Synthesis Of Esters Research Articles

Synthesis of Tetra-Substituted 3-Hydroxyphthalide Esters by Isothiourea-Catalysed Acylative Dynamic Kinetic Resolution.

A general and highly enantioselective method for the preparation of tetra-substituted 3-hydroxyphthalide esters via isothiourea-catalysed acylative dynamic kinetic resolution (DKR) is reported. Using (2S,3R)-HyperBTM (5 mol %) as the catalyst, the scope and limitations of this methodology have been extensively probed, with high enantioselectivity and good to excellent yields observed (>40 examples, up to 99 %, 99 : 1 er). Substitution of the aromatic core within the 3-hydroxyphthalide skeleton, as well as aliphatic and aromatic substitution at C(3), is readily tolerated. A diverse range of anhydrides, including those from bioactive and pharmaceutically relevant acids, can also be used. The high enantioselectivity observed in this DKR process has been probed computationally, with a key substrate heteroatom donor O⋅⋅⋅acyl-isothiouronium interaction identified through DFT analysis as necessary for enantiodiscrimination.

Quinoline sulfonates as the potent inhibitors of MDA-MB-231 and MCF-7 breast cancer cells: Synthesis, cytotoxicity, and molecular docking studies

Quinoline is a promising class of heterocycles with interesting biological and pharmacological properties including anti-cancer. Variety of quinoline-based derivatives have been synthesized previously and reported for diversed biological properties, which assisted in the development of new drug candidates. The current study describes the synthesis of quinoline-based sulfonic esters 1–42, and their cytotoxicity towards two breast cancer cell lines (MDA-MB-231, and MCF-7) and a normal human BJ cell line. Compounds 15, 20, and 28 showed the highest cytotoxicity against both breast cancer cell lines. Molecular docking studies predicted the hydrophobic interactions of test compounds with both estrogen α-receptor, and EGF-receptor.

Sustainable synthesis of 2-ethyl hexyl oleate via lipase-catalyzed esterification: A holistic simulation and cost analysis study

Lipase catalyzed synthesis of fatty acid esters has recently attracted much attention as it represents a cleaner production route compared to the conventional energy intensive chemical method. In this study, the technical and economic viability of 2-ethyl hexyl oleate (2-EHO) synthesis by the catalytic esterification of oleic acid (OA) and 2-ethyl hexyl alcohol (2-EHA) in a stirred tank reactor using Novozym 435 (Candida antarctica lipase B) was investigated. A conversion rate of 91% was obtained by adopting the subsequent optimized parameters: 4% enzyme amount, 2 h reaction time, 4:1 M ratio of alcohol to fatty acid, 150 rpm stirring speed, and 60 °C temperature. The lipase operational stability study showed that enzymes can be used for 30 successive cycles without significant lose in activity. The use of Aspen Plus simulator enabled the development of a detailed process flow diagram, which significantly improved the understanding of this clean production method and assessed the overall costs. A holistic cost analysis revealed a production cost of $2109 per ton of 2-EHO, thereby yielding an approximate 28% profit margin relative to prevailing market rates. Rigorous financial assessments corroborated the project's viability, substantiating a net present value (NPV) of $14.7 MM, a return on investment (ROI) of 583.91% (plant life time = 15 years), projected Payback Period stands at 6 years, and an internal rate of return (IRR) of 23%. These results confirm the technical and economic feasibility of lipase catalyzed production of 2-EHO, highlighting its potential as an environmentally and profitable approach in the synthesis of fatty acid esters.

Nickel-catalyzed carbonylation of arylboronic acids and alkylarenes to benzyl benzoates

Here, we report a nickel-catalyzed carbonylation of arylboronic acids and alkylarenes to benzyl benzoates. The reaction was well tolerated by various functional groups, resulting in the formation of wide range of functional group substituted esters in moderate to good yields. Furthermore, the reaction also allowed for the synthesis of 18O-labeled esters.

Copper‐Catalyzed Synthesis of Sulfinic Esters via Oxidative Coupling of Thiols or Disulfides with Alcohols

AbstractThe copper‐catalyzed coupling of thiols with alcohols was achieved under air atmosphere. The reaction proceeded smoothly in the presence of a base such as Cs2CO3 or Rb2CO3 affording sulfinic esters in good yields. Furthermore, disulfides were also available in the procedure. Both sulfide‐groups on disulfide were efficiently consumed.

1-Iodoglycal: A Versatile Intermediate for the Synthesis of d-Glyco Amides and Esters Employing Carbonylative Cross-Coupling Reaction.

In this study, we present the development of two catalytic processes: a Pd-PEPPSI-catalyzed aminocarbonylation and a Pd(OAc)2-Xantphos-catalyzed alkoxycarbonylation of d-glycals, utilizing carbonylative cross-coupling reactions. We explored successfully various types of aromatic amines, as well as alkyl amines and amino acids, to synthesize new d-glycal amides. However, we observed limitations in the reactivity of alkyl and heteroaromatic amines. The processes enabled the synthesis of 20 novel C1-branched glycoamides and 7 new d-gluco esters.

Batch and Continuous Flow Total Synthesis of Cannabidiol.

Herein, we present a comprehensive total synthesis of cannabidiol integrating both batch and continuous flow conditions. Our approach is planned to streamline the synthesis of olivetolic acid derivatives and utilize an enantiomerically pure monoterpene moiety obtained from naturally occurring (R)-(+)-limonene by photocatalysis. Key reactions, including the synthesis of olivetolic ester and a Friedel-Crafts alkylation, are successfully adapted to continuous flow, resulting in improved yields and selectivities. This study not only offers a scalable and efficient route for cannabidiol synthesis but also contributes to the synthetic approaches to access cannabinoids (diversity synthesis), with potential applications in medicinal and industrial contexts.

Cytotoxic Potential of Betulinic Acid Fatty Esters and Their Liposomal Formulations: Targeting Breast, Colon, and Lung Cancer Cell Lines.

Betulinic acid is a lupane-type pentacyclic triterpene mostly found in birch bark and thoroughly explored for its wide range of pharmacological activities. Despite its impressive biological potential, its low bioavailability has challenged many researchers to develop different formulations for achieving better in vitro and in vivo effects. We previously reported the synthesis of fatty acid esters of betulinic acid using butyric, stearic, and palmitic acids (But-BA, St-BA, and Pal-BA) and included them in surfaced-modified liposomes (But-BA-Lip, St-BA-Lip, Pal-BA-Lip). In the current study, we evaluated the cytotoxic effects of both fatty acid esters and their respective liposomal formulations against MCF-7, HT-29, and NCI-H460 cell line. The cytotoxic assessment of BA derivatives revealed that both the fatty esters and their liposomal formulations acted as cytotoxic agents in a dose- and time-dependent manner. But-BA-Lip exerted stronger cytotoxic effects than the parent compound, BA and its liposomal formulation, and even stronger effects than 5-FU against HT-29 cells (IC50 of 30.57 μM) and NCI-H460 cells (IC50 of 30.74 μM). BA's fatty esters and their respective liposomal formulations facilitated apoptosis in cancer cells by inducing nuclear morphological changes and increasing caspase-3/-7 activity. The HET-CAM assay proved that none of the tested compounds induced any irritative effect, suggesting that they can be used safely for local applications.

Exploring lipase-based biocatalysts derived from Yarrowia lipolytica for fatty acid ethyl esters synthesis

Exploring lipase-based biocatalysts derived from Yarrowia lipolytica for fatty acid ethyl esters synthesis

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.

Mechanochemical Synthesis of α-halo Alkylboronic Esters.

α-halo alkylboronic esters, acting as ambiphilic synthons, play a pivotal role as versatile intermediates in fields like pharmaceutical science and organic chemistry. The sequential transformation of carbon-boron and carbon-halogen bonds into a broad range of carbon-X bonds allows for programmable bond formation, facilitating the incorporation of multiple substituents at a single position and streamlining the synthesis of complex molecules. Nevertheless, the synthetic potential of these compounds is constrained by limited reaction patterns. Additionally, the conventional methods often necessitate the use of bulk toxic solvents, exhibit sensitivity to air/moisture, rely on expensive metal catalysts, and involve extended reaction times. In this report, a ball milling technique is introduced that overcomes these limitations, enabling the external catalyst-free multicomponent coupling of aryl diazonium salts, alkenes, and simple metal halides. This approach offers a general and straightforward method for obtaining a diverse array of α-halo alkylboronic esters, thereby paving the way for the extensive utilization of these synthons in the synthesis of fine chemicals.

Synthesis of phenyl esters 2-oxo-2H-1-benzopyran-3-carboxylic acids as promising antimicrobial agents

Corresponding chloroanhydrides were synthesized by the interaction of coumarin-3-carboxylic and 6-methoxycoumarin-3-carboxylic acids with an excess of thionyl chloride under heating. Due to the quantitative yields and the formation of volatile products within the reaction, chloroanhydrides were used without additional purification in acylation of substituted phenols for the synthesis of phenyl esters of 2-oxo-2H-1-benzopyran-3-carboxylic acids. The reaction was carried out by heating in anhydrous dioxane environment in the presence of pyridine as a catalyst. The structure of the obtained esters was proven using instrumental methods of analysis. The antimicrobial and antifungal activity of the synthesized compounds was studied in vitro by the method of two-fold serial dilutions in liquid and solid nutrient environments. Antimicrobial activity screening showed that the synthesized esters have a moderate activity against gram-negative microorganisms and C. albicans. It was found that the 4-methyl-2-chlorophenyl ester of coumarin-3-carboxylic acid had the greatest bacteriostatic activity against Ps. aeruginosa and Pr. vulgaris, 2-chlorophenyl ester of coumarin-3-carboxylic acid against Ps. aeruginosa and E. coli, coumarin-3-carboxylic acid 4-hydroxyphenyl ester against Pr. vulgaris, and coumarin-3-carboxylic acid 2-isopropyl-5-methylphenyl ester against E. coli at a concentration of 31.25 g/ml. 2-Chlorophenyl ester also showed a bactericidal effect against E. coli. The synthesized compounds also have an antifungal effect against the C. albicans. strain used in the experiment. Thus, 4-methyl-2-chlorophenyl ester, 4-fluorophenyl ester, 4-hydroxyphenyl ester, 2,3-dihydroxyphenyl ester, 2-isopropyl-5-methylphenyl ester of coumarin-3-carboxylic acid are active at a concentration of 31.25 g/ml.

Enzymatic synthesis and parameters affecting on citronellyl acetate ester by trans-esterification reaction

Abstract Citronellyl acetate is a crucial component of flavor and fragrance in the food, cosmetic, and pharmaceutical sectors. In non-aqueous media, it can be successfully produced via lipase catalysis. This study focuses on the lipase-catalyzed trans-esterification of citronellol alcohol with geranyl acetate ester in a non-aqueous medium to produce citronellyl acetate. For the synthesis of citronellyl acetate, crude acetone powders isolated from several plant seedlings of black cumin, fenugreek, coriander, flax, and rape seed were examined for lipase activity. Black cumin seedling lipase had the highest level of citronella acetate production with a yield of 76.32% in 72 h of reaction time. To assess the impact of different reaction parameters on citronellyl acetate production in organic solvents, hexane was chosen as the best solvent, and black cumin seedling lipase was selected as the best biocatalyst. The highest conversion yield of ester (76.32%) was found when 0.25 M of geraniol acetate and 0.25 M of citronellol reacted at 41 oC after 72 h in the presence of 0.25 g of seedling lipase enzyme in n-hexane. It has been determined that crude black cumin seedling lipase is inexpensive yet effective and has the potential to be used industrially for the synthesis of terpene esters.

Proteome and metabolome of Caryocar brasiliense camb. fruit and their interaction during development

Considered the symbol fruit of the Brazilian Cerrado, pequi (Caryocar brasiliense Camb.) is an exotic and much-appreciated fruit with an internal mesocarp (edible part) with an eye-catching golden yellow color. In an unprecedented way, this study characterized the proteome throughout pequi development. The most influential and essential transcription factors operating in the regulation of pequi ripening identified were members of the MAD-box family. A group of proteins related to the methionine cycle indicates the high consumption and recycling of methionine. However this consumption does not occur mainly for the biosynthesis of ethylene, a process dependent on methionine consumption. In the bioactive compounds presented, different proteins could be correlated with the presence of these phytochemicals, such as monodehydroascorbate reductase and ascorbate peroxidase in ascorbic acid recycling; pyruvate kinase, fructose bisphosphate aldolase and phytoene synthase with carotenoid biosynthesis; S-adenosylmethionine synthase 1 as a donor of methyl groups in the formation of trigonelline and aspartate aminotransferase as a biomarker of initial regulation of the trigonelline biosynthetic pathway; phenylalanine ammonia lyase, chorismate synthesis and chalcone-flavononone isomerase in the biosynthesis of phenolic compounds. Among the volatile organic compounds identified, the majority compound in pequi was ethyl hexanoate ester, with an area of 50.68 % in the ripe fruit, and in this group of esters that was the most representative, alcohol dehydrogenase, a fundamental enzyme in the synthesis of esters, was identified with an increase of approximately 7.2 times between the first and last stages. Therefore, an extensive group of proteins and some metabolites can serve as biomarkers of ripening in pequi, as most were more expressed in the last stage, which is the ripe fruit suitable for consumption.

Zinc‐mediated efficient and environmentally benign synthesis of salicylate esters

AbstractConsiderable synthetic effort has been devoted to acid‐ or base‐catalysed transesterification of alkyl salicylate with alcohol in order to synthesize salicylate esters efficiently. In this study, the transesterification of methyl salicylate with 12 different alcohols was carried out by the use of Zn dust as a catalyst. Depending on the alcohol used in the transesterification reaction, the completion of the reaction was within a range of 8–15 h at a temperature between 100 and 170°C. The use of Zn dust provided reusability and almost complete recovery with moderate to excellent yields (42%–97%). The structural elucidation of the products was performed using IR, 1H NMR, 13C NMR and GC–MS data obtained from the Wiley GC/MS Library and the in‐house “Parkim Fragrance House GC/MS Library.”

O-to-O acyl transfer for epimerization-free peptide C-terminal salicylaldehyde ester synthesis

O-to-O acyl transfer for epimerization-free peptide C-terminal salicylaldehyde ester synthesis

Contribution of Malang quartzite-based silica in K2O/zeolite Y catalyst for methyl ester synthesis of off grade crude palm oil

Malang quartzite contains a highly silica content. The silica changes the structural composition of Zeolite Y. Currently, a heterogeneous catalyst is developed to optimize transesterification of Off Grade CPO (Crude Palm Oil). The aims of this study are: (1) synthesize K2O/Zeolite Y using silica from Malang quartzite, (2) synthesize methyl esters from Off Grade CPO using K2O/Zeolite Y catalyst, and (3) to evaluate quartzite based-silica contribution in Zeolite Y for the reaction activity via GC-MS analysis. The experimental stages were: the oil preparation, esterification of the prepared oil, preparation of K2O/zeolite Y catalyst, and the transesterification. This study applied variations of [KOH] in Zeolite Y (10, 20, and 30 % w/w) and the concentration of the transesterification catalyst (2, 3, and 4 % w/w). The K2O/Zeolite Y catalyst was successfully synthesized by impregnation method. Methyl esters of Off Grade CPO resulted the highest yield of 95.05 % with 4 wt% of 30-K2O/Zeolite Y (30 % KOH impregnation). The synthesized methyl esters have a density of 0.877 g/mL, a viscosity of 4.6 cSt, a refractive index of 1.445 and an acid number of 0.384 mg/g according to the standard (SNI 7182:2015). The main components of the methyl ester based on GC-MS results were methyl octanoate, methyl decanoate, methyl dodecanoate, methyl 9-octadecanoate, methyl octadecanoate and methyl tetracosanoate. Using quartzite-based silica, a co-activity of the reaction has occurred.

Synthetic applications of the Cannizzaro reaction.

The Cannizzaro reaction has emerged as a versatile synthetic tool for the construction of functionalized molecules. Dating back to the 19th century, this reaction, though initially used for the synthesis of an alcohol and acid functionality from aldehydes, has henceforth proven useful to generate diverse molecular entities using both intermolecular and intramolecular synthetic strategies. Immense applications in the synthesis of hydroxy acids and esters, heterocycles, fused carbocycles, natural products, and others with broad substrate scope have raised profound interest from methodological and synthetic standpoints. The ongoing development of reagents, solvents, and technologies for the Cannizzaro reaction reflects the broader trend in organic synthesis towards more sustainable and efficient practices. The focus of this review is to highlight some recent advances in synthetic strategies and applications of the Cannizzaro reaction towards the synthesis of potentially useful molecules.

C(sp3)–H sulfinylation of light hydrocarbons with sulfur dioxide via hydrogen atom transfer photocatalysis in flow

Sulfur-containing scaffolds originating from small alkyl fragments play a crucial role in various pharmaceuticals, agrochemicals, and materials. Nonetheless, their synthesis using conventional methods presents significant challenges. In this study, we introduce a practical and efficient approach that harnesses hydrogen atom transfer photocatalysis to activate volatile alkanes, such as isobutane, butane, propane, ethane, and methane. Subsequently, these nucleophilic radicals react with SO2 to yield the corresponding sulfinates. These sulfinates then serve as versatile building blocks for the synthesis of diverse sulfur-containing organic compounds, including sulfones, sulfonamides, and sulfonate esters. Our use of flow technology offers a robust, safe and scalable platform for effectively activating these challenging gaseous alkanes, facilitating their transformation into valuable sulfinates.

Ring-Opening of Donor-Acceptor Cyclopropane Diester for the Synthesis of Oxime Esters and 2,3-Dihydroazete Ester

AbstractA simple and efficient approach for the synthesis of privileged oxime esters by employing donor-acceptor cyclopropane diesters (DACs) as one of the potential precursors is reported. The strategy involves Lewis acid catalyzed ring-opening of DACs, resulting in an open-chain intermediate followed by the base-mediated construction of the corresponding oxime esters in a one-pot reaction. Moreover, the process also features the synthesis of diethyl 4-(4-methoxyphenyl)azete-2,2(3H)-dicarboxylate.