Hexamethylphosphoramide
Encyclopedia
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
.
), 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.
for polymer
s, 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+. A molybdenum
peroxide
complex of HMPA is used as an oxidant in organic synthesis.
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 tetraalkylurea
s and the cyclic alkylurea
s like DMPU
.
. For laboratory uses it can be substituted by the less cancerogenic solvent DMI
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
of phosphoric acid
Phosphoric acid
Phosphoric acid, also known as orthophosphoric acid or phosphoric acid, is a mineral acid having the chemical formula H3PO4. Orthophosphoric acid molecules can combine with themselves to form a variety of compounds which are also referred to as phosphoric acids, but in a more general way...
) having the formula
Chemical formula
A chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....
[(CH3)2N]3PO. This colorless liquid is a useful polar aprotic solvent and additive in organic synthesis
Organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
.
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 oxideTriphenylphosphine oxide
Triphenylphosphine oxide is the chemical compound with the formula OP3. Often chemists abbreviate the formula by writing Ph3PO or PPh3O . This white crystalline compound is a common side product in reactions involving triphenylphosphine...
), 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
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
-phosphorus bond typically are degraded by hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....
to form a protonated amine and phosphate.
Applications
HMPA is used as a solventSolvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...
for polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
s, gases, and organometallic compounds. It improves the selectivity of lithiation reactions by breaking up the oligomers of lithium
Lithium
Lithium is a soft, silver-white metal that belongs to the alkali metal group of chemical elements. It is represented by the symbol Li, and it has the atomic number 3. Under standard conditions it is the lightest metal and the least dense solid element. Like all alkali metals, lithium is highly...
bases such as butyllithium. Because HMPA selectively solvates cations, it accelerates some difficult SN2 reactions. The basic oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
atom in HMPA coordinates strongly to Li+. A molybdenum
Molybdenum
Molybdenum , is a Group 6 chemical element with the symbol Mo and atomic number 42. The name is from Neo-Latin Molybdaenum, from Ancient Greek , meaning lead, itself proposed as a loanword from Anatolian Luvian and Lydian languages, since its ores were confused with lead ores...
peroxide
Peroxide
A peroxide is a compound containing an oxygen–oxygen single bond or the peroxide anion .The O−O group is called the peroxide group or peroxo group. In contrast to oxide ions, the oxygen atoms in the peroxide ion have an oxidation state of −1.The simplest stable peroxide is hydrogen peroxide...
complex of HMPA is used as an oxidant in organic synthesis.
Alternative reagents
Dimethyl sulfoxideDimethyl sulfoxide
Dimethyl sulfoxide is an organosulfur compound with the formula 2SO. This colorless liquid is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water...
can often be used in place of HMPA as a solvent. Both are strong hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...
acceptors, and their oxygen atoms bind metal cations. Other alternatives to HMPA include the tetraalkylurea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
s and the cyclic alkylurea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
s like DMPU
DMPU
1,3-Dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone is a cyclic urea sometimes used as a polar, aprotic organic solvent. In 1985, Dieter Seebach showed that it is possible to substitute the relatively toxic hexamethylphosphoramide with DMPU....
.
Toxicity
HMPA is only mildly toxic but has been shown to cause nasal cancers in rats. HMPA can be degraded to less toxic compounds by the action of hydrochloric acidHydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....
. For laboratory uses it can be substituted by the less cancerogenic solvent DMI
1,3-Dimethyl-2-imidazolidinone
1,3-Dimethyl-2-imidazolidinone is a cyclic urea used as a high-boiling polar aprotic solvent. It is colourless, transparent, highly polar and has high thermal and chemical stability. It is a homolog of the related solvent DMPU...
External links
- The substance profile of HMPA in the report on carcinogens
- Merck Index, 12th Edition, 4761.