Nucleophiles and the leaving group

So far, we have explored the substrate, the nucleophile, and the leaving group. This takes care of all of the parts of the compounds that are reacting with each other. Let s summarize substitution reactions in a way that allows us to see this ... 

So, by talking about the substrate, the nucleophile, and the leaving group, we have covered almost everything. But there is one more thing to take into account. What solvent are these compounds dissolved in It can make a difference. Let s see how. 

The transition state is a fleeting arrangement of the atoms in which the nucleophile and the leaving group are both bonded to the carbon atom undergoing attack. 

In Sn2 reactions, substituents at the central atom that can stabilise cationic character will also stabilise the SN2 transition state leading to products. As well as lowering the energy, such stabilisation moves SN2 saddle points in the direction of cationic species resulting in incipient cationic character in the transition structure and longer bonds to both the nucleophile and the leaving group.162 165... 

An alternative SN2-Si mechanism may be considered, without a penta-coordinate intermediate. In this alternative, the silicon is rehybridized from spy to sp2. If bond order is conserved, then it is reasonable to ascribe a bond order of 0.5 to the Si—O bond of both the entering nucleophile and the leaving group [52], It has been shown that the bond order is related to the bond distance [45]. Even though there are five substituents in the vicinity of the silicon in an SN2-Si type mechanism, two of the substituents are significantly further away from the central atom (silicon) than the other three substituents. A looser transition state structure than that for an SN2 -Si or an SN2 -Si process results. The steric effects of the alkyl group bonded to silicon should, therefore, be considerably less in an SN2-Si type mechanism. 

The alpha effect in the SN2 reactions of methyl substrates with three different nucleophiles was shown to correlate with Koopman s theorem ionization potentials for the leaving group.128 This was taken as evidence that (1) the size of the alpha effect in Sn2 reactions depends on the ability of the nucleophile and the leaving group to donate an electron to the methyl group and (2) these transition states have some SET character. The results support the Hoz model129 for the alpha effect. 

Similar reactions of substituted cyclobutenes are collected in Table 3, which lists the attacked system, the nucleophile and the leaving group, and the ratio of allylic to vinylic products. The following order of leaving ability of /3-substituents is obtained from the Table ... 

Routes (i) and (ii) differ only in the life-time of the intermediate, although the intermediate of route (i) might only be a transition state. We will see that the stereochemistry of the product and the element effect can give information on this question. Most of the evidence points to a short-lived carbanionic intermediate, but in some examples an a,j8-adduct seems essential. Since even the direct substitution is in itself an addition-elimination process involving the nucleophile and the leaving group, and since differentiation between the routes of Scheme 2 is not always possible, we will designate all routes of Scheme 2 as addition-elimination . 

In many cases the pentaco-ordinate species involved in the reaction is thought to be an intermediate (i.e. the nucleophile and the leaving group are attached to the silicon by fully-formed bonds as depicted in Equation Si 1.1) rather than a transition state as invoked in the analogous carbon Sjsf2 reaction. 

The reactions discussed so far have been intermolecular reactions that is, they involve two separate molecules the nucleophile and the compound with the leaving group. It is also possible for the nucleophile and the leaving group to be part of the same molecule. In such a case the reaction is intramolecular—that is, within the same mol-... 

Propose a mechanism for the reaction of benzyl acetate with methylamine. Label the attacking nucleophile and the leaving group, and draw the transition state in which the leaving group leaves. 

The nucleophile and the leaving group are both alkoxides, the only difference being R1 and R2. If R1 and R2 were the same, the energy profile diagram would be totally symmetrical and small differences between R1 and R2 are not going to affect the symmetry much. 

The nature of the nucleophile and the leaving group and the structure of the compound under attack all affect the S>j2 mechanism because its rate expression is rate = k2[nucleophile][MeX]... 

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