One of the effects of transannular strain is the difficulty of synthesizing medium-sized rings. Illuminati et al. have studied the kinetics of intramolecular ring closing using the simple nucleophilic substitution reaction of ortho-bromoalkoxyphenoxides. Specifically, they studied the ring closing of 5 to 10 carbon cyclic ethers. They found that as the number of carbons increased, so did the enthalpy of activation for the reaction. This indicates that strain within the cyclic transition states is higher if there are more carbons in the ring. Since transannular strain is the largest source of strain in rings this size, the larger enthalpies of activation result in much slower cyclizations due to transannular interactions in the cyclic ethers.