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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5852_Библиотеки_им_академика_М_И_Перельмана.pdf
C H A P T E R 12 u Alcohols
As there is only one active hydrogen, so 2 g atoms of Na will react with 2 moles of ROH to produce one
mole of H
.
2
— —
—
Ethyl alcohol
Sodium ethoxide
—
441
—
—
Isopropyl alcohol
—
—
Aluminium
isopropoxide
In these reactions alcohols behave as weak acids.
Explanation of acidic character of alcohols
The acidic character of alcohols is due to the presence of polar –OH group. Due to greater electronegativity
of oxygen atom, the shared pair of electrons between O and H atoms is drawn towards the oxygen atom.
This helps in the release of H
+
ions. Thus, alcohols behave as acids.
Alcohol
Alkoxide ion
Alcohols are the weak acids, because alkyl group, due to its +I effect (electron donation) increases the
electron density towards oxygen. As a result, the electron-attracting tendency of oxygen is decreased and
the shared electrons of O–H bond are not sufciently drawn towards oxygen and the release of proton is
rendered difcult. Alcohols are weak acids (K
(Weakest
= 1 × 10
a
alcohol
—
–16
to 10
–18
) even weaker than water (Kw = 10
–14
).
alcohol
—
alcohol
—
Comparison of acidic character of various alcohols
The acidic character of various alcohols is in the order: Primary > Secondary > Tertiary
Explanation: As we move from primary to secondary to tertiary alcohols, the number of alkyl groups
attached to the carbon having the
—
OH group increases from one to two to three. Due to the electron-
releasing inductive effect (+I effect), greater the number of alkyl groups attached to the carbon carrying
442
—
OH group, greater is the electron density on oxygen and lesser is the displacement of electrons of O—H
PH A R M A C EUT I C A L O R G ANIC C H E MIST RY
bond towards oxygen and more difcult is the release of proton.
—
— — —
W
Alcohol
Hence the decreasing order of acidic character of alcohols is 1º > 2º > 3º alcohol.
—
As a result of O
H cleavage, primary alcohols are most reactive and tertiary alcohols are least reactive.
Thus, this is also the order of reactivity of alcohols towards the reaction involving the cleavage of O—H
bond with sodium metal.
Comparison of acidic character of alcohols and water
Dissociation constants of alcohols (Ka = 10
= 10
a
–14
). This clearly indicates that alcohols are weaker acids than even water. This is also supported by
(K
–16
to 10
–18
) are much less than the dissociation constant of water
the following two facts:
1. Water can regenerate alcohols from their alkoxides.
2. Alcohols do not turn blue litmus red.
The weaker acidic character of an alcohol as compared with that of water can be explained on the basis
of electron-releasing inductive effect (+I effect) of alkyl group. Alkyl group due to its +I effect pushes the
shared pair of electrons towards the oxygen atom, thus increasing the electron density on the oxygen atom.
As a result, the electrons of the O
—
H bond are not sufciently attracted towards the oxygen atom and hence
the release of proton becomes difcult.
—
—
Alcohol
Water
We can say that the electron-releasing inductive effect of the alkyl group makes the alcohols weaker acids
than water.
2. Action with organic acids (esterication): When reacted with carboxylic acids in the presence of
small quantity of some dehydrating agent such as concentrated sulphuric acid or dry HCl gas, alcohols form sweet smelling ester. This reaction between an alcohol and carboxylic acid to form ester is
known as esterication.
—
Acid
(Ethanoic acid)
—
—
‘ ‘
Alcohol
Methyl alcohol
(Methanol) (Methyl ethanoate)
−
—
—
Ester
Methyl acetate
The esterication is reversible and hence is pushed forward by the use of any of the reactants (either acid
or the alcohol) or by removing any of the products (removal of water by Dean and Stark apparatus). The
C H A P T E R 12 u Alcohols
CH3CH(OCH )
3
2
bulkier the acid or alcohol, the slower the rate (steric hindrance). The order of reactivity for this reaction
follows the sequence:
a. CH
b. HCOOH > CH3COOH > (CH3)2CHCOOH > (CH3)3C—COOH
OH > CH3CH2OH > (CH3)2CHOH > (CH3)3C—OH
3
(When the reaction is carried out in the presence of dry HCl gas , it is called Fischer–Speier esterica-
tion.)
Mechanism of esterification: The carbonyl group of carboxylic group gets protonated and the protonated
acid is stabilized by resonance. The carboxyl carbon of the protonated acid being electron decient is then
readily attacked by the nucleophilic alcohol molecule. The resulting intermediate successively loses a water
molecule and a proton to yield ester as shown below, all the steps involved being reversible:
443
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
H
—
—
—
—
—
—
O
H
−
2
—
—
—
—
—
—
—
—
——
H
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
+
H
−
3. With aldehydes: Alcohols react with aldehydes in the presence of dry HCl gas to form hemiacetal
and acetals. Aldehyde and ketonic groups are protected by this reaction.
—
—
H
—
C
—
OCH
Acetal
—
—
—
Hemiacetal
OCH
+ H O
3
3
2
—
—
Acetaldehyde
Methyl
alcohol
OH
CH3CHOCH + CH OH
33
Hemiacetal
H lC
CH
—
3
444
PH A R M A C EUT I C A L O R G ANIC C H E MIST RY
4. Action with acid chlorides and acid anhydrides (acylation): When reacted with acid chlorides or
acid anhydrides, alcohols form esters.
This reaction which involves the replacement of hydrogen atom of alcohol (ROH) by acyl group
— —
group are called acylating agents.
is known as acylation and compounds like acid chlorides or anhydrides which supply acyl
–
O
— — —
—
R C Cl+H O R R C R C OR R C OR H+Cl
Acid chloride
Alcohol
Pyridine
O
—
— —
—
Cl
OH
—
+
R
O
—
H
— — — —
—
Cl
O
—
—
Ester
The acylation is usually carried out in the presence of a base such as pyridine or dimethyl aniline.
(CH CO) O +
3
2
CH COCI +
3
HOC H
HOC H
2 5
2 5
Pyridine
Pyridine
CH COOC H + CH COOH
3 2 2 3
CH COOC H + HCl
3 2 5
This reaction is used for protecting hydroxyl group in various reactions.
5. Reaction with Grignard reagent: When treated with Grignard reagent, alcohols form alkanes with
respect to alkyl group of the Grignard reagent.
–δ +δ +δ –δ
ʹ
—
R MgX + H OR R H + Mg
C H MgBr +
2 5
Ethyl magnesium
— —
C H OH
2 5
C H + Br Mg OC H
Ethane
bromide
CH
MgBr
3
+
C H
2
5
OH
CH
2
6
4
X
—
—
OR
—
—
—
—
+ Br Mg OC H
2 5
2 5
CH4 (methane) is evolved quantitatively by the reaction of CH3MgI with active hydrogen compounds like
ROH, RNH
, RSH, etc., and this method is called Zerewitinoff method for estimation of —OH, —NH2,
2
—SH groups in organic compounds.
6. Reaction with inorganic acids: Alcohols react with inorganic acids (except halogen acids) to form
inorganic esters.
C H O
5
2
H + HO NO
—
2
Nitric acid
C H O H + HO SO OH
5
2
——
2
Sulphuric acid
C H O NO + H O
—
5
2
Ethyl nitrate
2 2
C H OSO OH + H O
5
2
2 2
Ethyl hydrogen
sulphate
C H A P T E R 12 u Alcohols
7. Alkylation: Alcohols react with dialkyl sulphates to form ethers.
—
—
Dimethyl sulphate
Ethyl methyl ether
Methyl
Reaction involving cleavage of R—OH bond
Note: Energy required to break C— O bond is 81.5 kcal/mol.
1. Reaction with halogen acids: When treated with halogen acids, alcohols form alkyl halides. The
reaction is carried by passing dry hydrogen halides into heated alcohol or by heating the alcohol with
concentrated hydrogen halides solution.
Alternatively, good yield of alkyl iodides may be obtained by heating alcohols with sodium or potassium
iodide in 95% phosphoric acid.
Order of reactivity of hydrogen halides is HI > HBr > HCl
This is due to the fact that I– is a better nucleophile than Br–, which in turn is better than CI– ion.
Order or reactivity of alcohol is 3º > 2º > 1º.
Thus tertiary alcohols are most reactive and primary alcohols are least when there is cleavage of C
—
O
bond.
a. With hydrogen chlorides: For primary and secondary alcohols, hydrogen chloride is used in the
presence of zinc chloride but tertiary alcohols react readily with concentrated hydrochloric acid in
the absence of zinc chloride.
445
C H OH +
2 5
Ethyl
alcohol
(CH ) COH + Conc. HCl
3 3
HCl (g)
Anhyd. ZnCl
2
C H CI + H O
2 5
Ethyl chloride
(Chloroethane)
(CH ) CCI + H O
3 3 2
2
b. With hydrogen bromide: Constant boiling hydrobromic acid (48%) reacts with alcohols to alkyl
bromide. The reaction is carried out in the presence of a little concentrated sulphuric acid (as catalyst) for primary alcohols but not for secondary and tertiary alcohols since these tend to dehydrate
to alkenes.
Ethyl alcohol
(Ethanol)
Ethyl bromide
(Bromethane)
c. With hydrogen iodide: Upon constant boiling 57% HI reacts with alcohols to form alkyl iodides.
HI
Methyl alcohol
(Methanol)
H I
Methyl iodide
(Iodomethane)
446
( )Methanol
( )lodomethane
PH A R M A C EUT I C A L O R G ANIC C H E MIST RY
Note: If, however, an alcohol is heated with conc. HI in presence of red phosphorous, it is reduced to an
alkane. Thus
HI
I
Ethanol
2. Reaction with phosphorus halides (PX3 or PX5): It is a good method for replacing hydroxyl group
of alcohol by halogen atom and involves the action of PCl
Alkyl trihalides are prepared in situation from P and corresponding halogen (X
, PCl3, PBr3, PI3 to form an alkyl halide.
5
).
2
a. With PCl5: Alcohols react with PCl5 to form alkyl chlorides, phosphoryl chloride and HCl.
— —
R O H + PCI R Cl + POCl + HCl
5 3
Alcohol Phosphorus
pentachloride
PCl
Ethyl alcohol
(Ethanol)
Ethyl chloride
(Chlorethane)
—
Cl
Phosphoryl
chloride
POCl
Cl
b. With PX3: Alcohols react with phosphorus trihalides to form alkyl halide and phosphorus acid.
Phosphorus
trihalide
P + Cl
3
2
3C H CI +
Ethyl chloride
( )Chloroethane
H PO
3 3
With PCl
Alcohol
3
3C H OH + PCl
2 5 2 5
Ethyl alcohol
( )Ethanol
With PBr
3
Ethyl alcohol
(Ethanol)
With PI
3
CH OH + 2P + 3 H PO
6
3 3
Methyl alcohol
In the preparation of alkyl bromides and iodides, PBr3 or PI3 required for the reaction is generally obtained
in situ by the action of red phosphorus on bromine or iodine.
I
P + I
2
Ethyl bromide
(Bromoethane)
2
6CH I +
Methyl iodide
2
3 3
C H A P T E R 12 u Alcohols
OH + H
NH
C H
2
5
AI O
2
3
633 K
C H OH + H
2
AI O
2
3
633 K
C H NH +
2
5
2
5
NH
2
H O
C H N
2
5
C H
2
5
C H OH
2
5
Al O , 633 K
C H ) N + H O
2
5
3
(
2
2
3
H
2
Ethylamine (1º)
C H NH C H
2
5
2
5
C
H
2 5
Diethylamine (2º)
Diethylamine (2º)
Triethylamine (3º)
—
—
—
—
—
—
— —
—
CH3CH
2
OH
Ethyl alcohol
( )Ethanol
Conc. H SO
2 4
443 K
CH CH + H O
2 2 2
Ethylene
( )Ethene
—
—
3. Reaction with thionyl chloride (SOCl2): Alcohols react with thionyl chloride in presence of mild
base like pyridine to form alkyl chlorides.
447
Propyl alcohol
(Propanol)
Propyl chloride
(Chloropropane)
This method, known as Darzen's method, has advantage over phosphorous chloride because the byproducts SO
and HCl are gases which can be removed easily from the reaction mixture.
2
Note: Thionyl bromide is unstable and thionyl iodide does not exist.
4. Reaction with ammonia: When a mixture of the vapours of alcohol and ammonia are passed
overheated alumina (Al2O3) at 633 K, a mixture of 1º, 2º and 3º amines are produced.
Other reactions (involving both the alkyl and hydroxyl groups)
1. Dehydration: Alcohols may be dehydrated to alkenes or ethers depending upon the reaction condi-
tions. Ease of dehydration of alcohol is 3º > 2º > 1º.
a. Formation of alkenes: When alcohols are heated with concentrated sulphuric acid (433–444 K)
or by passing the vapours overheated Al
at 630 K, they get dehydrated to alkenes.
2O3
Methanol is not dehydrated as it contains only one carbon atom.
— —
—
Alcohol
Different types of alcohols require different conditions.
—
—
Butyl alcohol
—
—
Alkane
—
—
448
PH A R M A C EUT I C A L O R G ANIC C H E MIST RY
Formation of unexpected alkenes
CH
—
3
—
—
CH C OH
—
3
CH
3
tert-Butyl alcohol
(2-Methylpropan-2-ol)
20% H SO
2
363 K
4
CH
—
3
—
CH C + H O
3
CH
2
2
Isobutylene
( )Methyl propene
Mechanism of dehydration of alcohol to alkene
The reaction proceeds as follows in three steps:
1. Protonation of alcohol: Due to the presence of two lone pairs of electrons on oxygen, alcohols are
easily protonated by strong acids to form oxonium ions.
H SO
2 4
— —
H C CH O H
3
—
2
+
+ H
From
H SO
2 4
+
H +
— —
CH3CH
Protonated
alcohol (Oxonium ion)
H SO
2 4
2
–
+
—
O H
—
H
In this step, the alcohol acts as a base.
2. Loss of water molecule: The presence of positive charge on the highly electronegative oxygen atom
weakens the C–O bond. Therefore, the protonated ethyl alcohol easily eliminates molecule of water
to form ethyl carbocation.
— — —
CH
CH
3
2
+
O H
—
H
Slow
+
—
CH
3
CH
+ H O
2
Carbonium ion
2
Protonated
ethyl alcohol
It is a slow step and hence is rate-determining step of the reaction.
3. Formation of alkene: The carbocation formed in step (2) being a reactive species readily loses a
proton from the carbon to form ethane.
HHH
—
—
—
—
—
+
—
H C C + HSO
H
_
4
H H
—
—
—
H C C + H SO
—
2 4
H
The ease of dehydration of alcohols can be explained on the basis of stability of the intermediate carbocation formed in step (2). Greater the stability of the carbocation formed, greater will be the rate of the reaction. The order of stability of carbocation formed is:
C H A P T E R 12 u Alcohols
449
—
—
Butyl
—
Isopropyl
This is due to the electron releasing (+I) effect of the alkyl groups. Therefore, the ease of dehydration of
alcohols follows the order:
Tertiary > secondary > primary alcohol
b. Formation of ethers: If excess of alcohol is heated with conc. H2SO4 at 413 K, ether is formed. The
carbonium ion formed during the protonation of alcohol with conc. H
is attacked by the second
2SO4
alcohol molecule to form ether:
+
CH3 + H2O
+
H
— —
—
Ethyl methyl ether
—
—
—
Ethyl alcohol
—
CH3 OH
—
Ethers are also formed when the vapours of alcohol are passed overheated alumina at 513–523 K.
— —
4
— —
(Two molecules)
(
2. Action of conc. H2SO4 on ethyl alcohol under different conditions: When ethyl alcohol is heated
with conc. H
at 383 K, ethyl hydrogen sulphate is formed.
2SO4
383 K
Ethyl alcohol
sulphate
a. When ethyl hydrogen sulphate is heated under reduced pressure, it forms diethyl sulphate.
∆
2C H HSO
5
2
4
(
C H ) SO + H SO
252 4 2 4
Diethyl sulphate
b. When ethyl hydrogen sulphate is heated with excess of alcohol at 413 K, it forms diethyl ether.
C2H5HSO4+ HOC H C H O C H + H SO
413 K
Ethyl
hydrogen
sulphate
—
2 5 2 22 5
Diethyl ether
—
5 4
450
PH A R M A C EUT I C A L O R G ANIC C H E MIST RY
c. When ethyl hydrogen sulphate is heated with excess of sulphuric acid at 433–443 K, ethylene is
produced.
3. Oxidation: 1º, 2º and 3º alcohols give different products
on oxidation. Acidied sodium or potassium dichromate
or acidied or alkaline potassium permanganate or dilute
nitric acid are commonly employed to bring about oxidation.
a. 1º alcohols on oxidation with acidied potassium
dichromate (K2Cr2O7 + H2SO4) is rst oxidized to aldehyde and then to carboxylic acid containing the same number of carbon atoms as the original
alcohol. If the acidied Na
formation of Cr
H
—
— —
CR OH + [O]
—
H
Alcohol
H
—
—
—
CH C OH + [O]
—
3
H
Ethanol
(SO4)3.
2
(K Cr O + H SO )
2 2 7 2 4
(K Cr O + H SO )
2 2 7 2 4
–H O
is used then its colour changes from orange to green due to the
2Cr2O7
—
CH C O
2
Tertiary alcohol resist to oxidation due to lack of
a-hydrogens.
H
CR
—
—
—
–H O
OH C R O
2
OH
H
—
—
3
[O]
—
Aldehyde
—
CH
3
H
—
O
C OH
Ethanal Ethanoic acid
REMEMBER
[O]
—
OH
—
—
R C O
Carboxylic acid
b. 2º alcohols upon oxidation rst give ketones which on vigorous oxidation form carboxylic acids.
Thus, the orange colour of the acidied Na2Cr2O7 changes to green.
—
—
—
Isopropyl alcohol
(2-Propanol)
—
—
It may be noted that secondary alcohols and ketones have the same number of carbon atoms but the
carboxylic acids contain fewer carbon atoms than either the ketone or secondary alcohol.
In case of unsymmetrical ketones, the splitting of the ketonic chain takes place according to Popoff’s
rule, which states that during oxidation of ketones, the carbonyl group prefers to remain attached to the
smaller alkyl group.
C H CH
5
2
2
—
—
CH
3
2º Alcohol
CHOH
[O]
C H CH
5
2
CH
Ketone
—
2
C
—
3
O
[O]
CH CH COOH + CH COOH
3
2
3