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.     

A facile approach for the synthesis of novel substituted 4H-chromenes and condensation reactions of 4H-chromenes leading to chromenopyrrolones and triazolylchromenopyrrolones

A facile method has been developed for the synthesis of 4H-chromene-3-carboxylates 3a–d by the nucleophilic substitution reaction of 2-hydroxy-2H-chromene-3-carboxylates 2a–d with triethylsilane in the presence of BF₃·O(C₂H₅)₂. Cyclocondensation of 4H-chromene-3-carboxylates 3a–d with benzylamines 4a–d afforded a series of 2,3-dihydrochromenopyrrolones 5a–p and with propargylamine afforded 2-propynyl-2,3-dihydrochromenopyrrolones 6a–d. Click reaction of 6a–d with benzyl azides 7a–d provided a series of 1H-1,2,3-triazolylmethyl-2,3-dihydrochromenopyrrolones 8a–p. Thus synthesized compounds 3a–d, 5a–p, 6a–d, and 8a–p are novel heterocyclic compounds and being reported for the first time.     

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.     

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.     

An efficient regioselective reaction of indole with 2H-chromenes for the synthesis of new 4H-chromenes in environmentally benign media

An efficient regioselective, catalyst free, and green protocol has been developed for the synthesis of a novel class of 4H-chromene scaffolds at room temperature in ionic liquid. The method is general and applicable for a series of 2H-chromenes as well as indole derivatives.     

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.     

Enantioselective Michael reaction of 1,3-dicarbonyl compounds to 3-nitro-2H-chromenes catalyzed by chiral nickel complexes

A chiral nickel complexes-catalyzed enantioselective Michael addition of 1,3-dicarbonyl compounds to 3-nitro-2H-chromenes has been developed; the products could be obtained in high yields and good enantioselectivities.     

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.     

Highly diastereoselective 1,3-dipolar cycloaddition of nonstabilized azomethine ylides to 3-nitro-2-trihalomethyl-2H-chromenes: synthesis of 1-benzopyrano[3,4-c]pyrrolidines

Reactions of 3-nitro-2-trifluoro(trichloro)methyl-2H-chromenes, including 2-unsubstituted derivatives, with N-alkyl-α-amino acids (sarcosine, proline) and paraformaldehyde proceed diastereoselectively to give 1-benzopyrano[3,4-c]pyrrolidines in good yields as a result of a 1,3-dipolar cycloaddition of the intermediate nonstabilized azomethine ylide at the Δ³-bond of the chromene system.     

Synthesis of 4-dialkylaminopyridine derivatives through ring-rearrangement of 3-nitro-2H-pyran-2-one acetamidines

A new synthesis of substituted 4-dialkylaminopyridines was developed, starting from 3-nitropyran-2-one N-functionalized amidines. Secondary amines were reacted with the amidines in a sealed tube and in ethanol as the solvent yielding exclusively 4-dialkylaminopyridine derivatives or a mixture with 4-methylpyridine derivative, depending on the C-α-linked substituents of the starting amidine. Structural elucidation of the 4-dialkylaminopyridines revealed their existence as two tautomeric forms, depending on the solvent.     

Silver(I) and gold(I)-promoted synthesis of alkylidene lactones and 2H-chromenes from salicylic and anthranilic acid derivatives

Ag(I) and Au(I) efficiently catalyze the cycloisomerization of terminal alkynoic acids into methylene seven-membered ring lactones. Depending on the metal, divergent reaction pathways were found for non terminal alkynoic acids. While Ag(I) led to lactones, Au(I) led to 2H-chromenes coming from the hydroarylation of the alkyne.     

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.     

A solvent-free protocol for the synthesis of 3-formyl-2H-chromenes via domino oxa Michael/aldol reaction

A new solvent-free, TBD-catalyzed protocol for the synthesis of 3-formyl-2H-chromenes is presented. Substituted salicylaldehydes 1 and 3-methyl-2-butenal 2 in the presence of 10 mol % of TBD underwent a domino oxa Michael/aldol reaction to effectively yield the corresponding 2H-chromene derivatives 3. The methodology represents an improvement either in terms of efficiency and sustainability as a small amount of catalyst is required and the work-up procedure is simple and straightforward.     

Palladium-catalyzed synthesis of 4-alkoxycarbonyl-3,4-dihydroisoquinolin-1(2H)-ones

Palladium-catalyzed intermolecular cyclocarbonylation of diethyl (2-iodoaryl)malonates with N-tosylimines produces 4-ethoxycarbonyl-3,4-dihydroisoquinolin-1(2H)-ones in moderate to good yields. This reaction is highly stereoselective. This protocol involves Mannich addition, and subsequent cyclocarbonylation.     

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.     

Traceless solid-phase synthesis of 1,4-disubstituted-6-nitro-3,4-dihydro-1H-quinoline-2-ones

A traceless solid-phase route to 1,4-disubstituted-6-nitro-3,4-dihydro-1H-quinazolin-2-ones is described. N-Alloc-3-amino-3-(2-fluoro-5-nitrophenyl)propionic acid was tethered to Rink resin via its carboxylic group. The protected amine was coupled with an organic acid after Alloc-deprotection and the arylfluorine was displaced with a primary amine to generate a resin-bound aniline with two diversity points. The aniline was released via cleavage to produce the desired products in high yield and purity.     

Facile synthesis of 4-phenylquinolin-2(1H)-one derivatives from N-acyl-o-aminobenzophenones

An efficient synthesis of 4-phenylquinolin-2(1H)-one derivatives has been achieved in a one-pot reaction from N-acyl-o-aminobenzophenones 1a-c (a: acyl=acetyl; b: acyl=propanoyl; c: acyl=heptanoyl) using NaH as a base. Treatment of 1 with NaH provided the quinolones 2a-c with 62-83% yields, whereas the reaction in the presence of alkyl iodide (alkyl=methyl, ethyl, n-octyl) gave the corresponding N-alkylated quinolones 3a-g in 75-95% yields. The alkylation reaction of 4-phenylquinolin-2(1H)-one 2a with alkyl halide gave a mixture of N-alkylated and O-alkylated products. Comparison of IR and NMR data of the N-alkylated and O-alkylated compounds with those of 2a-c indicated that 2a-c exist as the lactam form.     

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.     

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.