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Enzymatic cleavage of C─F bonds in per- and polyfluoroalkyl substances (PFAS) is largely unknown but avidly sought to promote systems biology for PFAS bioremediation. Here, we report the reductive defluorination of α, β-unsaturated per- and polyfluorocarboxylic acids by Acetobacterium spp. The microbial defluorination products were structurally confirmed and showed regiospecificity and stereospecificity, consistent with their formation by enzymatic reactions. A comparison of defluorination activities among several Acetobacterium species indicated that a functional fluoride exporter was required for the detoxification of the released fluoride. Results from both in vivo inhibition tests and in silico enzyme modeling suggested the involvement of enzymes of the flavin-based electron-bifurcating caffeate reduction pathway [caffeoyl-CoA reductase (CarABCDE)] in the reductive defluorination. This is a report on specific microorganisms carrying out enzymatic reductive defluorination of PFAS, which could be linked to electron-bifurcating reductases that are environmentally widespread.

Halogenated phenazine meroterpenoids are a structurally unusual family of marine actinobacterial natural products that exhibit antibiotic, antibiofilm, and cytotoxic bioactivities. Despite a lack of established phenazine halogenation biochemistry, genomic analysis of Streptomyces sp. CNZ-289, a prolific lavanducyanin and C2-halogenated derivative producer, suggested the involvement of vanadium-dependent haloperoxidases. We subsequently discovered lavanducyanin halogenase (LvcH), characterized it in vitro as a regioselective vanadium-dependent chloroperoxidase, and applied it in late-stage chemoenzymatic synthesis.

A series of new small-molecule acceptors—NA9, NA10, and NA11—based on benzo[b]phenazine are synthesized. The chlorinated NA10 and brominated NA11 exhibit improved molecular packing and enhanced charge transport, resulting in higher power conversion efficiencies (PCEs) of 15.65% and 16.64%, respectively, compared to 11.66% for the non-halogenated NA9. These results underscore the great potential of peripheral halogenation particularly bromination, in achieving high-performance OSCs. [ABSTRACT FROM AUTHOR]

Fluorination is an efficient strategy for improving organic solar cells (OSCs) efficiency, particularly by fluorinating the end group of emerging nonfullerene acceptors. Here, the fluorination effect was investigated by using small molecule donors with fluorine‐free (SBz) and fluorinated (SBz‐F) end groups, paired with the emerging nonfullerene acceptor Y6. Interestingly and unexpectedly, fluorination of the end group negatively affects OSCs efficiency, with fluorine‐free SBz:Y6 OSCs achieving a higher power conversion efficiency (PCE) of 11.05 % compared to the fluorine‐containing SBz‐F:Y6 blends (PCE=9.61 %). Analysis of space‐charge limited currents reveals lower and unbalanced hole/electron mobility in SBz‐F:Y6 compared to the SBz:Y6 blends. These findings are further supported by charge recombination dynamics and donor‐acceptor miscibility analyses. [ABSTRACT FROM AUTHOR]

Discovered in 1822, the haloform reaction is one of the oldest synthetic organic reactions. The haloform reaction enables the synthesis of carboxylic acids, esters or amides from methyl ketones. The reaction proceeds via exhaustive α‐halogenation and then substitution by a nucleophile to liberate a haloform. The methyl group therefore behaves as a masked leaving group. The reaction methodology has undergone several important developments in the last 200 years, transitioning from a diagnostic test of methyl ketones to a synthetically useful tool for accessing complex esters and amides. The success of the general approach has been exhibited through the use of the reaction in the synthesis of many different complex molecules in fields ranging from natural product synthesis, pharmaceuticals, agrochemicals, fragrants and flavourings. The reaction has not been extensively reviewed since 1934. Therefore, herein we provide details of the history and mechanism of the haloform reaction, as well as an overview of the developments in the methodology and a survey of examples, particularly in natural product synthesis, in which the haloform reaction has been used. [ABSTRACT FROM AUTHOR]

An eco‐friendly electrochemical halogenation of 2‐amino‐1,4‐naphthoquinones has been developed. The new mild and energy efficient methodology comprises sustainable features like oxidant free and double role of the halogen source as electrolyte, originating twenty‐six amino‐halogenated naphthoquinoidal derivatives in good yields under mild conditions. This novel methodology permitted access to new potent trypanocidal prototypes, where six compounds were more active than benznidazole, the current market drug used in the treatment of Chagas Disease. [ABSTRACT FROM AUTHOR]

N,N′‐Diarylimidazolium salts containing haloalkyl functional groups that are reactive with various nucleophiles are considered to be promising reagents for the preparation of functionalized N‐heterocyclic carbene (NHC) ligands, which are in demand in catalysis, materials science, and biomedical research. Recently, 4‐chloromethyl‐functionalized N,N′‐diarylimidazolium salts became readily available via the condensation of N,N′‐diaryl‐2‐methyl‐1,4‐diaza‐1,3‐butadienes with ethyl orthoformate and Me3SiCl, but these compounds were found to have insufficient reactivity in reactions with many nucleophiles. These chloromethyl salts were studied as precursors in the synthesis of bromo‐ and iodomethyl‐functionalized imidazolium salts by halide anion exchange. The 4‐ICH2‐functionalized products were found to be unstable, whereas a series of novel 4‐bromomethyl functionalized N,N′‐diarylimidazolium salts were obtained in good yields. These bromomethyl‐functionalized imidazolium salts were found to be significantly more reactive towards various N, O and S nucleophiles than the chloromethyl counterparts and enabled the preparation of previously inaccessible heteroatom‐functionalized imidazolium salts, some of which were successfully used as NHC proligands in the preparation of Pd/NHC and Au/NHC complexes. [ABSTRACT FROM AUTHOR]

Copper-mediated reactions of α-diazo-β-keto sulfonamides led to a range of products, including alkynesulfonamides, enamines, and α-halosulfonamides, with no evidence for intramolecular C–H insertion in any of the reactions, in contrast to the reactivity of the comparable α-diazo-β-oxo sulfones. Use of copper(II) triflate (5 mol%) led to the isolation of a series of alkynesulfonamides (up to 12% yield) and enamines (up to 64% yield). Use of copper(II) chloride (5 mol%) led to the formation, in addition, of α-halosulfonamides; use of stoichiometric amounts of copper(II) chloride/bromide enabled facile halogenation of the β-keto sulfonamide to form α-halosulfonamides (up to 63% yield). [ABSTRACT FROM AUTHOR]

AbstractA novel method is developed for the synthesis of amine-substituted indole [3,4-b] azepine derivatives. In-situ chlorination, followed by nucleophilic substitution of 1,5-dichloro azepino[3,4-b] indole with respective amines yields the desired compounds. The reactivity of the azepinone ring toward chlorination reactions is intriguing and gives either rearranged or hydrolyzed products under aqueous work up conditions. In brominated azepinones, elimination is favored over nucleophilic substitution reaction. The synthesized compounds displayed in vitro cytotoxicity against human cancer cell lines. [ABSTRACT FROM AUTHOR]

Nitrogen‐containing compounds are valuable synthetic intermediates and targets in nearly every chemical industry. While methods for nitrogen‐carbon and nitrogen‐heteroatom bond formation have primarily relied on nucleophilic nitrogen atom reactivity, molecules containing nitrogen‐halogen bonds allow for electrophilic or radical reactivity modes at the nitrogen center. Despite the growing synthetic utility of nitrogen‐halogen bond‐containing compounds, selective catalytic strategies for their synthesis are largely underexplored. We recently discovered that the vanadium‐dependent haloperoxidase (VHPO) class of enzymes are a suitable biocatalyst platform for nitrogen‐halogen bond formation. Herein, we show that VHPOs perform selective halogenation of a range of substituted benzamidine hydrochlorides to produce the corresponding N'‐halobenzimidamides. This biocatalytic platform is applied to the synthesis of 1,2,4‐oxadiazoles from the corresponding N‐acylbenzamidines in high yield and with excellent chemoselectivity. Finally, the synthetic applicability of this biotechnology is demonstrated in an extension to nitrogen‐nitrogen bond formation and the chemoenzymatic synthesis of the Duchenne muscular dystrophy drug, ataluren. [ABSTRACT FROM AUTHOR]

Organohalogen compounds exhibit wide‐ranging bioactivities and potential applications. Understanding natural biosynthetic pathways and improving the production of halogenated compounds has garnered significant attention. Recently, the biosynthetic pathway of a cyanobacterial neurotoxin, aetokthonotoxin, was reported. It contains two unique enzymes: a single‐component flavin‐dependent halogenase AetF and a new type of nitril synthase AetD. The crystal structures of these enzymes in complex with their cofactors and substrates that were recently reported will be presented here. The AetF structures reveal a tri‐domain architecture, the transfer direction of the hydride ion, a possible path to deliver the hypohalous acid, and the unusual bispecific substrate‐recognition mode. The AetD structures demonstrate that the nitrile formation should occur through the action of a diiron cluster, implying that the enzyme should be capable of catalyzing the nitrile formation of alternative amino acids. This information is of central importance for understanding the mechanism of action as well as the applications of these two the‐first‐of‐its‐kind enzymes. [ABSTRACT FROM AUTHOR]

A straightforward protocol for the direct conversion of readily available coumarin‐3‐carboxylic acids to the corresponding 3‐iodocoumarins is described herein. Heating acetonitrile solution of coumarin‐3‐carboxylic acids, molecular iodine and potassium hydrogen phosphate resulted in the decarboxylative iodination of coumarin‐3‐carboxylic acids via radical mechanism. Various electron rich and electron poor coumarin‐3‐carboxylic acids were compatible with the established reaction conditions and consequently afforded the corresponding 3‐iodocoumarins in (46–93 %) reaction yields with minimum purification efforts. The formed products serve as valuable precursors to streamline more complex organic compounds incorporating coumarin core. [ABSTRACT FROM AUTHOR]

Halogenases are spurring a growing interest in the fields of biosynthesis and biocatalysis. Although various halogenases have been identified in numerous natural product biosynthetic pathways, the mechanisms for multiple halogenations and site‐selectivity remain largely unclear. In this study, we biochemically characterized FasV, a flavin‐dependent halogenase (FDH) that catalyzes five successive chlorinations in the biosynthesis of the naphthacene‐containing aromatic polyketide naphthacemycin. This multiple halogenation reaction was elucidated to occur in an orderly fashion, as evidenced by enzyme kinetics, time‐course assays, and computational simulations. Crystallographic analyses and mutagenesis studies revealed previously unrecognized amino acid residues, including T53, L81, F93, and I212, that are crucial for controlling regioselectivity and substrate specificity. Based on this, a I212T mutant was generated to exclusively catalyze selective monohalogenation. We propose a novel dual‐activation mechanism and demonstrate that the larger binding pocket of FasV makes it a valuable biocatalyst for other substrates with diverse structures. Therefore, this study provides new insight into multi‐site polyhalogenases and highlights the potential for engineering FasV‐like FDHs for biocatalytic applications. [ABSTRACT FROM AUTHOR]

Halogenation reactions are a vital area of study for the pharmaceutical industry. The study of the reaction conditions along with the reactors and their scale-up is a thrust area in drug synthesis and manufacturing. There is a shift in the research community towards accommodating renewable energy sources which has driven scientists to include energy sources that are sustainable and aid in making the overall process efficient. This review provides a comprehensive overview of the challenges in selecting the best catalyst, light source and reaction conditions for the fluorination, chlorination and bromination reactions. This paper goes a step further to explain the photoreactors’ design and modelling as well as the scale-up of the same. Overall, it provides a comprehensive view of diverse scientific areas, from halogenation in drug synthesis to the potential of photochemical batch and flow approaches in halogenation reactions. [ABSTRACT FROM AUTHOR]

Molecular stacking behavior exerts a significant influence on the blend film morphology of organic solar cells (OSCs), further affecting device performance and stability. Modulation of the molecular structure, such as central unit and end‐group, can profoundly impact this process. Herein, four quinoxaline (Qx)‐fused‐core‐based non‐fullerene acceptors (NFAs), Qx‐N4F and Qx‐o/m/p‐N4F are synthesized combining π‐extended end‐groups and optimized central units. The isomeric fluorinated central units lead to changes in the local dipole moments and electrostatic potential distribution, which influences the molecular stacking pattern and photoelectronic properties of NFAs. Consequently, binary and ternary devices based on PM6:Qx‐p‐N4F achieve superior power conversion efficiencies (PCE) of up to 18.75% and 19.48%, respectively. Grazing‐incidence wide‐angle X‐ray scattering (GIWAXS) characterization reveals Qx‐p‐N4F's stronger crystallinity, aggregation, and donor–acceptor interactions, which can separately enhance short‐circuit current density (JSC) and fill factor (FF) through higher phase purity and tighter molecular stacking based on maintaining more donor–acceptor interfaces. Furthermore, PM6:Qx‐p‐N4F‐based devices demonstrate exceptional thermal stability, retaining 93.2% of the initial PCE value after 3000 h of heating due to the best morphological stability with the most stable stacking structure. These results underscore the significance of synergistic optimization of NFAs through conjugation expansion and halogenation substitution for obtaining efficient and stable OSCs. [ABSTRACT FROM AUTHOR]

Polyphosphamides are normally good flame retardants. Herein a mesoporous polyphosphamide (p‐PPA) with an accessible average pore diameter of <10 nm and a surface area of 1.773 m2/g has been synthesized via condensation of 1,3‐diamino benzene (DAB) and phenyl phosphinic dichloride (PPDC). 31P, 13C CP‐MAS solid‐state NMR, Raman, and X‐ray photoelectron spectroscopic (XPS) characterizations confirm the presence of ‐{PV(O)‐NH}‐ in the repeating unit of the p‐PPA that is further used as a catalytic mediator to perform the Appel reaction i. e., conversion of alcohols to halides with a broad substrate scope and high TON (561). The heterogeneity of p‐PPA allows easy recovery of organic halides and recycling of the catalyst many times. Mesoporous p‐PPA has further given a scope to perform shape‐selective conversion of primary alcohols with linear alkyl chain (1‐dodecanol) while a low conversion for the bulky secondary (cyclo‐hexanol) and tertiary alcohol (tert‐butanol) is observed. Perhaps, the phosphamide units present inside the porous channel are non‐preferable sites for bulkier alcohols, as evident from the competitive experiments. A comparatively less catalytic conversion obtained with an analogous non‐porous n‐PPA, made of tris(2‐aminoethyl)amine (TREN) linker, highlights the role of porosity in p‐PPA to enhance the accessibility of numerous ‐{PV(O)‐NH}‐ reactive units to increase the TON. [ABSTRACT FROM AUTHOR]

High dark current density (Jd) severely hinders further advancement of near‐infrared organic photodetectors (NIR OPDs). Herein, we tackle this grand challenge by regulating molecular crystallinity and aggregation of fully non‐fused ring electron acceptors (FNREAs). TBT‐V‐F, which features fluorinated terminals, notably demonstrates crystalline intensification and a higher prevalence predominance of J‐aggregation compared to its chlorinated counterpart (TBT‐V‐Cl). The amalgamation of advantages confers TBT‐V‐F‐based OPDs with lower nonradiative energy loss, improved charge transport, decreased energetic disorder, and reduced trap density. Consequently, the corresponding self‐powered OPDs exhibit a 40‐fold decrease in Jd, a remarkable increase in detectivity (D*sh), faster response time, and superior thermal stability compared to TBT‐V‐Cl‐based OPDs. Further interfacial optimization results in an ultra‐low Jd of 7.30×10‐12 A cm−2 with D*sh over 1013 Jones in 320–920 nm wavelength and a climax of 2.2×1014 Jones at 800 nm for the TBT‐V‐F‐based OPDs, representing one of the best results reported to date. This work paves a compelling material‐based strategy to suppress Jd for highly sensitive NIR OPDs, while also illustrates the viability of FNREAs in construction of stable and affordable NIR OPDs for real‐world applications. [ABSTRACT FROM AUTHOR]

An efficient approach is reported for the direct halodecarboxylation of hydroxyaromatic acids by using a readily available N -halosuccinimide (halo = Cl, Br) as the sole promoter in ethanol at room temperature without any other catalyst or additive. This environmentally friendly route tolerates a wide substrate scope with good to excellent yields under convenient conditions. [ABSTRACT FROM AUTHOR]

Organic halogen compounds are cornerstones of applied chemical sciences. Halogen substitution is a smart molecular design strategy adopted to influence reactivity, membrane permeability and receptor interaction. Chiral bioreceptors may restrict the stereochemical requirements in the halo‐ligand design. Straightforward (but expensive) catalyzed stereospecific halogenation has been reported. Historically, PCl5 served access to uncatalyzed stereoselective chlorination although the stereochemical outcomes were influenced by steric parameters. Nonetheless, stereochemical investigation of PCl5 reaction mechanism with carbamoyl (RCONHX) compounds has never been addressed. Herein, we provide the first comprehensive stereochemical mechanistic explanation outlining halogenation of carbamoyl compounds with PCl5; the key regioselectivity‐limiting nitrilimine intermediate (8‐Z.HCl); how substitution pattern influences regioselectivity; why oxadiazole byproduct (P1) is encountered; stereo‐electronic factors influencing the hydrazonoyl chloride (P2) production; and discovery of two stereoselectivity‐limiting parallel mechanisms (stepwise and concerted) of elimination of HCl and POCl3. DFT calculations, synthetic methodology optimization, X‐ray evidence and experimental reaction kinetics study evidence all supported the suggested mechanism proposal (Scheme 2). Finally, we provide mechanism‐inspired future recommendations for directing the reaction stereoselectivity toward elusive and stereochemically inaccessible (E)‐bis‐hydrazonoyl chlorides along with potentially pivotal applications of both (E/Z)‐stereoisomers especially in medicinal chemistry and protein modification. [ABSTRACT FROM AUTHOR]

The ternary strategy proves effective for breakthroughs in organic photovoltaics (OPVs). Elevating three photovoltaic parameters synergistically, especially the proportion‐insensitive third component, is crucial for efficient ternary devices. This work introduces a molecular design strategy by comprehensively analyzing asymmetric end groups, side‐chain engineering, and halogenation to explore the outstanding optoelectronic properties of the proportion‐insensitive third component in efficient ternary systems. Three asymmetric non‐fullerene acceptors (BTP‐SA1, BTP‐SA2, and BTP‐SA3) are synthesized based on the Y6 framework and incorporated as the third component into the D18:Y6 binary system. BTP‐SA3, featuring asymmetric terminal (difluoro‐indone and dichloride‐cyanoindone terminal), with branched alkyl side chains, exhibited high open‐circuit voltage (VOC), balanced crystallinity and compatibility, achieving synergistic enhancements in VOC (0.862 V), short circuit‐current density (JSC, 27.52 mA cm−2), fill fact (FF, 81.01%), and power convert efficiency (PCE, 19.19%). Device based on D18/Y6:BTP‐SA3 (layer‐by‐layer processed) reached a high efficiency of 19.36%, demonstrating a high tolerance for BTP‐SA3 (10–50%). This work provides novel insights into optimizing OPVs performances in multi‐component systems and designing components with enhanced tolerance. [ABSTRACT FROM AUTHOR]

The stereochemistry of the uncatalyzed chlorolactonization of 4‐phenylpent‐4‐enoic acid at room temperature was examined to probe the reaction's intrinsic diastereoselectivities as a function of chlorenium ion donor, solvent polarity, and reactant concentration ranges. Kinetic studies using Variable Time Normalization Analysis (VTNA) revealed differing reaction orders for the syn and anti alkene addition processes. Aided and illustrated by quantum chemical modeling, this detailed mechanistic analysis of the substrate's intrinsic chlorolactonization reactions points to concerted AdE3‐type paths for both syn and anti additions. By illuminating the factors selecting for syn‐ vs anti‐addition paths, the results provide key reference points for future studies of stereocontrol in halofunctionalization reactions. [ABSTRACT FROM AUTHOR]

Organic solar cells (OSCs) based on non-fused ring electron acceptors (NFREAs) have shown significant potential for practical application owing to their easily tunable chemical structures and short synthesis routes. The merging of side-chain engineering and terminal-group halogenation has facilitated the optimization of NFREAs properties. Thus, in this study, we developed four NFREAs using a naphthalenediimide (NDI) unit with different alkyl side-chains (–C6C10 or –C8C12) as the building block and two different electron-withdrawing groups 2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene) malononitrile (IC) and chlorinated IC (IC-2Cl) as the terminal groups. These NFREAs were designated as NDI610-H, NDI610-Cl, NDI812-H, and NDI812-Cl, respectively. All four NFREAs exhibited similar optical bandgaps and molecular conformations. Under the synergistic effects of side-chain modification and terminal-group halogenation, the NFREAs-based active-layer morphologies were significantly different. The NDI610-Cl-based blended film demonstrated favorable phase-separation morphology, facilitating exciton dissociation and charge transport in the corresponding OSCs. Thus, the PM6:NDI610-Cl-based OSCs achieved a maximum power conversion efficiency (PCE) of 8.35%. Moreover, using D18 as the polymer donor further enhanced the device performance, with the D18:NDI610-Cl-based device yielding a higher PCE of 10.25% due to improved short-circuit current and fill factor. Our findings indicate that selecting an NDI unit as the building block and combining tailored alkyl side-chains with altered terminal groups are promising strategies for constructing highly efficient NFREAs. [ABSTRACT FROM AUTHOR]

By selectively interacting with acceptor components, various typed solid additives achieve boosted power conversion efficiency (PCE) in organic solar cells (OSCs). However, due to the efficient active layer being composed of donor and acceptor materials, it is difficult to obtain the desired morphology by manipulating the acceptor component alone, limiting further improvement of PCEs. Herein, two solid additives with a same backbone of thiophene‐benzene‐thiophene (halogen‐free D1‐H) but different halogen substituents (fluorinated D1‐F and chlorinated D1‐Cl) are developed to probe the working mechanism of halogenated variation of solid additives in OSCs. Unlike D1‐H with continuous charge distributions, D1‐F and D1‐Cl show isolated positive charge distribution in benzene‐core and negative charge distribution in thiophene, offering stronger non‐covalent interactions with both donor (PM6) and acceptor (L8‐BO), especially D1‐Cl. Consequently, D1‐Cl‐treated active layer obtains an optimized phase separation and improved molecular packing, boosting PCE to 18.59% and device stability of OSCs, with 17.62% for D1‐H‐treated counterparts. Moreover, using D18:L8‐BO and D18:BTP‐eC9 as active layers, D1‐Cl‐treated binary OSCs obtain impressive PCEs of 19.29% and 19.39%, respectively. This work indicates that halogenation engineering developed in solid additives can effectively regulate morphology for improving PCE and stability of OSCs, and elucidates the underlying mechanism. [ABSTRACT FROM AUTHOR]

Indigo is a commercially significant dye extensively used in the textile industry for dyeing denim and other fabrics. The synthesis of various colored indigo derivatives necessitates the halogenation of the indole ring in indigo. However, the scarcity of halogenating enzymes, especially those with high positional specificity and commercial availability, limits the biological synthesis of various halogenated indigos. This study presents the discovery of a novel halogenase from Pseudoalteromonas nigrifaciens that is similar to sttH from Streptomyces toxytricini, an enzyme that specifically halogenates the 6th carbon of the indole in indigo. The cloned halogenase gene was validated for halogenation activity and regioselectivity using a recombinant Escherichia coli whole-cell conversion system. The addition of either NaCl or NaBr resulted in the production of 6-chloro indigo or 6-bromo indigo, respectively. Notably, 6-chloro indigo displayed a red coloration, while 6-bromo indigo appeared blue. To optimize the whole-cell conversion system, we evaluated the conversion rate of halogenated indigo production in response to varying concentrations of tryptophan and E. coli cells. The maximum conversion rate (32%) was achieved using 30 mM tryptophan and an E. coli cell density corresponding to an OD50 reading. In conclusion, we have designed a recombinant E. coli whole-cell conversion system capable of producing 6-halogenated indigo by introducing a novel sttH-like halogenase from P. nigrifaciens. This system holds promise for the production of various indigo derivatives. [ABSTRACT FROM AUTHOR]

The chemistry of hypervalent iodine (HVI) reagents has gathered increased attention towards the synthesis of a wide range of chemical structures. HVI reagents are characterized by their diverse reactivity as oxidants and electrophilic reagents. In addition, they are inexpensive, non-toxic and considered to be environmentally friendly. An important application of HVI reagents is the synthesis of halogenated cyclic compounds, in particular, the intramolecular HVI-mediated halocyclisation of alkenes using carbon, oxygen, nitrogen or sulfur nucleophiles. Herein, we describe the examples reported in the literature, which are organised by the different halogens involved and the internal nucleophiles.

We performed chlorine inactivation experiments for Elizabethkingia anophelis and E. meningoseptica bacterial strains from clinical and environmental sources. Free chlorine concentration × contact time values

The use of household bleach cleaning products results in emissions of highly oxidative gaseous species, such as hypochlorous acid (HOCl) and chlorine (Cl2). These species readily react with volatile organic compounds (VOCs), such as limonene, one of the most abundant compounds found in indoor enviroments. In this study, reactions of HOCl/Cl2 with limonene in the gas phase and on indoor relevant surfaces were investigated. Using an environmental Teflon chamber, we show that silica (SiO2), a proxy for window glass, and rutile (TiO2), a component of paint and self-cleaning surfaces, act as a reservoir for adsorption of gas-phase products formed between HOCl/Cl2 and limonene. Furthermore, high-resolution mass spectrometry (HRMS) shows that the gas-phase reaction products of HOCl/Cl2 and limonene readily adsorb on both SiO2 and TiO2. Surface-mediated reactions can also occur, leading to the formation of new chlorine- and oxygen-containing products. Transmission Fourier-transform infrared (FTIR) spectroscopy of adsorption and desorption of bleach and terpene oxidation products indicates that these chlorine- and oxygen-containing products strongly adsorb on both SiO2 and TiO2 surfaces for days, providing potential sources of human exposure and sinks for additional heterogeneous reactions.

Enantioselective halolactonizations of sterically less hindered alkenoic acid substrates without substituents on the carbon–carbon double bond have remained a formidable challenge. To address this limitation, we report herein the asymmetric bromolactonization of 5-hexenoic acid derivatives catalyzed by a BINOL-derived chiral bifunctional sulfide.

Choline oxidase from Alcaligenes sp. (ChOx) is used to generate hydrogen peroxide in situ from choline‐based ionic liquids (ILs) to fuel peroxidase‐mediated biocatalysis while mitigating oxidative degradation of the heme‐dependent enzymes. Horseradish peroxidase (HRP) and chloroperoxidase from Caldariomyces fumago (CPO), in combination with the ChOx, are evaluated in enzymatic cascades for the ability of the biocatalytic systems to withstand elevated concentrations of different choline additives in oxidative and halogenative enzymatic assays. The findings are applied in various synthetic scenarios to produce important oxygen‐ and nitrogen‐containing heterocycles, using choline ILs in a dual‐purpose fashion, as a substrate‐solubilizing component in the reaction medium as well as the source for hydrogen peroxide. The ChOx/HRP couple is used to induce intramolecular cyclizations of hydroxamic acids and hydroxycarbamates in a nitroso‐ene‐type pathway with choline dihydrogen phosphate as IL additive. The ChOx/CPO cascade successfully mediates brominative cyclizations of α‐allenic alcohols, while amphiphilic surfactants are employed to turn the aqueous choline propionate IL media into a colloidal suspension. ChOx/CPO partnering is also evaluated in an oxygenative rearrangement of 1‐furylethanol with choline acetate IL. The results show the wide potential of choline oxidase for hydrogen peroxide‐driven biocatalysis with both aqueous and micellar choline ionic liquid solutions. [ABSTRACT FROM AUTHOR]

Efficient and environmentally benign regioselective halogenation protocols have been achieved through the mediation of oxone‐halide, with or without the assistance of aryl iodine. The key to the success of the regioselectivity process is the controlled generation of the active [X]+ or halogen‐substituted hypervalent iodine (III) by manipulating the components of the oxone‐halide‐aryl iodine system. [ABSTRACT FROM AUTHOR]

We disclose a benzylic C−H oxidative coupling reaction with alcohols that proceeds through a synergistic deprotonation, halogenation and substitution sequence. The combination of tert‐butoxide bases with 2‐halothiophene halogen oxidants enables the first general protocol for generating and using benzyl halides through a deprotonative pathway. In contrast to existing radical‐based methods for C−H functionalization, this process is guided by C−H acidity trends. This gives rise to new synthetic capabilities, including the ability to functionalize diverse methyl(hetero)arenes, tolerance of oxidizable and nucleophilic functional groups, precision site‐selectivity for polyalkylarenes and use of a double C−H etherification process to controllably oxidize methylarenes to benzaldehydes. [ABSTRACT FROM AUTHOR]

The high utility of halogenated organic compounds has prompted the development of numerous transformations that install the carbon‐halogen motif. Halogen functionalities, deemed as "functional and functionalizable" molecules due to their capacity to modulate diverse internal properties, constitute a pivotal strategy in drug discovery and development. Traditional routes to these building blocks have commonly involved multiple steps, harsh reaction conditions, and the use of stoichiometric and/or toxic reagents. With the emergence of solid halogen carriers such as N‐halosuccinimides, and halohydantoins as popular sources of halonium ions, the past decade has witnessed enormous growth in the development of new catalytic strategies for halofunctionalization. This review aims to provide a nuanced perspective on nucleophilic activators and their roles in halogen activation. It will highlight critical discoveries in effecting racemic and asymmetric variants of these reactions, driven by the development of new catalysts, activation modes, and improved understanding of chemical reactivity and reaction kinetics. [ABSTRACT FROM AUTHOR]

Benzocyclotrimers (BCTs) like trindane and dodecahydrotriphenylene (DDHTP) have attracted attention as key components for the construction of higher polycyclic aromatic hydrocarbons due to their aesthetic architecture that is useful in developing beautiful carbocycles of higher order. However, there are limited reports on these ring systems since their functionalization is a formidable task. Our personal engagement with these scaffolds prompted us to explore the synthesis of their synthetically useful derivatives. Herein, we report syntheses of a new series of their derivatives by exploiting the α–position of these cycloalkanones using classical Claisen‐Schmidt condensation reaction as well as simple and practical α‐Csp3–H halogenation with suitable halogenating agents. [ABSTRACT FROM AUTHOR]

Chemoselective arylation of 5-aminopyrazoles was performed through oxidative formation of orthoquinones from catechols catalyzed by Myceliophthora thermophila laccase (Novozym 51003), and subsequently nucleophilic attack of 5-aminopyrazole to the catechol intermediates. The C-4 arylated products were obtained under extremely mild conditions without the need for amine protection or halogenation of the substrates. From this method, 10 derivatives with moderate to good efficiency (42–94%) were prepared. [ABSTRACT FROM AUTHOR]

α‐halo alkylboronic esters, acting as ambiphilic synthons, play a pivotal role as versatile intermediates in fields like pharmaceutical science and organic chemistry. The sequential transformation of carbon–boron and carbon–halogen bonds into a broad range of carbon–X bonds allows for programmable bond formation, facilitating the incorporation of multiple substituents at a single position and streamlining the synthesis of complex molecules. Nevertheless, the synthetic potential of these compounds is constrained by limited reaction patterns. Additionally, the conventional methods often necessitate the use of bulk toxic solvents, exhibit sensitivity to air/moisture, rely on expensive metal catalysts, and involve extended reaction times. In this report, a ball milling technique is introduced that overcomes these limitations, enabling the external catalyst‐free multicomponent coupling of aryl diazonium salts, alkenes, and simple metal halides. This approach offers a general and straightforward method for obtaining a diverse array of α‐halo alkylboronic esters, thereby paving the way for the extensive utilization of these synthons in the synthesis of fine chemicals. [ABSTRACT FROM AUTHOR]

Quinazolines are biologically potent heterocyclic compounds; however, their synthesis poses high challenges. In this present study, we have developed an inexpensive cobalt metal‐catalyzed acceptorless dehydrogenative pathway for the sequential synthesis of alkenylated quinazolines from benzhydrol via dehydrogenation, cyclization, and subsequent dehydrogenative sp3 C−H functionalization. This transformation holds potential owing to its commercially available key starting materials, good functional tolerance, moderate reaction conditions, environmental friendliness, and applicability for gram‐scale synthesis. Furthermore, the synthetic utility of the synthesized derivatives has been explored through various reactions, including reduction, halogenation, methoxylation, Michael addition, and spiro cyclization. Additionally, the photophysical properties indicate that the nitrogen atom of the synthesized derivatives readily undergoes a reversible protonation, leading to significant changes in colour. This characteristic presents an opportunity for the creation of pH sensors with colourimetric capabilities. [ABSTRACT FROM AUTHOR]

Indoles are common motifs in functional agricultural and pharmaceutical molecules. Heteroatom alkylation is the most frequently used chemical reaction in the pharmaceutical field. Developing protocols for the nucleophilic substitution of (indol-2-yl)methyl electrophiles is important for functionalizing indoles. There are few studies on the nucleophilic substitution at the 2′-position of the electrophiles without an electron-withdrawing group at the 1-position or substituents at the 2′- and 3-positions, where the existing approaches require high temperatures and long reaction times. In this study, we demonstrated rapid (7–12 s) and mild (25 °C) microflow nucleophilic substitution at the 2′-position of indole derivatives without an electron-withdrawing group at the 1-position and substituents at the 2′- or 3-positions. Comparable batch conditions resulted in a lower yield. [ABSTRACT FROM AUTHOR]

Halogenation is one of the most important transformations in organic synthesis. Halogenated compounds are employed in many reactions to prepare useful molecules. Many methods have been developed to introduce halogens into different compounds. Visible light‐mediated reactions are the efficient, low‐toxic, and mild‐condition methods applied for various organic chemistry transformations. Remarkably, there has been an increasing development in the application of visible light‐induced halogenation in recent years. Herein, we present a comprehensive summary of halogenation reactions including chlorination, bromination, and iodination under visible light irradiation since 2020. [ABSTRACT FROM AUTHOR]

A practical and efficient synthetic route to construct a variety of 3-halochromones has been realized using Selectfluor reagent as a fluorine source, or Selectfluor-copper(I) halide combination as halogen source under mild conditions. This reaction proceeds via a sequence of electrophilic cation addition, and cyclization leading to a broad range of 3-halochromones in good to excellent yields in a short period of time. Additionally, the utilization of commercially available and cost-effective Selectfluor and copper(I) halide renders this system highly practical. [ABSTRACT FROM AUTHOR]

Alkenes are valuable feedstocks in organic synthesis. One effective method for synthesizing organic halides with functional groups in close proximity involves the direct difunctionalization of alkenes via three‐component reactions. This approach not only reduces the number of steps involved in the synthesis process, but also minimizes waste generation and enables the formation of complex molecules from simple starting materials. In this review, we mainly discuss decade developments (2013‐2023) in two categories: (1) halogenation via three‐membered ring intermediates, involving haliranium, thiiranium,seleniranium, aziridinium and epoxide species; (2) halogenation via a radical pathway. Reactions with I2, BiI3, NaI, Bu4N+[I(O2CAr)2]−, NIS, NBS, NCS, DBH, BsNMeBr, HBr, HCl, KI, NH4I, I2O5, Et3N ⋅ 3HF, Selectfluor, CuI, CuBr, CuCl, LiCl, KBr, NaCl, SOCl2, Py ⋅ 9HF, NFSI, TBSCl et al have been recorded and how the added reagents work will be discussed. We hope this review will do help for future research in this area. [ABSTRACT FROM AUTHOR]

We explored the ambiphilic reactivity of SF5‐alkynes, and we proved they can act as both nucleophiles and electrophiles. We selected halogenation reactions as benchmark reactions and developed highly selective stereodivergent hydrohalogenation (I, Br, Cl, F) reactions of SF5‐alkynes. The stereochemistry is finely controlled thanks to the nature of the acids used (strong or soft) in the presence of halide source, while the high regioselectivity is governed by the strong polarization of SF5‐alkynes. Mechanistic studies supported by DFT calculations shed light on two different reaction mechanisms responsible of the excellent stereocontrol. This stereoselectivity was quantitatively rationalized with the ASM and EDA methods. A few dihalogenation reactions are reported and DFT calculations rationalize this cis‐stereoselectivity. Relative configuration of all the SF5‐haloalkenes was unambiguously determined by X‐ray diffraction. Noteworthy, several post‐functionalization reactions such as cross‐couplings, cyanation and reductions are described to strengthen the synthetic potential. [ABSTRACT FROM AUTHOR]

Halogenation of Y‐series small‐molecule acceptors (Y‐SMAs) is identified as an effective strategy to optimize photoelectric properties for achieving improved power‐conversion‐efficiencies (PCEs) in binary organic solar cells (OSCs). However, the effect of different halogenation in the 2D‐structured large π‐fused core of guest Y‐SMAs on ternary OSCs has not yet been systematically studied. Herein, four 2D‐conjugated Y‐SMAs (X‐QTP‐4F, including halogen‐free H‐QTP‐4F, chlorinated Cl‐QTP‐4F, brominated Br‐QTP‐4F, and iodinated I‐QTP‐4F) by attaching different halogens into 2D‐conjugation extended dibenzo[f,h]quinoxaline core are developed. Among these X‐QTP‐4F, Cl‐QTP‐4F has a higher absorption coefficient, optimized molecular crystallinity and packing, suitable cascade energy levels, and complementary absorption with PM6:L8‐BO host. Moreover, among ternary PM6:L8‐BO:X‐QTP‐4F blends, PM6:L8‐BO:Cl‐QTP‐4F obtains a more uniform and size‐suitable fibrillary network morphology, improved molecular crystallinity and packing, as well as optimized vertical phase distribution, thus boosting charge generation, transport, extraction, and suppressing energy loss of OSCs. Consequently, the PM6:L8‐BO:Cl‐QTP‐4F‐based OSCs achieve a 19.0% efficiency, which is among the state‐of‐the‐art OSCs based on 2D‐conjugated Y‐SMAs and superior to these devices based on PM6:L8‐BO host (17.70%) and with guests of H‐QTP‐4F (18.23%), Br‐QTP‐4F (18.39%), and I‐QTP‐4F (17.62%). The work indicates that halogenation in 2D‐structured dibenzo[f,h]quinoxaline core of Y‐SMAs guests is a promising strategy to gain efficient ternary OSCs. [ABSTRACT FROM AUTHOR]

The structure of molecular aggregates is crucial for charge transport and photovoltaic performance in organic solar cells (OSCs). Herein, the intermolecular interactions and aggregated structures of nonfused‐ring electron acceptors (NFREAs) are precisely regulated through a halogen transposition strategy, resulting in a noteworthy transformation from a 2D‐layered structure to a 3D‐interconnected packing network. Based on the 3D electron transport pathway, the binary and ternary devices deliver outstanding power conversion efficiencies (PCEs) of 17.46 % and 18.24 %, respectively, marking the highest value for NFREA‐based OSCs. [ABSTRACT FROM AUTHOR]

An efficient and rapid protocol for the oxidative halogenation of tryptamines with 10 % aqueous NaClO has been developed. This reaction is featured by its operational simplicity, metal‐free conditions, no purification, and high yield. Notably, the resulting key intermediates are suitable for further functionalization with various nucleophiles, including amines, N‐aromatic heterocycles, indoles and phenols. The overall transformation exhibits broad functional‐group tolerance and is applicable to the late‐stage functionalization of complex biorelevant molecules. [ABSTRACT FROM AUTHOR]

Due to their high anisotropic behavior, liquid crystals possess strong nonlinear optical properties. The RM734 liquid crystal is famous for having high anisotropic behaviors compared to traditional liquid crystals. The present work focused on the evaluation of electronic, charge-transport, nonlinear optical, electro-optical, and thermochemical properties of the RM734 liquid crystal. Furthermore, the effect of halogenation on the above properties of RM734 was investigated and is discussed in depth as halogen substitution on the liquid crystal molecule can alter the quantum mechanical properties of any liquid crystal molecule. Density functional theory combined with B3LYP and dispersion correction were used to calculate the properties of RM734. The 6-311G** basis set was used for the estimation of these properties, whereas def2-TZVPD was used to evaluate the nonlinear optical parameters. Due to the halogenation of RM734, its electronic properties vary significantly. By halogenation, a better electron-transport molecule can be converted into a hole-transport molecule. The electro-optical properties were calculated with the application of an external electric field for all molecules. With the help of the order parameter, the nematic phase was observed for all reported molecules. The variation in the birefringence with respect to the external electric field was investigated and discussed in detail. Therefore, the present study reveals the significant impact of halogenation in terms of the nonlinear optical and thermochemical properties of RM734. [ABSTRACT FROM AUTHOR]

[Display omitted] Hard carbon as a negative electrode material for sodium-ion batteries (SIBs) has great commercial potential and has been widely studied. The sodium-ion intercalation in graphite domains and the filling of closed pores in the low voltage platform region still remain a subject of controversy. We have successfully constructed hard carbon materials with a pseudo-graphitic structure by using polymerizable p -phenylenediamine and dichloromethane as carbon sources. This was achieved by a halogenated amination reaction and oxidative polymerization. It was found that the capacity of hard carbon materials mainly originates from intercalation into graphite domains. The study found that the prepared hard carbon could store 339.33 mAh g−1 of sodium in a reversible way at a current density of 25 mA g−1, and it had an initial coulomb efficiency of 80.23%. It even maintained a reversible sodium storage capacity of 125.53 mAh g−1 at a high current density of 12.8 A g−1. Based on the analysis of hard carbon structure and electrochemical performance, it was shown that the materials conform with an "adsorption-intercalation" mechanism for sodium storage. [ABSTRACT FROM AUTHOR]

Herein, we disclose a new strategy that rapidly and reliably incorporates bromine atoms at distal, secondary C(sp3)−H sites in aliphatic amines with an excellent and predictable site‐selectivity pattern. The resulting halogenated building blocks serve as versatile linchpins to enable a series of carbon‐carbon and carbon‐heteroatom bond‐formations at remote C(sp3) sites, thus offering a new modular and unified platform that expediates the access to advanced sp3 architectures possessing valuable nitrogen‐containing saturated heterocycles of interest in medicinal chemistry settings. [ABSTRACT FROM AUTHOR]

Vicinal halohydrins are key building blocks to produce bioactive molecules and drugs, especially if they can be obtained in enantiomerically pure form. In this study, we present a bi‐enzymatic sequence that allows to obtain vic‐halohydrins through a photochemoenzymatic olefin hydroxy halogenation followed by a lipase catalysed kinetic resolution. The absolute configuration of the resulting products was determined using Mosher's method [ABSTRACT FROM AUTHOR]

The halogenation of alkenes is a crucial pathway in forming C-X bonds, with a significant impact on organic synthesis and pharmaceuticals. However, traditional methodologies present potential hazards to both the environment and human health, making the quest for green and efficient halogenation methods paramount. In this study, we introduce a novel iron catalyst based on a polyoxometalate, (NH4)3[FeMo6O18(OH)6], simplified as Fe(III)Mo6. Employing this catalyst, a plethora of styrene derivatives and alcohols were efficiently and successfully converted to the corresponding halogenated products. Also, our catalyst showed excellent performance toward the reaction with various substrates. Moreover, it demonstrates high stability and activity in the cycle test. In addition, we also described the reaction mechanism based on the control experiment. The catalyst exhibits non-toxic, green, and environmentally friendly characteristics that provide future industrialization potential. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Chemodivergent synthesis of benzofurans and 2,3‐dihydrobenzofurans has been realized. Under a reaction system consisting of DBDMH and K2CO3 as promotors, controlled conditions enabled the formation of two sets of valuable heterocycles from the tandem transformation of enaminones and salicylaldehydes. The key to success was the identification of the reaction parameters, in which the imine intermediate which was formed by transient halogenation coupling and substitution processes underwent either aldol condensation/annulation or imine hydrolysis/aldol condensation. The additives NH4Cl or Fe2(SO4)3 controlled the unique selectivity of this reaction. A broad substrate scope of enaminones and salicylaldehydes has been employed in this reaction, demonstrating excellent functional group tolerance and versatility. [ABSTRACT FROM AUTHOR]