General Reactivity of 2-Lithiobenzothiazole to Various Electrophiles and the Use as a Formyl Anion Equivalent in the Synthesis of α-Hydroxy Carbonyl Compounds

Abstract The reaction of 2-lithiobenzothiazole with a variety of electrophiles such as aldehydes, ketones, carboxylic esters, lactones, nitriles, and amides afforded the expected addition and substitution products. Trimethylsilyl chloride readily reacted with the benzothiazolyl anion to give 2-trimethylsilylbenzothiazole, while common alkyl halides including primary iodide and benzyl halides, as well as epoxides, did not react with the anion. This characteristic nucleophilicity of the anion was also demonstrated by its reaction with phenacyl halides and 5-chloro-2-pentanone leading to the formation of benzothiazolyl-substituted small-ring ethers. In order to demonstrate the value of 2-lithiobenzothiazole as a masked formyl anion, 2-(α-hydroxyalkyl)benzothiazoles were transformed into α-hydroxy carbonyl compounds in three reaction steps without masking the α-hydroxy groups. Quaternization of various 2-(α-hydroxyalkyl)benzothiazoles with methyl iodide in DMF afforded the corresponding 2-(α-hydroxyalkyl)-3-methylbenzothiazolium iodides in high yields and the subsequent alkylation or reduction of the C=N+ link was readily accomplished with organolithium and Grignard reagents or sodium borohydride leading to the corresponding 2-(α-hydroxyalkyl)-3-methylbenzothiazolines with or without another 2-substituents. Hydrolysis of former compounds performed in aqueous acetonitrile, buffered to pH 7 and containing AgNO3, gave the desired α-hydroxy ketones.