Fries rearrangement
Rearrangement reaction of a phenolic ester to a keto-substituted phenol
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Through Ketone, Phenol and Aryl group
Mechanism
A widely accepted mechanism involves initial formation of an acylium ion intermediate. A low reaction temperature favors para substitution and with high temperatures the ortho product prevails, this can be rationalised as exhibiting classic thermodynamic versus kinetic reaction control as the ortho product can form a more stable bidentate complex with the aluminium. Formation of the ortho product is also favoured in non-polar solvents; as the solvent polarity increases, the ratio of the para product also increases.
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Scope
Phenols react to form esters instead of hydroxyarylketones when reacted with acyl halides under Friedel-Crafts acylation conditions. Therefore, this reaction is of industrial importance for the synthesis of hydroxyarylketones, which are important intermediates for several pharmaceuticals. As an alternative to aluminium chloride, other Lewis acids such as boron trifluoride and bismuth triflate or strong protic acids such as hydrogen fluoride and methanesulfonic acid can also be used. In order to avoid the use of these corrosive and environmentally unfriendly catalysts altogether research into alternative heterogeneous catalysts is actively pursued.
Limits
In all instances only esters can be used with stable acyl components that can withstand the harsh conditions of the Fries rearrangement. If the aromatic or the acyl component is heavily substituted then the chemical yield will drop due to steric constraints. Deactivating meta-directing groups on the benzene group will also have an adverse effect as can be expected for a Friedel–Crafts acylation.
Photo-Fries rearrangement
In addition to the ordinary thermal phenyl ester reaction a photochemical variant is possible. The photo-Fries rearrangement can likewise give [1,3] and [1,5] products, which involves a radical reaction mechanism. This reaction is also possible with deactivating substituents on the aromatic group. Because the yields are low this procedure is not used in commercial production. However, photo-Fries rearrangement may occur naturally, for example when a plastic object made of aromatic polycarbonate, polyester or polyurethane, is exposed to the sun (aliphatic carbonyls undergo Norrish reactions, which are somewhat similar). In this case, photolysis of the ester groups would lead to leaching of phthalate from the plastic.
Anionic Fries rearrangement
In the anionic Fries rearrangement ortho-metalation of aryl esters, carbamates and carbonates with a strong base results in a rearrangement to give ortho-carbonyl species.
Historic readings
- Fries, K.; Pfaffendorf, W. (1910). "Über ein Kondensationsprodukt des Cumaranons und seine Umwandlung in Oxindirubin". Chemische Berichte. 43 (1): 212–219. doi:10.1002/cber.19100430131.
- Blatt, A. H. (1942). "Fries Reaction". Organic Reactions. 1: 342-369.