phosphorothioater

Phosphorothioater, commonly referred to as a phosphorothioate ester, is an organophosphorus compound in which a sulfur atom is bonded to phosphorus by a P=S bond and the phosphorus center carries three alkoxy or aryloxy substituents. The typical core is described by the skeleton P(=S)(OR1)(OR2)(OR3), where OR groups are alcohol-derived substituents. This class includes many triester derivatives of phosphorothioic acid.

Synthesis of phosphorothioaters generally involves thionation of phosphate esters. Common methods convert a phosphate ester or chlorophosphate intermediate into the corresponding phosphorothioate using thionating reagents such as Lawesson’s reagent or phosphorus sulfide (P4S10). Alternative routes include initial formation of a phosphoryl ester followed by thionation to replace a non-bridging oxygen with sulfur.

Chemical properties of phosphorothioaters are influenced by the P=S bond. The thionated phosphorus center can engage in nucleophilic substitution at the ester oxygens, and the substituents on phosphorus affect hydrolytic stability. They tend to be more lipophilic than their phosphate counterparts, and hydrolysis behavior depends on the substituents present on phosphorus.

Applications and significance include their historical and ongoing roles as insecticides and as biochemical tools. Parathion and chlorpyrifos are among well-known phosphorothioate insecticides. Some derivatives are used in flame retardants or as research probes due to their activity as acetylcholinesterase inhibitors. Because of significant toxicity to humans and wildlife, many phosphorothioates are subject to regulatory controls, and handling requires careful safety measures.

Safety and environmental considerations emphasize that these compounds inhibit acetylcholinesterase, leading to cholinergic syndrome in cases of exposure. Regulatory status varies by jurisdiction, with strict controls and monitoring often required for manufacture, use, and disposal.