Synthesis Of Acid Esters Research Articles

Effect of 2-hexanol and methanol on the <i>one-pot</i> process of dehydration and alkoxycarbonylation for the synthesis of esters

Objectives. To study the possibility of one-pot synthesis (combination of two processes in one reactor) for the following pairs of processes: (1) dehydration of 2-hexanol and isomerizing alkoxycarbonylation of the resulting 2-hexene, in order to obtain 2-hexyl heptanoate, and (2) dehydration of 2-hexanol and isomerizing methoxycarbonylation of the resulting 2-hexene, in order to obtain methyl esters of C7 carboxylic acids. To investigate the effect of the concentrations of 2-hexanol and methanol on the rate of the one-pot synthesis.Methods. One-pot synthesis was studied in a toluene medium in a steel batch reactor designed to operate at elevated pressure and equipped with a glass insert, a magnetic stirrer, a sampler, and gas input and discharge devices. Samples of the reaction mass were taken during the combined process and were analyzed by means of gas–liquid chromatography with a flame ionization detector.Results. The possibility of one-pot combination was demonstrated for 2-hexanol dehydration catalyzed by methanesulfonic acid, as well as for the isomerizing alkoxycarbonylation of the resulting 2-hexene with 2-hexanol and CO, catalyzed by the Pd(PPh3)2Cl2–XANTPHOS–methanesulfonic acid system. The dependencies of the rates of the dehydration of 2-hexanol and the formation of esters of C7 carboxylic acids on the concentration of 2-hexanol were shown to pass through a maximum. The possibility of the one-pot process was proved for the synthesis of esters from 2-hexanol, methanol, and CO with the predominant formation of heptanoic acid esters in the presence of the above catalytic system. The rates of dehydration of 2-hexanol and the formation of 2-hexyl esters of C7 carboxylic acids were found to decrease with increasing the concentration of methanol in the reaction mass. Under mild conditions (temperature 115°C, CO pressure 3 MPa) with the addition of methanol, the total fraction of 2-hexyl and methyl heptanoic acid esters among C7 carboxylic acid esters was determined to be 85.5%.Conclusions. The reactions of intramolecular acid–catalytic dehydration of 2-hexanol and isomerizing alkoxycarbonylation of the resulting 2-hexene, catalyzed by the Pd(PPh3)2Cl2–XANTPHOS–methanesulfonic acid system, can be performed as a one-pot process. Methanesulfonic acid simultaneously functions as a catalyst for the dehydration of 2-hexanol and a cocatalyst for the palladium–phosphine system for the alkoxycarbonylation of hexenes. In the presence of the Pd(PPh3) 2Cl2–XANTPHOS–methanesulfonic acid catalytic system, processes for the synthesis of heptanoic acid esters from 2-hexanol, methanol, and CO can be combined within one reactor. An increase in the methanol concentration negatively affects the rate of the dehydration of 2-hexanol and the formation of 2-hexyl esters of C7 carboxylic acids. A small amount of methanol in the reaction mass leads to an increase in the fraction of heptanoic acid esters among C7 carboxylic acid esters.

Ultrasound-Assisted Catalyst-free Synthesis of α,β -Unsaturated Amino Acid Esters and Unsaturated Amino Ketones

Introduction: Sonication has been introduced as a green and effective activation method for the selective monoamination of β-dicarbonyl compounds. The simple one-pot process resulted in different substituted β-amino-ɑ,β-unsaturated esters and ketones at room temperature with quantitative yields. Aqueous NH4OH was used as a safe and economical nitrogen source for pressurized NH3 gas. The process is considered green, accounting for not using any solvents and catalysts, besides some aqueous NH4OH-involved reactions using nontoxic water. A broad variety of useful synthetic intermediates, β- amino-ɑ,β-unsaturated esters and ketones have been prepared in short reaction time. Methods: Using this developed protocol, we were able to synthesize a series of structurally diverse β- amino-ɑ,β-unsaturated esters and unsaturated amino ketones. Results: The synthesis of target compounds was achieved in a truly green process with high atom economy and excellent yields in a catalyst-free one-pot system in an aqueous medium using simple, commercially available, inexpensive ammonium hydroxide as the source of the nitrogen. The high atom economy has been accompanied by the formation of a small amount of nontoxic waste, water. Conclusion: In conclusion, a simple, convenient, and high-yielding catalyst-free environmentally benign method was developed for the synthesis of unsaturated amino acid esters and unsaturated amino ketones.

4-Ketovalero lactone (KVL): A gateway molecule for diversification of the furanic platform

Diversification of the furanic platform has been developed from 4-ketovalerolactone (KVL), a platform molecule readily available from furfuryl alcohol. A halogen-free synthetic route to δ-aminolevulinic acid is reported alongside a further exploration of KVL in the synthesis of important 5-hyrdoxy levulinic acid esters. Flow chemistry approaches have been implemented for the synthesis of short- and long-chain esters that may find applications as biorenewable fuel oxygenates and lubricants, respectively.

Chitosan supported ionic liquid, a multifaceted catalyst for streamlined and efficient synthesis of carboxylic, amino acid and carbohydrate esters.

This work presents a sustainable approach for synthesizing esters from carboxylic acids, amino acids and carbohydrates using a robust and eco-friendly chitosan-incorporated ionic liquid under solvent-free conditions. Ionic liquids with carbon chain lengths ranging from 3 to 8 were integrated into the chitosan molecule, resulting in a heterogeneous catalyst optimized for esterification reactions. Among these, the 6-carbon chain ionic liquid demonstrated superior catalytic activity and substrate tolerance. The catalyst's effectiveness was confirmed using advanced analytical techniques. The acidity of the ionic liquid was assessed by observing the interaction between the synthesized IL6 (1,4-bis(5-carboxypentyl)pyrazine-1,4-diium ([BCPPD][Br])) and p-nitroaniline via UV-Vis studies. Chitosan-IL6, an ionic liquid supported on chitosan, functions as a heterogeneous catalytic system that can be easily removed from reaction mixtures through simple filtration. It also exhibits excellent reusability, maintaining high catalytic activity and structural integrity over 10 catalytic cycles. Moreover, the methodology was successfully scaled up for the gram-scale synthesis of key compounds such as diisopropyl azodicarboxylate, methyl nicotinate, methyl cysteinate, and glucose pentaacetate, highlighting its practical viability.

Synthesis of malonic acid esters

Synthesis of malonic acid esters

Microwave synthesis of novel chenodeoxycholic acid esters and comparative study of chromatographic behavior and lipophilicity

In this study, eco-friendly microwave-assisted esterification reactions of chenodeoxycholic acid with medium-chain diols (1,2-ethanediol, 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol, and 1,10-decanediol) or tetraethylene glycol were accomplished. The synthesized bile acid esters were obtained with high yields (up to 81 %) and purity in a short reaction time (15 min). It is shown that the microwave technique is a suitable method for the preparation of chenodeoxycholic acid esters. In order to obtain detailed insight into the lipophilic behavior of the studied chenodeoxycholic acid esters, a comparative study of chromatographic behavior and lipophilicity was performed. Also, the present study deals with the estimation of pH – logD profiles in order to get an overview of the changes in lipophilicity related to the pH value changes. The obtained results indicate that studied compounds have logD values in the range acceptable for potential drug candidates. Chromatographic lipophilicity of synthesized chenodeoxycholic acid esters successfully correlate with in silico lipophilicity descriptors.

Chemoselective reductive coupling of α, β-unsaturated esters and nitroarenes for sustainable synthesis of β-amino acid esters by a hierarchically porous cobalt nanocatalyst

Reductive coupling of two unsaturated substances for the construction of functional molecules remains a significant challenge due to the difficulty in controlling the chemoselective reduction. Here, by developing a cobalt and nitrogen co-doped hierarchically porous carbon material (Co/N-HPNC) deriving from the homomorphic Zr-based metal-organic framework (MOF), we describe, for the first time, its application as a bifunctional catalyst for direct access to β-amino acid esters via chemoselective reductive hydroamination of the α, β-unsaturated esters with cheap and air-stable nitroarenes. The catalyst structure-performance relationship reveals that the N-dopants benefit the adsorption of the nitroarenes and protons, and the active cobalt species run the transfer hydrogenation of the nitroarenes, such a synergetic effect results in chemoselective formation of the desired products. The developed catalytic transformation proceeds with good substrate and functionality tolerance, the use of easily accessible and reusable base metal catalyst, operational simplicity, high step and atom efficiency, and easy applicability for further fabrication of functional molecules, which offers a sustainable platform for direct synthesis of valuable products from bulk raw materials.

Organocatalyst Promoted Efficient Synthesis of Carboxylic Acid Esters and its Application as Plasticizer for Polyvinyl Chloride

AbstractThe present work is related to the synthesis of a carboxylic acid ester using lab synthesized triphenylphosphonium triflate catalyst and its application as a plasticizer for polyvinyl chloride (PVC) processing. The high thermal stability of this organocatalyst allows the synthesis of terephthalic acid di‐esters with high boiling alcohols such as 1‐butanol, 2‐ethyl hexanol with higher yield in the range of 55–97 %. Different ester derivatives like dioctyl phthalate (DOP), dioctyl terephthalate (DOTP), n‐butyl benzoate, dibutyl terephthalate, dibutyl phthalate, and di‐dodecanol terephthalate have been synthesized using triphenylphosphonium triflate organocatalyst. These synthesized ester derivatives are characterized using 1H NMR, GC‐MS and HPLC. The purity of different synthesized esters was in the range of 80–99 %. The synthesized Dioctyl terephthalate (DOTP) was used as a plasticizer in PVC and compared the results with commercial DOP plasticizer performance for PVC. The PVC/DOTP composition exhibited comparable performance in terms of mechanical properties like tensile and flexural strength and modulus. No significant change found in hardness and impact strength of both the compositions. Ease of processing observed in case of PVC/DOTP composition due to lower torque as compared to PVC/DOP composition. This indicates DOTP can be a potential alternative to the traditional dioctyl phthalate (DOP) plasticizer for PVC processing.

Synthesis and biological evaluation of gallic acid esters as phagocyte oxidative burst inhibitors

Several degenerative diseases, including cancer, are caused by oxidative stress, which is caused by the overproduction and accumulation of free radicals. The purpose of the study was to synthesize gallic acid (GA or 3,4,5-trihydroxybenzoic acid) esters and evaluate their anti-inflammatory potential through the inhibition of reactive oxygen species (ROS). The compounds methyl gallate (2), sec-butyl gallate (3), ethyl gallate (4), isopropyl gallate (5), 2-methoxyethyl gallate (6), 4-methoxybutyl gallate (7), 2-methylbutyl gallate (8) and pentan-3-yl gallate (9) were synthesized. 1H NMR, MS and IR data are reported for compounds 2-9, and 13C NMR data for compounds 2, 3, 5, and 6. The molecular formulae of compounds 3 and 7-9 were established by HREI-MS spectroscopic data. All the synthesized compounds were tested for their anti-inflammatory and cytotoxic activities by chemiluminescence and MTT cytotoxicity assay respectively. The results revealed the anti-inflammatory potential of compounds 2-8 with an IC50 range between (13.3 – 54.3 µM) as compared to the standard anti-inflammatory drug, Ibuprofen (IC50 = 54.3 ± 9.2 μM). The most potent inhibitors were found to be compound 3 (ROS IC50 = 15.0 ± 6.6 µM) and compound 7 (ROS IC50 = 13.3 ± 0.8 µM). All compounds were found to be non-cytotoxic in the NIH-3T3 fibroblast cell line. Compounds 3, 7- 9 were identified as new compounds.

Lithio Tris(methylthio)methane as Hydroxy/Thio/Aminocarbonyl Anion Equivalent: Asymmetric Synthesis of α-Amino Acid Esters, Thioesters, Amides, and Peptides.

The use of lithio tris(methylthio)methane as a hydroxy/thio/amino carbonyl anion equivalent in the synthesis of α-amino acids is reported. Addition of the reagent to nonracemic sulfinimines furnished the α-sulfinamido trithioformates in excellent diastereoselectivity. Unmasking the trithioformates to diverse functionalities, such as α-amino acid thioesters, esters, anilides, amides, and di/tri peptides, without epimerization of chiral centers was accomplished.

Single-Flask Enantioselective Synthesis of α-Amino Acid Esters by Organocatalysis.

An operationally simple Knoevenagel condensation/asymmetric epoxidation/domino ring-opening esterification (DROE) approach has been disclosed to successfully access a good variety of (R)- and (S)-α-arylglycine esters from commercially available aldehydes, phenylsulfonyl acetonitrile, cumyl hydroperoxide, anilines, and readily available Cinchona alkaloid-based catalysts using a single solvent and reaction vessel. DFT calculations performed on the key asymmetric epoxidation showed the importance of cooperative H-bonding interactions in affecting the stereocontrol.

Synthesis and Characterization of Dicarboxylic Acid Esters of 1‐Hexadecanol for a Thermal Energy Storage Application Range of 50–55 °C

Dicarboxylic acid esters for thermal energy storage (TES) have attracted increasing attention in recent years because of their easy production, offering different temperatures, and providing solutions to the handicaps of fatty alcohols, which are potential TES materials. Dicarboxylic acid esters of 1‐hexadecanol are synthesized herein from adipic, succinic, and oxalic acid for the first time as TES materials. The dicarboxylic acid esters are characterized by Fourier transform infrared and proton nuclear magnetic resonance spectroscopy. Furthermore, the thermophysical properties of the dicarboxylic acid esters are examined by differential scanning calorimetry and thermogravimetric analysis methods. Additionally, the surface morphology features of the dicarboxylic acid esters are determined by polarized optical microscopy. The synthesized dicarboxylic acid esters of 1‐hexadecanol exhibit curiously specific behaviors that they melt at 49.2, 54.1, 54.8, and 53.5 °C, respectively, and crystallize at 47.7, 50.4, 53.1, and 50.2 °C, respectively. The applicability analyses of the dicarboxylic acid esters are carried out with integral graphs showing the sum of sensible and latent heat in a certain temperature range, time‐dependent heating and cooling graphs in a constant increasing temperature environment, and structural and thermal stability analyses after 1000 times heating–cooling thermal cycle.

Photochemical Wolff Rearrangement Initiated Generation and Subsequent α-Chlorination of C1 Ammonium Enolates.

The enantioselective synthesis of α-chlorinated carboxylic acid esters with er up to 99:1 and yields up to 82% was achieved via a one-pot multistep protocol starting from α-diazoketones. This process proceeds via a photochemical Wolff rearrangement, trapping of the generated ketene with a chiral Lewis base catalyst, subsequent enantioselective α-chlorination, and a final nucleophilic displacement of the bound catalyst. The obtained products were successfully utilized for stereospecific nucleophilic displacement reactions with N- and S-nucleophiles.

Nickel-catalyzed mild synthesis of functional γ-amino butyric acid esters via direct α-C(sp3)-H allylation of N-alkyl anilines with allyl sulfones.

Herein, by employing a readily available Ni(OAc)2·4H2O/TBHP catalyst system, we present a new method for mild synthesis of α-methylene-γ-amino butyric acid esters via direct α-C(sp3)-H allylation of N-alkyl anilines with allyl sulfones under oxidative nickel catalysis. The synthetic protocol proceeds with good substrate and functional group compatibility, operational simplicity, the use of base metal catalysts and easily accessible feedstocks, and no need for pre-functionalization of the α-site of N-alkyl anilines. In addition, the obtained products are applicable for further elaboration of functional molecules.

Nickel-catalyzed esterification of mandelic acids with alcohols

Mandelates and their derivatives are widely used in organic synthesis, drug discovery, biodegradable polymers and other related fields. Therefore, the effective and simple synthesis of these compounds has attracted much attention. In this paper, a nickel(II)-catalyzed esterification of mandelic acids with different alcohols was realized for the synthesis of mandelic acid esters. This transformation was conducted under mild reaction conditions with yields up to 95%, and was successfully utilized in the gram-scale synthesis of medicine cyclandelate.

Design and Characterization of In-One Protease-Esterase PluriZyme.

Proteases are abundant in prokaryotic genomes (~10 per genome), but their recovery encounters expression problems, as only 1% can be produced at high levels; this value differs from that of similarly abundant esterases (1-15 per genome), 50% of which can be expressed at good levels. Here, we design a catalytically efficient artificial protease that can be easily produced. The PluriZyme EH1AB1 with two active sites supporting the esterase activity was employed. A Leu24Cys mutation in EH1AB1, remodelled one of the esterase sites into a proteolytic one through the incorporation of a catalytic dyad (Cys24 and His214). The resulting artificial enzyme, EH1AB1C, efficiently hydrolysed (azo)casein at pH 6.5-8.0 and 60-70 °C. The presence of both esterase and protease activities in the same scaffold allowed the one-pot cascade synthesis (55.0 ± 0.6% conversion, 24 h) of L-histidine methyl ester from the dipeptide L-carnosine in the presence of methanol. This study demonstrates that active sites supporting proteolytic activity can be artificially introduced into an esterase scaffold to design easy-to-produce in-one protease-esterase PluriZymes for cascade reactions, namely, the synthesis of amino acid esters from dipeptides. It is also possible to design artificial proteases with good production yields, in contrast to natural proteases that are difficult to express.

Lipase-catalyzed synthesis of fructosyl myristic acid esters as biosurfactants in a low solvent media: Optimization of the bioconversion

Lipase-catalyzed synthesis of fructosyl myristic acid esters as natural food biosurfactants in low solvent reaction media was investigated. The effect of chain length of fructose-based glycosides as acyl acceptors was found to be inversely proportional to the bioconversion yield. The application of molecular sieves proved unsuccessful in low-solvent media due to their saturation and mass transfer limitations. The substitution of low-solvent myristic acid reaction media with 5% oleic acid led to similar bioconversion yield than that achieved without oleic acid, while no solidification of the reaction media was observed. Response surface methodology using a 3-factor and 5-level central composite design was used to achieve a compromise between mass transfer limitations and catalytic activity of lipase in low-solvent myristic acid reaction media enriched with oleic acid. Modeling found reduced quadratic models accurately described the yield and productivity of the reaction. Maximum bioconversion yield (22%) was achieved using 0.2 mol/L of fructose and 5% (w/v) of Lipozyme® RM IM in a reaction media composed of 80% myristic acid and 10% oleic acid. Lipozyme® RM IM catalyzed successfully 5 consecutive reactions before showing reduction of its synthetic activity at the 6th cycle. The end-product profile analysis confirmed the selectivity of Lipozyme® RM IM towards saturated fatty acids over unsaturated one and the formation of fructosyl monoester and diester of myristic acids. This study lays the ground of a sustainable approach for the acylation of myristic or longer saturated fatty acids with carbohydrates for a great potential as functional ingredients.

Enhanced antioxidant capacity of lipoic acid in different food systems through lipase-mediated esterification with phytosterols.

α-Lipoic acid has excellent antioxidant activity, but its poor lipid solubility greatly limits its practical application. This study was undertaken (i) to develop a novel and efficient enzymatic synthesis of lipophilic lipoic acid esters using Candida sp. 99-125 lipase as a catalyst; and (ii) to systematically evaluate their antioxidant potential against bulk oil, oil-in-water emulsion (O/W) and cooked ground meat. Lipophilic lipoic acid esters were successfully and efficiently synthesized using phytosterols as acyl receptor in the presence of Candida sp. 99-125 lipase. The product was identified as phytosterol lipoate by mass spectrometry, Fourier transform infrared spectroscopy and nuclear magnetic resonance. The maximum conversion of phytosterol lipoate surpassed 90% within 12 h and its final yield exceeded 81%. Interestingly, the oil solubility of lipoic acid was increased at least 25-fold and other physicochemical properties were significantly improved. Most importantly, phytosterol lipoate exhibited higher antioxidant activity than lipoic acid in bulk oil, O/W emulsions and cooked ground meat. The antioxidant capacity of lipoic acid can be significantly enhanced by esterification with phytosterols. Therefore, phytosterol lipoate could be further developed as a new antioxidant for use in oil- and fat-based foods. © 2022 Society of Chemical Industry.

Mild, Organo-Catalysed Borono-Deamination as a Key to Late-Stage Pharmaceutical Precursors and 18F-Labelled Radiotracers.

A tris(pentafluorophenyl)borane catalysed method for the synthesis of boronic acid esters from aromatic amines in yields of up to 93% was devised. Mild conditions, benign reagents, short reaction times, low temperatures and a wide substrate scope characterize the method. The reaction was found applicable to the synthesis of boronic acid ester derivatives of complex drug molecules in up to 86% isolated yield and high purity suitable for labelling. These boronates were subsequently labelled with [18F]fluoride ion in radiochemical yields of up to 55% with and even without isolation of the boronate-intermediate.

Cobalt-Catalyzed Four-Component Carbonylation of Methylarenes with Ethylene and Alcohols.

Direct conversion of raw materials to fine chemicals is greatly economically influential. We developed a non-expensive cobalt-catalyzed multicomponent carbonylative reaction for the synthesis of γ-aryl carboxylic acid esters from readily available methylarene, ethylene, and CO, which are widely found in multiple FDA-approved drugs.