Substitution, electrophilic cyclic mechanisms

The nomenclature used in describing bimolecular electrophilic substitutions involving cyclic transition states reflects, in part, the above-mentioned difficulty. Ingold3 has adopted the nomenclature of Winstein et al.1 and refers to such substitutions as SEi, but to the present author this is not a particularly appropriate choice since it does not indicate the bimolecular nature of the substitution. Dessy et al.8 have used the term SF2 to describe a mechanism, such as that in reaction (5), in which a four-centred transition state is formed, but not only is such a term too restricted, it also provides no indication that the mechanism is one of electrophilic substitution. The view of Reutov4 is that the cyclic, synchronous mechanism is very close to the open mechanism and that both can be described as SE2 mechanisms. Dessy and Paulik9 used the term nucleophilic assisted mechanisms to describe these cyclic, synchronous mechanisms and Reutov4,10 has recently referred to them in terms of internal nucleophilic catalysis , internal nucleophilic assistance , and nucleophilic promotion . Abraham, et al,6 have attempted to reconcile these various descriptions and have denoted such mechanisms as SE2(cyclic). 

Even now, there are two further limiting cases, for if k equilibrium constant for complex formation. Experimentally it will be a matter of extreme difficulty to distinguish either of these possibilities from mechanism SE2(open) or SE2 (cyclic), since all of these mechanisms require the reaction to follow second-order kinetics. Indeed, Reutov4 appears to include a situation such as (7), if the complex is present but in very low concentration, under the mechanistic title of SE2. This is also the nomenclature used by Traylor and co-workers11, but Abraham and Hill5 refer to such a situation as SEC (substitution, electrophilic, via co-ordination). 

For substitutions proceeding by mechanism SE2(cyclic), it might be expected that substituent effects would reflect, at least in part, the relative importance of electrophilic attack at the carbon atom undergoing substitution compared with nucleophilic attack at the metal atom in the leaving group, i.e. the position of... 

The decarboxylation of aliphatic acids may take place as an aliphatic electrophilic substitution but also in some cases can be regarded as an elimination reaction using a cyclic mechanism as described in Section 2.1. 

This results from the fact that the tin mercaptide possess both nucleophilic and electrophilic properties, which permit substitution by the cyclic mechanism shown in Scheme 3.3.3, rather than the elimination which is normally observed with such structures. 

The mechanism for the conversion of the A -oxide (94) to the o-methylaminophenylquinoxaline (96) involves an initial protonation of the A -oxide function. This enhances the electrophilic reactivity of the a-carbon atom which then effects an intramolecular electrophilic substitution at an ortho position of the anilide ring to give the spiro-lactam (98). Hydrolytic ring cleavage of (98) gives the acid (99), which undergoes ready dehydration and decarboxylation to (96), the availability of the cyclic transition state facilitating these processes. ... 

Mechanism. The reaction is analogous to the addition of bromine molecules to an alkene. The electrophilic mercury of mercuric acetate adds to the double bond, and forms a cyclic mercurinium ion intermediate rather than a planer carbocation. In the next step, water attacks the most substituted carbon of the mercurinium ion to yield the addition product. The hydroxymercurial compound is reduced in situ using NaBH4 to give alcohol. The removal of Hg(OAc) in the second step is called demer-curation. Therefore, the reaction is also known as oxymercuration-demercuration. 

However, the mechanism is not limited to four-centred transition states, and cyclic six-centred transition states formed by synchronous electrophilic substitution and internal coordination have been postulated7, e.g. 

Abraham and Hill22 suggested that the mechanism of acidolysis was that of SE2(cyclic), in which electrophilic attack at the carbon atom undergoing substitution was an important feature the reactivity sequence p-toluidine > cyclo-hexylamine is that of acid strength. A transition state such as (IV) is thus indicated. 

In this chapter a number of electrophilic substitutions that have been the subject of kinetic studies are reviewed. Many of these substitutions have been suggested to proceed via mechanisms denoted, in the terminology used in the present work, as SE2(cyclic) and SE2(co-ord). Additionally, a short account of the stereochemical course of the carbonation reaction has been included, even though no kinetic studies have been reported. 

Abstract Synthesis methods of various C- and /V-nitroderivativcs of five-membered azoles - pyrazoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazoles, oxazoles, oxadiazoles, isoxazoles, thiazoles, thiadiazoles, isothiazoles, selenazoles and tetrazoles - are summarized and critically discussed. The special attention focuses on the nitration reaction of azoles with nitric acid or sulfuric-nitric acid mixture, one of the main synthetic routes to nitroazoles. The nitration reactions with such nitrating agents as acetylnitrate, nitric acid/trifluoroacetic anhydride, nitrogen dioxide, nitrogen tetrox-ide, nitronium tetrafluoroborate, V-nitropicolinium tetrafluoroborate are reported. General information on the theory of electrophilic nitration of aromatic compounds is included in the chapter covering synthetic methods. The kinetics and mechanisms of nitration of five-membered azoles are considered. The nitroazole preparation from different cyclic systems or from aminoazoles or based on heterocyclization is the subject of wide speculation. The particular section is devoted to the chemistry of extraordinary class of nitroazoles - polynitroazoles. Vicarious nucleophilic substitution (VNS) reaction in nitroazoles is reviewed in detail. 

Alternative reaction pathways exploring different synthetic possibilities have been studied. For instance, electron-rich dihydroazines also react with isocyanides in the presence of an electrophile, generating reactive iminium species that can then be trapped by the isocyanide. In this case, coordination of the electrophile with the isocyanide must be kinetically bypassed or reversible, to enable productive processes. Examples of this chemistry include the hydro-, halo- and seleno-carba-moylation of the DHPs 270, as well as analogous reactions of cyclic enol ethers (Scheme 42a) [223, 224]. p-Toluenesulfonic acid (as proton source), bromine and phenylselenyl chloride have reacted as electrophilic inputs, with DHPs and isocyanides to prepare the corresponding a-carbamoyl-(3-substituted tetrahydro-pyridines 272-274 (Scheme 42b). Wanner has recently, implemented a related and useful process that exploits M-silyl DHPs (275) to promote interesting MCRs. These substrates are reacted with a carboxylic acid and an isocyanide in an Ugi-Reissert-type reaction, that forms the polysubstituted tetrahydropyridines 276 with good diasteroselectivity (Scheme 42c) [225]. The mechanism involves initial protiodesilylation to form the dihydropyridinum salt S, which is then attacked by the isocyanide, en route to the final adducts. 

This mechanism is called the internal electrophilic substitution and is usually given the label SEi. However, it sometimes goes under the label of SF2 or SE2 (cyclic). 

The mechanism of the reaction has been studied in some detail by Hogberg i2,7i,72) jn contrast to the base-catalyzed oligomerization, the acid catalyzed process involves electrophilic aromatic substitutions by cations, as outlined in Fig. 8. Although formaldehyde does not react with resorcinol to produce cyclic oligomers, other aldehydes such as acetaldehyde and benzaldehyde give excellent yields of... 

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