Synthesis of 2-Amino-5-nitrothiazole

A new synthetic process for 2-Amino-5-nitrothiazole avoids dangerous nitration and rearrangement procedures.

The new synthetic process for 2-amino-5-nitrothiazole consists of the following steps: (1) halogenating (chlorinating or brominating) a N,N-dialkyl-2-nitro-etheneamine having the formula O2 NCH═CHNR1 R2 to obtain a compound(s) having the structure ##STR1## (2) reacting (I) with thiourea to obtain a compound having the formula ##STR2## and (3) treating (II) with water.  The specific reaction steps are shown below:

EXAMPLE 1: To a stirred mixture of 3.5 g (0.03 mol) of N,N-dimethyl-2-nitroetheneamine in 25 ml of ethanol chilled at 0°-5° C. under nitrogen was added 4.8 g (0.03 mol) of bromine dropwise so that the mixture stayed below 10° C. (30 minutes). Upon completion of bromine addition a solution was observed. To the resulting solution of the compound having the structure O2 N(Br)C═CHN(CH3)2.HBr was added 3 g (0.039 mol) of thiourea at ice temperature. The cooling bath was removed and the thiourea first dissolved. In 15 minutes a white precipitate appeared. This mixture was allowed to stir at room temperature for one hour, then again cooled to ice temperature. The precipitate was filtered, washed with a small amount of cold ethanol and then dried under a dry nitrogen atmosphere to give 8.05 g (99% yield) of product as a sandy well-packed solid. Mp. 130° C. (decomposed). The product had the formula ##STR5##

EXAMPLE 2: To 10 ml of water was added 2.71 g (0.01 mol) of the product of Example 1. The salt dissolved very quickly and in 5 minutes a yellow solid started to precipitate. The mixture was stirred an additional one hour and then the precipitate was filtered off, washed with water and then dried to give 1.2 g (82.8%) of 5-nitro-2-aminothiazole; m.p. 198° C. (decomposed).

EXAMPLE 3: To a stirred mixture of 3.5 g of N,N-dimethyl-2-nitroetheneamine in 25 ml of acetic acid cooled to 17° C. was added 4.8 g bromine at such a rate the reaction temperature did not exceed 25° C. During bromination an orange solid was formed. After stirring the resulting slurry for 10 minutes, 3.0 g thiourea was added and the reaction mixture exothermed to 32° C. A yellow solid formed. The mixture was stirred for 1 hour and then was diluted with 25 ml of water. This mixture and an approximately equal volume of 29% ammonium hydroxide were added simultaneously to 25 ml of acetic acid at such rates that the pH remained between 4 and 5 and the temperature did not exceed 30° C. After all of the reaction mixture had been added the pH was adjusted to 7 with 29% ammonium hydroxide. The product was then filtered off, washed with water and dried to give 2.7 g (62% yield, 92.9% assay) of 2-amino-5-nitrothiazole.

EXAMPLE 4: Dimethyl sulfate (126 g, 1.0 mol) was added dropwise over one-half hour to dimethylformamide (73 g, 1.0 mol) heated to 60° C. The solution was stirred at 60° C. for two hours after completion of addition before cooling to room temperature. Nitromethane (61 g, 1.0 mol) was added and mixed thoroughly. This mixture was added dropwise over one hour to a slurry of sodium acetate (82 g, 1 mol) in one liter of isopropanol at 50° C. The yellow slurry was stirred at 50° C. for two hours after completion of the addition. To this slurry, cooled to 5° C., was added bromine (128 g, 0.8 mol) at such a rate that the temperature did not exceed 10° C. After the resulting yellow solution was stirred for one-half hour at 5° C., thiourea (61 g, 0.8 mol) was added and the cooling means were removed. The mixture exothermed to 30° C., was stirred at room temperature for one hour and then was cooled to 5° C. The isopropanol was removed by using a filter leg and 500 ml isopropanol was added to the remaining solids, stirred and then removed. Water (500 ml) was added to the white solid and, upon stirring, a yellow solution was immediately obtained. The agitation was stopped and, upon cooling to 5° C., yellow needles precipitated. The 2-amino-5-nitrothiazole product was filtered off, washed with water and dried. The yield was 32% based on nitromethane and 42% based on bromine.