What do you mean by Reaction of Ethers?

Ethers (R-O-R’) are compounds formed by replacing hydrogen atoms of an alcohol (R-OH compound) or a phenol (C₆H₅OH) by an aryl/ acyl group (functional group after removing single hydrogen from an aromatic ring). In this section, reaction, preparation and behavior of ethers are discussed in the context of organic chemistry.

Preparation of Ethers

By dehydration of alcohols
Formation of Symmetrical Ethers is achieved by dehydration of alcohols in the presence of acids like H₂SO₄.

In presence of acids, alcohols either produce alkenes or ethers based on reaction conditions. 

Ethanol in presence of sulfuric acid at 443 K gives ethene, and at 413 K, it gives R-O-R’, ethoxyethane ($C_2{H}_{5}O{C}_2{H}_5$).

In SN₂ reactions, breaking and formation of bonds between molecules occur simultaneously in sync. These reactions are nucleophilic in nature. The formation of R-O-R’ here undergoes nucleophilic substitution reaction in a similar fashion.

Necessary requirements

• The alkyl group (R group) of the alcohols should be primary only, otherwise the alkene formation becomes the priority (elimination competes over substitution).
• The temperature should be low.

By Williamson synthesis

By this method, preparation of symmetrical and unsymmetrical ethers takes place. In this method, we allow alkyl halide group to react with Na-X, that is, sodium alkoxide.  

Also, R-O-R’ containing secondary or tertiary R groups can be the product of Williamson’s synthesis.

Primary alkyl halides are preferred over secondary (two R groups attached to C) or tertiary (three-membered C-R group) as in both cases elimination competes over substitution.

Usage of tertiary alkyl halide results only in the formation of alkene.

The reaction between sodium methoxide, CH₃ONa, and tert-butyl bromide, (CH₃ )₃C-Br, gives only 2- methylpropane as the primary product.

Alkoxides being nucleophiles as well as strong bases react with alkyl halides and elimination reaction takes place.

Chemical Reactions of Ethers

Cleavage of C-O bond in ethers

With halogen acids

Excess of hydrogen halides are made to react with ethers which leads to formation of corresponding alkyl halide molecules by the cleavage of carbon - oxygen bond of the respective molecular compound.

Example, dimethyl ether reacts with hydrogen iodide, to give methyl iodide and methanol.

Aryl – oxygen bond is more stable than alkyl – oxygen bond hence, reaction of alkyl aryl ethers (cyclic ethers) with hydrogen halides will cause cleavage at alkyl oxygen bond.

Mechanism

1. Protonation of ether molecule in the presence of acidic reagents such as HI or HBr.

2. Iodide being a good nucleophile, aims at the least substituted carbon of ox onium ion and displaces an alcohol molecule by SN₂ reaction. If heterogeneous alkyl groups constitute an R-O-R’, the lower alkyl group of the two, would form alkyl iodide.

3.

If heterogeneous alkyl groups constitute an ether with one of the alkyl group being a tertiary alkyl group, there would be a tertiary halide formed from the cleavage mechanism because in step 2 of the mechanism, leaving group OH-CH₃ departs, creating a stable carbocation [(CH₃)₃C⁺], the reaction then follows SN₁ process.

With sulfuric acid

1. Heating of R-O-R’with dilute H₂SO₄ under pressure, results in the hydrolysis of ethers to give alcohols

2. Heating of R-O-R’ with concentrated H₂SO₄ results in the formation of alcohols and alkyl hydrogen sulphates.

With phosphorous pentachloride

Also results in the formation of alkyl halides along with phosphoryl chloride.

With acid chlorides and anhydrides

Reaction of acid chlorides with anisole under the application of heat and in the presence of anhydrous ZnCl₂ or AlCl₃ gives alkyl halides and esters.

In the above reaction diethyl ether reacts with acetyl chloride to give ethyl chloride and ethyl acetate.

Electrophilic substitution

Alkoxy groups are electron donating group and hence are ortho, para directing.

Here benzylic O of the OR group acts as electron donating group and resonance is observed.

Following figure depicts activation of an aromatic ring towards electrophilic substitution just like phenol.

Halogenation

In organic chemistry, it is the process of addition of one or multiple halogen to a chemical compound in the presence of glacial carboxylic acids if required.

Anisole (C₇H₈O) undergoes bromination in presence of ethanoic acid (acetic acid) even without the presence of a catalyst as methoxy group activates the aromatic ring (C₆H₆).

Glacial acetic acid here acts as a solvent to dissolve C₇H₈O (both are polar). It can be removed easily in an aqueous workup removed.

Friedel – craft’s reaction

In Friedel craft’s reaction, alkyl and acyl groups are introduced at ortho and para positions by reaction with alkyl halide and acyl halide in the presence of lewis acid base catalyst. C₇H₈O is acid-catalyzed where the alkyl and acyl groups of alkyl and acyl halides gets ortho and para positioned on this cyclic ether in presence of anhydrous aluminium chloride (anhy. AlCl₃).

Nitration

Nitration as name suggests, is the reaction with nitric acid (HNO₃).

Reaction of C₇H₈O with a mixture of conc. sulfuric acid and nitric acid gives a mixture of ortho and para nitroanisoles as end products.

Reactions of Ethereal Oxygen

Action of concentrated acids

Oxygen in ethers have 2 lone pair of electrons, thus they act as Lewis bases and gets dissolved in concentrated inorganic acids and forms stable oxonium salts.

For example, ether reacts with hydrogen chloride to form alkyloxonium chloride salt.

Formation of coordination complexes

Ethers are lewis bases so they sometimes form coordination complexes called as etherates with lewis acids like, BF₃, AlCl₃, etc.

In the reaction below, diethyl ether reacts with boron trifluoride to form boron trifluoride etherate.

These complexes allow Grignard reagents to dissolve in ether. Therefore, they’re many times prepared in ethers.

Ether as solvents

Ethers can form hydrogen bonds with water similar to alcohols. Ethers can display good solvent properties for non-polar organic structures. Its strong dissolving power and low reactivity makes them suitable solvents to run reactions in.

Common Mistakes and Pitfalls

• Ethers not to be mistaken with esters. An ester is a derivative of carboxylic acid, a chemical compound made from an acid (organic or inorganic) where at least one hydroxyl group ( –OH ) is substituted by an alkoxy group (–O– R ; R is alkyl group) , as in the substitution reaction of a carboxylic acid and an alcohol.

• Students have issues to identify end product. Try to identify the mistakes in the following reaction for example

Here’s the answer. As sodium ethoxide is a strong nucleophile and strong base too, elimination reaction would be dominant over substitution reaction, and we would get 2-methyl-prop-1-ene as major product.

Context and Applications

This topic is significant in the professional exams for both undergraduate and graduate courses, especially for Bachelors and Masters in Chemistry and Chemical Engineering.

Related concepts

• Alcohols, carboxylic acids, acetic acid, acyl group, aryl group and esters.
• Biomolecules.
• Nitration.
• Phenols, halo alkanes, halo arenas.
• Phenyl, benzyl acyl groups.