Phenylisothiazoles, isomerization

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... 

Amino-5-phenylisothiazole is slightly less basic (pA 2.27) than the isomeric 5-amino-3-phenylisothiazole pK 2.65). Both 3- and 5-aminoisothiazoles can theoretically exist in tautomeric forms, but the presence of bands in the infrared spectrum at 3490 and 3400 cm (in CCI4) indicates that, at least in the case of 3-amino-5-phenylisothiazole, the amino form predominates. See also reference 17b. 

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>. 

Pavlik and coworkers reinvestigated the phototransposition chemistry of these compounds. Their results differ from those reported by Vernin in several ways. Most importantly, careful capillary colunm gas chromatographic analysis, including coinjections with authentic samples of the three isomeric phenylisothiazoles 47-49, confirmed that 5-phenylthiazole 52 transposes to 4-phenylisothiazole 48 but that 5-phenylisothiazole 49 and 3-phenylisothiazole 47 are not formed in this reaction. As a consequence, Pavlik and colleagues concluded that it was not necessary to evoke the Kellogg mechanism to explain the formation of any products in these photoreactions [36]. 

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. 

Maeda and Kojima reasoned that the bicyclic intermediates in the electro-cyclic ring closure heteroatom migration mechanism (Scheme 9) would not be expected to react with D2O to incorporate deuterium. Furthermore, they argued that if these intermediates did react with D2O, deuterium should also be incorporated into 4-phenylthiazole 51 during its formation from 2-phenyIthiazole 50. These workers thus concluded that deuterium incorporation demanded a car-banion intermediate. They therefore rejected the mechanism involving the interconversion of bicyclic intermediates and suggested that all three reactants isomerize to 3-phenylisothiazole 45 via a common tricyclic zwitterionic intermediate TC-1 (Scheme 11), which incorporates deuterium. 

From Oxathiazolones (Type B).—3-Phenyl-l,2,4-oxathiazol-5-one (17) is decomposed thermally to benzonitrile and sulphur, but condenses with activated dipolarophiles to yield 1,3-dipolar adducts that may arise from the intermediate benzonitrile sulphide (18). Thus, interaction of the oxathiazolone (17) and dimethyl acetylenedicarboxylate in chlorobenzene at 130 °C produces dimethyl 3-phenylisothiazole-4,5-dicarboxylate (19) in excellent yield. The use of ethyl propiolate (HC=CCOaEt) similarly affords the expected isomeric esters (20) and (21), each in 35% yield. The... 

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