Isonitriles, or isocyanides, are useful synthons in pharmaceutical synthesis through multicomponent reactions such as the Ugi and Passerini reactions because they provide a facile route to medicinal compounds such as lidocaine, bicyclomycin, and penicillin. Unfortunately, isonitriles have limited availability and stability, making them less attractive precursors. However, recent work on isonitriles has uncovered a new route to their synthesis through the deprotonation/metalation of oxazolic species at the C-2 position. This process produces an equilibrium between an open ring dianion (the isonitrile and a negatively charged oxygen atom) and a closed ring anion (where the negative charge is located at the C-2 positon). The open ring dianion can be favored by running the reaction at -78oC. From there, the isonitrile product can be recovered by the coupling of an electrophile (i.e. benzoyl chloride, chlorotrimethylsilane, or iodomethane) to the negatively charged oxygen atom. The objective of this research is to further explore the relationship between the aromaticity of oxazolic species and isonitrile stability by comparing the isonitriles prepared from benzoxazole, oxazole, and 4,4-dimethyloxazoline. The effect of the electrophiles on the yields of the isonitrile compounds for each oxazolic specie will also be presented. The synthesized isonitriles will be purified by recrystallization and column chromatography and then characterized using FT-IR, NMR (1H and 13C), and MS. These techniques will confirm the success of the reactions by determining the isonitrile product yields and identities of any side products that may have formed by pathways competing with the isonitrile syntheses. It is anticipated that the more aromatic oxazolic species will produce higher isonitrile yields and have longer shelf-lives due to the general stability of aromatic over non-aromatic compounds.

Effect of aromaticity on the stability of isonitriles prepared from the deprotonation/metalation of oxazolic species

249th National Meeting (2015)

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