Catalytic hydrogenation of persubstituted p-nitrosophenols

Abstract

Catalytic hydrogenation of dialkyl 2-hydroxy-4,6-dimethyl-5-nitrosobenzene-1,3-dicarboxylates over Pd/C gave the corresponding previously unknown dialkyl 5-amino-2-hydroxy-4,6-dimethylbenzene-1,3-dicarboxylates. The first-order rate constants for the hydrogenation process were found to be linearly related to steric constants of the alkyl groups. Scheme 1. R = Me (a), Et (b), Pr (c), Bu (d).We previously reported on exhaustively substituted nitrosophenols having ethoxycarbonyl groups in the ortho positions with respect to the hydroxy group [1,2]. We synthesized analogous nitrosophenols with methoxy-, propoxy-, and butoxycarbonyl groups and performed their hydrogenation with a view to obtain new p-aminophenols. The expected products contain both salicylic acid ester and p-aminophenol fragments that are typical of known medicines [3]; therefore, they attracted interest from the viewpoint of synthesis of biologically active compounds.Dialkyl 2-hydroxy-4,6-dimethyl-5-nitrosobenzene-1,3-dicarboxylates Ia-Id were subjected to hydrogenation over carbon-supported palladium in anhydrous ethyl acetate. The reactions were carried out in a reduction cell maintained at a constant temperature.The cell was charged with the solvent, initial nitrosophenol, and catalyst, and hydrogen (from a steel cylinder) was bubbled through the mixture. The target products were isolated as follows: the reaction mixture was filtered from the catalyst and was saturated with dry hydrogen chloride. Dialkyl 5-amino-2-hydroxy-4,6-dimethylbenzene-1,3-dicarboxylate hydrochlorides separated from the solution and were filtered off.We also performed kinetic measurements. Kinetic curves were plotted for the consumption of hydrogen, and dependences of ln(V o -V x ) versus time were obtained. The regression equation for the hydrogenation of compound Ia was as follows: y = -0.05 x + 3.38, r = 0.994. The dependences for other substituted nitrosophenols Ib-Id of this series were also linear and were characterized by high correlation coefficients, indicating that catalytic hydrogenation of compounds Ia-Id under the given conditions conforms to first-order kinetics. From the obtained dependences we calculated the first-order rate constants (k, s -1 ) for hydrogenation of all the examined dialkyl 2-hydroxy-4,6-dimethyl-5-nitrosobenzene-1,3-dicarboxylates Ia-Id: Ia, 5.01; Ib, 3.03; Ic, 0.92; Id, 0.83. It is seen that the hydrogenation rate constant strongly depends on the length of the alkyl radical in the ester moiety: it decreases in going from methyl to butyl esters.We revealed a linear relation between the logarithms of hydrogenation rate constants and steric constants of alkyl groups E s . The following steric constants E s were used: 0.00 (Me), -0.09 (Et), -0.30 (Pr), and -0.34 (Bu) [4]. The regression equation was y = 2.35 x + 1.30, r = 0.998. We can conclude that the difference in the rates of catalytic hydrogenation is determined exclusively by the size of the alkyl group in the ester fragments.

Acidity of new exhaustively substituted p-nitrosophenols

“…Hydrogenation of such polysubstituted nitrosophenols makes it possible to readily obtain the corresponding exhaustively substituted aminophenols [3] which are used in the synthesis of modern antiarrhythmic agents [4]. On the other hand, the acidity of compounds I was not studied.…”