Phenothiazine ring with rearrangement

Without additional reagents Phenothiazine ring with rearrangement... 

Nowhere, perhaps, is this phenomenon better illustrated than in the phenothiazine class. The earlier volume devoted a full chapter to the discussion of this important structural class, which was represented by both major tranquilizers and antihistamines. The lone phenothiazine below, flutiazin (130), in fact fails to show the activities characteristic of its class. Instead, the ring system is used as the aromatic nucleus for a nonsteroidal antiinflammatory agent. Preparation of 130 starts with formylation of the rather complex aniline 123. Reaction with alcoholic sodium hydroxide results in net overall transformation to the phenothiazine by the Smiles rearrangement. The sequence begins with formation of the anion on the amide nitrogen addition to the carbon bearing sulfur affords the corresponding transient spiro intermediate 126. Rearomatization... 

Among the more recent approaches to phenoxazines and phenothiazines the reductive cyclization of 2-nitrodiphenyl ethers and sulfides with trialkyl phosphites is the most interesting. Here too a spiro intermediate is involved, produced by attack of an initially formed aryl nitrene on the second aromatic ring. The sulfide (252), for example, reacts with triethyl phosphite to yield 1-methylphenothiazine (253) and it is clear that in this case ring opening of the spiro intermediate also proceeds with a rearrangement of the Smiles type (Scheme 113) (75JCS(P1)2396). 

The eighth volume of this serial publication comprises eight contributions from international authors. Four of these deal with well-defined groups of compounds thiopyrones (R. Zahradnik, R. Mayer, and W. Broy), phenoxazines and phenothiazines (M. Ionescu and H. Mantsch), diazepines (F. D. Popp and A. Catala Noble), and benz-isoxazoles (anthranils and indoxazenes) (K.-H. Wiinsch and A. J. Boulton). J. M. Tedder has surveyed the field of the heteroaromatic diazo compounds which are derived from a variety of heterocyclic ring systems, and M. Schulz and K. Kirschke discuss heterocyclic peroxides. The remaining two chapters survey well-known reactions the Hilbert-Johnson reaction is covered by J. Pliml and M. PrystaS, and heterocyclic Claisen rearrangements by B. S. Thyagarajan. 

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