title: Mechanistic Aspects of Phosphate Diester Cleavage Assisted by Imidazole. A Template Reaction for Obtaining Aryl Phosphoimidazoles.
abstract: Phosphoimidazole-containing compounds are versatile players in biological and chemical processes. We explore catalytic and mechanistic criteria for the efficient formation of cyclic aryl phosphoimidazoles in aqueous solution, viewed as a template reaction for the in situ synthesis of related compounds. To provide a detailed analysis for this reaction a series of o-(2'-imidazolyl)naphthyl (4-nitrophenyl) phosphate isomers were examined to provide a basis for analysis of both mechanism and the influence of structural factors affecting the nucleophilic attack of the imidazolyl group on the phosphorus center of the substrate. Formation of the cyclic aryl phosphoimidazoles was probed by NMR and ESI-MS techniques. Kinetic experiments show that cyclization is faster under alkaline conditions, with an effective molarity up to 2900 M for the imidazolyl group, ruling out competition from external nucleophiles. Heavy atom isotope effect and computational studies show that the reaction occurs through a SN2(P)-type mechanism involving a pentacoordinated phosphorus TS, with apical positions occupied by the incoming imidazolyl nucleophile and the p-nitrophenolate leaving group. The P-O bond to the leaving group is about 50-60% broken in the transition state.
authors.affiliation: Department of Chemistry, ICEX, Federal University of Minas Gerais , Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Mozart S
authors.initials: MS
authors.lastname: Pereira
authors.affiliation: Department of Chemistry, ICEX, Federal University of Minas Gerais , Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Murta
authors.affiliation: Department of Chemistry, ICEX, Federal University of Minas Gerais , Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Thaís C F
authors.initials: TC
authors.lastname: Oliveira
authors.affiliation: Department of Chemistry, Federal University of Santa Catarina , Florianópolis, SC 88040-900, Brazil.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Manfredi
authors.affiliation: Department of Chemistry, Federal University of Santa Catarina , Florianópolis, SC 88040-900, Brazil.
authors.forename: Faruk
authors.initials: F
authors.lastname: Nome
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University , Logan, Utah 84322-0300, United States.
authors.forename: Alvan C
authors.initials: AC
authors.lastname: Hengge
authors.affiliation: Department of Chemistry, ICEX, Federal University of Minas Gerais , Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Tiago A S
authors.initials: TA
authors.lastname: Brandão