Pseudo four-component reaction of salicylaldehydes and cyclic ketones with two molecules of malononitrile: A facile and efficient way to synthesize 4-[2-(dicyanomethylene)cyclic or heterocyclic]-2-amino-4H-chromenes

A new type of catalytic cascade pseudo four-component reaction has been found. The simple and facile pseudo four-component reaction of salicylaldehydes and cyclic or heterocyclic ketones with two molecules of malononitrile catalyzed by sodium acetate at ambient temperature results in the formation of 4-substituted 2-amino-4H-chromenes in 70–90% yields. Thus, a new simple and efficient ‘one-pot’ method to synthesize substituted 2-amino-4H-chromenes was found directly from such reasonable starting compounds as salicylaldehydes, cyclic or heterocyclic ketones and malononitrile.     

A new type of cascade reaction: direct conversion of carbonyl compounds and malononitrile into substituted tetracyanocyclopropanes

A new type of chemical cascade reaction was found: the direct formation of cyclopropanes from carbonyl compounds and C-H acid. The action of free halogen or active halogen containing compounds on a mixture of 1 equiv of carbonyl compound and 2 equiv of malononitrile in a basic alcohol solution results in the formation of substituted 1,1,2,2-tetracyanocyclopropanes in 15-80% yield. The latter are well-known precursors for the different bicyclic heterosystems, among them compounds containing a cyclopropane ring and possessing different types of pharmacological activity. Thus, the new, simple and efficient ‘one-pot’ way to substituted tetracyanocyclopropanes in 50-80% yield was found directly from such simple and reasonable starting compounds as aldehydes, or some cyclic ketones, or substituted cyclohexanones and malononitrile.     

Chemoselective Synthesis of Novel Heterocyclic [3.3.3]Propellane Derivatives via a One‐pot Three‐component Reaction

A highly chemoselective method for the synthesis of heterocyclic [3.3.3]propellane derivatives was developed via sequential three‐component reactions of acenaphthenequinone, malononitrile/cyanoacetate and a variety of 1,3‐dicarbonyl compounds under mild conditions in ethanol. A plausible mechanism for this type of reaction was proposed. The value of this method was highlighted by its high selectivity, simple procedures, and good yields.     

One-pot three-component synthesis of the spiroacenaphthylene derivatives

A facile and efficient one-pot three-component synthesis of the spiroacenaphthylene derivatives was achieved, via the reaction of acenaphthequinone, malononitrile/ethylcyanoacetate and various reagents including α-methylencarbonyl compounds/enols.     

Electro-oxidation of paracetamol in the presence of malononitrile: Application for green,efficient, none-catalyst,simple and one-pot electro-synthesis of new paracetamols

Electrochemical oxidation of paracetamol has been studied in the presence of malononitrile as a nucleophile in a phosphate buffer solution (0.15 mol/L, pH 7), using cyclic voltammetric techniques. The results indicated that the N-acetyl-p-benzoquinone-imine derived from paracetamol participates in a 1,4-Michael-type addition reaction with the malononitrile to form the corresponding paracetamol derivatives (6a, 7a). The present study has led to the development of a simple, green, non-catalyst and one-pot electrochemical method with high atom economy under mild conditions.     

Ag3[PMo12O40]: An efficient and green catalyst for the synthesis of highly functionalized pyran‐annulated heterocycles via multicomponent reaction

A facile, efficient and eco‐friendly catalytic protocol was developed for the synthesis of medicinally important pyran‐annulated heterocycles via multicomponent reaction (MCR). Cyclocondensation of differently substituted aromatic aldehydes, malononitrile/ethyl cyanoacetate and various β‐dicarbonyl compounds in the presence of Ag₃[PMo₁₂O₄₀]?nH₂O as heterogeneous catalyst, in EtOH–H₂O, afforded diverse pyran‐fused chromene analogues. The merits observed for this approach were it being conducted via MCR, using commercially available or easily accessible starting materials in the presence of a green and easily separable heterogeneous and reusable catalyst, and affording high yields of desired products in very short reaction times with high purity in one‐pot fashion, thus providing a superior alternative approach for the synthesis of pyran‐annulated heterocycles.     

Polyethylene glycol in water: Simple,efficient, and catalyst-free synthesis of 4H-pyran derivatives

A green, one-pot, multicomponent method for the synthesis of diverse library of 4H-pyran derivatives such as 4-phenyl-4H-pyrans, spirochromenes, and dihydropyrano[3,2-c]chromines was developed using polyethylene glycol (PEG-600) as promoting reaction medium in water. The 4-phenyl-4H-pyran dihydropyrano[3,2-c]chromine derivatives were synthesized by a three-component reaction of aromatic aldehyde, malononitrile, and cyclic 1,3-dione/4-hydroxy coumarin at room temperature and reflux respectively. The promising points for the present methodology are efficiency, generality, high yield, short reaction time, cleaner reaction profile, ease of product isolation, potential to recycle reaction medium, and agreement with green chemistry protocols, making it a useful and attractive process for the synthesis of 4H-pyran derivatives.     

Na<Subscript>2</Subscript>EDTA: an efficient,green and reusable catalyst for the synthesis of biologically important spirooxindoles,spiroacenaphthylenes and spiro-2-amino-4<Emphasis Type="Italic">H</Emphasis>-pyrans under solvent-free conditions

For the first time, the organic salt Na₂EDTA was used as a catalyst for an effective and facile preparation of spiro-4H-pyrans via single-pot three-component condensation of isatin/acenaphthoquinone/ninhydrin, malononitrile, and CH-acids through Knoevenagel–Michael–annulation sequence. This new protocol employing Na₂EDTA, which is a green, recyclable, and inexpensive catalyst, offers advantages such as solvent-free and highly efficient reaction conditions, short reaction times (10–15 min), easy work-up and high yields which make it more economic than other environmentally synthetic methods.     

Versatility of Alternative Reaction Media: Water-Mediated Domino and Green Chemical Synthesis of Pyrimido[1,2-a]benzimidazole Under Nonconventional Conditions

A convenient and clean water-mediated synthesis of a series of 4-amino-2-aryl-1,2-dihydro pyrimido[1,2-a]benzimidazoles (4) is reported using alternative nonconventional energy sources. The products are obtained in shorter times with excellent yields (78–89%) from the multicomponent reaction of 2-aminobenzimidazole (1), malononitrile/ethylcyanoacetate (2a/b), and carbonyl compounds (3). The reaction is found to be general with respect to the cyclic and acyclic carbonyl compounds. The procedure does not involve the use of any additional reagent/catalyst, produces no waste, and represents a green synthetic protocol with high atom economy.     

A new strategy of the chemical route to the cyclopropane structure: direct transformation of benzylidenemalononitriles and malononitrile into 1,1,2,2-tetracyanocyclopropanes

The new reaction was found: the direct formation of cyclopropanes from activated olefins and C-H acids. The action of free halogen or active halogen containing compounds on the equal amounts of benzylidenemalononitriles and malononitrile in basic alcohol solutions results in the formation of 3-aryl-1,1,2,2-tetracyanocyclopropanes in 65-95% yields. Thus, the new simple and efficient way to 3-aryl substituted tetracyanocyclopropanes was found directly from such simple and reasonable starting compounds as benzylidenemalononitriles and malononitrile.     

SnCl2/nano SiO2：A green and reusable heterogeneous catalyst for the synthesis of polyfunctionalized 4H-pyrans

A highly efficient and general method for the synthesis of polyfunctionalized 4H-pyrans is established through a one-pot multicomponent cyclocondensation of aromatic aldehydes with CH acids, malononitrile and ethyl acetoacetate using nano silica supported tin (Ⅱ) chloride as a catalyst. In this method SnCl2/nano SiO2 was used as green and reusable catalyst. Excellent yields, short reaction times, simple workup, and inexpensiveness and commercially availability of the catalyst are the advantages of this method.     

Green access to novel spiro pyranopyrazole derivatives

A catalyst-free multicomponent reaction (MCR) capable of affording a wide range of novel spiro pyranopyrazole derivatives from pyrazolone in situ formed from acetylenic esters with hydrazine hydrate at room temperature with isatin and malononitrile is reported. A plausible mechanism is suggested. Catalyst-free conditions along with green solvent system make the process ecofriendly as well as economical. Simple reaction conditions and easy work-up procedure that resulted into simple isolation and purification of products by non-chromatographic methods, that is, by simple recrystallization from methanol as well as novelty are the significant advantages of the present protocol.     

Electrocatalytic multicomponent transformation of cyclic 1,3-diketones, isatins, and malononitrile: facile and convenient way to functionalized spirocyclic (5,6,7,8-tetrahydro-4H-chromene)-4,3′-oxindole system

An electrochemically induced catalytic multicomponent transformation of cyclic 1,3-diketones, isatins, and malononitrile in alcohols in an undivided cell in the presence of sodium bromide as an electrolyte results in the formation of spirooxindoles with fused functionalized 5,6,7,8-tetrahydro-4H-chromene system in 83-98% yields. The application of this efficient electrocatalytic method to the formation of medicinally relevant spirocyclic (4H-chromene)-4,3′-oxindoles is beneficial from the viewpoint of diversity-oriented large-scale processes and represents novel, facile, and environmentally benign synthetic concept for multicomponent reaction strategy.     

Phenyliodonium Derivatives of N-Heterocycles and CH-Acids, Their Synthesis, and Their Use in the Chemistry of Heterocycles. (Review)

The reactions of iodosylbenzene with CH-acids, including -dicarbonyl and N-heterocyclic compounds in the presence of alkali, which lead to the aryliodonium ylides (betaines) used in the synthesis of new derivatives of heterocycles, are examined. Both -dicarbonyl compounds and the anions of various heterocyclic compounds (pyrrole, indole, pyrazolidinedione, hydroxypyrones, hydroxypyridones, oxo- and dioxopyrimidines) and -keto sulfones, -disulfones, cyclopentadienes, and malononitrile enter into the reaction.     

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.     

Sodium Formate‐Catalyzed One‐Pot Synthesis of Benzopyranopyrimidines and 4‐Thio‐substituted 4H‐Chromenes via Multicomponent Reaction at Room Temperature

A simple, straightforward and highly efficient multicomponent one‐pot synthesis of a series of pharmaceutically interesting benzopyranopyrimidine and 4H‐chromene derivatives has been developed on the basis of low‐cost and environment‐friendly sodium formate catalyst via tandem reactions of salicylic aldehydes, malononitrile, and cyclic secondary amines in ethanol at room temperature. Nature of nucleophile used in this reaction directs the course of the reaction; cyclic secondary amines result in the formation of benzopyrano[2,3‐d]pyrimidines, whereas thiophenol furnish corresponding 4‐thio‐subtituted 4H‐chromenes under the same reaction conditions. High atom‐economy, good yields, eco‐friendly, and mild reaction conditions are some of the important features of this protocol.     

5-Diazouracils in Azo Coupling Reactions

6-Hydroxy-5-diazo-6H-uracil and 6-hydroxy-5-diazo-1,3-dimethyl-6H-uracil enter into azo coupling reaction with CH-acids, active phenols, arylamines, and heterocycles. The conditions of reaction depend on the substrate character.     

Multicomponent Reactions with Cyclic Tertiary Amines Enabled by Facile C−N Bond Cleavage

A novel and catalyst‐free multicomponent reaction with cyclic tertiary amines, electron‐deficient aryl halides or heteroaromatic halides, and Na₂S enabled by facile C−N bond cleavage of the cyclic tertiary amines was developed. This direct and operationally simple method can be applied with a wide range of functional groups and provides an efficient and rapid approach to potentially drug‐like products containing amine, azaarene, thioether, or phenol ether functionalities in good to excellent yields. The utility of this method was demonstrated by the rapid synthesis of the analgesic ruzadolane.     

The first chemoselective synthesis of functionalized 3-vinylpyrroles

3-(1-Alkylthio-2-cyano-2-X-ethenyl)pyrroles (X=CN, CONH₂, CO₂Et) have been synthesized in 28-58% yields by the reaction of pyrrole-3-carbodithioates with CH-acids (malononitrile, cyanoacetamide, cyanoacetate) in the KOH-DMSO system.     

One‐Pot Multicomponent Synthesis of Novel 2‐Tosyloxyphenylpyrans under Green and Conventional Condition with Anti‐inflammatory Activity

A mild, efficient, and environmentally green protocol for the synthesis of 2‐tosyloxyphenylpyran derivatives 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 via reaction of 2‐tosyloxybenzaldehyde ( 1 ) with malononitrile and some ketonic reagents in one‐pot, three component reaction within few minutes under stirring in methanol in presence of ammonium hydroxide solution or ultrasonic irradiation. On the other hand, the same products 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 were obtained by traditional method, on treatment of 2‐tosyloxybenzilidinemalononitrile ( 2 ) with the same ketonic reagents in refluxing ethanol in presence of TEA. 2‐Tosyloxyphenylpyranopyrazoles 12 and 13 were obtained via treatment of compound 1 with malononitrile, hydrazine hydrate or phenyl hydrazine and ethyl acetoacetate, in one‐pot, multicomponent reaction (MCRs). The structures of the new compounds were elucidated by elemental and spectral analyses. The newly synthesized compounds showed promising anti‐inflammatory activity.