Hexamethylphosphoramide, often abbreviated HMPA, is an organophosphorus compound with the formula [(CH₃)₂N]₃PO. This a colorless liquid is a useful polar solvent and additive in organic synthesis.

Structure and reactivity

HMPA is the oxide of the highly basic tertiary phosphine Hexamethylphorous triamide (HMPT), P(NMe₂)₃. Like other phosphine oxides, e.g. Triphenylphosphine oxide, the molecule has tetrahedral core and the P-O bond is highly polarized, with significant negative charge residing on oxygen.

Compound containing a nitrogen-phosphorus bond typically are degraded by hydrochloric acid to form a protonated amine and phosphate.

Applications

HMPA is used as a solvent for polymers, gases, and organometallic reagents. It usefully improves the selectivity of lithiation reactions, because it breaks up the oligomers of lithium bases such as butyllithium. Because HMPA solvates cations so well, while not solvating anions, it accelerates some difficult S_N2 reactions. The basic oxygen atom in HMPA coordinates strongly to Li⁺.^[1] A molybdenum peroxide complex of HMPA is used as an oxidant in organic synthesis.

Alternative reagents

Dimethyl sulfoxide can often be used in place of HMPA as a solvent. Both are strong hydrogen bond acceptors, and their oxygen atoms are bind metal cations. Other alternatives to HMPA include the tetraalkylureas^[2] and the cyclic alkylureas like DMPU.^[3]

Toxicity

HMPA is only mildly toxic but has been shown to cause nasal cancers in rats.^[1] HMPA can be degraded to less toxic compounds by the action of hydrochloric acid.

References

1. ↑ ^{a b} Dykstra, R. R. "Hexamethylphosphoric Triamide" Encyclopedia of Reagents for Organic Synthesis, 2001 John Wiley & Sons.
2. ↑ Beck, A. K.; Seebach, D. "N,N'-Dimethylpropyleneurea" in Encyclopedia of Reagents for Organic Synthesis, 2001 John Wiley & Sons, New York. .
3. ↑

External links

• The substance profile of HMPA in the report on carcinogens
• Merck Index, 12th Edition, 4761.

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