Aldol Condensation

The aldol reaction is one of the most well-known processes for the formation of new C–C bonds, and it has found applications in both the chemical synthesis and biological realms. Traditional aldol reactions required the employment of a basic catalyst in a hydroalcoholic medium or the use of strong bases in poisonous and combustible organic solvents to achieve the desired results. As a result of the extended reaction periods, such conditions produce combinations of ketols and, unsaturated ketones, side products from competitive side reactions, and aldol products, as well as aldol products in isolation. A great deal of effort and interest has been directed into the development of catalytic methods for this transformation in a green environment over the last several years. Despite the fact that several homogeneous and heterogeneous catalyst types have been investigated in order to achieve better outcomes, there are environmental problems related to the catalytic aldol process. As environmental awareness and environmentally friendly reactions have grown in importance, chemists have begun to employ enhanced methodologies such as micellar medium, microwave irradiation, and ultrasonics as alternatives to traditional aldol condensation methods, among others. This review analyses and updates the research on these routes from a green perspective, and it is written in an accessible style. The reactions carried out under these techniques, with or without the use of heterogeneous catalysis, have been highlighted in accordance with the principles of green chemistry, as previously stated. The protocols have been compiled mostly from pedagogical journals, with green components depicted whenever appropriate to make them environmentally friendly.

Aldol Condensation Reaction

Aldol condensation can be characterised as a chemical process in which the enolate ion combines with a carbonyl compound to generate a hydroxy ketone or a hydroxy aldehyde, which is then dehydrated to yield a conjugated enone as a result of the reaction. The Aldol Condensation reaction is critical in organic synthesis because it provides a pathway for the formation of carbon-carbon bonds.

Aldol reaction is the very first component of this process, and the dehydration—elimination reaction is second (that Involves removal of a water or an alcohol molecule). Dehydration is likely to be followed by decarboxylation if an active carboxyl group is present. In an electrophilic mechanism, a strong base such as potassium t-butoxide, potassium hydroxide, or sodium hydride can be used to dehydrate the aldol addition product, whereas an acid can be used in an acid-catalyzed enol mechanism. Aldol condensation may be carried out under two types of situations in general: kinetic control and thermodynamic control. Which conditions are used will be determined by the nature of the targeted product.

APPLICATIONS

The Aldol condensation reaction can be utilised for the following types of synthetic reactions:

1. The production of fatty acids through enzyme action.
2. Epothilone B complex synthesis in a very condensed form.
3. Synthesis of high-molecular-weight polymers of polyethene (glutaraldehyde).
4. The synthesis of (±)-ephedrine was carried out in a stereoselective manner.
5. Production of a large number of macrolide and ionophore antibiotics (natural products).
6. Complete synthesis of distomadines A and B, two tetracyclic quinolones with distinct structural characteristics.

Crossed Aldol Condensation

The bridging aldol reaction is the condensation of two different molecules of an aldehyde or ketone in aprotic solvents like water or alcohol. The phrase “crossed aldol condensation” refers to condensation that happens between two separate carbonyl compounds. When both aldehydes include alpha hydrogens, they are capable of generating carbanions while also functioning as carbanion acceptors. As a consequence, an inefficient combination of four chemicals with limited synthetic value is produced.

If one of the aldehydes does not contain any alpha hydrogen, it can only function as a carbanion acceptor. The formation of only two products occurs in this situation. When performing the crossing aldol reaction, an aromatic aldehyde with no alpha position is a frequent substrate to be used. The dehydration of the first condensation product occurs quickly, resulting in the synthesis of the, -unsaturated ketone and the prevention of the retro-aldol reaction from occurring as a result.

Intramolecular Aldol Condensation

Internal aldol condensations are preferable to intermolecular aldol condensations because they are more favourable. Cyclization happens when the first carbonyl carbon atom and the second carbonyl carbon atom can form a five- or six-membered ring by forming a covalent link. If these rings may be produced by two or more reactions, it is required to determine which procedure is more favourable. Under equilibrium conditions, many potential enolates exist in low concentrations in diverse forms. As a result, the enolate, which is a better nucleophile, attacks the more reactive carbonyl carbon atom and takes over the majority of the product produced. Generalised intramolecular aldol condensations, such as those in which an aldehyde is attacked by an enolate, are preferred over the addition of an enolate to the carbonyl carbon atom of a ketone.

CONCLUSION

Despite the fact that aldol condensation is one of the most significant chemical reactions because it is capable of creating new C–C bonds, the mechanism of this reaction has never been fully understood. We have now concluded that the last loss of hydroxide and production of the C-C bond in the base-catalysed aldol condensation of benzaldehydes with acetophenones, which results in the formation of chalcones, is the rate-limiting phase in the process. According to the results of an investigation of the partitioning ratios of the intermediate ketols and the solvent kinetic isotope effects, the condensations occur more quickly in D2O than in H2O, regardless of the substituent used in the experiment.