“Greener” chemical syntheses using mechanochemical mixing or microwave and ultrasound irradiation

Abstract

Various emerging “greener” strategic pathways, researched primarily in the author's own laboratory, are summarized. They include solvent-free mechanochemical methods that involve the use of hypervalent iodine reagents at room temperature for the synthesis of heterocyclic entities, and useful conversion of ketones into β-keto sulfones and their α-tosyloxy derivatives in high yields. A solvent-free approach that involves microwave (MW) exposure of neat reactants (undiluted) catalyzed by the surfaces of less-expensive and recyclable mineral supports, such as alumina, silica, clay, or “doped” surfaces, is described; it is applicable to a wide range of cleavage, condensation, cyclization, rearrangement, oxidation, and reduction reactions, including rapid one-pot assembly of heterocyclic compounds from in situ generated reactive intermediates. The strategy is adaptable to multi-component reactions, e.g. Ugi and Biginelli reactions, for rapid assembly of a library of compounds. Synthesis of a wide variety of significant precursors and intermediates, namely enones, imines, enamines, nitroalkenes, and oxidized sulfur species, is possible and their value in concise MW synthesis of 2-aroylbenzofurans and thiazole derivatives is illustrated. Ultrasound- and MW-assisted solventless preparation of ionic liquids and their application in alkylation and metal-catalyzed multi-component reactions are described. With a view to consume greenhouse gas, carbon dioxide (CO₂), efficient reaction of epoxides with CO₂ provides ready access to cyclic carbonates using only a catalytic amount of recyclable indium-based ionic liquid. MW heating in aqueous reaction media enables expeditious N-alkylation reactions of amines and hydrazines to afford a series of heterocyclic ring systems, such as N-azacycloalkanes, 4,5-dihydropyrazoles, and pyrazolidines. A general and expeditious MW-enhanced nucleophilic substitution approach uses easily accessible starting materials such as halides or tosylates in reaction with alkali azides, thiocyanates, or sulfinates in the absence of any phase transfer catalyst to produce azides, thiocyanates, and sulfones, respectively, wherein a variety of reactive functional groups are tolerated. A three-component condensation (MCC) approach for the synthesis of useful 2-amino-2-chromenes is described using a recyclable nanosized magnesium oxide catalyst in aqueous poly (ethylene glycol) (PEG) medium at room temperature. A general greener approach to shape-selective generation of nanomaterials is summarized including their potential application as nanocomposites.     

Facile synthesis of trisubstituted imidazoles from 1,2-di(furan-2-yl)-2-oxoethyl carboxylates and their chemiluminescence

A facile synthesis of trisubstituted imidazoles containing furan rings was reported. Imidazoles were produced from 1,2-di(furan-2-yl)-2-oxoethyl carboxylates over solid alumina as solid support impregnated with ammonium acetate under solvent-free microwave-assisted conditions. The method possessed many remarkable advantages, such as the short reaction time (5–10 min), affording moderate to excellent yields and saving resources, conveniently operating process, which provided an attractive and environmentally-friendly approach for the synthesis of the important heterocyclic compounds. Moreover, the chemiluminescence property of some compounds synthesized has been investigated.     

Greener approach toward synthesis of biologically active s-Triazine (TCT) derivatives: A recent update

The greener methodology to synthesize s-triazine derivatives (also known as TCT) is described, including synthesis through microwave, ultrasound, and solvent-free conditions. This review mainly focuses on reactions of TCT (2,4,6-trichloro-1,3,5-triazine) with various substituents having amine and hydroxy functionalities to give corresponding triazine derivatives under a greener approach. The results of reactions indicate that, unlike classical methods, green methods result in better yields of the product, through a rapid reaction, under mild reaction conditions, and by easy workup procedures.     

Synthesis and Reactivity of 3‐oxoprop‐1‐en‐1‐olate Derivative as a Building Block for the Synthesis of Azole and Azine Derivatives

Several new heterocyclic compounds such as 7‐substituted pyrazolo[1,5‐a ]pyrimidine ( 5a–e ) derivatives have been synthesized by the reactions of the versatile unreported sodium 3‐(4‐methyl‐2‐(4‐methylphenylsulfonamido)thiazol‐5‐yl)‐3‐oxoprop‐1‐en‐1‐olate (2) with amino heterocyclic ( 3a–e ) derivatives. Reaction of (2) with hydrazonyl halide ( 7a–d ) and hydroximoyl chloride ( 11a,b ) derivatives followed by reaction with hydrazine hydrate afforded pyrazolo[3,4‐d ]pyridazine and isoxazolo[3,4‐d ]pyridazine derivatives, respectively incorporating a thiazole moiety have been described. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis.     

Mild and Efficient Synthesis of Benzoxazoles, Benzothiazoles, Benzimidazoles, and Oxazolo[4,5-b]pyridines Catalyzed by Bi(III) Salts Under Solvent-Free Conditions

Summary. A series of benzoxazoles, benzothiazoles, benzimidazoles, and oxazolo[4,5-b]pyridines was efficiently synthesized from the reactions of o-aminophenols, o-aminothiophenol, o-phenylenediamines, and 2-amino-3-hydroxypyridine with orthoesters in the presence of catalytic amounts of Bi(III) salts, such as Bi(TFA)₃, Bi(OTf)₃, and BiOClO₄ · xH₂O under solvent-free conditions. The remarkable features of this new protocol are high conversion, very short reaction times, cleaner reaction profiles under solvent-free conditions, straightforward procedure, and use of relatively non-toxic catalysts.     

Synthesis of Heterocyclic Pentavalent Phosphorus Compounds from Phosphite Derivatives and Indane-1,2,3-Trione

Reaction of trialkylphosphite derivatives with indane-1,2,3-trione proceeds smoothly at room temperature to afford the corresponding heterocyclic pentavalent [P(V)] phosphorus compounds via an intermolecular [4+1] cycloaddition reaction in excellent yields under solvent-free conditions. We also used dimethylphosphite and diethylphosphite instead of trialkylphosphites in this reaction, but the corresponding pentavalent phosphorus compounds were not isolated, and in both cases phosphate derivatives were obtained. The structures of the products were deduced from their IR, ¹H NMR, ¹³C NMR, and ³¹P NMR spectra, and mass spectrometry.     

Iodine-Catalyzed Synthesis of 12-Aryl-8,9,10,12-tetrahydro-benzo[a]xanthen-11-one Derivatives via Multicomponent Reaction

Iodine efficiently catalyzes the one-pot, three-component reaction of aryl aldehyde, 2-naphthol, and cyclic 1,3-dicarbonyl compound under solvent-free conventional heating conditions to afford the corresponding 12-aryl-8,9,10,12-tetrahydro-benzo[a]xanthen-11-one derivatives. The present approach offers several advantages such as shorter reaction times, good yields, low cost, and mild reaction conditions.     

Solvent-free, one-pot synthesis of amidoalkyl naphthols by a copper p-toluenesulfonate catalyzed multicomponent reaction

Abstract  

An efficient synthesis of amidoalkyl naphthols using copper p-toluenesulfonate (CPTS) as catalyst for the three-component condensation reaction of 2-naphthol, aldehydes, and amides under thermal, solvent-free conditions is described. This new approach has advantages such as short reaction time, high yield, simple work-up, and reusable catalyst.     

New general synthesis of benzo[4,5]imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine and benzo[4,5]imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>]quinazoline derivatives

The reactions of benzene-1,2-diamine with 5-substituted 2-(alkylsulfanyl)-4-methylpyrimidin-6(1H)-ones and 2-(propylsulfanyl)- and 5-iodo-2-(propylsulfanyl)-3,4-dihydroquinazolines at 175–185°C under solvent-free conditions unexpectedly afforded benzo[4,5]imidazo[1,2-a]pyrimidine, benzo[4,5]imidazo[2,1-b]-quinazoline, and 2,2′-(benzene-1,2-diyldiimino)bis[pyrimidin-4(3H)-ones]. The described reaction is the first example of synthesis of these heterocyclic systems by fusion of benzimidazole to pyrimidine or quinazoline and is likely to follow ANRORC mechanism.     

Efficient and Facile Synthesis of 3-Amino-1-aryl-9H-fluorene-2,4-dicarbonitrile Under Solvent-Free Conditions

A versatile and efficient route to 3-amino-1-aryl-9H-fluorene-2,4-dicarbonitrile via multicomponent reactions of 1-indanone, aromatic aldehydes, and malononitrile under solvent-free conditions using NaOH as the catalyst is described. This method provides several advantages over alternative procedures such as mild, solvent-free conditions at ambient temperature and direct isolation of the products in good yields.     

Green production and antioxidant activity study of new pyrrolo[2,1-a]isoquinolines

In current research, pyrrolo[2,1-a]isoquinoline derivative are synthesized via a new process of four component reaction of phthalaldehyde or its derivatives, primary amines, alkyl bromides, activated acetylenic compounds and potassium fluoride/Clinoptilolite nanoparticles (KF/CP NPs) under solvent-free conditions at room temperature. Also, Dielz-Alder reactions take place in the reaction of synthesized pyrrolo[2,1-a]isoquinoline derivatives, activated acetylenic compounds and triphenylphosphine in the presence of KF/CP NPs under solvent-free conditions at room temperature. As well, antioxidation property of some prepared pyrrolo[2,1-a]isoquinolines are investigated by employing of trapping diphenyl-picrylhydrazine (DPPH) radical and ability of ferric reduction experiment. Among investigated compounds, compounds 5c have good results relative to BHT and TBHQ as standard antioxidant. Our procedure has a few benefits relative to reported method such as good rate of reaction, product with high efficiency and simple removal of catalyst from mixture of reaction. In these reactions, KF/Clinoptilolite nanoparticles show a satisfactory recyclable activity.     

[3 + 3] Cycloaddition of aza-oxyallyl cations with 1,4-dithiane-2,5-diols for the construction of 3-thiomorpholinones

Abstract

Base-mediated [3?+?3] cycloaddition reaction of in-situ formed aza-oxyallyl cations and 1,4-dithiane-2,5-diols has been achieved under mild reaction conditions. This strategy provides direct and efficient access to prepare desired thiomorpholin-3-one derivatives in moderate-to-high yields. The approach features broad substrates scope and short reaction time. Moreover, the resulting products can be readily converted into other useful heterocyclic compounds including 2H-1,4-thiazin-3(4H)-ones and thiomorpholine-3,5-diones.     

A facile and efficient method for synthesis of xanthone derivatives catalyzed by HBF4/SiO2 under solvent-free conditions

Abstract  

HBF₄/SiO₂ was used as an efficient, green, and inexpensive catalytic system for synthesis of 12-aryl or 12-alkyl-8,9,10,12-tetrahydro-11H-benzo[a]xanthen-11-one derivatives via a one-pot three-component reaction of aldehydes, 2-naphthol, and cyclic 1,3-dicarbonyl compounds. The reactions proceeded rapidly at 80 °C under solvent-free conditions and the desired products were obtained in good to excellent yields.     

Synthesis of dimethyl heterocyclic‐o‐dicarboxylates using dimethyl acetylenedicarboxylate

Dimethyl acetylenedicarboxylate (DMAD) is a very important and useful reagent for the preparation of dimethyl heterocyclic‐o‐dicarboxylates, which are key intermediates in the synthesis of fused pyridazine derivatives. The synthesis of thiopyranes by the Diels‐Alder reaction of dithiocarboxylate derivatives, synthesis of various cyclazines by [2 + 8] cycloaddition reactions, and synthesis of dimethyl pyrazolo[3,4‐b]pyridine‐5,6‐dicarboxylates and polycyclic heterocycles containing the 1,6‐naphthyridine ring system by the reaction of o‐aminonitrile compounds with DMAD are described here.     

Fluoroboric Acid Adsorbed on Silica-Gel–Catalyzed Synthesis of 14-Aryl-14H-dibenzo[a,j]xanthene Derivatives

A simple and efficient procedure has been developed for the preparation of 14-aryl-14H-dibenzo[a,j]xanthene derivatives using fluoroboric acid adsorbed on silica gel as a heterogeneous catalyst. The methodology involves the one-pot condensation reaction of β-naphthol and aryl aldehydes under solvent-free conventional heating conditions. The present approach offers several advantages such as shorter reaction times, simple work-up, excellent yields, low cost, and mild reaction conditions. The catalyst is easily recoverable and reusable without loss of its catalytic activity.     

Synthèse d'hétérocycles en catalyse par transfert de phase

A general study of the chemical behavior of heterocyclic anions, dianions and dianionic reagents under phase transfer catalysis conditions allowed us to synthesize various heterocyclic compounds such as imidazo[2,1-b]thiazole and derivatives; imidazo[2,1-b]thiazine and imidazo[2,1-b]benzothiazepine. Reaction conditions e.g., catalyst, solvent, temperature, etc., are indicated.     

The synthesis of N-containing heterocyclic compounds catalyzed by copper/L-proline

N-containing heterocyclic compounds are one of the most important motifs prevalent in various bioactive natural products and pharmaceuticals. Given the significance of N-containing heterocyclic compounds, various synthetic strategies have been developed. Copper/ligand (abbreviated as [CuL])-catalyzed cascade reaction is a powerful and efficient tool for the construction of N-containing heterocyclic compounds. L-proline is one universal ligand and has been utilized in the copper-catalyzed reactions. In this review, copper/L-proline-catalyzed tandem reaction to synthesize the five- and six-membered compounds is emphatically introduced. By comparing the yields in the presence and absence of the ligand, the importance of L-proline is recorded. Moreover, the function of L-proline is expounded on the basis of the reaction mechanism from original article.     

One‐pot and green synthesis 1H-pyrazolo[1,2-b]phthalazine-5,10-dione and dihydropyrano[3,2-c]chromene derivatives by Fe3O4@SiO2-imine/phenoxy-Cu(II) as an efficient and reusable catalyst

In the current study, magnetite-silica core–shell nanoparticles modified with Cu-salen complex (Fe₃O₄@SiO₂-imine/phenoxy-Cu(II)) was utilized as a heterogeneous catalyst for the one-pot multicomponent synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione and dihydropyrano[3,2-c]chromene derivatives under solvent-free conditions, without using any harmful organic reagents/solvent. The current synthetic protocol demonstrates that the reactions proceeds to completing step, leading to the successful synthesis of high purity compounds. Advantages of this method include easy purification, reusability of the catalyst, green and mild procedure and synthesis of new derivatives in high yields within short reaction time.

     

Acetic acid catalysed solvent-free synthesis of spiro-isoxazolo[5,4-b]pyridines/quinolines by mechano-chemical grinding

A simple and efficient three-component procedure has been developed for the synthesis of a series of spiro-isoxazolo[5,4-b]pyridines/quinolines by one-pot condensation of isatins, 3-methylisoxazol-5-amine and enolizable cyclic carbonyl compounds. The protocol has been accomplished under solvent-free conditions by grinding the components at room temperature in presence of catalytic CH₃COOH. The described process offers environmentally benign reaction conditions for the synthesis of pharmacologically important spirooxindole fused heterocycles with the advantages ofoperational simplicity, short reaction time and good to excellent yields of isolated pure product.     

Organocatalytic approach toward the green one-pot synthesis of novel benzo[<Emphasis Type="Italic">f</Emphasis>]chromenes and 12<Emphasis Type="Italic">H</Emphasis>-benzo[5,6]chromeno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridines

An efficient tandem reaction approach is described to prepare novel benzo[f]chromenes from 2,3-dihydroxynaphthalene, malononitrile and aldehydes using 10 mol% guanidine hydrochloride as the catalyst under solvent-free conditions. The method was also extended to the preparation of novel 12H-benzo[5,6]chromeno[2,3-b]pyridines from 2-aminoprop-1-ene-1,1,3-tricarbonitrile instead of malononitrile under the same reaction conditions. The described one-pot three-component reaction is characterized by short reaction times, high-product yield, mild reaction conditions, simple workup procedure, and simple purification.