2-Nitrothiazole reaction with

Reactions of nitrothiazole derivatives with anions of nitroalkanes, such as shown in Eq. 5.34, proceed via a S l mechanism.52... 

The structure of anew alkylating agent, 2-(l-methyl-l-nitroethyl)-5-nitrothiazole and its C-alkylation product of the reaction with 2-nitropropane anion by SRN1 mechanism has been assigned by proton and carbon NMR spectroscopy (Table 3.20) [541, 542],... 

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... 

Reactions of 2-Hydrazino-thiazoles.— A report in 1971 that 2-hydrazino-5-nitrothiazole reacts with 2-chloroethyl isocyanate at the terminal N-atom has... 

Red crystals formed from the reaction of 2-nitrothiophen with aliphatic secondary amines in the cold are tentatively assigned the structure R2NCH=CHCH=C(N02) 2Sj a very similar cleavage reaction with amines involving a stable five-membered heteroaromatic system, 2-bromo-5-nitrothiazole, was reported some time ago. "... 

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,... 

Amino-5-nitrothiazole, on treatment with arenesulfonyl halides and dimethylformamide at 140 C, gives (5-nitro-2-thiazolyl)amidme (274) (Scheme 168) (507, 508). The condensation products of the reaction of 2-aminothiazole derivatives with various aldehydes are grouped in Tables... 

Methoxy-5-nitrothiazole (127) reacts with an equivalent of methox-ide ion to give complexes 128 and 129. which decompose (Scheme 65). 3-NO-.-thiazoline-2 One is also observed in that reaction (297). 

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). 

If the reactions are carried out using a concentration of CHsO slightly less than that of halogenothiazole, the reaction almost quantitatively yields the 2-methoxy-5-nitrothiazole. The reaction of methoxide ion in excess with regard to 2-haiogeno-5-nitrothiazole, previously reported as leading to a mixture of unidentified products together with the expected 2-methoxy-5-nitrothiazole in low yields (97), can be explained on the basis of Scheme 14. 

The reaction of 2-bromo-5-nitrothiazole with weakly basic secondary aliphatic amines gave the expected 2-amino products. The isomeric 5-bromo-2-nitrothiazole with such amines gave mixtures of the expected 5-amino products along with 2-aminated 5-nitrothiazole rearrangement products. A mechanism was proposed which involves the slow thermal isomerisation of the 5-bromo-2-nitrothiazole to the much more reactive 2-bromo isomer which competes, in the case of relatively weak amine nucleophiles, with direct but slow displacement of the 5-bromo group to form the normal displacement product <96JHC1191>. 

Niridazole Niridazole, l-(5-nitro-2-thiazolyl)-2-imidazolidinone (38.1.11), is made by reacting 2-amino-5-nitrothiazol with 2-chloroethylisocyanate to make the disubstituted urea (38.1.10). Heating this compound results in an intramolecular N-alkylation reaction to form the desired imidazolidine derivative, niridazole [7-11]. 

In this respect, the syntheses of a wide series of 2-amino-5-nitrothiazole 572 complexes with various metal(II) salts are representative. These reactions were carried out in methanol medium and led to adducts of type 573 [12] (3.13) ... 

Isolation of the carbinolamine intermediate (66) is possible in the reaction of 2-amino-5-nitrothiazole with acetaldehyde (Scheme 46) (216). 

Methyl-5-(2-furyl)-4-nitrothiazole and 2-methyl-4-nitrothiazole were isolated from the mixture of products from the reaction of 5-amino-2-methylthiazole-4-carboxylic acid with isoamyl nitrite in the presence of furan [421],... 

Nitrothiazoles can be obtained by the reaction of nitroaminoethenes with dithiocyanogen [498] or thiourea [499] (Scheme 73). 

NMR study of nitrothiazoles has been the subject of few number of works [525, 530-540], The proton chemical shifts of about 30 thiazole derivatives including 5-nitrothiazole and 2-nitrothiazole are presented in [536], The authors have found the coupling constants between H-2 and II-4 in most 5-substituted thiazoles to be negligible with the exception of 5-nitrothiazole and 5-thiazolecarboxylic acids [536], The change in the H-4 chemical shifts of the 2-substituted 5-nitrothiazole fragment enables the ratio of isomeric products of the reaction of 5-nitrothiazole 2-(T,3 -dicarbonyl) derivatives with hydrazine and hydroxylamine to be established (Scheme 3.8) [537],... 

Amino-5-nitrothiazoles 160 or 2-imino-5-nitrothiazolines 161 are obtained by the reaction of di(thiocyanogen) with / -nitroenamines, followed by a trace of acetic acid (equation 72)92. 

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). ... 

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... 

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. 

A serious limitation of VNS is connected with its mechanism, namely, conversion of intermediate ct adducts into the VNS products via bimolecular base-induced p-elimination. To cause the reaction, it is therefore necessary that these adducts be produced in a reasonable concentration. Indeed, low nucleophilic carbanions, such as dimethyl chloromalonate, do not react with moderately electrophilic nitrobenzene because of unfavorable equilibrium of the addition step, but react nicely with more electrophilic nitrothiazoles (Scheme 8) [34]. 

SCHEME 11.31 VNS reaction of carbanion of dimethyl chloromalonate with nitrothiazole [53]... 

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