Friedel—Crafts reaction product selectivity

Absolute rate data for Friedel-Crafts reactions are difficult to obtain. The reaction is complicated by sensitivity to moisture and heterogeneity. For this reason, most of the structure-reactivity trends have been developed using competitive methods, rather than by direct measurements. Relative rates are established by allowing the electrophile to compete for an excess of the two reagents. The product ratio establishes the relative reactivity. These studies reveal low substrate and position selectivity. 

A good deal of experimental care is often required to ensure that the product mixture at the end of a Friedel-Crafts reaction is determined by kinetic control. The strong Lewis acid catalysts can catalyze the isomerization of alkylbenzenes, and if isomerization takes place, the product composition is not informative about the position selectivity of electrophilic attack. Isomerization increases the amount of the meta isomer in the case of dialkylbenzenes, because this isomer is thermodynamically the most stable. ... 

The LAB production process (process 1) is mainly developed and licensed by UOP. The N-paraffins are partially converted to internal /z-olefins by a catalytic dehydrogenation. The resulting mixture of /z-paraffins and n-olefins is selectively hydrogenated to reduce diolefins and then fed into an alkylation reactor, together with an excess benzene and with concentrated hydrofluoric acid (HF) which acts as the catalyst in a Friedel-Crafts reaction. In successive sections of the plant the HF, benzene, and unconverted /z-paraffins are recovered and recycled to the previous reaction stages. In the final stage of distillation, the LAB is separated from the heavy alkylates. 

The synthesis of fluotrimazole starts from m-xylene. Peroxide catalyzed perchlorination converts this to m-trichloromethyl-benzo-trichloride. m-Trichloromethyl-benzotrifluoride is then obtained by selective chlorine/fluorine exchange. This key product is also readily accessible on a technical scale by conproportionation of the two corresponding m-trihalomethyl-benzotrihalogenides. Friedel-Crafts reaction with benzene leads to trifluoromethyl-tritylchloride, which reacts smoothly with 1,2,4-triazole in polar solvents to give fluotrimazole. 

Acidic chloroaluminate ionic liquids were used as reaction media for Friedel-Crafts reactions as early as 1976 [34], Systematic investigations into Friedel-Crafts alkylations of benzene with the same acidic systems followed in 1986 by Wilkes et al. [35]. The alkylation of benzene with alkenes in acidic imidazolium chloroaluminate melts was disclosed in a patent by BP Chemicals in 1994 [36]. Here, as advantages over the reaction with aluminum trichloride in organic solvents, claims are made regarding the easy isolation of the product, the practically total reusability of the liquid catalyst and the better selectivity to the desired products. 

As mentioned before, alkyl radicals and acyl radicals have a nucleophilic character therefore, radical alkylation and acylation of aromatics shows the opposite reactivity and selectivity to polar alkylation and acylation with the Friedel-Crafts reaction. Thus, alkyl radicals and acyl radicals do not react with anisole, but may react with pyridine. Eq. 5.1 shows the reaction of an alkyl radical with y-picoline (1). The nucleophilic alkyl radical reacts at the 2-position of y-picoline (1), where electron density is lower than that of the 3-position. So, 2-alkyl-4-methylpyridine (2) is obtained with complete regioselectivity. When pyridine is used instead of y-picoline, a mixture of 2-alkylpyridine and 4-alkylpyridine is obtained. Generally, radical alkylation or radical acylation onto aromatics is not a radical chain reaction, since it is just a substitution reaction of a hydrogen atom of aromatics by an alkyl radical or an acyl radical through the addition-elimination reaction. Therefore, the intermediate adduct radical (a complex) must be rearomatized to form a product and a hydrogen atom (or H+ and e ). Thus, this type of reactions proceeds effectively under oxidative conditions [1-6]. 

In a later study. Swanson and coworkers [81] studied the cure of acetylene-terminated poly(imide)s selectively labelled at various positions with nuclei. Curing of the sample, labelled at the imide carbonyl group, confirmed the completion of the imidization reaction on heating. The product of addition onto the carboxyl group was not observed. Four new peaks were identified in the spectrum of the cured sample labelled at the Ci-acetylene group, while a similar result was obtained for the sample labelled at the C2-acetylene position. Analysis of these results rules out the participation of coupling reactions and the biradical mechanism, which would produce triple-bond structures, but confirms the presence of the product of cyclotrimerization and Friedel-Crafts reactions. The latter mechanism is confirmed from the presence of small peaks due to aliphatic carbons in the spectra of the materials labelled at the acetylene groups. 

This example illustrates the influence of solvents on the selectivity and activity for hydrogenolysis in a triphasic gas / liquid / solid system. We use the concept of "reactive solvent" the by-product 3 results from a Friedel - Crafts reaction and can be controlled by changing the solvent and effect of dilution - 3 increases dramatically if hydrogenation is not under chemical control. This article attempts to suggest how the appropriate choice of solvent may improve selectivity. 

The key step is the selective C—H bond activation of two methyl groups of an ortho-tert-hutyl in the Schiff base 434. Treatment of 434 with Pd(OAc)2 afforded the palladacycle 435 in 75 % yield by the help of rather strong coordination to N and O functions. The first functionalization was achieved by the reaction with the alkenylboronic acid to yield the alkylated product 436 in 86 % yield, which was converted to 437 by the Friedel-Crafts reaction. Then the second palladacycle formation from 437 provided two diastereomers 438, which were, without isolation, subjected to carbonylation (40 atm) at room temperature. Treatment of crude reaction mixture with silica gel cleaved the Schiff base and spontaneous lactonization occurred to give a mixture of the lactones 439 and 440 (6 1). The main product was N-alkylated to yield 441. Finally, the fourth ring was constructed by a Heck-type reaction on the aromatic ring to give the desired compound. 

A series of arylations of olefins by C-H bond cleavage without direction by an ortho functional group has also been reported, and these reactions can be divided into two sets. In one case, the C-H bond of an arene adds across an olefin to form an alkylarene product. This reaction has been called hydroarylation. In a second case, oxidative coupling of an arene with an olefin has been reported. This reaction forms an aryl-substituted olefin as product, and has been called an oxidative arylation of olefins. The first reaction forms the same t)q)es of products that are formed from Friedel-Crafts reactions, but with selectivity controlled by the irietal catalyst. For example, the metal-catalyzed process can form products enriched in the isomer resulting from anti-Markovnikov addition, or it could form the products from Markovnikov addition with control of absolute stereochemistry. Examples of hydroarylation and oxidative arylation of olefins are shown in Equations 18.63 - and 18.64. ... 

HfCU showed good activity for dehydroxylative Friedel-Crafts reaction of alcohols as shown below. Hf(OTf)4 supported on MCM-41 was used for a reaction of benzyl alcohol with benzene to afford diphenylmethane in good selectivity (Equation 23) [29]. Compared with other metal catalysts, selectivity for monoben-zylation product was much higher. 

Inspired by their previous work and following the same strategy, Sibi and co-workers later described a Friedel-Craft reaction of pyrroles 93 with methacrylamide 94 (Scheme 31.33). The use of Zn-(Ph-(/ ,/ )-4,6-dibenzofur-andiyl-2,2 -bis(4-phenyloxazoline) (DBFOX) complex as a Lewis acid was found to be effective to achieve the enantio-selective protonation, affording the corresponding enan-tioenrichied products 95 in good yields (70-98%) with modest to good enantioselectivities (43-93% ee). 

Like Friedel-Crafts reactions, halogenation such as bromination and iodination of aromatic compounds are classified as electrophilic aromatic substitution reactions. Bromine and iodine substituents are weakly electron-withdrawing groups, and introduction of such substituents causes a decrease in reactivity, and therefore, the first halogenation is faster than the second halogenation. However, the reactions in batch macroreactors suffer from the problem of disguised chemical selectivity, i.e, the formation of dihalogenated products. 

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