Thiazoles nitro

Halothiazoles are usually obtained from 2-aminothiazoles through the Sandmeyer reaction. Nevertheless, ammonolysis has sometimes proved useful for the preparation of 2-aminothiazole derivatives. Detweiler et al. (18) obtained 2-(u-pyridinylamino)thiazole (1) from 2-bromothiazole (Scheme 1). The reaction is easier if a nitro group occupies the 5-position of the thiazole ring (19-21). Ethylene diamine derivatives undergo this reaction with 2-haiothiazoles (22-24). 

Reduction of 2.4-dimethyl-5-nitrothiazole with activated iron gives a product that after acetylation yields 25% 2.4-dimethyl-5-acetamido-thiazole (58). The reduction of 2-methyl 5-nitrothiazole is also reported (351 to give a mixture of products. The nitro group of 2-acetylhydrazino-5-nitrothiazole is reduced by TiCl in hydrochloric acid or by Zn in acetic acid (591. 

Oxalyl chloride reacts at 25°Cin tetrahydrofuran with 2-amino-5-nitro-thiazole. yielding structure 98 (Scheme 68) (261). 

The nitro group increases the acidity of the hydrogen born by the exocyclic nitrogen, and alkylation of 2-nitraminothiazole with diazomethane is possible (87), The formed 2-(A"-methylnitramino)-thiazole also may be obtained from the reaction of 2-nitraminothiazole with dimethylsulfate in basic medium (194). 

Esters of 2-thiazole carboxylic acids (75) (383) are also prepared from ethyl monothiooxamate (74) (Scheme 34), and several compounds of this type with hydrogen, alkyl, or aryl groups in the 4- or 5-position (201, 209, 210, 242, 294) or a nitro group in the 5-position (674) have been reported. 

A large number of variously 2-, 4-, and 5-substituted thiazoles with alkyl, aryl, hydroxy, methylthio, mercapto, halo, and nitro groups have been analyzed by thin-layer chromatography on silica and alumina by the Stahl s technique (167, 170, 172). Among the many systems recommended for the elution of these compounds are the following ... 

The overall reactivity of the 4- and 5-positions compared to benzene has been determined by competitive methods, and the results agreed with kinetic constants established by nitration of the same thiazoles in sulfuric acid at very low concentrations (242). In fact, nitration of alkylthiazoles in a mixture of nitric and sulfuric acid at 100°C for 4 hr gives nitro compounds in preparative yield, though some alkylthiazoles are oxidized. Results of competitive nitrations are summarized in Table III-43 (241, 243). For 2-alkylthiazoles, reactivities were too low to be measured accurately. 

Thiazole, 5-amino-4-ethoxycarbonyl-2-methyl-synthesis, 6, 306 Thiazole, 2-amino-4-(2 -furyl)-bromination, 6, 256 Thiazole, 2-amino-4-hydroxy-synthesis, 6, 296 Thiazole, 5-amino-2-hydroxy-synthesis, 6, 301 Thiazole, 5-amino-2-mercapto-synthesis, 6, 301 Thiazole, 2-amino-4-methyl-alkylation, 6, 256 synthesis, 6, 300 Thiazole, 2-amino-5-nitro-antiparasitic activity, 1, 180... 

In 1972, van Leusen, Hoogenboom and Siderius introduced the utility of TosMIC for the synthesis of azoles (pyrroles, oxazoles, imidazoles, thiazoles, etc.) by delivering a C-N-C fragment to polarized double bonds. In addition to the synthesis of 5-phenyloxazole, they also described reaction of TosMIC with /7-nitro- and /7-chloro-benzaldehyde (3) to provide analogous oxazoles 4 in 91% and 57% yield, respectively. Reaction of TosMIC with acid chlorides, anhydrides, or esters leads to oxazoles in which the tosyl group is retained. For example, reaction of acetic anhydride and TosMIC furnish oxazole 5 in 73% yield. ... 

A variation of the general method for the synthesis of 2-amino-selenazoles is to avoid the use of the free a-halogenocarbonyl compound and in its place react the corresponding ketone and iodine with selenourea.This procedure is also taken from thiazole chemistry. By contrast with thiourea, the reaction with selenourea needs a longer reaction time and the work up of the reaction mixture is somewhat more difficult. Usually an excess of the ketone is used. In the preparation of 2-amino-4-( n-nitrophenyl)selenazole, a very high yield, calculated on the amount of iodine used, was obtained. To explain this peculiar result, the oxidative action of the nitro group was invoked. This liberates free iodine from some of the hydrogen iodide eliminated in the condensation reaction, and the free iodine then re-enters into the reaction. 

As demonstrated above, nitro derivatives of five-membered heterocycles have found extensive use as antiinfective agents. It is therefore of interest that the nitro derivative of a substituted thiazole was at one time used as an antitrichomonal agent. Bro-mination of 2-aminothiazole (136) (obtained from condensation of thiourea with chloroacetaldehyde) gives the 4-bromo derivative (138) this is then acetylated to 139. Treatment of 139 with nitric acid leads to an interesting displacement of bromine by a nitro group to afford aminitrazole (140)... 

The chlorodifluoromethylated ketone 130 proved to be a valuable substrate for promoting SrnI subtitution reaction with sodium phenylthiolate and to generate a new a-(phenylthio)-a,a-difluoroacetophenone derivative 131 (Equation 57) <2001TL3459>. Upon treatment with nitronate anions under classical SrnI reaction conditions or MW irradiation, 6-chloromethyl-5-nitro-imidazo[2,l- ]thiazole 132 yielded 5-nitroimidazothiazoles bearing a trisubstituted ethylenic double bond at the 6-position (Equation 58) <2001SC1257>. 

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