MBC 233.

1 [Organic Chemistry]

ETHER

Dr. Hamilton Opurum

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 Learning Objectives
• Creating a learning guide for ether involves
covering its
–chemical structure,
–properties,
–preparation methods,
–applications,
–safety considerations.
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 Ether
• Ether, refers to a class of
organic compounds
characterized by an
oxygen atom bonded to
two alkyl or aryl groups.

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 Nomenclature
 Ethers are commonly named by listing the names
of the groups attached to the oxygen atom and
adding the word ether.
 Examples include:

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 IUPAC nomenclature names ethers as alkoxy
alkanes, alkoxy alkenes, or alkoxy alkynes.
 The group in the chain that has the greatest
number of carbon atoms is designated the parent
compound.
 In the case of aromatic ethers, the benzene ring is
the parent compound.

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Cyclic ethers, oxygen‐containing ring
systems, are normally called by their
common names.

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 Physical properties:

• Ethers are typically colorless, volatile

liquids with a characteristic sweet odour.
• They have relatively low boiling points
compared to alcohols and other organic
compounds of similar molecular weight.

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 Physical properties
 The bonds between the oxygen atom and the
carbon atoms of the alkyl groups in an ether
molecule are polarized due to a difference in
electro-negativities between carbon and
oxygen.
 In addition, the bond angle between the alkyl
groups on the oxygen is 110°.

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 Chemical Structure:
• Ether molecules have the general
structure R-O-R', where R and R'
represent alkyl or aryl groups.
• The oxygen atom is bonded to two
carbon atoms, which can be part of
the same or different organic groups.
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 However, in water the hydrogen atoms have a
greater partial positive charge than the
hydrogen atoms on ether.
 In water, the charge is localized (only on) the
hydrogens and not delocalized (spread
throughout) as with the alkyl groups, so the
charge is stronger in water than in ethers.

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 Like water, ether is capable of forming hydrogen
bonds.
 However, because of the delocalized nature of the
positive charge on the ether molecule's hydrogen
atoms, the hydrogens cannot partake in hydrogen
bonding.
 Thus, ethers only form hydrogen bonds to other
molecules that have hydrogen atoms with strong
partial positive charges.

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 Therefore, ether molecules cannot form
hydrogen bonds with other ether molecules.
 This leads to the high volatility of ethers.
 Ethers are capable, of forming hydrogen
bonds to water, which accounts for the good
solubility of low molecular weight ethers in
water.

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 Table shows boiling points for some simple ethers and the
boiling points of alcohols of the same number of carbon atoms.
 Notice that due to the hydrogen bonding between alcohol
molecules, all alcohols have appreciably higher boiling points
than their isomeric ethers.

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 Solvent properties:
• Ethers are good solvents for a wide
range of organic and inorganic
substances.
• They are particularly useful for
extracting non-polar compounds
from aqueous solutions.
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 Preparation:
• Ethers can be prepared by several methods
• Williamson ether synthesis:
– This involves the reaction of an alkoxide ion with a primary alkyl
halide or sulfonate ester.
• Acid-catalyzed dehydration of alcohols:
– In this reaction, an alcohol reacts with a strong acid catalyst to
eliminate water and form an ether.

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 Williamson method
 The Williamson ether synthesis proceeds via an S N2
mechanism, in which an alkoxide ion displaces a halogen
ion.

 This method cannot be used with tertiary alkyl halides,

because the competing elimination reaction predominates.
 The elimination reaction occurs because the rearward
approach that is needed for an S N2 mechanism is
impossible due to steric hindrance.

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 An S N1 mechanism is likewise unfavored, because as the 3°
carbon attempts to become a carbocation, the hydrogens on the
adjacent carbons become acidic.
 Under these conditions, the alkoxide ion begins to show less
nucleophilic character and, correspondingly, more basic
character.
 This basic character leads to an acid‐base reaction, which results
in the generation of an elimination product (an alkene).

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 Williamson ether synthesis
• The general method for the synthesis of ether is
Williamson ether synthesis, involves nucleophilic
displacement of a halide ion or other good leaving group
by an alkoxide ion.
• The name of the reaction was coined after Alexander
William Williamson developed it in 1850.
• Williamson Ether Synthesis is a reaction that uses
deprotonated alcohol and an organohalide to form an
ether.
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 Williamson ether synthesis cont’d
• Williamson Ether Synthesis usually takes place as an SN2
reaction of a primary alkyl halide with an alkoxide ion.
• The structure of ethers was proved due to this chemical
reaction.
• SN2 pathway is required for the synthesis this reaction is
useful only when the alkyl halide is primary or secondary.
• The Ethers produced in this way have more carbon atoms
than either of the starting materials and thus are more
complex structures.
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The basic mechanism of the reaction is:

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 The Williamson Ether Synthesis
• In the Williamson Ether Synthesis, an alkyl halide (or
sulfonate, such as a tosylate or mesylate) undergoes
nucleophilic substitution (SN2) by an alkoxide to give
an ether.
• Being an SN2 reaction, best results are obtained
with primary alkyl halides or methyl halides.
• Tertiary alkyl halides give elimination instead of ethers.
• Secondary alkyl halides will give a mixture of elimination
and substitution.
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 The Williamson Ether Synthesis
• The alkoxide RO– can be those of methyl, primary,
secondary, or tertiary alcohols.
• The reaction is often run with a mixture of the alkoxide
and its parent alcohol (e.g. NaOEt/EtOH or
CH3ONa/CH3OH).
• Alternatively, a strong base may be added to the alcohol
to give the alkoxide.
• Sodium hydride (NaH) or potassium hydride (KH) are
popular choices.
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 The Williamson Ether Synthesis
• When an alkoxide and alkyl halide are present on the
same molecule, an intramolecular reaction may result to
give a new ring.
• This works best for 5- and 6-membered rings.
• When planning the synthesis of ethers using the
Williamson, take care to select the best starting materials
for an SN2 reaction.
• Avoid planning a Williamson involving a tertiary alkyl halide
or a phenyl halide!
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 Williamson ether synthesis cont’d
• Two alcohols are used to produce ethers by Williamson
reaction.
• The two are reacted together after one of them is
transformed to a leaving group (tosylate).
• The alkylating agent is preferred to be primary whereas
the alkoxide could be primary secondary or tertiary.
• If not a Halide, a sulfonate ester created for the purpose
of the reaction are the leaving group.
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 Mechanism of the Reaction
• The nucleophile attacks the alkyl halide forming an
ether from the back.
• This response takes place in a single step, which
is both cleavage and bond formation.
• If halides are sterically impeded then alkoxide acts
as a basis and protons in β-place are accessible.
• The products derived from a response to
elimination.
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 Williamson method
 The Williamson ether synthesis proceeds via an S N2
mechanism, in which an alkoxide ion displaces a
halogen ion.

 This method cannot be used with tertiary alkyl halides,

because the competing elimination reaction
predominates.
 The elimination reaction occurs because the rearward
approach that is needed for an S N2 mechanism is
impossible due to steric hindrance.
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 An S N1 mechanism is likewise unfavored, because as the
3° carbon attempts to become a carbocation, the
hydrogens on the adjacent carbons become acidic.
 Under these conditions, the alkoxide ion begins to show
less nucleophilic character and, correspondingly, more
basic character.
 This basic character leads to an acid‐base reaction, which
results in the generation of an elimination product (an
alkene).

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 Sulfuric acid process
 This method is used to make sterically hindered
symmetrical ethers.

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• The mechanism of the sulfuric acid process involves the
following five steps.
1. Sulfuric acid dissociates, giving a proton plus the
bisulfate ion.

2. The alcohol's oxygen atom is protonated via an acid‐base

reaction, leading to the formation of an oxonium ion.

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• 3. The oxonium ion decomposes, generating a
3° carbocation and water. Because
carbocations are planar, this decomposition
destroys the steric hindrance effect that the
t‐butyl group created.

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• 4. In this step, the acid‐base reaction
between the carbocation and a second
molecule of alcohol takes place, which
forms an oxonium ion.

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• 5. The oxonium ion liberates a proton
to yield the ether.

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 Reactivity

• Ethers are relatively inert compounds

under normal conditions, but they can
undergo reactions such as cleavage
of the C-O bond under acidic or
oxidative conditions.

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Although ethers are relatively inert
toward reaction, they usually show good
solvent properties for many nonpolar
organic compounds.
This strong dissolving power coupled
with low reactivity makes ethers good
solvents in which to run reactions.

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An acid‐catalyzed cleavage that occurs
when hydriodic acid (HI) mixes with ethers
is the most significant reaction that ethers
experience.
This reaction proceeds via a nucleophilic
substitution mechanism.

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Primary and secondary alkyl ethers
react by an S N2 mechanism, while
tertiary, benzylic, and alcylic ethers
cleave by an S N1 mechanism.

A typical S N2 reaction would be the

reaction of ethylisopropyl ether with
HI.

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 The mechanism for this reaction is:

 Notice that for S N2 substitution, the alkyl halide came from

the less sterically hindered group.
 For S N1 type reactions, the alkyl halide forms from the
fragment of the original molecule that forms the more
stable cation.
 Thus, the reaction of t‐butyl ethyl ether with HI gives t‐butyl
iodide and ethyl alcohol.

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 The following mechanism occurs:

 Notice that if the original ionization of the t‐butyl ethyl

ether formed a t‐butoxide ion and an ethyl
carbocation, this would be a less stable arrangement.
 (Remember, the order of stability of carbocations is 3°
> 2° > 1°.)
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 Uses of Ether
There are many uses of ethers in various
fields:
medicine,
laboratory purposes,
perfume,
flavouring agents etc.
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 Uses of Ether in Medicine
• 1. Anaesthesia:
 Ethers are volatile liquids, that release vapours which are inhaled
by the patients or administered intravenously.
 They cause loss of consciousness to the patients before surgery.
For example, diethyl ether is used as potent anaesthesia, and its
actions are accompanied by analgesic drugs and also in the
relaxation of muscles.
• 2. Halogenated ethers such as Isoflurane, Desflurane and many
others are used as effective anaesthesia because of their low
toxicity and flammability.

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• 3. Ethers were used in the treatment of diseases like
scurvy and pulmonary inflammation.

• 4. Antiseptic: Ethers were also used as antiseptics.

During World War II, Ether was used to disinfect the
wounds of patients and save them from deadly
infections. Still, they are used as antiseptics.

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• 5. Recreational Drugs: Due to their intoxicating and
anaesthetic effects, ethers such as diethyl ethers are used
as recreational drugs. This means they cause
unconsciousness and desired effects in drug addicts and
can be used in recreational activities as they are harmless
when taken in therapeutic doses.
•
6. Spirit of Ether: This is a solution of one part diethyl ether
and three parts of alcohol (ethanol) and is used as an
anodyne (pain killer or hypnotic effect).

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 Uses of Ether as Solvents
 Ethers are quite unreactive.
 As a result, they are commonly used as solvents
for oil, fats, resins, wax, perfumes, etc.
 Their ability to form Hydrogen-bonds and combine
with the weak London forces of the alkyl groups
that are bonded to the oxygen makes ethers a
good solvent for a wide range of organic
compounds.

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 Some examples of the use of Ether as solvents
are:
• 1. Diethyl ether -
• commonly used in laboratories as an aprotic solvent. It is
mostly used as a solvent in Grignard’s reactions.
• 2. Tetrahydrofuran (THF) –
• cyclic Ether commonly used as a solvent in organic
compounds. They have a low boiling point that makes their
use more favourable as a solvent because they can be
removed easily after a chemical reaction from the
compound by evaporation.
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• 3. Dimethyl ether (DME) –
• solvent that is quite miscible in water and is
used as a solvent in lithium batteries.

• 4. 1,4-Dioxane -
• cyclic Ether that is soluble in water and is
widely used as a solvent in laboratories for
the synthesis of chemicals.

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 Uses of Ether as Perfuming and Flavouring Agents
 Ethers are widely used in the perfumery
and aroma industry due to their olfactory
and organoleptic properties.
 They provide flavours to a variety of
food and drugs, including fruit-based
foods and beverages, desserts, fruit
jams, yoghurts, ice cream, chewing
gum, or some pharmaceutical
preparations.
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 Common examples:
1. diethyl ether, are particularly useful in
the preparation of perfumes or
perfumed articles, including soaps,
detergents, and household materials in
general use such as essential oils,
medicines, etc.
2. 1-methoxy-3-hexanethiol, imparts the
flavour of grapefruit, giving beverages a
fruity-green, exotic type flavour. 48
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 Common examples:
3. Some ethers are also used in giving salty
aromas, particularly meat-like aromas, to
impart the typical meaty taste to food such as
soups and broths, seasonings, snacks, sauces,
or ready-to-eat non-veg meals.

4. Methoxy benzene (anisole) is commonly used as

a constituent to impart fragrance in the
essential oil of anise seeds.
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 Uses of Ether in Paints
 Ethers are used in dyes and paint industries. e.g.
 Cellulose Ethers- polymers used extensively in paint
industries as thickening agents.
 cellulose ethers are used as adhesives, ceramics, food,
and pharmaceutical industry to provide colours to food
and drugs because they are biodegradable.
 Glycol ether is used as a solvent in spray paints as they do
not dry in mid-air. Due to their slow drying character, they
give smooth and flawless paint to cars.

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 Other Uses of Ether in Our Daily Life
 Ethers are used as cleansing agents e.g. Glycol ether is
used as cleaners for window glasses, carpets, floors, etc.
 Ethers are highly volatile compounds, therefore, their
vapours are used as insecticides, miticides, and fumigants
for soil microorganisms.
 Dimethyl ethers are used to manufacture cosmetic products.

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 Other Uses of Ether in Our Daily Life
Dimethyl ethers (DME) are used as refrigerants
with carbon dioxide in the air conditioning
system for space ground-based infrastructure.
 Aerosol spray propellant.
Dimethyl ethers are used as an alternative fuel
for diesel engines as they are renewable in
nature.
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 Complex Compound of Ether
• There are some very useful ether
compounds besides simple compounds
like dimethyl ether, diethyl ether, and
methoxy benzene. Examples of such
compounds are:
• Crown Ether: Crown ethers are cyclic
chemical compounds that consist of
several ether groups in a cyclic manner.
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Crown Ether:

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 Uses of Crown Ether
• Crown ethers are useful for dissolving ionic
substances such as potassium permanganate in
organic solvents such as isopropanol as they have
cavities of different sizes, hence allows binding of
specific cations and to be solvated with a high
degree of selectivity.

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 Ether Lipid:
 Ether Lipid is a glycerophospholipid in which the SN–1SN–
1 position of the glycerol backbone has a lipid attached by an
alkyl group and a lipid attached to the SN–1SN–1 position by
an acyl group.
 They form a major part of cell membranes in mammals and
even in some anaerobic bacteria’s.
 Ether lipids are also known for their antioxidant properties.

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 Disadvantages of Using Ether
 Ethers are highly flammable compounds that catch
fire very easily. Hence they should be handled with
utmost care in laboratories and industries.
 Under certain conditions, Ether gets oxidised and
turns into an explosive.
 Ether is an anaesthetic, but may lead to nausea and
unconsciousness while working with it chemistry
laboratories.

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 Disadvantages of Using Ether
Uncontrolled exposure to Ether may be toxic to
our health and cause many harmful side effects to
the major organs of our body.

As Ether is a very volatile liquid, its vapour is

dense and will spread around the floor of the
place where it is used and on meeting a flame or
even a small spark cause an explosion.

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 Summary
Ethers are a class of organic compounds having
the general formula R–O–R′,R–O–R′, and they
are very useful in different fields.
Ethers were the first used anesthesia in the
history of the medical field. They are also widely
used in medicines as antiseptics.

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 Summary
 Some common ether compounds, such as dimethyl ether,
diethyl ether, etc., are used as solvents as well as in other
fields like perfumery due to their pleasant smell, food
flavouring techniques, adding colour and flavours to
medicines, paints, and many more.
 Like alcohols, ethers are very useful chemical compounds.
 Toxic exposure to ethers may cause severe side effects to
our health.

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 Safety Considerations:

• Ethers are flammable liquids and should

be handled with care in the laboratory.
• Proper ventilation and storage procedures
should be followed to minimize the risk of
fire and exposure to vapors.

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 Model questions:
• Basic Level:
• Define ether in terms of its chemical structure.
• What is the general formula for ethers?
• Name one common method for synthesizing ethers.
• Describe a physical property of ethers.
• Why were ethers historically significant in medicine?

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 Intermediate Level:
• Compare the boiling points of ethers with alcohols of similar
molecular weight. Explain the difference.
• How does acid-catalyzed dehydration of alcohols lead to the
formation of ethers?
• Discuss the solvent properties of ethers and provide an example of a
common organic compound that is soluble in ether.
• Explain the role of ethers as starting materials in organic synthesis,
providing an example reaction.
• Why are ethers considered relatively inert compared to other
functional groups like alcohols or halides?
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 Advanced Level:
• Investigate the stereochemistry of ethers. How does the orientation of
substituents affect the properties of chiral ethers?
• Discuss the mechanism of the Williamson ether synthesis, including the role
of the alkoxide ion and the alkyl halide.
• Explore the historical development of ether as an anesthetic. What were
some challenges associated with its early use in surgery?
• Analyze the safety considerations associated with handling ethers in
laboratory settings. What precautions should be taken to minimize risks?
• Investigate recent advancements in the use of ethers in organic synthesis or
industrial applications. How have these advancements expanded the utility of
ethers in modern chemistry?

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