Reactions of β-substituted amines-IV: Kinetics and stereochemistry of the thermal to (r) 3-chloro-1-ethylpiperidine, and the stereo-chemical course of their reactions with nucleophiles

Abstract

The rate of the thermal rearrangement of ( S) 2 chloromethyl-1-ethylpyrrolidine [( S)- 1a] to ( R)-3-chloro-1-ethylpiperidine [( R) 2a] has been examined at three temperatures in benzene by PMR and polarimetry. The rearrangement was shown to be completely stereospecific and to obey a simple first order rate law. The calculated E a ΔH‡ and ΔS‡ were 22 ± 2 kcal mole (25°), 21 ± 2.5 kcal mole (25°) and - 10 ± 2 e.u. (0°K) respectively. The effect of solvents having differing dielectric constants was also studied. A transition state 9'a and an ion pair intermediate 3a are suggested for the rearrangement. The stereochemical course of the reactions of ( S)- 1a, (R)- 2a and ( S)- 2a with hydroxide and methoxide ions have been shown to be 100% stereospecific with an uncertainty of about 1%. The absolute configurations of all optically active reactants and products [(S)- and ( R)- 4a, ( S)- 4b ( R)- and ( S)- 5a, ( R)- 5b, ( S, S')- 6a, ( S, R')- 7a and ( R, R')- 8a] were established by chemical correlations with known compounds or by ORD and chemical inference. The ring opening of both the primary and secondary aziridinium ion positions of 1-azonia-1-ethylbicyclo [3.1.0]hexane [( S)- 3a] by nucleophiles proceeds entirely by S N2 processes. The conversion of ( R)-1-ethyl-3-hydroxypiperidine [( R)- 5a] to ( S)- 2a. HCl with thionyl chloride in chloroform proceeds by inversion with 4.8% racemization, whereas the thermal rearrangement of ( S)- 1a to ( R)- 2a occurs with complete retention of absolute configuration.