Hexamethylphosphoramide

Hexamethylphosphoramide, often abbreviated HMPA, is a phosphoramide (i.e. an amide of phosphoric acid) having the formula [(CH3)2N]3PO. This colorless liquid is a useful polar aprotic solvent and additive in organic synthesis.


HMPA is a speciality 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 SN2 reactions by generating more "naked" anions. The basic oxygen 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.
HMPA is only mildly toxic but has been shown to cause nasal cancers in rats.Still, many organic chemists regard HMPA as an exceptionally hazardous molecule due to its known carcinogenicity, and avoid its use when possible. HMPA can be degraded to less toxic compounds by the action of hydrochloric acid. For laboratory uses it can be substituted by the less carcinogenic solvent DMI.