Electrophilic substitution reaction mechanism

Acyl-pyrroles, -furans and -thiophenes in general have a similar pattern of reactivity to benzenoid ketones. Acyl groups in 2,5-disubstituted derivatives are sometimes displaced during the course of electrophilic substitution reactions. iV-Alkyl-2-acylpyrroles are converted by strong anhydrous acid to A-alkyl-3-acylpyrroles. Similar treatment of N-unsubstituted 2- or 3-acyIpyrroles yields an equilibrium mixture of 2- and 3-acylpyrroles pyrrolecarbaldehydes also afford isomeric mixtures 81JOC839). The probable mechanism of these rearrangements is shown in Scheme 65. A similar mechanism has been proposed for the isomerization of acetylindoles. 

At this point, attention can be given to specific electrophilic substitution reactions. The kinds of data that have been especially useful for determining mechanistic details include linear ffee-energy relationships, kinetic studies, isotope effects, and selectivity patterns. In general, the basic questions that need to be asked about each mechanism are (1) What is the active electrophile (2) Which step in the general mechanism for electrophilic aromatic substitution is rate-determining (3) What are the orientation and selectivity patterns ... 

The nature of species (II), whether an unstable intermediate or transition state, requires discussion because of its possible importance in catalytic reaction mechanisms. By analogy to homogeneous substitution reactions a distinction can be made between electrophilic and radical attack. Electrophilic substitution reactions, with a proton for example, appear to proceed via a charge-transfer complex... 

As noted in the earlier section Basics of Electrophilic Substitution Reactions, the loss of the hydrogen ion (H ) requires the presence of a strong base. The chloride ion (CL) is a base, but it isn t strong enough to accomplish this task. However, as shown in the mechanism, the tetrachloro-aluminate ion (A1C1 ) is a sufficiently strong base. This process also regenerates the catalyst so that it s available to continue the process. 

Once formed, the electrophile behaves like any other electrophile, so the mechanism of the attack is the same as that for the previous situation where a nucleophile attacked the electrophile (described in the earlier section Basics of Electrophilic Substitution Reactions ). The attack leads to the formation of the resonance-stabilized sigma complex, followed by the loss of a hydrogen ion to a base. 

The mechanism for these electrophilic substitution reactions involves formation of a dication intermediate (13) which, as in the case of benzenoid substitution reactions, loses a proton and reverts to the original stable system. 

In the electrophilic substitution reactions of coordinated aromatic ligands for which rate data are presently available, there is every indication that the mechanism of the reaction is unchanged in its essentials. Following the lead of the physical organic chemists the course of the reaction of the complex and the diazonium ion can be depicted as ... 

The protonation studies are of interest in another connection. If protonation of metallocenes can be considered to be a simple form of electrophilic attack, it is possible that other types of electrophilic substitution reactions may proceed through initial coordination of the electrophile with the central metal atom (14, 93). The mechanism of acylation of metallocenes may therefore be more complex than might be expected by analogy to similar reactions of benzenoid compounds. Clearly more studies are needed along these lines, better to define specific metal effects on the properties and reactions of these remarkable compounds. 

Therefore in an attempt to distinguish among mechanisms A, B, and C the acetylacetonates of chromium(III), cobalt(III), and rhodium(III) were partially resolved and the optically active chelates were then subjected to several electrophilic substitution reactions. 

It is well known that not all attempts to explain the reactivity of individual positions in electrophilic substitution reactions have been successful. There are three main lines along which attempts have been made to remove discrepancies between theory and experiment (for a summary, see ref. 147) (1) introduction into the HMO treatment of additional empirical parameters (inductive effect), (2) invoking the addition-elimination mechanism, and (3) invoking different reactivity of the protonated and unprotonated forms. 

Mechanism. Addition of hypohalous acids to olcfinic double bonds is generally regarded as a typical electrophilic substitution reaction, and therefore subject- to the same governing principles v. others of the same typo. 

Electrophilic substitution reactions to olefins have been recorded on vinyl silanes116 (57). Scheme 27 reports the electrophilic substitution of the SiMe3 group by acyl halides. Probably, this reaction too occurs via a complex between the electrophilic part of the reagent and the tt system of the olefin, but other mechanisms are possible. 

However, Jensen et al.40,43, have correctly pointed out that the fourth-order coefficient (k4 in equation (18)) or the second-order coefficient (k°2 in equation (28)) are actually complex coefficients and include K, the equilibrium constant for reaction (24) or (26). In terms of mechanism B, k4 = K(24) xk(25) and in terms of mechanism C, k4 = Ki26)xkl2V. Thus substituent effects may well refer to the equilibrium (24) or (26) rather than to the actual electrophilic substitution, reaction (25) or (27). In this connection it is worth recalling that in the bimolecular one-alkyl exchange (13) the sequence of / -substituents in the benzyl group is p-Cl < H < p-Pr1, but in the anion-catalysed exchange (13), which takes place via a pre-rate-determining equilibrium, the sequence is p-C 1 > H > p-Pr (see Table 4, p. 45) it seems to the author that the substituent effects shown in Table 9 may also be explained as effects on the equilibrium constants K(24) or K(26). 

On the other hand, a pure Eley-Rideal mechanism, in which the aromatic compound in the liquid phase reacts with the adsorbed acylating agent was first proposed by Venuto et alP1,22] and more recently by others.[23] However, for acylation reactions of polar substrates (anisole, veratrole), chemisorption of the latter must be taken into account in the kinetic law. A modification, the modified Eley-Rideal mechanism, has been proposed 114,24-26 an adsorbed molecule of acylating agent should react with a nonadsorbed aromatic substrate, within the porous volume of the catalyst. However, the substrate is also competitively adsorbed on the active sites of the zeolite, acting somehow as a poison of the acid sites. That is what we checked through different kinetic studies of various aromatic electrophilic substitution reactions.[24-26]... 

Fig. 12.10. Mechanism of the a-oxygenation of ketones in reactions with selenium dioxide an electrophilic substitution reaction (—> —> C) is followed by a /(-elimination at the C-0 single bond.

The mechanism of electrophilic substitution reactions in ferrocene is illustrated below... 

This section presents several additional reactions that are very useful in the synthesis of aromatic compounds because they provide methods to convert substituents that can be attached by electrophilic substitution reactions to other substituents that cannot be attached directly. The mechanisms of these reactions need not concern us here. 

Because metal ions are electrophiles, a reaction of this type is known as electrophilic substitution (the mechanism may be described as SE1 or SE2). In this reaction, the ligands are transferred from one metal to another, which is equivalent to one metal replacing the other. This type of reaction is much less common than the nucleophilic substitution reactions that will be considered in this section. 

The ability of azoles to electrophilic substitution reactions is determined by the activity of reagents, the basicity of substrates, and the acidity of media. This caused some uncertainty in the interpretation of results and complicated a comparison of the reactivity of various azoles. The situation has changed after Katritzky and Johnson [1] have reported the criteria allowing, with a sufficient degree of reliance, the establishment in what form (base or conjugative acid) the compound reacts. The information on the mechanism of nitration of azoles was basically borrowed from the extensive literature on the nitration of aromatic hydrocarbons [2-8] therefore, we have found expedient to discuss briefly some works in this field. 

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