Ring-closing metathesis for the synthesis of 2H- and 4H-chromenes

Six 4H-chromenes were synthesized from substituted phenols using vinylstannylation and ring-closing metathesis (RCM) as key steps. In addition, a different approach involving amongst other steps, an aryl allyl isomerization and RCM afforded a set of seven 2H-chromenes from phenolic precursors.     

Ca(OH)2-mediated efficient synthesis of 2-amino-5-hydroxy-4H-chromene derivatives with various substituents

A variety of novel 2-amino-5-hydroxy-4H-chromene derivatives with various substituents on the 4H-chromene ring were efficiently synthesized by one-pot reactions of substituted resorcinols and various 2-benzylidenemalononitriles in the presence of calcium hydroxide in methanol at room temperature. This simple method provided 2-amino-5-hydroxy-4H-chromenes with high yields under mild reaction conditions.     

New HA 14-1 analogues: synthesis of 2-amino-4-cyano-4H-chromenes

The synthesis of 2-amino-4-cyano-4H-chromene derivatives as new HA 14-1 analogues by a simple and efficient method is reported. In addition, the reaction of 2-amino-2H-chromene-3-carbonitriles, salicylaldehydes and amines results in the formation of new chromeno[2,3-d]pyrimidine derivatives.     

Synthesis of 2,2-difluoro-2H-chromenes through the tandem reaction of ethyl 3-bromo-3,3-difluoropropionate with salicylaldehyde derivatives

A series of 2,2-difluoro-2H-chromenes were synthesized from the tandem reactions of ethyl 3-bromo-3,3-difluoropropionate with salicylaldehyde derivatives in good yields under basic conditions. In acidic environment defluorination took place during the reaction. A plausible mechanism was proposed based on the experimental results.     

l-Proline catalyzed efficient and convenient synthesis of substituted 2H-chromenes by three-component reaction

A convenient and efficient method is described for the synthesis of alkoxy substituted 2H-chromens by l-proline catalyzed reaction of salicylaldehydes with diketone in alcohol. The method is applicable for various substituted salicylaldehydes and aliphatic as well as benzylic alcohols.     

Synthesis of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes

A combinatorial library of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes was synthesized in high yield by C4-SMe substitution in N-alkyl/phenyl 4-(methylthio)-3-nitro-4H-chromen-2-amines with a variety of phenols. The reaction always provided C2 substitution in the phenol ring, dictated by hydrogen bond interactions between the phenolic hydroxyl group and the nitro group in 3-nitro-4H-chromenes. Reduction of the nitro group with concomitant hydrolysis of the enamine in 4-(2-hydroxyaryl)-3-nitro-4H-chromenes with Zn, Ac₂O in AcOH furnished hybrid amino-acid lactone incorporating ortho-tyrosine and phenyl alanine moieties.     

Chemical and electrocatalytic cascade cyclization of salicylaldehyde with three molecules of malononitrile: ‘one-pot’ simple and efficient way to the chromeno[2,3-b]pyridine scaffold

А new type of catalytic cascade cyclization was found: the direct ‘one-pot’ simple and efficient transformation of salicylaldehyde and three molecules of malononitrile into the chromeno[2,3-b]pyridine systems. Chemical and electrochemical methods result in direct ‘one-pot’ formation of chromeno[2,3-b]pyridines in 60–90% yields. The implication of electrocatalysis in complex cascade cyclization reaction is an efficient approach to medicinally relevant chromeno[2,3-b]pyridines—the promising small-molecule ligands with pronounced antihistamic, antirheumatic and antiasthmatic activities. The electrocatalytic method is beneficial from the viewpoint of diversity-oriented large-scale processes and represents fast efficient and environmentally benign synthetic concept for cascade reactions strategy.     

A simple and convenient synthesis of 2-(perfluoroalkyl)-4H-chromenes from salicyl N-tosylimines or salicylaldehydes and methyl 2-perfluoroalkynoates

Et₃N-catalyzed reactions of salicyl N-tosylimines or salicylaldehydes with methyl 2-perfluoroalkynoates proceed smoothly at room temperature in dichloromethane (DCM) or dimethyl sulfoxide (DMSO) to give the corresponding fluorinated chromenes in good to excellent yields with high regioselectivity.     

Nitroketene acetal chemistry: efficient synthesis of 2-amino-3-nitro-4H-chromenes

Base-catalyzed reaction of the nitroketene N,S-acetals and the ring substituted 2-hydroxybenzaldehydes afforded a combinatorial library of the 2-alkylamino-3-nitro-4-alkylsulfanyl 4H-chromenes in excellent yields. Nucleophilic displacement of the C4 alkylsulfanyl group with different thiols afforded 4H-chromenes with structural diversity.     

A simple and convenient synthesis of 4-methyl-3-nitro-2-trihalomethyl-2H-chromenes from N-unsubstituted imines of 2-hydroxyacetophenones and trichloro(trifluoro)ethylidene nitromethanes

The reaction of N-unsubstituted imines of 2-hydroxyacetophenones with trichloro(trifluoro)ethylidene nitromethanes in the presence of DABCO proceeds via tandem oxa-Michael/aza-Henry additions (in dichloromethane) or aza-Michael addition (in benzene) to give 4-methyl-3-nitro-2-trichloro(trifluoro)methyl-2H-chromenes or 1,1,1-trichloro(trifluoro)-3-nitro-N-[1-(2-hydroxyaryl)ethylidene]propan-2-amines, respectively.     

Multicomponent assembling of salicylaldehydes,malononitrile and cyanoacetamides: A simple and efficient approach to medicinally relevant 2-amino-4H-chromene scaffold

Sodium hydroxide catalyzed a new multicomponent reaction of salicylaldehydes, malononitrile and cyanoacetamides under ‘on-water’ conditions, which results in the facile and efficient formation of the corresponding substituted 2-amino-4H-chromenes in 80–95% yields. The convenient approach to the substituted 2-amino-4H-chromenes developed here — the promising small-molecule ligands for different biomedical applications with known spasmolitic, diuretic and antianaphylactic activities — is beneficial from the viewpoint of diversity-oriented large-scale processes and represents a fast, efficient and environmentally benign ‘on-water’ synthetic concept for multicomponent reactions strategy.     

Solvent-free microwave synthesis of 4-hydroxy-3-phenylquinolin-2(1H)-ones and variants using activated arylmalonates

The disclosure herein describes the rapid synthesis of 4-hydroxy-3-phenylquinolin-2(1H)-ones and variants via a solvent-free microwave cyclocondensation reaction using di-(2,4,6-trichlorophenyl)-2-phenylmalonate, which improves the general scope of this reaction.     

Cyanamide: a convenient building block to synthesize 4-aryl-2-cyanoimino-3,4-dihydro-1H-pyrimidine systems via a multicomponent reaction

4-Aryl-2-cyanoimino-3,4-dihydro-1H-pyrimidine derivatives were prepared using a multicomponent reaction by reacting a mixture of arene or heteroarenecarbaldehyde, 1,3-dicarbonyl compounds, and cyanamide under acidic conditions. The novelty of this approach derives from its use of cyanamide as a building block in a four-component Biginelli-type reaction. Varying the reaction conditions led to the formation of either N-(2-imino-6-phenyl-1,3,5-oxadiazinan-4-ylidene) cyanamide or 3,4-dihydropyrimidin-2(1H)-one. The type of heterocycle skeleton synthesized depends on the nature of the acid catalyst as well as the reaction conditions employed.     

Multicomponent assembling of salicylaldehydes,malononitrile, and 4-hydroxy-6-methyl-2H-pyran-2-one: A fast and efficient approach to medicinally relevant 2-amino-4H-chromene scaffold

A new multicomponent reaction (MCR) was found: a sodium acetate-catalyzed transformation of salicylaldehydes, malononitrile and 4-hydroxy-6-methyl-2H-pyran-2-one in ethanol results in the fast (30 min) and efficient formation of new 4-pyrano-substituted 2-amino-4H-chromenes in 86–96% yields. The same transformation initiated by grinding in mortar in the presence of sodium acetate or potassium fluoride results in a faster (15 min) formation of 4-pyrano-substituted 2-amino-4H-chromenes in 80–90% yields. This novel ‘one-pot’ process opens an effective and convenient way to pyrano-functionalized 2-amino-4H-chromene systems, which are promising compounds for different biomedical applications.     

Reaction between alkyl isocyanides and dimethyl acetylenedicarboxylate in the presence of polyhydroxybenzenes. Synthesis of 4H-chromene derivatives

The reactive intermediate generated by the addition of alkyl isocyanides to dimethyl acetylenedicarboxylate was trapped by phenols such as resorcinol, catechol, hydroquinone, pyrogallol, 2,4-dihydroxybenzaldehyde, or 8-hydroxyquinoline to produce highly functionalized 4H-chromenes in fairly good yields.     

Synthesis of 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-ones via Pd-catalyzed regioselective cross-coupling reaction and cyclization

An efficient and novel route for the synthesis of 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-one 1 via palladium-catalyzed site-selective cross-coupling reaction and cyclization process was described. Reaction of 3-bromo-4-trifloxy-quinolin-2(1H)-one 3 with arylboronic acid catalyzed by PdCl₂(PPh₃)₂ afforded 3-bromo-4-aryl-quinolin-2(1H)-one 4, which then reacted with 2-ethynylaniline 5 via Pd-catalyzed Sonogashira coupling and CuI-mediated cyclization leading to the desired 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-one 1 in good yields.     

A novel, one-pot, solvent-, and catalyst-free synthesis of 2-aryl/alkyl-4(3H)-quinazolinones

A novel and one-pot synthesis of 2-aryl/alkyl-4(3H)-quinazolinones is described. The in situ prepared amidoximes from the reaction between nitriles and hydroxylamine are condensed with anthranilic acids under solvent- and catalyst-free conditions to produce the title compounds in excellent yields.     

An efficient, greener, and solvent-free one-pot multicomponent synthesis of 3-substituted quinazolin-4(3H)ones and thienopyrimidin-4(3H)ones

Herein, we report an efficient, greener, and solvent-free novel method for the synthesis of 3-substituted quinazolin-4(3H)ones and thienopyrimidin-4(3H)ones in a one-pot sequence using methyl anthranilate or 2-aminothiophene-3-carboxylate with N,N′-dimethyl formamide dimethyl acetal and various anilines. The driving force for this reaction is the removal of N,N′-dimethylamine by various anilines resulting in 3-substituted quinazolin-4(3H)ones and thienopyrimidin-4(3H)ones.