Skip to main content
U.S. flag

An official website of the United States government

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

Rapid Fixation of Methylene Chloride By a Macrocyclic Amine



J C. Lee, Keith J. Stanger, Bruce C. Noll, Carlos A. Gonzalez, M Marquez, Bradley D. Smith


A simple macrocyclic amine is alkylated by methylene chloride to give a quaternary ammonium chloride salt. When methylene chloride is the solvent, the reaction exhibits pseudo first order kinetics, and the reaction half-life at 25.0 C is 2.0 minutes. The reaction half-life for a structurally related, acyclic amine is approximately 50,000 times longer. Detailed calculations favor a mechanism where the methylene chloride associates with the macrocycle to form an activated pre-reaction complex. The macrocyclic nitrogen subsequently attacks the methylene chloride 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. X-ray crystal structures of the starting amine and the product salt, as well as kinetic data, support this mechanism.
Journal of the American Chemical Society
No. 12


Ab initio molecular orbitals, C-CI activation, halide removal, macrocycles, Menschutkin reaction, supermolecule


Lee, J. , Stanger, K. , Noll, B. , Gonzalez, C. , Marquez, M. and Smith, B. (2005), Rapid Fixation of Methylene Chloride By a Macrocyclic Amine, Journal of the American Chemical Society (Accessed May 19, 2024)


If you have any questions about this publication or are having problems accessing it, please contact

Created February 28, 2005, Updated October 12, 2021