Mechanism, aromatization compounds

The observation already discussed ( 2.2, 2.3, 2.4) of nitrations, in concentrated and aqueous mineral acids and in pure nitric acid, which depend on the first power of the concentration of the aromatic compound, does not help much in elucidating the mechanisms of nitrations under these conditions. In contrast, the observation of zeroth-order... 

Dewar and his co-workers, as mentioned above, investigated the reactivities of a number of polycyclic aromatic compounds because such compounds could provide data especially suitable for comparison with theoretical predictions ( 7.2.3). This work was extended to include some compounds related to biphenyl. The results were obtained by successively compounding pairs of results from competitive nitrations to obtain a scale of reactivities relative to that of benzene. Because the compounds studied were very reactive, the concentrations of nitric acid used were relatively small, being o-i8 mol 1 in the comparison of benzene with naphthalene, 5 x io mol 1 when naphthalene and anthanthrene were compared, and 3 x io mol 1 in the experiments with diphenylamine and carbazole. The observed partial rate factors are collected in table 5.3. Use of the competitive method in these experiments makes them of little value as sources of information about the mechanisms of the substitutions which occurred this shortcoming is important because in the experiments fuming nitric acid was used, rather than nitric acid free of nitrous acid, and with the most reactive compounds this leads to a... 

The authors of this work were concerned chiefly with additions to alkenes, and evidence about the mechanism of aromatic nitration arises by analogy. Certain aspects of their work have been repeated to investigate whether the nitration of aromatic compounds shows the same phenomena ( 5-3-6). It was shown that solutions of acetyl nitrate in acetic anhydride were more powerful nitrating media for anisole and biphenyl than the corresponding solutions of nitric acid in which acetyl nitrate had not been formed furthermore, it appeared that the formation of acetyl nitrate was faster when 95-98% nitric acid was used than when 70 % nitric acid was used. 

The behaviour of benzene is the datum from which any discussion of aromatic compoimds must start the reactivity of an aromatic compound is its rate of reaction relative to that of benzene when both are taking part in reactions occurring under the same conditions and proceeding by the same mechanism. 

Ten years ago we became interested in the possibility of using nitration as a process with which to study the reactivity of hetero-aromatic compounds towards electrophilic substitution. The choice of nitration was determined by the consideration that its mechanism was probably better imderstood than that of any other electrophilic substitution. Others also were pursuing the same objective, and a considerable amount of information has now been compiled. 

Nitrations are highly exothermic, ie, ca 126 kj/mol (30 kcal/mol). However, the heat of reaction varies with the hydrocarbon that is nitrated. The mechanism of a nitration depends on the reactants and the operating conditions. The reactions usually are either ionic or free-radical. Ionic nitrations are commonly used for aromatics many heterocycHcs hydroxyl compounds, eg, simple alcohols, glycols, glycerol, and cellulose and amines. Nitration of paraffins, cycloparaffins, and olefins frequentiy involves a free-radical reaction. Aromatic compounds and other hydrocarbons sometimes can be nitrated by free-radical reactions, but generally such reactions are less successful. 

Mechanism. The NO2 mechanism has been accepted since about 1950 for the nitration of most aromatic hydrocarbons, glycerol, glycols, and numerous other hydrocarbons in which mixed acids or highly concentrated nitric acid are used. The mechanism has been discussed in detail and critically analy2ed (1). NO2 attacks an aromatic compound (ArH) as follows ... 

Aromatic Compounds. The accepted general mechanism (38—40,51) for the reaction of an aromatic compound with sulfur trioxide involves an activated intermediate as shown in equation 1. 

The mechanism of reaction with steroids has not been elucidated. Various nonquantitative reactions occur simultaneously. Cyclopentenyl cations have been postulated as intermediates which condense with anisaldehyde to yield colored compounds [4]. It is probable that triphenylmethane dyes are also formed with aromatic compounds. 

Various other observations of Krapcho and Bothner-By are accommodated by the radical-anion reduction mechanism. Thus, the position of the initial equilibrium [Eq. (3g)] would be expected to be determined by the reduction potential of the metal and the oxidation potential of the aromatic compound. In spite of small differences in their reduction potentials, lithium, sodium, potassium and calcium afford sufficiently high concentrations of the radical-anion so that all four metals can effect Birch reductions. The few compounds for which comparative data are available are reduced in nearly identical yields by the four metals. However, lithium ion can coordinate strongly with the radical-anion, unlike sodium and potassium ions, and consequently equilibrium (3g) for lithium is shifted considerably... 

Perfluoroalkylation of substituted benzenes and heterocyclic substrates has been accomplished through thermolysis of perfluoroalkyl iodides in the presence of the appropriate aromatic compound Isomeric mixtures are often obtained W-Methylpyrrole [143] and furan [148] yield only the a-substituted products (equation 128) Imidazoles are perfluoroalkylated under LTV irradiation [149] (equation 129). 4-Perfluoroalkylimidazoles are obtained regioselectively by SET reactions of an imidazole anion with fluoroalkyl iodides or bromides under mild conditions [150] (equation 130) (for the SET mechanism, see equation 57)... 

The scope of electrophilic aromatic substitution is quite large both the aromatic compound and the electrophilic reagent are capable of wide variation. Indeed, it is this breadth of scope that makes electrophilic aromatic substitution so important. Electrophilic aromatic substitution is the method by which substituted derivatives of benzene are prepar ed. We can gain a feeling for these reactions by examining a few typical examples in which benzene is the substrate. These examples are listed in Table 12.1, and each will be discussed in more detail in Sections 12.3 through 12.7. First, however, let us look at the general mechanism of electrophilic aromatic substitution. 

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 commonly employed reagent for the hydroxylation of aromatic compounds is that consisting of ferrous ion and hydrogen peroxide. The suggestion that hydroxyl radicals are intermediates in this reaction was first made by Haber and Weiss, who proposed the following radical-chain mechanism for the process ... 

Aromatic hydrocarbons, like paraffin hydrocarbons, react by substitution, but by a different reaction mechanism and under milder conditions. Aromatic compounds react by addition only under severe conditions. For example, electrophilic substitution of benzene using nitric acid produces nitrobenzene under normal conditions, while the addition of hydrogen to benzene occurs in presence of catalyst only under high pressure to... 

The C-nitrosation of aromatic compounds is characterized by similar reaction conditions and mechanisms to those discussed earlier in this section. The reaction is normally carried out in a strongly acidic solution, and in most cases it is the nitrosyl ion which attacks the aromatic ring in the manner of an electrophilic aromatic substitution, i. e., via a a-complex as steady-state intermediate (see review by Williams, 1988, p. 58). We mention C-nitrosation here because it may interfere with diazotization of strongly basic aromatic amines if the reaction is carried out in concentrated sulfuric acid. Little information on such unwanted C-nitrosations of aromatic amines has been published (Blangey, 1938 see Sec. 2.2). 

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. 

Rearrangement is possible even with a non-carbocation mechanism. The rearrangement could occur before the attack on the ring takes place. It has been shown that treatment of CH3 CH2Br with AlBt3 in the absence of any aromatic compound... 

The exact mechanism has still not been completely worked out. Opinions have been expressed that it is completely intermolecular, completely intramolecular, and partially inter- and intramolecular. " One way to decide between inter- and intramolecular processes is to run the reaction of the phenolic ester in the presence of another aromatic compound, say, toluene. If some of the toluene is acylated, the reaction must be, at least in part, interraolecular. If the toluene is not acylated, the presumption is that the reaction is intramolecular, though this is not certain, for it may be that the toluene is not attacked because it is less active than the other. A number of such experiments (called crossover experiments) have been carried out sometimes crossover products have been found and sometimes not. As in 11-14, an initial complex (40) is formed between the substrate and the catalyst, so that a catalyst/substrate molar ratio of at least 1 1 is required. 

Mercuration of aromatic compounds can be accomplished with mercuric salts, most often Hg(OAc)2 ° to give ArHgOAc. This is ordinary electrophilic aromatic substitution and takes place by the arenium ion mechanism (p. 675). ° Aromatic compounds can also be converted to arylthallium bis(trifluoroacetates), ArTl(OOCCF3)2, by treatment with thallium(III) trifluoroacetate in trifluoroace-tic acid. ° These arylthallium compounds can be converted to phenols, aryl iodides or fluorides (12-28), aryl cyanides (12-31), aryl nitro compounds, or aryl esters (12-30). The mechanism of thallation appears to be complex, with electrophilic and electron-transfer mechanisms both taking place. 

The reaction has been applied to nonheterocyclic aromatic compounds Benzene, naphthalene, and phenanthrene have been alkylated with alkyllithium reagents, though the usual reaction with these reagents is 12-20, and Grignard reagents have been used to alkylate naphthalene. The addition-elimination mechanism apparently applies in these cases too. A protected form of benzaldehyde (protected as the benzyl imine) has been similarly alkylated at the ortho position with butyl-lithium. ... 

Aromatic compounds can also be arylated by aryllead tricarboxylates. Best yields ( 70-85%) are obtained when the substrate contains alkyl groups an electrophilic mechanism is likely. Phenols are phenylated ortho to the OH group (and enols are a phenylated) by triphenylbismuth dichloride or by certain other Bi(V) reagents. O-Phenylation is a possible side reaction. As with the aryllead tricarboxylate reactions, a free-radical mechanism is unlikely. ... 

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