Chemistry of Thiamine
Soon after the purification and crystallization of thiamine it was evident that a pyrimidine nucleus was a part of the molecule and that there also was present a substituted thiazole ring. In the synthesis of Williams and co-workers, the substituted pyrimidine (2 methyl-5romomethyl-6-aminopy-rimidine hydrobromide) was reacted with 4 methyl-5-b-hydroxyethylthiazole to yield the bromidehydrobromide of the vitamin. The naturally occurring ---:amine is a chloride-hydrochloride. After Williams converted the bromide derivative to the oride-hydrochloride, it was identical with thiamine isolated from natural sources.
The work required for the synthesis of this molecule is, of course, not depicted by the reaction. Years of investigation by many scientists allover the world culminated in success. e gram of thiamine can be dissolved in 1 ml of water; this gives an acid solution due to the bchloride on the amino group. It is soluble to about 1 per cent in alcohol but rather insoluble in other common organic solvents. Thiamine exhibits, absorption bands in the ultraviolet spectrum. At pH 7 (aqueous solution) the maxima are at 235 and 267 mil. At lower pH values the absorption spectrum changes. This influence of hydrogen ion on absorption is characteristic of many basic nitrogen compounds. The molecule reacts with platinum chloride to form microcrystalline rosettes. It also forms insoluble compounds with phosphotungstic and tannic acids. Thiamine picrate was one of the early derivatives to be crystallized.
Sulfates, nitrates, etc., have also been prepared. Many of these derivatives have vitamin activity. The melting point is between 248 and 25_0°C. This is for the hemihydrate, which crystallizes as white monoclinic needles. The odor of thiamine is highly characteristic and very like that of yeast. The characteristic odor of yeast is due in large part to the contained thiamine. Thiamine is destroyed at elevated temperatures unless the pH is low. In alkaline solution complete destruction results from boiling for short periods. At a pH of 3.5 boiling results in little destruction.
In yeast, autoclaving at 120°C for short periods does' not destroy the vitamin, but after two or three hours nearly complete destruction is accomplished. Thiamine is readily oxidized; under controlled conditions thiochrome is formed, and this is the basis for a quantitative determination of the vitamin. On reduction, hydrogen is added to the thiamine molecule, and vitamin activity disappears. Schultz prepared a series of 39 compounds chemically related to thiamine; 16 of these showed some vitamin activity. The structure of thiamine as the free base is shown in the following. The naturally occurring molecule and the synthetic vitamin contain a hydrochloride on the amino group and a chloride ion neutralizing the positive charge on the nitrogen atom of the thiazole ring.
