The SnI mechanism for nucleophilic

If we mix f-BuOH and HBr in an NMR tube and let the reaction run inside the NMR machine, we see no signals belonging to the cation. This proves nothing. We would not expect a reactive intermediate to be present in any significant concentration. There is a simple reason for this. If the cation is unstable, it will react very quickly with any nucleophile around and there will never be any appreciable amount of cation in solution. Its rate of formation will be less, much less, than its rate of reaction. We need only annotate the mechanism you have already seen, the SnI mechanism for nucleophilic substitution at saturated carbon stage 1 formation of the carbocation... 

The SnI mechanism for nucleophilic aromatic substitution—diazonium compounds... 

These sections show how a variety of experimental observations led to the proposal of the SnI and the Sn2 mechanisms for nucleophilic substitution. Summary Table 8.9 integrates the material in these sections. 

Carbenium ions have three bonds to the carbon atom and are planar, with six outer electrons and a vacant p-orbital. Ions of this type are intermediates in a number of organic reactions (for example, in the SnI mechanism of nucleophilic substitution). Certain carbenium ions ate stabilized by de-localization of the charge. An example is the orange-red salt (CgHjlsC CI. Carbenium ions can be produced by supetacids. 

This chain reaction is analogous to radical chain mechanisms for nucleophilic aliphatic nucleophilic substitution that had been suggested independently by Russell and by Komblum and their co-workers. The descriptive title SrnI (substitution radical-nucleophilic unimolecular) was suggested for this reaction by analogy to the SnI mechanism for aliphatic substitution. The lUPAC notation for the SrkjI reaction is (T -t- Dm -t- An), in which the symbol T refers to an electron transfer. When the reaction was carried out in Ihe presence of solvated electrons formed by adding potassium metal to the ammonia solution, virtually no aryne (rearranged) products were observed. Instead, reaction of 95c produced only 98 (40%) and 94 (40%) but no 99, and reaction of 96c produced 99 (54%) and 94 (30%) with only a trace of 98. ... 

R2CHX (2°) SnI orSN2 The mechanism depends on the conditions. Strong nucleophiles favor the Sn2 mechanism over the SnI mechanism. For example, RO is a stronger nucleophile than ROH, so RO" favors the Sn2 reaction and ROH favors the Sn1 reaction. Protic solvents favor the SnI mechanism and aprotic solvents favor the Sn2 mechanism. For example, H2O and CH3OH are polar protic solvents that favor the Sn1 mechanism, whereas acetone [(CH3)2C = 0] and DMSO [(CH3)2S = 0] are polar aprotic solvents that favor the Sn2 mechanism. 

In Summary We have seen further evidence supporting the SnI mechanism for the reaction of tertiary (and secondary) haloalkanes with certain nucleophiles. The stereochemistry of the process, the effects of the solvent and the leaving-group ability on the rate, and the absence of such effects when the strength of the nucleophile is varied, are consistent with the unimolecular route. 

There are alternatives to the addition-elimination mechanism for nucleophilic substitution of acyl chlorides. Certain acyl chlorides are known to react with alcohols by a dissociative mechanism in which acylium ions are intermediates. This mechanism is observed with aroyl halides having electron-releasing substituents. Other acyl halides show reactivity indicative of mixed or borderline mechanisms. The existence of the SnI-like dissociative mechanism reflects the relative stability of acylium ions. 

The SnI mechanism is an ionization mechanism. The nucleophile does not participate until after the rate-deter-rnining step has taken place. Thus, the effects of nucleophile and alkyl halide structure are expected to be different from those observed for reactions proceeding by the Sn2 pathway. Flow the structure of the alkyl halide affects the rate of SnI reactions is the topic of the next section. 

The notion of concurrent SnI and Sn2 reactions has been invoked to account for kinetic observations in the presence of an added nucleophile and for heat capacities of activation,but the hypothesis is not strongly supported. Interpretations of borderline reactions in terms of one mechanism rather than two have been more widely accepted. Winstein et al. have proposed a classification of mechanisms according to the covalent participation by the solvent in the transition state of the rate-determining step. If such covalent interaction occurs, the reaction is assigned to the nucleophilic (N) class if covalent interaction is absent, the reaction is in the limiting (Lim) class. At their extremes these categories become equivalent to Sn and Sn , respectively, but the dividing line between Sn and Sn does not coincide with that between N and Lim. For example, a mass-law effect, which is evidence of an intermediate and therefore of the SnI mechanism, can be observed for some isopropyl compounds, but these appear to be in the N class in aqueous media. 

Kinetic studies also provide other evidence for the SnI mechanism. One technique used F NMR to follow the solvolysis of trifluoroacetyl esters. If this mechanism operates essentially as shown on page 393, the rate should be the same for a given substrate under a given set of conditions, regardless of the identity of the nucleophile or its concentration. In one experiment that demonstrates this, benzhy-dryl chloride (Ph2CHCl) was treated in SO2 with the nucleophiles fluoride ion, pyridine, and triethylamine at several concentrations of each nucleophile. In each case, the initial rate of the reaction was approximately the same when corrections were made for the salt effect. The same type of behavior has been shown in a number of other cases, even when the reagents are as different in their nucleophilicities (see p. 438) as H2O and OH . 

Like the kinetic evidence, the stereochemical evidence for the SnI mechanism is less clear-cut than it is for the Sn2 mechanism. If there is a free carbocation, it is planar (p. 224), and the nucleophile should attack with equal facility from either side of the plane, resulting in complete racemization. Although many first-order substitutions do give complete racemization, many others do not. Typically there is 5-20% inversion, though in a few cases, a small amount of retention of configuration has been found. These and other results have led to the conclusion that in many SnI reactions at least some of the products are not formed from free carbocations but rather from ion pairs. According to this concept," SnI reactions proceed in this manner ... 

When a molecule has in an allylic position a nucleofuge capable of giving the SnI reaction, it is possible for the nucleophile to attack at the y position instead of the a position. This is called the SnI mechanism and has been demonstrated on 2-buten-l-ol and 3-buten-2-ol, both of which gave 100% allylic rearrangement when treated... 

We mentioned before that we need to consider four factors when choosing whether a reaction will go by an SnI or Sn2 mechanism. These four factors are electrophile, nucleophile, leaving group, and solvent. We will go through each factor one at a time, and we will see that the difference between the two mechanisms is the key to understanding each of these four factors. Before we move on, it is very important that you understand the two mechanisms. For practice, try to draw them in the space below without looking back to see them again. 

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. 

Alkyl halides (RX) are good substrates for substitution reactions. The nucleophile (Nu ) displaces the leaving group (X ) from the carbon atom by using its electron parr or lone pair to form a new a bond to the carbon atom. Two different mechanisms for nucleophilic substitution are SnI and 8 2 mechanisms. In fact, the preference between S l and 8 2 mechanisms depends on the structure of the alkyl halide, the reactivity and structure of the nucleophile, the concentration of the nucleophile and the solvent in which reaction is carried out. 

Anhydrides are somewhat more difficult to hydrolyze than acyl halides, but here too water is usually a strong enough nucleophile. The mechanism is usually tetrahedral. Only under acid catalysis does the SnI mechanism occur and seldom even then.s06 Anhydride hydrolysis can also be catalyzed by bases. Of course, OH- attacks more readily than water, but other bases can also catalyze the reaction. This phenomenon, called nucleophilic catalysis (p. 334). is actually the result of two successive tetrahedral mechanisms. For example, pyridine catalyzes the hydrolysis of acetic anhydride in this manner.507... 

The diazonium group can be replaced by a number of groups.222 Some of these are nucleophilic substitutions, with SnI mechanisms (p. 644), but others are free-radical reactions and are treated in Chapter 14. The solvent in all these reactions is usually water. With other solvents it has beeen shown that the SnI mechanism is favored by solvents of low nucleo-philicity, while those of high nucleophilicity favor free-radical mechanisms.222 (For formation of diazonium ions, see 2-49.) The N2 group can be replaced by Cl, Br. and CN, by a nucleophilic mechanism (see OS IV, 182). but the Sandmeyer reaction is much more useful (4-25 and 4-28). As mentioned on p. 651 it must be kept in mind that the N2 group can activate the removal of another group on the ring. 

Shifts of half-wave potentials towards more positive values in the presence of bulky groups can be explained in some cases also by changes in the mechanism of the electrode process. The most thoroughly studied example is the reduction of alkyl and cycloalkyl bromides (141). Departures of the half-wave potentials from predicted values for a-branched alkyl bromides, increasing in the sequence Et < — Pr nucleophilic substitutions. Hence a similar explanation, i.e. varying participation of SnI and 5N2-like... 

You will often read that t-alkyl compounds do not react by the Sfj2 mechanism because the steric hindrance would be too great. This is a reasonable assumption given that secondary alkyl compounds are already reacting quite slowly. The truth Is that t-alkyl compounds react so fast by the SnI mechanism that the Sn2 mechanism wouldn t get a chance even if it went as fast as it goes with methyl compounds. The nucleophile would have to be about 100 molar in concentration to compensate for the difference in rates and this is impossible Even pure water is only 55 molar (Chapter 8). You see only the faster of the two possible mechanisms,... 

It should be mentioned that a solvent change affects not only the reaction rate, but also the reaction mechanism (see Section 5.5.7). The reaction mechanism for some haloalkanes changes from SnI to Sn2 when the solvent is changed from aqueous ethanol to acetone. On the other hand, reactions of halomethanes, which proceed in aqueous ethanol by an Sn2 mechanism, can become Sn 1 in more strongly ionizing solvents such as formic acid. For a comparison of solvent effects on nucleophilic substitution reactions at primary, secondary, and tertiary carbon atoms, see references [72, 784]. 

As we learned in Section 7.10, this suggests that the SnI mechanism involves more than one step, and that the slow step is unimolecular, involving only the alkyl halide. The identity and concentration of the nucleophile have no effect on the reaction rate. For example, doubling the concentration of (CH3)3CBr doubles the rate, but doubling the concentration of the nucleophile has no effect. 

SnI and Sn2 reactions occur only at sp hybridized carbon atoms. Now that we have learned about the mechanisms for nucleophilic substitution we ean understand why vinyl halides and aryl halides, which have a halogen atom bonded to an sp hybridized C, do not undergo nucleophilic substitution by either the S l or Sn2 mechanism. The diseussion here eenters on vinyl halides, but similar arguments hold for aryl halides as well. 

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