[15706-68-0] · C12H11N4O2P · Phenyl Phosphorodi(1-imidazolate) · (MW 274.24)
Alternate Name: phenyl diimidazol-1-ylphosphinate.
Solubility: sol acetonitrile, dioxane, THF; relatively insol benzene, ether.
Form Supplied in: not commercially available.
Preparative Methods: this reagent was first prepared in 81% yield by reaction of 4 equiv of imidazole with 1 equiv of phenyl phosphorodichloridate in benzene at 60 °C.4 The use of 2 equiv of imidazole and 2 equiv of triethylamine as base has been reported to give a yield of 98% of (1) (eq 1).2
Purification: recrystallization from benzene, filtration under a water-free atmosphere, and drying under vacuum.
Handling, Storage, and Precautions: owing to its hygroscopic nature, exclusion of moisture in handling and use is essential; should be stored in a sealed tube at -20 °C.3
The title reagent (1) reacts with amines, alcohols, and water to give amides and esters of phenyl phosphate (eqs 2-4).1 The monoimidazole derivatives are formed rapidly with a much slower reaction to give the disubstitution products.1
This behavior can be used to synthesize mixed diphosphates by treatment with a small excess of alcohol followed by hydrolysis of the monoimidazole derivative. In this manner the monophenyl ester of 2´,3´-isopropylideneadenosine 5´-phosphate (2) has been synthesized in 53.5% yield (eq 5).1
Reagent (1) has been used as a coupling reagent in the synthesis of benzyloxycarbonylalanylalanine (3).1 Initial treatment of benzyloxycarbonylalanine with (1) in acetonitrile at 45 °C for 12 h followed by reaction with an excess of an aqueous solution (pH 8-9) of alanine gave the protected dipeptide in 85% yield (eq 6). No reference to the stereochemistry of the starting materials or product was made.
Acylimidazolides have been isolated from the reaction of (1) with carboxylic acids1 and may be involved in the above reaction.
Reagent (1) has been shown to be excellent for the dehydration of aldoximes of both aromatic and aliphatic aldehydes.2 This is accomplished by reacting the aldoxime with (1) in dioxane at 20 °C for 20 h (eq 7).2
Reagent (1) is superior in terms of yield to a variety of phosphorochloridates, including Phosphorus Oxychloride. For example, in the case of 2-pyridyl aldoxime, with (1) a yield of 52% was obtained, whereas with phosphorus oxychloride the yield was 33% and with phenyl phosphorodichloridate the yield was 47%.2 The reaction is thought to proceed via an intermediate formed by O-phosphorylation of the aldoxime.2 The use of spin-labeled versions of (1) has been explored, in which the phenyl is replaced with the 2,2,6,6-tetramethylpiperidyl N-oxide group.3,5
King's College London, UK