Lithium diisopropylamide

Chembox new
Name = Lithium diisopropylamide
ImageFile = lithium diisopropylamide.png ImageSize = 150px
ImageName = Lithium diisopropylamide
IUPACName = Lithium diisopropylamide
OtherNames = LDA
Section1 = Chembox Identifiers
SMILES = CC(C) [N-] C(C)C. [Li+]
CASNo = 4111-54-0
RTECS =
Section2 = Chembox Properties
Formula = C₆H₁₄LiN or LiN(C₃H₇)₂
MolarMass = 107.1233 g/mol
Appearance =
Density = 0.79 g/cm³
Solubility = Reacts with water
MeltingPt =
BoilingPt =
pKa = 34
pKb =
Viscosity =
Section7 = Chembox Hazards
ExternalMSDS =
MainHazards = corrosive
FlashPt =
RPhrases =
SPhrases =
Section8 = Chembox Related
OtherAnions =
OtherCations =
OtherCpds = Superbases

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.

Preparation and structure

LDA is commonly formed by treating a cooled (0 to −78 °C) tetrahydrofuran (THF) solution of diisopropylamine with "n"-butyllithium. [OrgSynth | author = Smith, A. P.; Lamba, J. J. S.; Fraser, C. L. | title = Efficient Synthesis of Halomethyl-2,2'-Bipyridines: 4,4'-Bis(chloromethyl)-2,2'-Bipyridine | collvol = 10 | collvolpages = 107 | year = 2004 | prep = v78p0082]

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 [cite journal|author=Williard, P. G.; Salvino, J. M. |journal=Journal of Organic Chemistry|date=1993| volume=58|issue=1|pages= 1–3|title=Synthesis, isolation, and structure of an LDA-THF complex |doi=10.1021/jo00053a001] [cite journal| journal=Journal of the American Chemical Society|date=1991|volume=113|issue=21|title= 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|doi=10.1021/ja00021a066|author=N.D.R. Barnett, R.E. Mulvey, W. Clegg and P.A. O'Neil|pages= 8187] 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.

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.Fact|date=March 2007 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] ^-).

References

Further reading

* [http://www.tkk.fi/Yksikot/Orgaaninen/Opetus/moderni_synteettinen/luennot/Organometallics1.pdf Non-nucleophilic Bases Helsinki University of Technology]