Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• polymeric macromolecular catalysts, e.g., PEG 200 and PEG 10000 as solid auxiliaries to enhance crystallization under LAG mechanochemical conditions in "polymer and liquid-assisted grinding" or POLAG [22][23]. While the focus in these investigations has been on the improvement of the macroscopic parameters

Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

• Spyros D. Chatziefthimiou,
• Mario Inclán,
• Petros Giastas,
• Athanasios Papakyriakou,
• Konstantina Yannakopoulou and
• Irene M. Mavridis

Beilstein J. Org. Chem. 2017, 13, 1572–1582, doi:10.3762/bjoc.13.157

• crystallization, as a consequence of accumulation of many soft host–guest interactions and of the imposed crystallographic order, thus resulting in very dissimilar propensity of each enantiomer to produce crystals with β-CD. Keywords: β-cyclodextrin; enantiomeric discrimination; N-acetyltryptophan; NMR; X-ray

• lead to the grown crystals and differentiates them slight from hydrated β-CD. It is worth noting that hydrothermal treatment in crystallization trials has yielded uncommon structures such as, novel packing of β-CD–ethanol crystals [31] during trials to crystallize the β-CD–N-(1-adamantyl

• of the NAcPhe enantiomers. Numerous crystallization trials failed to produce crystals of the β-CD–D-NAcTrp complex yielding only hydrated β-CD crystals. The fact that β-CD–D-NAcTrp could not be crystallized in dimers as the β-CD–L-NAcTrp might be due to destabilization of the interface between dimers

Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• -diphenylethanol was isolated, although the origin of water was not clear (possibly trapped by the diazonium salts during crystallization since, due to their potential explosivity in the dry state, they were not dried under vacuum). At this stage we postulated that A could be more favourably attacked in an

1-Imidoalkylphosphonium salts with modulated C_α–P⁺ bond strength: synthesis and application as new active α-imidoalkylating agents

• Jakub Adamek,
• Roman Mazurkiewicz,
• Anna Węgrzyk and
• Karol Erfurt

Beilstein J. Org. Chem. 2017, 13, 1446–1455, doi:10.3762/bjoc.13.142

• –N bond instead of the Cα–OMe bond more favorable in this case. The phosphonium salts 5 were purified by crystallization, usually from a mixture of CH2Cl2/Et2O. However, in a few cases preliminary purification by column chromatography proved to be necessary. Their structures were confirmed by 1H, 13C

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• syn-configured CCR product (Table 1, entries 3, 8, 11 and 13, anti/syn ratio ranging from 3.3:1 to 6.5:1), the latter was removed by crystallization and the respective pure anti-diastereomers (anti-10c, 10h, 10k and 10m) were obtained and characterized. In certain instances (Table 1, entries 5–7, and

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• -irritant phorboid mixture from croton oil was telescoped to only five operational steps, and phorbol could then be purified by gravity column chromatography and crystallization. Evidence is provided that two distinct phorboid chemotypes of croton oil exist, differing in the relative proportion of type-A

• crystallization step. A solution for these issues is provided, suggesting that the poor-reproducibility of croton oil-based anti-inflammatory assays are the result of poor quality and/or inconsistent composition of croton oil. Keywords: croton oil; diterpenoids; natural products; phorbol; transesterification

• issues with this protocol. The first one is the repeated handling of croton oil, a very toxic and obnoxious material, during the methanol extraction step, that requires several hours of stirring and then of resting to achieve a good phase separation, and the second one is the capricious crystallization

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• regioisomers was purified by crystallization from DMSO to yield 64.6 mg (0.19 mmol, 48%) of 16d (SYN). Mp: 363.0–365.0 °C (DMSO), yellow solid compound. 1H NMR (600 MHz, DMSO-d6) δ 13.48 (s, 1H, H-NA(4)), 12.92 (br s, 1H, -COOH), 12.26 (s, 1H, H-NA(1)), 8.04 (d, J(A5,A7) = 1.5 Hz, 1H, H-CA(5)), 7.99 (d, J(B2

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• dimensions of 0.5 × 0.01 × 0.01 mm, could be grown using protein crystallization methods. Data were collected using synchrotron radiation, and the structure was solved using direct methods. Four independent molecules were found in each asymmetric unit (which contains 284 non-hydrogen atoms) in a highly

• dramatic impact on the throughput and on the complexity of the structures determined. However, despite the development in nano-volume liquid handling for high-throughput screens, the crystallization of biological macromolecules still represents an important bottleneck in structure determination. Nanoliter

• handling devices allow the screening of hundreds of crystallization conditions even with a limited amount of sample of a few tens of microliters [19]. Furthermore, a successful example of automation in crystal harvesting were recently reported [20], while robots are now used to handle cryo-cooled samples

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• -polar regions of the GPCR, especially intracellular loop 3 (IL3), that do not form the rigid, specific interactions needed for crystallization. Such problems are sometimes overcome by truncating the flexible termini, complexing the GPCR with antibody fragments [9], or by replacing IL3 with a stable

• stable enough for crystallization. The solution to this problem has been to use the variable domains of camelid antibodies, which are generally designated protein nanobodies, as a surrogate for the G-protein [18]. This technique will be discussed in the context of the simulations below. Note, however

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• , for the reaction with p-methoxyphenyl isothiocyanate we were able to obtain, by crystallization, the major product, C(1)-substituted thioamide 3n, contaminated with only ≈5% of its C4-substituted counterpart. We tentatively explain this poorer regioselectivity by possible π–π interaction of pyrene

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

Inclusion complexes of β-cyclodextrin with tricyclic drugs: an X-ray diffraction, NMR and molecular dynamics study

• Franca Castiglione,
• Fabio Ganazzoli,
• Luciana Malpezzi,
• Andrea Mele,
• Walter Panzeri and
• Giuseppina Raffaini

Beilstein J. Org. Chem. 2017, 13, 714–719, doi:10.3762/bjoc.13.70

• secondary rim of the host. Conclusion The integrated approach X-ray/NMR/MD was successfully applied to the structure assessment of 1/β-CD and 2/β-CD complexes. The crystallization of a single enantiomer of 1 encapsulated into β-CD showed that the latter acts as chiral selector towards racemic 1. The

Substitution of fluorine in M[C₆F₅BF₃] with organolithium compounds: distinctions between O- and N-nucleophiles

• Anton Yu. Shabalin,
• Nicolay Yu. Adonin and
• Vadim V. Bardin

Beilstein J. Org. Chem. 2017, 13, 703–713, doi:10.3762/bjoc.13.69

• [C6F5BF3] (1-Li) or [Bu4N][C6F5BF3] (1-N) gives the corresponding salts 6-Li, 7-Li and 6-N, 7-N (Table 2, entries 4–6) (Scheme 3). An analytically pure sample of 6-K was isolated by crystallization of a mixture of 6-K and 7-N from MeCN. Reactions with PhLi The addition of PhLi in ether to a solution of 1-K

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• very compact in size [1.0 m × 0.7 m × 1.8 m, (W × L × H)], and low-weighing (about 100 kg) and was able to perform complex multistep synthesis, work-up procedures as well as purification operations such as crystallization. This platform was also equipped with devices for real-time monitoring and final

A novel method for heterocyclic amide–thioamide transformations

• Walid Fathalla,
• Ibrahim A. I. Ali and
• Pavel Pazdera

Beilstein J. Org. Chem. 2017, 13, 174–181, doi:10.3762/bjoc.13.20

• . Purification of products for analysis was achieved by crystallization from the appropriate solvent; chromatographed with the appropriate eluent or by repeated dissolution in KOH and reprecipitation by acetic acid. The filtrate was evaporated once again and the solid obtained was crystalized from ethanol water

• purposes. Purification of products for analysis was achieved by crystallization from the appropriate solvent; chromatographed with the appropriate eluent or by repeated dissolution in KOH and reprecipitation by acetic acid. Dicyclohexylthiourea (3) [42]: Yield 65% (ethanol 95%–H2O) white crystals, mp 180

Supramolecular frameworks based on [60]fullerene hexakisadducts

• Andreas Kraft,
• Johannes Stangl,
• Ana-Maria Krause,
• Klaus Müller-Buschbaum and
• Florian Beuerle

Beilstein J. Org. Chem. 2017, 13, 1–9, doi:10.3762/bjoc.13.1

• promising alternative thus combining low-weight materials with easy processing. However, the crystallization of stable organic structures possessing permanent porosity is still quite challenging and only a limited number of examples for supramolecular crystals based on hydrogen bonding [29][30][31][32][33

• retaining permanent porosity in the solvent-free state have been reported so far. Here, we report on the crystallization of three-dimensional hydrogen-bonding frameworks based on [60]fullerene hexakisadducts bearing twelve carboxylic acid groups icosahedrally arranged on the fullerene surface. By varying

• crystallization of C3 and also synthesized the next homologue C4 starting from malonate 1 [59] according to a standard two-step protocol via a sixfold Bingel reaction followed by acidic deprotection (Scheme 1). As we observed the insertion of MeOH molecules into the hydrogen-bonding network of HFF-1 [57], we also

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• positionally undefined heavy atoms obtained after an unspecific ligand-soaking procedure, new methods were developed. One highly defined method is to directly substitute methionine by selenomethionine in recombinantly expressed proteins [19][20]. On the other hand, the co-crystallization of a protein in

• Fischer-type glycosylation and pure allyl α-fucoside (7) was obtained after crystallization in 43% yield (Scheme 2). Selective protection of the 3,4-cis-diol as an acetonide followed by methylation of the hydroxy group in position 2 yielded derivative 8 in 85% yield over two steps. Then, the acetonide

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

• -cyclooctadiene)rhodium(I) dimer, or with bis(triphenylphosphine)rhodium(I) carbonyl chloride in anhydrous toluene at reflux temperature, respectively. During these reactions, the water of crystallization of the starting material is – at least partially – removed by azeotropic distillation and Rh(I) is obviously

• the solution in vacuo, filtration and crystallization of the mother liquor in the presence of one drop of water gave 6A/B in quantitative yield. Yield of 7: 0.02 g (100%). 1H NMR (600 MHz, pyridine-d5) δ 7.44 (d, J = 0.8 Hz, 1H, H-5), 7.40 (dd, J1 = 1.0 Hz, J2 = 7.6 Hz, 1H, H-11), 7.16–7.12 (m, 2H, H

Effects of solvent additive on “s-shaped” curves in solution-processed small molecule solar cells

• John A. Love,
• Shu-Hua Chou,
• Ye Huang,
• Guilllermo C. Bazan and
• Thuc-Quyen Nguyen

Beilstein J. Org. Chem. 2016, 12, 2543–2555, doi:10.3762/bjoc.12.249

• acceptor materials. It is found that films cast from chlorobenzene yield devices with strongly s-shaped current–voltage curves, drastically limiting performance. We find that addition of the common solvent additive diiodooctane, in addition to facilitating crystallization, leads to improved vertical phase

• ) and crystallization (Tc) temperatures of p-SIDT(FBTThCA8)2 are increased by 76.9 and 117.1 °C, respectively, which implies an enhancement of the intermolecular interaction in the solid state. This improved rigidity of p-SIDT(FBTThCA8)2 is correlated to a noticeable decrease in solubility, which was

• kinetics of phase separation. In this class of small molecule systems, this is often attributed to asserting control over the crystallization and phase-separation processes within the blend; DIO helps induce crystallinity of the donor material [40][41][42][54][55][56]. Grazing incidence wide-angle X-ray

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

• 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

A new protocol for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane

• Donghui Pan,
• Yanbin Wang and
• Guomin Xiao

Beilstein J. Org. Chem. 2016, 12, 2443–2449, doi:10.3762/bjoc.12.237

• prepare tetrachloroparacyclophane, but a pure polysubstituted product is difficult to obtain by electrophilic substitution without repeated crystallization or chromatographic purification [9]. Thus, we report an improved synthesis method using the Winberg dimerization of 2,5-dichloro-(4-methylbenzyl

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• , washed with EtOH and purified by silica gel (60–120) column chromatography (EtOAc/hexane, CHCl3/EtOH, CH2Cl2) or crystallization from EtOH to afford the desired isoxazole 4. 4-(1-Methyl-5-nitro-1H-imidazol-4-yl)-3-phenylisoxazole (4a). Colorless powder, yield 53%, mp 130–132 °С (column, CHCl3/EtOH 20:1

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

• and thioester compounds [8][30] and the CD thiouronium salt intermediates are not isolated [8] despite their good crystallization properties, while the excess/residual TU and used solvents are removed upon the conversion to thiols only. However, the easy crystallization of these salts is a nice

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

• single melt temperature recorded for BMR, BBR and BPR at 179 °C, 215 °C and 196 °C, respectively. Subsequent crystallization was observed at 154 °C, 175 °C and 174 °C for BMR, BBR and BPR, respectively. The phase behaviour for BTR has been previously reported and shows three phase transitions on heating

• transmitted spectrum during the phase change recorded at 164 °C, Figure 2, suggestive of significant structural rearrangements occurring during crystallization. The POM/heating stage apparatus was coupled to a fibre-optic based spectrometer to enable collection of variable temperature UV–vis and fluorescence

• heating/cooling impacts on the crystallization of the thin films, with the slower rates used for the fully enclosed, temperature ramped POM stage, leading to equilibrium phases, while rapid thermal quenching of isolated thin films on glass slides gives different results. To further probe this effect, the