Selective Aromatic Substitution Directed by Cyclodextrin Complexing

1 Selective Aromatic Substitution Directed by Cyclodextrin Complexing 

In the full study [64], it was found that a lesser but similar effect was seen with j8-cyclodextrin (cycloheptaamylose), which has a larger cavity in which anisole is both more weakly and more flexibly bound. Within this looser complex, ortho chlorination is 

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. 

As a test of this mechanism, the coupling of p-benzenediazonium sulfonate 21 with phenol was examined. In solution it couples in the para position, but a-cyclodextrin 

One interesting feature of this work is that the enzyme chlorinase also can chlorinate anisole in water solution, but it gives a random mixture of ortho and para products [65]. Apparently the enzyme merely makes a chlorinating reagent, probably HOCl, and this then acts on the unbound anisole in free solution. However, the selectivity seen in our anisole complex chlorination is typical of that seen in other enzymes that do indeed direct reactions by geometric control within an enzyme-substrate complex. 

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