Kinetics of the formation of N-isobutylidenemethylamine from isobutyraldehyde and methylamine in aqueous solution

Abstract

Stopped-flow spectrophotometric measurements on the reaction of isobutyraldehyde with methylamine in water at 35°over the pH range 10.1-11.5 gave a value of 8.5 ± 0.5 M-1 for the equilibrium constant for addition of the amine to the aldehyde, and a value of 6.2 ± 0.7 sec-1 for kc, the rate constant for dehydration of the carbinolamine to N-isobutylidenemethylamine. Kinetic studies of methylammonium chloride catalysis of the oximation of isobutyraldehyde at pH 8.5-9.8 gave values of kcKc* in agreement with the stopped-flow measurement, but at pH 7.6 larger values were obtained, suggesting acid catalysis of the dehydration of the carbinolamine. The equilibrium constant for the addition of hydroxylamine to isobutyraldehyde was found to be 105 ± 11 M~\ and the rate constant for dehydration of the adduct to give oxime fit the equation kd = (6.5 X 105[H+] + 3.2 X 10~12/ [H+] + 4.6 X 10-3) sec-1. A kinetic study of the hydration of isobutyraldehyde in the presence of N-methylmorpholine buffers showed that the reaction was fast enough that the hydration-dehydration equilibrium could be treated as continually established throughout the studies of the reaction of isobutyraldehyde. Structural effects on equilibrium constants for addition to isobutyraldehyde are discussed.

Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives

“…(b) Carbinolammonium B can then either be converted back into starting material involving basemediated deprotonation of the OH group, or, via its conjugate base, carbinolamine C, undergo rate-determining acid-medicated dehydration to iminium D. Similarly, Hine and coworkers have shown that acid-mediated dehydration of carbinolamines derived from aldehydes and primary amines to give the corresponding iminium ion is rate determining in acidic to neutral aqueous solution. 20 (c) In D 2 O, the corresponding OD group of carbinolammonium B undergoes dedeuteronation at a slower rate owing to a primary isotope effect, thus leading to greater partitioning of carbinolamine C into iminium D and a faster rate of exchange, a situation that manifests as a large inverse solvent isotope effect. Large inverse solvent isotope effects are rare but are observed in E1cB reactions, where rate-determining expulsion of the βpositioned leaving group competes with protonation of the intermediate carbanion.…”

Mechanisms of the formation of imines in aqueous solution and the effect of the pH: a theoretical analysis

“…For pH < 3.2 the decomposition occurs mainly via TS5H and above of this pH the process occurs mainly via TS5. Based on the above equations, the concentration of MS3H+ can be written as: (10) Thus, in pH = 7, we can estimate that [MS3H + ] = 5 x 10 -6 [MS1H + ][MS2], confirming the very low concentration of this stationary species. Based on the above analysis, the reaction rate for formation of the product is the same reaction rate for decomposition of the initial reactants (slow step) and is given by: (11) Equation ( 11) point out that the reaction is first order in both amine and aldehyde and the reaction rate increases with the pH until it reaches 10.6, the pKa of methylamine.…”

“…The mechanism and kinetics of this reaction has been experimentally investigated by Cordes and Jencks 9 and also by Hine and coworker. [10][11] The reaction proceeds quickly in aqueous solution. For example, in the addition of methylamine to isobutyraldehyde, the experiments have indicated that the rate-determining step in a medium with pH = 10.1 to 11.5 is the carbinolamine decomposition with a rate constant of 6.2 s -1 , which translate to a G ‡ barrier of 16.4 kcal mol -1 .…”

“…19 Furthermore, the calculated barrier in the carbinolamine dehydration step is 10 kcal mol -1 above of the experimental value for a similar system. 10 Szefczyk et al reported the reaction between methylamine and acetaldehyde at B3LYP level. 15 Solvent effect was included through just adding one explicit water and free energies were not provided.…”

Glykosylierte Hämoglobine - Bildung und Beseitigung der Aldiminform

“…Diese Autoren konnten zeigen, daß Schiffsche Basen .aus nichtaromatischen Aldehyden und Aminen bei schwach saurem pH-Wert labil sind. Andere Autoren (15)(16)(17) …”