Methylmagnesium Bromide1

MeMgX
(X = Br)

[75-16-1]  · CH3BrMg  · Methylmagnesium Bromide  · (MW 119.25) (X = Cl)

[676-58-4]  · CH3ClMg  · Methylmagnesium Chloride  · (MW 74.80) (X = I)

[917-64-6]  · CH3IMg  · Methylmagnesium Iodide  · (MW 166.25)

(adds to many unsaturated functional groups; methyl can displace halide and like groups; can function as a strong base and a Lewis acid)1b-f

Physical Data: NMR, IR, kinetic, and calorimetric observations indicate that MeMgBr in Et2O and THF, and MeMgCl in Et2O, actually are mixtures of MeMgX, Me2Mg, and MgX2.2 MeMgBr is essentially monomeric in THF, but it and MeMgI are associated significantly in Et2O except at low concentrations.3 Solids isolated include MeMgBr(THF)3,4 shown by X-ray diffraction to have five-coordinate Mg, and (low-melting) MeMgX(Et2O)2 (X = Br or I).5 Complete removal of Et2O leaves a mixture of Me2Mg and MgX2 (X = Cl or Br).6

Solubility: MeMgBr and MeMgI sol Et2O; MeMgCl and MeMgBr sol THF. MgI2 precipitates when MeMgI is prepared in THF, leaving mainly Me2Mg in solution; some MgCl2 generally precipitates when MeMgCl is prepared in Et2O, particularly if the solution stands for several days. All are insoluble in hydrocarbons.

Form Supplied in: solutions of MeMgCl in THF, MeMgBr and MeMgI in Et2O and Bu2O, and MeMgBr in toluene/THF are commercially available.

Analysis of Reagent Purity: a small excess is used ordinarily to ensure that sufficient reagent is present, but concentration should be determined when exact stoichiometry is important.7 R-Mg is conveniently determined by hydrolysis of an aliquot followed by addition of excess acid and back-titration with base.8 Since this procedure does not distinguish R-Mg from HO-Mg and RO-Mg formed from reaction of the Grignard reagent with water and oxygen, respectively, a direct titration9 more specific for R-Mg or a double titration procedure10 should be used when such exposure is suspected. A qualitative color test is convenient for detecting the presence of Grignard reagent.11

Preparative Methods: 1c,e,12,13 in spite of their commercial availability, solutions of MeMgCl,14,15 MeMgBr,14,16 and MeMgI17 are often prepared from reaction of a methyl halide and Mg, usually in Et2O or THF.

Handling, Storage, and Precautions: Grignard reagents react readily with oxygen, water, and carbon dioxide. Reactants and apparatus used in their preparations and reactions should be dry throughout preparation, storage, and use; Grignard reagent solutions should be maintained under nitrogen or argon, though the vapor of a volatile solvent (especially Et2O) provides some protection for short periods of time. Methyl Grignard reagents do not significantly attack Et2O or THF at normal reaction temperatures.

Structure.1a,c

The structure of a Grignard reagent, an important influence on reactions, is more elaborate than implied by the formula RMgX. In solution, a Grignard reagent is a mixture (Schlenk equilibrium) of RMgX, R2Mg, and MgX2, the composition varying with solvent and X. Mg is most commonly four-coordinate in solids but may have even higher coordination;18 all evidence indicates similar coordination in solutions. The additional bonds to Mg result from some combination of association by bridging of the X atom (or R group) between two Mg atoms and coordination by donor molecules (usually solvent). Coordination by donor groups of substrates can play an important role in reactions.

Workup Procedures.13

Workup of a Grignard reaction requires adding a proton source and removing magnesium salts. This is done conveniently by adding an aqueous HCl or H2SO4 solution and separating the organic and aqueous layers. When products cannot tolerate acids, however, a saturated aqueous ammonium chloride solution is generally used, either a large volume19 sufficient to dissolve all magnesium salts or, alternatively, just enough15 to completely precipitate the magnesium salts, leaving a nearly anhydrous solution of the product.

Representative Applications.1b-f

A Grignard reagent is used in an extraordinary variety of reactions, the majority leading to attachment of its organic group to an electrophilic carbon atom of the substrate. Most common are additions to carbonyl groups (eq 1),20 nitriles, and imines (eq 2),21 and displacements of halide and like leaving groups. Although generally less reactive than organolithium compounds, Grignard reagents are often used for convenience, because of a different reactivity pattern, or to minimize competing reactions. MeMgX and MeLi, for example, sometimes exhibit quite different regioselectivities (eq 1) and stereoselectivities (eq 2). The key step in the synthesis of chiral O=CHCH(Me)NH2 (eq 2) also illustrates the common practice in Grignard reagent additions of using a disposable group whose coordination or steric effects impart stereoselectivity.

Grignard reagents are strong bases and Lewis acids, a problem in many reactions but of use in others. MeMgX, for example, extracts a proton from most N-H and O-H bonds and from particularly acidic C-H bonds. Volumetric measurement of the methane evolved from reaction with a compound of MeMgI was once a significant procedure (Zerewitinoff determination) for quantitative determination of its active hydrogens.22 MeMgX still is used as a base, for example in forming magnesium amides (eq 3)23 and enolates. Cleavage of aryl-alkyl ethers (eq 4)24 is a displacement that must require the Lewis acid properties of the Grignard reagent. Me2Mg is sometimes used in place of MeMgX to minimize reactions, such as isomerization of oxiranes to aldehydes or ketones,25 that involve Lewis acidity but not displacement.

Strongly coordinating solvents tend to reduce reactivity in additions to unsaturated functions but to increase reactivity in reactions with alkyl halides and as bases. The greater rate and stereoselectivity of an addition (eq 2) in toluene than in Et2O illustrate the importance of solvent.

Transition metal impurities, often introduced in the Mg used to prepare a Grignard reagent, can lead to unwanted products,26 and where this is a problem particularly pure Mg should be used. Catalytic or stoichiometric amounts of transition metal compounds, of course, often are added deliberately to Grignard reagents.27 Examples are copper compounds28 to promote 1,4-additions to a,b-unsaturated carbonyl compounds (one variant of organocuprate chemistry) and nickel compounds29 to promote substitution of aryl and vinyl halides.

Related Reagents.

Methylcopper; Methylcopper-Boron Trifluoride Etherate; Methylcopper-Tributylphosphine; Methyllithium; Methyltitanium Trichloride.


1. (a) Lindsell, W. E. In Comprehensive Organometallic Chemistry; Wilkinson G.; Stone, F. G. A.; Abel, E. W., Eds.; Pergamon: Oxford, 1982; Chapter 4. (b) Wakefield, B. J. In Comprehensive Organometallic Chemistry; Wilkinson G.; Stone, F. G. A.; Abel, E. W., Eds.; Pergamon: Oxford, 1982; Chapter 44. (c) Nützel, K. MOC 1973, 13/2a, 47. (d) Raston, C. L.; Salem, G. In The Chemistry of the Metal-Carbon Bond; Hartley, F. R.; Ed.; Wiley: Chichester, 1987; Vol. 4, Chapter 2. (e) Old but still extremely useful is Kharasch, M.; Reinmuth, O. Grignard Reactions of Nonmetallic Substances; Prentice-Hall: New York, 1954. (f) Ioffe, S. T.; Nesmeyanov, A. N. The Organic Compounds of Magnesium, Beryllium, Calcium, Strontium and Barium; North-Holland: Amsterdam, 1967.
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6. Weiss, E. CB 1965, 98, 2805.
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19. Skattebøl, L.; Jones, E. R. H.; Whiting, M. C. OSC 1963, 4, 792.
20. Liotta, D.; Saindane, M.; Barnum, C. JOC 1981, 46, 3369.
21. Alexakis, A.; Lensen, N.; Tranchier, J.-P.; Mangeney, P. JOC 1992, 57, 4563. Alexakis, A.; Lensen, N.; Mangeney, P. TL 1991, 32, 1171.
22. Siggia, S.; Hanna, J. G. Quantitative Organic Analysis via Functional Groups, 4th ed.; Wiley: New York, 1979; Chapter 8.
23. Kametani, T.; Huang, S.-P.; Yokohama, S.; Suzuki, Y.; Ihara, M. JACS 1980, 102, 2060.
24. Mechoulam, R.; Gaoni, Y. JACS 1965, 87, 3273.
25. Christensen, B. G.; Strachan, R. G.; Trenner, N. R.; Arison, B. H.; Hirschmann, R.; Chemerda, J. M. JACS 1960, 82, 3995.
26. Ashby, E. C.; Neumann, H. M.; Walker, F. W.; Laemmle, J.; Chao, L.-C. JACS 1973, 95, 3330; Ashby, E. C.; Wiesemann, T. L. JACS 1978, 100, 189.
27. Felkin, H.; Swierczewski, G. T 1975, 31, 2735.
28. Erdik., E. T 1984, 40, 641; Rossiter, B. E.; Swingle, N. M. CRV 1992, 92, 771.
29. Tamao, K. COS 1991, 3, 435; Jolly, P. W. In Comprehensive Organometallic Chemistry; Wilkinson G.; Stone, F. G. A.; Abel, E. W., Eds.; Pergamon: Oxford, 1982; Chapter 56.5.

Herman G. Richey, Jr.

The Pennsylvania State University, University Park, PA, USA



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