SN1 reaction kinetics

SN1 Reactions Kinetic and Stereochemical Analysis Substituent Effects on Reactivity... 

The reaction of an alkyl halide or los3 late with a nucleophiJe/base results eithe in substitution or in diminution. Nucleophilic substitutions are of two types S 2 reactions and SN1 reactions, in the SN2 reaction, the entering nucleophih approaches the halide from a direction 180° away from the leaving group, result ing in an umbrella-like inversion of configuration at the carbon atom. The reaction is kinetically second-order and is strongly inhibited by increasing stork bulk of the reactants. Thus, S 2 reactions are favored for primary and secondary substrates. 

The S il reaction occurs when the substrate spontaneously dissociates to a carbocation in a slow rate-limiting step, followed by a rapid reaction with the nucleophile. As a result, SN1 reactions are kinetically first-order and take place with racemization of configuration at the carbon atom. They are most favored for tertiary substrates. Both S l and S 2 reactions occur in biological pathways, although the leaving group is typically a diphosphate ion rather than a halide. 

As the understanding of the ionic intermediates has progressed, advantage has been taken of the fact that bromination, like SN1 heterolysis, is a carbocation-forming reaction. Kinetic data on this addition have therefore been used to examine in detail how the basic concepts of physical organic chemistry work as regards transition-state shifts with reactivity (Ruasse et al, 1984). Bromination lends itself particularly well to the quantitative application of the BEMA HAPOTHLE (acronym for Bell, Marcus, Hammond, Polanyi, Thornton and Leffler Jencks, 1985). In particular, it has been possible to evaluate the transition-state dependence on the solvent and substituents. The major disadvantage that bromination shares with many... 

Lysozyme and /3-galactosidase, which are both glycosidases, catalyze very similar reactions. Both enzymes are found to catalyze the alcoholysis of their polysaccharide substrates with retention of configuration at the C-l carbon (equation 8.25).14-17 This is consistent with the evidence presented in Chapter 7, section C3, that there is at least one (but probably only one) intermediate on the reaction pathway. However, kinetic isotope data are consistent with the interpretation that the intermediate in the reaction of /3-galactosidase is covalent and that there are two successive SN2 displacements, whereas the intermediate with lysozyme is a bound carbonium ion formed in an SN1 reaction (Chapter 16). The carbonium ion, unlike an analogous one in solution, reacts stereospecifically on the enzyme. Thus, the stereochemical evidence by itself has given no indication of the nature of the intermediate. 

The intermediate carbocation formed by SN1 reactions of either 3-chloro-3-methyl-1-butene or 4-chloro-2-methyl-2-butene reacts with water to give a mixture of 2-methyl-3-buten-2-ol and 3-methyl-2-buten-1-ol. Which alcohol would you expect to predominate under conditions of equilibrium control On the basis of steric hindrance, charge distribution in the cation, and so on, which alcohol should be favored under conditions of kinetic control (Review Sections 6-5C, 10-4A, and 11-3.) Give your reasoning. 

The reaction of azide ions with carbocations is the basis of the azide clock method for estimating carbocation lifetimes in hydroxylic solvents (lifetime = 1 lkiy where lq, is the first-order rate constant for attack of water on the carbocation) this is analogous to the radical clock technique discussed in Chapter 10. In the present case, a rate-product correlation is assumed for the very rapid competing product-forming steps of SN1 reactions (Scheme 2.24). Because the slow step of an SN1 reaction is formation of a carbocation, typical kinetic data do not provide information about this step. Furthermore, the rate constant for the reaction of azide ion with a carbocation (kaz) is assumed to be diffusion controlled (ca. 5 x 109 M 1 s 1). The rate constant for attack by water can then be obtained from the mole ratio of azide product/solvolysis product, and the molar concentrations of azide (Equation 2.18, equivalent to Equation 2.14) [48]. The reliability of the estimated lifetimes was later... 

On the basis of the general reaction scheme (see p. 248) the kinetic dependence is caused by the fact that the rate of the SN2 reaction, Eq. (7), is dependent on the concentration of diazomethane but that the rate of the SN1 reaction, Eq. (6), is not. (For unimolecular reactions, the half-life does not depend on the concentration but it does in the case of bimolecular reactions.124 We have, assuming fast pre-equilibrium ... 

Cyanide ions react with the soft (see pp. 151-152) alkyl halides in Sn2 reactions and with the hard carbocations in SN1 reactions to give, almost always, the nitrile 4.42, which is thermodynamically preferred.289 Isonitrile products are formed along with the nitrile products when the cation is so reactive that the rate has reached the diffusion-controlled limit, and the reversible reaction that would equilibrate the products is too slow.290 It is hardly surprising that reactions between a cyanide ion and a carbocation can be fast enough to reach the diffusion controlled limit, since they are ion-with-ion reactions, which are rather rare in organic chemistry. One consequence when reactions are as fast as this is that there is a barrierless combination of ions, and selectivity is not then controlled by the kinetic factors associated with the principle of HSAB. 

The observation of first-order kinetics for the SN1 reaction of (C ljCl with HzO tells us that the alkyl halide is involved in a unimolecular rah limiting step. In other words, 2-bromo-2-methylpropane undergoes a spa taneous, rate-limiting reaction without involvement of the nucleophile. Hi nucleophile must be involved at some other step. The mechanism showni Figure 11.9 accounts for the kinetic observations. 

Because the El process involves the same rate-determining step as the SN1 reaction, its kinetics are the same first order. El elimination almost always accompanies SN1 substitution. The difference is simple In SN1, the nucleophile attaches to the cationic carbon in El, it attaches to and removes a proton. For the practical purposes of synthesis, the presence of the El side reaction can limit the usefulness of SN1 substitution. 

Simple kinetic measurements can, however, be an inadequate guide to which of the above two mechanisms, SN1 or SN2, is actually operating in, for example, the hydrolysis of a halide. Thus, as we have seen (p. 45), where the solvent can act as a nucleophile (solvolysis), e.g. H20, we would expect for an S 2 type reaction,... 

A kinetic distinction between the operation of the SN1 and SN2 modes can often be made by observing the effect on the overall reaction rate of adding a competing nucleophile, e.g. azide anion, N3e. The total nucleophile concentration is thus increased, and for the SN2 mode where [Nu ] appears in the rate equation, this will result in an increased reaction rate due to the increased [Nut]. By contrast, for the Stfl mode [Nut] does not appear in the rate equation, i.e. is not involved in the rate-limiting step, and addition of N3e will thus be without significant effect on the observed reaction rate, though it will naturally influence the composition of the product. 

In solvolytic reactions like those we have just been considering, where the solvent itself is the nucleophile, such mixed kinetics may not be detectable, irrespective of what is actually happening, as both SN1 and Sn2 pathways are likely to follow a rate equation of the form ... 

The propensity of S-S dications to undergo dealkylation was found to decrease in the order of methyl > ethyl > benzyl. This order of reactivity parallels the increase in the stability of the corresponding carbocations.94 Dealkylation of dication 77 affords thiosulfonium salt 78 in quantitative yield.95 Kinetic studies suggest SN1 mechanism of dealkylation. In addition, reaction of sulfoxide 79 with a substituent chiral at the a-carbon results in racemic amide 80 after hydrolysis. 

Other terms that he invented include the system of classification for mechanisms of aromatic and aliphatic substitution and elimination reactions, designated SN1, SN2, El, and E2. "S" and "E" refer to substitution and elimination, respectively, "N" to nucleophilic, and "1" and "2" to "molecularity," or the number of molecules involved in a reaction step (not kinetic order, having to do with the equation for reaction rate and the concentration of reactants). Ingold first introduced some of these ideas in 1928 in a... 

It is worth noting that Murr and Donnelly (1970a,b) have demonstrated that the secondary a-deuterium KIE is only approximately 75% of the theoretical maximum kinetic isotope effect when the ionization (ki) step of the reaction (Scheme 1) is fully rate determining, i.e. when the reaction occurs via a limiting SN1 mechanism (Shiner, 1970b Westaway, 1987c). 

Platinum(IV) is kinetically inert, but substitution reactions are observed. Deceptively simple substitution reactions such as that in equation (554) do not proceed by a simple SN1 or 5 2 process. In almost all cases the reaction mechanism involves redox steps. The platinum(II)-catalyzed substitution of platinum(IV) is the common kind of redox reaction which leads to formal nucleophilic substitution of platinum(IV) complexes. In such cases substitution results from an atom-transfer redox reaction between the platinum(IV) complex and a five-coordinate adduct of the platinum(II) compound (Scheme 22). The platinum(II) complex can be added to the solution, or it may be present as an impurity, possibly being formed by a reductive elimination step. These reactions show characteristic third-order kinetics, first order each in the platinum(IV) complex, the entering ligand Y, and the platinum(II) complex. The pathway is catalytic in PtnL4, but a consequence of such a mechanism is the transfer of platinum between the catalyst and the substrate. 10 This premise has been verified using a 195Pt tracer.2011... 

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