Friedel drawback

One drawback to Fnedel-Crafts alkylation is that rearrangements can occur espe cially when primary alkyl halides are used For example Friedel-Crafts alkylation of benzene with isobutyl chloride (a primary alkyl halide) yields only tert butylbenzene... 

Drawbacks as known from the Friedel-Crafts alkylation are not found for the Friedel-Crafts acylation. In some cases a decarbonylation may be observed as a side-reaction, e.g. if loss of CO from the acylium ion will lead to a stable carbenium species 8. The reaction product of the attempted acylation will then be rather an alkylated aromatic compound 9 ... 

Another drawback to the use of amino-substituted benzenes in electrophilic aromatic substitution reactions is that Friedel-Crafts reactions are not successful (Section 16.3). The amino group forms an acid-base complex with the AICI3 catalyst, which prevents further reaction from occurring. Both drawbacks can be overcome, however, b3 carrying out electrophilic aromatic substitution reactions on the corresponding amide rather than on the free amine. 

Apart from the possibility of rearrangement, the main drawback in the preparative use of this Friedel-Crafts reaction is polyalkylation (cf. p. 153). The presence of an electron-withdrawing substituent is generally sufficient to inhibit Friedel-Crafts alkylation thus nitrobenzene is often used as a solvent for the reaction because A1C13 dissolves readily in it, thus avoiding a heterogeneous reaction. 

The Friedel-Crafts reaction has one major drawback. It doesn t stop at the mono-substitution stage. That is, the catalyst works so well, that the benzene will pick up two, three, or more ethylene molecules, forming diethylbenzene, triethylbenzene, or higher polyethylbenzenes. See Figure 8 2.) The problem is that chemically its easier to alkylate EB than it is benzene. One way to control the problem is to carry out the reaction in the presence of a large excess of benzene. When an ethylene molecule is in the neighborhood of one..EB molecule and 20 benzene molecules, chances are that the ethylene will hook up with benzene, even though it prefers EB. 

First developments in the Friedel-Crafts alkylation were concentrated on the use of stoichiometric amounts of Lewis acids, such as A1C13, BF3 or TiCl4, to produce stoichiometric amounts of salt by-products [5-9]. However, in recent years more and more catalytic methods have been developed. In particular, rare earth metal triflates, including Sc(OTf)3, La(OTf)3 and Yb(OTf)3, have been extensively used as Lewis acid catalysts in various C-C and C-X bond forming reactions [10-13], Despite the benefit of their versatility for organic synthesis, these Lewis acids possess major drawbacks. They are expensive, rather toxic [14], and air- and moisture-sensitive. 

On the basis of these initial results, various rare earth metal triflates, including Sc(OTf)3, Hf(OTf)4 and Yb(OTf)3 were applied as catalysts [27-29]. Recently Beller and coworkers developed efficient Friedel-Crafts alkylations with catalytic amounts of Rh, W, Pd, Pt and Ir complexes [30] or FeCl3 [31-34] as Lewis acid catalysts. However, in the latter cases high catalyst loadings had to be applied. To overcome these major drawbacks, we decided to develop a Bi(III)-catalyzed Friedel-Crafts alkylation of arenes with benzyl alcohols. Although bismuth-catalyzed Friedel-Crafts acylations were well known at this time, Friedel-Crafts alkylations using benzyl alcohols had not been reported. 

Frequently substantially more than catalytic amounts of a Lewis acid metal halide are required to effect Friedel-Crafts alkylation. This is due partly to complex formation between the metal halide and the reagents or products, especially if they contain oxygen or other donor atoms. Another reason is the formation of red oils. Red oils consist of protonated (alkylated) aromatics (i.e., arenium ions) containing metal halides in the counterions or complexed with olefin oligomers. This considerable drawback, however, can be eliminated when using solid acids such as clays,97 98 zeolites (H-ZSM-5),99,100 acidic cation-exchange resins, and perfluoro-alkanesulfonic acid resins (Nafion-H).101-104... 

The third case shows the immobilisation of Lewis-acidic ionic liquids. The resulting catalysts, named Novel Lewis-Acidic Catalysts (NLACs), are highly active in the Friedel-Crafts alkylation of aromatic compounds with dodecene. Conversions and selectivities to the desired monoalkylated products were excellent. No leaching of the catalytically active component could be observed. The isomer distribution of the monoalkyated products is very similar to that obtained over pure aluminum(III)chloride. The main drawback of the NLACs is that thy are very sensitive towards water, which leads to irreversible deactivation. A second problem is the deactivation after long reaction times. The most likely cause is olefin oligomerisation. 

Because of the extensive amount of waste generated in traditional Friedel-Crafts reactions, it is not surprising that this reaction has been studied in RTIL. Early examples included the use of catalytic chloroaluminate ionic liquids. However, the moisture sensitivity of such systems was a drawback. Therefore, water-stable rare-earth Lewis acids, such as Sc(CF3S03)3, have come to be used for these reactions.The same Lewis acid has also been used to catalyse Diels-Alder reactions in RTILs.Interestingly, in this example, the RTIL not only provided a means for recycling the catalyst but also accelerated the rate and improved selectivity. It has also been demonstrated that a moisture stable, Lewis acidic, catalytic ionic liquid could be prepared from choline chloride and zinc dichloride, and that this was an excellent medium for the Diels-Alder reaction. Yields of 90% or more were achieved in reaction times of between 8 min and 5h for a range of dienes and dienophiles. 

The Friedel-Crafts alkylation of aromatic compounds is of great importance in laboratory synthesis and industrial production. For example, the industrial processes for ethylbenzene, cumene and linear alkylbenzenes, etc., are on the base of this kind of reaction. It is well known that the drawbacks of the traditional acid catalysts such as A1Q3, H SO, and HF do great harm to the equipment and the environment, and these catalysts cannot be reused after the usual aqueous work-up besides, most of the reactions are carried out in the harmful and volatile organic solvents which can cause the environmental pollution aU of these problems need the replacement of the solvents or the acid catalysts. In this context, room-temperature ionic liquids have been iuCTeasingly employed as green solvents. 

The conventional method for preparation of these aromatic ketones involves reaction of the aromatic hydrocarbon with a carboxylic acid derivatives using a Lewis acid (AICI3, FeCb, BF3, ZnCb, TiCl4) or Bronsted acids (polyphosphoric acid, HF). The major drawback of the Friedel-Crafts reaction is the need to use a stoicheiometrical quantity of Lewis acid relative to the formed ketone. This quantity is required due to the fact that the... 

The Friedel-Crafts reaction was discovered at the end of the nineteenth century, and despite intensive studies a general solution to this initial drawback has not been found.3 Studies have been carried out to find mild Lewis acids forming less stable complexes with the ketone and still able to catalyze the reaction. Some successes have been obtained using rare earth triflate4 or bismuth HI salts.5 These methods, if they proved to be catalytic, still require significant quantities of catalysts (a few percent) and the recycling of the catalyst is not simple. 

A range of PEG-based resins are available, including PEGA [24], POEPOP [25] and POEPS [26,27], that do not stand up to the harsh conditions employed during Friedel-Crafts reactions or acetolysis. To circumvent these drawbacks, the SPOCC that contains only primary ether bonds, secondary and quartemary carbon atoms was introduced. The synthesis of SPOCC resin is summarized in Scheme 20.3 [27]. 

The major drawback of the Friedel-Crafts reaction lies in the need to use the Lewis acid in stoichiometrical quantities relative to the acetone formed, which in industrial terms poses large effluent problems. 

Given the broad field of application of Friedel-Crafts reactions and the above problems, in particular the formation of large quantities of aluminic waste, a major drawback for industry, considerable investigation has recently been undertaken in search for catalysts (eqn. 5, refs. 22-31). 

The use of traditional Friedel-Crafts catalysts usually leads to complex product mixtures. During alkylation several reactions can take place concurrently, e. g. polymerization, polyalkylation, isomerization, transalkylation, cracking, etc., and complexation of the reactants with the catalyst often occurs. One of the most important drawbacks of these catalysts is probably increasing environmental concern. 

As already underlined in the introduction to this book, catalytic homogeneous acylation reactions represent a remarkable improvement in the preparation of aromatic ketones because, in the conventional Lewis-acid-promoted reactions, formation of a stable complex between the ketone product and the catalyst implies that at least a stoichiometric amount of catalyst must be utilized. This drawback prompted a great number of studies aimed at setting up the experimental conditions to make catalytic Friedel-Crafts acylation reactions. Some positive results from fhe homogeneous catalytic Friedel-Crafts acylations are described here, with special attention to crucial economic and environmental advantages such as the recycling of expensive catalysts and the development of solvenf-free and highly selective synthetic processes. 

The use of Y, BEA, and ZSM-5 zeolites in the Friedel-Crafts acylation of aromatics shows some limitations when large-sized molecules are utilized. In fact, because of the dimension of their pores, the access to the internal active sites of these zeolites is restricted to molecules with kinetic diameter up to 8 A. Trying to overcome this drawback, mesoporous molecular sieve MCM-41 can be utilized as interesting catalyst or support for catalysts for reactions involving larger molecules. 

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