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

• 3–5 h (TLC control). Meanwhile, the disappearance of the diazo reagent was considerably slower in the case of more basic heterocycles (pyrazoles, indolines, tetrahydroquinolines), taking anywhere from 16 to 24 hours, and in some cases (imidazole, 7-azaindazole, ethyl isonipecotate, hexamethylenimine

• 5 in the presence of symmetrically substituted pyrazoles produced the relevant products of N–H insertion 6d–f in high yields. The substitution of methyl groups with phenyl groups (6d vs 6e) had no significant impact on the outcome of the reaction. The synthesis of compound 6f was conducted on a gram

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

• . 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

• presence of Brønsted acid. In their pioneering research, Tanaka et al. reported the [3 + 2] cycloaddition reactions of trifluoroacetaldehyde hydrazones and glyoxals to give 4-hydroxy-3-trifluoromethylpyrazoles. The resultant pyrazoles containing a free 4-hydroxy group were easily converted to a variety of

• -pyrazoles and CF3-1,6-dihydropyridazines from readily available trifluoromethylated N-propargylic hydrazones. These reactions proceed through intermediate diazoallenes, and were conducted with catalytic PtCl4 [41] or AgOTf [42] (Scheme 5). Their study explored the effects of fluorine through reactions with

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

• 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

• cyclization of β,γ-unsaturated oximes with N-(arylthio)succinimide. Synthesis of 4-chalcogenyl pyrazoles via chalcogenation/cyclization of α,β-alkynic hydrazones. Controllable synthesis of 3-thiolated pyrroles and pyrrolines. Possible mechanism for controllable synthesis of 3-thiolated pyrroles and pyrrolines

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

• potential of such compounds. The most common method for obtaining 3,5-disubstituted pyrazoles is the cyclocondensation of 1,3-bielectrophilic reagents with hydrazine, which acts as a 1,2-dinucleophile [15][16]. It is worthy to note that a small number of methods for the synthesis of 3,5-diaminopyrazoles are

• presented in the literature. These syntheses are multistage [17] or are essentially a transformation of the structure of the previously obtained pyrazoles [18] (Scheme 1A). Methods for the synthesis of pyrazoles containing thioamide and amino groups in a molecule are even less developed than methods for

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• activation of aryl pyrazoles, followed by the asymmetric conjugate addition to the Michael acceptor. Then, the formed cobalt enolate participates in the intermolecular aldol reaction with an aldehyde 207. The stereochemistry of this tandem procedure is controlled by the chiral Co(III) complex C4 bearing

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

• ; pyrazole carbaldehydes; sulfur insertion; thioamides; Introduction During the past years, the significance of pyrazole chemistry has been notably escalated which is attributed to the discovery of their amazing biological properties. Among the heterocyclic molecules, pyrazoles are considered as privileged

• ]. Substituted pyrazoles are also of considerable interest because of their synthetic utility as chiral auxiliaries [32], synthetic reagents in multicomponent reactions [33][34], and guanylating agents [35]. The installation of a thioamide functionality has attracted an immense attention in medicinal chemistry

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

• -time IR and automated pump control to facilitate reagent addition and column robustness have been demonstrated in the synthesis of pyrazoles and other valuable building blocks [79]. In the same fashion as inline phase separations, the use of such cartridges is often considered to remove a reagent

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• cycloaddition reaction of α-diazomethylphosphonates with o-(trimethylsilyl)phenyl triflate in the presence of CsF [13], Cu2+-mediated N−N bond formation from ketimines in the presence of oxygen [14], Pd2+-mediated oxidative benzannulation from pyrazoles and internal alkynes [15], Pd-catalyzed Aza–Nenitzescu

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

• established by X-ray diffraction. Keywords: allomaltol; ESIPT process; photochemistry; pyrazoles; terarylenes; Introduction The investigation of the photochemical behavior of organic products is a significant part of modern materials science and technology. The UV-induced processes are extensively employed

• Discussion The starting pyrazoles 12 containing the 3-hydroxypyran-4-one fragment were obtained by a literature method [33]. The methoxy derivative 16 was synthesized by methylation of the corresponding pyrazole 12a according to the standard procedure [24][26] (Scheme 2). Initially, based on the previously

• 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

• -nitro-1H-pyrazoles bearing a dichloromethyl and an amino or thio moiety at C3 and C5 has been prepared in yields up to 72% from the reaction of 1,1-bisazolyl-, 1-azolyl-1-amino-, and 1-thioperchloro-2-nitrobuta-1,3-dienes with 7-chloro-4-hydrazinylquinoline. A new way for the formation of a pyrazole

• ± 0.04 µM (100 ng/mL, 200 nM), respectively. Two compounds (3b and 10d) have also been tested for anti-SARS-CoV-2, antibacterial, and cytotoxic activity. Keywords: antimalarial activity; anti-SARS-CoV-2 activity; chloroquine; 2-nitroperchlorobutadiene; nucleophilic vinylic substitution; 1H-pyrazoles

• , hydroxychloroquine, and amodiaquine (Figure 1) against a SARS-CoV-2 infection is currently under discussion [3][4][5][6][7]. As the 4-amino-substituted 7-chloroquinoline is the essential fragment of chloroquine and its derivatives, we have designed and synthesized a series of pyrazoles containing this fragment in

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• the range of 14.4–14.7 Hz, while the 3JHN values were in the range of 1–3 Hz [42][43]. The coupling constants 13C,15N of a series of 15N-labeled pyrazoles gave 1JCN values of 8–11 Hz, while 2JCN were less than 2 Hz [44]. The 15N-labeled 1,2-thiazole moiety was readily determined by measuring the

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• 4,6-dihydro-3H-pyrazolo[3,4-d][1,2,3]triazines, were not successful under similar conditions due to the higher stability of the triazene functionality in the regioisomeric precursors and thus, the failure of the removal of the protective group. Keywords: cyclization; diazonium chemistry; pyrazoles

• = diisopropylamine. Cleavage of the triazene protective group and cyclization of the resulting diazonium intermediate yielding pyrazolo[3,4-d][1,2,3]-3H-triazine derivatives 5a–i. Synthesis of N-substituted pyrazoles 12 and 13. Synthesis of amides 9a–i via reduction of nitriles 12a–g to pyrazolo-ortho-methylamines

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

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

• stability and could be isolated in moderate yield (53%). The presented method offers a straightforward access to hitherto little known trifluoromethylated polycyclic pyrazoles. All products were isolated as pale colored solids with medium-intensity absorption maxima in the range of 310–340 nm for

• naphthoquinone-derived products and low-intensity bands in the visible region (≈400 nm) for the anthraquinone series. Keywords: [3 + 2]-cycloadditions; fluorinated compounds; fused pyrazoles; N-heterocycles; nitrile imines; 1,4-quinones; Introduction The 1,4-quinone scaffold belongs to the most important

• reported in the 1960s [17]. The latter 1,3-dipole was generated thermally from the respective tetrazole derivative 3, and the observed [3 + 2]-cycloadditions occurred chemoselectively to provide fused pyrazoles of the type 4 as exclusive products (Scheme 1). This type of cycloaddition attracted

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

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

• -assisted protocol for the construction of imidazopyrimidine clubbed pyrazoles 105. The one-pot one step/two step approach by the authors employed a KOH-mediated reaction of 4-carbaldehyde pyrazoles 102, acetophenones 103 and 2-aminobenzimidazole (104) in a greener solvent mixture of ethanol/water (1:1

• derivatives via a reaction between 5-(4-R-benzyl amino)pyrazoles 137, cyclic 1,3-diketones 6 and formaldehyde (138) in ethanol as solvent. The protocol shows good functional group tolerance with both EDG and EWG on pyrazoles resulting in moderate to good yields (Scheme 53). An interesting observation revealed

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• heterocycles, a mixture of substituted pyrazolines and corresponding pyrazoles was obtained [42], and also for the reaction with arylmethylidenemalononitriles [43]. It was assumed that the expected compounds initially had formed, but under the reaction conditions, they underwent a ring opening with the

• [1,2-a]pyrazoles (Michael-type adducts). For the first time it was shown, that under heating the cycloadducts can undergo cycloreversion with the generation of new azomethine imines, which can be trapped with suitable dipolarophiles. Single-crystal X-ray structure of compound 3e. Single-crystal X-ray

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• photocatalyst Ru(bpy)3Cl2·6H2O and Pd(OAc)2 promoted the formation of the coupling products in high yields when the reaction was irradiated with visible light. This new procedure exhibited a good functional group tolerance and turned out to be compatible with a wide range of DGs, including amides, pyrazoles

• expected products in good to excellent yields (Figure 37 and Figure 38). The addition of diphenylphosphoric acid as a ligand guaranteed higher yields and a broader reaction scope [100], including C–H activation substrates bearing alternative and modifiable DGs such as pyrazoles or oxazolines, as well as

Synthesis of new fluorescent molecules having an aggregation-induced emission property derived from 4-fluoroisoxazoles

• Kazuyuki Sato,
• Akira Kawasaki,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2020, 16, 1411–1417, doi:10.3762/bjoc.16.117

• heteroaromatic systems, especially those comprising two heteroatoms such as pyrazoles [28][29], isoxazoles [30], and thiazoles [31][32]. Recently, we reported the selective fluorination of isoxazoles, to give monofluorinated isoxazoles 3 or trifluorinated isoxazolines 4 in moderate to good yields (Scheme 1) [33

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

• heterocycles; fluorine; pyrazoles; pyrimidines; Introduction Due to its extremely widespread application in virtually all areas of synthetic organic chemistry, fluorine is considered a “magic” element. It confers metabolic stability and other unique properties to organic molecules and a large fraction of

• stage [15][16][17][18][19]. Fluorinated pyrimidines, pyrimidine analogues and pyrazoles [20][21] play a prominent role in several clinically important pharmaceuticals [22][23][24][25]. These compounds act against HIV or HIV-related diseases [26], such as opportunistic fungal infections, and represent

• fluorinated C3 building block recently described and used by our laboratory for the synthesis of 2 [36]. Herein, we present the synthesis of fluorinated pyrimidines and pyrazoles from the same precursor. Potassium (Z)-2-cyano-2-fluoroethenolate (8) was synthesized in three steps starting from chloroacetamide

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

• commercialized and applied in the agrochemical industry. These herbicides are mainly divided into three categories: triketones, pyrazoles, and isoxazoles [9][15][16]. Figure 1 shows some HPPD-inhibiting herbicides, namely mesotrione, tefuryltrione, isoxaflutole, topramezone, and pyrasulfotole. Among them

Photochromic diarylethene ligands featuring 2-(imidazol-2-yl)pyridine coordination site and their iron(II) complexes

• Andrey G. Lvov,
• Max Mörtel,
• Anton V. Yadykov,
• Frank W. Heinemann,
• Valerii Z. Shirinian and
• Marat M. Khusniyarov

Beilstein J. Org. Chem. 2019, 15, 2428–2437, doi:10.3762/bjoc.15.235

• imidazole and pyridine groups of another moelcule 6. The distorted octahedral coordination sphere is completed by a H2B(pz)21− anion. Fe–N bond distances of 2.1602(15)–2.1615(15) Å for the pyrazoles and 2.2489(14)–2.2462(14) Å for the imidazole and pyridine moieties are typical for high-spin (HS) iron(II

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

• . However, even the triazoles 2, 3, and 5 can be considered as safe compounds, but still deserve a common precaution due to the narrow decomposition process. Pyrazoles 6 and 7 are thermally more stable (Tpeak = 168.9 and 196.5 °C) with a remarkably lower ΔHdec value. NH-pyrazole 6 shows the lowest ΔHdec

• thermal stability of pyrazoles and indazoles (6–8) in direct comparison to triazoles (2–5) is very likely connected with the lower C/N ratio. Benzimidazoles 9–11 showed increased ΔHdec values (58.5–76.4 kJ/mol) in comparison with pyrazoles 6–8. Broad decomposition peaks (up to 14 °C peak width – see

• . The MS analysis revealed the formation of the N-arylated pyrazoles 33a and 33b as the main products (Scheme 1b). Both decomposition studies let us conclude, that intermolecular N-arylation is the major decomposition pathway of (pseudo)cyclic N-heterocycle-stabilized mesityl(phenyl)-λ3-iodanes

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• reaction [14]. Recently, several hydroxyalkylation reactions followed by alkylation of arenes have been reported involving heterocycle-based superelectrophiles: pyridines, thiazoles, quinolines, isoquinolines, pyrazines, pyrazoles, imidazole and furans, bearing a formyl (carbonyl) group [15][16][17][18][19