Editing Lithium diisopropylamide

{{Chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 450704638
| Name = Lithium diisopropylamide
| ImageFile = lithium diisopropylamide.png
| ImageSize = 150px
| ImageFile1 = File:Lithiumdiisopropylamid_v1.svg
| ImageSize1 = 
| ImageName = Lithium diisopropylamide
| PIN = Lithium ''N''-(propan-2-yl)propan-2-aminide
| OtherNames = LDA
|Section1={{Chembox Identifiers
| SMILES = [Li+].CC(C)[N-]C(C)C
| SMILES_Comment = ionic form
| SMILES1 = CC(C)N([Li])C(C)C
| SMILES1_Comment = covalent form
| SMILES2 = C1CCC[O+]1[Li-2]0[N+](C(C)C)(C(C)C)[Li-2]([O+]1CCCC1)[N+]0(C(C)C)C(C)C
| SMILES2_Comment = dimer with THF
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2006804
| InChI = 1/C6H14N.Li/c1-5(2)7-6(3)4;/h5-6H,1-4H3;/q-1;+1
| InChIKey = ZCSHNCUQKCANBX-UHFFFAOYAP
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C6H14N.Li/c1-5(2)7-6(3)4;/h5-6H,1-4H3;/q-1;+1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ZCSHNCUQKCANBX-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 4111-54-0
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = OL028KIW1I
| RTECS =
| PubChem = 2724682
  }}
|Section2={{Chembox Properties
| Formula = {{chem2|LiN(CH(CH3)2)2}}
| MolarMass = 107.1233 g/mol
| Appearance = colourless solid
| Density = 0.79 g/cm<sup>3</sup>
| Solubility = Reacts with water
| MeltingPt = 
| BoilingPt = 
| pKa = 36 (THF)<ref>[http://evans.rc.fas.harvard.edu/pdf/evans_pKa_table.pdf Evans pKa Table]</ref>
| pKb = 
| Viscosity = 
  }}
|Section7={{Chembox Hazards
| ExternalSDS =
| MainHazards = corrosive
| FlashPt = 
}}
|Section8={{Chembox Related
| OtherAnions =
| OtherCations =
| OtherCompounds = [[Superbase]]s
  }}
}}

'''Lithium diisopropylamide''' (commonly abbreviated '''LDA''') is a [[chemical compound]] with the [[molecular formula]] {{chem2|LiN(CH(CH3)2)2}}. It is used as a strong [[base (chemistry)|base]] and has been widely utilized due to its good [[solubility]] in non-polar organic solvents and [[non-nucleophilic base|non-nucleophilic]] nature. It is a colorless solid, but is usually generated and observed only in solution. It was first prepared by Hamell and Levine in 1950 along with several other hindered lithium diorganylamides to effect the [[deprotonation]] of esters at the α position without attack of the carbonyl group.<ref>{{cite journal |language=en |title=Condensations Effected by the Alkali Amides. IV. The Reactions of Esters with Lithium Amide and Certain Substituted Lithium Amides1 |journal=The Journal of Organic Chemistry |volume=15 |pages=162–168 |year=1950 |last1=Hamell |first1=Matthew |last2=Levine |first2=Robert |doi=10.1021/jo01147a026}}</ref>

==Preparation and structure==
[[File:dimerliamide.jpg|thumb|left|LDA dimer with THF coordinated to Li centers]]
LDA is commonly formed by treating a cooled (0 to −78&nbsp;°C) mixture of [[tetrahydrofuran]] and [[diisopropylamine]] with [[N-Butyllithium|''n''-butyllithium]].<ref>{{OrgSynth |author=Smith, A. P. |author2=Lamba, J. J. S. |author3=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}}</ref>

When dissociated, the diisopropylamide anion can become [[protonation|protonated]] to form diisopropylamine. Diisopropylamine has a [[Acid dissociation constant|p''K''<sub>a</sub>]] value of 36. Therefore, its [[conjugate base]] is suitable for the deprotonation of compounds with greater acidity, importantly, such weakly acidic compounds (carbon acids) of the type {{chem2|HC(Z)R2}}, where Z = C(O)R', C(O)OR' or CN. Conventional protic functional groups such as alcohols and carboxylic acids are readily deprotonated.

Like most [[organolithium reagent]]s, LDA is not a salt, but is highly polar. It forms 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 (chemistry)|dimer]].<ref>{{cite journal |author1=Williard, P. G. |author2=Salvino, J. M. |journal=[[Journal of Organic Chemistry]] |year=1993 |volume=58 |issue=1 |pages=1–3 |title=Synthesis, isolation, and structure of an LDA-THF complex |doi=10.1021/jo00053a001}}</ref><ref>{{cite journal |journal=[[Journal of the American Chemical Society]] |year=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 |author1=N.D.R. Barnett |author2=R.E. Mulvey |author3=W. Clegg |author4=P.A. O'Neil |pages=8187 |doi=10.1021/ja00021a066|bibcode=1991JAChS.113.8187B }}</ref> In nonpolar solvents such as [[toluene]], it forms a temperature-dependent oligomer equilibrium. At room temperature trimers and tetramers are the most likely structures. With decreasing temperature the aggregation extends to pentameric and higher oligomeric structures.<ref>{{cite journal |author=Neufeld, R. |author2=John, M. |author3=Stalke, D. |name-list-style=amp |journal=[[Angewandte Chemie International Edition]] |year=2015 |volume=54 |issue=24 |pages=6994–6998 |title=The Donor-Base-Free Aggregation of Lithium Diisopropyl Amide in Hydrocarbons Revealed by a DOSY Method |doi=10.1002/anie.201502576 |pmid=26014367}}</ref>

Solid LDA is [[pyrophoricity|pyrophoric]],<ref>[https://www.sigmaaldrich.com/US/en/sds/ALDRICH/246611 SDS] at [[Sigma-Aldrich]]</ref> 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&nbsp;mmol), it is common and more cost effective to prepare LDA [[in situ#Chemistry and chemical engineering|''in situ'']].
[[File:LDArxn.png|thumb|left|Deprotonation using LDA.<ref>{{cite journal |title=Preparation of Ethyl 1-Benzyl-4-Fluoropiperidine-4-Carboxylate |journal=Organic Syntheses |year=2010 |volume=87 |pages=137 |author=Jianshe Kong |author2=Tao Meng |author3=Pauline Ting |author4=Jesse Wong |name-list-style=amp |doi=10.15227/orgsyn.087.0137 |doi-access=free}}</ref>]]

==Kinetic vs thermodynamic bases==
The deprotonation of carbon acids can proceed with either [[thermodynamic versus kinetic reaction control|kinetic or thermodynamic reaction control]]. Kinetic controlled deprotonation requires a base that is sterically hindered and strong enough to remove the proton irreversibly. For example, in the case of [[phenylacetone]], deprotonation can produce two different [[enolate]]s. LDA has been shown to deprotonate the methyl group, which is the kinetic course of the deprotonation. To ensure the production of the kinetic product, a slight excess (1.1 equiv) of lithium diisopropylamide is used, and the ketone is added to the base at –78&nbsp;°C. Because the ketone is quickly and quantitatively converted to the enolate and base is present in excess at all times, the ketone is unable to act as a proton shuttle to catalyze the gradual formation of the thermodynamic product. 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 [[ketone]]s 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.

==See also==
*[[Lithium amide]]
*[[Lithium bis(trimethylsilyl)amide]] (LiHMDS)
*[[Lithium tetramethylpiperidide]] (LiTMP)

==References==
{{Reflist}}

{{Lithium compounds}}

[[Category:Diisopropylamino compounds]]
[[Category:Lithium compounds]]
[[Category:Metal amides]]
[[Category:Non-nucleophilic bases]]
[[Category:Organolithium compounds]]
[[Category:Reagents for organic chemistry]]
[[Category:Superbases]]