Multicomponent Reaction in Ionic Liquid: A Novel and Green Synthesis of 1, 4-Dihydropyridine Derivatives

An efficient and green method for the synthesis of 1, 4-dihydropyridine derivatives mediated in an ionic liquid, [bmim][BF4], through a four-component condensation process of aldehydes, 1, 3-dione, Meldrum＇s acid and ammonium acetate is disclosed in this paper.

Prediction of Multicomponent Reaction Yields Using Machine Learning

Prediction of reaction yields using machine learning(ML)can help chemists select high-yielding reactions and provide prior experience before wet-lab experimenting to improve efficiency.However,the exploration of a multicomponent organic reaction features many complex variables and limited number of experimental data,which are challenging for the application of ML.Herein,we perform yield prediction for the synthesis of 2-oxazolidones via Cu-catalyzed radical-type oxy-alkylation of allylamines and herteroaryl-methylamines with CO_(2),which is a three-component reaction.Using physicochemical descriptors as features to launch ML modelling,we find that XGBoost shows significantly improved performance over linear models and these features are effective for the yield prediction.Moreover,out-of-sample prediction indicates the application potential of the model.This study demonstrates great potential of regression-modelling-based ML in organic synthesis even with complex factors and a general small size of reaction data,which are generated from the classical research pattern of method for the inquiry of multicomponent reactions.

Pillar[5]arene-based [3]rotaxanes: Convenient construction via multicomponent reaction and pH responsive self-assembly in water

Four pillar[5]arene based[3]rotaxanes(1-4)involving two 1,4-diethoxypillar[5]arene(DEP5)rings and a dumbbell-shaped component were successfully synthesized.The dumbbell-shape molecules contain one longer bridge,two triazole sites and two multicomponent stoppers.After threading DEP5 rings with linear guests(G1-G4)which contain two benzaldehyde units,the base catalyzed three-component reaction of dimedone,malononitrile and benzaldehyde was performed to construct the stoppers and connected the pseudorotaxanes with stoppers to generate 1-4.The structures of[3]rotaxanes and their self-assembly behaviors were characterized by 1 H NMR,13C NMR,NOESY,HR-ESI-MS,DLS and TEM technologies.We hope that pillar[5]arene based[3]rotaxanes may have potential applications in drug delivery systems and molecular devices.

An Environmentally Benign Catalytic Method for Versatile Synthesis of 1,4-Dihydropyridines via Multicomponent Reactions

The synthesis of diverse 1,4-dihydropyridines have been achieved via the multicomponent reactions of aldehydes,enaminones and amines.The reactions have been smoothly performed in water to provide all products with moderate to excellent yields by using lactic acid as a green catalyst.

Sustainable functionalization and modification of materials via multicomponent reactions in water

In materials chemistry,green chemistry has established firm ground providing essential design criteria to develop advanced tools for efficient functionalization and modification of materials.Particularly,the combination of multicomponent reactions in water and aqueous media with materials chemistry unlocks a new sustainable way for constructing multi-functionalized structures with unique features,playing significant roles in the plethora of applications.Multicomponent reactions have received significant consideration from the community of material chemistry because of their great efficiency,simple operations,intrinsic molecular diversity,and an atom and a pot economy.Also,by rational design of multicomponent reactions in water and aqueous media,the performance of some multicomponent reactions could be enhanced by the contributing“natural”form of water-soluble materials,the exclusive solvating features of water,and simple separating and recovering materials.To date,there is no exclusive review to report the sustainable functionalization and modification of materials in water.This critical review highlights the utility of various kinds of multicomponent reactions in water and aqueous media as green methods for functionalization and modification of siliceous,magnetic,and carbonaceous materials,oligosaccharides,polysaccharides,peptides,proteins,and synthetic polymers.The detailed discussion of synthetic procedures,properties,and related applicability of each functionalized/modified material is fully deliberated in this review.

Multicomponent Reactions for Diverse Synthesis of N-Substituted and NH 1,4-Dihydropyridines

The multicomponent reactions of aldehydes,electron deficient alkynes and amines have been successfully per-formed to yield a number of symmetrical 2,6-unsubstituted 1,4-dihydropyridines(1,4-DHPs).This method has been found generally applicable for the synthesis of both N-substituted and N-unsubstituted 1,4-DHPs by employing secondary amine to activate the alkyne component via enaminoester intermediates.The present method runs through an enamine type activation,which is different from the known approach employing AcOH as solvent.

Multifunctional Polymer-Protein Conjugates Generated by Multicomponent Reactions

Recently,multifunctional polymers for protein conjugation have been facilely synthesized through the multicomponent reactions(MCRs).In this mini-review,current progress in the generation of multifuncti onal polymers with protei n-reactive groups via MCRs is summarized.These mult functional polymers react with model therapeutic proteins,forming multifunctional polymer-protein conjugates,which are prototypes of sophisticated theranostic agents and antibacterial vaccine candidates.In comparison with the traditional multi-step synthesis,the preparation of multifunctional polymers for protein conjugation through MCRs is straightforward and convenient.Due to these properties,MCRs have the potential to become a new general strategy to achieve polymer-protein conjugates for biological and medical applications.

Bismuth (III) Triflate Catalyzed Multicomponent Synthesis of 2,4,5-Trisubstituted Imidazoles

Substituted imidazoles are of interest because of their useful biological activities. While several methods have been developed for the synthesis of such compounds, some of the reported methods utilize corrosive or toxic catalysts. We report a bismuth (III) triflate catalyzed multicomponent synthesis of 2,4,5-trisubstituted imidazoles. Bismuth (III) compounds are attractive from a green chemistry perspective because they are remarkably non-toxic and non-corrosive. Multicomponent syntheses save time and generate less waste.

Bismuth (III) Triflate Catalyzed Multicomponent Synthesis of 2,4,5-Trisubstituted Imidazoles

Substituted imidazoles are of interest because of their useful biological activities. While several methods have been developed for the synthesis of such compounds, some of the reported methods utilize corrosive or toxic catalysts. We report a bismuth (III) triflate catalyzed multicomponent synthesis of 2,4,5-trisubstituted imidazoles. Bismuth (III) compounds are attractive from a green chemistry perspective because they are remarkably non-toxic and non-corrosive. Multicomponent syntheses save time and generate less waste.

AN ENGINEERING MODEL FOR MULTICOMPONENT REVERSIBLE REACTION NETWORK

The treatment of a multicomponent reversible reaction network is extremely complicated because largenumber of rate constants must be precisely determined and because the calculation based on these rateconstants is tedious.In order to reduce the degrees of freedom of the process,the authors propose a methodin which the reactor and the separator are regarded as a whole.Based on this approach,an N-componentreversible reaction system can be dealt with as a two—component system.Consequently,a simple and ac-cessible way of the apparent rate determination is suggested.For fiist-order reactions,an explicit,simplifiedexpression has been derived for both lumped and distributed parameter reaction systems.

Three-component Reaction of Aromatic Aldehyde,Malononitrile and Aliphatic Amine Leading to Different Pyridine Derivatives

The three-component reaction of aromatic aldehyde,malononitrile and aliphatic amine in a mixed solvent of methanol and water exhibited very interesting molecular diversity and gave the derivatives of polysubstituted N-methyldihydropyridines,2-dialkylaminopyridines and 2-methoxypyridines as main products according to the structure of aliphatic amines used.

Synthesis of 2,4-Diarylcyclooctenopyridines with One-pot Four-component Reactions

An efficient one-pot four-component reaction has been developed for the synthesis of 2,4-diarylcyclooctenopyridines, in moderate yields. This route is an effective modified two-step synthesis of Krohnke pyridine and involves a four-component tandem reaction of pyridinium bromide with aromatic aldehydes and cyclooctanone in a system of NHaOAc/HOAc under microwave irradiation.

Bismuth (III) Chloride Catalyzed Multicomponent Synthesis of Substituted Hexahydroimidazo[1, 2-<i>a</i>]Pyridines

The synthesis of nitrogen containing heterocycles is of particular interest in the pharmaceutical industry due to the range of biological activities exhibited by such compounds. Their synthesis using multicomponent reactions saves steps and minimizes waste generation. The bismuth (III) chloride multicomponent synthesis of a series of hexahydroimidazo[1, 2-a]pyridines is reported. Bismuth (III) compounds are especially attractive from a green chemistry perspective because they are remarkably nontoxic, non-corrosive and relatively inexpensive. The reported method avoids chromatography and an aqueous waste stream to afford the products in a very mass efficient manner.

Silica supported perchloric acid(HClO_4-SiO_2):A mild,reusable and highly efficient heterogeneous catalyst for the synthesis of amidoalkyl naphthols

An efficient and direct procedure has been developed for the preparation of amidoalkyl naphthols by a one-pot condensation of aryl aldehydes, 2-naphthol and urea or amides, in the presence of HClO4-SiO2 as a heterogeneous catalyst. The reactions were carried out under reflux and solvent-free conditions. The present methodology offers several advantages such as excellent yields, simple procedure, easy work-up and ecofriendly reaction condition. The catalyst is easily prepared, stable, reusable and efficient under the reaction conditions.

Facile Synthesis of Chiral α-Hydroxy Ketones by a Ni-Catalyzed Multicomponent Hydrometallation–CO Insertion–Enantioconvergent Alkylation Cascade

NiH-catalyzed multicomponent reductive hydrofunctionalization of alkenes is an attractive but poorly explored approach to rapidly increasing molecular complexity.In this process,the selective generation of the desired product can be challenging.Herein,we report that a highly chemo-,regio-and enantioselective reductive hydrocarbonylation of alkenes has been achieved using a chloroformate ester as a source of CO.A wide range of structurally diverseα-hydroxy ketones,privileged structural elements in bioactive molecules and useful building blocks,were obtained from such reactions with high enantiomeric purity.

Crystal Structure of 2-Amino-5,10-dioxo-4-aryl-5,10-dihydro-4H-naphtho [2,3-b]pyran-3-carboxylic Acid Ethyl Ester

The title compounds have been synthesized via a three-component reaction and their structures were characterized by IR, ^1H NMR, ^13C NMR and X-ray single-crystal diffraction. The crystal of compound 4a belongs to monoclinic, space group P121/c1 with a = 8.575（3）, b = 9.590（3）, c = 21.431（6）A, β = 91.172（3）°, V = 1762.1（9）A^3, Mr = 393.36, Z = 4, Dc= 1.483 g/cm^3, μ（MoKα） = 0.113 mm^-1, F（000） = 816, the final R = 0.0366 and wR = 0.0941. The crystal of compound 4b is of triclinic, space group P-1 with a = 8.6420（17）, b = 9.761（2）, c = 11.132（2） A, α = 97.51（3）, β = 97.86（3）, γ = 92.85（3）°, V = 920.1（3） A^3, Mr = 393.36, Z = 2, Dc = 1.420 g/cm^3, μ（MoKα） = 0.108 mm^-1, F（000） = 408, the final R = 0.0612 and wR = 0.1781. In each molecular structure, the naphthalene rings and pyran rings are almost coplanar with the latter in an envelope conformation. The rings formed by the N-H…O intramolecular hydrogen bonds are almost planar in these compounds. Their crystal packing is stabilized by intermolecular hydrogen bonds together with C-H…π and π-π stacking interactions.

Apatite phosphate doped by cobalt as hight efficient catalyst of multi-component synthesis of therapeutic spiropyrimidine compound

Spiropyrimidines vanquish a significant situation in the field of heterocyclic chemistry, they are broadly utilized as an antibacterial, an inhibitor of multidrug opposition, or an antiplatelet and antithrombotic drug. Phosphate, the principal Moroccan mineral wealth occupies a vital spot in the economic sector and its valuation is a goal continually looked for. Among the conceivable outcomes of valorization, its utilization in heterogeneous catalysis which thought about an exceptionally encouraging new way. In this context, the focus on the reaction of the synthesis of spiropy-rimidine, catalyzed by natural phosphate (NP) and by fluoroapatite (Fap), are used alone or doped by cobalt. These phosphate catalysts were characterized by XRD, IR and SEM, while the synthesized spiropyrimidine was identified by IR, GC-MS and NMR. The obtained yield with fluorapatite doped by cobalt (Co/Fap), at room temperature in ethanol is very high and shows a high impact performance induced by a synergistic effect compared to that of NP alone.

Synthesis and Crystal Structure of 3-Methyl-10-(4-nitrophenyl)-7,8,10,10a-tetrahydropyrano[4,3-b]chromene-1,9(4aH,6H)-dione

The title compound （C19H15NO6） was synthesized via a three-component reaction and characterized by means of IR and 1H NMR. Its crystal and molecular structures were determined by X-ray diffractometry. It belongs to the monoclinic system, space group P21/c with a = 11.670（3）, b = 12.076（3）, c = 11.613（3）, β = 99.490（4）°, V = 1614.2（7）3, Mr = 353.32, Z = 4, Dc = 1.454 g/cm3, λ = 0.71073, μ = 0.110 mm-1, F（000） = 736, the final R = 0.0503 and wR = 0.1311. A total of 8454 reflections were collected, of which 3497 were independent （Rint = 0.0333） and 2102 were observed with I 2σ（I）.

Synthesis and Crystal Structure of 8-Methyl-7-(3-nitrophenyl)-10-phenyl-10,11-dihydrochro-meno[4,3-b]pyrazolo[4,3-e]pyridin-6-(7H)-one

The title compound（C26H18N4O4） has been synthesized via a three-component reaction and it was characterized by means of IR and 1H NMR.Its crystal and molecular structures were determined by X-ray diffractometry.It belongs to the triclinic system,space group P1 with a = 7.7288（15）,b = 11.168（2）,c = 12.645（3） ,α = 107.02（3）,β = 90.85（3）,γ = 101.93（3）°,V = 1017.9（3） 3,Mr = 450.44,Z = 2,Dc = 1.470 g/cm3,λ = 1.54178 ,μ = 0.836 mm-1,F（000） = 468,the final R = 0.0488 and wR = 0.1180.A total of 11903 reflections were collected,of which 3642 were independent（Rint = 0.0377） and 3025 were observed with I 2σ（I）.

Synthesis and Molecular Structure of 5-Amino-7-(benzo[d][1,3]dioxol-5-yl)-2,3-dihydro-1H-indene-4,6-dicarbonitrile

The title compound, C18H13N3O2, has been synthesized for the first time by the multicomponent reaction of cyclopentanone, malononitrile and benzo[d][1,3]dioxole-5-carbalde-hyde in the presence of triethylamine. The structure has been determined by NMR, MS and single-crystal X-ray diffraction. The crystal belongs to the triclinic system, space group P with a = 10.476（5）, b = 10.973（5）, c = 13.825（5）, α = 87.244（5）, β = 73.296（5）, γ = 82.097（5）°, C18H13N3O2, Mr = 303.31, V = 1507.6（11） 3, Z = 4, Dc = 1.336 g/cm3, F（000） = 632, μ = 0.090 mm-1, R = 0.0431 and wR = 0.1051. There exist intermolecular N-H…N hydrogen bonds in the title compound.