The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• product 6. The structure of products 6 was confirmed by NMR spectroscopy; in addition to that, X-ray diffraction studies were performed with single crystals of compound 6f (see Figure 2). Since the application of the obtained compounds in early drug discovery is anticipated, it is important to assess

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• configuration at C-8 was confirmed. Similarly to C-homotetrazoles, magnetic anisotropy effects of the aromatic tetrazole ring are obvious in 1H NMR spectra of compounds 17 and 18. For example, the chemical shift of the H-4α proton is much lower than expected (0.45 ppm). Interestingly, we noticed that crystals

• of protected B-homotetrazoles were not obtained after repeated attempts of crystallization, while obtaining high-quality crystals of C-homotetrazoles was straightforward. In the final part of our synthetic work, all tetrazole compounds were converted to free bile acid-fused tetrazoles with ethanolic

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• solution is then cooled to below the freezing point of water, whereby ice crystals form. Importantly, here the solvent (water) solidifies (freezes) and forms solid solvent porogens within the structure allowing the polymer network to form around these crystals, templating the porous structure of the final

• cryogel. In chemically crosslinked cryogels (Figure 1a), the monomers polymerise and crosslink (in the presence of a crosslinker) around the ice crystals to form a network. In physically crosslinked cryogels (Figure 1b), once the solution is cooled below the freezing temperature the polymeric precursors

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• . In this work, we report a new synthetic strategy to the photochemical reduction of CuII to CuI for the CuAAC reaction using BPNs as the photo-initiator under NIR light. Results and Discussion The detailed preparation and characterization of the initial BP crystals and BPNs were previously reported

• -angle annular dark field (HAADF) scanning transmission microscope (STEM) images and the associated EDS elemental mapping images. Synthesis of black phosphorus crystals and preparation of its nanosheets Black phosphorus (BP) was prepared using a modified low-pressure chemical vapor transport method [40

• cooled to 393 K in 5 h, and it was left for natural cooling afterwards. After the heating process, the ampoule was cracked in dry toluene and the crystalline BP was separated. In order to remove surface impurities, the BP crystals were transferred into absolute ethanol and sonicated for 30 minutes. The

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• methylene protons of –N–CH2-CH2–N3. A singlet peak at δ 2.50 was due to methyl protons on the imidazole ring. The high-resolution mass spectrometric data at 197.0737 (M + H)+ confirmed the structure of metronidazide 3. Single crystals of metroazide compound 3 were grown from slow evaporation of DCM solution

• + H)+ supported the structure of 1H-1,2,3-triazole compound 5c. Single crystals of 1H-1,2,3-triazole compound 5c were grown from slow evaporation of MeOH. The structure of 1H-1,2,3-triazole compound 5c was unambiguously confirmed by single crystal X-ray analysis (Figure 4). Synthesis of carboxylate

• spectrometric data at 321.0842 (M + H)+ supported the structure of compound 7b. Single crystals of compound 7b were grown from slow evaporation of MeOH + DCM (1:1) solution. The structure of compound 7b was unambiguously confirmed by single crystal X-ray analysis (Figure 5). In this article, chemical

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• NMR spectra. For structural confirmation of these new derivatives, we also carried out an X-ray diffraction study of compound 2b. Yellow single crystals suitable for X-ray diffraction analysis were obtained by slow evaporation of a solution of 2b in dichloromethane. Based on the X-ray crystallographic

• crystallization and X-ray diffraction experiments for compound 2b were performed. All samples evaluated had low scattering patterns and germinated crystals. This resulted in poor quality data, which limited the quality of the refinement. Structure illustrations were generated using ORTEP-3 for Mercury [45], and

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• structures, albeit with no control over the DP, could be prepared via chemoenzymatic polymerization of α-laminaribiosyl fluoride donors catalyzed by the mutated barley β(1–3)-glucanase [144][145]. Linear β(1–3)-glucans with DP of 30–40 appeared as lamellar, hexagonal crystals. Electron and X-ray diffraction

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• crystalline solid with a high decomposition point of ca. 170 °C. The bisOTf salt 22-1a, bisBF4 22-1d, bisSbF6 22-1e, and bisPF6 22-1f are easy-to-handle because they are non-hygroscopic and stable crystals. As shown in Figure 6, 22-1a,d,e mediated a quantitative conversion of anisole to isomers of

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• silica-gel chromatography (100% hexane), to furnish (±)-4 as a yellow solid (6.70 g, 26.5 mmol, 55%), (±)-5 as a yellow crystalline solid (1.68 g, 6.24 mmol, 13%), and 6 as light yellow crystals (2.61 g, 9.15 mmol, 19%). 4-Nitro[2.2]paracyclophane (4) 1H NMR (500 MHz, CDCl3) δ (ppm) 7.22 (d, J = 1.2 Hz

• ) to give 6 (2.40 g, 8.41 mmol, 48%) and a mixture of 12 and 13. Slow evaporation of fractions containing 12 and 13 initially gave clear crystals that could be separated to obtain pure characterization of 12 (1.95 g, 6.14 mmol, 35%) leaving behind 13, which could be isolated as a light brown solid

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• configuration assignment made by NMR analysis, the sulfonate derivative 21 from 14af was prepared by reaction with tosyl chloride. For compound 21, we were able to obtain single crystals suitable for X-ray analysis and the X-ray diffraction studies on 21 confirmed undoubtedly its trans-configuration. The ORTEP

Co-crystallization of an organic solid and a tetraaryladamantane at room temperature

• Fabian Rami,
• Jan Nowak,
• Felix Krupp,
• Wolfgang Frey and
• Clemens Richert

Beilstein J. Org. Chem. 2021, 17, 1476–1480, doi:10.3762/bjoc.17.103

• that do not readily crystallize by themselves. The co-crystals are often useful for structure elucidation. Usually, the small molecules are encapsulated in the crystal lattice of the aryladamantane that forms during rapid thermal crystallization. Thus far, co-crystallization has been limited to liquids

• as guest molecules. Here we report the co-crystal structures of phenol, which is solid at room temperature, with both 1,3,5,7-tetrakis(2,4-dimethoxyphenyl)adamantane (TDA) and 1,3,5,7-tetrakis(2,4-diethoxyphenyl)adamantane (TEO). The co-crystals were obtained from solutions in dichloromethane by slow

• evaporation or diffusion. The implications for generating other co-crystals of two solids are briefly discussed. Keywords: adamantanes; crystallization; organic solids; structure elucidation; X-ray crystallography; Introduction Obtaining a crystal suitable for X-ray crystallography can be a challenge for

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• close to the OTBS center. At this point, it was crucial to conclusively characterize the unexpected product 9. Fortuitously, we were able to obtain crystals for this compound after several recrystallization attempts. The crystal structure for 9 (Figure 2) very surprisingly showed the OTBS group on the

A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry

• Marine Vallet,
• Filip Kaftan,
• Veit Grabe,
• Fatemeh Ghaderiardakani,
• Simona Fenizia,
• Aleš Svatoš,
• Georg Pohnert and
• Thomas Wichard

Beilstein J. Org. Chem. 2021, 17, 1313–1322, doi:10.3762/bjoc.17.91

• Information File 1). Even though most of the seawater media was removed from the Ulva samples during sample preparation, crystallisation of seawater salts on the sample surface occurred. The size of the crystals and their distribution within an imaged area were examined using a digital microscope and found to

• be homogeneous and consistent across the samples and experiments. As a result, the ion suppression effect caused by the presence of seawater crystals on the Ulva samples and surroundings was consistent across all measurements (Supporting Information File 1, Figures S1 and S2). Ectoine was detected in

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

• formation of the crystal networks. This is complemented with the use of density functional theory (DFT) calculation of structures that have currently not been determined due to difficulties of obtained crystals of sufficient quality for X-ray determination. Additionally, DFT calculations were conducted for

• 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

• , recrystallization from DCM and methanol was performed and gave purple crystals of the title compound. Mp > 300 °C; Rf = 0.48 (SiO2, hexane/DCM, 2:1, v/ v); 1H NMR (400 MHz, CDCl3) δ −2.69 (s, 2H, NH), −2.72 (s, 6H, CH3), 7.57 (d, 3J = 7.7 Hz, 4H, Hm-tolyl), 7.72–7.79 (m, 3H, Hm-phenyl and Hp-phenyl), 8.08 (d, 3J

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

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• Maryna O. Mazur Oleksii S. Zhelavskyi Eugene M. Zviagin Svitlana V. Shishkina Vladimir I. Musatov Maksim A. Kolosov Elena H. Shvets Anna Yu. Andryushchenko Valentyn A. Chebanov Division of Chemistry of Functional Materials, State Scientific Institution “Institute for Single Crystals” of National

Synthesis, structural characterization, and optical properties of benzo[f]naphtho[2,3-b]phosphoindoles

• Mio Matsumura,
• Takahiro Teramoto,
• Masato Kawakubo,
• Masatoshi Kawahata,
• Yuki Murata,
• Kentaro Yamaguchi,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2021, 17, 671–677, doi:10.3762/bjoc.17.56

• shift for P-modified phospholes 3–7 (δ = 22.5−39.3 ppm) relative to that of the parent compound 2 (δ = −13.27 ppm). These results suggest that the electron densities of the latter were reduced in comparison to that of 2. Single crystals of 2 suitable for X-ray analysis were obtained by repeated

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

• ) [10][11][12]. Since 10 was obtained as crystals, the configurational analysis was thereafter confirmed by single-crystal X-ray analysis, as shown in Figure 4. The conformational differences for 10 between the results of the calculations and the analysis of the NMR data compared to the situation in the

• crystal are arising from the four contiguous single bonds between the heterocycle and the menthyl group. These take a stable extended conformation in the calculations and in the NMR experiment, whereas a rather folded conformation is taken in the crystals. Such a discrepancy is often observed and reported

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• less effective for emulsifying liquid crystals than those with an even number of carbons [44]. The behavior of the hydrocarbon lipopeptide 4 was markedly different, with a decrease of the surface pressure over time, and a much lower πeq. This not only means that the hydrocarbon analog is not recruited

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

• ten proline positions [117]. The incorporation of R-Flp resulted in an insoluble protein, indicating associated folding issues. In contrast, the protein containing S-Flp produced a well-structured fluorescent protein, exhibiting faster folding kinetics and producing crystals suitable for diffraction

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• -2-thione species 6a in a high yield (Scheme 1, route 2). The red color of the reaction mixture belonging to the parent o-quinone rapidly turns into a brown color of o-quinone 6a. o-Quinone 6a was isolated as red-brown crystals by cooling the acetone/ether mixture. It is a structural analogue of o

• was discussed previously [29]. The reaction of 4 with malononitrile-derived gem-dithiolate (5b, Scheme 1, route 2) also proceeded under mild conditions in DMF and bicyclic o-quinone 6b was obtained in a good yield. The brown crystals suitable for X-ray analysis were grown from an acetone/diethyl ether

• . Heating the mixture at 60 °C for 4 h does not result in any change of the color from that characteristic of o-quinone 4. After cooling of the solution red crystals of adduct 8 were isolated (see Figure 2 and Figure S6 in Supporting Information File 1). The X-ray diffraction study reveals that adduct 8 is

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• , the solution was cooled to room temperature, hexane (40 mL) was added, and the mixture was left in the freezer (−20 °C) for 10 h. The precipitated colorless crystals of 2a were filtered and washed with cold hexane (4 × 5 mL). Colorless crystals (1.15 g, 82%). mp 57–59 °C; IR ν̃max (cm−1): 2924, 2858

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• , due to sample decomposition. Attempts to obtain crystals for X-ray analysis by slow diffusion of n-pentane into a DCM solution of the complexes were unsuccessful. Catalytic activity For evaluation of the catalytic ability of the new Au(III) complexes, alkyne carboalkoxylation [47][48] and

Tuning the solid-state emission of liquid crystalline nitro-cyanostilbene by halogen bonding

• Subrata Nath,
• Alexander Kappelt,
• Matthias Spengler,
• Bibhisan Roy,
• Jens Voskuhl and
• Michael Giese

Beilstein J. Org. Chem. 2021, 17, 124–131, doi:10.3762/bjoc.17.13

• Subrata Nath Alexander Kappelt Matthias Spengler Bibhisan Roy Jens Voskuhl Michael Giese Organic Chemistry, University of Duisburg Essen, Universitätsstraße 7, 45141 Essen, Germany 10.3762/bjoc.17.13 Abstract The first example of halogen-bonded fluorescent liquid crystals based on the interaction

• supramolecular liquid crystals, especially hydrogen bonding and halogen bonding have gained considerable attention [3][4][5][6][7]. In 2004, Bruce and co-workers reported the first example of a halogen-bonded liquid crystal based on pentafluoroiodobenzene and 4-alkoxystilbazole [5]. Ever since, several other

• fluorine substitution of the aromatic halogen bond donor on the liquid crystallinity and the photo-response of halogen-bonded liquid crystals [12]. However, all reported halogen-bonded liquid crystals rely on the halogen-bond-acceptor capability of pyridyl units and so far, no study on the fluorescence

Control over size, shape, and photonics of self-assembled organic nanocrystals

• Chen Shahar,
• Yaron Tidhar,
• Yunmin Jung,
• Haim Weissman,
• Sidney R. Cohen,
• Ronit Bitton,
• Iddo Pinkas,
• Gilad Haran and
• Boris Rybtchinski

Beilstein J. Org. Chem. 2021, 17, 42–51, doi:10.3762/bjoc.17.5

• ]. These crystals found use in optoelectronic materials [14][15][16], as markers for imaging applications [12][13], and demonstrated anticancer properties [17]. However, control over the size and shape in such systems is challenging [8][9][10][11][12][13][14][15][16][17][18][19]. Surface chemistry

• mobility [20], but no control over the crystal size and morphology was demonstrated. Using self-assembled monolayers as templates for the seeding and growth of molecular crystals may offer control over structure and polymorphism [21]. However, in this method, the crystal formation is limited by the

• solutions can be manipulated to result in different polymorphs [35], 3D crystals with dissimilar structures and morphologies. We envisaged that the crystallization of 1 in a basic aqueous medium can lead to 2D arrays (bilayers) due to the higher solubility of the assemblies as a result of the charged