Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• capable of modulating reaction stereoselectivity. Hydrazone Hydrazones undergo trans–cis isomerization at the C=N bond when exposed to light, and in some instances, they can also undergo thermal isomerization (Figure 2) [69]. Although there are early reports of hydrazone derivatives in rotaxanes [70], the

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• -dioxides, we aimed at elaborating a synthetic procedure for the preparation of their pyrrole-fused counterparts, 2,9-dihydro[1,2,3]thiadiazino[5,6-g]indole 1,1-dioxide derivatives. The simple and versatile process led, via Fischer indole cyclization of the corresponding hydrazones, to a wide structural

• variety of new tri-, tetra- and pentacyclic ring systems. The structural characterization of (E)- and (Z)-hydrazones was supported by 2D NMR techniques, while that of the target compounds by single-crystal X-ray measurements. The hydrazone intermediates and the new title compounds were subjected to a

• synthesis [18][19][20][21]. Sudhakara et al. described the advantages of using bismuth nitrate as catalyst in the synthesis of hydrazones and in the one-pot Fischer synthesis of indoles from ketones and hydrazines [22][23]. Adopting this method, hydrazone intermediates 7a–j were obtained by treatment of

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• the thermal stability from hundreds of years to a few days. The addition of a further hydrogen-bond acceptor on the stator led to the discovery of hydrazones with a thermal stability of thousands of years (Scheme 34, left) [111]. The extra H-bond in 106-E and 107-E raises the energy of the linear

• weaken the hydrogen bonds between N–H and the ester moieties of the rotor and the stator. The Cigáň group focused on the synthesis of benzoylpyridine hydrazones with different substitutions in the rotor benzene [97]. The p-NMe2 group causes red-shift of both absorption maxima of the E- and Z-isomer

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• on our earlier publications and the data presented here, it is reasonable to predict that the high-pressure activation strategy will gain broad application possibilities in the future. Experimental Materials and methods Materials: All substrates (aldehydes, hydrazones, alcohols, p-aminophenol

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• . Therefore, my team reviewed the recent progress in organocatalytic syntheses of axially chiral compounds [28]. The final article within this thematic issue was contributed by Tsogoeva, Harder, and co-workers. They developed and mechanistically studied the hydrocyanation of hydrazones. This interesting

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• hydrocyanation of hydrazones, catalyzed by a calcium–BINOL phosphate complex, has been studied for the first time both experimentally and computationally with DFT methods. A full catalytic cycle for the enantioselective synthesis of α-hydrazinonitriles is proposed based on insights gained from DFT calculations

• ; hydrazones; isocyanides; Introduction Catalytic applications of non-toxic earth abundant metals like calcium are currently on the rise [1][2][3][4]. Prominent recent examples that witness the versatility of calcium catalysis include calcium-catalyzed amination of π-activated alcohols [5], the Beckmann

• [40][41][42][43][44]. However, this catalytic system has not yet been employed explicitly in the hydrocyanation of hydrazones. In 2010, our group reported the first organocatalytic enantioselective hydrocyanation of hydrazones catalyzed by BINOL phosphate [45], giving valuable and potentially

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• synthesis of tripeptides incorporating new fluorinated heterocyclic hydrazino acids, based on the tetrahydropyridazine scaffold is described. Starting from simple fluorinated hydrazones, these non-proteinogenic cyclic β-amino acids were easily prepared by a zinc-catalyzed aza-Barbier reaction followed by an

• for peptide synthesis. Consequently, developing a simple and efficient methodology is still challenging. Our new strategy to synthesize these compounds is based on an aza-Barbier reaction on difluoro- or trifluoromethylated hydrazones. The thus obtained compounds will then be oxidized and cyclized in

• order to lead to the expected fluorinated tetrahydropyridazines (Figure 4). Results and Discussion First, the difluoro- and trifluoromethylated hydrazones 3a–f were synthesized by condensing the corresponding hydrazide with the fluorinated aldehyde hemiacetal 2a or 2b (Scheme 2). Benzyl and tert-butyl

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• /Education Center for Excellence in Molecular Sciences Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China 10.3762/bjoc.20.242 Abstract The selective C–H trifluoromethylthiolation of aldehyde hydrazones afforded interesting fluorinated building blocks, which could be used as a

• synthetic platform. Starting from readily available (hetero)aromatic and aliphatic hydrazones, the formation of a C–SCF3 bond was achieved under oxidative and mild reaction conditions in the presence of the readily available AgSCF3 salt via a one-pot sequential process (28 examples, up to 91% yield

• ). Mechanistic investigations revealed that AgSCF3 was the active species in the transformation. Keywords: C–H bond functionalization; C–S bond formation; hydrazones; synthetic method; trifluoromethylthiolation; Introduction Fluorinated molecules are of paramount importance [1][2][3][4][5][6][7][8][9][10][11

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• separate peaks on chiral HPLC. Kinetic resolution of chiral secondary allylboronates [15][30]. (E)-Stereospecific asymmetric α-trifluoromethylallylation of cyclic imines and hydrazones [31]. Hosomi–Sakurai-type allylation of in situ-formed N-Fmoc aldimines [32]. Chiral squaramide-catalysed hydrogen bond

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• their synthesis have been extensively reviewed [93]. When hydrazones undergo cyclization with β-ketoesters or ketones, the stability of the enol form of the carbonyl compounds plays a crucial role in the reaction. Recognizing this, a series of multicomponent reactions has been developed to synthesize

• , facilitating their cyclization with intermediary formed hydrazones to yield 5-hydroxypyrazolines. After subsequent interaction with atmospheric oxygen, the product 65 is formed. This method exhibits a high degree of substituent tolerance, and aliphatic compounds generally lead to higher yields. A special

• the process for both electron-rich and electron-poor aldehydes. In addition to fully substituted pyrazoles, the method also provides access to anellated products. Lellek's team has developed an alternative method for cyclizing hydrazones. In contrast to the previously mentioned method, intermediately

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• Aurelie Claraz Institut de Chimie des Substances Naturelles, CNRS, Univ. Paris-Saclay, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France 10.3762/bjoc.20.175 Abstract Hydrazones are important structural motifs in organic synthesis, providing a useful molecular platform for the

• construction of valuable compounds. Electrooxidative transformations of hydrazones constitute an attractive opportunity to take advantage of the versatility of these reagents. By directly harnessing the electrical current to perform the oxidative process, a large panel of organic molecules can be accessed from

• readily available hydrazones under mild, safe and oxidant-free reaction conditions. This review presents a comprehensive overview of oxidative electrosynthetic transformations of hydrazones. It includes the construction of azacycles, the C(sp2)−H functionalization of aldehyde-derived hydrazones and the

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• ]isoxazolone derivatives with various hydrazines was studied. It was shown that the considered process includes formation of corresponding hydrazones followed by Boulton–Katritzky rearrangement. As a result, the general method for the synthesis of substituted 1,2,3-triazoles bearing an allomaltol fragment was

• types of aforementioned structures were proved by X-ray analysis. Keywords: allomaltol; Boulton–Katritzky rearrangement; hydrazones; pyrano[2,3-d]isoxazolones; recyclization; 1,2,3-triazoles; Introduction The Boulton–Katritzky rearrangement (BKR) also known as mononuclear heterocyclic rearrangement is

• participation of hydrazones attract special attention. This reaction is a general method for the preparation of 1,2,3-triazoles bearing various substituents at position 2. Wherein, depending on the type of starting heterocycles various functional derivatives are formed. So, the well-known Boulton–Katritzky

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• hydride. In 2018, the Milstein group demonstrated a partial hydrogen-borrowing reaction with a manganese-pincer complex by coupling alcohols and hydrazine to form N-substituted hydrazones. Benzylic and aliphatic alcohols were studied with hydrazine using Mn(t-Bu-PNN)(CO)2Br (Mn5, 3 mol %) and a catalytic

• condenses with hydrazine followed by reduction and condensation with another aldehyde to afford the N-substituted hydrazones (Scheme 8). Balaraman and co-workers established a phosphine-free manganese catalyst generated in situ from a manganese precursor and a ligand for the N-alkylation of anilines with

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• us to try another protecting group for the formyl function, namely arylhydrazone. Thus, reactions of compounds 7a–c with a number of arylhydrazines afforded the corresponding hydrazones 11 which were not isolated and subjected to cyclization under the action of K2CO3 (Scheme 5). In most cases the

• were performed for compounds 12c and 13c,d (Figure 3; see Supporting Information File 1 for details) that allowed us to unambiguously establish the structures of both the starting hydrazones and rearrangement products. Conclusion In summary, we have developed an efficient method for the synthesis of

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• ][20][21][22][23][24][25][26][27], which can be readily generated in situ from α-halogeno hydrazones, have been extensively applied in recent years as versatile building blocks in inverse-electron-demand Diels–Alder (IEDDA) reactions [28][29][30] to construct diverse nitrogen-containing heterocycles

• follows: 1a (1.0 mmol), 2a (1.5 mmol), Et3N (2.0 mmol), in acetonitrile at 25 °C with stirring for 2 hours (Table 1, entry 14). With the optimized reaction conditions in hand, we next investigated the scope of the current reaction (Scheme 2). As shown in Scheme 2, a series of α-halogeno hydrazones 2b–l

• was tested, resulting in the expected spiropyridazine-benzosultams 3ab–al in good to excellent yields with high diastereoselectivity. For N-benzoyl hydrazones 2b–g, the electronic effect of R3 group on the [4 + 2] annulation reaction was significant. Electron-withdrawing groups gave relatively higher

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• of transannular cycloadditions of cycloalkenone hydrazones catalyzed by BINOL-derived phosphoric acid are reported in the Full Research Paper by Vicario, Merino, and co-workers [10]. Their methodologies can now be used to predict the reactivity of different substrates in other cycloaddition reactions

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• [indoline-3,5'-[1,2]diazepines] 3a–m were obtained in reasonable to good yields. Both, α-chloro- and α-bromo-N-acylhydrazones could be successfully used in the reaction and gave similar results. Also, hydrazones with different benzoyl-protecting groups were well tolerated in the reaction. In general, α

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• in various pharmaceutical and agrochemical products. This review focuses on the reactivity, synthesis, and applications of fluoromethylated hydrazones and acylhydrazones. It summarizes recent methodologies that have been used for the synthesis of various nitrogen-containing organofluorine compounds

• . Keywords: acylhydrazones; difluoromethylation; dihydropyridazine; fluorinated building blocks; hydrazones; imidazolidines; pyrazoles; pyrazolidines; pyrazolines; trifluoromethylation; Introduction The introduction of fluorine into pharmaceuticals, agrochemicals, and materials can significantly enhance

• building blocks offers another mainstream approach to introducing fluorine. Among these, di/trifluorodiazoethane [19][20][21][22], trifluoromethyl aldimines [23][24][25], trifluoroacetimidoyl halides [26], and fluoroalkyl N-sulfonyl hydrazones [27] have emerged as powerful nitrogen-containing fluorinated

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• studied and reported biological properties of this class [2][18][19][20]. Angelova and co-workers, for example, reported the ability of sulfonyl hydrazones and 4-methyl-1,2,3-thiadiazole-based hydrazone derivatives to inhibit the growth of several bacterial strains by interfering with their metabolism or

• cell membrane integrity [21]. In the context of cancer therapy development, metal complexes of N-acylhydrazones stand out. For example, Firmino et al. demonstrated that gallium(III) complexes of isoniazid-derived hydrazones exhibit strong cytotoxicity against HL-60 and HCT-116 cancer cell lines [22

• in AD. As a continuation of our long-term effort on the development of potentially bioactive N-acylhydrazones, the present work comprises a structural and spectroscopic comparison, from both experimental and theoretical viewpoints, of two structure-related hydrazones. Both compounds are new, and

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• , chalcogensuccinimide as an electrophile, and cyclopropane as a zwitterion component (Scheme 21) [58]. In 2020, a Lewis acid-mediated cyclization of β,γ-unsaturated oximes 51 and hydrazones 52 with N-(arylsulfenyl)succinimide 1 and N-(arylseleno)succinimide 1’’ was extended for the formation of isoxazoles 53 and

• construction of 4-chalcogenylated pyrazoles 57 and 59 was carried out starting from α,β-alkynic hydrazones 55 (Scheme 24) [60]. In the procedure, α,β-alkynic hydrazones were subjected to S- or Se-electrophiles 56 and cyclization reaction. Additionally, NCS and ArSH produced the S-electrophile for the

• cyclization reaction with arylpropynal hydrazones. Also, the reaction of 1-(1,3-diphenylprop-2-yn-1-ylidene)-2-phenylhydrazine 58 as the substrate with N-sulfenylsuccinimides 1 afforded fully substituted pyrazoles 59 in up to 98% yield. In 2021, a solvent-controllable approach for the construction of 3

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• significantly affect the C–H alkylation reaction and the reaction also proceeded well with hydrazones 13 obtained from aliphatic aldehydes or ketones. Based on mechanistic experiments and DFT calculations, the reaction presumably proceeds via a Cu–carbene migratory insertion (Scheme 4b). In the presence of CuI

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• Bilbao, Spain Instituto de Síntesis Química y Catálisis Homogénea (SQCH), Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain 10.3762/bjoc.19.37 Abstract The contribution to the energy barrier of a series of tethers in transannular cycloadditions of cycloalkenes with hydrazones has been computationally

• by the tethers, the entropy effects caused by them has also been studied. The analysis of the evolution of the electron localization function along the reaction revealed the highly concerted character of the reaction. Keywords: DFT; distortion model; hydrazones; transannular cycloadditions

• and co-workers demonstrated for transannular Diels–Alder cycloaddition reactions of symmetrically tethered large systems (10–18-membered rings) [29]. In this context, we have recently reported the transannular enantioselective (3 + 2) cycloaddition of cycloalkenone hydrazones under Brønsted acid

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• evaporation, to waste, if it is the undesired phase, or to a further telescoped step. One example of this approach to separate hydrazones in dichloromethane after the aqueous quench is depicted in Scheme 6. This setup, although widely used in the above-mentioned group, has not been reported by other groups or

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• hydrazone groups. The use of N-TAAD derivatives as potential ligands and receptors was showcased through forming boron chelates and host–guest complexes with water and simple alcohols. Keywords: azaadamantanes; cyclotrimerization; hydrazones; inclusion complexes; molecular recognition; Introduction

• cyclization of the corresponding tris-hydrazones, as well as the assembly of unsymmetrically substituted TAADs having both amino(amido) and hydroxy groups at bridge nitrogen atoms (2N,1O-TAADs and 1N,2O-TAADs) via a hitherto unknown co-trimerization of oxime and hydrazone units [35]. Also, structural studies

• -oxime form 1). Previous experimental and computational data evidence that cyclotrimerization of hydrazone groups proceeds more readily compared to oximes [18]. Hence, hydrazones 3 were expected to cyclize to corresponding TAADs 4 with high efficiency. On the other hand, cyclization of mixed oxime