Phototransposition Chemistry of 4-Substituted Isothiazoles. The P₄ Permutation Pathway

Abstract

Upon irradiation in the presence of a small quantity of base, 4-substituted isothiazoles undergo photocleavage to yield substituted cyanosulfides, which can be trapped as their benzyl thioether derivatives, and substituted isocyanosulfides. Both products are suggested to arise via initial photocleavage of the sulfur−nitrogen bond, resulting in the formation of a substituted β-thioformylvinyl nitrene, which can rearrange to the observed cyanosulfide, or cyclize to an undetected thioformylazirine. Deprotonation of the azirine leads directly to the isocyanosulfide. The plight of the isocyanosulfide depends on the C-4 substituent. If the substituent is aromatic, the isocyanosulfide is reprotonated at the isocyanide carbon and spontaneously cyclizes to a 4-substituted thiazole, the observed transposition product. If the substituent is not aromatic, the isocyanosulfide is reprotonated at sulfur and the resulting species has a higher energy barrier to cyclization. In these cases, the isocyanosulfides can be observed spectroscopically and can be trapped as their N-formylaminobenzyl thioether derivatives.

Photochemistry of 4- and 5- phenyl substituted isoxazoles

“…This was also observed upon irradiation of isoxazole 4. These results clearly show that β-benzoylvinyl nitrene 46, formed photochemically from azide 45, can cyclize to 5-phenylisoxazole (4) and can also rearrange to the observed P 4 phototransposition product, 5-phenyloxazole (5), presumably via azirine 47, and to the photo-ring cleavage product, benzoylacetonitrile (9). These results are consistent with the suggestion that both 5-phenylisoxazole (4) and 3-azido-1-phenylpropen-1-one (45) undergo photoreaction by way of the same intermediate, namely, β-benzoylvinyl nitrene 46, as shown in Scheme 5.…”

“…These studies show that the photochemistry of 4-phenylisoxazole (22) is similar to the photochemistry of 1-methyl-4-phenylpyrazole (27) [4] and 4-phenylisothiazole (28) [9]. All three of these compounds phototranspose solely via the P 4 pathway (Path B, Scheme 1) which involves only interchange of the N2-C3 ring atoms.…”

“…If the initial heterocycle bears a hydrogen atom at ring position 3, this rearrangement occurs via detectable nitrile and/or isocyanide photocleavage products as shown in Scheme 1 [3,9,12,13]. This P 4 scrambling pattern involves only interchange of the N2 and C3 ring atoms.…”

“…These products were identified as 5-phenyloxazole (5) and benzoylacetonitrile (9) by GC and mass spectral comparison of the products formed with authentic samples of these two compounds. Quantitative GC showed that after 10 minutes of irradiation 48% of 4 had been consumed and that 5 and 9 were formed in yields of 41% and 21% respectively.…”

Five‐Membered Heterocycles: 1,2‐Azoles. Part 2. Isoxazoles and Isothiazoles

“…The resulting products are phenylthiazoles, phenylisothiazoles isomeric of the starting materials and ring-opened compounds. The relative proportions of these products are strongly dependent on the presence of a base or acid and, in some cases, on the polarity of the solvent used [340][341][342].…”