Leaving group Subject

The factors that determine whether syn or anti elimination predominates are still subject to investigation. One factor that is believed to be important is whether the base is free or present in an ion pair. The evidence is that an ion pair promotes syn elimination of anionic leaving groups. This effect can be explained by proposing a transition state in which the anion functions as a base and the cation assists in the departure of the leaving group. 

The parameters Ci, t2 were postulated to be dependent only upon the substrate, and d, d2, upon the solvent. A large body of kinetic data, embodying many structural types and leaving groups, was subjected to a statistical analysis. In order to achieve a unique solution, these arbitrary conditions were imposed cj = 3.0 C2 for MeBr Cl = C2 = 1.0 for f-BuCl 3.0 Ci = C2 for PhsCF. Some remarkably successful correlations [calculated vs. experimental log (fc/fco)l were achieved, but the approach appeared to lack physical significance and was not much used. Many years later Peterson et al. - showed a correspondence between Eqs. (8-69) and (8-74) in particular, the very simple result di + d, = T was found. 

The scope of heteroaryne or elimination-addition type of substitution in aromatic azines seems likely to be limited by its requirement for a relatively unactivated leaving group, for an adjacent ionizable substituent or hydrogen atom, and for a very strong base. However, reaction via the heteroaryne mechanism may occur more frequently than is presently appreciated. For example, it has been recently shown that in the reaction of 4-chloropyridine with lithium piperidide, at least a small amount of aryne substitution accompanies direct displacement. The ratio of 4- to 3-substitution was 996 4 and, therefore, there was 0.8% or more pyridyne participation. Heteroarynes are undoubtedly subject to orientation and steric effects which frequently lead to the overwhelming predominance of... 

Since heteroarynes are thus seen to be subject to strong orientation effects, the detection of the occurrence of the aryne mechanism and the evaluation of the extent of its participation require a special approach. Both the aryne and Sj Arl mechanisms can occur together, and variation of the leaving group on a substrate (e.g., 2-halonaphthalenes) can cause a complete shift from the aryne (2-chloro, -bromo, and -iodo) to the Sj Arl mechanism (2-fluoro) see also Section II, D, 1. 

These pyridazines are subject to direct deactivation of the leaving group. It would appear from the conditions used in its reactions with ammonia (115°) and methylamine (50°) that 4-chloro-2-ethylthiopyrimidine (225) is somewhat deactivated (indirect). In various aminations of pyrimidines, the effect of an alkylthio group seems to be very mildly deactivating, like that of methyl groups. However, these surmises from the conditions used are not as reliable as the direct qualitative comparison described above and the kinetic data. 

To derive the maximum amount of information about intranuclear and intemuclear activation for nucleophilic substitution of bicyclo-aromatics, the kinetic studies on quinolines and isoquinolines are related herein to those on halo-1- and -2-nitro-naphthalenes, and data on polyazanaphthalenes are compared with those on poly-nitronaphthalenes. The reactivity rules thereby deduced are based on such limited data, however, that they should be regarded as tentative and subject to confirmation or modification on the basis of further experimental study. In many cases, only a single reaction has been investigated. From the data in Tables IX to XVI, one can derive certain conclusions about the effects of the nucleophile, leaving group, other substituents, solvent, and comparison temperature, all of which are summarized at the end of this section. 

Alkylation reactions are subject to the same constraints that affect all Sn2 reactions (Section 11.3). Thus, the leaving group X in the alkylating agent R—X can be chloride, bromide, iodide, or tosylate. The alkyl group R should be primary or methyl, and preferably should be allylic or benzylic. Secondary halides react poorly, and tertiary halides don t react at all because a competing E2 elimination of HX occurs instead. Vinylic and aryl halides are also unreactive because backside approach is sterically prevented. 

This approach allows one to functionalize the j3-C atom of AN. For this purpose, AN are initially subjected to double silylation to prepare BENAs, which are then coupled with various stabilized carbocations (512, 513), as well as with sulfenyl and episulfonium cations (514). Molecules containing good leaving groups (e.g., arenesulfenyl chlorides (514)) are used as sources (or precursors) of... 

Bimolecular reactions of aniline with /V-acyloxy-/V-alkoxyamides are model Sn2 processes in which reactivity is dictated by a transition state that resembles normal Sn2 processes at carbon. Electronic influences of substituents support a non-synchronous process which has strong charge separation at the transition state and which is subject to steric effects around the reactive centre, at the nucleophile but not on the leaving group. The sp3 character of nitrogen and disconnection between the amino group and the amide carbonyl renders these reactions analogous to the displacement of halides in a-haloketones. 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

Azide ion is a modest leaving group in An + Dn nucleophilic substitution reactions, and at the same time a potent nucleophile for addition to the carbocation reaction intermediate. Consequently, ring-substituted benzaldehyde g m-diazides (X-2-N3) undergo solvolysis in water in reactions that are subject to strong common-ion inhibition by added azide ion from reversible trapping of an o -azido carbocation intermediate (X-2 ) by diffusion controlled addition of azide anion (Scheme... 

Low basicity, even in combination with a reasonably stable carbonium ion intermediate, will not permit general acid catalysis if the leaving group is not sufficiently good. Thus, hydrolysis of benzaldehyde methyl S-phenyl thioacetals [67] is not subject to general acid catalysis (Fife and Anderson, 1970) even though... 

Alkyl azides are conveniently prepared from the reaction of alkali metal azides with an alkyl halide, tosylate, mesylate, nitrate ester or any other alkyl derivative containing a good leaving group. Reactions usually work well for primary and secondary alkyl substrates and are best conducted in polar aprotic solvents like DMF and DMSO. The synthesis and chemistry of azido compounds is the subject of a functional group series. ... 

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