With halogenothiazoles

Retro-Hantzsch, mechanism of, 84, 85, 102 Rhodanine, alkylation of, 419 ambident reactivity of. 419 reaction with aryldiazonium salts, 419 reaction with halogenothiazoles, 79 Rice cultures, 135, 136, 137 Ring-chain tautomerism, 113 Ring opening, of A-2-thiazoline-5-one, 433 Ring transformation, 5 amino-A-4-thiazo-line-2-thione to 4-mercapto-imidazoline-2-thione, 399 5,5-diphenyl-2,4-thiazolidinedithione, to 4,5-diphenyl-A-4-thiazoline-2-thione, 37 3... 

Diazomethane alkylation of A-4-thiazoline-2-ones (36, 214) or the Williamson reaction of 2-halogenothiazoles (6. 287-300) provide good yields of 2-alkoxythiazole otherwise obtained by reaction between O-esters of monothiocarbamic acid with a-halocarbonyl compounds (see Chapter II). 

All four 2-halogenothiazoles are known. 2-Chloro (l- ll). 2 bromo (1, 2. 5, 8-10, 12-24), and 2-iodothiazole (8, 10, 25, 26) can be prepared from 2-aminothiazole by Sandmeyer reactions, with yields between 30... 

The nucleophiles used are OH (32) [the 2-hydroxythiazole can also be obtained by acidic hydrolysis with strong mineral acids (33)], OR" (5, 8, 30, 34), SR" (8, 9, 12), ArSH (35), and amines (4, 7, 14, 33). Benzamide also reacts with 2-bromothiazole, yielding 2-benzamidothiazole (36). Sulfonamide also reacts with 2-halogenothiazoles in presence of a base and copper powder, yielding 2-sulfonamidothiazoles (37, 38). 

The higher reactivity of 2-halogenothiazoles with respect to halogenopyridines can be related to the different aromaticity of the two systems, less for thiazole than for pyridine, for example, the relatively stronger fixation of the tt bond in the thiazole than in the case of pyridine. As the data reported in Table V-1 (footnote a) indicates, the free thiophenol is more reactive than the thiolate anion toward the 2-halogenothiazoles. This fact should be considered when one prepares the thiazolyl sulfides. 

The role of the quaternization of the azasubstituent in the nucleophilic substitution at 2-halogenothiazoles is in fact emphasized by the reactivity of 2-halogenothiazoles with undissociated thiophenol (35), which proceeds faster than the corresponding reaction of 2-halogenothiazoles with thiophenolate anion, through the pathways shown in Scheme 6. Moreover, the 4-halogenothiazoles do not react with undissociated thiophenols, while the 5-halogenothiazoles react well (48). 

The nucleophilic reactivity of 2-halogenothiazoles is strongly affected by the substituent effect, depending on the kind of substitution reaction. Positions 4 and 5 can be considered as meta and para , respectively, with regard to carbon 2 and to groups linked to it consequently, it is possible to correlate the reactivity data with Hammett s relationships. 

Treating 2-bromothiazole with copper at 170°C in cumene as solvent affords the 2.2 -bisthiazole (Scheme 9) (69). The 2-halogenothiazoles can... 

All the halogenothiazoles, depending on the electron-withdrawing power of the halosubstituent, together with the electron-withdrawing power of the azasubstituent, are only slightly susceptible to electrophilic substitution reactions such as nitration, sulfonation, and so on, while the polyhalogenatjon reaction can take place. 

The polarographic properties of the halogenothiazoles in comparison with other thiazole compounds have also been investigated (73, 74). Infrared, Raman, ultraviolet, and NMR spectra of mono-halogenothiazoles have been measured (2, 3, 6, 10, 15, 17, 24, 29) (Table V-4). 

Taking into account the previous discussion of the reactivities of simple halogenothiazoles or nitrothiazoles, the mechanism of nucleophilic reac tivity of 2-halogeno-5-nitrothiazoles with an excess of basic nucleophile such as CHjO can be proposed (Scheme 14). 

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. 

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... 

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