An Efficient Protocol for the Synthesis of Novel 1,2,3‐Triazole Substituted 4H‐Chromene Derivatives

A facile and an efficient protocol has been developed for the synthesis of novel 1,2,3‐triazole substituted 4H‐chromene derivatives 4 in single pot by multicomponent reaction of 1,3‐cyclohexanedione, malononitrile and 1‐substituted 1,2,3‐triazole‐5‐aldehyde using potassium carbonate as catalyst.     

An Efficient and Chemoselective Knoevenagel/Hemiketalization Process for the Synthesis of New 2H‐Chromenes in a One‐Pot Three‐Component Reaction

A novel L ‐proline‐catalyzed mild and ecological approach towards the synthesis of 2H‐chromene derivatives was achieved by Knoevenagel reaction followed by an intramolecular hemiketalization process. In the present protocol, chemoselectivity has been successfully achieved by using L ‐proline as catalyst. This eco‐friendly and chemoselective reaction provided an alternative synthetic method to prepare previously unknown 2H‐chromene derivatives in a one‐pot reaction.     

Synthesis of Multi‐substituted Benzamide Derivatives under Microwave Irradiation Conditions

A facile microwave‐assisted synthesis of N‐[(Z)‐1‐(substituted carbamoyl)‐2‐arylvinyl] benzamide derivatives is accomplished via reactions of 4‐arylmethylene‐2‐phenyloxazol‐5(4H)‐ones with different amines (for example methylamine, cyclopropylamine, para‐toluidine, phenylamine) in ethylene glycol. This protocol broadens the scope of the reaction for the synthesis of N‐benzamide derivatives.     

One‐Pot Knoevenagel–Michael–Cyclization Cascade Reaction for the Synthesis of Functionalized Novel 4H‐pyrans by Using ZnCl2 as a Catalyst

An expedient and cost‐effective protocol has been developed for the synthesis of novel 2‐methyl‐6‐(methylamino)‐5‐nitro‐4‐(4‐aryl)‐4H‐pyran‐3‐carboxylate derivatives. This domino, one‐pot, three‐component reaction was carried out between β‐ketoesters, aromatic aldehydes, and (E)‐N‐methyl‐1‐(methylthio)‐2‐nitroethenamine (NMSM) in the presence of 30 mol% anhydrous ZnCl₂ under the neat condition at 120°C. The synthesized 4H‐pyran derivatives were characterized by spectroscopic techniques such as IR, ¹H NMR, ¹³C NMR, CHNS, and HRMS. The molecular structure of compound methyl‐2‐methyl‐6‐(methylamino)‐5‐nitro‐4‐(4‐nitrophenyl)‐4H‐pyran‐3‐carboxylate 4a was confirmed by the single crystal X‐ray analysis. This solvent‐free protocol has several advantages such as shorter reaction time, an inexpensive catalyst, good yields, simple workup, and column‐free purification.     

Hypervalent Iodine(III)‐Mediated Benzannulation of Enamines with Alkynes: an Efficient Synthesis of Substituted Aminonaphthoic Acid Derivatives

An intermolecular two C? C bond formation procedure for the synthesis of carbocycles mediated by hypervalent iodine(III) reagents was developed. This metal free protocol provided a new approach for the synthesis of useful substituted 1‐amino‐2‐naphthoic acid derivatives via benzannulation reactions. Various N‐unsubstituted and N‐alkyl substituted aromatic enamines with terminal alkynes and non‐terminal alkynes can be converted into corresponding 1‐amino‐2‐naphthoic acid derivatives under mild reaction conditions. When meta‐substituted phenyl enamines were employed in the reaction, two cyclization paths were detected in the reaction and ortho‐cyclization products were the only or major products. Good functional group tolerance, readily available material and high atom utilization efficiency make this method a potential procedure which may find broad application in organic synthesis.     

One‐pot Synthesis of 3,4‐Dihydropyrimidin‐2(1H)‐ones Catalysed by Cupric Acetate under Solvent‐free Conditions

A solvent‐free synthesis of 3,4‐dihydropyrimidin‐2(1H)‐ones from aromatic aldehydes, β‐keto ester/acetyl acetone and urea catalysed by cupric acetate under thermal condition is reported as a simple and an efficient protocol. Compared with classical Biginelli reaction reported in 1893, this new method provides much improved modification in terms of yield and reaction time. The usage of milder catalyst, environmental friendly procedures and excellent yields within a very short time (5–15 min) are the advantages of the method in which the involvement of solvent‐free condition adds an edge to the method. Thus, the efficiency of the protocol enabled the rapid synthesis of 3,4‐dihydropyrimidin‐2(1H)‐one derivatives in a short duration.     

A Rapid and an Efficient Route to the One‐pot,Multicomponent Synthesis of 1H‐Pyrazolo[1,2‐b]phthalazine‐5,10‐dione Ring Systems

CAN is found to be an efficient catalyst for the synthesis of 1H‐pyrazolo[1,2‐b]phthalazine‐5,10‐dione derivatives via one‐pot coupling reaction of phthalhydrazide, aromatic aldehydes, and malononitrile or ethyl cyanoacetate in PEG as solvent. The major attributes of this synthetic protocol are the use of nontoxic, inexpensive, and readily available catalyst, mild conditions, easy work up, improved yields, and the PEG 400 as solvent that is environmentally benign as well as recyclable.     

An Efficient Synthesis of Pyrazolyl‐1,2,3‐thiadiazoles via Hurd–Mori Reaction

An efficient synthetic strategy has been developed for the synthesis of pyrazolyl‐1,2,3‐thiadiazoles via Hurd–Mori cyclization reaction. The reaction of various pyrazolyl‐phenylethanones with semicarbazide hydrochloride in the presence of sodium acetate/methanol gave the corresponding semicarbazones ( 3a – i ). These semicarbazones were further reacted with thionyl chloride via the Hurd–Mori cyclization conditions to accomplish the title products ( 4a – i ). The present protocol favored for the formation of both pyrazolyl semicarbazone derivatives and pyrazolyl‐1,2,3‐thiadiazole derivatives by forming C─S, N─S, and C═N bonds in excellent yields with variety of substrates. The final compounds were characterized by analytical and spectral studies.     

Methanesulfonic Acid‐Catalyzed One‐Pot Synthesis of 12‐Aryl or 12‐Alkyl‐8,9,10,12‐tetrahydrobenzo[a]xanthen‐11‐one Derivatives

An efficient synthesis of 12‐aryl or 12‐alkyl‐8,9,10,12‐tetrahydrobenzo[a]xanthen‐11‐one derivatives has been developed under solvent‐free conditions by one‐pot condensation of aldehydes, 2‐naphthol, and cyclic 1,3‐dicarbonyl compounds in the presence of a catalytic amount of methanesulfonic acid. The protocol has advantages of mild condition, short reaction time, high yield, and operational simplicity.     

Silica‐Supported P2O5 as an Efficient Heterogeneous Catalyst for the One Pot Synthesis of 3‐Amino‐imidazo[2,1‐b](1,3)benzothiazole under Green Conditions

The new approach involving the solid supported catalyst for the formation of C–N bond followed by cyclization has been reported. In this work we have reported a facile, efficient, and environment‐friendly protocol for the synthesis of some new 3‐amino‐imidazo[2,1‐b](1,3)benzothiazole derivatives by one‐pot condensation of 2‐aminobenzothiazole, indole‐3‐carbaldehyde, and aryl isocyanide in the presence of silica‐supported P₂O₅ as a heterogeneous solid acid catalyst. The reaction was performed using conventional method under green conditions. The present approach offers the advantages of simple methodology, inexpensive acid catalyst, short reaction time, easy work up with excellent yield, simple purification and use of green solvent. All the newly synthesized compounds were characterized in details using physical and chemical techniques such as melting point, ¹H NMR, ¹³C NMR, and FTIR spectroscopy.     

Intramolecular Hetero‐Diels–Alder Reactions Catalyzed by BiCl3: Stereoselective Synthesis of Benzo‐Annelated Decahydrofuro[3,2‐h][1,6]naphthyridine Derivatives

A novel, efficient synthesis of a series of functionalized, benzo‐annelated decahydrofuro[3,2‐h][1,6]naphthyridine derivatives 3 has been achieved. The protocol is based on the intramolecular hetero‐Diels–Alder (IMHDA) reaction of in situ formed imines derived from an N‐prenylated sugar aldehyde 1 and different aromatic amines 2 in the presence of bismuth(III) chloride as catalyst. The reactions could be run under very mild conditions at room temperature, and were complete within 30 min, affording exclusively and stereoselectively the corresponding trans‐fused products 3 in good‐to‐excellent yields (Table).     

An Improved Protocol for the Synthesis of Quinoline‐2,3‐dicarboxylates under Neutral Conditions via Biomimetic Approach

A mild and efficient protocol for synthesis of quinoline derivatives in aqueous medium under neutral conditions is described. The reaction proceeded smoothly in H₂O catalyzed by supramolecular catalyst β‐CD. By this protocol, various quinoline derivatives were synthesized in excellent yields.     

Highly Regio‐ and Enantioselective Synthesis of N‐Substituted 2‐Pyridones: Iridium‐Catalyzed Intermolecular Asymmetric Allylic Amination

The first iridium‐catalyzed intermolecular asymmetric allylic amination reaction with 2‐hydroxypyridines has been developed, thus providing a highly efficient synthesis of enantioenriched N‐substituted 2‐pyridone derivatives from readily available starting materials. This protocol features a good tolerance of functional groups in both the allylic carbonates and 2‐hydroxypyridines, thereby delivering multifunctionalized heterocyclic products with up to 98 % yield and 99 % ee.     

Synthesis of Spirooxindoles through Cyclocondensation of Isatin and Cyclic 1,3‐Diones

A simple, clean, and efficient method for the synthesis of spirooxindole derivatives via condensation of isatin with enolizable cyclic β‐diketones has been developed. The use of water as a solvent allows avoiding the use of toxic organic solvents, which makes this reaction safe and environmentally friendly. The mechanism of the condensation reaction has been investigated using first‐principles‐based density functional theory calculations.     

MOF‐promoted Three‐component Synthesis of Functionalized Pyrano[3,2‐c]chromen under Mild Conditions

A convenient and efficient route for synthesis of various derivatives of 3‐benzoyl‐4‐phenyl‐2‐(trifluoromethyl)pyrano[3,2‐c]chromen‐5(4H)‐one has been used via tandem Knoevenagel condensation–Michael addition and intramolecular cyclization sequence. These products have been synthesized in the presence of catalytic amount of metal–organic framework (MOF) and potassium carbonate as one‐pot, three‐component reaction. MOF catalyst has been separated easily with external magnet, and high purity of products has been obtained after washing with ethanol. This protocol has advantages of simplicity, mild condition, and high yield. More importantly, MOF has been easily recycled for three times.     

Tandem One‐pot Synthesis of Polysubstituted 1,3‐Thiazine Derivatives

A tandem one‐pot synthesis of polysubstituted 1,3‐thiazines has been developed by reacting with cyanoacetamide and isothiocyanate derivatives to give rise to 2‐cyano‐3‐mercaptoacrylamides, which are trapped in situ by various aldehydes or diversely substituted ketones through intermolecular cyclization, providing polysubstituted 1,3‐thiazine derivatives in short reaction times with good to excellent yields. The salient features of this novel protocol are operational simplicity, accessing the desired products from the readily available starting materials and easy of product isolation and may find wide spread applications in medicinal chemistry.     

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.     

A Novel and Efficient Synthesis of 3‐[(4,5‐Dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐chromen‐2‐ones (=3‐[(4,5‐Dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐1‐benzopyran‐2‐ones)

An efficient one‐pot synthesis of 3‐[(4,5‐dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐chromen‐2‐one (=3‐[(4,5‐dihydro‐1H‐pyrrol‐3yl)carbonyl]‐2H‐1‐benzopyran‐2‐one) derivatives 4 by a four‐component reaction of a salicylaldehyde 1 , 4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one, a benzylamine 2 , and a diaroylacetylene (=1,4‐diarylbut‐2‐yne‐1,4‐dione) 3 in EtOH is reported. This new protocol has the advantages of high yields (Table), and convenient operation. The structures of these coumarin (=2H‐1‐benzopyran‐2‐one) derivatives, which are important compounds in organic chemistry, were confirmed spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme 2).     

Chemoselective Route for Synthesis of N‐Aryl‐3‐oxochromeno[2,3‐c]pyrazole‐2(3H)‐carbothioamide Derivatives

A chemoselective route for the synthesis of chromeno[2,3‐c]pyrazole‐2(3H)‐carbothioamide derivatives by a five‐component reaction of salicylaldehyde, malononitrile, NH₂NH₂?H₂O, aryl isothiocyanate, and H₂O in EtOH/AcOH mixture is reported. This new protocol has the advantages of high yields, short reaction times, ease of operation, and simple purification. All structures were confirmed by IR, ¹H‐ and ¹³C‐NMR, and MS analyses. A plausible mechanism for this type of reaction is proposed (Scheme 2).     

A New Pathway for Phthalazine Derivatives via Metal‐Free Cyclization of ortho‐Alkynylphenyl Ketones and Hydrazine

A one‐step synthetic protocol for phthalazine derivatives has been developed. In the presence of Et₃N, a series of phthalazine derivatives were conveniently prepared in high yield by the reaction of ortho‐alkynylphenyl ketones and hydrazine under mild reaction conditions. The structure was unambiguously confirmed by X‐ray crystallographic analysis of product 2i .