How is Grignard reagent formed?
A Grignard reagent or Grignard compound has the general formula R-Mg-X, where X is a halogen and R is an organic group, usually an alkyl or aryl. Methylmagnesium chloride (Cl-Mg-CH3)and phenylmagnesium bromide ((C6H5)-Mg-Br) are two common examples. They are an organomagnesium compound subclass.
Grignard compounds are commonly used to form new carbon-carbon bonds in chemical synthesis. When combined with another halogenated chemical R’X’ in the presence of a sufficient catalyst, they often generate RR’ and the magnesium halide MgXX’ as a byproduct, which is insoluble in most solvents. They are comparable to organolithium reagents in this regard.
Grignard reagents in their purest form are highly reactive solids. They’re usually handled as solutions in solvents like diethyl ether or tetrahydrofuran, which are relatively stable when water isn’t present.A Grignard reagent is always present as a complex in such a media, with the magnesium atom coupled to the two ether oxygens via coordination bonds.
The Nobel Prize for Chemistry was granted in 1912 for the discovery of the Grignard reaction in 1900. Victor Grignard has more information about the history.
Grignard reagents are made by combining an organic halide (usually organobromine) and magnesium metal. To stabilise the organomagnesium complex, cyclic or acyclic ethers are required. Using air-free procedures, water and air, which quickly degrade the reagent by protonolysis or oxidation, are removed. Although the reagents must still be dry, ultrasound can activate the magnesium and cause it to devour the water, allowing Grignard reagents to form in moist solvents.
Synthesis of Grignard reagent:
The creation of Grignard reagents is frequently subjected to an induction time, as is customary for solid-liquid reactions. The passivating oxide on the magnesium is removed at this stage. The reactions might be substantially exothermic after this induction time. When a reaction is ramped up from the lab to a manufacturing plant, this exothermicity must be taken into account. Except for particularly activated magnesium, most organohalides will work, but carbon-fluorine linkages are often unreactive (through Rieke metals).
Typically, magnesium ribbon is used in the procedure to create Grignard reagents. A passivating coating of magnesium oxide coats all magnesium, preventing reactions with organic halides. Many techniques have been discovered to degrade this passivating layer, allowing highly reactive magnesium to come into contact with the organic halide. Crushing the Mg bits in place, quick churning, and sonication are all mechanical processes. Common activation agents include iodine, methyl iodide, and 1,2-dibromoethane. The use of 1,2-dibromoethane is useful since its action may be observed by looking for ethylene bubbles. Furthermore, the by-products are completely harmless:
Mg + BrC2H4Br → C2H4 + MgBr2
In most cases, the amount of Mg used by these activating agents is negligible. A little amount of mercuric chloride amalgamates on the metal’s surface, increasing its reactivity. As an initiator, premade Grignard reagent is frequently employed.
This problem is avoided by using specially activated magnesium, such as Rieke magnesium. Ultrasound, scratching the oxidized layer off with a stirring stick, or adding a few drops of iodine or 1,2-Diiodoethane can also be used to break up the oxide layer. Another alternative is to employ magnesium anthracene or sublimed magnesium.
Reactions of Grignard Reagents
It is vital to ensure that no water is present during a reaction utilizing Grignard chemicals, as this would cause the reagent to degrade fast otherwise. Because the oxygen in these solvents stabilizes the magnesium reagent, the bulk of Grignard reactions take place in anhydrous diethyl ether or tetrahydrofuran.
Grignard reagents are crucial in organic chemistry because they may react with a wide range of molecules to produce a variety of products. The reactions of some of these reagents are listed below.
- Reactions with Carbonyl Group
When these reagents react with diverse carbonyl compounds, they produce a variety of products. The alkylation of ketones and aldehydes with R-Mg-X is the most typical reaction of Grignard reagents.
- Reactions with Non-Carbon Electrophiles
Grignard reagents and some organolithium compounds are highly useful for forming novel carbon-heteroatom bonds. These chemicals can also be used to make dialkyl cadmium by transmetallating them with cadmium chloride. The following is an example of a reaction.
2R-Mg-X + CdCl2→ R2Cd + 2Mg(X)Cl
These chemicals can be used to attach alkyl chains to a variety of metals and metalloids.
- Reactions with Organic Halides
These reagents are often non-reactive with organic halides, in contrast to their behavior with other halides. When a metal catalyst is introduced, however, carbon-carbon coupling reactions occur with Grignard reagents functioning as a reactant.
The reaction between methyl p-chlorobenzoate and nonyl magnesium bromide, which produces p-nonyl benzoic acid in the presence of the catalyst Tris(acetylaceto) iron, is an example of such a coupling reaction (III).
- Industrial Reactions
The Grignard reagent is an important element of the non-stereoselective method used to make Tamoxifen, a drug used to prevent and cure breast cancer.
