Neighboring group effects reaction mechanism

When the 3-bromo-2-butanol with the stereochemical structure A is treated with concentrated HBr, it yields meso-2,3-dibromobutane a similar reaction of the 3-bromo-2-butanol B yields ( )-2,3-dibromobulane. This classic experiment performed in 1939 by S. Winstein and H. J. Lucas was the starting point for a series of investigations of what are called neighboring group effects. Propose mechanisms that will account for the stereochemistry of these reactions. 

The Prins reaction often yields stereospecifically the and-addition product this observation is not rationalized by the above mechanism. Investigations of the sulfuric acid-catalyzed reaction of cyclohexene 8 with formaldehyde in acetic acid as solvent suggest that the carbenium ion species 7 is stabilized by a neighboring-group effect as shown in 9. The further reaction then proceeds from the face opposite to the coordinating OH-group " ... 

El reaction and, 392 E2 reaction and, 386 S l reaction and, 373-374 Sjxj2 reaction and, 362-363 Kishner, N. L. 715 Knoevenagel reaction, 913 Knowles, William S., 734, 1027 Kodel, structure of, 1222 Koenigs-Knorr reaction, 990 mechanism of, 990 neighboring-group effect in, 990-991... 

A reaction that offers a closer parallel to the neighboring group effect of carbonium ion chemistry is a possible concerted mechanism for the Michael rearrangement ... 

In a few reactions, nucleophilic substitution proceeds with retention of configuration, even where there is no possibility of a neighboring-group effect. In the SNi mechanism (substitution nucleophilic internal) part of the leaving group must be able to attack the substrate, detaching... 

During the period between 1927 and 1940, in collaboration with Ward Pigman and Harriet Frush, Isbell recognized for the first time the important role that neighboring-group effects play in substitution reactions. The formation of methyl 3,6-anhydro-j3-D-glucoside via an intermediate 2,3-anhydro-alloside was elegantly explained by the mechanism shown in Fig. 5. 

Figure 25.6 Mechanism of the Koenigs-Knorr reaction, showing the neighboring-group effect of a nearby acetate.

These studies involved the concept of neighboring-group effects and laid the basis for interpretations of reaction mechanisms that were later to be developed by other carbohydrate chemists and then, eventually, be adopted by organic chemists in general. 

The neighboring-groups effect , which is exhibited in the change of the mechanism and kinetics of the reaction due to the change in the immediate entiron-ment of the functioiud group upon conversion. 

The formation of the wrong stereoisomer is the clue to the operation of a neighboring group effect in the reaction of Figure 21.21. The product is formed not with the inversion of configuration required by the mechanism, but with retention (clue 1). After the hydroxyl group is protonated, it is displaced not by an external bromide ion, but by the bromine atom lurking in the same molecule (Fig. 21.22). It is most important at this point to keep the stereochemical relationships clear. Displacement must be from the rear, as this is an intramolecular Sn2 reaction. 

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