Friedel-Crafts electrophilic substitution

Two main limitations of CHAOS are i) it does not recognise stereochemical features and ii) it does not deal with typical aromatic electrophilic substitution (only Friedel-Craft-type disconnections are performed). 

One of the most common examples of an electrophilic aromatic substitution is Friedel-Crafts alkylation [40], These days, many important industrial processes are based on this type of Friedel-Crafts-chemistry [41]. The manufacture of high-octane gasoline, ethylbenzene, synthetic rubber, plastics and detergent alkylates are examples. Moreover, the Friedel-Crafts alkylation is among the most fundamental and convenient processes for C—C bond formation on arenes, especially for the synthesis of fine chemicals and agrochemicals containing functionalized arenes and heteroarenes. 

Iron tricarbonyl forms exceptionally stable complexes with 1,3-dienes. The complexes are uncharged, readily soluble species, chromatographable and, for the simpler versions, distillable. They are formed by direct reaction of the 1,3-diene with Fe(CO)5, Fc2(CO)9, or Fe3(CO)i2. These iron diene complexes are known to be reactive toward electrophiles, undergoing the analogous reaction to electrophilic aromatic substitution under Friedel-Crafts conditions. However, it is clear that the metal-ligand unit increases the polarizibility of the diene unit, and, with a sufficiently reactive nucleophile, can provide a sink for electron density. How reactive does the nucleophile need to be The other important selectivity question for 1,3-dienes concerns the regioselectivity. 

Acetanilide, having a much less basic N atom compared to aniline, undergoes electrophilic aromatic substitution under Friedel-Crafts conditions, forming a mixture of ortho and para products. 

The Friedel-Crafts alkylation is a classic illustration of the general class of electrophilic aromatic substitutions. Traditionally, Friedel-Crafts reactions require an alkyl halide as the electrophile source and at least a molar equivalent of aluminum chloride, a hygroscopic and caustic powder that is rather problematic to use in the introductory lab. An easy variant of this procedure utilizes the reactive substrate 1,4-dimethoxybenzene, /er butyl alcohol as the electrophile precursor, and sulfuric acid as the catalyst (72). We run this reaction on a microscale, and use commercial rubbing alcohol (70% aqueous 2-propanol) in place of methanol as the recystallization solvent. The product, l,4-di-7er/-butyl-2,5-dimethoxybenzene, exhibits simple and NMR, and... 

Electrophilic Aromatic Substitution Reactions. Friedel-Crafts alkylation, acylation, and the Vilsmeier-Haack formylation, shown below, are excellent reactions for the synthesis of substituted aromatic compounds. 

The stability of the -C -Si< bond has been known for a long time But on the other hand they are reactive compounds which undergo either - as precursors to vinylsilanes - various types of addition reactions or - as only silyl-protected acetylenes - an electrophilic substitution under Friedel-Crafts conditions in presence of catalytic amounts of Lewis acids The — SiR3 moiety has a highly useful protecting and/or activating function. 

Cornelis, A., Laszlo, R, and Wang, S.-F. 1993. Side-product inhibition of the catalyst in electrophilic aromatic substitution and Friedel-Crafts reactions. Catal. Lett. 17 63-69. 

The alkylation of pyridine [110-86-1] takes place through nucleophilic or homolytic substitution because the 7C-electron-deficient pyridine nucleus does not allow electrophilic substitution, eg, Friedel-Crafts alkylation. Nucleophilic substitution, which occurs with alkali or alkaline metal compounds, and free-radical processes are not attractive for commercial applications. Commercially, catalytic alkylation processes via homolytic substitution of pyridine rings are important. The catalysts effective for this reaction include boron phosphate, alumina, silica—alumina, and Raney nickel (122). 

The iR NMR spectrum of pyrrole is slightly less convincing as the two types of proton on the ring resonate at higher field (6.5 and 6.2 ppm) than those of benzene or pyridine but they still fall in the aromatic rather than the alkene region. Pyrrole is also more reactive towards electrophiles than benzene or pyridine, but it does the usual aromatic substitution reactions (Friedel— Crafts, nitration, halogenation) rather than addition reactions pyrrole is also aromatic. 

Electrophilic aromatic substitution, using Friedel-Crafts catalysts and... 

Similar electrophilic Friedel-Crafts-Uke reactions allow the most reactive dichloride 17 to furnish 1,4-diarylcyclobutenedione derivatives [44,45] for example, l,4-thieno[3,2-fo]pyrrole-substituted cyclobutenedione 23 was prepared by this method and an oxygen-inserted conjugation system 24 was attained as a photochromic devise [46] (Scheme 4). 

Bronsted Acids. Sulfuric acid (H2SO4) is an inexpensive, easy to handle protic acid used widely as catalyst in hydrolysis, hydration and dehydration, elimination, substitution, and rearrangements. It also catalyzes aromatic electrophilic substitutions mostly Friedel-Crafts acylations and alkylations (22). A very important application of sulfuric acid is its use in commercial isoalkane-alkene alkylation technologies. These commercial processes are still based on the use of sulfuric acid (and hydrogen fluoride) catalysts (23). 

Other Synthesis Routes. Several alternative routes to the nucleophilic substitution synthesis of polysulfones are possible. Polyethersulfone can be synthesized by the electrophilic Friedel-Crafts reaction of bis(4-chlorosulfonylphenyl)ether [121-63-1] with diphenyl ether [101-84-8] (11-13). 

In this chapter, two general synthetic methods of poly (aryl ether ketone) copolymers were introduced, that is, (1) nucleophilic substitution step copolycondensation of at least two different monomers of bisphenol and at least one dihalobenzoid compound or at least one monomer of bisphenol and at least two different dihalobenzoid compounds (2) electrophilic Friedel-Crafts copolycondensation of at least two different monomer of diphenyl ether and terephthaloyl chloride or at least one monomer of diphenyl ether and terephthaloyl chloride as well as isophthaloyl chloride. Some representative monomers were included. By the method (1), the synthesis and characterization of structural poly (aryl ether ketone) copolymers—poly (ether ether ketone)-poly (ether ether ketone ketone) (PEEK-PEEKK), poly (ether ether ketone)-poly (ether biphenyl ether ketone) (PEEK-PEDEK), poly (ether ether ketone ketone)-poly (ether biphenyl ether ketone ketone) (PEEKK-PEDEKK), poly (ether ether ketone)-poly (ether ether ketone biphenyl ketone) (PEEK-PEEKDK) and poly (ether biphenyl ether ketone)-poly (ether biphenyl ether ketone biphenyl ketone) (PEDEK-PEDEKDK) were discussed. The s5mthesis and characterization of the functional PAEK copolymers, such as liquid crystal poly (aryl ether ketone) copol5oners, poly (aryl ether ketone) copolymers with pendent group of low dielectric constant and poly (aryl ether ketone) copolymers with crosslinking moieties were also discussed in details. These PAEK copolymers showed a lot of special performance and can maybe be applied in optical waveguides, microelectronics, display devices, membrane materials and so on. 

In contrast with other electrophilic substitutions, including Friedel-Crafts acylations, Friedel-Crafts alkylations activate the aromatic ring to further electrophilic substitution, leading to product mixtures. 

The most widely used reactions are those of electrophilic substitution, and under controlled conditions a maximum of three substituting groups, e.g. -NO2 (in the 1,3,5 positions) can be introduced by a nitric acid/sul-phuric acid mixture. Hot cone, sulphuric acid gives sulphonalion whilst halogens and a Lewis acid catalyst allow, e.g., chlorination or brom-ination. Other methods are required for introducing fluorine and iodine atoms. Benzene undergoes the Friedel-Crafts reaction. ... 

The nitration, sulphonation and Friedel-Crafts acylation of aromatic compounds (e.g. benzene) are typical examples of electrophilic aromatic substitution. 

The selectivity of an electrophile, measured by the extent to which it discriminated either between benzene and toluene, or between the meta- and ara-positions in toluene, was considered to be related to its reactivity. Thus, powerful electrophiles, of which the species operating in Friedel-Crafts alkylation reactions were considered to be examples, would be less able to distinguish between compounds and positions than a weakly electrophilic reagent. The ultimate electrophilic species would be entirely insensitive to the differences between compounds and positions, and would bring about reaction in the statistical ratio of the various sites for substitution available to it. The idea has gained wide acceptance that the electrophiles operative in reactions which have low selectivity factors Sf) or reaction constants (p+), are intrinsically more reactive than the effective electrophiles in reactions which have higher values of these parameters. However, there are several aspects of this supposed relationship which merit discussion. 

Nitration in sulphuric acid is a reaction for which the nature and concentrations of the electrophile, the nitronium ion, are well established. In these solutions compounds reacting one or two orders of magnitude faster than benzene do so at the rate of encounter of the aromatic molecules and the nitronium ion ( 2.5). If there were a connection between selectivity and reactivity in electrophilic aromatic substitutions, then electrophiles such as those operating in mercuration and Friedel-Crafts alkylation should be subject to control by encounter at a lower threshold of substrate reactivity than in nitration this does not appear to occur. 

Friedel-Crafts acylation of aromatic compounds (Section 12 7) Acyl chlorides and carboxylic acid anhydrides acylate aromatic rings in the presence of alumi num chloride The reaction is electrophil ic aromatic substitution in which acylium ions are generated and attack the ring... 

Electrophilic aromatic substitution (Sec tion 22 14) Arylamines are very reac tive toward electrophilic aromatic sub stitution It IS customary to protect arylamines as their N acyl derivatives before carrying out ring nitration chio rination bromination sulfonation or Friedel-Crafts reactions... 

Other typical electrophilic aromatic substitution reactions—nitration (second entry) sul fonation (fourth entry) and Friedel-Crafts alkylation and acylation (fifth and sixth entnes)—take place readily and are synthetically useful Phenols also undergo elec trophilic substitution reactions that are limited to only the most active aromatic com pounds these include mtrosation (third entry) and coupling with diazomum salts (sev enth entry)... 

Friedel-Crafts acylation (Section 12 7) An electrophilic aro matic substitution in which an aromatic compound reacts with an acyl chloride or a carboxylic acid anhydride in the presence of aluminum chlonde An acyl group becomes bonded to the nng... 

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