Aluminum Chloride1

AlCl3

[7446-70-0]  · AlCl3  · Aluminum Chloride  · (MW 133.34)

(Lewis acid catalyst for Friedel-Crafts, Diels-Alder, [2 + 2] cycloadditions, ene reactions, rearrangements, and other reactions)

Physical Data: mp 190 °C (193-194 °C sealed tube); sublimes at 180 °C; d 2.44 g cm-3.

Solubility: sol many organic solvents, e.g. benzene, nitrobenzene, carbon tetrachloride, chloroform, methylene chloride, nitromethane, and 1,2-dichloroethane; insol carbon disulfide.

Form Supplied in: colorless solid when pure, typically a gray or yellow-green solid; also available as a 1.0 M nitrobenzene solution.

Handling, Storage, and Precautions: fumes in air with a strong odor of HCl. AlCl3 reacts violently with H2O. All containers should be kept tightly closed and protected from moisture.1c Use in a fume hood.

Friedel-Crafts Chemistry.1,2

AlCl3 has traditionally been used in stoichiometric or catalytic3 amounts to mediate Friedel-Crafts alkylations and acylations of aromatic systems (eq 1).

This is a result of the Lewis acidity of AlCl3 which complexes strongly with carbonyl groups.4 Adaptations of these basic reactions have been reported.5 In chiral systems, inter- and intramolecular acylations have been achieved without the loss of optical activity (eq 2).6

Friedel-Crafts chemistry at an asymmetric center generally proceeds with racemization, but the use of mesylates or chlorosulfonates as leaving groups has resulted in alkylations with excellent control of stereochemistry.7 The reactions proceed with inversion of configuration (eq 3). Cyclopropane derivatives have been used as three-carbon units in acylation reactions (eq 4).8 In conjunction with triethylsilane, a net alkylation is possible under acylation conditions (eq 5).9 These conditions are compatible with halogen atoms present elsewhere in the molecule. Acylation reactions of phenolic compounds with heteroaromatic systems have also been accomplished (eq 6).10

Treatment of aryl azides with AlCl3 has been reported to give polycyclic aromatic compounds (eq 7),11 or aziridines when the reactions are run in the presence of alkenes (eq 8).12

The scope of Friedel-Crafts chemistry has been expanded beyond aromatic systems to nonaromatic systems, such as alkenes and alkynes and the mechanistic details have been investigated.13 The Friedel-Crafts alkylation14 and acylation15 of alkenes provide access to a variety of organic systems (eq 9). The acylation of alkynes provides access to cyclopentenone derivatives (eq 10).16 In addition, one can use this chemistry to access indenyl systems17 and vinyl chlorides.18 Allylic sulfones can undergo allylation chemistry (eq 11).19

The use of silyl derivatives in Friedel-Crafts chemistry has not only improved the regioselectivity but extended the scope of these reactions. Substitution at the ipso position occurs with aryl silanes (eq 12).20 The ability of silyl groups to stablize b-carbenium ions (b-effect) affords acylated products with complete control of regiochemistry (eq 13).21

The use of silylacetylenes gives ynones (eq 14),22 cyclopentenone derivatives (eq 15),23 and a-amino acid derivatives (eq 16).24

Propargylic silanes undergo acylation to generate allenyl ketones (eq 17),25 while alkylsilanes afford cycloalkanones (eq 18).26

Several name reactions are promoted by AlCl3. For example, the Darzens-Nenitzescu reaction is simply the acylation of alkenes. The Ferrario reaction generates phenoxathiins from diphenyl ethers (eq 19).27 The rearrangement of acyloxy aromatic systems is known as the Fries rearrangement (eq 20).28 Aryl aldehydes are produced by the Gatterman aldehyde synthesis (eq 21).29 The initial step of the Haworth phenanthrene synthesis makes use of a Friedel-Crafts acylation.30 The acylation of phenolic compounds is called the Houben-Hoesch reaction (eq 22).31 The Leuckart amide synthesis generates aryl amides from isocyanates (eq 23).32

Amides can also be obtained by AlCl3 catalyzed ester amine exchange which proceeds primarily without racemization of chiral centers (eq 24).33 The reaction of phenols with b-keto esters is known as the Pechmann condensation (eq 25).34 Aryl amines are used in the Riehm quinoline synthesis (eq 26).35 Aromatic systems may be coupled via the Scholl reaction (eq 27)36 and indole derivatives are prepared in the Stolle synthesis (eq 28).37 In the Zincke-Suhl reaction, phenols are converted to dienones (eq 29).38

Diels-Alder Reactions.

There is some evidence that AlCl3 catalysis of Diels-Alder reactions changes the transition state from a synchronous to an asynchronous one.39 This also enhances asymmetric induction by increasing steric interactions at one end of the dieneophile. There are many examples of AlCl3 promoted Diels-Alder reactions (eq 30).40 Hetero-Diels-Alder reactions can be used to generate oxygen (eq 31)41 and nitrogen (eq 32)42 containing heterocycles.

AlCl3 can also be used to catalyze [2 + 2] cycloaddition reactions (eq 33)43 and ene reactions (eq 34).44

Rearrangements.

AlCl3 catalyzed rearrangement of hydrocarbon derivatives to adamantanes has been well documented (eq 35).45 Other rearrangements have been used in triquinane synthesis (eq 36).46

Miscellaneous Reactions.

AlCl3 has been used to catalyze the addition of allylsilanes to aldehydes and acid chlorides (eq 37).47 Cyclic ethers (pyrans and oxepins) have been prepared with hydroxyalkenes (eq 38).48 The course of reactions between aldehydes and allylic Grignard reagents can be completely diverted to a-allylation by AlCl3 (eq 39).49 The normal course of the reaction gives g-allylation products.

AlCl3 can be used to remove t-butyl groups from aromatic rings (eq 40),50 thereby using this group as a protecting element for a ring position. AlCl3 has also been used to remove p-nitrobenzyl (PNB) and benzhydryl protecting groups (eq 41).51 The combination of AlCl3 and Ethanethiol has formed the basis of a push-pull mechanism for the cleavage of many types of bonds including C-X,52 C-NO2,53 C=C,54 and C-O.55 Furthermore, AlCl3 has been used to catalyze chlorination of aromatic rings,56 open epoxides,57 and mediate addition of dichlorophosphoryl groups to alkanes.58


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Paul Galatsis

University of Guelph, Ontario, Canada



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