Ethyl 2-hydroxy-2-phenyl-2-(thiazol-2-yl)acetate

This short note describes the synthesis of the title compound through spontaneous aerobic oxidation of ethyl 2-phenyl-2-(thiazol-2-yl)acetate. Due to the prevalence of such functional motifs in biologically active substances, we believe the oxidation encountered highlights an important degradation pathway worthy of note.


Introduction
The synthesis of thiazole containing compounds has been the focus of much research due to their importance in both pharmaceuticals [1] and agrochemicals [2].
Recently, we have reported on the synthesis of 2-substituted thiazoles through a modified Gewald reaction [3].Serendipitously, the natural air oxidation of one of the 2-substituted thiazoles led to an interesting hydroxylated thiazole which yields a glycolate moiety.This previously unreported compound is important because of its implications regarding metabolic and environmental degradation pathways for related compounds.
The air oxidation of 1 slowly gives rise to the corresponding glycolate 3 when simply left standing and open to the atmosphere; the parent compound is stable if preserved under an inert environment.The resultant glycolate 3 can be easily isolated through simple column chromatography purification.

OPEN ACCESS
Molbank 2015 M857 (Page 2) Some related oxygenations have been previously described, however, these processes have employed either a palladium catalyst [4] or strong bases such as Cs2CO3 [5] in the presence of oxygen.
We hypothesise that the two oxidation derivatives (2 and 3) are generated through initial enolisation and reactive trapping of oxygen.Even though no base is present for the deprotonation, the natural enolisation is enough for the reactive trapping of oxygen, albeit rather slowly.The resultant peroxide intermediate 1b could then potentially cyclise onto the adjacent ester moiety forming a dioxetane which, after extrusion of CO2, would furnish product 2 (Scheme 1) [7].Alternatively, the peroxide intermediate 1c could undergo homolytic cleave to form the oxygen-centred radical that abstracts a hydrogen atom to form the glycolate 3 [8].It is also possible that compound 2 is the result of ester hydrolysis (water generated in the formation of 3), followed by decarboxylation to yield the simple 2benzyl thiazole.Such compounds are known to oxidise to their corresponding ketones [9] or undergo a 1,2-rearrangement to form an α-hydroperoxy α-alkoxy ketone which would form 2 after spontaneous decomposition [10].
An alternative mechanism, not involving the initial enolisation, would be one including an intial homolytic cleavage of the C-H bond, forming a carbon centred radical 1e which can react with oxygen to form the peroxo-radical 1f (Scheme 2).The peroxo-radical can either react with a hydrogen atom to form 1c as part of the formation of 3, or form the dioxetane intermediate to yield 2. Similar to mechanism A, there is nothing that induces the initial homolytic cleavage to initiate the reaction, however, we are convinced that considering the long reaction time needed for the transformation, small amounts of 1a or 1e are naturally formed due to the acidic C-H bond present in 1.