Green route synthesis of 4-thiazolidinone analogs of isonicotinic acid hydrazide

Abstract

The broad and potent activity of 4-thiazolidinones has established it as one of the biologically important scaffolds. The synthesis of N-(2-aryl-4-oxothiazolidin-3-yl)isonicotinamide by a novel method of stirring and sonication is described. The conventional method for synthesis of 4-thiazolidinones involves use of a Dean-Stark water separator for the removal of water from the reaction with long reaction times (12–48 h), and the stirring procedure also involves the use of DCC (dicyclohexylcarbodiimide) as a dehydrating agent. We report the synthesis of 4-thiazolidinone analogs of isonicotinic acid hydrazide by novel, green route methods of sonication and stirring using molecular sieves. Results indicate that high yields and shorter reaction times can be achieved by employing novel green route methods of synthesis.     

Green route synthesis of Schiff's bases of isonicotinic acid hydrazide

Abstract

Imines constitute a class of therapeutic agents that possess a broad spectrum of pharmacological activity. The conventional method for synthesis of imines by nucleophilic addition of amines to ketones or aldehydes requires long reaction times along with the use of organic solvents and a glacial acetic acid catalyst. We report the synthesis of Schiff's bases of isonicotinic acid hydrazide by novel, green routes using sonication, stirring, and microwave irradiation, respectively. Initial results are reported and indicate that by employing greener methods under aqueous conditions, high yields and shorter reaction times can be achieved.     

Synthesis of Schiff's bases in aqueous medium: a green alternative approach with effective mass yield and high reaction rates

Abstract

Schiff's bases constitute a class of pharmaceutical and medicinally important molecules. The conventional methods for the synthesis of Schiff's bases require long reaction times and use of organic solvents. We report a novel and eco-friendly condensation reaction method permitting the “green synthesis” of various Schiff's bases by stirring 1,2-diaminobenzene with various aromatic aldehydes in water as solvent. This method is experimentally simple, clean, high yielding, green, and with reduced reaction times. The product is purified by simple filtration followed by washing with water and drying processes.     

Tween-20: An Efficient Catalyst for One-Pot Synthesis of α-Aminophosphonates in Aqueous Media

Abstract

A green one-pot three-component synthesis has been developed for α-aminophosphonates by condensation of aldehydes, amines, and diethylphosphite by using nonionic surfactant Tween-20 as catalyst in aqueous media. The results showed that this synthetic route for α-aminophosphonates takes just 25–60 min for completion at 60 °C and affords 64%–91% yields depending on the nature of the amine substrates. The major advantages of this novel method are green reaction conditions with water as solvent, simple workup, less reaction times, and high to moderate yields.     

Facile and green synthesis of dapagliflozin

A facile and green synthetic route was developed for the preparation of dapagliflozin (1), a selective sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes. Key reaction steps include a direct Friedel–Crafts acylation and a synthesis of diaryl ketal moiety in one-pot manner without waste water generation. Furthermore, the reduction of the diaryl ketone and C-phenylglucoside were achieved in one-pot manner to generate dapagliflozin (1) more efficiently. The synthetic route featured the usage of commercial available and easily handling reagents with shorter reaction steps and less waste disposal.     

Facile one-pot green synthesis of 2-amino-4H-benzo[g]chromenes in aqueous ethanol under ultrasound irradiation

Abstract

We report an efficient green one-pot approach for the synthesis of eighteen novel dihydro-4H-benzo[g]chromene derivatives under ultrasound irradiation conditions. The three-component condensation reaction proceeded through Knoevenagel-Michael reaction of chosen active methylene compounds and 2-hydroxynaphthalene-1,4-dione with different substituted aldehydes in the presence of ammonium acetate in water and ethanol mixture at room temperature, which furnished high yields of products (91–98%) in a rapid reaction time of 5–15?min. This procedure offers 95% of the atom economy and 100% of carbon efficiency together with other eco-friendly benefits.     

Synthesis of new thioxanthenes by organocatalytic intramolecular Friedel–Crafts reaction

An efficient organocatalytic route has been developed to synthesize novel substituted thioxanthenes (2a–2v) starting from diaryl thioether alcohols (1a–1v) using the intramolecular Friedel–Crafts reaction. The starting materials were obtained in two stages via a coupling reaction followed by the Grignard reaction. In this study, we tried for the first time to use some organic Brønsted acids as organocatalysts (3a–3h) in the intramolecular Friedel–Crafts cyclization reaction of thioether alcohols. The synthesis of original substituted thioxanthenes was achieved within 15?minutes by using N-triflylphosphoramide (3h) with quantitative yields in THF at room temperature.     

Novel pyrimidine derivatives by sonication and traditional thermal methods

Abstract

A series of bis-compounds (2) were synthesized by condensing dihydro-1,3-(disubstituted)phenyl-2-thioxopyrimidine-4,6(1H,5H)-dione with hippuric acid in presence of acetic anhydride. The compound (2) on further treatment with aromatic amine afforded dihydropyrimidine (3) through an eco-friendly procedure by sonication. The sonication method reduces time and gives higher yields, and also the effluent produced is free from hazardous contamination and organic by-products. The novel pyrimidines were also synthesized by traditional methods for comparison purposes and sonication method was found to be superior. Structures of the synthesized compounds have been elucidated on the basis of elemental analysis and spectral data.     

The influence of ultrasonic irradiation on catalytic performance of ZnO nanoparticles toward the synthesis of chiral 1-substituted-1H-tetrazolederivatives from α-amino acid ethyl esters

In this work, a simple and greener protocol for the synthesis of 1-substituted 1H-tetrazole derived from α-amino acid ethyl esters was demonstrated in the presence of zinc oxide nanoparticles (ZnO NPs) under conventional conditions, with heating (at 60 and 80°C and under reflux) compared with ultrasonic. The effect of solvent was investigated to reveal that the solvent system CH₃CN/H₂O was optimum to obtain 1-substituted 1H-tetrazole in high yield. In addition, the effect of irradiation power was studied, which showed that the yield of the reaction was improved at 200 W and the reaction time was shortened to be 30 min. Also, an improvement in the rate of the reaction and the yield of the products was observed when reactions were carried out under sonication conditions in the presence of ZnO NPs compared with conventional methods using various zinc salts as catalysts. The yields of tetrazole compounds 2a–i under sonication were determined (88–96%). Furthermore, the investigated heterogeneous catalytic system was recycled and reused for five runs with significant production of tetrazole 2a as a model target compound in excellent yields at each reaction cycle. In general, the investigated synthetic strategy for the heterocyclization of α-amino acid ethyl ester derivatives to 1-substituted 1H-tetrazoles was in agreement with the green chemistry point of view.     

Expeditious one-pot multicomponent microwave-assisted green synthesis of substituted 2-phenyl Quinoxaline and 7-bromo-3-(4-ethylphenyl) pyrido[2,3-b]pyrazine in water–PEG and water–ethanol

An eco-friendly, expeditious one-pot multicomponent synthesis of substituted 2-phenyl quinoxaline and 7-bromo-3-(4-ethylphenyl) pyrido[2,3-b]pyrazine 4a–k in water–ethanol from easily available starting materials as acetophenone 1, succinamide 2, aromatic amine 3, in situ-generated α-iodo acetophenone from acetophenone, succinamide and catalyzed by silver iodide in combination with green solvent polyethylene glycol-400 and water (2:1) under microwave irradiation. The newly developed protocol with excellent yield of products in very short time of reaction by avoiding the use of lacrimatic α-chloro and α-bromocarbonyl compounds, volatile, toxic organic hazardous solvents, and reagents is the advantage of this research work. The final products were confirmed by their characterization data such as FTIR, ¹H NMR, ¹³C NMR, Mass, HRMS and were compared with its reported method.     

A novel eco-friendly on-water protocol for the synthesis of 2,2-disubstituted 2,3-dihydro-1H-perimidines

An efficient green on-water protocol for the synthesis of 2,2-disubstituted 2,3-dihydro-1H-perimidines is demonstrated. The reaction used safer p-toluenesulfonic acid (PTSA) as a catalyst on water at 80°C, for 2 hours affording a novel method for the synthesis of various disubstituted perimidines in moderate to excellent yields.     

Optimization of the synthesis of het/aryl-amidoximes using an efficient green chemistry

Abstract

This work focuses on optimizing an efficient green synthesis of arylamidoximes from appropriate nitrile and hydroxylamine hydrochloride in water and triethylamine (1.6?mol equivalent) as a base at room temperature for 6?h. This new green synthetic methodology is compared with previously known methods. The main advantages of this new process reported are good yield, easier work-up and short reaction times. Moreover, some of the synthesized arylamidoximes converted to 1,2,4-oxadiazole derivatives 13a,b and 14 via the reaction with (4-acetylphenoxy)acetic acid 12.     

Water-mediated,green, and efficient synthesis of bisquinolones under catalyst-free conditions

Water-mediated, green, and efficient synthesis involving condensation of 4-hydroxy-1-methylquinoline-2(1H)-one (3) with different aromatic and heterocyclic aldehydes (4a–n) leading to 3,3′-(arylmethylene)-bis-(4-hydroxy-1-methylquinolin-2(1H)-one) 5(a–n) under catalyst-free conditions is described. This reaction has an easy workup without using column chromatography and provides excellent yields of the products in shorter reaction times. It does not require any catalyst and uses water as the medium which is the greenest solvent. 3 required in this work was itself obtained by condensation of N-methylaniline (1) with malonic acid (2) in the presence of POCl₃ using a previously reported procedure.     

Ligand‐free,copper‐catalyzed,one‐pot,three‐component synthesis of novel 1,2,3‐triazole‐linked indoles in magnetized water

Magnetized water (MW) is used as a green and new solvent‐promoting medium for the one‐pot, three‐component synthesis of novel 1,2,3‐triazole‐linked indoles catalyzed by copper iodide. A broad range of 2‐aryl‐1‐(prop‐2‐ynyl)‐1H‐indole‐3‐carbaldehydes were reacted with alkyl halides and sodium azide via copper‐catalyzed azide–alkyne cycloaddition reactions in MW in the absence of any ligand. This method offers the advantages of short reaction times, green procedure, low cost, simple work‐up, quantitative reaction yields, and no need for any organic solvent.     

Solvent-free reductive amination of aromatic aldehydes catalyzed by CeCl3·7H2O

Abstract

CeCl₃·7H₂O is found to be an efficient catalyst in the one-pot reductive amination of aromatic aldehydes under solvent-free conditions. Selectivity is observed in the reaction of cinnamaldehyde with aromatic amines, providing an alternative green route to the synthesis of N-cinnamyl anilines. The reaction conditions are mild and the desired product is obtained in good yields.     

Preparation of 2-azetidinones by cyclocondensation of carboxylic acids and imines via diphosphorustetraiodide

One-pot mild synthesis of 2-azetidinones was carried out by the reaction of imines and carboxylic acids in dry dichloromethane at room temperature using diphosphorus tetraiodide. It was also applied for synthesis of 3-spiro-2-azetidinones. The synthesized compounds were characterized by analytical and spectral (infrared, ¹H NMR, ¹³C NMR, and elemental analysis) data.     

A new strategy for the synthesis of 2-mercaptobenzazole derivatives by green chemistry metrics

Abstract

A green and efficient method has been developed for the synthesis of 2-mercaptobenzazole derivatives via the reaction of commercially available aniline derivatives with low-cost and nontoxic potassium thiocyanate in water. The reactions proceeded smoothly under catalyst- and ligand-free conditions to give the corresponding products in good to excellent yields. The versatility, low cost, and environmental friendliness, in combination with high yields and easy work-up makes the procedure noteworthy.     

Microwave-Assisted Synthesis of N,N-Dialkyl-P-Alkylphosphonamidic Anhydrides

A new rapid, efficient, solvent-free, microwave-assisted, and high-yielding method for the synthesis of N,N-dialkyl-P-alkylphosphonamidic anhydrides has been developed. The method involves the use of 4-dimethylaminopyridine and water under microwave irradiation. The reaction of N,N-dialkylaminoalkyl/phenyl phosphonochloridates 2a–h with 4-dimethylaminopyridine (DMAP) gave pyridinium salts, which were converted into N,N-dialkyl-P-alkylphosphonamidic anhydrides 4a–h.     

Systematic approach to the chemical synthesis of arabidopyrones,the unique α-pyrones of Arabidopsis metabolites

Abstract

Total synthesis of two arabidopyrones, iso-arabidopyl alcohol (1) and iso-arabidopic acid (2) isolated from Arabidopsis thaliana was achieved for the first time using Claisen condensation and Wittig reaction as the key steps. In addition, arabidopic acid (4) was synthesized from the methyl ester of arabidopyl alcohol (3). Thus, chemical synthesis of the unique natural α-pyrones 1–4 was accomplished with a short synthetic route by a systematic approach from readily available substances.     

An efficient synthesis of 3-benzylquinazolin-4(1H)-one derivatives under catalyst-free and solvent-free conditions

Abstract

An efficient and convenient method for the preparation of 3-benzylquinazolin-4(1H)-one derivatives under solvent-free and catalyst-free conditions by the reaction of isatoic anhydride, benzylamine, and aromatic aldehydes was reported. In reported papers, ammonia water, ammonium salt, and aromatic amine were often used to synthesize quinazolin-4(1H)-one derivative, but benzylamine was seldom used in this synthesis. This article offers a green method for the synthesis of 3-benzylquinazolin-4(1H)-one derivative used benzylamine as starting material. This methodology has the advantages of short reaction time, mild reaction conditions, easy work-up, and environmental friendliness.