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Chapter 5:- Alkyl halides and Grignard Reagent

B.sc 1st year Book
Organic Chemistry
(Page 3)

Grignard reagents 

Organomagnesium halides are commonly called as “Grignard reagents“. They are named after Victor ignored who discovered them and developed their use in the synthesis of various organic compounds ch as alkanes, alkenes, alkynes, alcohols, aldehydes, ketones, carboxylic acids, amines etc. The highly active nature of Grignard reagents is the cause of their wide use. They have the general formula RMgX, mare R= any organic group which is derived from aliphatic, aromatic, alicyclic or heterocyclic compounds. In neral R= alkyl or aryl group and X=Cl, Br or I

Grignard reagents

 

Methods of Preparation:

Grignard reagents are prepared in the laboratory by the reaction of dry alkyl or aryl halides (preferably bromides or iodides) on magnesium metal in the presence of dry diethyl ether. it general,
$$ RX_{\left(Alkyl\:Halide\right)}\:+\:Mg\frac{dry\:ether}{reflux}\:RMgX_{\left(Alkyl\:magnesium\:halide\right)} $$
$$ ArX_{\left(Alkyl\:Halide\right)}\:+\:Mg\frac{dry\:ether}{reflux}\:ArMgX_{\left(Alkyl\:magnesium\:halide\right)} $$

Examples :

$$ CH_3CH_2Br_{\left(ethyl\:bromide\right)}\:+\:Mg\frac{dry\:diethyl\:ether}{ }CH_3CH_2MgBr_{ethyl\:magnesium\:bromide\left(Grignard\:reagent\right)} $$

$$ C_6CH_5Br_{\left(ethyl\:bromide\right)}\:+\:Mg\frac{dry\:diethyl\:ether}{\:}C_6H_5MgBr_{phenyl\:magnesium\:bromide\left(Grignard\:reagent\right)} $$

Besides ether, tetrahydrofuran (THF), dioxane, dimethyl ethane (DME), or dimethyl ether of diethylene glycol: (diglyme), tertiary amines etc. can also be used as solvents. Among these solvents, THF is considered to t= the best solvent since it increases the reactivity of an alkyl or aryl halide towards magnesium. It is because of this reason, Grignard reagents of less reactive aryl and vinyl halides (which are difficult to prepare in ether) are: prepared in THF.
For example :
$$ C_6CH_5Cl_{\left(chlorobenzene\right)}\:+\:Mg\frac{Tetrahydrafuran}{\:}C_6H_5MgCl_{phenyl\:magnesium\:bromide\left(Grignard\:reagent\right)} $$
$$ H_2C=CH-Cl_{\left(vinyl\:chloride\right)}\:+\:Mg\frac{Tetrahydrafuran}{\:}H_2C=CH-MgCl_{\left(vinyl\:magnesium\:chloride\right)} $$
Further, it has been found that for a given alkyl group, the ease of formation of the Grignard reagent is of the order: 
iodide > bromide > chloride
The alkyl or aryl magnesium fluorides RMgF are however not formed. Also for a given halogen atom, the order of reactivity is :
CH3X < CH3CH2X < CH3CH2CH2X……etc. 
i.e. the formation of the Grignard reagent becomes increasingly difficult with an increase in the number of carbon atoms in the alkyl groups. The use of tert. alkyl iodides are avoided because they readily lose a molecule HI to form an alkene.
Procedure: Adds alkyl halide or aryl halide slowly to a perfectly cleaned and dry flask containing magnesium turning covered by a layer of absolutely dry ether or THF. The reaction mixture is warmed a little when an exothermic reaction would soon start. If the reaction does not start within five minutes add a few crystals of iodine and the reaction mixture is warmed until a vigorous reaction does not start. As the magnesium gradually dissolves a cloudy solution of the Grignard reagent is obtained.

Precautions in the preparation of Grignard reagents:

During the preparation of Grignard, reagents following precautions must be kept in mind :
(i) The apparatus should be perfectly dry and protected from moisture by using an anhydrous calcium iodide guard tube.
(ii) All reagents and solvents used must be absolutely dried.

(iii) Ether used as solvent must be absolutely free from alcohol this can be done by first washing eth several times with water followed by drying over anhydrous CaCl2 for 1−2 days and subsequent distillation over sodium.

(iv) One atmosphere of dry nitrogen (free from O2 and CO2 ) should be maintained throughout the course of the reaction. Otherwise, Grignard reagents are decomposed by moisture and react with O2 and CO2 to form alcohols and carboxylic acids respectively.

$$ RMgX_{\left(alkyl\:magnesium\:halide\right)}+\frac{1}{2}O_2\:\rightarrow \:ROMgX\frac{\frac{H^+}{H_2O}}{hydrolysis}ROH_{\left(alcohol\right)}+Mg\left(OH\right)X $$

$$ RMgX_{\left(alkyl\:magnesium\:halide\right)}+CO_2\:\rightarrow \:ROOMg^+X_{\left(alcohol\right)}\frac{\frac{H^+}{H_2O}}{hydrolysis}RCOOH_{\left(carboxylic\:acid\right)}+Mg\left(OH\right)X $$

Mechanism :

The mechanism of the formation of Grignard reagents is still not certain. Gomberg and Beckmann in 1930 pointed out that the reaction begins with the formation of a small amount of free radical magnesium halide MgX) in the previous step which starts the reaction through a free radical mechanism as shown below :
Step I:
R—X(alkyl halide) + Mg + X—R’(alkyl halide) → R—R’alkane + MgX2
Step II:
MgX2 + Mg → 2MgXfree radical
Step III:
R—X + Mg·X → R·(alkyl free radical) + MgX2
Step IV:
R’ + Ma’X(free radicals) + RMgX(Grignard reagent)
Structure of Grignard reagent:
From recent research work, it has been observed that the structure of a Grignard reagent depends particularly on its type and the solvent used for its preparation. Grignard and Blaise in 1901 suggested that two ether molecules were present as the ether of crystallisation.
X-ray analysis of these dietherates suggests that four groups are arranged tetrahedrally as shown in figure 5.06.
Grignard reagents
Thus, it is concluded that the solvent ether not only provides a medium for the reaction but also he dissolves the Grignard reagent formed due to solvation by ether molecules. This is supported by observation. The Grignard reagent can also be prepared even in benzene solution in the presence o tertiary amine which coordinates with magnesium-like ether and thus dissolves it. Further, the abs formula shows that the Grignard reagent is in the monomeric form. But physical studies have shown t Grignard reagents exist as a 1:1 complex of a dialkyl or diaryl magnesium and magnesium ha coordinated with two molecules of ether. These two species are held together by halogen bridges shown in figure 5.06(b).

Physical properties:

Grignard reagents are non-volatile colourless solids. It is very difficult to Isola them because of their explosive nature. So far synthetic purposes the Grignard reagents are always prepared and used in ether solution.
Chemical properties:
Carbon-magnesium bond in the Grignard reagent is highly polar due to the large electronegative difference between more electronegative carbon and less electronegative magnesium atom.
Element Carbon Magnesium
Electronegativity 2.5 1.2
Electronegativity difference (2.5−1.2) 1.3
Thus, the electrons of the carbon-magnesium bond are drawn towards the carbon atom. As a result, the carbon atom has a partial negative (δ−) and the magnesium atom has a partial positive (δ+) charge as shown below
Grignard reagents
The alkyl group in the Grignard reagent, therefore, acts as a carbanion or a nucleophile and it attacks pole molecules at points of low electron density.
Grignard reagents

Type of Grignard Reagent

Grignard reagent mainly undergoes two types of reactions :
I. Nucleophilic substitution reactions and
II. Nucleophilic addition reactions

(I) Nucleophilic substitution reactions :

The nucleophilic substitutions reaction involves the nucleophilic attack of the alkyl group of the Grignard reagent on the electron-deficient centre of the reacting molecules as shown below :
Grignard reagents

(II) Nucleophilic addition reactions:

Grignard reagents give addition reactions with compounds having multiple bonds such as >C=O, C≡N> C=S etc which on acid hydrolysis yield a vast variety of compounds. All such reactions proceed through the following mechanism :
Grignard reagents

 Synthetic application of Grignard reagents

The usefulness of the Grignard reagent is due to its high reactivity. It reacts with a variety of inorganic (H2OO2 etc ) and organic reagents. So it has acquired great synthetic values. Some of the important hectic uses are described below :

Preparation of Alkanes :

 1. By reaction with Compounds containing active hydrogen:

Active hydrogen-containing sounds such as water, alcohols, carboxylic acids, hydrogen sulphide, thioalcohol, ammonia, terminal acetylenes etc when treated with Grignard reagents yield alkanes corresponding to the alkyl or the aryl group of the Grignard reagents. In general
Grignard reagents,
Where R= any alkyl group and A=OH, SH, OR, OCOR, NH2, NHR, NR2, C≡CH etc. examples are :
Grignard reagents
Grignard reagents
Alkane evolved in the above reactions and can be measured quantitatively. Therefore, these reactions can b used for the estimation of −OH,−NH2,−SH groups in organic compounds. This method of estimating: such groups are called “Zerevitinov’s method“.

(2) By reaction with reactive alkyl halides:

Grignard reagents react with reactive alkyl halides for higher alkanes. In general
Grignard reagents
For examples :
Grignard reagents

(3) Preparation of Alkenes:

Compounds containing more reactive halogens such as allyl iodide when reacting with Grignard reagents to form alkenes.
Grignard reagents

(4) Preparation of Alkynes:

Grignard reagents react with terminal acetylenes to form alky magnesium halides which on subsequent treatment with alkyl halides give higher alkynes.
Grignard reagents, preparation of alkynes
Grignard reagents

(5) Synthesis of Primary Alcohols ( 1 Alcohol):

From Grignard reagents primary alcohols are obtained by the following methods :

(a) Reaction with oxygen:

When dry oxygen is passed through the solution of a Grignard reagent, forms a product that on acid hydrolysis yields primary alcohol. In general

grignard reagents

(b) Reaction with Ethylene oxide followed by acid hydrolysis:

Grignard reagents react with ethylene oxide to give an adduct which on hydrolysis with dilute HCl forms primary alcohols. Primary alcohols so obtained containing two carbon atoms more than the alkyl group of its corresponding Grignard reagents. For example.
grignard reagents

(C) Reaction with Formaldehyde followed by acid hydrolysis (1 Alcohol):

Formaldehyde reacts with Grignard reagents to give additional products which on hydrolysis with dil. HCl yields primary alcohols.
grignard reagents

(6) Synthesis of Secondary Alcohols ( 2 Alcohols):

(a) Reaction with Aldehydes other than Formaldehyde followed by acid hydrolysis:

When a Grignard reagent is treated with aldehydes other than formaldehyde gives an adduct that on acid hydrolysis yields secondary alcohol.
 grignard reagents
grignard reagents

(b) Reaction with Ethyl formate: This reaction occurs in two steps :

Step I: Ethyl formate reacts with Grignard reagents to form aldehyde.
grignard reagents
Step II: The aldehyde formed in the above step I when reacts with excess of Grignard reagent to give an additional product which on acid hydrolysis gives secondary alcohol.
grignard reagents

 

(7) Synthesis of Tertiary A/cohols (3 Alcohols ):

They are prepared by the following methods:

(i) Reaction of the Grignard reagent with Acetone followed by acid hydrolysis :

grignard reagents

(ii) Reaction of the Grignard reagent with Acid chloride followed by acid hydrolysis :

grignard reagents

(8) Synthesis of Aldehydes :

(i) An aldehyde is formed when ethyl formate and Grignard reagent react in a 1:1 molar ratio. The excess Grignard reagent is avoided as it further reacts with the resultant aldehyde to give secondary alcohol.
 
grignard reagents
However, it is impossible to totally avoid the interaction of aldehyde and Grignard reagent to form 2∘ alcohol and therefore the yield of the aldehyde is affected.
(ii) ethyl orthoformate is used instead of ethyl formate, aldehydes are obtained in a better yield.
grignard reagents

(iii) The Reaction of the Grignard reagent with HCN:

The grignard reagent reacts with HCN to give an additional product which on treatment with dilute mineral acids gives aldehyde. eg.
grignard reagents

(9) Synthesis of Ketones:

They are formed by the reaction of Grignard reagents with either an acid chloride, alkyl cyanide or an amide.
For examples :
(i). Reaction of the Grignard reagent with Acid chloride :
grignard reagents
(ii). Reaction of the Grignard reagent with Alkyl cyanides :
 

grignard reagents

grignard reagents

(10) Synthesis of Ethers:

When an α-halogenated lower ether is treated with Grignard reagent a higher ether is formed.

(11) Synthesis of Mono carboxylic acid:

Grignard reagents react with dry ice (CO2) to give addition: products which on acid hydrolysis yield monocarboxylic acid. In general,
Examples :

(12) Synthesis of Esters:

When the equimolar amount of Grignard reagent and ethyl chloroformate is reacted: together form higher esters. In general,

(13) Synthesis of Primary amines:

Chloramine reacts with Grignard reagents to yield primary amines. F= example :
Primary amines can also be prepared when O-methyl hydroxylamine reacts with Grignard reagents. e.g.

(14) Synthesis of Sulphinic acids:

On passing SO2 gas into a well-cooled solution of Grignard reagents, additional products are formed which on treatment with dilute hydrochloric acid yield sulphinic acids.
In general,

(15) Synthesis of Dithionic acids:

Dithionic acids are synthesised by the reaction of carbon disulphides with Grignard reagents followed by hydrolysis. In general,

(16) Synthesis of Phenols:

Grignard reagents of the type Ar MgX when treated with oxygen form an unstable addition product which on hydrolysis yield phenols. In general

(17) Synthesis of Organometallic compounds:

Various organometallic compounds may be synthesised when Inorganic halides react with suitable Grignard reagents. For examples :
(i)  4C2H5MgBr + 2PbCl2⟶ (C2H5)4 Pb(tetraethyl lead)(TEL) + 4MgBr(Cl) + Pb
(ii) 4CH3MgBr+SiCl4⟶(CH3)4Si(tetramethyl silane)(TMS) + 4MgBr(Cl) 
(iii) 2CH3CH2MgBr + HgCl2 ⟶ (CH3CH2)2Hg(diethyl mercury) + 2MgBr(Cl) 

(18) Synthesis of Alkyl cyanides:

Alkyl cyanides(alkyl nitriles) may be synthesised by the reaction of cyanogen or cyanogen chloride with Grignard reagents. e.g.

 

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