Grignard reaction

In the Grignard reaction [ ɡriɲa ː r ] is a name reaction in organic chemistry, which was named after its discoverer, Victor Grignard, who was awarded for this discovery in 1912 with the Nobel Prize., The Grignard reaction is a metal organic chemical reaction such as, for example, to react carbonyl groups with the alkyl or aryl magnesium halides (see Grignard reagent ) as the nucleophile to electrophilic groups. It is used for the synthesis of carbon-carbon single bonds.

, The Grignard reaction is a very important reaction for the knotting of carbon-carbon, carbon-phosphorus, tin - carbon, carbon-silicon or carbon -boron bonds. The organomagnesium Grignard compound is not an ionic compound. Instead, depending on the solvent different structures before, which are in equilibrium with each other, see Schlenk equilibrium.

Since Grignard reagents are sensitive to protic solvents, the Grignard reaction must be free of water, are usually carried out in dried ethers such as diethyl ether or tetrahydrofuran.

Overview reaction

In the Grignard reaction, a Grignard compound reacts ( metal organic compound, in this example with bromine as a halogen ) as a nucleophile with an electrophilic compound - in this case, for example, the carbonyl group in an aldehyde or ketone - to an alcohol:

Mechanism

Mechanistically, it is in the Grignard reaction is a nucleophilic addition in which the negatively polarized carbon atom ( carbanion ) the Grignard compound is added to the carbon atom of a carbonyl group. Thus, a new carbon -carbon bond is formed. It is believed that the transition state of the reaction, two molecules of the Grignard compound are involved, resulting in a six-membered transition state. The oxygen atom of the carbonyl compound accepts the metal to form a metal alkoxide. In the next step of this oxygen atom is protonated by dilute aqueous acid first and then hydrolyzed. Deprotonation created an alcohol.

Reactions

In the following the general formula RMgX is frequently used in the Grignard reagent, wherein the X is one of the halogens, bromine, chlorine or iodine. The Grignard reaction provides, depending on the carbonyl compound used in primary, secondary or tertiary alcohols.

Ester yield with the addition of two equivalents of Grignard compounds tertiary alcohols, a ketone initially created by a single addition as intermediate. However, this can not be isolated because it rapidly reacts with the Grignard compound as the starting ester.

Next to aldehydes, ketones and esters, carbon dioxide, nitriles, imines, epoxides, thioesters, etc. can be reacted with Grignard reagents:

However, the most significant application is the reaction of a Grignard compound with aldehydes, ketones or esters to produce alcohols.

A Grignard reaction may be carried out with a number of other carbon electrophiles.

, The Grignard reaction may be used for the production of various other elements carbon bonds. Particularly important here are the boron compounds which are for the Suzuki coupling in use.

Previously, the Grignard reaction had a great industrial importance in the production of the fuel additive tetraethyl lead, which is but due to the ban today meaningless.

Aryl- alkyl coupling reactions

By means of the Grignard reaction can be in the presence of iron to perform (III ) acetylacetonate aryl - alkyl cross-coupling. ,

Also nickel chloride ( Kumada coupling ) or dilithium tetrachlorocuprate are ( prepared in situ from lithium chloride and copper ( II) chloride in tetrahydrofuran) are good catalysts for such coupling reactions.

Stereoselective Grignard reaction

Since many of ketones and aldehydes are prochiral all (except formaldehyde) compounds result in a Grignard reaction frequently pairs of enantiomers or in an already existing stereogenic center diastereomers. To extend the Grignard reaction stereoselectively, Dieter Seebach has the chiral reagent TADDOL, a tartaric acid derivative developed. Utilizing the Schlenk equilibrium enantiomeric excesses of 84-96 % have been achieved in the reaction with aldehydes.

Competing reactions

In sterically complex Grignard compounds or hindered carbonyl addition reactions can occur. The most important are the reduction of the carbonyl compound, referred to as Grignard reduction, and existing α - hydrogen atom, the enolization of the carbonyl compound.

Practical Implementation

In the laboratory the required Grignard reagents are usually formed in situ in an ether as a solvent and reacted directly with the carbonyl compound. Then the reaction mixture is worked up in a slightly or highly acidic aqueous solution, and the reaction product isolated therefrom.

Use

An application of the Grignard reaction for the quantitative determination of CH-acidic compound is the Zerewitinoff reaction.