3 -Phenylisothiazole, irradiation

Vernin et al. independently observed that during the irradiation in benzene of 2-iodothiazole to generate 2-thiazolyl radicals, the resulting 2-phenylthiazole (216) isomerized into a mixture of 4-phenylthiazole (214) and 3-phenylisothiazole (213) (Scheme 103) (489). Marking the 4- and... 

However, such an explanation was not convincing for other authors. Maeda and Kojima found that the irradiation of 2-phenylthiazole in ethanol at 80°C led to the same products described before but in a different ratio. Under the same reaction conditions, 5-phenylthiazole gave 4-phenylisothiazole, while 4-phenyl-thiazole was converted into 3-phenylisothiazole. The most important observation those authors made was that deuterium incorporation occurred when the reaction was carried out in benzene at 80°C in the presence of deuterium oxide. In fact, 2-phenylthiazole furnished deuterated 3-phenyl-4-deuteroisothiazole and... 

Recently, the photochemical behavior of 4-phenylisothiazole has been reanalyzed (98JOC5592). This compound, on irradiation in ether, gave ring-opening products and 4-phenylthiazole (3% yield) (Scheme 40). The irradiation in methanol... 

The anhydro-5-hydroxy-l,3,2-oxathiazolylium hydroxide system (83) and DMAD thermally yielded an intermediate 1 1 cycloadduct (84) which lost C02 forming dimethyl 2-phenylisothiazole-3,4-dicarboxylate (85) (72CB196). Irradiation of (83) in neat DMAD formed the valence tautomer (82) which lost C02 to give the nitrile sulfide dipole (81) captured by DMAD to form dimethyl 3-phenylisothiazole-4,5-dicarboxylate (80) (75JA6197) (see also CHEC 4.17). 

Syntheses and reactions of lithiated isothiazoles and thiazoles were reviewed. [95H533] Phenylisothiazoles and phenylthiazoles are known to undergo a variety of phototranspositions upon irradiation in benzene solvent. These reactions were reinvestigated. [94JA2292]... 

In the dyad, because of the symmetry of the 3-phenylazetine ring in BC-53 (Scheme 29), insertion of sulfur between ring positions C-l and C-4 or CC-1 and C-2 leads to the same compound, 5-phenylthiazole (53). Similarly, insertion of a sulfur atom between N3 and C4 or N3 and C2 leads to 4-phenylisothiazole (55). Accordingly, because of this symmetry, only a dyad results. This symmetry is removed, however, in the case of 2-deuterio-5-phenylthiazole (53-2d). Thus, irradiation of 53-2d resulted in the formation of three isomeric products (Scheme 30), viz., 4-deuterio-5-phenylthiazole (53-4d), 5-deuterio-4-phenylisothiazole (55-5d), and 3-deuterio-4-phenylisothiazole (55-3d). D euterium 1 abelling h as t hus e xpanded t he d yad i nto a tetrad. These results are entirely consistent with the electrocyclic ring closure - heteroatom migration mechanism shown in Scheme 31 <94JA2292>. 

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. 

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>. 

Nitrile sulfides are well suited for the synthesis of isothiazoles incorporating the C=N-S unit via their 1,3-dipolar cycloaddition reactions with double or triple-bonded dipolarophiles. Benzonitrile sulfide 210 is readily prepared from decarboxylation of oxathiazolone 209 using microwave irradiation <05SC807>. Subsequent cycloadditions to dimethyl acetylene-dicarboxylate (DMAD) and dimethyl fumarate afford 211 and 212, respectively. In the case of ethyl propiolate, a 1 1 regioisomeric mixture of phenylisothiazoles 213 and 214 is obtained. 

According to the observed photochemical products and the results of deuterium labeling studies, the six isomeric phenylisothiazoles and phenyl-thiazoles can be organized into a tetrad of four isomers that interconvert mainly via P5, Pg, and P, transposition pathways and a dyad in which 5-phenylthiazole 52 transposes via P5 and P7 pathways to 4-phenylisothiazole 48 (Scheme 8), the only isomer that did not yield a transposition product upon irradiation in benzene solution. With one minor exception, no interconversions between the tetrad and dyad were observed. In that case, in addition to transposing to members of the tetrad, 5-phenylisothiazole 49 also transposed to 5-phenylthiazole 52, the first member of the dyad, in less than 1 % yield. This conversion was assumed to occur via a P4 permutation process. 

DjO [37-40]. These workers reported that irradiation of 2-phenylthiazole 50, 4-phenylthiazole 51, or 5-phenylisothiazole 49 under these conditions resulted in the formation of 3-phenylisothiazole 47-4d with deuterium incorporation into ring position 4. In the case of 2-phenylthiazole 50, 4-phenylthiazole 51 was also formed but without deuterium incorporation. Finally, they reported that none of the reactants underwent photodeuteration prior to isomerization. 

Reinvestigation of these reactions, however, gave substantially different results. Thus Pavlik and coworkers observed that 3-phenylisothiazole 47 is formed with deuterium incorporation at C-4 upon irradiation of either 2-phenylthiazole 50 or 5-phenylisothiazole 49 but with approximately twice the extent of incorporation from the latter reactant. Furthermore, although Maeda... 

Thus upon prolonged irradiation the initially formed 2-deuterio-4-phenylthiazole 51-2d transposes to 5-deuterio-3-phenylisothiazole 47-5d without additional deuterium incorporation [36]. 

In a similar way, irradiation converts many simpler pyrazoles into imidazoles, phenylisothiazoles and methylisothiazoles partially into the corresponding thiazoles, and 3,5-diarylisoxazoles converted into 2,5-disubstituted oxazoles. " 3-Alkoxyisoxazoles undergo an extraordinary ring contraction with iron(II) chloride, producing azirine esters... 

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). 

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