Fries Rearrangement with mechanism and it’s Application

The Fries rearrangement is an organic reaction which involves the conversion of phenolic esters into hydroxyaryl ketones on heating in the presence of a catalyst Such as HF, AlCl3, BF3 etc. Phenolic esters on heating with aluminium trichloride (Lewis acid) give o and p- acyl phenol. This is known as Fries rearrangement.

Fries Rearrangement

A mixture of ortho- and para-isomers is obtained. Electron-withdrawing groups in the substrate retard the reaction as in the case of Friedel-Crafts reaction. In general, low temperature favours the para-product and high temperature favours the ortho-product.

Mechanism: Exact mechanism is still not clearly understood. There is evidence for both intermolecular and intramolecular reaction mechanisms. It is, therefore, suggested that both mechanisms are operating simultaneously.

Two-step mechanism It may be taken to be Friedel-Crafts acylation in which the acylium ion, (MECO) is supplied by the substrate, i.e., it is self-acylation. At first, AICI, complexes with the oxygen of the phenoxy group from which the acylium ion is generated. The acylium ion then attacks the benzene ring as in the case of Friedel-Crafts reaction.

Fries-rearrangement-mechanism1

Similar attack at p-positior gives the para-isomer. Concerted or single-step mechanism

Fries-rearrangement-mechanism2

In practice, both o and p-isomers are obtained. The amount of each isomer depends on temperature, solvent, amount of catalyst and on the structure of the substrate. At low temperature (< 100°C) para-isomer is the major product while at high temperature (> 100°C) ortho-isomer is the major product. This is because the intermediate of ortho-isomer is stabilized by chelation and is hence thermodynamically more stable.

Solvent is generally not required for the reaction. Nitrobenzene may be used which reduces the reaction temperature. Fries rearrangement has also been observed to be catalysed by light (photo Fries rearrangement). It is suggested that the reaction in this case is intramolecular free radical process, the attacking species being RCO.

Application: The Fries rearrangement has found application in the following areas:

1. This reaction is useful for the preparation of aromatic hydroxyketones since direct acylation of phenols gives very poor yield. The effect of this rearrangement on substrates bearing methyl groups at ortho, meta and para positions shows that when the para position is occupied, the acyl group substitutes exclusively to the ortho position.

2. Synthesis of o– and p-hydroxyacetophenones

3. Synthesis of acyl catechols from ester catechol

4. Diphenyl esters also undergo fries Rearrangement

5. Avery useful application is in the synthesis of adrenaline which is a heart stimulant.

 

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