Aromatic substitution reactions mechanisms

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... 

The preceding Sections illustrate several experimental features of heteroaromatic substitutions. It is now intended to comment on some of these features which are most significant in terms of reaction mechanism. As stated in the Introduction, a possible mechanism of nucleophilic bimolecular aromatic substitution reactions is that represented by Eq. (14), where an intermediate of some stability... 

As we ve seen, aromatic substitution reactions usually occur by an electrophilic mechanism. Aryl halides that have electron-withdrawing substituents, however, can also undergo nucleophilic aromatic substitution. For example. 2,4,6-trinitrochlorobenzene reacts with aqueous NaOH at room temperature to give 2,4,6-trinitrophenol. The nucleophile OH- has substituted for Cl-. 

It is regrettable that the evidence afforded by reaction kinetics is rarely, if ever, uniquely consistent with a single mechanism or a single explanation. The results for nucleophilic aromatic substitution reactions are no exception. Legitimate questions can be raised with respect to the extent to which observations made on a particular system permit generalization to other systems. Even for the specific systems studied points of detail arise, and choices have to be made where alternatives are possible. Every such choice introduces an element of uncertainty and imposes a limitation on the extent to which the reaction mechanism is, in fact, known. 

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. 

Aromatic substitution, a quantitative treatment of directive effects in, 1, 35 Aromatic substitution reactions, hydrogen isotope effects in, 2, 163 Aromatic systems, planar and non-planar, 1, 203 Aryl halides and related compounds, photochemistry of, 20, 191 Arynes, mechanisms of formation and reactions at high temperatures, 6, I A-Se2 reactions, developments in the study of, 6,63... 

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+. 

The base may deprotonate either C3 or C4. Deprotonation of C3 makes it nucleophilic. We need to form a new bond from C3 to C8 via substitution. The mechanism of this aromatic substitution reaction could be addition-elimination or Sr I. The requirement of light strongly suggests SRN1. See Chap. 2, section C.2, for the details of drawing an SRN1 reaction mechanism. 

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. 

The title system in acetonitrile forms a homogeneous solution. The generation of NO+ cation takes place. As already known, NO+ is a remarkable, diverse reagent, not only for nitrosation and nitration but also for oxidation. Kochi and co-workers recently christened a new general mechanism oxidative aromatic substitution to describe aromatic substitution reactions (Kochi 1990 Bosch Kochi 1994). The mechanism incorporates ground-state electron transfer prior to the substitution step (see also Skokov Wheeler 1999). 

Most aromatic substitution reactions conform to a simple mechanism. In the rate-determining step, a new bond is formed between an aromatic carbon atom and the electrophilic reagent yielding an intermediate... 

The mechanism for the displacement reactions has also received considerable attention (Eaborn, 1960). A two-step process is generally regarded as satisfying the facts. Reasoning by analogy with conventional aromatic substitution reactions, the first step is presumed to be... 

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

Leaving groups at C5 of 2-substituted 1,2,3-triazoles are predicted to be the most reactive in nucleophilic aromatic substitution reactions following an AE mechanism (see Section 1.4.2). Accordingly, chlorine at C5 of 360 could be replaced by strong nucleophiles like methanethiolate or methoxide to give 377 or 378. The unactivated 2-phenyl-4-chloro-l,2,3-triazole 380 (R=Ph) was inert toward these nucleophiles (1981JCS(P1)503) (Scheme 115). 

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

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