REACTIONS OF β-SUBSTITUTED AMINES-IV. KINETICS AND STEREOCHEMISTRY OF THE THERMAL REARRANGEMENT OF (S)-2-CHLOROMETYL-1-ETHYLPYRROLIDINE TO (R)-3-CHLORO-1-ETHYLPIPERIDINE, AND THE STEREO-CHEMICAL COURSE OF THEIR REACTIONS WITH NUCLEOPHILES

Article abstract of DOI:10.1016/S0040-4020(01)97976-1

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 law.The calculated E_a, ΔH(excit.) and ΔS(excit.) were 22+/-2 kcal/mole (25 deg C), 21+/-2.5 kcal/mole (25 deg C) and -10+/-2 e.u. (0 deg 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 100percent stereospecific with an uncertainity of about 1percent.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 4.8percent racemization, whereas the thermal rearrangement of (S)-1a to (R)-2a occurs with complete retention of absolute configuration.