Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

The effect of dark states on the intersystem crossing and thermally activated delayed fluorescence of naphthalimide-phenothiazine dyads

• Liyuan Cao,
• Xi Liu,
• Xue Zhang,
• Jianzhang Zhao,
• Fabiao Yu and
• Yan Wan

Beilstein J. Org. Chem. 2023, 19, 1028–1046, doi:10.3762/bjoc.19.79

• , the fs-TA spectroscopy was not used to study their photophysical processes [47]. Femtosecond transient spectra of NI-PTZ-F-O were also studied (Figure 7c and 7d). The solubility of NI-PTZ-F-O in HEX is poor, which leads to a poor transient spectral signal (Figure S35c and S35d in Supporting

CO₂ complexation with cyclodextrins

• Cecilie Høgfeldt Jessen,
• Jesper Bendix,
• Theis Brock Nannestad,
• Heloisa Bordallo,
• Martin Jæger Pedersen,
• Christian Marcus Pedersen and
• Mikael Bols

Beilstein J. Org. Chem. 2023, 19, 1021–1027, doi:10.3762/bjoc.19.78

• solubility of this complex in water. X-ray crystallography of the crystals showed a 1:1 complex of CO2 to α-CD with CO2 bound in the center of the wide, secondary rim of the α-CD cavity (Figure 2). Two of the hydroxymethyl side groups on the primary narrow rim are disordered. The disordering was modeled over

• water under a partial pressure of CO2. Using a literature value of the solubility of CO2 in water at 1 bar (34 mM) and Henrys law the more traditional aqueous binding constant Ka = [CD·CO2]/[CD][CO2] in molar terms could be calculated (Table 2). For α-cyclodextrin (1) a Kg of 0.18 bar−1 was obtained – a

• temperature dependence on solubility in water [16]. Therefore, binding of the unipolar CO2 molecule is expected to cause less water H-bond disruption in this host. Conclusion This work shows that CO2 is bound 1:1 by α-cyclodextrins and that the affinity can be improved with a smaller cavity and more

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

• cleavage is probably influenced by glycan structure, solubility, and aggregation tendency [26]. Lastly, purification of the protected glycan upon cleavage could be affected by the presence or absence of a linker. L1 or L2 were conjugated to Merrifield resins with initial loadings of 0.5 mmol/g and 1.0 mmol

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• solubility in water. Among exceptional properties belongs to easy post-transformation of acylimidazoles to common carbonyl analogs. These tunable properties allow the use of acylimidazoles in chemical biology research, which includes chemical synthesis of proteins/peptides, structure analysis, and functional

• earlier experience, we employed the tropylium ion with the more lipophilic bis(trifluoromethane)sulfinimide (NTf2) anion because of its better solubility in the applied organic solvents than the commercially available tetrafluoroborate (BF4) form [22][23][24]. The cyclic urea DMEU (1,3-dimethyl-2

A fluorescent probe for detection of Hg²⁺ ions constructed by tetramethyl cucurbit[6]uril and 1,2-bis(4-pyridyl)ethene

• Xiaoqian Chen,
• Naqin Yang,
• Yue Ma,
• Xinan Yang and
• Peihua Ma

Beilstein J. Org. Chem. 2023, 19, 864–872, doi:10.3762/bjoc.19.63

• change in fluorescence intensity can be used for the recognition of Cd2+ and Zn2+ ions [35]. The symmetric tetramethyl cucurbit[6]uril (TMeQ[6]) is one of the earliest characterized modified cucurbit[6]urils [36]. Compared with Q[6], tetramethyl cucurbit[6]uril (TMeQ[6]) has good solubility in water

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• materials [1][2][3][4][5][6][7][8][9][10]. Due to its different characteristics such as basicity, stability, water solubility, small molecular size, and ability to form hydrogen bonds, pyridine continues to be a suitable moiety in organic synthesis. In addition, it has been observed that pyridine rings

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• made it difficult to confirm the solubility due to the deep black color of the reaction mixture. This can increase the risk of clogging under continuous-flow conditions due to undissolved catalyst. From this reaction screening, we concluded that Table 1, entry 3 was the most suitable catalytic system

• improved greatly with the O2 balloon, and the reaction was completed in 20 min. The proposed catalytic cycle for aerobic oxidation is shown in Scheme 1 [40][46][47]. At room temperature, the solubility of O2 in the reaction solution is relatively high, and the catalytic cycle A, which is associated with

• the solubility of O2, is not the rate-determining step. Therefore, the reaction rates under open air and O2 balloon did not differ. On the other hand, increasing the temperature decreased the solubility of O2, which converted the catalytic cycle A to the rate-determining step at 60 °C. When the

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• 24 hours at room temperature in DMF with catalytic amounts of HClO4. The yield of compound 4a in this case was 76%. Then new heterocyclic acids were used as reagents for the Ugi four-component reaction. Due to the rather low solubility of the acids in methanol, it was necessary to increase the

• -chlorobenzaldehyde (5b), 4-methoxyaniline (6a) and tert-butyl isocyanide (3a). It should be especially noted that the solubility of compound 8a is very low (soluble in DMSO and N-methyl-2-pyrrolidone (NMP), slightly soluble in methanol, 1- and 2-propanol, acetone, DMF and insoluble in water, ethanol, acetonitrile

• imidazo[1,2-a]pyridine and peptidomimetic fragments it is better to use acids with a linker between the carboxyl group and aryl ring. This molecular fragment increases the solubility of the whole molecule, which leads to an improvement in the reactivity of the acids, whereas the reactivity of acids 8a and

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• due to the solubility of the starting amine 11d and the corresponding products 12. In addition, in the reaction of APBTT 1a with mesidine (11b), we succeeded to isolate a side-product 14ab (Scheme 19). Similar side-products 14 were observed in all reactions of APBTTs 1 with arylamines 11 (UPLC–UV–MS

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene

• Nan Yang,
• Yi-Yan Zhu,
• Wei-Xiu Lin,
• Yi-Long Lu and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2023, 19, 635–645, doi:10.3762/bjoc.19.45

• solution was increased to 10.4, the nanoparticles collapsed and aggregated (Figure 3d–f), which could be attributed to the poor solubility of the samples bearing neutral amino groups of CS-TPE under alkaline conditions, leading to the accumulation of molecular chains. The pH-responsive behavior of CS-TPE

• solubility of CS-TPS-10% after combining with TBTQ-C6. Furthermore, the complex reassembled into spherical nanoparticles when the pH of the solution was restored to 5.3 (Figure 6c). These results are consistent with the transmittance measurements, and similar phenomena were observed for the TBTQ-C6/CS-TPE-2

• improved water solubility of the supra-amphiphile due to the highly water-soluble behavior of TBTQ-C6 under alkaline conditions in its carboxyl anion form. As a result, the polymer chains were extended, releasing the entanglement and wrapping of the TPE fluorogens, thereby reducing the emission of the

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

• . Unfortunately, with this catalyst, repeatability problems were detected (yield fluctuation of approximately 20%) which could be assigned to the low solubility of this catalyst in toluene. In order to overcome these problems, we synthesized triruthenium carbonyl complexes with phosphine ligand(s), namely

• (L1)3] (comp3) catalysts allowed to show, on the one hand, the absence of solubility problems, and to discover, on the other hand, that the presence of three L1 ligands (comp3) leads to a reaction rate clearly lower than that of a catalyst carrying one or two ligands (see p. S7 of Supporting

• compared to [Ru3(CO)12] at 200 °C (Table 1, entries 3 and 4). This can be attributed, as mentioned above, to the slightly faster reaction kinetics of the [Ru3(CO)12] catalyst compared to that of comp1. Nevertheless, the better solubility of comp1 in toluene allows to get around the problems of

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• complex. Solubility of the t-Bu-containing ligand and its Schiff base complexes is increased, facilitating scaling-up the reaction procedure and isolation of the functionalized amino acid. Keywords: asymmetric synthesis; chiral auxiliaries; cysteine derivatives; Ni–Schiff base complexes; voltammetry

• the modification of the chiral auxiliaries as well as of the other fragments of the tridentate ligand have been made to improve stereocontrolling efficiency and to modify physicochemical properties of the template (such as solubility, lipophilicity, etc). Thus, various substituents (4,5-di-CH3 [21], 2

• stereoselectivity level. Additionally, Schiff base derivatives of L7 have a considerably higher solubility in acetonitrile as compared to the L4-based complexes (see Table 3 and Supporting Information File 1); this makes it easier to scale-up the synthesis (e.g., for the SN2 alkylations or nucleophilic addition

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

• result of the reactions carried out, the dipeptide analogues of α- and β-fluorinated aminophosphonic acids 8 and 10 were obtained. All the samples were solids, with very poor solubility in water and organic solvents such as DMSO and MeOH. The final step of the synthesis was the reaction of the resulting

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• bond of 28 leads to compounds of increasing activity, being the more polar hydroxy-substituted derivatives the most active (Table 2) [73]. One of the major obstacles in the development of highly potent drugs is the water solubility. Pettit and co-workers [55] conducted an extensive study in an attempt

• to improve the water solubility of combretastatin D-2 (2) by converting it into a series of phosphate salts and other prodrugs. Thus, phosphorylation of combretastatin D-2 (2) using dibenzyl phosphite gave derivative 183. Further cleavage of the benzyl groups using TMSBr followed by the reaction of

• the obtained phosphoric acid derivative with a series of bases led to the formation of different phosphate salts 184–187 (Scheme 35) [55]. The authors observed that the prodrug salts had substantially improved solubility in water, an important feature for transport to metastatic cancer (Table 3) [75

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

• solubility and bioaccessibility of the hazelnut oil components and antioxidants can be increased, as well as the controlled release of bioactive compounds (fatty acid glycerides and antioxidant flavonoids, namely hesperidin, naringin, rutin, and silymarin). The appropriate method for obtaining the ternary

• , leading to high water solubility. On the other hand, the tetrahydropyran moieties of the Glcp units provide the hydrophobic property of the CD cavity [4]. As a consequence of their unique structure, CDs can encapsulate hydrophobic molecules or hydrophobic moieties of geometrically compatible bioactive

• compounds [5]. The resulting supramolecular inclusion complexes provide enhanced water solubility and bioavailability/bioaccessibility of the nanoencapsulated bioactive compounds, higher oxidative and thermal stability or photostability of labile compounds, and their controlled release [6][7]. Vegetable oil

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• -base analogues 41a,b were also obtained by the treatment with HCl in dioxane. The conjugation of carbohydrate with porphyrin improves the solubility of porphyrin in aqueous medium and also improves the optical and medicinal properties of porphyrins [30]. Considering these properties of glycoporphyrins

• porphyrin 174 and stirred at room temperature for 24 h, solubilization occurred, resulting in a homogeneous solution. This is due to the formation of a supramolecular assembly in which the hydrophobic adamantane arms of 176b are sequestered by the β-CD arms of porphyrin 174, resulting in water solubility

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• , the reaction of 4aa in DCE at 50 °C gave the product 5aa in 23% yield (Table 1, entries 1 and 2). A larger amount of TfOH turned out to increase the solubility of the product and therefore impeded the purification process. However, an excess of acid is required for the electrophilic aromatic

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

• complexation can lead to a significant solubility enhancement of poorly water-soluble molecules, and therefore it can enable the biological testing of drugs, which would otherwise not be possible by any other means [2][3]. Monosubstituted CDs contain only one hydroxy group modified with a functional group. In

• -toluenesulfonyl)-β-CD (Ts-β-CD, 2) There are three standard methods for the preparation of this general and functional CD derivative. Two of them take advantage of the lower aqueous solubility of β-CD (1) and Ts-β-CD (2) compared to α- and γ-CD analogs. The third method is mainly used for Ts-α-CD and Ts-γ-CD

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

• biomedical applications, in particular as an alternative to the hydrophilic poly(ethylene glycol) (PEG), which is the polymer of choice for many biomedical applications due to its high solubility, low cytotoxicity and biocompatibility [3][4][5][6][7][8][9]. However, an ongoing discussion about pre-existing

• /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

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• ). Accordingly, the internal double bond in 25a stayed unaffected whereas the triple bond, as expected, selectively formed the double bond with (E)-configuration. Note that a reaction temperature of 50 °C is required in the first step of the sequence to obtain rapid solubility of the Schwartz reagent in the

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• improve solubility and metabolic stability while retaining potency [5]. Late-stage functionalisation (LSF) is a strategy involving the use of C–H bonds as chemical handles for the introduction of various functional groups, which has been widely employed by medicinal chemists to generate new analogues of

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

• the reactivity of a thiophene-fused dihydropyridine as a cyclic imine. The tricyclic α-methylene-γ-lactam product 19k was obtained in 40% yield and as single diastereomer. It should be noted that due to the low solubility of the imine substrate in CH3CN, this reaction was carried out in CH2Cl2 at 23

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

• further by increasing the charge (Table 2, entry 5). For a final combination of the two reaction steps, benzyl acetate 3a was chosen as a model substrate due to its high solubility and good reactivity as was previously demonstrated by us (Table 3) [28]. We determined an optimal reaction time of 20 min for

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

• Alexios I. Vicatos Zakiena Hoossen Mino R. Caira Centre for Supramolecular Chemistry Research (CSCR), Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa 10.3762/bjoc.18.184 Abstract Overcoming the challenges of poor aqueous solubility of active pharmaceutical

• ingredients (APIs) is necessary to render them bioavailable. This study addresses the poor solubility of two potent steroid hormones, 17β-estradiol (BES) and progesterone (PRO), via their complexation with two water-soluble native cyclodextrins (CDs) namely β-CD and γ-CD. The hydrated inclusion complexes β

• 1H NMR spectroscopy. Subsequent measurements of the aqueous solubilities of the four complexes confirmed significant solubility improvements effected by encapsulation of the steroids within the CDs, yielding solubility enhancement factors for BES and PRO in the approximate range 5–20. Keywords