2-Methyl-2-thiopseudourea → Creatine

Participants

Reaction Steps

To a 20% (w/w) unprocessed aqueous solution of 833.1 g (about 1.5 mol) of sodium N-methylglycinate, a concentrated hydrochloric acid was added under stirring and cooling in an ice-salt liquor or an ice-water bath to adjust pH to 9.5. The temperature was kept below 15° C. in this process. Under the condition that the internal temperature was kept at 35° C., 291.9 g (1.1 mol) of S-methylisothiourea sulfate was slowly added into the solution under stirring within about 60 minutes. Then the solution was stirred for another 10 minutes at the internal temperature below 35° C. Thereafter, stirring was stopped, and the internal temperature was kept at 32° C. Reaction was allowed to proceed for 6 hours. Then a hot vapor was fed into the reaction solution for 35 minutes. A crystal was precipitated. After staying for 7 hours, the solution was centrifuged. After the liquid was removed, it was washed with distilled water (100 ml each time) until the pH value of the filtrate becomes to ≦7.5. Then the product was washed once with 140 ml of 95% ethanol, and a crude product was obtained. 1500 ml of water was added to the crude product, and the mixture was heated to 45° C. under stirring. Then pH was adjusted to 7.0 with addition of 10% sulfuric acid. Thereafter, the temperature was raised to 80° C. Then 0.3 g of disodium EDTA was added thereto, and the temperature was raised to 90° C. After stirring for 15 minutes, the solution was filtered. The filtrate was cooled to 20° C., and a crystal was obtained. The crystalline product was recovered by centrifugation, washed with 30 ml of distilled water and with 40 ml of 95% ethanol, respectively, and dried in a vacuum drier at 40° C. under 20 millibar pressure. 1044 g of the product was obtained. The yield of creatine-monohydrate was 72.0% (S-methylisothiourea was used as the standard), and the content or purity (HPLC) was 99.3%. After dehydrated at 80° C., creatine was obtained. There was substantially no product loss in this process.

Provenance & Evidence