Acid In Aprotic Solvents Research Articles

Thermodynamic and kinetic aspects of epichlorohydrin acetolysis under catalysis by triethylamine in solvents of various polarities

The ring-opening reaction of epichlorohydrin with acetic acid in aprotic solvents under the catalysis by triethylamine in the temperature range of 313–353 K was studied by methods of chemical kinetics. The binary mixtures epichlorohydrin:tetrahydrofuran and epichlorohydrin:nitrobenzene (1:1 vol.) were chosen as solvents, which allowed preserving a significant excess of epichlorohydrin in the reaction system and varying the solvent polarity in the range of =15.1–28.7. The kinetic law of the reaction was established for the studied reaction series, and the observed and catalytic constants were obtained for epichlorohydrin acetolysis. It was demonstrated that the increase in temperature and solvent polarity accelerates the reaction. The temperature dependences plotted in Arrhenius coordinates exhibited linear behavior. The joint effect of temperature and solvents on activation parameters (energy, enthalpy, entropy, and Gibbs energy) of the reaction was investigated. The values of Gibbs energy of activation were found to be similar in all studied reaction systems. The isokinetic temperature of the epichlorohydrin acetolysis in epichlorohydrin and binary solvents epichlorohydrin:tetrahydrofuran and epichlorohydrin:nitrobenzene was established, and the enthalpy–entropy compensation effect was stated by correlation methods.

Study on synthesis of ursodeoxycholic acid by reduction of 7-ketolithocholic acid in double aprotic solvents and molecular simulations

Ursodeoxycholic acid (UDCA) is not only safer than chenodeoxycholic acid in the treatment of hepatobiliary diseases, but also has a wide range of applications in Acute Kidney Injury and Parkinson’s Disease. The purpose of this experiment is to improve the conversion rate of 7-ketocholic acid (7K-LCA) and the yield of ursodeoxycholic acid in aprotic solvents during electrochemical reduction process. Three aprotic solvents were investigated as electrolytes. 1,3-Dimethyl-2-imidazolidinone (DMI) has a stable five-membered ring structure, and 7K-LCA has undergone two nucleophilic reactions and “Walden” inversion, the 7K-LCK was stereoselectively reduced to UDCA. Hexamethylphosphoramide (HMPA) and 1,3-methyl-3,4,5,6-Tetrahydro-2(1H)-pyrimidinone (DMPU) can be attacked by chloride ions to produce by-products. Molecular orbital theory-based simulations were conducted to study the reducibility of three aprotic solvents [hexamethylphosphoramide (HMPA), 1,3-methyl-3,4,5,6-Tetrahydro-2(1H)-pyrimidinone (DMPU), and 1,3-Dimethyl-2-imidazolidinone (DMI)] in combination with experiments. Choose the best solvent based on the simulation results, the electrolysis reaction can be carried out by applying current and voltage when lithium chloride is used as electrolytes. Calculations using Materials Studio showed that Cu, Pb, Hg–Cu, and Ni exhibited the highest binding energies to the substrate in this system. Using Cu as the electrode when the solvent is a 1:1 mix of DMI and HMPA, the conversion rate of 7-ketocholic acid (could reach 98%, the yield of ursodeoxycholic acid was up to 80%. Under the same conditions, linear voltammetry was performed on the electrochemical workstation to study the electrolysis behavior, and the obtained results were consistent with the experiment.Graphical

Synthesis of ursodeoxycholic acid by electrochemical stereoselective reduction of 7-ketolithocholic acid in aprotic solvents

A novel method of producing ursodeoxycholic acid was developed through electrochemical stereoselective reduction of 7-ketolithocholic acid (7K-LCA) in a undivided electrolytic cell and aprotic solvents as electrolyte. Five aprotic solvents were investigated as electrolytes, the simple structure of dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF) were easily attacked by chloride ions and undergo nucleophilic reactions, resulting in no target reactions. The structure of hexamethylphosphoric triamide (HMPA) and 1,3-methyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinone (DMPU) is relatively complex, but chloride ions can still attack them, and it was easier for 7K-LCA to directly undergo a reduction reaction under the action of electric current, because of the small steric hindrance of chenodeoxycholic acid (CDCA), 7K-LCA was stereoselectively reduced to CDCA. Due to the stable structure of the five-membered imidazole ring of 1,3-dimethyl-2-imidazolidinone (DMI), 7K-LCA undergoes two nucleophilic and a "Walden inversion", thereby stereoselective reduction of 7K-LCA to UDCA. In DMI, the highest conversion rate of 7K-LCA was 58.3%, the yield of UDCA was 34.9%, ee value was 100%. Linear sweep voltammetry was used to explore the electrochemical behavior of the reaction, and the electrolysis results were consistent with the linear sweep voltammetry. The product was characterized by using IR, 1H NMR and 13C NMR, it confirm the product was UDCA. The method developed in this paper provides a relatively environmentally friendly and low-consumption method for large-scale production of ursodeoxycholic acid, and provides a valuable reference for the asymmetric electrochemical reduction of ketone groups.

Binary Zinc Azides.

Pure, solvent-free Zn(N3 )2 was prepared by reaction of diethyl zinc and hydrazoic acid in aprotic solvents. The single-crystal structure determination, along with the comprehensive characterization of α-Zn(N3 )2 and two metastable polymorphs, could be achieved for the first time. Since these data disagree in large parts with the known, previously reported values, all previous syntheses of Zn(N3 )2 , and for comparison Zn(N3 )2 ⋅2.5 H2 O and Zn(OH)N3 were reinvestigated, indicating that some of the earlier work has to be revised.

Effect of water on product yields of 2-azidobenzoic acid photolysis in aprotic solvents

The effect of water admixtures on the formation of 2-oxo-(3H)-azepine-3-carboxylic acid and 2,1-benzisoxazol-3(1H)-one in the photolysis of 2-azidobenzoic acid in aprotic solvents has been investigated. It has been shown that the addition of nucleophilic agents to the reaction mixture determines the yields of not only 3H-azepines, the products of benzene ring expansion, but also the intramolecular cyclization product 2,1-benzisoxazol-3(1H)-one. Participation of the formed 2,1-benzisoxazol-3(1H)-one in the reaction has been suggested as an explanation of the effect of nucleophilic compounds (water, ethanol, and 2,1-benzisoxazol-3(1H)-one) on the product yield of the monomolecular reaction.

Kinetic Study of the Reaction of Tertiary Phosphines with Acrylic Acid in Aprotic Solvents

The kinetics of the reaction of tertiary phosphines with acrylic acid in a series of aprotic solvents was studied by spectrophotometry. The data obtained suggest a stepwise mechanism of interaction including initial formation of zwitterionic intermediate followed by intermolecular proton transfer to the generated carbanionic center from the second molecule of acrylic acid.

On the mechanism of the organocatalyzed Beckmann rearrangement of cyclohexanone oxime by trifluoroacetic acid in aprotic solvent

The Beckmann rearrangement of cyclohexanone oxime to ɛ-caprolactam in high yield catalyzed by trifluoroacetic acid in aprotic solvents is described. The influence of the concentration of reagents, intermediates, solvents on reaction rate and selectivity in ɛ-caprolactam is studied. The identification of the key intermediate and its role in the catalysis are reported together with the influence of the acid on the reaction rate. In addition, the study of the hydrolysis reactions of reagent and intermediates highlights what are the parameters that influence the selectivity to ɛ-caprolactam. On the basis of these results a likely catalytic cycle based only on the experimentally verified intermediates is also given.

Effects of solvent and structure on the reactivity of 6-substituted nicotinic acids with diazodiphenylmethane in aprotic solvents

The rate constants for the reactions of diazodiphenylmethane (DDM) with 6-substituted nicotinic acids in aprotic solvents at 30?C were determined. The obtained second order rate constants in aprotic solvents, together with literature data for benzoic and nicotinic acids in protic solvents, were used for the calculation of solvent effects, employing the Kamlet-Taft solvatochromic equation (linear solvation energy relationship - LSER) in the form: log k = log k0 + + s?*+ a? + b?. The correlations of the kinetic data were performed by means of multiple linear regression analysis taking appropriate solvent parameters. The sign of the equation coefficients (s, a and b) were in agreement with the postulated reaction mechanism, and the mode of the solvent influences on the reaction rate is discussed based on the correlation results. A similar contribution of the non-specific solvent effect and electrophilic solvation was observed for all acids, while the highest contribution of nucleophilic solvation was influenced by their high acidity. Correlation analysis of the rate data with substituent ?p parameters in an appropriate solvent using the Hammett equation was also performed. The substituent effect on the acid reactivity was higher in aprotic solvents of higher dipolarity/polarizability. The mode of the transmission of the substituent effect is discussed in light of the contribution of solute-solvent interaction on the acid reactivity.

Organocatalyzed Beckmann rearrangement of cyclohexanone oxime by trifluoroacetic acid in aprotic solvent

The Beckmann rearrangement of cyclohexanone oxime to ε-caprolactam catalyzed by trifluoroacetic acid in aprotic solvents such as toluene, 1,2-dichloroethane, acetonitrile, benzonitrile, nitromethane and their mixtures is described. High yield and selectivity in ε-caprolactam have been observed. Data relative to cyclohexanone oxime protonation equilibrium, interaction of ε-caprolactam with the acid, solvent effect on reaction kinetics and apparent activation energy are given together with some thoughts on the reaction mechanism.

Unprecedented Catalytic Three Component One-Pot Condensation Reaction: An Efficient Synthesis of 5-Alkoxycarbonyl- 4-aryl-3,4-dihydropyrimidin-2(1H)-ones

In the past decade, 4-aryl-dihydropyrimidinones 1 have emerged as the integral backbones of several calcium channel blockers, antihypertensive agents, and alpha-1 a-antagonists.1 Strategies for the synthesis of the dihydropyrimidinone nucleus have varied from one-pot to multistep approaches. Biginelli’s initial one-pot reflux of â-keto ester 2, aryl aldehyde 3, and urea, 4, with catalytic acid in a protic solvent frequently afforded low (20-50%) yields.2,3 Subsequent multistep syntheses produced somewhat higher yields but lacked the simplicity of the one-pot, one-step synthesis.3

Proton self‐exchange of para‐substituted N,N‐dimethylanilines and their conjugate acids in aprotic solvents

AbstractThe intermolecular proton transfer between the title compounds was investigated by dynamic NMR spectroscopy. The mechanism was found to be direct proton transfer, other transfer pathways being excluded by the experimental conditions (aprotic solvents with an extremely low water content of about 5×10−4M). It was shown that the observed exchange rates are identical with the rates of the proton transfer proper; association or dissociation pre‐ or postequilibria are not rate determining. Magnitude and solvent dependence of the kinetic isotope effects, as well as the influence of the solvent polarity on the intrinsic activation barrier ΔG‡int indicate considerable solvent reorganization during the transfer. These observations, as well as correlations between the activation parameters of proton self‐exchange and electron self‐exchange of the substrates studied provide some evidence that inner‐sphere and outer‐sphere contributions to ΔG‡int might be separable.

Enantioselective tautomerization of a new metastable enol

A new metastable enol was prepared by the reaction of 2-benzyl acrolein with thiobenzoic acid in aprotic solvents. The enantioselective tautomerization of this enol was studied and enantiomeric excesses up to 71% were found. The absolute configuration of the resulting aldehyde was assigned.

Ring-enlargement of cyclopropylacylsilanes with sulfuric or triflic acid. Selective formation of cyclobutanones or 2-silyl-4,5-dihydrofurans

Reaction of cyclopropylacylsilanes with sulfuric or triflic acid in aprotic solvent affords the corresponding cyclobutanone or 2-silyl-4,5-dihydrofuran derivatives, depending upon the substituents on the three-membered ring or acid used. The use of triflic acid results in the selective formation of the dihydrofurans.

Protonation of pyridines by phenols, thiophenol, trifluoroacetic acid and methanesulfonic acid in aprotic solvents

At moderately low temperatures, 293–213 K, phenols and pyridines form complexes linked by hydrogen bridges as a way for proton migration: A—H⋯B ⇄ A–⋯H—B+. The enthalpy and entropy variations induced by this intracomplex proton transfer have been evaluated for the 2,6-dichloro-4-nitrophenol-3,5-lutidine complex from the temperature dependences of the phenol 13C chemical shifts. At lower temperatures, down to 110 K, 1H NMR results provided direct evidence for the homoconjugation equilibrium: A–⋯H—B++ B ⇄(A–)(B2—H+). Separate 1H signals of the B—H+ and B2—H+ species were recorded for solutions of pyridines with thiophenol, trifluoroacetic acid or methanesulfonic acid with molar excess of the base. The hydrogen-bridge protons in the homoconjugated cations were strongly deshielded, at ca. 20.5 ppm, and this observation suggests their central or near-central position in the bonds: δ+B⋯H⋯Bδ+. The thermodynamic quantities of the homoconjugation equilibrium were calculated for selected systems.

Nature of interactions between phosphines and HO acids in aprotic solvents: nuclear magnetic resonance low-temperature studies

Interactions between phosphines [PPhnMe3–n(3 n 1)] and pentachlorophenol, CF3CO2H and CH3SO3H in C2H5Cl–CDCl3 solutions are examined by 1H and 31P NMR experiments. The last two acids (AH) protonate the phosphines at –100 °C and the resulting cations are stabilized in (A—H)n⋯A—H⋯A–⋯H—PR+3(n 0) hydrogen-bonded ion pairs and by homoconjugated ions: (A⋯H⋯A)–(H—PR3)+.

Relation between the formation constant and the local structure of various bases and reference acids for the 1 : 1 hydrogen-bond complexation in aprotic solvents

For the 1 : 1 hydrogen-bond complexation of various bases against reference acids in aprotic solvents, the formation constant has been correlated with the local structure of acids and bases by regarding a base or an acid as composed of two local structural units, a functional group and a residual moiety. The following equation has been introduced to correlate log K, where K is the formation constant with the local structures: log K=(ηy+ηx)ωbωa+ log K0 where ηy and ηx represent the nature of the functional group of the base and acid, respectively, ωb and ωa represent the electronic effects of the residual moiety of the base and acid, respectively, and log K0 is a constant.Family-independent and -dependent behaviour observed for log K of 26 bases against p-fluorophenol, phenol and 5-fluoroindole in CCl4 are reasonably interpreted by applying the above equation. Formal ωb values of the bases have been evaluated. It has been pointed out that Maria–Gal's angle θ which represents the electrostatic: covalent ratio of hydrogen bonding reflects the nature of the functional group of reference acids, as well as ηx.

Reactions of 1-acyl-2-bromoacetylenes with dithiocarbamic acids

2-Acyl-2-bromoacetylenes react with dithiocarbamic acids in aprotic solvents (acetonitrile, chloroform, or ether) to give 5-acyl-2-diethylamino(heteryl)-1,3-dithiolium bromides, which on reaction with secondary amines (diethylamine or morpholine) undergo cleavage of the 1,3-dithiole ring to give 1-acyl-2-diethyl(morpholyl)dithiocarbamoyl-2-diethylamino(morpholyl)ethylenes. X-ray crystallographic studies on the product from one of these reactions has shown it to be 5-thenoyl-2-diethylamino-1,3-dithiolium bromide.

Hydrogen bonding of a hydroxy proton to an indenide carbanion observed by n.m.r. and i.r. spectroscopy. The use of cryptand to make the alcohol group less acidic than the carbon acid in aprotic solvents of low dielectric constant

The indene moiety in 4-(inden-3′-yl)-2,3,4-trimethylpentan-2-ol (1) is a stronger acid than the hydroxy group in dipolar aprotic solvents but the acidity is reversed in non-polar aprotic solvents; addition of cryptand makes the hydrogen-bonded carbanion (2) the most favoured species in all solvents.

Self‐consistent reaction field calculations on the proton transfer in ammonia‐formic acid systems as a model for hydrogen bonding in amino acids in solution

AbstractThe reaction field (RF) model of solvent effects, implemented within the SCF‐CNDO/2 scheme of calculation, has been applied to analyze the proton transfer in the NH3…HCOOH system in the presence of several polarizable media. The aim of such a study was to characterize the tatutomeric equilibrium between the neutral and zwiterionic forms of H‐bonded amino acids in aprotic solvents. Qualitative results concerning the energetics of this equilbrium show the stabilization of two different H‐bonded complexes, corresponding to two separate minima in the free energy surface. These well known double minima potentials are found to be dependent on both the intermolecular NO distance and the strength of the reaction field. The behavior of this model is qualitatively consistent with experimental observations of nitrogen‐substituted amino acids in solution: both show, for low values of the dielectric constant, tautomeric equilibria where the H‐bonded complexes appear to be more stable than the corresponding monomeric forms. The charge transfer process associated with the proton migration along the H‐bond is also discussed. It is found that the amount of charge transferred increases with the NO distance and with the RF strength, In order to test the general approach and compare it with previous work, calculations on the real monomeric systems glycine, β‐alanine, and γ‐amino butyric acid was also performed.

Voltammetric evaluation of the effective acidities (pKa') for Brønsted acids in aprotic solvents.

Voltammetric evaluation of the effective acidities (pKa') for Brønsted acids in aprotic solvents.