Microwave-assisted,regioselective one-pot synthesis of quinolines and bis-quinolines catalyzed by Bi(III) immobilized on triazine dendrimer stabilized magnetic nanoparticles

Fe₃O₄-TDSN-Bi(III) was utilized as an efficient and reusable catalyst for the regioselective one-pot synthesis of quinoline derivatives from arylamines, arylaldehydes and methyl propiolate under microwave irradiation and solvent-free conditions. Also, bis-quinolines were obtained in high yields from dialdehydes or diamines. Atom-economy, high to excellent yields, easy work-up, as well as simple catalyst recovery and reusability are the key features of this procedure.     

An expedient one-pot sequential five-component synthesis of highly substituted spiro-pyrrolidine heterocycles

An expedient one-pot sequential five-component synthesis of highly substituted pyrrolidine heterocycles involving [3+2]-cycloaddition of azomethine ylides as the key step is described. The protocol provides a mild reaction condition, high yield of the products, high regioselectivity and operational simplicity to assemble complex structural entity in a single operation. The structure of the product was confirmed by spectroscopic and single crystal X-ray analysis.     

Multicomponent synthesis of polysubstituted dihydroquinoline derivatives

A series of new poly-functionalized dihydroquinoline derivatives (26 examples) were synthesized via three-component reactions of aldehydes (1 equiv) and 1-arylethylidenemalononitriles (2 equiv) in ethylene glycol using NaOH as a base promoter under microwave irradiation. During these reaction processes, the domino construction of dihydroquinoline skeleton with concomitant formation of two new cycles was readily achieved in a one-pot operation and in an intermolecular manner.     

TMSCl-promoted isocyanide-based MCR of ethylenediamines: an efficient assembling of 2-aminopyrazine core

New trimethylchlorosilane (TMSCl) promoted multicomponent reaction (MCR) of ethylenediamine(s), diverse carbonyl compounds, and isocyanides is proposed for the synthesis of a variety of highly substituted 3,4,5,6-tetrahydropyrazin-2-amines including corresponding spirocyclic compounds.     

Multicomponent one-pot solvent-free synthesis of functionalized unsymmetrical dihydro-1H-indeno[1,2-b]pyridines

A simple and efficient synthesis of 4-aryl-4,5-dihydro-1H-indeno[1,2-b]pyridine derivatives has been achieved via a four-component cyclocondensation of 1,3-indanedione, aromatic aldehydes, β-ketoesters and ammonium acetate in one-pot in the absence of catalyst and solvent at room temperature on grinding. The present approach offers several advantages such as shorter reaction times, higher yields, low cost, simple work-up and easy purification.     

Synthesis of Some Functionalized Peptomers via Ugi Four-Component Reaction

This article describes the synthesis of new peptomers through a simple and efficient route using a one-pot Ugi four-component reaction. The synthesis started from either carboxylic acids or protected amino acids, primary amines, aldehydes, and isocyanides in anhydrous methanol and proceeded under stirring at room temperature. The reaction produced several functionalized peptomers in good yields (67–80%). These compounds are versatile multifunctional intermediates that can be further unprotected or functionalized to generate new molecules with numerous applications in the field of biomedicine.     

Multicomponent synthesis,cytotoxicity, and computational studies of novel imidazopyridazine-based N-phenylbenzamides

A one-pot multicomponent synthesis and application of new imidazopyridazine based N-phenylbenzamides is described. An atom-economical method involving dimethyl phthalate, substituted anilines, and pyridazine-4,5-diamine provided the desired compounds in 120–150 min with 80–85% yield. The reaction was catalyzed with phosphoric acid, and glycerol was used as a safer, greener solvent. Anticancer evaluation against selected cancer cell lines revealed that compound 4e was the most active from the series and exhibited IC₅₀ values below 9.1 µM. Compounds 4h and 4d also displayed good and comparable IC₅₀ values (10.2–12.1 µM). Molecular docking and molecular dynamic studies showed that compound 4e exhibit good binding affinity and stable complex formation with ABL1-kinase protein, respectively. Additional computational predictions such as ADME and drug-likeness demonstrated the potential of the new benzamides as leads for further development.     

Three-component couplings for the synthesis of pyrroloquinoxalinones by azomethine ylide 1,3-dipolar cycloaddition chemistry

1-Methyl-3,4-dihydroquinoxalin-2(1H)-one was heated with a range of aldehydes to generate intermediate azomethine ylides which underwent [3 + 2] cycloaddition reactions with N-methyl or N-phenylmaleimide to give substituted tetrahydropyrroloquinoxalinones. Only one (racemic) stereoisomer was formed in each case and the stereochemical outcome was verified by single crystal X-ray analysis. The products from this multicomponent reaction could be oxidised with DDQ to the pyrroloquinoxalinones.     

Multicomponent synthesis of dihydropyridines catalyzed by L-proline

Multicomponent synthesis of mono and bis 4-substituted-1,4-dihydropyridines from aldehydes,dimedone and ammonium acetate in the presence of an efficient recyclable catalyst,L-proline,in high yield and short reaction time is reported.     

Multicomponent reactions in PEG-400: ruthenium-catalyzed synthesis of substituted pyrroles

An efficient and eco-friendly method for the synthesis of substituted pyrroles has been developed via ruthenium-catalyzed multicomponent reaction of ketone, amine, and ethylene glycol in PEG-400 as solvent medium without using any external ligand. The catalytic system and solvent can be recycled with the same, as well as different, ketones with minimum loss of Ru-catalyst activity.     

Multicomponent synthesis of substituted 3-styryl-1H-quinoxalin-2-ones in an aqueous medium

A multicomponent synthesis of substituted 3-styryl-1H-quinoxalin-2-ones is described. Sequential reactions of o-phenylenediamine with sodium pyruvate and aldehydes in 20% aqueous acetic acid containing sodium acetate provided the target products in good to high yields. The reaction is proposed to proceed via initial condensation of the diamine and pyruvate partners followed by an aldol condensation-type mechanism.     

Multicomponent reactions for synthesis of bioactive polyheterocyclic ring systems under controlled microwave irradiation

The multi-component reaction of 1-benzothiopyran-4-ones with heterocyclic amines and dimethylformamide-dimethylacetal (DMFDMA) in DMF at 150 °C under controlled microwave heating afforded novel poly-heterocyclic ring systems. Also, reaction of 3-dimethylaminomethylene-1-benzothiopyran-4-one with activemethylene derivatives was investigated. The structure of all products was established on the bases of spectral data and elemental analyses and alternative synthesis if possible. The prepared compounds were screened for their antitumor activity against HCT-116 “colon” cancer cell line and some derivatives showed promising activity.     

Synthesis of [1,2,4,5]tetrazino[6′,1′:2,3]imidazo[4,5-c]isoquinolin-5-ones by microwave-assisted three-component reaction

An efficient and original Ugi multicomponent reaction of aminopyridines and aminopyrimidines is reported. Starting from aminotetrazine 6 or 7, an isocyanide and an ortho-carboxybenzaldehyde, tetrazinoimidazoisoquinolinones were isolated, after few minutes of microwave irradiation, in good to excellent yields. The scope of this method was extended by using different isocyanides.     

Multicomponent synthesis of dihydropyrimidines and thiazines

A broad range of differently substituted dihydropyrimidines and thiazines can be efficiently prepared by using a four-component reaction between phosphonates, nitriles, aldehydes, and iso(thio)cyanates. The scope and limitations of this multicomponent reaction are fully described. Variation of all four components has been investigated. The nitrile and aldehyde inputs can be varied extensively, but variation of the phosphonate input remains limited. An interesting rearrangement leading to phosphoramidates has been observed. Furthermore, the multicomponent reaction seems to be restricted to the use of isocyanates with strongly electron-withdrawing substituents, but an interesting additional exchange reaction under microwave conditions leads to dihydropyrimidines with less electron-withdrawing substituents at N3. In addition, a diastereoselective formation of dihydropyrimidines has been observed when using a chiral aldehyde as the input. Finally, by changing the isocyanate component to an isothiocyanate, thiazines are efficiently formed instead of the corresponding thio-dihydropyrimidines.     

Synthesis of α-aminonitriles under mild catalytic,metal-free conditions

α-Aminonitriles have been synthesized by a Strecker synthesis from aldehydes and ketones under mild catalytic, metal-free conditions. Aromatic aldehydes (1 equiv) were reacted with aromatic and 1° or 2° aliphatic amines (1 equiv) in EtOH containing 3 mol % of NH₄Cl to give high yields of α-aminonitriles. An alternative to adding NH₄Cl as a catalyst involved the use of excess TMSCN (1 equiv) and to promote the process. The reaction was also successful under microwave conditions using excess TMSCN with no solvent. Ketones similarly reacted with aromatic amines and excess TMSCN under conventional and microwave heating, but 30 mol % of added NH₄Cl was required for optimum conversion.     

Multicomponent synthesis of 4-aryl-NH-1,2,3-triazoles in the presence of Al-MCM-41 and sulfated zirconia

The acid properties of Al-MCM-41 and sulfated zirconia were used to develop a strategy for the synthesis of 4-aryl-NH-1,2,3-triazoles via a multicomponent reaction involving various benzaldehydes, sodium azide and nitromethane. The efficiency of the process is analysed from the perspective of the difference in acids among the catalysts used.     

Multicomponent reactions of amino alcohols with CH2O and dithiols in the synthesis of 1,3,5-dithiazepanes and macroheterocycles

A series of new hydroxyl-substituted 1,3,5-dithiazepanes and N,N′-(2-hydroxyethyl)tetrathiadiazacycloalkanes were synthesized by the multicomponent reactions ₍MCRs) of amino alcohols with formaldehyde and α,ω-dithiols. The MCR with 1,2-dithiol proceeds via a (1+2+1)-cyclocondensation with selective formation of 1,3,5-dithiazepanes. Stereochemistry of the dithiazepane ring was determined by X-ray diffraction. The reaction with higher α,ω-dithiols (1,3-propane-, 1,4-butane-, 1,5-pentane-, 1,6-hexanedithiol and 2-[2-(2-sulfanyletoxy)ethoxy]-1-ethanethiol) yielded OH-substituted macroheterocycles as a result of (2+4+2)-cyclocondensation. The structure of the latter was determined by NMR spectroscopy, MALDI–TOF and electrospray ionization methods. The doubly charged ions like [M+2H]²⁺ are found in the ESI spectra of the macrocycles.     

A new and versatile one-pot synthesis of indol-2-ones by a novel Ugi-four-component-Heck reaction

A novel one-pot-synthesis of highly substituted indol-2-ones using a combination of Ugi and Heck reaction (U-4CR-Heck) is described. The synthesized indol-2-ones represent an interesting pharmacological scaffold with four potential points of diversity. Thus, this novel reaction-type is amenable to combinatorial high-throughput screening.     

Novel synthesis of perfluoroalkylated indolizinylphosphonates via a DIPEA-promoted one-pot process

DIPEA-promoted one-pot synthesis of perfluoroalkylated indolizinylphosphonates by the reaction of pyridines 1, bromomethyl ketones 2 with perfluoroalkynylphosphonates 3 is described. This procedure is compatible with a broad range of functional groups in both pyridines and ketones with good yields. The reaction proceeds through a tandem CN bond formation followed by an intramolecular cyclization.     

Efficient,One-Pot Synthesis of Triazolothiadiazinyl-pyrazolone and Pyrazolyl-triazolothiadiazine Derivatives via Multicomponent Reaction

A one-pot, multicomponent reaction of 3-(2-bromo acetyl)coumarins, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and different derivatives of ethyl 2-(2-(aryl)hydrazono)-3-oxobutanoates provide an efficient and direct method for the synthesis of 4-(arylydrazono)-3-methyl-1-(6-(coumarin-3-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)-1H-pyrazol-5(4H)-ones (4a–h). A similar methodology was also developed for the synthesis of pyrazolyl-triazolothiadiazines (9a–f) using acetyl acetone, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and different derivatives of phenacylbromide. The resulting products were characterized by analytical and spectral data.