Lithium diisopropylamide

Chemical properties

dark yellow to orange or dark red-brown solution. Lithium Diisopropylamide (LDA) [4111- 54-0], LiN(CH(CH3)2)2, Mr 107.14 is a white pyrophoric powder. Freshly prepared, it is soluble in hydrocarbons (in hexane about 10 %), but it tends to precipitate irreversibly from solution as a polymer on heating or prolonged storage. In ethers the solubility is much higher, but with the exception of tetrahydropyran, LDA is decomposed at a rate depending on the ether, concentration, and temperature.

Chemical properties

Lithium diisopropylamide (LDA) is a white pyrophoric powder. Freshly prepared, it is soluble in hydrocarbons (in hexane about 10 %), but it tends to precipitate irreversibly from solution as a polymer on heating or prolonged storage. In ethers the solubility is much higher, but with the exception of tetrahydropyran, LDA is decomposed at a rate depending on the ether, concentration, and temperature.
Lithium diisopropylamide can be conveniently prepared from butyllithium and diisopropylamine or purchased as a 2 mol/L (25 %) solution in THF and a mixture of various hydrocarbons. Although LDA is unstable in pure THF (at room temperature a 25% solution loses about 1% of its activity per day), the commercially available compositions containing only a limited amount of THF are satisfactory stable for technical applications.

The Uses of Lithium diisopropylamide

Lithium diisopropylamide is a sterically hindered nonnucleophilic strong base used for selective deprotonations, especially for the production of kinetic enolates (i.e., the thermodynamically less favored isomer) and (hetero-)aromatic carbanions. In the production of the serum lipid regulating agent Gemfibrozil one key intermediate is formed by quenching an ester enolate with 1-bromo-3-chloropropane.

The Uses of Lithium diisopropylamide

To a solution of the SM (4.0 g, 14.6 mmol) in THF (30 mL) at -78 C was added dropwise LDA (2.0M in THF/heptane/ethylbenzene, 9.6 mL, 16.9 mmol). The mixture was stirred at -78 C for 1 h. A solution of DMF (1.7 mL, 22.0 mmol) in THF (5 mL) was added slowly at - 78 C, and the reaction mixture was stirred for 3 h. The mixture was quenched with sat aq NH4Cl (50 mL) and extracted with EtOAc (2 x 30 mL). The combined organics were washed with H2O (50 mL), brine (50 mL), dried (Na2SO4), and concentrated. The resulting material was purified by silica gel column chromatography (20% EtOAc/hexane) to provide the product as a colorless oil. [1.4 g, 32%]

The Uses of Lithium diisopropylamide

pH adjuster in colognes and toilet waters. In organic synthesis, particularly, the lithium salt.

The Uses of Lithium diisopropylamide

Lithium diisopropylamide solution (LDA) can be used:

• As an initiator in the anionic polymerization of D,L-lactide and methyl methacrylate.
• To facilitate ester enolization.
• To convert carboxylic acids to enediolate intermediates for preparing trifluoromethyl ketones.
• In ortho-lithiation of arylsulfonyloxazolidinones to prepare N-substituted saccharin analogs.
• To catalyze ortholithiation and Fries rearrangement of aryl carbamates.
• As a promoter in the isomerization of allylic ethers to (Z)-propenyl ethers.

Synthesis

Lithium diisopropylamide has been synthesized by two classical routes. Th 1ost widely adopted route involves in situ formation by deprotonation of diisopropylamineby an alkyllithium reagent, such as butyllithium.Addition of a solutionof butyllithium (in hexane) to a stirred solution of diisopropylamine (freshly distilledfrom CaCl) in tetrahydrofuran directly gives the required solution of lithium diisopropylamide in tetrahydrofuran. This deprotonation process has been reported to be efficient over a wide temperature range (from -78°C to 25°C). The resulting solution of lithium diisopropylamide in tetrahydrofuran appears to be stable, and consequently canbe stored at room temperature for a short period without loss of basicity.
Lithium diisopropylamide can also be synthesized directly by addition of lithium todiisopropylamine.This approach gives better quality crystalline lithium diisopropylamide, especially if required for single-crystal X-raystructure determination, than the butyllithium route.The synthesis of lithium diiso-propylamide by in situ deprotonation of diisopropylamine in tetrahydrofuran by analkyllithium reagent is, however, the most commonly used method.Butyllithium isusually the alkyllithium of choice, but otheralkyllithiums have been used (e.g., MeLi)

General Description

This material is in a solution of THF/Hexanes (ca. 1:7 ratio, respectively)

Flammability and Explosibility

Spontaneously flammable in air (pyrophoric)

Purification Methods

It is purified by refluxing over Na wire or NaH for 30minutes and then distilled into a receiver under N2. Because of the low boiling point of the amine, a dispersion of NaH in mineral oil can be used directly in this purification without prior removal of the oil. It is HIGHLY FLAMMABLE, and is decomposed by air and moisture. [Wittig & Hesse Org Synth 50 69 1970, Beilstein 4 H 154, 4 I 369, 4 II 630, 4 III 274, 4 IV 510.]