Supramolecular Enhancement of the Menshutkin Reaction

This dissertation describes an acceleration of the Menshutkin reaction, a distortion of halide leaving group order, and fluorescence sensing of chloroalkanes. The first section is the unprecedentedly accelerated Menshutkin reaction of new designed macrocyclic amines with haloalkanes. When methylene chloride is the solvent, the reaction exhibits pseudo first order kinetics, and the reaction half-life at 25 Ìâå¡C is 2.0 min. The reaction half-life for a structurally related acyclic amine is approximately 50,000 times longer. The second section demonstrates a major distortion of the halide leaving group order. For example, with benzyl halides the relative leaving group order with a control amine is Cl (1.0) < Br (71) < I (160), whereas the leaving group order with the macrocyclic amine is I (0.4) < Cl (1.0) < Br (8.5). Enzyme-like mechanistic studies indicate that haloalkanes associate with the macrocycle to form an activated pre-reaction complex. The macrocyclic nitrogen subsequently attacks the haloalkanes with a classic SN2 trajectory, and although the carbon-chlorine bond breaks, the chloride leaving group does not separate from the newly formed cationic macrocycle, such that the product is a tightly associated ion-pair. In additon, the free energy of activation is selectively decreased for organohalides having smaller and more charge dense leaving groups. Likely reasons for this selective enhancement effect are: (a) increased transition-state stabilization due to hydrogen bonding in the macrocyclic pocket and (b) reduced entropic penalty in the transition state due to an increased fraction of pre-reaction complexes that are oriented in a near attack conformation. The last portion of this dissertation describes as PET fluorescent sensors two structurally related macrocyclic amines with naphthalene groups for reactive chloroalkanes, including the common industrial solvent methylene chloride and carcinogenic chloromethyl methylether.