Phosphoric acid Friedel-Crafts reaction

Cumene as a pure chemical intermediate is produced in modified Friedel-Crafts reaction processes that use acidic catalysts to alkylate benzene with propylene (see Alkylation Friedel-CRAFTSreactions). The majority of cumene is manufactured with a soHd phosphoric acid catalyst (7). The remainder is made with aluminum chloride catalyst (8). 

Raston has reported an acid-catalyzed Friedel-Crafts reaction [89] in which compounds such as 3,4-dimethoxyphenylmethanol were cyclized to cyclotriveratrylene (Scheme 5.1-57). The reactions were carried out in tributylhexylammonium bis(tri-fluoromethanesulfonyl)amide [NBu3(QHi3)][(CF3S02)2N] with phosphoric or p-toluenesulfonic acid catalysts. The product was isolated by dissolving the ionic liq-uid/catalyst in methanol and filtering off the cyclotriveratrylene product as white crystals. Evaporation of the methanol allowed the ionic liquid and catalyst to be regenerated. 

Apart from the alkyl halide-Lewis acid combination, two other sources of carbo-cations are often used in Friedel-Crafts reactions. Alcohols can serve as carbocation precursors in strong acids such as sulfuric or phosphoric acid. Alkylation can also be effected by alcohols in combination with BF3 or A1C13.37 Alkenes can serve as alkylating agents when a protic acid, especially H2S04, H3P04, and HF, or a Lewis acid, such as BF3 and A1C13, is used as a catalyst.38... 

Friedel-Crafts alkylation can occur intramolecularly to form a fused ring. Intramolecular Friedel-Crafts reactions provide an important method for constructing polycyclic hydrocarbon frameworks. It is somewhat easier to form six-membered than five-membered rings in such reactions. Thus, whereas 4-phenyl-1-butanol gives a 50% yield of a cyclized product in phosphoric acid, 3-phenyl-1-propanol is mainly dehydrated to alkenes.43... 

Kadyrov R, Riermeier TH (2003) Highly enantioselective hydrogen-transfer reductive amination catalytic asymmetric synthesis of primary amines. Angew Chem Int Ed Engl 42 5472-5474 Kang Q, Zhao ZA, You SL (2007) Highly enantioselective Friedel-Crafts reaction of indoles with imines by a chiral phosphoric acid. J Am Chem Soc 129 1484-1485... 

Phosphoric acid protonates 2-methylpropene, forming a rerr-butyl carbocation. The carbocation acts as an electrophile in a Friedel-Crafts reaction to yield ten-butylbenzene. 

The conventional method for preparation of these aromatic ketones involves reaction of the aromatic hydrocarbon with a carboxylic acid derivative in the presence of a Lewis acid (AICI3, FeClj, BF3, ZnCl2, TiCy or Brpnsted acids (poly-phosphoric acid, FIF). The major drawback of the Friedel-Crafts reaction is the need to use a stoichiometric quantity of Lewis acid relative to the ketone formed. This stoichiometric quantity is required because the ketone (product of the reaction) forms a stable stoichiometric complex with the Lewis acid. The decomposition of this complex is generally performed with water, leading to total destruction and loss of the Lewis acid. 

Phenylacetyl chloride 1095 Phenylacetic acid (0.5 mole) and PC13 (0.25 mole) are heated on a steam-bath for an hour. Dry benzene (400 ml) is added to the warm mixture and the benzene solution of phenylacetyl chloride is decanted from the deposited phosphorous acid. If this solution is added to anhydrous A1C13, a Friedel-Crafts reaction results, giving an 82% yield of deoxybenzoin. 

A tandem, double Friedel-Crafts reaction of 2-formylbiphenyl (182) with 2-substituted indoles leading to 9-(3-indolyl)fluorene derivatives (183) with up to 96% ee which was catalyzed by chiral phosphoric acid ( S)-(184), have been reported by You and co-workers (Scheme 50). ... 

The highly efficient enantioselective Friedel-Crafts reaction of pyrroles (203) with nitroolefins (204) catalyzed by the chiral phosphoric acid (154), afforded 2-substituted or 2,5-disubstituted pyrroles (205) in up to 94% ee for a wide range of substrates (Scheme 57). ... 

Luo et al. exploited the enantioselective Friedel-Crafts reaction of phenols 35 with p,y-unsaturated ot-ketoesters 32 to form compounds 36. In their preliminary studies, they found that neither a phosphoric acid nor magnesium fluoride could catalyse the reaction. However, the combination of a phosphoric acid with magnesium fluoride (4 1 ratio) could efficiently catalyse the reaction in good yields (59-82%) and selectivity (79-99%), but using preformed sodium phosphate with magnesium fluoride resulted in no... 

Alkylation of Aromatics. Aromatic hydrocarbons containing a replaceable hydrogen can be alkylated unless steric effects prevent introduction of the alkyl group (61,78-82). The reaction is called the Friedel-Crafts alkylation, first realized in the presence of aluminum chloride, which is the catalyst still the most frequently used and studied in Friedel-Crafts reactions. In addition, many other acid catalysts are effective (80,82-84). These include other Lewis acids (other aluminum halides, gallium chloride, boron trifluoride, ferric chloride, zinc chloride, stannous and stannic chloride, antimony chloride) and protic acids (hydrogen fluoride, concentrated sulfuric acid, phosphoric acid, polyphosphoric acid, trifluo-romethanesulfonic acid, and alkane- and arenesulfonic acids). 

The chiral phosphoric acid catalyst 121 forms hydrogen bonds with enethiourea 203 and the imine, formed in situ from amine 201 and aldehyde 202. The enethiourea 203 attacks then that imine in a pseudointramolecular manner from the si-face to form iminium ion depicted in TS-5. After intramolecular aza-Friedel-Crafts reaction, hexahydropyrroloquinolines 204 were obtained. 

For other examples of use of chiral phosphoric acid as catalyst in the synthesis of indole derivatives, see (a) Q. Kang, Z.-A. Zhao, S.-L. You, Tetrahedron 2009, 65, 1603-1607. Enantioselective synthesis of (3-indolyl)glycine derivatives via asymmetric Friedel-Crafts reaction between indoles and glyoxylate imines. (b) M. Terada, K. Machioka, K. Sorimachi, Angew. Chem. Int. Ed. 2009, 48, 2553-2556. Activation of hemiaminal ethers by chiral Brpnsted acids for facile access to enantioselective two-carbon homologation using enecarbamates. 

Hirata, T. Yamanaka, M. DFT Study of Chiral-Phosphoric-Acid-Catalyzed Enantioselective Friedel-Crafts Reaction of Indole with Nitroalkene Bifunctionality and Substituent Effect of Phosphoric Acid. Chem. Asian J. 2011, 6, 510-516. 

Scheme 2.36 Three-component tandem ot-alkylation-double Friedel-Crafts reaction catalysed by a chiral thiourea, an iV-Boc-protected amino acid, and a chiral phosphoric acid.

Scheme 7.41 Domino cross-metathesis-Friedel-Crafts reaction catalysed by chiral phosphoric acid catalysis and ruthenium catalysis.

The synthesis of STRIP was achieved according to the route shown in Scheme 17. In a simultaneous report, Ling, Wang, and coworkers showed that the corresponding naphthyl-substituted SPlNOL-derived phosphoric acid is a competent catalyst for the venerable asymmetric Friedel-Crafts reaction of indoles with imines [44], giving comparable results to BlNOL-derived phosphoric acids. Subsequently, several groups have utilized SPlNOL-based phosphoric acids as Brpnsted... 

A polystyrene-supported l,l -bi-2-naphthol phosphoric acid derivative (296) has been synthesised and applied in the enantioselective Friedel-Crafts reaction. The immohilised catalyst (296) has been found to be highly active and selective for the reaction of indoles (293) and sulfony-limines (294), and gave corresponding 3-indolylmethanamines (295) with high excellent enantioselectivities (up to 98% ee) (Scheme 79). Moreover, the recycling of (296) (14 cycles) was possible with no substantial loss in catal34ic performance. ... 

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