Hexamethylphosphoramide

Hexamethylphosphoramide
IUPAC name

Hexamethylphosphoramide
Preferred IUPAC name

Hexamethylphosphoric triamide
Other names

Hexametapol
HMPA
Identifiers
CAS number 680-31-9 Y
PubChem 12679
ChemSpider 12158 Y
KEGG C19250 N
ChEBI CHEBI:24565 N
Jmol-3D images Image 1
Properties
Molecular formula C6H18N3OP
Molar mass 179.2 g mol−1
Density 1.03 g/cm3
Melting point

7.20 °C, 280 K, 45 °F
Boiling point

232.5 °C, 506 K, 451 °F (CRC[1])
Hazards
MSDS Oxford MSDS
EU classification Xn
 N (verify) (what is: Y/N?)
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 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.

Contents

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 improves the selectivity of lithiation reactions by breaking up the oligomers of lithium bases such as butyllithium. Because HMPA selectively solvates cations, it accelerates some difficult SN2 reactions. The basic oxygen atom in HMPA coordinates strongly to Li+.[2] 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[3] and the cyclic alkylureas like DMPU.[4]

Toxicity

HMPA is only mildly toxic but has been shown to cause nasal cancers in rats.[2] HMPA can be degraded to less toxic compounds by the action of hydrochloric acid. For laboratory uses it can be substituted by the less cancerogenic solvent DMI [5]

References

  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. "Hexamethylphosphoric Triamide" Encyclopedia of Reagents for Organic Synthesis, 2001 John Wiley & Sons. doi:10.1002/047084289X.rh020
  3. ^ 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.
  4. ^ 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. 
  5. ^ Lo, Chi-Chu; Chao, Pei -Min (1992). "Replacement of carcinogenic solvent HMPA by DMI in insect sex pheromone synthesis". Journal of Chemical Ecology 18 (2): 3245. doi:10.1007/BF00982095. 

External links

Only P-O bonds
P(III)
P(V)
With P-C bonds
One P-C bonds
P(III)
P(V)
Two P-C bonds
P(III)
P(V)
Three P-C bonds
P(III)
P(V)
With P-N bonds
One P-N bond
P(III)
P(V)
Two P-N bond
P(III)
Phosphorodiamidite
P(V)
Three P-N bond
P(V)
Phosphoramide (e.g. Hexamethylphosphoramide, Metepa)
With P-C and P-N bonds
One P-C bond and one P-N bond
P(V)
Phosphonamidate
One P-C bond and two P-N bond
P(V)
Phosphonamide
Two P-C bond and one P-N bond
P(V)
Phosphinamide
With P-S bonds
One P-S bond
P(III)
Phosphorothioite
P(V)
Two P-S bond
P(III)
Phosphorodithioite
P(V)