Leaving group reactivity

Unsymmetrically substituted dipyrromethanes are obtained from n-unsubstitued pyrroles and fl(-(bromomethyl)pyiToIes in hot acetic acid within a few minutes. These reaction conditions are relatively mild and the o-unsubstituted pyrrole may even bear an electron withdrawing carboxylic ester function. It is still sufficiently nucleophilic to substitute bromine or acetoxy groups on an a-pyrrolic methyl group. Hetero atoms in this position are extremely reactive leaving groups since the a-pyrrolylmethenium( = azafulvenium ) cation formed as an intermediate is highly resonance-stabilized. 

Allylic amine is a less reactive leaving group[7], but the allylic ammonium salts 214 (quaternary ammonium salts) can be used for allylalion(l30,131]. Allylic sulfonium salts are also used for the allylation[130]. The allylic nitrile in the cyclic aminonitrile 215 can be displaced probably via x-allylic complex formation. The possibility of the formation of the dihydropyridinium salts 216 and subsequent conjugate addition are less likelyfl 32],... 

It is evident from the foregoing sections that simple alkylvinyl halides do not react via an Sn 1 mechanism, if at all, even under extreme solvolytic conditions (146,149). More reactive leaving groups, such as arylsulfonates, were clearly needed to investigate the possible solvolytic behavior of simple alkylvinyl systems, but the preparation of vinyl sulfonates until recently was unknown. Peterson and Indelicato (154) were the first to report the preparation of vinyl arylsulfonates via reaction of the appropriate disulfonate with potassium t-butoxide in refluxing f-butanol. They prepared and investigated the solvolysis of 1-cyclohexenyl tosylate 169 and c/s-2-buten-2-yl tosylate 170 and the corresponding p-bromobenzenesulfonates (brosylates). Reaction... 

Provides an intermediate with a reactive leaving group already incorporated. 

Slightly smaller p values are obtained with more polar solvents, where the medium is able to stabilize the transition state more effectively, and thus the response to the electronic effects of substituents is less critical. For the alkaline hydrolysis of the phenyl esters of substituted benzoates in 33% aqueous acetonitrile Kirsch et al.235 find p = 1.98. The value is not significantly different for more or less reactive leaving groups under the same conditions... 

Several methods for the formation of amide bonds have been discussed in Sections 18-7A and 24-3 A. The most general reaction is shown below, in which X is some reactive leaving group (see Table 24-1) ... 

Addition of BHT and employment of milder conditions achieved by either selection of more reactive leaving group or effective additives may improve the selectivity. 

Affinity labels (RL) consist of a biologically active moiety (R), capable of forming a reversible complex with a given protein (P) and a properly positioned, chemically reactive leaving group (L) The affinity label interacts with the protein counterpart resulting in an irreversible protein-ligand complex (see Fig. 9)... 

P. .. protein, R—L. .. affinity label (R. .. biologically active moiety, L. .. chemically reactive leaving group) (R roduced by kind permission of Academic Press... 

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