Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• the moment, there are no data on the preparation of 1,2,4-oxadiazoles containing a conjugated acetylenic substituent in the position 5 of the heterocyclic ring. Based on our previous works on the chemistry of 1,2,4-oxadiazoles in superacids [24][25], we undertook this study on further investigation of

• the transformations of these heterocyclic compounds in electrophilic media. The main goals of this work were the synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and the study of their reactions with/without arenes under the conditions of superelectrophilic activation by the Brønsted superacid CF3SO3H

• heterocyclic core gave no corresponding 5-acetylenyloxadiazoles 3 in the system NaNH2–NH3(liq.), only mixtures of oligomeric materials were formed. Moreover, compound 3e was obtained as an inseparable mixture with styryloxadiazole 1e. The latter may be formed from 3e under the reduction by the solution that

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

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• chemists. Many transition-metal-salt-mediated cyclizations are reported in literature. Hg(II) salts have been successfully employed in cyclizations to form complex heterocyclic and carbocyclic structures that are impossible to synthesize with other transition metal salts. In this review, we have summarized

• cyclization reactions that are performed with Hg(II) salts. These salts are also successfully applied in stoichiometric or catalytic amounts to form complex cyclic structures and natural products. Keywords: carbocyclic; catalyzed; cyclization; heterocyclic; mercury(II) salts; Introduction The use of

• diastereomers 30a,b and 32a,b was obtained, respectively. trans-Isomers were formed as major products over cis-isomers (Scheme 12) [52]. Five- and six-membered N-containing heterocyclic phosphonates were synthesized by intramolecular cyclization of alkenyl α-aminophosphonates in a similar way with the treatment

(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

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• xanthenes has increased remarkably in recent years due to their wide range of biological and pharmacological properties. Xanthenes are important biologically active oxygen-containing heterocyclic compounds. These types of compounds have some biological and pharmacological properties, such as

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• and asymmetric alkynes with heterocyclic compounds and obtained reasonable to satisfactory results (examples 12h–k) [35]. Cu(OAc)2 proved to be an essential oxidant for the success of both the Miura and the Bao methodologies [34][35]. In 2013, Ye and co-workers reported a concise method to synthesize

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• stereogenic centers. Review A plethora of highly effective small‐molecule organocatalysts have enriched the field of organic synthesis [27], including chiral proline derivatives, N‐heterocyclic carbenes, chiral thioureas and Brønsted acids as well as phase‐transfer catalysts (PTC), such as the quaternary

• ]coumarins are formed with good to excellent yields and enantioselectivities (Scheme 14). N-heterocyclic carbenes (NHC) have also been successfully used as organocatalysts, in particular, to obtain coumarin derivatives [47]. In this context, Yetra et al. reported a NHC catalyzed reaction of 2-bromoenals 46

• with various heterocyclic C–H acids, resulting in the synthesis of coumarin/quinolinone fused dihydropyranones and dihydropyridinones 47. The reaction optimization and the scope and limitations study were carried out using an achiral NHC, but the enantioselective version was also performed using 4

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• regioselectivity is absent (ratio 75:76 and 77:78 ≈ 1:1, Table 6, entries 7–9) under conditions B, most likely due to solvent-separated ion pair formation. Conclusion Both 1H- and 2H-indazoles represent a core heterocyclic motif in many therapeutic small molecule drugs. Thus, from a synthetic perspective, the

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

• are crucial. In 2018, Ackermann and co-workers described a novel room temperature C–H arylation by using a continuous visible light photo-flow technique, allied with a manganese photocatalyst CpMn(CO)3 [142]. The new flow protocol enabled the synthesis of several arene- and heterocyclic-based

•  34B and 34C) [170]. The new method presented broad scope in the construction of tetrasubstituted carbon centers from methylenes to access a wide range of spiro N-heterocyclic oxindoles in excellent yields, including diamine, benzamide, and spirothiazole scaffolds. The high potential of the reaction

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• epipolythiodioxopiperazine (ETP’s) class toxin of several fungal genera including Aspergillus, Penicillium, Trichoderma, and Leptosphaera (Figure 3) [112]. Among the ascomycetes, A. fumigatus may well be the major GT producer and the identification of its heterocyclic structure by Bell and colleagues in 1958 builds the

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• external Lewis acid and trimethylaluminum as a methyl source (Scheme 7) [61]. The late-stage methylation of simple heterocyclic motifs was initially investigated using (S,S)-Mn(CF3–PDP) (21), providing methylated lactams 22a–e. Notably, methylation site selectivity was observed for the carbon atoms

• =NTces were used. Mn-catalyzed C–H methylation of heterocyclic scaffolds commonly found in small-molecule drugs. aDAST activation. bBF3⋅OEt2 activation. c1 mol % of (S,S)-Mn(CF3–PDP) was used. Examples of late-stage C–H methylation of bioactive molecules. aDAST activation. bFor insoluble substrates

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

• Girish Suresh Yedase,
• Sumit Kumar,
• Jessica Stahl,
• Burkhard König and
• Veera Reddy Yatham

Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121

• -dichlorobenzaldehyde (2w) in 70% yield. The sulfur-containing compounds 4-(phenylthio)benzyl alcohol (1r) and the heterocyclic compound thiophene-2-ylmethanol (1x) gave the corresponding aldehydes 2r and 2x in 61 and 80% yield, respectively. Finally, 2-naphthylmethanol (1y) was subjected to the reaction conditions and

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• prepared with nucleophilic catalysis using 10 mol % N-heterocyclic carbenes such as 1,3,4-triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene or 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene. The polymerization was carried out at room temperature for 24 h and no solvent was used. The resulting reaction

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• of writing, E remains the most commonly used PNA nucleobase for recognition of U–A base pairs in dsDNA and RNA [117]. Several heterocyclic nucleobases in triplex-forming oligonucleotides have been designed to form a single hydrogen bond with the exocyclic -NH2 of cytosine [94][109]. Rozners and co

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• attention for their inspiring applications in the fields of solar cells [1][2][3], organic devices [4][5][6][7][8], and as chemosensors [9][10]. The acridine core (Figure 1), formed by two benzenes fused to a pyridine ring, is among the most extensively studied heterocyclic aromatic compounds. It has first

• chlorine atom is located at the more reactive electron-poor pyridine moiety of the heterocyclic core structure. In fact, the chlorine position proved to be quite unreactive and all attempts to isolate 2,4,9-tris(phenylethynyl)-5,6,7,8-tetrahydroacridine failed even after using an excess of phenylacetylene

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

• -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

• compounds with not only biological but also industrial significance [9][10][11]. It possesses a cyclic scaffold with carbon and three nitrogen elements in the ring [12][13][14][15]. An immense versatility of biological properties is possessed by 1,2,3‐triazole heterocyclic systems, and many strategies are

• Figure 1 [8][23][24][25][26][27]. As such, there is still a demand for the expansion of ways to access new 1,2,3-triazole heterocyclic rings in rapid, efficient, and versatile ways. Triazole rings could serve as important intermediates for numerous important organic transformations [28][29][30]. Diverse

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• electrophilic substitutes were well tolerated. Moreover, substrates with a highly reactive unprotected amino group also delivered the corresponding product 3cn with good yield. The robustness of this protocol was further highlighted by the excellent reactivity of heterocyclic acetylenes (see 2p–r). However, a

Recent advances in the application of isoindigo derivatives in materials chemistry

• Andrei V. Bogdanov and
• Vladimir F. Mironov

Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

• areas of research is the design of low-molecular-weight structures containing one or two isoindigo fragments in a unified conjugated electronic system. Currently, to improve the key characteristics of OSCs, some directions of studies are related to the design of substituents both on the heterocyclic

• characterized by a high short-circuit current (JSC = 13.92 mA/cm2), with a 5-fold better PCE value (Table 3). Expansion of the conjugation chain by introducing additional electron-enriched condensed heterocyclic fragments (see compounds 20 and 21) makes it possible to achieve a PCE of almost 6% (Scheme 13) [31

• based on more complex condensed analogs 31 containing a heterocyclic fragment showed a 2-times better efficiency (5.6% for difluorothiophene, 5.0% for selenophene) [46]. The effect of the length and branching of the alkyl substituent at the endocyclic nitrogen atom in a series of this type of donor

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

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• metal-catalyzed arylation [17][18][19]. We have recently successfully applied this approach to synthesize the new luminescent heterocyclic system pyrido[2,1-a]pyrrolo[3,2-c]isoquinoline A [17], which turned out to be useful for bioimaging [13] and as a ligand for the preparation of luminescent metal

• reagents (Scheme 2). Luckily, 4-(2-iodophenyl)pyrrole 2 gave under these conditions target heterocyclic skeleton 3a in 50% yield (Scheme 2). Salt 3a was characterized by 1H, 13C NMR and HRMS, its structure was also confirmed by single-crystal X-ray diffraction analysis (Figure 1). Since iodo-substituted

• selectivity of intramolecular arylation. Thus compound 10 was obtained from iodo/bromo-substituted salt 9 using 1.5 equiv of TTMSS. Dibromo-substituted salt 12 under the same conditions with 4 equiv of TTMSS gave the product of the double arylation, new heterocyclic skeleton 13, 1H-dibenzo[b,g]pyrido[2,1,6-de

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• salts has been discovered. Results and Discussion Optimization of reaction conditions and chemical synthesis The base-catalyzed imination of aromatic aldehydes is a valuable method in organic synthesis to synthesize a variety of heterocyclic building blocks [29]. Among all the reported iminoesters

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

• literature search regarding double-headed nucleosides disclosed that these modified nucleosides were constituted with any two naturally occurring nucleobases, i.e., adenine, guanine, thymine, uracil, and cytosine [9][10] or one naturally occurring nucleobase and one heterocyclic/carbocyclic moiety either

• attached directly to the sugar or via a linker. Further modifications were introduced by the substitution of some of the naturally occurring nucleobases by halogens or alkyl groups. On the other hand, a variety of heterocyclic/carbocyclic moieties were considered as the head of these modified nucleosides

• . The heterocyclic structures which were found to be attached to these double-headed nucleosides include triazolophthalazine [11], 4,6-di-tert-butylbenzoxazole [12], mesitylisoxazole [13], 5-trimethylsilyl-1,2,3-triazole [14], 1-pivaloyloxymethyl-1H-1,2,3-triazole [15], 1,3,4-oxadiazino[6,5-b]indole [16

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• -closing metathesis (RCM), Clauson–Kaas and Ullmann-type coupling reactions as key steps. Moreover, we have also assembled some other interesting heterocyclic systems possessing oxazole, imidazole, benzimidazole, and benzoxazole in the framework of truxene. Additionally, the preliminary photophysical

• synthetic strategies and also novel truxene-based functional materials with unique properties. Bearing in mind the importance of the truxene framework, herein, we report diverse C3-symmetric heterocyclic systems possessing the truxene scaffold in their structures by means of cyclotrimerization, ring-closing

• could open-up the challenging opportunities to magnify the chemical space not only for the pyrrole derivatives but also of the truxene-based architectures, and the present contribution would definitely add value to both heterocyclic systems as well as to the truxene chemistry. Results and Discussion

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• Guareschi” [42]. Triacetonamine bears a certain similarity to tropinone (9), the heterocyclic core of tropane alkaloids, and the one-pot preparation from acetone and ammonia reminds of, and anticipates by two decades, the Robinson synthesis of tropinone and the Willstätter synthesis of the corresponding 2

• to name type-I Guareschi pyridone synthesis the two-component reaction between a β-aminocarbonyl and a cyanoacetic ester, a reaction first reported in 1893 [34]. It is a classic combination of a Knoevenagel condensation and ester aminolysis typical for many heterocyclic syntheses. The type-II

• ”, formally an internal redox reaction where the heterocyclic system is oxidatively aromatized and one of the substituents at C-4 reductively lost as a hydrocarbon. The reaction involves the treatment of a ketone with a solution of ethylcyanoacetate in ethanolic ammonia [7]. A precipitate of the ammonium salt

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