Amide, sodium pyrrolidine, reaction with

Of the several syntheses available for the phenothiazine ring system, perhaps the simplest is the sulfuration reaction. This consists of treating the corresponding diphenylamine with a mixture of sulfur and iodine to afford directly the desired heterocycle. Since the proton on the nitrogen of the resultant molecule is but weakly acidic, strong bases are required to form the corresponding anion in order to carry out subsequent alkylation reactions. In practice such diverse bases as ethylmagnesium bromide, sodium amide, and sodium hydride have all been used. Alkylation with (chloroethyl)diethylamine affords diethazine (1), a compound that exhibits both antihista-minic and antiParkinsonian activity. Substitution of w-(2-chloroethyl)pyrrolidine in this sequence leads to pyrathiazine (2), an antihistamine of moderate potency. 

Prop-2-ynyl)-5-(trifluoromethyl)-l,3,4-thiadiazol-2(3//)-one 322 reacts with nucleophiles (ammonia, pyrrolidine, or potassium methylthiolate) to form 6-methylene-2-(trifluoromethyl)-5,6-dihydro-4//-l,3,4-thiadiazine-4-carbox-amides or j -methyl 6-methylene-2-(trifluoromethyl)-5,6-dihydro-4//-l,3,4-thiadiazine-4-thiocarboxylates 323. The reaction of aqueous sodium hydroxide with 322 gives the 4//-l,3,4-thiadiazine 324, which also bears an exocyclic methylene group (Scheme 43) <1998HOU(E9c)483>. 

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