One-pot Conditions Research Articles

Graphene-supported organoiridium clusters catalyze N-alkylation of amines via hydrogen borrowing reaction.

Graphene-supported organic iridium clusters (GSOICs) have been designed, prepared, characterized, and used for N-alkylation of amines via hydrogen borrowing reactions. Structural analysis data (including IR, XPS, TEM and EDS) show that organoiridium clusters are uniformly formed on the surface of graphene, and the grain size of GSOIC is between 1 and 3 nm. After being activated by the auxiliary ligand TMPP (tris(4-methoxyphenyl)phosphine), GSOIC showed excellent catalytic performance for hydrogen borrowing reaction, with its turnover frequency (TOF) reaching 13.67 h-1. Multi-cycle catalysis shows that the GSOIC/TMPP catalytic system exhibits high stability and reliability, with the turnover number (TON) of each catalytic cycle reaching 328, and the cumulative TON of 10 consecutive catalytic cycles reaching 3280. These systems exhibit excellent N-alkylation for a variety of substrates under one-pot conditions without the need for bases, solvents, and other additives, representing a sustainable and environmentally friendly catalytic reaction strategy.

Utilizing perhalopyridine-based alkynes as suitable precursors for the synthesis of novel poly(1,2,3-triazolyl)-substituted perhalopyridines.

A novel series of poly(1,2,3-triazolyl)-substituted perhalopyridines 5a-f were successfully synthesized from the click reaction of the terminal alkynes (drived from the nucleophilic substitution reactions of PFP 1a and PCP 1b with excess amounts of propargyl alcohol) with aryl azides 4a-c under ultrasonic irradiation. Likewise, the sonication of reaction mixtures containing pyridyl cores 3, alkyl bromides 6a,b, and NaN3 under one-pot conditions afforded their respective aliphatic 1,2,3-triazoles 7a-d in yields ranging from 71% to 83%. We next developed an effective method for the regioselective preparation of 2,3,4,5-tetrachloro-6-(prop-2-yn-1-yloxy)pyridine 3c through SNAr reaction of PCP with propargyl alcohol without the utilization of any catalyst. It was then used to fabricate several ((1,2,3-triazol-4-yl)methoxy)-3,4,5,6-tetrachloropyridines 8a-c under the reaction conditions. Finally, the Pd(PPh3)4-catalyzed SMC reaction of tris-triazoles 5b,e with arylboronic acids 9a-c offered a practical method for the synthesis of biaryl-embedded poly(1,2,3-triazoles) 10a-f in good yields.

Dithionite-Mediated Tandem Nitro Reduction/Imine Formation/Intramolecular Cyclization for the Synthesis of Dihydro-benzothiadiazine-1,1-dioxides.

A one-pot, tandem reductive annulation of 2-nitrobenzenesulfonamides with aldehydes to the synthesis of substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxides in the presence of sodium dithionite (Na2S2O4) is reported under mild conditions. The method involves in situ reduction of the nitro group followed by condensation with aldehydes to form an imine, which upon subsequent intramolecular cyclization forms the product under one-pot conditions. The protocol features use of inexpensive Na2S2O4 as the exclusive reagent, appreciable functional group tolerance, broad substrate scope, high product yields, and scalability.

Alkaline hydrolysis of spent aromatic biomass for production of phenolic aldehydes, lignin, and cellulose

In order to combat the environmental issues associated with the burning of spent aromatic biomass (SAB), a method for alkaline hydrolysis of SAB has been developed to afford phenolic acids, predominantly the p-coumaric acid, lignin, and cellulose. Lignin (∼15 wt%) from alkaline hydrolysate was separated by precipitation while a mixture of phenolic acids obtained was directly reacted with a green reagent, PhI(OAc)2, under one-pot condition to afford a mixture of p-hydroxybenzaldehyde (>90 wt%) and vanillin (<10 wt%). Unreacted biomass obtained in the process was successfully used as a substrate for the production of cellulose (∼40 wt%). The developed method exhibits potential for application on an industrial scale.

Implementation of Zincke reaction in one-pot synthesis of switchable, Ag+ and Hg2+ sensing aza-merocyanines based on α-aminopyridin-3,5-dicarbonitrile moiety

We report on the synthesis of new aza-merocyanines, which were synthesized via a modified Zincke reaction under one-pot conditions. These compounds exhibit a reversible color change from yellow to deep blue in solution upon exposure to trace bases. The blue form demonstrates some sensing ability for Ag+ and Hg2+ ions at concentrations above approximately 10−6 M, which is accompanied by a λmaxabs hypsochromic shift of about 20 nm and 100 nm, respectively. Furthermore, the presence of most other metal cations in solution does not affect this process. These results suggest that the synthesized aza-merocyanines hold promise for chemosensory applications.

Immobilization of cytochrome P450 enzymes onto magnetic beads: An approach to drug metabolism and biocatalysis

Cytochrome P450 (CYP, P450) presents a wide range of applicability in drug metabolism studies and in biocatalysis as a great alternative to synthesizing compounds. Nonetheless, their lack of stability is one of their major drawbacks. Aiming the possibility of enhancing the catalytic activity and promoting higher stability, liver microsomal fractions have been immobilized on magnetic beads (Mb). The immobilized procedure was modulated by using rat liver microsomal fractions (RLM-Mb). The optimal condition achieved was further employed for the immobilization of the human microsomal fractions on magnetic beads (HLM-Mb). In vitro metabolism assays were conducted using albendazole (ABZ) as a model drug, and the formation of albendazole sulfoxide (ABZSO) was monitored. Biotransformation reactions applying the produced HLM-Mb were examined for the best temperature to increase the production of metabolites and their reuse cycles. A kinetic study was carried out for HLM-Mbs monitoring the production of ABZO by the oxidation reaction of ABZ by CYP3A4. The Km value was 25.6 µmol L−1 and Vmax was 121.0 µmol L−1. Inhibition assays were conducted in the presence of ketoconazole and the production of ABZSO decreased by 46.8 ± 2.5%. Enzymatic activities for CYP2C9 and CYP2D6 on HLM-Mbs were evaluated by monitoring the hydroxylation reactions of diclofenac and bufuralol as substrates. The immobilization of CYP P450 on magnetic beads increased not only the production of ABZSO metabolites but also the stability of CYP. The use of HLM-Mbs jointly with immobilized glucose-6-phosphate dehydrogenase (G6PDH-Mbs) as a unique dual generator system to produce NADPH has established the one-pot conditions for biocatalysis in a greener approach with reuse of the biocatalyst (G6PDH-HLM-Mbs). To this end, the herein reported HLM-Mbs and G6PDH-HLM-Mbs are excellent analytical tools to be explored either in biocatalysis reactions or in in vitro metabolism studies.

Nanozymes with versatile redox capabilities inspired in metalloenzymes.

Metalloenzymes represent exemplary systems in which an organic scaffold combines with a functional inorganic entity, resulting in excellent redox catalysts. Inspired by these natural hybrid biomolecules, biomolecular templates have garnered significant attention for the controlled synthesis of inorganic nanostructures. These nanostructures ultimately benefit from the protection and colloidal stabilization provided by the biomacromolecule. In this study, we have employed this strategy to prepare nanozymes with redox capabilities, utilizing the versatile catalytic profile of Pt-loaded nanomaterials. Thus, we have investigated protein-templated Pt-based nanoclusters of different sizes and compositions, which exhibit remarkable oxidase, catalase, and reductase-like activities. The interplay between the composition and catalytic activity highlighted the size of the nanocluster as the most prominent factor in determining the performance of the nanozymes. Additionally, we have demonstrated the use of protein-templated nanozymes as potential co-catalysts in combination with enzymes for coupled reactions, under both sequential and concurrent one-pot conditions. This study provides valuable insights into nanozyme design and its wide range of applications in the design of complex catalytic systems.

A Green Blue LED-Driven Two-Liquid-Phase One-Pot Procedure for the Synthesis of Estrogen-Related Quinol Prodrugs.

Quinol derivatives of estrogens are effective pro-drugs in steroid replacement therapy. Here, we report that these compounds can be synthesized in one-pot conditions and high yield by blue LED-driven photo-oxygenation of parent estrogens. The oxidation was performed in buffer and eco-certified 2-methyltetrahydrofuran as the two-liquid-phase reaction solvent, and in the presence of meso-tetraphenyl porphyrin as the photosensitizer. Two steroidal prodrugs 10β, 17β-dihydroxyestra-1,4-dien-3-one (DHED) and 10β-Hydroxyestra-1,4-diene-3,17-dione (HEDD) were obtained with high yield and selectivity.

Amino acids in electrochemical metal-free benzylic C[sbnd]H amidation

This report describes the mild electrochemical metal-, oxidant-, additive-free site-selective direct CH amidation of benzyl C(sp3)-H bonds in an undivided cell using α-amino acids as a source of an amide bond moiety. Practically significant amides are obtained under electrochemical mild one-pot conditions (without strong external oxidants, at room temperature), with total yields up to 73%. This electrochemical approach features a functional selectivity and a broad scope of substrates with benzyl bond and different amino acids.

Series of the Largest Dish-Shaped Dysprosium Nanoclusters Formed by In Situ Reactions.

A three-dimensional supermolecule structure is easily formed due to the diverse coordination modes of high-oxidation-state lanthanide metal ions. However, the design and construction of zero-dimensional (0 D) dish-shaped high-nuclearity lanthanide clusters are difficult. Herein, for the first time, we synthesized a series of the largest dish-shaped high-nuclearity lanthanide nanoclusters (1-4) by in situ tandem reactions under solvothermal one-pot conditions. The formation of 1 and 2 involved an in situ reaction of aldehydes and amines, while the condensation reactions between aldehydes occurred in 3 and 4. Based on the structural characteristics of the dish-shaped lanthanide clusters, we proposed two possible assembly mechanisms involving Dy1 → Dy7 → Dy13 → Dy19 (planar epitaxial growth mechanism) and Dy1 → Dy12 → Dy18 → Dy19 (planar internal growth mechanism).

One-Pot Synthesis of 2-Phenylquinoline-4-Carboxylic Acid: Iron(III) Trifluoromethanesulfonate Catalysed Doebner Reaction

Iron (III) trifluoromethanesulfonate [Fe (OTF)3] has been proven to be an effective catalyst in the synthesis of 2-phenylquinoline-4-carboxylic acid by the Doebner reaction using one-pot pyruvic acid, aniline, and benzaldehyde. This method shows attractive characteristics including concise one-pot conditions, high atom economy, very limited energy consumption, and the sequential catalytic process requires only a catalytic (15 mol%) amount of Fe (OTf)3 with short reaction periods (3 h) . Meanwhile, the catalyst was easily recovered from the reaction system and reused smoothly with only a little loss of activity.

Transition-Metal-Free Synthesis of Polyfunctional Triarylmethanes and 1,1-Diarylalkanes by Sequential Cross-Coupling of Benzal Diacetates with Organozinc Reagents.

A variety of functionalized triarylmethane and 1,1‐diarylalkane derivatives were prepared via a transition‐metal‐free, one‐pot and two‐step procedure, involving the reaction of various benzal diacetates with organozinc reagents. A sequential cross‐coupling is enabled by changing the solvent from THF to toluene, and a two‐step SN1‐type mechanism was proposed and evidenced by experimental studies. The synthetic utility of the method is further demonstrated by the synthesis of several biologically relevant molecules, such as an anti‐tuberculosis agent, an anti‐breast cancer agent, a precursor of a sphingosine‐1‐phosphate (S1P) receptor modulator, and a FLAP inhibitor.

Terpyridinebenzaldehyde isomers: One-pot facile synthesis

We have explored the use of (diethoxymethyl)benzaldehyde readily available as a starting material allowing us to end up with Terpyridinebenzaldehyde isomers. An environmentally friendly procedure was undertaken for the synthesis of a series of 4, 3 and 2-([2,2′:6′,2″-terpyridin]-4′-yl)benzaldehyde isomers (para, meta and ortho position). These compounds have been synthesized in one-pot conditions using ethanol and aqueous ammonia as solvents, at room temperature. This methodology offers substantial advantages with respect to its simplicity of operation, reaction time, satisfying yield of products and easy work-up procedure under mild reaction conditions. Apart from spectroscopic characterization, the structure of one of the Terpyridinebenzaldehyde derivative is confirmed by single-crystal X-ray diffraction.

Bimetallic RuNi nanoparticles as catalysts for upgrading biomass: metal dilution and solvent effects on selectivity shifts

Core–shell RuNi catalysts are prepared from organometallic complexes and PVP as stabilizers under one-pot conditions. The synergistic effect between Ru and Ni activity in furfural hydrogenation depends on the nanoparticle composition.

Synthesis of Highly Functionalized Quinazoline-2,4(1H,3H)-diones from Isocyanides, Aniline and Isocyanate via Cu-Catalyzed Intermolecular C-H Activation Reactions

A simple and appropriate procedure for the synthesis of quinazoline-2,4(1H,3H)-dione derivatives from isocyanides, aniline and isocyanate via the Cu-catalyzed intramolecular C-H activation reaction is reported. The advantages of this method are one-pot conditions, accessible starting materials- catalyst, high yield of products, and short reaction times. The structures are confirmed spectroscopically (1H- and 13C-NMR, IR and EI-MS) and by elemental analyses.

Enantioselective Synthesis of 2‐Substituted Indoles Bearing Trifluoromethyl Moiety by the Friedel‐Crafts Alkylation Reaction of 4,7‐Dihydroindole with N−H Trifluoromethyl Ketimines

AbstractThe Friedel‐Crafts alkylation reaction of 4,7‐dihydroindole with N‐unprotected trifluoromethyl ketimines by means of chiral phosphoric acid and the subsequent oxidation with DDQ afforded chiral 2‐indolylmethylamines bearing a trifluoromethyl moiety in good to high yields with excellent enantioselectivities under one‐pot conditions. The adduct was transformed without loss of enantioselectivity and the absolute stereochemistry was determined by X‐ray crystallographic analysis.

Metal-free regioselective construction of 2-aryl-substituted quinolines via Aza-Henry (Nitro-Mannich) reactions under neat conditions

A new and practical synthetic approach to construct 2-aryl-quinoline derivatives has been described through the sequential Aza-Henry (Nitro-Mannich) reaction using readily available 2,3-dihydro-1H-inden-5-amines, aldehydes and nitroalkanes under one-pot solvent-free reaction conditions using TsOH·H2O as the sustainable catalyst. In this regioselective approach, we described a cascade that proceeds through a sequential imine formation/Aza-Henry reaction/cyclization/denitration/rearrangement followed by oxidative aromatization to afford diverse 2-aryl-quinolines. This approach features large substrate scope, good functional group tolerance, mild reaction conditions and excellent yields with gram scale synthetic utility.

Formation of epoxychromeno[4,3-c]isoquinolines through diastereoselective one-pot IMDA reaction of 4-chloro-3-[(1E)-3-oxo-3-phenyl-1-propen-1-yl]-2H-chromen-2-one and furfurylamine

An intramolecular Diels–Alder mediated reaction of (2E)-3-(4-chloro-2-methylene-2H-chromen-3-yl)-1-phenyl-2-propen-1-one, which was obtained in situ from the reaction of 4-chloro-2-oxo-2H-chromene-3-carbaldehyde and Wittig reagent, with furfurylamine leads to fused epoxychromeno[4,3-c]isoquinolines. Reaction performed in one-pot condition and only one diastereomer was obtained. In this method, the key step for the formation of the final product is IMDA reaction. A series of fused epoxychromeno[4,3-c]isoquinoline compounds containing chromene skeleton have been synthesized through the cyclization strategy, from 4-chloro-2-oxo-2H-chromene-3-carbaldehyde, Wittig reagent, and furfurylamine. The reactions were carried out under reflux condition in DCM/toluene.

An Efficient One-Pot Protocol for Direct Access to Diarylmethyl Thioglycosides with para-Quinone Methides via S-Glycosyl Isothiouronium Salts

An efficient one-pot protocol has been developed for the direct preparation of diarylmethyl thioglycosides starting from per-O-acetylated sugars via glycosyl isothiouronium salts. The one-pot reaction conditions involve rapid conversion of the per-O-acetylated sugar with thiourea in the presence of boron trifluoride etherate as catalyst to give the corresponding glycosyl isothiouronium salt, which is subsequently treated with a para-quinone methide in the presence of a base to give the a diarylmethyl thioglycoside in excellent yield.

Insights on Absolute and Relative Stereocontrol in Stereodivergent Cooperative Catalysis.

An increasing number of examples demonstrate that the use of two mutually compatible chiral catalysts in one-pot conditions can help realize the long-cherished goal of simultaneous control of absolute and relative configurations in asymmetric catalysis. Engaging two transition metal catalysts for this goal presents a considerable degree of mechanistic challenge to control the mode of substrate activation as well as origin of enantio- and diastereoselectivities, both of which are central to the burgeoning domain of stereodivergent catalysis. We have employed density functional theory (B3LYP-D3) computations to investigate an important stereodivergent reaction between azaaryl acetamide and cinnamyl methyl carbonate. These compounds participate in the stereocontrolling C-C bond formation in the form of activated substrates, respectively, when bound to chiral Cu-Walphos and Ir-phosphoramidite catalysts. Herein, we provide the molecular origin of how all four stereoisomers of the product bearing two contiguous stereogenic centers could be accessed by changing the combinations of chiral catalysts (C1(R,Rp) or C2(S,Sp) of Cu-Walphos in conjunction with P1(R,R,R) or P2(S,S,S) of Ir-phosphoramidite catalysts). The origin of stereodivergence is identified to depend on the differences in the number and nature of noncovalent interactions (NCIs) in the stereocontrolling transition states. In particular, NCIs between the chiral catalysts (C-H···π in C1-P1 catalyst dyad and C-H···π, C-H···F, and π···π in C2-P1) in stereocontrolling transition states are found to be the differentiating factors rendering one of the four stereochemically distinct transition states to be the lowest energy one for a given catalyst combination. These molecular insights suggest that subtle modifications to the catalyst framework could be further exploited in stereodivergent catalysis.