| Fries rearrangement | |
|---|---|
| Named after | Karl Theophil Fries |
| Reaction type | Rearrangement reaction |
| Identifiers | |
| Organic Chemistry Portal | fries-rearrangement |
| RSC ontology ID | RXNO:0000444 |
TheFries rearrangement, named for the German chemistKarl Theophil Fries, is arearrangement reaction of a phenolic ester to ahydroxyarylketone bycatalysis ofLewis acids.[1][2][3][4]
It involves migration of anacyl group ofphenol ester to thearyl ring. The reaction isortho and para selective and one of the two products can be favoured by changing reaction conditions, such astemperature andsolvent.
Despite many efforts, a definitivereaction mechanism for the Fries rearrangement has not been determined. Evidence for inter- andintramolecular mechanisms have been obtained bycrossover experiments with mixed reactants.[citation needed]The reaction progress is not dependent onsolvent orsubstrate. A widely accepted mechanism involves acarbocation intermediate.
In the first reaction step aLewis acid for instancealuminium chlorideAlCl
3 co-ordinates to thecarbonyl oxygen atom of theacyl group. This oxygen atom is moreelectron rich than thephenolic oxygen atom and is the preferredLewis base. This interactionpolarizes thebond between the acyl residue and the phenolic oxygen atom and the aluminium chloride group rearranges to the phenolic oxygen atom. This generates a freeacyliumcarbocation which reacts in a classicalelectrophilic aromatic substitution with the aromatic ring. The abstracted proton is released ashydrochloric acid where the chlorine is derived from aluminium chloride. The orientation of the substitution reaction is temperature dependent. A low reaction temperature favorspara substitution and with high temperatures theortho product prevails, this can be rationalised as exhibiting classicthermodynamic versus kinetic reaction control as the ortho product can form a more stable bidentate complex with the aluminium.[5] 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.[6]
Phenols react to formesters instead of hydroxyarylketones when reacted withacyl halides underFriedel-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 toaluminium chloride, otherLewis acids such asboron trifluoride andbismuthtriflate or strong protic acids such ashydrogen fluoride andmethanesulfonic acid can also be used.[citation needed] In order to avoid the use of these corrosive and environmentally unfriendlycatalysts altogether research into alternativeheterogeneous catalysts is actively pursued.
In all instances onlyesters 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 thechemical yield will drop due tosteric constraints. Deactivating meta-directing groups on the benzene group will also have an adverse effect as can be expected for aFriedel–Crafts acylation.
In addition to the ordinary thermal phenyl ester reaction aphotochemical variant is possible. Thephoto-Fries rearrangement can likewise give [1,3] and [1,5] products,[7][8] which involves aradicalreaction mechanism. This reaction is also possible with deactivatingsubstituents 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 aromaticpolycarbonate,polyester orpolyurethane, is exposed to the sun (aliphatic carbonyls undergoNorrish reactions, which are somewhat similar). In this case,photolysis of the ester groups would lead to leaching of phthalate from the plastic.[9]
.svg)
In the anionic Fries rearrangementortho-metalation of aryl esters,carbamates and carbonates with a strong base results in a rearrangement to give ortho-carbonyl species.[10]
