Hexamethylphosphoramide

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Hexamethylphosphoramide
Chemical structure of HMPA
3D stick model of HMPA
Identifiers
CAS number 680-31-9 YesY
PubChem 12679
ChemSpider 12158 YesY
KEGG C19250 N
ChEBI CHEBI:24565 YesY
Jmol-3D images Image 1
Properties
Molecular formula C6H18N3OP
Molar mass 179.20 g mol−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[1]
Hazards
MSDS Oxford MSDS
EU classification Harmful Xn
Flash point 104.4 °C (219.9 °F; 377.5 K)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
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[edit]

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[edit]

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+.[2]

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.[3]

Alternative reagents[edit]

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

Toxicity[edit]

HMPA is only mildly toxic but has been shown to cause nasal cancers in rats.[2] 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.[6]

References[edit]

  1. ^ Haynes, William M. (2010). Handbook of Chemistry and Physics (91 ed.). Boca Raton, Florida: CRC Press. p. 3-280. ISBN 978-1439820773. 
  2. ^ a b Dykstra, R. R. (2001). "Hexamethylphosphoric Triamide". Encyclopedia of Reagents for Organic Synthesis. New York: John Wiley & Sons. doi:10.1002/047084289X.rh020. 
  3. ^ Dickman, Michael H.; Pope, Michael T. "Peroxo and Superoxo Complexes of Chromium, Molybdenum, and Tungsten" Chemical Reviews,1994, vol. 94, pp. 569-84. doi:10.1021/cr00027a002
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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[edit]

  • "Hexamethylphosphoramide CAS No. 680-31-9" (pdf). Report on Carcinogens, Twelfth Edition. National Toxicology Program, Department of Health and Human Services. 2011. 
  • "Hexamethyl phosphoramide". NIOSH Pocket Guide to Chemical Hazards. Centers for Disease Control and Prevention, Department of Health and Human Services. 2011. 
  • Merck Index, 12th Edition, 4761.