Journal of Organic Chemistry p. 2153 - 2159 (1989)
Update date:2022-08-28
Topics:
Castro, Enrique A.
Ureta, Carmen
Second-order rate constants (kN) for the nucleophilic reactions of piperidine, morpholine, piperazine, and N-substituted piperazines with the title substrates are reported in water, at 25 deg C, ionic strength 0.2 M (maintained with KCl).The Broensted-type plot obtained for the aminolysis of phenyl thiolacetate is linear while that for the p-nitrophenyl derivative (NPTA) is curved, with the center of curvature at pKa=10.5 (pKa0).According to these results the most likely mechanism involves a zwitterionic tetrahedral intermediate (T+/-), for which decomposition to products is the rate-limiting step for all the reactions, except that of NPTA with piperidine.For this reaction the formation of T+/- is rate determining.A semiempirical equation based on the above hypothesis accounts for the Broensted-type curve obtained in the aminolysis of NPTA.Estimation of the microscopic rate constants involved, in a possible more general reaction scheme and evaluation of the pKa's of T+/- indicate that expulsion of the leaving group of the substrate from T+/- is faster than deprotonation of T+/- by a base, precluding therefore the formation of an anionic tetrahedral intermediate.The fact that pKa0=10.5 for the NPTA reactions means that an (hypothetical) amine of pKa=10.5 leaves T+/- as readily as p-nitrothiophenoxide ion (pKa=4.6).From these and other data it is calculated that the nucleofugality from T+/- of an amine of pKa=4.6 is ca. 3*104 times larger than that of p-nitrothiophenoxide ion.The estimated pKa0 values for the aminolysis of (hipothetical) aryl acetates with leaving groups of pKa=4.6 and 6.5 (the same pKa as thiophenol) are pKa0=8.0 and 9.0, respectively, which gives nucleofugality ratios (a given amine/aryl oxide ion) from the oxy T+/- smaller than those from the corresponding sulfur T+/-.It is claimed that expulsion of ArS- from T+/- is only slightly slower than that of an isobasic ArO- from the oxy T+/-.Therefore, the above results indicate that the "push" provided by ArS in T+/- to expel a given amine is much stronger than that exerted by an isobasic ArO in the oxy T+/-.Activation parameters are reported for the reactions of the title substrates with piperidine, piperazine, and N-formylpiperazine.
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