Grignard reagent

A metal-organic compound with the general formula of RMgX(R stands for hydrocarbon group and x stands for halogen). 190 1 was first prepared by the reaction of halogenated hydrocarbon RX with magnesium in ether solution from F.-A.V. Grignard. Also known as Grignard reagent. Grignard reagents are widely used in organic synthesis. RH, R-COOH, R-CHO, R-CH2OH, R-OH, CROHRR', CRR'O and RnM(n is the valence of metal and m is other metal) can be prepared from RMgX. Under suitable conditions, RMgX can also react with α, β-unsaturated carbonyl compounds through * * * yoke addition reaction. Grignard reagent exists in the form of monomer in dilute solution of ether, complexed with two molecular ethers, and exists in the form of dimer in concentrated solution.

principle

Because the magnesium atom is directly connected to the carbon chain, the carbon atom adjacent to the magnesium atom is negatively charged as a result of polarization, which makes this C-Mg bond extremely active. In order to ensure that Grignard reagent does not react, the reaction is usually carried out in ether solvent, such as ether or tetrahydrofuran. In the reverse synthesis method, Greenia reagent is nucleophilic hydrocarbon group d 1 synthetic agent.

[Edit this paragraph] Synthesis method

The preparation method of Grignard reagent is to slowly add the ether solution of halogenated hydrocarbon (generally chloroalkane or bromoalkane) into the magnesium chips soaked in ether, and the feeding speed should be able to maintain the slight boiling of ether until the magnesium chips disappear, thus obtaining Grignard reagent. This reaction is exothermic. If the reaction starts slowly, a small grain of iodine can be added to start the reaction. Once the reaction starts, the vapor of ether is enough to eliminate the oxidation of air in the system, but water is not allowed. Grignard reagent is easy to react with air or water, and should be reacted in the nearest container after preparation. Vinyl chloride and chlorine combined with alkene and carbon cannot react with magnesium in ether. If tetrahydrofuran is used instead of ether, vinyl magnesium chloride reagent can be prepared. Some people call this reagent Norman reagent.

Due to the slow start of the reaction, in order to better start the reaction between magnesium and halogenated hydrocarbons, a small amount of iodine, methyl iodide or 1, 2- dibromoethane is often used to accelerate the start of the reaction. 1, 2- dibromoethane should be the first choice to start the reaction, especially when there is a small amount of water in ether, dibromoethane will quickly react with magnesium to produce magnesium bromide and ethylene. Magnesium bromide can be dehydrated and dried, and the reaction rate can be judged by observing the bubbles of ethylene. In addition, the generated magnesium bromide and ethylene are non-toxic. The three reagents added at the start-up accelerated the reaction by removing the passivation layer on the surface of magnesium.

[Edit this paragraph] Discovery history

19 12 years, the Nobel Prize in chemistry was awarded to the French chemist Victor Griya. He found that metallic magnesium reacted with ether solutions of many halogenated hydrocarbons to form an organic synthesis intermediate-organometallic magnesium compound, that is, Grignard reagent.

Victor Griya's family is rich, but he doesn't like reading, and he has become a "worthless playboy". 1892, at a banquet, he invited a countess to dance. The countess refused, saying that she hated a playboy like him most. He endured humiliation and repented, and finally came to his senses, determined to abandon his bad habits and strive for progress. He left home.

Grignard ran away from home and came to Lyon. He wants to study at the University of Lyon, but he has never studied hard. There are too many neglected studies in primary and secondary schools. How can such a foundation be admitted to a university? Grignard had to start from scratch. Fortunately, an educator named Louis Bough sympathized with his experience and was willing to help him with his lessons. After the careful guidance of the old professor and his own efforts, it took two years to finish the make-up lessons. In this way, grignard entered the University of Lyon for placement. He knows that the opportunity to learn is hard-won, and there is only one way at present: work hard, work hard, and work hard again; Energetic, energetic, energetic again. At that time, Barbier, the authority of organic chemistry in our school, took a fancy to his diligence and talent, so grignard studied and engaged in research work under the guidance of Professor Barbier. 190 1 was awarded the doctorate for discovering Grignard reagent in grignard.

When grignard discovered Grignard reagent, he named it grignard-Barbier reagent to show his gratitude to his tutor. However, Barbier insisted that he had not made any efforts in the process of discovery, and asked to change the name of the reagent to Greenia reagent. Barbier's justice and indifference are praised, and the affection between teachers and students of grignard and Barbier is also evident.

[Edit this paragraph] Chemical properties

1. Strong nucleophilicity

Grignard reagent can react with active hydrogen in substances (such as water, hydroxyl hydrogen of ethanol and terminal hydrogen of acetylene) to generate corresponding hydrocarbon groups. For example:

X-Mg-CH2CH3 + H2O === CH3CH3

X-Mg-CH2CH3 + CH3CH2OH === CH3CH3

X-Mg-CH2CH3 + HC≡CH === CH3CH3

2. Reaction with CO2 or O2

Grignard reagent can undergo nucleophilic addition reaction with carbon dioxide or oxygen to generate carboxylic acid or peroxy compound with the same carbon number. The addition reaction of Grignard reagent with carbon dioxide is also of great significance in organic synthesis. It not only realizes the growth of carbon chain by forming new C-C bonds, but also only adds one carbon atom and introduces carboxyl functional groups, which is one of the most commonly used methods to prepare carboxylic acids with one carbon atom added.

3. Coupling reaction between Grignard reagent of active halogenated hydrocarbon and active halogenated hydrocarbon

This reaction realizes the coupling of Grignard reagent prepared from active halogenated hydrocarbon with active halogenated hydrocarbon group, such as Grignard reagent prepared from benzyl halide, allyl halide or tertiary halogenated hydrocarbon.

To some extent, this reaction can be regarded as a supplement to Wurtz reaction, Wurtz-Fittig reaction and Ullmann reaction, because these reactions can only realize the coupling of inactive hydrocarbon groups, and the coupling reaction realized by Grignard reagent not only introduces active groups, but also can realize the coupling between different hydrocarbon groups because of its special structure.

Various hydrocarbons are prepared from alkyl groups of halogenated hydrocarbons by coupling reaction. These reaction types are of great significance to the growth of carbon chains in synthesis, so we should master them flexibly.

4. Addition with aldehydes and ketones to form alcohols.

This may be one of the most important properties of Grignard reagent in synthesis. This kind of reaction is that the negative carbon atom of Grignard reagent shows good nucleophilicity, the carbonyl carbon atom of aldehyde ketone with electron deficiency is nucleophilically added, and the positively charged magnesium ion is added to the carbonyl oxygen atom to generate the structure of -c-c-o-mg-x, and then the magnesium part is removed by acid-catalyzed hydrolysis to generate alcohol and the structures of magnesium halide and magnesium hydroxide.

This kind of reaction can be used to synthesize various alcohols, and it is also the most commonly used method to synthesize alcohols in organic synthesis. In the complex analysis of alcohol counter-synthesis, we should clearly realize that the α carbon atom of alcohol hydroxyl group is carbonyl carbon in protoaldone molecule, and a β carbon atom of alcohol hydroxyl group may be a negatively charged functional carbon in protogrignard reagent, and the single bond between α carbon atom and β carbon atom is newly formed through this nucleophilic addition reaction.

Usually Grignard reagent reacts with aldehyde to produce secondary alcohol; The nucleophilic addition reaction of Grignard reagent with ketone produces tertiary alcohol; Only the nucleophilic addition reaction of Grignard reagent with formaldehyde can produce primary alcohol, which is also a common method to prepare alcohol with one carbon added. In addition, the addition of Grignard reagent with ethylene oxide can obtain the first-order alcohol with an increase of 2 carbon atoms.