Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• scalable (i.e., a maximum of 15% by 1H NMR). Finally, due to the concentration of α-iodopropiophenone (6) employed, we detected the formation of a byproduct in the last stages of the optimization, namely the condensation of the desired product with α-propiophenone in the form of an enol ether. Once this

• byproduct was fully characterized by NMR, and the structure was confirmed by SCXRD, we conceived a hydrolysis protocol to break apart the formed enol ether (fully described in section 2.4 of Supporting Information File 1). After brief optimization, we succeeded at recovering the portion of

• shorter wavelengths. During this optimization, the use of 2 to 3 equivalents of the reagents 1 resulted in better yields, along with more concentrated reaction mixtures, reaching almost quantitative yields (by NMR) for the perfluorohexylation of TMB (10b) and 83% NMR yield for its perfluorooctylation (10c

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• report a continuous flow synthesis of non-symmetric AB compounds via the Baeyer–Mills reaction, which allows to obtain large quantities of products from different substrates in a fast and efficient manner. Results and Discussion For optimization of the Baeyer–Mills coupling in continuous flow the

• under the previously optimized conditions. By collection of the reactor output for 2 h, 582 mg of AB were obtained. Further purification was not necessary as the product was satisfactorily pure with the described workup. After successful optimization of the synthesis of unsubstituted AB (1a) the setup

• . Low yields in case of electron-poor aniline derivatives can be explained by the reduced nucleophilicity. To exemplarily demonstrate the optimization for electron-poor derivatives, the synthesis of p-cyano-substituted AB 1o was repeated at higher temperatures. Thereby the yield of 1o could be increased

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• optimization of the reaction conditions for improving the yield of the cycloadduct 3a. A broad range of solvents was screened at different temperatures. As presented in Table 1, aprotic solvents such as 1,4-dioxane, acetonitrile, and dimethylformamide (DMF) at 65 °C favored the formation of the desired

• the most basic site in the molecule. We carried out full geometry optimization of all possible tautomers 1, 1', 1'', and aza-allylic anion Ruhemann's purple to calculate the Gibbs free energy change for the corresponding acid–base reactions (Scheme 7). As expected, the calculation data showed that the

• optimization of both transition states TS-4-NI and TS-4'-NI corresponding to pyramidal inversion in cycloadducts 4 and 4' and two pairs of invertomers, we have found that each of the diastereomers 4 and 4' is a mixture of two easily interconverting invertomers (ΔG‡4-exo->4-endo = 1.2 kcal/mol and ΔG‡4-endo->4

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• . Optimization of process parameters revealed that at a conversion of 75% a good selectivity of 89% for hydrogenation of alkyne 31 to alkene 32 is achieved affording a mixture of (Z)- and (E)-isomers in a ratio of 80:20 [37]. Floral odorants Floral notes, such as rose, jasmine, orange blossom, or lavender, are

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• envisaged that the absence of solvent under mechanochemical conditions should prevent the formation of products from tetrahydrofuran and therefore allow cycloaddition to take place. Results and Discussion Reaction optimization Anthracene addition to dibromide 10 (Scheme 1) was used as the model reaction

• Table 1. The results of the optimization experiments showed that the solution reaction conditions could be transferred to mechanochemical conditions without significant loss of reactivity and identical side-products were formed. Initial experiments were performed with the Zn/Ag couple prepared by a

• . Optimization of reaction conditions for reaction of 10 with anthracene.a Supporting Information Supporting Information File 146: Details of experimental procedures and characterization data of selected compounds. Funding This work is funded by the Croatian Science Foundation (grant No. IP-2018-01-3298

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• for the formation of dispiro compounds 8. Optimization of reaction conditions.a Reaction of isatylidene malononitriles and bis-chalcones.a Reaction of 3-(ethoxycarbonylmethylene)oxindoles and bis-chalcones.a Reaction of ethyl isatylidene cyanoacetates and isatins.a Supporting Information

Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide

• Kyoko Mandai,
• Tetsuya Yamamoto,
• Hiroki Mandai and
• Aiichiro Nagaki

Beilstein J. Org. Chem. 2022, 18, 660–668, doi:10.3762/bjoc.18.67

• epoxidation was obtained in the reaction at 100 °C which is the temperature of choice for the following optimization of the flow epoxidation. Investigation of the residence time The residence time of the flow epoxidation was examined at 100 °C from 0.35 to 2 min (Figure 4). Both conversion of cyclohexene and

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• . A plausible reaction mechanism. Optimization of the reaction conditions.a Supporting Information Supporting Information File 48: Synthetic schemes for products, characterization data, and copies of 1H, 13C, and 19F NMR spectra. Funding We gratefully acknowledge funding from Jiangsu Provincial

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• ). Results and Discussion Towards the optimization study, (E)-N-(2-((2-bromobenzylidene)amino)phenyl)-4-methylbenzenesulfonamide (1a) was considered as a model substrate for the synthesis of 2-(2-bromophenyl)-1-tosyl-1H-benzo[d]imidazole (2a, Table 1). Initially, with 1.0 equiv of DDQ, product 2a was

• conditions: reactants were milled at 21 Hz in a 25 mL milling jar containing one stainless-steel grinding ball (15 mm in diameter). Optimization of the reaction conditions.a Supporting Information Supporting Information File 46: Experimental details, characterization data, copies of NMR spectra and X-ray

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

• with 10,000 iterations and a 0.001 kJ (mol Å)−1 convergence threshold on the root mean quare (RMS) gradient. All the conformers of 1–3 within 3 kJ/mol of each global minimum were subjected to geometry optimization using the Gaussian 16 package (Gaussian Inc.) in the gas phase at B3LYP/6-31G(d) level

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• test systems, show EC50 values in the lower nM range [36][37][38][39]. Thus, the newly reported compounds are a valuable enrichment from the chemical perspective and have promising potential for further optimization or combination with other compounds. The structures of chloroquine, hydroxychloroquine

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• and activation ability. Catalytic reaction optimization The synthesized macrocycles were then applied as catalysts in the decarboxylative addition of malonic acid half thioesters (MAHTs) to isatin-derived ketimines [48]. The reaction between ketimine 6a and MAHT 7a was initially performed in THF at

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• the structure of the product 3a. With 3-phenacylidene oxindole 1a and tosylhydrazine (2) as model substrates, we started the optimization of the reaction upon various parameters such as temperature, base and solvent. A variety of bases were examined in the reaction, both inorganic and organic bases

• equiv) at 60 °C for 6 h in 6 mL CH3CN. Plausible mechanism of the reaction. Control experiment. Optimization study for the formation of 3a.a Supporting Information Supporting Information File 128: Experimental and analytical data. Supporting Information File 129: CIF-file of compound 3g. Supporting

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• ). In addition, there are competing reactions leading to the O-trapping product and the C-trapping product of the nitrile oxides (Figure 2, paths C and D). We were interested in the optimization of the reaction conditions leading to the isoxazole products (path D, Figure 2). For this purpose, we chose 4

• plausible mechanism for the formation of the 3,4,5-trisubstituted isoxazoles 3 in the presence of DIPEA in polar solvents like water or methanol. Structures of β-lactamase-resistant antibiotics oxacillin, cloxacillin, dicloxacillin, and flucloxacillin. Optimization of the reaction conditions for the

• synthesis of 3,4,5-trisubstituted isoxazoles 3.a Optimization of the reaction conditions to synthesize the trifluoromethyl-substituted isoxazole 3x.a Supporting Information Supporting Information File 150: Synthetic schemes for phenyl hydroximoyl chlorides and 1,3-diketones, characterization data, and

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• bromopropargylic alcohol 1a and phenol (2a)a. Supporting Information Supporting Information File 36: General information, synthetic procedures and additional optimization results, NMR spectra and characterization of synthesized compounds. Acknowledgements The main results were obtained using the equipment of the

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

• using lawsone (4) and after optimization of the reaction conditions, it was extended to other quinones, including menadione (10). The best conditions were 1,2-dimethoxyethane (DME) as solvent, temperature 25 °C, under ultraviolet light irradiation (125 W lamp) using a Pyrex filter in an immersion-well

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• derivatives from readily available compounds in a single step, but also has the advantage of eliminating the use of expensive or toxic reagents. In addition to optimization of the general parameters for the electrolytic reaction, the effect of base addition was also investigated, and was determined to

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• of 3,4-dihydroquinazoline 8a. Preparation of 3,4-dihydroquinazolines 8. Preparation of 4H-3,1-benzothiazines 11. Optimization of the reaction conditions for the preparation of compound 8a. Yields of 3,4-dihydroquinazolines 8. Yields of 4H-3,1-benzothiazines 11. Supporting Information Supporting

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

• , recyclable, and selective for the coupling between aryl halides and phenylacetylene in PEG as the solvent (Scheme 22). The effect of various reaction parameters such as solvent, base, temperature, and catalyst loading was assessed by the model reaction between bromobenzene and phenylacetylene. Optimization

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• optimization and frequency calculations. Frequency analyses and single-point energies were calculated with the M06 functional [69] with the triple-ζ basis set def2TZVP [70] with the PCM (1,4-dioxane) solvent model [72]. The Gibbs free energies of formation of the reactants, products, and transition states were

• ). Nishimura’s seminal report on iridium-catalyzed hydroacylation reactions of bicyclic alkenes and the context of this work. Iridium-catalyzed hydroacylation of C1-substituted OBDs 13a–k with salicylaldehyde 14. Competition reaction of different C1-substituted OBDs. Optimization of the hydroacylation reaction

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• this mixture dissolved in EtOAc, precipitation of the amine salt enabled the removal of naphthalene in the solvent. Beside the choice of the solvent for the crystallization which strongly depends on the solubility of the protonated amine salts involved, we first focused on the optimization of the

• decarboxylation conditions (Table 1, see Supporting Information File 1 for additional optimization). From the solid amine salt, different conditions were thus tested for a rapid decarboxylation. When stirring the amine salt in EtOAc, only a partial decarboxylation was observed even after 24 hours (Table 1, entry

• machinery using TCA (a) and our application to amines purification (b). Application of the TCA purification from a crude reaction mixture. Optimization of the decarboxylation. Examples of impurities removed from dicyclohexylamine. Scope of purified amines. Supporting Information Supporting Information File

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• chromatography. Enantioselectivities were determined by chiral HPLC analysis. aReaction run for 6 h. Synthetic transformation. Optimization of the reaction conditions.a Supporting Information Supporting Information File 202: Detailed experimental procedures, complete characterization data for all compounds

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

• conduct a high-throughput screening we initially carried out the milling experiments in Eppendorf vials before using standard milling jars made of stainless steel or poly(methyl methacrylate) (PMMA). This simple approach accelerated the optimization of the milling and reaction parameters [26]. From a

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• particular enzymes. Preliminary results indicate that scaffold C shows good affinity to proto-oncogene tyrosine-protein kinase Src, a well-known anticancer target [47], with IC50 = 0.26 µM and is a suitable candidate for further structural optimization. Paullone related indolobenzazepinone isomers. 7,12

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• further increasing this quantity did not result in an enhanced yield. As such, the optimized conditions were sonication for 15 min in ethanol using 30 mg of the Ni–chitosan NPs (Table 2, entry 17). The optimization studies using this standard amount of catalyst are summarized in Table 2. Substrate scope

• derivatives using the Ni–chitosan nanocatalyst. ICP–OES analysis of the Ni–chitosan NPs. Optimization of the reaction conditions.a Comparison between the previous reports on the synthesis of C5–C6-unsubstituted 1,4-DHPs and the present work. Supporting Information Supporting Information File 21