Electrophilic reactions of aromatic

General Order of Rate Constants. The rate constants of electrophilic reactions of aromatic ligands and their metal complexes fall in the order fo, > kML > kffL. The difference between these rate constants becomes greater as the activity of the attacking reagent decreases. When L is a phenolate, HL is the phenol when L is an amine, HL is the corresponding ammonium derivative. The possible synthetic applications of this sequence can be appreciated from the fact that 8-hydroxyquinoline is usually sulfonated with 15 to 30% oleum, while its copper (II) complex can be readily sulfonated in 70% sulfuric add (5). 

This type of duality of action is presumably present in other situations, such as the Fries rearrangement (78), the Friedel-Crafts reaction with acid chlorides (65) or acid anhydrides (21), and the catalytic chlorination of nitrobenzene (17). In these reactions it appears that the uncoordinated Lewis acid is the effective catalyst. The same situation is illustrated by recent work on aromatic amination (32, 33) and halogenation (57, 58, 71) and seems to be general feature of Lewis acid-catalyzed electrophilic reactions of aromatic compounds containing suitable donor groups. 

Borodkin GI, Shubin VG (2006) Electrophilic reactions of aromatic and heteroaromatic compounds in ionic liquids. Russian J Org Chem 42 1745—1770... 

Electrophilic reactions of aromatic and heteroaromatic compounds in ionic liquids 06ZOR1761. 

Reactions of aromatic and heteroaromatic rings are usually only found with highly reactive compounds containing strongly electron donating substituents or hetero atoms (e.g. phenols, anilines, pyrroles, indoles). Such molecules can be substituted by weak electrophiles, and the reagent of choice in nature as well as in the laboratory is usually a Mannich reagent or... 

Whereas the above reactions are appHcable to activated aromatics, deactivated aromatics can be formylated by reaction with hexamethylenetetramine in strong acids such as 75% polyphosphoric acid, methanesulfonic acid, or trifluoroacetic acid to give saUcylaldehyde derivatives (117). Formyl fluoride (HCOF) has also been used as formyl a ting agent in the Friedel-Crafts reaction of aromatics (118). Formyl fluoride [1493-02-3] in the presence of BF was found to be an efficient electrophilic formyl a ting agent, giving 53% para-, 43% ortho- and 3.5% meta-tolualdehydes upon formylation of toluene (110). 

The major organic reactions of BrCl consist of electrophilic brominations of aromatic compounds. Many aromatic compounds do not react in aqueous solution unless the reaction involves activated aromatic compounds (an example being phenol). Bromine chloride undergoes free-radical reactions more readily than bromine. 

Arynes are intermediates in certain reactions of aromatic compounds, especially in some nucleophilic substitution reactions. They are generated by abstraction of atoms or atomic groups from adjacent positions in the nucleus and react as strong electrophiles and as dienophiles in fast addition reactions. An example of a reaction occurring via an aryne is the amination of o-chlorotoluene (1) with potassium amide in liquid ammonia. According to the mechanism given, the intermediate 3-methylbenzyne (2) is first formed and subsequent addition of ammonia to the triple bond yields o-amino-toluene (3) and m-aminotoluene (4). It was found that partial rearrangement of the ortho to the meta isomer actually occurs. 

The most common reaction of aromatic compounds is electrophilic aromatic substitution. That is, an electrophile reacts with an aromatic ring and substitutes for one of the hydrogens. The reaction is characteristic of all aromatic rings, not just benzene and substituted benzenes. In fact, the ability of a compound to undergo electrophilic substitution is a good test of aromaticity- . 

Volume 8 Volume 9 Volume 10 Volume 12 Volume 13 Proton Transfer Addition and Elimination Reactions of Aliphatic Compounds Ester Formation and Hydrolysis and Related Reactions Electrophilic Substitution at a Saturated Carbon Atom Reactions of Aromatic Compounds Section 5. POLYMERISATION REACTIONS (3 volumes)... 

In Volume 13 reactions of aromatic compounds, excluding homolytic processes due to attack of atoms and radicals (treated in a later volume), are covered. The first chapter on electrophilic substitution (nitration, sulphonation, halogenation, hydrogen exchange, etc.) constitutes the bulk of the text, and in the other two chapters nucleophilic substitution and rearrangement reactions are considered. 

Our recent studies on effective bromination and oxidation using benzyltrimethylammonium tribromide (BTMA Br3), stable solid, are described. Those involve electrophilic bromination of aromatic compounds such as phenols, aromatic amines, aromatic ethers, acetanilides, arenes, and thiophene, a-bromination of arenes and acetophenones, and also bromo-addition to alkenes by the use of BTMA Br3. Furthermore, oxidation of alcohols, ethers, 1,4-benzenediols, hindered phenols, primary amines, hydrazo compounds, sulfides, and thiols, haloform reaction of methylketones, N-bromination of amides, Hofmann degradation of amides, and preparation of acylureas and carbamates by the use of BTMA Br3 are also presented. 

Systematic studies of the selectivity of electrophilic bromine addition to ethylenic bonds are almost inexistent whereas the selectivity of electrophilic bromination of aromatic compounds has been extensively investigated (ref. 1). This surprising difference arises probably from particular features of their reaction mechanisms. Aromatic substitution exhibits only regioselectivity, which is determined by the bromine attack itself, i.e. the selectivity- and rate-determining steps are identical. 

The complex that is formed can dissociate to form a cation (n-tr-complex) and an iodide anion, with the iodide ion reacting with the excess iodine molecules that are present. In addition the decomposition of the n-cr-complex can lead to the formation of highly reactive iodine cations, which can initiate further reactions — e.g. oxidations or electrophilic substitutions of aromatic systems [11, 13]. 

A simple, high-yield procedure for the conversion of ArTlXj into ArjTlX compounds has recently been described 90). This symmetrization reaction, the mechanism of which is not known, can be effected by treatment of the ArTlX2 compound either with triethyl phosphite or with hot aqueous acetone. As a wide variety of ArTlXj compounds can now be easily prepared by electrophilic thallation of aromatic substrates with thallium(III) trifluoroacetate (q. v.), symmetrization represents the method of choice for the preparation of the majority of ArjTlX compounds. Only about twenty mixed compounds, RR TIX, have been prepared so far, and the only general synthetic procedure available consists of a disproportionation reaction between an RTIX2 species and another organometallic reagent [e.g., Eqs. (5)-(7)]. 

Mixed condensations of esters are subject to the same general restrictions as outlined for mixed aldol reactions (Section 2.1.2). One reactant must act preferentially as the acceptor and another as the nucleophile for good yields to be obtained. Combinations that work best involve one ester that cannot form an enolate but is relatively reactive as an electrophile. Esters of aromatic acids, formic acid, and oxalic acid are especially useful. Some examples of mixed ester condensations are shown in Section C of Scheme 2.14. Entries 9 and 10 show diethyl oxalate as the acceptor, and aromatic esters function as acceptors in Entries 11 and 12. 

A second group of aromatic substitution reactions involves aryl diazonium ions. As for electrophilic aromatic substitution, many of the reactions of aromatic diazonium ions date to the nineteenth century. There have continued to be methodological developments for substitution reactions of diazonium intermediates. These reactions provide routes to aryl halides, cyanides, and azides, phenols, and in some cases to alkenyl derivatives. 

The asymmetric Baylis-Hillman reaction of sugar-derived aldehydes as chiral electrophiles with an activated olefin in dioxane water (1 1) proceeded with 36-86% de and in good yields of the corresponding glycosides (Eq. 10.47).104 The use of chiral /V-mcthylprolinol as a chiral base catalyst for the Baylis-Hillman reaction of aromatic aldehydes with ethyl acrylate or methyl vinyl ketone gave the adducts in good yields with moderate-to-good enantioselectivities in l,4-dioxane water (1 1, vol/vol) under ambient conditions.105... 

If we are correct in our assumption that the electrophilic substitution of aromatic species involves such a complexes as intermediates—and it has proved possible actually to isolate them in the course of some such substitutions (p. 136)—then what we commonly refer to as aromatic substitution really involves initial addition followed by subsequent elimination. How this basic theory is borne out in the common electrophilic substitution reactions of benzene will now be considered. 

Friedel-Crafts acylation reactions of aromatics are promoted by Tilv complexes.104 In some cases, a catalytic amount of the titanium compound works well (Scheme 28). In addition to acyl halides or acid anhydrides, aldehydes, ketones, and acetals can serve as electrophile equivalents for this reaction.105 The formylation of aromatic substrates in the presence of TiCl4 is known as the Rieche-Gross formylation metalated aromatics or olefins are also formylated under these conditions.106... 

On the other hand, the involvement of vinyl cationic species in the reaction cannot be ruled out in some cases, as shown in Scheme 4. In this context, it was found that the reaction of 3-butyn-2-one with mesitylene can occur without Pd(OAc)2, clearly indicating the involvement of vinyl cations generated from alkynes and H+ in this reaction.47 1 The yield difference in the presence and in the absence of Pd(OAc)2 may be explained by the competition between [Pd(n)02CF3]+ and vinyl cationic species in the electrophilic substitution of aromatic G-H bonds. Recent kinetic isotope experiments suggest a mechanism involving alkyne coordination to Pd(n) followed by electrophilic aromatic substitution.476... 

Friedel-Crafts reactions involving electrophilic substitution of aromatic compounds have been reported on solid base catalysts such as thallium oxide and MgO. The rates of benzylation of toluene by benzyl chloride over MgO nanocrystals were found to be of the order CP-MgO > CM-MgO > AP-MgO.56 An important observation in the study was that x-ray diffraction of the spent catalyst... 

The main problem encountered during electrophilic substitution reactions of aromatic amines is that of their veiy high reactivity. Substitution tends to occur at ortho- and para-positions. If we have to prepare monosubstituted aniline derivative, how can the activating effect of -NH group be controlled This can be done by protecting the -NH group by acetylation with acetic anhydride, then carrying out the desired substitution followed by hydrolysis of the substituted amide to the substituted amine. 

In Part 11 we concentrate on aromatic systems, starting with the basics of structure and properties of benzene and then moving on to related ciromatic compounds. We even throw in a section of spectroscopy of aromatic compounds. Chapters 7 and 8 finish up this pcirt by going into detail about substitution reactions of aromatic compounds. You find out all you ever wanted to know (and maybe more) about electrophilic and nucleophilic substitutions, along with a little about elimination reactions. 

The triflic acid catalyzed electrophilic hydroxylation of aromatics with BTSP gives the corresponding phenols in high yields without apparent polyhydroxylation or secondary oxidation. Thus, treatment of CeHe with CF3SO3H followed by BTSP gave 11% PhOH. The isomer distributions are in accord with the electrophilic nature of the reaction. The observed ortho/para ratio in the case of toluene agrees with the expected trends (Scheme 4 and Table ll) . 

Scheme 25. The arenium ion mechanism of electrophilic fluorination of aromatic rings via fluorodehydrogenation or fluorodemetallation reactions.

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