Ester to Aldehyde Conversion and Reformatsky Reaction

One of the components in synthetic flavours, perfumes and cosmetics is ester. Ester is an organic compound which reacts with water and gives alcohol and acid. RCO2R' is the chemical formula of esters. Aldehydes are another important class of organic compounds which can be used as fungicides, insecticides and germicides in plants and vegetables and also used for the production of polymeric materials. The chemical formula of aldehyde is RCHO. Esters can be reduced to aldehyde.

The ester and aldehyde can also react together. A special type of organic reaction where an alpha halo ester reacts with aldehyde or ketone to give beta hydroxy ester is called the Reformatsky reaction. Beta hydroxy ester has a lot of importance in cosmetics and pharmaceutical industries. In this topic, we are discussing all the details of the Reformatsky reaction, the reaction mechanism and the advantages of the Reformatsky reaction.

What is Reformatsky Reaction?

The Reformatsky reaction was discovered in 1887 by a Russian chemist named Sergey Nikolaevich Reformatsky. The reaction usually takes place between a carbonyl compound and alpha halo ester. The reaction takes place in the presence of zinc metal where inorganic solvents like diethyl ether or THF can be used. This is a condensation reaction and can be adapted to intramolecular aldol condensation. The isolation of organo zinc reagent is not required in a Reformatsky reaction. During the reaction, a new carbon-carbon bond is formed along with the formation of a zinc halide.

Definition of Reformatsky Reaction

Reformatsky reaction is a condensation reaction. Reformatsky reaction can be defined as a reaction between aldehyde or ketones with alpha halo ester and beta hydroxy ester by using zinc metal. Here, zinc helps to produce the organo zinc reagent called Reformatsky enolate. Reformatsky enolate is less reactive compared to the Grignard reagent. Hence, there is no possibility for a nucleophilic addition to the ester group. The reaction is an extended reaction between two carbonyl compounds in the presence of zinc. The solvent used in the reaction is diethyl ether or tetrahydrofuran.

Reaction Mechanism

• Formation of zinc enolate: By oxidative addition, zinc metal is inserted to the carbon halogen bond of alpha halo ester.

• This compound undergoes dimerisation and rearrangement and forms two zinc enolates.

• The oxygen on the aldehyde or ketone coordinates with zinc and a new six-membered transition state is formed.

• Zinc moves to the oxygen of aldehyde or ketone and a new carbon-carbon bond is formed.

• An acid work up is taken place and zinc is removed by it. Zinc forms Zn(II) salt and we get beta hydroxy ester.

Reformatsky Reaction Mechanism

Advantages of Reformatsky Reaction

• Since the Reformatsky enolate is less reactive; hence, the ester group does not undergo nucleophilic addition.

• Highly hindered aldehyde or ketones can successfully undergo Reformatsky reaction and nucleophiles can successfully be added to the delta positive carbon of ketones.

• The reaction can be adapted to intramolecular aldol condensation very easily.

• The organo zinc halide is very stable and it is available in the market.

• Reformatsky enolate is an alternative to lithium enolate of ester. Hence, the reaction can be conveniently carried out.

• Freshly prepared zinc powder or a heated column of zinc dust can improve the yield of a Reformatsky reaction.

• Reformatsky reactions can successfully add carbon nucleophiles to the readily enolizable cyclopentanone ring system.

Uses of Reformatsky Reaction

Reformatsky reaction can be used to produce beta hydroxy ester from alpha halo ester and other carbonyl compounds. The beta hydroxy ester can hydrolysed to produce beta hydroxy acids. Beta hydroxy acids have a large commercial value especially in the cosmetic industry. Beta hydroxy acids can be used in anti-ageing creams and in the pharmaceutical industry.

How Esters can Convert to Aldehyde?

Ester to aldehyde reduction reaction occurs using certain reducing agents. DIBAL-H is the common reducing agent by which ester can be reduced to aldehyde. DIBAL-H is diisobutyl aluminium hydroxide. In order to prevent further reaction of aldehyde, the reaction is carried out at a very low temperature, approximately -780C. Alcohol is a byproduct of this reaction.

Conversion of Ester to Aldehyde

Interesting Facts

• THF complexes of Reformatsky reagents form eight-membered dimers in the solid state.

• Various Metals like iron, cobalt, nickel, germanium, cerium, barium, indium, cadmium etc. can be used instead of zinc in the Reformatsky reaction.

• Reformatsky reactions of over 500 aldehydes or ketones are identified.

Key Features

• Ester can be reduced to aldehyde by using DIBAL-H.

• Aldehyde or ketones can react with alpha halo esters and form beta hydroxy esters. This reaction is called the Reformatsky reaction.

• Zinc metal is used to generate Reformatsky reagents which are comparatively stable and less reactive than Grignard reagents.