Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• group, to determine the effect of the spacer length on POSS crystallization ability and the composition dependence of physical properties of the copolymers [49]. A series of homopolymers and random copolymers were synthesized in the presence of third generation Grubbs catalyst Ru-6 in CH2Cl2, at room

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• trimethyl orthoacetate the enantiomerically pure bromomethoxy derivative (4R,5R)-37 was prepared after crystallization of the reaction mixture. The precursor of the carboxymethyl group was first introduced with full retention of configuration employing a stannate chemistry to give (4R,5R)-38 after removal

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• in a trans-orientation with H(4). In addition, various crystallization tests were carried out in order to confirm the absolute stereochemistry by X-ray diffraction. The chiral 3-(2-(methylthio)ethyl)-1-(phenylamino)-1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)dione (5f) crystallized [44][45][46][47][48][49

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• values of 0.9 ± 0.3 µM for 24 and 19.6 ± 3.7 µM for 26. The highly enthalpy-driven binding indicates a specific noncovalent interaction of 24 to the protein. To further investigate the binding mode of the hit fragments in the protein crystallization experiments were performed. Since the native substrate

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• possible by careful crystallization from methanol. The structure and configuration of the products 12–14 were established by NMR as well as the single-crystals X-ray analysis (see Supporting Information File 1 for details). The data presented in Table 4 clearly indicate that the substituent change from

A novel and practical asymmetric synthesis of eptazocine hydrobromide

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan,
• Kuaile Lin and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209

• reaction was scaled up (60 g of 2) according to the conditions in entry 5, and similar results were obtained (Table 1, entry 8). After the screening of many solvents, the pure isomer 4 was isolated from the crude reaction mixture through crystallization from ethyl acetate with 48% yield and >99% chiral

Selective formation of a zwitterion adduct and bicarbonate salt in the efficient CO₂ fixation by N-benzyl cyclic guanidine under dry and wet conditions

• Yoshiaki Yoshida,
• Naoto Aoyagi and
• Takeshi Endo

Beilstein J. Org. Chem. 2018, 14, 2204–2211, doi:10.3762/bjoc.14.194

• water during the crystallization process [28]. On the other hand, Villiers and Ephritikhine et al. synthesized and characterized successfully the zwitterion adduct of CO2 and TBD under strictly anhydrous conditions [31]. They also described that the obtained zwitterion adduct of TBD–CO2 was stable at

Synthesis and post-functionalization of alternate-linked-meta-para-[2ⁿ.1ⁿ]thiacyclophanes

• Wout De Leger,
• Koen Adriaensen,
• Koen Robeyns,
• Luc Van Meervelt,
• Joice Thomas,
• Björn Meijers,
• Mario Smet and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2190–2197, doi:10.3762/bjoc.14.192

• thermodynamically stable [2 + 2] macrocycle 6 (41%, see Figure S13, Supporting Information File 1). Due to the instability of the macrocycles, purification of the reaction mixtures via column chromatography (silica/alumina) or selective crystallization was difficult. Changing the biselectrophile precursor to

Evaluation of dispersion type metal···π arene interaction in arylbismuth compounds – an experimental and theoretical study

• Ana-Maria Preda,
• Małgorzata Krasowska,
• Lydia Wrobel,
• Philipp Kitschke,
• Phil C. Andrews,
• Jonathan G. MacLellan,
• Lutz Mertens,
• Marcus Korb,
• Tobias Rüffer,
• Heinrich Lang,
• Alexander A. Auer and
• Michael Mehring

Beilstein J. Org. Chem. 2018, 14, 2125–2145, doi:10.3762/bjoc.14.187

• ][47]. A more convenient synthetic route makes use of the Grignard reagent phenylmagnesium bromide and its reaction with bismuth trichloride [48]. Following this approach with slight modifications provides Ph3Bi with a yield of more than 80%. Crystallization from EtOH gave single crystals of the

• monoclinic C2/c polymorph 1a, which was already subject of several studies including the description of its crystal structure [39][40][41][42][43]. Therefore, it is somewhat surprising that the bismuth···π interaction was not noted so far. We obtained polymorph 1a upon crystallization from solution, but we

• isolated another polymorph 1b by crystallization from the melt. Polymorph 1b was obtained starting from 1a in a temperature-dependent PXRD experiment (see Supporting Information File 1, Figure S1). The polymorph 1b was obtained as a microcrystalline material, but Andrews and MacLellan did obtain single

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• the throughput in the start or anywhere else gets changed in the sequence. This is very important for synthesis steps where downstream processing is also in sequence. Usually time scales for work-up procedures like extraction, crystallization, solvent switch etc. are longer compared to the main

• . Here the reactor was maintained at a temperature of 70–100 °C for 1–3 hours. The product was crystallized in CT1 with the anti-solvent methanol pumped through P4 into the crystallization tank. The crystallized product was filtered and separated in S2. Deprotection: The second-stage product from the

• was pumped through pump P3 to form the final lactate salt of the product. Here the excess of formic acid and lactic acid was removed by the rotary evaporator RE1, then passes through TR4 into the crystallization tank CT1. The solid product formed was filtered in F1 and stored in a tank T1. Challenges

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• , so that the pure products were only available by crystallization from appropriate solvents, which resulted in lower yields of these products. Single crystal X-ray diffraction analysis of 9-(arylethynyl)benzo[b]quinolizinium derivatives 2a and 2b Single crystals of derivatives 2a and 2b were obtained

• by crystallization from acetone and CHCl3/MeOH, respectively (Figure 2 and Figure S1, Supporting Information File 1). Derivative 2a crystallizes in the triclinic space group with two molecules in the unit cell. The crystals were twinned and the compound shows some considerable disorder. The chemical

First thia-Diels–Alder reactions of thiochalcones with 1,4-quinones

• Grzegorz Mlostoń,
• Katarzyna Urbaniak,
• Paweł Urbaniak,
• Anna Marko,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2018, 14, 1834–1839, doi:10.3762/bjoc.14.156

• –l, analytically pure samples were obtained by crystallization from petroleum ether with a small amount of dichloromethane. All attempts to obtain analytically pure samples for 4m, 4n and 6 were unsuccessful and the purification procedure led to formation of some decomposition products. 2,4-Diphenyl

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• the slow cooling crystallization technique. More specific, 10.22 mg (0.026 mmoles) of CHL were added in a 2 mL equimolar aqueous solution of β-CD. The mixture was stirred at 70 °C for 4 h and gradually cooled to room temperature over a period of seven days. X-ray crystallography A prismatic colorless

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• crystallization. We note that the neighboring group participation proposed should be limited to leaving groups with a second nucleophilic site at the appropriate position. Other leaving groups than methylimidazole should not be able to react via the same dominant reaction pathway. In our hands, compounds with a

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• bearing an array of acrylamide groups (Scheme 3). Substrate 6a bearing a (R)-α-methylbenzyl chiral auxiliary led to isoindolinone 3a in 80% de and a pure diastereoisomer was recovered after chromatography on silica gel (EtOAc/hexanes 3:7) and crystallization from hexanes/toluene. Reactions of substrates

• crystallization (70% yield, >96% de). Lactam (2R,3S)-25 bearing a α-methyl-para-methoxyphenyl chiral auxiliary was then deprotected with trifluoroacetic acid at room temperature to deliver the NH-free isoindolinone (3S)-26 (76% yield, 98% ee) which is a key building block in the synthesis of benzodiazepine

• isoindolinones (3S)-1 and (3S)-2. Synthesis of parent benzamides 6–8. Synthesis of isoindolinones 3a–d, 4a–e, 5; isolated yield, de by HPLC and 1H NMR. aAfter flash chromatography on silica gel (EtOAc/hexanes 3:7) and crystallization from hexanes/toluene; bafter flash chromatography.on silica gel (EtOAc/hexanes

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• reaction. We synthesized eight different dithi(ol)anylium TFBs 1a–d and 2a–d from commercial carbonyl chlorides, isolated them via crystallization or separation and extraction and added them to a set of eight α,β-unsaturated non-cyclic ketones (Scheme 2 and Table 1). It was shown that dithi(ol)anylium TFBs

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• spectroscopic studies. However, X-ray crystallographic studies indicated that the 4,7-dihydropyrazolo[3,4-b]pyridine-5-nitriles 92 underwent aerial oxidation to its aromatic counterpart pyrazolo[3,4-b]pyridine 93 during crystallization and is propeller in shape. Additionally, non-planar rings due to propeller

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• to be prepared in several steps) with MnO2 in poor yield (24% crude product; yield of the final crystallization step for purification not given). In 1965, Bruderer and Brossi [12] reported on an approach whose central step was a Pictet–Gams cyclization of N-acetylated β,3-dimethoxy-4

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• was achieved by fractional crystallization [24]. Chirality of the bisdioxine dicarbaldehyde, 2,6,9-trioxabicyclo[3.3.l]nona-3,7-diene-4,8-dicarbaldehyde, obtained by extrusion of water from triformylmethane, has also been demonstrated [25], and X-ray crystallography confirmed the structure of this

Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

• Artur Jabłoński,
• Yannic Fritz,
• Hans-Achim Wagenknecht,
• Rafał Czerwieniec,
• Tytus Bernaś,
• Damian Trzybiński,
• Krzysztof Woźniak and
• Konrad Kowalski

Beilstein J. Org. Chem. 2017, 13, 2521–2534, doi:10.3762/bjoc.13.249

• . Subsequently, the solvent was evaporated to dryness and the residue subjected to column chromatography on SiO2 (2, eluent chloroform/methanol 50:0.5 (v/v), 3, eluent chloroform/methanol 50:1 (v/v)). Crystallization from chloroform/n-hexane afforded pure 2 (54%, 208 mg, yellow solid), or 3 (56%, 220 mg, yellow

• MgSO4, filtered and evaporated to dryness. The residue was subjected to column chromatography on SiO2 (eluent chloroform/methanol 50:2 (v/v)). Crystallization from chloroform/n-hexane gave the pure compound 4 as colourless solid in 91% yield (245 mg). 1H NMR (600 MHz, DMSO-d6) δ 11.14 (s, 1H, NH), 8.38

• chloroform/methanol 50:2 (v/v)). Crystallization from chloroform/n-pentane afforded the pure compound 5 as colourless solid in 85% yield (167 mg). 1H NMR (600 MHz, DMSO-d6) δ 8.28–8.26 (m, 4H, Pyr, adenine), 8.18 (s, 1H, H-2 adenine), 8.17 (d, JH,H = 9.6 Hz, 1H, Pyr), 8.15–8.14 (m, 2H, Pyr, adenine), 8.10 (d

Syntheses, structures, and stabilities of aliphatic and aromatic fluorous iodine(I) and iodine(III) compounds: the role of iodine Lewis basicity

• Tathagata Mukherjee,
• Soumik Biswas,
• Andreas Ehnbom,
• Subrata K. Ghosh,
• Ibrahim El-Zoghbi,
• Nattamai Bhuvanesh,
• Hassan S. Bazzi and
• John A. Gladysz

Beilstein J. Org. Chem. 2017, 13, 2486–2501, doi:10.3762/bjoc.13.246

• cases, CF2CF2OCF(CF3)CF2OCF(CF3)- segments have been found to impart higher fluorophilicites than similar perfluoroalkyl groups [42]. However, the multiple CF(CF3) stereocenters are disadvantageous, as they render such compounds mixtures of diastereomers, presenting an impediment to crystallization. In

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• ). Surprisingly, in the solid state (after the crystallization process), compounds 6i (or 7i – azide form) were not observed. In this case, the 7-substituted 5-(trichloromethyl)tetrazolo[1,5-a]pyrimidine was found, in which the CCl3 group is bonded at the 5-position of the heterocyclic ring, while CH3 is bound at

• the 7-position (8i, Figure 6). The observation was supported by DFT data, in which the tetrazole form was found to be 2.84 kcal mol−1 more stable than its azide form. This indicates that an unusual equilibrium is established for 6i (i.e., when R = CH3) in the crystallization process (Figure 7

• of the CX3 group at the 7-position of the ring. In addition, an unusual equilibrium was observed for compound 6i. The result of 8i from 6i crystallization was attributed to the equilibrium 6i7i (in which 7i is the azide form). Lastly, the evaluated series were very important to elucidate the factors

Structure–property relationships and third-order nonlinearities in diketopyrrolopyrrole based D–π–A–π–D molecules

• Jan Podlesný,
• Lenka Dokládalová,
• Oldřich Pytela,
• Adam Urbanec,
• Milan Klikar,
• Numan Almonasy,
• Tomáš Mikysek,
• Jaroslav Jedryka,
• Iwan V. Kityk and
• Filip Bureš

Beilstein J. Org. Chem. 2017, 13, 2374–2384, doi:10.3762/bjoc.13.235

• two large alkyl groups, the solubility of the target chromophores is relatively low, which partially complicated their purification. Hence, column chromatography with very slow elution followed by subsequent crystallization has been necessary. Only derivative 5b was sufficiently pure after column

• chromatography without a need of further crystallization. Hence, this ferrocene derivative was prepared with the highest yield of 73%. In the solid state, all target chromophores resemble dark metallic solids. Differential scanning calorimetry The thermal behaviour of compounds 1–5b was studied by differential

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• product since crystallization, precipitation and dialysis constitute the possible methods of purification. The purification by chromatography requires, due to the high polarity of phosphonic acids, reversed-phase chromatography and is therefore limited to preparative RP-HPLC [218]. Despites these