A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• simplify the work-up of the reaction with LR, this newly developed method was extended to synthesize two pincer ligands, N2,N6-di(n-butyl)pyridine-2,6-bis(carbothioamide) (4, Scheme 1) and N2,N6-bis(2,4,6-trimethylphenyl)pyridine-2,6-bis(carbothioamide) (6, Scheme 2) [34][35][43][44]. With a slight excess

• . The solvent was removed under reduced pressure. The reside was purified by silica gel column chromatography using petroleum ether/ethyl acetate as the eluent to afford the desired thioamide 2. Synthesis of N2,N6-di(n-butyl)pyridine-2,6-(carbothioamide) (3) [34] To a 500 mL four-necked flask were added

• 50.1 g of pyridine-2,6-dicarboxylic acid (0.3 mol), 1 mL of DMF and 55 mL of SOCl2. The mixture was heated to 80 °C to get a clear solution and stirred for 30 min. Then, SOCl2 was removed in vacuum and the crude acyl chloride was dissolved in 50 mL of toluene. To a 1 L flask were added 48 g of n

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

• an EDA complex. First, the N-hydroxyphthalimide (NHPI) ester 142 is excited to electron acceptor 142* through visible-light intersystem crossing (ISC); diborate 143 combining with pyridine results in electron donor 145. Upon the formation of the EDA complex between 145 and 142*, electron transfer

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

• functionalization of triazoles under metal-free conditions has been reported. These include the Broensted acid-catalysed N2 alkylation [27], organocatalytic N1 alkylation [28][29], N2-arylation using hypervalent iodine (Scheme 1c) [30], N2-alkylation involving radical intermediate [31], pyridine-N-oxide-mediated N1

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• TsN3 in MeCN or 0.7 M 4-(azidosulfonyl)-N,N,N-trimethylbutan-1-aminium iodide in DMF) was introduced as replacement of a standard iodine/pyridine oxidation step to react with 3',5'-dinucleoside β-cyanoethyl phosphites (Scheme 1, I), forming the N-modified iminophosphorane (Scheme 1, II). ONs bearing

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• heterocyclic compounds by constructing fused pyridine ring systems based on a thermal electrocyclization of an azahexatriene moiety [14][15]. It has been hoped that the development of compounds with enhanced biological activity would be possible using these natural products and their derivatives [16][17][18

• ]. We have previously reported the total syntheses of indolo[3,2-c]quinoline (isocryptolepine) [19], azaanthracenones (kalasinamide, marcanine A, and geovanine) [20], imidazo[4',5':4,5]pyrido[2,3-b]indole (grossularine-1 and -2) [21][22], imidazo[4,5-b]pyridine (2-amino-1-methyl-6-phenylimidazo[4,5-b

• ]pyridine and 2-amino-1,6-dimethylimidazo[4,5-b]pyridine) [23], and imidazo[4,5-c]quinoline (imiquimod) [24] based on the electrocyclization of 2-azahexatriene involving an isocyanate moiety as the key intermediate. In addition, we recently reported the total syntheses of marinoquinolines A (3a), B (3b

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• reacted with SO3·pyridine to form sulfonic acid derivatives A1–21 after purification by preparative HPLC. The sodium salts of these compounds were obtained by ion exchange using a column filled with Dowex-50wx Na+ resin using water as the eluent, followed by lyophilization. In case of compound A18, Boc

• %; (iii) SO3·pyridine, pyridine, or SO3·pyridine, TEA, THF/water, rt, 16 h, or then Dowex-50wx Na+, 8–99%. Synthesis of compounds A22 and A23. Reagents and conditions: (i) HATU, DIPEA or DCC, DMAP, DMF or THF, rt, 16 h, 62% (B22), 80% (B23); (ii) TBAF, THF, 80% (C22), 92% (C23); (iii) SO3·pyridine

• , pyridine, or SO3·pyridine, TEA, THF/water, rt, 16 h, then Dowex-50wx Na+, 83% (A22), 35% (A23). In vitro antibacterial activity of avibactam and compounds A1-23 alone as well as in combination with meropenem (MER). Supporting Information Supporting Information File 106: Detailed experimental protocols, 1H

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• oxidation of the double bond gave diacetatediol 7 [33]. Treatment of diacetatediol 7 with thionyl chloride in pyridine gave the corresponding cyclic sulfite 8 in 95% yield (Scheme 1). Oxidation of the cyclic sulfite 8 with sodium periodate in the presence of ruthenium trichloride provided the corresponding

• converted into the corresponding triacetate 11 with acetic anhydride in pyridine and 4-(dimethylamino)pyridine (DMAP) (yield 76%). To determine the exact configurations of the substituents in 11, we made full assignments for the H-3 and the acetoxy protons with the help of the 1D and 2D NMR experiments

• ] (79% yield) as the sole product (Scheme 3). Ring opening of trans-epoxide 13 by HBr(g)–MeOH gave bromotriol 14, which is an ideal substrate for the synthesis of the aminocyclooctanetriol 18. For structural proof, bromotriol 14 was converted into the corresponding acetate 15 using Ac2O in pyridine and

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• reaction of 4,4'-bis(N-acetyl-2-aminoethyl)diphenyldiazomethane with C60 in toluene gave adduct 25 that was isolated in 38% yield in the first stage. After that, it was quantitatively converted into primary diamine compound 26 in an acid medium. Upon addition of succinic anhydride in dry pyridine

• heating, or photochemically in a nitrogen atmosphere (Scheme 23) [109]. The reaction of spiro[10-anthron-9,61'-methanofullerene] (79) [110] with bis(trimethylsilyl)carbodiimide and malononitrile in pyridine in the presence of TiCl4 resulted in spirocyclic blocks 80 and 81, respectively (Scheme 24) [111

• solar cells, [60]PCBM, as an example (Scheme 26). The mechanism of fullerene cyclopropanation is presented in Scheme 27. Using a similar procedure, the reaction of C60 and alkyl-4-benzoyl butyrate p-tosylhydrazone in the presence of sodium methoxide and pyridine, the following [6,6]-phenyl-C61-butyric

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• , 303.1961. 11β-Acetoxyandrost-4-ene-3,17-dione (3) Starting steroid 2 (202 mg, 0.67 mmol, 1 equiv) was dissolved in dry dichloromethane (9.8 mL), and after that 4-(dimethylamino)pyridine (8.2 mg, 0.067 mmol, 0.1 equiv), triethylamine (373 μL, 2.67 mmol, 4 equiv) and acetic anhydride (316 μL, 3.34 mmol, 5

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• pyridine–P4S10 as sulfurization agent. The tertiary thiobenzamides 4a–c were synthetized by a one-pot acylation/thionation from the corresponding acid chlorides and dimethylamine [55]. Other chemicals and solvents were purchased from Acros Organics, Sigma-Aldrich, or Fluorochem and were used as received

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

• ][37][38][39][40][41][42][43][44][45]. For example, Yin and co-workers developed a protocol for the deoxygenative C2-amination of pyridine/quinoline N-oxides using t-BuNH2 and Ts2O/TFA in 2007 (Scheme 1a) [48]. Later, Londregan and co-workers were successful in achieving C2-amination employing

• to amination and amidation, there are few reports on metal-free C2-heteroarylation of pyridine N-oxides. In 1984, Rogers demonstrated the synthesis of 2-triazolylpyridines from 2-azidopyridines and phenylacetylene [51]. Along the same lines, Keith reported methodologies for the C2-imidazolylation and

• pyridine N-oxides [54]. Despite the versatility of these methods, the above reports involve the use of external additives for activating the N-oxides and suffer from other disadvantages, including prolonged reaction time, high temperature and limited substrate scope. At the same time, with the advent of Cu

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• common nitrogen-containing compounds such as pyridine, pyrazine, 1H-pyrazole, 1H-indole, 1-methyl-1H-indole, piperidine, and piperazine were subjected to screening. Pyridine and piperidine slightly hamper the reaction of 1g (Table 2, entries 2 and 7, 80–82%). Other nitrogen-containing compounds have more

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• %. Naphthalene 6h and 2-pyridine 6i were also successfully obtained, however, the reactions with the 3- and 4-pyridines 5j and 5k resulted in complex mixtures from which no desired product, nor starting material, could be observed. The scope of this chemistry also extends to substrates with a shorter

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• electrophiles [101]) generated in superacid media [102]. Hence, when trifluoroacetyl pyridine 156 was treated with benzene in triflic acid, alcohol derivative 157 was obtained. In a superacid, 156 generates a dication 158 in which the electrophilicity is enhanced through a strong charge repulsion (Scheme 39

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• pyridine as a scavenger for the liberated HCl, gave solutions of crude diacylated product 18 in acceptable purity after simple filtration as work-up. It was reasoned that the activation of the electron-rich pyrrole (with generic electrophile X2 as shown) would hasten cleavage of the ester and that

• which a −78 °C solution of the crude diacylated species 18 in methanol-d4 was treated sequentially with a solution of I2 (1.0 equiv) in methanol-d4 and pyridine-d5 (≈4.5 equiv). The 1H NMR spectrum acquired after 20 min showed loss of the triplet at 3.76 ppm arising from the enantiotopic CH2N protons in

• work-up and chromatography options. To a mixture of 3-aminopyrrolizine hydrochloride derivative 17 (2.0 g, 10.6 mmol), distilled pyridine (3.42 mL, 42.4 mmol), and acetonitrile (21 mL) at rt was added isovaleryl chloride (2.58 mL, 21.2 mmol). The mixture was stirred for 1 h, then half of the reaction

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

• traces of the 1,4-dihydropyridazine 4af were detected following the two-step, one-pot protocol (Scheme 3). Apparently, the basic pyridine nitrogen atoms of intermediate 3af deactivate the acid catalyst, whilst the use of 3.4 equiv of TFA causes the full protonation of the pyridine rings thus making them

Decarboxylative trifluoromethylthiolation of pyridylacetates

• Ryouta Kawanishi,
• Kosuke Nakada and
• Kazutaka Shibatomi

Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23

• subsequent decarboxylative trifluoromethylthiolation were performed in a one-pot fashion. Keywords: decarboxylation; fluorinated compounds; pyridine compounds; trifluoromethylthiolation; Introduction The pyridine ring is found in numerous biologically active compounds. Therefore, efficient methods for

• mechanism for this reaction, as outlined in Scheme 5. An electrophilic sulfur atom of 6 approaches the nitrogen atom on the pyridine ring to promote decarboxylation via the formation of N-trifluoromethylthio-2-alkylidene-1,2-dihydropyridine intermediate I, which immediately isomerizes to afford 2 (Scheme 5

• trifluoromethylthiolated product at all, despite complete saponification of the methyl ester. Conclusion In conclusion, we demonstrated the decarboxylative trifluoromethylthiolation of lithium 2- and 4-pyridylacetates to synthesize pyridine derivatives with a trifluoromethylthio group at a tertiary carbon center adjacent

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• protected with tert-butyldimethylsilyl chloride in the presence of 4-(dimethylamino)pyridine (DMAP) and imidazole (Scheme 2) according to a published procedure [20]. The thus obtained bis(silylether) 3 was then brominated with N-bromosuccinimide (NBS), where the utilization of acetonitrile as solvent [21

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• ]. In contrast, gold(III) catalysis was for a long time mostly based on inorganic salts, such as AuCl3, AuBr3, or pyridine–AuCl3 and Pic–AuCl2. However, Au(III) complexes with various coordinated ligands are about to become more explored. Different from the linear coordination mode of gold(I), gold(III

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• , 60, Avenue Rockefeller, Bioparc, Bioserra 1 Building, 69008 Lyon, France 10.3762/bjoc.17.16 Abstract In our hands, efficient access to the 4-amino-3-carboxamide disubstituted pyridine-2(1H)-one kinase hinge-binder motif proved to be more challenging than anticipated requiring a significant

• -azabenzotriazole; hinge-binder; ionic hydrogenation; library; pyridine-2(1H)-one; Introduction During a recent medicinal chemistry program targeting a kinase to treat skin disorders, we identified the 4-amino-3-carboxamide disubstituted pyridine-2(1H)-one motif (1) as an interesting starting point. Recently, both

• goal of creating a rapid, 3-step route requiring a single preparative LC–MS purification at the end of the sequence (Figure 1). Results and Discussion Exploration of the C-3 amide vector: formation of the pyridine-2-(1H)-one motif by palladium catalysis We decided to validate the route by preparing

Tuning the solid-state emission of liquid crystalline nitro-cyanostilbene by halogen bonding

• Subrata Nath,
• Alexander Kappelt,
• Matthias Spengler,
• Bibhisan Roy,
• Jens Voskuhl and
• Michael Giese

Beilstein J. Org. Chem. 2021, 17, 124–131, doi:10.3762/bjoc.17.13

• . This is in accordance with our previous results on pyridine-based assemblies and supports the assumption that a reduction of the fluorination degree at the iodobenzene yields a weaker polarisation of the iodine and thus a weaker halogen bond [12]. To investigate this effect experimentally, a series of

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• Charette et al. In their procedure the combination of triflic anhydride and pyridine [6] (or its 2-fluoro derivative [7]) was used as an activating agent to transform amides into reactive iminium complexes. Another stoichiometric approach was presented by Georg et al. by utilization of zirconocene chloride

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• 90% yield. The transformation of acid (+)-73 to acetate (+)-76 using acetic anhydride in pyridine followed by acid activation with oxalyl chloride and then in situ treatment with 28% ammonium hydroxide afforded amide (−)-77 in 90% yield. Finally, deacetylation of (−)-77 using lithium hydroxide

• performed successfully to afford geometrically pure (4Z,6E,8E)-triene (+)-146b in 85% yield following the synthesis of inthomycin B ((+)-2). Careful deprotection of silyl ether of (+)-146a with HF∙pyridine in THF/pyridine delivered alcohol (+)-147a. Next, the Swern oxidation of the resulting alcohol

Circularly polarized luminescent systems fabricated by Tröger's base derivatives through two different strategies

• Cheng Qian,
• Yuan Chen,
• Qian Zhao,
• Ming Cheng,
• Chen Lin,
• Juli Jiang and
• Leyong Wang

Beilstein J. Org. Chem. 2021, 17, 52–57, doi:10.3762/bjoc.17.6

• rac-TBPP/DGG = 1:80, a mirror symmetry was observed in the CPL spectra of the co-gel at the molar ratio of rac-TBPP/LGG = 1:80 (Figure 2d). rac-TBPP contains pyridine units, and the gelator DGG has the carboxyl groups. Therefore, hydrogen bonds might be formed between pyridine in rac-TBPP and the

• FTIR (fourier transform infrared) spectra. UV–vis absorption spectra of rac-TBPP/DGG co-gels exhibited a strong absorption band at 333 nm, assigned to the conjugated structure of benzene and pyridine in the rac-TBPP (Figure 3a). However, a red-shift broaden absorption band situated at 372 nm appears in

• results demonstrate that some of the acid–acid hydrogen bonds between DGG molecules might be replaced by acid–pyridine hydrogen bonds between DGG and rac-TBPP [27]. In addition, the possible influence of the stoichiometric ratios to the morphologies of rac-TBPP/DGG co-gels was investigated using a

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• . Kovalevskaya Str., 22, Yekaterinburg 620219, Russian Federation 10.3762/bjoc.17.2 Abstract Novel carbazole-based [6]helicenes fused with an azine ring (pyridine, pyrazine or quinoxaline) have been prepared through a five-step synthetic sequence in good overall yields. Commercially available 2,3-dihaloazines

• , we synthesized carbazole-based [6]helicenes fused with an azine ring (quinoxaline, pyrazine or pyridine ones). Scheme 2 represents the current work. We envisaged that combining the carbazole unit with the readily available azine building block would result in the formation of donor–acceptor hybrid

• synthesized in 97% yield by the treatment with a 3-fold excess of ICl on monoiodide 7b. The ICl-induced cyclization of the pyridine-based starting compound 6 proceeded smoothly giving rise to product 7c in 62% (Table 3, entry 5). It should be noted that compounds 7a, 7b and 7c are derivatives of the