Hexamethylphosphoramide

Hexamethylphosphoramide, often abbreviated HMPA, is a phosphoramide (i.e. an amide of phosphoric acid) with the formula 3PO. This colorless liquid is a useful polar aprotic solvent and additive in organic synthesis. Hexamethylphosphoramide, often abbreviated HMPA, is a phosphoramide (i.e. an amide of phosphoric acid) with the formula 3PO. This colorless liquid is a useful polar aprotic solvent and additive in organic synthesis. HMPA is the oxide of the highly basic tertiary phosphine hexamethylphosphorous triamide (HMPT), P(NMe2)3. Like other phosphine oxides (e.g., triphenylphosphine oxide), the molecule has a tetrahedral core and a P-O bond that is highly polarized, with significant negative charge residing on the oxygen atom. Compounds containing a nitrogen-phosphorus bond typically are degraded by hydrochloric acid to form a protonated amine and phosphate. It dissolves alkali metals forming blue solutions which are stable for a few hours. Solvated electrons are present in these blue solutions. HMPA is a specialty solvent for polymers, gases, and organometallic compounds. It improves the selectivity of lithiation reactions by breaking up the oligomers of lithium bases such as butyllithium. Because HMPA selectively solvates cations, it accelerates otherwise slow SN2 reactions by generating more 'naked' anions. The basic nitrogen centers in HMPA coordinate strongly to Li+. HMPA is a ligand in the useful reagents based on molybdenum peroxide complexes, e.g., MoO(O2)2(HMPA)(H2O) is used as an oxidant in organic synthesis. Dimethyl sulfoxide can often be used in place of HMPA as a cosolvent. Both are strong hydrogen bond acceptors, and their oxygen atoms bind metal cations. Other alternatives to HMPA include the N,N′-tetraalkylureas DMPU (dimethylpropyleneurea) or DMI (1,3-dimethyl-2-imidazolidinone). Tripyrrolidinophosphoric acid triamide (TPPA) has been reported to be a good substitute reagent for HMPA in reductions with samarium diiodide and as a Lewis base additive to many reactions involving samarium ketyls . HMPA is only mildly toxic but has been shown to cause nasal cancers in rats.. HMPA can be degraded to less toxic compounds by the action of hydrochloric acid.