Benzene ring, electrophile introduction

Among the most useful electrophilic aromatic substitution reactions In the laboratory is alkylation—the introduction of an alkyl group onto the benzene ring. Called the Friedel-Crafts reaction after its discoverers, the reaction is carried out... 

This completes our preliminary survey of the most important reactions in aromatic electrophilic substitution. We shall switch our attention to the benzene ring itself now and see what effects various types of substituent have on these reactions. During this discussion we will return to each of the main reactions and discuss them in more detail. Meanwhile, we leave the introduction with an energy profile diagram in the style of Chapter 13 for a typical substitution. 

In contrast to aliphatic alcohols, which are mostly less acidic than phenol, phenol forms salts with aqueous alkali hydroxide solutions. At room temperature, phenol can be liberated from the salts even with carbon dioxide. At temperatures near the boiling point of phenol, it can displace carboxylic acids, e.g. acetic acid, from their salts, and then phenolates are formed. The contribution of ortho- and -quinonoid resonance structures allows electrophilic substitution reactions such as chlorination, sulphonation, nitration, nitrosation and mercuration. The introduction of two or three nitro groups into the benzene ring can only be achieved indirectly because of the sensitivity of phenol towards oxidation. Nitrosation in the para position can be carried out even at ice bath temperature. Phenol readily reacts with carbonyl compounds in the presence of acid or basic catalysts. Formaldehyde reacts with phenol to yield hydroxybenzyl alcohols, and synthetic resins on further reaction. Reaction of acetone with phenol yields bisphenol A [2,2-bis(4-hydroxyphenyl)propane]. 

Thermolysis of complex VIII-3 in c/fi-benzene leads to the appearance of the intramolecular metalation product VIII-5 [28], The reaction takes place in several steps and the intermediate complex VIII-4 has been isolated. The introduction of several substituents into the benzene ring has virtually no effect on the rate of metalation, which enables the authors to regard the transformation VIII-4 — VIIl-S not as a typical electrophilic metalation by the Hf(IV) ion but as a process which proceeds via a four-membered transition state. 

A noteworthy example of electrophilic aromatic substitution in nature, as mentioned in the introduction, is biosynthesis of the thyroid hormone thyroxine, where iodine is incorporated into benzene rings that are derived from tyrosine. 

Trifluoromethylation. (5)-(Trifluoromethyl)diphenylsulfo-nium triflate is used as an electrophilic trifluoromethylation reagent. The reactivity can be modified through the introduction of different substituents into the ring. When there is an electron-withdrawing group present on the benzene ring, the electrophilic trifluoromethylation ability is greatly enhanced. ... 

The simplest acyl chloride, formyl chloride, H-C-Cl, is unstable, decomposing to HCl and CO upon attempted preparation. ThCTefore, direct Friedel-Crafts formylation of benzene is impossible. An alternative process, the Gattermann-Koch reaction, enables the introduction of the formyl group, -CHO, into the benzene ring by treatment with CO under pressure, in the presence of HCl and Lewis acid catalysts. For example, methylbenzene (toluene) can be formylated at the para position in this way in 51% yield. The electrophile in this process was observed directly for the first time in 1997 by treating CO with HF-SbFs under high pressure C NMR 8 139.5 ppm IR V = 2110 cm . What is the structure of this species and the mechanism of its reaction with methylbenzene Explain the spectral data. (Hints Draw the Lewis structure of CO and proceed by considering the species that may arise in the presence of acid. The comparative spectral data for free CO are C NMR 8 = 181.3 ppm IR P = 2143 cm . )... 

In Section 14-8 we discussed the effect that substituents have on the efficiency of the Diels-Alder reaction Electron donors on the diene and acceptors on the dienophile are beneficial to the outcome of the cycloaddition. Chapter 15 revealed another manifestation of these effects Introduction of electron-withdrawing substituents into the benzene ring (e.g., as in nitration) caused further electrophilic aromatic substitution (EAS) to slow down, whereas the incorporation of donors, as in the Friedel-Crafts alkylation, caused substitution to accelerate. What are the factors that contribute to the activating or deactivating nature of substituents in these processes How do they make a monosubstituted benzene more or less susceptible to further electrophilic attack ... 

There have been only a few reports of direct hydroxylation362 by an electrophilic process (see, however, 2-26 and 4-5).363 In general, poor results are obtained, partly because the introduction of an OH group activates the ring to further attack. Quinone formation is common. However, alkyl-substituted benzenes such as mesitylene or durene can be hy-droxylated in good yield with trifluoroperacetic acid and boron trifluoride.364 In the case of mesitylene, the product is not subject to further attack ... 

These reactions, called electrophilic aromatic substitutions (EAS), allow the direct introduction of groups onto aromatic rings such as benzene, and they provide synthetic routes to many important compounds. Figure 15.1 outlines five different types of electrophilic aromatic substitutions that we will study in this chapter, including carbon—carbon bond-forming reactions and halogenations. 

Polysubstituted benzenes are widely used both in industry and in research laboratories. Regioselective construction of polysubstituted benzenes is usually achieved through the gradual introduction of substituents in the aromatic ring by Friedel-Crafts reaction or similar reactions of electrophilic substitution or through organometallic synthesis. In 1948, Reppe reported the [2+2+2] trimerization of substituted acetylenes in the presence of transition metals to form polysubstituted benzenes (Scheme 1.1) [1]. 

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