In organic chemistry, phosphonates or phosphonic acids are organophosphorus compounds containing groups (where R = alkyl, aryl, or just hydrogen). Phosphonic acids, typically handled as salts, are generally nonvolatile solids that are poorly soluble in organic solvents, but soluble in water and common alcohols. Many commercially important compounds are phosphonates, including glyphosate (the active molecule of the herbicide Roundup), and ethephon, a widely used plant growth regulator. Bisphosphonates are popular drugs for treatment of osteoporosis. In biochemistry and medicinal chemistry, phosphonate groups are used as stable bioisosteres for phosphate, such as in the antiviral nucleotide analog, Tenofovir, one of the cornerstones of anti-HIV therapy. And there is an indication that phosphonate derivatives are "promising ligands for nuclear medicine." Basic properties Phosphonates feature tetrahedral phosphorus centers. They are structurally closely related to (and often prepared from) phosphorous acid. Phosphonate salts are the result of deprotonation of phosphonic acids, which are diprotic acids: RPO(OH)2 + NaOH → H2O + RPO(OH)(ONa) (monosodium phosphonate) RPO(OH)(ONa) + NaOH → H2O + RPO(ONa)2 (disodium phosphonate) Phosphonate esters are the result of condensation of phosphonic acids with alcohols. Synthesis Several methods exist for the preparation of phosphonic acids and their salts. From phosphonic acid Most processes begin with phosphorous acid (aka phosphonic acid, H3PO3), exploiting its reactive P−H bond. Phosphonic acid can be alkylated under Mannich conditions to give aminomethylated phosphonates, which are useful as complexants. One example is the industrial preparation of nitrilotris(methylenephosphonic acid): NH3 + 3 H3PO3 + 3 CH2O → N(CH2PO3H2)3 + 3 H2O Phosphonic acid also can be alkylated with acrylic acid derivatives to afford carboxyl functionalized phosphonic acids. This reaction is a variant of the Michael addition: CH2=CHCO2R + 3 H3PO3 → (HO)2P(O)CH2CH2CO2R In the Hirao coupling dialkyl phosphites (which can also be viewed as di-esters of phosphonic acid: (O=PH(OR)2) undergo a palladium-catalyzed coupling reaction with an aryl halide to form a phosphonate. Michaelis-Arbuzov reaction Phosphonic esters are prepared using the Michaelis–Arbuzov reaction. For example, methyl iodide catalyses the conversion of trimethylphosphite to the phosphonate ester dimethyl methylphosphonate: P(OMe)3 → MePO(OMe)2 These esters can be hydrolysed to the acid (Me = methyl): MePO(OMe)2 + H2O → MePO(OH)2 + 2 MeOH In the Michaelis–Becker reaction, a hydrogen phosphonate diester is first deprotonated and the resulting anion is alkylated. From phosphorus trichloride Vinylphosphonic acid can be prepared by the reaction of PCl3 and acetaldehyde: PCl3 + CH3CHO → CH3CH(O−) This adduct reacts with acetic