Dione Derivatives Research Articles

Na2S2O8‐Promoted Radical Cyclization for the Synthesis of Azaspiro[4.5]deca‐3,6,9‐triene‐2,8‐dione and Pyrrolo[2,1‐j]quinolone Derivatives

An efficient radical cyclization of N‐(4‐methoxyphenyl)‐N‐methyl‐3‐phenylpropiolamides with 1‐phenylcyclopropan‐1‐ols has been developed using Na2S2O8 to produce azaspiro[4.5]deca‐3,6,9‐triene‐2,8‐diones in good yields with high selectivity. Similarly, the reaction of 1‐[6‐methoxy‐3,4‐dihydroquinolin‐1(2H)‐yl]‐3‐phenylprop‐2‐yn‐1‐ones with 1‐phenylcyclopropan‐1‐ols provides 6,7‐dihydro‐3H‐pyrrolo[2,1‐j]quinoline‐3,9(5H)‐dione derivatives. This is the first report on the use of cyclopropanols for the radical cyclization of N‐(4‐methoxyphenyl)‐N‐methyl‐3‐phenylpropiolamides and 1‐[6‐methoxy‐3,4‐dihydroquinolin‐1(2H)‐yl]‐3‐phenylprop‐2‐yn‐1‐ones.

One-pot synthesis of 9-arylxanthenediones and 9-pyrazoloxanthenediones using [DBU]OAc

The synthesis of 9-aryl-1H-xanthene-1,8(2H)-dione derivatives starting from benzaldehydes or synthesized pyrazolcarbaldehydes and dimedone in the presence of 2,3,4,5,7,8,9,10-octahydropyrido[1,2-a]-[1,3]diazepin-1-ium acetate in high yields is reported. The synthesis provides several advantages, including short reaction time, simple work-up, and environmental friendliness.

A novel three-component method for the synthesis of spiro[chromeno [4′,3′:4,5] pyrimido[1,2-b] indazole-7,3′-indoline]-2′,6(9H)-dione

A green, efficient, and rapid procedure for the synthesis of novel spiro[chromeno[4′,3′:4,5] pyrimido[1,2-b]indazole-7,3′-indoline]-2′,6(9 H)-dione derivatives has been developed by one-pot condensation of 4-hydroxy-2H-chromen-2-one, isatin, and 1H-indazole-3-amine, in the presence of acetic acid in EtOH. This method has the advantages of operational simplicity, and high yield of products via a simple experimental and work-up procedure as compared to the conventional methods. The reaction mechanism and substrate scope of this novel reaction is briefly discussed.

One-pot three component isocyanide-based reaction: Synthesis of novel tetracyclic fused furo[2′,3′:4,5]pyrimido[2,1-b][1,3]benzothiazole

A rapid, efficient and benign protocol has been developed for the construction of potentially biologically active furo[2′,3′:4,5]pyrimido[2,1-b][1,3]benzothiazole derivatives as major products along with (3E)-3-[(alkylamino)methylene]-2H-pyrimido[2,1-b][1,3]benzothiazole-2,4(3H)-dione derivatives as minor products using a one-pot, multi-component reaction of isocyanides, aromatic aldehydes and 2-hydroxy-4H-pyrimido[2,1-b][1,3]benzothiazol-4-one. The significant features of this protocol are the readily available and low-cost starting materials, short reaction time, mild reaction conditions, high yield of products and avoidance of toxic solvents and catalysts. Structures of compounds 4b and 5a were confirmed from single crystal X-ray studies.

An Efficient and Facile Multicomponent Reaction for the Synthesis of 5′,6′‐dihydro‐6′‐hydroxy‐6′‐(trifluoromethyl)‐1′H‐spiro[indoline‐3,4′‐pyrimidine]‐2,2′(3′H)‐dione Derivatives under Solvent‐Free Conditions

The reactions of isatins, urea, and different diketones under solvent‐free conditions have been developed for the preparation of novel spiroheterocycles. It was found that these reactions could be given higher yields and required shorter time compared with commonly used volatile organic solvent conditions. In this synthesis, the important group trifluoromethyl was introduced into the structure of the products. The pure products could be obtained only through removing TsOH, isatins, and urea from hot water. At same time, diketone was eliminated through a small amount of EtOH. Other advantages of this method are simple setup, mild conditions, and minimal environment impact.

Pd‐catalyzed C‐H Arylation: A General Route for the Synthesis of Benzo[b]carbazolenaphthoquinones

A short, efficient and general methodology for benzo[b]carbazolenaphthoquinones was developed via Pd‐catalyzed C‐H arylation process. This methodology was successfully applied to the synthesis of highly biologically active compound 5H–benzo[b]carbazole‐6,11‐diones. Additionally, one‐pot synthesis of benzo[b]phenazine‐6,11(5H,12H)‐dione derivatives was also explored in aqueous medium.

ZrO2 nano particle catalyzed multi-component synthesis of 3-benzylidene-1-phenylquinoline-2,4(1H,3H)-diones and its antimicrobial activity

Zirconium nanoparticles (ZrO2 NPs) used for the multi-component synthesis of 3-benzylidene-1-phenylquinoline-2,4(1H,3H)-dione derivatives were synthesized starting from easily available reactant molecule such as aryaldehyde 1, diphenyl amine 2, di-ethyl malonate 3 in water–ethanol as green solvent. The ZrO2 NPs gave better yield for the first four cycles of reactions. The characterizations of the ZrO2 NPs were performed by using X-ray diffraction (XRD), infrared spectroscopy (IR), and ultraviolet–visible (UV–vis) absorption spectroscopy. The morphological property revealed the formation of nanoscale particles. They developed a greener path for the synthesis of quinolinone derivatives using ZrO2 NPs and water–ethanol as catalyst and solvent. The expected results reveal the catalytic activity, reaction time, and the reusability of catalyst. All the prepared compounds 4a–4j (Q1–Q11) were evaluated for their antibacterial and antifungal activity. The compounds Q1, Q2, Q3, Q5 Q6, Q7, and Q10 were more potent for antibacterial strains, and Q2, Q3, Q4, Q5 Q7, Q8, and Q10 were potent for C. Albicans—an antifungal strain—compared to ciprofloxacin and miconazole as a standard drug. ZrO2 nanoparticle catalyzed multi-component synthesis of 3-benzylidene-1- phenylquinoline-2,4(1H,3H)-diones and their antimicrobial activity

Sulfamic Acid Catalyzed Atom Economic, Eco‐friendly Synthesis of Novel 7‐(Aryl)‐10‐thioxo‐7,9,10,11‐tetrahedro‐6H‐pyrimido‐[5′4′:5,6]pyrano[3,2‐c]quinoline‐6,8(5H)‐dione and its Derivatives

A series of novel 7‐(3‐chloro‐phenyl)‐10‐thioxo‐7,9,10,11‐tetrahedro‐6H‐pyrimido‐[5′4′:5,6] pyrano[3,2‐c]quinoline‐6,8(5H)‐dione derivatives have been synthesized through the multi‐component condensation of aromatic aldehydes, barbituric acid, and 2,4‐dihydroxy quinoline, using heterogeneous sulfamic acid catalyst in water‐ethanol (4:1) solvent system under reflux condition. The present protocol is endowed with charming description such as green synthetic procedure, short reaction time, easy work‐up procedure, and excellent yield and high atom economy of pyranoquinoline derivatives. In this study, sulfamic acid is used as a heterogeneous catalyst that is easily recoverable and recyclable. The proposed multi‐component reaction has been studied with detail mechanism and spectroscopic data. This is one of the potential greener synthetic approaches to build up the series of pyranoquinoline heterocycles.

Uncatalyzed synthesis of new substituted dihydro-2H-dipyrimido[1,2-a,4,5-d]pyrimidine-2,4(3H)-dione

A convenient and new method has been developed for the synthesis of highly substituted dihydro-2H-dipyrimido[1,2-a,4,5-d]pyrimidine-2,4(3H)-dione derivatives by one-pot three-component reactions of barbituric acid, aromatic aldehydes and 2-aminopyrimidine in ethanol under reflux condition without the support of any catalyst. The benefits of this protocol are catalyst-free, clean reaction procedure and providing excellent yields, and the use of ethanol as a solvent, which has been measured to be comparatively environmentally benign.

A novel synthesis and preliminary in vitro cytotoxic evaluation of dihydropyrimidine-2,4(1H, 3 H)-dione derivatives

We report the synthesis and characterization of four new compounds: 6-(2-(1H-inden-2-yl) phenyl)-3-(2-morpholinoethyl)dihydropyrimidine-2,4(1H,3H)-dione (13a), 6-(2-(1H-inden-2-yl)phenyl)-3-(2- (pyrrolidin-1-yl)ethyl)dihydropyrimidine-2,4(1H,3H)-dione (13b), 6-(2-(1H-inden-2-yl)phenyl)-3-phenethyldihydropyrimidine-2,4(1H,3H)-dione (13c) and 3-(3-(1H-imidazol-1-yl)propyl)-6-(2-(1H-inden-2-yl)phenyl) dihydropyrimidine-2,4(1H,3H)-dione (13d). A series of dihydropyrimidine-2,4(1H,3H)-dione moieties was derived from methyl 3-amino-3-(2-chlorophenyl)propanoate precursor in a multi-step synthesis. Acid-amine coupling of 3-(2-(1H-inden-2-yl)phenyl)-3-((tert-butoxycarbonyl)amino)propanoic acid with a series of amine derivatives under mild reaction conditions led to form the corresponding dihydropyrimidine-2,4(1H,3H)-dione derivatives via de-Boc and cyclization reaction in modest yield. Spectroscopic (1H, 13C NMR, and Mass) and analytical techniques have been used to identify and confirm the structure of the products. We have developed a new method for the synthesis of dihydropyrimidine-2,4-(1H,3H)-dione derivatives through a multi-step reaction with modest to high yields. NMR spectroscopy confirmed the structures of the synthesized compounds in each step. The biological evaluation of the synthesized compounds was tested against A431 cancer cell line.

Aerobic thiyl radical addition/cyclization of N-methacryloyl benzamides for the synthesis of isoquinoline-1,3(2H,4H)-dione derivatives.

A highly effective oxidative thiyl radical addition/cyclization of N-methacryloylbenzamides was explored using dioxygen as the sole terminal oxidant without the use of precious and/or toxic transition-metal catalysts. This method provides convenient access to a variety of useful sulfide-containing 4,4-disubstituted isoquinoline-1,3-diones by constructing C-S and C-C bonds in one step.

Facile and rapid synthesis of divers xanthene derivatives using lanthanum(III) chloride/chloroacetic acid as an efficient and reusable catalytic system under solvent-free conditions

LaCl3/ClCH2COOH was used as an efficient, and recyclable catalytic system for synthesis of 11H-benzo[a]xanthene-11-one, hexahydro-1H-xanthene- 1,8(2H)-dione and 11-aryl-10H-diindeno[1,2-b:2?,1?-e]pyran-10,12(11H)-dione derivatives via a one-pot three-component reaction of aldehydes, 2-naphthol, and cyclic 1,3-dicarbonyl compounds. The reactions proceeded rapidly at 70?C under solvent-free conditions and the desired products were obtained in good to excellent yields.

Synthesis, characterization, anticancer, antimicrobial and carbonic anhydrase inhibition profiles of novel (3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl)acryloyl) phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives

In the present study, a series of new hybrid compounds containing chalcone and methanoisoindole units 7a-n ((3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl)acryloyl) phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione) were synthesized, characterized and investigated for their anticancer activity against C6 gliocarcinoma cell in rats, and antimicrobial activity against some human pathogen microorganisms. The compounds 7e, 7h, 7j, 7k, 7L and 7n showed very high anticancer activity with the inhibition range of 80.51–97.02% compared to 5-FU. Some of the compounds exhibited anti-microbial activity. Also, they evaluated for inhibition effects against human carbonic anhydrase I, and II isoenzymes (hCA I and II) with Ki values in the range of 405.26–635.68pM for hCA I, and 245.40–489.60pM for hCA II, respectively. These results demonstrated that 3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives could be used in different biomedical applications.

Green synthesis of novel spiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-2,3′(7′H)- dione, spiro[indeno[1,2-b]pyrazolo[4,3-e]pyridine-4,3′-indoline]-2′,3-dione, and spiro[benzo [h]pyrazolo[3,4-b]quinoline-7,3′-indoline]-2′,8(5H)-dione derivatives in aqueous medium

The green synthesis of novel spiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]- 2,3′(7′H)-dione, spiro[indeno[1,2-b]pyrazolo[4,3-e]pyridine-4,3′-indoline]-2′,3-dione, and spiro[benzo[h]pyrazolo[3,4-b]quinoline-7,3′-indoline]-2′,8(5H)-dione derivatives was reported. The reactions were carried out smoothly in water in the presence of acetic acid with high yields. Some products could be obtained by direct filtration from the water without further purification. The advantages of this approach were simple operation, mild reaction conditions, easy isolation, and wide scope substrates. Most important of all, this reaction process is green.

ChemInform Abstract: Green Synthesis of Spiro[indoline‐3,4′‐pyrazolo[3,4‐b][1,6]naphthyridine]‐2,5′(1′H)‐diones Catalyzed by TsOH in Ionic Liquids.

A three-component reaction of isatin, 3-methyl-1-phenyl-1H-pyrazol-5-amine, and piperidine-2,4-dione was treated in ionic liquids catalyzed by TsOH and provided an efficient and green method for the synthesis of spiro[indoline-3,4′-pyrazolo[3, 4-b][1,6]naphthyridine]-2,5′(1′H)-dione derivatives in high yields.

Novel and highly efficient synthesis of 3-(alkyl/benzylthio)-9b-hydroxy-1H-imidazo[5,1-a]isoindole-1,5(9bH)-dione derivatives

The oxidation of 3a,8a-dihydroxy-2-(alkyl/benzylthio)indeno[1,2-d]imidazol-8(3H)-ones to give the corresponding 3-(alkyl/benzylthio)-9b-hydroxy-1H-imidazo[5,1-a]isoindole-1,5(9bH)-dione derivatives in good to excellent yields at room temperature using two oxidants, periodic acid in aqueous ethanol and lead(IV) acetate in acetic acid, has been reported.

Synthesis and Carbonic Anhydrase Inhibition of Novel 2-(4-(Aryl)thiazole-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione Derivatives.

Carbonic anhydrase (CA, EC 4.2.1.1) is a member of the metalloenzyme family. It catalyzes the rapid conversion of carbon dioxide (CO2 ) and water to bicarbonate (HCO3- ) and protons (H+ ) and also plays an important role in biochemical and physiological processes. In this study, a number of novel 2-(4-(aryl)thiazole-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives were synthesized and evaluated for their inhibitory characteristics against the human CA isoenzymes I and II (hCA I and hCA II). The structures of the new molecules 8a-i were confirmed by means of IR, 1 H NMR, 13 C NMR, and elemental analysis. These compounds exhibited excellent inhibitory effects, in the low nanomolar range, with Ki values in the range of 27.07-37.80 nM against hCA I and in the range of 11.80-25.81 nM against hCA II. Our findings suggest that the new isoindolylthiazole derivatives have superior inhibitory effect over acetazolamide (AZA), which is used as clinical CA inhibitor with Ki values of 34.50 and 28.93 nM against the hCA I and hCA II isoenzymes, respectively.

ChemInform Abstract: Metal‐Free Oxidative Functionalization of C(sp3)—H of Ketones and Alcohols for the Synthesis of Isoquinolinonediones.

A metal-free alkyl radical induced addition/cyclization reaction of acrylamide has been developed. The process involved C(sp3)–H bond cleavage, alkylation of the double bond, and intramolecular cyclization, which provides a new method for the synthesis of 4-substituted isoquinoline-1,3(2H,4H)-dione derivatives. In addition, the product can be easily transformed into tetrahydrofuro[2,3-c]isoquinolin-5(2H)-one derivatives in moderate yield.

Sequential N‐Heterocyclic Carbene‐Catalyzed Reactions of Enals and Cyclic Aryldiene‐1,3‐Diones: Synthesis of Tricyclic Chromenones and Related Compounds

AbstractN‐Heterocyclic carbene (NHC)‐catalyzed synthesis of highly functionalized pyrano[3,2‐c]chromene‐2,5‐dione derivatives, pyrano[3,2‐c]quinoline‐2,5(6 H)‐dione derivatives, and pyrano[4,3‐b]pyran‐2,5‐dione derivatives with potential biological activities is reported. The reaction occurs through a Knoevenagel condensation and NHC‐catalyzed enolate addition in one pot.

New route to synthesis of unexpected 1,5-bis(1-benzofuran-2-yl) pentane-1,5-dione derivatives: Their structure determination with spectroscopic and X-ray methods

The new 1,5-bis(1-benzofuran-2-yl)-1,5-dione derivatives were obtained by the reaction of 2-acetyl benzofuran derivatives (1a–b) and suitable aromatic aldehyde derivatives (2-pyridinecarboxaldehyde, 2-fluoro and 3-fluorobenzaldehyde) in the presence of sodium hydroxide as the base. Importantly, a new process was explored for the synthesis of new bis benzofuran dione derivatives. The structures of the compounds was identified with infrared (IR), 1H-NMR, 13C-NMR, HSQC and HMBC spectroscopic methods and elemental analysis. A representative X-ray crystallographic analysis of 3c was given, and its X-ray data were discussed in detail.