Oxazolium cations

The oxazole (232) heated with formamide gave the imidazole (233) oxazolium cations undergo similar conversions. Primary amines convert oxazole-4-carboxylic acids (234) at 150°C into imidazoles (235) with accompanying decarboxylation (53CB88) (see CHEC 4.07 and 4.18). 

I have been pursuing enzyme mimics, artificial enzymes that perform biomimetic chemistry, since starting my independent career in 1956. In the first work [52-59] my co-workers and I studied models for the function of thiamine pyrophosphate 1 as a coenzyme in enzymes such as carboxylase. We discovered the mechanism by which it acts, by forming an anion 2 that we also described as a stabilized carbene, one of its resonance forms. We examined the related anions from imidazolium cations and oxazolium cations, which produce anions 3 and 4 that can also be described as nucleophilic carbenes. We were able to explain the structure-activity relationships in this series, and the reasons why the thiazolium ring is best suited to act as a biological... 

Attempts to carry out substitution reactions on oxazoles in acid media, such as nitration with nitric and sulfuric acids or chlorosulfonation, fail because the highly electron-deficient oxazolium cation is involved. Phenyloxazoles are nitrated at the para positions of the phenyl groups 2,5-diphenyloxazole affords 5-(4-nitrophenyl)-2-phenyloxazole, as expected. Nitrooxazoles are now available by the action of dinitrogen tetroxide on the corresponding iodo compounds (81JHC885). Benzoxazoles are nitrated at the benzene ring thus 2-methyl-benzoxazole gives a mixture of 5- and 6-nitro derivatives. 

It was shown that the electron-rich oxazolium anions decrease the rate of reaction for NEDDA, and increase the activation barrier however, electron-poor oxazolium cations have low activation barriers for lEDDA and reactivity can be promoted by adding alkyl, Lewis, and Br0nsted acids to the oxazole nitrogen atom. The dehydration of cationic Diels-Alder cycloadducts was also found to be a highly exothermic process, favoring formation of pyridinium cations. Therefore, the best strategy to harness the potential of oxazole as a diene in lEDDA reaction is to use a proton-assisted process (i.e., to exploit the electron-poor oxazolium cation). 

Unlike their thiazolium, imidazolium, and oxazolium analogs, the dithiolium systems have not been extensively studied. Where measurements have been reported they indicate that hydrogen atoms at positions 2 or 3 possess considerable acidity. The 1,3-dithiolium cation (33, R = CH3) exchanged its 2-H in CF3COOD-D2O at 34°, OD probably being the effective catalyst. When 1,3-dithiolium salts dissolved in an... 

Figure 1 shows some five-membered cations including imidazolium, pyrazolium, triazolium, thiazolium and oxazolium. While the halide salts are usually solids at room temperature there are many anions that lower the melting points of the salts... 

As mentioned earlier the compound with R = benzyl for instance has been synthesized and found to act as an excellent catalyst in the benzoin condensation. Interestingly, oxazolium salts are also well known by organic chemists and they exchange protons faster than thiazolium salts. i-Overlap to stabilize the cation and electron withdrawal (inductive effect) to stabilize the anion are both superior in oxygen than in sulfur chemistry. 

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