GRIGNARD'S REAGENT PREPARATION AND IT'S USES .pptx

Grignard's reagent, named after the French chemist Victor Grignard, who discovered it in 1900, is one of the most important and widely used organometallic compounds in organic chemistry. These reagents have the general formula R-Mg-X, where R is an alkyl or aryl group, Mg represents magnesium, and X is a halogen (typically chlorine, bromine, or iodine). Grignard reagents are synthesized by reacting an organohalide with magnesium metal in the presence of an anhydrous ether solvent, such as diethyl ether or tetrahydrofuran (THF). The role of the solvent is crucial because it stabilizes the reagent by coordinating to the magnesium center, thereby ensuring its reactivity.

Grignard reagents are highly reactive and serve as powerful nucleophiles in organic synthesis. One of their primary applications is in the formation of carbon-carbon bonds, making them essential for constructing complex organic molecules. This reactivity stems from the polar nature of the carbon-magnesium bond, which gives the carbon atom a partial negative charge, allowing it to attack electrophilic centers, such as carbonyl groups in aldehydes, ketones, and esters. This reaction typically leads to the formation of alcohols, which can be further modified to produce a wide range of organic compounds.

The versatility of Grignard reagents extends to their ability to react with various electrophiles beyond carbonyl compounds. For instance, they can be used to form carboxylic acids by reacting with carbon dioxide, or they can generate alkenes through reactions with alkyl halides. Additionally, Grignard reagents can act as intermediates in the synthesis of pharmaceuticals, natural products, and other fine chemicals, demonstrating their significant role in industrial and laboratory applications.

One of the challenges associated with Grignard reagents is their sensitivity to moisture. Water, oxygen, or even traces of atmospheric humidity can rapidly deactivate the reagent by causing hydrolysis of the magnesium-carbon bond, resulting in the formation of an alkane and a magnesium hydroxide salt. Therefore, reactions involving Grignard reagents must be performed under strictly anhydrous conditions, often in an inert atmosphere, such as nitrogen or argon, to prevent degradation.

1. GRIGNARD’S REAGENT PREPaRATION AND IT’S USES SUBMITTED TO : Dr. MANMOHAN SIR SUBMITTED BY : NISHTHA SRIVASTAVA

2. CONTENTS :- WHAT IS GRIGNARD’S REAGENT ? GRIGNARD REAGENTS PREPARATION OF GRIGNARD REAGENTS REACTIONS OF GRIGNARD REAGENTS

3. WHAT IS GRIGNARD’S REAGENT ? A Grignard reagent is an organomagnesium compound which can be described by the  chemical formula ‘R-Mg-X’   where R refers to an alkyl or aryl group and X refers to a halogen. They are generally produced by reacting an aryl halide or an alkyl halide with magnesium. These reagents were discovered by the  French chemist Victor Grignard , who won the Nobel Prize in Chemistry in the year 1912 for his work on these compounds.

4. GRIGNARD REAGENTS Grignard reagents ( RMgX ) are commonly used for organic synthesis. However, these highly reactive compounds are supplied inflammable  solvents , which cause extra complexity in their transport. Herein we note that Grignard reagents with linear alkyl chains can be trapped and stabilized by the macrocyclic host pillar arene while retaining their reactivity. Reactions that form carbon-carbon bonds are among the most beneficial to synthetic organic chemist. In 1912, Victor Grignard was awarded the Nobel Prize in Chemistry for his discovery of a new sequence of reactions resulting in the creation of a carbon-carbon bond. Grignard synthesis involves the preparation of an organomagnesium reagent through the reaction of an alkyl bromide with magnesium metal.

5. The Grignard reaction is an organic reaction used to produce a variety of products through the reaction of an organomagnesium compound, also known as an electrophilic “Grignard reagent,” followed by an acidic reaction. The Grignard reagent is formed by the reaction of an alkyl or aryl halide with magnesium metal via a radical mechanism.

6. The process of preparing Grignard reagents is described in the points provided below. It can be noted that many of these reagents can also be purchased commercially. These reagents are prepared via the treatment of magnesium with organic halides such as alkyl or  aryl halides . This is done with the help of solvents comprising ethers (which are described by the formula R-O-R’) because the ligands provided by these solvents help in the stabilization of the  organomagnesium compound. PREPARATION OF GRIGNARD REAGENTS

7. 4. Water and air are very harmful to this synthesis and can quickly destroy the Grignard reagent which is being formed via protonolysis or via oxidation of the reagent. Therefore, the process must be carried out in air-free conditions. 5. Alternatively, the magnesium can be activated to make it consume water when wet solvents are used with the help of ultrasound. 6. After the slow induction period of the reaction, the process can be quite exothermic. This is a very important factor to consider while industrially producing the Grignard reagent. The organic halides used in these reactions include aryl or alkyl chlorides, bromides, and iodides.  Aryl fluorides and alkyl fluorides are not very reactive and are hence not commonly used. However, with the help of Rieke metals, the magnesium can be activated to make the fluoride more reactive

8. An illustration detailing the preparation of these reagents is provided below. The quality testing of the synthesized Grignard reagents is done via titrations involving protic reagents that do not contain water (since these reagents are highly sensitive to oxygen and water) and a  colour indicator . One suitable compound for these titrations is methanol.

9. REACTIONS OF GRIGNARD REAGENTS During a reaction involving Grignard reagents, it is necessary to ensure that no water is present which would otherwise cause the reagent to decompose rapidly. Therefore, the majority of Grignard reactions occur in solvents such as anhydrous  diethyl ether  or tetrahydrofuran because the oxygen in these solvents stabilizes the magnesium reagent. Grignard reagents are very important reagents in organic chemistry since they can be reacted with a wide range of compounds to form different products.

10. Reactions of Grignard REAGENT :-  Reactions with Carbonyl Group Reactions with Non-Carbon Electrophiles Reactions with Organic Halides Reaction between Acetone and Methyl Magnesium Chloride Industrial Reactions

11. 1. Reactions with Carbonyl Group These reagents form various products when reacted with different carbonyl compounds. The most common reaction of Grignard reagents is the alkylation of  ketones and aldehydes  with the help of R-Mg-X. This reaction depicted above is also referred to as the Grignard reaction. The solvents that are used in this reaction include tetrahydrofuran and diethyl ether.

12. 2. Reactions with Non-Carbon Electrophiles For the  formation of new carbon-heteroatom bonds, Grignard reagents and some organolithium compounds are very useful.  These reagents can also undergo a transmetallation reaction with cadmium chloride, yielding dialkyl cadmium. This reaction can be written as follows. 2R-Mg-X + CdCl 2  → R 2 Cd + 2Mg(X)Cl Alkyl chains can be attached to many metals and metalloids with the help of these reagents.

13. 3. Reactions with Organic Halides Typically, these reagents are quite unreactive towards  organic halides  which highly contrasts their behaviour towards other halides. However, carbon-carbon coupling reactions occur with Grignard reagents acting as a reactant when a metal catalyst is introduced. An example of such a coupling reaction is the reaction between methyl p-chlorobenzoate and nonyl magnesium bromide which yields the compound p-nonyl benzoic acid in the presence of the catalyst – Tris( acetylaceto ) iron(III).

14. 4. Reaction between Acetone and Methyl Magnesium Chloride The reaction of methyl magnesium bromide with acetone followed by hydrolysis gives tertiary alcohol. Acetone reacts with methyl magnesium bromide followed by hydrolysis to give secondary alcohols.

15. 5. Industrial Reactions For the production of Tamoxifen, a type of medication used to prevent and treat breast cancer, the Grignard reagent is a vital part of the non-stereoselective process.

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