Reusable Reaction Medium Research Articles

Green synthesis and antitumor activity of (E)-diethyl 2-styrylquinoline-3,4-dicarboxylates.

In this work, a green, efficient and catalyst-free synthesis of a series of structurally novel (E)-diethyl 2-styrylquinoline-3,4-dicarboxylates via a direct olefination reaction between diethyl 2-methylquinoline-3,4-dicarboxylate and various aromatic aldehydes was successfully accomplished by employing eco-friendly 1,3-dimethylurea/l-(+)-tartaric acid (DMU/LTA) as an inexpensive, non-toxic and reusable reaction medium. This methodology has the attractive advantages of mild reaction conditions, simple experimental operation, and the absence of any dangerous catalysts or unsafe volatile organic solvents, with satisfactory to good yields. Subsequently, a primary in vitro evaluation for their anti-proliferative activity against human cancer cell lines A549, HT29 and T24 revealed that the compound with the 3,4,5-trimethoxystyryl moiety exhibited potent anti-tumor activity with IC50 values of 2.38, 4.52 and 9.86 μmol L-1, respectively, thereby being equipotent or even better than the reference cisplatin.

Regioselective synthesis of 4-arylamino-1,2-naphthoquinones in eutectogel as a confined reaction medium using LED light.

Predicting selectivity and conversion in a confined reaction medium under photochemical conditions is highly challenging as compared to the corresponding conventional synthesis. Herein, we report the use of a simple carbohydrate-derived eutectogel to facilitate LED-light-induced regioselective synthesis of 4-arylamino-1,2-naphthoquinones in good yield. This methodology, by including a reusable reaction medium, proved to have the potential of affording the regioselective formation of various desired products in good yields.

Copper(i)-catalyzed click chemistry in deep eutectic solvent for the syntheses of β-d-glucopyranosyltriazoles.

In the last two decades, click chemistry has progressed as a powerful tool in joining two different molecular units to generate fascinating structures with a widespread application in various branch of sciences. copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, also known as click chemistry, has been extensively utilized as a versatile strategy for the rapid and selective formation of 1,4-disubstituted 1,2,3-triazoles. The successful use of CuAAC reaction for the preparation of biologically active triazole-attached carbohydrate-containing molecular architectures is an emerging area of glycoscience. In this regard, a well-defined copper(i)-iodide complex (1) with a tridentate NNO ligand (L1) was synthesized and effectively utilized as an active catalyst. Instead of using potentially hazardous reaction media such as DCM or toluene, the use of deep eutectic solvent (DES), an emerging class of green solvent, is advantageous for the syntheses of triazole-glycohybrids. The present work shows, for the first time, the successful use of DES as a reaction medium to click various glycosides and terminal alkynes in the presence of sodium azide. Various 1,4-disubstituted 1,2,3-glucopyranosyltriazoles were synthesized and the pure products were isolated by using a very simple work-up process (filtration). The reaction media was recovered and recycled in five consecutive runs. The presented catalytic protocol generated very minimum waste as reflected by a low E-factor (2.21-3.12). Finally, the optimized reaction conditions were evaluated with the CHEM21 green metrics toolkit.

Azide-Alkyne Cycloaddition Catalyzed by Copper(I) Coordination Polymers in PPM Levels Using Deep Eutectic Solvents as Reusable Reaction Media: A Waste-Minimized Sustainable Approach.

Two air-stable copper(I)-halide coordination polymers 1 and 2 with NNS and NNO ligand frameworks were synthesized and successfully utilized as efficient catalysts in an important organic reaction, namely, copper-catalyzed azide-alkyne cycloaddition, which is generally conducted in a mixture of water and organic solvents. The azide-alkyne "click" reaction was successfully conducted in pure water at r.t. under aerobic conditions. Other green solvents, including ethanol and glycerol, were also effectively used. Finally, deep eutectic solvents as green and sustainable reaction media were successfully utilized. In deep eutectic solvents, complete conversion with excellent isolated yield was achieved in a short period of time (1 h) with low catalyst loading (1 mol %) at r.t. Full conversion could also be achieved within 24 h with ppm-level (50 ppm) catalyst loading at 70 °C. Optimized reaction conditions were used for the syntheses of a large number of 1,4-disubstituted 1,2,3-triazoles with various functionalities. Triazole products were easily isolated by simple filtration. The reaction media, such as water and deep eutectic solvents, were recovered and recycled in three consecutive runs. The limited waste production is reflected in a very low E-factor (0.3-2.8). Finally, the CHEM21 green metrics toolkit was employed to evaluate the sustainability credentials of different optimized protocols in various green solvents such as water, ethanol, glycerol, and deep eutectic solvents.

Water mediated TBAB catalyzed synthesis of spiro-indoline-pyrano[3,2-c]quinolines as α-amylase inhibitor and in silico studies

Herein, an efficient synthesis of spiro-indoline-pyrano[3,2-c]quinolines derivatives of spiroxindolines by the water-mediated three-component condensation reaction of 2-hydroxyquinoline-4-one 1(a-b), isatin derivatives 2(a-n), and malononitrile 3 in the presence of water-soluble and phase transfer Tetrabutylammonium bromide (TBAB) catalyst is described. The present protocol shows features such as excellent yield of product, mild reaction condition, reusable reaction medium with catalyst and low E-factor. This blossomed the reaction with the green synthetic condition and provide a safe and clean alternative for the synthesis of spiropyrano[3,2-c] quinolines derivatives. All the synthesized compounds were screened against the pancreatic α-amylase. Many of those synthesized compounds possess noticeably good α-amylase inhibitory action. From the activity profile, analogous 4g and 4h were found to be more active than the others with IC50 values ranges for α-amylase inhibition (IC50 = 73.82 -76.65 µg/ml) in comparison with the standard acarbose (IC50 = 79.64 ± 0.46 µg/ml). Molecular docking results showed key interactions of 4g, 4h and acarbose with α-amylase, compound 4g shows H-bonding interaction with GLN63, HIS101 and compound 4h shows H-bonding interaction with ASP300. In silico ADMET prediction was carried out to check the physicochemical properties of the synthesized compound.

Chickpea Leaf Exudates: A Highly Efficient Natural Brønsted Acidic Medium for the Synthesis of Pyran-annulated Heterocycles

Abstract:We reported Chickpea leaf exudates (CLEs) as a Brønsted acid, naturally available biodegradable, eco-friendly, and reusable reaction medium for highly efficient and facile one-pot synthesis of pyran-annulated heterocyclic systems, like 7-aryl-benzopyrano[4,3-b]benzopyran-6,8- diones,tetrahydrobenzo[b]pyran, and dihydropyrano[c]chromenes scaffolds. The analogous products were obtained via tandem Knoevengel-Michael addition and cyclo condensation reaction in ethanol at room temperature with 90-96% yields in a short reaction time. Moreover, the reaction media containing Bronsted acids can be easily recovered and reused up to five times, slightly decreasing product yields.

Synthesis of β-keto-sulfones using alkyl/aryl sulphinates in ionic liquids [bmim-BF4] as an efficient and reusable reaction medium

Synthesis of β-keto-sulfones using alkyl/aryl sulphinates in ionic liquids [bmim-BF4] as an efficient and reusable reaction medium

Nitration of aromatics with dinitrogen pentoxide in a liquefied 1,1,1,2-tetrafluoroethane medium.

Regardless of the sustainable development path, today, there are highly demanded chemical productions still operating that bear environmental and technological risks inherited from the previous century. The fabrication of nitro compounds, and nitroarenes in particular, is traditionally associated with acidic wastes formed in nitration reactions exploiting mixed acids. However, nitroarenes are indispensable for industrial and military applications. We faced the challenge and developed a greener, safer, and yet effective method for the production of nitroaromatics. The proposed approach comprises the application of an eco-friendly nitrating agent, namely dinitrogen pentoxide (DNP), in the medium of liquefied 1,1,1,2-tetrafluoroethane (TFE) – one of the most non-hazardous Freons. Importantly, the used TFE is not emitted into the atmosphere but is effortlessly recondensed and returned into the process. DNP is obtained via the oxidation of dinitrogen tetroxide with ozone. The elaborated method is characterized by high yields of the targeted nitro arenes, mild reaction conditions, and minimal amount of easy-to-utilize wastes.

Imidazole mediated synthesis of spirooxindoles in water using isatin as a privileged scaffold

This work describes the synthesis of complex small molecules spirooxindoles using imidazole as an efficient organocatalyst. The three components coupling reactions of isatin, malononitrile and enolizable 4-hydroxycoumarin were performed in water as a green solvent. The reaction is done with imidazole an amphoteric organocatalyst to construct spiro-molecules in high yields. The significant features of this protocol are neutral reaction condition, readily available low cost catalyst, metal free, strong acid/base free, and reusable reaction medium with no column chromatography separation. This methodology is useful for the easy access of structurally complex, highly functionalized spirooxindole molecules with important medicinal chemistry applications.

Tromethamine organocatalyzed efficient tandem-multicomponent synthesis of new thiazolyl-4-thiazolidinones in aqueous medium

The catalytic potential of tris(hydroxymethyl)aminomethane (Tromethamine) has been assessed for the one pot three component tandem reaction involving a thiazolylmethoxy phenyl/aromatic carboxaldehyde, substituted amines and thioglycolic acid to form new thiazolyl-4-thiazolidinones and known substituted-4-thiazolidinones. This strategy involves the use of tromethamine as a reusable promoter and water as an eco-friendly reaction medium. The merits of this protocol are high atom economy, mild reaction conditions, good yields of desired products in short reaction times, and reusable reaction medium. The generality and functional tolerance of this convergent and environmentally benign method is demonstrated.

Fast, Base-Free and Aqueous Synthesis of Quinolin-2(1H)-ones under Ambient Conditions

Without using any base and organic solvent, an environmentally benign methodology was developed for the aqueous synthesis of various functionalized quinolin-2(1H)-ones at ambient temperature. The developed protocol has a wide substrate scope, excellent to quantitative yields, short reaction time (1–8 min), operational simplicity, reusable reaction medium and avoids further chromatographic purification. More importantly, this methodology is markedly greener than the traditional routes with an E-factor of 1.6 and eco-scale score of 89.5.

ChemInform Abstract: Glycerol Mediated Green and One‐Pot Synthesis of 6‐Amino‐1,4‐dihydropyrano[2,3‐c]‐pyrazole‐5‐carbonitriles under Catalyst Free Conditions.

AbstractThe method proceeds in a green reaction media under mild and catalyst‐free reaction conditions.

Enzymatic synthesis of phytosterol esters catalyzed by Candida rugosa lipase in water-in-[Bmim]PF6 microemulsion.

A water-in-ionic liquid microemulsion ([Bmim]PF6/Tween20/H2O) was applied as reusable reaction medium to esterify phytosterols with fatty acid by Candida rugosa lipase (CRL) successfully. Two kinds of commercial CRLs, AY30 and AYS which cannot effectively catalyze esterification in conventional reaction system were found effective in the microemulsion system. Effects of reaction parameters on esterification were investigated; results showed that the conversion rate of 87.9 and 95.1% was obtained in 24 and 48h of reaction, respectively, under the optimized condition: the molar ratio of water to Tween 20 (w 0 value) at 5.4, Tween 20 at a concentration of 305mM, 50°C,pH 7.4, 10% of enzyme loading (w/w, with respect to total reactants), and phytosterols/lauric acid molar ratio of 1:2. Moreover, by using n-hexane as the extraction agent, the lipase-encapsulated microemulsion could be reused at least seven times (>168h) without significant changes in the conversion rate, while achieving a purpose of simple separation and purification.

Amine-based ionic liquids (R3N+PPh2) as a reusable reaction medium and Pd(II) ligand in Heck reactions of aryl halides with styrene and n-butyl acrylate

Amine-based ionic liquids (R3N+PPh2) are reported as an effective reusable medium, suitable Pd(II) ligand and also reducing agent for the Heck coupling reaction of aryl iodides and bromides with styrene and n-butyl acrylate. The ionic liquid, still containing its corresponding Pd(0) complex, was easily recovered and reused in several runs without losing its efficiency.

Catalyst free, regioselective one-pot three-component synthesis of thiazol-2-imine derivatives in ionic liquid

A one-pot three-component approach for the synthesis of thiazol-2-imines has been described by the reaction of amine, phenyl isothiocyanate and β-nitroacrylate in [Hbim]BF4 ionic liquid. The method is applicable for aromatic, benzylic, aliphatic and cyclic amines. Reusable reaction media, regioselectivity, mild reaction condition, catalyst free and high yield of products are the salient features of this protocol.

ChemInform Abstract: One‐Pot, Three‐Component Synthesis of Novel Spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐diones in an Ionic Liquid as a Reusable Reaction Media.

A facile one-pot, three-component protocol for the synthesis of novel spiro[3H-indole-3,2′-thiazolidine]-2,4′(1H)-diones by condensing 1H-indole-2,3-diones, 4H-1,2,4-triazol-4-amine and 2-sulfanylpropanoic acid in [bmim]PF6 (1-butyl-3-methyl-1H-imidazolium hexafluorophosphate) as a recyclable ionic-liquid solvent gave good to excellent yields in the absence of any catalyst (Scheme 1 and Table 2). The advantages of this protocol over conventional methods are the mild reaction conditions, the high product yields, a shorter reaction time, as well as the eco-friendly conditions.

One‐Pot, Three‐Component Synthesis of Novel Spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐diones in an Ionic Liquid as a Reusable Reaction Media

AbstractA facile one‐pot, three‐component protocol for the synthesis of novel spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐diones by condensing 1H‐indole‐2,3‐diones, 4H‐1,2,4‐triazol‐4‐amine and 2‐sulfanylpropanoic acid in [bmim]PF6 (1‐butyl‐3‐methyl‐1H‐imidazolium hexafluorophosphate) as a recyclable ionic‐liquid solvent gave good to excellent yields in the absence of any catalyst (Scheme 1 and Table 2). The advantages of this protocol over conventional methods are the mild reaction conditions, the high product yields, a shorter reaction time, as well as the eco‐friendly conditions.

An efficient synthesis of hemiaminal of indoles by using tetrabutylammonium fluoride (TBAF) in water as a reusable reaction media

The synthesis of hemiaminal of indole is described by the reaction of indole with formaldehyde in the presence of TBAF in water at ambient temperature. The procedure is very efficient, mild, convenient, and environmentally benign with high yield of product. Moreover, the reuse of reaction media makes the procedure an attractive alternative to earlier methods.

Catalyst-free four-component protocol for the synthesis of substituted pyrroles under reusable reaction media

An efficient four-component protocol is described for the synthesis of diversely functionalized pyrroles under catalyst-free condition by using ionic liquid as a reaction media. The developed method is mild, high yielding, and amenable for a variety of amines as well as aldehydes. Moreover the procedure is of environmentally benign nature in which ionic liquid 1-n-butylimidazolium tetrafluoroborate [Hbim]BF4 is used as a reusable and efficient reaction medium without using any additional catalyst or promoter.

PTSA/[bmim][BF4] Ionic Liquid: A Powerful Recyclable Catalytic System for the Synthesis of α-2-Deoxyglycosides

α-2-Deoxyglycosides were synthesized in ionic liquid ([bmim]BF4)by stereoselective glycosylation of endo-glycals with various o-nucleophiles in the presence of catalytic amount of pTSAin 71–95 % yield. High yields, easy recovery of the products, and reusable reaction medium (pTSA/IL couple) with consistent activity makes this protocol efficient and environmentally benign.