Is the atmospheric pressure chemical ionisation and collisionally induced methanol loss from protonated dehydroamino acids a retrosynthetic process?

Abstract

Unsaturated 5(4H)-oxazolones lead, by methanolysis, to the corresponding dehydroamino acid derivatives. Interestingly, under atmospheric pressure chemical ionisation (APCI) conditions, the latter give rise, aside from abundant [M+H](+) ions, to [MHbondCH(3)OH](+) species, formally corresponding to the protonated oxazolones employed for their synthesis. Retrosynthetic processes have often been described as energetically favoured decompositions of odd-electron molecular ions but never invoked in APCI-activated fragmentations. To investigate this possible retrosynthetic process, occurring also under collisional conditions, some experiments on the deuterated analogues have been undertaken. The breakdown curves of [M+H](+) of oxazolones and [MHbondCH(3)OH](+) of the dehydroamino acid derivatives are superimposable, proving their structural identity and giving experimental evidence of the occurrence of a real retrosynthetic process from even-electron protonated molecules.

Study of the factors influencing oxazolone ring formation from α‐benzamido methyl esters: differences between electrospray and atmospheric pressure chemical ionization

“…2(a) and 2(b) can be explained either by a different protonation site, or by a higher internal energy content of the APCI-generated molecular species due to thermal conditions inside the APCI vaporizer. Interestingly, the ESIgenerated protonated molecule (m/z 360) behaves, under collision conditions, in a way analogous to that observed in the previous investigation 5 on the a,b-dehydroamino acid derivative 3. Thus, as shown by the MS/MS spectrum reported in Fig.…”

“…Furthermore, the high reactivity of the exocyclic double bond of unsaturated 5(4H)-oxazolones allows their use as dienophiles in DielsAlder cycloadditions and as dipolarophiles in cyclopropanation reactions, thus giving access to a wide variety of cyclic quaternary a-amino acids. 3,4 We have recently reported 5 the mass spectrometric characterization of the unsaturated 5(4H)-oxazolones 1 and 2, as well as that of their respective a,bdehydroamino acid derivatives 3 and 4, which are obtained by methanolysis of the oxazolone ring (Scheme 1). We found that in the atmospheric pressure chemical ionization (APCI) mass spectra of the latter derivatives, [MH-CH 3 OH] þ ions are present, and that the APCI-generated protonated molecules, when activated in collisions with He, lose methanol and give rise to the oxazolones from which they originated.…”

“…Interestingly, such a decomposition pathway proved to be related to the dehydroamino acid structure. 5 In order to gain a deeper knowledge of the structural factors that may affect the retrosynthetic process described above, we decided to extend this study to compounds 5-8 (Fig. 1).…”

α,β-Dehydroamino Acids

“…The mechanistic investigations of the ring-opening reaction were recently supplemented by a mass spectrometric study conducted by Traldi. 58 Ring-opening reactions with acylhydrazines gave the desired N-acyl-a,b-dehydroamino hydrazide (37) only in small amounts. The major product was the triazole 36 (Scheme 10).…”