Electrophilic substitutions insertion

Nitration by nitric acid in sulphuric acid has also been by Modro and Ridd52 in a kinetic study of the mechanism by which the substituent effects of positive poles are transmitted in electrophilic substitution. The rate coefficients for nitration of the compounds Pl CHi NMej (n = 0-3) given in Table 10 show that insertion of methylene groups causes a substantial decrease in deactivation by the NMej group as expected. Since analysis of this effect is complicated by the superimposed activation by the introduced alkyl group, the reactivities of the... 

The synthesized CPMV-alkyne 42 was subjected to the CuAAC reaction with 38. Due to the strong fluorescence of the cycloaddition product 43 as low as 0.5 nM, it could be detected without the interference of starting materials. TMV was initially subjected to an electrophilic substitution reaction at the ortho-position of the phenol ring of tyrosine-139 residues with diazonium salts to insert the alkyne functionality, giving derivative 44 [100]. The sequential CuAAC reaction was achieved with greatest efficiency yielding compound 45, and it was found that the TMV remained intact and stable throughout the reaction. 

In one possible mechanism, oxidative addition of iodobenzene to Pd(0) gives Pd(II) intermediate 74, which subsequently inserts into thiazole regioselectively at the C(5) position to form the a-adduct of arylpalladium(II) 75. The order of reactivity is similar to the electrophilic substitution, which is known to be C(5) > C(4) > C(2) [74]. Treatment of the insertion adduct 75 with a base regains the aromaticity after deprotonation, giving rise to 73 along with Pd(0) for the next catalytic cycle. 

The reaction is believed to begin with the metalation of the substrate via aromatic electrophilic substitution (SEAr) followed by CO insertion and nucleophilic displacement by water or another protic nucleophile such as tri-fluoroacetic acid (TFFA) to give, respectively, the aromatic carboxylic acid or its mixed anhydride derivative, from which the acid is freed by hydrolysis (Scheme 24). 

Cyclic epoxides such as 124 can react in two ways with strong bases (a) via abstraction of a /3-proton to form allylic alcoholates 125 or (b) by deprotonation at the epoxide carbon atom forming the intermediate 126 and, after electrophilic substitution, the epoxides 128. If there is a suitable C—H bond in the vicinity of the C-Li moiety, intramolecular carbenoid insertion reactions to 127 may take place (equation 27) ° . ... 

Indolizines were arylated under similar conditions selectively in the 3-position (6.90.). A detailed mechanistic study of the transformation revealed that in this reaction the arylpalladium species, formed in the first step of the catalytic cycle, is attached to the indolizine core in an electrophilic substitution step, which is followed by reductive elimination. The presence of alternate routes such as Heck-type insertion, oxidative addition of the C-H bond, or transmetalation were excluded on the basis of experimental evidence.121... 

The overall mechanistic picture of these reactions is poorly understood, and it is conceivable that more than one pathway may be involved. It is generally considered that cycloheptatrienes are generated from an initially formed norcaradiene, as shown in Scheme 30. Equilibration between the cycloheptatriene and norcaradiene is quite facile and under acidic conditions the cycloheptatriene may readily rearrange to give a substitution product, presumably via a norcaradiene intermediate (Schemes 32 and 34). When alkylated products are directly formed from the intermolecular reaction of carbenoids with benzenes (Scheme 33 and equation 36) a norcaradiene considered as an intermediate alternatively, a mechanism may be related to an electrophilic substitution may be involved leading to a zwitterionic intermediate. A similar intermediate has been proposed143 in the intramolecular reactions of carbenoids with benzenes, which result in substitution products (equations 37-40). It has been reported,144 however, that a considerable kinetic deuterium isotope effect was observed in some of these systems. Unless the electrophilic attack is reversible, this would indicate that a C—H insertion mechanism is involved in the rate-determining step. 

The products derived from guanidines show aromatic reactivity. They are strongly nucleophilic and may be brominated and methylated in the heterocyclic ring. Reaction occurs with dimethylacetylene dicarboxylate to form the eight-membered insertion product 85. However, this is possibly produced by a two-step process involving electrophilic substitution of the heteroring rather than direct Diels-Alder addition, and this proposal is supported by the simultaneous formation of the substitution product 86. 

The first stage of the process is the strong adsorption and activation of the N2O molecule accompanied by the formation of a chemisorbed monoatomic singlet oxygen species. The latter is involved in further stages in the reactions of electrophilic substitution in the aromatic riing (or insertion of the oxygen atom into the C-H bond. 

Giacomelli and Lardicci have treated bromoalkynes with trialkylaluminum in the presence of bis(A/-methylsalicylaldimine)nickel and obtained an alkyl-substituted alkyne (Scheme 33). This reaction probably involves (i) insertion of the nickel into die alkyne-bromine bond (ii) exchange of alkyl for bromine and (iii) formation of the alkyne-alkyl bond. TTius, although the process appears to be an electrophilic substitution, it is actually nucleophilic in character. 

Electrophilic substitution of methane is to be considered as an insertion process into a C-H bond.This step, however, could be followed by a very facile bond-to-bond proton migration to the more symmetrical, energetically favored form EH2CH2, which subsequently gives the substituted methane by proton elimination [Eq. (6.46)]. 

Ab initio molecular orbital theory has been applied by Olah and coworkers to investigate the reactions of NO and the protonitrosonium ion HNO with methane. The reaction path was found to involve attack of NO on carbon instead of C-H bond insertion in accord with the studies of Schreiner et al. It was, however, pointed out that this is the consequence of the ambident electrophilic nature of NO and does not represent a general electrophilic reaction pathway for the reactions of methane. In fact, Schreiner and coworkers suggested that the electrophilic substitution of methane occurs by substitution of the nonbonded electron pair of methane instead of insertion of the electrophile into a C-H bond via 3c-2e bonding. Nonbonded electron pair formation in methane, however, can be considered only when methane would tend to flatten out (58) from its tetrahedral form, but this would be prohibitively energetic (>100 kcal mol ) and thus unlikely. 

In 1984, Hegedus and Harrington reported a synthesis of 3- and 4-substituled indoles [77] employing Heck s well-established process Pd(O)-catalyzed functionalization of aryl halides by the oxidative addition-olefin insertion-P-hydride elimination. In this instance. 4-bromo-I-tosylindole (161, Scheme 28) was converted to several diversely functionalized 4-substituted I-tosylindoles. Selective electrophilic substitutions at the C(3) position of 161 provided access to 3-(chloromcrcurio)-l-tosylindole and 3-iodo-l-tosylindole (162), which then underwent a Heck... 

Several types of anhydrides of tervalent phosphorus acids are known and have been prepared by electrophilic substitution reactions at phosphorus. Examples are the phosphi-nous acid anhydrides 52 (equation 157), 53 (equation 158), prepared from a chlorophos-phine or an aminophosphine , and 54 (equation 159) Aminophosphines react with carbon disulphide to give ionic addition compounds at low temperatures, but dithiocar-bamate anhydrides (55) at room temperature (equation 160) Aminophosphines form analogous carbamate anhydrides with carbon dioxide, but isothiocyanates give ionic addition products, not insertion products ... 

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