Mathias

Traditional chemical nitration faces many problems, while biocatalytic nitration, as a promising alternative, can utilize natural nitrifying enzymes to prepare aromatic and heterocyclic nitro compounds. This review summarizes the representative nitrifying enzyme and discusses the current challenges and future opportunities faced by bio-nitration, to provide references for the synthesis of natural and non-natural nitro compounds.

Nitro compounds are widely utilized as value added pharmaceuticals and explosives, the majority of which contain a nitro group on an aromatic or heterocyclic ring. Nitration of aromatic or heterocyclic rings typically relies on well-established chemical methods, but the harsh conditions, unsatisfying selectivity, and low efficiency need to be solved for practical application. In contrast, biocatalytic nitration offers a promising alternative in the preparation of nitro compounds with complex aromatic and heterocyclic structures. The earliest nitrifying enzymes were found in the metabolic pathways of several natural products having aromatic or heterocyclic nitro groups. With evolved and engineered nitrifying enzymes, bio-nitration can be achieved for the preparation of a broader range of unnatural nitro group containing compounds. This study provides a comprehensive summary of the representative nitro compounds having nitro groups on the aromatic and heterocyclic rings, the associated nitrifying enzymes, and the characteristics of representative nitrifying enzymes which present specific nitration mechanisms. This study also discusses challenges with current bio-nitration techniques and proposes future opportunities for the application of bio-nitration as a powerful tool in the synthesis of natural and unnatural nitro compounds.

Synthesis
DOI: 10.1055/a-2779-1020

Nitroarenes are versatile building blocks in organic synthesis, and their photochemical reactivity has recently enabled new transformations, including oxidative cleavage reactions. Here, we disclose a sustainable isomerization strategy in which nitroarenes function as energy-transfer (EnT) photocatalysts to convert cinnamyl chlorides into cyclopropanes. In contrast to conventional methods that rely on transition-metal photocatalysts, this approach capitalizes on the intrinsic triplet energy of nitroarenes, offering a metal-free and operationally simple solution. Preliminary studies indicate that the π,π* triplet state of nitroarenes is more efficient in EnT than the n,π* state, revealing a distinct divergence in their excited-state reactivity. Standard silica gel (SiO₂) serves as an effective additive to promote the reverse isomerization of the resulting 1-arylallyl chlorides to cinnamyl chlorides, further enhancing the overall process efficiency.
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Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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Synthesis
DOI: 10.1055/a-2779-3996

Organic N-nitro reagents are emerging as efficient nitrating agents in modern organic chemistry. Traditionally, nitration methodologies rely on the use of mixed acids employing harsh reaction conditions. The use of N-nitro compounds offers milder, greener, and more sustainable alternatives. These organic reagents facilitate the introduction of nitro groups into a variety of aromatic and aliphatic substrates with improved regio- and chemoselectivity, as well as excellent functional group tolerance. Their growing utility in pharmaceutical and materials synthesis highlights their significance as valuable tools for sustainable nitration processes. In this review, we have described the organic transformation involving N-nitro reagents.
[...]

Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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Nature Catalysis, Published online: 22 December 2025; doi:10.1038/s41929-025-01458-8

Nature Catalysis, Published online: 17 December 2025; doi:10.1038/s41929-025-01453-z

A straightforward one-step protocol enables the synthesis of bio-based and biologically active isochromans through the Oxa-Pictet cyclization involving diverse aldehydes, including vanillin in combination with lignin-derivable homovanillyl alcohol, a prominent aromatic platform chemical obtainable via diol-assisted fractionation of lignocellulose, employing tunable deep eutectic solvents as benign reaction media.

ABSTRACT

Clean synthetic strategies that embrace the inherent structural features of renewable building blocks to obtain biologically active compounds hold great potential to improve the economic viability of emerging biorefineries. Importantly, such an approach is highly beneficial for the sustainable manufacturing of pharmaceutically relevant molecules. Here, we demonstrate a one-step protocol toward biologically active isochromans through the Oxa-Pictet cyclization involving both aromatic aldehydes, including vanillin, and aliphatic aldehydes in combination with lignin-derivable homovanillyl alcohol (1), a prominent aromatic platform chemical obtainable via diol-assisted fractionation. Employing tunable deep eutectic solvents as benign reaction media allows for modulating reactivity under mild reaction conditions, and opens access to a library of isochromans in a single step. Several compounds exhibit promising properties, including PPI inhibition, anticancer, and antibacterial activities, highlighting the benefits of this synthetic strategy and its potential for drug discovery.

The aviation sector's reliance on fossil kerosene is a major source of CO₂ emissions, while wood waste represents an abundant, renewable carbon resource that can help reduce its footprint. Hemicellulose and lignin are catalytically converted into kerosene-like naphthenes via Friedel–Crafts alkylation and hydrodeoxygenation, enabling sustainable drop-in aviation fuels compatible with existing engines and infrastructure.

Abstract

To address the aviation sector's growing carbon footprint, this study presents a novel route for producing sustainable aviation fuel precursors via acid-catalyzed Friedel–Crafts alkylation of wood-derived lignin monomers with furfuryl alcohol. Using guaiacol as a model compound, key catalytic requirements were investigated in batch mode. Although heterogeneous zeolites showed initial promise, pore blocking by oligomerized furfuryl alcohol limited performance, leading to the selection of para-toluenesulfonic acid as an effective homogeneous catalyst. A fed-batch strategy was employed to suppress oligomerization by controlling furfuryl alcohol concentration. The resulting alkylated products, structurally aligned with conventional kerosene, were further upgraded via metal-catalyzed hydrodeoxygenation, achieving final overall yields up to 92 C%.

Publication date: March 2026

Source: Tetrahedron, Volume 191

Author(s): Qing Shen, Shuangqiao Li, Xianglin Zhong, Yang-Bao Miao, Jiahong Li

A visible-light-driven, iron-catalyzed cascade enables the one-pot synthesis of 3-arylamino-2-aryl-2H-indazoles from readily available o-nitrobenzyl alcohols and anilines under mild, sustainable conditions. The process involves photoinduced formation of o-nitrosobenzaldehyde, followed by condensation, cyclization, and aromatization. The resulting indazoles exhibit a selective fluorescence quenching response toward hypochlorite, highlighting their potential for ClO⁻ detection.

2H-Indazole scaffolds represent privileged structural motifs prevalent in a wide range of bioactive compounds and pharmaceutical agents. Despite their significance, conventional synthetic approaches to 2H-indazole derivatives often suffer from limitations such as harsh reaction conditions, the use of expensive or toxic catalysts, and multistep procedures. To address these challenges, we report a cost-effective, environmentally benign, and one-pot strategy for the synthesis of biologically and synthetically valuable 3-arylamino-2-aryl-2H-indazoles. This method employs readily available o-nitrobenzyl alcohols as key building blocks and utilizes a Lewis acid iron salt as a catalyst under visible light irradiation, harnessing the excited-state reactivity of the substrates. The transformation proceeds efficiently without the need for precious metal catalysts, external oxidants, or additives and operates under mild and sustainable conditions. The protocol enables the construction of structurally complex 2H-indazoles, including those embedded in medium-sized rings. Notably, the synthesized 3-arylamino-2-aryl-2H-indazoles exhibit a selective fluorescence quenching response toward hypochlorite, highlighting their potential as an effective probe for ClO⁻ detection.

Double trouble lignin is first reductively depolymerized with a palladium catalyst to form smaller lignin macromolecules enriched in phenolic hydroxyl groups. Afterward, these macromolecules are exposed to Co(salen)-catalyzed oxidative cleavage, initiated at the phenolic OH sites, to form benzoquinones and benzaldehydes.

This study investigates a tandem Pd-catalyzed reductive depolymerization of lignin and subsequent Co(salen)-catalyzed oxidative cleavage to obtain benzoquinones and benzaldehydes. The reductive depolymerization will result in lignin macromolecules with heavily increased phenolic OH content, which are then selectively cleaved by the Co(salen) catalyst to yield benzoquinones and benzaldehydes. Compared to lignin samples that do not undergo reductive depolymerization first, benzoquinone yields are substantially increased.

Cobalamin-dependent aryl methyl ether O-demethylases have high potential for biocatalytic applications, including lignin valorization and synthetic chemistry. In this review, we provide a detailed overview of such O-demethylase systems identified to date from various microorganisms, including their mechanism, substrate scope and selectivity, and further discuss their potential for biocatalytic applications.

Abstract

Cobalamin-dependent aryl methyl ether O-demethylase is a multi-component enzyme system that converts O-methylated aromatic compounds into demethylated phenolics. The central enzyme of the system is a cobalamin-dependent protein that interacts with methyltransferase enzymes for transferring the methyl group between O-methyl groups of aryl methyl ethers and various methyl acceptors. Besides their role in energy metabolism of certain anaerobic bacteria, O-demethylases possess high potential for biocatalysis, including lignin valorization and use in organic synthesis for reversible (de)methylation reactions. An increasing number of cobalamin-dependent O-demethylase enzyme systems from various bacteria, including gut microorganisms, with different substrate scopes and regioselectivity profiles have been identified in the recent decade. Moreover, biocatalytic studies have been carried out on O-demethylase systems demonstrating their potential in synthetic applications. In this review, we provide a comprehensive overview of the cobalamin-dependent aryl methyl ether O-demethylase systems identified to date in various microorganisms. We present the mechanism, biological function, substrate scope and selectivity of the studied systems and discuss their potential for biocatalytic applications.

N═O/NHOH redox chemistry, inspired by biological processes, enables proton-coupled two-electron storage with high voltage and fast kinetics, providing a blueprint for high-capacity organic cathode materials for aqueous proton batteries.

Abstract

Organic cathode materials are emerging candidates for aqueous proton batteries due to their structural tunability and sustainability. However, the simultaneous realization of high voltage, low solubility, and high capacity remains a major challenge. In this study, we introduce a biomimetic redox pair, nitroso/hydroxylamine (─N═O ⇌ ─NH─OH), for the first time in energy storage systems. We report 1-(hydroxyamino)anthracene-9,10-dione (NHOH-A), a rationally designed aromatic hydroxylamine compound capable of undergoing a highly reversible proton-coupled two-electron redox process. Benefiting from its strong hydrogen bonding, uniform charge distribution, and extended π-conjugation, NHOH-A delivers a high discharge voltage of 1.15 V, excellent capacity of 224 mAh g⁻¹, and remarkable cyclability (> 13,000 cycles) when coupled with a Zn anode. Furthermore, leveraging its intrinsic proton-donating capability, we construct a rocking-chair type all-organic proton battery by pairing NHOH-A with an alloxazine anode. The full cell maintains 164 mAh g⁻¹ at 100 C (1 C = 224 mA g⁻¹) and delivers an energy density of 125 Wh kg⁻¹, among the highest for all-organic proton batteries. This work establishes the N═O/NHOH chemistry as a promising redox platform, opening new avenues for developing advanced organic cathodes in energy storage systems.

A palladium-catalyzed denitrative decarboxylation protocol is developed, which couples nitroarenes with terminal alkynyl carboxylic acids bearing silyl, aliphatic, and aryl substituents. 48 aryl alkynes can be directly constructed from readily available nitro precursors and the yield is up to 85%. Significantly, the cost-effective and ecofriendly protocol permits efficient regiochemical synthesis of 3-substituted benzofuran or isochromen-1-one derivatives.

A general approach for the decarboxylation of alkynyl carboxylic acids with nitroarenes via denitrative coupling is reported for the first time. The methodology demonstrates broad substrate generality, accommodating diverse nitroaromatics, including electron-deficient heteroarenes, to deliver aryl alkynes with high efficiency. Notably, this methodology enables the use of nitroarenes and aryl-substituted carboxylic acids to access diarylacetylene products. Furthermore, this protocol permits efficient synthesis of 3-substituted benzofuran or isochromen-1-one derivatives, which is a challenging regiochemical outcome unattainable through conventional coupling strategies.

A commercially available copper-hydride complex was utilized as an effective catalyst for the hydrosilylation of nitroarenes to aromatic amines. Nitroarenes with diverse functionalities were efficiently reduced to anilines with good chemoselectivity. The practicality of this reduction protocol was demonstrated through the synthesis of pharmaceuticals.

Abstract

Herein we report an effective catalytic hydrosilylation protocol for the reduction of nitroarenes to aromatic amines using a commercially available copper(I) complex as catalyst. This effective hydrosilylation of nitroarenes provides a legitimate and easier alternative to classical hydrogenation and Béchamp reduction. Various nitroarenes with wide functionalities were successfully reduced to the corresponding anilines, and chemoselective reduction of nitroarene was observed. The practical applicability of this protocol was also demonstrated by synthesizing various drug molecules and pharmaceutical intermediates.

This review aims to provide a comprehensive exploration of diboron compounds as new greener reducing agents in organic synthesis. It will cover their unique properties, mechanisms of action, and versatility in reducing various functional groups, such as carbonyls, nitro groups, alkenes, and alkynes. By highlighting their advantages over traditional hydride-based reagents and catalytic hydrogenation, the review emphasizes their role in advancing sustainable and safe chemical practices. Additionally, practical guidelines for employing diboron compounds in laboratory and industrial settings will be included, along with comparisons to alternative methodologies. This review intends to serve as an educational and practical resource for chemists, researchers, and industries adopting greener reduction strategies.

Reduction of various organic functionality including aldehyde, ketone, nitro, imine, and alkyne has gained noteworthy attention due to its vast application of products in organic transformation reactions. To attempt hydrogenation several approaches have been reported by using molecular hydrogen as a reducing source. Besides, this diboron (tetrahydroxy diboron, bispinacolato diboron, neoglycolato diboron) has shown a promising and alternative approach for the reduction of the reducible functional group without using any molecular hydrogen. The ligand-free reduction approach of commercially available diboron reduces the organic compound by using water or organic solvent and metal salt making it an attractive protocol in the recent era of reduction as well as hydrogenation. Herein, we provide an extensive and collective overview of the diboron-mediated reduction approach of various organic compounds.

Spontaneous and ultrafast C─O/C─C bond cleavage of various lignin models was achieved by taking advantage of the unique and strong alkaline environment at the air–water interface of a negatively charged water microdroplet, yielding value-added aromatic chemicals.

Abstract

Bulk water serves as an inert environment for lignin linkages, resulting in their natural half-lives that extend over centuries. In this study, we present the striking results of the spontaneous and ultrafast C─O/C─C bond cleavage of various lignin models in water microdroplets, yielding value-added aromatic chemicals. The β-O-4 linkages, the most abundant interunit linkages in natural lignin, were selectively cleaved at C_β─O bonds, producing phenols in yields exceeding 70%. Mechanistic studies elucidated that the cleavage of β-O-4 linkages is derived from the unique alkaline environment at the air–water interface of a negatively charged water microdroplet, even in the absence of extra alkalis. The challenging cleavage of the highly stable C_α─C_β bonds in β-O-4 and β-1 lignin linkages was also accomplished, yielding valuable benzoic acid product. Mechanistic investigations revealed that the oxidation of the substrates by molecular oxygen is the key step for the C_α─C_β bond cleavage. Notably, all intermediates, including the fragile peroxide intermediates, were identified using mass spectrometry. Accompanied by evidence from radical scavenging and ¹⁸O labeling, the mechanisms for the selective C─O/C─C bond cleavages have been unambiguously characterized, paving a new and green way for the cleavage of lignin linkages.

Synthesis
DOI: 10.1055/a-2593-4458

The environmentally friendly reduction of nitro compounds to their corresponding amino compounds has been a practical and challenging task. In this paper, a method has been developed for the reduction of nitroaromatics to aromatic amines by ball milling. The method uses cheap and available tetrakis(dimethylamino)diboron as the reducing agent and NaOH as the base, and the reduction reaction can be achieved by wet ball milling assisted by chitosan. A range of nitroaromatic compounds containing a variety of alkyl, halogen, polynitro, and other groups were chemoselectively reduced to the corresponding anilines in good yields. This protocol will enrich functional group transformations of nitroaromatics to amines.
[...]

Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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Publication date: 1 October 2025

Source: Tetrahedron, Volume 184

Author(s): Meijun Zhu, Lanqin Liu, Yujie Zhi, Hong Hou