Mechanisms of SN Reactions

Nucleophilic substitutions are especially important for alkyl halides, but they should not be considered to be confined to alkyl halides. Many other alkyl derivatives such as alcohols, ethers, esters, and onium ions 3 also can undergo SN reactions if conditions are appropriate. The scope of SN reactions is so broad that it is impossible to include all the various alkyl compounds and nucleophiles that react in this manner. Rather we shall approach the subject here through consideration of the mechanisms of SN reactions, and then develop the scope of the reactions in later chapters. 

Two simple mechanisms can be written for the reaction of chloromethane with hydroxide ion in aqueous solution that differ in the timing of bond breaking relative to bond making. In the first mechanism, A, the overall reaction is the result of two steps, the first of which involves a slow dissociation of chloro- 

In the second mechanism, B, the reaction proceeds in a single step. Attack of hydroxide ion at carbon occurs simultaneously with the loss of chloride ion that is, the carbon-oxygen bond is formed as the carbon-chlorine bond is broken. 

Both of these mechanisms are important in the displacement reactions of alkyl compounds, although chloromethane appears to react only by Mechanism B. Now we will discuss the criteria for distinguishing between the concerted and stepwise mechanisms. 

Of the two mechanisms, A requires that the reaction rate be determined solely by the rate of the first step (cf. earlier discussion in Section 4-4C). This means that the rate at which methanol is formed (measured in moles per unit volume per unit time) will depend on the chloromethane concentration, but not on the hydroxide ion concentration, because hydroxide ion is not utilized except in a 

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Secondary a-deuterium kinetic isotope effects (KIEs) have been widely used to determine the mechanism of SN reactions and to elucidate the structure of their transition states (Shiner, 1970a Westaway, 1987a). Some of the significant studies illustrating these principles are presented in this section. 

Fig. 6.2. Mechanism of SN reactions of good nucleophiles at the carboxyl carbon kM is the rate constant of the addition of the nucleophile, kMm is the rate constant of the back-reaction, and kelim is the rate constant of the elimination of the leaving group K is the equilibrium constant for the protonation of the tetrahedral intermediate at the negatively charged oxygen atom.

Fig. 6.4. Mechanism of SN reactions at the carboxyl carbon via a stable tetrahedral intermediate.

This type of primary KIE is observed when the a-carbon is labeled in an SN2 reaction, a-carbon KIEs have been used extensively to determine the mechanism of SN reactions.20 Small a-carbon KIEs near 1 % are indicative of a carbenium ion SN (an SN1) reaction while larger KIEs of up to 8% for a 12C/13C KIE,21 16% for a 12C/14C KIE22 and 22% for an nC/14C KIE23 are indicative of an SN2 mechanism. 

The real world of Sn reactions is not quite as simple as the discussion has so far suggested. The preceding treatment in terms of two clearly distinct mechanisms, SnI and Sn2, implies that all substitution reactions will follow one or the other of these mechanisms. This is an oversimplification. The strength of the dual mechanism hypothesis and its limitations are revealed by these relative rates of solvolysis of alkyl bromides in 80% ethanol methyl bromide, 2.51 ethyl bromide, 1.00 isopropyl bromide, 1.70 /er/-butyl bromide, 8600. Addition of lyate ions increases the rate for the methyl, ethyl, and isopropyl bromides, whereas the tert-butyl bromide solvolysis rate is unchanged. The reaction with lyate ions is overall second-order for methyl and ethyl, first-order for tert-butyl, and first- or second-order for the isopropyl member, depending upon the concentrations. Similar results are found in other solvents. These data show that the methyl and ethyl bromides solvolyze by the Sn2 mechanism, and tert-butyl bromide by the SnI mech-... 

The above-mentioned method is useful but metals that form strong M-S bonds (e.g., Hg, Ag, Sn) do not dissolve in W-Melm solutions of sulfur. This problem has been solved by the addition of Mg to the reaction mixture. Metal polysulfides having a variety of metals can be synthesized by the 7 T-Melm/ M-i-Mg/Sg method (Scheme 11) [48]. For example, a mixture of Mg, Sb powder (1 eq.), Sg (15 eq. as S) and W-Melm is heated at 80 °C for 48 h to afford the orange powder of [Mg(N-MeIm)5]Sb2Sj ( x 15) in 88% yield. Rauchfuss et al. proposed the mechanism of these reactions as follows. First, the reduction of Sg with Mg occurs to give the [Mg(W-MeIm)6] salt of Sg , which is probably in equilibrium with Sg, Ss ", Ss" and other species. Independently, the sulfuration of the thiophilic metal takes place. Next, the polysulfide an-... 

SCHEME 2. Mechanism of SN(P) reaction for the alkaline hydrolysis of phosphonium salts... 

Long et al. (1957), amplifying a suggestion of Taft and co-workers (1955), have proposed the use of AS as a criterion of the mechanism of hydrolysis reactions. These reactions are usually classified as unimolecular (A-l, SN-1) or bimolecular (A-2, SN-2). In the former case a water molecule does not participate in the rate-determining step, while a water molecule is usually considered to be bound in the activated... 

Most theoretical work on group-14 organometallic compounds was devoted to neutral closed-shell species. We divided the presentation of the papers into two parts. The first part focuses on theoretical studies of geometries and properties of molecules. The second part describes work where reaction mechanisms of chemical reactions of organometallic Ge-, Sn- and Pb-organic compounds have been investigated theoretically. 

Mechanism and Rate Laws of SN Reactions at the Carboxyl Carbon... 

The tetrahedral intermediate is a high-energy intermediate. Therefore, independently of its charge and also independently of the detailed formation mechanism, it is formed via a late transition state. It also reacts further via an early transition state. Both properties follow from the Hammond postulate. Whether the transition state of the formation of the tetrahedral intermediate has a higher or a lower energy than the transition state of the subsequent reaction of the tetrahedral intermediate determines whether this intermediate is formed in an irreversible or in a reversible reaction, respectively. Yet, in any case, the tetrahedral intermediate is a transition state model of the rate-determining step of the vast majority of SN reactions at the carboxyl carbon. In the following sections, we will support this statement by formal kinetic analyses of the most important substitution mechanisms. 

As the last example of an SN reaction at the carboxyl carbon of a carbonic acid derivative, consider the synthesis of dicyclohexylurea in Figure 6.39. In this synthesis, two equivalents of cyclohexylamine replace the two methoxy groups of dimethyl carbonate. Dicyclohexylurea can be converted into the carbodiimide dicyclohexylcarbodiimide (DCC) by treatment with tosyl chloride and triethylamine. The urea is dehydrated. The mechanism of this reaction is identical to the mechanism that is presented in Figure 8.9 for the similar preparation of a different carbodiimide. 

Margitfalvi and coworkers (e.g. 73-76) have utilized as a means of catalyst preparation a controlled surface reaction in which a volatile Sn (or Pt) compound is allowed to react with Pt (or Sn) already present on a support. They employed conventional and transient kinetic approaches to study the mechanism of hydrocarbon reactions on these catalysts conversions were effected at atmospheric or lower pressures. These authors found a perplexing variety of activity patterns, depending upon the manner and sequence in which Pt and Sn was added. Depending upon preparation conditions, the added tin may either enhance or decrease Pt activity and increase or decrease the selectivity for hydrogenolysis (73). 

The variety of difficulties encountered when trying to fit the solvolysis of secondary substrates into the Sn 2-Sn 1 framework has led to much research and much discussion of the mechanisms of these reactions. Consideration has been given to intermediate mechanisms, possibly involving ion pairs, as well as to a spectrum of mechanisms between the SN 2 and SN 1 extremes. Since a vague theory cannot be proved wrong (Feynman, 1965), scientific progress... 

The kinetics and mechanisms of substitution reactions studied in detail have been reviewed elsewhere 1-3). Here we shall summarize some recent data obtained in this field. As far as terminology is concerned, in the majority of cases that of Ingold 4) has been used, in which substitution of one ligand by another is regarded as a nucleophilic (SN) reaction. However, such a classification is rather rigid, and the term nucleophilicity is imprecise if one considers the variety of ligands from the simplest anions to olefins, acetylenes, arenes, etc. 

The reaction of terminal olefins can be catalysed by a small amount of the corresponding trialkylaluminium compound (or of BuSAlII which is alkylated by the olefin).88 The mechanism of these reactions has not been studied in detail, but there appears to be no evidence for the involvement of free radicals, and the steps which are believed to be involved are shown in equations 4-50-4-52 (sn = l/4Sn, al = 1/3Al). 

Sawyer1 lists 20 different routes to hexaphenylditin, most of which can be understood in terms of these basic reactions. The detailed mechanisms of the reactions in which the Sn-Sn bond is formed, however, are often unclear, and even the broad distinction between homolytic and heterolytic mechanisms is sometimes in doubt. 

The year has seen a considerable extension of the principles of hypervalent phosphorus chemistry into the fields of other elements notably Si, Sn, Ge and Sb and in this context the well-known Martin ligand has proved to be especially valuable. Particularly interesting contributions have been provided by Ju et al on the relative rates of reaction of pentoses and hexoses with pentacoordinate phosphorus, by Bentrude et on the mechanism of the reaction of hy-dridophosphoranes with dimethyl disulfide and by Kawashima et alP on the isolation of two carbaphosphatranes containing covalent P-C bonds. Holmes et al report on the fluxional properties of propeller shaped phosphoranes and Buono et have also demonstrated the utility of hydridophosphoranes in some highly diastereoselective reactions with isocyanates. In summary, although the number of reports was small, the year was noteworthy for some very sophisticated contributions to the field. 

Repeating the experiment with lb, but quenching the reaction by addition of diethyl ether as soon as the effervescence had subsided, afforded the tetrathiafulva-lenium salt 2b this compound was then subjected to solvolysis in undried deutero-acetone and afforded the corresponding alcohol 3b, consistent with its intermediacy in the reaction. The basic mechanism of the reaction can thus be represented by Scheme 2. Aryl radicals are formed following electron transfer to the diazonium cation and subsequent loss of dinitrogen. Rapid cyclization is followed by formation of the sulfonium salt 2b, and a facile solvolysis occurs to afford the alcohol 3b. Since the tertiary alcohol 3c was formed from substrate Ic, a similar pathway may have been followed, but the direct oxidation of the tertiary radical by electron transfer to a diazonium cation cannot yet be ruled out. The resistance of the primary salt to solvolysis is a classic hallmark of an Sn 1 reaction. (A refinement for the mechanism of the solvolysis step will be presented in Section 2.7.3.1 of this review, backed by very recent results). 

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