Hexamethylphosphoramide

Hexamethylphosphoramide
IUPAC name	Hexamethylphosphoramide
Other names	Hexametapol HMPA
Identifiers
CAS number	680-31-9 Y
SMILES	CN(C)P(=O)(N(C)C)N(C)C
Properties
Molecular formula	C6H18N3OP
Molar mass	179.20 g/mol
Density	1.03 g/cm³
Melting point	7.20 °C
Boiling point	235 °C
Hazards
MSDS	Oxford MSDS
EU classification	Xn
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

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

Structure and reactivity

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.

Applications

HMPA is used as a solvent for polymers, gases, and organometallic compounds. 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 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. doi:10.1002/047084289X.rh020
2. ^ Beck, A. K.; Seebach, D. "N,N'-Dimethylpropyleneurea" in Encyclopedia of Reagents for Organic Synthesis, 2001 John Wiley & Sons, New York. doi:10.1002/047084289X.rd366.
3. ^ Triptikumar Mukhopadhyay, Dieter Seebach (1982). "Substitution of HMPT by the cyclic urea DMPU as a cosolvent for highly reactive nucleophiles and bases". Helvetica Chimica Acta 65 (1): 385–391. doi:10.1002/hlca.19820650141. 

External links

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