A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• of 1,2-aminoalcohol 110 (90% yield, anti/syn 7:3, 78% ee). At the end of the Henry reaction an in-line plug of silica gel removes the catalyst before the second reduction step to prevent issues of chelation and palladium deactivation. Knoevenagel condensations are also of considerable interest to the

• aminopropyl-functionalised silica gel (AP-T). The reagents (10 mmol) were eluted through the column in the same way as gravimetric chromatography is performed (Scheme 27). In this way, the authors claimed the product was completely collected after 250 mL of toluene elution. The silianol groups on the AP-T

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• analytical grade and supplied by Sigma-Aldrich, Frontier Scientific, Inc., Tokyo Chemical Company and Acros chemicals and used without further purification unless otherwise stated. Flash column chromatography was carried out using Fluka Silica Gel 60 (230–400 mesh; Merck. Melting points are uncorrected and

• pressure. The residue was filtered through silica gel using DCM. Column chromatography was performed through silica gel (hexane/DCM, 15:1–2:1, v/v). Further column chromatography was carried out on silica gel (hexane/DCM, 15:1–1:1, v/v) yielding the purple solid 4 (51 mg, 51%). To obtain single crystals

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• deoxyfluorination, which would likely occur with the β-anomers of 14–19 [41]. The complete separation of the α-anomer by conventional silica gel column chromatography was possible for thioglycosides 14, 16, 17, and 19, while the products 15 and 18 were obtainable as enriched α-anomers (α/β ≥ 3.3:1). Cleavage of the

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• 30 min. The products were separated by filtration and repeatedly washed in cold water. Finally, the derivatives were purified by column chromatography on silica gel to yield the compounds with moderate to good yields (40–81%). Previously some other examples have been described, and they all followed

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• chloride, affording both 2'-OMe and 3'-OMe regioisomers. Fortunately, these isomers could be separated by silica gel column chromatography. Other synthetic approaches have since been developed [109][110][111], however, this pioneering work should be appreciated as nowadays, the 2'-OMe phosphoramidites of

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• sticky-bridge motif of the RNA aptamers was confirmed using an electromobility shift assay (EMSA) using an 8% tris/borate/ethylenediaminetetraacetic acid (TBE)-buffered gel (Novex™ Thermo Fisher Scientific, MA), under native conditions (Supporting Information File 1, Figure S1A). RNA aptamers A-1 or

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• was complete, sulfur (3 equiv) was added under inert atmosphere and then the mixture was stirred at 60 °C for 6 h to provide the stable adduct 3. The purification of the products was performed by silica gel column chromatography using isohexane/MeOAc as an eluent. Radical addition of Ph2PPPh2 and Ph2P

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

• -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

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• reference data. Melting points were determined on a Büchi M-565 apparatus. All reagents were obtained from commercial suppliers and used without further purification. The reactions were monitored by thin-layer chromatography. Column chromatography was performed using silica gel (300–400 mesh). Amides 1a–l

• . The solvent was removed under reduced pressure. The reside was purified by silica gel column chromatography using petroleum ether/ethyl acetate as the eluent to afford the desired thioamide 2. Synthesis of N2,N6-di(n-butyl)pyridine-2,6-(carbothioamide) (3) [34] To a 500 mL four-necked flask were added

Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane

• David Weinzierl and
• Mario Waser

Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68

• recovered (Rp)-2 and ester (Sp)-3a with reasonable enantiomeric excesses around 90%, depending on the conversion. These two compounds can easily be separated by silica gel column chromatography in almost quantitative yields, thus providing a novel entry to obtain these interesting planar chiral motives in

• alcohol 2 and ester 3a were separated by silica gel column chromatography (heptanes/ethyl acetate 10:1), yielding (Sp)-3a in 53% (175 mg) and (Rp)-2 in 43% (98 mg) (39%). (Rp)-2a: Analytical data match those reported in literature [18][19][20][26][28][39]. TLC (heptanes/ethyl acetate 10:1; Rf = 0.11). [α

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• excellent yields. Nucleophilic addition to 5- and 6-membered cyclic tosyloxyenones. Synthesis, functionalization and applications of triazoles. The reaction was performed using 0.2 mmol N-tosyl-1,2,3-triazole 1 and 0.2 mmol of cyclohexyl-1,3-dione 2. Yields are determined after silica gel column

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• bearing BCNS groups comprising nine and ten synthetic steps, respectively. In comparison, the synthesis of an N+ monomer requires only four synthetic steps starting from commercially available 1,4-butane sultone that does not have any silica gel purification [38]. The incorporation of the N+ modification

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• solution (5 drops), diluted with diethyl ether (10 mL), and filtered through a pad of silica gel, which was washed with a fresh portion of diethyl ether. The filtrate was evaporated, and the crude inhomogeneous mixture was purified by flash chromatography (gradient, hexanes/EtOAc 20:1 to 5:1) to give pure

Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

• Naohiro Horie,
• Takao Yamaguchi,
• Shinji Kumagai and
• Satoshi Obika

Beilstein J. Org. Chem. 2021, 17, 622–629, doi:10.3762/bjoc.17.54

• of all compounds. For column chromatography, silica gel PSQ 60B or 100B was used. The progress of the reactions was monitored by analytical thin-layer chromatography on glass plates (TLC Silica gel 60 F254), and the products were visualized using UV light. Synthesis of phosphoramidites (1R,3R,4R,7S

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• the low solubility of corticosteroids in aqueous solution. The expression of KshA5 and KshB was verified from the cell lysate by polyacrylamide gel electrophoresis and western blotting (see Supporting Information File 1, Figure S1). The product distribution between the cellular pellet and supernatant

• was approximately 1:10 (estimated by HRMS analysis). The steroid compounds were extracted from the supernatant and purified by column chromatography on silica gel as the stationary phase. The outcome of the enzymatic hydroxylation in position C9 using KSH-based biocatalysis is given in Table 1. With

• . The residue was chromatographed on silica gel with gradient 10% to 40% acetone in petroleum ether to give acetate 3 (213.2 mg, 93%) as pale yellow oil. [α]D20 +180.0 (c 0.58, CHCl3); 1H NMR (CDCl3, 400 MHz) δ 5.68 (d, J = 1.4 Hz, 1H), 5.47 (q, J = 3.1 Hz, 1H), 2.57–2.21 (m, 6H), 2.20–2.05 (m, 4H

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• (weak), m (medium), and s (strong). Synthesis of allyl DMSP derivatives A mixture of acrylic acid (0.72 g, 10 mmol) and diallyl sulfide or allylmethyl sulfide (10 mmol) was treated with 2 N HCl at 80 °C for 4 h. The reaction mixture was concentrated in vacuo and the residue was purified by silica gel

• water and extracted with ethyl acetate. The extracts were dried with MgSO4 and concentrated in vacuo. The obtained residue was purified by silica gel column chromatography (cyclohexane/EtOAc 5:1) to give compound 26 (0.23 g, 1.20 mmol, 57%). TLC Rf = 0.72 (cyclohexane/EtOAc = 1:1); IR (diamond-ATR) ν̃

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• yield (28%). The carboxylic acid (rac)-19 was then esterified with ʟ-(−)-menthol (8) for a chiral resolution. The reaction was mediated smoothly by MNBA [9] in 85% yield to give a diastereomeric mixture of menthyl esters 20* and 20 after silica gel column chromatography. As shown in Figure 6, the clean

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• × 60 mL) and the combined organic layers were washed with water (2 × 40 mL) and brine (40 mL), dried with anhydrous Na2SO4 and evaporated. The solid residue was dissolved in methanol and filtered through a plug of Celite. The filtrate was evaporated with silica gel and submitted to preparative flash

• chromatography (silica gel or alumina cartridge; mobile phase and gradient are specified in Supporting Information File 1). Analytically pure samples were obtained by crystallization from the appropriate solvent. Compounds 5ea and 5eb were isolated as follows: After the reaction of 1e with 2a,b (4 h) the

• reaction mixture was poured into cold EtOAc/EtOH 20:1 (80 mL) and stirred for 30 min. The precipitated product was filtered off and washed with EtOAc (2 × 5 mL). The crude 5ea or 5eb was dissolved in boiling CHCl3/CH3OH 1:1 (ca 125 mL) and filtered through a short plug of silica gel which was then washed

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• , Fluka, Merck) and were used without further purification. Commercially available cobalt(II) chloride hexahydrate was dehydrated upon heating under vacuum (150 °C, 1.0 mmHg, 45 min) prior to use for the preparation of CoNPs. Column chromatography was performed with Merck silica gel 60 (0.040–0.063 μm

• , 240–400 mesh). Thin-layer chromatography (TLC) was performed on precoated silica gel plates (Merck 60, F254, 0.25 mm). Instrumentation and analysis Nuclear magnetic resonance (NMR) spectra were recorded on a Bruker ARX-300 spectrophotometer using CDCl3 as the solvent and tetramethylsilane (TMS) as

• (82 °C), and stirred at this temperature until total conversion of the starting alkene (TLC, GC). Then, the reaction mixture was centrifuged and the supernatant removed. The solvent was evaporated in vacuo, and the crude product was purified by flash column chromatography (silica gel, hexane/AcOEt

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• building blocks of new potential drug molecules. Experimental Materials and methods All chemicals were purchased from Sigma-Aldrich or Acros Organics. Column chromatography was performed using silica gel 60 (200–300 mesh) as supporting material. All eluents were distilled prior to use. 1H NMR and 13C NMR

• vial. To this mixture, 2,4,6-trimethyl-3-nitrobenzenesulfonyl chloride 4 (184.59 mg, 0.70 mmol) was added at 0 °C. The mixture was then allowed to warm up to room temperature and stirred overnight. The crude product was directly loaded on a silica gel column, with ethyl acetate/triethylamine (98:2) as

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• disappeared completely after purification by silica gel column chromatography [73]. Given the relevance of this trifluoromethylation reaction system for drug discovery, we conducted a robustness screening experiment to gain further information on its tolerance to various pharmacophores (Table 2). A range of

• 4 h. Thereafter, 1 M HCl aq (1.0 mL) was added, and the aqueous layer was extracted with CH2Cl2 (1.0 mL × 3). The combined organic layer was washed with brine, dried over Na2SO4, concentrated under reduced pressure, and purified by column chromatography on silica gel to give products 2

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• were obtained by the Michael addition of NaSMe to ethyl propiolate (45), yielding a mixture of stereoisomers inseparable by silica gel column chromatography (92%). The major stereoisomer was found to be (Z)-42 (dr 94:6), whose preferred formation may be a result of a chalcogen–chalcogen interaction

• flasks under Ar atmosphere and using distilled and dried solvents. Chemicals were obtained from Sigma-Aldrich (St. Louis, USA). Column chromatography was performed on silica gel (0.04–0.06 nm) purchased from Acros Organics (Geel, Belgium) with distilled solvents. NMR spectroscopy was performed on a

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• singlet, tq – triplet of quartets. Analytical thin-layer chromatography (TLC) was performed on Merck 60 Å silica gel F254 plates. Column chromatography was performed on Merck 40–60 µm 60 Å silica gel. Yields of products refer to chromatographically and spectroscopically homogeneous materials. The solvents

• DMF (0.5 mL) was added and the reaction mixture was stirred for 15 min at rt, controlled by HPLC. Then toluene or ethyl acetate (25 mL) was added to the mixture and it was extracted with 5% LiCl solution (3 × 5 mL). The organic phase was dried over anhydrous Na2SO4, filtered and evaporated. Silica gel

• ) were added and the reaction mixture was stirred for 30 min at rt, controlled by HPLC. Then ethyl acetate (25 mL) was added and the mixture was extracted with 5% LiCl solution (3 × 5 mL). The organic phase was dried over anhydrous Na2SO4, filtered and evaporated. Silica gel column chromatography

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• mass spectrometry and so it was converted to carboxylic acids 14 and 15 by the treatment with silica gel and NaOH, respectively, in order to confirm its identity. A possible mechanism for the formation of 13 from 5n could involve the formation of a terminal carbocation from trichloroalkanone 8n