acid: CH3CH(O−) + 2 CH3CO2H → CH3CH(Cl)PO(OH)2 + 2 CH3COCl This chloride undergoes dehydrochlorination to afford the target: CH3CH(Cl)PO(OH)2 → CH2=CHPO(OH)2 + HCl In the Kinnear–Perren reaction alkylphosphonyl dichlorides and esters are generated by alkylation of phosphorus trichloride in the presence of aluminium trichloride. Alkyltrichlorophosphonium salts are intermediates: PCl3 + RCl + AlCl3 → RPCl + AlCl The RPCl product can then be decomposed with water to produce an alkylphosphonic dichloride RP(=O)Cl2. Reactions Hydrolysis Phosphonate esters are generally susceptible to hydrolysis under both acidic and basic conditions. Cleavage of the P-C bond is harder but can be achieved under aggressive conditions. O=PC(OR)2 + 2 H2O → O=PC(OH)2 + 2 ROH Horner–Wadsworth–Emmons reaction In the Horner–Wadsworth–Emmons reaction dialkyl-phosphonates are deprotonated to give stabilized carbanions, which react with aldehydes to give E-alkenes with elimination of a dialkyl-phosphate. Structural sub-classes Bisphosphonates Compounds containing 2 geminal phosphonate groups are known as bisphosphonates. They were first synthesized in 1897 by Von Baeyer and Hofmann and now form the basis for an important class of drugs, used to treat osteoporosis and similar diseases. Examples include HEDP (etidronic acid or Didronel), which is prepared from phosphorous acid and acetic anhydride: 2 H3PO3 + (CH3CO)2O → CH3C(OH)(PO3H2)2 + CH3CO2H Thiophosphonates A thiophosphonate group is a functional group related to phosphonate by substitution of an oxygen atom for a sulphur. They are a reactive component of many pesticides and nerve agents. Substituted thiophosphonates can have 2 main structural isomers bonding though either O or S groups to give thione and thiol forms respectively. This is a property they share with related functional groups such as thiocarboxylic acids and organothiophosphates. Phosphonamidates Phosphonamidates are related to phosphonates by substitution of an oxygen atom for a nitrogen. They are a rarely encountered functional group. The nerve agent Tabun is an example. Occurrence in nature Phosphonates are one of the three sources of phosphate intake in biological cells. The other two are inorganic phosphate and organophosphates. The naturally occurring phosphonate 2-aminoethylphosphonic acid was first identified in 1959 in plants and many animals, where it is localized in membranes. Phosphonates are quite common among different organisms, from prokaryotes to eubacteria and mushrooms, mollusks, insects and others. They were first reported in natural soils by Newman and Tate (1980). The biological role of the natural phosphonates is still poorly understood. Bis- or polyphosphonates have not been found to occur naturally. A number of natural product