Synthetic Operation Research Articles

Exposing the Forgery Clues of DeepFakes via Exploring the Inconsistent Expression Cues

The pervasive prevalence of DeepFakes poses a profound threat to individual privacy and the stability of society. Believing the synthetic videos of a celebrity and trumping up impersonated forgery videos as authentic are just a few consequences generated by DeepFakes. We investigate current detectors that blindly deploy deep learning techniques that are not effective in capturing subtle clues of forgery when generative models produce remarkably realistic faces. Inspired by the fact that synthetic operations inevitably modify the regions of eyes and mouth to match the target face with the identity or expression of the source face, we conjecture that the continuity of facial movement patterns representing expressions that existed in the veritable faces will be disrupted or completely broken in synthetic faces, making it a potentially formidable indicator for DeepFake detection. To prove this conjecture, we utilize a dual‐branch network to capture the inconsistent patterns of facial movements within eyes and mouth regions separately. Extensive experiments on popular FaceForensics++, Celeb‐DF‐v1, Celeb‐DF‐v2, and DFDC‐Preview datasets have demonstrated not only effectiveness but also the robust capability of our method to outperform the state‐of‐the‐art baselines. Moreover, this work represents greater robustness against adversarial attacks, achieving ASR of 54.8% in the I‐FGSM attack and 43.1% in the PGD attack on the DeepFakes dataset of FaceForensics++, respectively.

Enantioselective Total Synthesis of (-)-Cyathin B2: A Desymmetric Double-Allylboration Approach.

A powerful Pt-catalyzed asymmetric diboration/desymmetric double-allylboration cascade reaction has been developed for the construction of synthetically useful, densely functionalized hydrindanes with five stereocenters, including three quaternary ones, in good yields and excellent enantiomeric excess (ee) values within a single synthetic operation. A unified strategy utilizing this key tandem methodology enabled the concise asymmetric total synthesis of cyathane diterpene (-)-Cyathin B2 in 14 steps from commercially available starting materials, thereby demonstrating its remarkable potential in the synthesis of hydrindane-containing natural products and pharmaceuticals.

InCl3-Catalyzed One-Pot Synthesis of Pyrrolo/Indolo- and Benzooxazepino-Fused Quinoxalines.

In this paper, we describe an efficient InCl3-catalyzed two-component reaction of 1-(2-aminophenyl)pyrroles/indoles and 2-propargyloxybenzaldehydes for the direct synthesis of 12bH-benzo[6,7]1,4-oxazepino[4,5-a]pyrrolo/indolo[2,1-c]quinoxalines. This high atom- and step-economical one-pot process generates three new C/N-C bonds in a single synthetic operation, resulting in the formation of new six- and seven-membered heterocyclic rings. The easy availability of the starting materials, the use of the relatively inexpensive indium catalyst, and the good substrate scope are the salient features of this strategy. The proposed mechanistic pathway involves imine formation, two consecutive cyclizations via electrophilic aromatic substitution and nucleophilic addition reactions, and the H shift step.

Regio- and diastereoselective synthesis of thioxothiazolidin-indolin-2-ones, oxoindolin-carbamodithioate hybrids, and their base-catalyzed conversion into dispirocyclopentanebisoxindoles

In this publication, we reported a regio-, diastereoselective, and kinetically controlled reaction for synthesizing thioxothiazolidin-indolin-2-ones, oxoindolin-carbamodithioate hybrids, and their base-catalyzed conversion into dispirocyclopentanebisoxindoles. Obtaining only the kinetic thioxothiazolidin-indolin-2-one products together with their straightforward conversion to dispirocyclopentanebisoxindoles, excellent regio- and diastereoselectivity, easy reaction workup, and one-pot synthetic operation are considerable advantages of this work.

Optimizing Drug Development: Harnessing the Sustainability of Pharmaceutical Cocrystals.

Environmental impacts of the industrial revolution necessitate adoption of sustainable practices in all areas of development. The pharmaceutical industry faces increasing pressure to minimize its ecological footprint due to its significant contribution to environmental pollution. Over the past two decades, pharmaceutical cocrystals have received immense popularity due to their ability to optimize the critical attributes of active pharmaceutical ingredients and presented an avenue to bring improved drug products to the market. This review explores the potential of pharmaceutical cocrystals as an ecofriendly alternative to traditional solid forms, offering a sustainable approach to drug development. From reducing the number of required doses to improving the stability of actives, from eliminating synthetic operations to using pharmaceutically approved chemicals, from the use of continuous and solvent-free manufacturing methods to leveraging published data on the safety and toxicology, the cocrystallization approach contributes to sustainability of drug development. The latest trends suggest a promising role of pharmaceutical cocrystals in bringing novel and improved medicines to the market, which has been further fuelled by the recent guidance from the major regulatory agencies.

Highly efficient and air-tolerant calcium-based Birch reduction using mechanochemistry

Abstract In this study, we report a mechanochemical protocol for highly efficient and air-tolerant calcium-based Birch reduction. The developed mechanochemical approach allows the use of readily available calcium metal as a safer-to-handle reductant for Birch reduction of various aromatic compounds. The reaction was rapid and the desired dearomatization products were obtained in good yields within 15 min at ambient temperature. Notably, all synthetic operations can be performed under ambient conditions without a complicated reaction setup involving inert gases. The feasibility of the gram-scale synthesis was demonstrated, further highlighting the practical utility of this protocol.

One‐Pot Synthesis of 2‐(Alkylsulfanyl)quinolines from Aryl Isothiocyanates and Allenes or Alkynes

AbstractIn this work, a conceptually novel approach to diversely substituted 2‐(alkylsulfanyl)quinolines is described. The approach includes the assembly of the target molecules from allenic or acetylenic carbanions, aromatic isothiocyanates, and alkylating agents. The process proceeds in a single synthetic operation via the formation and 6π‐electrocyclization of N‐aryl‐1‐aza‐1,3,4‐trienes, R2R3C=C=C(R1)C(SAlk)=NAr, with the participation of the carbon‐carbon double bond of the phenyl group and the azadiene fragment of the azatrienic system.

Polar Molecules Regulating the Regio- and Stereoselectivity of Polymerization of Conjugated Dienes Catalyzed by CGC-Type Rare-Earth Metal Catalysts.

Herein, a concise, effective, and scalable strategy is reported that the introduction of polar molecules (PMs) (e.g., anisole (PhOMe), phenetole (PhOEt), 2-methoxynaphthalene (NaphOMe), thioanisole (PhSMe), and N,N-dimethylaniline (PhNMe2)) as continuously coordinated neutral ligand of cationic active species in situ generated from the constrain-geometry-configuration-type rare-earth metal complexes A-F/AliBu3/[Ph3C][B(C6F5)4] ternary systems can easily switch the regio- and stereoselectivity of the polymerization of conjugated dienes (CDs, including 2-subsituted CDs such as isoprene (IP) and myrcene (MY), 1,2-disubstituted CD ocimene (OC), and 1-substituted polar CD 1-(para-methoxyphenyl)-1,3-butadiene (p-MOPB)) from poor selectivities to high selectivities (for IP and MY: 3,4-selectivity up to 99%; for OC: trans-1,2-selectivity up to 93% (mm up to 90%); for p-MOPB: 3,4-syndioselectivity (3,4- up to 99%, rrrr up to 96%)). DFT calculations explain the continuous coordination roles of PMs on the regulation of the regio- and stereoselectivity of the polymerization of CDs. In comparison with the traditional strategies, this strategy by adding some common PMs is easier and more convenient, decreasing the synthetic cost and complex operation of new metal catalyst and cocatalyst. Such regio- and stereoselective regulation method by using PMs is not reported for the coordination polymerization of olefins catalyzed by rare-earth metal and early transition metal complexes.

Stepwise strategies for overcoming limitations of membraneless electrolysis for direct seawater electrolysis

Direct seawater electrolysis (DSWE) has been investigated as a candidate solution for hydrogen (H2) production using abundant seawater without the water purification requirements of conventional electrolyzers. Costly perfluorinated membranes employed in contemporary water electrolyzers (PEMWE) fail in the presence of trace contaminants due to cation exchange for H+ and scaling resulting from Mg2+/Ca2+ hydroxide precipitation caused by local pH increases. Herein, we disclose a membraneless electrolyzer and explore how symmetric and asymmetric electrolyte recirculation schemes impact pH gradients and performance of the system using in-house developed near-neutral pH electrocatalysts. Under the asymmetric recycle scheme, unbuffered seawater feed can be used whereby pH differentials caused by electrolysis are re-balanced by recirculating the liquid anode and cathode effluent streams to the cathode and anode inlet ports, respectively. Cell voltages of 2.61 and 3.50 V were required to attain 100 mA cm−2 of current density under buffered (0.5 M phosphate buffer; pH 6.71) and unbuffered synthetic seawater operation, respectively, and 50 h of chronoamperometric stability at the same current density was achieved for the former. A mere 0.18 % of H2 crossover from the catholyte to the anolyte at 250 mA cm−2 of current density was recorded at prolonged operation.

Mechanochemistry enabling highly efficient Birch reduction using sodium lumps and d-(+)-glucose.

In this study, a mechanochemical protocol for highly efficient and ammonia-free sodium-based Birch reduction was developed, leveraging the use of cheap and easy-to-handle sodium lumps. The key to achieving this transformation is the use of d-(+)-glucose as a proton source, which solidifies the reaction mixture in bulk state, enhancing the efficiency of the in situ mechanical activation of sodium lumps through the ball-milling process. Under the developed conditions, a diverse array of aromatic and heteroaromatic compounds were selectively reduced to produce the corresponding 1,4-cyclohexadiene derivatives in high yields within 30 min. Notably, all synthetic operations can be carried out without inert gases or the need for dry or bulk organic solvents. Furthermore, a scaled-up synthesis can be conducted without any yield losses. These results suggest that the present mechanochemical approach offers a more convenient, economically attractive, and sustainable alternative to previously established Birch reduction protocols.

Cobalt-catalyzed conformationally restricted alkylarylation enables divergent access to Csp3-rich N-heterocycles.

Due to the intrinsic spatial orientation and structural novelty, Csp3-rich N-heterocycles have been recognized as increasingly sought-after scaffolds as compared to the aromatic ring-based moieties, which have generated considerable recent attention in drug discovery. Hence, we disclose a modular cobalt-catalyzed conformationally restricted alkylarylation strategy for the divergent access to Csp3-rich N-hetero(spiro)cycles. Herein, multiple effects, including radical rebound and conformational restriction, play critical roles in the stabilization of the stereospecific alkyl-cobalt-aryl intermediate. Under simple and mild reaction conditions, cobalt catalyst combines a range of polyfunctionalized cyclenyl bromides and organozinc pivalates to rapidly and reliably forge the architecturally complex Csp3-rich N-hetero(spiro)cycles (>70 examples, >20 : 1 dr), including but not limited to the [5,5]-, [5,6]-, [5,7]-, [5,12]-bicycles, tri- and tetracyclic N-heterocycles, as well as various novel N-heterospirocyclic scaffolds in one synthetic operation. Preliminary kinetic investigations suggested that the final reductive elimination might be the rate-determining step. Moreover, ample substrate scope, good functional group compatibility and facile derivatizations to the pharmaceutically active molecules show the potential applications of this technology to organic syntheses and drug discoveries in medicinal chemistry.

Interface engineering of Ce/La-doped hydrochar-supported nickel catalysts for enhanced tar reforming performance at low temperature

Catalytic reforming of biomass tar to syngas-especially under mild temperature-is an attractive albeit elusive route, necessitating the manufacture of highly efficient catalysts, in particular, from inexpensive, sustainable, and renewable resources as a prerequisite. Two interface-engineering strategies, including one-pot hydrothermal carbonization (HTC) approach and two-step HTC-impregnation method, were applied to fabricate a series of Ce/La-doped hydrochar-supported nickel catalysts, employing pinewood sawdust-derived hydrochar as the support, nickel as the active sites, and Ce or La as the promoter species. After the optimization of synthetic variables and operation conditions, the Ni0.1/Ce0.05-HC catalysts prepared by the two-step HTC-impregnation method simultaneously exhibited boosted activity, selectivity and recyclability than the Ni/HC counterpart without Ce addition as well as reported state-of-the-art catalysts in steam reforming of biomass tar at a low temperature of 600 °C. This exceptional catalytic performance was mainly attributed to the modulation of geometric structure and electronic structure of the exposed active sites by appropriate inclusion of cerium on the hydrochar-based nickel catalyst, which favored the water-gas shift, boudouard reaction and coke gasification, thereby imparting the materials with remarkable resistance against metal sintering and coke deposition during the steam reforming process. The result in this work underscores that the controlled interface between Ni species and hydrochar support by addition of Ce, which pertain to the hydrothermal processing technique, is a promising blueprint toward effective fuel production from waste biomass.

Copper-catalysed perarylation of cyclopentadiene: synthesis of hexaarylcyclopentadienes.

While hexaphenylsilacyclopentadiene (hexaphenylsilole) is viewed as an archetypal Aggregation-Induced Emission (AIE) luminogen, its isostructural hydrocarbon surrogate hexaphenylcyclopentadiene has strikingly never been investigated in this context, most probably due to a lack of synthetic availability. Herein, we report a straightforward synthesis of hexaphenylcyclopentadiene, via the direct perarylation of cyclopentadiene upon copper(i) catalysis under microwave activation, with the formation of six new C-C bonds in a single synthetic operation. Using zirconocene dichloride as a convenient source of cyclopentadiene and a variety of aryl iodides as coupling partners, this copper-catalysed cross-coupling reaction gave rise to a series of unprecedented hexaarylcyclopentadienes. The latter are direct precursors of extended π-conjugated polycyclic compounds, and their cyclodehydrogenation under Scholl reaction conditions yielded helicenic 17,17-diarylcyclopenta[l,l']diphenanthrenes. These structurally complex polyannelated fluorene derivatives can now be prepared in only two synthetic steps from cyclopentadiene.

Zn(OAc)2•2H2O- Catalyzed Synthesis of Chromeno[2,3-d] Pyrimidinones under Solvent-free Conditions

Due to their high synthetic efficiency, multi-component reactions (MCRs) have shown to be extraordinarily effective at producing compounds in a single synthetic operation. The chromeno[2,3-d] pyrimidine moieties represent important building blocks in synthetic bioactive compounds. The reaction of barbituric acid, aldehydes, and cyclohexane-1,3-diones in the presence of zinc acetate (5 mol%) under neat conditions at 70 0C, yielded a facile and one-pot synthesis of corresponding chromeno[2,3-d]pyrimidineones. Thirteen compounds containing neutral, withdrawing and electron donating groups (H, NO2, -CN, -Cl; -OH, -CH3 and -OCH3) were synthesized in good, isolated yields ranging from 78-91%. The successful involvement of o-, m-, and p- substituted nitro benzaldehydes suggested that steric hindrance had no effect. All of the synthesized compounds are well-known, and this process is unique in that it makes use of zinc acetate, an accessible, low-cost Lewis acid catalyst.

Recent trends in the synthesis and applications of β-iodovinyl sulfones: a decade of progress.

Direct vicinal difunctionalization of π-systems has emerged as a powerful platform for constructing multiple bonds in a single synthetic operation using simple chemical feedstocks. Over the past decade, there has been exponential growth in the direct construction of successive C-S and C-I bonds using a wide variety of sulfonyl and iodide reactants through 1,2-iodosulfonylation of alkynes in a regio- and stereo-selective manner. In this review, we mainly focus on the recent developments in the preparation of β-iodovinyl sulfones and their practical applications in organic synthesis. The most promising photoredox and electrochemical transformations for synthesizing β-iodovinyl sulfones are also reviewed. The multifunctional β-iodovinyl sulfones have recently been burgeoning as versatile synthetic precursors due to the combination of vinyl iodide and vinyl sulfone moieties, essential building blocks for diverse synthetic manipulations. We hereby present the chemistry of β-iodovinyl sulfones, which can be classified into numerous sections based on the sulfonyl surrogates, and potential synthetic approaches are systematically outlined.

A Study on the Mechanism of Synthetic Operations for Combating Telecom Network Fraud Crimes: Starting from the “Internal Cooperation” of “Four Specializations and Two Joint Forces”

A Study on the Mechanism of Synthetic Operations for Combating Telecom Network Fraud Crimes: Starting from the “Internal Cooperation” of “Four Specializations and Two Joint Forces”

Self-Assembly of 4,4'-Linked Dipyrromethanes from Unconventional Reactants─Propargylamines, 2-(Vinyloxy)ethyl Isothiocyanate, and Alkylating Agents under Basic Conditions.

Self-assembly of 4,4'-linked dipyrromethanes from 2-(vinyloxy)ethyl isothiocyanate, tertiary propargylamines, and alkylating agents has been discovered. The plausible reaction mechanism, the major stages of which have been confirmed experimentally, includes (1) the lithiation of propargylamine (with n-BuLi); (2) the formation of lithium N-[2-(vinyloxy)ethyl]but-2-ynimidothioate (product of the addition of monolithiated propargylamine to isothiocyanate); (3) isomerization of the latter in the corresponding allenylimidothioate (under the action of the t-BuOK/t-BuOH system); (4) low-temperature (<15 °C) intramolecular cyclization of the latter into potassium N-(5-amino-2-thienyl)-N-[2-(vinyloxy)ethyl]amide; (5) the base-induced cleavage of the C-O bond of the N-[2-(vinyloxy)ethyl] group and removal of vinyloxide-anion leading to acetaldehyde; (6) interaction of acetaldehyde with two molecules of N-(5-amino-2-thienyl)-N-[2-(vinyloxy)ethyl]amide-anion resulting in dithienomethane N-anionic intermediate; (7) recyclization of the latter into dipyrromethane S-anionic intermediate. Final S-alkylation affords synthetically challenging 4,4'-dipyrromethanes in a yield of 22-51%. The whole process is carried out in a single synthetic operation in a very short time (∼10-15 min, excluding alkylation time).

Synconn_build: A python based synthetic dataset generator for testing and validating control-oriented neural networks for building dynamics prediction

Applying model-based predictive control in buildings requires a control-oriented model capable of learning how various control actions influence building dynamics, such as indoor air temperature and energy use. However, there is currently a shortage of empirical or synthetic datasets with the appropriate features, variability, quality and volume to properly benchmark these control-oriented models. Addressing this need, a flexible, open-source, Python-based tool, synconn_build, capable of generating synthetic building operation data using EnergyPlus as the main building energy simulation engine is introduced. The uniqueness of synconn_build lies in its capability to automate multiple aspects of the simulation process, guided by user inputs drawn from a text-based configuration file. It generates various kinds of unique random signals for control inputs, performs co-simulation to create unique occupancy schedules, and acquires weather data. Additionally, it simplifies the typically tedious and complex task of configuring EnergyPlus files with all user inputs. Unlike other synthetic datasets for building operations, synconn_build offers a user-friendly generator that selectively creates data based on user inputs, preventing overwhelming data overproduction. Instead of emulating the operational schedules of real buildings, synconn_build generates test signals with more frequent variation to cover a broader range of operating conditions.•Synconn_build is an open-source tool designed to address the lack of datasets for benchmarking control-oriented building dynamics prediction models.•The tool automates simulations, data acquisition, and EnergyPlus configuration, guided by user inputs.•Synconn_build prevents data overproduction by selectively creating data, offering a user-friendly approach to dataset generation.

Synthesis, structural determination, in vitro antioxidant and antibacterial efficacy of dispirooxindolopyrrolidine embedded indole heterocycle

Synthesis of dispirooxindolopyrrolidine embedded indole hybrid heterocycle was achieved in excellent yield employing intermolecular 1,3-dipolar cycloaddition cascade reaction sequence. The non-stabilized 1,3-dipole component was derived from isatin and l-tryptophan under decarboxylative condensation methodology, was reacts with 3-(4-fluorobenzylidene)indolin-2-one to form 5-benzyl-spiro[2.3′]oxindolo-spiro[3.3′′]-oxindolo-4-[4-fluorophenyl-pyrrolidinewith four stereogenic center via two CC and one CN bonds in single synthetic operation. The structure of compound was undoubtably determined by 1D and 2D NMR spectroscopic analysis. The stereo and regiochemistry of cycloadduct was confirmed through single crystal X-ray diffraction studies. The packing aspects of compound 4 were analyzed using Hirshfeld calculations. It is found that the O…H, N…H, C…H and H…H interactions have major role in the crystal stability. Their percentages are estimated to be 10.1, 3.4, 25.0 and 51.0%, respectively indicating that the H…H contacts are the most dominant. Different electronic parameters such as charge population, dipole moment, molecular electrostatic potential map and frontier molecular orbitals as well as their derived reactivity descriptors were presented. Compound 4 showed potent antibacterial efficacy against E. coli with MIC value of >7.8 µg/mL, besides, compound 4 displayed significant antioxidant activity (84.05%) at the concentration of 500 µg/mL.

Dual Nickel(II)/Mechanoredox Catalysis: Mechanical-Force-Driven Aryl-Amination Reactions Using Ball Milling and Piezoelectric Materials.

The combination of a nickel(II) catalyst and a mechanoredox catalyst under ball-milling conditions promotes mechanical-force-driven C-N cross-coupling reactions. In this nickel(II)/mechanoredox cocatalyst system, the modulation of the oxidation state of the nickel center, induced by piezoelectricity, is used to facilitate a highly efficient aryl-amination reaction, which is characterized by a broad substrate scope, an inexpensive combination of catalysts (NiBr2 and BaTiO3 ), short reaction times, and an almost negligible quantity of solvents. Moreover, this reaction can be readily up-scaled to the multi-gram scale, and all synthetic operations can be carried out under atmospheric conditions without the need for complicated reaction setups. Furthermore, this force-induced system is suitable for excitation-energy-accepting molecules and poorly soluble polyaromatic substrates that are incompatible with solution-based nickel(II)/photoredox cocatalysts.