Friedel phosphoric acid catalysts

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). 

The Friedel Crafts (F C) reaction via activation of electrophiles functionalized by a nitrogen atom, such as imines, is undoubtedly the most practical and atom eco nomical approach to introduce a nitrogen substituted side chain to aromatic com pounds. The enantioselective version of the F C reaction of nitrogen substituted substrates, including imines, with electron rich aromatic compounds enables effi cient access to enantioenriched aryl methanamine derivatives [37[. Several excellent approaches to highly enantioselective F C reactions have been established using chiral phosphoric acid catalysts. 

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. 

One interesting feature of these reactions is that the absolute configurations of the corresponding adducts were switched by employing the same (R)-phosphoric acid catalysts in both Friedel-Crafts reactions. In the case of dihydroindole, the enriched enantiomer was the (S)-enantiomer, whereas the (R)-isomer was the major product in the indole Friedel-Crafts reaction (Figure 11.5). 

An enantioselective, organocatalytic domino Friedel-Crafts aminoalkylation with imines generated in situ from trifluoroacetaldehyde hemiacetal (219) and aniline 220 for the synthesis of chiral trifluoromethyl-containing compounds was reported by Ma and coworkers (Scheme 42.51). Very high activity and selectivity was obtained using chiral phosphoric acid catalysts [109]. 

Alkylation of furan and thiophene has been effected with alkenes and catalysts such as phosphoric acid and boron trifluoride. In general, Friedel-Crafts alkylation of furans or thiophenes is not preparatively useful, partly because of polymerization by the catalyst and partly because of polyalkylation. 

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... 

As a true testament to the potential long-term impact of H-bonding activation, a number of ureas, thioureas, and acid catalysts are now finding broad application in a large number of classical and modem carbon-carbon bond-forming processes. On one hand, Johnston s chiral amidinium ion 28 was elegantly applied to the asymmetric aza-Henry reactions (Scheme 11.12d). On the other hand, chiral phosphoric acids (e.g., 29 and 30), initially developed by Akiyama and Terada, have been successfully employed in Mannich reactions, hydrophosphonylation reac-tions, aza-Friedel-Crafts alkylations (Scheme 11.12e), and in the first example... 

Moreover, phosphoric acid (5)-3r (5 mol%, R = SiPhj) bearing a bulky triphe-nylsilyl group turned out to be a suitable catalyst for the asymmetric Friedel-Crafts alkylation of iV-alkyl pyrroles 31 with M-benzoyl-protected aldimines 32 (Scheme 12) [23]. 2-Pyrrolyl amines 33 were obtained in high yields (66-97%) and moderate to high enantioselectivities (42 to >99% ee). 

The exceedingly high reactivity of ferrocene to Friedel-Crafts acylation is exemplified by the fact that mild catalysts such as stannic chloride (63), boron trifluoride (32), zinc chloride (86), and phosphoric acid (29), can be used with considerable success. When ferrocene and anisole were allowed to compete for limited amounts of acetyl chloride and aluminum chloride, acetylferrocene was the sole product isolated, again illustrating the high reactivity of ferrocene toward electrophilic reagents (6). 

Friedel-Crafts alkylation of benzo[6]thiophene has received little attention. The published results, which deserve reexamination, indicate that exclusive 3-substitution occurs in some cases, whereas in others, 2-substitution predominates. Benzo[6]thiophene is alkylated with isopropyl chloride, isopropanol, or propene in the presence of various acid catalysts under a variety of reaction conditions to give a mixture of 2- and 3-isopropylbenzo[6]thiophene in which the 2-isomer predominates (78-92%).358 410 In contrast, alkylation with isobutene in the presence of either 80% sulfuric acid415 or 100% phosphoric acid416 is said to afford exclusively 3-/er<-butylbenzo[6]thiophene in yields of 100 and 75%, respectively. In neither case was the structure of the product rigorously confirmed. Likewise, 3-Jeri-amylbenzo [63-thiophene is the exclusive product of alkylation with tert-amyl alcohol in the presence of stannic chloride414 alkylation with pent-l-ene, hex-l-ene, and a Ci8 propylene polymer is also claimed to give... 

An enantioselective Friedel-Crafts alkylation of pyrroles with /V-acylimincs has been reported <070L4065>. The reactions were run in the presence of chiral phosphoric acids. A novel C-H bond activation procedure was developed for the preparation of heteroarylamides including pyrrole-3-carboxamides <07CL872>. The reactions involved imine-substituted pyrroles, isocyanate electrophiles, and a rhenium catalyst. 

Friedel-Crafts alkylation processes were traditionally operated at 65-70°C with AICI3 and at 40-60°C with HF. A variety of solid acid catalysts have been developed at the laboratory level, mainly based on zeolites, heteropolyacids or sulfated zirconia (zirconia treated with sulfuric acid). The most recent industrial achievement is the Detal process (UOP-CEPSA) which is based on silica-alumina impregnated with HF. The selectivity towards linear alkylbenzenes exceeds 95%. The cymene processes use AICI3 in the liquid phase or supported phosphoric acid as catalysts. 

Cumene is an important intermediate in the industrial production of phenol, acetone and a-methylstyrene. The large-scale production of cumene is based on the alkylation of benzene with propene over Friedel-Crafts [1] or phosphoric acid on silica catalysts [2]. Zeolites, namely ZSM-5 and ZSM-11, have also been shown to be potential catalysts for this process [3, 4]. However, the formation of cumene (isopropylbenzene. IPB) on this catalysts is accompanied by its isomerization to n-propylbenzene (NPB). The latter is considered as an undesired by-product with respect to further processing of cumene to phenol and acetone. Therefore, preventing the formation of NPB would enable the substitution of the current catalysts used in the industrial process by ZSM-5 or ZSM-11 type solid acids which have major advantages in terms of environmental protection, safety, and avoidance of corrosion. 

Friedel-Crafts Acylation of Cedrene. Let us now look in a little more detail at the Friedel-Crafts acylation of cedrene. This reaction can be carried out using acetic acid or acetic anhydride with an acid catalyst such as formic acid, phosphoric acid or sulfuric acid. The species which attacks the double bond of cedrene is the protonated acid or anhydride molecule. When sulfuric acid is used as a catalyst with acetic anhydride as the reagent, it is thought that the sulfuric acid first sulfonates the acetic anhydride to give sulfoacetic anhydride (6.122) as the acylating species. This results in a faster reaction as the sulfoacetate anion (6.126) is a... 

Nitroalkenes are not the only substrates employed as electrophiles in these conjugate Friedel-Crafts alkylations using chiral phosphoric acids as catalysts. In fact, the first reports in this field were focused on the reaction of indoles with p,y-unsaturated ot-ketoesters as Michael acceptors, which underwent clean... 

Mesoporous Metal Oxide Solid Acids Three-dimensional porous metal oxides have been recently synthesized and applied to acid-catalyzed reactions. The use of mesoporous metal oxides is an interesting approach to develop a solid acid catalyst with enhanced activity. The mesopores in the oxide allow the reactants to access additional active acid sites in the pores, resulting in improved rates of acid catalysis. Mesoporous niobium oxides and tantalum oxides treated with phosphoric acid or sulfuric acid have been examined as solid acid catalysts [57-59]. These mesoporous oxides exhibited remarkable activity in Friedel-Crafts alkylation and 1-hexene isomerization in the liquid phase. For sulfated mesoporous tantalum oxides /m-TsL O ), the effect of pore size has been investigated using... 

Under anhydrous conditions, traditional mineral acid and Friedel-Crafts systems (liquid phase), as well as supported phosphoric acid (gas phase), can be used to produce dimers and trimers through to relatively high molecular weight viscous liquid polymers from C3 and C4 olefins. These same catalyst systems are also used in the alkylation of aromatic hydrocarbons. 

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