Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• may be both significant dispersion along the length of the reactor and the product is slow in clearing the flow cell. Dispersion is the consequence of laminar flow and some of the material takes longer to travel through the reactor than the rest. Thus, when a flow reactor is used to process a finite

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• calculated values of the rate constant for the 5-exo cyclization of the hexenyl radical with the experimental values. The dispersion-corrected PW6B95-D3 functional provided very good results with deviations for the free activation barrier compared to the experimental values of only about 0.5 kcal mol−1 and

• was therefore employed in further calculations. Corrections for intramolecular London dispersion and solvation effects in the quantum chemical treatment are essential to obtain consistent and accurate theoretical data. For the investigated radical addition reaction it turned out that the polarity of

• problems, e.g., self-interaction error (SIE) leading to underestimated reaction barriers and the lack of long-range electron correlation (London dispersion) effects. Regarding the latter problem, one of the most successful and widely used dispersion correction schemes is DFT-D3, in which a damped, atom

Controlled synthesis of poly(3-hexylthiophene) in continuous flow

• Helga Seyler,
• Jegadesan Subbiah,
• David J. Jones,
• Andrew B. Holmes and
• Wallace W. H. Wong

Beilstein J. Org. Chem. 2013, 9, 1492–1500, doi:10.3762/bjoc.9.170

• dried by first flushing with anhydrous methanol followed by dried acetone before refilling with anhydrous reaction solvent. Reported yields do not account for axial dispersion of the reaction mixture and the formation of the regioisomer 2b. Gel permeation chromatography (GPC) data was obtained by using

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• more convenient, nonaqueous workup, involving the near quantitative removal of the produced TMG-p-toluenesulfinate salt [41] by filtration of a diethyl ether dispersion of the crude reaction mixture. This modification thus allowed for gram-scale preparations of the desired diazoacetamides. The α

A³-Coupling catalyzed by robust Au nanoparticles covalently bonded to HS-functionalized cellulose nanocrystalline films

• Jian-Lin Huang,
• Derek G. Gray and
• Chao-Jun Li

Beilstein J. Org. Chem. 2013, 9, 1388–1396, doi:10.3762/bjoc.9.155

• show lower catalytic activities compared with homogeneous catalysts, which may be caused by blocking the diffusion and adsorption of organic reactant molecules and products or the poor dispersion of active sites [22][23]. Cellulose nanocrystals (CNCs) have emerged as a new class of nanomaterials owing

Synthesis and spectroscopic properties of 4-amino-1,8-naphthalimide derivatives involving the carboxylic group: a new molecular probe for ZnO nanoparticles with unusual fluorescence features

• Laura Bekere,
• David Gachet,
• Vladimir Lokshin,
• Wladimir Marine and
• Vladimir Khodorkovsky

Beilstein J. Org. Chem. 2013, 9, 1311–1318, doi:10.3762/bjoc.9.147

• . The ZnO NPs in ethanol were prepared by laser ablation according to [14]. The typical NP size was 17 nm with the dispersion about 25%. A freshly prepared ZnO NP solution in ethanol was added to the 1.4 × 10−6 M solution of 4 in ethanol. Under one-photon CW excitation at 325 nm, the fluorescence

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• washing away any impurities, pure material was then released with a base in order to perform the final palladium-catalysed coupling process (Figure 24). Passage of the reacting solution through two columns of immobilised reagent caused significant dispersion of the product, resulting in a long and

• of this device was for the preparation of a series of hydrazones. A continuous aqueous extraction to remove the excess hydrazine enabled the product to be collected in high purity (Figure 29). Other applications reported in this work include alkene epoxidation and dithiane preparation. Dispersion of

• compounds passing through the continuous extractor was measured by a computer vision technique. The dilution of a red dye injected as a plug was measured by observing the intensity of red colour in the flow tube as observed by a USB microscope camera (Figure 30). Since this dispersion profile should remain

A computational study of base-catalyzed reactions of cyclic 1,2-diones: cyclobutane-1,2-dione

• Nargis Sultana and
• Walter M. F. Fabian

Beilstein J. Org. Chem. 2013, 9, 594–601, doi:10.3762/bjoc.9.64

• trends agree very well with that obtained with CEPA/1 [Supporting Information File 1; the corresponding correlation coefficients R2 are 0.992 (M06-2X); 0.997 (MP2 and SCS-MP2); and 0.999 (EC)]. Inclusion of an empirical dispersion correction (DFTD3 [28]) in the M06-2X results further lowers the relative

• correction for the standard state conversion 1 atm to 1 mol L–1 at T = 298.15 K. Dispersion corrections to the M06-2X results were added by Grimme’s DFTD3 procedure [28]. Programs used were ORCA [42], Gaussian 09 [43], GAMESS [44], and DFTD3 [45]; MOLDEN [46] and MOLEKEL [47] were used for structure building

A new intermediate in the Prins reaction

• Shinichi Yamabe,
• Takeshi Fukuda and
• Shoko Yamazaki

Beilstein J. Org. Chem. 2013, 9, 476–485, doi:10.3762/bjoc.9.51

• dispersion correction method (ωB97XD [29]) were applied to the rate-determining step of the propene reaction TS1(Me). The basis sets employed were 6-31G(d) and 6-311+G(d,p). Transition states (TSs) were sought first by partial optimizations at bond interchange regions. Second, by the use of Hessian matrices

The β-cyclodextrin/benzene complex and its hydrogen bonds – a theoretical study using molecular dynamics, quantum mechanics and COSMO-RS

• Jutta Erika Helga Köhler and
• Nicole Grczelschak-Mick

Beilstein J. Org. Chem. 2013, 9, 118–134, doi:10.3762/bjoc.9.15

• Turbomole allows the calculation of more detailed energy hypersurfaces especially for hydrogen bonds (keyword BP-TZVP-DISP3) since Grimme’s dispersion corrections for nonbonded interactions were implemented recently [32]. The current release of COSMO-RS C30_1201 allows, for the first time, a more detailed σ

• ). Although all optimisations were started from the AM1-optimised parallel and vertical geometries (from which the naming stems), the BP/TZVP-DISP3 method with its enhanced description of dispersion forces led in general to structures in which the benzene molecule adopts a more oblique position [14][20][32

A new family of four-ring bent-core nematic liquid crystals with highly polar transverse and end groups

• Kalpana Upadhyaya,
• Venkatesh Gude,
• Golam Mohiuddin and
• Rao V. S. Nandiraju

Beilstein J. Org. Chem. 2013, 9, 26–35, doi:10.3762/bjoc.9.4

• -range order was confirmed. The highly polarizable aromatic parts, which have conjugated electrons, contribute to the anisotropic dispersion potential between them. This is due to the arrangement of two neighbouring molecules in an antiparallel orientation and, hence, the aromatic moieties of the two

• molecule and, hence, leads to an increase in the bending angle. An increase in bending angle may contribute to increased van der Waals interactions and dispersion forces and, hence, promote mesomorphism during the cooling cycle in these compounds. The absence of mesomorphism in 1e and 1f may be attributed

Influence of cyclodextrin on the solubility and the polymerization of (meth)acrylated Triton^® X-100

• Melanie Kemnitz and
• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 2176–2183, doi:10.3762/bjoc.8.245

• RAMEB-CD. Above 27 °C the 2:1 complex of RAMEB-CD with the methacrylic monomer 2 precipitates as a result of slipping off the RAMEB-CD. If the solution is cooled down the complex is reformed and the dispersion became completely transparent again. With increasing concentration of RAMEB-CD and decreasing

New enzymatically polymerized copolymers from 4-tert-butylphenol and 4-ferrocenylphenol and their modification and inclusion complexes with β-cyclodextrin

• Adam Mondrzyk,
• Beate Mondrzik,
• Sabrina Gingter and
• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 2118–2123, doi:10.3762/bjoc.8.238

• mmol) propargyl bromide and 0.14 g (1.0 mmol) potassium carbonate are dispersed in 20 mL dry THF in a one-neck flask under an argon atmosphere. The dispersion is stirred under reflux for 24 hours. The product is precipitated in hexane and dried in vacuo to give 0.28 g (80% yield). FTIR (diamond) : 2962

Cyclodextrin-based nanosponges as drug carriers

• Francesco Trotta,
• Marco Zanetti and
• Roberta Cavalli

Beilstein J. Org. Chem. 2012, 8, 2091–2099, doi:10.3762/bjoc.8.235

• than 1 µm and narrow size distribution and form opalescent suspensions on dispersion in water. The zeta potential of carbonate nanosponges is about −25 mV, which is sufficiently high to produce stable water suspensions that do not undergo aggregation over time. For parenteral application it is possible

Influence of intramolecular hydrogen bonds on the binding potential of methylated β-cyclodextrin derivatives

• Gerhard Wenz

Beilstein J. Org. Chem. 2012, 8, 1890–1895, doi:10.3762/bjoc.8.218

• ]. The host–guest complexes, so-called cyclodextrin inclusion compounds, find many applications such as solubilization of pharmaceutical drugs, dispersion of cosmetics, catalysis, or chromatographic separation of enantiomers [2][7][8]. Application of β-CD 1 is hampered by its low solubility of 18.8 g L−1

Molecular solubilization of fullerene C₆₀ in water by γ-cyclodextrin thioethers

• Hai Ming Wang and
• Gerhard Wenz

Beilstein J. Org. Chem. 2012, 8, 1644–1651, doi:10.3762/bjoc.8.188

• CDs (see Figure 1, [29]). Andersson et al. reported that C60 formed a water-soluble 1:2 inclusion complex with γ-CD after heating under reflux in water [21]. Mixing of an aqueous solution of γ-CD with a methanolic solution of C60 led to a C60 dispersion with a concentration of ca. 70 mg/L [30]. Even

• homogenous molecular solution and a dispersion of aggregates [47][48]. The size distribution of the solution of C60 in 6 mM γ-CD thioether 5 before centrifugation, shown in Figure 6, comprised two peaks at particle sizes of 3 and 300 nm. The first peak was attributed to the molecular CD/C60 complex, the

Influence of cyclodextrin on the solubility of a classically prepared 2-vinylcyclopropane macromonomer in aqueous solution

• Helmut Ritter,
• Jia Cheng and
• Monir Tabatabai

Beilstein J. Org. Chem. 2012, 8, 1528–1535, doi:10.3762/bjoc.8.173

• solubility of 5 at room temperature (about 25 °C). However, the turbid dispersion becomes completely clear by the addition of methylated β-cyclodextrin (Me2-β-CD). This means that a water-soluble inclusion complex 7 of 5 with Me2-β-CD is formed (Figure 3). The 2D ROESY NMR spectrum of 7 indicates the

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• . Extensive DFT calculations, including solvent effects and dispersion corrections, as well as ab initio calculations provide a plausible description of the reaction mechanism. Keywords: bifunctional organocatalyst; DFT calculations; guanidine-thiourea; Michael addition; organocatalysis; transition states

• rigid catalyst is proposed. We would like to stress here that studies on systems of this size are influenced quite strongly by dispersion contributions [60][61][62][63][64][65][66] and that standard DFT calculations should be supplemented by at least single-point MP2 energy corrections with an extensive

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• Lewis base as well as the cationic adduct (LB+-methyl, LB+-benzhydryl, LB+-trityl, LB+-MOSCA, LB+-acetyl). Unfortunately, the actual conformational rank depends on the used level of theory, especially if dispersion interactions play an important role. This problem will gain more relevance when the

Superstructures with cyclodextrins: Chemistry and applications

• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 1303–1304, doi:10.3762/bjoc.8.148

• instance, release and molecular dispersion of antihistamines in the tear fluid are achieved very quickly by means of amylase catalysis. Regarding the interactions of CDs with low-molecular and macromolecular compounds, respectively, the reactivity of complexed molecules is another key factor besides

• established. More recently, the use of CDs as food additives was approved. For example, dispersion of triglycerides can be achieved by the addition of α-CD. In organic synthesis and polymer chemistry, the interest in CDs has increased significantly during the past decades. For instance, in the latter case

Cyanoethylation of the glucans dextran and pullulan: Substitution pattern and formation of nanostructures and entrapment of magnetic nanoparticles

• Kathrin Fiege,
• Heinrich Lünsdorf,
• Sevil Atarijabarzadeh and
• Petra Mischnick

Beilstein J. Org. Chem. 2012, 8, 551–566, doi:10.3762/bjoc.8.63

• were fixed with strong magnets and washed with distilled water. Monodisperse and regularly shaped iron oxide nanoparticles were obtained as shown by TEM (Figure 9). The iron concentration of the nanoparticle dispersion, as analyzed with inductively coupled plasma optical emission spectroscopy (ICP–OES

• stabilization. At pH 2 the iron oxide dispersion is stable for several months without precipitation. After the dialysis process of the high-DS cyanoethyldextran and pullulan (20 mg, CED-3, DSGC = 2.40; CEP-3, DSGC = 2.42) the hydrodynamic diameter of the particles was determined by DLS. Additionally, scanning

• . According to the micrographs, the morphology of the cyanoethyl nanoparticles can be considered as spherical. Representative SEM pictures of CEP-3 + Fe-np (Table 3, entry 2) are shown in Figure 10. The influence of different amounts of ferromagnetic nanoparticle dispersion was investigated (10–200 μL or

Catalyst-free and solvent-free Michael addition of 1,3-dicarbonyl compounds to nitroalkenes by a grinding method

• Zong-Bo Xie,
• Na Wang,
• Ming-Yu Wu,
• Ting He,
• Zhang-Gao Le and
• Xiao-Qi Yu

Beilstein J. Org. Chem. 2012, 8, 534–538, doi:10.3762/bjoc.8.61

• degrees, and the primary reason may be that the two reactants could come into contact more effectively after dispersion by the grinding aids. It was found that kieselguhr was slightly better than quartz sand in terms of grinding efficiency, and both gave excellent yields. Although kieselguhr is often used

The interplay of configuration and conformation in helical perylenequinones: Insights from chirality induction in liquid crystals and calculations

• Elisa Frezza,
• Silvia Pieraccini,
• Stefania Mazzini,
• Alberta Ferrarini and
• Gian Piero Spada

Beilstein J. Org. Chem. 2012, 8, 155–163, doi:10.3762/bjoc.8.16

• for the treatment of dispersion interactions, and by augmenting the basis set with diffuse functions. Experimental Helical twisting power measurement Cholesteric pitch and handedness were obtained at T = 298 K by using the lens version of the Grandjean–Cano method [38][39]. The commercially available

Continuous preparation of carbon-nanotube-supported platinum catalysts in a flow reactor directly heated by electric current

• Alicja Schlange,
• Antonio Rodolfo dos Santos,
• Ulrich Kunz and
• Thomas Turek

Beilstein J. Org. Chem. 2011, 7, 1412–1420, doi:10.3762/bjoc.7.165

• process for the production of highly active Pt catalysts supported by carbon nanotubes by use of an electrically heated tubular reactor. The synthesized catalysts show a high degree of dispersion and narrow distributions of cluster sizes. In comparison to catalysts synthesized by the conventional oil-bath

• electrochemical activity, resulting in higher power density values. It is known that the catalyst preparation method strongly influences the noble metal cluster size and its dispersion on the carbon and therefore the electrocatalytic activity [19]. DMFC electrocatalysts are mostly prepared in batch processes

• hot spots. This can lead to temperature gradients in the reacting solution, resulting in poor dispersion of Pt on the carbon support. For this reason, in the past few years heating by means of microwave ovens was introduced. The microwave-assisted polyol synthesis method has many advantages over the

Synthesis of enantiomerically enriched (R)-¹³C-labelled 2-aminoisobutyric acid (Aib) by conformational memory in the alkylation of a derivative of L-alanine

• Stephen P. Fletcher,
• Jordi Solà,
• Dean Holt,
• Robert A. Brown and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1304–1309, doi:10.3762/bjoc.7.152

• , protected Aib (R)-6* for use in the synthesis, on gram scale, of spectroscopic probes for helicity [56]. Experimental (S)-2,2-Dimethyl-4-methyl-3-(1-naphthoyl)-oxazolidin-5-one (3): By a modification of the method of Branca [36][57], sodium hydride (575 mg of a 60% dispersion in mineral oil, 12.4 mmol) was