Reactions involving neighbouring groups

Capon (1964 Capon and McManus, 1976) introduced a simple classification for reactions involving neighbouring group participation, in which G-n indicates participation by a nucleophilic group G in an n-membered cyclic transition state. For present purposes an extension of this symbolism is necessary in order that the abbreviations indicate the electrophilic centre also. 

The mechanism of the novel transformation of a-nitro- to a-hydroxy-ketones has been probed. The reaction, which proceeds under basic aqueous conditions, requires that the Q -nitro substrate be CH-acidic in the a -position, and that it be readily depro-tonated under the conditions employed. NO2 -OH exchange occurs with retention of configuration, with the hydroxyl oxygen being predominantly derived from the solvent. A mechanism involving neighbouring-group participation, via a Favorskii-like cyclopropanone intermediate, is proposed. 

Reactions no. 8 [205] and no. 9 [206] of Table 5-9 show special behaviour. These reactions, which show larger medium effects, involve neighbouring group participation by the alkene or phenylthio groups in the homolytic cleavage of the O—O bond, as shown for the thermolysis of tert-butyl 2-(phenylthio)perbenzoate in Eq. (5-64) [206]. The... 

A novel variation on the Hanesslan-type reaction of certain benzylldene acetals with N -bromosuccinimide involves neighbouring-group participation by a trichloroacetlmidoyl group in the opening of an intermediate dloxolanylium ion. The reaction has been applied to the synthesis of the 3-amino-l,6-anhydro-3-deoxy-6-D-... 

The Mannich Reaction involves the condensation of formaldehyde with ammonia or a primary or secondary amine and with a third compound containing a reactive methylene group these compounds are most frequently those in which the methylene group is activated by a neighbouring keto group. Thus when acetophenone is boiled in ethanolic solution with paraformaldehyde and dimethylamine hydrochloride, condensation occurs readily with the formation of... 

The overall reaction involves replacing the halogen atom of the alkyl halide with an NH, unit. Another method is the Gabriel synthesis of amines. This involves treating phthalimide with KOH to abstract the N-H proton. The N-H proton of phthalimide is more acidic (pK9) than the N-H proton of an amide since the anion formed can be stabilised by resonance with both neighbouring carbonyl groups. The phthalimide ion can then be alkylated by treating it with an alkyl halide in nucleophilic substitution. 

How do we know that neighbouring group participation is taking place Well, the first bit of evidence is the increase in rate. The neighbouring groups will become involved only if they can increase the rate of the substitution reaction—otherwise the mechanism will just follow the ordinary S 2 pathway. But more important information comes from reactions where stereochemistry is involved, and one of these is the last of the four examples above. Here it is again in more detail. Not only does the first of these reactions go faster than the second—its stereochemical course is different too. 

The initial suggestion that a remote double bond could be involved in a displacement reaction was made by Shoppee in 1946 in order to account for the stereochemical results of the transformations of 3-cholesteryl derivatives Building on the considerable work then underway on neighbouring group participation in ionization reactions Shoppee suggested that the double bond in the cholesteryl system, 1, could function in a similar manner to Lewis base containing groups such as acetate or alkoxy, etc. 

In this section, we have seen the formation of three-membered ring intermediates when a neighbouring group participates in a reaction. We will now look at some other reactions involving three-membered rings, but this time ones that exist in either the starting material or the product, rather than just as an intermediate. 

This cyclic free radical has obvious similarities to the involvement of a neighbouring group in SN2 reactions. In those situations, the rate of the reaction was often increased, because of the favourable entropic factor. Normally in... 

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