The Fries rearrangement is a rearrangement reaction of a phenyl ester to a hydroxy aryl ketone by catalysis of lewis acids ^{[1] [2] [3]}. A rearrangement reaction is a broad class of organic reactions where the carbon skeleton of a molecule is rearranged to give a structural isomer of the original molecule. ... In chemistry, the phenyl group or phenyl ring (often abbreviated as -Ph) is the functional group with the formula -C6H5 Picture where the six carbon atoms are arranged in a cyclic manner. ... In organic chemistry and biochemistry, esters are organic compounds where an organic group (symbolised by R in this article) replaces a hydrogen atom (or more than one) in an oxygen acid. ... This prefix in chemical nomenclature indicates the presence of a hydroxyl functional group (-OH). ... An aryl is a functional group of an organic molecule derived from an aromatic compound such as benzene. ... A ketone is either the functional group characterized by a carbonyl group linked to two other carbon atoms or a compound that contains this functional group. ... In chemistry and biology, catalysis is the acceleration of the reaction rate of a chemical reaction by means of a substance, called a catalyst, that is itself unchanged chemically by the overall reaction. ... In chemistry, a Lewis acid can accept a pair of electrons and form a coordinate covalent bond, after the American chemist Gilbert Lewis. ...

Mechanism

Despite many efforts a definitive reaction mechanism for the Fries rearrangement is not available. Evidence for inter- and intramolecular mechanisms have been obtained by so-called cross-experiments with mixed reactants. Reaction progress is not dependent on solvent or substrate. A widely accepted mechanism involves a carbocation intermediate. Image File history File links Friesrearrangement. ... An overall description of how a reaction occurs. ... Intramolecular describes a process or characteristic limited within the structure of a single, or each molecule; a property or phenomenon limited to the extent of a single, or each molecule. ... A solvent is a liquid that dissolves a solid, liquid, or gaseous solute, resulting in a solution. ... The word substrate can mean the following: In biochemistry, a substrate is a molecule which is acted upon by an enzyme. ... A carbocation is an ion with a positively-charged carbon atom. ...

In the first reaction step a lewis acid for instance aluminium chloride AlCl₃ attacks the carbonyl oxygen atom of the acyl group. This oxygen atom is more electron deficient than the phenolic oxygen atom and is the preferred lewis base. This interaction polarizes the bond between the acyl residue and the phenolic oxygen atom and the aluminium chloride group rearranges to the phenolic oxygen atom. This generates a free acylium carbocation which reacts in a classical electrophilic aromatic substitution with the aromat. The abstracted proton is released as hydrochloric acid where the chlorine is derived from aluminium chloride. The orientation of the substitution reaction is temperature dependent. A low reaction temperature favors para substitution and with high temperatures the ortho product prevails. In chemistry, a Lewis acid can accept a pair of electrons and form a coordinate covalent bond, after the American chemist Gilbert Lewis. ... Aluminium chloride (AlCl3) is a compound of aluminium and chlorine. ... In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom. ... Acyl is an organic radical (or functional group) obtained from an organic acid by the removal of the carboxylic hydroxyl group. ... Properties The electron is a fundamental subatomic particle which carries a negative electric charge. ... Phenol, also known under the old name carbolic acid, is a colorless crystalline solid with a typical sweet tarry odor. ... A Lewis base is any molecule or ion that can form a new covalent bond by donating a pair of electrons. ... This article treats polarization in electrodynamics. ... Covalently bonded hydrogen and carbon in a molecule of methane. ... A carbocation is an ion with a positively-charged carbon atom. ... An electrophilic aromatic substitution is a chemical reaction in which a hydrogen atom of an aromatic ring is replaced by an electrophile. ... The chemical substance hydrochloric acid is the aqueous (water-based) solution of hydrogen chloride (HCl) gas. ... Arene substitution patterns are part of organic chemistry IUPAC nomenclature and pinpoint the position of substituents other than hydrogen in relation to each other on an aromatic hydrocarbon. ... Arene substitution patterns are part of organic chemistry IUPAC nomenclature and pinpoint the position of substituents other than hydrogen in relation to each other on an aromatic hydrocarbon. ...

Scope

Phenols react to esters but do not react to hydroxyarylketones with acylhalogen compounds under Friedel-Crafts acylation reaction conditions and therefore this reaction is of industrial importance for the synthesis of hydroxyarylketones which are important intermediates for several pharmaceutics such as paracetamol and salbutamol. As an alternative to aluminium chloride, other Lewis acids such as boron trifluoride and bismuth triflate or stong 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 alltogether research into alternative heterogeneous catalysts is actively persued. Phenol, also known under the old name carbolic acid, is a colorless crystalline solid with a typical sweet tarry odor. ... In organic chemistry and biochemistry, esters are organic compounds where an organic group (symbolised by R in this article) replaces a hydrogen atom (or more than one) in an oxygen acid. ... The Friedel-Crafts reactions were developed by Charles Friedel and James Crafts in 1877. ... Paracetamol (INN) or acetaminophen (USAN) (popular brand name Tylenol), is a popular analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains. ... Salbutamol (INN) or albuterol (USAN) is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and COPD. It is marketed by the Allen & Hanburys respiratory division of GlaxoSmithKline under the trade name Ventolin. ... Aluminium chloride (AlCl3) is a compound of aluminium and chlorine. ... In chemistry, a Lewis acid can accept a pair of electrons and form a coordinate covalent bond, after the American chemist Gilbert Lewis. ... Boron trifluoride (BF3, trifluoroborane) is a pungent colourless toxic gas. ... General Name, Symbol, Number bismuth, Bi, 83 Chemical series poor metals Group, Period, Block 15, 6, p Appearance lustrous reddish white Atomic mass 208. ... Triflate, more formally known as trifluoromethanesulfonate, has the structure CF3SO3-. It is an extremely stable polyatomic ion, being the conjugate base of triflic acid (CF3SO3H), one of the strongest acids known and a super acid. ... Hydrofluoric acid is a highly corrosive solution of the chemical compound hydrogen fluoride in water. ... It has been suggested that Sulfonic acid/Temp be merged into this article or section. ... A catalyst (Greek: καταλύτης, catalytēs) is a substance that accelerates the rate (speed) of a chemical reaction without itself being transformed or consumed by the reaction (see also catalysis). ... Look up Heterogeneous on Wiktionary, the free dictionary A heterogeneous compound, mixture, or other such object is one that consists of many different items, which are often not easily sorted or separated, though they are clearly distinct. ...

Limits

In all instances only esters can be used with stable acyl components that can withstand the harsch conditions of the Fries rearrangement. Is the aromat or the acyl component 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. In organic chemistry and biochemistry, esters are organic compounds where an organic group (symbolised by R in this article) replaces a hydrogen atom (or more than one) in an oxygen acid. ... Yield in chemistry, also known as chemical yield and reaction yield, is the amount of product obtained in a chemical reaction. ... Steric effects are the interaction of molecules dictated by their shape and/or spatial relationships. ... The Friedel-Crafts reactions were developed by Charles Friedel and James Crafts in 1877. ...

Photo Fries rearrangement

In addition to the ordinary thermal phenyl ester reaction a so-called photochemical Photo Fries rearrangement ^[4] exists that 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 confined to the laboratory. Image File history File links Fries02. ... Photochemistry is the study of the interaction of light and chemicals. ... In chemistry, radicals (often refered to as free radicals) are atomic or molecular species with unpaired electrons or an otherwise open shell configuration. ... An overall description of how a reaction occurs. ... In organic chemistry, a substituent is an atom or group of atoms subsituted in place of a hydrogen atom on the parent chain of a hydrocarbon. ...

References

1. ^  Fries, K.; Finck, G. Ber., 1908, 41, 2447.
2. ^  Fries, K.; Pfaffendorf, W. Ber., 1910, 43, 212.
3. ^  J. March Advanced Organic Chemistry 3rdEd. John Wiley & Sons 1985, S. 499f.
4. ^  Bellus D. Advances in Photochemistry, Vol. 8, J. Wiley & Sons Inc.,1971, 109-159