Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• heating in polyphosphoric acid, the nitroalkanes 1 convert into the phosphorylated nitronates 2, which exhibit strong electrophilic properties. This allowed for the employment of these species in reactions wherein electron-rich arenes serve as carbon-based nucleophilies [38][39][40]. It was also

• GC and 1H NMR to reveal that the desired product 16a was formed in a disappointingly low yield (Table 1, entry 1). Heating of the reaction mixture to 130 °C, together with the employment of even more highly concentrated 87% PPA, resulted in an improved conversion, but only insignificantly so (Table 1

• smoothly with 1-nitropropane (1b), 1-nitrobutane (1c), and 1-nitrohexane (1d) in the presence of 87% PPA, although this required heating to 160 °C to bring the reaction to completion. The corresponding imidazo[1,5-a]pyridines 16b–d were isolated in good practical yield in all three cases (Scheme 3). This

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• . Nevertheless, we investigated the preparation of 1,6-anhydro-2,3,4-trideoxy-2,3,4-trifluoro-β-ᴅ-hexopyranose analogues from previously described 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-ᴅ-hexopyranoses 2–5 using DAST (Table 1). We thus used 2 equivalents of DAST at 100 °C under microwave heating for 1 h and

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• catalysis. For the evaluation of this property, the state SelfSORT-I was heated at 50 °C with 1.0 equiv of the catalyst 42 (with respect to the rotor), and 10.0 equiv (with respect to the rotor) of substrates 43, 44, 46, and 47 in CD2Cl2/CD3CN 5:1. After heating the mixture for 2 h, 30% of the product 45

• but no click product 48 was observed (Figure 14b). The addition of 1.0 equiv of zinc(II) ions (with respect to the rotor) generated the state SelfSORT-II. After heating this mixture using the identical conditions, 55% of the click product 48 was detected but no further conversion of the product 45

• SelfSORT-II disassembled the host–guest complex [Zn4(64')4]8+•(C6H12) with the concomitant release of the encapsulated cyclohexane thus generating the state SelfSORT-III. In this process, the 1H NMR signals corresponding to [Zn4(66')4]8+•(NO3−) remained unchanged. At last, heating the mixture to 70 °C for

Dirhamnolipid ester – formation of reverse wormlike micelles in a binary (primerless) system

• David Liese,
• Hans Henning Wenk,
• Xin Lu,
• Jochen Kleinen and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2020, 16, 2820–2830, doi:10.3762/bjoc.16.232

• for the samples with dirhamnolipid esters of different alkyl chain length and the bola structure. Figure S1a in Supporting Information File 1 represent the plots for the change in the elastic (storage) modulus G' and the viscous (loss) modulus G'' with respect to the temperature while heating. The

• (G'' > G'). Fluids are unable to store mechanical stress. Thus, the storage modulus drops to almost zero. For the cooling process, the change of the moduli mirrors the ones of the heating process (Figure S1b in Supporting Information File 1). We performed concentration-dependent temperature sweeps

• structure 7 has transition temperatures that are between the ones of 2 and 3. Different transition temperatures were found for the heating and cooling process, with TGS > TSG. This hysteresis amounts to ΔT = 2–3 °C for the different samples. The lower transition temperatures from solution to gel can be

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• investigated using only convection heating. The aim of the current work is to investigate the regio- and diastereoselectivity of the microwave-assisted (3 + 2) cycloaddition of 6-aryldiazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones. Results and Discussion Herein, we report the 1,3-dipolar

• formation of adduct 3m and pyrazoline 4b (Scheme 3). Thus, the azomethine imine A, formed by heating of DABCH 1a, either reacts with propenone 2f giving the adduct 3m or undergoes isomerization affording pyrazoline 4a. On the basis of this observation we suppose that the reaction products undergo

• liberation of the aromatic aldehyde and formation of the new azomethine imines. Conclusion The cycloaddition of azomethine imines, generated from 6-aryl-1,5-diazabicyclo[3.1.0]hexanes under microwave heating, with 1,3-diarylpropenones occurs regioselective with the formation of 2-benzoyl-substituted pyrazolo

Anion exchange resins in phosphate form as versatile carriers for the reactions catalyzed by nucleoside phosphorylases

• Julia N. Artsemyeva,
• Ekaterina A. Remeeva,
• Tatiana N. Buravskaya,
• Irina D. Konstantinova,
• Roman S. Esipov,
• Anatoly I. Miroshnikov,
• Natalia M. Litvinko and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2020, 16, 2607–2622, doi:10.3762/bjoc.16.212

• kept overnight in a refrigerator. The precipitate formed was filtered off, washed with ethanol, dried in vacuum under CaCl2 at room temperature to give Ara-1Pi (Ba2+) as white powder (244 mg, 96%; TLC: iPrOH/25% NH4OH/water, 11:2:5 (vol), Rf 0.30, development by heating). The NMR data were similar to

• those published earlier [29]. The barium salt of Ara-1Pi (73 mg, 0.2 mmol) and E. coli PNP (280 IU; 2,333 IU per 1 mmol of heterocyclic base) were added to an aqueous solution of OMG (20 mg, 0.12 mmol, dissolved by heating) in distilled water (50 mL) at room temperature, and the reaction mixture was

• ), except where otherwise indicated. TLC was performed on TLC glass plates covered with silica gel 60 F254 (Merck, Germany). The TLC control of the PF-1Pis synthesis and conversions was tested first by UV light then by heating of the plates. UV–vis spectra were recorded with a Shimadzu UV-Mini 1240

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

• Emine Kayahan,
• Mathias Jacobs,
• Leen Braeken,
• Leen C.J. Thomassen,
• Simon Kuhn,
• Tom van Gerven and
• M. Enis Leblebici

Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202

• energy efficiency. In addition, the solvent should not absorb light strongly nor be a quencher of the photoreaction. In order to avoid excessive heating of the light source, cooling systems might be necessary. The distribution of light inside the reactor brings a lot of complexity into the design. Since

A proposed sustainability index for synthesis plans based on input provenance and output fate: application to academic and industrial synthesis plans for vanillin as a case study

• John Andraos

Beilstein J. Org. Chem. 2020, 16, 2346–2362, doi:10.3762/bjoc.16.196

• input materials and fate of output materials, we may now examine the energy source provenance for conducting all heating and cooling operations involved in all reaction steps in a synthesis plan. We define a total input enthalpy energy, (IEE)total, as shown in Equation 8 where it is divided into

• renewable and non-renewable energy sources. The explicit formulation of (IEE)total is shown in Equation 9 where it is obtained as a sum of all energy consumptions as a result of heating and cooling over all input materials used in a synthesis plan above or below a reference state representing the ambient

• plans had higher values in the range 1.2 to 92, except for the Eilks – Pt 1 and Lampman plans that used isoeugenol and sawdust, respectively, as starting materials. With respect to energy consumption, the two percolation extraction procedures using cut or whole cured vanilla beans with no heating of

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• mL/1 mL/0.1 mL) with [(CH3CN)4Cu]PF6 and ascorbic acid (see Scheme S2 in Supporting Information File 1). After removal of the solvent, the cutting step was performed by heating the crude product with KOH in a water/THF/ethanol mixture to saponify the esters. The pH of the mixture was adjusted to

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• , with acetonitrile used as a solvent, the yield of product 3a reached 83%. When the reaction in acetonitrile was prolonged to 96 h, the yield improved to 92% (Table 1, entries 16 and 17). Unlike the experiment in dichloromethane at 40 °С (Table 1, entry 5), heating to 80 °С and reduction of the reaction

• time to 8 h did not reduce the yield, which remained essentially the same, about 90% (Table 1, entry 18). Heating the reaction mixture also allowed the copper salt and pyridine to be used in substantially lower (catalytic) amounts, though sacrificing the yield to some extent (79%, Table 1, entry 19

• partners. As established in the first experiments, stirring the reaction mixture at room temperature for 24 h followed by heating at 80 °С in acetonitrile results in a considerably increased yield of the corresponding pyrimidones 3. The thus optimized reaction conditions were applied to obtain a series of

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• ) complex 123 as an endo-coordinated complex at the concave side. The complex 123a was prepared through the metalation of sumanene involving ligand exchange with a cyclopentadienyl (Cp) group of ferrocene by heating in the presence of Al powder and AlCl3 under solvent-free conditions followed by a counter

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• molecules in water. The absorption maxima and corresponding molar extinction coefficients (ε) are given in Table S1 (Supporting Information File 1). Heating of the aqueous solution of 4 up to 90 °C did not yield any significant changes in its UV–vis spectrum, suggesting that the chromophores are not

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• synthesis of 2,4,5-trisubstituted oxazole from azirine. a) I2, PPh3; b) NaH, 1H-pyrazole; c) 2-bromoacetyl bromide, NaN3; d) heating; e) t-BuOK; f) Ph-CHO, visible light; g) KSCN, K2S2O8. Scope of the α-azidochalcones. The reactions were carried out at reflux temperature, using 1 (1 mmol), 2 (3 mmol

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• sequence. On the other hand, the successful thermal iminium-ion induced SE(Ar) reactions shown in Scheme 2 were not applicable to the iminium-substituted norbornadiene 2, which suffered undefined polymerization on moderate heating in various solvents. In contrast to so far unknown 9‑amino-9

• -substituted propyn-1-iminium salts is also exemplified by the Diels–Alder reaction of 1a with anthracene (Scheme 3). After 12 h at room temperature, a 91% conversion was observed, and subsequent moderate heating gave the cycloaddition product 10 in 95% yield. The subsequent iminium-induced electrophilic

• cyclization required extended heating in refluxing toluene and finally furnished the neutral polycycle 11 in good yield. The paddlewheel-shaped structure of 11 was established by an XRD structure determination and is shown in Figure 1. The reactivity of 1a in the Diels–Alder reaction with anthracene may be

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• examined first by means of the thermal denaturation method. Various double-stranded DNA or RNA are known upon heating to dissociate into two single-stranded polynucleotides at a characteristic well-defined temperature (Tm value). A non-covalent interaction of small molecules usually increases the thermal

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• equiv) in dichloromethane. The reaction was slow and required heating (50–65 °C) for 26 h to reach a 75% conversion and afforded a mixture of E/Z-1a in 60% yield. However, a low E/Z selectivity (40:60) was observed (Table 1, entry 1). When using neat benzylic alcohol, completion was achieved after 20 h

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• putative azide tautomer 4, the latter deriving from the corresponding α-phenacyl azide precursor 2 via an acid-catalyzed enolization process [34]. The pyrolysis of α-azido ketones in conventional VOCs (trichlorobenzene) is known to take place under harsh conditions, which are based on heating the mixture

• chloride (ChCl)/urea (1:2 mol/mol)] were prepared by heating under stirring up to 80 °C for 10–15 min the corresponding individual components until a clear solution was obtained. 1H NMR and 13C NMR spectra were recorded on a Varian Mercury 300 or on a Bruker 400 or 600 MHz spectrometer and chemical shifts

• heating to 473 K until blue spots appeared. Column chromatography was conducted by using silica gel 60 with a particle size distribution of 40–63 μm and 230–400 ASTM, using hexane/EtOAc mixtures as the eluent. High-resolution mass spectrometry (HRMS) analyses were performed using a Bruker microTOF QII

Three new O-isocrotonyl-3-hydroxybutyric acid congeners produced by a sea anemone-derived marine bacterium of the genus Vibrio

• Dandan Li,
• Enjuro Harunari,
• Tao Zhou,
• Naoya Oku and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1869–1874, doi:10.3762/bjoc.16.154

• was stirred for 30 min at room temperature. The production of the amide was monitored by thin-layer chromatography (TLC), developed using ethyl acetate/n-hexane 1:1, followed by heating with phosphomolybdic acid. After removing the solvent, the residue was subjected to HPLC on a Cosmosil π-NAP column

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

• Ilya V. Taydakov and
• Mikhail A. Kiskin

Beilstein J. Org. Chem. 2020, 16, 1863–1868, doi:10.3762/bjoc.16.153

• [26]. The product was isolated on 150 mmol scale by simple vacuum distillation. Hydrolysis of diethyl 2-(perfluorophenyl)malonate (3) unexpectedly turned out to be quite challenging. Unsubstituted diethyl or dimethyl 2-phenylmalonate can be readily hydrolyzed under basic conditions by heating with

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• -nitrocyclohexanones. When the reaction was conducted in the presence of water, the cyclohexenes were efficiently hydrolyzed into cyclohexanones. Subsequent aromatization by heating the cyclohexanone with a catalytic amount of iodine in dimethyl sulfoxide gave 3-arylated-4-nitrophenols. The reaction of nitrostyrenes

• trimethylsiloxy group of the diene can be converted to a phenolic hydroxy group by hydrolysis) [20], followed by the oxidation and aromatization of the obtained cyclohexanone 4 (Scheme 1). Results and Discussion Heating an acetonitrile solution of nitrostyrene 1a with Danishefsky’s diene (2) at 60 °C for 18 h

• even at 120 °C (Table 1, entry 8). Cyclohexene 3a was efficiently converted to the cyclohexanone 4a upon heating at 120 °C in toluene in the presence of 10 equiv water (Scheme 2). This result prompted us to synthesize 4a in one pot from 1a and 2 by Diels–Alder reaction and subsequent heating with water

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• construction of nitrogen-containing heterocycles from common substrates: 1,4-diketones and primary amines. Indeed, by just varying the substrates, the substituents, or the heating mode, it is possible to selectively synthesize indole, indolone (1,5,6,7-tetrahydroindol-4-one), or cinnoline (5,6,7,8

• under air. Herein, we report our investigations on this reaction, and we have shown that it can be selectively directed towards the synthesis of indole, indolone, or cinnoline derivatives by just changing the substrates, substituents, or heating mode (Scheme 1). Results and Discussion The synthesis of

• with a diamine. Synthesis of the indoles 6h–l. Synthesis of the indolone derivatives 7b, 7d, and 7g–k. Synthesis of the cinnoline derivatives 8a–k. Proposed mechanism for the preparation of the compounds 6, 7, and 8. Effects of solvent and heating mode on the 6b:7b ratio. Optimization of the reaction

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• developed by reacting 5-amino-1,2,3,4-tetrazole with aromatic aldehydes and cyanamide in pyridine under controlled microwave heating with high yields. X-ray crystallography confirmed the structure of the obtained products. Keywords: microwave irradiation; N2-(tetrazol-5-yl)-6-aryl/heteroaryl-1,3,5-triazine

• -triazine-2,4-diamines in 44–72% yields that employed the reaction of isothiocyanates with sodium hydrogen cyanamide and amidines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and heating at 75 °C for 3 h. Recently, Ma et al. [33] described a one-pot two step procedure for

• green methodologies in synthetic heterocyclic chemistry. The utilization of microwave heating as an energy source has several advantages including operational simplicity, high reaction yields, enhanced rates, and increased energy efficiency [34][35][36][37][38][39][40]. In continuation of our efforts in

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• endotermic process is the rate-limiting step and long reaction times are generally associated to this. However, the reaction can be accelerated in conditions that facilitate the dissociation of CO ligands such as heating, microwave irradiation [37][38], visible light, or ultrasonication [39]. Alternatively

• and co-workers [73] allowed the efficient preparation of a small library of substrates bearing aryl, alkyl, and alkenyl substitutents. These were isolated after complexation to Co2(CO)8 as the corresponding adducts 64, due to difficulties in their isolation. Subsequent heating with norbornadiene

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• points but they are not the primary interest. Varying purity, heating rates, and even if the experimentalist is actually looking when the compound melts, affect the results strongly. Measuring the melting point is a necessary chore. The result is that the data are of very poor quality. This can be seen

Five-component, one-pot synthesis of an electroactive rotaxane comprising a bisferrocene macrocycle

• Natalie Lagesse,
• Luca Pisciottani,
• Maxime Douarre,
• Pascale Godard,
• Brice Kauffmann,
• Vicente Martí-Centelles and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2020, 16, 1564–1571, doi:10.3762/bjoc.16.128

• free ferrocene macrocycle, the ferrocene rotaxane 1a was soluble in CDCl3 suggesting a complementary macrocycle-thread hydrogen-bonding interaction. While the rotaxane 1a was insoluble at room temperature in DMSO-d6, heating at 160 °C dissolved the rotaxane. Macrocycle dethreading in DMSO-d6 at 160 °C

• was monitored by 1H NMR (Figures S12 and S13 in Supporting Information File 1). After 1 h of heating at 160 °C, the integration of the NMR signals showed circa 58% of rotaxane 1a, along with free macrocycle 2 and thread 4a. After 23 h of reaction, no starting material remained and only 34% of the