2-Diazo-1-(4-hydroxyphenyl)ethanone: a versatile photochemical and synthetic reagent.

α-Diazo arylketones are well-known substrates for Wolff rearrangement to phenylacetic acids through a ketene intermediate by either thermal or photochemical activation. Likewise, α-substituted p-hydroxyphenacyl (pHP) esters are substrates for photo-Favorskii rearrangements to phenylacetic acids by a different pathway that purportedly involves a cyclopropanone intermediate. In this paper, we show that the photolysis of a series of α-diazo-p-hydroxyacetophenones and p-hydroxyphenacyl (pHP) α-esters both generate the identical rearranged phenylacetates as major products. Since α-diazo-p-hydroxyacetophenone (1a, pHP N2) contains all the necessary functionalities for either Wolff or Favorskii rearrangement, we were prompted to probe this intriguing mechanistic dichotomy under conditions favorable to the photo-Favorskii rearrangement, i.e., photolysis in hydroxylic media. An investigation of the mechanism for conversion of 1a to p-hydroxyphenyl acetic acid (4a) using time-resolved infrared (TRIR) spectroscopy clearly demonstrates the formation of a ketene intermediate that is subsequently trapped by solvent or nucleophiles. The photoreaction of 1a is quenched by oxygen and sensitized by triplet sensitizers and the quantum yields for 1a-c range from 0.19 to a robust 0.25. The lifetime of the triplet, determined by Stern-Volmer quenching, is 31 ns with a rate for appearance of 4a of k = 7.1 × 10(6) s(-1) in aq. acetonitrile (1 : 1 v : v). These studies establish that the primary rearrangement pathway for 1a involves ketene formation in accordance with the photo-Wolff rearrangement. Furthermore we have also demonstrated the synthetic utility of 1a as an esterification and etherification reagent with a variety of substituted α-diazo-p-hydroxyacetophenones, using them as synthons for efficiently coupling it to acids and phenols to produce pHP protect substrates.

Nanosecond time-resolved IR study of thiobenzoylnitrene.

Nanosecond time-resolved infrared (TRIR) spectroscopy has been used to observe singlet thiobenzoylnitrene at 1740 cm(-1) upon photolysis of 5-phenyl-1,2,3,4-thiatriazole in acetonitrile and dichloromethane. Consistent with the experimental observations, thiobenzoylnitrene is predicted by B3LYP/6-31G* calculations to have a singlet ground state with an intense IR band at 1752 cm(-1). Phenyl isothiocyanate is also produced. Kinetic measurements indicate that it is not formed from singlet thiobenzoylnitrene, but rather directly from the thiatriazole. Unlike benzoylnitrene, singlet thiobenzoylnitrene does not react with acetonitrile or dichloromethane on the nanosecond timescale. However, it does react with dimethyl sulfoxide (DMSO) to produce a sulfoximine detected at 1180 cm(-1) (k(DMSO) = 3 × 10(5) M(-1) s(-1)). Benzonitrile (observed at 2230 cm(-1)) is produced from both singlet thiobenzoylnitrene (presumably through a short-lived, unobservable benzonitrile sulfide intermediate) and directly from the thiatriazole. B3LYP/6-31G* calculations also show that the structure of singlet thiobenzoylnitrene is analogous to that of related acylnitrenes, with a significant bonding interaction between the nitrogen and sulfur. Triplet thiobenzoylnitrene, on the other hand, is predicted computationally to have a biradical structure.

Weinreb amides in carbene chemistry: a time-resolved IR investigation into a potential intramolecular stabilization mechanism.

A chloromethylhydroxamiccarbene was generated photochemically in an attempt to form an intramolecularly stabilized carbene. A rapidly formed intermediate at 1645 cm(-1) decayed with an observed rate of 1.99 × 10(6) s(-1). Other intermediates were also observed. These also decayed, albeit much more slowly (k(obs) = 3.47 × 10(3) and 1.98 × 10(4) s(-1)). Multiple intermediates are apparently a function of both the proximal N,O-dimethylhydroxamic ester and multiple conformers of both the carbene and precursor.

2-Hydroxy-5-nitrobenzyl as a diazeniumdiolate protecting group: application in NO-releasing polymers with enhanced biocompatibility.

The 2-hydroxy-5-nitrobenzyl group is shown to be an effective protecting group for diazeniumdiolates. O(2)-(2-hydroxy-5-nitrobenzyl)-substituted diazeniumdiolates display enhanced thermal stability, but efficiently release nitric oxide (NO) in pH 7.4 aqueous solutions. A lipophilic analogue incorporated into hydrophobic polymers shows NO surface flux rates comparable to that of the natural endothelium. Importantly, these polymer formulations also show significantly enhanced biocompatibility in vivo with use of a porcine implant model.