Transcript Addition of Alcohols to Form Hemiacetals and Acetals

17-7
Addition of Alcohols to Form Hemiacetals and
Acetals
Aldehydes and ketones form hemiacetals reversibly.
The reaction of alcohols with aldehydes and ketones parallels the reaction with
water:
These equilibria usually favor the starting carbonyl compound.
Stable hemiacetals are formed from reactive carbonyl compounds (formaldehyde
or 2,2,2-trichloroacetaldehyde) or when relatively strain-free, five- and sixmembered rings are formed:
Acids catalyze acetal formation.
In the presence of excess alcohol, two molecules of alcohol are added to an
aldehyde or ketone in the acid-catalyzed reaction.
The resulting compounds are called acetals (an older term for an acetal derived
from a ketone is a ketal).
Each step is reversible in the presence of acid. The equilibrium can be shifted
towards acetal by using excess alcohol or removing water or towards aldehyde or
ketone by adding excess water (acetal hydrolysis).
Acetals, unlike hydrates and hemiacetals, may be isolated as pure substances by
neutralizing the acid used as the catalyst.
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Acetals as Protecting Groups
Cyclic acetal formation protects carbonyl groups from attack by
nucleophiles.
1,2-Ethanediol is a particularly effective reagent for forming acetals compared to
ordinary alcohols because it forms a more stable cyclic intermediate.
The stability of the cyclic
acetal is due to a more
favorable entropy change
upon formation (2
reactant molecules
become 2 product
molecules) compared to a
non-cyclic acetal (3
reactant molecules
become 2 product
molecules).
Cyclic acetals can be hydrolized by aqueous acid, but are stable to many basic,
organometallic and hydride reagents.
These properties allow cyclic acetals to be used as protecting groups for the
carbonyl function in aldehydes and ketones.
The alkynyl anion attacks the carbonyl group in the unprotected 3-iodopropanal.
Thiols react with the carbonyl group to form thioacetals.
Thiols react with aldehydes and ketones in the presence of a Lewis acid, such as
BF3 or ZnCl2, to form thioacetals.
The cyclic thioacetal is stable in aqueous acid.
Thioacetals are hydrolyzed by using mercuric chloride in aqueous acetonitrile
(formation of insoluble mercuric sulfides drives the reaction).
Thioacetals can be desulfurized to the corresponding hydrocarbon using Raney
nickel:
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Nucleophilic Addition of Ammonia and Its Derivatives
Ammonia and primary amines add to aldehydes and ketones in a manner
analogous to water and alcohols.
However, the products of these reactions then lose water, forming imines and
enamines.
Ammonia and primary amines form imines.
Amines and aldehydes or ketones react to form hemiaminals, the nitrogen
analogs of hemiacetals.
The hemiaminals of primary amines then lose water to form an imine (previously,
Schiff base). This is the nitrogen analog of the carbonyl group.
Reactions between a primary amine and an aldehyde or ketone, in which two
molecules are joined with the elimination of water, are called “condensations.”
When an imine is used as reaction intermediate, the carbonyl compound and
amine are usually mixed with the subsequent reagent and the imine is consumed
immediately upon formation.
Imines can be isolated, often in high yield, if water formed is removed from the
condensation process (continuous distillation).
Special imines aid in the identification of aldehydes and ketones.
Several amine derivatives condense with aldehydes and ketones to form imines
that are highly crystalline and have sharp melting points.
These derivatives are more stable than simple imines due to resonance
stabilization. For instance, in an oxime:
Comparison of the melting point of an unknown imine derivative to a catalog of
known values was used as a method of identification of aldehydes and ketones
prior to the development of spectroscopic methods.