Anisole cyclodextrin catalysis

From all this we concluded that the catalysis by cyclodextrin involves the reversible formation of a cyclodextrin hypochlorite (64), which can transfer chlorine to the anisole para position but cannot reach the ortho position. The reaction is faster when the RO-Cl group is held closer and more rigidly in the smaller a-cyclodextrin. 

Cyclodextrins exhibit remarkable ortho-para selectivity in the chlorination of aromatic compounds by hypochlorous acid (HOCl) [22] (Scheme 5). Chlorination takes place via formation of a covalent intermediate, a hypochlorite ester of cyclodextrin. In the chlorination of anisole by hypochlorous acid, pura-chlorination occurs almost exclusively in the presence of sufficient cyclodextrin, although in control experiments maltose had no effect on the product ratio. For example, selectivity for para-chlorination in the presence of 9.4 X 10 M a-cyclodextrin is 96%, which is much larger than that in the absence of a-cyclodextrin (60%). In the proposed mechanism, one of the secondary hydroxyl groups reacts with HOCl to form a hypochlorite ester, which attacks the sterically favorable para position of the anisole molecule included in the cyclodextrin cavity in an intracomplex reaction. The participation of one of the secondary hydroxyl groups at the C-3 position in the catalysis was shown by the fact that dodecamethyl-a-cyclodextrin, in which all the primary hydroxyl groups and all the secondary hydroxyl groups at the C-2 positions are methylated, exhibited equal or larger ortho-para specificity than native a-cyclo-... 

Still completely blocked, but para chlorination has the same rate as it has in free solution. With 10 mM j5-cyclodextrin anisole is only 59% bound, not 72%, and the para/ortho chlorination ratio becomes only 3.8 1, not 21.6 1 as with a-cyclodextrin. Thus, the catalysis of para chlorination in the a-cyclodextrin complex is promoted by rigid inclusion of the anisole into a tight-fitting cavity. 

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