Nitric Acid → O-methyl-N-(2-chloro-5-thiazolylmethyl)-N'-nitroisourea

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Reaction Steps

Urea [99%] (3.03 g, 0.05 mol) and dimethyl sulfate [95%](6.64 g, 0.05 mol) were mixed at room temperature and stirred for a few minutes. The mixture was heated in an oil bath and stirred at 80° C. for 15 hours. The mixture was cooled to room temperature and sulfuric acid [95%, d 1.84] (11.2 ml, 0.2 mol) was added, and then the mixture was further cooled to 5° C. Fuming nitric acid [97%, d 1.52] (6.4 ml, 0.15 mol) was added dropwise over 25 minutes while maintaining the interior temperature to below 10° C. Then, the ice bath was removed and the temperature was gradually raised to room temperature. After stirring for total 2 hours, the mixture was poured into ice-water (60 g-40 g) and neutralized (about pH 2) by adding an aqueous 40% sodium hydroxide solution. 5-(Aminomethyl)-2-chlorothiazole (3.34 g, 0.023 mol) was added (pH 3.8) and then the pH was adjusted to about 6.7 with 40% aqueous sodium hydroxide solution, and then the mixture was stirred at room temperature for 20 hours. The deposited crystal was collected by filtration, washed and then dried to obtain 3.63 g of O-methyl-N-(2-chloro-5-thiazolylmethyl)-N′-nitroisourea. The yield was 64.4%. based on 5-(aminomethyl)-2-chlorothiazole, and 29.0% based on urea.

Provenance & Evidence