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set of reactions to attach substituents to an aromatic ring
Furthermore, the reaction is only useful for primary alkyl halides in an intramolecular sense when a 5- or 6-membered ring is formed. For the intermolecular case, the reaction is limited to tertiary alkylating agents, some secondary alkylating agents (ones for which carbocation rearrangement is degenerate), or alkylating agents that yield stabilized carbocations (e.g., benzylic or allylic ones). In the case of primary alkyl halides, the carbocation-like complex (R(+)---X---Al(-)Cl3) will undergo a carbocationrearrangement reaction to give almost exclusively the rearranged product derived from a secondary or tertiary carbocation.
In this reaction samarium(III) triflate is believed to activate the NBS halogen donor in halonium ion formation.
Friedel-Crafts alkylation has been hypothesized to be reversible. In a retro-Friedel-Crafts reaction or Friedel-Crafts dealkylation, alkyl groups are removed in the presence of protons or other Lewis acid.
Friedel-Crafts acylation involves the acylation of aromatic rings. Typical acylating agents are acyl chlorides. Typical Lewis acid catalysts are acids and aluminium trichloride. However, because the product ketone forms a rather stable complex with Lewis acids such as AlCl3, a stoichiometric amount or more of the "catalyst" must generally be employed, unlike the case of the Friedel-Crafts alkylation, in which the catalyst is constantly regenerated. Friedel-Crafts acylation is also possible with acid anhydrides. Reaction conditions are similar to the Friedel-Crafts alkylation. 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 acylium ion is stabilized by a resonance structure in which the positive charge is on the oxygen.
The reaction proceeds through generation of an acylium center. The reaction is completed by deprotonation of the arenium ion by AlCl4-, regenerating the AlCl3 catalyst. However, in contrast to the truly catalytic alkylation reaction, the formed ketone is a moderate Lewis base, which forms a complex with the strong Lewis acid aluminum trichloride. The formation of this complex is typically irreversible under reaction conditions. Thus, a stochiometric quantity of AlCl3 is needed. The complex is destroyed upon aqueous workup to give the desired ketone. For example, the classical synthesis of deoxybenzoin calls for 1.1 equivalents of AlCl3 with respect to the limiting reagent, phenylacetyl chloride. In certain cases, generally when the benzene ring is activated, Friedel-Crafts acylation can also be carried out with catalytic amounts of a milder Lewis acid (e.g. Zn(II) salts) or a Brønsted acid catalyst using the anhydride or even the carboxylic acid itself as the acylation agent.
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 except that rearrangement is not possible.
Arenes react with certain aldehydes and ketones to form the hydroxyalkylated products, for example in the reaction of the mesityl derivative of glyoxal with benzene:
As usual, the aldehyde group is more reactive electrophile than the phenone.
Scope and variations
This reaction is related to several classic named reactions:
The Haworth reaction is a classic method for the synthesis of 1-tetralone. In this reaction, benzene is reacted with succinic anhydride, the intermediate product is reduced and a second FC acylation takes place with addition of acid.
In a related reaction, phenanthrene is synthesized from naphthalene and succinic anhydride in a series of steps which begin with FC acylation.
Friedel-Crafts test for aromatic hydrocarbons
Reaction of chloroform 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.
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