Grignard Reactions

Abstract

AbstractThe termGrignard reactionrefers to both the preparation of a class of organomagnesium halide compounds and their subsequent reaction with a wide variety of organic and inorganic substrates.The general sequence of the reactions is now embodied in the following generic forms, where RX = an organic halide (most typically a chloride or bromide, although fluorides can be induced to react); S = a coordinating solvent (such as an ether or an amine); and AZ = a substrate with an electronegative group, Z: RX + Mg +nS → RMgX·SnRMgX·Sn+ AZ → RAZMgX·SnRAZMgX·Sn→ RA + ZMgX·Sn.The development of improved industrial procedures, including the substitution of tetrahydrofuran (THF) for diethyl ether and the demonstration that the less reactive, but significantly less expensive, vinyl and aryl chlorides could be successfully used, has greatly expanded the commercial possibilities of this reaction. In the flavor, fragrance, pharmaceutical, and fine chemical industries, its use can generally be regarded as routine.The great value of the Grignard reaction to the synthetic chemist is its general applicability as a building block for an impressive range of structures and functional groups.Preparation of Grignard ReagentsA Grignard reagent is prepared by first adding magnesium and a partial charge of solvent to the reactor, followed by the addition of RX, in the remaining solvent, to the reaction flask.In spite of its industrial use for many years, the commercial‐scale production of Grignard reagents has not been extensively described.The Grignard reaction has been commercially important for a number of years, and for certain industrial processes it remains the favored (or only) practical route to construct various element‐to‐carbon bonds.There are five components to the cost of using a Grignard reagent:(1)magnesium metal,(2)the halide,(3)the solvent,(4)the substrate, and(5)disposal of the by‐products.Reactions and applications of Grignard reagents include asymmetric syntheses using Grignard reagents, Grignard reactions with inorganic chlorides, Grignard reagents as bases, metal‐assisted modified Grignard reactions, intramolecular Grignard reactions, Grignards as methacrylate polymerization catalysts, and Grignard reagents as supports for the Ziegler‐Natta process.