Dramatic Acceleration of the Menschutkin Reaction and Distortion of Halide Leaving-Group Order

Abstract

Compared to structurally related linear trialkylamines, a simple macrocyclic amine with an anion-binding cavity exhibits very large rate enhancements (>10(5)) for stoichiometric N-alkylation with primary alkyl, allyl, and benzyl halides in the weakly polar solvent CDCl3. There is also 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) < Br (71) < I (160), whereas the leaving-group order with the macrocyclic amine is I (0.4) < Cl (1) < Br (8.5). Reaction with the macrocyclic amine is inhibited by the addition of DMSO, which is unusual because the Menschutkin reaction is normally enhanced by the presence of a polar aprotic solvent. Competitive inhibition studies indicate that the reaction proceeds through a prereaction complex. Effective molarities for the subsequent unimolecular N-alkylation step with 4-t-butylbenzyl halides are 4-t-BuBnCl (62,000 M) > 4-t-BuBnBr (2200 M) > 4-t-BuBnI (35 M); thus, 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 prereaction complexes that are oriented in a near attack conformation. The study suggests that it should be possible to develop highly reactive macrocyclic amines that selectively sense or scavenge carcinogenic haloalkanes from the atmosphere.

Kinetic Modeling of Palmitamidopropyl Betaine Synthesis

“…In the acylation reaction, carboxylic acids containing carbonyl carbon in their molecules reacted with amine existed in the nucleophiles, because normally the carbonyl carbon atom is electropositive to some extent (Fox, Dmitrenko, Liao, & Bach, 2004;Procopiou, Baugh, Flack, & Inglis, 1998;Richard, Guillaume, & Jacquin, 2016;Sarvari & Sharghi, 2004). Moreover, in the quaternization reaction, the tertiary amine, as a nucleophile, was converted to a quaternary ammonium salt by reacting with halogenated hydrocarbon (the Menshutkin reaction in organic chemistry) (Ishida & Kato, 2003;Mekala & Goli, 2015;Stanger, Lee, & Smith, 2007). The acylation reaction and the quaternization reaction followed the S E 2 reaction mechanism (Hill, Rendina, & Puddephatt, 1995) and the S N 2 reaction mechanism (Bentley, Llewellyn, & McAlister, 1996), respectively.…”

Rotaxanes Based on the 1,2‐Bis(pyridinio)ethane–24‐Crown‐8 Templating Motif

“…The best yields were always with DB24C8 while those for 24C8 were reduced, presumably because the K a is lower for pseudorotaxane formation [38] while the lower yields for rotaxanes containing DN24C8 were attributed to the relatively poor solubility of this www.eurjoc.orgcrown which limits its concentration in the reaction solution. [38] Since it is known that microwave (μW) energy can drastically accelerate the Menshutkin reaction [51][52] used to add the tert-butylbenzyl stoppers, a commercial μW reactor was employed for [2]rotaxane formation involving DB24C8. Using the same two layer system and optimization for time and temperature improved the yield to essentially quantitative (NMR) while reaction times were reduced to 20 min.…”

A C18 Quaternary Ammonium Library

“…Obviously, this involves formation of a negatively charged counter ion, thus forming an ion pair. In accordance with the S N 2 mechanism, the reaction is accelerated by more nucleophilic amines, increased leaving group ability, increased pressure and elevated temperatures (Figure ) . Polar solvents also kinetically enhance the reaction by stabilizing the charged transition state .…”

“…In accordance with the S N 2 mechanism, the reaction is accelerated by more nucleophilic amines, increased leaving group ability, increased pressure and elevated temperatures ( Figure 1). [9] Polar solvents also kinetically enhance the reaction by stabilizing the charged transition state. [10] With alkyl tosyl or mesylates, the reaction is often carried out at lower temperatures and in polar protic solvents in order to avoid a competing elimination reaction.…”