Micellar effects upon the hydrogen ion and general acid catalyzed hydration of 1,4-dihydropyridines

Abstract

The rate-limiting step in the hydration of 1-benzyldihydronicotinamide (la) and l-benzyl-3-acetyl-l,4-dihydropyridine (lb) is a slow proton transfer, as shown by the kinetic deuterium solvent isotope effects and buffer catalysis. Reactions in dilute HCI are strongly inhibited by cationic micelles of cetyltrimethylammonium bromide (CTABr) and the inhibition can he related to the micellar binding of the substrates determined spectrophotometrically or by solubility. Anionic micelles of sodium lauryl sulfate (NaLS) only weakly catalyze hydration in dilute HCI, and rate constants go through maxima with increasing [NaLS]. The dependence of rate on [NaLS] can he explained quantitatively in terms of substrate and hydrogen ion incorporation in the micelle and formation of an unreactive conjugate acid in the micelle. The equilibrium constants for unproductive protonation in the micelle corrected for reagent distribution are similar to those in water hut the rate constants are lower. Micelles of sodium ndode(:yl hydrogen phosphate are good catalysts, giving rate enhancements of -lo3 relative to those in water.The acid hydration of dihydropyridine derivatives (1) in aqueous solution is an enamine addition and involves proton transfer from HA followed by rapid attack of water upon the cation (2).4 13ecause of the biological importance of dihy- Rdropyridine nucleotides catalysis of this reaction is of considerable interest and we examined micellar effects in a model system. To date much of the mechanistic work has been on nucleotide derivatives, which are too hydrophilic to be good substrates for use with aqueous micelles, and therefore we first examined hydration of our substrates la,b in the absence of surfactants for purposes of comparison with the reactions in the presence of micellized surfactants. The protonations are irreversible in aqueous acid, but not in nonpolar solvents,5 and the reactions in aqueous solution are general acid catalyzed.6The slow protonation is assisted by electron release by the ring nitrogen, which is reduced by conjugation with the carbonyl group. The charge in the transition state, or the cation 2, is delocalized, but probably it is largely on the ring nitrogen as shown, and substrate protonation, probably on the carbonyl group, 3, should inhibit reaction. I CH,Ph 3Micelles of anionic surfactants typically speed hydrogen ion catalyzed reaction^,^ and we were interested in micellar effects upon the hydration of dihydropyridines because to date specific hydrogen ion catalyzed reactions have generally been examined. In these reactions the proton is fully transferred in the transition state whose formation involves other bond making or breaking steps.Cationic micelles of cetyltrimethylammonium bromide, CTABr, inhibit and anionic micelles of sodium lauryl sulfate, NaLS, weakly catalyze hydration of dihydronicotinamide derivatives.12 These experiments were in phosphate buffer so that the micelles could affect the buffer equilibria and have different, and perhaps opposite, effects upon the hydrogen io...

Formation and characterization of surfactant stabilized silver nanoparticles: A kinetic study

“…The observed results in presence of CTAB are summarized in Table 1. It is not surprising because ionic micelles shows a marked difference in the effective local pH to exist at its micellar surface over that in bulk aqueous solvent [44,45]. The different pH in the micellar pseudo phase of ionic micelles is understandable because most of the acidic and/or basic species should be in the micellar phase and in addition pKs in micellar systems are all most of time different from the pKs measured in water.…”

Effect of Cationic Micelles on the Kinetics of Interaction of Ninhydrin withl-Leucine andl-Phenylalanine

“…[2]. The binding constant, K N , was determined independently also by following the spectrophotometric method (26). The chosen wavelength was 251 nm at which the changes in absorbances were maximum for the ninhydrin binding with CTAB.…”

Micellar catalysis on the redox reaction of glycolic acid with chromium(VI)

“…4), suggesting that binds to cationic micelles despite 9.0 ϫ 10 dm binding constants were calculated by Bunton's method [30], which were 1412 and 108 dm 3 for CTAB Ϫ1 mol and CPB, respectively. The associated may Ϫ HCrO 4 exist either inside the Stern layer or at the interface between the micellar surface and the bulk solvent.…”