Anomalous diffusion of Ibuprofen in cyclodextrin nanosponge hydrogels: an HRMAS NMR study

• Monica Ferro,
• Franca Castiglione,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2014, 10, 2715–2723, doi:10.3762/bjoc.10.286

• , such as the chemical compositions of the nanosponge (e.g., CDNSPMA, CDNSEDTA are swellable, CDNSDPC are not) and the cross-linker to CD mole ratio n [17]. Recently, we demonstrated that the CDNS hydrogels undergo phase transitions by changing the hydration level h = m(H2O)/mCDNS by a complex interplay

Phosphinocyclodextrins as confining units for catalytic metal centres. Applications to carbon–carbon bond forming reactions

• Matthieu Jouffroy,
• Rafael Gramage-Doria,
• David Sémeril,
• Dominique Armspach,
• Dominique Matt,
• Werner Oberhauser and
• Loïc Toupet

Beilstein J. Org. Chem. 2014, 10, 2388–2405, doi:10.3762/bjoc.10.249

• , 2JC,P = 22.8 Hz, CO) ppm; 31P{1H} NMR (161.9 MHz, CDCl3, 25 °C) δ 40.5 (d, 1JP,Rh = 172 Hz) ppm; IR: 2086 (vs, CO), 2026 (vs, CO), 2004 (s, CO) cm−1; We do not provide microanalytical data for this compound because of strong hydration; MS (ESI–TOF): m/z (%): 1799.44 (70) [M – Cl]+, 1857.40 (100) [M

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• alternate between A, B and Z forms depending on the hydration and the type and concentration of metal ions, which is also reflected in the conformation of the sugar part. Finally, the conformation of ribose or its mimics also significantly predetermines the binding of a nucleoside, nucleotide or an analog

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• the corresponding ketones. The hydration of C–C triple bonds under the influence of various catalytic systems, including also Pd-based catalysts, is a well-known reaction [21][22]. It should be emphasized that NMR investigations with compounds 8a,c unambiguously revealed the methylene group adjacent

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• layer of amphiphile prior to hydration of the material. The microscope slide was placed into a Linkam PE94 hot stage (Linkam Scientific Instruments Ltd.; Surrey, England) and a water drop added at the side of the cover slip to flood the sample and create a concentration gradient as water was absorbed

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• as drugs in various therapies and as recognition units in diagnostics and sensing. However, the development of synthetic lectins poses a phenomenal challenge for supramolecular chemistry [37] because a carbohydrate receptor in order to be useful must not only compete with the strong hydration of

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• both β-CD cavities (Figure 3d) are the least stable by PM3(COSMO) (in the presence of water), although highly favorable by PM3 (in the absence of solvent). This was attributed to insufficient hydration of the primary hydroxy groups due to steric crowding around the primary sides of the two β-CD tori

Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

• Richard J. Ingham,
• Claudio Battilocchio,
• Joel M. Hawkins and
• Steven V. Ley

Beilstein J. Org. Chem. 2014, 10, 641–652, doi:10.3762/bjoc.10.56

• treatment of tuberculosis – and its reduced derivative piperazine-2-carboxamide. Keywords: automation; flow chemistry; hydration; hydrogenation; sustainable processing; Introduction Enabling synthesis technologies such as flow chemistry are becoming commonplace in modern laboratories (for recent reviews

• explored the possibility of developing a machine-automated synthesis of this compound which might later be extended to analogous structures. For the facile machine-assisted synthesis of 1 we devised and optimised the fully continuous sequential hydration of nitrile 3 to amide 2 and hydrogenation of

• pyrazine 2 to piperazine 1 (Figure 2b). Both of these steps involve flowing through heterogeneous catalysts, a metal oxide for the hydration of the nitrile and a supported precious metal for the hydrogenation of the heteroaromatic ring. Furthermore, both steps involve the addition of a volatile small

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

• Yumeng Xi,
• Boliang Dong and
• Xiaodong Shi

Beilstein J. Org. Chem. 2013, 9, 2537–2543, doi:10.3762/bjoc.9.288

• as essential tools in organic synthesis. Generally with the unique reactivity and mild reaction conditions, this type of transformation has found widespread applications in complex molecule synthesis [10][11]. Among those reactions, the gold-catalyzed hydration of alkynes is regarded as one of the

• signature reactions in the field (known as Teles hydration) [12]. This reaction usually utilized the combination of methanol and water, wherein methanol served as the nucleophile to attack the triple bond, forming the vinyl ether intermediate. This vinyl ether then collapsed to give a ketone as the final

• 1,3-diketones with unactivated alkynes at ambient temperature. Results and Discussion As indicated in Scheme 1, the main challenge for the intermolecular O-nucleophile addition to alkynes is the competitive hydration side reaction. Although, theoretically, strictly anhydrous conditions shall prevent

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• fluorine, its hydration and thus reduced nucleophilicity [21]. The importance of this developing research field is reflected by the various review articles which have been published dealing with transition metal mediated or catalyzed fluorination [22][23][24], difluoromethylation [24], and

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• condensation of primary amines with o-diacylbenzene 19 (Scheme 2) [13]. After initial formation of 20, isomerization to 21 and 22 can occur through a sequential dehydration–hydration process. Dimerization of 21 and 22 generates 23, the substrate for a formal retro-Aldol reaction. Loss of formaldehyde gives 24

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• the total synthesis of the anticancer guaiane (−)-englerin A. A regio- and diastereoselective Co(II)-catalyzed hydration of the olefin and a transannular epoxide opening were used as the key reactions. Keywords: asymmetric synthesis; hydration; natural products; terpenes; transannular epoxide opening

• completion of the synthesis of (−)-oxyphyllol (1) from 4. To our delight, a direct regio- and diastereoselective Co(II)-catalyzed hydration [12] of the olefin in 4 succeeded to give the required α-stereoisomer 3 in 58% isolated yield after chromatographic separation of the minor β-alcohol. Compared to the

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• stereoisomers of Ile are less hydrophobic than Aha. F6Leu is similar to Aha in hydrophobicity, while exhibiting a much larger volume. In a free energy perturbation study, the hydration energy of F6Leu was shown to be 1.1 kcal/mol higher than that of leucine [29]. This, together with our previous and new

• findings, suggests that there are two factors determining the overall hydrophobicity of fluorinated amino acids [26]. On one hand, substitutions of hydrogen by fluorine increase the solvent accessible surface area and thus lead to an increase in hydration energy. On the other hand, the C–F bond is more

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• triethylsilane and BF3·Et2O [53], affording 11. Oxidative cleavage of 11 with KMnO4/Bu4NBr [54] afforded iso-C12 acid 1. Alternatively, anti-Markovnikov hydration of 11, using I2/NaBH4 then hydrogen peroxide [55], afforded the alcohol 12, and oxidation of 12 with KMnO4/Bu4NBr afforded iso-C13 acid 2

Gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones

• Marie Hoffmann,
• Solène Miaskiewicz,
• Jean-Marc Weibel,
• Patrick Pale and
• Aurélien Blanc

Beilstein J. Org. Chem. 2013, 9, 1774–1780, doi:10.3762/bjoc.9.206

• formation of the hydration product 3 (Table 1, entries 2 and 3 versus entry 1). We found out that running the reaction at 70 °C instead of at room temperature completely prevented the byproduct formation. At this temperature good to quantitative yields of furans 2a were achieved in less than 30 min, and 5

• °C, no trace of furan 2a could be detected by 1H NMR analysis. Interestingly, decreasing the catalytic loading from 5 to 1 mol % still provided the furan in less than 1 h and in high yields (Table 1, entries 6 and 7 versus entry 5). However, hydration started to compete again at low loading, as

• hydration product, the reaction took 6 h to reach almost full conversion. Beside the expected furan 2d, its corresponding regioisomer 2d’ arising from 1,3-migration of the pivaloyl group is formed in this reaction and both products were obtained in a combined yield of 68% (Table 2, entry 4). We next varied

Aerobic radical multifunctionalization of alkenes using tert-butyl nitrite and water

• Daisuke Hirose and
• Tsuyoshi Taniguchi

Beilstein J. Org. Chem. 2013, 9, 1713–1717, doi:10.3762/bjoc.9.196

• hydroxy group arising from hydration of the olefin (entry 6). Functionalization reactions involving oxygenation of methylene C–H bonds of alkenes 11–13 also proceeded to afford secondary nitrate compounds 21–23, though no diastereoselectivity was observed (Table 2, entries 7–9). Unfortunately, no tertiary

Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo-methylenetetrahydrofurans from β-hydroxyketones

• István E. Markó and
• Florian T. Schevenels

Beilstein J. Org. Chem. 2013, 9, 1319–1325, doi:10.3762/bjoc.9.148

• 13 was treated with aqueous hydrochloric acid, in the hope of generating the corresponding dihydrofuran carbaldehyde 33. Instead, the diol 34 was obtained in 52% yield as a 1:1 mixture of diastereoisomers. It thus transpires that protonation and hydration of the exo-methylene double bond of 13

• of two new dimers. Formation of (Z)-chloro-exo-methyleneketals. Mechanism of formation of (Z)-chloro-exo-methylenetetrahydrofurans. Stepwise formation of (Z)-chloro-exo-methylenetetrahydrofurans. Optimized protocols to form (Z)-chloro-exo-methylenetetrahydrofurans. Hydration of (Z)-chloro-exo

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

• transition states, intermediates and products shown in Scheme 3, hydration by six water molecules is implied. Relative Gibbs free energies with respect to the separated reactants 1·(H2O)2 + [OH(H2O)4]– including bulk aqueous solvation energies (SMD solvation model [21]) obtained by various computational

Alkyne hydroarylation with Au N-heterocyclic carbene catalysts

• Cristina Tubaro,
• Marco Baron,
• Andrea Biffis and
• Marino Basato

Beilstein J. Org. Chem. 2013, 9, 246–253, doi:10.3762/bjoc.9.29

• selectivity compared to the previously published complex AuCl(PPh3). Preliminary results on intramolecular hydroarylations using this catalytic system indicate, however, that alkyne hydration by traces of water may become a serious competing reaction. Keywords: alkyne; C–H functionalization; cyclisation

• VI moderate to very good conversions of the substrates were obtained, but the main reaction product was invariably the product of hydration of the triple bond 8, whereas the 6-endo-dig cyclisation product 7 was present in minor amounts. Gold(I) NHC complexes such as VI are known to be extremely

• efficient catalysts for alkyne hydration [61], hence it can be expected that alkyne hydration by traces of water may become a serious competitive reaction despite the low concentration of water in the reaction mixture. On the basis of the above, it can be hypothesised that in order to steer the reaction

Presence or absence of a novel charge-transfer complex in the base-catalyzed hydrolysis of N-ethylbenzamide or ethyl benzoate

• Shinichi Yamabe,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2013, 9, 185–196, doi:10.3762/bjoc.9.22

• water molecules in the first hydration shell of an alanine molecule was found to be seven [44]. Thus, more than seven water molecules would be required to examine the reaction paths of hydrolyses reliably. However, less than six water molecules are included in the precedent computational studies [26][27

• TS1(es) is enlarged appreciably (= +17.87 kcal/mol) in spite of the positional assumption (ii) in Figure 7. Thus, the counter ion works unfavorably on the rate-determining step TS1(es). The Na+ ion has a very large hydration energy (= −97 kcal/mol), and the cation needs to be surrounded by many water

• molecules in the hydration shell far from the reaction region. Figure 8 shows energy changes for the amide hydrolysis of Figure 5. Those of Na+-containing paths in the system, Ph–C(=O)–NH–Et + NaOH(H2O)16 in Figure S4 (Supporting Information File 1), are also shown in green. In energies of the Na+-free

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• position for adsorption to the ice surface; a similar situation applies to the retro-inverso peptide 7. Moreover, these conformational changes may possibly also alter the water hydration shell around the peptide, which has been suggested to be essential for the antifreeze activity of AFGPs and AFGP

• backbone as well as on the hydration shell around the peptide. Experimental All chemicals were acquired from Sigma Aldrich (Hamburg, Germany), Acros (Geel, Belgium), Alfa Aesar (Ward Hill, USA) and VWR (Darmstadt, Germany) and were employed without additional purification. Moisture- and air-sensitive

Mannose-decorated cyclodextrin vesicles: The interplay of multivalency and surface density in lectin–carbohydrate recognition

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2012, 8, 1543–1551, doi:10.3762/bjoc.8.175

• functionalized by self-assembly [27]. To this end, cyclodextrins are modified with long alkyl chains (“tails”) and short oligo(ethylene glycol) head groups. These macrocyclic amphiphiles form unilamellar bilayer vesicles in aqueous solution upon hydration of a thin film cast by evaporation from organic solution

Synthesis of a novel chemotype via sequential metal-catalyzed cycloisomerizations

• Bo Leng,
• Stephanie Chichetti,
• Shun Su,
• Aaron B. Beeler and
• John A. Porco Jr.

Beilstein J. Org. Chem. 2012, 8, 1338–1343, doi:10.3762/bjoc.8.153

• , evaluating a number of metal catalysts in the presence of diethyl malonate. From this focused reaction screen we identified three types of reactivity: (1) no reaction; (2) alkyne hydration (4); and (3) cycloisomerization leading to isochromene (5) (Figure 1). Many catalysts resulted in no reaction, including

• ones that might have been expected to catalyze cycloisomerization, such as AgOTf. Two catalysts, Cu(OTf)2 and Pd(MeCN)2Cl2, afforded only hydration of the alkyne. Interestingly, hydration was regioselective, which is possibly due to direction from the ether oxygen. We were most interested in metal

Continuous-flow hydration–condensation reaction: Synthesis of α,β-unsaturated ketones from alkynes and aldehydes by using a heterogeneous solid acid catalyst

• Magnus Rueping,
• Teerawut Bootwicha,
• Hannah Baars and
• Erli Sugiono

Beilstein J. Org. Chem. 2011, 7, 1680–1687, doi:10.3762/bjoc.7.198

• Magnus Rueping Teerawut Bootwicha Hannah Baars Erli Sugiono Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.7.198 Abstract A simple, practical and efficient continuous-flow hydration–condensation protocol was developed for the synthesis

• of valuable differently substituted chalcones. Starting from commercially available alkynes and aldehydes, a continuous-flow hydration–condensation protocol leads to the desired products in good to excellent yields. The reactions were sequentially introduced into the flow cell and performed several

• General procedure for hydration–condensation reaction of phenylacetylene (1a) and benzaldehyde (2a). A solution of phenylacetylene (1a) (0.4 mmol) and benzaldehyde (2a) (1.6 mmol) was pumped through the flow cell filled with amberlyst-15 resin (16–50 mesh) (10.0 g) and dry 1,2-dichloroethane at a flow