Losses of CO and CO2 upon collision-activated dissociation of substituted 2-methoxyphenoxides after methyl radical loss

Some deprotonated, substituted 2-methoxyphenols fragment by methyl radical loss followed by competing losses of CO and CO2 upon collisional activation in linear quadrupole ion trap mass spectrometers. These reactions were examined experimentally and computationally in order to determine their mechanisms. For deprotonated vanillin, the CO loss was found to involve ring contraction, with the highest free energy barrier of 58.0 kcal mol−1 (for the syn rotamer; here, syn refers to the relationship between the aldehyde oxygen atom and the oxygen atom of the methoxy group) for the entire process. The atoms lost in this fragmentation are the oxygen atom that was bound to the first eliminated methyl group and the aromatic carbon atom bound to this oxygen. Examination of carbon-13 labeled vanillin supports these assignments. Examination of several model compounds revealed that this reaction requires the presence of an electron-withdrawing substituent in the para-position relative to the phenol moiety. In contrast, the CO2 loss from deprotonated vanillin occurs via ring opening followed by re-cyclization and then ring contraction, leading to the loss of CO2 in a process wherein the highest free energy barrier is 84.5 kcal mol−1 (for the syn isomer). The atoms lost in this fragmentation are the carbon and oxygen atoms from the phenoxide group and the oxygen atom that was bound to the first eliminated methyl group, which is supported by examination of carbon-13 labeled vanillin. Despite the higher total free energy requirement, the CO2 loss is competitive with CO loss, possibly due to favorable entropy and low activation energy (free energy barrier of 48.9 kcal mol−1) for the first reaction step (the analogous value for CO loss is 58.0 kcal mol−1). The extent of CO2 loss is strongly affected by substituents – it either is not observed or is very slow for the other compounds studied here. For example, it is substantially less favorable than CO loss (highest free energy barrier 60.9 kcal mol−1) for deprotonated acetovanillone for which the first reaction step for CO2 loss has a substantially greater free energy barrier (60.6 kcal mol−1) than for vanillin.