SYNTHESIS AND PROPERTIES OF 2-(ALPHA-HYDROXYALKYL) AND 2-ALPHA-ALKOXYCARBONYL) SUBSTITUTED 4-METHYL-5-(BETA-HYDROXYETHYL)-THIAZOLES AND THIAZOLIUM SALTS

Condensation of the tetrahydropyranyl ether of the α‐hydroxyalkyl‐thioamides with 3‐bromo‐4‐hydroxy‐2‐pentanones yields DL‐2‐(α‐hydroxyalkyl)‐4‐methyl‐5‐(β‐hydroxyethyl)‐thiazoles. By oxidation with chromic anhydride 2‐hydroxymethyl‐4‐methyl‐5‐(β‐acetoxyethyl)‐thiazole yields the corresponding 2‐formyl derivative. The latter compound reacted with GRIGNARD complexes gives the homologous DL‐2‐(α‐hydroxyalkyl)‐4‐methyl‐5‐(β‐hydroxyethyl)‐thiazoles. This is a general method for the synthesis of the thiazole part of the «active aldehydes». 2‐Acetyl‐4‐methyl‐5‐(β‐hydroxyethyl)‐thiazole is also obtained by chromic oxidation of the suitable methylthiazol‐2‐yl‐carbinol. The condensation of the thioamides obtained from the α‐ethoxycarbonyl‐nitriles with 3‐bromo‐5‐acetoxy‐2‐pentanone results in the DL‐2‐(α‐ethoxycarbonyl‐alkyl)‐4‐methyl‐5‐(β‐acetoxyethyl)‐thiazoles. The α‐hydroxyl function is introduced into the 2‐(α‐ethoxycarbonyl‐alkyl) group by chlorination with sulfuryl chloride and replacement of the introduced chlorine by acetate. The latter compounds are the esters of the thiazole part of the «active α‐oxo‐carboxylic acids» (e.g. active pyruvate, etc.). The reaction of 2‐(α‐hydroxyalkyl)‐4‐methyl‐5‐(β‐hydroxyethyl)‐thiazoles and 2‐(α‐ethoxycarbonyl‐α‐acetoxy‐alkyl)‐4‐methyl‐5‐(β‐acetoxyethyl)‐thiazoles, respectively, with alkyl, alkenyl and aralkyl haloids, or with 2‐methyl‐4‐amino‐5‐bromomethyl‐pyrimidine hydrobromide results in the quaternary thiazolium compounds belonging to the group of the active aldehydes, active α‐oxo‐carboxylic acids, etc. According to this method 2‐hydroxymethyl‐thiamine bromide hydro‐bromide has been synthesized, which can be considered as the pyrophosphate‐free «active formal‐dehyde». The 2‐α‐hydrogen atom in 2‐(α‐hydroxyalkyl)‐thiazolium compounds cannot be replaced by deuterium under conditions similar to those used for the H → D exchange in thiamine. The main peaks in the mass spectra of 2‐(α‐hydroxyalkyl) substituted thiazoles and thiazolium quaternary salts are listed. Copyright © 1968 Verlag GmbH & Co. KGaA, Weinheim