Photolytic Cleavage of 1-(2-Nitrophenyl)ethyl Ethers Involves Two Parallel Pathways and Product Release Is Rate-Limited by Decomposition of a Common Hemiacetal Intermediate

Abstract

Time-resolved FTIR spectroscopic studies of the flash photolysis of several 1-(2-nitrophenyl)ethyl ethers derived from aliphatic alcohols showed that a long-lived hemiacetal intermediate was formed during the reaction. Breakdown of this intermediate was rate-limiting for product release. One of these compounds (methyl 2-[1-(2-nitrophenyl)ethoxy]ethyl phosphate, 9) was studied in detail by a combination of time-resolved FTIR and UV-vis spectroscopy. In addition, product studies confirmed clean photolytic decomposition to the expected alcohol, 2-hydroxyethyl methyl phosphate, and the 2-nitrosoacetophenone byproduct. At pH 7.0, 1 degrees C, the rate constant for product release was 0.11 s(-1), very much slower than the 5020 s(-1) rate constant for decay of the photochemically generated aci-nitro intermediate (pH 7.0, 2 degrees C). Time-resolved UV-vis measurements showed that the hemiacetal intermediate is formed by two competing pathways, with fast (approximately 80% of the reaction flux) and slow (approximately 20% of the flux) components. Only the minor, slower path is responsible for the observed aci-nitro decay process. These competing reactions are interpreted with the aid of semiempirical PM3 calculations of reaction barriers. Furthermore, AMSOL calculations indicate that the pK(a) of the nitronic acid isomer formed by photolysis is likely to determine partition into the alternate paths. These unusual results appear to be general for 1-(2-nitrophenyl)ethyl ethers and contrast with a related 2-nitrobenzyl ether that photolyzed without involvement of a long-lived hemiacetal.

o‐Nitrobenzyl Photolabile Protecting Groups with Red‐Shifted Absorption: Syntheses and Uncaging Cross‐Sections for One‐ and Two‐Photon Excitation

“…Action uncaging cross-section for one-photon excitation at l ð1Þ exc = 325 nm, e u (325)F ð1Þ u (AE 5 %), and estimate of the quantum yields of uncaging after one-photon excitation F ð1Þ u (AE 10 %) for the caged model compounds nb and nc; estimate of the action uncaging cross-section for one-photon excitation of the present o-nitrobenzyl protecting groups at l (1) , e u (l (1) www.chemeurj.org Scheme 8a. [24,25] For FCS analysis, the most significant information is that: 1) the primary photoreaction of 2-nitrobenzyl compounds provides aci-nitro tautomers AH within 5 ps; 2) AH ionization giving the basic state A À occurs above pK a (AH/A À1 ) % 4 at a rate faster than 1 10 6 s À1 ; [25] 3) the formation of the acetal intermediate state {BH,B À } should not occur at a rate much faster than 1 10 3 s À1 at the pH of 9 that was used throughout the present experiments. [25] On the relevant timescale of analysis of the experimental autocorrelation function G(t), the full mechanism displayed in Scheme 8a can be reduced consequently to the mechanism displayed in Scheme 8b: the caged species nc provides in a single step the basic state of the corresponding intermediate aci-nitro tautomers ncA À .…”

“…Among the available photoremovable protecting groups, the 2-nitrobenzyl functionality has gained wide acceptance and most of the caged biologically active compounds that have been synthesized belong to this series. [13,[17][18][19][20][21][22][23] The mechanism leading to the photolytic release of the protected substrate has been extensively investigated both experimentally [24][25][26] and theoretically. [27] In contrast, 2-nitrobenzyl caged compounds have not attracted considerable attention regarding biological applications that rely specifically on two-photon excitation.…”

Photolysis of ortho-nitrobenzylic derivatives: the importance of the leaving group

“…17 ln the growing family of PPGs, the o-nitrobenzyl group is one of the oldest, but still widely used groups, mainly due to its robustness and relative photophysical insensitivity to interfering influences. There have been many studies, both experimental and computational, on the mechanism of the photoinduced decomposition of this kind of PPGs [18][19][20][21][22][23][24][25][26] but many unanswered questions remain, such as the impact of substituents in various positions, and the origin of an intriguing kinetic isotope effect. 27,28 For example, it has been shown that the quantum yields ϕ for the disappearance of nitrobenzyl PPGs, or those for the release of the leaving groups, depend strongly on the chemical character of the leaving group (LG).…”

Micropatterning of polymethacrylates by single‐ or two‐photon irradiation using π‐conjugated o‐nitrobenzyl ester phototrigger as side chains

“…[2][3][4] Among the reported photoactivated groups, o-nitrobenzyl derivatives (ONB) have gained wide acceptance due to their versatile modification and well-known photorearrangement mechanism to generate o-nitrosobenzaldehyde. 3,[5][6][7] Besides its application as an orthogonal protecting group in organic synthesis, 8 it has been extensively used in the side chains of polymer as a photochemically labile group and also exhibited utility in photoresist [9][10][11][12][13] and photocontrolled release in light-dissociable block copolymer micelles. 14 In addition, a lot of caged biological active compounds have been prepared by using ONB phototrigger groups.…”