Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• the structure of the prepared compounds. To explain the outcome of the tandem reaction of 3,3-diaminoacrylonitriles to heterocyclic azides, a tentative mechanism for the formation of 1,2,3-triazoles 3 from acrylonitriles 1 and azides 2 is shown in Scheme 3. Firstly, treatment with a base, leads to

• formal cycloaddition reaction of readily available heterocyclic azides with 3,3-diaminoacrylonitriles. The reaction represents a novel method for the preparation of 1,2,3-triazoles bearing an N-hetaryl amidine moiety and thus this reaction offers a novel method for the preparation of new types of 1

• -substituted-1,2,3-triazoles, widening the synthetic applications of both azides and derivatives of acrylonitrile. Some of the prepared compounds exhibited a mild toxic effect on tumor cells in comparison with normal human embryonic cells. Experimental 3,3-Diaminoacrylonitriles 1b and 1f were synthesized from

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• gem-difluoroalkenes with organic azides in morpholine as a solvent to construct fully decorated morpholine-substituted 1,2,3-triazoles. Mechanistic studies revealed the formation of an addition–elimination intermediate of morpholine and gem-difluoroalkenes prior to the triazolization reaction via two

• plausible pathways. Attractive elements include the regioselective and straightforward direct synthesis of fully substituted 1,2,3-triazoles, which are otherwise difficult to access, from readily available starting materials. Keywords: [3 + 2] cycloaddition; defluorination; fully decorated 1,2,3-triazoles

• -trisubstituted-1,2,3-triazoles, with a pendant morpholine at the C-4 position are formed with complete regiocontrol via β-fluoride elimination in an SNV-like transformation (Figure 1C). 1,2,3-Triazoles are a privileged scaffold in medicinal chemistry with a myriad of pharmacological activities against cancer [11

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• nucleophilic substitutions employing sodium azide and organic substrates with potential leaving groups have been reported. The resulting organic azides were trapped in situ by a suitable alkyne to give the 1,2,3-triazoles [26][27][28][29][30][31][32][33][34][35][36]. Fairly recent review articles summarize

• was also discussed in a review article [57] dealing with the various types of bis(1,2,3-triazoles). Since we were not interested in compounds such as 4 we did not further investigate details in order to optimize this process. Instead, we looked at the one-pot nucleophilic substitution to generate

• led to the expected bis(1,2,3-triazoles) 20 or 21 in moderate or very good yield (Scheme 6). We cannot decide whether the lower yields in this series are caused by the unprotected hydroxy group of precursor 19 or the corresponding products. Although we did not isolate the conceivable mono-adducts we

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

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

• –Prakash reagent (TMSCF3) in the presence of Cs2CO3 as base in MeCN at 0 °C gave product 7 with a trifluoromethyl group. Stefani et al. reported the 1,3-dipolar azide–alkyne cycloaddition (AAC) of organotellanyl alkynes with organic azides in the presence of a copper reagent to form 5-organotellanyl-1,2,3

• -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

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

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

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

• azides and alkynes [14][15]. However, the formation of the nitrogenated azoles by the classical Huisgen methodology is slow due to its high activation energies and also lack of regiochemical control, in general, leading to a mixture of 1,4- and 1,5-regioisomers of 1,2,3-triazoles. Later, Sharpless and

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

• -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

• derivatives is highly desired. The continuous interest and efforts of our group for the derivatization of quinoline moieties [57] and use of N-sulfonyl-1,2,3-triazoles as heterocyclic precursors encouraged us to develop a new strategy for the regioselective C2-triazolylation of quinoline N-oxide under mild

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

• 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

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

• comparatively afforded cinnamyl-1,4-disubstituted 1,2,3-triazoles at an improved yield compared to that of the methyl and ethyl counterparts. Notably, the MBH adducts derived from the para-bromo-, para-chloro-, and para-nitrobenzaldehydes favourably assisted the formation of the corresponding (E)-cinnamyl-1,4

• adducts. In contrast to the contending reports on the synthesis of 1,2,3-triazoles and halomethylcoumarins from MBH adducts, our studies report moderate reaction conditions with an improved yield. The above investigation provides a useful synthetic tool for synthetic organic chemists. The synthesis of

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• nanomagnetic catalyst for “click” reactions and tandem syntheses of 1,2,3-triazoles substituted at the 1- and 4-position in water [98]. The synthetic approach to 131 is shown in Scheme 28. First, magnetic CuFe2O4 nanoparticles 126 were treated with (3-chloropropyl)triethoxysilane in dry toluene to produce the

• magnetic nanoparticles CuFe2O4@starch (131). The catalytic activity of 131 was studied in the synthesis of 1,2,3-triazoles substituted at the 1- and 4-position by regioselective “click“ reactions of benzyl/alkyl bromides or arylboronic acids, sodium azide, and aromatic/alkyl alkynes in the presence of low

Halogen-bonding-induced diverse aggregation of 4,5-diiodo-1,2,3-triazolium salts with different anions

• Xingyu Xu,
• Shiqing Huang,
• Zengyu Zhang,
• Lei Cao and
• Xiaoyu Yan

Beilstein J. Org. Chem. 2020, 16, 78–87, doi:10.3762/bjoc.16.10

• chemistry, anion recognition, organocatalysis, materials science and tuning of biomolecular systems [17][18][19][20][21][22][23][24][25][26][27]. 1,2,3-Triazole-based XB-donors, such as 5-iodo-1,2,3-triazoles A [28][29][30][31][32][33] and 5-iodo-1,2,3-triazolium B [34][35][36][37] (Figure 1), are promising

• candidates for XB donors, which is mainly due to the ease of preparation via a copper-catalyzed click reaction between azide and alkyne [38][39]. 1,2,3-Triazoles and 1,2,3-triazolium-based XB activators have been found applications in catalytic reactions [40][41] and anion recognition [42]. Recently, we

Influence of the cis/trans configuration on the supramolecular aggregation of aryltriazoles

• Sara Tejera,
• Giada Caniglia,
• Rosa L. Dorta,
• Andrea Favero,
• Javier González-Platas and
• Jesús T. Vázquez

Beilstein J. Org. Chem. 2019, 15, 2881–2888, doi:10.3762/bjoc.15.282

• disposition to one of them (see Figure 5). Conclusion In summary, the capacity of di-1,4-disubstituted 1,2,3-triazoles to form gels was studied taking the dependence on the trans/cis configuration of the molecules into account. The results clearly show that compounds having the cis configuration are more