Chloromethyl p-tolyl sulfide

The action of buQ Uithium on thioanisole in THF generates (phenylthio)methyllithium in a low yield of 35%. - Corey and Seebach found that reaction of equimolar amounts of bu Uithium, DABCO and thioanisole in THF at 0 "C produces (phenylthio)methyllithium in ca. 97% yield. Dimethyl sulfide can be metalated with a butyllithium-TMEDA complex at room temperature (equation 1). Treatment of chloromethyl p-tolyl sulfide with magnesium produces the corresponding Grignard reagent a reaction temperature between 10 and 20 C is crucial for its efficient generation (equation 2). ... 

In an attempt to further extend the foregoing methodology to include the preparation of o,p-epoxy sulfides, the condensation of chloromethyl p-tolyl sulfide and benzaldehyde using a protocol similar to that employed successfully in the sulfone case (Bu OK) gave only poor conversion to the desired epoxide. However, addition of the hindered amine base 1,4-diazabicyclo[2.2.2]octane (DABCO) results in the formation of the isomeric expoxides (29) in good yield (equation 9). In the case of benzaldehyde, the cis-epoxide predominates over the trans-epoxide (29b 82% versus 18%), while in the corresponding condensation with pivalaldehyde, the only epoxy sulfide obtained is the cis isomer (29c). Several attempts to effect an analogous reaction with ketones were unsuccessful formation of (30) (displacement-elimination) becomes the favored process (equation 10). 

P-Alkylation. The Michael-Arbuzov reaction of chloromethyl p-tolyl sulfide with trimethyl Phosphite or triethyl phosphite yields dimethyl- or diethylphosphonylmethyl p-tolyl sulfides, which are important intermediates for the synthesis of vinyl sulfides and sulfoxides, as well as for optically active derivatives of dimethylphosphonylmethyl p-tolyl sulfoxide (eq 7). This method of preparation of the chiral p-tolylthio monosulfoxide is complementary to the reaction using dimethylphosphonyl-methyllithium and (—)-(5)-menthyl p-toluenesulfinate in which the (+)-(7 isomer is obtained in high 3ueld and high optical purity (eq 8). The lithio dimethylphosphonylmethyl p-tolyl sulfoxide reacts with aldehydes and ketones to give the corresponding vinyl sulfoxides, which can be converted into optically active allylic alcohols (eq 9). ... 

Oxidation. Huoromethyl /7-tolyl sulfide, which can be oxidized to fluoromethyl /7-tolyl sulfoxide with (V-bromo-succinimide in methanol, is synthesized by the reaction of chloromethyl />-tolyl sulfide with potassium fluoride in the presence of 18-crown-6 (eq 11). Chloromethyl />-tolyl sulfoxide can be S3mthesized by a one-pot operation from methyl />-tolyl sulfide with silver(I) nitrate and sulfuryl chloride via the intermediacy of chloromethyl p-tolyl sulfide (eq 12). ... 

Self-condensation. Bis(p-tolylthio)methane, an important dithioacetal for nucleophilic alkylation, is formed by selfalkylation of chloromethyl / tolyl sulfide using neutral alumina as a catalyst (eq 10). ... 

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