Hydrolysis of amides. Kinetics and mechanism of the basic hydrolysis of N-acylpyrroles,N-acylindoles and N-acylcarbazoles

The hydroxide ion catalyzed hydrolysis of N-formyl, N-acetyl and N-benzoylpyrroles, -indoles and -carbazoles has been studied in water at 25.0°. The rate constants of formation of the tetrahedral intermediate are strongly increased by releasing steric hindrance in the acyl portion as shown by the higher reactivity of N-formyl derivatives in comparison with N-acetyl and N-benzoyl derivatives.     

Hydrolysis of amides. Electronic effects on kinetics and mechanism of the basic hydrolysis of TV-substituted benzoylpyrroles

The hydroxide ion catalyzed hydrolysis of a series of N-substituted benzoylpyrroles has been studied in water at 25°. Hammett treatment of data shows that substituents affect in a very similar way the rate of formation and of decomposition of the tetrahedral intermediate.     

Hydrolysis of Fischer carbene complexes. Steric effects of the pi-donor group

Rate constants for the hydrolysis of Fischer carbenes (CO)5Cr=C(OR)Ph (R = n-propyl, neopentyl, isopropyl, and menthyl) in 50% MeCN-50% water (v/v) at 25 degrees C are reported. The rate constants for the addition of -OH to the carbene carbon are 5.3, 3.7, 0.84, and 0.01 M(-1) s(-1), respectively. These rate constants give linear correlations with the corresponding rate constants for the hydrolysis of esters such as acetate, benzoate, and formiate. The slopes of the plots of the observed rate constants for the carbenes vs the rate constants for the esters are 1.4 and 1.2 for acetate and benzoate, respectively, indicating that the factors that decrease the reactivity of the two types of compounds are similar, but the carbenes show higher sensitivity. The rate constants are well correlated with several steric parameters giving a value of -3.84 for the Charton's psi parameter. The results show that the steric bulkiness of the R group is the main factor determining the reactivity differences for these carbene complexes.     

Hydrolysis in the absence of bulk water 1. Chemoselective hydrolysis of amides using tetrahalophthalic anhydrides

The reaction of primary and secondary amides with tetrafluorophthalic or tetrachlorophthalic anhydride gives carboxylic acids in good yield. The reaction is chemoselective in that the amide functionality can be hydrolyzed in the presence of ester groups.     

Theoretical study on the reaction mechanism for the hydrolysis of esters and amides under acidic conditions

The mechanisms underlying the hydrolysis of methyl acetate and acetamide under acidic conditions were investigated using the MP2/6-311+G(d,p)//MP2/6-31+G(d,p) level of theory. It was necessary to include two water molecules as reactants to obtain a tetrahedral (TD) intermediate for the A_AC2 mechanism that Ingold classified for the hydrolysis of methyl acetate. This mechanism includes two TS structures, one for the formation of the TD intermediate and the other for its decomposition. Since the activation energies were calculated to be 15.7 and 18.3 kcal mol⁻¹, the second step determines the rate of hydrolysis. The calculated value was close to that observed at ∼16 kcal mol⁻¹. It was confirmed that the A_AC2 mechanism had a barrier lower by 9.9 kcal mol⁻¹ than the A_AL2 mechanism. The A_AC2 mechanism is also applicable to the acid-catalyzed hydrolysis of acetamide. It is not the TD intermediate with which the NH₃⁺ moiety forms, but one further step is required to produce the final products, acetic acid and ammonium ion.     

On the kinetics and mechanism of Nb(V) hydrolysis

Kinetics of Nb(V) hydrolysis in MgCl₂, Mg(ClO₄)₂ mixtures has been investigated by electroanalytical methods and the rate constants determined. A hydrolysis model based on species postulated in the literature is proposed. Resolution of the corresponding differential equations led to results consistent with experimental data obtained from polarographic current vs. time curves. © 1993 John Wiley & Sons, Inc.     

Steric effects in the complexation kinetics of copper(II) with rac-5,5,7,12,12,14-hexamethyl 1,4,8,11-tetraazacyclotetradecane in basic aqueous media

Copper(II) reacts with rac-5,5,7,12,12,14-hexamethyl-l,4,8,11-tetraazacyclotetradecane (tet-b) in strongly basic aqueous media to give [Cu(tet-b) (OH) (blue)]⁺ which contains trigonal bipyramidally co-ordinated Cu²⁺ with the tet-b ligand in its most stable, folded form. The kinetics of formation of this blue complex have been studied at 25.0° ± 0.1°C using the stopped-flow technique. Second-bond formation is proposed as the rate-determining step for tet-b reaction with Cu(OH)^-₃ and Cu(OH)^2-₄. Possible mechanisms for the reaction and the steric effects resulting from the methyl groups on the alkyl backbone of the macrocyclic ligand are considered.     

Substituent effects on the kinetics of acid-catalyzed hydrolysis of methyl cellulose

The kinetics of the hydrolysis of methyl cellulose (MC, DS 1.27 and 1.95) was studied by a two-step procedure, comprising partial hydrolysis in 1 M TFA in water and water/acetone at 120 °C for various time periods, labeling of generated reducing ends by reductive amination, complete depolymerization by methanolysis followed by trimethylsilylation, and gas chromatographic analysis of the two sets of partially O-methylated glucose derivatives. Rate constants of MCs were all in the order of 10^?4 s^?1. In aqueous TFA, overall rate of hydrolysis of the MC with lower DS was faster than of the MC with higher DS. When substituting half of the water by acetone, reaction was slowed down while selectivity regarding different O-methyl glucosyl residues increased. Compared to the parent glucosyl unit methylation at O-2 and at O-6 decreased rate of hydrolysis, while 3-O-methyl favored it especially in the early stage of the conversion of the macromolecules. Beside slight differences between the two MCs and reaction conditions, rate constants k _i (i = position of methyl) followed the order k ₃₆ ≈ k ₃ > k ₀ ≈ k ₂₃ > k ₆ > k ₂ ≥ k ₂₃₆ > k ₂₆. For the higher substituted MC2 an initial slow phase with more pronounced differences of k _i, followed by a faster less selective period was observed. Regioselectivity of hydrolysis with respect to methyl positions was expressed as standard deviation of k _i and was between 16 and 46% depending on MC and conditions. Findings are discussed with respect to electronic effects, solvent-effect, H-bonding pattern and solution state.     

The kinetics and mechanism of alkaline hydrolysis of N-substituted phthalimides

The aqueous cleavage of N-(2-bromoethyl)phthalimide (NBEPH), N-(3-bromopropyl)phthalimide (NBPPH), and N-carbethoxyphthalimide (NCPH) have been studied within the [ōH] range of 5 × 10^?4 M to 2 × 10^?3 M, pH range of 8.82 to 10.62 and 8.06 to 8.66, respectively. The observed pseudo-first-order rate constants, k_obs, reveal a linear relationship with [ōH] with essentially zero intercept. The alkaline hydrolysis of N-(hydroxymethyl)phthalimide (NHMPH) has been studied within the [ōH] range of 5.64 × 10^?6 M to 2.0 M. The [OH]-rate profile reveals that both ionized and nonionized NHMPH are reactive toward ōH. The second-order rate constant, k_OH, for the reaction of ōH with non-ionized NHMPH is ca. 10⁴ times larger than that with ionized NHMPH. The values of k_OH obtained for NBEPH, NBPPH, NCPH, and nonionized NHMPH show a reasonable linear relationship with Taft substituent constants, and the slope (ρ*) of the plot is 1.01 ± 0.10. The low value of ρ* of 1.01 is attributed to nucleophilic attack as the rate-limiting. The k_OH value for ionized NHMPH reveals nearly 10³-fold negative deviation from the linear Taft plot.     

Effects of solvent on TEOS hydrolysis kinetics and silica particle size under basic conditions

In-situ liquid-state ²⁹Si nuclear magnetic resonance was used to investigate the temporal concentration changes during ammonia-catalyzed initial hydrolysis of tetraethyl orthosilicate in different solvents (methanol, ethanol, n-propanol, iso-propanol and n-butanol). Dynamic light scattering was employed to monitor simultaneous changes in the average diameter of silica particles and atomic force microscopy was used to image the particles within this time frame. Solvent effects on initial hydrolysis kinetics, size and polydispersity of silica particles were discussed in terms of polarity and hydrogen-bonding characteristics of the solvents. Initial hydrolysis rate and average particle size increased with molecular weight of the primary alcohols. In comparison, lower hydrolysis rate and larger particle size were obtained in the secondary alcohol. Exceptionally, reactions in methanol exhibited the highest hydrolysis rate and the smallest particle size. Ultimately, our investigation elaborated, and hence confirmed, the influences of chemical structure and nature of the solvent on the formation and growth of the silica particles under applied conditions.     

On the hydrolysis mechanisms of amides and peptides

Here the possibility is raised that peptide hydrolysis, in the absence of catalysis by proteases or buffers, may still have a self‐catalyzing mechanism that differs from ordinary amide hydrolysis. Second, an attempt is made to clarify the ongoing confusion in the computational chemistry literature regarding the rate‐limiting step in ordinary amide hydrolysis. Third, Gibbs activation energies (free‐energy barriers) for formamide hydrolysis are derived from rate constants and presented under different concentration conventions, for ease of comparison to values from computational chemistry predictions past and future.     

Steric effects are not the cause of the rate difference in hydrolysis of stereoisomeric glycosides

[structure: see text] A long-lived and plausible explanation as to why glycosides with axial substituents are more reactive than those with equatorial substituents was given in 1955 by Edward based on sterical hindrance being relieved in the transition state. Using model compounds 5, 6, 8, and 10, we here show conclusively that sterical hindrance is not the controlling factor in glycoside hydrolysis.     

Hydrolysis of 4-imino-imidazolidin-2-ones in acid and the mechanism of cyclization of hydantoic acid amides

The hydrolysis of iminohydantoins generates the same tetrahedral intermediate as that obtained in the cyclization of hydantoic acid amides to hydantoins. The ratio of the products of imine hydrolysis under kinetic control is determined by the relative height of the barriers of the breakdown of to amide or to hydantoin. Thus the partitioning of products unequivocally proves which is the rate determining step in the cyclization reaction-formation or breakdown of . UV and 1H NMR monitoring of the acid catalyzed hydrolysis of four 5-substituted 4-imino-1-methyl-3-(4-nitrophenyl)imidazolidin-2-ones found hydantoins as the only products. The kinetics of hydrolysis of imines were measured in 0.001-1 M HCl. Contrary to the remaining imines, 1,5-dimethyl-4-imino-3-(4-nitrophenyl)imidazolidin-2-one is readily oxidized as stock solution in THF containing peroxides to 1,5-dimethyl-5-hydroxy-4-imino-3-(4-nitrophenyl)imidazolidin-2-one . In all cases, hydrolysis was found to be zero order with respect to [H+]. As imines are fully protonated under the acidity studied, this is evidence of a transition state of a single positive charge. Comparison of imine hydrolysis rates with previous data on rates of cyclization of the corresponding amides of hydantoic acids allowed conditions (acid concentration, substitution pattern-gem-dimethyl effect) to be found that guaranteed kinetic control of the products obtained. Thus it was unequivocally proven that formation of the tetrahedral intermediate is rate determining in the cyclization of hydantoic acid amides. The small steric effects upon methyl substitution at 5-C and a solvent kinetic isotope effect kH/kD of 1.72 favour a mechanism for imine hydrolysis whereby the rate is limited by water attack on the protonated imine concerted with proton transfer from attacking water to a second water molecule.     

Hydrolysis of ureas. Kinetics and mechanism of the basic hydrolysis of indole-1-carboxamides and (5H-dibenz[b,f]azepine)-5-carboxamide

The hydroxide ion catalyzed hydrolysis of indole-1-carboxamide and indole-1-(N,N-dimethyl)carboxamide has been studied in water at 60.0° and [OH⁻] concentration between 0.3--2.4N. The rate constants of formation of the tetrahedral intermediate are strongly increased by N-substitution with a heteroaromatic ring in comparison with simple amides. Carbamazepine, (5H-dibenz[b,f]azepine)-5-carboxamide, a potent anticonvulsant drug, is particularly stable under these conditions.     

Quantum-chemical study of the mechanism of the hydrolysis of amides in the gas phase and in aqueous solution

The MNDO, AM1, and MNDO/M methods have been used to calculate the profile of the potential energy surface for the hydrolysis of formamide in the gas phase and in aqueous solution. Estimates have been made of the changes in the energy barrier in specific acid and base catalysis, and it is shown that in the absence of proton exchange between the reacting system and the solvent the interaction of the charged reactants with a polar medium impedes the reaction.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1785–1792, August 1989.     

Steric and electronic effects in the resolution of enantiomeric amides on a commercially available Pirkle-type high-performance liquid chromatographic chiral stationary phase

The steric and electronic effects in the resolution of enantiomeric amides on a commercially available (R)-N-(3,5-dinitrobenzoyl)phenylglycine chiral stationary phase (CSP) have been investigated. Several homologous series of enantiomeric amides were synthesized from alkyl and aromatic amines and from alkyl and aromatic acids. The results of the study indicate that chiral recognition is based on the formation of diastereomeric solute-CSP complexes that are due to attractive interactions located on a single bond in both the solute and CSP and on steric interactions within the complexes. The magnitude of the chiral resolution appears to depend on the steric bulk at the chiral center. In addition, when the amides synthesized from chiral amines were chromatographed, the (R)-enantiomers eluted first, whereas the opposite elution order was found for the amides synthesized from enantiomeric carboxylic acids. Thus, the amide moiety not only provides the sites of attractive interaction between the solute and CSP, but also influences the spatial orientation of the two molecules, thereby affecting the relative stabilities of the two diastereomeric complexes and determining the enantiomeric elution order.