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

• Fabian Rami Jan Nowak Felix Krupp Wolfgang Frey Clemens Richert Institute of Organic Chemistry, University of Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany 10.3762/bjoc.17.103 Abstract Tetraaryladamantanes have proven useful as chaperones for the co-crystallization of small molecules

• 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

• 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

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

• need of crystallization, using DFT calculations with a high degree of accuracy. Keywords: conformational analysis; crystal engineering; halogenation; macrocycles; porphyrins; Introduction Crystal engineering using porphyrins as a scaffolding unit has been a topic of increasing interest over the past

• increasing the library of simulated data and use this as a model to predict the most appealing structures for generating halogen bonded supramolecular networks followed by targeted synthesis and crystallization of such compounds. Experimental General information All commercial chemicals used were of

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• 4c–g,j–n bearing phenyl substituents contained no impurities of the corresponding isomers 5, while the structures 4a,b,h,i were isolated in individual form only during fractional crystallization from the reaction mixtures. It was previously shown [24][25][26] that the products of aldol condensation

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

• , we herein reported an efficient work-up procedure of applying LR by utilizing ethylene glycol to decompose the compound A (Figure 2). With a combination of some usual operations, such as, phase separation, extraction and crystallization, the desired thioamide products were efficiently obtained in

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

• /or crystallization. Aliphatic thioamides Although our concern was mainly dedicated to the synthesis of 3-[amino(aryl)methylidene]oxindoles many of which display a significant tyrosin kinase inhibiting activity, we also verified the versatility of our method for the analogous oxindoles 10a–c carrying

• 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

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

• crystallization. Finally, the study revealed a few polar interactions of the fluoropyrrolidine ring within the protein microenvironment. In a study on thioredoxin, four out of five proline residues were mutated to alanine, and the only remaining proline residue was the one adopting a cis-amide-bond conformation

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

•  3. The telescoped approach provided the quantitative conversion of benzyl alcohol into benzyl butyrate which could be removed by crystallization (from heptanes) after evaporation of toluene and residual vinyl butyrate. The resulting telescoped flow approach thus enabled the facile generation and

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

• the assembly. In general, gaining control over the crystal formation represents a long-standing challenge [29][30][31][32]. In this respect, understanding and controlling the crystallization process is key to fabricating organic nanocrystals with a predesigned morphology and properties [33][34][35

• ][37][38]. Additionally, the aqueous self-assembly incorporating carboxylic acid groups in the covalent unit design has been shown to result in complex and tunable self-assembly modes [39][40][41][42]. Crystalline self-assembly We have found that the nonclassical crystallization of 1 in neutral aqueous

• 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

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• ]. A major benefit of sonocrystallization appeared to be the induction of nucleation and therefore, crystallization improvements were operated for several organic compounds of low to medium molecular weight with the possibility of scaling up of this technology for industrial use [7]. Low ultrasonic

• molecules of the synthesized α-(arylamino)acetonitrile derivatives in the aggregated crystalline state, single crystals suitable for X-ray analysis were obtained by crystallization from isopropanol. The crystallographic data for the structure 2a reported in this paper have been deposited at the Cambridge

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• functions were removed. We used TEA·3HF in DMF for this purpose, allowing easy purification of the deprotected nucleoside derivative 5 by crystallization from DCM with a yield of 60% over two reaction steps. Next, the 5’-hydroxy group was protected with DMT, and the linker on C8 was introduced by

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• , CH2Cl2/MeOH 5→10%). After crystallization of the major fraction from MeOH/Et2O 7:3 the desired product was obtained as yellow solid. 9-O-{β-{4'-[(9''-Adenyl)methyl]-1H-1',2',3'-triazol-1'-yl}ethyl}berberine bromide (4a) According to the GP, a solution of 3a (150 mg, 292 µmol), 2 (60.6 mg, 350 µmol

• ), CuSO4 (5.83 mg, 36.5 µmol) and Na-ascorbate (36.3 mg, 183 µmol) was stirred at reflux in THF/H2O/MeCN 2:2:1 (25 mL). After purification by column chromatography (Rf = 0.11; 10% MeOH) and crystallization the product 4a was obtained as orange-colored amorphous solid (30.0 mg, 46.5 µmol, 16%); mp 191–194

• µmol) was stirred at reflux in THF/H2O/MeCN 2:2:1 (25 mL). After purification by column chromatography (Rf = 0.12, 10% MeOH) and crystallization the product 4b was obtained as yellow, amorphous solid (42.3 mg, 64.0 µmol, 26%); mp 189–192 °C (dec.); 1H NMR (600 MHz, DMSO-d6) δ 2.41 (tt, 3J = 7 Hz, 3J

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• hexane layer was dried, and the solvent was removed under vacuum to leave 0.6 g of a white solid, which was found to be the 99% pure minor isomer 2b (mp 122–123 °C after the second crystallization from hexane; this sample was used for X-ray diffraction studies). The rest of the reaction mixture was

Anion exchange resins in phosphate form as versatile carriers for the reactions catalyzed by nucleoside phosphorylases

• Julia N. Artsemyeva,
• Ekaterina A. Remeeva,
• Tatiana N. Buravskaya,
• Irina D. Konstantinova,
• Roman S. Esipov,
• Anatoly I. Miroshnikov,
• Natalia M. Litvinko and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2020, 16, 2607–2622, doi:10.3762/bjoc.16.212

• % base → nelarabine conversion. Work-up of reaction mixture and purification/crystallization as described above gave nelarabine in 52% yield (14 mg; 99.0% purity according to HPLC). Synthesis of kinetin riboside Synthesis of α-ᴅ-ribofuranosyl-1-phosphate as barium salt (Rib-1Pi, Ba2+) by phosphorolysis

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• the MUC1 VNTR domain. Thus, a synthetic 8-amino acid peptide (APDTRPAP) and the corresponding Tn glycopeptide were synthesized. It was found from the co-crystallization of the AR20.5 antigen-binding fragment (Fab) with the MUC1 peptide and glycopeptide that the glycan moiety of the glycopeptide did

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• negatively charged patches, depending on the functional groups present. X-ray crystallography is a useful tool to obtain structural information about the binding modes of supramolecular ligands on proteins (reviewed in [76]). However, the crystallization of proteins with supramolecular ligands can be very

• crystallization. Crystallization seems to succeed best for ligands that can adopt a defined conformation upon binding without flexible loops protruding from the protein surface. Even in these cases, the ligand is preferably found at binding sites that are facing solvent channels but at the same time enable

• they have been used to serve as scaffolds for the assembly of protein arrays and crystallization aids [23][24][25][26][27][28]. In addition, a terbiumIII complex termed crystallophore has been developed as a crystallographic nucleation and phasing tool for protein crystallography that can also easily

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• non-radiative transitions can be achieved by the host–guest method [50][51][52] or by crystallization [53][54][55][56][57]. In difference to the liquid phase, the highly ordered packing and the restriction of molecular motions in the crystalline state favor a persistent luminescence. The promotion of

Five-component, one-pot synthesis of an electroactive rotaxane comprising a bisferrocene macrocycle

• Natalie Lagesse,
• Luca Pisciottani,
• Maxime Douarre,
• Pascale Godard,
• Brice Kauffmann,
• Vicente Martí-Centelles and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2020, 16, 1564–1571, doi:10.3762/bjoc.16.128

• macrocycle–thread hydrogen bonds, with the other two macrocycle amides forming hydrogen bonds with the competitive crystallization solvent DMF. In contrast, rotaxane 1a presented four thread–macrocycle hydrogen bonds (Figure 7 and Table 1). The strength of the hydrogen bonds could be estimated by the donor

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• structure unambiguously, as a representative example, the structure of 6aa was also confirmed by single crystal X-ray diffraction (XRD) studies after crystallization from ethyl acetate/hexane (Figure 2). CCDC 1991859 (for 6aa) contains the supplementary crystallographic data for this paper. These data are

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• optimization (Table S4, Supporting Information File 1), solubility issues hindered the formation of a concentrated solution (>0.8 M). The crystallization of iPrMgBr in the collection flask forced us to reduce the initial concentration of the organic halide to 0.9 M, yielding iPrMgBr (0.75 M, 82%, note: the

• GC–MS, after being washed with pentane at 0 °C and dried under vacuum, showed no evidence of organic compounds. It seemed that TMPMgCl⋅LiCl coordinated less LiCl than the corresponding iPrMgCl⋅LiCl and triggered LiCl crystallization. To solve this issue, the packed-bed column temperature was decrease

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• the slightly more polar one was isolated and identified as the minor isomer of 9d. In the course of crystallization from hexane the less polar fraction gave single crystals suitable for the X-ray diffraction analysis, which unambiguously confirmed that in this molecule the Ph(C-5) and Fc(C-2) groups

• dichloromethane as the eluent. Analytically pure samples of tetrahydrothiophenes 9 were obtained by crystallization from petroleum ether or hexane with a small amount of dichloromethane. The diastereoselectivity of the studied reactions was determined by integration of the crude 1H NMR. Preliminary purification

Development of fluorinated benzils and bisbenzils as room-temperature phosphorescent molecules

• Shigeyuki Yamada,
• Takuya Higashida,
• Yizhou Wang,
• Masato Morita,
• Takuya Hosokai,
• Kaveendra Maduwantha,
• Kaveenga Rasika Koswattage and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 1154–1162, doi:10.3762/bjoc.16.102

• efforts, several molecular designs have been proposed as alternatives, particularly the use of pure organic phosphorescent molecules [22]. For example, methyl 4-bromobenzoate (Figure 1B) exhibits phosphorescence in the crystalline state via nonradiative ISC to the T1 state owing to crystallization-induced

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• 1, that only showed a crystallization signal (TCR = 138 °C) during the cooling scan. The 10% weight-loss temperature (TD−10%) of the quinazoline-based compounds decreased in the order of 3 (409 °C) > 2 (345 °C) > 1 (247 °C). For compounds 1 and 2 a complete weight loss was observed in the TGA

The charge-assisted hydrogen-bonded organic framework (CAHOF) self-assembled from the conjugated acid of tetrakis(4-aminophenyl)methane and 2,6-naphthalenedisulfonate as a new class of recyclable Brønsted acid catalysts

• Svetlana A. Kuznetsova,
• Alexander S. Gak,
• Yulia V. Nelyubina,
• Vladimir A. Larionov,
• Han Li,
• Michael North,
• Vladimir P. Zhereb,
• Alexander F. Smol'yakov,
• Artem O. Dmitrienko,
• Michael G. Medvedev,
• Igor S. Gerasimov,
• Ashot S. Saghyan and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2020, 16, 1124–1134, doi:10.3762/bjoc.16.99

• before the crystallization, as confirmed by powder diffraction data collected at room temperature for the white precipitate obtained from the mixed water solutions of TAPM and NDS. Space group P21/c, a = 20.9609(10) Å, b = 19.7563(9) Å, c = 22.6642(10) Å, β = 92.694(3)°, cell volume = 9375.1(8) Å3. When

Aryl-substituted acridanes as hosts for TADF-based OLEDs

• Naveen Masimukku,
• Dalius Gudeika,
• Oleksandr Bezvikonnyi,
• Ihor Syvorotka,
• Rasa Keruckiene,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 989–1000, doi:10.3762/bjoc.16.88

• transition (Tg) was noticed at 86 °C, followed by an exothermic crystallization (Tcr) signal observed at 183 °C to obtain crystals, which melted at 201 °C. The crystalline sample of derivative 3 demonstrated a similar behavior. It melted upon the first heating at 174 °C and exhibited a glass transition at Tg

• (250 mL) with vigorous stirring. After filtration and crystallization from methanol compound 2 was obtained as white crystals. Yield (0.60 g, 80%); mp 83–84 °C; 1H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 2.3 Hz, 2H), 7.30 (dd, J = 8.7, 2.3 Hz, 2H), 6.84 (d, J = 8.7 Hz, 2H), 3.98 (q, J = 7.0 Hz, 2H), 1.48

Towards triptycene functionalization and triptycene-linked porphyrin arrays

• Gemma M. Locke,
• Keith J. Flanagan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2020, 16, 763–777, doi:10.3762/bjoc.16.70

• Supporting Information File 1). While this feature is an interesting take on the selective homo interactions, the explanation of this motif formation is potentially more mundane in this case. Considering that during the crystallization process, the spontaneous formation of the homo or hetero π-stacking of