Nitration aminothiazole

Dimethylaminothiazole reacts as 2-aminothiazole with nitrating reagents (375. 384), but the other dialkylaminothiazoles (32a, 32b, 32c p. 32) are reported to be cleaved rather than nitrated (385). 

Experimental requirements for the isolation of these nitramino derivatives are developed in Ref. 87. They rearrange easily to ring nitro-substituted isomers (see Section V.6). In the 2-aminothiazole series, nitration may proceed through direct electrophilic substitution competing with rearrangement of nitramino derivatives. Dickey et al. have shown that the rearrangement proceeds rapidly in 96% sulfuric acid at 2(fC, but in 85% sulfuric add it is very slow so. according the concentration of add various mechanisms can participate in the formation of the 5-nitro derivative. 

These compounds are isolated when the nitration of 2-aminothiazoles is carried out under mild conditions (see p. 73). 

The 2-nitrothiazole can be reduced to the corresponding aminothiazole by catalytic or chemical reduction (82, 85, 89). The 5-nitrothiazole can also be reduced with low yield to impure 5-aminothiazole (1, 85). All electrophilic substitution reactions are largely inhibited by the presence of the nitro substituent. Nevertheless, the nitration of 2-nitrothiazoIe to 2,4-dinitrothiazole can be accomplished (see Section IV). 

In an attempt to produce the nitrate salt, 2-aminothiazole was added to the required amount of nitric acid and the mixture stirred and heated the mixture exploded without warning. 

One of the earliest diazo components of this type to be introduced was 2-amino-5-nitrothiazole (4.81), prepared by condensation of thiourea with chloroacetaldehyde and nitration of the resultant 2-aminothiazole (Scheme 4.32). This component yields bright dischargeable blues, such as Cl Disperse Blue 82 (4.82), which have outstanding build-up, very high extinction coefficients and good fastness to burnt gas fumes. Use of diazo component 4.81 with coupling component 4.83 yields a greenish blue dye. 

As noted above, nitrofurans and nitroimidazoles have proven useful moieties for the preparation of antibacterial and antiprotozoal agents. It is thus of note that nitrothiazoles have also been used successfully in the preparation of antiparasitic agents. Condensation of 6-nitro-2-aminothiazole (194, available from nitration of aminothiazole) with ethylisocyanate yields the antiprotozoal agent... 

Ganapathi and Venkataraman [29] found that aminothiazole and its homologues can be nitrated in the same way, using a double excess of nitrating mixture. 

In addition to the compound (I), a certain amount of a compound (II) nitrated in the ring is formed when a stoichiometric quantity of HN03 is used. As the investigations of Wright et al. [30] subsequently showed, the compound (II) is also obtainable when aminothiazole is treated with a nitrating mixture containing 10-30% of water. 

Solid, mp 197—8°(decomp). Can be prepd by refluxing a soln of 2-acetamido-5-nitrothia-zole in aq H3 S04 fot 1 hr, followed by cooling and treatment with phosphoric acid(Refs 2 3) or by nitrating 2-aminothiazole with mixed nitric-sulfuric acids(Ref 4)... 

Amino-5-nitrothiazole is prepared (59JOC187, 55JOC499) by the reaction between 2-chloroacetaldehyde and thiourea followed by nitration of the free amine. It has been shown that the nitration proceeds by the N-nitration of the 2-amino group followed by rearrangement. Several other derivatives of 2-aminothiazole have been described in patents but none have reached any commercial significance. 

Nitration of 2-aminothiazole with nitric—sulfuric acids was normally effected by mixing the reactants at low temperature, heating to 90°C during 30 min and then applying cooling. When the cooling was omitted, a violent explosion occurred. 

Aminothiazole and Sulfuric Acid. Nitration of 2-aminothiazole with H2S04/HN03 may result in a violent explosion if cooling is omitted.15... 

Aryl amines, 403 4-Aryl-2-aminothiazoles, 178-182 mercuration of, 81 nitration of, 72 reduction of, 86 Schiff bases from, 99 Aryl diazonium salts, reaction with, rho-danine, 419... 

Sulfonimidothiazolines, 317, 318 Sulfonyl halides, with 2-aminothiazoles, 69 Sulfur (Sg), in synthesis of, A-4-thiazoline-2-thione, 373 Sulfur compounds, 69 Sulfuric acid, with alcohols, 38, 47, 80, 90 in bromination, 77 dealkylation by, 39 deuterated, 92 diazotization with, 66 in nitrations, 72 rearrangements in, 73, 113 Sulfuryl chloride, 432 Symbiotic behavior, see HSAB theory Symmetry. C2v and C2p, 120 Synthetic fibers, 154... 

Aminothiazole is converted by the action of ethyl nitrate into the 5-nitro derivative [352], As already mentioned 2-phenyloxazole and 2-phenylthiazole are nitrated into benzene ring by the sulfuric-nitric acid mixture. At the same time their nitration under conditions excluding protonation of the azole ring (with the use of acetylnitrate or /V-nitropicolinium tetrafluoroborate as nitrating agent) leads to the 5-nitro derivatives [353] (Scheme 40). 

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