Isothiazoles chemistry

A more significant difference between 1 -methylpyrazole and isothiazole photochemistry, however, appears to be the minor role of the N-2-C-3 interchange pathway in isothiazole chemistry. Thus, although N2-C3 interchange is a major transposition pathway in pyrazole chemistry, it is only a minor pathway upon irradiation of phenylisothiazoles in benzene solution. In fact, 4-phenylisothiazole (55), the compound most expected to react via the N-2-C-3 interchange pathway, was the only isomer that did not yield a transposition product upon irradiation in benzene solution (Scheme 27). This is not due to the photostability of the compound. Indeed, 55 is the most reactive of the six isomers. Nevertheless, even after consumption of 85% of 55, no phototransposition product could be detected. 

The exploration of novel preparative routes commands much attention in isothiazole chemistry. Especially interesting are the reactions of 3-phenyl-l,2,4-oxathiazol-5-one with acetylenic esters which afford isothiazoles in high yield (72, 7). The reaction is envisaged as a 1,3-dipolar addition of benzonitrile 7V-sulphide, produced as a transient intermediate, to the dipolarophilic dimethyl acetylenedicarboxylate or propiolic ester. Isothiazoles are also produced by photoisomerization of thiazoles (72, 19). Nitrenes may be implicated in the thermal decomposition of 2-azidoaryl thioketones into benzoisothiazoles (72, 51). 

In azole chemistry the total effect of the several heteroatoms in one ring approximates the superposition of their separate effects. It is found that pyrazole, imidazole and isoxazole undergo nitration and sulfonation about as readily as nitrobenzene thiazole and isothiazole react less readily ica. equal to m-dinitrobenzene), and oxadiazoles, thiadiazoles, triazoles, etc. with great difficulty. In each case, halogenation is easier than the corresponding nitration or sulfonation. Strong electron-donor substituents help the reaction. 

Cyclotrithiazyl chloride is also a useful reagent in organic chemistry in the fusion of 1,2,5-thiadiazoles to quinones as well as the synthesis of (a) isothiazoles from 2,5-disubstituted furans and (b) bis-1,2,5-thiadiazoles from A-alkylpyrroles (Scheme 8.4). Alkenes and alkynes react readily with (NSC1)3 to give 1,2,5-thiadiazoles, while 1,4-diphenyl-1,3-butadiene gives a variety of heterocyclic products including a bis(l, 2,5-thiadiazole). ... 

The chemistry of mononuclear isothiazoles has been developed since 1956 without the aid of thiohydroxylamine, the preparation of this very unstable substance having only recently been reported. Bicyclic and polycyclic systems involving the isothiazole (1,2-thiazole) structure have long been known and were fully reviewed in 1952, but little new work has been reported since then and the present review... 

Papers dealing with this topic are exhaustively reviewed in Comprehensive Heterocyclic Chemistry I (84CHEC-I(6)235) and II (96CHEC-II(3)373). Nevertheless, little information is available on the 5-oxides. Recently, the heteroaromaticity of thiazole compared with isothiazole and thiadiazole 5,5-dioxide systems was studied (97MI1). Quantum-chemical calculations and X-ray studies were performed on 3,3 -di[l,3-thiazolidin-4-one] derivatives (95JCC(25)589) studied for their potential biological activity (97FA(52)43). 

Clerici F, Gelmi ML, Pellegrino S, Pocar D (2007) Recent developments in the chemistry of biologically active isothiazoles. 9 179-264... 

Much has been said about the application of this heterocyclic system in supramolecular chemistry and in materials chemistry, particularly in the preparation of organic conductors and superconductors. It should not be forgotten however that heterocyclic compounds in general are extremely important medicinal compounds. Although medicinal applications of this heterocyclic system have been rare in the years since CHEC-II(1996), some have been reported. Townsend and co-workers have described the preparation of imidazo[4,5-r/ isothiazole nucleosides 174-177 and have demonstrated their properties as antiproliferative and antiviral analogues of the antibiotic nebularine 172 and the highly cytotoxic 6-methylpurine nucleoside 173 <1997JME771>. 

Details of bond lengths and bond angles for the X-ray structures of heterocyclic compounds through 1970 are listed in Physical Methods in Heterocyclic Chemistry , volume 5. This compilation contains many examples for five-membered rings containing two heteroatoms, particularly pyrazoles, imidazoles, isoxazoles, oxazoles, isothiazoles, thiazoles, 1,2-dithioles and 1,3-dithioles. Further examples of more recent measurements on these heterocyclic compounds can be found in the monograph chapters of CHEC and CHEC-II. 

Recent Advances in the Chemistry of Benzisothiazoles and Other Polycyclic Isothiazoles, 38, 105 Sulfur Transfer Reagents in Heterocyclic Synthesis, 30, 47. 

Isoquinolinones and their saturated derivatives, 52, 155 Isothiazoles, 4, 107 recent advances in the chemistry of monocyclic, 14, 1... 

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