Halide ions as nucleophiles

FIGURE 9.30 OH can be converted into a good leaving group by protonation. 

FIGURE 9.39 5 2 chlorination of alcohols using thionyl chloride in pyridine. 

FIGURE 9.41 Displacement of tosylates and mesylates by halide anions. Boc is a protecting group for amino groups—well learn about this in Section 22.4.2. 

FIGURE 9.42 Formation of iodides by displacement of other halides. 

Explain the previous reaction, drawing mechanisms, with particular regard to the stereochemical outcome  

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In non-aqueous media the relative order of reactivity of the attacking halide ions, as nucleophiles in these processes, is F > Cl > 1 [83]. This in itself indicates that the... 

It is not difficult to incorporate this result into the general mechanism for hydrogen halide additions. These products are formed as the result of solvent competing with halide ion as the nucleophilic component in the addition. Solvent addition can occur via a concerted mechanism or by capture of a carbocation intermediate. Addition of a halide salt increases the likelihood of capture of a carbocation intermediate by halide ion. The effect of added halide salt can be detected kinetically. For example, the presence of tetramethylammonium... 

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. 

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. 

Not only radical scavengers, radical reduction and/or radical dimerization products but also radical probes were used in order to prove the presence of radicals as intermediates along the S l propagation cycle. Thus the formation of cyclized and uncyclized substitution products was taken as an indication of radical intermediates in the reaction of neopentyl-type halides containing a cyclizable probe of the 5-hexenyl type 2. These reactions were performed with PhS and Ph2P ions as nucleophiles (equation 13)52. 

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 ... 

Hitherto we have concentrated on electrophilic aromatic substitution. However, certain n-deficient aromatic rings are deactivated towards electrophilic attack but are susceptible to nucleophilic addition and a subsequent elimination. A particular example is 2,4-dinitrochloroben-zene. The electron-withdrawing nitro groups facilitate a Michael-type addition of a nucleophile to give a so-called Meisenheimer intermediate (Scheme 4.8). Collapse of the Meisenheimer intermediate and reversion to the aromatic system may lead to expulsion of the halide ion, as exemplified by the preparation of 2,4-dinitrophenylhydrazine. 2,4-Dinitrofluorobenzene is known as Sanger s reagent and is used for the detection of the N-terminal amino acids in peptides. 

Vinylsilanes react with chloral in the presence of Lewis acids (Scheme 33), but this type of reaction is little used, probably because the products are allylic alcohols, which are apt to undergo ionization in the presence of Lewis acids to give allyl cations, and hence further reaction. Reactions employing nucleophilic catalysis, although free of this problem, are also limited, only anion-stabilized systems undergoing reaction (Scheme 34). On the other hand, there is less of a problem with 3-elimination of a halide ion, as there would be with most metals 3 to a halogen. ... 

Many different mechanisms have been proposed for the Perkow reaction.2-4 It involves nucleophilic attack of the phosphite at the carbonyl carbon and affords a zwitterionic intermediate 5 which rearranges to form a cationic species 6 that subsequently dealkylates to give the corresponding vinyl phosphate 7. The conversion proceeds via a Michaelis-Arbuzov cleavage of an alkoxy group by halide ion as shown. 

The ion-paired or free-ion nature of the nucleophile is also crucial on the selection of mechanisms. When the nucleophile is ion-paired (Eq. 3 of Scheme 26), it is intrinsically less reactive with ArPdX(5 )L2 than the free nucleophile. A 2[Nu] is then smaller and the deviation through the trans-AxP6XL2 complex (left side cycle of Scheme 25) is favored with respect to the same situation but in the presence of non-ion-pairing cations. Thus, the metal nature also controls the deviation toward the side mechanism through its influence on the nucleophile reactivity. Conversely, when the nucleophile is a free anion, the metal cation has no influence (Eq. 4 of Scheme 26) except if it makes ion pairs with the hahdes (Eq. 2 of Scheme 26) and thus controls the availability of free halide ions as described above. 

Strong nucleophilic reagents (e.g., OH" and RO") favour Sj,2 mechanism as they are powerful enough to pushout the halide ion. Weak nucleophilic reagents favour S l mechanism as they can attack the already formed carbocation more readily... 

The hydrolysis of primary halides by OH ions as nucleophile takes place through S 2 mechanism in which product is said to have inversion in configuration. 

Carbon is partially bonded to both the incoming nucleophile and the departing halide at the transition state Progress is made toward the transition state as the nucleophile begins to share a pair of its electrons with carbon and the halide ion leaves taking with it the pair of electrons m its bond to carbon... 

Partial but not complete loss of optical activity m S l reactions probably results from the carbocation not being completely free when it is attacked by the nucleophile Ionization of the alkyl halide gives a carbocation-hahde ion pair as depicted m Figure 8 8 The halide ion shields one side of the carbocation and the nucleophile captures the carbocation faster from the opposite side More product of inverted configuration is formed than product of retained configuration In spite of the observation that the products of S l reactions are only partially racemic the fact that these reactions are not stereospecific is more consistent with a carbocation intermediate than a concerted bimolecular mechanism... 

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