Tetraethyl methylenediphosphonate

Hachemi, M., Puciova-Sebova, M., Toma, S. and Villemin, D. Dry reaction of diethyl cyanomethylphosphonate and tetraethyl methylenediphosphonate with benzaldehyde on solid bases, Phosphorus, Sulfur Silicon Relat. Elem, 1996, 113, 131-136. 

Diethyl iodomethylphosphonate was obtained for the first time in 1936 by A. E. Arbuzov and Kushkova by the reaction of diiodomethane with triethyl phosphite in 60% yield (Scheme 3.1). Similar results were obtained in later studies (30-59%),even after experimental modifications aimed at limiting the formation of the major byproduct, tetraethyl methylenediphosphonate. Under the optimized conditions, dimethyl iodomethylphosphonate is obtained in 27% yield. This low yield can be explained by a second side reaction, the Michaelis-Arbuzov rearrangement between trimethyl phosphite and the methyl iodide coproduct, which gives dimethyl methylphosphonate. ... 

The reaction of sodium diethyl phosphite with a large excess of dichloromethane at room temperature generates mainly tetraethyl methylenediphosphonate (51% yield) and diethyl chloro-methylphosphonate (14% yield). These results clearly demonstrate that diethyl chloromethylphos-phonate is a more reactive substrate in a nucleophilic substitution reaction than dichloromethane. ... 

Tetraethyl methylenediphosphonate can be prepared from diethyl chloromethylphosphonate by reaction either with triethyl phosphite nnder drastic conditions (neat, 190°C, 27%, Michaelis-Arbuzov reaction)- or with sodium diethyl phosphite in refluxing CgHg (47%, Michaelis-Becker reaction).- - However, the yields are significantly lower than those obtained by SNP(V) reaction of diethyl 1-lithiomethylphosphonate with diethyl chlorophosphate (Scheme 3.54). 

A quite similar method is employed in the one-carbon chain extension of a 5 -phosphonate isostere of pyridoxal 5 -phosphate (Scheme 5.50) The a , 3-O-isopropylideneisopyridoxal is converted into an oc,P-unsaturated phosphonate in yields up to 65% by condensation with sodium tetraethyl methylenediphosphonate. Selective hydrolysis with 10% HCOjH at reflux gives the key diethyl 2-(3-hydroxy-4-hydroxymethyl-2-methyl-5-pyridyl)vinylphosphonate intermediate in 98% yield. After catalytic hydrogenation of the double bond using 5% Pd/C in EtOH, a comparison of methods for the oxidation of the alcohol has been made, including use of MnOi in water, CrO, Py, and DMSO-DCC. Finally, oxidation with activated MnO2 in CHCl, was found to proceed smoothly to give the diethyl 2-(4-formyl-3-hydroxy-2-methyl-5-pyridyl)cthylphosphonate. ... 

Unsuccessful attempts to form 1 1 adducts selectively from the Michael addition of diethyl 1-(ethoxycaibonyl)methylphosphonate or tetraethyl methylenediphosphonate to acrylonitrile under phase-Uansfer catalysis conditions (KjCDj/TEBAC/C, 1,) have been reported. Despite variation of the reaction conditions, mixtures of 1 1 and 1 2 adducts are obtained.- ... 

In the presence of EtONa/EtOH, tetraethyl methylenediphosphonate adds to unsaturated electrophilic compounds, methyl acrylate and diethyl vinylphosphonate. Only products of addition to one molecule of the unsatiuated compound are obtained. ... 

Pudovik. A.N., Yastrebova, G.E., and Pudovik, O.A., Tetraethyl methylenediphosphonate in condensation reactions and in addition reactions with unsaturated compounds, Zh. Obshch. Khim., 40, 499, 1970 Gen. Chem. USSR (Engl. Transl.), 40, 462, 1970. 

A sequence of Michael addition, iodination, and intramolecular alkylation is involved in the formation of 2-substituted cyclopropane-1,1-diphosphonate esters from tetraethyl methylenediphosphonate. The reagents are KF-AI2O3 and I2. 

Tetraethyl methylenediphosphonate added at room temp, to a stirred mixture of 50%-NaH iii Oil and benzene, a, 3-0-isopropylideneisopyridoxal in benzene then added dropwise with stirring at room temp., stirring continued 1 hr., treated with diloroform-water, and the product isolated as the hydrochloride -> diethyl a, 3-0-isopropylidene-a5-isopyridoxylidenemethylphosphonate hydrochloride. Y 93%. T. L. Hullar, J. Med. Chem. 72, 58 (1969). 

The MBH reactions of diethyl vinylphosphonate dates back to 1990, and they present similar reactivities to alkyl acrylates. It was found that diethyl vinylphosphonate can be coupled with various aliphatic aldehydes in the presence of DABCO to give moderate to high yields of the corresponding a-hydroxyalkyl phosphonates 85. However, this approach was not effective for aqueous formaldehyde and polyoxymethylene, and the corresponding a-hydroxymethyl phosphonates 87 can only be obtained through a Wittig Horner-type reaction from tetraethyl methylenediphosphonate 86 and formaldehyde (30% aq.) in the presence of a weak base K2CO3 (6-8 m) (Scheme 1.42). 

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