Anchimeric Assistance in Ring Closure Reactions

Freundlich and Kroepelin measured the rates of reaction of a series of co-bromoalkylamines in water and found that their order of reactivity with ring size was 5 6 3 7 4 (Table 1). This order parallels that of analogous co-hydroxy and co-methoxy compounds. In 1936 Salomon discussed some of the above-mentioned complications that affect the interpretation of the rate data. He derived the relative rates for ring closure (Table 1) from a combination of kinetic and preparative experiments. Undoubltedly, modern analytical methods would have been beneficial to Salomon in dissecting the various rate processes. 

A similar ring closure order is observed when an arylamino group is the nucleophile (Table 2). The precursor for formation of the five-membered ring, PhNH(CH2)4Br, could not be obtained for rate studies. This may be a consequence of its fast rate of ring closure under the conditions of its synthesis. 

It is interesting to note that it is apparently an enthalapy of activation effect that results in the relative slow rate of formation of the azetidine from N-y-bromopropylaniline (see Table 2) since the measured AS values for three- and four-membered ring formation are identical. In each case a high yield of cyclic product is obtained, and hence the activation parameters are for the ring closure reaction. 

PhNH—(CH2) -i—Br, n = ring size (25°C) AH (kcal mole ) AS (cal mole °K ) %cyclic product  

Substrate fc ,(25°C) (kcal mole ) (cal mole °K %cyclic product  

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