Gas-Phase Fragmentation of Deprotonated p-Hydroxyphenacyl Derivatives

Abstract

Electrospray ionization of methanolic solutions of p-hydroxyphenacyl derivatives HO-C 6 H 4 -C(O)-CH 2 -X (X = leaving group) provides abundant signals for the deprotonated species which are assigned to the corresponding phenolate anions − O-C 6 H 4 -C(O)-CH 2 -X. Upon collisional activation in the gas phase, these anions inter alia undergo loss of a neutral "C 8 H 6 O 2 " species concomitant with formation of the corresponding anions X − . The energies required for the loss of neutral roughly correlate with the gas phase acidities of the conjugate acids (HX). Extensive theoretical studies performed for X = CF 3 COO in order to reveal the energetically most favorable pathway for the formation of neutral "C 8 H 6 O 2 " suggest three different routes of similar energy demands, involving a spirocyclopropanone, epoxide formation, and a diradical, respectively.

Applications of p-hydroxyphenacyl (pHP) and coumarin-4-ylmethyl photoremovable protecting groups

“…8 The Brønsted β LG = −0.24 for the photochemical reaction finds precedence in gas-phase collision-induced dissociation (CID) fragmentation measurements of the conjugate base of the p HP derivatives in Table 1. 12 A correlation coefficient of β LG = −0.19 ± 0.02 for the appearance energies (AEs) vs. gas-phase acidities of the leaving groups (−Δ H acid ) reveals a similar extent (19% vs. 24%) of bond breaking at the transition state for the fragmentation process.…”

Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy

“…93 This approach is particularly useful for protection of highly reactive or base-sensitive leaving groups. Advantages of the diazoketone approach include the ease of synthesis of a variety of substituted diazoacetophenones and the mild conditions for the coupling reaction.…”

“…The most efficacious leaving groups are conjugate bases of moderate to strong acids, e.g., sulfates, 85d,93 phosphates 7,9u,82−85,99 (thiophosphate), 100,111 carboxylates, 7b,9u,85a−85c,93−95,97b,97c,112 phenolates, 9u,93 and thiolates. 111,113 In general, quantum yields monotonically decrease with an increase in the acid leaving group’s p K a (Table 4), conforming to a Brønsted leaving group relationship (β LG ), which correlates the pHP release rate constant with the K a of the leaving group.…”

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

“…Conversion to acetyl-protected diazo- p -hydroxyacetophenones 7 in 65–69 % yield occurred with addition of excess diazomethane. 17,19,20 Deacetylative deprotection of the phenol with NH 4 OAc in aqueous methanol occurred in the workup step and gave quantitative yields of 1a–d . The acetyl analog 1d 21 was synthesized by first converting p -acetoxybenzoic acid 6a to 3-acetyl-4-hydroxybenzoic acid through a Fries rearrangement followed by re-acetylation of the phenolic group to give 6d .…”

“…To further demonstrate the utility of 1a , it was employed as a synthon to cage several other functional groups (Scheme 5), i. e., as a general entrée for the synthesis of pHP esters of dibenzyl phosphate, 10b,21 three examples of sulfonates esters, 17,21 two phenol ethers, 21 and several carboxylate esters 9,17 including the pHP protected, neuro active agents glutamate 9,18a and GABA. 9 Previous syntheses of these pHP derivatives employed Sn2 strategies using protected bromoacetophenones (pHP Br), a more cumbersome route.…”