Unexpected polymorphism during a catalyzed mechanochemical Knoevenagel condensation

• Sebastian Haferkamp,
• Andrea Paul,
• Adam A. L. Michalchuk and
• Franziska Emmerling

Beilstein J. Org. Chem. 2019, 15, 1141–1148, doi:10.3762/bjoc.15.110

• monitoring multi-phase reactions during ball milling. Keywords: ball milling; C–C coupling; in situ; mechanochemistry; multivariate data analysis; Introduction Mechanochemistry offers a wide array of applications. It is used widely for synthesis of inorganic, metal-organic, and organic molecules and

• ] in understanding reaction kinetics of these processes. Early insight into formation pathways was provided ex situ, in which the mechanical treatment was stopped, and powder removed for analysis [10][11]. More recently, further detail has been gained by monitoring mechanochemical transformations in

• is of great interest. The characteristic bands are usually well separated, and the course of the reaction can be followed easily. The advantage of Raman spectroscopy was recently demonstrated [19], where its combination with XRPD allowed monitoring of the mechanochemically catalyzed Knoevenagel

Precious metal-free molecular machines for solar thermal energy storage

• Meglena I. Kandinska,
• Snejana M. Kitova,
• Vladimira S. Videva,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• Stanislav B. Baluschev,
• Silvia E. Angelova and
• Aleksey A. Vasilev

Beilstein J. Org. Chem. 2019, 15, 1096–1106, doi:10.3762/bjoc.15.106

• excess of crown ether 3 was easily removed. In general the zwitterionic salts 2a–d reacted to complete depletion in ethanol and in the presence of piperidine as catalyst with the crown ether benzaldehyde 3 (TLC monitoring, ethyl acetate/ethanol 4.5:0.5). After the addition of ethyl acetate the

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• 100% acetonitrile. Monitoring and collection based on UV–vis absorbance at 210 nm and 254 nm, respectively. Purity analysis was performed using UPLC–MS with UV–vis detection on a Waters Acquity UPLC + Waters XEVO-G2 system using a Waters Acquity CSH C18, 1.7 µm, 2.1 × 100 mm column. Samples were run

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• by others [24][25], then the myristoyl group (C14:0) was added using myristoyl chloride in the presence of DMAP (Scheme 1) [26]. NMR monitoring Following the formation of thioglycosides by 1H NMR analysis A test reaction, based on 10 mg of 1a, was performed in deuterated methanol (MeOD) and the

• were kept as significant. Pictures were prepared using PyMOL (version 0.99rc6, DeLano Scientific, San Carlos, CA, 700). Structure of the β-thiols 1a and 1b and of the commercial alkenes 2a and 2b. Periodic monitoring by 1H NMR (300 MHz, DMF-d7) of the formation of product 8 from a mixture compounds 1b

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• thermal half-lives (THL) of the cis-isomers of compounds 5a, 5b, 12a, 16a–d, 23, and 28 was accomplished by monitoring the increase in absorbance which corresponds to the evolution of the trans-isomer after irradiation and exposure to dark. In contrast to the heterocyclic compounds 5a, 5b, 12a, and 16a–d

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• , 220.1825). PTP1B inhibitory activity assay The recombinant PTP1B catalytic domain was expressed and purified according to a previous report [24]. The enzymatic activities of the PTP1B catalytic domain were determined at 30 °C by monitoring the hydrolysis of pNPP. Dephosphorylation of pNPP generated the

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• intracellular monitoring and validation of T cell antigen presentation. This new probe would also be linked to the surface of a polyanhydride copolymer microparticle based on 1,6-bis(p-carboxyphenoxy)hexane (CPH) and sebacic anhydride (SA) to allow for enhanced internalization and uptake of the immunogenic

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• Stuart SMP30 apparatus with automatic temperature monitoring. Starting materials: Adamantyloxyamine (4) was prepared following a modified published procedure [20]. For the first step, the O-adamantylation of N-hydroxyphthalimide, the recommended diethyl ether as a solvent was replaced by 1,2

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• CAL-B. It is worth noting that this amount represents a ≈8 fold decrease of used enzyme as compared to the corresponding small scale reaction (Table 2, entry 8). After 24 h, we were delighted to find that no enolester was detected by TLC monitoring, and after extraction and silica gel column

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• stirred at room temperature for 1 h. At the conclusion of the reaction (TLC monitoring), the reaction mixture was concentrated at reduced pressure and dried under vacuum. The crude product was purified by silica gel column chromatography (2% MeOH/CHCl3) to obtain the Boc-deprotection product 14 (68 mg, 95

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• transformations and ex situ NMR monitoring of the dyad composition evolution [90]. It was found that Gr1 first interacts with PCOE so that all Ru-carbenes become bound to those macromolecules approximately within one hour (Scheme 9, reaction 1 and Figure 7). Recall that the addition of Gr1 to a mixture of NB and

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• (TLC monitoring: dichloromethane/methanol 10:1). The reaction mixture was then cooled to room temperature, diluted with toluene (5 mL), and acetonitrile was removed in vacuum. The remaining toluene solution was passed through a short pad of Celite, concentrated, and the residue was purified by flash

• ’-penta-O-benzylsucrose (17): To a solution of triol 2 (88 mg; 0.11 mmol) in toluene (3 mL), allyl bromide (56 μL, 0.66 mmole, 6 equiv) was added followed by 50% aq NaOH (3 mL), and the heterogeneous mixture was vigorously stirred at 50 °C for 18 h (TLC monitoring hexane/ethyl acetate 4:1). The mixture

• borohydride (400 mg), and the mixture was stirred for 16 h (TLC monitoring dichloromethane/methanol 20:1). Water (5 mL) was added followed by 10% aq NaOH (5 mL) and brine (5 mL), and the mixture was stirred at rt for another 30 min. The organic phase was separated and the aqueous one was extracted with CH2Cl2

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• -phase synthesis, such as easy reaction monitoring by standard techniques and low consumption of donor building blocks to complete glycosylations. During the course of this investigation, unexpected stereochemical outcomes were observed in glycosylations involving glycosyl donors containing an N

• leads to the selective formation of the desired 1,2-trans glycosidic linkages and can be easily removed at the end of the synthesis [7][8][36][42]. Moreover, 19F NMR experiments can be employed to assist in the analysis and monitoring of reactions involving N-TFA building blocks. First, we describe the

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• very easily loses CO2 which causes the signal at m/z 309. This behavior could be confirmed by induced fragmentation experiments (see below). Monitoring the temporal progress of reaction R3 was achieved by taking small samples at regular intervals, diluting and swiftly feeding them into the spectrometer

• nm): 368.0 nm global maximum. HRESIMS: [M]+ calcd for C33H26N4P+, 509.1890; found, 509.1884. ESI-CID (Figure S4, Supporting Information File 1). Charge-tagged L-proline-derived catalyst 1∙Cl [18]. NMR monitoring of reaction R1 in deuterated DMSO (concentration of tetrazine 0.005 mmol/mL). a) ESI mass

• spectrum of reaction R1 after 26 min. b) ESIMS monitoring of reaction R1. To better visualize the trend of III1, the signal intensities of III1 have been multiplied by a factor of two. ESI mass spectrum of reaction R1 with preformed I1 8 minutes after adding substrate 2. ESI mass spectrum of reaction R2

Degenerative xanthate transfer to olefins under visible-light photocatalysis

• Atsushi Kaga,
• Xiangyang Wu,
• Joel Yi Jie Lim,
• Hirohito Hayashi,
• Yunpeng Lu,
• Edwin K. L. Yeow and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2018, 14, 3047–3058, doi:10.3762/bjoc.14.283

• DMSO, 410 nm pulse excitation and monitoring emission at 480 nm) were recorded in the absence of a quencher, and in the presence of xanthate 1a and 1-octene (2a, 40 mM, Figure 1C). The lifetime profiles were described using a mono-exponential decay function with a lifetime of 1.40 μs in the absence of

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• the water formed in situ. The 1H NMR monitoring of crude samples pointed out a complete conversion, most often overnight at 60 °C, and the resulting solutions of alkylidenemalonates 6a–al were then directly reduced to give the malonates 3a–al. For this reduction step, palladium-based catalytic

• results, we first sought an explanation for the modest yields observed for the preparation of the 2, 3 or 4-chlorophenyl-α-hydroxyimino esters 2t–v. As depicted in Scheme 2, the 1H NMR monitoring of the ethanolic solution of the alkylidenemalonate 6u pointed out a slow but steady 1,4-addition of ethanol

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• . As seen by 1H NMR monitoring, the treatment of arylaldehydes 3a–s with trimethyl orthoformate and an acid-bearing resin in dry methanol led to full conversion into the corresponding acetals 5a–s. Then, as reported [7][8], heating the crude acetals 5a–s and ethyl nitroacetate (4) in the presence of

• focused on the model preparation of the trifluoromethyl-bearing α-nitro ester 6j from acylals 7 depicted in Scheme 2. As well reviewed [14], acylals can be prepared from aldehydes and anhydrides using a variety of acids as catalysts. In our case, 1H NMR monitoring of the reaction between 2

• monitoring of the reaction between compounds 7 or 8 and ethyl nitroacetate (4) in the presence of a catalytic amount of indium(III) chloride pointed out the occurrence of tangibly more of the expected acrylate 2j, although along with many byproducts. Indeed, in a typical experiment, upon reduction of the

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• reacted with hydrazine hydrate (5a) in refluxing ethanol containing a catalytic amount of AcOH (Scheme 2). TLC monitoring of the reaction indicated full conversion of 4 within 4 h reaction time to afford a fairly polar product insoluble or only slightly soluble in all commonly used NMR solvents. However

Design and synthesis of C₃-symmetric molecules bearing propellane moieties via cyclotrimerization and a ring-closing metathesis sequence

• Sambasivarao Kotha,
• Saidulu Todeti and
• Vikas R. Aswar

Beilstein J. Org. Chem. 2018, 14, 2537–2544, doi:10.3762/bjoc.14.230

• ), silicon tetrachloride (SiCl4, 0.61 mL, 5.36 mmol) was added dropwise at 0 °C and the reaction mixture was stirred for 10–15 min at the same temperature. Later, the reaction mixture was stirred at room temperature for 20 h. After completion of the reaction (TLC monitoring), the reaction mixture was

• ethylene atmosphere at rt. After completion of the reaction (TLC monitoring), the solvent was removed under reduced pressure. Later, the crude product was purified by silica gel column chromatography (30% EtOAc/petroleum ether) to obtain the ROM product 13 as a colourless solid (310 mg, 56%); Rf = 0.68 (4

• monitoring), the reaction mixture was quenched with 1 M aq HCl solution, and the aqueous layer was extracted by EtOAc (3 × 10 mL). Then the organic fraction was washed with brine solution, dried over Na2SO4 and concentrated. The crude residue was purified by silica gel column chromatography (10% EtOAc

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• cell movement or locomotion) of conjugates were investigated by monitoring the locomotion of A2058 cells with holographic microscopy under the condition that the conjugates (10−7 to 10−5 M) were added directly to the cells in a uniform concentration. For the characterization of cellular movement, three

Efficient catalytic alkyne metathesis with a fluoroalkoxy-supported ditungsten(III) complex

• Henrike Ehrhorn,
• Janin Schlösser,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2018, 14, 2425–2434, doi:10.3762/bjoc.14.220

• . The maximum conversion of around 97% is reached for both catalysts within 60 minutes. Accordingly, we aimed at further monitoring the substrate scope of the complexes including the metathesis of terminal alkynes as well as ring-closing alkyne metathesis (RCAM). Table 2 summarizes the isolated yields

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• ) sulfate and ascorbic acid. TLC monitoring showed that the cyclization failed. Then, tris(benzyltriazoylmethyl)amine (TBTA) [40][41][42] was added as catalyst and macrocycle 4 was formed in 71% yield, which is extremely high for an intramolecular cyclization. The dimeric product 3 and the cyclic dimer 5

Novel photochemical reactions of carbocyclic diazodiketones without elimination of nitrogen – a suitable way to N-hydrazonation of C–H-bonds

• Liudmila L. Rodina,
• Xenia V. Azarova,
• Jury J. Medvedev,
• Dmitrij V. Semenok and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2018, 14, 2250–2258, doi:10.3762/bjoc.14.200

• methods All reactions were carried out under argon atmosphere in solvents that were purified and dried before use by common methods. Monitoring of the reaction course was accomplished by thin layer chromatography (TLC) on silica gel SIL G/UV254 plates (Marcherey, Nagel & Co.). Chromatography was performed

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• monitoring of the steady-state conversion in continuous flow by 1H NMR. Following an optimization study, it was found that the Cu catalyst could be omitted when operating at 100 °C for 1 hour reaction time in batch, providing quantitative conversion to product (Table 2, entry 4). Conducting the same reaction

Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3-triazoles

• James T. Fletcher,
• Matthew D. Hanson,
• Joseph A. Christensen and
• Eric M. Villa

Beilstein J. Org. Chem. 2018, 14, 2098–2105, doi:10.3762/bjoc.14.184

• over time was used to calculate initial reaction rates for each of the amines studied, as described in the experimental section. It is important to note that this monitoring detects only the endpoint of the three-step sequence of condensation, rearrangement and hydrolysis steps, whereupon para