Steric effects on the mechanism of reaction of nucleophilic substitution of β‐substituted alkoxyvinyl trifluoromethyl ketones with four secondary amines

Abstract

AbstractThe kinetics of the reaction of β‐substituted β‐alkoxyvinyl trifluoromethyl ketones R1O‐CR2CH‐COCF3 (1a–e) [(1a), R1C2H5, R2H; (1b), R1R2CH3; (1c), R1C2H5, R2C6H5; (1d), R1C2H5, R2V−pNO2C6H4; (1e), R1C2H5, R2C(CH3)3] with four aliphatic amines (2a–d) [(2a), (C2H5)2NH; (2b), (i‐C3H7)2NH; (2c), (CH2)5NH; (2d), O(CH2CH2)2NH] was studied in two aprotic solvents, hexane and acetonitrile. The least reactive stereoisomeric form of (1a–d) was the most populated (E‐s‐Z‐o‐Z) form, whereas in (1e), the more reactive form (Z‐s‐Z‐o‐Z) dominated. The reactions studied proceeded via common transition state formation whose decomposition occurred by ‘uncatalyzed’ and/or ‘catalyzed’ route. Shielding of the reaction centre by bulky β‐substituents lowered abruptly both k′ (‘uncatalyzed’ rate constant) and k″ (‘catalyzed’ rate constant) of this reaction. Bulky amines reduced k″ to a greater extent than k′ as a result of an additional steric retardation to the approach of the bulky amine to its ammonium ion in the transition state. An increase in the electron‐withdrawing ability of the β‐substituent increased ‘uncatalyzed’ k′ due to the acceleration of the initial nucleophile attack (k1) and ‘uncatalyzed’ decomposition of transition state (k2) via promoting electrophilic assistance (through transition state 8). The amine basicity determined the route of the reaction: the higher amine basicity, the higher k3/k2 ratio (a measure of the ‘catalyzed’ route contribution as compared to the ‘uncatalyzed’ process) was. ‘Uncatalyzed’ route predominated for all reactions; however in polar acetonitrile the contribution of the ‘catalyzed’ route was significant for amines with high pKa and small bulk. Copyright © 2007 John Wiley & Sons, Ltd.