19-02-2013, 12:55 PM
Grignard reaction
INTRODUCTION
The Grignard reaction (pronounced /ɡriɲar/) is an organometallic chemical reaction in which alkyl- or aryl-magnesium halides (Grignard reagents) add to a carbonyl group in an aldehyde or ketone.[1] This reaction is an important tool for the formation of carbon–carbon bonds.[2][3] The reaction of an organic halide with magnesium is not a Grignard reaction, but provides a Grignard reagent.[4]
Grignard reactions and reagents were discovered by and are named after the French chemist François Auguste Victor Grignard (University of Nancy, France), who was awarded the 1912 Nobel Prize in Chemistry for this work.[5] Grignard reagents are similar to organolithium reagents because both are strong nucleophiles that can form new carbon-carbon bonds.
Reaction mechanism
The Grignard reagent functions as nucleophiles attacking electrophilic carbon atoms that are present within the polar bond of the carbonyl group. The addition of the Grignard reagent to the carbonyl typically proceeds through a six-membered ring transition state
Preparation of Grignard reagent
Grignard reagents form via the reaction of an alkyl or aryl halide with magnesium metal. The reaction is conducted by adding the organic halide to a suspension of magnesium in an etherialsolvent, which provides ligands required to stabilize the organomagnesium compound. Empirical evidence suggests that the reaction takes place on the surface of the metal. The reaction proceeds through single electron transfer:[7][8][9] In the Grignard formation reaction, radicals may be converted into carbanions through a second electron transfer.[10][11]
Reaction conditions
In reactions involving Grignard reagents, it is important to exclude water and air, which rapidly destroy the reagent by protonolysis or oxidation. Since most Grignard reactions are conducted in anhydrous diethyl ether or tetrahydrofuran, side-reactions with air are limited by the protective blanket provided by solvent vapors. Small-scale or quantitative preparations should be conducted under nitrogen or argon atmospheres, using air-free techniques. Although the reagents still need to be dry, ultrasound can allow Grignard reagents to form in wet solvents by activating the magnesium such that it consumes the water.[13]
The organic halide
Grignard reactions often start slowly. As is common for reactions involving solids and solution, initiation follows an induction period during which reactive magnesium becomes exposed to the organic reagents. After this induction period, the reactions can be highly exothermic. Alkyl and aryl bromides and iodides are common substrates. Chlorides are also used, but fluorides are generally unreactive, except with specially activated magnesium.
INTRODUCTION
The Grignard reaction (pronounced /ɡriɲar/) is an organometallic chemical reaction in which alkyl- or aryl-magnesium halides (Grignard reagents) add to a carbonyl group in an aldehyde or ketone.[1] This reaction is an important tool for the formation of carbon–carbon bonds.[2][3] The reaction of an organic halide with magnesium is not a Grignard reaction, but provides a Grignard reagent.[4]
Grignard reactions and reagents were discovered by and are named after the French chemist François Auguste Victor Grignard (University of Nancy, France), who was awarded the 1912 Nobel Prize in Chemistry for this work.[5] Grignard reagents are similar to organolithium reagents because both are strong nucleophiles that can form new carbon-carbon bonds.
Reaction mechanism
The Grignard reagent functions as nucleophiles attacking electrophilic carbon atoms that are present within the polar bond of the carbonyl group. The addition of the Grignard reagent to the carbonyl typically proceeds through a six-membered ring transition state
Preparation of Grignard reagent
Grignard reagents form via the reaction of an alkyl or aryl halide with magnesium metal. The reaction is conducted by adding the organic halide to a suspension of magnesium in an etherialsolvent, which provides ligands required to stabilize the organomagnesium compound. Empirical evidence suggests that the reaction takes place on the surface of the metal. The reaction proceeds through single electron transfer:[7][8][9] In the Grignard formation reaction, radicals may be converted into carbanions through a second electron transfer.[10][11]
Reaction conditions
In reactions involving Grignard reagents, it is important to exclude water and air, which rapidly destroy the reagent by protonolysis or oxidation. Since most Grignard reactions are conducted in anhydrous diethyl ether or tetrahydrofuran, side-reactions with air are limited by the protective blanket provided by solvent vapors. Small-scale or quantitative preparations should be conducted under nitrogen or argon atmospheres, using air-free techniques. Although the reagents still need to be dry, ultrasound can allow Grignard reagents to form in wet solvents by activating the magnesium such that it consumes the water.[13]
The organic halide
Grignard reactions often start slowly. As is common for reactions involving solids and solution, initiation follows an induction period during which reactive magnesium becomes exposed to the organic reagents. After this induction period, the reactions can be highly exothermic. Alkyl and aryl bromides and iodides are common substrates. Chlorides are also used, but fluorides are generally unreactive, except with specially activated magnesium.