Nucleophilicity at Saturated Carbon

The Sn2 direct displacement reaction at saturated carbon can be represented as Y + R3CX R3CY + X  

As a consequence, it appears to be valid to apply Marcus theory (Section 5.3) to Sn2 reactions. Note that we may expect structure-reactivity relationships in Sn2 reactions to be functions of both the bond formation and bond cleavage processes, just as in acyl transfers. 

There is another type of reaction to be considered, namely, 

This is the reverse of the first step in the SnI mechanism. As written here, this reaction is called cation-anion recombination, or an electrophile-nucleophile reaction. This type of reaction lacks the symmetry of a group transfer reaction, and we should therefore not expect Marcus theory to be applicable, as Ritchie et al. have emphasized. Nevertheless, the electrophile-nucleophile reaction possesses the simplifying feature that bond formation occurs in the absence of bond cleavage. 

We consider first the Sn2 type of process. (In some important Sn2 reactions the solvent may function as the nucleophile. We will treat solvent nucleophilicity as a separate topic in Chapter 8.) Basicity toward the proton, that is, the pKa of the conjugate acid of the nucleophile, has been found to be less successful as a model property for reactions at saturated carbon than for nucleophilic acyl transfers, although basicity must have some relationship to nucleophilicity. Bordwell et al. have demonstrated very satisfactory Brjinsted-type plots for nucleophilic displacements at saturated carbon when the basicities and reactivities are measured in polar aprotic solvents like dimethylsulfoxide. The problem of establishing such simple correlations in hydroxylic solvents lies in the varying solvation stabilization within a reaction series in H-bond donor solvents. 

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Stereochemical course of the reaction. This kind of information was critical in the elucidation of the SnI and Sn2 pathways for nucleophilic substitution at saturated carbon. 

Most of the kinetic measures of solvent effects have been developed for the study of nucleophilic substitution (Sn) at saturated carbon, solvolytic reactions in particular. It may, therefore, be helpful to give a brief review of aliphatic nucleophilic substitution. Two mechanistic routes have been clearly identified. One of these is shown by... 

The parameter 5 is a measure of the susceptibility of the substrate to nucleophilic attack, and n a measure of the nucleophilic reactivity as defined by a reference reaction. The rate constants for attack at saturated carbon are used to define the values of n.14 Table 10-4 lists the values of n for certain nucleophiles. This particular compilation lists the... 

Alkyl halides can be hydrolyzed to alcohols. Hydroxide ion is usually required, except that especially active substrates such as allylic or benzylic types can be hydrolyzed by water. Ordinary halides can also be hydrolyzed by water, if the solvent is HMPA or A-methyl-2-pyrrolidinone." In contrast to most nucleophilic substitutions at saturated carbons, this reaction can be performed on tertiary substrates without significant interference from elimination side reactions. Tertiary alkyl a-halocarbonyl compounds can be converted to the corresponding alcohol with silver oxide in aqueous acetonitrile." The reaction is not frequently used for synthetic purposes, because alkyl halides are usually obtained from alcohols. 

Carbonyl reactions are extremely important in chemistry and biochemistry, yet they are often given short shrift in textbooks on physical organic chemistry, partly because the subject was historically developed by the study of nucleophilic substitution at saturated carbon, and partly because carbonyl reactions are often more difhcult to study. They are generally reversible under usual conditions and involve complicated multistep mechanisms and general acid/base catalysis. In thinking about carbonyl reactions, 1 find it helpful to consider the carbonyl group as a (very) stabilized carbenium ion, with an O substituent. Then one can immediately draw on everything one has learned about carbenium ion reactivity and see that the reactivity order for carbonyl compounds ... 

Chapters 1 and 2 dealt with formation of new carbon-carbon bonds by reactions in which one carbon acts as the nucleophile and another as the electrophile. In this chapter we turn our attention to noncarbon nucleophiles. Nucleophilic substitution is used in a variety of interconversions of functional groups. We discuss substitution at both sp3 carbon and carbonyl groups. Substitution at saturated carbon usually involves the Sjv2 mechanism, whereas substitution at carbonyl groups usually occurs by addition-elimination. 

The mechanistic aspects of nucleophilic substitutions at saturated carbon and carbonyl centers were considered in Part A, Chapters 4 and 7, respectively. In this chapter we discuss some of the important synthetic transformations that involve these types of... 

Introduction of Functional Groups by Nucleophilic Substitution at Saturated Carbon... 

Synthetically important substitutions of aromatic compounds can also be done by nucleophilic reagents. There are several general mechanism for substitution by nucleophiles. Unlike nucleophilic substitution at saturated carbon, aromatic nucleophilic substitution does not occur by a single-step mechanism. The broad mechanistic classes that can be recognized include addition-elimination, elimination-addition, and metal-catalyzed processes. (See Section 9.5 of Part A to review these mechanisms.) We first discuss diazonium ions, which can react by several mechanisms. Depending on the substitution pattern, aryl halides can react by either addition-elimination or elimination-addition. Aryl halides and sulfonates also react with nucleophiles by metal-catalyzed mechanisms and these are discussed in Section 11.3. 

Fig. 23 Entropy effects on intramolecular reactions of polymethylene chains. Plot of 9AS (e.u.) against number of single bonds for (O) nucleophilic substitutions at saturated carbon ( ) electron-exchange reactions (A) quenching of benzophenone phosphorescence. The straight line has intercept +30 e.u. and slope —4.0 e.u. per rotor. The right-hand ordinate reports the purely entropic EM s calculated as exp(0AS /J )...

Additional Transformation Reactions. Other reactions that can be catalyzed by mineral surfaces are substitution, elimination, and addition reactions of organic molecules. Substitution and elimination are two general types of reactions that occur at saturated carbon atoms of organic molecules. Both types are initiated by nucleophilic attack however, in elimination reactions it is the basicity of the nucleophile that determine its reactivity rather than its nucleophilicity. Since mineral surfaces are expected to have both nucleophilic and basic properties, these types of reactions should also occur at mineral-water interfaces (see Chapter 22). It remains to be shown whether or not these reactions are catalyzed under environmental conditions. 

SECTION 3.2. INTRODUCTION OF FUNCTIONAL GROUPS BY NUCLEOPHILIC SUBSTITUTION AT SATURATED CARBON... 

A. Williams, Concerted Organic and Bioorganic Mechanisms, CRC Press, New York, 2000. W. P. Jencks, How Does a Reaction Choose Its Mechanism , Chem. Soc. Rev. 1981,10, 345. J. P. Richard, Simple Relationships between Carbocation Lifetime and the Mechanism for Nucleophilic Substitution at Saturated Carbon, Adv. Carbocation Chem. 1989, 1, 122. T. W. Bentley and G. Llewellyn, Scales of Solvent Ionizing Power, Prog. Phys. Org. Chem. 1990, 17, 121. 

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