Photoisomerization isothiazoles

In 1969 Lablache-Combi er et al. (110) found that in the presence of primary amines isothiazole photoisomerizes to thiazoie (Scheme 100). 

Isothiazole behaves as a typical stable aromatic molecule. Thermolysis of substituted isothiazoles at 590 °C leads to the formation of thioketenes (80MI41700) and phenyl-isothiazoles undergo photoisomerism (Section 4.17.6.2) (73BSF1743, 81T3627). 1,2-Benzisothiazole boils at 220 °C without appreciable decomposition, and the 2,1-isomer... 

Photoisomerization of pyrazoles, isoxazoles and isothiazoles into imidazoles, oxazoles and thiazoles, respectively, is described in Section 3.4.1.2.4. 

In contrast, the thiophenone (204) undergoes a stereospecific conrotatory photocyclization via the enol (205) to give cis fused dihydrobenzo[b] thiophen (206).165 Initial nitrogen-sulfur bond homolysis is believed to be responsible for the photoisomerization of isothiazol-3(2//)-ones to thiazol-2(3//)-ones.166... 

The photochemistry of TV-substituted pyrazoles and of isothiazoles has been of considerable interest <76PHC123 80RGES501 94PP803 94PP1063 970P57> since the first report that 1-methylpyrazole (1) undergoes photoisomerization to 1-methylimidazole (Scheme 1) <67HCA44>. 

The photoisomerization of isothiazole (47a) (Scheme 24) to thiazole (48a) was the first reported phototransposition in the isothiazole-thiazole heterocyclic system <69CC1018>. 

Irradiation of isothiazole gives thiazole in low yield. Irradiation of 3-, 4-, or 5-phenyl-substituted isothiazoles generates an equilibrium mixture of phenylthiazoles with the starting phenylisothiazole <2000JOC3626>. A mechanism for 2-phenylthiazole/3-phenylisothiazole/4-phenylthiazole photoisomerization is shown in Scheme 12 <2002T8037>. 

Photoisomerization of isothiazole to thiazole was reported (Eq. 20).4 1 The intermediate was proposed to be a valence-shell extended one comparable to that proposed by Wynberg or an azirin. Reverse isomerization of thiazole to isothiazole was not observed. 

A dipolar intermediate with a valence-shell extension was proposed for the photoisomerization of phenyl isothiazoles (Eq. 21 ).47... 

The difference between such valence-shell extended intermediates and those proposed by Wynberg for his reactions is the presence of the 2,4 bonding or the 2,5 bonding. Significantly, the photoisomerization of methyl-isothiazoles depends on the polarity of the solvents, an observation which supports the suggested formation of zwitterionic intermediates (Eq. 22).48... 

The photoisomerization of isothiazole 3 to thiazole 4 was the first reported phototransposition in the isothiazole-thiazole heterocyclic system [3]. Methylisothiazoles have also been shown to undergo transposition. In neutral solvents, Lablache-Combier and coworkers reported that 3-methylisothiazole 41 and 4-methylisothiazole 42 each transpose to a single product, 2-methylthiazole 44 and 4-methylthiazole 45 respectively. According to this report, however, 5-methyl-isothiazole 43 transposes to three primary products, 5-methylthiazole 46, 3-methylisothiazole 41, and 4-methylisothiazole 42 [26]. 

Reactions of Isothiazoles.—Photolytic. Whilst photoisomerization of isothiazoles to thiazoles is well documented, examples of this reaction occurring with isothiazol-3(2H)-ones have not previously been reported. Irradiation of (10 R = alkyl or Ph) gave the corresponding thiazolone (11). The isomerization probably involves homolysis to a biradical, which cyclizes to an a-lactam and subsequently undergoes ring-expansion. Support for the homolytic step comes from the isolation of a small amount of (12) from the photolysis of (10 R = Ph). 

From Thiazoles.— Isothiazoles are formed in the photoisomerization of thiazoles. Irradiation of 2,5-diphenylthiazole in benzene affords 3,4-diphenylisothiazole (32%), together with 4,5-diphenylthiazole (8%) and phenanthro[9,10-flf]thiazole (8%). 2,4-Diphenylisothiazole similarly produces minor quantities (3%) of 3,5-diphenylisothiazole. Amongst possible mechanisms of this photorearrangement, the formation of bicyclic intermediates such as (58) or (59), or tricyclic sulphonium cations [(60) or (61)], was considered. ... 

Preliminary observations on the photochemical behaviour of isothiazoles have been briefly reported. The parent base is partially converted into thiazole on irradiation (7% in propylamine, 1% in ether), several unidentified products being formed (15%) side by side. 3-Phenyl- and 3,5-diphenyl-isothiazole are converted into 4-phenyl- (12%) and 2,4-diphenyl-thiazole (48%), respectively, but 5-phenylisothiazole preserves its ring system, merely producing small quantities (2.3%) of the 3-phenyl isomer. The reactions are believed to proceed by way of tricyclic sulphonium cations of the type previously postulated by Kojima and Maeda. It is recalled that the reverse photoisomerization is also on record (see syntheses, above). 

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). 

The photoisomerization of isothiazole 5 to thiazole 6 (Scheme 3) was the first reported phototransposition in the isothiazole-thiazole heterocyclic system. Later work published during the period 1971 to 1978 by Lablache-Combier and co-workers, by Vernin and colleagues,"" andby Maeda and Kojima " also showed that methylisothiazoles phototranspose to methylthiazoles and that phenyl-substituted isothiazoles and thiazoles also undergo phototransposition reactions. A surprising finding, however, was that phenyhsothiazoles were not observed to react via the N2—C3 interchange pathway, an important pathway in pyrazole photochemistry. Furthermore, a common conclusion of these studies was that these photoisomerizations proceed by way of tricyclic zwitterionic intermediates, which had no counterparts in pyrazole photochemistry. 

Catteau, J.P., Lablache-Combier, A., and Pollet, A, Isothiazole photoisomerization, /. Chem. Soc., Chem. Commun., 1018,1969. 

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