ALCOHOLS
CH4 R OH
R can be any alkyl or substituted alkyl group
The group may be primary, secondary or tertiary alkyl
May be open chain or cyclic
May contain a double bond, a halogen atom or an aromatic ring
OH
OH OH
OH
H3C CH3 H2C
CH3
tert-butyl alcohol Allyl alcohol Cyclohexanol Benzyl alcohol
Cl OH OH OH OH
Ethylene chlorhydrin Glycerol
(2-chloro ethanol)
Characteristic properties of these compounds are due to -OH group
Compounds in which -OH is directly attached to the phenyl group are not classified as alcohols; they
are called phenols, an entirely different chemical class.
Classification
H R R
HO R HO R HO R
H H R
1o 2o 3o
Oxidation is one reaction in which all the three types of alcohols behave differently; usually however,
alcohols of different classes differ only in rate or mechanism of reaction and in a way consistant with
their structures.
Looks like primary, but
OH behaves like tertiary alcohol
Nomenclature
Common names
OH
H3C
Propyl alcohol
Carbinol system
OH
H3C H3C OH (Carbinol) HO
Ethyl carbinol
Triphenyl carbinol
IUPAC system
OH OH
OH
H3C
H3C CH3 H3C CH3
Cl
Propanol HO O
3-chloro-Pent-2-ol 2-ethyl-3-hydroxy-
butanoic acid
Physical Properties
R O H O R O H O
H R H H
Hydrogen bond between Hydrogen bond between
two alcohol molecules alcohol and water
(Increases boiling point) (Increases solubility)
Methods of preparation
Oxymecruration demercuration
Hydroboration oxidation
Grignard synthesis
Hydrolysis of alkyl halides
Aldol condensation
Reduction of carbonyl compounds
Reduction of acids and esters
Hydroxylation of alkenes
Alcohols can be made convenientyl from alkenes in two ways: Oxymercuration-demercuration
(involving Markovnikov addition) and hydroboration-oxidation (Anti-Markovnikov addition).
Oxymecruration demercuration
O A A
A O CH3 NaBH4
H H
CH2 + Hg + H2O
H O OH Hg OAc OH H
CH3
O Markovnikov
Mercuric acetate addition
CH3
CH3 H
H3C CH2
CH3
HgOAc2
+ H2O H3C CH3
CH3 OH
3,3-dimethyl-but-1-ene 3,3-dimethyl-butan-2-ol
Hydroboration-Oxidation
A A
–
A H 2O 2 HO
H H
CH2 + H2B BH2
H OH
H H BH2
Diborane Antimarkovnikov
alkyl borane
addition
CH3
H2B BH2 – CH3 H
H 2O 2 HO
H3C CH2
H3C
CH3
OH
CH3 H
3,3-dimethyl-but-1-ene 3,3-dimethyl-butan-1-ol
By these methods, alcohols of same carbon skeleton as that of the reactants are obtained.
By far the most important method of preparing alcohols is the Grignard synthesis. It results in
generation of new, bigger carbon skeleton of alcohols.
Grignard synthesis C=O: Carbonyl group
A
A A
– + H2O 2+
O + R Mg X A O Mg X A OH + Mg
A R
Alkyl magnesium halide R
(Grignard reagent) General reaction
H
H H
– + H2O 2+
O + R Mg X H O Mg X H OH + Mg
H R
R
Formaldehyde Primary alcohol
RCHO H
H H
1 – + H2O
1 2+
O + R Mg X R O Mg X R OH + Mg
1 R
R
R
Secondary alcohol
Higher aldehyde
2
2 R 2
R R
1 – + H2O
1 2+
O + R Mg X R O Mg X R OH + Mg
1 R
R
R
Ketone RR'CO Tertiary alcohol
O – + H2O OH
O Mg X
+ R Mg X
R
R
Ethylene oxide
R
O R Mg X R
1 H2O
R + R
1
O
–
Mg X R
1
OH + Mg
2+
O C 2H 5 R Mg X
R
R
Tertiary alcohol
This method leads to alcohols with formation of new carbon-carbon bonds, thus resulting in alcohols
with bigger carbon skeletons than the reactants.
Examples of Grignard synthesis
O Mg
H3C
Mg
Br
+ H
H3C O Br
H CH3
CH3
Sec- Butylmagnesium Formaldehyde H2O
bromide
H
H3C O
CH3
2-Methyl-1-butanol
A 1o alcohol
H 3C
CH3 H
O CH 3
Mg
H3C Br + H3C H 3C
H
Acetaldehyde O
Mg
isoButylmagnesium
bromide Br
H2O
H 3C
H CH 3
H 3C
O
H
4-Methyl-2-pentanol
A 2o alcohol
Similarly try to prepare 2-Methyl-2-hexanol from n-Butylmagnesium bromide.
Planning a Grignard synthesis
how do we decide which Grignard reagent and which carbonyl compound to use in preparing a
particular alcohol?
For this, just have a look at the structure of alcohol to be prepared; There is one carbon bearing the
-OH group and other alkyl groups / hydrogens.
Among these alkyl groups / hydrogens one must come from the Grignard reagent and the other alkyl
groups / hydrogens must come from the carbonyl compound.
CH3 O
H3C H3C Mg
Br
+ H3C
CH3 CH3
HO
2-Methyl-2-hexanol n-Butylmagnesium Acetone
Bromide
Most alcohols can be obtained from more than one combination of reagents. e.g. in the above
example of formation of 2-methyl-2-butanol, the other combination of Grignard reagent and the ketone
can be changed in the following way:
CH3 O
H3C H3C + H3C Mg Br
CH3
HO CH3
2-Methyl-2-hexanol Methyl n-butyl Methylmagnesium
ketone Bromide
Therefore we must choose the combination that is most readily available; like in the example above,
the first route should be preferred as it uses the more readily available carbonyl compound.
Limitations of Grignard synthesis
While performing any Grignard reaction, we must bear in mind that the very reactivity that makes
Grignard reagent so versatile also puts severe limitations to its uses.
Any compound containing hydrogen attached to a more electronegative atom such as oxygen,
nitrogen, sulfur or even triple bonded carbon is acidic enough to decompose a Grignard reagent.
A Grignard reagent reacts rapidly with oxygen and carbon dioxide, and with nearly every organic
compound containing a carbon-oxygen or cabon-nitrogen double bond.
We can not prepare a Grignard reagent from a compound (e.g., HOCH2CH2Br) that contains, in
addition to halogen, any other group prone to react with Grignard reagent. In such situations, the
Grignard reagent will react with the other active group as fast as it is formed and yield an undesirable
product. (HOCH2CH2-H)
Similarly, the aldehyde or any other compound that is to react with Grignard reagent may not contain
other groups that may decompose Grignard reagent.
These may seem to be severe limitations; but the number of acceptable combinations is so large the
the Grignard reagent is one of the most valuable tools for an organic chemist.
So, what precautions should be taken while performing a Grignard synthesis
Therefore, all alkyl halide, aldehyde and the ether used as a solvent must be scrupulously dried and
freed of any alcohol from which each was probably made; a Grignard reagent will not even be formed
in the presence of water.
We must protect the reaction system from the water vapour, oxygen, and carbon dioxide of the air:
The use of calcium chloride tube can keep the water vapor out, while a dry nitrogen environment must
be used to get rid of oxygen and carbon dioxide.
For other substitutions on the reacting groups, we can introduce a protecting group to prevent an
unwanted reaction.
Hydrolysis of alkyl halides
R X + HO
–
Or H2O R OH + X- Or H X
Aq. NaOH
Cl OH
Hydrolysis of alkyl halides is severly limited as a method of synthesizing alcohols, since alcohols are
usually more available than the corresponding halides.
Aldol condensation
Reduction of carbonyl compounds
Reduction of acids and esters
Hydrolysis of alkenes
KMnO4
syn-Hydroxylation
OH OH
H2C CH2
OH
RCO2OH H2O +
H
O OH
anti-Hydroxylation
Chemical Reactions
Due to cleavage of C----OH bond Due to cleavage of C-O----H bond
Reaction with hydrogen halides Reaction as acids: reaction with active metals
Reaction with phosphorous trihalides Ester formation
Dehydration Oxidation
Reaction with hydrogen halides
R OH + H X R X + H2O
Reactivity R X + H2O R OH
H X HI > HBr > HCl
R OH primary < secondary < Tertiary < benzyl < allyl
Example
OH Br
Conc. HBr
H3C CH3 NaBr, H2SO4 H3C CH3
Isopropyl alcohol Isopropyl bromide
OH HCl, ZnCl2
Cl
H3C H3C
Heat
n-Pentyl alcohol n-Pentyl chloride
CH3 CH3
H3C CH3 Conc. HCl
H3C CH3
OH Room temperature Cl
tert-Butyl alcohol tert-Butyl chloride
R
X H
H X +
Y R OH R O
H
R X + H2O
Alkyl
Z Alcohol Protonated halide
alcohol
B
C
Reaction with phosphorous trihalides
3R OH + PX3 3R X + H3PO 3
PX3 = PBr3, PI3
Example
PBr3
H3C OH H3C Br
CH3 CH3
OH Br
PBr3
H 5C 6 CH3 H 5C 6 CH3
1-Phenyl ethanol 1-Bromo-1-phenyl ethane
PI3
H3C I
H3C OH
Dehydration
1 2
R R 1 2
3 Acid R R
R R 3
R R
H OH
Reactivity of ROH: 3o > 2o > 1o
H2SO4, Heat CH3 CH2
H3C OH H3C + H3C
2-butene
(Major product)
CH3 CH3
H 5C 6 CH3 H 5C 6 CH2
OH
2-Phenylpropene
2-Phenyl-2-propanol
1 2 1 2 1 2 + 1 2
R R H X R R H2O R R H R R
3 3 + 3 3
R R R R R C R R R
+
H OH H OH2 H
Each of these reactions requires the presence of acid to convert the alcohol into the actual substrate,
the protonated alcohol.
Whether the reaction is substitution or elimination, and whether it follows a bimolecular or unimolecular
mechanism, the carbon-oxygen bond must undergo heterolytic cleavage-the substrate must lose a
leaving group.
The protonated alcohol readily loses the weakly basic water molecule.
The unprotonated alcohol would have to lose the strongly basic hydroxide ion, a process so difficult
that it seldom if ever happens.
Thus, although alcohols are precursors for a wide range of compounds, the loss of -OH can not be
brought about indirectly, but by converting the alcohol to something else; the very poor leaving group
must be converted to a good leaving group.
The simplest way to accomplish the above is to protonate the alcohol.
Due to cleavage of C-O----H bond
Reaction as acids: reaction with active metals
Ester formation
Oxidation
Reaction as acids: reaction with active metals
R OH + Na R-O-Na+
H 5C 2 OH + Na C2H5-O-Na+
Ethyl alcohol Sodium ethoxide
CH3 CH3
K - +
H3C OH H3C O K
CH3 CH3
tert-Butyl alcohol Potassium tert-Butoxide
Alcohols are weaker acids than water in solution; therefore their acidity is a result of solvation effect
rather than polar effects.
Since an alcohol is a weaker acid than water, an alkoxide is not prepared by the reaction of the
alcohol with sodium hydroxide, but rather by reaction of the alcohol with the active metal directly.
Alkoxides are extremely useful reagents. They are powerful bases, stronger than hydroxide- and,
by varying the alkyl group, we can vary their degree of basicity, their steric requirements, and their
solubility properties.
As we have already seen, the alkoxides can be used to introduce the alkoxy group into molecules.
Ester foramtion or formation of alkyl sulfonates
O O
–
–
Ar S OH + PCl 5 Ar S Cl + POCl 3 + HCl
O O
Substituted
sulfonyl chloride
O O
– – –
Ar S Cl + R OH Ar S O R + Cl + H2O
O O
Substituted Alkyl sulfonate
sulfonyl chloride
H X Or PX3 Nucleophiles
R OH R X
O O
– – Nucleophiles
R O H + Cl S Ar RO S Ar
O O
Oxidation of alcohols
Primary alcohol K2Cr2O7 or
H CrO3 in
H H
glacial acetic O
R OH acid KMnO4
R O R OH H3C
OH
H Aldehyde H
1o Alcohol 1o Alcohol Carboxylic acid
Secondary alcohol
H 1 One of the best and most
R convenient reagents to
R OH convert aldehydes and curb
R O further oxidation of these
1 aldehydes to acids is
R
Ketone Pyridinium chlorochromate
2o Alcohol (C5H5NHCrO3Cl)
Tertiary alcohol
2
R
R OH No reaction
1
R
RCH2OH + KMnO4 RCOO-K+ + MnO2 + KOH
Salt Brown
Soluble
in water
+
H
RCOOH
Acid
Insoluble
in water
Synthesis of complicated alcohols
2+
HX Mg Grignard
Alcohol Alkyl
halide Reagent
More
complicated
alcohols
Alcohol Aldehyde
or ketone
2+
Mg Br
H3C Br H3C Mg
HBr
H3C
H3C OH OH
Ethanol C5H5NHCrO3Cl H
O H3C
H3C H 2-butanol
