Fenotiacina

THE CHEMISTRY OF PHENOTHIAZINE
SAMUEL P. MASSIE
Department of Chemistry, Fisk University, Nashville, Tennessee Received July I , 1954
CONTENTS

I. 11. 111. IV. V,

VI. VII. VIII. IX. X.

Introduction.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 797 Nomenclature.. . . . . . .................... ........... . . . . 798Historical., . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ......................... 798 Properties of phenothiazine,, . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 800 Preparation of phenothiazine and its derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . A. Ring-closure methods . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Diphenylamine derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 800 2. Diphenylaminosulfinic acids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 802 3 . Smiles rearrangement, . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8034. Diphenylsulfides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 806 5. Miscellaneous ring-closure methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 808 B. hTuclear substitution react,ions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 809 1. Nitration.. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . 810 2. Halogenation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 810 3. Mercuration. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 812 ................................................... 812 5. Acylation via the Friedel-Crafts reaction.. . . . . . . . . .. . . . . . . . . . . . . . . . . . 813 6. Miscellaneous nuclear substitution met,hods. . . . . . . . . . . . . . . . . . . . . . . . . . . 814 C. Substitution of the amino hydrogen., . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 815 1. Alkylation reactions, . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) Alcohols as alkylating agents.. . . . . .. . . . . . . . . . . . . . . (b) Sulfates as alkylating agents.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 816 (c) Halides as alkylating agents.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 816 2. Acylation reactions, . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 819 D. Modification of the sulfidelinkage.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 820 1. Oxidation of the sulfide linkage t o sulfoxides and sulfones, . . . . . . . . . 2. Reduction of the sulfoxides and sulfones.. . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Removal of the sulfur a t o m . ......................... . . . . . . . . . . 822 ....................................... 822Phenothiazine drugs. . . . . . . . . . . . . . Oxidized forms of phenothiazine, . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Phenothiazine and its compounds as antioxidants. . . . . . . . . . . . . References.. . . . . . . . . . . . . . . . . . . . . . ..... ........................ 825 Appendix: tables of derivatives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . .829

I. INTRODUCTION Phenothiazine was first prepared by Bernthsen (12) in 1883 in the course of proof of structure studies on Lauth’s violet and methylene blue. Since then it has played an important role in dye chemistry as the parent compound of the thiazine dyes (161). In the last twenty years phenothiazine and its derivatives have found numerous applications in other fields, and this has...