Lithium diisopropylamide

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Lithium diisopropylamide
Lithium diisopropylamide
IUPAC name Lithium diisopropylamide
Other names LDA
Identifiers
CAS number [4111-54-0]
SMILES CC(C)[N-]C(C)C.[Li+]
Properties
Molecular formula C6H14LiN or LiN(C3H7)2
Molar mass 107.1233 g/mol
Density 0.79 g/cm³
Solubility in water Reacts with water
Acidity (pKa) 34
Hazards
Main hazards corrosive
Related compounds
Related compounds Superbases
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

Lithium diisopropylamide is the chemical compound with the formula [(CH3)2CH]2NLi. Generally abbreviated LDA, it is a strong base used in organic chemistry for the deprotonation of weakly acidic compounds. The reagent has been widely accepted because it is soluble in non-polar organic solvents and it is non-pyrophoric. LDA is a non-nucleophilic base.

Contents

[edit] Preparation and structure

LDA dimer with THF coordinated to Li cations
LDA dimer with THF coordinated to Li cations

LDA is commonly formed by treating a cooled (0 to -78 °C) tetrahydrofuran (THF) solution of diisopropylamine with n-butyllithium. Diisopropylamine has pKa value of 36; therefore, it is suitable for the deprotonation of most common carbon acids including alcohols and carbonyl compounds (acids, esters, aldehydes and ketones) possessing an alpha carbon with hydrogens. In THF solution, LDA exists primarily as a dimer[1][2] and is proposed to dissociate to afford the active base.

LDA is commercially available as a solution with polar, aprotic solvents such as THF and ether, though in practice and for small scale use (less than 50 mmol) it is common and more cost effective to prepare LDA in situ.

[edit] Kinetic vs thermodynamic bases

The deprotonation of carbon acids can proceed with either kinetic or thermodynamic reaction control. Kinetic controlled deprotonation requires a base that is sterically hindered. For example, in the case of phenylacetone, deprotonation can produce two different enolates. LDA has been shown to deprotonate the methyl group, which is the kinetic course of the deprotonation. A weaker base such as an alkoxide, which reversibly deprotonates the substrate, affords the more thermodynamically stable benzylic enolate. An alternative to the weaker base is to use a strong base which is present at a lower concentration than the ketone. For instance, with a slurry of sodium hydride in THF or dimethylformamide (DMF), the base only reacts at the solution-solid interface. A ketone molecule might be deprotonated at the kinetic site. This enolate may then encounter other ketones and the thermodynamic enolate will form through the exchange of protons, even in an aprotic solvent which does not contain hydronium ions.

LDA can, however, act as a nucleophile under certain conditions. For instance, it can react with tungsten hexacarbonyl as part of the synthesis of a diisopropylaminocarbyne.[citation needed] If given the proper conditions, LDA will act like any other nucleophile and perform condensation reactions. Other even more hindered amide bases are known, for instance the deprotonation of hexamethyldisilazane (Me3SiNHSiMe3) forms such a base ([(Me3SiNSiMe3]-).

[edit] References

  1. ^ Williard, P. G.; Salvino, J. M. (1993). "Synthesis, isolation, and structure of an LDA-THF complex". Journal of Organic Chemistry 58 (1): 1-3. doi:10.1021/jo00053a001. 
  2. ^ N.D.R. Barnett, R.E. Mulvey, W. Clegg and P.A. O'Neil (1991). "Crystal structure of lithium diisopropylamide (LDA): an infinite helical arrangement composed of near-linear nitrogen-lithium-nitrogen units with four units per turn of helix". Journal of the American Chemical Society 113 (21): 8187. doi:10.1021/ja00021a066. 

[edit] Further reading