Kinetics and Mechanism of the Formation and Decomposition of Imidazolin-4-ones from 2-(N-Benzoylamino)alkanamides in Aqueous Medium

Abstract

The cyclization reactions of substituted 2-(N-benzoyl-N-methyl)aminoalkanamides 1a-1g have been studied in aqueous medium. The Hammett reaction constant is ρ = 1.4 for the cyclization reactions of compounds 1a-1e in sodium hydroxide solutions. 2-[N-Methyl- N-(4-nitrobenzoyl)amino]-2-(4-nitrophenyl)propanamide (1g) is cyclized to imidazolinone 2g in aqueous amine buffers of pH 9-11.5; the reaction is subject to specific base catalysis in these media, and the rate-limiting step is the formation of a tetrahedral intermediate. In sodium hydroxide solution, the primary cyclization product is hydrolyzed to give an intermediate M which is subsequently decomposed to sodium 4-nitrobenzoate and 2-methylamino- 2-(4-nitrophenyl)propanamide. At low sodium hydroxide concentration, the rate-limiting step of the opening of imidazoline ring of compound 2g is non-catalyzed decomposition of the intermediate. At higher sodium hydroxide concentrations, the other reaction path begins to make itself felt: hydroxide-ion-catalyzed decomposition of the intermediate. The dependence of observed rate constant of cyclization of compound 1f on sodium hydroxide concentration was used to determine kinetically the value of pKa = 13.5 ± 0.1. The kinetic deuterium isotope effect of cyclization of compounds 1f giving 2f (kCH/kCD = 1.7) was determined in solutions of NaOD in D2O.

Electrochemical Studies on New Chelating Compounds of the Mono‐ and Bis(imidazolyl)pyridine Type

“…Product VI: 2-(2'-pyridyl)-4-methyl-4-isopropyl-imidazolidine- 5 3 ), 34.6 (CH), 64.7 (C-4), 71.2 (C-2), 121.1 (C-5'), 123.5 (C-3'), 137.1 (C-4'), 149.3 (C-6'), 159.0 (C-2'), 180.9 (C-5).…”

Kinetics and Mechanism of the Base-Catalyzed Rearrangement and Hydrolysis of Ezetimibe

“…Therefore, the combined solvent isotope effect for a pathway involving attack of OH − on In 3 − would have value 2 × 0.79 = 1.58 that is close to the observed value (1.29). A similar positive value of solvent isotope effect was also found during cyclizations of amides to imidazolinones …”

“…A similar positive value of solvent isotope effect was also found during cyclizations of amides to imidazolinones. 23…”

2-Amino-2-alkyl(aryl)propanenitriles as key building blocks for the synthesis of five-membered heterocycles

“…The prepared aminonitriles were partially hydrolyzed to give the respective aminoamides, which were acylated with aromatic acid chlorides; the acylation products were cyclized to prepare several series of substituted 4,5-dihydro-1H-imidazol-5-ones. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] The substituted 4,5-dihydro-1H-imidazol-5-ones prepared in this way were used in studies of their physico-chemical properties [20][21][22][23][24][25][26][27][28] also including studies of kinetics and mechanism of their formation and decomposition. [23][24][25] The substituted 4,5-dihydro-1H-imidazol-5-ones attached to a benzene ring or to a pyridine ring at 2-or 2,6-position(s) were used for preparation and characterization of the corresponding coordination [29][30][31][32][33][34][35][36] or organometallic 37 compounds with the following transition metals: Fe(III), 29,[30][31][32][33]…”