N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• [16][18][19], isopropyl 5c [16] and tert-butyl 5d [16][20] as well as for 4-methoxyphenyl ester 5e [21]. However, the corresponding (−)-menthyl esters (2R,1'R)-5f and (2S,1'R)-5f were separated by solvent-driven selective crystallization at low-temperature from ethanol and hexane, respectively. The

• presence of acetic anhydride produced a crude acetamido ester (R)-132 which was transformed into the final N-benzyl amide (R)-130 with of 99.9% ee after crystallization. ʟ-(+)-Furanomycin (Scheme 35) is a natural nonproteinogenic amino acid which showed pronounced antibacterial activity. From several

• pyrrolidin-2-ones (3S,4R,5R,1'R)-183b (by crystallization from cold ethanol) and (3R,4S,5R,1'R)-183b (by flash chromatography). After reduction and hydrogenolysis they were converted into 1,4-dideoxy-1,4-imino-ᴅ-arabinitol and ((2R,3R,4R)-182) and 1,4-dideoxy-1,4-imino-ᴅ-xylitol ((2R,3S,4S)-182

Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• , an X-ray crystallization analysis was conducted. The apo structure of AmbP1 was solved at 2.35 Å, and it adopted an ABBA fold [4][5][13]. Interestingly, the apo structure unusually includes the Mg2+ ion in a position nearby the β-barrel, stabilized by hydrogen bonding with N41, E63, and D65 (Figure

• same pH as in the reservoir for crystallization. In this structure (Mg2+-free structure), the distance from C-1 of GSPP to C-2 of 1 (Figure 4A, a: 3.3 Å) is closer than that to C-3 of 1 (Figure 4A, b: 4.6 Å), unexpectedly indicating that this is a model for the C-2 prenylation. Next, the soaking

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

• the inclusion of the base led to crystallization of the corresponding products 3a–c during the milling process. In contrast, crystallization during the base-free reaction required an ex situ aging step. Figure 1 shows the XRPD pattern of the substrate 2 and the product 3a. Due to the liquid state of

• inclusion of base catalyst in the final product, we suggest this difference to be the result of a templating effect, which dominates at higher concentrations. For the reaction of meta- and ortho-substituted substrates, crystallization occurs directly into the monoclinic phase, regardless of milling

Fabrication, characterization and adsorption properties of cucurbit[7]uril-functionalized polycaprolactone electrospun nanofibrous membranes

• Changzhong Chen,
• Fengbo Liu,
• Xiongzhi Zhang,
• Zhiyong Zhao and
• Simin Liu

Beilstein J. Org. Chem. 2019, 15, 992–999, doi:10.3762/bjoc.15.97

• dispersion and crystallization of CB[7] and PCL in the composite nanofibers, XRD patterns of neat PCL nanofibers and all PCL/CB[7] nanofibers were recorded (Figure 2). PCL is a semi-crystalline polymer, and neat PCL nanofibers elicit two strong and sharp characteristic diffraction peaks at 2θ = 22° and 2θ

• continuous phase and crystal aggregates of PCL and CB[7]. At low CB[7] contents, the majority of the CB[7] molecules could disperse homogeneously in the PCL matrix, partly causing the disruption of continuous phase and crystallization of PCL and CB[7]. With the increase of CB[7] content, there are more

• that temperature. There is only a very wide and weak peak in the heating cycle, which was caused by evaporating of water from the cavity of CB[7] (Figure S7 in Supporting Information File 1). As can be deduced from Figure 3, all electrospun webs exhibit obvious melting and crystallization peaks below

Halogen bonding and host–guest chemistry between N-alkylammonium resorcinarene halides, diiodoperfluorobutane and neutral guests

• Fangfang Pan,
• Mohadeseh Dashti,
• Michael R. Reynolds,
• Kari Rissanen,
• John F. Trant and
• Ngong Kodiah Beyeh

Beilstein J. Org. Chem. 2019, 15, 947–954, doi:10.3762/bjoc.15.91

• . employing substitutional disorder, achieved the co-crystallization of six components [28]. As for positional disorder, it generally indicates the same molecule or assembly can adopt more than one favourable conformation. From this perspective, disorder can be considered as a special case of a co-crystal or

Coordination chemistry and photoswitching of dinuclear macrocyclic cadmium-, nickel-, and zinc complexes containing azobenzene carboxylato co-ligands

• Jennifer Klose,
• Tobias Severin,
• Peter Hahn,
• Alexander Jeremies,
• Jens Bergmann,
• Daniel Fuhrmann,
• Jan Griebel,
• Bernd Abel and
• Berthold Kersting

Beilstein J. Org. Chem. 2019, 15, 840–851, doi:10.3762/bjoc.15.81

• to crystallization of [Zn2L(μ-azo-OH)][Zn2L(μ-azo-O)]·BPh4·4MeCN·3H2O (3'·4MeCN·3H2O). The asymmetric unit contains one [Zn2L(μ-azo-OH)]+ cation (Figure 4), one [Zn2L(μ-azo-O)] neutral complex (comprising a doubly deprotonated co-ligand), one BPh4− anion, and MeCN and H2O solvate molecules. Both

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• , which has to be separated either by selective crystallization or by chromatography. The first concern was to verify that using the two most commonly used procedures for 6-monotosylation, the substitution by the second tosyl moiety is still selective for the primary rim of β-CD. For a straightforward

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

• ; no crystallization was observed even after several days at rt. Similar properties were displayed by product 13d, which did not crystallize at all and was analyzed as an oily material. 1-Adamantyloxy-4,5-dimethyl-3-pentyloxy-1H-imidazolium bromide (13a): Yield: 325 mg (79%). Beige crystals; mp 73 °C

• mixture) as an eluent. The required product was isolated as a crystalline material. Additional crystallization from diisopropyl ether/CH2Cl2 mixture afforded analytically pure imidazolium salt 15. 1,3-Di(adamantyloxy)imidazolium bromide (15): Yield: 190 mg (41%). Colorless crystals; mp ca. 160 °C (dec

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• (1R,3S)-HPA-12 (2) used the chiral pool approach [15][16], crystallization-induced asymmetric transformation [17], diastereoselective reduction of γ-aryl-γ-oxo-β-amino alcohol [18], cycloaddition of oxime with alkenes [19], enantioselective carbonyl reduction followed by an organocatalyzed α-amination

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• generation of the protected β-NR+Br− 8a, which was isolated by crystallization from a 5:1 acetone/t-BuOMe mixture in 90% overall yield from 2a [27]. Note that dry acetonitrile was also used as a solvent in the glycosylation step instead of liquid SO2 but the yields of acetylated NR+Br− 8a were lowered (65

• %) [27]. Removal of the acetyl groups from 8a under optimized conditions (3 equivalents of NH3, 1 M in MeOH, at −3 to −5 °C for 20 h), followed by crystallization from a 1:5 mixture of MeOH/acetone afforded β-NR+Br− as a crystalline solid in high yield (80%) [27]. It should be noted that Lee et al. [27

• % of the α-anomer. This anomer was removed from the crude mixture by chromatography on activated charcoal and crystallization to afford the desired β-NR+OTf− in 58% yield. The predominant formation of the β-isomer of NR+ is due to the generation of a type F cationic intermediate in the course of

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• group, to determine the effect of the spacer length on POSS crystallization ability and the composition dependence of physical properties of the copolymers [49]. A series of homopolymers and random copolymers were synthesized in the presence of third generation Grubbs catalyst Ru-6 in CH2Cl2, at room

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• trimethyl orthoacetate the enantiomerically pure bromomethoxy derivative (4R,5R)-37 was prepared after crystallization of the reaction mixture. The precursor of the carboxymethyl group was first introduced with full retention of configuration employing a stannate chemistry to give (4R,5R)-38 after removal

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• in a trans-orientation with H(4). In addition, various crystallization tests were carried out in order to confirm the absolute stereochemistry by X-ray diffraction. The chiral 3-(2-(methylthio)ethyl)-1-(phenylamino)-1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)dione (5f) crystallized [44][45][46][47][48][49

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• values of 0.9 ± 0.3 µM for 24 and 19.6 ± 3.7 µM for 26. The highly enthalpy-driven binding indicates a specific noncovalent interaction of 24 to the protein. To further investigate the binding mode of the hit fragments in the protein crystallization experiments were performed. Since the native substrate

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• possible by careful crystallization from methanol. The structure and configuration of the products 12–14 were established by NMR as well as the single-crystals X-ray analysis (see Supporting Information File 1 for details). The data presented in Table 4 clearly indicate that the substituent change from

A novel and practical asymmetric synthesis of eptazocine hydrobromide

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan,
• Kuaile Lin and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209

• reaction was scaled up (60 g of 2) according to the conditions in entry 5, and similar results were obtained (Table 1, entry 8). After the screening of many solvents, the pure isomer 4 was isolated from the crude reaction mixture through crystallization from ethyl acetate with 48% yield and >99% chiral

Selective formation of a zwitterion adduct and bicarbonate salt in the efficient CO₂ fixation by N-benzyl cyclic guanidine under dry and wet conditions

• Yoshiaki Yoshida,
• Naoto Aoyagi and
• Takeshi Endo

Beilstein J. Org. Chem. 2018, 14, 2204–2211, doi:10.3762/bjoc.14.194

• water during the crystallization process [28]. On the other hand, Villiers and Ephritikhine et al. synthesized and characterized successfully the zwitterion adduct of CO2 and TBD under strictly anhydrous conditions [31]. They also described that the obtained zwitterion adduct of TBD–CO2 was stable at

Synthesis and post-functionalization of alternate-linked-meta-para-[2ⁿ.1ⁿ]thiacyclophanes

• Wout De Leger,
• Koen Adriaensen,
• Koen Robeyns,
• Luc Van Meervelt,
• Joice Thomas,
• Björn Meijers,
• Mario Smet and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2190–2197, doi:10.3762/bjoc.14.192

• thermodynamically stable [2 + 2] macrocycle 6 (41%, see Figure S13, Supporting Information File 1). Due to the instability of the macrocycles, purification of the reaction mixtures via column chromatography (silica/alumina) or selective crystallization was difficult. Changing the biselectrophile precursor to

Evaluation of dispersion type metal···π arene interaction in arylbismuth compounds – an experimental and theoretical study

• Ana-Maria Preda,
• Małgorzata Krasowska,
• Lydia Wrobel,
• Philipp Kitschke,
• Phil C. Andrews,
• Jonathan G. MacLellan,
• Lutz Mertens,
• Marcus Korb,
• Tobias Rüffer,
• Heinrich Lang,
• Alexander A. Auer and
• Michael Mehring

Beilstein J. Org. Chem. 2018, 14, 2125–2145, doi:10.3762/bjoc.14.187

• ][47]. A more convenient synthetic route makes use of the Grignard reagent phenylmagnesium bromide and its reaction with bismuth trichloride [48]. Following this approach with slight modifications provides Ph3Bi with a yield of more than 80%. Crystallization from EtOH gave single crystals of the

• monoclinic C2/c polymorph 1a, which was already subject of several studies including the description of its crystal structure [39][40][41][42][43]. Therefore, it is somewhat surprising that the bismuth···π interaction was not noted so far. We obtained polymorph 1a upon crystallization from solution, but we

• isolated another polymorph 1b by crystallization from the melt. Polymorph 1b was obtained starting from 1a in a temperature-dependent PXRD experiment (see Supporting Information File 1, Figure S1). The polymorph 1b was obtained as a microcrystalline material, but Andrews and MacLellan did obtain single

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• the throughput in the start or anywhere else gets changed in the sequence. This is very important for synthesis steps where downstream processing is also in sequence. Usually time scales for work-up procedures like extraction, crystallization, solvent switch etc. are longer compared to the main

• . Here the reactor was maintained at a temperature of 70–100 °C for 1–3 hours. The product was crystallized in CT1 with the anti-solvent methanol pumped through P4 into the crystallization tank. The crystallized product was filtered and separated in S2. Deprotection: The second-stage product from the

• was pumped through pump P3 to form the final lactate salt of the product. Here the excess of formic acid and lactic acid was removed by the rotary evaporator RE1, then passes through TR4 into the crystallization tank CT1. The solid product formed was filtered in F1 and stored in a tank T1. Challenges

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• , so that the pure products were only available by crystallization from appropriate solvents, which resulted in lower yields of these products. Single crystal X-ray diffraction analysis of 9-(arylethynyl)benzo[b]quinolizinium derivatives 2a and 2b Single crystals of derivatives 2a and 2b were obtained

• by crystallization from acetone and CHCl3/MeOH, respectively (Figure 2 and Figure S1, Supporting Information File 1). Derivative 2a crystallizes in the triclinic space group with two molecules in the unit cell. The crystals were twinned and the compound shows some considerable disorder. The chemical

First thia-Diels–Alder reactions of thiochalcones with 1,4-quinones

• Grzegorz Mlostoń,
• Katarzyna Urbaniak,
• Paweł Urbaniak,
• Anna Marko,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2018, 14, 1834–1839, doi:10.3762/bjoc.14.156

• –l, analytically pure samples were obtained by crystallization from petroleum ether with a small amount of dichloromethane. All attempts to obtain analytically pure samples for 4m, 4n and 6 were unsuccessful and the purification procedure led to formation of some decomposition products. 2,4-Diphenyl

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

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

• the slow cooling crystallization technique. More specific, 10.22 mg (0.026 mmoles) of CHL were added in a 2 mL equimolar aqueous solution of β-CD. The mixture was stirred at 70 °C for 4 h and gradually cooled to room temperature over a period of seven days. X-ray crystallography A prismatic colorless

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• crystallization. We note that the neighboring group participation proposed should be limited to leaving groups with a second nucleophilic site at the appropriate position. Other leaving groups than methylimidazole should not be able to react via the same dominant reaction pathway. In our hands, compounds with a