2-Chlorobenzoxazole, nucleophilic substitution reactions

Only two examples of the fluorine atom incorporation into position 2 of ben-zoxazole via nucleophilic substitution of the chlorine atom are known. Thus, the reaction of 2-chlorobenzoxazole (1) with KF in the presence of catalytic amounts of 18-crown-6 (15-25 h at 110-120 °C) gave 2-fluorobenzoxazole (2) in 45-65 % yield [1]. 

Like thiazole, oxazole is a jt-electron-excessive heterocycle. The electronegativity of the N-atom attracts electrons so that C(2) is partially electropositive and therefore susceptible to nucleophilic attack. However, electrophilic substitution of oxazoles takes place at the electron-rich position C(5) preferentially. More relevant to palladium chemistry, 2-halooxazoles or 2-halobenzoxazoles are prone to oxidative addition to Pd(0). Even 2-chlorooxazole and 2-chlorobenzoxazole are viable substrates for Pd-catalyzed reactions. 

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See also in sourсe #XX -- [ ]

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