Hexamethylphosphoramide, often abbreviated HMPA, is a
phosphoramide
Phosphoramide is a chemical compound with the molecular formula . It is a derivative of phosphoric acid in which each of the hydroxyl groups have been replaced with an amino group. In bulk, the compound is a white solid which is soluble in polar s ...
(an
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...
of
phosphoric acid
Phosphoric acid (orthophosphoric acid, monophosphoric acid or phosphoric(V) acid) is a colorless, odorless phosphorus-containing solid, and inorganic compound with the chemical formula . It is commonly encountered as an 85% aqueous solution, ...
) with the
formula
In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwe ...
This colorless liquid is used as a solvent in
organic synthesis
Organic synthesis is a branch of chemical synthesis concerned with the construction of organic compounds. Organic compounds are molecules consisting of combinations of covalently-linked hydrogen, carbon, oxygen, and nitrogen atoms. Within the gen ...
.
Structure and reactivity
HMPA is the oxide of
tris(dimethylamino)phosphine, P(NMe
2)
3. Like other phosphine oxides (such as
triphenylphosphine oxide
Triphenylphosphine oxide (often abbreviated TPPO) is the organophosphorus compound with the formula , also written as or (Ph = ). It is one of the more common phosphine oxides. This colourless crystalline compound is a common but potentially u ...
), 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
Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...
–phosphorus bond typically are degraded by
hydrochloric acid
Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...
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
A solvent (from the Latin language, Latin ''wikt:solvo#Latin, solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a Solution (chemistry), solution. A solvent is usually a liquid but can also be a solid, a gas ...
for
polymer
A polymer () is a chemical substance, substance or material that consists of very large molecules, or macromolecules, that are constituted by many repeat unit, repeating subunits derived from one or more species of monomers. Due to their br ...
s,
gases
Gas is a state of matter that has neither a fixed volume nor a fixed shape and is a compressible fluid. A ''pure gas'' is made up of individual atoms (e.g. a noble gas like neon) or molecules of either a single type of atom ( elements such ...
, and
organometallic compounds
Organometallic chemistry is the study of organometallic compounds, chemical compounds containing at least one chemical bond between a carbon atom of an organic molecule and a metal, including alkali, alkaline earth, and transition metals, an ...
. It improves the selectivity of lithiation reactions by breaking up the
oligomers
In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...
of
lithium
Lithium (from , , ) is a chemical element; it has chemical symbol, symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard temperature and pressure, standard conditions, it is the least dense metal and the ...
bases such as
butyllithium Butyllithium may refer to one of 5 isomeric organolithium reagents of which 3 are commonly used in chemical synthesis:
* ''n''-Butyllithium, abbreviated BuLi or nBuLi
* ''sec''-Butyllithium, abbreviated ''sec''-BuLi or sBuLi, has 2 stereoisomers, ...
. Because HMPA selectively solvates cations, it accelerates otherwise slow
SN2 reactions by generating more bare anions. The basic
nitrogen
Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...
centers in HMPA
coordinate
In geometry, a coordinate system is a system that uses one or more numbers, or coordinates, to uniquely determine and standardize the position of the points or other geometric elements on a manifold such as Euclidean space. The coordinates are ...
strongly to Li
+.
HMPA is a ligand in the useful reagents based on
molybdenum
Molybdenum is a chemical element; it has Symbol (chemistry), symbol Mo (from Neo-Latin ''molybdaenum'') and atomic number 42. The name derived from Ancient Greek ', meaning lead, since its ores were confused with lead ores. Molybdenum minerals hav ...
peroxide
In chemistry, peroxides are a group of Chemical compound, compounds with the structure , where the R's represent a radical (a portion of a complete molecule; not necessarily a free radical) and O's are single oxygen atoms. Oxygen atoms are joined ...
complexes, for example, MoO(O
2)
2(HMPA)(H
2O) is used as an
oxidant
An oxidizing agent (also known as an oxidant, oxidizer, electron recipient, or electron acceptor) is a substance in a redox chemical reaction that gains or "Electron acceptor, accepts"/"receives" an electron from a (called the , , or ''electr ...
in organic synthesis.
Alternative reagents
Dimethyl sulfoxide
Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula . This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is ...
can often be used in place of HMPA as a cosolvent. Both are strong
hydrogen bond
In chemistry, a hydrogen bond (H-bond) is a specific type of molecular interaction that exhibits partial covalent character and cannot be described as a purely electrostatic force. It occurs when a hydrogen (H) atom, Covalent bond, covalently b ...
acceptors, and their oxygen atoms bind metal
cation
An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
s. Other alternatives to HMPA include the ''N'',''N''′-tetraalkylureas
DMPU
''N'',''N''′-Dimethylpropyleneurea (DMPU) is a cyclic urea sometimes used as a polar, aprotic organic solvent. Along with the dimethylethyleneurea, it was introduced as an analog of tetramethylurea.
In 1985, Dieter Seebach showed that it is ...
(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
A Lewis acid (named for the American physical chemist Gilbert N. Lewis) is a chemical species that contains an empty orbital which is capable of accepting an electron pair from a Lewis base to form a Lewis adduct. A Lewis base, then, is any sp ...
additive to many reactions involving
samarium
Samarium is a chemical element; it has symbol Sm and atomic number 62. It is a moderately hard silvery metal that slowly oxidizes in air. Being a typical member of the lanthanide series, samarium usually has the oxidation state +3. Compounds of s ...
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
Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...
.
References
External links
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*
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{{Authority control
Phosphoramides
Solvents
IARC Group 2B carcinogens