Electrophilic aromatic substitution reactions mechanism

As shown in Scheme 34, [4,6- H2]-tryptophan and [5,7- H2]-tryptophan were synthesized and fed to cultures of Aspergillus amstelodami. The [5,7- H2]-tryptophan was incorporated into echinulin and neoechinulin B with 2% and 103% retention of tritium activity, respectively. The [4,6- H2l-tryptophan was incorporated into echinulin with 102% retention of tritium activity and into neoechinulin with 48% loss of tritium activity. These experiments are complementary and clearly demonstrate that the introduction of the isoprene units go via a direct electrophilic aromatic substitution reaction mechanism. It shoidd also be noted that Fuganti et al. isolated cryptoechinulin from Aspergillus amstelodami during the course of their biosynthetic work on echinulin [58]. 

The catalyst functions exactly as expected (compare the role of AICI3 here to the role that it plays in Section 19.2). The result here is the formation of a carbocation, which is an excellent electrophile and is capable of reacting with benzene in an electrophilic aromatic substitution reaction (Mechanism 19.6). 

If the Lewis base ( Y ) had acted as a nucleophile and bonded to carbon the prod uct would have been a nonaromatic cyclohexadiene derivative Addition and substitution products arise by alternative reaction paths of a cyclohexadienyl cation Substitution occurs preferentially because there is a substantial driving force favoring rearomatization Figure 12 1 is a potential energy diagram describing the general mechanism of electrophilic aromatic substitution For electrophilic aromatic substitution reactions to... 

Electrophilic aromatic substitution reactions are important for synthetic purposes and also are one of the most thoroughly studied classes of organic reactions from a mechanistic point of view. The synthetic aspects of these reactions are discussed in Chapter 11 of Part B. The discussion here will emphasize the mechanisms of several of the most completely studied reactions. These mechanistic ideas are the foundation for the structure-reactivity relationships in aromatic electrophilic substitution which will be discussed in Section 10.2... 

Isotope effects are also useful in providing insight into other aspects of the mechanisms of individual electrophilic aromatic substitution reactions. In particular, because primary isotope effects are expected only when the breakdown of the c-complex to product is rate-determining, the observation of a substantial points to a rate-... 

Figure 12.1 is a potential energy diagram describing the general mechanism of electrophilic aromatic substitution. For electrophilic aromatic substitution reactions to... 

Resole syntheses entail substitution of formaldehyde (or formaldehyde derivatives) on phenolic ortho and para positions followed by methylol condensation reactions which form dimers and oligomers. Under basic conditions, pheno-late rings are the reactive species for electrophilic aromatic substitution reactions. A simplified mechanism is generally used to depict the formaldehyde substitution on the phenol rings (Fig. 7.21). It should be noted that this mechanism does not account for pH effects, the type of catalyst, or the formation of hemiformals. Mixtures of mono-, di-, and trihydroxymethyl-substituted phenols are produced. 

Thiadiazolines and thiadiazolium salts can undergo a thermally promoted rearrangement to yield 2-guanidinoben-zothiazoles. Thus the thiadiazoline 42 when heated in ethanol at reflux affords the benzothiazole 43 (Equation 11). There is evidence to suggest that this could be an electrophilic aromatic substitution reaction but a free radical mechanism was also proposed <2003SC2053>. 

Hammond postulate has been used to explain the effect of substituents on the rate of benzilic acid rearrangements, mechanism of electrophillic aromatic substitution reactions and reactions involving highly reactive intermediates such as carbonium ions and carbon ions. 

The first product is derived from a normal electrophilic aromatic substitution reaction of the kind described in the text. The second product is derived from ipso electrophilic aromatic substitution. The mechanism is exactly the same, but in the last step z-Pr+ is lost instead of H+. 

This chapter is concerned with reactions that introduce or replace substituent groups on aromatic rings. The most important group of reactions is electrophilic aromatic substitution. The mechanism of electrophile aromatic substitution has been studied in great detail, and much information is available about structure-reactivity relationships. There are also important reactions which occur by nucleophilic substitution, including reactions of diazonium ion intermediates and metal-catalyzed substitution. The mechanistic aspects of these reactions were discussed in Chapter 10 of Part A. In this chapter, the synthetic aspects of aromatic substitution will be emphasized. 

Stack and co-workers recently reported a related jx-rf / -peroxodi-copper(II) complex 28 with a bulky bidentate amine ligand capable of hydroxylating phenolates at - 80 °C. At - 120 °C, a bis(yu,-oxo)dicopper(III) phenolate complex 29 with a fully cleaved 0-0 bond was spectroscopically detected (Scheme 13) [190]. These observations imply an alternative mechanism for the catalytic hydroxylation of phenols, as carried out by the tyrosinase metalloenzyme, in which 0-0 bond scission precedes C - 0 bond formation. Hence, the hydroxylation of 2,4-di-tert-butylphenolate would proceed via an electrophilic aromatic substitution reaction. 

All electrophilic aromatic substitution reactions share a common mechanism. This mechanism consists of a series of steps. 

Write the steps in the mechanism for an electrophilic aromatic substitution reaction. 

Write the mechanism of electrophilic aromatic substitution reactions of pyridine. 

Regioselectivity in the formation of regioisomers is also observed in electrophilic aromatic substitution reactions. In the case of monosubstituted benzene derivatives, there are three possible regiosomeric products that form at different rates, based on the mechanism of the reaction (see Figure 13). see also Berzelius, Jons Jakob Chirality Dalton, John Davy, Humphry Molecular Structure Scheele, Carl Wohler, Friedrich. 

A general mechanism for the electrophilic aromatic substitution reaction is outlined in Figure 17.1. The process... 

All of the electrophilic aromatic substitution reactions follow this same general mechanism. The only difference is the structure of the electrophile and how it is generated. Let s look at a specific example, the nitration of benzene. This reaction is accomplished by reacting benzene with nitric acid in the presence of sulfuric acid ... 

Please note that while the Friedel-Crafts acylation reaction is presented in discussions of addition-elimination reaction mechanisms, this reaction is actually an electrophilic aromatic substitution reaction. The correct mechanisms for a Freidel-Crafts acylation was presented in the solution for Problem 6 (h) from Chapter 7. 

No matter what electrophile is used, all electrophilic aromatic substitution reactions occur via a two-step mechanism addition of the electrophile to form a resonance-stabilized carboca-tion, followed by deprotonation with base, as shown in Mechanism 18.1. 

Electrophilic aromatic substitution reactions seem, then, to proceed by a single mechanism, whatever the particular reagent involved. This can be summarized for the reagent YZ as follows ... 

Problem 3.10. Draw mechanisms for the following electrophilic aromatic substitution reactions. 

Obviously, more work is required to further substantiate the presence of the proposed radical intermediates in the p-hydroxybenzoate hydroxylase reaction, possibly via EPR and spin-trapping studies. Studies by Detmer and Massey 247) on phenol hydroxylase have indicated that the reaction rate constants for the conversion of meta-substituted substrates plotted versus the Hammett parameters yield a straight line of slope equal to 0.5. This is consistent with the mechanism proposed by Anderson, as the negative slope is expected for an electrophilic aromatic substitution reaction, while the small magnitude of the slope may be indicative of a radical mechanism. Furthermore, recent work by Massey and co-workers on p-hydroxybenzoate hydroxylase utilizing 6-hydroxy-FAD as cofactor and p-aminobenzoate as substrate indicated that the absorption spectrum of intermediate 67 exhibited a satellite band at 440 nm 248). Anderson et al. suggest that the satellite band may result from the formation of an aromatic phenoxyl radical at the C-6 position of the isoalloxazine ring of the flavin 244). This species would result from a shift of the initial peroxyl radical center from C(4a) to C-6 via N(5) 245). 

Section 15.9 General Mechanism for Electrophilic Aromatic Substitution Reactions... 

All of these electrophilic aromatic substitution reactions take place by the same two-step mechanism. In the first step, benzene reacts with an electrophile (Y ), forming a carbocation intermediate. The structure of the carbocation intermediate can be approximated by three resonance contributors. In the second step of the reaction, a base in the reaction mixture pulls off a proton from the carbocation intermediate, and the electrons that held the proton move into the ring to reestablish its aromaticity. Notice that the proton is always removed from the carbon that has formed the new bond with the electrophile. 

We will look at each of these five electrophilic aromatic substitution reactions individually. As you study them, notice that they differ only in how the electrophile (Y" ") needed to start the reaction is generated. Once the electrophile is formed, all five reactions follow the same two-step mechanism for electrophilic aromatic substitution. 

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