Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• all of these authors confirmed, after analyzing the position of the deuterium atoms in the final compound, that the methylene unit incorporated into the heterocycle came from DMSO. In the case of pyrazole synthesis, Guo et al. proposed a three-component cascade reaction of enaminones, hydrazines, and

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

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

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• process with hydrazine derivatives is known in the literature. Therefore, the study of recyclizations of heterocyclic systems containing the 3-acylfuran-2(5H)-one core under action of various hydrazines is of a great interest. Ongoing our research in the field of allomaltol chemistry in the present

•  4). The suggested method allows one to utilize arylhydrazines both with donor and acceptor substituents in the aromatic ring. Besides that, heterocyclic hydrazines also can be used in the considered transformation. In addition, we have tried to carry out the process under investigation with

• h) failed in the case of aliphatic hydrazines (methylhydrazine, tert-butylhydrazine) leading to a complex mixture of products. Besides that, the use of hydrochlorides of aforementioned alkylhydrazines and EtOH as a solvent gave analogous negative results. At the same time, the disclosed

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• , hydrazines and alkenes with Cu(OTf)2 (20 mol %) in CH2Cl2 at reflux is a useful tool to access substituted 4,5-dihydropyrazoles 31 (Scheme 23) [40]. The products reasonably result from a Mannich/cyclization/oxidative transformation of the substrates in which Cu(OTf)2 is involved in more steps. The reaction

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• benziodoxolone was generated in situ, via a reaction of chlorobenziodoxolone with sulfinate salts, followed by the addition of amines or hydrazines, respectively. On the follow-up on our research, we envisaged to extend the diversity of BBX reagents as electrophilic amine reagents and investigated their

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

• . Allylation of fluorinated hydrazones 3a–f to obtain 5a–f. Oxidation of hydrazines 5a–f to obtain hydrazones 6a–f. Intramolecular cyclization of compounds 6a–f to obtain tetrahydropyridazines 7a–f. Preparation of tripeptides 8e, 8e’, 8f, and 8f’. Yields refer to the yield over 2 steps. Supporting Information

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• obtain α-acylaminoamides. Innovation in recent years with alternative reagents, like N-hydroxyimides or nitric acid in place of an acid, N-alkylated hydrazines, or nitrobenzene derivatives (reduced in situ to anilines) instead of amines, and in situ-prepared isocyanides, makes it a versatile method for

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• carbonates and 1,3-dicarbonyls. Proposed mechanism. Formal [4 + 1] annulations with amines. Formal [4 + 2] annulations with hydrazines. Proposed mechanism. Dearomative annulation of 1-naphthols and yne-allylic esters. Dearomative annulation of phenols or 2-naphthols and yne-allylic esters. Postulated

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• ketene dithioacetals [67] or β-ethylthio-β-indolyl-substituted α,β-unsaturated ketones [68], the cyclocondensation reaction of β-ethylthio-β-indolyl-substituted α,β-unsaturated ketones with hydrazines/hydroxylamine [69][70][71] and the tandem [5C + 1C/1N]-cycloaromatization of α-alkenoyl ketene

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

• syntheses known in the literature are based on the condensation of 1,3-dielectrophiles and their synthesis equivalents as C3-building blocks, along with hydrazines as N2-building blocks [25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Conceptually, the en route generation of these C3-building

• blocks or their transformation with additional components besides hydrazines is a logical entry to MCR syntheses of pyrazoles. Therefore, 1,3-dielectrophiles encompass 1,3-dicarbonyl compounds and α,β-unsaturated carbonyl compounds, including alkenoyl and alkynoyl systems, across various oxidation states

• of the carbonyl groups and their derivatives. 1,3-Dicarbonyl compounds as key intermediates The most common and classic synthesis of ring-forming pyrazoles is the cyclocondensation of 1,3-dicarbonyl compounds with hydrazines (Knorr synthesis) [42][43]. Therefore, the in situ generation of 1,3

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

• elaborated. The suggested approach can be applied to various aromatic and heterocyclic hydrazines. At the same time for unsubstituted hydrazine the Boulton–Katritzky recyclization is not implemented. In this case the opening of the pyranone ring was observed leading to pyrazolylisoxazole derivatives. Both

• , intramolecular recyclization accompanied by opening of the isoxazole ring and formation of the N–N bond leads to intermediate B. Finally, target 1,2,3-triazole 4 is produced via acidification of anion B. Next, we tried to expand the presented rearrangement to hydrazones derived from aliphatic hydrazines (MeNHNH2

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• the ability to be readily transformed into various valuable functional molecules, including amines, hydrazines, and nitrogen-containing heterocycles [13]. In a significant advancement in 2021, Lopchuk et al. revealed a novel method for the photodecarboxylative alkylation of diazirines 12 using the

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

• of the product, while benzoyl peroxide (BPO) gave a low yield. Various nucleophiles 161, including ammonia, alkylamines, hydrazines, alcohols and alkoxides, indole, N-alkylpyrrole, N-substituted anilines, PhSH, and PhMgBr worked well under these conditions. Asymmetric thiolation of 4-substituted

Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives

• Valeriy O. Filimonov,
• Alexandra I. Topchiy,
• Vladimir G. Ilkin,
• Tetyana V. Beryozkina and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2023, 19, 1191–1197, doi:10.3762/bjoc.19.87

• pyrazoles has been thus synthesized. The structure of the reaction products was studied using NMR spectroscopy and mass spectrometry and confirmed by X-ray diffraction analysis. Keywords: aminopyrazoles; 2-cyanothioacetamides; enamines; hydrazines; Introduction Compounds containing a pyrazole cycle

• -(substituted)phenylsulfonyl-4-thiocarbamoylpyrazoles in moderate to high yields. It was concluded that in 2-cyanothioacetamides, cyano and enamino groups are more active in the reaction with hydrazines than the thiocarbamoyl function. Experimental X-ray structure determination of 5b, 6a, 7a 5b: Crystal data

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

• ). Alternatively, removal of Boc groups could be performed by treatment with aqueous HCl to give the corresponding hydrochloride salts, which could be converted into free hydrazines by treatment with excess NaHCO3 in ethanol (as demonstrated for product 19c). Note that TAADs 19–21 with free amino groups are more

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• hydrazines in a closed ampoule at 75 °C in methanol in the presence of molecular sieves (4 Å) [46]. General procedure To a stirred solution of the respective 1,4-quinone 1 (1.0 mmol) and K2CO3 in dry THF (10 mL), a hydrazonoyl bromide 8 (1.1 mmol) was added, and stirring was continued at room temperature

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

• ][9] or calcium carbide [10]) with hydrazines (Scheme 1) [11][12]. The reaction is operationally simple and tolerates a wide range of hydrazines including alkyl-, aryl-, and hetarylhydrazines [11] as well as semicarbazide and its derivatives [12]. However, the scope of this method with a special

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• ][45][46][47]. Moreover, arylhydrazones and arylhydrazines/hydrazines can be used as well, respectively, as partners in [4 + 2] cyclization reactions [48][49][50][51] or by reacting mostly with carbonyl derivatives [52][53][54][55]. From the state-of-the-art, a strategy that promotes the synthesis of

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• developed, starting from sulfonyl hydrazines in place of sulfonyl chlorides. In this case, the RuII-based photocatalyst was able to reduce tert-butyl peroxybenzoate, triggering the release of a tert-butoxyl radical. This was in turn able to oxidize the hydrazine, allowing the liberation of the desired

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• -workers exploited the copper-catalysed asymmetric ring opening of polycyclic meso hydrazines with organoaluminium reagents (Scheme 13) [43]. This reaction followed a classical allylic substitution pathway. Interestingly, the organoaluminium reagents in this reaction did not only act as alkyl donors but

• oxabicyclic substrates with organolithium reagents (selected examples). Copper-catalysed ring opening of polycyclic meso hydrazines. Copper-catalysed ACA of Grignard reagents to alkenyl-substituted aromatic N-heterocycles. Copper-catalysed ACA of Grignard reagents to β-substituted alkenylpyridines. Copper

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

• Tobias Lucas,
• Jule-Philipp Dietz and
• Till Opatz

Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41

• the formation of fluorinated heterocycles. While attempts to obtain an aminooxazole upon reaction with hydroxylamine were unsuccessful, substituted hydrazines turned out to provide moderate yields of fluorinated pyrazoles. Phenylhydrazine (12a) was chosen as the model substrate for optimization (Table

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• -(2-iodoaryl)acrylamides 113, DABCO·(SO2)2 (69) and hydrazines 114. Proposed mechanism for the preparation of oxindoles 115. Three-component reaction of acrylamide 113, CO (23) and 1,4-benzodiazepine 121. Multicomponent reaction of sulfonylacrylamides 123, aryldiazonium tetrafluoroborates 68 and DABCO

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• photochromic derivatives with varying electronic and thus photochromic properties. The respective arylamines 13a–c were converted into their corresponding hydrazines 14a–c via diazonium-salt formation using sodium nitrite and subsequent reduction using tin(II) chloride [70]. The following nucleophilic

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• of interest from a pharmacological point of view. The first and probably most frequently used method for the synthesis of pyrazolones is based on the Knorr condensation of β-ketoesters with substituted or unsubstituted hydrazines. However, these reactions often suffer from certain disadvantages, such

• preliminary results concerning the cancer selectivity of the selected agents. Results and Discussion Synthetic studies The steroidal β-ketoester precursor 4, suitable for the attempted heterocyclization reaction with hydrazines was synthesized from commercially available pregnenolone acetate (1) via a

• magnesium enolate. Although the presence of a C16–C17 double bond as in 4' is assumed to be beneficial for a P45017α-inhibitory effect, further transformations of this compound were abandoned because of the insufficient yield and its potential tendency to react with monosubstituted hydrazines – not only