Halide ions as leaving groups

Such rate difference as there is for attack on (86) depends on the ability of X, through electron-withdrawal, to influence the relative ease of attack on the substrate by the nucleophile it is in the reverse order of the relative ability of the halide ions as leaving groups. When the same series of halides is reacted with C HsNHMe (in nitrobenzene at 120°), however, the relative rates for X = F, Cl and Br were found to be 1, 15 and 46, e.g. in the order of their relative ability as leaving groups, so that in this latter reaction it would appear that step (2) is now involved, to some extent at least, in the rate-limiting step overall. 

The lower the bond enthalpy of the bond between the C atom and the leaving group, the better the leaving group. This again follows from the Hammond postulate. For this reason as well, the suitability of the halide ions as leaving groups is predicted as I- > Br > Cl > F . 

The extent of this failure is evident from comparisons of experimental measurements of rate and equilibrium constants. One comparison in the literature is provided by Ritchie and coworkers study of the relatively stable cation, pyronin (the 3,6-bis(dimethylamino)xanthylium cation 71) with a series of nucleophiles.252 Another example is McClelland s measurements of rate and equilibrium constants for the reactions of halide and acetate ions with the trityl cation.19 As already mentioned fluoride and acetate are less reactive than bromide and chloride despite their equilibrium affinities being much greater. This is reflected indeed in the much lower rates of solvolysis of the fluoride and acetate than bromide or chloride as leaving groups... 

A similar picture holds for other nucleophiles. As a consequence, there might seem little hope for a nucleophile-based reactivity relationship. Indeed this has been implicitly recognized in the popularity of Pearson s concept of hard and soft acids and bases, which provides a qualitative rationalization of, for example, the similar orders of reactivities of halide ions as both nucleophiles and leaving groups in (Sn2) substitution reactions, without attempting a quantitative analysis. Surprisingly, however, despite the failure of rate-equilibrium relationships, correlations between reactivities of nucleophiles, that is, comparisons of rates of reactions for one carbocation with those of another, are strikingly successful. In other words, correlations exist between rate constants and rate constants where correlations between rate and equilibrium constants fail. 

A final method sometimes employed to prepare alkyl halides uses an SN2 reaction with one halogen as the leaving group and a different halide ion as the nucleophile, as shown in the following general equation ... 

Unexpected chiral adducts were formed in the thermal reaction of Cgo with enamines such as (V-cyclopent- l-cnylpipcridinc and N--cyclohex- 1-enylpyr-rolidine.402 Fullerene derivatives with chiral side chains can also be obtained in nucleophilic substitution reactions between fullerenide ions and electrophiles such as halides having the leaving group attached to a stereogenic center.403... 

So, unlike the leaving group of a protonated alcohol, the leaving group of a protonated amine cannot dissociate to form a carbocation or be replaced by a halide ion. Protonated amino groups also cannot be displaced by strongly basic nucleophiles such as HO because the base would react immediately with the acidic hydrogen, and protonation would convert it into a poor nucleophile. 

The catalytic effect of protons has been noted on many occasions (cf. Section II,D,2,c) and autocatalysis frequently occurs when the nucleophile is not a strong base. Acid catalysis of reactions with water, alcohols, mercaptans, amines, or halide ions has been observed for halogeno derivatives of pyridine, pyrimidine (92), s-triazine (93), quinoline, and phthalazine as well as for many other ring systems and leaving groups. An interesting displacement is that of a 4-oxo group in the reaction of quinolines with thiophenols, which is made possible by the acid catalysis. 

Note that in the S l reaction, which is often carried out under acidic conditions, neutral water can act as a leaving group. This occurs, for example, when an alkyl halide is prepared from a tertiary alcohol by reaction with HBr or HC1 (Section 10.6). The alcohol is first protonated and then spontaneously loses H2O to generate a carbocation, which reacts with halide ion to give the alkyl halide (Figure 11.13). Knowing that an SN1 reaction is involved in the conversion of alcohols to alkyl halides explains why the reaction works well only for tertiary alcohols. Tertiary alcohols react fastest because they give the most stable carbocation intermediates. 

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. 

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