Nucleophilic substitution reactions general features

The synthesis of nitro dyes is relatively simple, a feature which accounts to a certain extent for their low cost. The synthesis, illustrated in Scheme 6.5 for compounds 140 and 141, generally involves a nucleophilic substitution reaction between an aromatic amine and a chloronitroaromatic compound. The synthesis of C. I. Disperse Yellow 14 (140) involves the reaction of aniline with l-chloro-2,4-dinitroaniline while compound 141 is prepared by reacting aniline (2 mol) with compound 144 (1 mol). 

Unlike the nucleophilic substitution reactions which generate stable onium halide after the reaction, nucleophilic additions to electrophilic C=X double bonds (X=C, N, O) provide rather basic onium anion species as an initial product. If the anion is sufficiently stable under the reaction conditions, onium anion will then exchange the counter ion for the other metal carbanion at the interface to regenerate the reactive onium carbanion Q+R. In another scenario, the basic onium anion may abstract the acidic hydrogen atom of the other substrate to provide Q 1 R directly. Such a reaction system ideally requires only a catalytic amount of the base although, in general, a substoichiometric or excess amount of the base is used to lead the reaction to completion. An additional feature of this system is the substantial possibility of a retro-process at the crucial asymmetric induction step, which might be problematic in some cases. 

The term nucleophilicity is generally accepted to refer to the effect of a Lewis base on the rate of a nucleophilic substitution reaction and may be contrasted with basicity, which is defined in terms of the position of an equilibrium reaction with a proton or some other acid. Nucleophilicity then is used to describe trends in the kinetic aspects of reactions. The relative nucleophilicity of a given species may differ from substrate to substrate. It has not been possible to devise an absolute scale of nucleophilicity. The situation is analogous to that for basicity, in which the basicity is defined with respect to some specific acid. We need to gain some impression of the structural features that govern nucleophilicity and to understand the relationship between nucleophilicity and basicity. ... 

The points that we have emphasized in this brief overview of the S l and 8 2 mechanisms are kinetics and stereochemistry. These features of a reaction provide important evidence for ascertaining whether a particular nucleophilic substitution follows an ionization or a direct displacement pathway. There are limitations to the generalization that reactions exhibiting first-order kinetics react by the Sj l mechanism and those exhibiting second-order kinetics react by the 8 2 mechanism. Many nucleophilic substitutions are carried out under conditions in which the nucleophile is present in large excess. When this is the case, the concentration of the nucleophile is essentially constant during die reaction and the observed kinetics become pseudo-first-order. This is true, for example, when the solvent is the nucleophile (solvolysis). In this case, the kinetics of the reaction provide no evidence as to whether the 8 1 or 8 2 mechanism operates. 

All the reactions discussed in this review are aromatic nucleophilic substitutions in the ordinary sense. These reactions are briefiy described in the following sections with respect to their general kinetic features and mainly involve aza-activated six-membered ring systems, although a few studies of other heteroaromatic compounds are also available. 

The ability of a nitro group in the substrate to bring about electron-transfer free radical chain nucleophilic substitution (SrnI) at a saturated carbon atom is well documented.39 Such electron transfer reactions are one of the characteristic features of nitro compounds. Komblum and Russell have established the SrnI reaction independently the details of the early history have been well reviewed by them.39 The reaction of p-nitrobenzyl chloride with a salt of nitroalkane is in sharp contrast to the general behavior of the alkylation of the carbanions derived from nitroalkanes here, carbon alkylation is predominant. The carbon alkylation process proceeds via a chain reaction involving anion radicals and free radicals, as shown in Eq. 5.24 and Scheme... 

The essential features of the mechanism for aliphatic nucleophilic substitution at tertiary carbon were established in studies by Hughes and Ingold." ° However, as chemists probed more deeply, the problems associated with the characterization of borderline reaction mechanisms were encountered, and controversy remains to this day about whether these problems have been entirely solved." What is generally accepted is that ferf-butyl derivatives undergo borderline solvolysis reactions through a ferf-butyl carbocation intermediate that is too unstable to diffuse freely through nucleophilic solvents such as methanol and water. The borderline nature of substitution reactions at tertiary carbon is exemplihed by the following observations. 

The oxidation of carbonyl compounds can be achieved with hypervalent iodine reagents quite easily. A general feature of these reactions is the electrophilic attack of the hypervalent iodine reagent at the a-carbon atom of a carbonyl group and a review on this chemistry has been published recently [6]. This leads to hypervalent iodine intermediates of type 55. These phenyliodinated intermediates are quite unstable and a variety of subsequent reactions are possible. Intermediates 55, Scheme 24, can be considered as umpoled substrates regarding the reactivity of the a-position of the initial carbonyl compounds. Major processes are the substitution by a nucleophile (see Sect. 3.5.1 Functionalization in the a-Position) or the introduction of a carbon-carbon double bond (see Sect. 3.5.2 Introduction of an a,/ -Unsaturation). 

The reaction of (CH3)3CBr with CH3COO is an example of the second mechanism for nucleophilic substitution, the S l mechanism. What are the general features of this mechanism ... 

Figure 24.6 compares the general reaction for nucleophilic substitution of an ester with the Claisen reaction. Sample Problem 24.3 reinforces the basic features of the Claisen reaction. 

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