5-Nitrothiazole preparation

The reaction of 2-amino-5-nitrothiazole with (3-chloroethyl isocyanate gives the corresponding thiazolyl urea (137) (Scheme 90) (298). Other examples are given in Section V.l.B, where the preparation of thiazolyl-thioureas is discussed,... 

Nitrothiazole and 5-nitrothiazole are known products, while 4-nitrothiazole does not appear to have been prepared. 2-Nitrothiazole (2,... 

Some 2-halogeno-5-nitrothiazoles and 2-nitro-5-halogenothiazoles are known. 2-Halogeno-5-nitrothiazoles can be prepared by a Sandmeyer reaction from 2-amino-5-nitrothiazole (1, 85), while 2-nitro-5-halo-genothiazoles can be analogously prepared by decomposition of dia-zonium salts arising from 2-amino-5-halogenothiazoles in presence of nitrite anion (82, 84). 

Many 2-substituted 5-nitrothiazoles are prepared (by nucleophilic substitution reactions on 2-halogeno-5-nitrothiazoles) for use as biocides or for their biological activity (31, 91-95). 

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. 

To a solution of 1 kg (7 moles) of 2-amino-5-nitrothiazole in 5 L of pyridine (dried with potassium hydroxide) was added dropwise for 2-3 hours 8.5 moles of 2-thienoylchloride. N-(5-Nitro-2-thiazolyl)-2-thiophenecarboxamide was prepared as a yellow crystals with melting point 255-256°C. 

This reaction is convenient for preparative synthesis, since it can be conducted in a single stage [529], cc-Halogeno-cc-nitro ketones are also used for the synthesis of 5-nitrothiazoles [213] (Scheme 88). 

Recently a large number of papers have been devoted to the preparation of nitro-pyrazoles [377-380], nitroimidazoles [381-388], nitroisoxazoles [389-391], nitrothiazoles [392], nitrotriazoles [393-396], and nitrobenzazoles [397-399] due... 

Partition coefficients in the octanol-pH 7.4-phosphate-buffer system. c Nitrothiazole oxidation-reduction potentials (volts) as calculated from their half-wave potentials, as determined using a Polarecord E 261 polarograph (Metrohm AG, Herisau, Switzerland) and a saturated Ag/AgCl reference electrode. Measurements were performed at 20°C and a drop time of 1 drop/2.8 sec. The compounds were dissolved in 1 ml dimethyl formamide and added to 24 ml of a borax-potassium biphosphate buffer of pH 7.3 [prepared according to J. M. Kolthoff, J. Biol. Chem. (1925) 68, 135]. A pH of 7.4 resulted. Standard error of determination 3 mv. 

Heterocyclic compounds bearing nitro groups were among some of the earliest antiparasitic agents. A nitrothiazole has recently been approved for treating diarrhea due to such infections. This rather venerable compound, nitazoxanide (155) is prepared in a single step by reaction of the acid chloride (153) from aspirin with the aminonitrothiazole (154). ... 

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... 

Nitrothiazole, 576 preparation of, 577 reduction of, 577 ring opening reaction, 577 Nitrothiazoles, chemical shift, proton, 68 coupling constants in EPR, 84 ionization potential, 5 2 reduction of, 381 ultraviolet absorption, 48 Nuclear magnetic resonance, 66 of alkyl thiazoles, 342 of aryl thiazoles, 342 correlation with theoretical calculations, 70... 

A few nitrothiophenes have been shown to possess marked schistosomicidal activity, though weaker than nitrofurans or nitrothiazoles. Of these, compounds 9 and 10 exhibited potent activity. Compound 9, which bears a close resemblance with furapyrimidone, caused 100% elimination of S. mansoni from mice at a dose of 250 mg/kg [19], while 10 was found to be active against S. mansoni, S. japoniaim and S. haematobium infections in experimental animals and also proved to be less toxic in dogs and cebus monkeys [20a]. Alaimo and Hatton [20b] have prepared a... 

Henry [36] prepared a series of 5-nitrothiazoles with a C-C rather than C-N bond at their 2-position. Interestingly, compounds 27a and 27b were found to cause reversible abnormalities in the reproductive system of female blood flukes [37]. 

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