Effects of CH3OH‐H2O and CH3OH solvents on rate of reaction of phthalimide with piperidine

Pseudo‐first‐order rate constants (k_obs) for the cleavage of phthalimide in the presence of piperidine (Pip) vary linearly with the total concentration of Pip (Pip]_T) at a constant content of methanol in mixed aqueous solvents containing 2% v/v acetonitrile. Such linear variation of k_obs against Pip]_T exists within the methanol content range 10%–～80% v/v. The change in k_obs with the change in Pip]_T at 98% v/v CH₃OH in mixed methanol‐acetonitrile solvent shows the relationship: k_obs = kPip]_T + kPip], where respective k and k represent apparent second‐order and third‐order rate constants for nucleophilic and general base‐catalyzed piperidinolysis of phthalimide. The values of k_obs, obtained within Pip]_T range 0.02–0.40 M at 0.03 M NaOH and 20 as well as 50% v/v CH₃OH reveal the relationship: k_obs = k₀/(1 + {k_nPip]/k_OX^?OX]_T}), where k₀ is the pseudo‐first‐order rate constant for hydrolysis of phthalimide, k_n and k_OX represent nucleophilic second‐order rate constants for the reaction of Pip with phthalimide and for the XO^?‐catalyzed cyclization of N‐piperidinylphthalamide to phthalimide, respectively, and ^?OX]_T = NaOH] + ^?OX_re], where ^?OX_re] = ^?OH_re] + CH₃O_re^?]. The reversible reactions of Pip with H₂O and CH₃OH produce ^?OH_re and CH₃O_re^? ions. The effects of mixed methanol‐water solvents on the rates of piperidinolysis of PTH reveal a nonlinear decrease in k with the increase in the content of methanol. © 2000 John Wiley & Sons, Inc. Int J Chem Kinet 33: 29–40, 2001