Alkaline Hydrolysis Of Esters Research Articles

The Synthesis and Acid-base Properties of α-(Fluoromethyl)- and α-(Difluoromethyl)-substituted Cyclobutane Building Blocks

Aim. To synthesize cyclobutane-derived amines and carboxylic acids bearing CH2F or CHF2 groups in the α position; to determine the regularities of the effect of fluoroalkyl substituents on the acid-base properties of the title compounds.Results and discussion. Synthetic approaches to 1-(fluoromethyl)- and 1-(difluoromethyl)cyclobutanamines, 1-(fluoromethyl)- and 1-(difluoromethyl)cyclobutanecarboxylic acids have been developed. It has been found that the pKa (pKa(H)) values measured for the title compounds, as well as for their non-substituted and CF3-substituted analogues, are consistent with the electron-withdrawing effect of the corresponding fluoroalkyl substituents.Experimental part. The synthesis of the title compounds commenced from the known ethyl 1-(hydroxymethyl)cyclobutanecarboxylate or the product of its Swern oxidation (the corresponding aldehyde) and included fluorination, alkaline ester hydrolysis (for carboxylic acids), and modified Curtius rearrangement (for amines). The pKa value was determined from the pre-equivalence point part of the titration curve using the standard acid-base titration.Conclusions. A newly developed synthetic approach to 1-(fluoromethyl)- and 1-(difluoromethyl)cyclobutanamines, 1-(fluoromethyl)- and 1-(difluoromethyl)cyclobutanecarboxylic acids allows to obtain the title compounds in multigram quantities (up to 97 g). With a single exception, the acid-base properties of these products, as well as their parent non-substituted and CF3-substituted analogues, change in a monotonous manner in accordance with inductive electronic effect of the fluorine atom(s).

Experimental study of micromixing in curved tube reactors by the reactive tracer method

The effect of basic process conditions and the initial distribution of mixed liquids on mixing on the molecular scale was studied experimentally for helical and twisted bends reactors. The selectivity of two competitive-parallel reactions, acid-base neutralization and alkaline ester hydrolysis, carried out in aqueous solutions between initially unmixed reactants, was used to quantify micromixing in steady-state, isothermal and laminar flow. Faster micromixing is achieved in the twisted bends mixer than in the helical mixer due to the periodic reorientation of Dean vortices, present in curved conduits. The difference in micromixing performance of the two reactors decreases for high Reynolds numbers (Re>1000) when ester hydrolysis is no longer controlled by mixing. Micromixing for lower Reynolds numbers can be improved by changing the ratio of volumetric flows of the reactant solutions and by using a distribution head, which at the reactor entrance creates the contact surface between mixed liquids perpendicular to the curvature plane of the first pipe bend. When micromixing in the reactor becomes so slow that the final selectivity approaches its maximum value, changing the ester to a slower reacting one helps to adjust the sensitivity of the test reaction system to the deteriorating mixing conditions.

How do electronic substituent effects work? – Additional contrasting cases for a differentiated inquiry illustrated by the example of alkaline ester hydrolysis

AbstractDer Einfluss elektronischer Substituenteneffekte auf den Verlauf von Reaktionen ist für Studierende insbesondere dann schwer vorhersagbar, wenn mehrere Effekte einander überlagern und/oder geringfügige strukturelle Variationen zu einem deutlich veränderten Reaktionsverhalten führen. Fachgerechte Erklärungen bieten in diesem Zusammenhang nur detaillierte Analysen vorliegender Struktur‐Reaktivitäts‐Beziehungen. Zum Erlernen entsprechender Erklärungsstrategien haben wir bereits eine Lerngelegenheit für Studierende des gymnasialen Lehramts publiziert, die einen innovativen Zugang zur Wirkungsweise elektronischer Substituenteneffekte am Modellbeispiel der alkalischen Hydrolyse substituierter Benzoesäureethylester eröffnet. Deren Fokus ist bislang auf die Wirkungsweise mesomerer Effekte gerichtet. Mit diesem Beitrag ergänzen wir das vorliegende Reaktionssystem um drei neue Contrasting‐Case‐Sets (CC‐Sets) zur Wirkungsweise induktiver Effekte sowie zur Stellungsabhängigkeit mesomerer und induktiver Effekte. Diese ermöglichen es, weitere Facetten elektronischer Substituenteneffekte entlang eines Compare‐Predict‐Observe‐Explain‐Zyklus (CPOE) differenziert zu erarbeiten. Die zusätzlichen CC‐Sets können nahtlos in das didaktische Konzept der Lerngelegenheit integriert werden und schaffen eine Grundlage für die sukzessive Vertiefung des Verständnisses elektronischer Substituenteneffekte.

The reactivity of ethyl esters of 2-(benzoylamino) (1-R-2-oxoindoline-3-ylidene) acetic acids

The studies in a series of 2-(benzoylamino)(1-R-2-oxoindoline-3-ylidene) acetic acids and their derivatives have shown that compounds of the isostructural series exhibit the nootropic, antihypoxic, anabolic activity. Aim. To study the reactivity of esters of 2-(benzoylamino)(1-R-2-oxoindoline-3-ylidene) acetic acids. Materials and methods. The concentration of NaOH in the solution was determined by potentiometric titration on an EV-74 ionomer using the standard aqueous HCl solution. The reaction kinetics was performed in triplicates, the experiments contained 6-8 measurements (the depth of the change was not less than 80 %). The accuracy of the results obtained was assessed by the methods of mathematical statistics of small samples with statistical significance of 0.95. Results and discussion. The reaction rate constants of alkaline hydrolysis of esters of 2-(benzoylamino)(1-R-2-oxoindoline-3-ylidene) acetic acids depend on the structure and the length of the hydrocarbon chain at the heterocyclic nitrogen atom. Introduction of hydrocarbon radicals to the structure of the heterocycle slows down the reaction, while the chain extension accelerates it. The effect of the electronic nature of the substituents on the reactivity of ethyl esters was quantitatively assessed by Hammett equation. The data obtained suggest that the values of the reaction parameter ρ are positive in the temperature range studied; it is additionally confirmed by the BAC2 mechanism of this reaction. Conclusions. The reaction kinetics of alkaline hydrolysis of biologically active ethyl esters of 2-(benzoylamino) (1-R-2-oxoindoline-3-ylidene) acetic acids has been studied in a wide temperature range; its BAC2 mechanism has been proven with formation of highly symmetrical intermediate. The effect of the substituents at the heterocyclic nitrogen atom on the numerous kinetic and activation parameters of the reaction has been analyzed; isokineticity and synchronicity of the reaction have been proven using independent tests.

A novel method for the determination of glycidyl and 3-monochloropropanediol esters in fish oil by gas chromatography tandem mass spectrometry

Today, food security is one of the most important global issues with food quality control and identification of contaminants in foods and beverages, being crucial for human health and safety. In this paper, a novel single-step method for the simultaneous determination of 3-monochloropropanediol (3-MCPD) and glycidyl esters in samples of winterized and non-winterized fish oil by using gas chromatography tandem mass spectrometry (GC-MS/MS) is validated. The method is based on alkaline hydrolysis of esters at room temperature, using only 3-MCPD-d5 as internal standard, and a derivatization step with phenylboronic acid (PBA) at 90°C. The use of GC-MS/MS results in a simplified sample treatment and improvement of the limits of quantification and precision of the analytical method with no need of additional concentration of the extracts. A backflush tee placed between two HP-5 MS UI columns (15m×0.25µm×0.25mm) was used in order to minimize matrix effects and peak shape degradation usually observed in routine analyses. The method was validated in winterized and non-winterized fish oil, achieving a limit of quantification of 100ngg−1 and 50ngg−1 for 3-MCPD and glycidol, respectively. Method validation was accomplished by comparing our laboratory results with results obtained by an accredited reference laboratory (SGS Germany GmbH) and by calculating the recoveries obtained in an assay with spiked samples. For glycidol quantification, a mathematical equation was developed in order to compensate for the partial conversion of 3-MCPD into glycidol. This expression involves the quantification of 3-MBPD-d5 generated during hydrolysis reaction.

A glutamic acid-based polymer keeping intact the integrity of all the three original functionalities of the amino acid

Dimethyl glutamate, on treatment with allyl bromide, afforded dimethyl N,N-diallylglutamate which upon alkaline ester hydrolysis followed by acidification with aqueous HCl gave N,N-diallylglutamic acid hydrochloride [(CH2=CH–CH2)2NH+CH(CO2H)(CH2)2CO2H Cl−] I. Using Butler’s cyclopolymerization protocol, new monomer I underwent ammonium persulfate-initiated polymerization to give pyrrolidine ring-embedded linear cyclopolymer II i.e. −[−CH2(C4H6)NH+{CH(CO2H)(CH2)2CO2H Cl−}CH2−]−n retaining the integrity of all the three functionalities of glutamic acid. Under the influence of pH, the repeating units of triprotic acid (+) in II were equilibrated to those of water-insoluble diprotic polyzwitterionic acid (±) III, water-soluble monoprotic poly(zwitterion-anion) (±−) IV, and its conjugate base polydianion (=) V. The critical salt concentration required to promote water solubility of (±) III has been determined to be 0.548 M NaCl, 0.271 M NaBr, 0.133 M NaI. The basicity constants of the carboxyl groups and trivalent nitrogen in (=) V have been determined. A 5 ppm and 20 ppm concentrations of III are effective in inhibiting the precipitation of CaSO4 from its supersaturated solution with a ≈100% scale inhibition efficiency at 40 °C for a duration of over 3 and 16 h, respectively.

Preparation of hydrophilic activated carbon through alkaline hydrolysis of ester for effective water-vapor adsorption

Hydrophilic activated carbon was prepared by a novel ethyl acetate hydrolysis method. Surface area analysis, spectroscopies, and microscopy were used to examine characteristic differences between raw and hydrophilic activated carbons. Results showed that hydrophilic groups were introduced onto the surface of activated carbon through ethyl acetate hydrolysis in an alkaline environment. The modified activated carbon exhibited higher water vapor adsorption capacity because the hydrophilic groups on its surface bound with water molecules through H-bonding. Adsorption isotherms of water vapor were well fitted by an adsorption model. The optimal temperature for thermal regeneration was determined to be 398 K.

An accurate theoretical study of energy barriers of alkaline hydrolysis of carboxylic esters

Hydrolysis of esters is one of the most important and frequently used reactions in both organic synthesis and biochemistry. While the reaction mechanism in solution is reasonably well understood, many questions still remain to be answered. In the present study, the combination method, MPW1B95/6-311++G(3df,2p)//B3LYP/6-31+G(d)//HF//CPCM/UA0, was found to be reliably predict the energy barriers of alkaline hydrolysis of various esters. The MAD and RMSE were equal to 1.03 and 1.06 kcal/mol, respectively. With this authorized theoretical protocol in hand, we systematically studied the mechanisms of alkaline hydrolysis of ethyl benzoate. The acyl-oxygen cleavage BAC2 route is preferred over the alkyl-oxygen cleavage BAL2 route. Then, the total activation energy barriers of BAC2 and BAL2 routes of over 40 esters have been calculated. And this large body of data allows us to systematically study the various effects controlling the alkaline ester hydrolysis, including the polar effect, the steric effect, and the remote substituent effect. Also, the solvent effect has been extensively studied in this work. Furthermore, the differences between BAC2 and BAL2 routes of these effects are also discussed. The results enable us to predict the energy barrier of the hydrolysis of cyhalofop-butyl in aquatic solution.

ChemInform Abstract: Synthesis, Spectral Studies and C-S Bond Fission of Some Novel Alkyl (( Substituted Phenylsulfonyl)-methyl)-3-nitrobenzoates and Their Sulfinyl Derivatives.

Abstract Methyl and ethyl-4-[(4′-substituted phenylsulfonyl)methyl]-3-nitrobenzoates and the corresponding sulfinyl derivatives have been synthesized. The structure of these esters were proved by IR, NMR and mass spectra. A linear relationship between δ-ppm values of the benzylic protons and [sgrave]-Hammett values of the 4′-substituents has been found. The carbon-sulfur bond fission with 5% sodium hydroxide solution in addition to the alkaline ester hydrolysis is discussed.

Controlled Release of Perfumery Alcohols by Neighboring‐Group Participation. Comparison of the Rate Constants for the Alkaline Hydrolysis of 2‐Acyl‐, 2‐(Hydroxymethyl)‐, and 2‐Carbamoylbenzoates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Controlled Release of Perfumery Alcohols by Neighboring‐Group Participation. Comparison of the Rate Constants for the Alkaline Hydrolysis of 2‐Acyl‐, 2‐(Hydroxymethyl)‐, and 2‐Carbamoylbenzoates

AbstractA series of 2‐acylbenzoates 1 and 2, 2‐(hydroxymethyl)benzoates 3, 2‐carbamoylbenzoates 4–6, as well as the carbamoyl esters 7 or 8 of maleate or succinate, respectively (see Fig. 2), were prepared in a few reaction steps, and the potential use of these compounds as chemical delivery systems for the controlled release of primary, secondary, and tertiary fragrance alcohols was investigated. The rate constants for the neighboring‐group‐assisted alkaline ester hydrolysis were determined by anal. HPLC in buffered H2O/MeCN solution at different pH (Table 1). The rates of hydrolysis were found to depend on the structure of the alcohol, together with the precursor skeleton and the structure of the neighboring nucleophile that attacks the ester function. Primary alcohols were released more rapidly than secondary and tertiary alcohols, and benzoates of allylic primary alcohols (e.g., geraniol) were hydrolyzed 2–4 times faster than their homologous saturated alcohols (e.g., citronellol). For the same leaving alcohol, 2‐[(ethylamino)carbonyl]benzoates cyclized faster than the corresponding 2‐(hydroxymethyl)benzoates, and much faster than their 2‐formyl and 2‐acetyl analogues (see, e.g., Fig. 4). Within the carbamoyl ester series, 2‐[(ethylamino)carbonyl]benzoates were found to have the highest rate constants for the alkaline ester hydrolysis, followed by unsubstituted 2‐(aminocarbonyl)benzoates, or the corresponding isopropyl derivatives. To rationalize the influence of the different structural changes on the hydrolysis kinetics, the experimental data obtained for the 2‐[(alkylamino)carbonyl]benzoates were compared with the results of density‐functional computer simulations (Table 2 and Scheme 4). Based on a preliminary semi‐empirical conformation analysis, density‐functional calculations at the B3LYP/6‐31G** level were carried out for the starting precursor molecules, several reaction intermediates, and the cyclized phthalimides. For the same precursor skeleton, these simple calculations were found to model the experimental data correctly. With an understanding of the influence of structural parameters on the rate constants obtained in this work, it is now possible to influence the rates of hydrolysis over several orders of magnitude, to design tailor‐made precursors for a large variety of fragrance alcohols, and to predict their efficiency as controlled‐release systems in practical applications.

Theoretical Studies of Competing Reaction Pathways and Energy Barriers for Alkaline Ester Hydrolysis of Cocaine

Reaction pathways, solvent effects, and energy barriers have been determined for the base-catalyzed hydrolysis of the benzoyl-ester and methyl-ester groups of neutral cocaine and three smaller alkyl esters in aqueous solution by performing a series of ab initio molecular orbital and density functional theory calculations. The reaction coordinate calculations indicate that both the benzoyl-ester hydrolysis and the methyl-ester hydrolysis occur through a two-step process known for the majority of alkyl esters, i.e., the formation of a tetrahedral intermediate by the attack of hydroxide oxygen at the carbonyl carbon (first step) followed by the decomposition of the tetrahedral intermediate to products (second step). This is the first first-principles study of the whole reaction pathway for cocaine benzoyl- and methyl-ester hydrolyses. The decomposition of the tetrahedral intermediate requires a proton transfer from the hydroxide/hydroxyl oxygen to the ester oxygen, as the C−O bond between carbonyl carbon and...

Kinetics of alkaline hydrolysis of esters of phosphorus acids in micellar and hexagonal phases in the cetyldimethylethylammonium bromide—NaOH—water system

The influence of micellar (Mi) and hexagonal (E) mesophases of the cetyldimethylethylammonium bromide—NaOH—water system (I) on the rates on alkaline hydrolysis ofO-p-nitrophenyl-O,O-diethyl phosphate (2),O-p-nitrophenyl-O-ethylethyl phosphonate (3), andO,O-di(p-nitrophenyl)methyl phosphonate (4) was studied by UV spectrophotometry. The binding constants of the substrates, critical micelle concentrations, and rate constants of reactions in the micellar phase were determined. In micellar solutions of systemI, a tenfold increase in the rates of alkaline hydrolysis of2–4 was observed. An increase in the degree of medium ordering during the formation of the E-phase results in a twofold acceleration of alkaline hydrolysis of2 and3 and in the inhibition of this process in the case of4.

A nonlinear regression model applied to kinetic studies of ester hydrolysis with a surface acoustic wave sensor

A non-linear regression model was derived for the simultaneous determination of the rate constant in alkaline hydrolysis of esters and the initial concentration of esters based on the linear relationship between the frequency response of the surface acoustic wave sensor system and the conductivity of the solution. The model was tested theoretically and experimentally with the methyl-, ethyl-, and n-propyl-acetate systems. The corresponding rate constants estimated at 25 °C are 0.147, 0.103 and 0.0671 respectively.

SYNTHESIS, SPECTRAL STUDIES AND C-S BOND FISSION OF SOME NOVEL ALKYL [(SUBSTITUTED PHENYLSULFONYL)-METHYL]-3-NITROBENZOATES AND THEIR SULFINYL DERIVATIVES

Abstract Methyl and ethyl-4-[(4′-substituted phenylsulfonyl)methyl]-3-nitrobenzoates and the corresponding sulfinyl derivatives have been synthesized. The structure of these esters were proved by IR, NMR and mass spectra. A linear relationship between δ-ppm values of the benzylic protons and [sgrave]-Hammett values of the 4′-substituents has been found. The carbon-sulfur bond fission with 5% sodium hydroxide solution in addition to the alkaline ester hydrolysis is discussed.

1,2,3-Triazabutadiene. XXII. Photochemie der 1-(Carbmethoxy-aryl)- und 1-(Carboxy-aryl)-3-(3-alkyl-benzthiazolinyliden-(2))-triazene als potentielle CEL-Farbstoffe

1,2,3-Triazabutadienes. XXII. Photochemistry of 1-(Carbmethoxy-aryl)- and 1-(Carboxy-aryl)-3-(3-alkyl-benzthiazolinyliden-(2))-triazenes as potential CEL-dyes 1-(Carbmethoxy-aryl)-3-(3-alkyl-benzthiazolinyliden-(2))-triazenes (ester-triazenes) (1) were synthesized by coupling of substituted 3-alkyl-2-imino-benzthiazolines-(1,3) with 2-, 3- and 4-carbmethoxy-benzenediazonium salts. The Z-isomers obtained can be transformed into the E-isomers 2 photochemically or by heating. In the presence of acids the E-ester-triazenes are protonated. From the E-ester-triazenes the potassium-salts (4) can be produced by alkaline ester hydrolysis. With hydrochloric acid the E-triazene-potassium salts (4) can be transformed into the protonated (at the N(1)-Atom) E-acid-triazenes (5). Their photochemical properties are identical with those of the protonated E-ester-triazenes (3). The 1-(carboxy-aryl)-3-(3-alkyl-benzthiazolinyliden-(2))-triazenes (E-acid-triazenes) (6) can be obtained from the protonated derivates by deprotonation in the presence of water. The photochemical behaviour of the E-acid-triazenes (6) and of the E-triazene-potassium-salts (4) depends on the position of the carboxy-group (2-position: photolysis, 3- and 4-position: photoisomerization). The uv/vis-spectroscopical and photochemical properties of the triazene-derivates in solution and in polymeric layers are discussed.

Effect of metal-ion complexation on the rate of the alkaline ester hydrolysis and the carbon acid dissociation of crown malonates in ethanol–water mixtures

The initial rates of the alkaline hydrolysis of 19-crown-6 malonate (1) and 16-crown-5 malonate (2) in ethanol–water mixtures are increased to limiting values by the addition of NaCl and KCl. For 1 in 76%(w/w) ethanol–water the addition of 0.015 mol dm–3 KCl produces a 65-fold increase in the rate compared with that in the absence of metal ions. The results are compatible with the formation of metal ion–crown malonate complexes which undergo hydrolysis more rapidly than the uncomplexed ligands. Values of the equilibrium constants (K) for complex formation and values of the rate coefficients for hydrolysis of the complexes at hypothetical zero ionic strength (k°c) are derived. For the K+–19-crown-6 malonate complex the values of K and k°c/kf, where kf, is the rate coefficient for hydrolysis of the uncomplexed ligand, increase as the relative permittivity (Iµr) of the solvent mixture decreases. The magnitude of the k°c/kf values indicate that the relative permittivity of the space between the bound cation and the reaction centre is about twofold lower than the value of Iµr for the bulk solvent. Spectrophotometric results for the formation of carbanions from 1 and 2 permit qualitative conclusions to be reached about the effect of cation binding on the dissociation of the crown malonates as carbon acids.

Effect of metal ion complexation on the rate of the alkaline ester hydrolysis of 4′-(4-nitrophenoxycarbonyl)benzo-15-crown-5 in ethanol–water mixtures

The second-order rate coefficient for the hydroxide ion-promoted hydrolysis of 4′-(4-nitrophenoxycarbonyl)benzo-15-crown-5 in 54%(w/w) ethanol–water is increased by addition ol NaCl, KCl, RbCl and CsCl. For each salt a limiting value of the rate coefficient is reached at high concentrations of salt. The limiting values are up to two times higher than the rate coefficient ir the absence of salt and decrease in the order Na+ > K+ > Rb+ > Cs+. For reaction in the presence of K+ the limiting value decreases as the solvent is changed from 54% to 49% and to 39%(w/w) ethanol-water. The kinetic results are compatible with the formation of a complex between the crown ester and the metal ion which is more susceptible to alkaline hydrolysis than the uncomplexed crown ester. The crown ester is unable to bind Li+ and the presence of LiCl results in a small reduction in the rate. For the other cations, the results have been analysed to give values for the equilibrium constant for complex formation (K) and the rate coefficient (k0c) for hydrolysis of the crown ester/cation complexes. After allowance is made for electrolyte effects, it is found that the rate coefficients (corrected to infinite dilution) for hydrolysis of the crown ester/catior complexes are seven to twelve times greater than that for hydrolysis of the uncomplexed crowr ester. The trends in the values of K and k0c with cation size and solvent are discussed.

(Benzo[4, 5]cyclohepta[l, 2‐b]thiophen‐4‐ylidene)acetic Acids: Novel Non‐ulcerogenic Antiinflammatory Agents

AbstractCompound (Z)‐8a has been found to display interesting antiinflammatory activity. In order to prepare derivatives with a wide variety of substituents in the aromatic part of the molecule, a new synthesis of the key intermediates 9a‐g was developed starting from thiophene‐3‐carboxylic acid (11) and substituted benzyl bromides. The conversion of 9a‐g to 10a‐g follows a known procedure. Ketones 10a‐g, on reaction with alkyl (dialkoxy‐phosphoryl)acetate, followed by isomer separation and alkaline ester hydrolysis, yielded the desired derivatives (Z)‐8a‐g and (E)‐8a‐g. The biologically most interesting compound (Z)‐8a is currently undergoing clinical trials.

Parallel behavior in kinetic and NMR effects: secondary deuterium isotope effects on the alkaline hydrolysis of esters

..beta..-Deuterium secondary kinetic isotope effects (..beta..-D KIEs) on the alkaline hydrolysis of the p-nitrophenyl esters of acetic, propanoic, butanoic, and pentanoic acids in pH 10.70, 0.20 M carbonate buffer at 25/sup 0/C tend to increase with increasing chain length of the esters up to the pentanoate. The ..beta..-D KIEs are respectively 0.975 +/- 0.004, 0.960 +/- 0.002, 0.940 +/- 0.001, and 0.948 +/- 0.004. The activation energies of the esterolyses of the isotopically light esters follow a similar pattern, as do the /sup 13/C NMR nuclear shieldings in CDCl/sub 3/ of the isotopically light parent carboxylic acids (20.9, 27.4, 35.9, and 33.8 (ppm)) and /sup 13/C NMR one-bond isotope shifts produced by disubstitution of deuterium for hydrogen at the ..cap alpha..-carbons of the acids (0.45, 0.55, 0.60, and 0.59 (ppm)). Correlation of nuclear shieldings and isotope shifts is known from previous work. The possibility is considered that all of the kinetics-based and NMR relationships are linked through the operation of a common ground-state feature of the ester and acid alkyl chains.