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Hexamethylphosphoramide

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Hexamethylphosphoramide
Chemical structure of HMPA
3D stick model of HMPA
Names
Preferred IUPAC name Hexamethylphosphoric triamide
Other names
  • Hexamethylphosphoramide
  • Hexametapol
  • HMPA
  • Phosphoric tris(dimethylamide)
  • HMPT
Identifiers
CAS Number
3D model (JSmol)
Beilstein Reference 1099903
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.010.595 Edit this at Wikidata
EC Number
  • 211-653-8
Gmelin Reference 3259
KEGG
PubChem CID
RTECS number
  • TD0875000
UNII
UN number 2810 3082
CompTox Dashboard (EPA)
InChI
  • InChI=1S/C6H18N3OP/c1-7(2)11(10,8(3)4)9(5)6/h1-6H3Key: GNOIPBMMFNIUFM-UHFFFAOYSA-N
  • InChI=1/C6H18N3OP/c1-7(2)11(10,8(3)4)9(5)6/h1-6H3Key: GNOIPBMMFNIUFM-UHFFFAOYAP
SMILES
  • O=P(N(C)C)(N(C)C)N(C)C
Properties
Chemical formula C6H18N3OP
Molar mass 179.20 g/mol
Appearance colorless liquid
Odor aromatic, mild, amine-like
Density 1.03 g/cm
Melting point 7.20 °C (44.96 °F; 280.35 K)
Boiling point 232.5 °C (450.5 °F; 505.6 K) CRC
Solubility in water miscible
Vapor pressure 0.03 mmHg (4.0 Pa) at 20 °C
Hazards
Occupational safety and health (OHS/OSH):
Main hazards Suspected Carcinogen
GHS labelling:
Pictograms GHS08: Health hazard
Signal word Danger
Hazard statements H340, H350
Precautionary statements P201, P202, P281, P308+P313, P405, P501
Flash point 104.4 °C (219.9 °F; 377.5 K)
NIOSH (US health exposure limits):
PEL (Permissible) none
REL (Recommended) Ca
IDLH (Immediate danger) Ca
Safety data sheet (SDS) Oxford MSDS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). ☒N verify (what is  ?) Infobox references
Chemical compound

Hexamethylphosphoramide, often abbreviated HMPA, is a phosphoramide (an amide of phosphoric acid) with the formula 3PO. This colorless liquid is used as a solvent in organic synthesis.

Structure and reactivity

HMPA is the oxide of tris(dimethylamino)phosphine, P(NMe2)3. Like other phosphine oxides (such as 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.

It dissolves alkali metal salts and alkali metals, forming blue solutions which are stable for a few hours. Solvated electrons are present in these blue solutions.

Applications

HMPA is a specialty 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 slow SN2 reactions by generating more bare anions. The basic nitrogen centers in HMPA coordinate strongly to Li.

HMPA is a ligand in the useful reagents based on molybdenum peroxide complexes, for example, MoO(O2)2(HMPA)(H2O) is used as an oxidant in organic synthesis.

Alternative reagents

Dimethyl sulfoxide can often be used in place of HMPA as a cosolvent. Both are strong hydrogen bond acceptors, and their oxygen atoms bind metal cations. Other alternatives to HMPA include the N,N′-tetraalkylureas DMPU (dimethylpropyleneurea) or DMI (1,3-dimethyl-2-imidazolidinone). Tripyrrolidinophosphoric acid triamide (TPPA) has been reported to be a good substitute reagent for HMPA in reductions with samarium diiodide and as a Lewis base additive to many reactions involving samarium ketyls.

Toxicity

HMPA is only mildly toxic but has been shown to cause cancer in rats. HMPA can be degraded by the action of hydrochloric acid.

References

  1. Not recommended: see Blue Book reference.
  2. This name is also used to refer to tris(dimethylamino)phosphine
  3. "Front Matter". Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. pp. P001–P004. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4.
  4. ^ NIOSH Pocket Guide to Chemical Hazards. "#0321". National Institute for Occupational Safety and Health (NIOSH).
  5. Haynes, William M. (2010). Handbook of Chemistry and Physics (91 ed.). Boca Raton, Florida, USA: CRC Press. p. 3-280. ISBN 978-1-43982077-3.
  6. Luehrs, Dean C.; Kohut, John P. (1974). "Hexamethylphosphoramide solvates of alkali metal salts". Journal of Inorganic and Nuclear Chemistry. 36 (7): 1459–1460. doi:10.1016/0022-1902(74)80605-6.
  7. Gremmo, Norberto; Randles, John E. B. (1974). "Solvated electrons in hexamethylphosphoramide. Part 1.—Conductivity of solutions of alkali metals". Journal of the Chemical Society, Faraday Transactions 1: Physical Chemistry in Condensed Phases. 70: 1480–1487. doi:10.1039/F19747001480.
  8. ^ Dykstra, R. R. (2001). "Hexamethylphosphoric Triamide". Hexamethylphosphoric Triamide. Encyclopedia of Reagents for Organic Synthesis. New York, NY: John Wiley & Sons. doi:10.1002/047084289X.rh020. ISBN 978-0471936237.
  9. Dickman, Michael H.; Pope, Michael T. (1994). "Peroxo and Superoxo Complexes of Chromium, Molybdenum, and Tungsten". Chemical Reviews. 94 (3): 569–584. doi:10.1021/cr00027a002.
  10. 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.
  11. Beck, A. K.; Seebach, D. (2001). "N,N′-Dimethylpropyleneurea". N,N′-Dimethylpropyleneurea. Encyclopedia of Reagents for Organic Synthesis. New York: John Wiley & Sons. doi:10.1002/047084289X.rd366. ISBN 978-0471936237.
  12. Lo, Chi-Chu; Chao, Pei-Min (1990). "Replacement of carcinogenic solvent HMPA by DMI in insect sex pheromone synthesis". Journal of Chemical Ecology. 16 (12): 3245–3253. doi:10.1007/BF00982095. PMID 24263426. S2CID 9859086.
  13. McDonald, Chriss E.; Ramsey, Jeremy D.; Sampsell, David G.; Butler, Julie A.; Cecchini, Michael R. (2010). "Tripyrrolidinophosphoric Acid Triamide as an Activator in Samarium Diiodide Reductions". Organic Letters. 12 (22): 5178–5181. doi:10.1021/ol102040s. PMID 20979412.
  14. Berndt, Mathias; Hölemann, Alexandra; Niermann, André; Bentz, Christoph; Zimmer, Reinhold; Reissig, Hans-Ulrich (2012). "Replacement of HMPA in Samarium Diiodide Promoted Cyclizations and Reactions of Organolithium Compounds". European Journal of Organic Chemistry. 2012 (7): 1299–1302. doi:10.1002/ejoc.201101830. ISSN 1099-0690. Tripyrrolidinophosphoric acid triamide (TPPA) can replace carcinogenic HMPA as a Lewis basic additive in many reactions involving samarium ketyls. In most cases, yields and selectivities of cyclizations of (het)aryl, alkenyl, and alkynyl ketones are similar.

External links

  • "Hexamethylphosphoramide CAS No. 680-31-9" (PDF). Report on Carcinogens (12th ed.). 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. Vol. 4761 (12th ed.).
Organophosphorus
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