The Fries rearrangement, named for the German chemist
Karl Theophil Fries, is a
rearrangement reaction of a phenolic ester to a
hydroxy aryl
In organic chemistry, an aryl is any functional group or substituent derived from an aromaticity, aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar ...
ketone by
catalysis
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
of
Lewis acids.
It involves migration of an
acyl
In chemistry, an acyl group is a moiety derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids. It contains a double-bonded oxygen atom and an alkyl group (). In organic chemistry, the acyl group (IUPAC ...
group of
phenol
Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it ...
ester to the
aryl
In organic chemistry, an aryl is any functional group or substituent derived from an aromaticity, aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar ...
ring. The reaction is
ortho and para selective and one of the two products can be favoured by changing reaction conditions, such as
temperature
Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measurement, measured with a thermometer.
Thermometers are calibrated in various Conversion of units of temperature, temp ...
and
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
.
Mechanism
Despite many efforts, a definitive
reaction mechanism for the Fries rearrangement has not been determined. Evidence for inter- and
intramolecular mechanisms have been obtained by
crossover experiments with mixed reactants. The reaction progress is not dependent on
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
or
substrate. A widely accepted mechanism involves a
carbocation intermediate.
In the first reaction step a
Lewis acid for instance
aluminium chloride
Aluminium chloride, also known as aluminium trichloride, is an inorganic compound with the formula . It forms hexahydrate with the formula , containing six water molecules of hydration. Both are colourless crystals, but samples are often contam ...
co-ordinates to the
carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containi ...
oxygen atom of the
acyl
In chemistry, an acyl group is a moiety derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids. It contains a double-bonded oxygen atom and an alkyl group (). In organic chemistry, the acyl group (IUPAC ...
group. This oxygen atom is more
electron
The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family,
and are generally thought to be elementary particles because they have no ...
rich than the
phenol
Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it ...
ic oxygen atom and is the preferred
Lewis base. This interaction
polarizes the
bond
Bond or bonds may refer to:
Common meanings
* Bond (finance), a type of debt security
* Bail bond, a commercial third-party guarantor of surety bonds in the United States
* Chemical bond, the attraction of atoms, ions or molecules to form chemica ...
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
In chemistry, an acyl group is a moiety derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids. It contains a double-bonded oxygen atom and an alkyl group (). In organic chemistry, the acyl group (IUPAC n ...
carbocation which reacts in a classical
electrophilic aromatic substitution
Electrophilic aromatic substitution is an organic reaction in which an atom that is attached to an aromatic system (usually hydrogen) is replaced by an electrophile. Some of the most important electrophilic aromatic substitutions are aromatic n ...
with the aromatic ring. The abstracted proton is released as
hydrochloric acid
Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid
Acid strength is the tendency of an acid, symbol ...
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, 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.
Scope
Phenol
Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it ...
s react to form
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...
s instead of hydroxyarylketones when reacted with
acyl halide
In organic chemistry, an acyl halide (also known as an acid halide) is a chemical compound derived from an oxoacid by replacing a hydroxyl group () with a halide group (, where X is a halogen).
If the acid is a carboxylic acid (), the compoun ...
s 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
Aluminium chloride, also known as aluminium trichloride, is an inorganic compound with the formula . It forms hexahydrate with the formula , containing six water molecules of hydration. Both are colourless crystals, but samples are often contam ...
, other
Lewis acids such as
boron trifluoride and
bismuth
Bismuth is a chemical element with the symbol Bi and atomic number 83. It is a post-transition metal and one of the pnictogens, with chemical properties resembling its lighter group 15 siblings arsenic and antimony. Elemental bismuth occurs ...
triflate
In organic chemistry, triflate ( systematic name: trifluoromethanesulfonate), is a functional group with the formula and structure . The triflate group is often represented by , as opposed to −Tf, which is the triflyl group, . For example, ...
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
catalyst
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
s altogether research into alternative
heterogeneous catalysts is actively pursued.
Limits
In all instances only
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...
s 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
In chemistry, yield, also referred to as reaction yield, is a measure of the quantity of moles of a product formed in relation to the reactant consumed, obtained in a chemical reaction, usually expressed as a percentage. Yield is one of the pr ...
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
Photochemistry is the branch of chemistry concerned with the chemical effects of light. Generally, this term is used to describe a chemical reaction caused by absorption of ultraviolet (wavelength from 100 to 400 nm), visible light (400–7 ...
variant is possible. The photo-Fries rearrangement can likewise give
,3and
,5products, 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
Polyurethane (; often abbreviated PUR and PU) refers to a class of polymers composed of organic units joined by carbamate (urethane) links. In contrast to other common polymers such as polyethylene and polystyrene, polyurethane is produced from ...
, 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
In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formally o ...
and carbonates with a strong base results in a rearrangement to give ortho-carbonyl species.
See also
*
Friedel–Crafts alkylation-like reactions:
**
Hofmann–Martius rearrangement The Hofmann–Martius rearrangement in organic chemistry is a rearrangement reaction converting an N-alkylated aniline to the corresponding ortho and / or para aryl-alkylated aniline. The reaction requires heat, and the catalyst is an acid like h ...
**
Fischer–Hepp rearrangement
*
Duff reaction The Duff reaction or hexamine aromatic formylation is a formylation reaction used in organic chemistry for the synthesis of benzaldehydes with hexamine as the formyl carbon source. It is named after James Cooper Duff, who was a chemist at the Col ...
References
{{DEFAULTSORT:Fries Rearrangement
Rearrangement reactions
Name reactions
Free radical reactions