Synthesis of Spiro Pyrrolobenzothiazole Derivatives via a Three‐Component Reaction

A novel three‐component reaction involving 2‐methylbenzothiazole or 2,5‐dimethylbenzothiazole, acetylenic esters and 1,3‐dicarbonyl compounds such as (1,3‐dimethylbarbituric acid or 1,3‐indanedione) leading to the synthesis of spiro pyrrolobenzothiazole derivatives. The reactions proceeded smoothly at room temperature without using any catalyst. This method is very useful to functionalize benzothiazole derivatives in a one‐pot operation. The structures of the synthesized compounds have been characterized by spectral studies.     

Synthesis of 2‐Oxopyridine‐Fused 1,3‐Diazaheterocyclic Compounds via a Three‐Component Reaction

An efficient and simple route for the preparation of 2‐oxopyridine‐fused 1,3‐diazaheterocyclic compounds via a three component reaction is described. It involves the reaction between alkylenediamines 1 , 1,1‐bis(methylsulfanyl)‐2‐nitroethene, and alkyl prop‐2‐ynoates 2 in refluxing THF (Table). The structures were corroborated by spectroscopic (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and elemental analyses. A plausible mechanism for this type of cyclization is proposed (Scheme).     

Direct Three‐Component Synthesis of α‐Cyano Acrylates Involving Cascade Knoevenagel Reaction and Esterification

A direct three‐component approach has been developed for the synthesis of α‐cyano acrylates starting from aldehydes, alcohols and α‐cyano acetamide by employing cyanuric chloride as an organocatalyst. A class of structurally diverse α‐cyano acrylates have been provided with good to excellent yields via the cascade transformation of Knoevenagel condensation and amide esterification.     

Synthesis of 3,3‐Disubstituted Oxindoles via a Three‐Component Condensation Reaction in H2O

An efficient method has been developed for the synthesis of a novel series of unsymmetrically 3,3‐disubstituted oxindoles in good‐to‐high yields by a one‐pot three‐component condensation reaction of 2‐hydroxynaphthalene‐1,4‐dione, an isatin, and a barbituric acid derivative, in H₂O, and with p‐toluenesulfonic acid as a catalyst, at 90°. The effects of solvent, temperature, and the amount of catalyst on the yield of the reaction have been investigated. Additionally, the influence of hydrophilicity and hydrophobicity of the reactants on the selectivity of products has been examined.     

Three‐Component Synthesis of Highly Functionalized 5‐Acetyloxazoles

By a flexible three‐component synthesis, alkoxy‐substituted enamides are easily available from lithiated alkoxyallenes, nitriles and carboxylic acids (see scheme). The treatment of these versatile intermediates with trifluoroacetic acid provided 5‐acetyloxazoles in moderate to good yields. Different substituents are possible at C‐2 and C‐5 and the 5‐acetyl group is a suitable handle for further synthetic transformations.

     

An Efficient Synthesis of New Dispiropyrrolidine Derivatives via Three‐Component 1,3‐Dipolar Cycloaddition Reaction

A series of new dispiropyrrolidine derivatives were synthesized via the three‐component 1,3‐dipolar cycloaddition reaction of azomethine ylides generated in situ by the decarboxylative condensation of acenaphthenequinone and sarcosine or l ‐thioproline with 5‐benzylidene‐1,3‐dimethylpyrimidine‐2,4,6‐trione. The structures of the products were identified by IR, ¹H‐NMR, and HRMS spectra.     

Divergent Dendrimer Synthesis via the Passerini Three‐Component Reaction and Olefin Cross‐Metathesis

The combination of the Passerini reaction and olefin cross‐metathesis is shown to be a very useful approach for the divergent synthesis of dendrimers. Castor oil‐derived platform chemicals, such as 10‐undecenoic acid and 10‐undecenal, are reacted in a Passerini reaction with an unsaturated isocyanide to obtain a core unit having three terminal double bonds. Subsequent olefin cross‐metathesis with tert‐butyl acrylate, followed by hydrogenation of the double bonds and hydrolysis of the tert‐butyl ester, leads to an active core unit bearing three carboxylic acid groups as reactive sites. Iterative steps of the Passerini reaction with 10‐undecenal and 10‐isocyanodec‐1‐ene for branching, and olefin cross‐metathesis with tert‐butyl acrylate, followed by hydrogenation and hydrolysis allow the synthesis of a third‐generation dendrimer. All steps of the synthesis are carefully characterized by NMR, GPC, MS, and IR.

     

Catalyst‐Free Reaction in Water: Synthesis of Functionalized Tetrahydroindole Derivatives via Three‐Component Domino Reaction

An environmentally benign and efficient method has been developed for the synthesis of functionalized tetrahydroindole derivatives in aqueous media under catalyst‐free conditions, by simply combining a phenylglyoxal monohydrate, an enaminone, and a barbituric acid. The advantages of this method are that it is catalyst free, has an easy workup, provides good yields, and uses water as solvent, which make this procedure facile and practical.     

Synthesis of 2‐Oxopyrrole‐fused 1,n‐Diazaheterocyclic Compounds and Substituted 2‐Oxopyrroles via a Three‐Component Reaction

An effective route to 2‐oxopyrrole‐fused 1,n‐diazaheterocyclic compounds and substituted 2‐oxopyrroles is described. This involves reaction of 1,n‐diamines or monoamines 1 and nitroketene dithioacetal (1,1‐di(methylthio)‐2‐nitroethene) in the presence of dialkyl acetylenedicarboxylate 2 in EtOH to give 2‐oxopyrrole derivatives 3 in good yields (Table 1). The structures were corroborated spectroscopically (IR, ¹H and ¹³C NMR, and EIMS) and by elemental analyses. A plausible mechanism for this type of cyclization is proposed (Scheme 1).     

One‐Pot Synthesis of Fused [1,6]Naphthyridine Derivatives via Three‐Component Reaction

A simple, convenient, and eco‐friendly synthetic protocol has been developed via a one‐pot three‐component reaction between 2‐chloroquinoline‐4‐amines, different substituted aromatic aldehydes, and malononitrile using ethanol as reaction medium. Employing this protocol, a series of 5‐chloro‐4‐phenyl benzo[f ][1,6] naphthyridine‐2‐amino‐3‐carbonitrile derivatives were synthesized in an environmentally friendly approach under operational simplicity, short time reactions, easy work‐up procedure, and comparatively high yields. This chemistry provides a convenient and promising synthetic strategy for the construction of the napthyridine skeleton. All synthesized compounds were identified on the basis of their spectral data.     

A Novel and Efficient Synthesis of Pyrido[1,2‐a]‐Fused 1,3‐Diazaheterocyclic Compounds via a One‐Pot Three‐Component Reaction

An efficient one‐pot synthesis of pyrido[1,2‐a]‐fused 1,3‐diazaheterocyclic compounds by three‐component reaction of diamine, nitroketene dithioacetal (=1,1‐bis(methylsulfanyl)‐2‐nitroethene), and electron‐poor itaconic anhydride (=2‐methylidenesuccinic anhydride=2‐methylidenebutanedioic anhydride) in aqueous EtOH is reported. This protocol has the advantages of easiness, higher yields, and shorter reaction times. The structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of cyclization is proposed (Scheme 2).     

Synthesis of 1,5‐Disubstituted 1H‐Tetrazole Derivatives via a Three‐Component Reaction of Carbodiimides,Isocyanides, and Trimethylsilyl Azide

The three‐component reaction of isocyanides 1 , carbodiimides 2 , and trimethylsilyl azide ( 3 ) occurs at room temperature, and the produced 1,5‐disubstituted 1H‐tetrazole derivatives 4 are formed in 81–98% yields (Scheme 1, Table). The reaction proceeds smoothly and cleanly under mild conditions, and no side reactions are observed.     

Synthesis of Spiropyrazolines via a Pseudo‐Six Component Reaction

A novel and eco‐friendly route for the synthesis of highly functionalized spiropyrazolines via a pseudo‐six component reaction of hydrazine hydrate, nitro ketene dithioacetal, isatin, and active methylene under mild condition at room temperature in ethanol media has been developed. The key steps in the synthetic strategy involve the formation of 1,1‐dihydrazino‐2‐nitroethylene from hydrazine hydrate with nitro ketene dithioacetal and its reaction with Knoevenagel adduct derived from the corresponding isatin and active methylene. The reaction is particularly attractive due to features such as high bond‐forming efficiency, optimum convergence, mild condition, atom economy, easy work‐up/purification, and reduced waste production without using any additive.     

A Metal‐Free Three‐Component Reaction for the Regioselective Synthesis of 1,4,5‐Trisubstituted 1,2,3‐Triazoles

A metal‐free three‐component reaction to synthesize 1,4,5‐trisubstituted 1,2,3‐triazoles from readily available building blocks, such as aldehydes, nitroalkanes, and organic azides, is described. The process is enabled by an organocatalyzed Knoevenagel condensation of the formyl group with the nitro compound, which is followed by the 1,3‐dipolar cycloaddition of the azide to the activated alkene. The reaction features an excellent substrate scope, and the products are obtained with high yield and regioselectivity. This method can be utilized for the synthesis of fused triazole heterocycles and materials with several triazole moieties.     

Three‐Component Triple Organocascade Synthesis of Hexahydropyridazine Derivatives via a Sequential Michael/Amination/Cyclization Reaction

The organocatalytic asymmetric synthesis of hexahydropyridazines were performed through a unique Michael/amination/cyclization reaction. The organocascade reaction proceeded smoothly between 2‐arylidene‐1,3‐indandiones and aldehydes followed by the addition of azodicarboxylates catalyzed by the privileged organocatalyst α,‐α‐L‐diphenylprolinol trimethylsilyl ether (10 mol%) in the presence of a base additive Et₃N (20 mo%) at 0 °C. A series of substituted hexahydropyridazines were obtained in good to high chemical yields (55–78 %) and reasonable to high levels of stereoselectivities (51–93 % ee and 4 : 1 d.r.).