Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• pyridines via C–N, C–C, and C–S bond formations in a mixture of ethanol and H2O under ultrasound irradiation. The catalyst is characterized by XRD, FTIR, Raman spectroscopy, SEM, and EDAX analysis. The main advantages of this methodology include the wide substrate scope, cleaner reaction profile, short

• : benzimidazoles; dihydropyrimidinones; highly substituted pyridines; natural dolomitic limestone; ultrasound irradiation; Introduction Nitrogen heterocycles are recognized as “privileged medicinal scaffolds” because these compounds are found in a wide variety of bioactive natural products and pharmaceuticals [1

• ][2][3]. Among them, benzimidazoles, dihydropyrimidinones, and pyridines have emerged as promising and valuable structural units in many pharmaceutical lead compounds (Figure 1) [4][5][6][7][8][9]. Hence, there is a great need for the development of a green and sustainable synthetic route to the

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

• , heterocycles such as, pyrroles (e.g., IV) [24], keto pyrroles (e.g., V) [25], pyridines (e.g., VI) [26], pyrrolotriazoles (e.g., VII) [27], and triazolobenzoxazonines (e.g., VIII) [28] result from MBH acetates (Scheme 1). From these synthetic elaborations, three successive steps are universally utilized: (i

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• cleavage and aromatization to give substituted pyridines 255 [75] (Scheme 49). In 1989, Kanaoka and co-workers further studied the photo [2 + 2] cycloadditions of thiobarbiturates 256–258, whose skeletons consisted of a combination of a thioamide and an amide or a thioamide (two-imides system), and olefins

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• SET. After the reduction, a fragmentation affords the desired amidyl radicals together with the corresponding pyridines. The reduction potential of such species was around −0.75 V vs Ag/Ag+, depending on the substitution pattern. This scaffold was employed recently by the Hong group to achieve an

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• medicinal chemistry [19][20]. A number of clinically used drugs and clinical candidates, such as zolpidem, alpidem, saripidem, zolimidine, necopidem, and GSK812397 contain the imidazo[1,2-a]pyridine scaffold [21][22][23][24][25][26]. 3-(Arylselanyl)imidazo[1,2-a]pyridines IV were reported to act as

• potential antioxidants and showed antiproliferative activity [27][28]. Consequently, they have attracted much attention, and methods for their syntheses have been actively pursued. A powerful method for the synthesis of 3-selanylimidazo[1,2-a]pyridines involves the C–H selenation using imidazopyridine and a

• ]pyridines, which are isomers of imidazo[1,2-a]pyridines, with Se powder [34]. However, in this reaction, selenides and diselenides were generated in ratios of approximately 1:1; hence, an efficient selective synthesis has not yet been achieved. Inspired by the aforementioned reports and our continuing

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• azaenolate with reactive Michael acceptors in a follow-up study [45]. While pyridines are among the most important classes of heterocyclic moieties that occur in many bioactive molecules, such as natural products, pharmaceuticals, and agrochemicals, the initial report by the Harutyunyan group did not include

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• , meta and para positions. Moreover, the methodology also showed effectiveness for heteroarenes such as pyridines and benzothiazoles. The authors also evaluated the use of NiTPP as a photoredox catalyst for other transformations involving both oxidative and reductive quenchings. The NiTPP-catalyzed

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• proceeding at the C2 carbon atom of the seleniranium cation 2 with dithiocarbomates [31], thiourea [32], alcohols [42], functionalized organic acids [43][44], functionalized pyridines [45], ammonium thiocyanate [46], and mercapto benzazoles [40] were developed (Scheme 4). The new methodology of a

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• lithium halogen elimination, halide migration, and ring-opening reactions [56][57]. Butylphosphines are also formed alongside the main product, and in most cases pure phosphine pyridines are obtained using column chromatography followed by extractions adding to the number of synthesis steps. This method

Synthesis and circularly polarized luminescence properties of BINOL-derived bisbenzofuro[2,3-b:3’,2’-e]pyridines (BBZFPys)

• Ryo Takishima,
• Yuji Nishii,
• Tomoaki Hinoue,
• Yoshitane Imai and
• Masahiro Miura

Beilstein J. Org. Chem. 2020, 16, 325–336, doi:10.3762/bjoc.16.32

• dehydrogenative coupling adopting oxygen atom as the linker [12][13][14][15][16][17]. In particular, bisbenzofuro[2,3-b:3′,2′-e]pyridines (BBZFPys) were found to exhibit intense photoluminescence with relatively high quantum efficiency (Φflu up to 0.70), indicating that the BBFZPy scaffold may serve as a key

• unsymmetrically substituted pyridines 3a–c in high yields. We then examined the oxidative cyclization of these compounds under the standard conditions adopting Pd(TFA)2 (30 mol %, TFA = trifluoroacetate) and AgOAc (3.0 equiv) as catalyst and oxidant, respectively, in pivalic acid as solvent (Scheme 3). Since the

Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• Strukturchemie, Universitätsstraße 1, D-40225 Düsseldorf, Germany 10.3762/bjoc.15.262 Abstract Starting from substituted alkynones, α-pyrones and/or 1H-pyridines were generated in a Michael addition–cyclocondensation with ethyl cyanoacetate. The peculiar product formation depends on the reaction conditions as

• well as on the electronic substitution pattern of the alkynone. While electron-donating groups furnish α-pyrones as main products, electron-withdrawing groups predominantly give the corresponding 1H-pyridines. Both heterocycle classes fluoresce in solution and in the solid state. In particular

• emission solvatochromism. Also a donor-substituted α-pyrone shows pronounced aggregation-induced emission enhancement. Keywords: cyclocondensation; DFT calculations; fluorescence; heterocycles; 1H-pyridines; α-pyrones; Introduction A high sensitivity and precise tuneability of fluorescence colors are

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• pyridinyl motif. In fact, only two pyridinyl silicon rhodamines (13 and 14) are known so far, although halogenated pyridines are highly interesting for further functionalization or vector conjugation by nucleophilic aromatic substitution. For the implementation of the dihalogenated pyridine motif into the

• ., tetrasubstituted pyridines [48]) with substitution patterns difficult to obtain otherwise [49][50][51]. Results and Discussion Approaches to synthesize the pyridinyl silicon rhodamine 15 Table 2 and Scheme 3 summarize the experimental results towards the synthesis of the radiofluorinatable near-infrared dye 15. To

• HD reactions of nicotinic acids can be found in the literature. In fact, if 2,3-dihalogenated pyridines are used for the HD rearrangement as starting materials, only methyl groups are tolerated as carbon substituents. Optical properties of the pyridinyl silicon rhodamine 15 The dihalogenated

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• 38% yield; whereas the use of 2-chlorobenzonitrile afforded 12 in 62% regioselectivity and in 34% yield. In both cases, partial conversions of the aryl chlorides were observed. Pyridines and quinoline heterocycles are very important structures in pharmaceutical chemistry as more than 100 currently

• marketed drugs contain these units. Therefore, the reactivity of 3- and 4-bromo-substituted pyridines, 3-bromoquinoline and 4-bromoisoquinoline for the α-arylation of lilolidine was also studied. In all cases, the desired N-containing coupling products 16–19 were obtained in high regioselectivities and in

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• constructing tetracyclic aromatic heterocycles containing selenium. For example, the reaction of 2-(2-iodophenyl)indoles with selenium powder in the presence of CuO as catalyst resulted in benzoselenopheno[3,2-b]indole derivatives [14]. The reaction of 2-(2-haloaryl)imidazo[1,2-a]pyridines with selenium using

• a CuI catalyst for the synthesis of benzo[b]selenophene-fused imidazo[1,2-a]pyridines occurred smoothly [15][16]. Performing these types of reactions without the addition of a transition metal catalyst is more challenging, but would alleviate the environmental burden of removing and disposing of the

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• reaction [14]. Recently, several hydroxyalkylation reactions followed by alkylation of arenes have been reported involving heterocycle-based superelectrophiles: pyridines, thiazoles, quinolines, isoquinolines, pyrazines, pyrazoles, imidazole and furans, bearing a formyl (carbonyl) group [15][16][17][18][19

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• been given much attention in various research fields, such as the discovery of lead compounds in medicinal chemistry, or combinatorial chemistry [95][96]. Copper-catalyzed synthetic protocols Ghosh and Mishra [97] have successfully reported the synthesis of imidazo[1,2-a]pyridines in a three-component

• -benzenedicarboxylate), Puthiaraj and co-workers have unprecedently discovered the catalytic activity of this metal-organic framework (MOF) for the synthesis of imidazo[1,2-a]pyridines [100]. The three-component, one-pot reaction between 1, 3 and nitromethane (10, Scheme 5) involved an intermolecular aza-Michael

• heterogeneously catalyzed synthesis of imidazo[1,2-a]pyridines from 3 and ketones 20 has been reported (Scheme 7) [101]. Titania-supported CuCl2 (CuCl2/nano TiO2) played the role of catalyst in this transformation under aerobic conditions. Titania support helped in recyclability of the copper salt to four

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• ]triazolo[4,3-a]pyridines was accessed through a 5-exo-dig-type cyclization of chloroethynylphosphonates and commercially available N-unsubstituted 2-hydrazinylpyridines. In addition, 3-methylphosphonylated [1,2,4]triazolo[4,3-a]quinolines and 1-methylphosphonylated [1,2,4]triazolo[3,4-a]isoquinolines were

• synthesized in a similar manner. The presence of a NO2 group in the starting hydrazinylpyridine induces a Dimroth-type rearrangement leading to 2-methylphosphonylated [1,2,4]triazolo[1,5-a]pyridines. Keywords: cyclization; fused-ring systems; nitrogen heterocycles; phosphorylation; rearrangement

• imidazo[1,2-a]pyridines [4]. In continuation of this study, herein we report an effective approach to the synthesis of new phosphonylated triazolopyridine derivatives by reacting chloroethynylphosphonates with 2-hydrazinylpyridines. The triazolopyridine ring is a structural fragment that is present in a

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• )-2-oxobut-3-enoic acid (5b) [52][53] with 5-amino-3-methyl-N-phenylpyrazole (6) (HOAc, Δ, 5 h). As a result, two different types of pyrazolo[3,4-b]pyridines containing the carboxylic group either at C4 position (compounds 4a,b) or at the C6 position (compound 7b) were synthetized (Scheme 2). We

• easier work-up stage as well as due to avoiding the formation of impurities of the dihydropyrazolo[3,4-b]pyridines. Thus, starting from the same set of reactants two different types of heterocyclic acids 4 and 7 containing two diversity points were obtained. Afterwards compounds 4a,b were introduced into

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• , Boruah’s group has been very active in the synthesis of nitrogen heterocycles such as pyrimidines, pyrazolopyrimidines and disubstituted pyridines fused to rings A and D of steroids [47][48][49]. Thus far, most applications of MCRs in steroid derivatization aimed at producing derivatives for screening

Design of a double-decker coordination cage revisited to make new cages and exemplify ligand isomerism

• Sagarika Samantray,
• Sreenivasulu Bandi and
• Dillip K. Chand

Beilstein J. Org. Chem. 2019, 15, 1129–1140, doi:10.3762/bjoc.15.109

• spectrum of compound 1a showed single set of peaks (Figure 2(ii)) characterized by complexation-induced downfield shifts of protons belonging to the terminal pyridines (Δδ = 0.77, 0.52, and 0.29 ppm for Ha, Hb, and Hc, respectively) as compared to the free ligand L1. The peak positions of Hf and Hg

• S27–S31). The 1H NMR spectrum of compound 3a showed a single set of peaks (Figure 3) featured with complexation-induced downfield shifts of protons belonging to the terminal pyridines (Δδ = 0.79, and 0.47 ppm for Ha, and Hb, respectively) as compared to the free ligand L1. The peak position of Hf did

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• ). Condensation of 1,2-diketones DK with o-phenylenediamine to quinoxalines QU1–7 (CAN = cerium ammonium nitrate). The LANCA three-component reaction leading to β-ketoenamides KE and the structure of functionalized pyridines PY, pyrimidines PM, pyrimidine N-oxides PO, oxazoles OX, 1,2-diketones DK and

Intramolecular cascade annulation triggered by rhodium(III)-catalyzed sequential C(sp²)–H activation and C(sp³)–H amination

• Liangliang Song,
• Guilong Tian,
• Johan Van der Eycken and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 571–576, doi:10.3762/bjoc.15.52

• -catalyzed intramolecular annulation of alkyne-tethered hydroxamic esters for the synthesis of isoquinolones and pyridines without using external oxidants (Scheme 1a) [22]. Recently, we reported an intramolecular annulation of benzamides to synthesize indolizinones through RhIII-catalyzed C(sp2)–H activation

Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• approaches towards this tempting scaffold are reported in the literature. They can be divided into two groups: oxidation of pyrrolo[3,2-c]pyridines [13][15][16] and annulation of pyridine by a pyrrole-2,3-dione moiety (cyclization of 2-(4-((alkoxycarbonyl)amino)pyridin-3-yl)-2-oxoacetates [11], interaction

Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• -triflate pyrazinium salts to also generate γ-lactones [12]. Grignard reagents have been used as nucleophiles on a variety of N-acyl-activated pyridines in the production of natural products and biologically active small molecules [13][14][15][16][17][18][19][20]. To our surprise, there are no reports on

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• annulation patterns. Biologically relevant imidazo[1,2-a]pyridines and chromenes. General view of the molecule 7b in the crystal state (CCDC 1849215). Anisotropic displacement parameters are drawn at 50% probability. Domino formation of imidazopyridines and current work. Scope of the reaction between N