Mixed Bromochloromethanes

Hydrogen bromide, trimethylsilyl bromide and acetyl bromide have all been proven to be suitable bromide transfer agents [e.g. 12, 13]. Tetra-n-butylammonium salts catalyse the interconversion of dichloroalkanes into bromochloroalkanes and chloroiodoalkanes upon reaction with an excess of bromo- and iodobutane, respectively [14]. Similarly, mixed bromochloromethanes are obtained from the reaction of dibromochloromethane with benzyltriethylammonium chloride under basic conditions [15]. 

When drinking water containing trace bromine is chlorinated, small amounts of mixed bromochloromethanes result. When the bromo- and chlo-romethanes shown in Fig. 1 were irradiated [13], inorganic halides and formaldehyde were produced stoichiometrically. Brominated compounds were most efficiently destroyed. 

Reaction of etio acid 67 with N,N-dimethylthioformamidoyl chloride probably gives initially the mixed anhydride 71 this is not isolated but undergoes O to S carbonyl migration to the anhydride 72. Saponification then leads to the thioacid 73. Reaction of the sodium salt of the acid witli bromochloromethane affords cloticasone propionate (74). The corresponding reaction with hioniofluoromethane leads to fluticasone propionate (75) [16]. 

An ester derived from prednisolone has found use as a topical ophthalmic antiinflammatory dmg. Cleavage of the side chain in prednisolone (31-1) with sodium periodate affords the corresponding carboxylic acid (30-2). Treatment of that product with propionyl chloride affords initially the ester at 17 along with some of the mixed anhydride. The anhydride is then hydrolyzed with a mild base to afford the 17-ester (31-3). Alkylation of the carboxylic acid with chloromethylchlorosufonyl chloride (from bromochloromethane and sulfonyl chloride) leads to the chloromethyl ester (31-4) and thus loteprednol [26]. 

After mixing the oxygen-free solutions of halocarbons with solutions of pyridinyl radicals, the rate of the reaction may be followed spectroscopically. Reaction of l-isopropyl-4-carbomethoxypyridinyl, (i-Pr)4, with bromochloromethane in acetonitrile gave l-isopropyl-4-carbomethoxypyridinium bromide, (i-Pr) , in 35% yield. The identification of two isomeric, air-sensitive dihydropyridines was facili-tat l by the characteristic patterns (NMR) for the isopropyl groups (Eq. 25),... 

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