Acetalisation
Encyclopedia
Acetalisation is an organic reaction
that involves the formation of an acetal
or ketal. One way of acetal formation is the nucleophilic addition
of an alcohol
to a ketone
or an aldehyde
. Acetalisation is often used in organic synthesis
to create a protecting group
because it is a reversible reaction.
catalysed
with elimination of water. The reaction can be driven to the acetal when water is removed from the reaction system either by azeotropic distillation
or trapping water with molecular sieve
s or aluminium oxide
. The general reaction mechanism for acetalisation of a carbonyl group is shown to the right.
The carbonyl group in 1 abstracts a proton from hydrochloric acid
. The protonated carbonyl group 2 is activated for nucleophilic addition
of the alcohol. The structures 2a and 2b are mesomers. After deprotonation
of 3 by water the hemiacetal
or hemiketal 4 is formed. The hydroxyl group in 4 is protonated leading to the oxonium ion
6 which accepts a second alcohol group to 7 with a final deprotonation to the acetal 8. The reverse reaction takes place by adding water in the same acidic medium. Acetals are stable towards basic
media. In a transacetalisation or crossacetalisation a diol reacts with an acetal or two different acetals react with each other. Again this is possible because all the reaction steps are equilibria.
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
that involves the formation of an acetal
Acetal
An acetal is a molecule with two single-bonded oxygen atoms attached to the same carbon atom.Traditional usages distinguish ketals from acetals...
or ketal. One way of acetal formation is the nucleophilic addition
Nucleophilic addition
In organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a π bond is removed by the creation of two new covalent bonds by the addition of a nucleophile....
of an alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
to a ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
or an aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
. Acetalisation is often used in organic synthesis
Organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
to create a protecting group
Protecting group
A protecting group or protective group is introduced into a molecule by chemical modification of a functional group in order to obtain chemoselectivity in a subsequent chemical reaction...
because it is a reversible reaction.
Acetalisation of carbonyl groups by alcohols
Acetalisation is acidAcid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
catalysed
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
with elimination of water. The reaction can be driven to the acetal when water is removed from the reaction system either by azeotropic distillation
Azeotropic distillation
In chemistry, azeotropic distillation is any of a range of techniques used to break an azeotrope in distillation. In chemical engineering, azeotropic distillation usually refers to the specific technique of adding another component to generate a new, lower-boiling azeotrope that is heterogeneous...
or trapping water with molecular sieve
Molecular sieve
A molecular sieve is a material containing tiny pores of a precise and uniform size that is used as an adsorbent for gases and liquids.Molecules small enough to pass through the pores are adsorbed while larger molecules are not. It is different from a common filter in that it operates on a...
s or aluminium oxide
Aluminium oxide
Aluminium oxide is an amphoteric oxide with the chemical formula 23. It is commonly referred to as alumina, or corundum in its crystalline form, as well as many other names, reflecting its widespread occurrence in nature and industry...
. The general reaction mechanism for acetalisation of a carbonyl group is shown to the right.
The carbonyl group in 1 abstracts a proton from hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....
. The protonated carbonyl group 2 is activated for nucleophilic addition
Nucleophilic addition
In organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a π bond is removed by the creation of two new covalent bonds by the addition of a nucleophile....
of the alcohol. The structures 2a and 2b are mesomers. After deprotonation
Deprotonation
Deprotonation is the removal of a proton from a molecule, forming the conjugate base.The relative ability of a molecule to give up a proton is measured by its pKa value. A low pKa value indicates that the compound is acidic and will easily give up its proton to a base...
of 3 by water the hemiacetal
Hemiacetal
Hemiacetals and hemiketals are compounds that are derived from aldehydes and ketones respectively. The Greek word hèmi means half...
or hemiketal 4 is formed. The hydroxyl group in 4 is protonated leading to the oxonium ion
Oxonium ion
The oxonium ion in chemistry is any oxygen cation with three bonds. The simplest oxonium ion is the hydronium ion H3O+. Another oxonium ion frequently encountered in organic chemistry is obtained by protonation or alkylation of a carbonyl group e.g...
6 which accepts a second alcohol group to 7 with a final deprotonation to the acetal 8. The reverse reaction takes place by adding water in the same acidic medium. Acetals are stable towards basic
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
media. In a transacetalisation or crossacetalisation a diol reacts with an acetal or two different acetals react with each other. Again this is possible because all the reaction steps are equilibria.