Organolithium Reagent - Production

Production

Organolithium reagents are industrially prepared by the reaction of an halocarbon with lithium metal, i.e. R–X + 2 Li → R–Li + LiX. A side reaction of this synthesis, especially with alkyl iodides, is the Wurtz reaction, in which an R–Li species reacts with an R–X species forming an R-R coupled product. This side reaction can be almost completely avoided by using alkyl chlorides or bromides.

A second method is the reaction of an alkyl halide or aryl alkyl sulfide with a radical anion lithium salt, such as lithium naphthalide. These radical anions can be prepared by the reduction of an aromatic system such as naphthalene with metallic lithium. As the organic reduction of alkyl halides is much faster with radical anions than it is with direct reaction with lithium metal, this reaction enables a number of more exotic organolithium compounds to be prepared.

A third method involves the metal-halogen exchange between an organic halide compound (usually an iodide or bromide) and an organolithium species (usually n-BuLi, s-BuLi or t-BuLi). As this is an equilibrium reaction, the reaction is successful only if the formed lithium reagent has a more stable carbanion than the starting lithium reagent. This method is often used to prepare vinyl- aryl- and primary alkyllithium reagents, and is especially valuable for the preparation of functionalized lithium reagents where the harsher conditions required for reaction with lithium metal may be precluded.

A fourth method is another exchange, this time between an organolithium compound and another organometallic compound. This is again an equilibrium reaction, where the most electropositive metal (lithium) will end up attached to the most electronegative organic group. An example is the synthesis of vinyllithium out of tetravinyltin and phenyllithium. Vinyllithium is very difficult to prepare with other methods.

A fifth method is the deprotonation of organic compound with an organolithium species, an acid-base reaction.