1. Ethers, Sulphides and Epoxides
Reference:
Organic Chemistry by Morrison and Boyd
Organic Chemistry by Francis A. Carey
Organic Chemistry Volume 1: The Fundamental Principles by L. Finar
2. Ethers
Structures and nomenclature of ethers
Ethers are compounds of the general formula R–O–R, Ar–O–R, or Ar–O–Ar.
To name ethers we usually name the two groups that are attached to oxygen,
and follow these names by the word ether:
If one group has no simple name, the compound may be named as an alkoxy
derivative:
3. The simplest alkyl aryl ether, methyl phenyl ether, has the special name of anisole.
If the two groups are identical, the ether is said to be symmetrical (e.g., diethyl
ether, diisopropyl ether); if different, unsymmetrical (e.g., tert-butyl methyl ether).
Physical properties of ethers
1. Since the C–O–C bond angle is not 1800
, the dipole moment of the two C–O
bonds do not cancel each other; consequently, ethers possess a small net dipole
moment (e.g., 1.18 D for diethyl ether).
This weak polarity does not appreciably affect the boiling points of ethers, which
are about the same as those of alkanes having comparable molecular weights, and
much lower than those of isomeric alcohols. For example, the boiling points of n-
heptane (980
C), methyl n-pentyl ether (1000
C), and n-hexanol (1570
C).
4. The hydrogen bonding that holds alcohol molecules strongly together is not
possible for ethers, since they contain hydrogen bonded only to carbon.
2. Ethers show very little solubility in water -comparable to that of alcohols - both
diethyl ether and n-butyl alcohol, for example, being soluble to the extent of about
8 g per 100 g water. We attribute the solubility of lower ethers to hydrogen
bonding between water molecules and ether molecules.
3. Ethers cannot furnish an acidic proton for hydrogen bonding. They are
aprotic solvents, but – the simple ones, at least – not very polar, and are
essentially insoluble in water. Diethyl ether is very commonly used to extract
organic materials from an aqueous solution, leaving ionic compounds behind
in the water layer.
Industrial Sources of Ethers. Dehydration of alcohols
A number of symmetrical ethers containing the lower alkyl groups are prepared
on a large scale, chiefly for use as solvents. The most important of these is diethyl
ether, the familiar solvent we use in extractions and in the preparation of
Grignard reagents; others include diisopropyl ether
and di-n-butyl ether.
These ethers are prepared by reactions of the corresponding alcohols with
sulfuric acid. Since a molecule of water is lost for every pair of alcohol molecules,
the reaction is a kind of dehydration.
5. Dehydration to ethers rather than to alkenes is controlled by the choice of reaction
conditions. For
example, ethylene is prepared by heating ethyl alcohol with concentrated sulfuric
acid at 1800
C;
diethyl ether is prepared by heating a mixture of ethyl alcohol and concentrated
sulfuric acid to
1400
C, alcohol being continuously added to keep it in excess.
Dehydration is generally limited to the preparation of symmetrical ethers, because
as we might expect, a combination of two different alcohols usually yields a
mixture of three ethers.
Hazards of using Ethers
1. On standing in contact with air, most aliphatic ethers are converted slowly into
unstable peroxides. Although present in only low concentrations, these peroxides
are very dangerous, since they can cause violent explosions during the distillation
that normally follow extractions with ether.
The presence of peroxides is indicated by formation of a red color when the ether
is shaken with an aqueous solution of ferrous ammonium sulfate and potassium
thiocyanate; the peroxide oxidizes the ferrous ion to ferric ion, which reacts with
thiocyanate ion to give the characteristic blood-red color of the complex.
6. ferrous ion (which reduces peroxides), or distillation from concentrated H2SO4
(which oxidizes
peroxides)
2. Even when the ether is free of peroxides; it is highly volatile, and the
flammability of its vapors
makes explosions and fires ever-present dangers unless proper precautions are
observed.
Absolute Ether
For use in the preparation of Grignard reagents, the ether (usually diethyl) must
be free of traces of water and alcohols. This so-called absolute ether can be
prepared by distillation of ordinary ether from concentrated H2SO4 (which
removes not only water and alcohol but also peroxides), and subsequent storing
over metallic sodium.
Preparation of ethers
The following methods are generally used for the laboratory preparation of ethers.
(The Williamson synthesis is used for the preparation of alkyl aryl ethers
industrially, as well.)
1. Preparation of ethers. Williamson synthesis
In the laboratory, the Williamson synthesis of ethers is important because of its
versatility: it can be used to make unsymmetrical ethers as well as symmetrical
7. In the Williamson synthesis an alkyl halide (or substituted alkyl halide) is allowed
to react with a sodium alkoxide or a sodium phenoxide.
For the preparation of aryl methyl ethers, methyl sulfate, (CH3)2SO4, is frequently
used instead of
the more expensive methyl halides.
8. The Williamson synthesis involves nucleophilic substitution of alkoxide ion or
phenoxide ion for halide ion. Aryl halides cannot in general be used, because of
their low reactivity toward nucleophilic substitution.
In this method, we must consider the danger of elimination competing with the
desired substitution; elimination should be particularly serious here because of
the strong basicity of the alkoxide reagent.
2. Preparation of ethers. Alkoxymercuration-demercuration
Alkenes react with mercuric trifluoroacetate in the presence of an alcohol to give
alkoxymercurial
compounds which on reduction yields ethers.
This two-stage process as the exact analog of the oxymercuration-demercuration
synthesis of alcohols. In the place of water we use an alcohol which can play
exactly the same role. Instead of introducing the hydroxy group to make an
alcohol, we introduce an alkoxy group to make an ether. This example of
solvomercuration-demercuration amounts to Markovnikov addition of an alcohol
to a carbon-carbon double bond.
9. Alkoxymercuration-demercuration has all the advantages we for its counterpart:
speed, convenience, high yield, and the virtual absence of rearrangement.
Comparing with the Williamson synthesis, it has one tremendous advantage:
there is no competing elimination reaction.
Instead of the mercuric acetate which was used in the preparation of alcohols,
here
mercuric trifluoroacetate is used. With a bulky alcohol – secondary or tertiary – as
solvent, the
trifluoroacetate is required for a good yield of ether.
Reactions of ethers. Cleavage by acids
Ethers are comparatively unreactive compounds. The ether linkage is quite stable
toward bases, oxidizing agents, and reducing agents. In so far as the ether linkage
itself is concerned, ethers undergo just one kind of reaction, cleavage by acids:
Cleavage takes place only under quite vigorous conditions: concentrated acids
(usually HI or HBr) and high temperatures.
10. A dialkyl ether yields initially an alkyl halide and an alcohol; the alcohol may
react further to form a second mole of alkyl halide. Because of the low reactivity
at the bond between oxygen and
an aromatic ring, an alkyl aryl ether undergoes cleavage of the alkyl–oxygen bond
and yields a phenol and an alkyl halide. For example:
Ethers as Protecting Groups: Use of Tetrahydropyranyl (THP) Ethers
The unsaturated cyclic ether 2,3-dihydro-4H-pyran (DHP) reacts readily with
alcohols (ROH) in the presence of acid to give tetrahydropyranyl ethers ( RO- THP).
11. Like other ethers, a THP ether is resistant to base and many other reagents, and is
cleaved by acid. However, because of its special structure-there are two ether
oxygens attached to the same carbon, making it acetal- a THP ether is very readily
cleaved by dilute aqueous acid.
The THP group thus has the qualities necessary for a protecting group: it is easily
attached and easily removed, and under conditions that will not harm other
functioning groups in the molecule; and while it is present it is resistant to certain
reagents that would otherwise attack the group it protects.
The –OH group, for example, is acidic and rapidly destroys organometallic
compounds like the Grignard reagents or organolithiums. We cannot, therefore,
prepare a Grignard reagent from organic halide that contains –OH, or allow a
Grignard reagent to react with an aldehyde or ketone that contains an -OH. But if the
–OH is first converted into –OTHP, we can carry out such reactions; and then, when
they are over, simply remove the THP group.
Crown Ethers
Let us first understand cyclic ethers. Most cyclic ethers are analogous to the ethers
we have studied so fat: the chemistry of the ether linkage is essentially the same
whether it forms part of an open chain or part of an aliphatic ring.
12. The rings contain more than one kind of atom, and hence are heterocyclic rings (See
next chapter).
Since divalent oxygen has bond angles not very different from those of carbon, the
rings of cyclic ethers can exist in much the same conformations as the cycloalkane
rings: they can be puckered and if they are small, can be strained.
Ethers cannot furnish an acidic proton for hydrogen bonding. Hence they are aprotic
solvents, but – the simple ones, at least – not very polar and are essentially insoluble
in water. Diethyl ether is very commonly used to extract organic materials from an
aqueous solution, leaving ionic compounds behind in the water layer.
But the oxygen of ethers carries unshared electrons, and through these unshared
pairs ethers can solvate cations. Diethyl ethers and Tetrahydrofurans are the solvents
in which Grignard reagents are usually prepared and used. They are able to dissolve
these important reagents because they strongly solvate the magnesium of the RMg+
cation.
13. Now, crown ethers are cyclic ethers containing several-4,5,6 or more oxygen
atoms. Let us take as our example the crown ether I, which is one of the most
effective and widely used of these catalysts. It is called 18-crown-6, to show that
there are 18 atoms in the ring, of which 6 are
oxygen. As we would expect for a ring of this size, it is puckered.
Thus, crown ethers are phase-transfer catalysts, and very powerful ones.
They are used to transfer ionic compounds into an organic phase either
from a water phase, or more commonly, from the solid crystal.
Let us understand the structure of 18-crown-6. Unfolded, the molecule is shaped
like a doughnut, and has a hole in the middle. Facing into the hole are the oxygen
atoms; facing outward are the twelve -CH2- groups. There is thus a hydrophilic
interior and a lipophilic exterior. The hole has a diameter of 2.7Å.
Now, K+
has a diameter of 2.66 Å and just fits into the hole in the crown,
where it is held by unshared pairs of electrons on the six oxygen atoms. Because
of the close fit and because there are six oxygens, K+
is bound very tightly. The
crown ether is not a solvent, but it holds K+
by the same forces that a solvent uses;
the forces are simply much stronger here.
14. Together, K+
and the crown ether form a new cation. It is lipophilic on the outside, and
has the positive charge buried within the molecule. The lipophilicity makes it soluble
in organic solvents of low polarity. When it enters such solvents, it takes an anion with
it. This anion is shielded from the positive charge on K+
by the bulky crown, thus
forming only loose ion pairs, and is highly reactive.
Figure: 18-crown-6 holding a potassium ion through ion-dipole bonds to the oxygen. Here, violet
color indicates the potassium ion with a diameter of 2.66 Å . The molecule has a hole inside with a
diameter of 2.7 Å, and is lined with oxygens indicated by the red color, and therefore is hydrophilic.
The outside is lipophilic.
15. Analysis of ethers
Because of the low reactivity of the functional group, the chemical behavior of
ethers – both aliphatic and aromatic – resembles that of the hydrocarbons to
which they are related. They are distinguished from hydrocarbons, however, by
their solubility in cold concentrated sulfuric acid through formation of oxonium
salts.
Identification as a previously reported ether is accomplished through the usual
comparison of physical properties. This can be confirmed by cleavage with hot
concentrated hydriodic acid and identification of one or both products. This
process also helps to identify and establish the structure of a new ether.
16. Epoxides
Nomenclature
Epoxides are compounds containing the three-membered ring:
They are ethers, but the three-membered ring gives them unusual properties.
Cyclic ethers have their oxygen as part of a ring – they are heterocyclic compounds.
Three membered heterocycles containing oxygen are called oxirane. The IUPAC
rules also permit
oxirane (without substituents) to be called ethylene oxide.
17. Preparation
By far the most important epoxide is the simplest one, ethylene oxide. It is
prepared on an industrial scale by catalytic oxidation of ethylene by air.
Other epoxides are prepared by the following methods.
1. From Halohydrins.
Example:
18. The conversion of halohydrins into epoxides by the action of base is simply an
adaptation of the Williamson synthesis; a cyclic compounds is obtained because
both alcohol and halide happen to be part of the same molecule. In the presence
of hydroxide ion a small proportion of the alcohol exists as alkoxide; this alkoxide
displaces halide ion from another portion of the same molecule to yield the cyclic
ether.
Since halohydrins are nearly always prepared from alkenes by addition of
halogen and water to the carbon-carbon double bond, this method amounts to the
conversion of an alkene into an epoxide.
19. 2. Peroxidation of carbon-carbon double bonds.
The carbon-carbon double bond may be oxidized directly to the epoxide group by
peroxy compounds, such as peroxybenzoic acid. When allowed to stand in ether or
chloroform solution, the peroxy acid and the unsaturated compound react to yield
benzoic acid and the epoxide. The general reaction is as follows:
The unsaturated compound need not be simple alkene, for example:
20. eact o s o epo des
Epoxides owe their importance to their high reactivity, which is due to the ease of
opening of the highly three-membered ring. The bond angles of the ring, which
average 600
, are considerably less than the normal tetrahedral angle of 109.50
, or
the divalent oxygen angle of 1100
for open-chain ethers. Hence the bonds are
weaker (due to angle strain) than in an ordinary ether, and the molecule is less
stable.
Epoxides undergo acid-catalyzed reactions with extreme ease, and – unlike
ordinary ethers – can even be cleaved by bases. Some of the important reactions
are outlined below:
1. Acid-catalyzed cleavage of epoxides.
Like other ethers, an epoxide is protonated by acid; the protonated epoxide can
then undergo attack by any of a number of nucleophilic reagents.
An important feature of the reaction of epoxides is the formation of compounds
that contain two functional groups. Thus the reaction with water yields a 1,2-diol;
reaction with an alcohol yields a compound that is both ether and alcohol.
23. Base-catalyzed cleavage of epoxides
Unlike ordinary ethers, epoxides can be cleaved under alkaline conditions. Here it
is the epoxide itself, not the protonated epoxide, that undergoes nucleophilic
attack:
The lower reactivity of the non-protonated epoxide is compensated for by the
more basic, more
strongly nucleophilic reagents that are compatible with the alkaline solution:
alkoxides, phenoxides, ammonia, etc.
Examples:
24. Let us look, for example, at the reaction of ethylene oxide with phenol. Acid
catalyzes reaction by converting the epoxide into the highly reactive protonated
epoxide. Base catalyzes reaction by converting the phenol into the more strongly
nucleophilic phenoxide ion.
25. Like carbonyl compounds, epoxides are an important source of electrophilic
carbon: of carbon that is highly susceptible to attack by a wide variety of
nucleophiles.
Reaction of ethylene oxide with Grignard reagents
Reaction of Grignard reagents with ethylene oxide is an important method of
preparing primary alcohols since the product contains two carbons more than the
alkyl or aryl group of the Grignard reagent. As in reaction with the carbonyl group,
we see the nucleophilic alkyl or aryl group of the Grignard reagent attach itself to
the electrophilic carbon of the epoxide, with the formation of a carbon-carbon
bond. Use of higher epoxides is complicated by rearrangements and formation of
mixtures.
Examples:
26. Organic Sulphides
Structure and Nomenclature
Organic sulphides were previously known as Thioethers and have a general formula
of R-S-R, Ar-S-R and Ar-S-Ar. To name sulphides we usually name the two groups that
are attached to sulphur and follow these names by the word sulphide. They are
actually sulphur analogues to ethers. in substitutive nomenclature with "alkylthio-" or
"arylthio-",etc., in place of "alkyloxy-", etc., in radicofunctional nomenclature with
"sulfide" in place of "ether" or "oxide", and for assemblies of identical units with "thio-
" in place of "oxy”.
27. General Methods of Preparation
1. By heating potassium sulphide (K2S) with an alkyl halide, potassium alkyl
sulphate, or a tosylate; e.g.,
K2S + RX = KX + KSR
KSR + RX = R2S + KX
2. Heating an ether with phosphorous pentasulphide:
5R2O + P2S5 = 5R2S + P2O5
3. By heating an alkyl halide with a sodium mercaptide:
R1
X + R2
S-
Na+
= R1
–S–R2
+ NaX
4. By passing a thiol over a mixture of alumina and zinc sulphide at 3000
C:
5. By the addition of a thiol to an alkene in the presence of peroxides; in the
absence of the latter very little reaction occurs (Kharasch et al., 1939)
28. General Properties and Reactions
1. The thioethers or sulphides are unpleasant-smelling oils, insoluble in water but
soluble in organic solvents.
2. Like the ethers, thioethers are weak bases, e.g., they dissolve in 100% sulphuric
acid to form sulphonium salts, [R2SH]+
HSO4
-
.
3. Sulphides may be oxidized to sulphoxides which, on further oxidation, are
converted into sulphones: e.g., ethyl sulphide, on oxidation with hydrogen
peroxide in glacial acetic acid, gives first diethyl sulphoxides and then diethyl
sulphone:
4. Alkyl sulphide readily undergo desulphurisation with Raney nickel:
5. The alkyl sulphide reacts with bromine to form the alkyl sulphide dibromide:
6. Alkyl sulphides combine with a molecule of alkyl halide to form sulphonium
salts, in which the
sulphur is tercovalent unielectrovalent.
29. When the sulphonium salt is heated, it decomposes into the alkyl sulphide and
alkyl halide.
7. When the sulphonium salt is treated with moist silver oxide, the sulphonium
hydroxide is formed:
Sulphonium hydroxides are strongly basic, and on heating form alkyl sulphide
and alkene, e.g.,
THE END
