Ionization of a leaving group

The slow step in the SnI is the loss of the leaving group. The ionization of a leaving group depends primarily on three factors, the ability of the solvent to stabilize the charges formed, the stability of the carbocation, and the quality of the leaving group. 

Account for the different rates in the ionization of the leaving group X. Hint What factors influence the ease of ionization of a leaving group ... 

Proton Transfer to a Lone Pair ionization of a Leaving Group Trapping of an Electron-Deficient Species Electrophile Addition to a Multiple Bond Electrofuge Loss from a Cation to Form a Pi Bond The S m2 Substitution The E2 Elimination The AdeS Addition... 

Figure 7.2 Ionization of a leaving group with the transition state in the center.

The electrophile is the acylium ion, R-C +, generated by Lewis acid-catalyzed ionization of a leaving group (path Dn) from acyl halides or acid anhydrides (shown in the previous section). The proton that is lost comes from the same carbon that the electrophile attacked. The reaction fails for deactivated rings (Ai wg, meta directors). After the electrophile adds it deactivates the ring toward further attack. No rearrangement of the electrophile occurs. 

The first procedure involves ionization of a leaving group attached to Ccarbene (perhaps more accurately described as an electrophilic abstraction, Section 8-4-2). The second procedure occurs when an electrophile (usually H+) undergoes electrophilic addition (Section 8-4-2) to a nq vinyl complex. The cationic iron complexes produced are usually thermally unstable and may either react with a nucleophile or rearrange at low temperature to an alkene complex via a 1,2-H-shift (Scheme 10.5). 

Figure 6.2 Orbital picture of the transition state for a 1,2-shift in which migration is concerted with ionization of the leaving group.

The use of the 2R,3R isomer led to formation of only 2R,3R-2-ethoxy-3-phenylbutane. Thus the configuration at each chiral center was retained in the product. These stereochemical data rule out simple ionization and solvent capture as a reaction mechanism since this would lead to a mixture of 2R and 2S configurations. From these observations it has been postulated that the phenyl group assists ionization of the leaving group by electron donation to produce a bridged ion. 

It is best to consider a Sn1/Sn2 spectrum where there is competition between two rates the rate of ionization of the leaving group and the rate of nucleophilic attack on the substrate or partially ionized substrate. Table 4.4 outlines the extremes of the spectrum. 

The stability of both path Dn product carbocations must be checked the lone-pair-stabilized tertiary cation is much more stable and therefore is favored over the unstabilized primary cation. Ionization of the leaving group (path Dn) creates a somewhat less stable cation than the protonated ketal, so ionization of the leaving group is uphill in energy. 

Answer The SjmI rate-determining step is the ionization of the leaving group to form a carbocation and a chloride ion. The solvent must stabilize these charged species, or the reaction will be slowed or stopped. The Sn2 reaction rate would be expected to increase slightly since the charge is dispersed in the transition state. The observed solvent effect is inconsistent with an S[sf2 mechanism and consistent with the SnI. ... 

One possibility involves the ionization of the leaving group in the first, rate-limiting step of the reaction, and then removal of the proton and formation of the double bond in a second, fast, step... 

Important reasons for these solvent effects have to do with (a) minimizing the solvents interaction with the nucleophile in 5 2 reactions, and (b) facilitating ionization of the leaving group and stabilizing ionic intermediates by solvents in S l reactions. In the following subsections we will explain these factors in further detail. 

The rate-determining step in an El reaction is ionization of the leaving group (often a halide, X) to form a carbocation. Because this step involves only the haloalkane, the reaction is said to be unimolecular and follows first-order kinetics. 

Second, there is a unimolecular El elimination reaction that parallels (and competes with) the SnI substitution reaction. The SnI and El reactions share the same intermediate, the carbocation formed by ionization of the leaving group. Once this carbocation is formed it can be captured by nucleophiles (SnI) or deprotonated to give an alkene (El). Saytzeff elimination is the rule. 

The Hammond-Leffler Postulate If you review the free-energy diagrams that accompany the mechanism for the SnI reaction of tert-butyl chloride and water (Section 6.10), you will see that step 1, the ionization of the leaving group to form the carbocation, is uphill in terms of free energy (AG° for this step is positive). It is also uphill in terms of enthalpy (AH° is also positive), and, therefore, this step is endothermic. According to the Hammond-Leffler postulate, the transition-state structure for a step that is uphill in energy should show... 

As depicted, the E2 mechanism involves a bimolecular transition state in which removal of a proton to the leaving group is concerted with departure of the leaving group. In contrast, the rate-determining step in the El mechanism is the unimolecular ionization of... 

It should be mentioned here that if no other leaving group is present, sulfonyl can act as its own leaving group in hydroxide- or alkoxide-catalyzed elimination from sulfones. Carbanion formation is not involved in this but the promotion of the ionization of a C—H bond by the sulfonyl group is seen at the /1-carbon rather than the a-carbon, e.g. equation 21. 

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