The Synthesis and Evaluation of the Biological Activity of Heterocyclic Analogs of Phencyclidine

Author

Julian Dew McKenney Jr., Old Dominion University

Date of Award

Spring 1981

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry & Biochemistry

Program/Concentration

Chemistry

Committee Director

Roy L. Williams

Committee Member

Frank E. Scully, Jr.

Committee Member

Billy T. Upchurch

Committee Member

John D. Van Norman

Call Number for Print

Special Collections LD4331.C45 M354

Abstract

Using the classical synthetic approach described by Maddox and co-workers⁴³, the decyanation reaction of 1- piperidinocyclohexane carbonitrile (PCC), 5, was attempted using the heterocyclic anions of 2-methyl-5-nitropyridine, 22, 2-amino-5-nitropyridine, 23, and 2-hydroxy-5-nitropyridine, 24; however, the desired pyridine analogs of phencyclidine (PCP), 1, could not be prepared under these conditions. Attempts to prepare the same analogs via addition of these anions to the iminium tosylate and hydrobromide salts also proved unsuccessful.

The failure to observe the desired decyanation reaction has been attributed to the special sterochemical restrictions of the hindered nitrile of PCC in that facile displacement by the above heteroaromatic anions is impossible. The nucleophilic character of these anions together with their size can also be considered as contributing to their lack of reactivity.

A series of heterocyclic PCP analogs, 1-(1-phenyl-4- thiacyclohexyl) piperidine, 15, 1-(1-phenyl-N-methyl-4- piperidyl) piperidine, 16, and 1-(1-phenyl-4-oxacyclohexyl) piperidine, 20, was prepared from commercially available heterocyclic ketones via the classical synthetic approach described by Maddox.

A gross behavioral study of the potential activity of these analogs was carried out together with a specific measurement of their effects on motor performance as determined by the "Screen Test"⁵³.

A general order of PCP-like activity was established using these techniques, and some structure-activity relationships could be assessed with regard to the potency and duration of action of certain of these analogs.

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DOI

10.25777/eejg-7x73

Recommended Citation

McKenney, Julian D.. "The Synthesis and Evaluation of the Biological Activity of Heterocyclic Analogs of Phencyclidine" (1981). Master of Science (MS), Thesis, Chemistry & Biochemistry, Old Dominion University, DOI: 10.25777/eejg-7x73
https://digitalcommons.odu.edu/chemistry_etds/175