Leaving groups hahdes

All lation. In alkylation, the dialkyl sulfates react much faster than do the alkyl haHdes, because the monoalkyl sulfate anion (ROSO ) is more effective as a leaving group than a haHde ion. The high rate is most apparent with small primary alkyl groups, eg, methyl and ethyl. Some leaving groups, such as the fluorinated sulfonate anion, eg, the triflate anion, CF SO, react even faster in ester form (4). Against phenoxide anion, the reaction rate is methyl triflate [333-27-7] dimethyl sulfate methyl toluenesulfonate [23373-38-8] (5). Dialkyl sulfates, as compared to alkyl chlorides, lack chloride ions in their products chloride corrodes and requires the use of a gas instead of a Hquid. The lower sulfates are much less expensive than lower bromides or iodides, and they also alkylate quickly. 

Of the hahde leaving groups, iodide is most easily displaced, but also most reactive in metal halogen exchange bromide and chloride are successively less reactive. Grignard... 

The chemistry of selenones (11) has not been studied as extensively as that of selenoxides. However, it has been demonstrated that selenones function as good leaving groups, comparable to tosylates or hahdes. For example, they are readily solvolyzed in methanol and produce rearranged products when -substituents with high migratory aptitudes are present (equations 7 and 8). Vinyhc selenones also act as Michael acceptors, as in the first step of the process shown in equation (9). 

The coupling of aryl halides with copper is called the Ullmann reaction The reaction is clearly related to 13-9, but involves aryl copper intermediates. The reaction is of broad scope and has been used to prepare many symmetrical and unsym-metrical biaryls." When a mixture of two different aryl hahdes is used, there are three possible products, but often only one is obtained. For example, picryl chloride and iodobenzene gave only 2,4,6-trinitrobiphenyl." The best leaving group is iodo, and the reaction is most often done on aryl iodides, but bromides, chlorides, and even thiocyanates have been used. 

Since, as we have seen, the nucleophile attacks the substrate in the ratedetermining step of the Sn2 mechanism, it follows that the rate at which substitution occurs may vary from nucleophile to nucleophile. Just as some alkyl hahdes are more reactive than others, some nucleophiles are more reactive than others. Nucleophilic strength, or nucleophilicity, is a measure of how fast a Lewis base displaces a leaving group from a suitable substrate. By measuring the rate at which various Lewis bases react with methyl iodide in methanol, a list of their nucleophihcities relative to methanol as the standard nucleophile has been compiled. It is presented in Table 8.4. 

Leaving group (Section 5.15) The group, normally a hahde ion, that is lost from carbon in a nucleophihc substitution or elimination. 

There is also a problem with i-PrCl it is a secondary hahde and chloride is the worst leaving group among the halogens Cl, Br, I—it is prone to ehmination rather than substitution reactions. To make the required product, an aza-enolate (p. 593 in the textbook) or a silyl enol ether (p. 595 in the textbook) would be a better bet. 

Both the Sn2 reaction in Chapter 11 (Section 11.2) and the E2 reaction discussed before follow second-order kinetics (see Chapter 7, Section 7.11.2) and are bimolecular. The E2 reaction involves a collision of the base with the P-hydrogen atom to initiate the elimination. In effect, collision of the base with the P-hydrogen will initiate the elimination sequence that expels the leaving group. Similarly, collision of a nucleophile with the alkyl hahde will kick out the leaving group for an Sn2. 

Elimination bimolecular (E2) mechanism Mechanism for elimination of alkyl halides characterized by a transition state in which the attacking base removes a proton at the same time that the bond to the hahde leaving group is broken. 

NTlcleopliilic attack The nucleophilic enolate attacks the alkyl hahde, displacing the halide (a good leaving group) and forming the alkylation product by an Sn2 reaction. 

Later we shall see examples of leaving groups other than hahde anions. Some of these leaving groups depart as neutral species. For the time being, however, our examples will involve alkyl halides, which we represent generally as R—X =. 

The reactions of carboxyhc anhydrides with nucleophiles, although less vigorous, are completely analogous to those of the acyl hahdes. The leaving group is a carboxylate instead of a haUde ion. 

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