Synthesis of sterically hindered 1-arylpyrrolidines and 1-arylpiperidines by condensation of primary aromatic amines with cyclic ethers or diols

✍ Scribed by Robert E. Walkup; Scott Searles Jr.

• Publisher: Elsevier Science
• Year: 1985
• Tongue: French
• Weight: 365 KB
• Volume: 41
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(01)83473-6

✦ Synopsis

A variety of 1-(g-alkylphenyl)-and 1-(o-o'-dialkylphenyl)--pyrrolidines and -piperidines were prepared by the gas phase alumina mediated condensation of tetrahydrofuran (THF), tetrahydropyran (THP) or the corresponding diols with primary aromatic amines in fair to high yield. This methodology can also be used for the synthesis of 1-phenylhexahydroaxepine from aniline. A mechanistic interpretation of the catalytic action of alumina is presented.

When a need arose to prepare several ortho-and di-ortho-alkylated iphenyl-pyrrolidines and -piperidines 1 and 2 2, methodology for such syntheses was found to be limited 3-5. We now report that the gas phase, aluminamediated reaction of primary aromatic amines with tetrahydrofuran (THF)6t7 or tetrahydropyran (THP)', (Scheme I) presents a general method for the preparation of a variety of highly hindered 1-aryl-pyrrolidines and -piperLdines'.

Scheme I.