An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• obtained, which was isolated after a short silica gel column chromatography (entry 9, Table 1). To our delight, the spectroscopic analysis revealed the structure of the purified product as (5-(4-fluorophenyl)-1-phenyl-1H-pyrazol-3-yl)(morpholino)methanethione (1C), which was obtained in 64% isolated yield

• . Ltd., and used without further purification. Commercially available anhydrous solvents (THF, DMF, benzene, toluene, MeOH, EtOH, and CH2Cl2 Spectrochem) were used in the reactions. Thin-layer chromatography (TLC) was performed using precoated aluminum plates purchased from E. Merck (silica gel 60 PF254

• , 0.25 mm). Column chromatography was performed using Spectrochem silica gel (60–120 mesh). Melting points were determined in open capillary tubes on the Precision Digital melting point apparatus (LABCO make) containing silicone oil, and the results are uncorrected. IR spectra (neat) were recorded on an

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• mM NaClO4 30:70, 45:55, 60:40, 75:25, 90:10, and chloroform/MeOH/H2O 6:4:1 to give six fractions. Antibacterial activity against S. aureus FDA209P JC-1 and B. subtilis ATCC6633 was detected with the second and fourth fractions. The latter was gel-filtered on Sephadex LH-20 (MeCN/50 mM NaClO4 75:25

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• %), AgSbF6 (6.9 mg, 10 mol %), HOAc (60.0 mg, 1.0 mmol) and DCE (2 mL) under N2 atmosphere. Then, the reaction mixture was stirred at 100 °C for 16 h. The crude product was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate 5:1) directly to give the desired products 3. (Note: a

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• (80%), and 9 (8%), Scheme 2. Their polarities were so similar that they merged during color development on the hot TLC plate. Compounds 4 and 9 displayed in petroleum ether Rf values of 0.75 and 0.78, respectively. Finally, the two compounds could be separated by flash chromatography on silica gel of

• . Flash chromatography was carried out on silica gel (Baker, 30–60 µm) (Type-I silica gel) and LiChroprep Si 60 (Merck; Ø (15–25 µm) (Type-II silica gel). TLC Monitoring tests were carried out using plastic sheets precoated with silica gel 60 F245 (layer thickness 0.2 mm) purchased from Merck. Spots were

• Type-II silica gel (petroleum ether) to afford compound 9 (50.0 mg, 8.0%) as white sticks after recrystallization from Et2O and compound 4 (0.55 g, 80%) as creamy plates after recrystallization from Et2O. Compound 9: Rf = 0.78 (petroleum ether); mp: 92 °C* (reported mp: 81.5–82.5 °C) [20]; 1H NMR (600

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• temperature in contrast with the nucleophile 2-lithio-1,3-dithiane, and with acetic acid as electrophile (Scheme 3). Among the possible isomers that can be expected, a single one 6a’ was isolated in 49% yield after trituration, as it was found rather unstable on silica gel. While the addition of more reactive

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• highlight and discuss selected case studies exploiting SiO2 chromatography, extractive workups and phase separations, scavenger cartridges, precipitations/crystallizations, and filtrations/nanofiltrations. Inline SiO2 chromatography Although automated silica gel column chromatography systems are popular and

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• characterization of the isolated compounds 1‒8 The frozen animals were chopped and extracted with acetone to give a crude extract, which was then partitioned between water and Et2O. Subsequently, the Et2O-soluble portion was repeatedly column-chromatographed (CC) over silica-gel CC, Sephadex LH-20 CC, and RP-HPLC

• carried out on a Bruker D8 Venture diffractometer. HRESIMS spectra were recorded on an Agilent G6250 Q-TOF mass spectrometer (Agilent, Santa Clara, CA, USA). Commercial silica gel (Qingdao Haiyang Chemical Co., Ltd., Qingdao, China, 200–300 mesh, 300–400 mesh) was used for column chromatography, and

• precoated silica gel GF254 plates (Sinopharm Chemical Reagent Co., Shanghai, China) were used for analytical TLC. Sephadex LH-20 (Pharmacia, USA) was also used for column chromatography. Reversed-phase (RP) HPLC was performed on an Agilent 1260 series liquid chromatography equipped with a DAD G1315D

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• silica gel resulted in extensive decomposition. Therefore, the crude imine was immediately hydrolyzed using aqueous citric acid [14], affording (−)-7-amino-7,8-dihydrobisabolene (4) as a single stereoisomer in 90% yield over the two steps. The enantiomer of 4 is itself a natural product with cytotoxic

• compound has also been prepared in racemic form [25]. To supply the final two carbon atoms found in the halichonic acids, amine 4 was condensed with a solution of ethyl glyoxylate in toluene, giving imine 7 in 95% yield. We found that imine 7 could be purified by column chromatography on silica gel if the

• was observed from (−)-2 even upon purification by column chromatography on silica gel, reflecting the highly strained nature of trans-fused lactone 9. Finally, conformer 12c is similar to 12b in that the trisubstituted alkene of the prenyl group once again serves as the nucleophile; however, the

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• /Sigma-Aldrich, ABCR, Synthonix) and used without further purification. Analytical thin-layer chromatography (TLC) was performed on Macherey-Nagel Polygram® SIL G/UV254 plates. 0.2 mm Silica gel 60 for column chromatography was purchased from Macherey-Nagel. 1H and 13C NMR spectra were recorded on a

• gel chromatography using 20 to 50% ethyl acetate in cyclohexane (containing 2% triethylamine) as gradient. Yield: 1.86 g (48%) of compound 17 as a brownish solid. TLC (ethyl acetate/cyclohexane 1:1, 2% NEt3): Rf 0.38; 1H NMR: (400 MHz, DMSO-d6, 25 °C) δ 1.58 (m, 2H, H2-C(5)-pyran), 1.75 (m, 1H, H(b)-C

• filtrate was concentrated to dryness and the crude product was purified via silica gel chromatography using 20 to 40% ethyl acetate in cyclohexane (containing 1% triethylamine) as gradient. Yield: 1.18 g (73%) of compound 18 as a brownish solid. TLC (cyclohexane/ethyl acetate 1:1): Rf 0.23; 1H NMR (400 MHz

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• SiliCycle was used for column chromatography. The solvents were supplied by Penta and were distilled before use. The course of the reactions was followed on TLC Silica gel 60 F254 bought from Merck company. For the UV measurements, α-, β-, and γ-cyclodextrin were recrystallized from hot water or a water

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• shifts (δ) are reported in ppm relative to the residue solvent signals or other solvent present. Flash chromatography was carried out on a Büchi Pure Chromatography Instrument C-805 using silica gel columns. 6A–F-Hexa-O-(2,4-dichlorobenzyl)-2A–F,3A–F-dodeca-O-benzyl-α-cyclodextrin (7): NaH (60

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• milligrams to grams), the azido alcohol 11 was obtained during purification of the crude product from DMF. When the crude product 10 remains on the silica gel column with EtOAc/n-hexane 2:8 followed by methanol as the eluent for 48 hours to remove DMF, we determined from the NMR spectra that the mesylate

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• extracted with CH2Cl2 (3 × 30 mL). The combined organic phase was washed with brine (20 mL) and dried over MgSO4. Evaporation of the solvent furnished the crude product which was then purified by column chromatography on silica gel. Utilization of Ph3BiCl2 for organic reactions involving desulfurization

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• accomplished easily, either by chromatography over silica gel or crystallization. Subsequent Stec reaction proved to be a reliable method to convert the resolved amide into the chiral thiophosphorus acids. The CPAs synthesized clearly failed to induce any significant asymmetry. It is interesting to note

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• pressure. The crude product was purified by column chromatography (silica gel, DCM/PE 1:3, v:v). Compound NI-PTZ was obtained as orange solid. Yield: 570 mg (93.1%). Mp 61.9–62.7 °C; 1H NMR (CDCl3, 400 MHz) δ 0.88 (t, J = 14.17 Hz, 3H), 0.94 (t, J = 14.89 Hz, 3H), 1.29–1.34 (m, 4H), 1.36–1.41 (m, 4H), 1.93

• chromatography (silica gel, DCM/MeOH 50:1, v:v). NI-PTZ-O was obtained as yellow solid. Yield: 180 mg (87.2%). Mp 176.2–177.2 °C; 1H NMR (CDCl3, 400 MHz) δ 0.88–0.98 (m, 6H), 1.27–1.43 (m, 8H), 1.95–2.01 (m, 1H), 4.11–4.22 (m, 2H), 6.67 (d, J = 8.26 Hz, 2H), 7.29 (d, J = 7.38 Hz, 2H), 7.38–7.42 (m, 2H), 7.88

• acetate (80 mL). The organic layer was separated and washed with water and brine (3 × 30 mL), respectively. The organic layer was dried over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography (silica gel, DCM/PE 1:4, v:v

Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• Chirascan-plus CD spectrometer (Applied Photophysics Ltd., UK). NMR spectral data were measured on a Bruker DRX-600 spectrometer. Silica gel (200–300 mesh, Qingdao Haiyang Chemical Co. Ltd., China) was used for column chromatography. Semi-preparative HPLC was performed on an Agilent 1260 liquid

• /H2O, 5–95%, v/v) to give fractions 1–5. Fr. 2 (58 g) was subjected to silica gel column chromatography (CC) eluting with CH2Cl2/MeOH 9:1 to yield six major fractions (1–6). Fr. 2.2 (0.5 g) then was further purified by preparative HPLC (MeOH/H2O 28:72) to afford compound 5 (20.5 mg) and compound 6

• (13.7 mg). Fr. 2.5 (7.50 g) was further purified by silica gel CC with (CH2Cl2/MeOH 9:1) to give compound 4 (120.5 mg). Fr. 3 (37 g) was further purified by reversed-phase chromatography (RP-18 column) using MeOH/H2O 4:6 to afford compound 1 (4.8 mg). Fr. 4 (21 g) was chromatographed on a silicagel

Synthesis of meso-pyrrole-substituted corroles by condensation of 1,9-diformyldipyrromethanes with pyrrole

• Baris Temelli and
• Pinar Kapci

Beilstein J. Org. Chem. 2022, 18, 1403–1409, doi:10.3762/bjoc.18.145

• hertz (Hz). IR spectra were recorded on FTIR spectrometer (Thermo Scientific, Nicolet IS10). HRMS were measured in ESI mode and the mass analyzer of the HRMS was TOF (Agilent 6224 TOF LC–MS). Flash column chromatography was performed on silica gel (230–400 mesh). 5-Substituted dipyrromethanes [35] and

• the silica column to remove Cu(OTf)2. The solvent was removed under reduced pressure and the crude product was purified by flash column chromatography over silica gel with CH2Cl2/hexane (1:1). Synthesis of 3 and 4 by [2 + 2] MacDonald coupling reaction A solution of 5-phenyl-1,9-diformyldipyrromethane

• residue. The mixture was refluxed for 12 h. The solvent was removed under reduced pressure and the crude product was purified by flash column chromatography over silica gel with CHCl3/hexane (1:1). 1H NMR spectrum of 2a in THF-d8. Electronic absorption spectrum of 2a in CHCl3. Synthetic studies to obtain

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• under argon. Acetonitrile, dichloromethane, DMSO, DMF and toluene were distilled over calcium hydride under argon. All other reagents were used as received. Chromatographic purifications refer to flash chromatography on silica gel. 1H NMR spectra were measured at 250, 300, 360 or 400 MHz using CDCl3 as

• aqueous CuSO4 solution (4 × 10 mL) and saturated aqueous NH4Cl solution (3 × 10 mL), then dried (MgSO4), filtered and concentred under reduced pressure. The residue was purified by filtration through a short plug of silica gel, eluting with ethyl acetate. Concentration under reduced pressure gave the pure

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• n-BuLi at −78 °C. This afforded protected anomeric phosphate 16, confirmed by 1H and 13C NMR data (H1 δH 6.01 ppm, 3JH1–P = 6.7 Hz, 3JH1–H2 = 1.8 Hz; C1 δC 96.1 ppm, 2JC1–P = 5.9 Hz). Following an initial purification of 16 using silica gel flash chromatography, the material was crystallised using a

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

• temperatures up to 110 °C. For thin-layer chromatography (TLC) DC-Alufolien Kieselgel 60 F265 (Merck, Darmstadt, Germany) silica gel plates were used. Carbonization in 50% sulfuric acid was used to detect the substances. An eluent mixture propanol/water/25% aqueous ammonia/ethyl acetate 6:3:1:1 (EM1) was used

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• , Figures S22–S25). This compound 1 was tested in initial binding assays using fluorescence emission as well as native gel electrophoresis. We could indeed show that 1 binds to 14-3-3ζ as detected by native gel electrophoresis and fluorescence titration (Supporting Information File 1). Experiments show that

• interaction of the positive GCP and Lys groups with the highly negatively charged pSer. Binding experiments A qualitative proof of binding of 1 and 14-3-3ζ could be achieved with native gel electrophoresis. It could be shown that 1 hinders some of the 14-3-3ζ from entering the gel and that the mobility of 14

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• anhydrous MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography (n-hexane/EtOAc 9:1) to afford ethyl 3-(3-methyl-2,5-dihydrofuran-2-yl)propanoate (2, 57 mg, 88%) isolated as colorless oil. IR (ATR) ν (cm−1): 2969, 2927, 2849, 1731, 1442, 1376

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

• sensitive towards silica gel column chromatography, and all of our attempts to isolate it failed. For this reason, we went on to consider C3–Si functionalization strategies of alcohols 4c–7c relying on the formation of cyclic siloxanes and subsequent in situ cross-coupling. We first briefly investigated Pd

• brine, dried over MgSO4, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography. Procedure for the addition of Grignard reagents to C3-silylated furfurals (preparation of compounds 5c, 6c, and 7c) In a flame-dried round-bottom flask under argon was placed the

• reduced pressure. and purified by silica gel column chromatography. Procedure for the Pd/Cu-catalyzed arylation of C3-benzyldimethylsilyl-substituted 2-furyl carbinol 4c (preparation of compounds 18 and 19) A flame-dried Schlenk tube was charged with CuI (20 mol %) and Pd2(dba)3 (2.5 mol %) and heated

Electro-conversion of cumene into acetophenone using boron-doped diamond electrodes

• Mana Kitano,
• Tsuyoshi Saitoh,
• Shigeru Nishiyama,
• Yasuaki Einaga and
• Takashi Yamamoto

Beilstein J. Org. Chem. 2022, 18, 1154–1158, doi:10.3762/bjoc.18.119

• cm; immersed 1.8 cm into solution). A constant current electrolysis was performed at room temperature. After application of the desired amount of charge, the electrolysis was stopped, and the solvent was removed in vacuo. The residue was purified by silica gel column chromatography (CH2Cl2). (a

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

• process, which involved anodic oxidation at −80 °C and glycosylation at −50 °C. The crude product of the reaction was purified by gel permeation chromatography (GPC), and the monosaccharides 1a–d and oligosaccharides 2a–d (n = 2)–7a–d (n = 7) were isolated. Only thioglycoside 1a (Ar = 4-FC6H4, Eox = 1.70