Ring-closure reactions. Part 23. Kinetics of formation of three- to seven-membered-ring N-tosylazacycloalkanes. The role of ring strain in small- and common-sized-ring formation

Abstract
Rates of cyclisation of a series of anions derived from N-tosyl-ω-bromoalkylamines to nitrogen heterocycles with three to seven members in Me2SO–H2O (99 : 1) have been studied. Rates vary markedly with ring size in the order 5 > 3 > 6 > 7 ∼ 4. First-order rate constants for cyclisation have been translated into effective molarities (EM) with reference to an appropriate intermolecular model reaction. Comparison of the present results with available literature data on SN2 ring-closure reactions leading to small- and common-sized rings reveals that the ease of formation of three-membered rings is much more structure-dependent than that of the higher homologues. This remarkable behaviour is believed to parallel the unique way in which the stability of three-membered rings is affected by structure. As a rule, the ease of cyclisation appears to bear an inverted relationship to the assumed strain energy of the ring product. The apparent opposition of this rule to earlier conclusions in the literature is discussed.

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