Friedel-Crafts reaction
Overview
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
developed by Charles Friedel
Charles Friedel
Charles Friedel was a French chemist and mineralogist. A native of Strasbourg, France, he was a student of Louis Pasteur at the Sorbonne...
and James Crafts
James Crafts
James Mason Crafts was an American chemist, best known for developing the Friedel-Crafts alkylation and acylation reactions with Charles Friedel in 1876.-Biography:...
in 1877. There are two main types of Friedel–Crafts reactions: alkylation
Alkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...
reactions and acylation
Acylation
In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....
reactions. This reaction type is a form of electrophilic aromatic substitution
Electrophilic aromatic substitution
Electrophilic aromatic substitution EAS is an organic reaction in which an atom, usually hydrogen, appended to an aromatic system is replaced by an electrophile...
. The general reaction scheme is shown below.
Several reviews have been written.
Friedel–Crafts alkylation involves the alkylation of an aromatic ring with an alkyl halide using a strong Lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...
catalyst.
Unanswered Questions
Encyclopedia
The Friedel–Crafts reactions are a set of reactions
developed by Charles Friedel
and James Crafts
in 1877. There are two main types of Friedel–Crafts reactions: alkylation
reactions and acylation
reactions. This reaction type is a form of electrophilic aromatic substitution
. The general reaction scheme is shown below.
Several reviews have been written.
catalyst. With anhydrous ferric chloride as a catalyst, the alkyl group attaches at the former site of the chloride ion. The general mechanism is shown below.
This reaction has one big disadvantage, namely that the product is more nucleophilic
than the reactant due to the electron donating alkyl-chain. Therefore, another hydrogen is substituted with an alkyl-chain, which leads to overalkylation of the molecule. Also, if the chlorine is not on a tertiary carbon, carbocation
rearrangement reaction
will occur. This is due to the relative stability of the tertiary carbocation
over the secondary and primary carbocations.
Steric hindrance can be exploited to limit the number of alkylations, as in the t-butylation of 1,4-dimethoxybenzene.
Alkylations are not limited to alkyl halides: Friedel–Crafts reactions are possible with any carbocation
ic intermediate such as those derived from alkene
s and a protic acid, Lewis acid
, enone
s, and epoxide
s. An example is the synthesis of neophyl chloride
from benzene and methallyl chloride:
In one study the electrophile is a bromonium ion derived from an alkene and NBS
:
In this reaction samarium(III) triflate is believed to activate the NBS halogen donor in halonium ion formation.
. In a reversed Friedel–Crafts reaction or Friedel–Crafts dealkylation, alkyl groups can be removed in the presence of protons and a Lewis acid
.
For example, in a multiple addition of ethyl bromide
to benzene
, ortho and para substitution
is expected after the first monosubstitution step because an alkyl group is an activating group
. However, the actual reaction product is 1,3,5-triethylbenzene with all alkyl groups as a meta substituent. Thermodynamic reaction control
makes sure that thermodynamically favored meta substitution with steric hindrance minimized takes prevalence over less favorable ortho and para substitution by chemical equilibration
. The ultimate reaction product is thus the result of a series of alkylations and dealkylations.
of aromatic rings with an acyl chloride
using a strong Lewis acid
catalyst. Friedel–Crafts acylation is also possible with acid anhydrides. Reaction conditions are similar to the Friedel–Crafts alkylation mentioned above. This reaction has several advantages over the alkylation reaction. Due to the electron-withdrawing effect of the carbonyl
group, the ketone
product is always less reactive than the original molecule, so multiple acylations do not occur. Also, there are no carbocation
rearrangements, as the carbonium ion
is stabilized by a resonance structure in which the positive charge is on the oxygen.
The viability of the Friedel–Crafts acylation depends on the stability of the acyl chloride reagent. Formyl chloride, for example, is too unstable to be isolated. Thus, synthesis of benzaldehyde
via the Friedel–Crafts pathway requires that formyl chloride be synthesized in situ. This is accomplished via the Gattermann-Koch reaction
, accomplished by treating benzene
with carbon monoxide
and hydrogen chloride
under high pressure, catalyzed by a mixture of aluminium chloride
and cuprous chloride.
cation ("acylium ion"):
In some cases, the Lewis acid binds to the oxygen of the acyl chloride to form an adduct. Regardless, the resulting acylium ion or a related adduct is subject to nucleophilic attack by the arene:
Finally, chloride anion (or AlCl4-) deprotonates the ring (an "arenium ion
") to form HCl, and the AlCl3 catalyst is regenerated:
If desired, the resulting ketone can be subsequently reduced to the corresponding alkane substituent by either Wolff–Kishner reduction or Clemmensen reduction
. The net result is the same as the Friedel–Crafts alkylation.
s and ketone
s to form the hydroxyalkylated product for example in the reaction of the mesityl derivative of glyoxal
with benzene to form a benzoin
with an alcohol
rather than a carbonyl
group:
and xanthene
dye
s. Examples are the synthesis of thymolphthalein
(a pH indicator) from two equivalents of thymol
and phthalic anhydride
:
A reaction of phthalic anhydride with resorcinol
in the presence of zinc chloride
gives the fluorophore Fluorescein. Replacing resorcinol by N,N-diethylaminophenol in this reaction gives rhodamine B
:
. In it benzene
is reacted with succinic anhydride
, the intermediate product is reduced and a second FC acylation takes place with addition of acid (see also: http://books.google.co.uk/books?id=6mZJ3084ouAC&pg=PA175&lpg=PA175).
In a related reaction, phenanthrene
is synthesized from naphthalene
and succinic anhydride
in a series of steps.
with aromatic compounds using an aluminium chloride
catalyst gives triarylmethanes, which are often brightly colored, as is the case in triarylmethane dyes. This is a bench test for aromatic compounds.
:
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
developed by Charles Friedel
Charles Friedel
Charles Friedel was a French chemist and mineralogist. A native of Strasbourg, France, he was a student of Louis Pasteur at the Sorbonne...
and James Crafts
James Crafts
James Mason Crafts was an American chemist, best known for developing the Friedel-Crafts alkylation and acylation reactions with Charles Friedel in 1876.-Biography:...
in 1877. There are two main types of Friedel–Crafts reactions: alkylation
Alkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...
reactions and acylation
Acylation
In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....
reactions. This reaction type is a form of electrophilic aromatic substitution
Electrophilic aromatic substitution
Electrophilic aromatic substitution EAS is an organic reaction in which an atom, usually hydrogen, appended to an aromatic system is replaced by an electrophile...
. The general reaction scheme is shown below.
Several reviews have been written.
Friedel–Crafts alkylation
Friedel–Crafts alkylation involves the alkylation of an aromatic ring with an alkyl halide using a strong Lewis acidLewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...
catalyst. With anhydrous ferric chloride as a catalyst, the alkyl group attaches at the former site of the chloride ion. The general mechanism is shown below.
This reaction has one big disadvantage, namely that the product is more nucleophilic
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...
than the reactant due to the electron donating alkyl-chain. Therefore, another hydrogen is substituted with an alkyl-chain, which leads to overalkylation of the molecule. Also, if the chlorine is not on a tertiary carbon, carbocation
Carbocation
A carbocation is an ion with a positively-charged carbon atom. The charged carbon atom in a carbocation is a "sextet", i.e. it has only six electrons in its outer valence shell instead of the eight valence electrons that ensures maximum stability . Therefore carbocations are often reactive,...
rearrangement reaction
Rearrangement reaction
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. Often a substituent moves from one atom to another atom in the same molecule...
will occur. This is due to the relative stability of the tertiary carbocation
Carbocation
A carbocation is an ion with a positively-charged carbon atom. The charged carbon atom in a carbocation is a "sextet", i.e. it has only six electrons in its outer valence shell instead of the eight valence electrons that ensures maximum stability . Therefore carbocations are often reactive,...
over the secondary and primary carbocations.
Steric hindrance can be exploited to limit the number of alkylations, as in the t-butylation of 1,4-dimethoxybenzene.
Alkylations are not limited to alkyl halides: Friedel–Crafts reactions are possible with any carbocation
Carbocation
A carbocation is an ion with a positively-charged carbon atom. The charged carbon atom in a carbocation is a "sextet", i.e. it has only six electrons in its outer valence shell instead of the eight valence electrons that ensures maximum stability . Therefore carbocations are often reactive,...
ic intermediate such as those derived from alkene
Alkene
In organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
s and a protic acid, Lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...
, enone
Enone
An enone is an unsaturated chemical compound or functional group consisting of a conjugated system of an alkene and a ketone. The simplest enone is methyl vinyl ketone or CH2=CHCOCH3....
s, and epoxide
Epoxide
An epoxide is a cyclic ether with three ring atoms. This ring approximately defines an equilateral triangle, which makes it highly strained. The strained ring makes epoxides more reactive than other ethers. Simple epoxides are named from the parent compound ethylene oxide or oxirane, such as in...
s. An example is the synthesis of neophyl chloride
Neophyl chloride
Neophyl chloride, C6H5C2CH2Cl, is a halogenated organic compound with unusual nucleophilic substitution properties. Neophyl chloride is used to form a versatile organolithium reagent, neophyl lithium, by reaction with lithium.- Preparation :...
from benzene and methallyl chloride:
- H2C=C(CH3)CH2Cl + C6H6 → C6H5C(CH3)2CH2Cl
In one study the electrophile is a bromonium ion derived from an alkene and NBS
N-Bromosuccinimide
N-Bromosuccinimide or NBS is a chemical reagent which is used in radical substitution and electrophilic addition reactions in organic chemistry. NBS can be considered a convenient source of cationic bromine.-Preparation:...
:
In this reaction samarium(III) triflate is believed to activate the NBS halogen donor in halonium ion formation.
Friedel–Crafts dealkylation
Friedel–Crafts alkylation is a reversible reactionReversible reaction
A reversible reaction is a chemical reaction that results in an equilibrium mixture of reactants and products. For a reaction involving two reactants and two products this can be expressed symbolically as...
. In a reversed Friedel–Crafts reaction or Friedel–Crafts dealkylation, alkyl groups can be removed in the presence of protons and a Lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...
.
For example, in a multiple addition of ethyl bromide
Bromoethane
Bromoethane, also known as ethyl bromide, is a chemical compound of the haloalkanes group. It is abbreviated by chemists as EtBr. This volatile compound has an ether-like odour.-Preparation:...
to benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
, ortho and para substitution
Arene substitution patterns
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.- Ortho, meta, and para substitution :...
is expected after the first monosubstitution step because an alkyl group is an activating group
Activating group
In organic chemistry, a functional group is called an activating group if a benzene molecule to which it is attached more readily participates in electrophilic substitution reactions...
. However, the actual reaction product is 1,3,5-triethylbenzene with all alkyl groups as a meta substituent. Thermodynamic reaction control
Thermodynamic reaction control
Thermodynamic reaction control or kinetic reaction control in a chemical reaction can decide the composition in a reaction product mixture when competing pathways lead to different products and the reaction conditions influence the selectivity...
makes sure that thermodynamically favored meta substitution with steric hindrance minimized takes prevalence over less favorable ortho and para substitution by chemical equilibration
Chemical equilibrium
In a chemical reaction, chemical equilibrium is the state in which the concentrations of the reactants and products have not yet changed with time. It occurs only in reversible reactions, and not in irreversible reactions. Usually, this state results when the forward reaction proceeds at the same...
. The ultimate reaction product is thus the result of a series of alkylations and dealkylations.
Friedel–Crafts acylation
Friedel–Crafts acylation is the acylationAcylation
In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....
of aromatic rings with an acyl chloride
Acyl chloride
In organic chemistry, an acyl chloride is an organic compound with the functional group -CO-Cl. Their formula is usually written RCOCl, where R is a side chain. They are usually considered to be reactive derivatives of carboxylic acids. A specific example of an acyl chloride is acetyl chloride,...
using a strong Lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...
catalyst. Friedel–Crafts acylation is also possible with acid anhydrides. Reaction conditions are similar to the Friedel–Crafts alkylation mentioned above. This reaction has several advantages over the alkylation reaction. Due to the electron-withdrawing effect of the carbonyl
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....
group, the ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
product is always less reactive than the original molecule, so multiple acylations do not occur. Also, there are no carbocation
Carbocation
A carbocation is an ion with a positively-charged carbon atom. The charged carbon atom in a carbocation is a "sextet", i.e. it has only six electrons in its outer valence shell instead of the eight valence electrons that ensures maximum stability . Therefore carbocations are often reactive,...
rearrangements, as the carbonium ion
Carbonium ion
A carbonium ion is a carbocation of the penta- or tetracoordinated nonclassical type such as an ion of the type R5C+.- Methanium:The parent compound methanium or CH5+ is protonated methane and a superacid. This ion exists as a reactive intermediate in the interstellar medium and can be produced in...
is stabilized by a resonance structure in which the positive charge is on the oxygen.
The viability of the Friedel–Crafts acylation depends on the stability of the acyl chloride reagent. Formyl chloride, for example, is too unstable to be isolated. Thus, synthesis of benzaldehyde
Benzaldehyde
Benzaldehyde is an organic compound consisting of a benzene ring with a formyl substituent. It is the simplest aromatic aldehyde and one of the most industrially useful. This colorless liquid has a characteristic pleasant almond-like odor...
via the Friedel–Crafts pathway requires that formyl chloride be synthesized in situ. This is accomplished via the Gattermann-Koch reaction
Gattermann-Koch reaction
The Gattermann–Koch reaction, named after the German chemists Ludwig Gattermann and Julius Arnold Koch, in organic chemistry refers to a Friedel–Crafts acylation reaction in which carbon monoxide and hydrochloric acid are used in situ with Friedel–Crafts catalyst, namely AlCl3 to produce a...
, accomplished by treating benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
with carbon monoxide
Carbon monoxide
Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...
and hydrogen chloride
Hydrogen chloride
The compound hydrogen chloride has the formula HCl. At room temperature, it is a colorless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric humidity. Hydrogen chloride gas and hydrochloric acid are important in technology and industry...
under high pressure, catalyzed by a mixture of aluminium chloride
Aluminium chloride
Aluminium chloride is the main compound of aluminium and chlorine. It is white, but samples are often contaminated with iron trichloride, giving it a yellow colour. The solid has a low melting and boiling point. It is mainly produced and consumed in the production of aluminium metal, but large...
and cuprous chloride.
Reaction mechanism
In a simple mechanistic view, the first step consists of dissociation of a chloride ion to form an acylAcyl
An acyl group is a functional group derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids.In organic chemistry, the acyl group is usually derived from a carboxylic acid . Therefore, it has the formula RCO-, where R represents an alkyl group that is...
cation ("acylium ion"):
In some cases, the Lewis acid binds to the oxygen of the acyl chloride to form an adduct. Regardless, the resulting acylium ion or a related adduct is subject to nucleophilic attack by the arene:
Finally, chloride anion (or AlCl4-) deprotonates the ring (an "arenium ion
Arenium ion
An arenium ion in organic chemistry is a cyclohexadienyl cation that appears as a reactive intermediate in electrophilic aromatic substitution. For historic reasons this complex is also called a Wheland intermediate or a sigma complex or σ-complex.Two hydrogen atoms bonded to one carbon lie in a...
") to form HCl, and the AlCl3 catalyst is regenerated:
If desired, the resulting ketone can be subsequently reduced to the corresponding alkane substituent by either Wolff–Kishner reduction or Clemmensen reduction
Clemmensen reduction
Clemmensen reduction is a chemical reaction described as a reduction of ketones to alkanes using zinc amalgam and hydrochloric acid. This reaction is named after Erik Christian Clemmensen, a Danish chemist....
. The net result is the same as the Friedel–Crafts alkylation.
Friedel–Crafts hydroxyalkylation
Arenes react with certain aldehydeAldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
s and ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
s to form the hydroxyalkylated product for example in the reaction of the mesityl derivative of glyoxal
Glyoxal
Glyoxal is an organic compound with the formula OCHCHO. This yellow colored liquid is the smallest dialdehyde . Its tautomer acetylenediol is unstable.-Production:...
with benzene to form a benzoin
Benzoin
Benzoin is an organic compound with the formula PhCHCPh. It is a hydroxy ketone attached to two phenyl groups. It appears as off-white crystals, with a light camphor-like odor. Benzoin is synthesized from benzaldehyde in the benzoin condensation...
with an alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
rather than a carbonyl
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....
group:
Scope and variations
This reaction is related to several classic named reactions:- The acylated reaction product can be converted into the alkylated product via a Clemmensen reductionClemmensen reductionClemmensen reduction is a chemical reaction described as a reduction of ketones to alkanes using zinc amalgam and hydrochloric acid. This reaction is named after Erik Christian Clemmensen, a Danish chemist....
. - The Gattermann–Koch reaction can be used to synthesize benzaldehyde from benzene.
- The Gatterman reaction describes arene reactions with hydrocyanic acid
- The Houben–Hoesch reaction describes arene reactions with nitriles
- A reaction modification with an aromatic phenyl ester as a reactant is called the Fries rearrangementFries rearrangementThe Fries rearrangement, named for the German chemist Karl Theophil Fries, is a rearrangement reaction of a phenyl ester to a hydroxy aryl ketone by catalysis of Lewis acids.It involves migration of an acyl group of phenyl ester to benzene ring.- Mechanism:...
. - In the Scholl reactionScholl reactionThe Scholl reaction is a coupling reaction between two arene compounds with the aid of a Lewis acid and a protic acid. It is named after its discoverer, Roland Scholl....
two arenes couple directly (sometimes called Friedel–Crafts arylation). - In the Zincke–Suhl reaction p-cresol is alkylated to a cyclohexadienone with tetrachloromethane
- In the Blanc chloromethylationBlanc chloromethylationThe Blanc chloromethylation is the chemical reaction of aromatic rings with formaldehyde and hydrogen chloride catalyzed by zinc chloride to form chloromethyl arenes.-References:# Gustave Louis Blanc Bull. Soc. Chim. France 1923, 33, 313....
a chloromethyl group is added to an arene with formaldehyde, hydrochloric acid and zinc chloride. - The Bogert-Cook Synthesis (1933) involves the dehydrationDehydrationIn physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
and isomerization of 1-β-phenylethylcyclohexanol to the octahydro derivative of phenanthrenePhenanthrenePhenanthrene is a polycyclic aromatic hydrocarbon composed of three fused benzene rings. The name phenanthrene is a composite of phenyl and anthracene. In its pure form, it is found in cigarette smoke and is a known irritant, photosensitizing skin to light...
- The Darzens–Nenitzescu Synthesis of Ketones (1910, 1936) involves the acylation of cyclohexeneCyclohexeneCyclohexene is a hydrocarbon with the formula C6H10. This cycloalkene is a colorless liquid with a sharp smell. It is an intermediate in various industrial processes...
with acetyl chlorideAcetyl chlorideAcetyl chloride, CH3COCl, also known as ethanoyl chloride or acyl chloride, is an acid chloride derived from acetic acid. It belongs to the class of organic compounds called acyl halides. It is a colorless liquid. Acetyl chloride does not exist in nature, because contact with water would hydrolyze...
to methylcyclohexenylketone. - In the related Nenitzescu reductive acylation (1936) a saturatedSaturation (chemistry)In chemistry, saturation has six different meanings, all based on reaching a maximum capacity...
hydrocarbonHydrocarbonIn organic chemistry, a hydrocarbon is an organic compound consisting entirely of hydrogen and carbon. Hydrocarbons from which one hydrogen atom has been removed are functional groups, called hydrocarbyls....
is added making it a reductive acylation to methylcyclohexylketone - In a green chemistryGreen chemistryGreen chemistry, also called sustainable chemistry, is a philosophy of chemical research and engineering that encourages the design of products and processes that minimize the use and generation of hazardous substances...
variation aluminium chlorideAluminium chlorideAluminium chloride is the main compound of aluminium and chlorine. It is white, but samples are often contaminated with iron trichloride, giving it a yellow colour. The solid has a low melting and boiling point. It is mainly produced and consumed in the production of aluminium metal, but large...
is replaced by graphiteGraphiteThe mineral graphite is one of the allotropes of carbon. It was named by Abraham Gottlob Werner in 1789 from the Ancient Greek γράφω , "to draw/write", for its use in pencils, where it is commonly called lead . Unlike diamond , graphite is an electrical conductor, a semimetal...
in an alkylation of p-xyleneP-Xylenep-Xylene is an aromatic hydrocarbon, based on benzene with two methyl substituents. The “p” stands for para, identifying the location of the methyl groups as across from one another....
with 2-bromobutane2-Bromobutane2-Bromobutane is an isomer of 1-bromobutane. Both compounds share the molecular formula C4H9Br. 2-Bromobutane is also known as sec-butyl bromide or methylethylbromomethane. Because it contains bromine, a halogen, it is part of a larger class of compounds known as alkyl halides. It is a...
. This variation will not work with primary halides from which less carbocation involvement is inferred.
Dyes
Friedel–Crafts reactions have been used in the synthesis of several triarylmethaneTriphenylmethane
Triphenylmethane, or triphenyl methane, is the hydrocarbon with the formula 3CH. This colorless solid is soluble in nonpolar organic solvents and not in water. Triphenylmethane has the basic skeleton of many synthetic dyes called triarylmethane dyes, many of them are pH indicators, and some display...
and xanthene
Xanthene
Xanthene is a yellow organic heterocyclic compound. Its chemical formula is 1310. It is soluble in diethyl ether. Its melting point is 101-102 °C and its boiling point is 310-312 °C...
dye
Dye
A dye is a colored substance that has an affinity to the substrate to which it is being applied. The dye is generally applied in an aqueous solution, and requires a mordant to improve the fastness of the dye on the fiber....
s. Examples are the synthesis of thymolphthalein
Thymolphthalein
Thymolphthalein is an acid-base indicator. Its transition range is at approximately pH 9.3-10.5. Below this pH, it is colorless; above this pH, it is blue. The molar extinction coefficient for the blue thymolphthalein dianion is 38000 M-1cm-1 at 595 nm....
(a pH indicator) from two equivalents of thymol
Thymol
Thymol is a natural monoterpene phenol derivative of cymene, C10H14O, isomeric with carvacrol, found in oil of thyme, and extracted from Thymus vulgaris and various other kinds of plants as a white crystalline substance of a pleasant aromatic odor and strong antiseptic properties...
and phthalic anhydride
Phthalic anhydride
Phthalic anhydride is the organic compound with the formula C6H42O. It is the anhydride of phthalic acid. This colourless solid is an important industrial chemical, especially for the large-scale production of plasticizers for plastics. In 2002, approximately 4.6 billion kilograms were...
:
A reaction of phthalic anhydride with resorcinol
Resorcinol
Resorcinol is a dihydroxy benzene. It is the 1,3-isomer of benzenediol with the formula C6H42.-Nomenclature:Benzene-1,3-diol is the name recommended by the International Union of Pure and Applied Chemistry in its 1993 Recommendations for the Nomenclature of Organic Chemistry.-Production:It is...
in the presence of zinc chloride
Zinc chloride
Zinc chloride is the name of chemical compound with the formula ZnCl2 and its hydrates. Zinc chlorides, of which nine crystalline forms are known, are colorless or white, and are highly soluble in water. ZnCl2 itself is hygroscopic and even deliquescent. Samples should therefore be protected from...
gives the fluorophore Fluorescein. Replacing resorcinol by N,N-diethylaminophenol in this reaction gives rhodamine B
Rhodamine B
Rhodamine B is a chemical compound and a dye. It is often used as a tracer dye within water to determine the rate and direction of flow and transport. Rhodamine dyes fluoresce and can thus be detected easily and inexpensively with instruments called fluorometers...
:
Haworth reactions
The Haworth reaction is a classic method for the synthesis of tetraloneTetralone
Tetralone is an organic chemical compound with the molecular formula C10H10O. It is a common intermediate in organic synthesis. It is a ketone derivative of tetralin.The Haworth reaction is a classic method for the synthesis of tetralone...
. In it benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
is reacted with succinic anhydride
Succinic anhydride
Succinic anhydride, also called dihydro-2,5-furandione, is an organic compound with the molecular formula C4H4O3. It is the acid anhydride of succinic acid.-Applications:...
, the intermediate product is reduced and a second FC acylation takes place with addition of acid (see also: http://books.google.co.uk/books?id=6mZJ3084ouAC&pg=PA175&lpg=PA175).
In a related reaction, phenanthrene
Phenanthrene
Phenanthrene is a polycyclic aromatic hydrocarbon composed of three fused benzene rings. The name phenanthrene is a composite of phenyl and anthracene. In its pure form, it is found in cigarette smoke and is a known irritant, photosensitizing skin to light...
is synthesized from naphthalene
Naphthalene
Naphthalene is an organic compound with formula . It is a white crystalline solid with a characteristic odor that is detectable at concentrations as low as 0.08 ppm by mass. As an aromatic hydrocarbon, naphthalene's structure consists of a fused pair of benzene rings...
and succinic anhydride
Succinic anhydride
Succinic anhydride, also called dihydro-2,5-furandione, is an organic compound with the molecular formula C4H4O3. It is the acid anhydride of succinic acid.-Applications:...
in a series of steps.
Friedel–Crafts test for aromatic hydrocarbons
Reaction of chloroformChloroform
Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...
with aromatic compounds using an aluminium chloride
Aluminium chloride
Aluminium chloride is the main compound of aluminium and chlorine. It is white, but samples are often contaminated with iron trichloride, giving it a yellow colour. The solid has a low melting and boiling point. It is mainly produced and consumed in the production of aluminium metal, but large...
catalyst gives triarylmethanes, which are often brightly colored, as is the case in triarylmethane dyes. This is a bench test for aromatic compounds.
See also
- Friedel familyFriedel familyFour French scientists with the same Friedel family name are in direct lineage, Charles, Georges, Edmond and Jacques:* Charles Friedel , French chemist known for the Friedel-Crafts reaction...
, a rich lineage of French scientists - HydrodealkylationHydrodealkylationHydrodealkylation is a chemical reaction that often involves reacting an aromatic hydrocarbon, such as toluene, in the presence of hydrogen gas to form a simpler aromatic hydrocarbon devoid of functional groups. An example is the conversion of 1,2,4-trimethylbenzene to xylene. This chemical process...
- TransalkylationTransalkylationTransalkylation is a chemical reaction of transfer of an alkyl group from one organic compound to another. Zeolite catalysts are often used. The reaction is widely used in the petrochemical industry to manufacture p-xylene, styrene, and other aromatic compounds....
FC (Friedel–Crafts) reactions in Org. Synth.
Friedel–Crafts reactions appear in Organic SynthesesOrganic Syntheses
Organic Syntheses is a scientific journal that since 1921 has provided the chemistry community with annual collections of detailed and checked procedures for the organic synthesis of organic compounds. The journal is peer reviewed...
:
- Alkylations:
- Diphenylacetone, Organic Syntheses, Coll. Vol. 3, p. 343 (1955); Vol. 29, p. 38 (1949) Article link.
- Reaction of p-xyleneP-Xylenep-Xylene is an aromatic hydrocarbon, based on benzene with two methyl substituents. The “p” stands for para, identifying the location of the methyl groups as across from one another....
with chloromethaneChloromethaneChloromethane, also called methyl chloride, R-40 or HCC 40, is a chemical compound of the group of organic compounds called haloalkanes. It was once widely used as a refrigerant. It is a colorless extremely flammable gas with a minorly sweet odor, which is, however, detected at possibly toxic levels...
to dureneDureneDurene, or 1,2,4,5-tetramethylbenzene, is an aromatic hydrocarbon used as a solvent. It is also an intermediate in the manufacture of pyromellitic acid, which is used for manufacturing curing agents, adhesives and coating materials...
Organic Syntheses, Coll. Vol. 2, p. 248 (1943); Vol. 10, p. 32 (1930). Article link - Synthesis of benzophenoneBenzophenoneBenzophenone is the organic compound with the formula 2CO, generally abbreviated Ph2CO. Benzophenone is a widely used building block in organic chemistry, being the parent diarylketone.-Uses:...
from benzeneBenzeneBenzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
and tetrachloromethane Organic Syntheses, Coll. Vol. 1, p. 95 (1941); Vol. 8, p. 26 (1928).Article link
- Acylations:
- Dibenzoylethylene Organic Syntheses, Coll. Vol. 3, p. 248 (1955); Vol. 20, p. 29 (1940) Article link.
- reaction of acenaphtheneAcenaphtheneAcenaphthene is a polycyclic aromatic hydrocarbon consisting of naphthalene with an ethylene bridge connecting positions 1 and 8. An alternative name, 1,2-dihydroacenaphthylene, emphasizes that it is a hydrogenated form of acenaphthylene...
plus succinic acidSuccinic acidSuccinic acid is a dicarboxylic acid. Succinate plays a biochemical role in the citric acid cycle. The name derives from Latin succinum, meaning amber, from which the acid may be obtained....
Organic Syntheses, Coll. Vol. 3, p. 6 (1955); Vol. 20, p. 1 (1940).Article link - Desoxybenzoin Organic Syntheses, Coll. Vol. 2, p. 156 (1943); Vol. 12, p. 16 (1932). Article link
- Acylation of a phenanthrenePhenanthrenePhenanthrene is a polycyclic aromatic hydrocarbon composed of three fused benzene rings. The name phenanthrene is a composite of phenyl and anthracene. In its pure form, it is found in cigarette smoke and is a known irritant, photosensitizing skin to light...
compound Organic Syntheses, Vol. 80, p. 227 Link - Reaction of bromobenzene with acetic anhydrideAcetic anhydrideAcetic anhydride, or ethanoic anhydride, is the chemical compound with the formula 2O. Commonly abbreviated Ac2O, it is the simplest isolatable acid anhydride and is a widely used reagent in organic synthesis...
Organic Syntheses, Coll. Vol. 1, p. 109 (1941); Vol. 5, p. 17 (1925). Article link - beta-methylanthraquinone, Organic Syntheses, Coll. Vol. 1, p. 353 (1941); Vol. 4, p. 43 (1925). Article link
- Benzoylation of ferroceneFerroceneFerrocene is an organometallic compound with the formula Fe2. It is the prototypical metallocene, a type of organometallic chemical compound consisting of two cyclopentadienyl rings bound on opposite sides of a central metal atom. Such organometallic compounds are also known as sandwich compounds...
Organic Syntheses, Coll. Vol. 6, p. 625 (1988); Vol. 56, p. 28 (1977). Article link