N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• pyrazole derivatives (including indazole), benzimidazole, 1,2,3-triazole, indole, carbazole, indoline, quinazoline, and isoquinoline. Nevertheless, many heterocyclic motifs still remain beyond the attention of researchers. For example, glutarimides that incorporate tetrazole and 1,2,4-triazole substituents

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

• as fluorinated building blocks for the synthesis of difluoromethylated pyrazole derivatives by such [3 + 2] cycloaddition reactions [73][84][85] (Scheme 13). These studies therefore emphasize that fluoromethylated nitrile imines are versatile building blocks for [3 + 2] and [3 + 3] cycloaddition

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• % yield, 19a, 84% yield), substituted pyrazole derivatives (6 examples, up to 55% yield, 19b, 55% yield), pyrimidine (19c, 31% yield) as well as quinoline and isoquinoline (19d and 19e, 65% and 66% yields, respectively). In addition, the trifluoromethylthiolated benzo[h]quinoline 20f was obtained in good

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• [7], estrogen receptor ligands [8], A2A receptor antagonists [9], and DNA intercalating agents [10]. Importantly, pyrazole derivatives can be traced in a spectrum of well-established drug candidates of various categories with diverse therapeutic properties such as antipyretic [11], antibacterial [12

• ], difenamizole [26], epirizole [27], rimonabant [28] etc. (Figure 1). Additionally, pyrazole derivatives hold a prominent position in the field of materials science as a result of their numerous applications in products like brightening agents [29], semiconductors [30], and organic light-emitting diodes [31

• pathway is outlined in Scheme 9 for the formation of the thioamide and amide-linked pyrazole derivatives 1C and 1F. It is proposed that initially pyrazole-3-carbaldehyde 1 reacted with morpholine (C) to furnish the iminium intermediate 13. Meanwhile, the intermediate polysulfide 14 formed by the

A study of the photochemical behavior of terarylenes containing allomaltol and pyrazole fragments

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

Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61

• bifunctional objects provides access to novel UV irradiation-based synthetic methods. Continuing our studies devoted to the photochemistry of terarylenes [27][28][29][30][31][32], in this communication we studied the UV-promoted reaction of pyrazole derivatives 12 containing a 3-hydroxypyran-4-one fragment

• we can assume that the key difference of the related pyrazole derivatives considered in this report is the absence of a pathway associated with 6π-electrocyclization. Therefore, we supposed that for the corresponding pyrazoles 12 containing a hydroxy group in the allomaltol fragment only ESIPT

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

• with four different substituents: in position 1 of the pyrazol cycle a 7-chloroquinolin-4-yl unit, in position 3 various amino or thio fragments, in position 4 a nitro and in position 5 a dichloromethyl group. Some biological activities of 7-chloroquinolinyl-substituted pyrazole derivatives have

• falciparum strain [19]. Certain 7-chloroquinolinyl-pyrazole derivatives have also shown antibacterial [20], hypoglycemic as well as antioxidant activity [21] or can be used as selective nonpeptide neurotensin receptor type 2 compounds [22]. Some azolylquinolines have been used as agrochemical fungicides

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• [69]. Herein, Li and co-workers developed a new asymmetric synthesis of atropisomeric pyrazole derivatives 56 via an enantioselective reaction of azonaphthalene 54 with pyrazolone 55 using 5 mol % chiral phosphoric acid CPA 16. Substrates bearing electron-donating and electron-withdrawing groups gave

• the desired axially chiral pyrazole derivatives 56 in good yields (up to 99%) with excellent enantioselectivities (up to 98% ee, Scheme 19). Density functional theory calculations revealed that the chiral phosphoric acid acts as a proton-transfer shuttle to assist proton transfer from the OH group of

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

• fused pyrazole derivatives as the exclusive products. The reactions proceed via the initially formed [3 + 2]-cycloadducts, which undergo spontaneous aerial oxidation to give aromatized heterocyclic products. Only for 2,3,5,6-tetramethyl-1,4-benzoquinone, the expected [3 + 2]-cycloadduct exhibited fair

• considerable attention of other groups [18][19] and recently has been applied for the preparation of some π-extended pyrazole derivatives, which exhibited promising biological activity [20]. In a series of our recent publications, efficient syntheses of fluoromethylated five- and six-membered N,S-heterocycles

• respective hydrazonoyl bromides 8 and smoothly undergo [3 + 2]-cycloadditions with both electron-rich C=C dipolarophiles [27][28][29] and arynes [30], yielding the corresponding pyrazole derivatives. Unexpectedly, they reacted also with electron-deficient polyfluorinated thioamides to give the desired 1,3,4

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

• Man-Man Wang,
• Hao Huang,
• Lei Shu,
• Jian-Min Liu,
• Jian-Qiu Zhang,
• Yi-Le Yan and
• Da-Yong Zhang

Beilstein J. Org. Chem. 2020, 16, 233–247, doi:10.3762/bjoc.16.25

• modifying pyrazole derivatives and the carbon−carbon bond between 1,3-dicarbonyl and aroyl moieties. Previously, a series of 2-(aryloxyacetyl)cyclohexane-1,3-diones was synthesized by Wang et al. [24]. We have been interested in inserting a carbon−oxygen bond between the triketone and aroyl moieties of HPPD

• pocket, as shown in Figure 6. In this work, two categories of HPPD inhibitors were synthesized, including triketone and pyrazole derivatives. Compared with the triketone derivatives, the pyrazole-containing derivatives were generally more herbicidally potent. For instance, pyrazole-containing compounds

Thermal stability of N-heterocycle-stabilized iodanes – a systematic investigation

• Andreas Boelke,
• Yulia A. Vlasenko,
• Mekhman S. Yusubov,
• Boris J. Nachtsheim and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2019, 15, 2311–2318, doi:10.3762/bjoc.15.223

• (phenyl)-λ3-iodanes. In particular, the (pseudo)cyclic pyrazole derivatives 24 and 33 show a comparable high ΔHdec value. These overall significant lower decomposition energies are in good agreement with published data in the field of reactivity and stability of hypervalent iodine compounds [32]. As

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• *(C6H6)][B(C6F5)4]2 and LiOAc gave alcohol products 62 with high diastereoselectivity at ambient reaction conditions. The unique nature of cobalt was well presented by its superior reactivity and diastereoselectivity and it outmatched the rhodium catalyst. Different pyrazole derivatives with a wide range

An unusual thionyl chloride-promoted C−C bond formation to obtain 4,4'-bipyrazolones

• Gernot A. Eller,
• Gytė Vilkauskaitė,
• Algirdas Šačkus,
• Vytas Martynaitis,
• Ashenafi Damtew Mamuye,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2018, 14, 1287–1292, doi:10.3762/bjoc.14.110

• (Viagra®) can be mentioned [1]. In a series of former publications we described the synthesis of condensed pyrazole systems using various 4,5-disubstituted pyrazole derivatives as precursors for the annellation reaction [9][10][11][12][13][14][15][16]. Amongst these precursors 5-chloropyrazoles carrying C

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

• pyrazole is one of the most widely studied nitrogen-containing heterocyclic nuclei. Fused pyrazole derivatives are composed of the pyrazole nucleus attached to other heterocyclic moieties which enable them to exhibit improved pharmacological activities compared to the isolated fragments. These compounds

• are currently used in several marketed drugs like cartazolate (1), zaleplon (2), sildenafil (3), allopurinol (4), indiplon (5), etazolate (6) etc. (Figure 1). Fused pyrazole derivatives, especially pyrazoloazines have been reported to mimic purine bases, present in DNA and RNA, due to close structural

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• dicyanofumarates E-1 with 1-azabicyclo[1.1.0]butanes 55. Formation of pyrazole derivatives in the reaction of hydrazines with E-1. Formation of 5-aminopyrazole-3,4-dicarboxylate 65 via heterocyclization reactions. Reactions of aryl- and hetarylcarbohydrazides 67 with E-1a. Multistep reaction leading to

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• that this nitrogen atom lacks of sufficient couplings to protons, thus disabling the necessary coherence transfer (19F,15N HMBC spectra were not possible with the equipment at hand). For N-1, with pyrazole derivatives 4 and 6 remarkably larger 15N chemical shifts were detected (−158.8 to −160.2 ppm

Regioselective S_N2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

• Silong Xu,
• Jian Shang,
• Junjie Zhang and
• Yuhai Tang

Beilstein J. Org. Chem. 2014, 10, 990–995, doi:10.3762/bjoc.10.98

• nitrogen-containing heterocyclic compounds, especially pyrazole derivatives [2][3][4][5][6][7]. Although various methods detailing the synthesis of hydrazines have been established [8], the development of an efficient synthesis of hydrazines with highly structural diversity from simple starting materials

Ugi post-condensation copper-triggered oxidative cascade towards pyrazoles

• Aurélie Dos Santos,
• Laurent El Kaim,
• Laurence Grimaud and
• Caroline Ronsseray

Beilstein J. Org. Chem. 2011, 7, 1310–1314, doi:10.3762/bjoc.7.153

• chloride. Considering our interest in IMCR, we envisioned that a similar cascade could be performed on a properly functionalized Ugi adduct allowing us to reach a new 4-component access to pyrazole derivatives. The present letter summarizes our efforts in this direction. Results and Discussion Among the

Continuous gas/liquid–liquid/liquid flow synthesis of 4-fluoropyrazole derivatives by selective direct fluorination

• Jessica R. Breen,
• Graham Sandford,
• Dmitrii S. Yufit,
• Judith A. K. Howard,
• Jonathan Fray and
• Bhairavi Patel

Beilstein J. Org. Chem. 2011, 7, 1048–1054, doi:10.3762/bjoc.7.120

• pyrazole derivatives [22][23]. Of relevance to this paper, pyrazole and its derivatives constitute an important class of compounds, which exhibit various biological and pharmaceutical activities ranging from antitumor to anti-inflammatory, antipsychotic, antimicrobial, antiviral and antifungal activities

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• herein report a detailed account of the synthetic methods available for 5-aminopyrazoles. As pyrazole derivatives do not exist in nature, probably, due to the difficulty in the construction of N–N bond by living organisms, their availability depends on the synthetic methods. A large number of synthetic

• chloride, which affords, again after Fmoc removal, the diglycylpyrazole 142 (Scheme 38) [80]. A new synthetic route [81] to 5-amino-1-aryl-4-benzoyl pyrazole derivatives 144 involves the reaction of β-ketonitriles with N,N’-diphenylformamidine to give initially the cyclocondensation precursors 143 which is

Michael-type addition of azoles of broad-scale acidity to methyl acrylate

• Sławomir Boncel,
• Kinga Saletra,
• Barbara Hefczyc and
• Krzysztof Z. Walczak

Beilstein J. Org. Chem. 2011, 7, 173–178, doi:10.3762/bjoc.7.24

• , no corresponding regioisomers were obtained. Keywords: imidazole derivatives; methyl acrylate; Michael-type addition; pyrazole derivatives; 1,2,4-triazole derivatives; Introduction Derivatives of azoles are important biologically active compounds. Many, especially those containing imidazole