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

• , which also improves safety issues as it traps toxic and explosive reactive intermediates (Scheme 7) [76]. Additional studies include a 3-step reaction to form triazoles in good yields [77], and the synthesis of the bisoxazole natural product siphonazole A using immobilized species [78]. The use of real

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• proceeded further, in uncatalyzed fashion at room temperature and yielded, after intramolecular azide–alkyne click reaction novel, structurally intriguing bistriazoles. Keywords: α-acetyl-α-diazomethane sulfonamide; intramolecular click reaction; uncatalyzed; room temperature; 1,2,3-triazoles

• ; Introduction 1,2,3-Triazoles are well-established heterocycles in drug discovery [1] and are even considered pharmacophores (i.e., structural motifs defining the compound’s biological activity profile) on their own [2]. Therefore, synthetic methods allowing to construct a 1,2,3-triazole heterocycle are a

• valuable part of the drug discovery chemistry toolbox. For the same reason, development of new methods [3] to either build 1,2,3-triazoles de novo and/or incorporate them into polycyclic scaffolds is a worthy undertaking which can help discover biological activity associated with hitherto unattainable

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• diversity of metal complexes incorporating 1,2,3-triazoles as ligands have been reported [16][17][18]. Triazole ligands with N-heterocycles such as Pyta (4-(2-pyridyl)-1,2,3-triazole) and related structures were employed to obtain novel metal complexes as catalysts [19][20] and imaging probes [21], as well

• desired product 16 whereas addition of zinc powder seems to have different effects depending on the derivative (see Supporting Information File 1). We could then show that the conversion of tetrazoles to both triazoles and imidazoles can occur together in the same molecule. When bis(tetrazolo)[1,5-a:5',1

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• -triazoles [33]. Based on these findings, we examined the reaction of Cu-mediated AAC. The reaction of 4aa with benzyl azide in the presence of one equivalent of CuI and pentamethyldiethylenetriamine (PMDETA) in THF at 60 °C gave the desired 5-selanyl-1,2,3-triazole 8 in 72% yield. This reaction yielded a

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• coupled with in situ generation of the azide from the corresponding bromide. The 1,2,3-triazoles are formed in up to 99% yield and in less than 10 minutes residence time, which includes azide formation prior to the cycloaddition step. Interestingly, this process could not be successfully repeated under

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• involving the addition of arylamines to β-NQS 18 followed by N-alkynylation and then Cu(I)-catalyzed heterocyclization with tosyl azide in toluene at room temperature, leading to triazoles 50c–k in moderate to excellent yields (Scheme 14). The research group that most explored the formation of heterocycles

• -naphthoquinones. Synthesis of 4-semicarbazide-1,2-naphthoquinone. Reactions of 4-azido-1,2-naphthoquinone. Derivatives of 1,2-naphthoquinones obtained from β-NQS. Oximes as well as 4-amino- and 4-phenoxy-1,2-naphthoquinone as potential anti-inflammatory agents. Synthesis of triazoles from β-NQS. Synthesis of

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• isomerization of N-allyl amides [20], but still possess drawbacks, especially for stereoselective synthesis of tri- and tetrasubstituted enamides. Recently, we have reported a triflic acid-mediated reaction of N-fluoroalkyl-1,2,3-triazoles leading to (Z)-β-enamido triflates [21] and Lewis acid-mediated reaction

• to (Z)-β-enamido fluorides [22] and halovinyl imidoyl halides [23]. In addition, Li and co-workers extended the scope of accessible (Z)-β-enamido triflates by denitrogenative reaction of N1-H-1,2,3-triazoles in the presence of acyl halides and sodium triflate [24]. These enamido triflates and halides

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• -1,2,3-triazoles 35 in good yields (up to ≈72%) and excellent enantioselectivity (up to 99% ee) (Table 7) [41]. In an interesting study, Wu et al. screened a number of cinchona derivatives and squaramides for their relative catalytic efficacies for the enantioselective aza-Michael additions between

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• this compounds are required. In this regard we suggested the modification of the alcohol tail of metronidazole by incorporating an N-heterocyclic moiety. Nitrogen-containing heterocycles play a vital role in agrochemicals and pharmaceuticals [3]. Among these heterocyclic systems, the 1H-1,2,3-triazoles

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• analogs [12][13], in this work, we designed a series of imatinib 1,2,3-triazole analogs 1a,b and 2a–j (Figure 1). The 1,2,3-triazoles are heterocyclic compounds, consisting of a five-membered ring, containing two carbon atoms and three nitrogen atoms [14]. The application of click chemistry, a concept

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• synthesis of a wide variety of relevant 1,4,5-trisubstituted 1,2,3-triazole molecules are reported. The synthesis of this category of diverse fully functionalized 1,2,3-triazoles has become a necessary and unique research subject in modern synthetic organic key transformations in academia, pharmacy, and

• industry. The current review aims to cover a wide literature survey of numerous synthetic strategies. Recent reports (2017–2021) in the field of 1,4,5-trisubstituted 1,2,3-triazoles are emphasized in this current review. Keywords: azides; Click reaction; [3 + 2]‐cycloaddition; fully functionalized 1,2,3

• -triazoles; N-containing heterocycles; 1,4,5-trisubstituted 1,2,3-triazoles; Introduction A high number of N-heterocycles [1][2][3][4] are identified, and this number is increasing very quickly [5][6][7][8]. Among them, the small heterocyclic ring of the 1,2,3-triazole is present in a broad variety of

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• into oligonucleotides resulted in the formation of unstable duplexes with complementary DNA and RNA strands whereas four consecutive incorporations led to increased duplex stability due to an efficient stacking of heteroaromatic triazoles as revealed by CD spectroscopy and molecular dynamics

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

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• ], antituberculosis [2], anti-inflammatory [3][4], anticancer [5], antidiabetic [6][7], and antiviral activities [8]. A significant number of biologically active thiazolidines amount to their heteroannelated derivatives, namely, condensed thiazolo[3,2-a]pyrimidines [9] and thiazolo[3,2-b]-1,2,4-triazoles [10], as

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

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

• regioselective construction of substituted 5-aza-adenines 113 using cyanamide (110), triethyl orthoformate (111) and 5-amino-1,2,4-triazoles 112 as structural units with methanol as solvent (Scheme 42). Simple filtration with no product isomer formation gives this protocol an edge over the other traditional

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• with electron-rich as well as electron-poor arenes and heteroarenes. Subsequently, in order to prove the practicability of this approach, 1,2,3-triazoles were assembled by reaction of 157 with alkynes. In 2019, Bosque and Bach [41] reported that 3-acetoxyquinuclidine (q-OAc) could be utilized as an

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• , MG, Brazil 10.3762/bjoc.17.66 Abstract Desulfonylative alkylation of N-tosyl-1,2,3-triazoles under metal-free conditions leading to β-triazolylenones is reported here. The present study encompasses the synthesis of triazoles with a new substitution pattern in a single step from cyclic 1,3-dicarbonyl

• synthesis of new functionalized 1,2,3-triazoles. Keywords: azoles; cycloaddition; enones; heterocycles; 1,2,3-triazoles; Introduction 1,2,3-Triazoles are significant non-natural heterocyclic scaffolds with extensive applications in biochemistry, agrochemistry and materials chemistry [1][2][3][4][5]. This

• , cefatrizine, rufinamide and JNJ-54175446 (Scheme 1a) [10]. In addition to their biological activities, triazolic compounds are widely employed in organic synthesis and have outstanding synthetic versatility. In this sense, extensive scientific research has been conducted using triazoles as synthetic

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• Prague, Czech Republic 10.3762/bjoc.17.44 Abstract The rhodium-catalyzed transannulation of N-perfluoroalkyl-1,2,3-triazoles with aromatic and aliphatic terminal alkynes under microwave heating conditions afforded N-perfluoroalkyl-3,4-disubstituted pyrroles (major products) and N-fluoroalkyl-2,4

• of pyrroles to the 3,4-disubstituted derivatives is challenging because an electrophilic aromatic substitution of pyrroles or the metalation of N-substituted pyrroles and the subsequent reaction with electrophiles take place in position two of the ring [6][7]. Recently, N-sulfonyl-1,2,3-triazoles

• -sulfonyl-1,2,3-triazoles (Scheme 1) [11][12][13][14][15][16][17]. We have recently reported that N-perfluoroalkyl-1,2,3-triazoles [18] undergo rhodium-catalyzed transannulation reactions leading to various nitrogen heterocycles, such as imidazoles, pyrrolones, imidazolones, oxazoles, azepines [19][20][21

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

• Geetanjali S. Sontakke,
• Rahul K. Shukla and
• Chandra M. R. Volla

Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42

• isoquinolines was achieved from readily available N-oxides and N-sulfonyl-1,2,3-triazoles. A variety of α-triazolylquinoline derivatives were synthesized with good regioselectivity and in excellent yields under mild reaction conditions. Further, a gram-scale and one-pot synthesis illustrated the efficacy and

• simplicity of the developed protocol. The current transformation was also found to be compatible for the late-stage modification of natural products. Keywords: amination; heteroarylation; quinoline N-oxides; regioselective; triazoles; Introduction Quinoline is a key heterocyclic moiety found in many

• -catalyzed “Click” chemistry, N-sulfonyl-1,2,3-triazoles have become useful precursors for accessing a variety of heterocyclic moieties [55][56]. In spite of the above methods for the C2-amination, the establishment of a simple, efficient and atom-economical method for the synthesis of 2-triazolylquinoline

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• ring at the C6 position of purine to act as leaving group. Keywords: 2,6-bistriazolyl purines; nucleophilic aromatic substitution; purine nucleosides; triazoles; Introduction Modified purine derivatives are an important class of compounds which possess a wide spectrum of biological activities [1][2

• of an SNAr process on partially deactivated purines as the introduced nucleophiles are mostly seen as electron-donating substituents (e.g., R2N-, RS-, RO-). Herein, we report a synthetic extension of this methodology. We have found that the pronounced leaving group character of 1,2,3-triazoles makes

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• new method for C–N bond transformations into C–P bonds was developed using 1,2,3-triazoles as leaving groups in SNAr–Arbuzov reactions. A series of C6-phosphonated 2-triazolylpurine derivatives was synthesized for the first time, with the isolated yields reaching up to 82% in the C–P-bond-forming

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• -arylamino-1,2,3-triazole-4-N-sulfonylcarbimidamides. 2,5-Dithiocarbamoylpyridine reacts with sulfonyl azides to form a pyridine bearing two sulfonyl amidine groups. Keywords: amidines; Dimroth rearrangement; isoxazoles; sulfonyl thiazoles; thioamides; 1,2,3-triazoles; Introduction The biological activity

• interesting building blocks in organic synthesis [17][18][19][20] (Figure 1). An N-sulfonyl amidine was recently found to be a key group in acid–base-induced rearrangements of 1,2,3-triazoles and thiadiazoles [22]. A variety of methods have been developed for the synthesis of N-sulfonyl amidines. The most

• (Table 1, entry 11 and Table 2, entry 14). Thus solvent-free conditions, a temperature of 88 °C and a thioamide/azide ratio of 1:2.5 are optimal to prepare N-sulfonyl amidine 1c (entry 11, Table 1). Next, these optimized conditions were used for the synthesis of a small library of 1-alkyl-1,2,3-triazoles

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• , Germany Institute for Inorganic and Crystallographic Chemistry, University of Bremen, Leobener Straße NW2, 28359 Bremen, Germany 10.3762/bjoc.16.139 Abstract Herein, we present a facile synthesis of three azide-functionalized fluorophores and their covalent attachment as triazoles in Huisgen-type

• reactions (CuAAC). For this, we treated the azide-functionalized luminophores with alkynes exhibiting different degrees of steric demand, including 1-decyne (29), phenylacetylene (30), 1-ethynyladamantane (31) and 1,3-di-tert-butyl-5-ethynylbenzene (32, see Scheme 5). All triazoles 33–44, based on the

• triazole 45 in 83% yield. Photophysical properties Finally, we examined the photophysical properties of both the azides and the triazoles. UV–vis absorption measurements of para-bromobenzaldehyde 3 and ortho-bromobenzaldehyde 4 as well as the corresponding triazoles 33–40 were conducted in chloroform

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• )-catalysed straight forward protocol for synthesising structurally demanding (E)/(Z)-cinnamyl-1H-1,2,3-triazoles and halomethylcoumarins from MBH adducts. The novel methodology, efficient catalyst, and direct utilization of MBH adducts under mild reaction conditions qualify the reported procedures as

• adducts, however, the vicinity of its (E)- and (Z)-isomers restricts their use as a favourable starting moiety [34]. After a careful bibliographic investigation, it became evident that there were no one-pot protocols for direct transformations of MBH adducts to cinnamyl triazoles. The outcome of

• developing a one-pot synthetic strategy will be worthwhile for pharmacologically important triazoles, such as isavuconazole, tazobactam, and ravuconazole [35]. Results and Discussion Initially, phosphonium salts were barely utilised or exploited in synthetic transformations. Later, in 2014, several organic