Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• . Meanwhile, some of the starting material 2l remained unreacted and we suspected the lower solubility of compound 2l in water was responsible for the low yield of the reaction. Since trifluoromethyl-substituted isoxazoles are an important and prevalent scaffold in biomedical research and drug discovery

• method. The results are collected in Table 2. First, we varied the proportion of methanol in the solvent mixture with water to increase the solubility of 4,4,4-trifluoro-1-phenyl-1,3-butanedione (2l). As the percentage of methanol in the solvent mixture increased from 5% to 50%, 75%, and 95%, with DIPEA

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water

• Zhihang Bai,
• Krishnasamy Velmurugan,
• Xueqi Tian,
• Minzan Zuo,
• Kaiya Wang and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45

• [31][32] and their detailed synthetic routes and characterization data are provided in Supporting Information File 1 (Figure S1). Since m-TPEWP5 and G have good solubility in water, therefore, the m-TPEWP5G and m-TPEWP5G-EsY supramolecular assemblies could be potentially fabricated in an aqueous

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• after Cs2CO3 convertion to CsBr (because of the very poor solubility of CsBr in DMF) has an influence on the rate of diphenoxyketone formation. In addition, the suppression of the di(nitrophenoxy)ketone formation can be due to the lower basicity of a reaction mixture since nitrophenols 2d,e are more

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• a quantitative yield. Still about reduction reactions, Niemczyk and Van Arnum described a green methodology for reduction of menadione (10), during the pegylation of 14 to improving the solubility of the studied compounds [118]. The authors reduced 10 with sodium dithionite under ultrasound

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• water solubility, and, on the other hand, these kinds of water-soluble moieties could also be introduced into the structures of other hosts to help them gain some extent of water solubility. In aqueous solution, the molecular containers provide hydrophobic pockets capable of binding a wide range of

• anthracene and phthalimide guests with unusual and controllable site-selectivity mediated by organopalladium-coordinated hosts in water (Figure 1) [34]. The water-solubility of the coordinated host traced from its ionic form, and the aqueous reaction conformed with the concept of green chemistry. In previous

• reported the cyclodextrin-mediated site-selective ring-opening reductive reaction of epoxide 16 by sodium borohydride in aqueous solution (Figure 4b) [58]. The sugar-based hosts show good water solubility and can be used for driving organic reactions in water. In this case, the cyclodextrin host and the

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• in a slight decrease in yield, and an increase in decomposition was observed with an increase in temperature despite the short residence times (entries 6 and 7, Table 2). The lack of solubility of the hydrazone substrates limited options with regards to variation in reaction solvent, with adequate

• solubility only being observed in DMF and DMSO. Despite the slightly lower yield observed using DMF (entry 8, Table 2), it provided the option of a co-solvent system in situations where solubility in DMSO is insufficient. A variety of acyl hydrazones were subsequently synthesised from the corresponding

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

• 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

• complex precipitation. For such purpose, EtOAc, pentane, CH3CN or Et2O have been used in this table depending on the solubility observed (see Supporting Information File 1 for details). Depending on the TCA–amine salt solubility in the solvent used, the purified primary amines could be isolated in 40–94

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• solubility. Additionally, providing sophisticated NMR spectra of 12 turned out to be a non-trivial issue. All commercially available deuterated solvents were tested as solvents and finally, recording the spectra in tetrachloroethane-d2 at elevated temperatures (100 °C) led to a clear solution and hence clean

• NMR spectra. The solubility issues forced us to investigate also other modification protocols. Thus, macrocycle 11 was subjected to an ozonolysis with subsequent Wittig reaction in a one-pot manner (Scheme 4). Performing the ozonolysis in presence of pyridine led to immediate reduction of the primary

• modifications, mainly for solubility reasons. Therefore, we decided to have a closer look into modifications of the longer side chain present in 11 and subjected it to thiol-ene click reactions. Since masked thiols are often found as zinc-coordinating functionalities in HDAC inhibitors, e.g., in the largazoles

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• not occur when starting compound 2p was tried. This was probably because of the very poor solubility of the starting material. Generally, the diastereoselectivities of the reactions were moderate (dr 2.1:1–3.6:1) throughout the scope. The diastereoselectivity was missing or was very low for the

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• enzyme active sites and/or improved selectivity [7]. One of the main drawbacks of paullones is their poor aqueous solubility. Therefore, in an attempt to overcome this shortcoming, the paullone backbone A was decorated with functional groups and coordinated to metal ions. Ruthenium(II), osmium(II), and

• copper(II) complexes prepared revealed an enhanced aqueous solubility and bioavailability indeed, along with very high cytotoxicity [8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Moreover, the metal-free ligands and copper(II) complexes derived from backbone D revealed cytotoxicity in the

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• , trihydroxy nucleoside 14b was protected with TBDPS to carry out the synthesis of the target nucleoside monomer 9b through a chemical pathway. However, the poor yield of this reaction compelled us to abandon the route as high solubility of the TBDPS-protected dihydroxy nucleoside in aqueous phase withstood

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• solubility to all substrates than toluene, the optimal reaction conditions were selected as: diazo ester 1a (0.36 mmol) and 2a (0.3 mmol) in DCE (1 mL) were heated at 130 °C for 20 min with microwave heating. With the optimal reaction conditions in hand, we evaluated the scopes and generalities of both diazo

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• solubility of this substrate. The absolute configuration of the chiral product 3ae was unambiguously identified on the basis of single-crystal X-ray diffraction analysis as (2S,3'S) (Figure 4) [33]. The configurations of the other products were assigned by analogy to 3ae. In order to further prove 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

• we made will behave similarly. In addition, PEGs are soluble in solvents such as water, toluene, DCM and many other solvents but not soluble in diethyl ether and hexanes. This solubility pattern is very different from most other organic compounds including the side products of the PEG elongation

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• ). Intramolecular cyclization of the salt forms 3a, which is extracted into the organic layer due to its low solubility in water. Because n-Bu4N+OH− is less-soluble in organic solvents than water, 3a is phase-separable from the base. To our delight, 2a was smoothly converted into 3a in 74% yield in this two-phase

• system, with the reaction time successfully reduced to 1 h (Table 2, entries 1–5). The use of a co-solvent to increase the solubility of 2a was investigated in detail; DMSO was found to be the most effective solvent, with 3a produced in 82% yield (Table 2, entries 5–12). We next optimized the base used

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• HQ[n]s with that of Q[n]s, Buschmann [26] observed that HQ[6] 2 (Scheme 1) formed complexes only with Ni2+, Co2+, and UO22+ with extremely low affinity, which may be caused by the poor solubility of HQ[6] 2 in aqueous solution and its universal “alternate” conformation. Most modified

• ions at submicromolar concentrations always by means of NMR spectroscopy [33]. Nevertheless, sensing by UV–vis or fluorescence spectra was hard to realize, for there is no chromophore in the frameworks. While hemicucurbit[n]urils with improvement in solubility, they still remain poor in derivatization

• % yield and 30.0% yield based on starting compounds 5 and 6, respectively (Scheme 2). With the trimers 7 and 8 in hand, the reaction conditions for the [3 + 3] macrocyclic condensation were examined. Due to the low solubility of compound 7, the subsequent reactions were conducted in DMF. With two

Host–guest interaction and properties of cucurbit[8]uril with chloramphenicol

• Lin Zhang,
• Jun Zheng,
• Guangyan Luo,
• Xiaoyue Li,
• Yunqian Zhang,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2021, 17, 2832–2839, doi:10.3762/bjoc.17.194

• in water and has a bitter taste. Upon forming an inclusion complex with cyclodextrin, the solubility and bitter taste of CPE can be improved [4][5]. Ramesh Gannimani et al. [6] reported that the inclusion complex of cyclodextrin and CPE loaded silver nanoparticles possessed stronger antibacterial

• cucurbit[n]urils can be used as non-toxic and safe drug carriers [29][30][31], among which cucurbit[8]uril (Q[8]) [32] has a large cavity. Q[8] interacts with a variety of small drug molecules such as chrysin, oroxin A and B, baicalein, etc., which can enhance the solubility, stability, antioxidant and

• , indicating the formation of a 1:1 host–guest inclusion complex. Due to the poor solubility of Q[8], an acid solution was selected as the medium to grow a crystal of the CPE@Q[8] host–guest inclusion complex. When the interaction between CPE and Q[8] was investigated using 1H NMR spectroscopy, a deuterated

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• properties and/or morphology. Often it can be characterised in terms of swelling, as the solubility of a polymer within a solvent, or solvation state, changes with temperature in thermally responsive cryogels. This leads to variation in cryogel volume, as at differing temperatures the nature of intra- and

• intermolecular hydrogen bonding changes, leading to variations on how hydrated the cryogel is, triggering a volume phase transition [34][35]. Changes in solubility can be described by the upper critical solution temperature (UCST) and lower critical solution temperatures (LCST). The UCST is the temperature at

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

• options for further functionalization. When 4-nitroaniline (4e) was used, the monoarylated product precipitated from the reaction mixture. Due to the very limited solubility of this intermediate, the latter was unable to react further. Changing the solvent to DMSO to try to tackle the solubility issue did

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• conditions, the chloro derivative 9b proved to be the most efficient catalyst – mediating the formation of product 10Aa in 62% ee after full conversion (Table 1, entries 12–15). Attention then turned to the 2-oxindole structure. Due to solubility issues chlorobenzene was chosen as the preferred solvent

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• original work that led to compound 3, and, additionally, they are able to act as acceptors and donors in hydrogen bonds and thus were expected to increase the aqueous solubility of the compounds. Additionally, Kalesh and co-workers demonstrated good results with derivative 4 which contains the amide group

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• by using [Pd(allyl)Cl]2 and JackiePhos as a ligand to obtain the polymer 30 in 52% yield. The deprotection of the N-Boc functionality led to the formation of poly[2,6-aminoazulene] 31 in excellent yields (Scheme 7C). The N-Boc-protected polymer 30 possessed good solubility in organic solvents and its

• , and 56 displayed good solubility in most of the commonly used organic solvents and GPC analysis revealed their number-average molecular weight (Mn) to be in the range of 25800 to 48600 Da with polydispersity in the range 1.29–1.9. They also exhibited excellent thermal stability as indicated by their

• )azulene (114) was required, and its synthesis was achieved from 2-bromofluorene (110) by following the protocol presented in Scheme 19B. The reaction of 114 with fluorene borates 102 and 104 under Suzuki conditions yielded polymers 115 and 116, respectively (Scheme 19C). The solubility of all polymers was

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• their physicochemical properties (e.g., solubility, viscosity) and can respond to stimuli in several ways by altering light transmitting abilities, shape, color, conductivity, as well as wettability [27][28]. Therefore, such functional polymers have a huge potential in numerous areas of application

• free polymer chains in solution is only conditionally applicable to constrained polymer topologies. The most commonly used stimulus to induce responsive behavior is the temperature [2][43][44][45]. The physicochemical basis for this is a temperature-dependent solubility of a polymer in one or a mixture

• of solvents. In solution, stimuli responsive polymers undergo a conformational, so-called coil-to-globule, transition. Depending on whether the solubility increases below (LCST for lower critical solution temperature [46][47][48][49]) or above (UCST for upper critical solution temperature [50][51][52

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• better understanding of cellulose’s properties are hindered by its poor solubility in most solvents. Relatively short oligomers with DPs of 6–10 tend to aggregate and precipitate out of solution [54], making isolation of pure samples troublesome. Much effort has been put to tune the synthetic conditions

• ), including the 6-deoxy [85], 13C-labelled [24], ʟ-Glc [86], and ethyl/methyl analogues [87][88][89]. Depending on the methyl/ethyl content, it was possible to tune the solubility of the polymer in water. 6-O-Methyl- and 6-O-ethyl-celluloses were poorly soluble in water, in contrast to heterogeneous polymers

• , fluorine, and carboxymethyl groups, prevented the formation of insoluble aggregates by disrupting hydrogen-bond networks. Dramatic differences in the conformation (e.g., radius of gyration and glycosidic bond conformation) and aggregation behaviour (i.e., crystallinity and solubility) were observed for

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• solubility of Cs2CO3 in toluene and 1,4-dioxane [24]. Using K2CO3 in MeCN, Longworth et al. have obtained 10 with a similar degree of N-1 regioselectivity (ratio N-1:N-2 = 2.8:1) [26]. However, altering solvent polarity when employing 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a base (Table 1, entries 15–17