Kinetics and Mechanism for Oxime Formation from Pyridine-2-, -3-, and -4-carboxaldehydes

Abstract

Oxime formation from pyridine-2-, -3-, and -4-carboxaldehydes occurs with Tate-limiting carbinolamine dehydration under both acidic and neutral conditions. Carbinolamine dehydration of pyridine-2carboxaldehyde occurs via a transition state bearing a single positive charge, unlike the corresponding reaction for formyl-l-methylpyridinium ion and the reaction under acidic conditions for pyridine-3and -4-carboxaldehydes.Although certain equilibrium constants2-3 456and rate constants3 for addition of amines to pyridinecarboxaldehydes and to structurally related aldehydes including

Kinetics and mechanism for oxime formation from 2-quinolinecarboxaldehyde

“…Previous investigations in this laboratory, have revealed that oxime formation from 2-, 3-, and 4-pyridinecarboxaldehydes occurs with rate-determining carbinolamine dehydration under acidic and neutral conditions [2]. Since 2-quinolinecarboxaldehyde is similar to 2-, 3-, and 4-pyridinecarboxaldehydes, it should be closely related in reactivity to them and it is reasonable to anticipate that the corresponding reaction of this substrate will occur with the same rate-limiting step.…”

“…This series of investigations was initiated with: (i) examination of the addition of semicarbazide, hydroxylamine, and phenylhydrazine to 2-, 3-, and 4-formyl-l-methylpyridinium ions, substrates in which the first factor does not enter and for which the second is less troublesome since the extent of substrate hydration becomes almost independent of pH [I] and (ii) examination of the addition of hydroxylamine to 2-, 3-, and 4-pyridinecarboxaldehydes, substrates in which both equilibria are presented [2]. We have elected to continue this work with an investigation of the addition of hydroxylamine to 2-quinolinecarboxaldehyde, consistent with the goal of understanding the mechanism and catalysis for imine formation from very activated aldehydes.…”

Kinetics and mechanism for oxime formation from 4-dimethylaminobenzaldehyde and 4-trimethylammoniobenzaldehyde iodide

“…On the other hand, a comparison between equilibrium constants in Table I and the same constants in oxime formation from pyridine-4-carboxaldehyde [4] and its N-methyl derivative [3] (Table 2) indicates that pyridinecarboxaldehydes have more affinity for the amine than 4-dimethylaminobenzaldehyde and its Nmethyl derivative. Note that in respect to 4-formyl-1-methylpyridinium ion, 4-trimethylammoniobenzaldehyde iodide has a 547-fold reduction in the equilibrium constant and an increment of 181-fold in the dehydration rate constant.…”

“…These include the addition of several amines to Nmethylpyridinecarboxaldehyde ions [3]; the addition of hydroxylamine to pyridine-2-, -3-, and 4-carboxaldehydes [4]; and to 2-quinolinecarboxaldehyde [5]. In the work described herein, attention is directed to oxime formation from 4-trimethylammoniobenzaldehyde iodide and 4-dimethylaminobenzaldehyde.…”

“…Such expulsion requires protonation of the leaving water molecule, and this requires formation of a dicationic specie. These arguments are reinforced by the behavior of oxime formation from the conjugate acids of pyridinecarboxaldehydes [4], 2-quinolinecarboxaldehyde [5] and by semicarbazone formation from the conjugate acid of pyridine-2-carboxaldehyde [6]. Pyridine-3-and 4-carboxaldehydes exhibit rate-limiting acid-catalyzed dehydration of their protonated carbinolamines (similar to the N-methyl derivatives) but the protonated carbinolamines from 2-quinolinecarboxaldehyde, and pyridine-2-carboxaldehyde prefer to lose a proton and then convert to the product, avoiding in this way the dicationic species.…”