Condensation Of Aldehydes Research Articles

Metal‐Free Oxidative Condensation of Catechols, Aldehydes and NH4OAc towards Benzoxazoles

AbstractBenzoxazoles extensively exist in biologically active compounds, natural products, pharmaceuticals and functional materials. Thus, facile and green synthesis of such valuable compounds from easily available substrates will make a contribution to drug, material, and fine chemistry. A method for the synthesis of benzoxazoles from catechols, aldehydes and ammonium acetate is developed using NaIO4 as oxidant under metal‐ and additive‐free conditions. A broad range of benzoxazoles including some fluorescent whitening agents, JTP‐426467 and tafamidis analogues are synthesized in 56–95% yields with outstanding functional group tolerance. Mechanistic investigations suggest that an interesting o‐iminocyclohexa‐diene alcohol intermediate is involved in the reaction. These salient features of the protocol make it an alternative for the synthesis of benzoxazoles.magnified image

Ball-Milling: A Productive, Economical, and Widely Applicable Method for Condensation of Biomass-Derived Aldehydes and Ketones at Mild Temperatures

Ball-Milling: A Productive, Economical, and Widely Applicable Method for Condensation of Biomass-Derived Aldehydes and Ketones at Mild Temperatures

Bis-Imino-Acenaphthenequinone Based Covalent Organic Framework for Lithium-Ion Battery Applications

Covalent organic frameworks (COF) are crystalline and porous, 2 or 3-dimensional structures. The precise structure tunability and high porosity make these materials interesting for various applications like gas adsorption, proton conduction, energy storage etc. Further, COFs synthesized from π-conjugated systems with short interlayer distances could exhibit electron conduction properties[1]. This property makes these materials promising candidates for secondary batteries as well. In this regard, there were reports on imine functional COFs synthesized by condensation of aldehyde and amine[2]. These COFs exhibit uniform porosity and a stable cycling performance as anodes in lithium ion and Sodium ion batteries. Further, the high porosity, the precise structure tunability and possibility of various functional groups presents a unique opportunity to produce heteroatom doped, highly porous and semi crystalline carbon upon pyrolysis. Owing to the drawbacks of graphite in fast charge and discharge, much effort is being directed towards synthesizing heteroatom doped carbonaceous materials among which, N-doped carbon shows promising results. In this regard, various strategies like pyrolysis of carbonaceous material with doping agents like urea, melamine etc., is extensively studied[3,4] However, these N-doped carbon materials suffer with lack of good conductivity and lack of precise control over the amount of heteroatom doping. In this regard, we present the synthesis of novel bis imino acenaphthoquinone (BIAN)-melamine based covalent organic framework and its bifold applications as 1) an organic alternative to graphite anode in lithium-ion battery and 2) a precursor material for synthesis of N-doped carbon with good rate capability.BIAN-melamine covalent organic framework (BM-COF) was synthesized by simple poly condensation method. Further, BM-COF was pyrolyzed at 800 ℃ to obtain N-doped carbon (Py-BM COF). Both the materials BM-COF and Py-BM-COF were systematically characterized and used to prepare anodes for Li ion batteries. The electrodes were coated using active material (BM-COF/Py-BM-COF), PVDF (binder), and acetylene black (conductive additive) in the weight ratios of 70:15:15 in case of BM COF as active material and 80:10:10 for Py-BM-COF as active material. Coin cells of 2025 type were fabricated using lithium as counter/reference electrode, 1 M LiPF6 in 1:1 EC: DEC as electrolyte, and the coated electrodes as anodes. Cyclic voltammetry was performed at various scan rates in a potential window of 0.01 V to 3.00 V for BM-COF anodes and 0.01 to 2.10 V for Py-BM-COF anodes. Galvanostatic charge discharge studies were carried out in the same potential windows at various current densities and the cycle life of the material was evaluated.The formation of imine bond in COF was confirmed by FT-IR and X-ray photoelectron spectroscopies. The pore size and surface area were evaluated by nitrogen adsorption-desorption studies. The surface area was found to be 31.6 m2/g and the pore size was found to be 1.7 nm. The XRD spectrum showed sharp peak at 13º corresponding to a d-spacing of 0.68 nm indicating high crystallinity and a stacked structure due to π interactions. The nitrogen content in Py-BM COF was found to be 13 atomic percentage using EDX. The XPS spectra showed the presence of pyridinic, pyrrolic and quaternary nitrogen. TEM micrographs showed macro pores. Li-ion battery with BM-COF anode material showed a reversible capacity of 317 mAh/g at 50 mA/g current density which was higher than that of graphite at 50 mA/g current density and the Py-BM-COF anode showed a capacity of 260 mAh/g at 1 A/g current with a capacity retention over 85% after 500 cycles (Figure-1). We report the synthesis and bifold applications of BIAN-melamine COF. The reported organic material and the N-doped carbon exhibits good electrochemical performance. These results present the material as interesting alternative to graphite anodic material.

Synthesis, Characterization and Evaluation of some newer Pyrimidine derivatives as Anti-inflammatory Agents

Pyrimidine is an important baseone of the base formed by hydrolysis of nucleosides. It is an interesting molecule in the medicinal chemistry because of its diversified biological activities. Alloxan which is an oxidation product of Uric acid is also a pyrimidine derivative of interest to a medicinal chemist. Several pyrimidines are reported as antimicrobial, analegesic, anti-inflammatory, antibacterial, and antiparasitic agents. Pyrimidine scaffold is considered as an interesting one due to its various pharmacological properties. In this scheme, an attempt is made to carry out synthesis of some new pyrimidine derivatives. The Starting material Chalcone is synthesized by condensation of various aromatic aldehyde and aromatic ketone. Chalcone is then treated with thiourea and KOH in presence of ethanol to yield pyrimidine derivatives. Then those pyrimidine derivatives were subjected to alkylation and acetylation. The synthesized compounds were characterized and confirmed by IR and 1HNMR spectroscopy and then evaluated for their anti-inflammatory activity. The anti-inflammatory activity of newly synthesized pyrimidine derivatives were carried out by the carrageenan induced rat hind paw edema method by taking Diclofenac sodium as standard.

Nano-SiO2/DBN: an efficacious and reusable catalyst for one-pot synthesis of tetrahydrobenzo[b]pyran derivatives

BackgroundThe nano-sized particles enhance the exposed surface area of the active part of the catalyst, thereby increasing the contact between precursors and catalyst considerably. In this study, nano-SiO2/1,5-diazabicyclo[4.3.0]non-5-en was synthesized, characterized and used as a heterogeneous nanocatalyst for the synthesis of tetrahydrobenzo[b]pyran derivatives. Fourier Transform Infrared Spectroscopy, Field Emission Scanning Electron Microscopy, Brunauer–Emmett–Teller plot, Energy Dispersive X-ray Spectroscopy and Thermo Gravimetric Analysis were used to discern nano-SiO2/1,5-diazabicyclo[4.3.0]non-5-en.ResultsTetrahydrobenzo[b]pyrans were synthesized by using nano-SiO2/1,5-diazabicyclo[4.3.0]non-5-en via one-pot three-component condensation of malononitrile, aldehydes and dimedone in H2O/EtOH at 60 °C. The results indicate that tetrahydrobenzo[b]pyrans were synthesized in good to high yields and short reaction times.ConclusionsThe fundamental privileges of this method are short reaction time, plain procedure, recyclability of catalyst and high yields of products.

Three-Component Condensation of Pyridinium Ylides, β-Ketonitriles, and Aldehydes with Divergent Regioselectivity: Synthesis of 4,5-Dihydrofuran-3- and 2H-Pyran-5-carbonitriles.

A library of trans-4,5-dihydrofuran-3-carbonitriles was synthesized in a diastereoselective manner in good yields by the three-component reaction of β-ketonitriles, carbonyl- and semistabilized pyridinium ylide precursors, and aldehydes in the presence of piperidine. This one-pot transformation generates two C-C and one C-O bond and proceeds through a cascade Knoevenagel condensation, a Michael addition, and intramolecular SN2 cyclization. Formation of cyclopropanecarbonitrile derivatives, which in some cases were obtained as major products, was found to be a competing reaction. The use of arylglyoxals changes regioselectivity and leads to 2-hydroxy-2H-pyran-5-carbonitriles.

Phosphinotripeptidic Inhibitors of Leucylaminopeptidases.

Phosphinate pseudopeptide are analogs of peptides containing phosphinate moiety in a place of the amide bond. Due to this, the organophosphorus fragment resembles the tetrahedral transition state of the amide bond hydrolysis. Additionally, it is also capable of coordinating metal ions, for example, zinc or magnesium ions. These two properties of phosphinate pseudopeptides make them an ideal candidate for metal-related protease inhibitors. This research investigates the influence of additional residue in the P2 position on the inhibitory properties of phosphinopeptides. The synthetic strategy is proposed, based on retrosynthetic analysis. The N-C-P bond formation in the desired compounds is conveniently available from the three-component condensation of appropriate amino components, aldehydes, and hypophosphorous acid. One of the crucial synthetic steps is the careful selection of the protecting groups for all the functionals. Determination of the inhibitor activity of the obtained compounds has been done using UV-Vis spectroscopy and standard substrate L-Leu-p-nitroanilide toward the enzymes isolated from the porcine kidney (SsLAP, Sus scrofa Leucine aminopeptidase) and barley seeds (HvLAP, Hordeum vulgare Leucine aminopeptidase). An efficient procedure for the preparation of phosphinotripeptides has been performed. Activity test shown that introduction of additional residue into P2 position obtains the micromolar range inhibitors of SsLAP and HvLAP. Moreover, careful selection of the residue in the P2 position should improve its selectivity toward mammalian and plant leucyl aminopeptidases.

One-pot three-component synthesis of a new series of tetrahydrobenzofuran-chromone conjugates

An efficient one-pot three-component protocol for the synthesis of novel tetrahydrobenzofuran-chromone conjugates using 3-formylchromones and 1,3-cyclohexandiones in the presence of a variety of alkyl or aryl isocyanides was developed. The reaction sequence consists of an initial Knoevenagel condensation of aromatic aldehydes with 1,3-cyclohexandione derivatives, followed by a [4 + 1] cycloaddition of with isocyanides, and then imine-enamine tautomerization to afford the products.

Fused chromeno and quinolino[1,8]naphthyridines: Synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents

The synthesis of 1,8-naphthyridine derivatives fused with other heterocycles, such as chromenes and quinolines, as well as their behaviour as topoisomerase I inhibitors is studied. The preparation is carried out through a direct and simple process as an intramolecular [4 + 2] cycloaddition reaction between functionalized aldimines, obtained by the condensation of 2-aminopyridine and unsaturated aldehydes, and olefins. In particular, while no clear inhibitory activity is observed for chromeno[4,3-b][1,8]naphthyridine fused heterocycles, a very different result is observed for quinolino[4,3-b][1,8]naphthyridine derivatives. Experimental assays indicated that quinolino[4,3-b][1,8]naphthyridines inhibited the topoisomerase I enzymatic reaction behaving like a poison, as occurs with the natural TopI inhibitor, camptothecin. Furthermore, the cytotoxic effect on cell lines derived from human lung adenocarcinoma (A549), human ovarian carcinoma (SKOV3), and on non-cancerous lung fibroblasts cell line (MRC5) was also screened.

Design, synthesis, and catalytic evaluation of aluminum‐incorporated magnetic core–shell mesoporous microsphere catalyst NiFe2O4@SiO2@Al‐MS for the synthesis of functionalized indenopyrazolones

A core–shell structured magnetic metal‐mesoporous microsphere materials NiFe2O4@SiO2@Al‐MS in which magnetic particles of NiFe2O4 are core and ordered mesoporous silica are shell, incorporated with aluminum to modify acid‐catalyzed reactions. The catalyst was synthesized by Pluronic P123 as a first surfactant and a small quantity of cetrimonium bromide as a template for assistant in acidic medium to create a porous layer. The structural characterization of the catalyst was assessed by Fourier transform infrared (FT‐IR), scanning electron microscopy (SEM), X‐ray diffraction (XRD), energy‐dispersive X‐ray (EDX), vibrating‐sample magnetometer (VSM), and Brunauer–Emmett–Teller (BET) analyses. The catalyst demonstrated considerable magnetic properties, a unique mesoporous structure with great surface area (370.36 m2 g−1), high‐value recovery, and reusability. The catalyst performance was evaluated for the synthesis of indenopyrazolones via the condensation of ninhydrin, phenylhydrazine, and various aldehydes. The mild conditions for the synthesis, easy workup, and short reaction time are the considerable benefits of the reaction in the presence of Nife2O4@SiO2@Al‐MS as a catalyst.

A Novel Fluorescent 1,10‐Phenanthroline‐2,9‐dicarboxaldehyde‐ 2,5‐diaminoterephthalicacid‐Schiff Base Polymer for Cu2+ Detection

AbstractA novel fluorescent Schiff base polymer (PTDA‐DATA‐SBP) is synthesized by amine aldehyde condensation reaction between 1,10‐phenanthroline‐2,9‐dicarboxaldehyde (PTDA) and 2,5‐diaminoterephthalicacid (DATA) as a selective fluorescent probe for Cu2+ detection. The as‐prepared PTDA‐DATA‐SBP displayed irregular nanospheres with a diameter of about 5 μm. Under the excitation of 338 nm, the PTDA‐DATA‐SBP had a characteristic emission peak at 565 nm. The PTDA groups in PTDA‐DATA‐SBP could coordinate with Cu2+ under help of carboxyl groups of DATA. Owing to the photoinduced electron transfer mechanism, the fluorescence of PTDA‐DATA‐SBP was weakened after the addition of Cu2+ in the presence of common ions. Hence, the PTDA‐DATA‐SBP was exploited as a fluorescent nanosensor for sensing Cu2+. The PTDA‐DATA‐SBP showed high selectivity and fast response towards Cu2+ even in presence of other relevant metal ions. The PTDA‐DATA‐SBP fluorescent sensor has a good linear range of 3.45 nM–8.00 μM, and the limit of detection was as low as 1.15 nM. The proposed PTDA‐DATA‐SBP sensor could also detect Cu2+ in actual samples. The work not only provided a good fluorescent probe for Cu2+ detection but also provided a feasible strategy to construct highly selective fluorescent probes.

Biocatalytic approaches for the synthesis of optically pure vic-halohydrins.

Enantiopure vicinal halohydrins (vic-halohydrins) are highly valuable building blocks for the synthesis of many different natural products and pharmaceuticals, and biocatalytic methods for their synthesis have received considerable interest. This review emphasizes the application of biocatalytic approaches as an efficient alternative or complement to conventional chemical reactions, with a special focus on the asymmetric reductions catalyzed by ketoreductases, kinetic resolution catalyzed using lipases or esterases, stereoselective biotransformation catalyzed by halohydrin dehalogenases, asymmetric hydroxylation catalyzed by cytochrome P450 monooxygenases, asymmetric dehalogenation catalyzed by haloalkane dehalogenases, and aldehyde condensation catalyzed by aldolases. Although many chiral vic-halohydrins have been successfully synthesized using wild-type biocatalysts, their enantioselectivity is often too low for enantiopure synthesis. To overcome these limitations, catalytic properties of wild-type enzymes have been improved by rational and semi-rational protein design or directed evolution. This review briefly introduces the research status in this field, highlighting aspects of basic academic research in the biocatalytic synthesis of optically active vic-halohydrins by employing such unconventional approaches. KEY POINTS: • Outlines the enzymatic strategies for the production of enantiopure vic-halohydrins • Highlights recent advances in biocatalytic production of enantiopure vic-halohydrins • Provide guidance for efficient preparation of enantiopure vic-halohydrins.

A facile and efficient synthesis of tetrahydrobenzo[b]pyrans and dihydropyrano[4,3-b]pyrans derivatives using phosphate fertilizers MAP, DAP, and TSP as heterogeneous catalysts

A simple and efficient one-pot synthesis of tetrahydrobenzo[b]pyrans and dihydropyrano[4,3-b]pyrans derivatives was described. These reactions were realized through a three-component condensation of aromatic aldehyde, malononitrile, and 5,5-dimethyl-1,3-cyclohexanedione or 4-hydroxy-6-methylpyran-2-one using phosphate fertilizers monoammonium phosphate, NH4(H2PO4)2, (MAP), diammonium phosphate, (NH4)2(HPO4), (DAP), and triple superphosphate, Ca(H2PO4)2.H2O, (TSP) as heterogeneous catalysts. Under optimal reaction conditions, these fertilizers show an excellent catalytic activity. Indeed, the tetrahydrobenzo[b]pyrans and dihydropyrano[4,3-b]pyrans derivatives were obtained with good yields in short reaction times. Also, these fertilizers can be reused at least four times without significant loss of their catalytic activity. Therefore, their application can be contributing to the development of green chemistry.

4,4'-trimethylenedipiperidine as a nitrogen heterocycle solvent and/or catalyst: Liquid phase tandem Knoevenagel-Michael condensation.

Liquid phase tandem Knoevenagel–Michael condensation of various aromatic and heteroaromatic aldehydes with barbituric acid or 2-thiobarbituric acid and malononitrile was studied in a one-pot three-component reaction. For the first time, TMDP was employed as a safe and efficient solvent and/or catalyst in the liquid and aqueous ethanol medium, respectively, for the practical and eco-friendly Knoevenagel–Michael condensation. The reactions were carried out by using greener procedures, including a) the use of TMDP as an N-heterocycle organocatalyst in a green medium including water and ethanol (1:1 v/v) at reflux temperature, and b) the use of TMDP as a dual solvent-catalyst at 65 °C in the absence of any solvent. High to excellent yields of the desired pyrano[2,3- d ]pyrimidinones were obtained under the two earlier mentioned conditions. The current methodologies have advantages, including (a) avoiding hazardous, toxic, volatile, and flammable materials and solvents, (b) avoiding tedious processes, harsh conditions, and multiple steps for the preparation of catalysts, (c) using a less toxic and noncorrosive catalyst, (d) minimizing hazardous waste generation and simple workup process, and (e) high recyclability of TMDP. Another important result of this work is that the TMDP can be a promising alternative for toxic, volatile, and flammable base reagents such as piperidine and triethylamine in liquid phase organic syntheses owing to its unique properties such as being less toxic, nonflammable, and nonvolatile, and having a low melting point, broad liquid range temperature, high thermal stability, and safe handling and storage.

Synthetic strategies of phosphonodepsipeptides

Phosphonodepsipeptides are phosphorus analogues of depsipeptides and phosphonate-linked analogues of naturally occurring peptides. They are more stable than phosphonopeptides and have been widely applied as enzyme inhibitors, haptens for the production of antibodies, biological agents, and prodrugs. The synthetic strategies towards phosphonodepsipeptides are reviewed, including the phosphonylation of hydroxy esters with phosphonochloridates, the condensation of phosphonic monoesters and hydroxy esters, the alkylation of phosphonic monoesters with 1-(alkoxycarbonyl)alkyl halides or sulfonates, multicomponent condensation of amides, aldehydes, and dichlorophosphites followed by alcoholysis with hydroxy esters, the phosphinylation of hydroxy esters with phosphonochloridites followed by oxidation, and the carbene insertion of N-protected amino acids with 1-diazoalkylphosphonates. This review includes the synthesis of α-, β-, and γ-phosphonodepsipeptides and phosphonodepsipeptides with C-1-hydroxyalkylphosphonic acids.

One-pot three-component condensation for the synthesis of 2,4,6-triarylpyridines and evaluation of their antimicrobial activity

A new series of 2,4,6-triarylpyridines are synthesised through one-pot three-component condensation of triazole pyrazolyl aldehydes and acetophenones with ammonium acetate in moderate to good yields. The structures of the synthesised compounds are confirmed by spectral methods viz. IR, 1H NMR, 13C NMR and mass spectral analysis. All these scaffolds are evaluated for their in vitro antimicrobial activity and found to exhibit promising antimicrobial potency. Synopsis: A library of new 2,4,6-triarylpyridine derivatives were synthesised through one-pot three-component condensation of triazole pyrazolyl aldehydes and acetophenones with ammonium acetate in good yields. The synthesised compounds were screened for their in vitro antimicrobial activity and exhibited moderate to good activity against various bacterial and fungal strains.

Low-Temperature Aldol Condensation of Aldehydes on R-TiO2(100)-(1 × 1): Exceptional Selectivity for α,β-Unsaturated Enal Production.

Selective C-C coupling of oxygenates via aldol condensation has the potential to produce useful chemicals from aldehydes and ketones. Here we report a combined experimental and theoretical study on the aldol condensation of unbranched aldehydes (CnH2n+1-CHO, n = 1-4) on rutile (R)-TiO2(100)-(1 × 1). Experimental results show that the R-TiO2(100)-(1 × 1) surface has a very high reactivity and selectivity for aldol product formation from tested aldehydes at room temperature. Theoretical calculations indicate that the CH3CHO enolization and the aldol dehydration occur with low energy barriers, and the 3-butanolal intermediate adsorbs on R-TiO2(100)-(1 × 1) stably, suggesting that the surface has a "modest" acid-base strength for efficient crotonaldehyde formation. The adsorption configuration of CH3CHO and surface structure of R-TiO2(100)-(1 × 1) may contribute to the exclusive selectivity of (E)-crotonaldehyde formation, which provides us a deep insight into the high selectivity of aldol condensation of aldehydes on the TiO2 catalyst.

Synthesis of quaternary metal oxides immobilized on APTMS-coated magnetite: an efficient and reusable nanocatalyst for Knoevenagel condensation under green conditions

A simple, green, and highly efficient procedure has been developed for Knoevenagel condensation of malononitrile and aromatic aldehydes to the corresponding benzylidenemalononitriles in the presence of Fe3O4@APTMS@Zr–Sb–Ni–Zn nanoparticles (NPs) as a durable nanocatalyst. The heterogeneous nanocomposite was prepared by immobilization of Zr–Sb–Ni–Zn mixed metal oxides on APTMS-coated magnetite. The synthesized catalyst was characterized using Fourier-transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), X-ray diffraction (XRD), vibration sample magnetometer (VSM), transmission electron microscopy (TEM), and Brunauer–Emmett–Teller analysis (BET). In this approach, the condensation of malononitrile and aromatic aldehydes were done in water under reflux conditions to give the corresponding products within 3–60 min in 89%–95% yields. The magnetically recoverable catalyst was recycled and reused about four times without remarkable loss of activity. This method offers various benefits such as mild and eco-friendly reaction conditions, short reaction times, high purity of products, excellent efficiency, use of water as green solvent, and reusability and recoverability of the nanostructure catalyst.

Synthetic Processes toward Nitriles without the Use of Cyanide: A Biocatalytic Concept Based on Dehydration of Aldoximes in Water.

While belonging to the most fundamental functional groups, nitriles represent a class of compound that still raises challenges in terms of an efficient, cost‐effective, general and, at the same time, sustainable way for their synthesis. Complementing existing chemical routes, recently a cyanide‐free enzymatic process technology based on the use of an aldoxime dehydratase (Oxd) as a biocatalyst component has been developed and successfully applied for the synthesis of a range of nitrile products. In these biotransformations, the Oxd enzymes catalyze the dehydration of aldoximes as readily available substrates to the nitrile products. Herein, these developments with such enzymes are summarized, with a strong focus on synthetic applications. It is demonstrated that this biocatalytic technology has the potential to “cross the bridge” between the production of fine chemicals and pharmaceuticals, on one hand, and bulk and commodity chemicals, on the other.

Facile synthesis and characterization of some new 5-arylidene-thiazolidine-2,4-diones and their antimicrobial evaluation

A series of novel 5-arylidene-thiazolidine-2,4-diones derivatives have been synthesized by the Knoevenagel condensation of aromatic aldehydes and N-substituted thiazolidinedione-2,4-diones. Use of KAl(SO 4 ) 2 •12(H 2 O) i . e . Alum for the reaction makes this synthesis facile because of several advantageous factors viz . non-toxicity, efficient catalytic ability and cheap cost of alum. Substitution of arylidene moiety at the position 5 on the thiazolidine-2,4-diones nucleus has occured using this facile approach. Synthesized derivatives have been characterized using various analytical tools and antimicrobial evaluation thereof has been performed against Gram-positive, Gram negative bacteria and a fungal strain. All synthesized compounds show moderate to very good activity against the microorganisms that they have been tested against.