Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• (1.026 g) was recrystallized from boiling DMF (255 mL). After precipitation completed, the solid was filtered, washed with cold DMF (3 × 5 mL). The filter cake was suspended in water (10 mL) for 5 min followed by suction, this procedure was repeated 3 times to remove DMF from crystals. After drying in a

• collected by filtration, the mother liquor was concentrated under vacuum. To the obtained dense oily residue was added H2O (35 mL), the resulting light pink solution was cooled (0 °C), and upon manual agitation the precipitation of product was initiated. After precipitation completed, the solid was filtered

A series of perylene diimide cathode interlayer materials for green solvent processing in conventional organic photovoltaics

• Kathryn M. Wolfe,
• Shahidul Alam,
• Eva German,
• Fahad N. Alduayji,
• Maryam Alqurashi,
• Frédéric Laquai and
• Gregory C. Welch

Beilstein J. Org. Chem. 2023, 19, 1620–1629, doi:10.3762/bjoc.19.119

• pressure that can lead to precipitation during coating and due to being a highly flammable and toxic solvent [20][33][34]. Figure S33 in Supporting Information File 1 compares the J–V characteristics of all N-annulated perylene diimides-based CILs cast from ethyl acetate and PFN-Br cast from methanol

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

• derivative synthesis. In accordance with the principles of green chemistry, we envisaged a procedure with temperatures not too high and reaction times not too long. We also wanted to isolate pure compounds by a simple filtration after precipitation in aqueous media without the need for extraction or

Functions of enzyme domains in 2-methylisoborneol biosynthesis and enzymatic synthesis of non-natural analogs

• Binbin Gu,
• Lin-Fu Liang and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1452–1459, doi:10.3762/bjoc.19.104

• elution buffer used for protein purification through Ni2+-NTA affinity chromatography. While domain B alone showed a substantial enzyme precipitation after 12 h at 4 °C, full length 2MIBS did not (Figure 1B), suggesting that the A domain increases enzyme solubility and long-term stability. This effect

• needs a covalent bond between the two domains A and B, as indicated by a similar precipitation of domain B alone and domain B in the presence of domain A. In these experiments, the N-terminal His-tags at both domains A and B may influence protein–protein interaction with the consequence that the mixture

• of the individually expressed domains shows a similarly rapid precipitation as domain B alone. However, some interaction between the individually expressed domains A and B can be concluded from their reduced productivity in comparison to domain B alone. Enzymatic synthesis of non-natural analogs of 2

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• attractive to produce more material in a single AGA run, but might suffer from insufficient mixing [27][28], causing slower kinetics [29], temperature gradients [30], and precipitation [31]. We set off to study the effect of these parameters on the AGA of three different glycan sequences (Figure 2). In an

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• we postulated on Scheme 4 could not be detected, a solid was recovered after evaporation of the solvent and precipitation in pentane. This solid displayed a 31P NMR signal at 55.1 ppm (see Supporting Information File 1, p. S24), a value completely different from comp4 (singlet at 35.06 ppm, see

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• diethyl ether in the next step should make precipitation more efficient [10]. This was done for compound 8a, but no improvement was observed. Much better results were obtained with additional double wash of the precipitate with methanol combined with evaporation of the solvent under reduced pressure. As a

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• the co-precipitation from a saturated solution. The peony oil content in the complex was almost 26%, with a high ratio of unsaturated FA glycerides of ≈90% [20]. In a very recent study, perilla (Perilla frutescens (L.) Britton) seed oil was complexed by γ-CD and the inclusion complex was used for

• unsaturated fatty acid glycerides significantly decreases the stability of hazelnut oil. Only one study was performed on the γ-CD nanoencapsulation of hazelnut oil by a co-precipitation method and the thermal decomposition of the complex was evaluated by TG [34]. One way of enhancing the oxidative stability

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• neutralization. The second method could bear the name homogeneous approach [8][14][35]. It is very similar to the previous method, however, TsCl dissolved in MeCN is added to the basic β-CD aqueous solution. Turbidity or even slight precipitation is observed during the process. After a few hours, the reaction

• mixture is filtered and neutralized to induce precipitation. The third method works with pyridine as a solvent [29][36][37]. In this method, β-CD is dissolved in pyridine and a pyridine solution of TsCl is added dropwise. After a few hours, the solvent is distilled off and the residue is precipitated in

• ensure good yields. However, the yields bring us to the second important point. As already mentioned, the yield of this reaction is not strongly influenced by the amount of TsCl, but by the purification method. If only the precipitation is carried out, then the crude product is always a mixture of Ts-β

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• TLC, cold water was added to the reaction mixture at room temperature which resulted in precipitation of the product. The product was collected by filtration under reduced pressure using a Büchner funnel and further purified by silica gel column chromatography (60–120 mesh silica gel) using hexane and

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• full monomer conversion. Monomer conversion was monitored by 1H NMR spectroscopy. After complete monomer consumption, the reaction was terminated by adding 3.0 equiv of water and left to react overnight at 45 °C. The polymer was purified by precipitation from cold diethyl ether (Et2O) or direct

• /or initiator did not yield considerable improvements. It is known that MeOx polymerization can be challenging due to the poor solubility of PMeOx in some solvents [30][31][34]. However, no precipitation was observed during polymerization, which rules out the solubility as an issue. Therefore, we

• no signals at 6.11–5.92 ppm and 5.93–5.83 ppm, but the appearance of new signals at ca. 1.45–2.00 ppm [46][48]. As a control experiment, DLG was incubated with MeOTf for 4 h at 90 °C. The resulting product was purified by precipitation from cold Et2O. The determination of Mn by SEC analysis was about

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• isolated in 54% yield (Table 1, entry 8). The exchange of chloride with the non-coordinating BF4− anion, driven by the precipitation of NaCl, is proposed to be responsible for this positive result. Next, we turned our attention to the use of hydrogen-bond donors as anion-binding catalysts [57][58]. To this

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• with only two equivalents of TfOH forming product 1a in 74% yield (Table 2, entry 1). We found that these reaction conditions cannot be applied in the proposed multi-step procedure since the added benzene clogs the flow reactor through precipitation of a black solid. We could overcome this issue by

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• -CD·BES, β-CD·PRO, γ-CD·BES and γ-CD·PRO were prepared via kneading and co-precipitation, and 1H NMR spectroscopic analysis of solutions of their pure complex crystals yielded the host–guest stoichiometries 2:1, 2:1, 1:1 and 3:2, respectively. Both powder X-ray diffraction (PXRD) and single-crystal X-ray

• size and quality. Co-precipitation experiments yielded single crystals of all four CD inclusion complexes with distinctive transparent monoclinic morphologies for β-CD·BES and β-CD·PRO, and transparent rods with a square cross-section for γ-CD·BES and γ-CD·PRO (Figure 4). PXRD analysis also confirmed

• that pure crystalline phases were obtained for each complex product via co-precipitation experiments and that each of these was the same crystalline phase as the respective complex product produced via kneading. These single crystals were of adequate quality for SCXRD except for the single crystals of

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• , this strategy is attractive for rapid small-scale syntheses of such scaffolds and the optimization of the used solvents can broaden the uptake of this strategy. Inline precipitation and crystallization One of the most widely acknowledged challenges within the field of flow chemistry is the necessity to

• operate under homogeneous conditions within the thin tubing that makes up the flow reactor components. The handling of slurries whether because of unintended precipitation or as a deliberate means to process insoluble materials presents the risk of clogging and pressure built-up which can severely

• compromise a flow run. Therefore, continuous flow crystallization and precipitation for the purification of a flow reaction mixture is not often reported and many of the protocols use a semi-continuous approach for instance via continuous stirred tank reactors to purify APIs. Wu and co-workers recently

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• binding event that is already occurring at the start of the experiment or a precipitation event (Figure 6). However, a precipitation event would cause a drop in current since precipitation of the protein onto a polymer-coated electrode prevents the mediator from reaching the electrodes below the polymer

• binding event being monitored has already started. b) Precipitation of the protein target. Four cycles vs. twelve cycles and the effect on binding curve location. Repeating the experiment on different arrays. (a) A comparison between a 4-cycle placement reaction and a 25-cycle placement reaction. (b) 3 vs

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

•  1). Purification of the products was straightforward as in many cases the bridged species could be isolated by precipitation with water and then recrystallization. The reaction of mildly electron-rich anisaldehyde and 4-methoxy-3-methylbenzaldehyde resulted in the bridged products 5b and 5d in good

Introducing a new 7-ring fused diindenone-dithieno[3,2-b:2',3'-d]thiophene unit as a promising component for organic semiconductor materials

• Valentin H. K. Fell,
• Joseph Cameron,
• Alexander L. Kanibolotsky,
• Eman J. Hussien and
• Peter J. Skabara

Beilstein J. Org. Chem. 2022, 18, 944–955, doi:10.3762/bjoc.18.94

• ]. This palladium-catalysed cross coupling is preferred over a Stille cross-coupling due to the high toxicity of organotin reagents [37]. Moreover, purification of compound 25 is facile since it can be used for further reactions after re-precipitation in petroleum ether. In a manner similar to [35], it is

• triethylamine to the eluent [44]. Also, using a solvent mixture with a low polarity, which is necessary to receive a good separation from the side products, led to a precipitation of the compound on the column, and many attempts were necessary to find an ideal solvent mixture. Additionally, the reaction was

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• (Table 2, entries 5 and 6 in comparison with entry 2). Trials using ethanol or isopropanol as a solvent (Table 2, entries 7 and 8) were not successful, plausibly because of a precipitation of the reaction medium before the end of the base addition. Trials with lithium or potassium hydroxide (Table 2

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• catalysis can be generated directly by the functionalized nanostructured particles (Scheme 12, case C) [50]. This was achieved by reductive precipitation of Pd(0) nanoparticles from ammonium-bound tetrachloropalladate [84][85], which showed good catalytic activity in various cross-coupling reactions under

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• . Inspired by recent work on out of equilibrium molecular machinery, using trichloroacetic acid (TCA), we disclose a purification technique considerably decreasing the number of operations and the waste generation required for such purifications. At first, TCA triggers the precipitation of the amines through

• from rotaxanes, cucurbit[8]uril, to supramolecular smart materials [11][12][13][14][15][16]. TCA is also known for its application in the precipitation of proteins through what is believed to be an unfolding of the proteins structures [17][18]. In this context, we hypothesized that TCA could be used to

• this mixture dissolved in EtOAc, precipitation of the amine salt enabled the removal of naphthalene in the solvent. Beside the choice of the solvent for the crystallization which strongly depends on the solubility of the protonated amine salts involved, we first focused on the optimization of the

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• reaction, which mainly include styrene and p-toluenesulfonic acid. As a result, when the reaction is performed at large scales, there is a high probability that the product can be purified by methods such as partition, precipitation and crystallization. The major advantage of using a base-labile protecting

Study on the interactions between melamine-cored Schiff bases with cucurbit[n]urils of different sizes and its application in detecting silver ions

• Jun-Xian Gou,
• Yang Luo,
• Xi-Nan Yang,
• Wei Zhang,
• Ji-Hong Lu,
• Zhu Tao and
• Xin Xiao

Beilstein J. Org. Chem. 2021, 17, 2950–2958, doi:10.3762/bjoc.17.204

• addition, the UV–vis spectrum in Figure 4a shows that the absorbance of TBT keeps on the decrease (ΔA = 0.623) without red shift or blue shift in the presence of Q[8]. Both of the above phenomena show that Q[8] interacted with the “arm” of TBT and produced precipitation due to aggregation, which is also

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• alumina column. Excess amount of THF was evaporated by a rotary evaporator. After precipitation of the mixture to cold methanol, the polymer was collected by filtration and dried under vacuum overnight. 1H NMR was demonstrated in Figure 4. Synthesis of polystyrene-b-poly(ε-caprolactone) (PS-b-PCL) Firstly

• rotary evaporator. After precipitation of the mixture to cold methanol, the polymer was collected by filtration and dried under vacuum overnight. Mn,GPC: 3510 g·mol−1, Mw/Mn: 1.10. Synthesis of cross-linked polymer Az-3 and Alk-5 was mixed in equal ratio (1 equiv) with CuIICl2 (0.05 equiv) and PMDETA

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• be a crucial discovery in the optimization process, since using methanol as a reaction solvent not only significantly simplified purification, but also increased the yield (Table 1, entry 4). Precipitation also occurred in acetonitrile, however, the yield was slightly lower (Table 1, entry 5). While