The SN1 Reactions

In the usual mechanism for the SnI reaction (equations 8.11 and 8.12), the rate-limiting step is the dissociation of the substrate to form a carbocation and an anion. Therefore, we commonly write that the rate of the reaction is effectively the rate of the unimolecular first step, as shown in equation 8.13. Clearly, equation 8.13 cannot be exact, however, because there must be some Y in the solution or the substitution step (equation 8.12) carmot occur. 

A more exact kinetic expression results from applying the steady-state approximation to [R ], which produces equation 8.16. 

The carbocation intermediate has been observed spectroscopically in some systems Mayr, H. Minegishi, S. Angew. Chem. Int. Ed. 2002,41,4493 Schaller, H. F. Tishkov, A. A. Feng, X. Mayr, H. /. Am. Chem. Soc. 2008, 130, 3012. For an example of carbocation watching in solvolysis, see Schaller, H. F. Mayr, H. Angew. Chem. Int. Ed. 2008,47,3958. 

In early phases of the reaction, [L ] is close to zero, so the term fc i[L ] is also about zero. Making the assumption thatfc i[L ] + fc2[Y ] w k2[Y ] allows us to cancel the C2[Y ] terms in the numerator and denominator of equation 8.16, which leads to the approximate expression of equation 8.13. As the reaction proceeds, [L ] increases and the apparent rate of the reaction may decrease if 1 [L ] becomes significant relative to /c2[Y ]. Adding L to the solution would also decrease the rate of formation of R—Y, a phenomenon known as the common ion effect or mass law effect. In solvolysis reactions, in which the solvent is the nucleophile, the concentration of the nucleophile is effectively constantandcannotbe varied.Thereactionisthereforemoreproperly described as pseudo-first order, since only the concentration of the substrate can be varied. 

Addition of other ionic species could increase the rate by changing the effective polarity of the microenvironment through a salt effect, and some salts exhibit a special salt effect. See the discussion on page 483. 

Good leaving groups (more stable anions) lower the energy of the transition state, thus decreasing AG and increasing the reaction rate. 

We ve now seen that the Sfj2 reaction is worst when carried out with a hindered substrate, a neutral nucleophile, and a protic solvent. You might therefore expect the reaction of a tertiary substrate (hindered) with water (neutral, protic) to be among the slowest of substitution reactions. Remarkably, however, the opposite is true. The reaction of the tertiary halide (CH ,)aCBr with HjO to give the alcohol 2-methyl-2-propanol is more than 1 million times as fast as the corresponding reaction of the methyl halide CH3Br to give methanol. 

What s going on here Clearly, a nucleophilic substitution reaction is occurring, yet the reactivity order seems backward. These reactions can t be taking place by the Sr2 mechanism we ve been discussing, and we must therefore conclude that they are occurring by an alternative substitution mechanism. This alternative mechanism is called the SN1 reaction (for substitution, nucleophilic, unimolecular). Let s see what evidence is available concerning the SN1 reaction. 

What s going on here Clearly, a nucleophilic substitution reaction is occurring—a halogen is replacing a hydroxyl group— yet the reactivity order seems backward. These reactions can t be taking place by the Sn2 mechanism we ve 

In contrast to the Sn2 reaction of CH3Br with OH , the S l reaction of (CH3)3CBr with H2O has a rate that depends only on the alkyl halide concentration and is independent of the H2O concentration. In other words, the reaction is a first-order process the concentration of the nucleophile does not appear in the rate equation. 

Reaction rate = Rate of disappearance of alkyl halide = k X [RX] 

The mechanism of the Sf l reaction of 2-bromo-2-methylpropanewith H2O involves three steps. StepQ—the spontaneous, unimolecular dissociation of the alkyl bromide to yield a carbo-cation—Is rate-llmiting. 

I Loss of a proton from the protonated alcohol intermediate then gives the neutral alcohol product. 

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The nature of the nucleophile plays a major role in the SN2 reaction but does not affect an S l reaction. Because the SN1 reaction occurs through a rale-limiting step in which the added nucleophile has no part, the nucleophile can t affect the reaction rate. The reaction of 2-methyl-2-propanoI with HX, for instance, occurs at the same rate regardless of whether X is Cl, Br, or 1. Furthermore, neutral nucleophiles are just as effective as negatively charged ones, so S 1 reactions frequently occur under neutral or acidic conditions. 

Just as the L2 reaction is analogous to the SK-2 reaction, the SN1 reaction has a close analog called the El reaction (for elimination, unimolecular). The El reaction can be formulated as shown in Figure 11.21 for the elimination of HC1 from 2-chloro-2-methylpropane. 

LFER. Consider the Sn2 reactions of XC6H4CH2CI with I- (ki) and the SN1 reactions. with OH (fc0H)- The reaction constants are given in Table 10-2. Sketch the appearance of a plot of log ki versus log kon- What is its slope ... 

In steric terms there is a relief of crowding on going from the initial halide, with a tetrahedral disposition of four substituents about the sp3 hybridised carbon atom, to the carbocation, with a planar disposition of only three substituents (cf. five for the SN2 T.S.) about the now sp2 hybridised carbon atom. The three substituents are as far apart from each other as they can get in the planar carbocation, and the relative relief of crowding (halide - carbocation) will increase as the substituents increase in size (H- Me- Me3C). The SN1 reaction rate would thus be expected to increase markedly (on both electronic and steric grounds) as the series of halides is traversed. It has not, however, proved possible to confirm this experimentally by setting up conditions such that the four halides of Fig. 4.1 (p. 82) all react via the SN1 pathway. 

Allylic nitro derivatives undergo the SN1 reaction in aqueous acetic acid. Allylic sulfones in the presence of a sulfinate salt (Eq. 7.21) or allylic lactones if the substrate contains a suitably located ester group are formed in these reactions (Eq. 7.22).22... 

Micellar microenvironments may be used for differentiating courses of reaction. Thus, cationic micelles efficiently suppressed the SN1 reaction of 1-bromo-2-phenylpropane (Lapinte and Viout, 1973) and of 3-bromo-3-phenylpropionate (Bunton et al., 1974). Tagaki et al. (1976) found that the facilitated formation of carbanion intermediates changed the course of reaction of p-nitrophenyl esters. 

TABLE 10.5 Relative rates for the Sn1 reaction between ROTs and ethanol at 25°C ... 

We note that in Eq. 13-11 we have introduced the El (elimination, unimolecular) reaction, which commonly competes with the SN1 reaction provided that an adjacent carbon atom carries one or several hydrogen atoms that may dissociate. We also note that similar to what we have stated earlier for nucleophilic substitution reactions, elimination reactions may occur by mechanisms between the E2 and El extremes. 

Many secondary and tertiary halides undergo El elimination in competition with the SN1 reaction in neutral or acidic solutions. For example, when tert-butyl chloride solvolyzes in 80% aqueous ethanol at 25°, it gives 83% tert-butyl alcohol by substitution and 17% 2-methylpropene by elimination ... 

Factors influencing the El reactions are expected to be similar to those for the SN1 reactions. An ionizing solvent is necessary, and for easy reaction the RX compound must have a good leaving group and form a relatively stable R cation. Therefore the El orders of reaction rates are X = I>Br>Cl>F and tertiary R > secondary R > primary R. 

The SN1 reactions of many RX derivatives that form moderately stable carbocat-ions are substantially retarded by adding X° ions. However, such retardation is diminished, at given X° concentrations, by adding another nucleophile such as N3 . Explain. 

Figure 4.2 Proposed reaction coordinate diagram for the SN1 reaction.

Why, then, does (CH3)3CBr react with the OH ion by the SN1 mechanism if CH3Br does not The SN1 reaction proceeds through a carbocation intermediate, and the stability of these ions decreases in the following order. 

The reaction takes place via an Sn1 mechanism because the substrate is a tertiary halide. The expected product is tert-butyl methyl ether. The reaction energy diagram resembles that for the SN1 reaction shown in Figure 6.2 ... 

Tertiary alcohols may undergo the SN1 reaction to produce tertiary alkyl halides (Following fig.). Since the reaction needs the loss of the hydroxide ion (a poor leaving group), so to convert the hydroxyl moiety into a better leaving group acidic conditions are achieved with the use of HC1 or HBr. The acid serves to protonate the hydroxyl moiety as the first step and then a normal SN1 mechanism occurs where water is lost from the molecule to form an intermediate carbocation. A halide ion then forms a bond to the carbocation centre in the third step. 

Under these conditions, the order of reactivity to nucleophilic substitution changes dramatically from that observed in the Sn2 reaction, such that tertiary alkyl halides are more reactive then secondary alkyl halides, with primary alkyl halides not reacting at all. Thus a different mechanism must be involved. For example, consider the reaction of 2-iodo-2-methylpropane with water. (Following fig.). In it, the rate of reaction depends on the concentration of the alkyl halide alone and the concentration of the attacking nucleophile has no effect. Thus, the nucleophile must present if the reaction is to occur, but it does not matter whether there is one equivalent of the nucleophile or an excess. Since the reaction rate depends only on the alkyl halide, the mechanism is called the SN1 reaction, where SN stands for substitution nucleophilic and the 1 shows that the reaction is first order or unimolecular, i.e. only one of the reactants affects the reaction rate. 

The SN1 mechanism is specially favoured when the polar protic solvent is also a non-basic nucleophile. Therefore, it is most likely to take place when an alkyl halide is dissolved in water or alcohol. Protic solvents are bad for the SN2 mechanism because they solvate the nucleophile, but they are good for the SN1 mechanism. This is because polar protic solvents can solvate and stabilise the carbocation intermediate. If the carbocation is stabilised, the transition state leading to it will also be stabilised and this determines whether the SN1 reaction is favoured or not. Protic solvents will also solvate the nucleophile by hydrogen bonding, but unlike the SN2 reaction, this does not affect the reaction rate since the rate of reaction is independent of the nucleophile. 

Because the rate of the SN1 reaction is independent of the incoming nucleophile, the nucleophilicity of the incoming nucleophile is not so important. 

Steric and electronic factors also play role in the rate of the SN1 reaction because the steric bulk of three alkyl substituents makes it very difficult for a nucleophile to reach the electrophilic carbon centre of tertiary alkyl halides, these structures undergo nucleophilic substitution by the SN1 mechanism. In this mechanism, the steric problem is relieved because loss of the halide ion creates a planar carbocation where the alkyl groups are much further apart and where the carbon centre is more accessible. Formation of the carbocation also relieves steric strain between the substituents. 

The E2 reaction is the most effective for the synthesis of alkenes from alkyl halides and can be used on primary, secondary, and tertiary alkyl halides. The El reaction is not so useful from a synthetic point of view and occurs in competition with the SN1 reaction of tertiary alkyl halides. Primary and secondary alkyl halides do not generally react by this mechanism. 

The El mechanism generally occurs when an alkyl halide is dissolved in protic solvent where the solvent can act as a non-basic nucleophile. These are the same conditions for the SN1 reaction and so both these reactions generally take place simultaneously forming a mixture of products. For example, the El mechanism is the reaction of 2-iodo-2-methyl-butane with methanol ... 

The conditions that favour El are the same which that favour the SN1 reaction (i.e. a protic solvent and a non-basic nucleophile). Therefore, the El reaction normally only takes place with tertiary alkyl halides and will be in competition with the SN1 reaction. 

Sulfur can be introduced into a diazonium salt by the SN1 reaction shown in Figure 5.51. In order to prevent the reagent from effecting a double (rather than a mono-) arylation at the sulfur atom, potassium xanthogenate instead of sodium sulfide is used as the sulfur nucleophile. The resulting S-aryl xanthogenate C is hydrolyzed. In this way diarylsulfide-free aryl thiol B is obtained. 

Carbocations are one of the most important types of reactive intermediates in organic chemistry. They are encountered in many reactions in addition to the SN1 reaction. 

How do the other groups bonded to the electrophilic carbon affect the rate of the SN1 reaction Table 8.2 lists the relative rates of the SN1 reaction for a number of compounds, compared to the rate for isopropyl chloride taken as 1. Methyl chloride and ethyl chloride are not listed in the table because methyl and simple primary alkyl chlorides do not react by the mechanism. Even under the most favorable SN1 conditions, these unhindered compounds react by the SN2 mechanism. 

For the SN1 reaction, formation of the carbocation is the rate-limiting step. We have already seen that the transition state for this step resembles the carbocation. Any change that makes the carbocation more stable will also make the transition state more stable, resulting in a faster reaction. Carbocation stability controls the rate of the SN1 reaction. Many studies have provided the following order of carbocation stabilities ... 

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