17.5 Alcohols from Reaction of Carbonyl Compounds: Grignard Reagents

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Objectives

After completing this lesson, you should be able to

write an equation to illustrate the formation of a Grignard reagent.
write a general equation to represent the reaction of an aldehyde or ketone with a Grignard reagent.
write the detailed mechanism for the reaction of an aldehyde or ketone with a Grignard reagent.
identify the product formed from the reaction of a given aldehyde or ketone with a given Grignard reagent.
identify the carbonyl compound, the Grignard reagent, or both, needed to prepare a given alcohol.
write the equation to describe the reaction of an ester with a Grignard reagent.
identify the product formed from the reaction of a given ester with a given Grignard reagent.
discuss the limitations of Grignard reagent formation, and determine whether a given compound can be used to form such a reagent.

Study Notes

Before you begin this section, you may wish to review Section 10.6 of the textbook (pages 355-356), in which McMurry discusses the formation of Grignard reagents. Grignard reagents are among the most frequently used reagents in organic synthesis. They react with a wide variety of substrates; however, in this lesson, we are concerned only with those reactions that produce alcohols. Notice that in a reaction involving a Grignard reagent, not only does the functional group get changed, but the number of carbon atoms present also changes. This fact provides us with a useful method for ascending a homologous series. For example:

One important route for producing an alcohol from a Grignard reagent has been omitted from the discussion in the textbook. It involves the reaction of the Grignard reagent with ethylene oxide to produce a primary alcohol containing two more carbon atoms than the original Grignard reagent.

A summary of the methods used to prepare alcohols from Grignard reagents is provided in Figure 17.1, below.

Figure 17.1

Because organometallic reagents react as their corresponding carbanion, they are excellent nucleophiles. The basic reaction involves the nucleophilic attack of the carbanionic carbon in the organometallic reagent with the electrophilic carbon in the carbonyl to form alcohols.

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Both Grignard and Organolithium Reagents will perform these reactions

Addition to formaldehyde gives 1o alcohols

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Addition to aldehydes gives 2^o alcohols

Addition to ketones gives 3o alcohols

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Examples
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Mechanism for the Addition to Carbonyls

The mechanism for a Grignard agent is shown. The mechanism for an organometallic reagent is the same.

1) Nucleophilic attack

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2) Protonation

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Grignard reagents convert esters to 3^o alcohols

In effect, the Grignard reagent adds twice.

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Example 1:

Limitation of Organometallic Reagents

As discussed above, Grignard and organolithium reagents are powerful bases. Because of this they cannot be used as nucleophiles on compounds which contain acidic hydrogens. If they are used they will act as a base and deprotonate the acidic hydrogen rather than act as a nucleophile and attack the carbonyl. A partial list of functional groups which cannot be used are: alcohols, amides, 1^o amines, 2^o amines, carboxylic acids, and terminal alkynes.

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Contributors

Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)

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Mechanism for the Addition to Carbonyls

Grignard reagents convert esters to 3o alcohols

Limitation of Organometallic Reagents

Contributors

Grignard reagents convert esters to 3^o alcohols