Thiamine hydrochloride, reaction with

An insight into the mechanistic details of this transformation has been gained from the extensive studies of Takamizawa and co-workers. Initially, the reaction of thiamine hydrochloride (96) with diethyl benzoyl-phosphonate in the presence of sodium hydroxide was shown to give the dihydrothiazinone 97. When the reaction was carried out in AT,JV-dimethyl-formamide containing triethylamine, compound 84 (R = H) was obtained ... 

Despite its favorable safety profile, it cannot be assumed that thiamine is completely innocuous. Thiamine hydrochloride is routinely given to patients with Wernicke s encephalopathy or malnourished states (such as malabsorption, beri-beri, cancer, AIDS, and chronic alcohol abuse). Systemic reactions are rare but deaths can occur. 

Thiamine hydrochloride is stable in acid but unstable in aqueous solutions with a pH above S. Under lhe.se conditions. it undergoes decomposition and inactivation. Exposure of thiamine to the atmosphere or to oxidizing reagents such as hydrogen peroxide, permanganate, or alkaline potassium ferricyanide oxidizes it readily to ihiochromc, shown below. Thiochromc exhibits a vivid blue fluorescence hence, this reaction is the basis for the quantitative fluoro-metric assay of thiamine in the USP. 

Figure 102. Effect of water content on the degradation of thiamine hydrochloride tablets composed of magnesium stearate and microcrystalline cellulose. The percent of drug remaining after reaction equilibrium at 55°C is plotted versus water content. (Reproduced from Ref. 453 with permission.)...

Several reagents and reaction conditions such as TMSI (generated in situ from TMSCl and Nal), magnesium nitride (Mg3N2), triphenylphosphine (PPhs), thiamine hydrochloride (vitamin mnding under solvent-free conditions, PTSA with ultrasonic irradiation were recently reported to mediate efficiently the Hantzsch dihydropyridine synthesis. For instance, 1,4-dihydropyridines 143 were obtained in good yields using thiamine hydrochloride (vitamin B ) as the catalyst under solvent-free conditions at room temperature. ... 

SCHIFF (1941) refers to a similar case in which a patient received a series of intramuscular injections of 25 mg dosages within a period of 7 months using three different commercial preparations. After the last injection, nausea, vomiting, profuse sweating, and collapse occurred showing the signs of severe shock. On closer interrogation, it was found that the patient had had several brief episodes of nasal symptoms and nausea after the previous injections. An intradermal test with an aqueous solution of thiamine hydrochloride was also positive in this case. In view of the rapidity with which the reaction occurred, the author assumed that some of the thiamine hydrochloride solution must have been administered intravenously at the last injection. 

Thiamine hydrochloride is structurally similar to thiamine pyrophosphate (TPP). TPP is a coenzyme universally present in all living systems. It catalyzes several biochemical reactions in natural systems. It was originally discovered as a required nutritional factor (vitamin) in humans by its link with the disease beriberi. Beriberi is a disease of the peripheral nervous system caused by a deficiency of Vitamin in the diet. Symptoms include pain and paralysis of the extremities, emaciation, and swelling of the body. The disease is most common in Asia. 

Properties—Synthetic thiamin is usually marketed as thiamin hydrochloride, which is more stable than the free vitamin. It is a crystalline white powder, with a faint yeastlike odor and a salty nutlike taste. It is stable when dry but readily soluble in water, slightly soluble in alcohol, and insoluble in fat solvents. Heating in solutions at 248 F (12CPQ in an acid medium (pH 5.0 or less) has little destructive effect. But cooking foods in neutral or alkaline reaction is very destructive. Also, autoclaving and ultraviolet light destroy thiamin. 

The distribution of products of the formose reaction carried out in aqueous DMF has been studied. Considerable control was possible by adjustment of the water content. When, for example, formaldehyde was heated at 75 C for 1 hour with triethylamine and thiamine hydrochloride in 8 1 DMF-H2O, DL-2-C-... 

Thiamine is another key sulphur precursor used for meat-like process flavours. Bid-mead and co-workers [95] used thiamine as precursor in combination with an aliphatic carboxylic acid to obtain roasted meat flavours. The reaction can be carried out in presence or absence of a carbohydrate. For example, refluxing thiamine, cysteine hydrochloride and a carbohydrate-free HVP (hydrolysed vegetable protein) for 4 hours results in a product with beef flavour. Giacino [69] proposes the reaction of thiamine with a cysteine-containing peptide, e.g. glutathione or an amino acid mixture containing cysteine, and adding aldehydes and ketones after the reaction. The reaction is preferably carried out in fat. 

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