Lithium diisopropylamide
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| Lithium diisopropylamide | |
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| General | |
| Systematic name | Lithium diisopropylamide |
| Other names | LDA |
| Molecular formula | C6H14LiN or LiN(C3H7)2 |
| SMILES | ? |
| Molar mass | 107.1233 g/mol |
| Appearance | ? |
| CAS number | [4111-54-0] |
| Properties | |
| Density and phase | 0.79 g/cm³, ? |
| Solubility in water | Reacts with water |
| Melting point | ?°C (? K) |
| Boiling point | ?°C (? K) |
| Acidity (pKa) | 34 |
| Basicity (pKb) | ? |
| Chiral rotation [α]D | ?° |
| Viscosity | ? cP at ?°C |
| Hazards | |
| MSDS | External MSDS |
| Main hazards | corrosive |
| NFPA 704 | |
| Flash point | ?°C |
| R/S statement | R: ? S: ? |
| RTECS number | ? |
| Related compounds | |
| Other anions | ? |
| Other cations | ? |
| Related ? | ? |
| Related compounds | Superacids |
| Except where noted otherwise, data are given for materials in their standard state (at 25°C, 100 kPa) Infobox disclaimer and references |
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Lithium diisopropylamide (LDA) with the formula [(CH3)2CH]2NLi, is a strong base, widely used in organic chemistry for the generation of carbanions. It is a convenient reagent for use in organic chemistry because it is soluble in organic solvents and also non-pyrophoric. LDA is less-nucleophilic and part of a class of harpoon bases. It is important to note that LDA can still act as a nucleophile, for instance it can react with tungsten hexacarbonyl as part of the synthesis of a diisopropylaminocarbyne synthesis. Other even more hindered amide bases are known, for instance the deprotonation of hexamethyldisilazane (Me3SiNHSiMe3) forms such a base ([(Me3SiNSiMe3]-).
It is formed by treating a cooled (-78 °C) THF solution of dried and distilled diisopropylamine (CAS 108-18-9) with 100 mol-% n-butyllithium (typically a hexane solution) and allowing the reaction temperature then reach either 0 °C or room temperature [1]. The LDA solution is a commercially available product. The conjugate acid 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 .
It has also been shown to be formed in combination with n-butyllithium at approximately 0°C, and several synthetic publications have demonstrated that dry ice/acetone temperatures (-78 °C) are not necessary in order to form LDA for a reaction. In practice andfor small scale use (less than 50 mmol), it is safer to prepare LDA in the lab than it is to buy an already prepared solution.
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[edit] Kinetic vs thermodynamic bases
The type of base can determine if a reaction takes place with kinetic or thermodynamic reaction control. It is the case that a hindered soluble base such as LDA will deprotonate a compound at an acidic site which is more readily accessed. For instance if phenylacetone is considered, then it is possible to form two different enolates. If the substrate is added to a cold (-78°C) solution of LDA in a solvent such as THF, ether or DME then a kinetic enolate will thus be formed. This would be the enolate where the terminal methyl is the deprotonation site.
If however a weaker base (such as an alkoxide) is used, which reversibly deprotonates the substrate then the more thermodynamically stable enolate will form. For this enolate the deprotonation site is the benzylic site. An alternative to the weaker base is to use a strong base which is present at a lower concentration than the ketone. For instance a slurry of sodium hydride in THF or DMF has almost no sodium hydride in solution, the base only reacts at its surface. It is the case that a ketone molecule might deprotonate at the kinetic site, this enolate will then encounter other ketone molecules. Through swapping of the protons around (even in a non-protic solvent {one that does not autoionize to form solvated protons and anions under normal conditions}) then the thermodynamic enolate will form.
For further reading see http://www-oc.chemie.uni-regensburg.de/OCP/ch/chb/oc5/Enolate_Chemistry.pdf
[edit] Oligomers
LDA is an organolithium compound which is has a rigorously characterized structure. It can form a polymer in the solid (N.D.R. Barnett, R.E. Mulvey, W. Clegg and P.A. O'Neil, Journal of the American Chemical Society, 1991, 113, 8187.) while in THF it is predominantly dimeric, although it often dissociates to engage in reactivity.
Other oligomers are known, for instance the lithium salt of 2,2,6,6-tetramethylpiperidine has been crystalised as a tetramer.
While the lithium salt of di-(1-phenylethyl)amine crystalises as a trimer.
It is also possible to make mixed oligomers of metal alkoxides and amides (K.W. Henderson, D.S. Walther and P.G. Williard, Journal of the American Chemical Society, 1995, 117, 8680), these are related to the super bases which are mixtures of metal alkoxides and alkyls. The cyclic oligomers form when the nitrogen of the amide forms a sigma bond to a lithium while the nitrogen lone pair binds to another metal centre.
Other organolithium compounds (such as BuLi) are generally considered to exist in and function via high-order, aggregated species.
