The Ortho Effect on the Acidic and Alkaline Hydrolysis of Substituted Formanilides

Abstract

The kinetics of formanilides hydrolysis were determined under first-order conditions in hydrochloric acid (0.01-8 M, 20-60°C) and in hydroxide solutions (0.01-3 M, 25 and 40°C). Under acidic conditions, second-order specific acid catalytic constants were used to construct Hammett plots. The ortho effect was analyzed using the Fujita-Nishioka method. In alkaline solutions, hydrolysis displayed both first-and second-order dependence in the hydroxide concentration. The specific base catalytic constants were used to construct Hammett plots. Ortho effects were evaluated for the first-order dependence on the hydroxide concentration. Formanilide hydrolyzes in acidic solutions by specific acid catalysis, and the kinetic study results were consistent with the A AC 2 mechanism. Ortho substitution led to a decrease in the rates of reaction due to steric inhibition of resonance, retardation due to steric bulk, and through space interactions. The primary hydrolytic pathway in alkaline solutions was consistent with a modified B AC 2 mechanism. The Hammett plots for hydrolysis of meta-and para-substituted formanilides in 0.10 M sodium hydroxide solutions did not show substituent effects; however, ortho substitution led to a decrease in rate constants proportional to the steric bulk of the substituent. C 2015 Wiley Periodicals, Inc. Int J Chem Kinet 47: [471][472][473][474][475][476][477][478][479][480][481][482][483][484][485][486][487][488] 2015

1-(Acylamino)alkylphosphonic Acids—Alkaline Deacylation

“…A kinetic study has been conducted on the alkaline hydrolyses of several types of amides, including formanilides [ 58 , 59 ], N -methylformanilides and N -acetanilides [ 60 ], 1,8-bis(trifluoroacetylamino)-naphthalene [ 61 ] also in addition to N -methylacetamide, N -methylbenzamide and acetanilide [ 62 ]. A mild protocol for the alkaline hydrolysis of secondary and tertiary amides in non-aqueous conditions at room temperature or under reflux has been recently described [ 63 ].…”

Acidic and alkaline bimolecular hydrolysis of substituted formanilides. Computational analysis and modelling of substitution effects

“…1. Hammett substituent constants (s p , s m ) (Hansch et al, 1991), acidic hydrolysis rate constants (k H ) (Desai et al, 2015) and corresponding B3LYP(water) reaction enthalpies (Δ r H). Tab.…”

“…Correlation coefficients evaluated for the linear regressions are lower than 0.70. As it was reported by Desai and Kirsch (2015), the possible linear dependence can be evaluated only between log k obs and the Taft-Kutter-Hansch steric substituent values, E s .…”

“…The amide bond in the formanilides and acetanilides is isolated, freely rotating, and it does not have any significant steric restrictions due to the acyl component of the moiety. Hydrolytic reactivity of formanilide and its 28 ring substituted derivatives with respect to the selected monosubstituted positions in acidic and alkaline environments was studied experimentally (Desai et al, 2015). In di-lute hydrochloric acid (0.01-8 M, 20-60 °C), the hydrolytic degradation runs via the acid catalysed acyl cleavage bimolecular A AC 2 mechanism.…”

Silver-Mediated Decarboxylation Reactions: Expanding Reaction Scope through Kinetic Analysis

“…The use of multiple of these parameters is also seen in literature. Multivarient LFERs such as the Fujita-Nishioka 22 equation have been used for a number of different transformations, including ester hydrolysis, [81,82] formanilide hydrolysis, [83] benzamide hydrolysis, [84] and Ag-catalyzed decarboxylation of benzoic acids. [52] As mentioned in section 1.4, the Fujita-Nishioka equation is a LFER allowing for the analysis of differently substituted benzoates (ortho-, meta-, para-, and multi-substituted) as a single data set.…”