A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

• Arno Verlee,
• Thomas Heugebaert,
• Tom van der Meer,
• Pavel I. Kerchev,
• Frank Van Breusegem and
• Christian V. Stevens

Beilstein J. Org. Chem. 2017, 13, 303–312, doi:10.3762/bjoc.13.33

• LC–MS analysis. In the initial screening, tetrahydrofuran (THF) was chosen as solvent (cfinal = 100 mM), however, precipitation of the ammonium salts was unavoidable. The results of this screening did show that the use of catalysts, such as pyridine or dimethylaminopyridine (DMAP), is unnecessary in

• batch or continuous flow. This is not surprising since a similar result is reported for the reaction of amines with sulfonyl chlorides [34]. Triethylamine was added as base for the capture of hydrogen chloride which is produced during the reaction. Nonetheless, the precipitation of anilinium salts and

• compared to THF, however, the salts which were formed during the reaction still precipitated (cfinal = 100 mM and 40 mM). At lower concentrations (cfinal = 10 mM), the precipitation of the formed salts was not observed. Furthermore, the chemoselectivity was increased, being 80% for 10 mM and 73% for 100 mM

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• , bubbles, precipitation and dirty flow cells among others) are present at this small scale [28]. Finally, Cronin et al. [50] described a synthetic platform that incorporates a flow reactor, an in-line benchtop NMR instrument (Spinsolve from Magritek) to monitor the organic reactions, and a control system

• limitations include: Clogging of the capillary tubing by precipitation of the sample, that produces a mechanical blockage and is increasingly important as the diameter of the capillary is reduced. Formation of bubbles it is always a problem but especially if they get into the flow NMR cell since they can

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• product 7 was observed by precipitation. After completion of the reaction, the solvent was evaporated and the residue purified by column chromatography. All products 5–7 were obtained in a highly regioselective manner and in good yields. Analogues of 5–7 with a carbonyl substituent have been previously

• the loss of heterocyclic aromaticity. However, aiming at the synthesis of new heterocycles, we next investigated the reaction of compounds 5–7 with different 1,2-diamines. Initially, the reaction between compound 5 and ethylenediamine (8a) was tested. Due to precipitation of the product during the

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• modified oligonucleotides were purified by ethanol precipitation in the presence of EDTA to remove copper ions and subsequently by semi-preparative HPLC. Finally, the modified oligonucleotides were identified by MALDI–TOF mass spectrometry (see Supporting Information File 1) and annealed with the

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

• Olga Eguaogie,
• Patrick F. Conlon,
• Francesco Ravalico,
• Jamie S. T. Sweet,
• Thomas B. Elder,
• Louis P. Conway,
• Marc E. Lennon,
• David R. W. Hodgson and
• Joseph S. Vyle

Beilstein J. Org. Chem. 2017, 13, 87–92, doi:10.3762/bjoc.13.11

• mixture from the jar in acetonitrile, precipitation from water under acid conditions and triturating the solids (see Supporting Information File 1 for details). We note that only 2b has been described previously in peer-reviewed literature although without details of its preparation [31]. Following

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• precipitation/filtration procedure (Table 1, entries 4 and 9), according to a well-established protocol [14][15][16]. Even when the PEG polymers were supposed to be homogeneously liquids (melting point around 55 °C) at the operational temperature, comparable yields could be obtained only by extending the

Stabilization of nanosized titanium dioxide by cyclodextrin polymers and its photocatalytic effect on the degradation of wastewater pollutants

• Tamás Zoltán Agócs,
• István Puskás,
• Erzsébet Varga,
• Mónika Molnár and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2016, 12, 2873–2882, doi:10.3762/bjoc.12.286

• here.) After diluting nanoTiO2 dispersions with tap water immediate precipitation was observed. Among the CD polymers studied the QABCD-P could not hinder this precipitation, the HPBCD-P slowed down the precipitation process, while in the presence of CMBCD-P no precipitation occurred in 120 min (Figure

From betaines to anionic N-heterocyclic carbenes. Borane, gold, rhodium, and nickel complexes starting from an imidazoliumphenolate and its carbene tautomer

• Ming Liu,
• Jan C. Namyslo,
• Martin Nieger,
• Mika Polamo and
• Andreas Schmidt

Beilstein J. Org. Chem. 2016, 12, 2673–2681, doi:10.3762/bjoc.12.264

• tautomer under these conditions; unfortunately the addition of less polar solvents induces a precipitation from solution so that detection of the NHC tautomer by NMR spectroscopy is not possible under these conditions. Base screening revealed that the anionic N-heterocyclic carbene 7 can be generated in

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• a one-dimensional columnar structure through a combination of intermolecular [C−H···O=Mo] and [O−H···O] interactions [30]. Unfortunately, the natural CDs as well as their inclusion complexes are of limited aqueous solubility leading to their precipitation. Fortunately, native CDs are effective

• of soluble and insoluble complexes [86]. CDs caused the precipitation of lipoproteins in the order γ-CD < α-CD < β-CD. This behavior could be ascribed to the formation of inclusion complexes. However, the presented data did not exclude the formation of exclusion complexes. Several years later, Horský

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

• Olga C. Dennehy,
• Valérie M. Y. Cacheux,
• Benjamin J. Deadman,
• Denis Lynch,
• Stuart G. Collins,
• Humphrey A. Moynihan and
• Anita R. Maguire

Beilstein J. Org. Chem. 2016, 12, 2511–2522, doi:10.3762/bjoc.12.246

• process scales caused us to consider alternative ‘greener’ solvent systems [27]. A screen of alternative solvents in batch test reactions revealed that, while the amide formation was tolerant to most solvents, rapid precipitation of triethylamine hydrochloride would be problematic in a continuous process

• ) was found to be a suitable base that allowed the continuous process to be carried out in ethyl acetate without any observed precipitation of the HCl salt. The ‘greener’ continuous amide formation (Scheme 4) was carried out on a large scale, producing 91 g (92% yield) of the α-chloroamide 1 over 5

• pure material, with direct product precipitation/crystallization from the reaction solution (>99% pure by HPLC analysis), which has removed the requirements for isolation by extraction and subsequent chromatographic purification. HPLC analysis of the current process – in either batch or flow

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• precipitation was observed during all enzymatic phosphorylation experiments, which is a further indicator for less aggregate formation. To learn more about the influence of phosphorylation components on the pathway of aggregation and at which state the growth of oligomers is stopped by phosphorylation, we

• order oligomers. Also no precipitation was observed. These results indicate high stability of the chemically phosphorylated peptide in comparison to the unphosphorylated analog. Discussion In the accepted model pathway of amyloid formation, a lag phase populated by functional soluble peptide structures

• soluble structures, as no further precipitation was observed. It remains unclear whether the decreasing effect of the phosphorylation during later stages of the aggregation is due to the lower flexibility of the recognition site, leading to slow reaction kinetics of the enzyme or to the competitive

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• their system is controlled by the influence of mechanical motion on nanostructure formation (the assembly of β-sheet-based fibres from the peptide building blocks in this example). Given the rapid precipitation of 3 at the phase interface observed in our N-tetrapropargylation reaction, it seems

Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

• Laszlo Jicsinszky,
• Marina Caporaso,
• Katia Martina,
• Emanuela Calcio Gaudino and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230

• thioether (6) the residual DMF increases the product solubility in methylene chloride and precipitation with MeOH removes the unreacted 1-dodecanethiol (DDS), whereas the absence of DMF, together with the strong complex formed between DDS and the product, meant that the product isolation was more difficult

• . The resulting crude mixture was only partially soluble in methylene chloride and MeOH precipitation gave a difficult-to-filter product, which still contained at least one mole of complexed DDS. This complexation resulted in not only technical difficulties, but also confounded the removal of impurities

High performance p-type molecular electron donors for OPV applications via alkylthiophene catenation chromophore extension

• Paul B. Geraghty,
• Calvin Lee,
• Jegadesan Subbiah,
• Wallace W. H. Wong,
• James L. Banal,
• Mohammed A. Jameel,
• Trevor A. Smith and
• David J. Jones

Beilstein J. Org. Chem. 2016, 12, 2298–2314, doi:10.3762/bjoc.12.223

• large scale use of tin reagents we required the key bis-borylated benzodithiophene (BDT) core 13, which was synthesised from the known BDT core 12 using iridium catalyzed borylation via CH-activation. The bis-borylated product was isolated by precipitation on addition of isopropanol (IPA), and an

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• (3.8 mL, 10 mmol NaHCO3) was added. After the evolution of CO2, the precipitation of the peracetylated product was observed. The products were separated by simple decantation. For compounds which do not precipitate upon addition of NaHCO3, an extraction with AcOEt was needed. The organic phase, after

Comparing blends and blocks: Synthesis of partially fluorinated diblock polythiophene copolymers to investigate the thermal stability of optical and morphological properties

• Pierre Boufflet,
• Sebastian Wood,
• Jessica Wade,
• Zhuping Fei,
• Ji-Seon Kim and
• Martin Heeney

Beilstein J. Org. Chem. 2016, 12, 2150–2163, doi:10.3762/bjoc.12.205

• [42]), which could result in a masking of the P3OT melt in the baseline. However, the apparent suppression of the P3OT melt could also be explained by some degree of frustration of the P3OT crystallization, likely due to the earlier precipitation of the less soluble F-P3OT during the film formation

• indeed the case, the solid was further washed with dichloromethane and finally extracted with chloroform, before precipitation into methanol and filtration. The resulting solid was dried under vacuum to give P3OT-b-F-P3OT 2:1 (50 mg, 25%). Mn 55 kg/mol, Mw 60 kg/mol; 1H NMR (400 MHz, TCE-d2, 403 K, δ

The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• temperature of 25 °C. It should be noted that the data generated was obtained in a very short time. On the down side, for a couple of experiments, samples could not be collected due to the limitations of the microreactor used. There were blockages observed due to precipitation of the product in the

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• ][21]. A kinetic resolution of the enantiomers was achieved by enzymatic hydrolysis with Amano lipase PS from Burkholderia cepacia [22][23], a method already optimized for technical use [24]. The best results were obtained with methyl tert-butyl ether as a cosolvent [24]. By simple precipitation

Cross-linked cyclodextrin-based material for treatment of metals and organic substances present in industrial discharge waters

• Élise Euvrard,
• Nadia Morin-Crini,
• Coline Druart,
• Justine Bugnet,
• Bernard Martel,
• Cesare Cosentino,
• Virginie Moutarlier and
• Grégorio Crini

Beilstein J. Org. Chem. 2016, 12, 1826–1838, doi:10.3762/bjoc.12.172

• groups and CD cavities, the adsorption mechanism involves four main interactions: ion exchange, electrostatic interactions and precipitation for metal removal, and inclusion complexes for organics removal. In industrial discharge waters, competition effects appeared, especially because of the presence of

• material was initially activated by NaHCO3. Discussion To explain the adsorption performance of polyBTCA-CD, a chemisorption mechanism involving several interactions can occur including ion exchange, electrostatic interactions, inclusion complexation and/or precipitation [3][12][13][14][15][16]. The

• interactions and ion exchange). Moreover, this treatment only converted carboxylic groups into carboxylate without altering the amorphous structure of the polymer, as seen from the X-ray spectra. Precipitation could also explain the removal efficiency enhancement observed with the activated polymer since it

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• . The optimal reagent concentration was determined to be 0.2 M, since higher concentrations led to the precipitation of reaction intermediates and lower yields. The scope of the reaction was investigated and the results are summarized in Table 1. Good yields were obtained independently from the

Synthesis and characterization of benzodithiophene and benzotriazole-based polymers for photovoltaic applications

• Desta Gedefaw,
• Marta Tessarolo,
• Margherita Bolognesi,
• Mario Prosa,
• Renee Kroon,
• Wenliu Zhuang,
• Patrik Henriksson,
• Kim Bini,
• Ergang Wang,
• Michele Muccini,
• Mirko Seri and
• Mats R. Andersson

Beilstein J. Org. Chem. 2016, 12, 1629–1637, doi:10.3762/bjoc.12.160

• ring) in comparison to PTzBDT-1, not only allows a higher donor content in the blend (enhanced light absorption) but also seems to be crucial in terms of precipitation/segregation kinetics during the deposition/drying process of the active blend, strongly influencing the self-organization, the quality

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• (Figure 7). In the case of substrate 40 precipitation occurred as soon as the two solutions came into contact at the T-piece mixer, which was probably due to strong coordination to the copper acetate by the imidazole ring. This made running this reaction problematic in flow due to the occurrence of

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• precipitation from the reaction mixture and n-BuOH proved to be the most suitable solvent in the reaction. Performing the reaction in refluxing n-BuOH in the presence of one equivalent of HClO4 for 8 h, compound 1a was obtained in 30% isolated yield. Other acids including p-toluenesulfonic acid (PTSA), HCl, and

Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides

• Grzegorz Mlostoń,
• Róża Hamera-Fałdyga,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 1421–1427, doi:10.3762/bjoc.12.136

• mixture was heated at 45 °C until the evolution of N2 ceased. Then, the solvent was evaporated and the crude products were purified by CC (SiO2, hexane/ethyl acetate 95:5). The major product was isolated using diethyl ether (precipitation). 4-Ferrocenyl-5,5-diphenyl-4-(selenophen-2-yl)-1,3-dithiolane (5c

Artificial Diels–Alderase based on the transmembrane protein FhuA

• Hassan Osseili,
• Daniel F. Sauer,
• Klaus Beckerle,
• Marcus Arlt,
• Tomoki Himiyama,
• Tino Polen,
• Akira Onoda,
• Ulrich Schwaneberg,
• Takashi Hayashi and
• Jun Okuda

Beilstein J. Org. Chem. 2016, 12, 1314–1321, doi:10.3762/bjoc.12.124

• oxidized to Cu(II) by contamination with air. Cu(II) led to protein aggregation and precipitation. This was shown in an independent experiment. When one equiv of Cu(NO3)2·3H2O was added to a solution of FhuA ΔCVFtev, the protein precipitated rapidly and quantitatively. MALDI–TOF–MS analysis for the whole