2-Nitrothiazole nitration

That numerous 2-amino-5-nitrothiazole derivatives exhibit antiamebic, antihistomonal, antitrichomonal, and antischistosomal properties (see Section VI.2) explains the large number of nitration reactions reported. Nitration in a mixture of concentrated nitric and concentrated sulfuric acids IS among the most common experimental methods (16, 27, 58, 374-377). 

Taurins reported that nitration of 2-nitramino-5-nitrothiazole yields the fully nitrated 2-imino-4-thiazoline (184) (Scheme 117) (87). This interesting compound should be studied by spectroscopic methods. 

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). 

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... 

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. 

Studies of the nitration of 4-chloromethyl-2-phenylthiazole have shown that the action of nitric acid (d 1.40) in sulfuric acid at 60°C gives the 4-nitrophenyl product and the use of nitric acid in acetic anhydride at 60°C forms the 5-nitrothiazole product. Chlorination and bromination also result in 5-substitution in the thiazole ring and nitration of these products using mixed acid gives the 4-nitrophenyl products. 2-(4-Bromophenyl)-4-chloromethylthiazole also nitrates at the 5-position of the thiazole ring using nitric acid in acetic anhydride below 60°C (65CB3446). 

Only one example of the nitration of thiazoles at position 2 has been described the action of the sulfuric-nitric acid mixture on 4,5-dimethylthiazole gave 4,5-dimethyl-2-nitrothiazole [199],... 

It would probably be useful to carry out a more detailed investigation of these reactions using ESR and CIDNP techniques. Further nitration of 2-nitroamino-5-nitrothiazole leads to 2-nitroimino-3,4,5-trinitro-3//-thiazoline [203] (Scheme 25). 

It was possible to obtain 2-amino-5-nitrothiazole while avoiding the risk of explosion at the nitration stage [499], The nitroaminoethene used for this purpose cannot be isolated in the pure form and is generated from nitromethane and dime-thylformamide during the reaction. 

This reaction acquires special significance as a result of the fact that it is possible to introduce a nitro group at position 3(5) of the pyrazole ring. This is impossible during direct nitration. /V-Nitroimida/oles [323, 326] and 1,2,4-triazoles [318, 577] enter into such a rearrangement. In a similar way A-nitroaminothiazoles isomerize to 2-amino-5-nitrothiazoles [231] (Scheme 110). 

Only the 2.4-dinitrothiazole is known, being prepared by nitration of 2-nitrothiazole by N2O4-NO2/BF3. The yield is 80% (90). The reduction with Raney Ni/AcjO of 2,4-dinitrothiazole proceeded smoothly, yielding the corresponding 2,4-diacetamidothiazole. 

Nitro-5-halogenothiazoles, 57 8 preparation of, 578 reaction with MeO", 580 2-(4-Nitrophenylimino)-4-thiazolidone, from 4-nitrophenylthiourea and chloroacetic acid, 296 2-Nitrothiazole, 576 nitration of, 577 preparation of, 576 reaction with KF, 566 reaction with MeO", 577 reduction of, 577... 

As in the case of oxazoles, the pyridine-like N-atom makes electrophilic substitution reactions more difficult. Thus thiazole does not react with halogens. Donor substituents enhance the reactivity, e.g. 2-methylthiazole reacts with bromine to give 5-bromo-2-methylthiazole. Thiazole cannot be nitrated. 4-Methylthiazole reacts slowly to yield the 5-nitro compound, 5-methylthiazole even more slowly to give the 4-nitro compound, but 2,4-dimethylthiazole reacts fastest producing 2,4-dimethyl-5-nitrothiazole. Sulfonation of thiazole demands the action of oleum at 250°C in the presence of mercury(II) acetate, and occurs at the 5-position. Acetoxymercuration of thiazole with mercury(II) acetate in acetic acid/water proceeds stepwise by way of the 5-acetoxymercury compound and the 4,5-disubstituted product to 2,4,5-tris(acetoxymercury)thiazole. 

C4H3NsS06 mw 249.18 N28.il OB to CO2 —22.47% white cryst mp 98° (explds). It is decompd by solvents such as benz, eth acetate and acetic acid. Prepn is by careful nitration of 4-methyl-2-nitramino-5-nitrothiazole with nitric acid-acetic anhydride mlxt (30/70) at 5°... 

Niter. See Potassium nitrate Nitramin. See 2-Amino-5-nitrothiazole Nitramyl. See Isoamyl nitrite 4-Nitraniline. See p-Nitroaniline m-Nitraniline. See m-Nitroaniline o-Nitraniline. See o-Nitroaniline p-Nitraniline. See p-Nitroaniline Nitrapyrin. See 2-Chloro-6-(trichloromethyl) pyridine... 

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