Mechanistic Aspects of Phosphate Diester Cleavage Assisted by Imidazole. A Template Reaction for Obtaining Aryl Phosphoimidazoles.

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.

Supramolecular phosphate transfer catalysis by pillar[5]arene.

A kinetic study on dinitrophenylphosphate monoester hydrolysis in the presence of a cationic pillararene, P5A, has been carried out. Formation of the supramolecular complex between phosphate ester and P5A has been studied by NMR showing complexation-induced upfield proton shifts indicative of aromatic ring inclusion in the pillararene cavity. Molecular dynamic calculations allow structure characterization for the 1 : 1 and 1 : 2 complexes. As a result of the supramolecular interaction both the acidity of DNPP and its hydrolysis rate constants are increased. Catalysis results from combination of both electrostatic stabilization reducing the negative electron density on the PO3(=) oxygens and monoester dianion destabilization by the steric effects of close NMe3(+) groups hindering the hydrogen-bonding with water and destabilising the monoester dianion.

Zwitterionic-surfactant-stabilized palladium nanoparticles as catalysts in the hydrogen transfer reductive amination of benzaldehydes.

Palladium nanoparticles (NPs) stabilized by a zwitterionic surfactant are revealed here to be good catalysts for the reductive amination of benzaldehydes using formate salts as hydrogen donors in aqueous isopropanol. In terms of environmental impact and economy, metallic NPs offer several advantages over homogeneous and traditional heterogeneous catalysts. NPs usually display greater activity due to the increased metal surface area and sometimes exhibit enhanced selectivity. Thus, it is possible to use very low loadings of expensive metal. The methodology eliminates the use of a hydrogen gas atmosphere or toxic or expensive reagents. A range of aromatic aldehydes were converted to benzylamines when reacted with primary and secondary amines in the presence of the Pd NPs, which also displayed good activity when supported on alumina. In every case, the Pd NPs could be easily recovered and reused up to three more times, and at the end of the process, the product was metal-free.

Dephosphorylation reactions of mono-, di-, and triesters of 2,4-dinitrophenyl phosphate with deferoxamine and benzohydroxamic acid.

This work presents a detailed kinetic and mechanistic study of biologically interesting dephosphorylation reactions involving the exceptionally reactive nucleophilic group, hydroxamate. We compare results for hydroxamate groups anchored on the simple molecular backbone of benzohydroxamate (BHA) and on the more complex structure of the widely used drug, deferoxamine (DFO). BHA shows extraordinary reactivity toward the triester diethyl 2,4-dinitrophenyl phosphate (DEDNPP) and the diester ethyl 2,4-dinitrophenyl phosphate (EDNPP) but reacts very slowly with the monoester 2,4-dinitrophenyl phosphate (DNPP). Nucleophilic attack on phosphorus is confirmed by the detection of the phosphorylated intermediates formed. These undergo Lossen-type rearrangements, resulting in the decomposition of the nucleophile. DFO, which is used therapeutically for the treatment of acute iron intoxication, carries three hydroxamate groups and shows correspondingly high nucleophilic activity toward both triester DEDNPP and diester EDNPP. This result suggests a potential use for DFO in cases of acute poisoning with phosphorus pesticides.

Hydroxylamine as an oxygen nucleophile. Chemical evidence from its reaction with a phosphate triester.

The reaction of hydroxylamine with 2,4-dinitrophenyl diethyl phosphate gives the O-phosphorylated product, which is rapidly converted to hydrazine and nitrogen gas in the presence of the excess of hydroxylamine.