Ether and epoxides

Introduction to Ether & Epoxides:

We know alcohols family with their rich chemical reactivity but ethers - compounds containing a R-O- R unit are less reactive and

gives relatively few chemical reactions. This lack of reactivity of ether makes them valuable as inert solvents in a number o f

chemical reactions.

Unlike most ethers, epoxides compounds in which the C O C unit forms a three-membered ring - are very reactive substances

due to molecular strain.

Ethers are defined as symmetrical or unsymmetrical depending on whether the two groups bonded to oxygen are the same or

different. Unsymmetrical ethers are also called mixed ethers. Dimethyl ether is a symmetrical while ethyl methyl ether is an

unsymmetrical ether.

Cyclic ethers have their oxygen as part of a ring. They are heterocyclic compounds. Oxygen heterocycles of commonly

encountered ring sizes have specific IUPAC nomenclature.

In each case the ring is numbered starting at the oxygen. The IUPAC rules also permit oxirane (without substituents) to be ca lled

ethylene oxide. Tetrahydrofuran and tetrahydropyran are acceptable synonyms for oxolane and oxane, respectively.

There are many compounds, often used as reaction solvents, are the

diethers

1,2,-dimethoxy ethane and 1,4-dioxane. Diglyme, also a commonly used solvent, is a

tri ether

The sulfur analogs (RS ) of alkoxy groups are called

alkyl thio

groups while RSH are known as alkane thiol. Sulfur hetero cycles have names analogous to their oxygen relatives, except that

ox

- is replaced by

thi-

Thus the sulfur heterocycles containing three-, four-, five-, and six- membered rings are named

thiirane, thietane, thiolane,

& thiane respectively.

Structure and bondangle in ethers and epoxides

Structure and bondangle in ethers and epoxides

Bonding in ethers is readily understood by comparing ethers with water and alcohols. Van der Waals strain involving alkyl groups

causes the bond angle at oxygen to be larger in ether than alcohols, and larger in alcohols than in water. An extreme example is di-

Isopropyl ether, where steric hindrance between the isopropyl groups is responsible for a dramatic increase in the C O C bond

angle.

Carbon-oxygen bond distances are some what shorter than carbon-carbon bond distances. The C O bond distances in dimethyl

ether (141 pm) and methanol (142pm) are similar to one another, and both are shorter than the C C bond distance in ethane (153

pm).

Insertion of an oxygen atom into a three-membered ring requires its bond angle to be seriously distorted form the normal

tetrahedral value. In ethylene oxide, for example, the bond angle at oxygen is 61.5.

Thus epoxides, like cyclopropanes, are strained. They tend to undergo reactions that open the three-membered ring by cleavage of

one of the carbon-oxygen bonds.

Physical properties

Physical properties of ethers are very similar with alkanes and alcohols. With respect to boiling point, ethers resemble alkanes

more than alcohols due to less polarity than alcohol while; with respect to solubility in water, ethers resemble alcohols more than

alkanes due to Hbonding with water.

In general, the boiling point of alcohols are unusually high because of hydrogen bonding. Attractive forces are present in liquid

phase of ethers and alkanes, but lack OH groups so cannot take part in intermolecular hydrogen bonding, are much weaker, so

their boiling points are less.

If we think about structure of ether, the presence of an oxygen atom permits ethers to participate in hydrogen bonding to water

molecules. These attractive forces are responsible for solubility of ethers in water to approximately the same extent as comparably

constituted alcohols. Alkanes cannot take part in hydrogen bonding with water.

Crown ethers

Cyclic compounds containing 4 or more ether linkages in a ring of 12 or more atoms. these compounds is known as

crown ethers

, because their molecular models are similar to crowns. Systematic nomenclature of crown ethers is actually a short hand

description where by the word

crown

is followed by the total number of atoms in the ring and is followed by the number of oxygen atoms.

15-Crown-5 and 18-crown-6 are a cyclic pentamer and hexamer, respectively, of repeating -OCH2CH2- units; they are polyethers

based on ethylene glycol (HOCH

2CH2OH) as the parent alcohol.

The metal ion-complexing nature of crown ethers are explain by their effects on the solubility and reactivity of salts in nonpolar

solvents. Potassium fluoride is ionic and insoluble in benzene (covalent), but 0.05

M

solutions can be prepared when 18-crown-6 is present. This high solubility of potassium fluoride in benzene is explain by the

formation of a stable complex, cage like structure, is stabilized by ion-dipole forces between K+

and the six oxygen atoms of the crownether. Potassium ion, with an ionic radius of 265 pm, adjust completely with in the 260- to

320-pm inside cavity of 18-crown-6. Nonpolar CH2

groups dominate the outer side of the complex, make its polar interior, and permit the complex to soluble in nonpolar so lvents such

as covalent benzene. Every K+

that is carried into benzene brings a fluoride ion (F) with it, resulting in a solution containing strongly complexed potassium ions

and relatively unsolvated fluoride ions.

In polar matrix such as water and alcohols, fluoride ion is strongly solvated by hydrogen bonding and is neither very basic nor very

nucleophilic. On the other part, the poorly solvated, or naked, fluoride ions that are present when potassium fluoride dissolves in

benzene in the presence of a crown ether are better able to express their anionic reactivity. Thus, alkyl halides react with ionic

potassium fluoride in covalent benzene solvent like 18-crown-6, easily gives a method of the preparation of different floride.

Preparation

Preparation

(i) Willamsons continous ethrification

Diethyl ether and many others, for example, are prepared by acid-catalyzed reaction of the corresponding alcohols, as we already

studuied in alkenes, known as williamson contineous etherification.

In general, this method is limited to the preparation of symmetrical ethers in which both alkyl groups are primary. Isopropyl

alcohol, however, is readily available at low cost and gives yields of diisopropyl ether high enough to justify making

(CH3)2CHOCH(CH3)2

by this method on an industrial approach.

(ii) Williamson synthesis

A method of long standing for the preparation of ethers is the Williamson ether synthesis. Nucleophilic substitution of an alkyl

halide by an alkoxide gives the carbon-oxygen bond of an ether.

Preparation of ethers by the Williamson ether synthesis is most successful when the alkyl halide is one that is reactive toward SN

2 substitution. Methyl halides and primary alkyl halides are the best reactants (least reactive in elimination).

Secondary and tertiary alkyl halides are not suitable reactants, because they tend to react with alkoxide base by E2 elimination

rather by SN

2 substitution. Whether the alkoxide base is primary, secondary, or tertiary is not very important than the nature of the alkyl halide.

Thus benzyl terbutyl ether is prepared in high yield from benzyl chloride, a primary chloride that is incapable of undergoing

elimination, with potassium ter. butoxide (base).

The alternative synthetic route using the sodium salt of benzyl alcohol and an terbutyl halide would be much less effective, because

of increased competition from elimination, as the alkyl halide becomes 3 than it easily undergo elimination.

We take some following example also, always prefer alkyl halide as primary.

The alternative combination, cyclohexyl bromide and sodium ethoxide, is not correct, because elimination will be the major

product.

(iii) Oximercuration demercuration of alkenes

Addition of ROH according to marknownikoffs rule without any molecular rearrangement occurs.

Alcohol with diazomethane

(iv) Alcohol with diazomethane

(v) Alkyl halide with dry Ag2O

This reaction is not carried out with moist Ag

2

O because moist Ag

2

O is actually AgOH where substitution occurs and formation of alcohols from alkyl halide takes place.

Chemical properties

(i) Oxidation

Ether are less reactive due to absence of polarity, along with an ability to soluble in nonpolar substances like CCl4, that makes

ethers so often used as solvents when carrying out many organic reactions. Nevertheless, most ethers are explosive and hazardous

materials, and precautions must be taken when using them. Diethyl ether is extremely flammable and because of its high volati lity

can form explosive mixtures in air very quickly. Open flames must never be present in laboratories where diethyl ether is being

used regularly.

A second dangerous property of ethers is when they undergo oxidation in presence of air to form explosive peroxides. Where air

oxidation of diethyl ether gives explosive strained peroxide proceeds according to the following equation.

The reaction is a free-radical type, and oxidation occurs at the carbon that contain the ether oxygen to form a hydroperoxide, a

compound of the type ROOH. Hydroperoxides tend to be unstable and shock-sensitive due to molecular strain. On standing, they

form related peroxidic derivatives, which are also. Due to this, one should never use old bottles of dialkyl ethers, and extreme care

must be taken in their uses.

(ii) Acidcatalyzed fission of ethers

When the carbon-oxygen bond of alcohols is undergo fission on reaction with hydrogen halides, just similar to an ether linkage

undergo breaking with hydrogen halides.

The fission of ethers is generally carried out under conditions like excess hydrogen halide, cold or hot HX, such that the alcohol

formed as one of the original products and by heating converted to an alkyl halide. Thus, the reaction with hot HX finally gives

two alkyl halide molecules :

Cyclic ethers yield one molecule of a dihalide :

The order of hydrogen halide reactivity is HI>HBr >HCl. Hydrogen fluoride is not effective so normally not considered in organic

chemistry.

A mechanism for the cleavage of diethyl ether by hydrogen bromide is given below where the key is an S

N

2-like attack on a dialkyloxonium ion by bromide.

Overall Reaction :

Overall Reaction :

Mechanism of reaction

Step A :

Ether reacts with proton to give a dialkyloxonium ion (oxonium salt)

Step B :

Halide attack on carbon of the dialkyloxonium ion. This step gives each molecule of an alkyl halide and an alcohol.

Step C :

In last step where an alcohol is converted to an alkyl halide.

(iii) Reaction with HI (fission reaction)

Reaction with HI is an example of fission reaction where cleavage is decided by structure of ether. If there is smaller alkyl group

up to secondary than fission is S

N

2 so back attack of nucleophile occurs while for large alkyl group always fission by S

N

1 mechanism because they prefer carbocation mechanism.

When ethers reacts with cold HI to form one mole of alkyl iodide. This when reacts with silver nitrate to form yellow precipitate of

AgI.

By finding out the weight of AgI we can find out the structure of ether. This method is known as of

zeisals method

for estimation of alkoxy group in the molecule for example.

Problem

0.74 gm of methyl ether forms 2.35 gm of AgI at NTP find out sturcture of methyl ether ?

(iv) Reaction with dil H2SO4

(v) Reaction with CO

Reaction with Lewis Acids

(vi) Reaction with Lewis Acids when reacts with Lewis acid to form acid base complex (oxonium salt.)

(vii) Oxidation with acidic K2Cr2O7

Epoxides (cyclic ether)

Preparation

There are two main laboratory methods for the preparation of epoxides :

(1) Epoxidation of alkenes by reaction with peroxy acids

The reaction is easy to carry out, and yields are usually high. Epoxidation is a stereospecific syn addition.

(2) Conversion of vicinal halohydrins to epoxides

The formation of vicinal halohydrins from alkenes was already described in hydrocarbon. Halohydrins are readily converted to

epoxides on treatment with base.

Properties

The chemical property that differ epoxide from normal inert ether is their far greater reactivity toward nucleophilic reagents

compared to simple ethers. This high reactivity results from the ring strain of epoxides.

An example of nucleophilic ring opening of epoxides in Grignard reagent, where Grignard reagents with ethylene oxide is used to

steeping up in alcohol series.

Nucleophiles other than Grignard reagents also responsible for ring opening of epoxides. There are two medium in which these

reactions are carried out.

The first involves anionic nucleophiles in neutral or basic solution.

These reactions are carried out in water or alcohols as solvents, and the alkoxide ion intermediate is rapidly changes in to an

alcohol by proton transfer.

Nucleophilic ring-opening reactions of epoxides may also be catalysed by acidic medium where the nucleophile is not an anion but

rather a solvent molecule.

There is very important difference in the ring-opening chemistry of epoxides depending on the reaction medium.

Unsymmetrically substituted epoxides tend to react with anionic nucleophiles in basic medium at the less hindered carbon of the

cycle. While under conditions of acid catalysis, the more highly substituted carbon is attacked because partial carbocation character

comes in this condition so molecule tends to prefer more stable intermediate.

Ring?cleavage reactions of epoxides by base catalysed

Ethylene oxide very reactive substance, reacts rapidly and exothermically with anionic nucleophiles to yield 2-substituted

derivatives of ethanol by cleaving the carbon-oxygen bond of the ring for example used for stepping up carbon atom in many

family.

Nucleophilic ring opening of epoxides has many of the features of an SN

2 reaction. Inversion of configuration is observed at the carbon at which substitution occurs.

Unsymmetrical epoxides prefer to attack at the less substituted, less sterically hindered carbon of the ring in basic medium while

opposite in acidic medium.

According to the mechanism the nucleophile attacks the less crowded carbon from the back side of the carbon-oxygen bond. Bond

formation with the nucleophile followed by carbon-oxygen bond cleavage, and the strain in the three-membered ring is gone as it

follows the opening of this ring from transition state. In this reaction initially an alkoxide anion is formed, which finally absorb a

proton from the solvent to give a

alcohol as final product.

Epoxides reduction takes place by lithium aluminum hydride or NaBH4

these are hydride donar so hydride is transferred to the less crowded carbon.

Remember here that epoxidation of an alkene, followed by lithium aluminum hydride reduction of epoxide, gives the same alcoho l

that would be given by same alkene by acid-catalyzed hydration or oxymercuration-demercuration.

(ii) Ringcleavage reaction of epoxides by acid-catalyzed

Here we discuss the preparation of ethylene glycol (HOCH2CH2

OH) by hydrolysis of ethylene oxide in dilute sulfuric acid. There is a significant difference between the ring openings of epoxides

the acid-catalyzed. Under conditions of acid catalysis, the species that is attacked by the nucleophile is not the epoxide itself, but

rather its conjugated acid. The transition state for ring opening has a fair amount of carbocation character so the total system

undergo strain. Breaking of the ring carbon-oxygen bond is more advanced than formation of the bond to the nucleophile.

Because carbocation character develops at the transition state, substitution is prefer at the carbon that can better support a

developing positive charge or stabilises intermediate. Thus, in comparison to the reaction epoxides with relatively basic med ium, in

which SN

2- like attack is faster at the less crowded carbon of the epoxide ring, acid catalysis promotes just opposite at the position that bears

the more number of alkyl groups for example.

Here substitution proceeds with inversion of configuration for example back attack of nucleophile takes place so trans product are

formed in these reactions.s

Deoxygenation of oxiranes

Although there is no general way to de oxygenate ethers, but oxiranes can be deoxygenated

(reduced) to alkenes by certain trivalent phosphorous compounds for example.

In this reaction oxirane derivatives which are originally cis end up trans in the alkene product

and vice versa so this reaction could be quite valuable. While per acids epoxidation preserves

the stereochemistry of the alkene, deoxygenation of the alkene, deoxygenation by the above

path create inversion of configuration

Mechanism

A nucleophilic ring opening of the oxirane at its less hindered carbon, formation of dipolar

ion that undergoes bond rotation followed by ring closure to the strained oxaprosphetane

(unstable) ultimately gives final product.

Problems

Find the products of following reaction and give stereochemistry where appropriate.

Answers:

(a) PhOH + ICH2Ph, SN

2 cleavage at the alkyl, as opposed to aryl, carbon of the protonated ether.

(b) (H3C)2CHOH + BrC(CH3)3, SN

1 cleavage at the more Su.

Ring?cleavage reactions of epoxides by base catalysed

Ethylene oxide very reactive substance, reacts rapidly and exothermically with anionic nucleophiles to yield 2-substituted

derivatives of ethanol by cleaving the carbon-oxygen bond of the ring for example used for stepping up carbon atom in many

family.

Nucleophilic ring opening of epoxides has many of the features of an SN

2 reaction. Inversion of configuration is observed at the carbon at which substitution occurs.

Unsymmetrical epoxides prefer to attack at the less substituted, less sterically hindered carbon of the ring in basic medium while

opposite in acidic medium.

According to the mechanism the nucleophile attacks the less crowded carbon from the back side of the carbon-oxygen bond. Bond

formation with the nucleophile followed by carbon-oxygen bond cleavage, and the strain in the three-membered ring is gone as it

follows the opening of this ring from transition state. In this reaction initially an alkoxide anion is formed, which finally absorb a

proton from the solvent to give a

alcohol as final product.

Epoxides reduction takes place by lithium aluminum hydride or NaBH4

these are hydride donar so hydride is transferred to the less crowded carbon.

Remember here that epoxidation of an alkene, followed by lithium aluminum hydride reduction of epoxide, gives the same alcoho l

that would be given by same alkene by acid-catalyzed hydration or oxymercuration-demercuration.

(ii) Ringcleavage reaction of epoxides by acid-catalyzed

Here we discuss the preparation of ethylene glycol (HOCH2CH2

OH) by hydrolysis of ethylene oxide in dilute sulfuric acid. There is a significant difference between the ring openings of epoxides

the acid-catalyzed. Under conditions of acid catalysis, the species that is attacked by the nucleophile is not the epoxide itself, but

rather its conjugated acid. The transition state for ring opening has a fair amount of carbocation character so the total system

undergo strain. Breaking of the ring carbon-oxygen bond is more advanced than formation of the bond to the nucleophile.

Because carbocation character develops at the transition state, substitution is prefer at the carbon that can better support a

developing positive charge or stabilises intermediate. Thus, in comparison to the reaction epoxides with relatively basic med ium, in

which SN

2- like attack is faster at the less crowded carbon of the epoxide ring, acid catalysis promotes just opposite at the position that bears

the more number of alkyl groups for example.

Here substitution proceeds with inversion of configuration for example back attack of nucleophile takes place so trans product are

formed in these reactions.s

Deoxygenation of oxiranes

Deoxygenation of oxiranes

Although there is no general way to de oxygenate ethers, but oxiranes can be deoxygenated (reduced) to alkenes by certain

trivalent phosphorous compounds for example.

In this reaction oxirane derivatives which are originally cis end up trans in the alkene product and vice versa so this reaction could

be quite valuable. While per acids epoxidation preserves the stereochemistry of the alkene, deoxygenation of the alkene,

deoxygenation by the above path create inversion of configuration

Mechanism

A nucleophilic ring opening of the oxirane at its less hindered carbon, formation of dipolar ion that undergoes bond rotation

followed by ring closure to the strained oxaprosphetane (unstable) ultimately gives final product.

Problems

Find the products of following reaction and give stereochemistry where appropriate.

Answers:

(a) PhOH + ICH2Ph, SN

2 cleavage at the alkyl, as opposed to aryl, carbon of the protonated ether.

(b) (H3C)2CHOH + BrC(CH3)3, SN

1 cleavage at the more Su.