It was found that molecular sieve was essential since it could absorb the water generated in the reaction. The choice of solvent depends on the solubility of amines and low boiling point solvent is preferred. This reaction usually completes in 6 hours at room temperature.In the appropriate conditions, a series of amines were used for this aromatization reaction to afford a variety of N-phenyl amines in good to excellent yields. The steric and electronic effects on the reaction were discussed. Oversized steric hindrance goes against the reaction, and electron-donating groups on the nitrogen of amines are in favor of the reaction while electron-withdrowing groups are not. As a result, the mechanism of the aromatization reaction may as well be that the nitrogen of amines attack carbonyl in 3-phenyl-2,4-dioxa-3-borabicyclo[3.3.1]nonan-7-one and undergoes a nucleophilic addition and then hydration and dehydration to give N-phenyl amines.This dissertation developed a new method for the prepation of N-phenyl amines via a mild and metal-free aromatization reaction, so it is of great theoretical value and practical prospect.