Protecting n-Butyllithium from Air and Moisture

Alkyllithium compounds such as n-butyllithium are versatile organometallic reagents that give chemists access to a diverse range of transformations. However, these compounds are corrosive and pyrophoric, igniting spontaneously in air.

Meticulous protection from the atmosphere during preparation, handling, and storage is essential for their safe and successful use in synthesis. Here is a look at an industry-leading packaging design that is helping chemists get the most from these important reagents.

N-Butyllithium in Organic Synthesis

Alkyllithium compounds are strongly basic and nucleophilic reagents due to the highly polar nature of their carbon–lithium bond. A commonly used alkyllithium reagent is n-butyllithium, a strong base with a pK_a of approximately 50.

Like other alkyllithium reagents, n-butyllithium is valued for its ability to generate other functionalized organolithium compounds by metalation. Metalation reactions rely on the ability of the alkyllithium reagents to deprotonate weakly acidic protons present in aldehydes, ketones, sulfones, nitriles, and other compounds.

The carbanions generated by deprotonation are valuable intermediates for a wide range of chiral transformations and other organic reactions. Stabilized organolithium compounds generated by metalation can also react as nucleophiles in a wide range of transformations: reactions with alkyl and allyl-halogenides, addition to carbonyl compounds, conjugate addition, and epoxide ring opening.

Organolithium reagents are also used to prepare other metalorganic compounds by transmetalation, a highly useful technique for producing organocopper and organotitanium compounds, which may have a higher selectivity than organolithium compounds.

Industrially, n-butyllithium is widely used as an initiator for anionic polymerization reactions for molecules like butadiene, isoprene, and styrene. These processes are essential for manufacturing a diverse range of goods, such as rubber tires and various plastics and packaging materials.

Safe Handling Methods

N-butyllithium is a pyrophoric reagent and must be handled under rigorously dry conditions to prevent it from igniting upon exposure to air. Typically, solutions of n-butyllithium are transferred from their original container to flame-dried reaction vessels under an inert atmosphere (nitrogen or argon) via syringe or cannula technique.

To prevent the n-butyllithium solution still inside the original bottle from also being exposed to the atmosphere, the volume of reagent removed is replaced with nitrogen or argon gas. Anhydrous solvents may also be used with reactions of alkyllithium compounds to minimize degradation of the reagent due to water present in the solvent.

When n-butyllithium is exposed to air or moisture during preparation or storage, its concentration can be diminished, leading to an inaccurate amount being used in a reaction. The use of partially degraded n-butyllithium solutions can cause poor yield, create a greater number of byproducts, require more complicated and time-consuming purification, and potentially produce a failed synthesis.

The packaging of n-butyllithium should be robust enough to protect the material during transport while also allowing the reagent to stay as dry as possible during repeat uses. Common laboratory attempts to maintain the quality of air- and moisture-sensitive reagents include:

Adding rubber bungs to opened reagent bottles
Sealing lids and caps with paraffin film wrap
Storing bottles in bags that contain desiccant
A combination of these and other tactics

These methods have serious limitations and are not adequate for the safe, long-term storage of organolithium reagents.

Packaging Improvements

Modern advances in packaging design help today’s chemists benefit from high-quality n-butyllithium that maintains its original reactivity. Acros Organics Anhydrous Alkyllithium Reagents are packaged in sturdy borosilicate bottles with special AcroSeal caps that offer increased protection against air and moisture.

Acros Organics Alkyllithium Reagents are packaged when the chemical is as dry as possible to deliver optimal reactivity, and the innovative AcroSeal system helps the reagent stay dry. And it can be handled safely during repeated use without compromising ease.

AcroSeal packaging provides a safe and effective way of handling n-butyllithium and other air- and moisture-sensitive organolithium reagents. It allows removal of the reagent from the bottle under an inert atmosphere. Caps are fitted with a wider septum (Figure 2) that is conveniently large and can be punctured up to 20 to 30 times and in multiple locations, letting you avoid entering the same hole twice (a common source of atmospheric exposure). The wide septum also makes it easier to keep the reagent dry when transferring it to dry labware. The multi-layered septum is lined with a polymeric elastomer with an inert fluoropolymer-coated surface, which improves resistance to damage from the reagents in the bottle.

Acros Organics Organolithium Reagents come in a range of sizes, helping to minimize waste and ineffective reagents by providing the precise amount that you need. In the end, there are no unused reagents sitting on the shelf — a common sight in many laboratories.

High-Quality Organolithium Reagents for High-Quality Syntheses

Unlocking the full potential of alkyllithium compounds requires the use of high-quality anhydrous reagents and solvents that haven’t been impaired by exposure to air or moisture. To allow all chemicals that are added to reaction vessels to be as dry as possible, the Acros Organics brand uses AcroSeal packaging to protect a comprehensive range of reagents and solvents. AcroSeal packaging facilitates the safe transfer of those reagents into the reaction vessel while allowing chemists to get the most from their reactions.

The Acros Organics brand offers many popular butyllithium products in AcroSeal packaging. Visit fishersci.com/organometallics to view our complete offering of alkyllithium products.

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Acros Organics Acroseal on n-butyllithium

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