Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• aldehydes were mixtures of isomers, but it was acceptable for our intended purpose – to study the controlled release of the aldehydes, i.e., volatile organic compounds (VOCs). The aldehyde selected for the optimization of reaction conditions was cinnamaldehyde (2a), as it is strongly UV absorbing, i.e

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• chemically, two possible conformations of 8b were considered, 8b-I and 8b-II (Figure 2). Similar to a previous report on 8c [37], both 8b-I and 8b-II adopted an almost eclipsed conformation during optimization. Computations predicted slightly lower energy (1 kcal⋅mol−1) for conformation 8b-I, with Cl

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• /P(OEt)3 (1.5 equiv), rt or 50 °C. Optimization of the reaction conditions for Cu-catalyzed methallylation of 2-[(3-benzyldimethylsilyl)furyl] carbinol 4c. Supporting Information Supporting Information File 224: General information, characterization data, and copies of NMR spectra. Acknowledgements

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• demonstrate the feasibility of our idea, ethyl acetoacetate (1a) and thiourea (2a) were chosen as model substrates for the optimization of reaction conditions. Based on our previous studies on the halide-mediated α-C–H functionalization of carbonyl compounds [32][33][34][35], graphite was chosen as the

• . Optimization of the reaction conditionsa. Supporting Information Supporting Information File 220: Experimental procedures, characterization data and copies of spectra of the all synthesized compounds (1H NMR, 13C NMR and HRMS). Funding This work was financially supported by the National Natural Science

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• material for 120 minutes at the frequency of 30 Hz. aIsolated yields. bAcetic acid and p-Ts-Im were ball-milled for 10 minutes, then the amine was added, and the mixture was ball-milled for additional 120 minutes. Optimization of reaction conditions for 2.a,b. Optimization of reaction conditions for

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• radical anions influenced by substituents in the cyclopropane ring are discussed. Optimization of the reaction conditions opens a route to the non-proteinogenic amino acid derivatives containing an α–β or β–γ double C=C bond in the side chain; the regioselectivity can be tuned by the addition of Lewis

• include disproportionation reaction yielding a mixture of alkenes and the corresponding hydrogenated derivatives, intramolecular cyclization and reaction with external electrophiles. Optimization of the reaction conditions opens a route to amino acid derivatives containing the α-β or β-γ double C=C bond

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• ), aniline (2), and ethyl 2,4-dioxovalerate (3) in glacial acetic acid was used for optimization (Scheme 1). Reacting equimolar amounts of 1a, 2, and 3, 0.5 M in acetic acid as solvent at room temperature [39], resulted in the formation of 1,5-diphenyl-4-acetyl-3-hydroxy-3-pyrrolin-2-one (4a) in a yield of

• :2:3 ratio optimization for the synthesis of product 4a. The thermodynamic parameters of possible reaction pathways in the gas phase (kcal·mol−1) at the B3LYP/6-311++G(2d,2p)// B3LYP/6-31+G(d,p) level of theory. The thermodynamic parameters of selected pathways (1), (2), (3), and (4) in ethanol

• (kcal·mol−1) at the B3LYP/6-311++G(2d,2p)// B3LYP/6-31+G(d,p) level of theory. Optimization of the reaction conditions for the synthesis of compound 10aa. Synthesis of a library of 1,4,5-trisubstituted pyrrolidine-2,3-diones. Supporting Information Supporting Information File 188: Experimental part

Synthesis of protected precursors of chitin oligosaccharides by electrochemical polyglycosylation of thioglycosides

• Md Azadur Rahman,
• Kana Kuroda,
• Hirofumi Endo,
• Norihiko Sasaki,
• Tomoaki Hamada,
• Hiraku Sakai and
• Toshiki Nokami

Beilstein J. Org. Chem. 2022, 18, 1133–1139, doi:10.3762/bjoc.18.117

• glucosamine monosaccharide. However, N-acetylglucosamines are linked by α-1,4-glycosidic bonds. Here, we report electrochemical polyglycosylation of thioglycosides to produce protected precursors of chitin oligosaccharides. Results and Discussion Optimization of electrochemical polyglycosylation We initiated

• our study with the optimization of the arylthio group of thioglycoside 1, carrying an unprotected 4-OH group, an acetyl-protected 3-OH unit, a benzyl-protected 6-OH group, and a phthaloyl-protected 2-NH2 unit (Figure 2) [3]. Electrochemical polyglycosylation was performed by a sequential two-step

Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

• Wei-Hsin Hsu,
• Susanne Reischauer,
• Peter H. Seeberger,
• Bartholomäus Pieber and
• Dario Cambié

Beilstein J. Org. Chem. 2022, 18, 1123–1130, doi:10.3762/bjoc.18.115

• point for applications in large-scale synthesis or automated reaction optimization. Based on literature precedents on catalyst leaching in packed-bed reactors [37][38], we assumed that the decreased activity could be linked to nickel leaching. Based on ICP results on the reactor outlet collected in the

• after chromatography might still be too high for use as API. If the remaining nickel content becomes an issue, a column packed with an immobilized scavenger could be used to further reduce the Ni content in the final product [39]. Reactor optimization Flow maldistribution and poor mixing efficiency in

• )-proline. Optimization of temperature and light intensity for the coupling of 4-iodobenzotrifluoride and sodium p-toluenesulfinate. Comparison of different reactors. Supporting Information Supporting Information File 104: Details of packed-bed assembly, experimental procedures, reaction optimization and

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• cyclopropanetricarboxylates. Previous reports (reactions 1–3) and this work (reaction 4). Plausible reaction mechanism. EGB = electrogenerated base. Reaction optimization. Effect of electricity around 1 F/mol and type of electrochemical cell. Scope and limitations. Scale-up experiments. Supporting Information Supporting

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• also catalyze isoflavone dimerization, the above results indicated that CYP158C1 dimerizes isoflavones and several plant-derived aromatic polyketides, albeit with low catalytic efficiency. Future optimization of the reductase partner or reaction conditions may be required to improve the enzyme activity

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• . Results and Discussion First, optimization of the reaction conditions was conducted using substrate 1a as a model according to Table 1. The molar ratio of 1a, the catalyst, the base, and the ligand used in Table 1, entry 1 was adapted from the literature [25]. The reaction mixture was stirred for 5 h at

• (Scheme 1). In the 1H NMR spectrum of the crude reaction mixture, only 3% of the desired product 2a was detected, together with an undefined amount of the intermediate hydrazone 1a (Figures S5 and S6, Supporting Information File 1). Next, the most effective conditions as determined from the optimization

• , hexane/AcOEt 80:20 for 4g, hexane/AcOEt 98:2 for 4h, and hexane/AcOEt 85:15 for 4i and 4i’. One-pot approach for the synthesis of 2a. aYield calculated vs trichloroethylene by 1H NMR spectroscopy. Regioselectivity of the reaction of arylhydrazones 1i and 3i, respectively. Optimization of the reaction

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• -1,2-diols through the formal homocoupling of sec-alcohols using platinum electrodes in an undivided cell (Scheme 1c). Results and Discussion We commenced the optimization study for the electrochemical formal homocoupling of sec-alcohols by using 1-phenylethanol (1a) as a model substrate. The results

• internal standard. bDetermined by 1H NMR analysis. Proposed mechanism. Optimization of reaction conditions.a Supporting Information Supporting Information File 116: Experimental procedure, characterization data, and copies of NMR spectra of the products. Funding This work was supported by the Japan

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• carboxylic acids or isocyanates. The acetamide group was well tolerated in our reduction, implying our method showed interesting reduction selectivity. The synthesis of formamides and monomethylamines. The possible reaction mechanism. RDS = rate determining step. Optimization of the reaction conditions.a

Electrochemical vicinal oxyazidation of α-arylvinyl acetates

• Yi-Lun Li,
• Zhaojiang Shi,
• Tao Shen and
• Ke-Yin Ye

Beilstein J. Org. Chem. 2022, 18, 1026–1031, doi:10.3762/bjoc.18.103

• (Ecell = 2.3 V, carbon cloth anode, and Pt cathode) of 1-phenylvinyl acetate (1) with azidotrimethylsilane was performed and the desired α-azidoketone (2) was obtained in 68% yield (Table 1, entry 1, for details of the reaction optimization see Supporting Information File 1). The cyclic voltammetry

• . Derivatization of α-azidoketone 2. Proposed mechanism. Optimization of reaction conditions.a Supporting Information Supporting Information File 186: Experimental procedures, characterization data, copies of 1H and 13C NMR spectra. Funding Financial support from the National Natural Science Foundation of China

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• ][57]. Herein, we report a sustainable and facile aromatic (mono-, di-, and tri-) halogenation protocol by controlling the stoichiometry of the N-halosuccinimide and PEG-400 as the grinding auxiliary in an electrical grinder (Scheme 2). Results and Discussion At the outset, the optimization of the

• initial optimization study showed that the presence of excess NBS could increase the yield of undesired dibromo products (Table 1, entry 10). Encouraged by this, a short series of dihalogenated derivatives was prepared under optimized grinding conditions by just changing the stoichiometry of NXS from 1

• grinder. Optimization of the reaction conditions for the bromination with NBS.a Trihalogenation of phenols and anilines with NXS by automated grinding.a Supporting Information Supporting Information File 226: Experimental procedures, spectral data, tables, and copies of spectra. Funding SERB, India

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

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

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• mechanism for compounds 3, 4, and 5. Control experiment. Optimization of reaction conditions.a Synthesis of functionalized cyclopentenes 3a–l.a Synthesis of compounds 4a–k.a Supporting Information The crystallographic data of the compounds 3k (CCDC 2176733), 4a (CCDC 2176734), 4b (CCDC 2176735), and 5

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• compared chemical yields of products (Table 4), although in different solvents. As far as the literature allows comparison of the two methodologies, the data in Table 4 show that, although further optimization of the flow electrochemistry conditions is required, it provides a valid alternative to batch

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• and Table 2, we undertook optimization trials focusing on the condensation between phenylglyoxal (1{1}) and the hydrochloride salts of either alanine amide (2{1}) or phenylalanine amide (2{2}). In the course of this, many reaction parameters were taken into account (i.e., base addition speed (s

• alanine amide (2{1})) was secured. As listed in Table 2, some of the results of the reaction optimization studies using compounds 1{1} and 2{2} followed the trends reported in Table 1. But for entries 16 and 17 in Table 2, a slow addition of the base, at −78 °C, was always used and we also checked that an

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• spectra were recorded after 15 minutes of sample preparation in 5 × 10−6 M concentration and fluorescence intensity was observed to be in the following order: CHCl3 > EtOAc > CH2Cl2 > DMF. The results of the optimization studies are presented in Figure 5 and it was concluded from the studies that C-3

• substituted frameworks. A summary of previous reports toward exploration of 3-formyl-9H-β-carbolines. Library of C-3-substituted pyrido[3,4-b]indole MBH derivatives 7, 8 and 10. Results of optimization for fluorescence studies: a) contact time; b) concentration; c) solvent. Pictorial representation of

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• to reinforce the supply of IPP and DMAPP via two sequential phosphorylation reactions. Optimization of these constructs provided terpentetriene and ent-kaurene titers of 66 ± 4 mg/L and 113 ± 7 mg/L, respectively, in shake-flask fermentation. The truncated pathways to overproduce clerodane and ent

• subsequent fermentation optimization. Optimizing the ISO/DMAA concentrations To determine the ideal concentrations of exogenous supplementary ISO/DMAA for producing terpentetriene and ent-kaurene, a series of feeding experiments was carried out with various concentrations of ISO/DMAA. When strains DL10004

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• Discussion Initially, we conducted an optimization study on the mechanochemical cross-coupling between 2-bromo-6-methoxynaphthalene (1a, 0.3 mmol) and bis(pinacolato)diboron (2, 1.2 equiv) in the presence of Pd(OAc)2 (2 mol %), KOAc (3.0 equiv), and H2O (60 μL) as a liquid additive [43][44][45] (Table 1

• using one stainless-steel ball that was 5 mm in diameter. The isolated yields are shown. The NMR yields are shown in parentheses. Solid-state borylation of aryl halides on a gram scale. Optimization of the reaction conditions.a Supporting Information Supporting Information File 112: Experimental

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• (d N…O = 2.88 Å, iN–H…O = 125°, Table S1 in Supporting Information File 1). Two hydrogen bonds were also present upon geometry optimization of the dimer model Ac-N-(NMe)2-NMe2 (Table S2 in Supporting Information File 1). In the crystallographic structure of dimer 2, the two constitutive monomers of a

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• highly depends on the molecular design and structures, including linkers, donor and acceptor units, which requires complex and time-consuming molecular synthesis and optimization [21][22][23]. In contrast, the introduction of specific Lewis acid–base pairs in existing molecules can be utilized to achieve

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• served as model substrates for the optimization of reaction conditions. Inspired by our previous work [75][76][77], we first screened different catalysts (Table 1, entries 1−5) with toluene as the solvent and found that CuSO4 was the best choice, providing 1a in 58% isolated yield. Notably, the yield of

• . Synthesis of 3,3'-(arylmethylene)bis(2-methyl-1H-indole). Reaction conditions: 2-methylindole (1.0 mmol), aromatic aldehyde (0.5 mmol), CuSO4 (0.1 mmol), toluene (6.0 mL), 110 °C, 3 h. Isolated yields are shown. Proposed reaction mechanism for the multicomponent reaction. Optimization of reaction