Lithium diisopropylamide

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Lithium diisopropylamide
Lithium diisopropylamide
Identifiers
CAS number 4111-54-0 YesY
PubChem 2724682
ChemSpider 2006804 YesY
Jmol-3D images Image 1
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) 36 (THF) [1]
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 (77 °F), 100 kPa)
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Infobox references

Lithium diisopropylamide (commonly abbreviated LDA) is a chemical compound with the molecular structure [(CH3)2CH]2NLi. It is used as a strong base and has been widely accepted due to its good solubility in non-polar organic solvents and non-nucleophilic nature. Potassium diisopropylamide (KDA) is a similar compound, but it has a potassium cation instead of a lithium cation. LDA is cheaper than KDA and is more widely used.

Preparation and structure[edit]

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.[2]

LDA has pKa value of 36; therefore, it is suitable for the deprotonation of alcohols and carbonyl compounds (acids, esters, aldehydes and ketones) possessing an alpha carbon with hydrogens.

Like many organolithium reagents, LDA tends to form aggregates in solution; with the extent of aggregation depending on the nature of the solvent. In THF its structure is primarily that of a solvated dimer.[3][4]

Pure LDA is pyrophoric[5] but its solutions are generally not. As such it is commercially available as a solution in polar aprotic solvents such as THF and ether, however for small scale use (less than 50 mmol) it is common and more cost effective to prepare LDA in situ.

Kinetic vs thermodynamic bases[edit]

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.

Reactions[edit]

Owing to its high basicity, LDA is capable, for example, of deprotonating alkenyl halides and even enol ethers, giving a mixture of alkene and alkyne products.[6]

See also[edit]

References[edit]

  1. ^ David Evans Research Group
  2. ^ Smith, A. P.; Lamba, J. J. S.; Fraser, C. L. (2004), "Efficient Synthesis of Halomethyl-2,2'-Bipyridines: 4,4'-Bis(chloromethyl)-2,2'-Bipyridine", Org. Synth. ; Coll. Vol. 10: 107 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ MSDS at Sigma-Aldrich
  6. ^ Grossman, Robert B. (2003). The Art of Writing Reasonable Organic Reaction Mechanisms (2nd ed.). New York: Springer-Verlag. ISBN 0-387-95468-6