Hexamethylphosphoramide

Hexamethylphosphoramide
Names
IUPAC name
Hexamethylphosphoramide
Preferred IUPAC name
Hexamethylphosphoric triamide
Other names
Hexametapol
HMPA
Identifiers
680-31-9 Yes
ChEBI CHEBI:24565 Yes
ChemSpider 12158 Yes
Jmol-3D images Image
KEGG C19250 
PubChem 12679
Properties
Molecular formula
 C6H18N3OP
Molar mass 179.20 g·mol−1
Appearance clear, colorless liquid[1]
Odor aromatic, mild, amine-like[1]
Density 1.03 g/cm3
Melting point 7.20 °C (44.96 °F; 280.35 K)
Boiling point 232.5 °C (450.5 °F; 505.6 K) CRC[2]
miscible[1]
Vapor pressure 0.03 mmHg (20°C)[1]
Hazards
MSDS Oxford MSDS
Main hazards carcinogen[1]
EU classification T
Flash point 104.4 °C (219.9 °F; 377.5 K)
US health exposure limits (NIOSH):
none[1]
Ca[1]
Ca [N.D.][1]
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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Infobox references

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.

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 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+.[3]

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.[4]

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[5] and the cyclic alkylureas like DMPU.[6]

Toxicity

HMPA is only mildly toxic but has been shown to cause nasal cancers in rats.[3] 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.[7]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "NIOSH Pocket Guide to Chemical Hazards #0321". National Institute for Occupational Safety and Health (NIOSH).
  2. ↑ Haynes, William M. (2010). Handbook of Chemistry and Physics (91 ed.). Boca Raton, Florida: CRC Press. p. 3-280. ISBN 978-1439820773.
  3. ↑ 3.0 3.1 Dykstra, R. R. (2001). "Hexamethylphosphoric Triamide". Encyclopedia of Reagents for Organic Synthesis. New York: John Wiley & Sons. doi:10.1002/047084289X.rh020.
  4. ↑ Dickman, Michael H.; Pope, Michael T. (1994). "Peroxo and Superoxo Complexes of Chromium, Molybdenum, and Tungsten". Chemical Reviews 94: 569–84. doi:10.1021/cr00027a002.
  5. ↑ Beck, A. K.; Seebach, D. (2001). "N,N'-Dimethylpropyleneurea". Encyclopedia of Reagents for Organic Synthesis. New York: John Wiley & Sons. doi:10.1002/047084289X.rd366.
  6. ↑ Mukhopadhyay, T.; Seebach, D. (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.
  7. ↑ Lo, C. C.; Chao, P. M. (1992). "Replacement of Carcinogenic Solvent HMPA by DMI in Insect Sex Pheromone Synthesis" (PDF). Journal of Chemical Ecology 18 (2): 3245–3253. doi:10.1007/BF00982095.

External links