Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• between 4-alkylidene-5-aminopyrazoles and alkyl trifluoropyruvates leading to highly functionalized tertiary alcohols bearing a trifluoromethyl group and a pyrazole ring is presented. The corresponding trifluoromethyl alcohols are obtained in moderate to good yields (up to 80%) and high

• on the regioselective electrophilic functionalization of this nitrogen heterocycle [15][16][17][18][19][20][21][22][23][24][25]. However, the vinylogous functionalization of 5-aminopyrazoles has not been described to the best of our knowledge (Figure 2). As a part of our ongoing interest in the

• functionalization of 5-aminopyrazoles [26], we decided to study 4-alkenyl-5-aminopyrazoles as nucleophiles in the vinylogous addition reaction to electrophiles. Herein, we report the regioselective and diastereoselective functionalization of 4-cyclohexenyl-5-aminopyrazoles using alkyl trifluoropyruvates [27][28][29

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• ]. It has already been noted that the preferred medium for recyclizations involving imides of itaconic and malic acids by various N,N- and C,N-dinucleophiles, in particular by 1,2-diaminoimidazole derivatives, 5-aminopyrazoles, and 3-aminocyclohexen-2-ones, are mixtures of polar solvents with acetic

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

• method holds promise for the development of biologically active substances. In addition to acetoacetylcoumarins, the synthesis was also successfully conducted using acetylacetone [66]. Likewise, complex functionalized pyrazoles, such as triazolo[3,4-b]-1,3,4-thiadiazin-3-yl substituted 5-aminopyrazoles

• -oxodithioesters 48 react with primary or cyclic aliphatic amines, resulting in the formation of β-oxothioamides 50, which can then be directly converted into the corresponding 5-aminopyrazoles 49 with aromatic hydrazines in the presence of catalytic amounts of acetic acid (Scheme 14) [68]. The process exhibits

• -unsaturated cyano derivatives, which in turn can cyclocondense with hydrazines to furnish aminopyrazoles after oxidation. Hasanijedad and Firoozi developed a one-pot process for synthesizing 5-aminopyrazoles 62 in a three-component fashion (Scheme 19) [78]. Interestingly, hydrazine acts both as a Brønsted

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

• aldehyde hydrazones and alkenes for the preparation of pyrazolines was proposed by Tong, Song, et al., achieving similar efficiency using oxone/KBr as an environmentally friendly oxidative system [59]. Most recently, Zhou and Ma et al. described the electrochemical access to 3‑aminopyrazoles 79 from

• -triazoles [49]. Synthesis of 1,3,5-trisubstituted 1,2,4-triazoles [50]. Alternative synthesis of 1,3,5-trisubstituted 1,2,4-triazoles [51]. Synthesis of 5-amino 1,2,4-triazoles [55]. Synthesis of 1-arylpyrazolines [58]. Synthesis of 3‑aminopyrazoles [60]. Synthesis of [1,2,4]triazolo[4,3-a]quinolines [61

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• , Yotphan and colleagues realized a direct thiocyanation of N-substituted pyrazolones under metal-free conditions [49]. Besides, Choudhury and co-workers developed an additive and metal-free methodology for the C–H thiocyanation of aminopyrazoles, using H2O2 as a benign oxidizing agent (Scheme 1b) [41]. Pan

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• cycloaddition of the gained synthesized azidopyrazoles with different alkynes was to be conducted. The 3-(3,3-diisopropyltriaz-1-en-1-yl)-1H-pyrazole precursors 15a–d were synthesized according to previously reported procedures [3][26][27] via the generation of a diazonium salt from aminopyrazoles 14a–d

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

• -aminopyrazoles with azlactones under solvent-free conditions, through subsequent elimination of a benzamide molecule in a superbasic medium, is described by the Fisyuk group [13]. A further facile one-pot process toward a new series of copper(II) benzo[f]chromeno[2,3-h]quinoxalinoporphyrin analogues is described

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

• : deposit@ccdc.cam.ac.uk). Examples of bioactive pyrazoles for the protection of cultivated plants and drugs containing a thiocarbonyl group. Structures of starting materials. Syntheses of 4,5-diamino- and 4-thiocarbamoyl-5-aminopyrazoles. Synthesis of 3,5-diaminopyrazoles 4а–с and thiocarbamoyl-NH

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• Ave., 55a, 644077 Omsk, Russian Federation 10.3762/bjoc.19.83 Abstract An effective one-pot strategy was developed for the synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones from pyrazolo[3,4-b]pyridin-6-ones, obtained by reacting 5-aminopyrazoles with 4-arylidene-2-phenyloxazol-5(4H)-ones (azlactones

• few (Scheme 1). To obtain 4-arylpyrazolo[3,4-b]pyridin-6-ones, the only known one-step method is most often used, including the acid-catalyzed condensation of aminopyrazoles with ketoesters [1][16][18] (method A). Its significant disadvantage is the low yields of the target products (11–60%). Yields

• are also low in two-stage synthesis methods. The first of them is based on the three-component condensation of aminopyrazoles, Meldrum's acid, and aromatic aldehydes, followed by the oxidation of the intermediate with DDQ [13][16][19] (method B). The second one includes the reaction of an aromatic

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• 3-indolyl-substituted aza-quaternary stereocenter. Here the stereoselectivity was attributed to an H-bonding interaction between the catalyst and the substrates (Scheme 21) [50]. In 2022, Lin and co-workers reported an unusual aza-Friedel–Crafts reaction using N-aryl-5-aminopyrazoles 92 as potential

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• acid. The next step of our investigation was the two-step synthesis of persubstituted aminopyrazoles 5 upon reaction of the benzotriazolyl derivative 2c with primary, secondary, aliphatic, or (het)aromatic amines (first step) and successive reaction of the obtained dienes 4 with 7-chloro-4

• group forming a six-membered ring system that upon reaction with 7-chloro-4-hydrazinylquinoline formed 5-aminopyrazoles 5a,l–o. Here, a nucleophilic attack of the NH2 group of the arylhydrazine on the C3 position of the butadiene chain is observed due to the sterically hindered rigidized six-membered

• ring system in the dienes 4a,l–o (Scheme 4). The obtained 5-aminopyrazoles 5a,l–o show the following 13C NMR shifts of the pyrazole ring and the dichloromethyl group: 149.5–149.9 ppm (C-NHR), 114.7–116.1 ppm (C-NO2), 147.0–147.2 ppm (C=N), and 62.2–62.3 ppm (CHCl2). On the other hand, the dienes 4b–k

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• resulting products were obtained in moderate to good yields. The authors observed the formation of pyrazolopyridine under conventional heating in lower yield (38%) with extended reaction time (20 h). Interestingly, the replacement of triaminopyrimidine with substituted aminopyrazoles 98 resulted in

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

• potassium 2-cyano-2-fluoroethenolate was developed. A broad substrate scope was tested and mostly excellent yields were obtained. The synthesis of fluorinated aminopyrazoles from the same fluorinated precursor could be demonstrated but proceeded with lower efficiency. Keywords: cyclization; fluorinated

• arginine, where the desired pyrimidine 10q was also only observed in trace amounts while the majority of the starting material remained unchanged. Synthesis of fluorinated aminopyrazoles As in the cyclocondensation with amidines, the reaction of 8 with other bifunctional nucleophiles could also result in

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• . Therefore, the present work is devoted to the study of multicomponent reactions involving 3-amino-1,2,4-triazole or 5-aminopyrazoles, aromatic aldehydes, and pyruvic acid or its esters under ultrasonication. Results and Discussion It was discovered that MCRs involving 3-amino-1,2,4-triazole or 5-amino-1H

• -aminopyrazoles bearing an electron-withdrawing substituent in the 4-position, such as a carbonitrile group, often behave similar to 3-amino-1,2,4-triazole; therefore, we studied the latter under the same reaction conditions. We showed that the pseudo four-component heterocyclization of two equivalents of 3-amino

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• accessible by variation of the binucleophilic component 1 (instead of 1, 3-amino-1,2,4-triazole, 2-aminobenzimidazole, 3-aminopyrazoles, 4-amino-1,2,3-triazoles, etc. can be used [13]). However, a relatively low reactivity of amine 1 due to the electron deficiency of the tetrazole ring has been reported

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• -type condensation of aminopyrazoles, aldehydes and pyruvic acid [45][46] with the isocyanide-based four-component Ugi reaction. As we have shown before [47][48] the application of the CBD strategy to multicomponent Doebner-type condensations involving aminoazoles allowed the synthesis of several

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles

• Camila S. Pires,
• Daniela H. de Oliveira,
• Maria R. B. Pontel,
• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Diego Alves,
• Raquel G. Jacob and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2018, 14, 2789–2798, doi:10.3762/bjoc.14.256

• -aminopyrazoles under iodine-catalyzed three-component reaction was not described so far. In view of this, we present a direct and selective multicomponent strategy to synthesize 5-amino-4-(arylselanyl)-1H-pyrazoles 4 by reacting benzoylacetonitrile derivatives 1, arylhydrazines 2 and diorganyl diselenides 3

Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation

• Mark Kelada,
• John M. D. Walsh,
• Robert W. Devine,
• Patrick McArdle and
• John C. Stephens

Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104

• [3,4-b]pyridines, pyrazolo[1,5-a]pyrimidines and pyrazolo[1,5-a]pyrimidinones [12][13][14][15][16][17][18]. The majority of methods used in the generation of the pyrazolo[1,5-a]pyrimidinones employ a two-step process, which first requires the synthesis and isolation of the intermediate 5-aminopyrazoles

• followed by their reaction with an appropriate β-dicarbonyl compound [1][2][3][4][19][20][21][22][23][24][25][26][27][28][29]. A very recent and excellent review by Aggarwal et al. covers the use and versatility of 5-aminopyrazoles in the synthesis of a range of pyrazoloazines [30]. As part of a study into

• conditions for the microwave-assisted generation of the intermediate 5-aminopyrazoles. Once established, this methodology could be expanded to generate a one-pot synthesis of pyrazolo[1,5-a]pyrimidinones. Typical methods for preparing 5-aminopyrazoles require conventional heating of the appropriate β

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• substituted pyrazoloazines by a broad range of organic reactions by means of 5-aminopyrazole as a precursor. Keywords: 5-aminopyrazoles; fused pyrazole derivatives; pyrazolopyridines; pyrazolopyrimidines; pyrazolotriazines; Review Pyrazole and its derivatives are known to exhibit significant biological and

• resemblance. In addition to the immense biological potential related to fused pyrazoles, their synthetic potential needs to be reviewed for further improvements and extension of interests. Various efforts have been developed for the synthesis of pyrazole-based fused heterocycles. 5-Aminopyrazoles have been

• ]-1,2,4-triazines 11 [23], pyrazolo[1,5-a]-1,3,5-triazines 12 [24], pyrazolo[3,4-d][1,2,3]triazines 13 [25] (Figure 2). A number of review articles have been published by us and others highlighting the synthetic and biological aspects of 5-aminopyrazoles [26][27][28] as well as on the synthesis of fused

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• -binucleophile, acid – catalyst). Literature data indicate [14][25][59][97][98][99][100][101] that 5-aminopyrazoles bearing in the fourth position electron-withdrawing substituents like carboxamide, carboxylate or a carbonitrile group, posses chemical properties being different from other 5-aminopyrazoles but

A convenient four-component one-pot strategy toward the synthesis of pyrazolo[3,4-d]pyrimidines

• Mingxing Liu,
• Jiarong Li,
• Hongxin Chai,
• Kai Zhang,
• Deli Yang,
• Qi Zhang and
• Daxin Shi

Beilstein J. Org. Chem. 2015, 11, 2125–2131, doi:10.3762/bjoc.11.229

• aminopyrazoles and amides [41][42]. In our previous studies, dihydropyrimidinone was synthesized through the condensation of 5-aminopyrazole-4-carbonitrile and ketones [29][30]. 5-Aminopyrazole-4-carbonitrile was prepared from the reaction of ethoxymethylenemalononitrile with phenylhydrazine in a step-wise

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• -aminotetrazole [9], 5-aminopyrazoles [11], and 5-amino-1,2,3-triazole [12] have previously been investigated. In some cases when the reaction could proceed in two alternative pathways the conditions enabling to control the interaction direction were determined, which made it possible to obtain the desired

• azoloazine with high chemo- and regioselectivity [11][13][14][15]. In particular, three-component heterocyclizations involving 3-amino-1,2,4-triazoles or 4-substituted 5-aminopyrazoles yielded either 4,5,6,7-tetrahydroazolo[1,5-a]pyrimidine-6-carboxamides under ultrasonication at room temperature (kinetic

• control) or 4,7-dihydroazolo[1,5-a]pyrimidine-6-carboxamides at reflux in an applicable solvent (thermodynamic control), respectively (Scheme 1). The behavior of the reaction of 5-aminopyrazoles containing substituents in the position 3 is influenced by the structure of aminoazoles and aldehydes, giving

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• ) inputs (Scheme 1). The transformations of either the 5-aminopyrazoles [28][29], or their 4-substituted ethoxycarbonyl [7][30][31][32] and carbonitrile [28][33][34][35][36] analogues via the GBB-3CR have not been appreciably examined so far. In the relevant literature [7][28][29][31][32][33], the products

• diversity arising from the pyrazole starting material. As far as we are aware, a one-pot two-step process involving the in situ formation of the desired amino-substituted N-heterocycles such as C4 functionalized 5-aminopyrazoles, followed by GBB-3CR has not been described to date. On the other hand, the

• protocol allowed the rapid synthesis of a 46-membered 1H-imidazo[1,2-b]pyrazole library with isolated yields up to 83%. Following the microwave-aided formation of functionalized 5-aminopyrazoles, the GBB-3CR transformations occurred during 10–60 min under mild conditions. This protocol offers operationally

Synthesis of spiro[dihydropyridine-oxindoles] via three-component reaction of arylamine, isatin and cyclopentane-1,3-dione

• Yan Sun,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 8–14, doi:10.3762/bjoc.9.2

• describing that either 2-naphthylamine [22][23][24][25], functionalized 5-aminopyrazoles [26][27][28], or 2-aminobenzothiazoles [29] reacted with isatin and cyclic 1,3-dicarbonyl compounds to give the similar spiro[dihydropyridine-oxindole] (II, III in Figure 2), in which both the amino group and the aryl

Features of the behavior of 4-amino-5-carboxamido-1,2,3-triazole in multicomponent heterocyclizations with carbonyl compounds

• Eugene S. Gladkov,
• Katerina A. Gura,
• Svetlana M. Sirko,
• Sergey M. Desenko,
• Ulrich Groth and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2012, 8, 2100–2105, doi:10.3762/bjoc.8.236

• synthesize different types of heterocyclic systems, with a high level of selectivity, from the same starting materials. For example, MCRs or 5-aminopyrazoles containing several nonequivalent nucleophilic reaction centers with aromatic aldehydes and derivatives of 1,3-cyclohexanedione [10][11] or pyruvic