Neat Reaction Conditions Research Articles

Erratum: Acceptorless Dehydrogenation under Neat Reaction Conditions: Synthesis of 2-Aryl/Alkyl Quinazolinones Using Supported Ni NPs as Catalyst

Erratum: Acceptorless Dehydrogenation under Neat Reaction Conditions: Synthesis of 2-Aryl/Alkyl Quinazolinones Using Supported Ni NPs as Catalyst

An acid-mediated synthesis of substituted naphthalenes from ortho-alkynyl tertiary benzylic alcohols

We present an efficient, acid-mediated cascade strategy for the construction of 1,3- and 1,2,3-substituted naphthalenes from readily accessible starting materials. This method employs ortho-alkynyl or arynyl tertiary benzylic alcohols as the substrates, which undergo a Lewis acid-triggered dehydration to form ortho-(alkynyl)-styrene intermediates. These intermediates subsequently undergo intramolecular cycloaromatization, resulting in the formation of substituted naphthalenes in a one-pot reaction. A significant advantage of this approach is its ability to proceed under sustainable and neat reaction conditions using ZnCl₂ as the sole Lewis acid, highlighting the simplicity and practicality of the process. Additionally, the strategy exhibits a broad substrate scope, efficiently yielding the desired naphthalene derivatives with practical and consistent yields. This method not only simplifies the synthetic pathway but also aligns with green chemistry principles by minimizing the use of solvents and reagents.

Acceptorless Dehydrogenation under Neat Reaction Conditions: Synthesis of 2-Aryl/Alkyl Quinazolinones Using Supported Ni NPs as Catalyst

AbstractWe report here a Ni-NPs-catalyzed one-pot synthesis of 2-alkyl/aryl quinazolinone motifs via acceptorless dehydrogenation of alcohol, condensation of an aldehyde intermediate with 2-aminobenzamide, followed by a second dehydrogenation of the cyclized intermediate. The protocol is atom-economical and require earth-abundant Ni as the catalyst. The present report involves the annulation of 2-aminobenzamide with various types of primary alcohols, including aryl/heteroaryl methanol, and aliphatic alcohols, and produces high yields of the desired products under neat conditions. The catalyst was synthesized via a high-temperature pyrolysis strategy, using ZIF-8 as the sacrificial template. The Ni NPs@N-C catalyst was characterized by XPS, HR-TEM, HAADF-STEM, XRD, and ICP-MS. The catalyst is stable even in air at room temperature and displayed excellent activity in the acceptorless dehydrogenative coupling synthesis of quinazolinones and could be recycled five times without appreciable loss of its activity.

Sustainable and Safe N-alkylation of N-heterocycles by Propylene Carbonate under Neat Reaction Conditions.

A new, eco-friendly process utilising the green solvent propylene carbonate (PC) has been developed to perform N-alkylation of N-, O- and/or S-containing heterocyclic compounds. PC in these reactions served as both the reagent and solvent. Importantly, no genotoxic alkyl halides were required. No auxiliary was necessary when using anhydrous PC. Product formation includes nucleophilic substitution with the concomitant loss of water and carbon dioxide. Substrates prepared, including the newly invented PROTAC drugs, are widely used.

Reaction engineering blocks ether cleavage for synthesizing chiral cyclic hemiacetals catalyzed by unspecific peroxygenase

Hemiacetal compounds are valuable building blocks in synthetic chemistry, but their enzymatic synthesis is limited and often hindered by the instability of hemiacetals in aqueous environments. Here, we show that this challenge can be addressed through reaction engineering by using immobilized peroxygenase from Agrocybe aegerita (AaeUPO) under neat reaction conditions, which allows for the selective C-H bond oxyfunctionalization of environmentally significant cyclic ethers to cyclic hemiacetals. A wide range of chiral cyclic hemiacetal products are prepared in >99% enantiomeric excess and 95170 turnover numbers of AaeUPO. Furthermore, by changing the reaction medium from pure organic solvent to alkaline aqueous conditions, cyclic hemiacetals are in situ transformed into lactones. Lactams are obtained under the applied conditions, albeit with low enzyme activity. These findings showcase the synthetic potential of AaeUPO and offer a practical enzymatic approach to produce chiral cyclic hemiacetals through C-H oxyfunctionalization under mild conditions.

Fused chromeno-pyrano-pyrimidinediones: Multi-component green synthesis and electrochemical properties

An efficient solvent-free green multi-component reaction strategy for the synthesis of diversified fused chromeno-pyrano-pyrimidinediones (4) by the reaction of 4-hydroxy-1-benzopyran-2-one (1), benzaldehydes (2) and thiobarbituric acid (3) in the presence of thiamine hydrochloride at room temperature in a single step operation has been developed. Simple to perform, neat reaction conditions, water workup, short reaction times, high product yields, scalability, catalyst reusability, products free from column purification and excellent greenness of the process are the noteworthy features of this multi-component reaction approach. Hence, the established methodology meets the concept of “benign by design”. Further, electrochemical properties of the synthesized compounds (4) have been studied by cyclic voltammetry. The HOMO/LUMO values of titled compounds (4) are obtained in the ranges of −5.72 to −5.37 eV/−2.57 to −2.21 eV that are comparable with the reported hole transporting materials.

Peroxygenase-Catalysed Sulfoxidations in Non-Aqueous Media.

Chiral sulfoxides are valuable building blocks in asymmetric synthesis. However, the biocatalytic synthesis of chiral sulfoxides is still challenged by low product titres. Herein, we report the use of peroxygenase as a catalyst for asymmetric sulfoxidation under non-aqueous conditions. Upon covalent immobilisation, the peroxygenase showed stability and activity under neat reaction conditions. A large variety of sulfides was converted into chiral sulfoxides in very high product concentration with moderate to satisfactory optical purity (e. g. 626 mM of (R)-methyl phenyl sulfoxide in approx. 89 % ee in 48 h). Further polishing of the ee value via cascading methionine reductase A (MsrA) gave>99 % ee of the sulfoxide. The robustness of the enzymes and high product titer is superior to the state-of-the-art methodologies. Gram-scale synthesis has been demonstrated. Overall, we demonstrated a practical and facile catalytic method to synthesize chiral sulfoxides.

Selective Peroxygenase‐Catalysed Oxidation of Toluene Derivates to Benzaldehydes

AbstractBiocatalytic oxidation reactions of toluene derivates to the corresponding aldehydes are typically challenged by regio‐ and chemoselectivity issues. In this contribution we address both challenges by a combined reactant‐ and reaction engineering approach. We demonstrate that the peroxygenase‐catalysed transformation of ring‐substituted toluenes proceeds highly regioselectively in benzylic position. Furthermore, neat reaction conditions not only enable attractive product concentrations (up to 185 mM) but also result in highly chemoselective oxidations to the aldehyde level.

Development of ZnO/PANI/Ag nanocomposite for synthesis of bioactive xanthene‐1,8(2H)‐dione derivatives

In this work, we have developed an effective and novel heterogeneous ZnO/polyaniline (PANI)/Ag nanocomposite, which was characterized by X‐ray diffraction (XRD), Fourier‐transform infrared spectroscopy (FTIR), energy‐dispersive X‐ray spectroscopy (EDAX), X‐ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM). ZnO nanoparticles were prepared by coprecipitation method at low temperature. The obtained ZnO nanoparticles were used for its surface functionalization with PANI‐supported silver nanoparticles via self‐assembly redox polymerization method. Further, the high catalytic activity of ZnO/PANI/Ag nanocatalyst was investigated for the one‐pot synthesis of xanthene derivatives via condensation of 5,5‐dimethylcyclohexane‐1,3‐dione and different aromatic aldehydes under neat reaction condition. The advantage of this current work includes short reaction time, easy work‐up, solvent free, high product yield, good chemistry metrices values, easily recoverable and reusable catalyst up to six cycles.

Heteroleptic Copper Complexes as Catalysts for the CuAAC Reaction: Counter-Ion Influence in Catalyst Efficiency

A series of nine cationic heteroleptic aryl-BIAN-copper(I) (BIAN = bis-iminoacenaphthene) complexes with the general formula [Cu((E-C6H4)2BIAN)(PPh3)2][X] (E = p-Me, p-iPr, o-iPr; X = BF4, OTf, NO3) 1X–3X were synthesized and fully characterized using several analytical techniques, including NMR spectroscopy and single-crystal X-ray diffraction. Except for complexes 2BF4 and 3BF4, which were already reported in our previous works, all remaining complexes are herein described for the first time. Two different strategies were used for the preparation of the complexes: complexes bearing BF4− or OTf− counter-ions (1BF4, 1OTf, 2OTf, and 3OTf) were obtained using the appropriate copper(I) precursors [Cu(NCMe)4][BF4] or [Cu(NCMe)4][OTf], whereas for derivatives 1NO3–3NO3, [Cu(PPh3)2NO3] was used. Their activity as catalysts for the copper azide-alkyne cycloaddition (CuAAC) was assessed alongside other high activity, previously reported Cu(I) complexes. Comparative studies to determine the influence of the counter-ion and of the aryl substituents were performed. All complexes behaved as active catalysts under neat reaction conditions, at 25 °C and in short reaction times without requiring the use of any additive, with complex 2NO3 being the most efficient derivative, along with other NO3−-bearing complexes.

Cobalt-Catalyzed Regioselective 1,2-Hydroboration of N-Heteroarenes.

Regioselective hydroboration of pyridines to 1,2-dihydropyridines remains a significant challenge for the synthesis of valuable nitrogenous bioactive molecules. Herein, we report a base free ligand-controlled cobalt-catalyzed 1,2-hydroboration of pyridines and quinolines with very low catalyst loading under neat reaction conditions. The choice of sterically demanding N-heterocyclic ligands led to the 1,2-regioselectivity and the scope was demonstrated by the N-heterocycles having a variety of functional groups. The preliminary mechanistic studies corroborate that the two ligands followed a distinct catalytic cycle with Co(I) as an active species.

Copper iodide nanoparticles (CuI NPs): an efficient catalyst for the synthesis of alkynyl esters.

An environmentally benign protocol for the synthesis of alkynyl esters, by the cross-coupling of diazoacetate with various substituted alkynes under neat reaction conditions, has been described. Copper iodide nanoparticles (CuI NPs) were found to promote the Sonogashira-type coupling to afford the corresponding alkynyl esters in good yields. The CuI nanoparticles were characterized by PXRD, FESEM, EDAX, and Raman techniques. The developed methodology has several advantages such as a broad substrate scope, less reaction time, atom economy, avoidance of an additive/base/solvent, and enhanced values of green chemistry. The catalyst was recycled up to threefold without the loss of its catalytic activity.

Design, synthesis, and pharmacological evaluation of [1, 3] dioxolo-chromeno[2,3-b]pyridines as anti-seizure agents.

An efficient one-pot three-component reaction for the synthesis of [1,3]dioxolo[4',5':6,7]chromeno[2,3-b]pyridines 4(a-i) has been developed. Synthesis was achieved by reacting sesamol (1), aromatic aldehydes 2(a-i), and 2-aminopropene-1,1,3-tricarbonitrile (3) in the presence of triethylamine at 100°C under neat reaction condition. Simple operational procedure, broad substrate scope, column chromatography free separations, and high yield of products make it an efficient and largely acceptable synthetic strategy. Synthesized compounds 4(a-i) were further screened for preliminary anticonvulsant activity using MES and scPTZ tests. These analogs were also checked for neurotoxicity and hepatotoxicity. Selected active compounds have been then screened quantitatively to determine ED50 and TD50 values. Analog 4h was found effective in both preclinical seizure models with significant therapeutic/toxicity profile (4h: ED50 = 34.7mg/kg, MES test; ED50 = 37.9mg/kg, scPTZ test; TD50 = 308.7mg/kg). Molecular dynamic simulation for 100ns of compound 4h-complexed with GABAA receptor revealed good thermodynamic behavior and fairly stable interactions (4h, Docking score = - 10.94). In conclusion, effective synthetic strategy, significant anticonvulsant activity with good toxicity profile and detailed molecular modeling studies led us to anticipate the emergence of these analogs as valid leads for the development of future effective neurotherapeutic agents.

Hydroboration of nitriles, esters, and amides catalyzed by simple neosilyllithium

We present here an efficient method for the hydroboration of organic nitriles, carboxylic esters, and carboxamides with pinacolborane (HBpin) using an alkali metal catalyst, neosilyllithium (LiCH2SiMe3), in neat reaction conditions. The reactions were accomplished with efficient catalytic reactivity and demonstrated by neosilyllithium at room temperature, in solvent-free condition, to afford a high yield of the corresponding N-boryl amines, boryl ethers, and amine hydrochlorides. The protocol for the catalytic reaction presented in this paper is simple and efficient, with diverse substrate scope for nitriles, carboxylic esters, and carboxamides showing excellent functional group tolerance. DLPNO-CCSD(T) calculations were also performed, showing that the hydroboration of nitriles catalyzed by neosilyllithium occurs through the pre-coordination of the nitrile at Lewis acid lithium followed by hydride migration from the B–H entity.

Visible Light-Emitting Diode Light-Driven Aerial Oxidation of Aldehydes under Catalyst and Solvent-Free Conditions

Background: Green and sustainable method for the oxidation of aldehydes into acids is now in demand as carboxylic acids are important and versatile intermediates. In this context, visible LED light-promoted aerial oxidation can be efficient and greener protocol. Objective: Herein, we have demonstrated a visible LED light-promoted efficient and greener protocol for the aerial oxidation of aromatic aldehydes into corresponding acids in the absence of any additives, base, catalyst, and oxidant. Methods: The oxidation of aromatic aldehydes was irradiated by an LED light at room temperature under an open atmosphere, monitored by TLC. The rate of oxidation was also monitored using different LED lights by UV-Vis studies. The products were purified by column chromatography using silica gel, and the mixture of ethyl acetate/petroleum ether as an eluting solvent and the pure products were confirmed by their melting point determination and NMR spectroscopic analysis. Results: The aldehydes were successfully converted into corresponding acids with good isolated yields (60-90 %) by this protocol, where blue LED light (l ~ 490 nm) was found to be the best choice. Conclusion: The present protocol of aerial oxidation of aromatic aldehydes into corresponding acids under visible LED light has been carried out in the absence of catalyst, oxidant, base, and any other additives. The higher isolated yields, no byproduct formation, and neat reaction conditions are the major advantages of the protocol.

Hydrogenation of n-octanoic acid over the MoPt alloy of Mo-Pt/SiO2 catalyst under solvent-free conditions.

SiO2-Supported bimetallic Mo and Pt worked as an effective heterogeneous catalyst for hydrogenation of n-octanoic acid at a low temperature of 373 K in the absence of solvent, providing 78% yield of hydrogenated products (62% yield of 1-octanol and 32% yield of octyl octanoate). Based on the catalyst characterization, MoPt alloy (Mo/Pt = 1) was formed by high-temperature reduction and was proposed to be the active site for the reaction.

Catalyst-free one-pot synthesis of Novel 4H,5H-pyrano[2,3-d]pyrido[1,2-a]pyrimidin-5-one derivatives

An efficient one-pot synthesis of novel 4H,5H-pyrano[2,3-d]pyrido [1,2-a]pyrimidin-5-one derivatives has been developed. This method involves the three-component condensation of 2‑hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one, aromatic aldehydes and (E)-N-methyl-1-(methylthio)-2-nitroethenamine at 120 °C under neat reaction conditions in Monowave 50 reactor. A simple procedure, catalyst free, short reaction time, high yields and non‐column chromatographic separation are attractive features of this process.

A Synergistic Magnetically Retrievable Inorganic‐Organic Hybrid Metal Oxide Catalyst for Scalable Selective Oxidation of Alcohols to Aldehydes and Ketones

AbstractHerein, we report a synergistic silica coated magnetic Fe3O4 catalyst functionalized with nitrogen rich organic moieties and immobilized with cobalt metal ion (FNP‐5) for selective oxidation of alcohols to aldehydes and ketones using tert‐butyl hydroperoxide (TBHP) as oxidant. The catalyst was rigorously characterized via several techniques which delineate its core‐shell structure, magnetic behavior, phase and crystal structure. The Co(III) acts as the active catalytic center for selective oxidation reaction. The control reactions revealed radical mechanistic pathway assisted by the synergism induced by the inorganic‐organic hybrid nature of FNP‐5. The other features of current protocol involve neat reaction conditions, high TOF values, scalability of product and low E‐factor value (1.92). Moreover, FNP‐5 could be effortlessly separated via an external magnet, displays recyclability over eight catalytic cycles and exhibits structural integrity even after rigorous use. Overall, these results manifest the understanding of synergistic architectures as sustainable surrogates for selective oxidation reactions.

α‐Amino Acids and α,β‐Dipeptides Intercalated into Hydrotalcite: Efficient Catalysts in the Asymmetric Michael Addition Reaction of Aldehydes to N‐Substituted Maleimides

AbstractIn this work, a series of α‐amino acids (L‐Phe, D‐Phe, L‐Trp) and several α,β‐dipeptides (H2N‐L‐Val‐N‐Bn‐β‐Ala‐COOH and H2N‐L‐Leu‐N‐Bn‐β‐Ala‐COOH) intercalated into hydrotalcite (Mg/Al, x=0.333) were prepared by high speed ball milling (HSBM) assisted rehydration/reconstruction methods, followed by sonication and mechanical stirring. All organic‐inorganic hybrid samples were characterized by powder X‐ray diffraction (XRD) and FTIR‐ATR spectroscopy. The catalytic activity of the resulting hydrotalcite‐supported materials (natural and hybrid) was evaluated in the asymmetric Michael addition reaction of α,α‐disubstituted‐aldehydes to N‐substituted‐maleimides. Pristine (HTS), calcined (HTC) and water‐reconstructed (HTR‐l) hydrotalcite‐derived materials exhibited very low catalytic activities, affording racemic mixtures of the anticipated Michael adduct. By contrast, hybrid materials showed better activities, especially HTR‐α‐amino acid catalysts afforded Michael products in up to 94 % yield and with rather high enantioselectivity (enantiomeric ratio (e.r.) up to 99 : 1) at room temperature under neat reaction conditions. The effect of solvents and Brønsted basic or acidic additives was evaluated using the best hybrid catalyst, HTR‐L‐Phe. In addition, recycling and reuse of the catalyst (up to 4 cycles) and large‐scale experiments was successfully carried out.

Reactivity of substrates with multiple competitive reactive sites toward NBS under neat reaction conditions promoted by visible light

Regioselectivity of visible-light-induced transformations of a range of (hetero)aryl alkyl-substituted ketones bearing several competitive reactive sites (α-carbonyl, benzyl and aromatic ring) with N-bromosuccinimide (NBS) was studied under solvent-free reaction conditions (SFRC) and in the absence of inert-gas atmosphere, radical initiators and catalysts. An 8-W energy-saving household lamp was used for irradiation. Heterogeneous reaction conditions were dealt with throughout the study. All substrates were mono- or dibrominated at the α-carbonyl position, and additionally, some benzylic or aromatic bromination was observed in substrates with benzylic carbon atoms or electron-donating methoxy groups, respectively. Surprisingly, ipso-substitution of the acyl group with a bromine atom took place with (4-methoxynaphthyl) alkyl ketones. While the addition of the radical scavenger TEMPO (2,2,6,6-tetramethylpiperidin-1-yloxy) decreased the extent of α- and ring bromination, it completely suppressed the benzylic bromination and α,α-dibromination with NBS under SFRC.