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.     

K2CO3-catalyzed synthesis of 2-amino-3-cyano-4H-chromene derivatives with different substituents in water

The direct three-component condensation of resorcinol, 1-(2,4-dihydroxyphenyl)ethanone or 2,4-dihydroxybenzophenone with benzaldehydes and malononitrile to generate some novel 2-amino-3-cyano-4H-chromene derivatives has been carried out over K₂CO₃ (25 mol%) with high efficiency in water as a green solvent at 70 °C.     

Reactions of 2-(trifluoromethyl)-2-hydroxy-2H-chromenes with thiophenols promoted by Lewis acid

A Lewis acid promoted nucleophilic substitution reaction between 2-(trifluoromethyl)-2-hydroxy-3-ethoxycarbonyl-2H-chromenes 1 and thiophenols affording thiophenyl substituted products, that is, 4-thiophenyl-2-trifluoromethyl-3-ethoxycarbonyl-4H-chromene and 2-thiophenyl-2-trifluoromethyl-3-ethoxycarbonyl-2H-chromene.     

Recyclization of dimedone adduct with 2-(2-oxo-2-phenylethylidene)propanedinitrile in the reaction with N-nucleophiles

Three-component condensation of dimedone with phenylglyoxal hydrate and malononitrile gave a polyfunctional 5,6,7,8-tetrahydro-4H-chromene derivative, 2-amino-4-benzoyl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile, which reacted with ammonium acetate to produce pyrrolo[3,4-c]quinoline ring system. Reactions of the condensation product with primary and secondary amines and hydroxylamine hydrochloride afforded polysubstituted pyrroles, whereas the reaction with hydrazine hydrate led to 3-amino-6-phenylpyridazine-4-carbonitrile.     

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.     

Reusable silica-bonded S-sulfonic acid catalyst for three-component synthesis of 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromenes and 2-amino-4H-pyrans in aqueous ethanol

Silica-bonded S-sulfonic acid (SBSSA)-catalyzed, facile, one-pot, three-component coupling of 5,5-dimethyl-1,3-cyclohexanedione (dimedone) or 5,5-dimethyl-1,3-cyclohexanedione, aromatic aldehydes, and malononitrile at reflux temperature is described for preparation of 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene derivatives. 2-Amino-3-cyano-6-methyl-4-phenyl-4H-pyran-5-ethylcarboxylate derivatives can also be prepared in good yield under the same experimental conditions by use of ethyl acetoacetate, aldehydes, and malononitrile. The catalyst, silica-bonded S-sulfonic acid, was reused and recycled without any loss of activity or product yield.     

Synthesis of function-oriented 2-phenyl-2H-chromene derivatives using l-pipecolinic acid and substituted guanidine organocatalysts

Organocatalytic domino oxa-Michael/aldol reactions between salicylaldehyde with electron deficient olefins are presented. We screened guanidine, 1,1,3,3-tetramethylguanidine (TMG) and l-pipecolinic acid as organocatalysts for this transformation. 3-Substituted 2-phenyl-2H-chromene derivatives are synthesized with high yields and with poor enantioselectivity (5-17% ee) using l-pipecolinic acid while TMG works well with cinnamaldehyde without using co-catalyst. These 3-substituted-2-phenyl-2H-chromene derivatives are further derivatized to synthesize triazole and biotin-containing chromene derivatives, to facilitate purification of protein targets.     

Amination of 5-Spiro-Substituted 3-Hydroxy-1,5-dihydro-2H-pyrrol-2-ones

The 3-hydroxy-1,5-dihydro-2H-pyrrol-2-one motif is a valuable scaffold in drug discovery. The replacement of the 3-oxy fragment in 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones-based compounds with a 3-amino one (3-amino analogs of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones, 3-amino-1,5-dihydro-2H-pyrrol-2-ones) can play a crucial role in their biological effect. Thus, approaches to 3-amino-1,5-dihydro-2H-pyrrol-2-ones are of significant interest. We developed an approach to 5-spiro-substituted 3-amino-1,5-dihydro-2H-pyrrol-2-ones that could not be obtained using previously reported approaches (reactions of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones with amines). The developed approach is based on the thermal decomposition of 1,3-disubstituted urea derivatives of 5-spiro-substituted 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones, which were prepared via their reaction with carbodiimides.     

Synthesis of 2-substituted 2H-chromenes using potassium vinyltrifluoroborates

2H-Chromenes were synthesized from salicylaldehyde using potassium vinylic borates in the presence of secondary amines. We synthesized these 2H-chromene derivatives as a part of an ongoing project to develop inhibitors for TGF-β receptors. Potassium vinyl trifluoroborates react with salicylaldehydes at 80 °C in the presence of a secondary amine and produced 2-substituted 2H-chromene derivatives with a 70-90% yield.     

A novel synthesis of new 2-aryl-6-(arylamino)-1H-imidazo[1,2-b]pyrazole-7-carbonitrile derivatives

New 2-aryl-6-(arylamino)-1H-imidazo[1,2-b]pyrazole-7-carbonitriles are synthesized in good yields, via cyclocondensation of 5-amino-1-(2-oxo-2-arylethyl)-3-(arylamino)-1H-pyrazole-4-carbonitriles, which are prepared by the reaction of 5-amino-3-arylamino-1H-pyrazole-4-carbonitriles and α-bromoacetophenone derivatives in the presence of K₂CO₃ using acetone as the solvent.     

Convenient and Efficient One-Pot Method for the Synthesis of 2-Amino-tetrahydro-4H-chromenes and 2-Amino-4H-benzo[h]-chromenes Using Catalytic Amount of Amino-Functionalized MCM-41 in Aqueous Media

A convenient and efficient one-pot method for the synthesis of 2-amino-tetrahydro-4H-chromene and 2-amino-4H-benzo[h]-chromene derivatives has been developed using a catalytic amount of amino-functionalized MCM-41 in aqueous medium. This efficient technique has the advantages of giving 4H-tetrahydro-chromene and 4H-benzo[h]chromene building blocks using a reusable catalyst in good to excellent yields, to be completed in short reaction times with a simple product isolation procedure.     

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.     

Chiral bifunctional squaramide catalyzed asymmetric tandem Michael-cyclization reaction: efficient synthesis of optically active 2-amino-4H-chromene-3-carbonitrile derivatives

We have developed an efficient bifunctional squaramide catalyst for the asymmetric tandem Michael addition–cyclization of malononitrile to functionalized nitroolefins. This organocatalytic asymmetric reaction provides convenient and valuable access to highly functionalized 2-amino-4H-chromene derivatives, which possess important biological activities, in good yields with moderate to high enantioselectivities (up to 95% ee).     

Cu@KCC-1-NH-CS2 as a new and highly efficient nanocatalyst for the synthesis of 2-amino-4H-chromene derivatives

In the present work, Cu@KCC-1-NH-CS₂ as a green, efficient, and reusable nano-reactor was designed and used for the one-pot, three-component synthesis of 2-amino-4H-chromene derivatives using the reaction of cyclic 1,3-diketones, arylglyoxals, and malononitrile, under reflux conditions in EtOH. Engineered nanocatalyst characterized using different methods including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), adsorption/desorption analysis (BET), and energy dispersive X-ray spectroscopy (EDS). According to the obtained results, presented protocol for the synthesis of 2-amino-4H-chromenes using Cu@KCC-1-NH-CS₂ gave the desired products in higher yields (89–98%) with short reaction times. Also, under mild reaction conditions this green nanocatalyst indicated recyclable behavior five times with minor reduce in its catalytic activity.     

Synthesis of uniquely substituted 4H-Chromeno[2,3-d] pyrimidin-2-one derivatives by l-Proline catalyzed green chemistry method

This paper describes synthesis of novel 4H-Chromeno[2,3-d] pyrimidin-2-one compounds by green chemistry method using l-proline as the catalyst. Firstly, a one-pot reaction of resorcinol, malononitrile, and benzaldehyde with proline in water at room temperature on reaction gave 2-amino-7-hydroxy-4-phenyl-4H-1-benzopyran-3-carbonitrile and in next step (2-amino-7-hydroxy-4-phenyl-4H-1-benzopyran-3-carbonitrile was alkylated in the presence of K₂CO₃ in dry acetone at 70–80 °C to give substituted benzopyran 3-carbonitriles. The amino and carbonitrile parts in the substrate were converted into different novel substituted chromeno derivatives on cyclization with urea. The presence of a pyrimidine ring makes this moiety highly biologically efficient.     

Efficient syntheses of novel indeno[1,2-b]chromenone derivatives via hetero-Diels-Alder reactions of 2-(arylmethylene)-1H-indene-1,3(2H)-diones with enaminones

Efficient syntheses of novel 10-aryl-5a-(arylamino)-9-hydroxy-5a,6,7,8-tetrahydroindeno[1,2-b]chromen-11(10H)-one derivatives has been reported by [4+2] cycloaddition reactions of electron-deficient 2-(arylmethylene)-1H-indene-1,3(2H)-dione heterodienes with electron-rich enaminones in [bmim]BF₄ at 80?°C and in acetic acid at 80?°C. Dimedone/cyclohexane-1,3-dione enaminones have been used as dienophiles in Inverse Electron Demand hetero-Diels-Alder reactions. The products were obtained in high yields by a simple work up.     

Solvent-free cascade reaction: direct multicomponent assembling of 2-amino-4H-chromene scaffold from salicylaldehyde, malononitrile or cyanoacetate and nitroalkanes

The new type of solvent-free cascade reaction was found: the direct heating of the mixture of salicylaldehyde, malononitrile or cyanoacetate and nitroalkanes at 60 °C in the presence of catalytic amounts of KF or NaOAc results in the formation of 2-amino-4-(1-nitroalkyl)-4H-chromene-3-carbonitriles or methyl 2-amino-4-(1-nitroalkyl)-4H-chromene-3-carboxylates in 80-90% yields. Thus, the new simple and efficient solvent-free ‘one-pot’ way to substituted medicinally privileged 2-amino-4H-chromene scaffold was found directly from such simple and reasonable starting compounds as salicylaldehyde, malononitrile or cyanoacetate and nitroalkanes.     

Dual reactivity of diazonium salts derived from 1-amino-2-ethynyl-9,10-anthraquinones

Diazotization of vicinal 1-amino-2-ethynyl-4-R-9,10-anthraquinones followed by a reaction with NaN₃ gave 5-hydroxy-3-R-1H-naphtho[2,3-g]indazole-6,11-diones or 3-ethynyl-5-R-6H-anthra[1,9-cd]isoxazol-6-ones, depending on the substituents at the triply bonded C atom and in position 4 of the anthraquinone framework.     

New polyfunctional spiropyran of 1,3-benzoxazin-4-one series with carbonyl-containing substituents in the [2H]-chromene moiety

A polyfunctional spiropyran of 1,3-benzoxazin-4-one series containing one hydroxy and two carbonyl substituents in the [2H]-chromene moiety was synthesized on the basis of a new analogue of 2,4-dihydroxyisophthalic aldehyde, methyl 3,5-diformyl-2,4-dihydroxybenzoate. The structure of resulting 6'-carbomethoxy-3,7-dimethyl-8'-formyl-5'-hydroxy-4-oxo-spiro-(1,3-benzoxazine-2,2'-[2H]-chromene) was unambiguously established by single crystal X-ray diffraction analysis. These data allowed us to reveal the route for the reaction of the new polyfunctional aldehyde with 1,3-benzoxazin-4-onium perchlorate.