Studies on Vitamin B₁ and Related Compounds. XXXVI

Synthesis of 3-[2′-β-Hydroxyethyl-4′-aminopyrimidyl-(5′)]-methyl-4-methyl-5-β-hydroxyethylthiazolium Compound

Abstract

2-β-Hydroxyethyl-4-amino-5-cyanopyrimidine (III) was prepared from β-hydroxypropionitrile by deriving it first to β-hydroxypropioimidoether by the application of the alcohol and hydrogen chloride, then to β-hydroxypropioamidine by the application of ammonia to the ether, and by the condensation of ethoxymethylenemalonitrile. (III) forms 2-β-chloroethyl derivative (IV) by the action of phosphoryl chloride, and 2-β-acetoxyethyl derivative (V) by acetylation with acetic anhydride in pyridine. Heating of (III) with acetic anhydride alone results in the formation of 2-vinyl derivative (VI) with (V). Electrolytic reduction of (III) in hydrochloric acid, with palladium-black as the cathode, yields 2-β-hydroxyethyl-4-amino-5-aminomethylpyrimidine (VII) hydrochloride. Application of carbon disulfide and γ-aceto-γ-chloropropyl acetate to (VII), in the presence of ammonia, results in the formation of α-aceto-γ-acetoxypropyl N-[2-β-hydroxyethyl-4-aminopyrimidyl(5)]-methyldithiocarbamate (VIII), whose heating with diluted hydrochloric acid yields 3-[2′-β-hydroxyethyl-4′-aminopyrimidyl(5′)]-methyl-4-methyl-5-β-hydroxyethylthiazol-2-thione (IX) The treatment of (VIII) with alkali yields 2-thio-7-β-hydroxyethyl-1, 2, 3, 4-tetrahydropyrimido-(4, 5-d)-pyrimidine (X). Application of ethyl iodide to (IX) yields 2, 9-di(β-hydroxyethyl)-3-methylthiochromine (XI), and application of hydrogen peroxide to the dil. hydrochloric acid solution of (IX) results in the formation of 3-[2′-β-hydroxyethyl-4′-aminopyrimidyl(5′)]-methyl-4-methyl-5-β-hydroxyethylthiazolium compound (II). The hydrochloride of (II) was found to possess one-third to one-quarter the effect of thiamine, tested with rice birds. (IX) was found to be totally ineffective.