Condensation Cascade Research Articles

Domino synthesis of novel 3-alkenyl benzofuran derivatives- base mediated condensation cascade reaction

A one-pot and efficient construction method for pharmacologically relevant molecular structures, 3-alkenyl benzofuran with excellent yields, has been developed via a green method. Products are obtained from 2-hydroxy chalcone with Phenacyl bromide, Bromo acetonitrile, and/or Ethyl-2-bromo acetate via an alkylation followed by a condensation reaction. This methodology features faster condensation over Michael addition, transition metal, catalyst-free medium, and an environmentally friendly synthetic route toward the synthesis of substituted 3-alkenyl benzofurans.

Construction of highly-stable covalent organic framework with combined enol-imine and keto-enamine linkages.

A novel covalent organic framework (COF) (Tp-BI-COF) with combined ketimine-type enol-imine and keto-enamine linkages was prepared through a cascade of ketimine condensation followed by aldimine condensation and characterized by XRD, solid state 13C NMR, IR, TGA and BET. Tp-BI-COF showed high stability toward acid, organic solvent, and boiling water. The 2D COF exhibited photochromic properties after being irradiated with a xenon lamp. The stable COF, with aligned one-dimensional nanochannels, provided nitrogen sites on pore walls, which confine and stabilize the H3PO4 in the channel via hydrogen-bonding interactions. After loading with H3PO4, the material showed excellent anhydrous proton conductivity.

Chemoselective and diastereoselective construction of 4-alkylidene-tetrahydroquinoline via a redox-neutral vinylogous cascade [1,7]-hydride transfer/6-endo-trig cyclization strategy.

Herein, we disclose a chemoselective and diastereoselective synthesis of the medicinally significant 4-alkylidene-tetrahydroquinoline via a redox-neutral vinylogous cascade condensation/[1,7]-hydride transfer/6-endo-trig cyclization strategy, which features a novel product skeleton, high chemoselectivity and diastereoselectivity, facile introduction of 4-alkylidenyl motifs, employment of α,β,γ,δ-unsaturated dicyanoalkenes as novel hydride acceptors, and green and metal-free conditions with water as the only by-product. Additionally, the versatility of α,α-dicyanoalkenes has been fully exploited as hydride acceptors and γ-exclusive nucleophiles consecutively for accessing novel heterocyclic skeletons.

Efficient Construction of Tetrahydroquinazolines via HFIP‐Promoted [1,5]‐Hydride Transfer/6‐Endo‐Trig Cyclization

AbstractDescribed herein is a practical and scalable protocol for the syntheses of pharmaceutically significant tetrahydroquinazolines in good yields via cascade condensation/[1,5]‐hydride transfer/6‐endo‐trig cyclization, which features mild, salt‐free & additive‐free conditions; broad substrate scope; and chemoselective N,N‐dialkylation of primary amine with two diverse alkyl groups in one step.

Bismuth(III)-catalyzed cascade condensation of alkynyl alcohols with terminal alkynes: A facile construction of propargyl cyclic ethers

Herein, we report a Bi(OTf)3-catalyzed cascade condensation between alkynols (particularly pent-4-yn-1-ols and hex-5-yn-1-ols) and terminal alkynes (aryl alkynes) to facile access to diverse propargyl cyclic ethers (2‑alkynyl tetrahydrofurans and 2‑alkynyl tetrahydropyrans). This simple and efficient cascade transformation proceeds through initial intramolecular hydroalkoxylation of alkynols to give corresponding cyclic enol ethers (via exo-dig or endo-dig mode of ring-closure) followed by hydroalkynylation. Cost-effective, naturally abundant, green Lewis acid catalysis, ambient reaction conditions, short reaction times, good substrate scope, and high yields are salient features of this strategy.

Design and characterization of an urea-bridged PMO supporting Cu(II) nanoparticles as highly efficient heterogeneous catalyst for synthesis of tetrazole derivatives

In this work, a new periodic mesoporous organosilica with urea-bridges produced by the reaction of (3-aminopropyl)triethoxysilane and toluene-2,4-diisocyanate (APS-TDU-PMO) is introduced. The obtained APS-TDU-PMO was found to be an appropriate support for loading of Cu(II) nanoparticles to afford supramolecular Cu@APS-TDU-PMO nanocomposite. Uniformity and mesoporosity of both synthesized nanomaterials including APS-TDU-PMO and Cu@APS-TDU-PMO were proved by different spectroscopic, microscopic or analytical techniques including FTIR, EDX, XRD, FESEM, TEM, BET, TGA and DTA. Furthermore, the prepared Cu@APS-TDU-PMO nanomaterial was also used, as a heterogeneous and recyclable catalyst, for the synthesis of tetrazole derivatives through cascade condensation, concerted cycloaddition and tautomerization reactions. Indeed, the main advantages of this Cu@APS-TDU-PMO is its simple preparation and high catalytic activity as well as proper surface area which enable it to work under solvent-free conditions. Also, the introduced Cu@APS-TDU-PMO heterogeneous catalyst showed good stability and reusability for six consecutive runs to address more green chemistry principles.

CsCu2I3 Nanoparticles Incorporated within a Mesoporous Metal-Organic Porphyrin Framework as a Catalyst for One-Pot Click Cycloaddition and Oxidation/Knoevenagel Tandem Reaction.

Metal-organic frameworks (MOFs) and metal halide perovskites are currently under much investigation due to their unique properties and applications. Herein, an innovative strategy has been developed combining an iron-porphyrin MOF, PCN-222(Fe), and an in situ-grown CsCu2I3 nontoxic lead-free halide perovskite based on an earth-abundant metal that becomes incorporated within the MOF channels [CsCu2I3@PCN-222(Fe)]. Encapsulation was designed to decrease and control the particle size and increase the stability of CsCu2I3. The hybrid materials were characterized by various techniques including FE-SEM, elemental mapping and line scanning EDX, TEM, PXRD, UV-Vis DRS, BET surface area, XPS, and photoemission measurements. Hybrid CsCu2I3@PCN-222(Fe) materials were examined as heterogeneous multifunctional (photo)catalysts for copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) and one-pot selective photo-oxidation/Knoevenagel condensation cascade reaction. Interestingly, CsCu2I3@PCN-222(Fe) outperforms not only its individual components CsCu2I3 and PCN-222(Fe) but also other reported (photo)catalysts for these transformations. This is attributed to cooperation and synergistic effects of the PCN-222(Fe) host and CsCu2I3 nanocrystals. To understand the catalytic and photocatalytic mechanisms, control and inhibition experiments, electron paramagnetic resonance (EPR) measurements, and time-resolved phosphorescence were performed, revealing the main role of active species of Cu(I) in the click reaction and the superoxide ion (O2•-) and singlet oxygen (1O2) in the photocatalytic reaction.

Synthesis of (E)-2-(1H-tetrazole-5-yl)-3-phenylacrylenenitrile derivatives catalyzed by new ZnO nanoparticles embedded in a thermally stable magnetic periodic mesoporous organosilica under green conditions

ZnO nanoparticles embedded in a magnetic isocyanurate-based periodic mesoporous organosilica (Fe3O4@PMO–ICS–ZnO) were prepared through a modified environmentally-benign procedure for the first time and properly characterized by appropriate spectroscopic and analytical methods or techniques used for mesoporous materials. The new thermally stable Fe3O4@PMO–ICS–ZnO nanomaterial with proper active sites and surface area as well as uniform particle size was investigated for the synthesis of medicinally important tetrazole derivatives through cascade condensation and concerted 1,3-cycloaddition reactions as a representative of the Click Chemistry concept. The desired 5-substituted-1H-tetrazole derivatives were smoothly prepared in high to quantitative yields and good purity in EtOH under reflux conditions. Low catalyst loading, short reaction time and the use of green solvents such as EtOH and water instead of carcinogenic DMF as well as easy separation and recyclability of the catalyst for at least five consecutive runs without significant loss of its activity are notable advantages of this new protocol compared to other recent introduced procedures.

Photochromic Lactone-Fused Phenanthropyrans with Broad Absorption and Rapid Color Change

Abstract New lactone-fused phenanthrol[1,2-b]pyrans were successfully synthesized in 4 steps from naphthaldehydes using, as the key step, the acid-catalyzed cascade condensation of methyl 1-hydroxyphenanthrene-3-carboxylates with diarylbut-2-yne-1,4-diols, which forms the pyran and lactone rings. After exposing CHCl3 solutions of these polyaromatic compounds to UV or sunlight, at room temperature, the color changes vividly from slightly yellow to deep red/brown in a matter of seconds, and fades spontaneously, in the dark, within 1.5 min.

Thermodynamic Study of Solar-Assisted Hybrid Cooling Systems with Consideration of Duration in Heat-Driven Processes

Solar-assisted hybrid cooling systems are promising for the energy saving of refrigeration systems. In most cases, the solar thermal gain is only able to power the heat-driven process of facilities during part of the working period. Therefore, the reduction of compressor power strongly depends upon the duration of heat-driven processes, which has not been addressed properly. Motivated by such a knowledge gap, the thermodynamic understanding of solar-assisted hybrid cooling systems is deepened through considering the duration in heat-driven processes. Three absorption–compression-integrated cooling cycles were taken as examples. It was found that optimal parameters, e.g., inter-stage pressure and temperature, corresponding to various performance indicators tend to be identical, as the duration of heat-driven processes is taken into account. Furthermore, the optimal parameter for different working conditions was obtained. The dimensionless optimal intermediate temperature of layout with the cascade condensation process varies slightly, e.g., 4%, for different conditions. Moreover, the fall of compressor power in the entire working period was nearly independent upon the intermediate temperature. The paper is favorable for the efficient design and operation of solar-assisted hybrid cooling systems.

Asymmetric Total Synthesis of Shizukaol J, Trichloranoid C and Trishizukaol A

AbstractThe asymmetric total synthesis of three lindenane sesquiterpenoid oligomers, shizukaol J, trichloranoid C and trishizukaol A, has been accomplished concisely in 15, 16 and 18 longest linear steps, respectively. The expeditious construction of molecular architectures was facilitated by Nelson's catalytic asymmetric ketene–aldehyde cycloaddition, a sequence of allylic alkylation/reduction/acidic cyclization to forge a lactone, and a double aldol condensation cascade to construct the 5/6 bicyclic system. Diastereoselective nucleophilic substitution promoted by a phase transfer catalyst constructed the C11 quaternary stereogenic center, thus prompting synthetic efficacy toward shizukaol J. The synthesis of trichloranoid C and trishizukaol A was achieved after a cascade involving furanyl diene formation and a Diels–Alder reaction, as well as a one‐pot sequence involving furan oxidation and global deprotection. Furthermore, our biological evaluation revealed that two compounds exhibited unexpected toxicity against tumor cell lines.

Asymmetric Total Synthesis of Shizukaol J, Trichloranoid C and Trishizukaol A.

The asymmetric total synthesis of three lindenane sesquiterpenoid oligomers, shizukaol J, trichloranoid C and trishizukaol A, has been accomplished concisely in 15, 16 and 18 longest linear steps, respectively. The expeditious construction of molecular architectures was facilitated by Nelson's catalytic asymmetric ketene-aldehyde cycloaddition, a sequence of allylic alkylation/reduction/acidic cyclization to forge a lactone, and a double aldol condensation cascade to construct the 5/6 bicyclic system. Diastereoselective nucleophilic substitution promoted by a phase transfer catalyst constructed the C11 quaternary stereogenic center, thus prompting synthetic efficacy toward shizukaol J. The synthesis of trichloranoid C and trishizukaol A was achieved after a cascade involving furanyl diene formation and a Diels-Alder reaction, as well as a one-pot sequence involving furan oxidation and global deprotection. Furthermore, our biological evaluation revealed that two compounds exhibited unexpected toxicity against tumor cell lines.

Encapsulating Electron-Rich Pd NPs with Lewis Acidic MOF: Reconciling the Electron-Preference Conflict of the Catalyst for Cascade Condensation via Nitro Reduction.

Cascade reactions take advantage of step-saving and facile operation for obtaining chemicals. Herein, catalytic hydrogenation of nitroarene coupled condensation with β-diketone to afford β-ketoenamines is achieved by an integrated nanocatalyst, Pd-e@UiO-66. The catalyst has the structure of an acid-rich metal-organic framework (MOF), UiO-66-encapsulated electron-rich Pd nanoparticles, and it reconciles the electron-effect contradiction of cascade catalytic reactions: catalytic hydrogenation requires an electron-rich catalyst, while condensation requires electron-deficient Lewis acid sites. The catalyst showed good activity, high chemoselectivity, and universal applicability for the synthesis of β-ketoenamines using nitroarenes. More than 30 β-ketoenamines have been successfully prepared with up to 99% yield via the methodology of relay catalysis. The catalyst exhibited excellent stability to maintain its catalytic performance for more than five cycles. Furthermore, we conducted an in-depth exploration of the reaction mechanism with theoretical calculations.

Copper‐Catalyzed Decarbonylative Cyclization of Isatins and Trifluoroacetimidohydrazides for the Synthesis of 2‐(5‐Trifluoromethyl‐1,2,4‐triazol‐3‐yl)anilines

AbstractA copper‐catalyzed intramolecular decarbonylative cyclization reaction of isatins and trifluoroacetimidohydrazides for the synthesis of 2‐(5‐trifluoromethyl‐1,2,4‐triazol‐3‐yl)aniline derivatives has been developed. This transformation proceeds through a cascade condensation, hydrolysis, decarboxylation, and intramolecular C−N bond formation sequence. The obtained 1,2,4‐triazole products bearing a free amino group can be readily converted into other useful compounds.magnified image

Tuning the Cyclopropane Ring-Opening Reaction over Electronic Bias by Fusion to a Pre-Aromatic Ring: TfOH-Promoted Aromatization of Dibenzonorcaradienes to Dibenzo[f,h]isocoumarins.

Fusion of the cyclopropane ring bearing two vicinal acceptors to the pre-aromatic dihydrophenanthrene ring, which is constructed by the Pd-catalyzed cross-coupling between the vicinal aromatic rings, is found to effectively direct the cleavage of the electronically unfavored cyclopropane bond between the vicinal acceptors. Consequently, a modular method for the rapid synthesis of dibenzo[f,h]isocoumarins from methyl ketones, aryl aldehydes, and α-keto esters via a reaction cascade of aldol condensation, Kukhtin-Ramirez cyclopropanation, Pd-catalyzed direct arylation, and acid-promoted aromatization has been realized.

Sulphonated graphene oxide catalyzed continuous flow synthesis of pyrazolo pyrimidinones, sildenafil and other PDE-5 inhibitors.

Sulphonated graphene oxide was used for cascade condensation and cyclization reactions towards accessing substituted pyrazolo pyrimidinones. Further, sulphonation and amination reactions were integrated through continuous flow chemistry to access PDE-5 inhibitors. Herein, we report a simple continuous synthetic platform that reduce tedious manual operations and accelerate the synthesis of several potent inhibitors of phosphodiesterase type-5. The developed platform enabled us to perform one-flow multi-step, multi-operational process to synthesize the PDE-5 inhibitors such as sildenafil and its analogues in 32.3 min of the reaction time, with minimal human intervention and single solvent.

Porous liquids unlock a new class of spatially orthogonal catalyst

Catalytic cascades epitomize green chemistry principles, enabling ultra-efficient transformations while minimizing unit operations. In the last Chem issue, Chen et al. demonstrate a new strategy to combine antagonistic catalytic functions by incorporating an acidic zeolite in the pores of a sterically hindered, basic ionic liquid to drive a deacetalization-Knoevenagel condensation cascade. Catalytic cascades epitomize green chemistry principles, enabling ultra-efficient transformations while minimizing unit operations. In the last Chem issue, Chen et al. demonstrate a new strategy to combine antagonistic catalytic functions by incorporating an acidic zeolite in the pores of a sterically hindered, basic ionic liquid to drive a deacetalization-Knoevenagel condensation cascade. A bifunctional zeolitic porous liquid with incompatible Lewis pairs for antagonistic cascade catalysisChen et al.ChemSeptember 22, 2021In BriefUnique bifunctional type III porous-liquid (PL)-based systems were facilely fabricated via assembly of zeolite nanosheets with ionic liquids. Rational structural design afforded PLs featured by high zeolite concentration, stable dispersion after 2 years, abundant cavity distribution, and involvement of antagonistic groups (acid and base sites) in separated and active form via steric hindrance control and electronic repulsion regulation. These unique properties worked cooperatively to fulfill the cascade deacetalization-Knoevenagel/Aldol condensation in one pot with catalytic efficiency outperforming the traditional systems. Full-Text PDF

Experimental comparison between R134a/R744 and R438A/R744 (drop‐in) cascade refrigeration systems based on energy consumption and greenhouse gases emissions

AbstractThis experimental study evaluates the energy performance and climatic changes of a cascade cooling system operating with the R134a/R744 pairs (cooling capacity of 4.5‐6 kW) and R438A/R744. In both cases, the low‐temperature refrigerant, R744, operated under subcritical conditions. The experimental apparatus basically consists of two vapor‐compression cycles coupled by a plate cascade condenser. Two operational variables, from R744 cycle, were controlled: the degree‐of‐superheat and the compressor frequency. The experiment was initially assembled to pair R134a/R744. Subsequently, the R134a refrigerant charge in the high‐temperature cycle was replaced by R438A, on a drop‐in basis. The two systems, R134a/R744 and R438A/R744, were compared for similar cooling capacities and cold chamber air temperatures. Results showed that the energy consumption of the high‐temperature compressor, operating with R438A, was higher than R134a for all tests. As a result, the COP values for R438A/R744 were 30% lower than those for R134a/R744. The greenhouse gases emissions of the two systems were evaluated using the total equivalent warming impact factor, TEWI, whose value for the R438A/R744 pair was approximately 29.5% higher, compared with R134a/R744. Since R438A was originally designed to substitute R22, a few comparative tests were carried out with the latter, always with R744 as the low‐temperature cycle working fluid.

Differences of energy saving quantities for absorption‐compression hybrid cooling systems with cascade condenser and cascade subcooler

Absorption-compression hybrid cooling systems with cascade condenser and cascade subcooler are able to effectively reduce compressor power by low-grade heat. However, differences of both energy saving quantities still cannot be explained exactly through various types of coefficient of performance (COP) indicators, which is adverse for the decision-making of appropriate layouts. In this regard, we attempt to illustrate the above-mentioned issue from the new standpoint, that is, by decoupling processes and considering the limitation of thermodynamic cycles and refrigerant characteristics. It is found that there is the critical heat quantity corresponding to the order transition of energy saving for both layouts at first. Subsequently, critical heat quantities for different working conditions are obtained and analyzed. Moreover, expressions regarding critical heat quantities for five refrigerants are fitted by the neural network. It is displayed that the average difference between the critical heat quantity for R1234yf, R1234ze(E), R290 and R32 and that for ammonia is 7.89%, 4.08%, 4.78%, and 4%, respectively. The paper is helpful for decision-making of absorption-compression hybrid cooling systems with cascade condenser and cascade subcooler to enhance the amount of energy saving for certain quantities of low-grade heat.

In Situ Growth of ZIF-8 Nanocrystals on the Pore Walls of 3D Ordered Macroporous TiO2 for a One-Pot Cascade Reaction

It is wise to mimic a bioinspired system to design a nanoreactor as a catalyst containing multiple components for a cascade reaction. Here, we report the uniform growth of well-dispersed nano-scale ZIF-8 crystals on the pore walls of 3DOM TiO2 via the TEA-assisted crystallization process. The UV-vis spectra indicate that the ZIF-8 photosensitizer can extend the visible-light absorption of 3DOM TiO2. The obtained nanoreactor can efficiently catalyze the one-pot aromatic alcohol oxidization and Knoevenagel condensation cascade reaction for larger molecules. This work offers an important strategy for preparing semiconductor–MOF multifunctional composites with a spatially separated compartmentation for the cascade reaction.