Nucleophilic substitution defined

Direct iodination or fluorination leads to ill-defined products and fragmentation, respectively. Sandmeyer chemistry and nucleophilic substitution of... 

The term nucleophilicity refers 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 is used to describe trends in the kinetic aspects of substitution reactions. The relative nucleophilicity of a given species may be different toward various reactants, and it has not been possible to devise an absolute scale of nucleophilicity. We need to gain some impression of the structural features that govern nucleophilicity and to understand the relationship between nucleophilicity and basicity. ... 

Additional control of the nucleophilic substitution pathways a and b should be possible by varying the properties of the heteroarylium moiety in 33 as well as the substituent R and, to a minor extent, by the nature of the C-bonded halogen. Tire cation of 7a appeared to be an especially useful model compound and was thus selected in order to systematically study these influences and to define a standard situation. Structure 7a is easily accessible in excellent yield, and its molecular size allowed high-level MO calculations. 

This mechanism is the same as the simple electrophilic one shown on page 970 except that the charges are reversed (lUPAC An- -Ae or A +Ah). When the alkene contains a good leaving group (as defined for nucleophilic substitution), substitution is a side reaction (this is nucleophilic substitution at a vinylic substrate, see p. 428). 

Reaction mechanisms divide the transformations between organic molecules into classes that can be understood by well-defined concepts. Thus, for example, the SnI or Sn2 nucleophilic substitutions are examples of organic reaction mechanisms. Each mechanism is characterized by transition states and intermediates that are passed over while the reaction proceeds. It defines the kinetic, stereochemical, and product features of the reaction. Reaction mechanisms are thus extremely important to optimize the respective conversion for conditions, selectivity, or yields of desired products. 

The first step in the addition of alkoxides to Cgg is, consistently, the formation of the alkoxy Cgg anion. The subsequent process is strongly dependent on the presence of oxygen. In the presence of oxygen, 1,3-dioxolane derivatives of Cgg are formed [110]. In the absence of oxygen the oligo alkoxy fullerenide anions can be formed [111, 112]. Reaction of alkoxides with Cgg usually results in complex mixtures. This may be why only a few reactions of Cgg with alkoxides have been described [113]. Nevertheless, defined alkoxy fullerenes can be obtained by nucleophilic substitution reactions of alkoxides with halogenofullerenes (Chapter 9) [113]. 

There is an ongoing controversy about whether there is any stabilization of the transition state for nucleophilic substitution at tertiary aliphatic carbon from interaction with nucleophilic solvent." ° This controversy has developed with the increasing sophistication of experiments to characterize solvent effects on the rate constants for solvolysis reactions. Grunwald and Winstein determined rate constants for solvolysis of tert-butyl chloride in a wide variety of solvents and used these data to define the solvent ionizing parameter T (Eq. 3). They next found that rate constants for solvolysis of primary and secondary aliphatic carbon show a smaller sensitivity (m) to changes in Y than those for the parent solvolysis reaction of tert-butyl chloride (for which m = 1 by definition). A second term was added ( N) to account for the effect of changes in solvent nucleophilicity on obsd that result from transition state stabilization by a nucleophilic interaction between solvent and substrate. It was first assumed that there is no significant stabilization of the transition state for solvolysis of tert-butyl chloride from such a nucleophilic interaction. However, a close examination of extensive rate data revealed, in some cases, a correlation between rate constants for solvolysis of fert-butyl derivatives and solvent nucleophicity. " ... 

Exercise 30-16 An ingenious and highly practical synthetic procedure for forming the steroid ring system has been developed by W. S. Johnson that closely mimics the squalene cyclization without the need for enzymes. The cyclizations occur by carbocationic intermediates under rather strictly defined conditions that are designed to prevent the reactants from being diverted to nucleophilic substitution or elimination... 

Since the title compounds can be stereoselectively functionalized in the 1-position by metal-catalyzed nucleophilic substitutions of the acetoxy group, a great number of 1,4-disubstituted 2-cyclohexenes with defined 1,4-relative stereochemistry are available. 

Considerable work must still be done before the scope and limitations of the nucleophilic substitution reaction are completely defined. 

The most important and well-defined reactions involving attack at nitrogen are those discovered by Schmitz and co-workers. A -Unsubstituted oxaziridines react with a variety of nucleophiles to effect transfer of the NH group from the oxa-ziridine to the nucleophile. Many of these reactions resemble nitrene or nitrenoid reactions although little mechanistic work has been reported, it seems better to classify them as involving nucleophilic substitution followed by elimination ... 

The mechanisms that occur in aliphatic electrophilic substitution reactions are less well defined than those that occur in aliphatic nucleophilic substitution and aromatic electrophilic reactions. There is still, however, the usual division between unimolecular and bimolecular pathways the former consisting of only the SE1 mechanism, while the latter consists of the SE2 (front), SE2 (back) and the SEi mechanism. 

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