Alcohols

Alcohols

• An alcohol has a hydroxyl group bonded to an sp3-hybridized

(tetrahedral) carbon atom.

• Depending on the nature of C atom properties may be varied.

• Alcohols are classified as primary (1°), secondary (2°), or tertiary (3°) according
to the number of carbon groups (R) directly bonded to the carbon bearing the
hydroxyl group.
 Alcohols
Hydroxyl group attract the electron toward it
There is a poor leaving group
from C-OH bond
(OH), however protonation
Electron density on C atom is low
will convert it to a good
That C tends to gather electrons from someone.
leaving group
Nucleophiles willing to attack this C by donating
Liable to substitutions and
their electrons
eliminations Substitutions are nucleophilic substitutions
(However there is a possibility to act the alcohol as a
nucleophile in front of more nucleophilic molecules
saturated such as alkyl halides, protonated alcohols etc.)
Additions are
impossible There is a chance to eliminate
hydrogen (H2)
Oxidations are possible

acidic No way to introduce hydrogen

Acid base reactions are possible Oxygen atoms are not available to remove
Direct(single step) reductions are impossible
 Reactions of alcohols
• You have to summarize all the reactions discussed under this lecture
after the completion of the lecture.
 Nucleophilic substitutions reactions where
alcohols are involved
• There are two situations

• Alcohol act as substrate

• Alcohols to alkyl halides conversion

• Alcohol act as the nucleophile

• Ether formation
 Alcohols in to alkyl halides
• Halide ion can act as a nucleophile and undergo a nucleophilic substitution
on the modified alcohol substrate (after converting the poor OH leaving
group to a strong leaving group) by replacing the hydroxyl group.
 Alcohols with HX to give alkyl halides
• Depending on the nature of the alcohol mechanism is varying.
• 2ry, 3ry and benzyl alcohols follow an SN1 mechanism, 1ry alcohols and methanol
follow the SN2 mechanism
SN1 mechanism SN2 mechanism

*Similar to the S 1 mechanism, protonation will happen.

N
After that, a single step conversion can be observed.
 However, Alcohols with H2SO4 to give alkene; Elimination
• Similar to the reaction with HX, in the
presence of H2SO4 carbocation will be
formed with 2ry, 3ry and benzyl
alcohols .

• However the two nucleophiles

available in the medium are H2O and
HSO4- .

• They are not strong enough to

undergo a substitution.

• In such conditions, highly reactive

carbocation stabilized itself by loosing
a proton and forming an alkene.

• Overall reaction is an elimination

which follows E1 mechanism.
 Continues…
• Similar to the reaction with HX,
in the presence of H2SO4 ,
protonation of alcohols will also
be observed for 1ry alcohols and
methanol.

• However they do not prefer

carbocation formation.

• In the presence of HX they follow

a simultaneous nucleophilic
attack with the leaving of H2O
group. Instead that simultaneous
base attack and abstract of
proton can be observed in the
presence of H2SO4.

• Overall reaction is an elimination

which follows E2 mechanism.
 Alkene as a by-product during the reaction
with HX

• The free energy of activations are somewhat close for the two
reactions of the carbocation namely substitution and elimination.

• Therefore in addition to alkyl halide, there is a possibility to form

alkenes during the reaction of alcohols with alkyl halide.
Activity:
• Find the mechanism of alkyl halide from alcohols using PBr3 and SOCl2
 nucleophilic substitutions of alcohols where
alcohol act as the nucleophile
• Second alcohol molecule will act as a nucleophile to a protonated alcohol
molecule to form an ether.

• Therefore in the presence of an acid ether formation can be happened in addition

to substitution and elimination. Major product will be decided by reaction
temperature.
 Oxidation of alcohols
• Depending on the nature of the alcohol and oxidizing agent, different
compounds can be obtained.

• Tertiary alcohols cannot be oxidized.

• Secondary alcohols will oxidize to ketones.

• Primary alcohols can be oxidized to Aldehydes or Carboxylic acids based on

the oxidizing agent.
 Oxidizing agents and related products
in Alcohol oxidation
• Secondary alcohols can be oxidized to ketones by
• Jones reagent (chromic acid(H2CrO4)/ chromium trioxide (CrO3) to aqueous sulfuric acid)
• Potassium permanganate (KMnO4)
• pyridinium chlorochromate (PCC)
• Swern oxidation (dimethylchlorosulfonium ion/ dimethylsulfoxide and oxalyl chloride,
followed by addition of a base such as triethylamine)

• Primary alcohols can be oxidized

• to carboxylic acid by
• Jones reagent (chromic acid(H2CrO4)/ chromium trioxide (CrO3) to aqueous sulfuric acid)
• Potassium permanganate (KMnO4)
• to aldehyde by
• pyridinium chlorochromate (PCC)
• Swern oxidation (dimethylchlorosulfonium ion/ dimethylsulfoxide and oxalyl chloride,
followed by addition of a base such as triethylamine)
 Acid base reactions of Alcohols

• Alcohols react with Na or NaH and form alkoxide ion while acting as a H+
donor or acid.

• RO- is a good nucleophile compared to ROH. Therefore when we need we can

convert alcohols into alkoxide ion via these acid base reactions and enhance
the nucleophilic activity of the alcohols.
• Eg: Willamson Ether synthesis
 Williamson ether synthesis
• Alcohols will convert to sodium alkoxide.
• Alkoxide ion reacts with alkyl halide/alkyl sulphonate/alkyl sulphate
via a SN2 mechanism.
 Fisher esterification
• In the presence of an acid, alcohol react with carboxylic acid to give
an ester.

• If you put a sudden look, reaction is looks like a acid base reaction.

• However actual mechanism is differ from an acid base reaction. It

follows a typical of acid-catalyzed nucleophilic addition–elimination
reactions at acyl carbon atoms.
Fisher esterification mechanism
 Alcohol protection
• From the content so far you have identified the reactivity of alcohols.
• Assume there is a molecule with a hydroxyl group and some other function group which is less reactive
towards a reaction with a particular reactant. However we need to keep hydroxyl group as it is and react
the other functional group with that reactant.
• What can we do?
• We have to protect the hydroxyl group.
• During the protection we have to be careful. We have to convert the hydroxyl group to a less
reactive functional group towards the particular reagent prior to the addition of that reactant.
And also after the completion of that particular reaction we should be able to recover the
hydroxyl group. It means protection reaction should be reversible.
• Alcohol can be protected by converting the hydroxyl group to
• an acetal or ketal
• an Ether
• an ester
 Application of alcohol protection in synthetic
routes
Assume you need to carry out an alkylation at the halide end of an alcohol
containing a halide substituent via the reaction with alkynide ion.
 Activation of alcohols
• Similar to the protection, there are situations we have to enhance the
reactivity of alcohols.
• We have already discussed two cases. What are those?
• Enhance the nucleophilicity by converting to alkoxide ion.
• Convert the poor leaving group to a good leaving group by protonation.

• There is a another common practice with alcohols to convert the poor

leaving group; hydroxyl to a good leaving group by converting it to a
sulfonate ester derivative.
• The most common sulfonate esters used for this purpose are
methanesulfonate esters (“mesylates”), p-toluenesulfonate esters
(“tosylates”), and trifluoromethanesulfonates (“triflates”).
 Common sulphonyl ester derivatives

• The desired sulfonate ester is usually prepared by reaction of the alcohol in pyridine with
the appropriate sulfonyl chloride.
 Reactions of sulfonate esters
• These sulfonate esters; mesylates, tosylates, and triflates are frequently
used as substrates for nucleophilic substitution reactions because they
have a very good leaving group with them.