10.6 Reactions of Alkyl Halides: Grignard Reagents

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Objectives

After completing this section, you should be able to

write an equation to describe the formation of a Grignard reagent.
give examples of Grignard reagents formed from aryl and vinyl halides as well as from alkyl halides.
explain the reactivity of Grignard reagents in terms of the polarity of the carbon-magnesium bond.
write an equation for the reaction of a Grignard reagent with a proton donor, such as water.
predict the product formed from the reaction of a given organohalide with magnesium followed by a proton donor.
identify the organohalide, the reagents, or both, needed to prepare a given alkane.
describe how a deuterium atom may be introduced at a specific location in an organic molecule through use of a Grignard reagent.
describe at least one limitation on the use of Grignard reagents in organic synthesis.
write an equation for the direct conversion of an alkyl halide to an alkane using a hydride donor, such as lithium aluminum hydride.

Key Terms

Make certain that you can define, and use in context, each of the key terms listed below.

carbanion
Grignard reagent (see the “Study Notes,” below)

Study Notes

The organomagnesium compounds formed by the reaction of an alkyl or aryl halide with magnesium are called Grignard reagents. As you will see throughout the remainder of this course, Grignard reagents can be used to synthesize a wide range of organic compounds and are extremely useful to the organic chemist. In the introductory section to this unit (Section 10.0), we tried to stress that the chemistry of alkyl halides is quite different from that of aryl (or vinyl) halides. However, both alkyl and aryl halides react with magnesium to form Grignard reagents. The reaction of a Grignard reagent with D₂O (“heavy water”) provides a convenient method for introducing a deuterium atom (remember D is equivalent to ^₂₁H) into a molecule at a specific location. For example:

Content

The alkali metals (Li, Na, K etc.) and the alkaline earth metals (Mg and Ca, together with Zn) are good reducing agents, the former being stronger than the latter. These same metals reduce the carbon-halogen bonds of alkyl halides. The halogen is converted to a halide anion, and the carbon bonds to the metal which has characteristics similar to a carbanion (R:-).

Formation of Organometallic Reagents

Many organometallic reagents are commercially available, however, it is often necessary to make then. The following equations illustrate these reactions for the commonly used metals lithium and magnesium (R may be hydrogen or alkyl groups in any combination).

An Alkyl Lithium Reagent

R 3 C - X + 2 Li \to R 3 C - Li + LiX

A Grignard Regent

R3C−X+Mg→R3C−MgX

Halide reactivity in these reactions increases in the order: Cl < Br < I and Fluorides are usually not used. The alkyl magnesium halides described in the second reaction are called Grignard Reagents after the French chemist, Victor Grignard, who discovered them and received the Nobel prize in 1912 for this work. The other metals mentioned above react in a similar manner, but Grignard and Alky Lithium Reagents most widely used. Although the formulas drawn here for the alkyl lithium and Grignard reagents reflect the stoichiometry of the reactions and are widely used in the chemical literature, they do not accurately depict the structural nature of these remarkable substances. Mixtures of polymeric and other associated and complexed species are in equilibrium under the conditions normally used for their preparation.

A suitable solvent must be used. For alkyl lithium formation pentane or hexane are usually used. Diethyl ether can also be used but the subsequent alkyl lithium reagent must be used immediately after preparation due to an interaction with the solvent. Ethyl ether or THF are essential for Grignard reagent formation. Lone pair electrons from two ether molecules form a complex with the magnesium in the Grignard reagent (As pictured below). This complex helps stabilize the organometallic and increases its ability to react.

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These reactions are obviously substitution reactions, but they cannot be classified as nucleophilic substitutions, as were the earlier reactions of alkyl halides. Because the functional carbon atom has been reduced, the polarity of the resulting functional group is inverted (an originally electrophilic carbon becomes nucleophilic). This change, shown below, makes alkyl lithium and Grignard reagents excellent nucleophiles and useful reactants in synthesis.

Examples
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Examples

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Common Organometallic Reagents

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Organometallic Reagents as Bases

These reagents are very strong bases (pKa's of saturated hydrocarbons range from 42 to 50). Although not usually done with Grignard reagents, organolithium reagents can be used as strong bases. Both Grignard reagents and organolithium reagents react with water to form the corresponding hydrocarbon. This is why so much care is needed to insure dry glassware and solvents when working with organometallic reagents.

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In fact, the reactivity of Grignard reagents and organolithium reagents can be exploited to create a new method for the conversion of halogens to the corresponding hydrocarbon (illustrated below). The halogen is converted to an organometallic reagent and then subsequently reacted with water to from an alkane.

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Conjugate base anions of terminal alkynes (acetylide anions) are nucleophiles, and can do both nucleophilic substitution and nucleophilic addition reactions.

Exercises

Do problems 10.9 and 10.10 on page 357 of Organic Chemistry, 8th ed.

Contributors

Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry