Aminolysis Of Esters Research Articles

Microwave effects in solvent-free esters aminolysis

Solvent-free ester aminolysis was studied under microwave or conventional heating either in the absence of base or induced by KO tBu with or without a phase transfer agent. The specific microwave effects were shown to be dependent on the conditions and discussed in terms of relative polarities of ground and transition states.

Computational study of the aminolysis of esters. The reaction of methylformate with ammonia.

The aminolysis of esters is a basic organic reaction considered as a model for the interaction of carbonyl group with nucleophiles. In the present computational study the different possible mechanistic pathways of the reaction are reinvestigated by applying higher level electronic structure theory, examining the general base catalysis by the nucleophile, and a more comprehensive study the solvent effect. Both the ab initio QCISD/6-31(d,p) method and density functional theory at the B3LYP/6-31G(d) level were employed to calculate the reaction pathways for the simplest model aminolysis reaction between methylformate and ammonia. Solvent effects were assessed by the PCM method. The results show that in the case of noncatalyzed aminolysis the addition/elimination stepwise mechanism involving two transition states and the concerted mechanism have very similar activation energies. However, in the case of catalyzed aminolysis by a second ammonia molecule the stepwise mechanism has a distinctly lower activation energy. All transition states in the catalyzed aminolysis are 10-17 kcal/mol lower than those for the uncatalyzed process.

Reaction of imidazole with toluene-4-sulfonate salts of substituted phenyl N-methylpyridinium-4-carboxylate esters: special base catalysis by imidazole.

The reaction of imidazole in aqueous solution with toluene-4-sulfonate salts of substituted phenyl N-methylpyridinium-4-carboxylate esters obeys the rate law: k(obs) - k(background) = k2[Im] + k3[Im]2 where [Im] is the imidazole concentration present as free base. The parameters k2 and k3 fit Brønsted type free energy correlations against the pKa of the leaving phenol with betaLg values of -0.65 and -0.42 respectively. The imidazolysis is insensitive to catalysis by general bases and yet k3 for the 3-cyanophenyl ester possesses a deuterium oxide solvent isotope effect of 4.43 consistent with rate limiting proton transfer. A special catalytic function is proposed for decomposition of the tetrahedral addition intermediate (T+/-) via k3 whereby the catalytic imidazole interacts electrophilically with the leaving phenolate ion and removes a proton from the nitrogen in the rate limiting step with subsequent non-rate limiting ArO-C bond fission. This is consistent with the change in effective charge on the leaving oxygen in the transition structure of k3 which is more positive (-0.42) than that expected (-0.60) for the equilibrium formation of the zwitterion intermediate. The catalytic function at the leaving oxygen is likely to be an electrophilic role of the NH as a hydrogen bond donor. In the k2 step the deuterium oxide solvent isotope effect of 1.51 for the 3-cyanophenyl ester and the betaLg of -0.65 are consistent with rate limiting expulsion of the phenolate ion from the T+/- intermediate. The absence of general base catalysis of imidazolysis rules out the established mechanism for aminolysis of esters where T+/- is stabilised by a standard rate limiting proton transfer. The kinetically equivalent term for k3 where T- reacts with the imidazolium ion as an acid catalyst would require this step to be rate limiting and involve proton transfer not consistent with departure of the good aryl oxide leaving group.

Modular evolution of a chiral auxiliary for the 1,3-dipolar cycloaddition of isomünchnones with vinyl ethers.

[reaction: see text]. The 1,3-dipolar cycloaddition reaction has long been recognized as a powerful methodology in organic synthesis. More recently, this reaction has become a popular manifold for the construction of chemical diversity. Herein, we report the development of a chiral template for the facially selective cycloaddition of isomünchnones, a common class of 1,3-dipoles. The modular format of the asymmetric unit allowed a systematic optimization of selectivity. In addition, the chiral auxiliary was removed through an unusually facile ester aminolysis.

Nucleophilic Substitution in Carboxylic Esters in Oil-In-Water Microemulsions

In hydrolysis and aminolysis of p-nitrophenyl esters of carboxylic acids in oil-in-water microemulsions on the basis of surfactants of various nature, a complex mechanism of the effect of the medium is operative, including shift of acid-base equilibria in the nucleophile. The rate constants of the processes studied are quantitatively related to the surface potential of the microdroplet. Varied hydrophobicity of the nucleophile and substrate changes the site of the reaction act and the relative contributions of aminolysis and hydrolysis.

Computer Simulation of Amide Bond Formation in Aqueous Solution

We report a theoretical study on ester aminolysis reaction mechanisms in aqueous solution. It is believed, in general, that the formation of a zwitterionic intermediate plays a key role in the aminolysis process whose rate determining step is the formation or breakdown of such an intermediate, depending on pH. However, the reaction mechanism has been object of some recent experimental controversy. We have investigated the model reaction ammonia + formic acid. Stepwise and concerted processes have been studied. Static and dynamic solvent effects have been analyzed by using a dielectric continuum model in the first case and molecular dynamics simulations together with the QM/MM method in the second case. The results show that a zwitterionic structure is always formed in the reaction path although its lifetime appears to be quite dependent on solvent dynamics.

Change in rate-determining step in an E1cB mechanism during aminolysis of sulfamate esters in acetonitrile.

The kinetics of the reactions of the nitrogen-sulfur(VI) esters 4-nitrophenyl N-methylsulfamate (NPMS) with a series of pyridines and a series of alicyclic amines and of 4-nitrophenyl N-benzylsulfamate (NPBS) with pyridines, alicyclic amines, and a series of quinuclidines have been investigated in acetonitrile (ACN) in the presence of excess amine at various temperatures. Pseudo-first-order rate constants (k(obsd)) have been obtained by monitoring the release of 4-nitrophenol/4-nitrophenoxide. From the slope of a plot of k(obsd) vs [amine], second-order rate constants (k'(2)) have been obtained for the pyridinolysis of NPMS, and a Brønsted plot of log k'(2) vs pK(a) of pyridine gave a straight line with beta = 0.45. However, aminolysis with alicyclic amines of NPMS gave a biphasic Brønsted plot (beta(1) = 0.6, beta(2) approximately equal to 0). Pyridinolysis and aminolysis with alicyclic amines and quinuclidines of NPBS also gave similar biphasic Brønsted plots. This biphasic behavior has been explained in terms of a mechanistic change within the E1cB mechanism from an (E1cB)(irrev) (less basic amines) to an (E1cB)(rev) (more basic amines), and the change occurs at approximately the pK(a)'s (in ACN) of NPMS (17.94) and NPBS (17.68). The straight line Brønsted plot for NPMS with pyridines occurs because the later bases are not strong enough to substantially remove the substrate proton and initiate the mechanistic change observed in the reaction of NPMS with the strong alicyclic amines and quinuclidines. An entropy study supports the change from a bimolecular to a unimolecular mechanism. This is the first clear demonstration of this E1cB mechanistic changeover involving a nitrogen acid substrate.

Quantum chemical study of ester aminolysis catalyzed by a single adenine: a reference reaction for the ribosomal peptide synthesis.

Herein we report the results of a HF/6-31+G** and B3LYP/6-31+G** computational investigation of the title reaction for the peptide bond synthesis catalyzed by a single adenine. This system constitutes a reference reaction to study the basic chemical events that have been proposed to occur at the peptidyl transferase active site of ribosomes on the basis of structural determinations (Science 2000, 239, 920--931). Thus, the analysis of the geometry, charge distribution, and energetics of the critical structures involved in this title reaction yields insight into the catalytic mode of action of RNA molecules. Our computational results give further support to the hypotheses that the activated nucleotide A2451 in the ribosome acts as a base catalyst and that this role is similar to that of the His residue in the catalytic triad of serine proteases.

The synthesis of l-proline derived hexaazamacrocyclic ligands of C3 symmetry via intramolecular methyl ester aminolysis

A convenient synthesis of enantiomerically pure 18-, 21-, and 24-membered hexaaza-crown ligands is presented. Linear α,ω-aminoesters, prepared from l-proline, undergo intramolecular aminolysis to afford the corresponding 18-, 21-, and 24-membered macrocyclic amides in satisfactory yields (42, 65, and 22%, respectively). These were subsequently transformed into the title macrocyclic hexamines via exhaustive reduction with a borane–dimethylsulfide complex. X-Ray structures of two larger macrocyclic amides are also presented.

A linear Br�nsted-type behavior in the aminolysis of substituted naphthyl acetates

The reactions of 4-acetyl-1-naphthyl acetate (1) and 6-acetyl-2-naphthyl acetate (2) with a series of amines of varying pKa,viz. morpholine, ammonia, ethanolamine, glycine, n-butylamine, piperidine, hydrazine, imidazole, and hydroxylamine, are subjected to a kinetic investigation in aqueous medium, 30°C, ionic strength 0.1 M (KCl ). Pseudo-first-order rate coefficients (kobs ) are found under amine excess. The plots of (kobs − kH) against free amine concentration are linear at constant pH. The macroscopic nucleophilic substitution rate coefficients (kN) are obtained as the slopes of these plots and found to be pH-independent for all the amines employed. The Brönsted-type plots obtained (log kN against amine pKa) for the aminolysis of both esters 1 and 2 are linear with slope values of β = 0.74 and β = 0.94, respectively. From these values, the kinetic law and the analysis of products, it is deduced that for both esters aminolysis proceed through a zwitterionic tetrahedral addition intermediate (T±) whereby its dissociation into products is rate-limiting (k2 step). Comparison of kN values among them shows that both esters follow an identical mechanistic pathway with 1 having higher reactivity than 2, the reasons for which are discussed. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 157–164, 2001

Resolution of Conflicting Mechanistic Observations in Ester Aminolysis. A Warning on the Qualitative Prediction of Isotope Effects for Reactive Intermediates

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTResolution of Conflicting Mechanistic Observations in Ester Aminolysis. A Warning on the Qualitative Prediction of Isotope Effects for Reactive IntermediatesDaniel A. Singleton and Steven R. MerriganView Author Information Department of Chemistry, Texas A&M University College Station, Texas 77843 Cite this: J. Am. Chem. Soc. 2000, 122, 44, 11035–11036Publication Date (Web):October 24, 2000Publication History Received10 August 2000Published online24 October 2000Published inissue 1 November 2000https://doi.org/10.1021/ja005519+Copyright © 2000 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views515Altmetric-Citations41LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (36 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Chemical structure,Equilibrium,Isotope effects,Reaction mechanisms,Substitution reactions Get e-Alerts

Catalysis of ester aminolysis by cyclodextrins. The reaction of alkylamines with p-nitrophenyl alkanoates

The effects of four cyclodextrins (alpha-CD, beta-CD, hydroxypropyl-beta-CD, and gamma-CD) on the aminolysis of p-nitrophenyl alkanoates (acetate to heptanoate) by primary amines (n-propyl to n-octyl, isobutyl, isopentyl, cyclopentyl, cyclohexyl, benzyl) in aqueous solution have been investigated. Rate constants for amine attack on the free and CD-bound esters (k(N) and k(cN)) have ratios (k(cN)/k(N)) varying from 0.08 (retardation) to 180 (catalysis). For the kinetically equivalent process of free ester reacting with CD-bound amine (k(Nc)), the ratios k(Nc)/k(N) vary from 0.2 to 28. Either way, there is evidence of catalysis in some cases and retardation in others. Changes in reactivity parameters with structure indicate more than one mode of transition state binding to the CDs. Short esters react with short alkylamines by attack of free amine on the ester bound by its aryl group, but for longer amines, free ester reacts with CD-bound amine. Reaction of long esters with long amines, which is catalyzed by beta-CD and gamma-CD, involves inclusion of the alkylamino group and possibly the ester acyl group. The larger cavity of gamma-CD may allow the inclusion of the ester aryl group, as well as the alkylamino group, in the transition state. Reaction between an ester bound to the CD by its acyl group and free amine appears not to be important.

Lipase-Catalyzed Synthesis of Carboxylic Amides: Nitrogen Nucleophiles as Acyl Acceptor

The lipase-catalyzed aminolysis of carboxylic esters is a fairly general reaction that has been performed with a wide range of esters and amines, generally in anhydrous organic media to avoid undesirable hydrolysis of the ester. Alternatively, carboxylic amides can be synthesized by lipase mediated condensation of carboxylic acids and amines if an excess of either reactant is avoided.

General base and general acid catalyzed intramolecular aminolysis of esters. Cyclization of esters of 2-aminomethylbenzoic acid to phthalimidine.

Plots of log k(0) vs pH for the cyclization of trifluoroethyl and phenyl 2-aminomethylbenzoate to phthalimidine at 30 degrees C in H(2)O are linear with slopes of 1.0 at pH >3. The values of the second-order rate constants k(OH) for apparent OH(-) catalysis in the cyclization reactions are 1.7 x 10(5) and 5.7 x 10(7) M(-)(1) s(-)(1), respectively. These rate constants are 10(5)- and 10(7)-fold greater than for alkaline hydrolysis of trifluoroethyl and phenyl benzoate. The k(OH) for cyclization of the methyl ester is 7.2 x 10(3) M(-)(1) s(-)(1). Bimolecular general base catalysis occurs in the intramolecular nucleophilic reactions of the neutral species. The value of the Bronsted coefficient beta for the trifluoroethyl ester is 0.7. The rate-limiting step in the general base catalyzed reaction involves proton transfer in concert with leaving group departure. The mechanism involving rate-determining proton transfer exemplified by the methyl ester in this series (beta = 1.0) can then be considered a limiting case of the concerted mechanism. General acid catalysis of the neutral species reaction or a kinetic equivalent also occurs when the leaving group is good (pK(a) </= 12.4). That the mechanism and/or rate-determining step of the intramolecular aminolysis reactions is different than in bimolecular reactions or the intramolecular reactions of other esters is attributed to the excellent steric fit of the nucleophile to the reaction center of the 2-aminomethylbenzoate esters.

Molecular organization of reactants in the kinetics and catalysis of liquid phase reactions: IX. The catalytic assistance of an alcohol as a component of the medium in the aminolysis of esters

The kinetics of the reaction ofp-nitrophenyl acetate with n-butylamine is studied in various solvents containing n-butanol as a component of the medium. The alcohol is shown to assist the aminolysis by the participation in the proton transfer from the amine molecule to ester. The stoichiometric composition of the polymolecular complexes of amine with the alcohol participating in the reaction is found from the kinetic data at low concentrations of n-butanol and the data on its association in solutions. At high concentrations of the alcohol, the kinetic data are described within the framework of a model that assumes the participation in the reaction of hydroxy groups of the alcohol in the composition of alcohol clusters. The rate of the process is determined by the concentration and sizes of the clusters. The complex kinetics of the catalytic assistance of the alcohol as a component of the medium are quantitatively interpreted according to the concepts on the role of the structural organization of the liquid in the kinetics of molecular reactions in solutions.

Active-site variants of Streptomyces griseus protease B with peptide-ligation activity

Background: Peptide-ligating technologies facilitate a range of manipulations for the study of protein structure and function that are not possible using conventional genetic or mutagenic methods. To different extents, the currently available enzymatic and nonenzymatic methodologies are synthetically demanding, sequence-dependent and/or sensitive to denaturants. No single coupling method is universally applicable. Accordingly, new strategies for peptide ligation are sought.Results: Site-specific variants (Ser195→Gly, S195G, and Ser195→Ala, S195A) of Streptomyces griseus protease B (SGPB) were generated that efficiently catalyze peptide ligation (i.e., aminolysis of ester-, thioester- and para-nitroanilide-activated peptides). The variants also showed reduced hydrolytic activity relative to the wild-type enzyme. The ratio of aminolysis to hydrolysis was greater for the S195A variant, which was also capable of catalyzing ligation in concentrations of urea as high as 2 M.Conclusions: Mutagenic substitution of the active-site serine residue of SGPB by either glycine or alanine has created a unique class of peptide-ligating catalysts that are useful for coupling relatively stable ester- and para-nitroanilide-activated substrates. Ligation proceeds through an acyl–enzyme intermediate involving His57. Serine to alanine mutations may provide a general strategy for converting proteases with chymotrypsin-like protein folds into peptide-coupling enzymes.

Aminolysis of 2-hydroxy esters catalyzed by Candida antarctica lipase

Candida antarctica lipase catalyzed the aminolysis of 2-hydroxy esters with amines in organic solvents to yield the corresponding 2-hydroxy amides. The reactions proceeded at 28–30 °C in dioxane for 6 h with 3 mM substrates with yields ranging between 45% (w/w) (for branched substrates) to 88% (w/w) (for linear substrates). Although the reaction was not enantioselective, because of its simplicity it represents an alternative method for the synthesis of functionalised amides.

Kinetics and mechanism of aminolysis of aliphatic esters in aprotic solvents

Kinetic studies were carried out on the aminolysis reactions of substituted aliphatic esters in a variety of aprotic solvents. The reaction rate is strongly affected by inductive and steric effects of substituents in the acyl group, rising more than 104-fold from cyanoacetate to trifluoroacetate. The quantitative treatment of solvent effects revealed a rate decrease by the polarity and π-basicity of the solvents, and also an accelerating effect of the polarizability of solvents. Cyclic transition states were assumed for both the first and second-order (in amine) reactions. Copyright © 1999 John Wiley & Sons, Ltd.

Hydrolysis and aminolysis of alkyl xanthate esters and cellulose analogues

The hydrolysis and aminolysis of a series of S-substituted O-alkylxanthate esters was studied in 20% v/v aqueous methanol at 35°C. The pH-rate profiles of the hydrolyses showed water and hydroxide-ion-catalyzed reactions. The reaction of 2,4-dinitrophenyl cellulose xanthate (CelXDNP) and p-nitrobenzyl cellulose xanthate (CelXNB) with polyalanine and lysozyme produced a covalent bond between the polypeptide and the cellulose matrix, as shown by solid-state 13C NMR. However, the nature of the bonding could not be identified. The reaction of nucleophiles (H2O, OH-, RNH2) and xanthic esters was consistent with an addition-elimination mechanism through a tetrahedral intermediate. Brønsted plots against the pKa of the nucleophile (βnu) or the nucleofuge of the substrate (βlg) were used to characterize the rate-determining step. The pKa values of the nucleophiles ranged between -1.74 and 15.74, and for the nucleofuges, they were in the range of 10.50-0.92. For nucleophiles with pKa values up to about 10, βlg was 0.10-0.15, and βnu changed from 0.48 to 0.35 for the strongest electron-withdrawing nucleofuge. It was concluded that the water-catalyzed hydrolyses, and also aminolyses with moderately basic amines, occur with rate-determining formation of the tetrahedral intermediate. For strong bases such as hydroxide ion, the disappearance of the intermediate becomes the slowest step. The reaction of cellulose xanthic esters with external nucleophiles as hydroxide ion and amines shows simple first-order kinetics and is slower than alkyl or sugar xanthates, probably due to the diffusion effect through the tight cybotactic region of cellulose. Key words: hydrolysis, aminolysis, alkyl xanthic esters, cellulose xanthic esters, sugar xanthic esters.

Hydrolysis and aminolysis of alkyl xanthate esters and cellulose analogues

The hydrolysis and aminolysis of a series of S-substituted O-alkylxanthate esters was studied in 20% v/v aqueous methanol at 35°C. The pH-rate profiles of the hydrolyses showed water and hydroxide-ion-catalyzed reactions. The reaction of 2,4-dinitrophenyl cellulose xanthate (CelXDNP) and p-nitrobenzyl cellulose xanthate (CelXNB) with polyalanine and lysozyme produced a covalent bond between the polypeptide and the cellulose matrix, as shown by solid-state 13C NMR. However, the nature of the bonding could not be identified. The reaction of nucleophiles (H2O, OH-, RNH2) and xanthic esters was consistent with an addition-elimination mechanism through a tetrahedral intermediate. Brønsted plots against the pKa of the nucleophile (βnu) or the nucleofuge of the substrate (βlg) were used to characterize the rate-determining step. The pKa values of the nucleophiles ranged between -1.74 and 15.74, and for the nucleofuges, they were in the range of 10.50-0.92. For nucleophiles with pKa values up to about 10, βlg was 0.10-0.15, and βnu changed from 0.48 to 0.35 for the strongest electron-withdrawing nucleofuge. It was concluded that the water-catalyzed hydrolyses, and also aminolyses with moderately basic amines, occur with rate-determining formation of the tetrahedral intermediate. For strong bases such as hydroxide ion, the disappearance of the intermediate becomes the slowest step. The reaction of cellulose xanthic esters with external nucleophiles as hydroxide ion and amines shows simple first-order kinetics and is slower than alkyl or sugar xanthates, probably due to the diffusion effect through the tight cybotactic region of cellulose. Key words: hydrolysis, aminolysis, alkyl xanthic esters, cellulose xanthic esters, sugar xanthic esters.