Syntheses of novel pyridine-based low-molecular-weight luminogens possessing aggregation-induced emission enhancement (AIEE) properties

• Masayori Hagimori,
• Tatsusada Yoshida,
• Yasuhisa Nishimura,
• Yukiko Ogawa and
• Keitaro Tanaka

Beilstein J. Org. Chem. 2022, 18, 580–587, doi:10.3762/bjoc.18.60

• , Japan Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7, Huis Ten Bosch, Sasebo 859-3298, Japan Graduate School of Engineering, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8131, Japan 10.3762/bjoc.18.60 Abstract Novel pyridine-based fluorescing compounds, viz

• have been reported [7][8][9][10]. Because the aggregated state of AIEE-based compounds is affected by the external environment, these compounds have found use in clinical applications as chemical sensors or fluorescent probes [7][8][9][10]. Pyridine is a nitrogen-containing heterocyclic compound found

• in many bioactive substances and medicines as one of the basic core skeletons [11][12]. In addition, pyridine is an essential skeleton for fluorescent compounds, and fluorescence can be enhanced by optimizing the internal charge transfer (ICT) state of pyridine by introducing electron-donating or

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• hydrolysis, was dissolved in pyridine (0.5 mL), then ʟ-cysteine methyl ester hydrochloride (2 mg) was added. The reaction mixture was stirred at 60 °C for 1 h. Then O-tolyl isothiocyanate (30 μL) was added and stirred at 60 °C for 1 h. The reaction mixture was analyzed without purification by LC–MS analysis

• using GC–MS. Monosaccharides (1, 0.4 mg; 2, 0.3 mg; 3, 0.4 mg; 4, 0.4 mg), obtained by hydrolysis, were dissolved in pyridine (0.5 mL), then ʟ-cysteine methyl ester hydrochloride (2 mg) was added. The reaction mixtures were then stirred at 60 °C for 2 h. After adding 1-trimethylsilylimidazole (0.1 mL

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• , Ph3P, Ac2O, reflux. aReported yields are 1H NMR yields. bIsolated yield. i) LiHMDS, MeI, THF, −78 °C. i) a) NaOH, MeOH/H2O, rt, Amberlyst 15 [H+], b) AcOH 70% aq, reflux, 2 h; ii) a) EtOCOCl, pyridine, b) Et3N, CH2Cl2; iii) (Ph3P)4Pd, BSA, THF. i) Lawesson’s reagent, HMDO, toluene, MW irradiation (120

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• )-38, featuring the BINOL unit on the axle, does not allow for higher stereoselectivities (19% ee), but interestingly gives the other product enantiomer as the main product (see Figure 9). In 2016, Takata and co-workers reported a pyridine-based rotaxane catalyst for the O-acylative asymmetric

• pyridine axle, followed by ion exchange, gave rise to the cationic rotaxanes 64a/b in 23/37% overall yield, both of which feature four iodotriazoles as XB donors. While rotaxane (S)-64a only possesses the BINOL unit as a stereogenic element, the system (S,S,S)-64b features two additional chiral centers on

• featuring BINOL-based [2]rotaxane side chains. Synthesis of Takata´s chiral thiazolium [2]rotaxanes (R)-35a/b and (R)-38. Results for the asymmetric benzoin condensation of benzaldehyde (39) with catalysts (R)-35a/b and (R)-38. Synthesis of Takata´s pyridine-based [2]rotaxane (R)-42. The asymmetric

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• three component catalyst system consisting of iron(III) chloride, pyridine-2,6-dicarboxylic acid (H2Pydic), and benzylamine (1:1:2.2) for the oxidation of 16 with H2O2, in tert-amyl alcohol (TAA), allowed to obtain 10 in 44% yield (Table 1, entry 9) [55]. Subsequently, Kulkarni’s group evaluated the

• H2O2 and acetic acid as oxidant. Additionally, the selectivity of this process was 99% (Table 2, entry 6). Beller et al. developed another approach using H2O2 as oxidizing agent in combination with a three component catalyst system consisting of FeCl3·6H2O, pyridine-2,6-dicarboxylic acid (H2Pydic), and

• steps whose main difficulties are the separation of pyridine byproducts and inorganic phosphate (Scheme 20). Kulkarni and co-workers reported a method for menadione reduction mediated by 5,6-O-isopropylidene-ʟ-ascorbic acid (70, R = H) under UV light irradiation [120]. Initial studies were carried out

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• iron complex B is formed by the oxidative addition of the iron catalyst to the pyridine derivative. Intermediate Fe species were obtained by transmetallation and finally a new carbon–carbon bond is formed by reductive elimination (Scheme 19). This method provided access to a diverse range of 7

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• aldehydes (Scheme 2) and subjected to the optimised flow conditions (Scheme 3). This resulted in full conversion of the substrate in all cases. Both thiophene and pyridine-containing substrates were well tolerated, with slightly higher yields observed in the case of the more electron-deficient CF3

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• and sugar, respectively. The aqueous residue was concentrated to dryness under N2. The aqueous residue, ᴅ-glucose (2 mg), and ᴅ-xylose standard (2 mg) were separately dissolved in 0.5 mL anhydrous pyridine, and ʟ-cysteine methyl ester hydrochloride (2.0 mg) was then added. Each reaction mixture was

• key correlations observed in the 1H-1H COSY (bold bonds), HMBC (blue) correlations of 1 (recorded in pyridine-d5, 600 MHz). The key correlations observed in the 1H-1H COSY (bold bonds), HMBC (blue), ROESY (red) of 1 (recorded in DMSO-d6, 800 MHz). 1H and 13C NMR Spectroscopic Data for 1 (δ in ppm, J

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• reactivity of pyridine derivatives with NFSI, which are known to generate phenylsulfonyl fluoride via a transient generation of N-sulfonylpyridinium salts [37]. Analysis by 19F NMR spectroscopy of the crude reaction mixture of 3b and NFSI revealed the presence of PhSO2F (Scheme 3d), thus confirming the

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• NMR spectra. The solubility issues forced us to investigate also other modification protocols. Thus, macrocycle 11 was subjected to an ozonolysis with subsequent Wittig reaction in a one-pot manner (Scheme 4). Performing the ozonolysis in presence of pyridine led to immediate reduction of the primary

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• -methyltetrahydrofuran following a chemoenzymatic pathway. Whereas, the protection of the primary hydroxy over the lone secondary hydroxy group in the key azido sugar precursor was achieved using bulky tert-butyldiphenylsilyl chloride (TBDPS-Cl) in pyridine in 92% yield following a chemical synthetic pathway. The

• pyridine to afford dimesylated nucleosides 16a,b in 93 and 94% yields, respectively. The reaction of nucleosides 16a,b with NaOH in dioxane/water (1:1) underwent a cascade reaction pathway to form 9a,b in 82 and 84% yields, respectively (Scheme 4). The overall yields for the synthesis of nucleosides 9a,b

• regioselective protection of the primary hydroxy group of diol 17 using TBDPS-Cl in pyridine at room temperature afforded TBDPS-protected furanoside 18, which on acetolysis using AcOH/Ac2O/H2SO4 (100:10:0.1) afforded the anomeric mixture of coupling sugar 19a,b in 80% yield. The Vorbrüggen coupling [29] of

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• HCl(g) in MeOH (Scheme 1). N-Boc protection of cis-amino ester 3 with (Boc)2O in pyridine and 4-(dimethylamino)pyridine (DMAP) gave N-Boc-amino ester 4 (yield 95%). The 1H and 13C NMR spectroscopic data of 4 were in agreement with the proposed structure. Treatment of 4 with OsO4/NMO gave the expected

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

• and reported that they were unable to obtain 4-arylamino-1,2-naphthoquinones from β-NQSNa but that these derivatives can be readily prepared from 4-ethoxy-1,2-naphthoquinone. Similarly, Yano and co-workers [72] studied the tautomeric equilibrium of 4-arylamino-1,2-naphthoquinones in DMSO-d6, pyridine

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• desired epoxide 5 in an acceptable 70% yield with excellent stereoselectivity as the sole syn isomer (dr > 95:5). It is worth noting that a small quantity of pyridine was added to prevent unwanted acid-catalyzed epoxide hydrolysis [31]. The stereochemistry of 5 was assigned later after pyrrolidine ring

• %; (c) 12WO3·H3PO4×H2O, H2O2 (35 wt % in H2O), pyridine, ethyl acetate, rt, 48 h, 70%; (d) BF3·OEt2, CH2Cl2, 0 °C, 15 min, 69%; (e) H2 (1 atm), Pd(OH)2/C (5 wt %), MeOH, rt, 2 h, (±)-2, 71%; (f) H2 (1 atm), Pd(OH)2/C (5 wt %), MeOH, rt, 2 h; then formaldehyde (37 wt % in H2O), H2 (1 atm), Pd(OH)2/C (5

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• provided the corresponding carboxylic acid, and further oxidative decarboxylation with lead tetraacetate and pyridine provided oxathiolane 20. Chu and co-workers [41][42] further established a more proficient system for the synthesis of (+)-BCH-189 (1a) from 1,6-thioanhydro-ᴅ-galactose (3d, Scheme 4

• reaction of benzoyl chloride in pyridine to protect the hydroxy group, which results in a high yield. The isopropylidene group was selectively deprotected using 10% HCl, followed by oxidative breakage of the carbon–carbon bond of the resulting diol using sodium periodate. Further reduction of the aldehyde

• afforded the thiol compound 3nb. Further treatment of the thiol 3nb with methyl glyoxylate in dichloromethane solvent along with molecular sieves (4 Å), followed by in situ acetylation using Ac2O, pyridine, and catalytic 4-(N,N-dimethylamino)pyridine (DMAP) provided compound 37. The second route involves

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• obtained via TBHP-mediated cyclization of 23 and subsequent TBS-deprotection of intermediate 24 with pyridine and HF·pyridine complex [66] in a total yield of 26% over the two steps. The longest linear sequence was 7 steps, with an overall yield of 5%. Finally, the reaction mechanism of the oxidative

• , imidazole, DMF, 50 °C, 18 h; f) LAH, AlCl3, THF, rt, 12 h; g) TBHPaq, DCE, 100 °C, 18 h; h) pyridine, HF·pyridine, EtOAc, rt, 14 h. Proposed mechanism for the oxidative cyclization of amines 2a and 2b to fluorenone (3). Reactivity of different functional groups towards TBHP-mediated cyclization to give

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• compounds with heterocyclic substituents are of high biological and medicinal relevance [34][35]. Therefore, we have decided to evaluate sulfinylurea and thiourea catalysts C1 and C2 also with (E)-2-(2-nitrovinyl)furan (9) and (E)-3-(2-nitrovinyl)pyridine (11) as Michael acceptors. As Michael donor, we

• ). The aliphatic aldehydes propanal (6d) and hexanal (6b) provided medium yields and diastereoselectivity and enantioselectivity. The Michael addition of 3-phenylpropanal (6c) to (E)-3-(2-nitrovinyl)pyridine (11) required long reaction times (120 h) in solution, similar to those for the reaction with (E

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• acid, reflux, 12 h (74% for 4; 69% for 8); d) SeO2, acetic acid, microwave irradiation, 150 °C, 15 min (74% for 4; 67% for 8); and e) Ac2O, benzene/pyridine, rt, 24 h (74%). Synthesis of 7-oxo intermediate 11 from chenodeoxycholic acid (9). Reagents and conditions: a) EtOAc, pTsOH, reflux, 12 h (66

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• conversion of 3 into the cyclohexanone product 4 (Figure 2) [4]. The best results were obtained with 2-[4-(S)-tert-butyloxazolin-2-yl]pyridine ((S)-5), which gave >90% yield of (S)-4 in 46% ee. In a similar investigation except with copper(II) as the metal and β-hydroxy-α-diketone 6 as the substrate, the

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• ; Morita–Baylis–Hillman carbonates; Introduction Pyridines are among the most important heterocyclic structural moieties in many biologically active natural products, pharmaceuticals, and agrochemicals [1][2][3]. Therefore, the development of efficient strategies for functionalized pyridine derivatives

• synergistic catalyzed allylic alkylation between electron-deficient 2-ethyl benzoxazoles and MBH carbonates by the combination of a Lewis base and a metal salt [24]. In their studies, although pyridine derivatives were also applicable in the reaction, the presence of a strong electron-withdrawing NO2 group

• the scope of various 2-alkypyridines to react with MBH carbonate 2a under the standard conditions and the results are shown in Scheme 4. Alkyl substituents at the 3 or 5-positions of pyridine were tolerated, giving the desired products in moderate to good yields (4b and 4c, 83% and 71% yield

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• in 2020, an enantioselective C–H annulation of ferrocenylformamides with alkynes was achieved by the Ye group enabled by Ni-Al bimetallic catalysis and a chiral secondary phosphine oxide (SPO) ligand [35]. Hou et al. also reported the asymmetric C−H alkenylation of quinoline- and pyridine-substituted

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• structural motifs to provide the functionalized pyridine and pyrrole derivatives. The functionalization reactions cover iodination, bromination, trifluoromethylation, azidation, carbonylation, arylation, alkylation, selenylation, sulfenylation, amidation, esterification, and hydroxylation. We also briefly

• introduce the applications of the products and the reaction mechanisms for the synthesis of corresponding N-heterocycles. Keywords: 1,3-enyne; functionalization; pyridine; pyrrole; tandem annulation; Introduction The pyridine moiety is an important class of six-membered N-heterocycles that is widely found

• in many natural products, pharmaceuticals, and bioactive molecules. For instance, some pyridine derivatives have been used for therapy of HIV, cancer, inflammation, microbial infection and so on [1][2][3][4][5]. In addition, it is also an important synthetic unit, which is frequently used as catalyst

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