Nucleophilic substitution—continued mechanism

How deeply one wishes to query the mechanism depends on the detail sought. In one sense, the quest is never done a finer and finer resolution of the mechanism may be obtained with further study. For example, the rates and mechanisms of electron transfer reactions have been studied experimentally and theoretically since the 1950s. but the research continues unabated as issues of ever finer detail and broader import are examined. The same can be said of other reactions—nucleophilic substitution, hydrolysis, etc. 

Overall, Eqs. (l)-(3) depict a nucleophilic substitution Eq. (4) in which radicals and radical anions are intermediates. Once the radical anion of the substrate is formed it fragments into a radical and the anion of the leaving group (Eq. (1)). The aryl radical can react with the nucleophile to furnish a radical anion (Eq. (2)), which by ET to the substrate forms the intermediates needed to continue the propagation cycle (Eq. (3)). The mechanism has termination steps that depend on the substrate, the nucleophile and experimental conditions. Not many initiation events are needed, but in this case, the propagation cycle must be fast and efficient to allow for long chains to build up. 

An Sjuyl-type (S l ) mechanism has been proposed in the synthesis of poly(2,6-dimethyl-l,4-phenylene ether) through the anion-radical polymerization of 4-bromo-2,6-dimethylphenoxide ions (204) under phase-transfer catalysed conditions269. Ions 204 are oxidized to give an oxygen radical 205. The propagation consists of the radical nucleophilic substitution by 205 at the ipso position of the bromine in 204 (equation 144). The anion-radical 206 thus formed eliminates a bromide ion to form a dimer phenoxy radical 207 (equation 145). A polymeric phenoxy radical results by continuation of this radical nucleophilic substitution. 

It has been suggested that there is a continuous spectrum of mechanisms for nucleophilic substitution ranging from the idealized S l reaction (called Lim, for limiting) at one end, to the idealized Sn2 reaction (called N) at the other. On progress-of-reaction plots, the energy minimum for the carbonium ion becomes shallower and shallower as We move away from the SnI end at the 8 2 end the minimum has disappeared, and we have a single maximum. 

Although much of the work of the past few years has suggested that the acid-promoted hydrolysis of phosphinic amides proceeds by a continuous spectrum of mechanisms ranging from direct nucleophilic substitution to unimolecular dissociation, depending upon the nucleophilicity of the leaving group and the nature of the... 

The research on the reaction mechanism of the oxidative polycondensation of 2,6-dimethylphenol (DMP) was also continued in the years around 1990. In several publications a Dutch research group reported on kinetic studies dedicated to the 02-promo ted polycondensation of DMP catalyzed by copper tetramethyl 1,2-diamino-ethane complexes [233-236] or by copper complexes of imidazole [237,238]. The speculative mechanistic scheme was based on dimeric copper complexes such as (147a) which were assumed to incorporate a DMP anion (147b) which was oxidized to yield a phenoxy cation and to coordinate another DMP molecule (148a). The growing step was then assumed to consist of a nucleophilic substitution at the phenoxy cation (149) with liberation of a reduced dimeric copper complex (148b). This complex was believed to be... 

Mechanistically, typical PTC reactions take place via two main mechanisms in liquid-liquid systems. The extraction mechanism (Starks, 1971) is the most commonly accepted one for simple nucleophilic substitution under neutral conditions for reactions with a range of anions (e.g halides, cyanide, thiocyanate, sulfite, nitrite, acetate, carbonate, etc.). According to this mechanism (Figure 16.2a), the PT catalyst, denoted by Q+X , is a vehicle to transfer the reactive anion Y of the metal salt from the aqueous phase into the organic phase, where it reacts with the organic substrate, RX, to give the desired product RY and regenerating Q+X , which can continue the PTC cycle. Typically, the active form of... 

The stereochemistry and mechanistic implication for nucleophilic substitution at silicon continue to receive attention, and have been the subject of a comprehensive reviewThe nucleophiles HMPA, DMSO, DMF, and PhaPO catalyze the hydrolysis of triorganochlorosilanes and also their racemization. Stable 1 1 ionic adducts of HMPA with MeaSiBr have been isolated in the past and suggested to be possible intermediates in the racemization process. However, it has now been shown that such ionic 1 1 adducts are not usually formed and that the reported example was a special case which should not be generalized into a mechanism involving displacement of halides by the nucleophile. The previously accepted mechanism involving the formation of five- and six-coordinate species still seems more feasible. 

Discussion of the borderline region between the pair mechanism is considered to be not proven. A kinetic study of the solvolyses of a range of secondary tosylates in a range of solvents has been interpreted as showing a range of nucleophilic solvent assistance with a spectrum of 5n1/ S n2 character. 

Hence Spj2 means that the reaction involves Substitution by a Nucleophile and that it follows second-order kinetics, i.e. two species are involved in the rate-determining step. The S 2 mechanism involves only one continuous step. 

The importance of the substitution pattern on the phosphole in this reaction was obvious from continued studies <78JHC1319> that showed that a much higher order of reactivity and the formation of a quite different 1 2 adduct (82) could be experienced with phospholes of structure (80) and (81). Structure (82) also is novel in heterocyclic phosphorus chemistry and does not seem to have been approached by any other method (Equation (12)). 1-Phenylphosphole also reacts rapidly with the ester, but gave a mixture of products in low yield. One product is probably of the same type as (82) the other is tentatively assigned structure (83). All of these early results with acetylenedicarboxylate have been summarized in a review <81H(15)637>. In terms of mechanism, in every case it appears that the initial step is the action of the phosphorus atom as a typical nucleophilic phosphine in attacking on the triple bond (Equation (13)). Subsequent reactions involve attack on the ring carbons and on a second alkynic group, but details of these processes have not been fully established. 

Binuclear Simple Carbonyls. Mechanisms of reactions of the binuclear carbonyls M2(CO)io continue to be a subject of research and discussion. The most recent paper in this field opens with a useful review of current data and opinions, and offers e.s.r. evidence for the intermediacy of radicals in reaction of Mii2(CO)io with tributylphosphine or triethyl-phosphine. Rates of substitution at Mn2(CO)io by poor nucleophiles are decreased by the presence of an excess of carbon monoxide, are independent of nucleophile concentration, and are associated with large positive activation energies. These, and earlier results reported by other workers, can all be accommodated by a mechanism involving reversible loss of carbon monoxide ... 

The generally accepted mechanism for Pd-catalyzed allylic substitution involves association of the palladium(0) catalyst to the substrate, and oxidative addition to provide a ir-aUyl complex. The equilibrium between the neutral 7r-allyl complex and the more reactive cationic 7r-allyl complex depends on the nature/concentration of phosphine Ugand. Nucleophilic addition to the ligand involves direct attack on the ligand when stabilized enolates are employed. After dissociation of the product, the palladium is able to continue in the next catalytic cycle (Scheme 2). In general, the reaction proceeds via a Pd(0)/Pd(II) shuttle, although a Pd(II)/Pd(IV) pathway is also possible. 

You first met amines in Chapter 2, and you have continued to encounter them in almost every chapter since. Chapter 20 starts by extending the coverage of amines. You have seen that amines do not undergo addition, substitution, or elimination reactions their importance lies in their reactions as bases and nucleophiles with other organic compounds. Chapter 20 also covers the reactions of aromatic heterocyclic compounds. You will see that they undergo the same reactions that benzene and substituted benzenes undergo and by the same mechanisms. 

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