Polar nucleophilic reactions, competition

In the context of this chapter, we demonstrate that only by considering polar nucleophilic processes as SET processes can the factors that govern the competition between polar and SET processes as well as nucleophilic reactions of radical cations be adequately understood. 

A study of debrominations of vtc-dibromides promoted by diaryl tellurides and din-hexyl telluride has established several key features of the elimination process the highly stereoselective reactions of e/7f/tro-dibromides are much more rapid than for fhreo-dibromides, to form trans- and cw-alkenes, respectively the reaction is accelerated in a more polar solvent, and by electron-donating substituents on the diaryl telluride or carbocation stabilizing substituents on the carbons bearing bromine. Alternative mechanistic interpretations of the reaction, which is of first-order dependence on both telluride and vtc-dibromide, have been considered. These have included involvement of TeAr2 in nucleophilic attack on carbon (with displacement of Br and formation of a telluronium intermediate), nucleophilic attack on bromine (concerted E2- k debromination) and abstraction of Br+ from an intermediate carbocation. These alternatives have been discounted in favour of a bromonium ion model (Scheme 9) in which the role of TeArs is to abstract Br+ in competition with reversal of the preequilibrium bromonium ion formation. The insensitivity of reaction rate to added LiBr suggests that the bromonium ion is tightly paired with Br. ... 

In connection with the substituent effects, the kinetic stability of benzyne is suggested to be increased by electron withdrawal (-/) and decreased by electron release (+/).73 However, the inference cannot be extrapolated to selectivity of substituted arynes in general. For example, in additions involving competition between phenyllithium and lithium piperidide, the methyl substituents (+/) on benzyne increase its selectivity, whereas methoxy groups (-/) decrease it (Scheme 6). On the other hand, in reactions of car-banions derived from acetonitrile in alkylamine solvents both +/ and -/ benzyne substituents lower selectivity and cause predominant amination. Thus, the method was found unsuitable for preparation of many substituted benzyl nitriles.74 In symmetrically disubstituted arynes there is partial cancellation of polarization, and in fact acceptable yields of acetonitrile adducts could be obtained from 3,6-dimethoxy-benzyne.75 The selectivity of substituted arynes varies with the set of nucleophiles in the competition and no comprehensive theory or simple generalization is available on this point. 

On the contrary, in the case of 1-iodonorbomane (a tertiary halide), the result of the reaction with trimethylstannyl reagents (Me3SnM, M = Li, Na), both in the absence and in the presence of trapping agents, confirmed that the nucleophilic substitution process is governed by competition between polar and radical mechanisms133. 

Examples of the solvent-dependent competition between nucleophilic substitution and / -elimination reactions [i.e. SnI versus Ei and Sn2 versus E2) have already been given in Section 5.3.1 [cf. Table 5-7). A nice example of a dichotomic y9-elimination reaction, which can proceed via an Ei or E2 mechanism depending on the solvent used, is shown in Eq. (5-140a) cf. also Eqs. (5-20) and (5-21) in Section 5.3.1. The thermolysis of the potassium salt of racemic 2,3-dibromo-l-phenylpropanoic acid (A), prepared by bromine addition to ( )-cinnamic acid, yields, in polar solvents [e.g. water), apart from carbon dioxide and potassium bromide, the ( )-isomer of l-bromo-2-phenylethene, while in solvents with low or intermediate polarity e.g. butanone) it yields the (Z)-isomer [851]. 

Azodicarboxylates are recognized for their ability to participate as 2ir components of HOMOdi e-con-trolled Diels-Alder reactions with dienes and for their participation in ene reactions with reactive al-kenes. 489 j, addition, electron-rich or reactive simple alkenes that do not contain a reactive allylic hydrogen atom have been shown to participate in competitive [2 + 2] and [4 + 2] cycloaddition reactions with azodicarboxylates in which the observed course of the reaction is dependent upon the solvent polarity and nucleophilic character of the alkene (Table 13). As may be anticipated, alkoxycarbonyl-aroyldiimides (4), diaroyldiimides (5), and aiylaroyldiimides (6) participate with increasing selectivity as 4tr components of [4 + 2] cycloaddition reactions. 

Most of the work concerned with micellar catalysis of nucleophilic substitution refers to reactions of the Aac2 and SN2 types and will not be reviewed here. To date only a few systems have been examined in which a micellar medium affects the partitioning of solvolytic reactions between unimolecular and bimolecular mechanisms. The effects of cationic (hexadecyltrimethylammonium bromide = CTAB) and anionic (sodium lauryl sulfate = NaLS) micelles on competitive SN1 and SN2 reactions of a-phenylallyl butanoate 193) have been investigated189. The rate of formation of the phenylallyl cation 194) is retarded by both surfactants probably as a consequence of the decreased polarity of the micellar pseudo phase. The bimolec-... 

Bromine Addition to Alkenes. Alumina can advantageously replace protic solvents thus avoiding secondary reactions due to their nucleophdicity. This situation is evidenced in the bromation of alkenes [14]. When performed in methanol, bromine addition leads to a mixture of a frans-dibromo adduct and a trans-bromo ether compound. The latter results from competitive attack by pro-tic solvent on the bromonium ion intermediate. This byproduct can be suppressed using Br2/alumina, as the support behaves as a non-nucleophilic polar medium (Scheme 3). 

Problem 8.4 Lower molecular weights and polymerization rates observed in anionic polymerizations of polar monomers are attributed to the reactivity of the polar substituents toward nucleophiles, leading to termination and side reactions that are competitive with both initiation and propagation. Explain this behavior considering the case of methyl methacrylate monomer. 

Key point. Alkyl halides are composed of an alkyl group bonded to a halogen atom (X = F, Cl, Br, I). As halogen atoms are more electronegative than carbon, the C-X bond is polar and nucleophiles can attack the slightly positive carbon atom. This leads to the halogen atom being replaced by the nucleophile in a nucleophilic substitution reaction, and this can occur by either an SN1 (two-step) mechanism or an Sn2 (concerted or one-step) mechanism. In competition with substitution is elimination, which results in the loss of HX from alkyl halides to form alkenes. This can occur by either an El (two-step) mechanism or an E2 (concerted) mechanism. The mechanism of the substitution or elimination reaction depends on the alkyl halide, the solvent and the nucleophile/base. 

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