Acetonitrile Derivatives as Carbonyl Synthons. One-Pot Preparation of Diheteroaryl Ketones via a Strategy of Sequential S_NAr Substitution and Oxidation

Abstract

The anion of 2-aryl acetonitrile derivatives reacted with a variety of heteroaryl chlorides or bromides in an S(N)Ar manifold to afford intermediate anions which were susceptible to oxidation. The addition of sodium peroxide and aqueous NH(4)OAc solution effected oxidation to afford aryl heteroaryl ketones in good yields. Aryl acetonitrile derivatives are thus umpolung-type synthons of the corresponding aryl carbonyl functionality.

Overview on Recent Approaches towards Synthesis of 2‐Keto‐annulated Oxazole Derivatives

“…The anion of 2‐phenyl acetonitrile ( 21 ) was reacted with 2‐chlorobenzoxazole ( 20 ) in a S N Ar manifold process to afford the intermediate anion 22 , which was susceptible to oxidation. The addition of sodium peroxide and aqueous NH 4 OAc solution led to the formation of 2‐benzoylbenzoxazole ( 10a ) in 36% yield (Scheme ).…”

“…There have been methods using the strategy of carbonylative C–H bond activation for the synthesis of 2‐keto‐annulated oxazoles using aryl halide, benzoxazole, and carbon monoxide as carbonyl source. The second position of oxazole or benzoxazole has been functionalized by using various carbonyl group synthon like acid chloride, amide, activated methylene group, acetylene, saccharin, isocyanide, and bromo ketone. There have been very few reports available in the literatures towards the synthesis of 2‐keto‐annulated oxazole derivatives.…”

Simple Synthesis of Dimethyl Nitrobenzhydrylphosphonates and Heteroarylnitroarylacetonitriles via Vicarious Nucleophilic Substitution (VNS) Reaction

“…16 Surprisingly, arylheteroarylacetonitriles are scarcely mentioned in literature. Phenylpyridyl 17 and phenylquinazolyl 18 acetonitriles were obtained via substitution of bromine in these azine rings by reaction with phenylacetonitrile carbanion. A series of diheteroarylacetonitriles have been obtained via reductive transformation of 1,1-diheteroaryl-2-nitroethanes.…”

Synthesis of Novel Benzo-Fused Heteroaryl Derivatives as Ca²⁺/Calmodulin-Dependent Protein Kinase II Inhibitors

“…According to a reported method, 23) the anion of 4-phenoxyphenylacetonitrile was reacted with the chloride 10 to afford the diarylacetonitrile. Oxidation of the acetonitrile moiety with sodium peroxide and aqueous NH 4 OAc solution gave 11.…”