1-Methylpyrazole, phototransposition

In order to study the 1-methylpyrazole to 1-methylimidazole phototransposition process with minimum substituent perturbation, the phototransposition chemistry of 3,4-dideuterio-l-methylpyrazole (1-3,4d2) has been studied. This labelling pattern allows distinction between the three pathways since Scheme 17 shows that the conversion of 1 to 2 via the three pathways is accompanied by transposition of C-5 of the reactant to ring position 5 by the N-2-C-3 interchange pathway or to ring positions 2 or 4 if the transposition occurs by electrocyclic ring closure followed by one or two nitrogen migrations respectively. 

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 phototransposition chemistry of iV-substituted pyrazoles and of isothiazoles has been of considerable interest [1] since the first reports that W-methylpyrazole 1 undergoes photoconversion to W-methylimidazole 2 [2] and that irradiation of isothiazole 3 leads to the formation of thiazole 4 [3]. 

According to this interpretation, the photochemistry of 1-methylpyrazoles involves a competition between photocleavage of the N-N bond to generate a diradical, the precursor of the P4 product, and electrocyclic ring closure to form a l,5-diazabicyclo[2.1.0]pentene, the precursor of the Pg and P7 phototransposition products. 

Pavlik and Kurzweil further studied the phototransposition chemistry of 1-methylpyrazoles in which the various ring carbon atoms are systematically labeled with a second methyl group. The primary products shown in Table 2 and the results of deuterium labeling studies shown in Table 3 confirm that these dimethylpyrazoles undergo only pyrazole to imidazole phototransposition by as many as three distinct permutation pathways. Thus, whereas 1,5-dimethyl-pyrazole 16 transposes by the P4, Pg. and P7 pathways to yield a mixture of 1,5-, 1,2-, and 1,4-dimethylimidazoles 19, 17, and 18 respectively, 1,3-dimethylpyrazole 14 transposes only via the P4 and Pg pathways to form 1,2-and 1,4-dimethylimidazoles 17 and 18. Finally, 1,4-dimethylpyrazole 15 trans-... 

Other routes to fluoroimidazoles have been reported, some of which are confined to specific structural motifs. For example, methyl and fluorine substituents were used in a study of the phototranspositions of the 1-methylpyrazole ring. The nitrogen walk mechanism produced ring-fluorinated imidazoles from the ring-fluorinated pyrazoles (Fig. 3.55). ° ... 

Pavlik, J.W. Kurzweil, E.M. Phototransposition chemistry of 1-methylpyrazole. Deuterium, methyl, and fluorine substitution. J. Org. Chem. 1991, 56, 6313-6320. 

The photochemistry of 1-methylpyrazoles 12 through 14, in which the various ring carbons are systematically labeled with a second methyl group, has also been studied. The primary products shown in Scheme 8, and the results of deuterium labeling studies shown in Scheme 9 confirm that these dimethyl-pyrazoles undergo only pyrazole-to-imidazole phototransposition by as many as three distinct pathways. 

After less than 10% photoconversion of l-3,4d2, H NMR analysis revealed that the product consisted of a mixture of 2-2,4d2,2-4,5d2, and 2-2,5d2, confirming that l-3,4d2 undergoes phototransposition via the P4, Pg, and P7 pathways in a ratio of 4.8 6.5 1.0. Thus, the phototransposition of 1-methylpyrazole 1 to 1-methylimidazole 2 is considerably more complicated than originally suggested. 

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