Nucleophilic substitution leaving group

General Nucleophilic Substitution, Leaving Groups, and Nucleophiles... 

The same phenomenon, i.e. that the secondary a-deuterium KIE is determined by the changes in only the shorter reacting bond in the SN2 transition state rather than by the nucleophile-leaving group distance, has been found in a completely different reaction system. Matsson, Westaway and co-workers (Matsson et al., 1996) used ku/k14 carbon incoming nucleophile, chlorine leaving group (Hill and Fry, 1962), and ku/ku a-carbon (Fry, 1970) KIEs to model the transition states for a series of SN2 reactions between p-substituted benzyl chlorides and labelled cyanide ion (reaction (17)). 

Lewis (1983) has posed the intriguing question What is the effect of simultaneous substitution on both nucleophile and leaving group on reactivity for an identity exchange process, such as (95) In other words, if we... 

Reactions (109) and (110) as well as nitroalkane deprotonation are all examples of central substitution so that for these reactions a does not measure the earliness or lateness of the transition state. End substitution, such as in the nucleophile or leaving group of SN2 reactions, in which the formal charge does vary between reactants and products generates -values which may be utilized as a relative measure of transition state charge this, provided that the reaction is composed of three configurations. Such applications were discussed in Section 3, p. 152. 

Such substitutions in saturated compounds can be carried out by a variety of strategics involving different nucleophiles and leaving groups, but the oxidation states remain the same. Acyl substitutions are analogous. For this reason carboxylic acid derivatives are treated as a common family of compounds. All have the same oxidation level and all can be converted from one to another by substitution reactions not requiring oxidation or reduction. 

A similar picture holds for other nucleophiles. As a consequence, there might seem little hope for a nucleophile-based reactivity relationship. Indeed this has been implicitly recognized in the popularity of Pearson s concept of hard and soft acids and bases, which provides a qualitative rationalization of, for example, the similar orders of reactivities of halide ions as both nucleophiles and leaving groups in (Sn2) substitution reactions, without attempting a quantitative analysis. Surprisingly, however, despite the failure of rate-equilibrium relationships, correlations between reactivities of nucleophiles, that is, comparisons of rates of reactions for one carbocation with those of another, are strikingly successful. In other words, correlations exist between rate constants and rate constants where correlations between rate and equilibrium constants fail. 

Acidic reaction conditions can also lead to protonation of some leaving groups, thereby increasing their reactivity in nucleophilic substitutions. Such groups include, for instance, alcohols, ethers, amines, amides, or alkyl fluorides. 

Know the meaning of nucleophilic substitution reaction, nucleophile, substrate, leaving group. 

The epimeric substituted aryloxy phosphorinanes 2- were hydro lyzed in 30% dioxane/water at 70 C with a variety of nucleophiles (11). The reactivities were sensitive to changes in both the nucleophile and leaving group. The Bronsted 6 s for the... 

Nucleophilic substitution reactions on unactivated alkyl halides have been known for a long time. The available mechanisms depend on the aliphatic moiety, the nucleophile, the leaving group and the reaction conditions118. Besides the polar mechanisms of nucleophilic substitution reactions (S l, S 2 and related mechanisms), several alkyl halides react with nucleophiles by an ET reaction. 

Studies on nucleophilic substitution reactions of cycloalkyl halides have shown their behaviour to depend on the ring size, the nucleophile, the leaving group and the reaction conditions. 

As we study these conversions of acid derivatives, it may seem that many individual mechanisms are involved. But all these mechanisms are variations on a single theme the addition-elimination mechanism of nucleophilic acyl substitution (Key Mechanism 21-1). These reactions differ only in the nature of the nucleophile, the leaving group, and proton transfers needed before or after the actual substitution. As we study these mechanisms, watch for these differences and don t feel that you must learn each specific mechanism. 

Given a particular nucleophile and leaving group, how can we determine whether the equilibrium will favor products in a nucleophilic substitution We can often correctly predict the direction of equilibrium by comparing the basicity of the nucleophile and the leaving group. 

How can these two different results be explained Although these two reactions have the same nucleophile and leaving group, there must he two different mechanisms because there are two different rate equations. These equations are specific examples of two well known mechanisms for nucleophilic substitution at an sp hybridized carbon ... 

Inversion of configuration (Section 7.11C) The opposite relative stereochemistry of a stereogenic center in the starting material and product of a chemical reaction. In a nucleophilic substitution reaction, inversion results when the nucleophile and leaving group are in the opposite position relative to the three other groups on carbon. 

The stereochemistry of the SN2 reaction has been shown to be variously syn (the nucleophile and leaving group are on the same face of the ally lie system) or anti, depending on the nature of the nucleophile and leaving group. For example, the cis isomer 26 with piperidine gave 27, in a clean syn allylic displacement, whereas Na+-SPr gave a ca. 2 1 mixture of isomers in which the trans isomer 28 was the major product. This trend toward anti substitution with RS- is more pronounced (almost exclusive) in the acyclic case 29. 

Adding appropriate nucleophiles with leaving group capabilities, such as phenylselenide (SePh) or dimethylamide (NMe2) gives access to precursors of a variety of modified cyclo-propylideneacetates bearing almost any substituent (X = OSiRj, N3, F, H, SMe, SPh). - ° The chiral methyl 2-cyclopropylidene-2-(phenylsulfinyl)acetate can be prepared from methyl 2-cyclopropylidene-2-(phenylsulfanyl)acetate under strictly anhydrous conditions. This bisac-ceptor-substituted methylenecyclopropane can be isolated, but it rapidly attracts water upon standing in air at room temperature. ... 

Much effort has been devoted to the theoretical elucidation of the mechanism of nucleophilic substitution at silicon. The calculations tried to answer two major questions (1) Does substitution occur by a one-step reaction via transition state 177 or by a two-step process via intermediate 178 (equation 58 where Nu = nucleophile, LG = leaving group) (2) What is the stereochemistry of the substitution and what are the factors which control it ... 

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