Mild and selective reduction of aldehydes utilising sodium dithionite under flow conditions

• Nicole C. Neyt and
• Darren L. Riley

Beilstein J. Org. Chem. 2018, 14, 1529–1536, doi:10.3762/bjoc.14.129

• laboratories because of its ease of use, safety and control [3][4][5][6]. Continuous flow technologies are generally more effective than traditional batch processes with key advantages including intensified heat and mass transfer, inline reaction monitoring, higher mass throughput, safer control of hazardous

Spectroelectrochemical studies on the effect of cations in the alkaline glycerol oxidation reaction over carbon nanotube-supported Pd nanoparticles

• Dennis Hiltrop,
• Steffen Cychy,
• Karina Elumeeva,
• Wolfgang Schuhmann and
• Martin Muhler

Beilstein J. Org. Chem. 2018, 14, 1428–1435, doi:10.3762/bjoc.14.120

• control of selectivity. Moreover, additional parameters such as pH value, the nature of the ions and the concentration of glycerol in the liquid phase can be tuned in liquid-phase processes [4]. Monitoring of electrocatalytic reactions is challenging as all products are dissolved in the electrolyte. High

Hypervalent iodine(III)-mediated decarboxylative acetoxylation at tertiary and benzylic carbon centers

• Kensuke Kiyokawa,
• Daichi Okumatsu and
• Satoshi Minakata

Beilstein J. Org. Chem. 2018, 14, 1046–1050, doi:10.3762/bjoc.14.92

• , followed by hydrolysis, offers an efficient and practical method for the synthesis of tertiary and benzylic alcohols. The following experiments were performed in attempts to gain insights into the reaction pathway. Monitoring the reaction by 1H NMR spectroscopy showed for the reaction of a mixture of 1a

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• monitoring the progress by TLC. The products were purified through PREP-TLC (hexane/ethyl acetate 90:10). Examples of the reductive iodonio-Claisen rearrangement compared to new reactivity seen with benzyl metalloids. Crossover reaction experiments. Suggested mechanism based on product formation and

Polysubstituted ferrocenes as tunable redox mediators

• Sven D. Waniek,
• Jan Klett,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2018, 14, 1004–1015, doi:10.3762/bjoc.14.86

• (E1/2 = 1140 mV in MeCN vs FcH/FcH+) in CD2Cl2 under NMR monitoring shows that the Cp proton resonances broaden upon oxidation and shift to lower field, while the methyl proton resonances of the ester substituents shift to higher field and remain much sharper (Figure 8, Table 2, Figures S36–S38

• chemical shifts of the Cp or ester methyl protons. Ongoing investigations focus on the spectroscopic monitoring of 1–4 as redox mediators in selected electrosynthetic transformations. Experimental Dichloromethane, CD2Cl2 and CD3CN were distilled from calcium hydride. Electrochemical experiments were

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• observations at a molecular scale [97] and from in situ monitoring of bulk-scale reactions [98]. The limited work relating to the chemical transformation of nucleoside and nucleotide substrates has been mainly focussed upon exploiting the (lack of) solvent requirements. This can allow access to unprecedented

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

• simulation time frame and calculate the host–guest binding affinity in each case. By monitoring the frames during the time interval of the simulations, we observed that the sterol group of the guest cholesterol molecule remains encapsulated inside the hydrophobic β-CD dimeric cavity while its aliphatic tail

Stepwise radical cation Diels–Alder reaction via multiple pathways

• Ryo Shimizu,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 704–708, doi:10.3762/bjoc.14.59

• development in our laboratory. GC–MS Monitoring of the oxidative SET-triggered reaction of aryl vinyl ether 1c. Radical cation Diels–Alder reaction of trans-anethole [17]. Radical cation Diels–Alder reactions of aryl vinyl ether and sulfides [17][25]. Radical cation Diels–Alder reaction of aryl vinyl ether (1

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• investigated using phenylboronic acid (3) in combination with different ortho- and para-substituted bromoarenes in aqueous ethanolic mixtures employing K2CO3 as base [38]. Monitoring of the reaction progress via inline UV–vis spectroscopy as well as offline HPLC analysis [38] led to the result that after an

• ). The stability of emulsions to gravity-induced creaming or coalescence was assessed by monitoring the position of the water–emulsion or oil–emulsion interfaces respectively. Microscopy images of the emulsions were recorded using an Olympus BX53 microscope with GXCAM-U318 camera attached and GXCapture-T

Investigating radical cation chain processes in the electrocatalytic Diels–Alder reaction

• Yasushi Imada,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 642–647, doi:10.3762/bjoc.14.51

• efficiency of up to 8000%. The reaction monitoring profiles showed sigmoidal curves with induction periods, suggesting the involvement of intermediate(s) in the rate determining step. Keywords: chain process; Diels–Alder reaction; electrocatalytic; radical cation; single electron transfer; Introduction

• electrochemical synthesis in that one electron can run the radical cation chain process up to 65 times. GC–MS monitoring showed a sigmoidal curve with an induction period. The monitoring was carried out in the presence of a large excess (10 equivalents) of isoprene (2), which might follow pseudo-first order

• ) and the aromatic radical cation (3·+) would impact the overall reaction rate. Indeed, when the monitoring was carried out with a lower concentration of trans-anethole (1), no induction period was observed and the reaction required nearly a stoichiometric amount of electricity to complete (Figure 3

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• ). HPLC monitoring of the formation of 2-(azidomethyl)oxazole 7a. Continuous sequential thermolysis of vinyl azides 1 and ring expansion of azirines 2 with bromoacetyl bromide to give 2-(bromomethyl)oxazoles 6. Continuous-flow three-step sequential synthesis of 2-(azidomethyl)oxazoles 7a–c from vinyl

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• lactose-2-aminothiazoline conjugate as a CT antagonist. Its affinity for CTB was determined by monitoring the change in fluorescence of tryptophan-88, located in the GM1 binding site, upon titration of the protein with the inhibitor. Compound 6 showed excellent binding with a Kd value of 23 µM [41

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives

• Shunsuke Kuribayashi,
• Tomoyuki Kurioka,
• Shinsuke Inagi,
• Ho-Jung Lu,
• Biing-Jiun Uang and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2018, 14, 389–396, doi:10.3762/bjoc.14.27

• current power supply model 5944 by monitoring electricity with a Hokutodenko Coulomb/Ampere-hour meter HF-201. Cyclic voltammetry measurements Cyclic voltammetry was carried out in 0.1 M Bu4NBF4/MeCN using a glass cell. A platinum disk electrode ( = 0.8 mm) was used as a working electrode. A platinum

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• into a measurable signal. Among several available modes of detection, fluorescence detection offers a number of distinct advantages, but mainly that it is relatively simple, selective, highly sensitive and can be used for real-time monitoring of the biological targets and even their interactions in

• unbound probes, which is most commonly achieved by solid phase hybridization followed by washing to eliminate the unbound probes before performing the fluorescence readout. These assays require multiple steps, and so are time-consuming making them unsuitable for real-time monitoring, such as nucleic acid

• amplification, monitoring of enzyme activities and localization and quantitation of nucleic acids in living cells. Therefore, it is highly desirable to develop a “smart” fluorogenic oligonucleotide probe that can directly report the presence of the target by a simple fluorescence readout in homogeneous and wash

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• straightforward applications is merely for monitoring whether a certain process involves a conformational change or not. A few examples of such applications are described below. In a collaborative investigation with Falkenberg and Gustafsson, we investigated the role of the transcription factor A (TFAM) in the

• structure resolution and monitoring of a different distance range with high accuracy. With the recent advent of new base–base FRET pairs, the coming years offer great prospects for increased use of such methodology. The combination of base–base FRET and single-molecule-based FRET on nucleic acids with

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• in the UV–vis range of the electromagnetic spectrum, where electronic transitions occur. The application of these polarization spectroscopy methods for the study of a complex between a small molecule (ligand) and DNA or RNA can generally be divided into two wavelength ranges: a) monitoring changes in

• chromophore also absorbs in this range, the deconvolution of all contributions is not trivial (see interpretation of results in the chapters of the corresponding methods); b) monitoring changes in polarization spectra at λ > 300 nm for ligands that have corresponding chromophores. This is the most common used

• same samples (Figure 4). Of course, this fact has very important practical applications in monitoring the polynucleotide structure change caused by outer stimuli like ligand binding, pH changes, melting, etc. Intriguingly, most of the single-stranded (ss) polynucleotides, if long enough, also show some

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• dimer was assigned as being trans, by X-ray crystallographic analysis. The kinetic reaction profile was determined by using 1H NMR reaction monitoring and revealed a second order overall kinetic profile. Furthermore, by employing this methodology, a diastereoselective total synthesis of a functionalized

• , initial azlactone 1a concentration, and initial base species 3 concentration; k1 and k−1 are the direct and reverse reaction rate constants for the formation of an azlactone enolate derivative 1’ and the azlactone 1a, respectively. In situ reaction monitoring by NMR spectroscopy allowed us to follow the

• NMR spectroscopic monitoring and revealed that the diastereoselectivity was determined during C–C bond formation step. A diastereoselective streptopyrrolidine analogue, containing three contiguous stereogenic centers, was smoothly obtained as a sole diastereomer in 70% yield. Structure of an azlactone

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• reaction in toluene in the presence of TEA (1 equiv) at 80 °C for 4 hours gave the best result in terms of regioselectivity and yield of 6a (Table 3, entry 1), virtually the only product formed in all the solvents used here (as evidenced by 19F NMR monitoring). The addition of malonic acid monophenyl ester

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• diaminoimidazole as a 1,3-C,N-dinucleophile to the activated C=C double bond to form intermediate 5 followed by recyclization involving the N1-amino group which leads to the formation of imidazo[1,5-b]pyridazines 9. Monitoring of the liquid phase composition of the reaction mixture by HPLC–HRMS showed that during

• the HPLC–HRESIMS monitoring of the reaction confirm its selectivity. Conclusion In summary, a new regioselective and chemoselective cascade reaction of N-arylitaconimides with 1,2-diamino-4-phenylimidazole as 1,3-C,N-dinucleophile was developed to synthesize tetrahydroimidazo[1,5-b]pyridazines. The

• monitoring of the reaction mixture composition in the synthesis of imidazopyridazine 9d. Supporting Information Supporting Information File 462: Experimental procedures, characterization data, copies of 1H, 13C spectra of the products and results of HPLC–HRESIMS monitoring of the reaction mixture

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• solution in deuterium oxide to give 0.5 mM analyte. The first NMR spectra were collected within 4 min following addition of the analyte. The monitoring was continued by recording 1H and 19F NMR spectra at regular time points until >50% hydrolysis. Ambient temperature was maintained at 298 ± 1 K. The decay

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• the reaction and generation of highly luminescent compounds which hindered in situ monitoring by Raman spectroscopy. However, in situ monitoring of the milling processes was enabled by using Cu(0) catalysts in the form of brass milling media which offered a direct insight into the reaction pathway of

• spin resonance (ESR) spectroscopy; in situ Raman monitoring; mechanochemistry; quinoline; solid-state click chemistry; Introduction The copper-catalyzed azide–alkyne cycloaddition (CuAAC) represents a prime example of click chemistry. Click chemistry describes “a set of near-perfect” reactions [1] for

• states for the mechanochemical CuAAC reaction of target quinoline derivatives and p-substituted phenyl azides. We have also investigated the effect of the p-substituent in the azide on the reaction progress and yields. Direct monitoring by in situ Raman spectroscopy was used to gain an insight into the

The effect of milling frequency on a mechanochemical organic reaction monitored by in situ Raman spectroscopy

• Patrick A. Julien,
• Ivani Malvestiti and
• Tomislav Friščić

Beilstein J. Org. Chem. 2017, 13, 2160–2168, doi:10.3762/bjoc.13.216

• milling frequency on the course of a mechanochemical organic reaction conducted using a vibratory shaker (mixer) ball mill. The use of in situ Raman spectroscopy for real-time monitoring of the mechanochemical synthesis of a 2,3-diphenylquinoxaline derivative revealed a pronounced dependence of chemical

• : green chemistry; mechanism; mechanochemistry; milling; monitoring; Raman spectroscopy; Introduction Over the past decade, mechanochemical reactions [1][2][3][4], i.e., chemical transformations induced or sustained through the application of mechanical force in the form of grinding, milling and shearing

• mechanochemical reactions. A significant recent advance in mechanistic studies of mechanochemical reaction mechanisms was the introduction of techniques for in situ, real-time monitoring of ball milling processes [27], first through synchrotron X-ray powder diffraction (XRPD) [28][29], and later by Raman

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• -aminopyridine (20 mg, 0.21 mmol, 1.2 equiv), enone 6a (51 mg, 0.17 mmol, 1 equiv), Cu(OAc)2·H2O (3.6 mg, 0.02 mmol, 10 mol %), and 1,10-phenanthroline (2.5 μL, 0.02 mmol, 10 mol %) in chlorobenzene (1 mL) was stirred in a reaction tube at 160 °C under an O2 atmosphere. After 25 h, 19F NMR monitoring indicated

• stirred in a reaction tube at 160 °C under an O2 atmosphere. After 4 h monitoring by 19F NMR indicated the disappearance of the starting material. Thus the mixture was cooled to room temperature, filtered, washed and extracted with dichloromethane. The organic phase was concentrated and the crude product

Solvent-free and room temperature synthesis of 3-arylquinolines from different anilines and styrene oxide in the presence of Al₂O₃/MeSO₃H

• Hashem Sharghi,
• Mahdi Aberi,
• Mohsen Khataminejad and
• Pezhman Shiri

Beilstein J. Org. Chem. 2017, 13, 1977–1981, doi:10.3762/bjoc.13.193

• methanesulfonic acid 98% and acidic alumina (Al2O3) type 540 C were purchased from Fluka. The elemental analyses were performed with a Thermo Finnigan CHNS-O analyzer, 1112 series. The purity determination of the substrates and reaction monitoring were accomplished by TLC on silica gel PolyGram SILG/UV 254 plates