THE CORRECT STRUCTURES OF DIHYDROTHIAMINE - RESOLUTION OF A LONG-STANDING CONTROVERSY

Reduction of thiamin (1) by a borohydride in water first gives bicycli c perhydrofuro[2,3-d]thiazole 3, Heating 3 in water generates fused tr icyclic pyrimido[4,5-d]thiazolo[3,4-a]pyrimidine 4. X-ray crystal stru ctures indicate the stereocenters are cis in 3 and cis-cis in 4, The k inetics of reduction of both 3 and 4 to tetrahydrothiamin 5 by additio nal aqueous borohydride show that 3 is the kinetic product of the redu ction of 1 while 4 is the thermodynamic product produced from 3 in an acid-catalyzed ring-opening ring-closing isomerization process. Severa l structural assignments of ''dihydrothiamine'' presented some 40 year s ago are incorrect, Subsequent reports based on the incorrect structu res need to be reinterpreted.