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

• analogues of metronidazole Compound 1 reacted with different acid chlorides (6a–e) in the presence of pyridine, a catalytic amount of DMAP and in dry DCM at room temperature. The reaction proceeded smoothly to give the desired metronidazole carboxylate derivatives 7a–e in 86–93% yields [21][22]. The

• compounds 5a–i and 7a–e. Reagents and conditions: (a) TsCl, Et3N, dry DCM, DMAP, 0 °C to room temperature, 5 h, 96%; (b) NaN3, DMF, 70 °C, 3 h, 88%; (c) alkyne derivative (4a–i), CuI, Et3N, CH3CN, room temperature, 3 h, (5a–i) 85–94%. Reagents and conditions: (a) acid chlorides 6a–e, pyridine, dry DCM, DMAP

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• 90 °C. The hydrolysate was extracted with EtOAc and the aqueous layer was neutralized by passing it through an Amberlite IRA-67 column to give the sugar. The sugar obtained from the hydrolysis was dissolved in anhydrous pyridine (0.5 mL) followed by adding of ʟ-cysteine methyl ester hydrochloride

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• -bis(trimethylsilyl)acetamide [34], simultaneous tritylation of N9 and the N2 atoms was achieved using 4,4'-dimethoxytrityl chloride in pyridine. The obtained derivative 4 was amenable to nitrile reduction using diisobutylaluminium hydride (DIBAL-H) in dichloromethane at −78 °C, followed by workup with

• (820 µL, 3.33 mmol) was added dropwise and the reaction mixture was stirred for three hours at room temperature upon which a solution was obtained. Afterwards, the volatile components were removed under reduced pressure and the residue was coevaporated three times with toluene and twice with pyridine

• . The residue was dissolved in pyridine (3.8 mL) and 4,4'-dimethoxytrityl chloride (1.18 g, 3.50 mmol) was added in portions. The solution was stirred for 18 h at 40 °C, subsequently poured into 5% aqueous sodium bicarbonate solution and the suspension was extracted three times with dichloromethane. The

(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

• )pyrimidine-pyridine (PAPP) group as a pharmacophoric fragment, and these compounds were biologically evaluated. The synthesis of twelve new compounds was performed in three steps and assisted by microwave irradiation in a 1,3-dipolar cycloaddition to obtain 1,2,3-triazole derivatives substituted on carbon C

• in the docking studies. Keywords: chronic myeloid leukemia; 1,3-dipolar cycloaddition; imatinib; (phenylamino)pyrimidine-pyridine; 1,2,3-triazole; Introduction Changes in tyrosine kinase proteins (TKPs), either by mutation or chromosomal translocation, can turn them into potent oncogenes

• 1980s, has led to the identification of the (phenylamino)pyrimidine (PAP) structure [5][6]. The addition of an additional pyridine ring to PAP raised its cellular activity, producing PAPP, which, after some more chemical modifications, culminated in imatinib (IMT) [7]. PAPP has been used to develop new

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• proved to not going via a Minisci-type silyl radical addition [55], as the reaction with pyridine did not afford any product. Bell studied the properties of such molecules which are similar to those used in OLED devices (organic light emitting diodes) in 2017. The molecule 34 was synthesized by base

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

• ] cyclotrimerization reactions in the presence of nickel and cobalt catalysts [38]. First, they employed diyne 15 in the reaction with a series of alkynes (16) or nitriles (17) bearing a variety of functional groups including alkyl and alkene chains, hydroxy groups, and benzene and pyridine rings, to achieve the

• corresponding anthraquinones 55 and 57 via a single-step reduction with either zinc/pyridine or zinc/NaOH (Scheme 12). The scope of their work consisted of six examples, and they obtained anthracene derivatives in moderate to good yields (50–87%) [45]. In 2014, Yucel and co-workers synthesized 12 novel

• -free conditions (Scheme 43) [79]. The authors used various heteroaromatic aldehydes and substituted aromatic aldehydes containing electron-donating and electron-withdrawing substituents, to obtain the ortho adducts 188 in variable yields (14–74%). The use of pyridine-3-carbaldehyde and 2,4,5

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

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• fluorination of pyridine or 2-fluoropyridine in anhydrous hydrogen fluoride [17][18] (Scheme 2). Not surprisingly, 1-1 did not become a popular reagent. In 1967, Banks et al. reported reactions of 1-1 with piperidine and triphenylphosphine, -arsine, and -stibine (Scheme 3, entries 1 and 2) [19]. The former

• -(trimethylsiloxy)pyridine was allowed to react with 5% F2 diluted with N2 in a freon solvent at −78 °C, 1-fluoro-2-pyridone was obtained in 63% yield (Scheme 5). The fluorination efficiency of 3-1 was higher than perfluoro-N-fluoropiperidine (1-1) and the yields of reaction with sodium diethyl malonates improved

• pyridine (10% F2/N2) at low temperature in a freon solvent, could undergo straightforward counteranion replacement with a non-nucleophilic anion. Therefore, exchange with salts such as sodium triflate in acetonitrile generated non-hygroscopic N-fluoropyridinium triflate salts as highly thermally stable

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

• multipeptides of varying ring size were successfully obtained with excellent functional group tolerance. In addition, selective N-methylation of the 2-pyridine directing group and successive hydrogenation processes provided an efficient traceless removal of the directing group, affording free-NH tryptophan

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

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

• ] auxiliaries (Figure 1a). Besides, the cobalt(II)- [31] or nickel(II)-catalyzed [32][33], pyridine oxide (PyO)-directed tandem alkynylation/annulation was realized by Niu and Song et al., which also provided the 3-methyleneisoindolin-1-one scaffolds (Figure 1b). Notably, a sustainable cupraelectro-catalyzed

• unfortunately proven elusive [35]. 2-(1-Methylhydrazinyl)pyridine (MHP) [36] was identified as a powerful removable bidentate directing group, which found widespread application in various cobalt-catalyzed C−H activations [37][38][39][40]. Thus, our group also accomplished a set of electrochemical cobalt

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• ) PPh3, DIAD, TMSN3, MeCN, 80 °C, 48 h. a) BzCl, DMAP, pyridine, CH2Cl2, rt, 24 h, 90%; b) TBSOTf, imidazole, DMAP, DMF, 40 °C, 24 h, 78%; c) Na(s), MeOH, THF, 16 h, 90%; d) DMSO, SO3·pyridine, Et3N, rt, 1 h, 98%; e) H2NOH·HCl, THF, H2O, Na2CO3, 24 h, 80%; f) POCl3, MeCN, 65 °C, 40%; g) TBSOTf, imidazole

• , DMAP, DMF, rt, 24 h, 87%; h) TMSN3, Bu2SnO, toluene, 120 °C, 51%. a) PMBCl, KI, K2CO3, DMF, rt, 53% for 11 and 12; b) BnBr, DMF, Et3N, DCM, rt, 31% for 13 and 14. a) DMSO, SO3·pyridine, Et3N, rt, 1 h, 96%; b) H2NOH·HCl, THF, H2O, Na2CO3, 89%; c) POCl3, MeCN, 65 °C, 59%; d) TMSN3, Bu2SnO, toluene, 120

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

• skeletons that are inaccessible via Pd-catalyzed cyclization. Keywords: arylation; pyridine; pyrrole; radical cyclization; tris(trimethylsilyl)silane; Introduction Polycyclic heteroaromatic molecules, which have a tunable electronic structure and excellent self-assembling properties, are highly desirable

• ). It is important that the reaction of iodide 1m with 2-pyridyl substituent gave a good yield of the product 3m, which could be used for the preparation of bidentate ligand for metal complexes. Reaction of salts 1 with electron-donating para-substituents (Me, MeO, Me2N) in the pyridine ring (1n–p,s

• electron-withdrawing para-substituents in the pyridine ring (1u–w) do not cyclize under used reaction conditions. The reaction of 2H-pyrido[2,1-a]pyrrolo[3,4-c]isoquinolin-4-ium bromides 3 with aq KOH at room temperature gave quantitatively the corresponding bases 6 (Table 2). Pyridopyrroloisoquinolinium

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• -hydroxy-4-furyl-tetralin 14af into the PAT analogue 22 (see Figure 1) [26]. The reaction of 14af with p-toluenesulfonyl chloride in pyridine afforded the tosylate 21 in 90% yield, which was then treated with 40% aqueous dimethylamine to produce the tertiary amine containing PAT analogue 22 (cis/trans

• ratio = 79:21) in 70% yield (Scheme 9). With regard to the partial epimerization of product 21, it may be due to the action of pyridine. In the preparation of compound 21, pyridine is used both as solvent and the acid acceptor. Because pyridine itself can show nucleophilic reactivity in addition to

• basicity, the long reaction time of 20 hours may lead to an ion-pair species with 21 and hence erode the stereochemistry. To prove this idea, we performed the reaction with CH2Cl2 as the solvent in the presence of 5.0 equivalents of pyridine and 2.0 equivalents of TsCl. Under these conditions, the tosylate

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• compound 4. Established route for the synthesis of intermediate 4 [1]. Alternative route. Reaction conditions: a) TrCl, pyridine, rt, overnight, 100%; b) DMAP, imidazole, TBS, DCM, rt, 12 h, 65%; c) LDA, (R)-methyl p-tolyl sulfoxide, THF, −78 °C to rt, 2.5 h, 55% yield of 8. Sequence showing the source 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

• -ribofuranose (30) [48]. The ribose derivative 30 was then reacted with triflic anhydride in the presence of pyridine followed by reaction with adenine in the presence of sodium hydride to afford nucleoside 34. The nucleoside 34 was further reacted with benzoyl chloride to afford the fully protected nucleoside

• nucleoside 102 with phenylacetylene in the presence of sodium ascorbate and copper sulfate in a solvent mixture of t-BuOH, water and pyridine, followed by the removal of the tert-butyldimethylsilyl protecting group gave nucleoside 103 (Scheme 22) [14]. Under similar reaction conditions, the treatment of

• was reduced in the presence of NaBH4 followed by the treatment with MsCl in pyridine to get the nucleoside salt 129. Next, the pyridinium group was replaced by an N3-protected thymine in basic medium followed by removal of the protecting groups and the selective DMTr protection of the C-5′-hydroxy

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• ; found, 431.1085. A mixture of the alcohol (1.66 g, 3.84 mmol), acetic anhydride (7.5 mL), pyridine (16.0 mL), and DMAP (93 mg, 0.76 mmol) was stirred under reflux for 24 h. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel

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

• , inorganic, and analytical branches and systematically crosses the divide between pure and applied science as well as between the history of chemistry and the personal contributions to its development. Keywords: Guareschi; history of chemistry; hydrocarbons; name reactions; pyridine; Introduction Modern

• eponymous reactions. His synthesis of cyanopyridones was at the basis of the first industrial synthesis of pyridoxine (vitamin B6, 1, Scheme 1) by Merck [2], is used for the preparation of the blockbuster drug gabapentin (2) [3], and features in countless medicinal chemistry projects based on the pyridine

• Guareschi pyridine synthesis is a modified two-component version, mechanistically similar to the Biginelli pyrimidine synthesis [33] and based on the condensation of cyanoacetamide and a β-dicarbonyl derivative [45][46]. This is the most famous Guareschi pyridine synthesis, both in textbooks and in other

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 multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• thioacetic acid [54][55]. Hence, the hemiacetals were reacted with thioacetic acid in pyridine to give acetamides 49–58 (Scheme 5) and the target trifluoro analogs 59 and 60. Reversing the order of hemiacetal and acetamide formation was not an option because NBS-promoted hydrolysis of 2-acetamido

• degree upon reaction with AcSH in pyridine and traces of O1 acetates were removed by chromatography or recrystallization. Palladium-catalyzed hydrogenolytic debenzylation of 49–58 then yielded the target fluoro analogs 61–70. To complete the series of fluorinated analogs for the purpose of comparing

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• (phosphines, NHC-carbenes, bisoxazolines, pyridine-oxazolines, and miscellaneous) is used. Review Catalytic systems based on phosphine ligands A pioneering work on the enantioselective addition of boron-derived carbon nucleophiles to cyclic enones was published by the group of Miyaura et al. in 2005 [32

• [46]. Catalytic systems based on pyridine-oxazolines ligands Currently, the most studied ligand class is focused on pyridine-oxazolines (PyOx). The first report for the use of this type of ligand for the asymmetric addition of arylboronic acids to cyclic enones was published by the Stoltz group in

• not estimated after each cycle [58]. In 2019, Lee et al. focused on the enantioselective desymmetrisation of polycyclic cyclohexenediones [59]. The variously substituted pyridine-oxazolines L9 and L12a,b were tested as ligands in combination with Pd(OAc)2 or Pd(TFA)2 (Table 31). As a suitable solvent

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

• corresponding bisamidinohydrazide product with a moderate 48% yield using the same conditions. Recently, the scope of the transformation was extended to other aminated nucleophiles such as hydroxylamine and methoxyamine. By using methoxyamine hydrochloride as a reactant along with 1 equivalent of pyridine, the

• addition of pyridine to cyanoguanidine was reported by Petersen et al. [50]. This resulted from an unexpected cyclization under acidic conditions, of different pyridylcyanoguanidines to 4-imino-4H-pyrido[1,2-a][1,3,5]triazin-2-amines (Scheme 20). In conclusion, the preparation of biguanides from

• -amidinopyrazole hydrochloride from cyanoguanidine, by the addition of pyrazole hydrochloride in refluxing pyridine, refluxing 3 M aqueous HCl or by a direct fusion at 140–200 °C (no yields disclosed) [66]. Later in 1992, Bernatowicz et al., in an attempt to produce guanidine derivatives of ornithine-containing

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• , Belgium 10.3762/bjoc.17.79 Abstract Several new heterocyclic systems based on a hydroxybenzofuro[2,3-b]pyridine building block were prepared. This benzofuropyridine is easily available from the Meerwein reaction of benzoquinone and a heterocyclic diazonium salt, followed by reduction and cyclization

• to hydroquinone 12 with N,N-diethylhydroxylamine (N,N-DEHA) and cyclized via intramolecular nucleophilic aromatic substitution to isolate 6-hydroxybenzofuro[2,3-b]pyridine (13) with 82% yield. Conveniently, the synthesis of 13 was achieved in a one-pot reaction from 11 with no significant differences

• in the yield. To the best of our knowledge, this is the first procedure toward compound 13, without additional substituents on the pyridine ring. Furthermore, this method is complementary to the most common routes towards the biologically active 1-aza-9-oxafluorenes [20][21][22][23][24][25][26]. To

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

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

• yields the desired products 127 (Scheme 50). 8.2 Fused pyridines Fused pyridines have been profoundly known for various pharmacological activities. Moreover, the imidazo[1,2-a]pyridine core is found in various drugs like zolpidem (128), alpidem (129), olprinone (130). They are also promising antiviral

• , antiulcer, anxiolytic, antiherpes agents [115][116][117][118][119]. Similarly, pyrazolo-pyridines are found to be potent antibacterial (131), cytotoxic (132), antiproliferative (133) and antimalarial (134) agents (Figure 10) [120][121]. 8.2.1 Imidazo[1,2-a]pyridine: Sun and co-workers [122] accomplished the

• between benzimidazole-linked aminopyridine and Lewis acid activated aldehyde which further on nucleophilic addition with substituted isocyanide leads to intermediate B. A 5-exo-dig intramolecular cyclization with isocyanide aids in the formation of the imidazo[1,2-a]pyridine intermediate C. The final