Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• work, just akin to previously mentioned methodology in Scheme 7, a wide range of imidazole N-oxides and CH-acids like dimedone, barbituric acid, Meldrum’s acid, 4-hydroxycoumarin, hydroxy-6-methylpyranone, and 4-hydroxy-7,7-dimethyl-7,8-dihydro-2H-chromene-2,5(6H)-dione were chosen along with

• -7,8-dihydro-2H-chromene-2,5(6H)-dione). Synthesis of imidazole-2-thiones containing cyclohexyl-substituents at 3-position. Preparation of optically active derivatives of 3-butoxyimidazole-2-thione. Funding The author (MH) highly acknowledges UGC-SRG-India (No.F.30-597/2021-BSR) for financial support

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• ]. The reaction is interesting as both furfural and 1 are present along with water in crude biomass pyrolysates, and so the reaction could affect yields of 1 [3][17][18]. Samet and co-workers have reported a similar condensation of 1 with salicylaldehyde resulting in chiral chromene derivative 4 [19][20

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• generated phosphinimines 218 followed by quenching with water and sequential loss of two molecules of dimethylamine. However, the mechanism of this transformation was not clearly investigated (Scheme 35) [16]. To develop new antitumor agents composed of chromene and 5-oxo-1,2-azaphospolidine 2-oxide motifs

• to the cyano group followed by hydrolysis to give the final product 223 (Scheme 36). The product 223 showed antitumor activity in a biological assay [20]. To develop antioxidants and antitumor agents, the same group synthesized chromene-fused 5-oxo-1,2-azaphospholidine 2-oxide derivatives. The

• reaction of 2-imino-2H-chromene-3-carboxamide (228) and diethyl phosphite at 80–90 °C under the catalysis of boron trifluoride, afforded 4-amino-1-ethoxy-9b-hydrochromeno[4,3-c][1,2]azaphosphol-3(2H)-one 1-oxide (229) in 40% yield through the Michael addition and subsequent tautomerization and

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• reactions (anthracene (33) and maleic anhydride (34) to the cycloaddition adduct 35 and chromene carbaldehyde 36 and enol ether 37 to the diastereomeric pyrano-chromenes 38), Alder-En reactions (oxomalonate diethyl ester (39) and β-pinene (40) to give the α-pinene derivative 41), and the thermal

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

• at the double bond underwent cyclization as the result of intramolecular interception of the rhodium carbene, which led to the formation of indolizine [6] or 2H-chromene [7] derivatives, respectively (Figure 1). At the same time, Rh2(esp)2-catalyzed reactions of DAS with nitriles and carbonyl

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

• side afforded 6-membered chromene derivatives 75 but no thiochromene derivatives were observed [76]. Compound 75 on refluxing with trifluoroacetic acid isomerized to form exocyclic trans-compound 76. It was reported that 1,4-di(arylthiol)-2-butyne derivatives only afforded usual Hg(II)-salt-mediated

• frameworks from various tosylanilinoallyl acetals. 4H-Chromene derivatives were also synthesized starting from phenol derivatives (Scheme 38). Cyclization involving alkynes (-C≡C-) Marson et al. had developed the synthesis of substituted furans 133a–c promoted by catalytic use of Hg(II) salt through

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

• hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside moieties (Scheme 2). Bojanowski and co-workers developed a methodology to synthetize 3,4-dihydrocoumarins 10 through a decarboxylative and dearomatizative cascade reaction [33]. This reaction was carried out using coumarin-3-carboxylic acids 8

• substituted methylene malononitriles 92, affording a variety of pyrano[3,2-c]chromene derivatives 93 (Scheme 29) [64]. The catalyst used in this reaction was the dehydroabietylamine-cinchone-squaramide derivative 94. The products were obtained with good to excellent yields and enantioselectivities with both

• [dihydrofurocoumarin/pyrazolone] 83. Michael/hemiketalization addition enantioselective of hydroxycoumarins (1) to: (a) enones 2 and (b) α-ketoesters 86. Synthesis of 2,3-dihydrofurocoumarins 89 through Michael addition of 4-hydroxycoumarins 1 to β-nitrostyrenes 88. Synthesis of pyrano[3,2-c]chromene derivatives 93

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

• dibenzofurans 4 were also explored for the treatment of various skin diseases [16]. Furthermore, 2-substituted benzofurobenzofurans 5 with antitubercular activity have been reported [17]. Prado et al. reported the antimycobacterial activity of furo[3,2-f]chromene analogue 6 [18]. The aza analogues of

• aza analogue 9 of previously reported furo[3,2-f]chromene 6 was examined for antimycobacterial activity [28]. This evidence encouraged us to investigate new methodologies for the synthesis of aza analogues of dibenzofuran from commercially available aminochloropyridines. Furthermore, a diverse set of

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

• (51) in presence of acetic acid under microwave irradiation for the synthesis of highly functionalized benzopyrans 52. The method was successfully employed for the construction of chromene and phenazine motifs exhibiting the applicability of the protocol to engender diverse chemical entities (Scheme

• -assisted four-component reaction involving chromene-aldehyde (61), amines 32, acyclic 1,3-diketones 54 and nitromethane using silica-gel-supported polyphoshoric acid as catalyst under neat conditions for the synthesis of tetra-substituted pyrroles 62. A comparative study of the protocol employing the

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

• undergo tandem Friedel–Crafts hydroarylation reactions to give derivatives 130 under TfOH activation at 50 °C. Finally, CF3-substituted chromene derivatives 132 were obtained under the same reaction conditions from ortho-hydroxy or ortho-silyloxy derivatives 131a and 131b, respectively. The common

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• pyrone or chromene-like structures and aromatic π electrons [108][124][125]. Nowicki et al. showed different acidic and basic conditions on the surface of the activated carbon materials resulting from different activation methods of cherry stones-based carbons. Activation by carbon dioxide led to basic

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• position of the absorption maximum and the quantum yields or the rate constants of the forward and reverse reaction also depend largely on the solvent polarity as well as on the position and the nature of the substituents either at the indoline or the chromene unit. Surprisingly, there are only a few

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• attempts have also been made to develop photochromic DNA binders. Thus, it has been shown with spiropyran [19][20][21], stilbene [22][23], azobenzene [24][25][26][27][28], dithienylethene [29][30][31][32], chromene [33], and spirooxazine [34] derivatives that specifically modified photochromic ligands bind

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• = 5.3 nM) properties [90][91][92]. Treating the obtained chromene-3-carboxylate 2l with LiOH [93] led to the formation of the chromene-3-carboxylic acid G. Heating compound G overnight in the presence of AgNO3 and K2S2O8 afforded frutinone A in an isolated yield of 45% (Scheme 5). Conclusion In summary

Design, synthesis and investigation of water-soluble hemi-indigo photoswitches for bioapplications

• Daria V. Berdnikova

Beilstein J. Org. Chem. 2019, 15, 2822–2829, doi:10.3762/bjoc.15.275

• photochemical properties. Along these lines, special efforts have been devoted to design, for example, water-soluble derivatives of spiropyran [1][2][3], azobenzene [4][5], diarylethene [6][7][8], or chromene [9] that keep efficient photochromism in aqueous medium. Although a significant progress has been made

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• coumarin 7. For a broader scope of this approach, bisindole triads 8{4,4,8}, 8{4,4,9}, 8{10,10,9} and 8{1,1,10} were also synthesized in good yields by replacing the corresponding quinoline-/quinolone aldehydes 6{1–6} with 4-oxo-4H-chromene-3-carbaldehyde (6{8}), 6-fluoro-4-oxo-4H-chromene-3-carbaldehyde

• extended to a variety of indoles 1, quinoline-/quinolone- and chromene aldehydes 6, and hydroxycoumarins 7 as illustrated in Schemes 3–5, leading to a set of novel tris(heteroaryl)methane triads 9{1,1,1} to 9{6,4,1}, as shown in Figure 2. Structures of the newly obtained triads 8 and 9 were ascertained by

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

• may be found in crolibulin, an antitumor agent, undergoing phase II clinical trials [31], chromenotacrine CT-6, a potential anti-Alzheimer agent [32], and pranoprofen, a marketed anti-inflammatory drug [33]. Combination of chromene and imidazopyridine rings led to the discovery of compound A with

• promising anticancer activity [34], thereby showing the importance of this merged heterocyclic skeleton (Figure 1). The formation of the chromene and imidazole rings in a single-step procedure was independently discovered by us [35][36] and Proença et al. [37][38], who identified 2-iminochromene 3 to be the

• key intermediate of the domino sequence (Scheme 1, reaction 1). Taking into account the capability of 2-iminochromenes to perform as Michael acceptors [39][40][41], we envisioned the diversification of the substitution pattern at the chromene ring to be a realizable and an appealing target

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• defined order. One class of products, pyrano[2,3-f]chromene-2,8-diones, were inaccessible through direct RCM of an acrylate, but became available from the analogous allyl ether via an assisted tandem catalytic RCM/allylic oxidation sequence. Keywords: coumarins; heterocycles; isomerization; olefin

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• was carried out for several salicylaldehydes and gave a clear improvement in the yield of the corresponding triazolochromenes and consequently showed to be a viable alternative for solid salicylaldehydes. Keywords: ball milling; multicomponent reaction; 3-nitro-2H-chromene; one-pot synthesis; 1,2,3

• search for new methodologies towards the rapid assembly of chromene analogs is of utmost importance for many researchers. In this regard, 3-nitrochromenes are easily available building blocks for chromene and chromane derivatives and are highly reactive due to the presence of the nitroalkene moiety

• , which enables them to undergo a high variety of reactions and functionalizations [15]. Combining the chromene core with the 1,2,3-triazole structural motif has led to some interesting new molecules [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Very recently, spiro-fused

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• the CAS while the chromene rings were located at the PAS. Compounds 9a, 9b, 9e, 9h, and 9i revealed similar orientations in the binding pocket whereas the binding of compounds 4a and 10a was partially different. The orientation of the chromene ring of compound 4a was shifted away from the others

• , whereas the chromene ring of compound 10a was flipped to the opposite site when compared with the other compounds. The binding interactions of each compound are shown in Figure 3. The most active compound 9h (Figure 3e) formed H-bond interactions to the residues in the following binding sites: (1) the

• methylene unit of the benzyl group to the CT amino acid residue His447; (2) the carbonyl of the amide moiety and fluorine atoms to the amino acid residues Trp86, Tyr337, and Phe338 in the CAS; (3) the carbonyl group of the chromene ring to the acyl pocket amino acid residue Phe295; (4) the nitrogen atom of

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• protic solvents such as H2O or EtOH at 100 °C, the desired products were formed in short reactions (1–20 min) and chromene-2-carbonitriles 12–15 were isolated in 61–88% yields. Saito et al. generated o-QMs starting from Mannich bases by low-energy UV irradiation in aqueous acetonitrile [68]. In the

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• . Reactions with oxygen nucleophiles: In 1964 Schweizer reported the synthesis of 2H-chromene (39) by reaction of vinyltriphenylphosphonium bromide (8) with salicylaldehyde sodium salt in a yield of 62–71%, depending on the reaction conditions (Scheme 27) [1]. In a similar reaction with the use of 3-hydroxy-2

• -butanone, 2,5-dihydro-2,3-dimethylfuran (40) was obtained in a yield of 89% (Scheme 28) [1]. Several years later, Schweizer et al. applied analogous reaction conditions to the synthesis of 3-substituted derivative of 2H-chromene 41 and 2,5-dihydrofuran derivative 42 in yields in the range of 30–58% and 36

• vinylphosphonium halides and nucleophiles containing carbonyl function in the molecule. Synthesis of 2H-chromene by reaction of vinyltriphenylphosphonium bromide with sodium 2-formylphenolate. Synthesis of 2,5-dihydro-2,3-dimethylfuran by reaction of vinylphosphonium bromide with 3-hydroxy-2-butanone in the

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• dicyanofumarates E-1 via competitive nucleophilic attack of C4 or NH2. Heterocyclization reaction of thiosemicarbazone 86 with E-1a. Formation of diethyl 4-cyano-5-oxotetrahydro-4H-chromene-3,4-dicarboxylate (90) from E-1a via heterocyclization reaction. Reaction of dialkyl dicyanofumarates E-1 with cysteamine (92

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• , benzaldehydes and electron-rich phenols in presence of 5 mol % of POPI, afforded near quantitative yield of chromene derivatives within 20 min (Scheme 40). Similarly, various benzaldehydes with electron-withdrawing groups at the o/p-position accelerated the reaction and electron-donating groups slowed that down

• particles [146]. Mechanochemical synthesis of 1,2-di-substituted benzimidazoles [149]. Mechanochemical click reaction using an alumina-supported Cu-catalyst [152]. Mechanochemical click reaction using copper vial [155]. Mechanochemical indole synthesis [157]. Mechanochemical synthesis of chromene [158

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• showed that benzimidazoles, Biginelli adducts, dihydropyridines, furans, pyrans, pyridinones, and thiophenes had a high representation of intrinsic greenness; whereas, a high proportion of MCRs producing chromene-4-ones, coumarins, indoles, and pyrazoles had low probabilities of achieving intrinsic