A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions

• Vitor A. S. Almodovar and
• Augusto C. Tomé

Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169

• aromatic substitution; phenol; thiol; Introduction Diketopyrrolopyrroles (DPPs) are a class of organic pigments discovered by serendipity in the 1970s [1][2]. Generally, N-unsubstituted DPP derivatives exhibit high melting points, low solubility in most solvents, and strong absorption in the visible

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• - based Keggin-type polyoxometalate α-[SiW9O37{Ni(H2O)}3] into a Zn3Al-based layered double hydroxide (LDH) [18]. Polyoxometalates are known for their tunable acidic (Brønsted/Lewis) properties, but also for their high solubility in polar solvents, therefore intercalation into a layered double hydroxide

• limited to methanol due to solubility problems, and HClO4 was selected because other Brønsted acids caused amine deprotection. The GBB adducts 58 could be further elaborated through a Buchwald intramolecular nucleophilic substitution/cyclization, as it will be described in section 3.3. 3 Novel scaffolds

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• shown), where methanol further served as nucleophile. Some THF was needed to improve the solubility of some of the substrates. Acidic conditions (Table 1, entry 5) or methanol/water (Table 1, entry 6) gave a complex mixture with overoxidized products. Although the desired oxidation is a 4-electon

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• -iodanes have drawbacks, in particular low solubility and moisture sensitivity [11]. Hypervalent iodine compounds in a lower oxidation state (λ3-iodanes), such as iodosobenzene (PhIO)n or phenyliodine(III) diacetate (PIDA) have been reported in alcohol oxidations but they often result in overoxidation to

• was added, no significant shifts in the NMR spectral signals were detected, probably due to the poor solubility of the iodane. Conversely, with the addition of the red tetrazine salt 1c, a significant downfield shift was observed for the alpha-carbon protons from 3.51 ppm to 4.55 ppm, as illustrated

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• were investigated in aqueous medium. An aqueous solution of 5.0 wt % DA11 in Milli-Q water was prepared, followed by deprotonation with 1.0 equivalent of NaOH, showing excellent solubility up to 93 mM, giving a deep purple solution. An aqueous 43 µM solution DA11, diluted from the 5.0 wt % stock

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• attributed this to the increased solubility and concentration of NFSI in the AIBN conditions, which were performed at elevated temperatures, promoting facile trapping of a primary radical. In contrast, the decatungstate conditions, which operated at room temperature where NFSI is not completely dissolved and

• solubility issues of metal fluoride salts, safety issues with hydrogen fluoride, poor nucleophilicity [79], and side reactivity as a base [75][79], a few elegant examples of nucleophilic benzylic C(sp3)–H fluorination have been reported. Metal catalysis Fluoride sources have been used in combination with

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• is introduced on the azobenzene to increase the water solubility. The influence of ortho, meta, and para-substitution patterns of the azobenzene on the lectin binding has also been studied. Synthesis The β-O-galactosyl p,p'-bis-substituted azobenzene derivative 1 was prepared from galactose and

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• compounds by changing their metabolic stability, hydrogen bonding ability, lipophilicity, solubility, bioavailability, conformation and general structure [1][2][3][4]. About 20% of commercially available drugs contain fluorine, and this ratio is estimated to increase further [5][6]. Among organofluorines

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• reactions in water due to the remarkable lack of water solubility of the highly hydrophobic aminofurans selected in this study. Therefore, the decision was made to perform these reactions using vegetable oil as an alternative green solvent system. For this purpose, SSO, OO, OA and LM, which can act as

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• chromatographic purification due to much lower solubility of 4b compared to 4a. The metal complex of 4b with copper(II) was prepared, because copper(II) exhibited better extraction and separation abilities than cobalt(II) and palladium(II) in the case of Cu-tethered rectangular nanobrackets 1a [11]. Before SWNT

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells

• Yong-Chang Zhai,
• Shimon Oiwa,
• Shinobu Aoyagi,
• Shohei Ohno,
• Tsubasa Mikie,
• Jun-Zhuo Wang,
• Hirofumi Amada,
• Koki Yamanaka,
• Kazuhira Miwa,
• Naoyuki Imai,
• Takeshi Igarashi,
• Itaru Osaka and
• Yutaka Matsuo

Beilstein J. Org. Chem. 2024, 20, 1270–1277, doi:10.3762/bjoc.20.109

• derivatives with an emphasis on tuning solubility and energy levels. Meanwhile, less attention has been devoted to improving the thermal stability of fullerene derivatives. One well-known example is [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), which is recognized for its excellent solubility in solution

• results were not fully satisfactory. Considering the poor solubility of fullerene derivatives, toluene, carbon disulfide (CS2), and ortho-dichlorobenzene (o-DCB) were tested as solvent. Surprisingly, the conversion from ketone to thioketone did not occur as anticipated. In another attempt, where the

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• a 2-fluorophenyl group, the regioselectivity was different and product 26 was obtained (see Scheme 12). The yields were, in general, very good. The best yield (84%) was obtained for the reaction of 6-methyl-substituted 3-(2-nitrobenzoyl)chromone 13b, presumably due to a better solubility of the

• explained by a better solubility. For the other substituents of the chromone, no clear trend was observed. Product 29c underwent cleavage of the perfluoroalkyl group upon treatment with potassium hydroxide in methanol to give benzocoumarine 30. 1,3-Bis(silyloxy)-1,3-butadienes The reaction of 3

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• 2,6-bis-alkynylated quinolines 9 were obtained in good yields of 77–85%, except for 9c containing a cyano group (20%), most likely due to its low solubility. The yields are generally lower as compared to isomeric 2,8-bis-alkynylated products 6a–g, which might be due to a slightly lower reactivity of

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• better solubility in organic solvents than benzyl bromides, reducing precipitation issues. Applying now the first-ring-then-benzylic halogenation strategy to p-xylene, dibromide 3b was successfully converted into 3c, by means of the method herein developed for the benzylic bromination. The process was

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• equiv) of KOH in a 1:1 THF/H2O mixture to improve the solubility of the corresponding DCPQs (Scheme 4) at room temperature. A small amount of 1,4-dioxane (THF/H2O/1,4-dioxane 4:5:1) was also added to improve the solubility of 3a. The solution was rendered neutral by the addition of conc. HCl until

• recrystallization from boiling DMSO to obtain highly insoluble red-brown microcrystalline material. 1H and 13C NMR could not be recorded for the compound 3a given its extremely poor solubility in common organic solvents. Rf (CH2Cl2): 0.75, fluorescent orange spot; HRMS (DART): [M + NH4]+ calcd for C22H8N6, 374.1154

• , 47%). 1H NMR (500 MHz, CDCl3) δ 8.04–8.06 (t, J = 7.5 Hz, 2H), 8.40–8.42 (d, J = 8.5 Hz, 2H), 8.71–8.73 (d, J = 7 Hz, 2H); 13C NMR could not be obtained due to the poor solubility of the compound; HRMS (DART): [M + NH4]+ calcd for C18H6N6, 324.0997; found, 324.0978. 6,7-Diphenylpyrazino[2,3-b

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• , commercially available option. Initial conditions were based on previously reported work with similar structures [21][22]. We planned to perform the reaction using water as the solvent, but due to solubility challenges with the probe, this was not a viable option. After completing a solvent screen, it was

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• . Trimethylsilyl azide is considered as a safe replacement of metal azides. We started the solvent optimization with MeOH and H2O as solvent system at room temperature, however, it did not yield any product even after 3 days (Table 1, entry 1). The use of DMF to improve the solubility of the paraformaldehyde solid

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• candidates in development. Bioisosteres of para-benzenes, such as those based on bicyclo[1.1.1]pentane, are now very common and can be used to increase aqueous solubility and improve metabolic stability, among other benefits. Bioisosteres of ortho- and meta-benzenes were for a long time severely

• early drug discovery process. In many cases, the primary aim is the enhancement of biological activity, but in others, modulation of other critical properties such as aqueous solubility, metabolic stability, polarity, or lipophilicity is the target. In the latter cases, there is often a desire to retain

• fluorothalidomide [8]. Similarly, the reduction in the number of aromatic groups and increase in the level of saturation have risen to prominence as a way of improving low aqueous solubility, metabolic instability, or low lipophilicity in drug candidates that contain a high number of these functionalities [9][10

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• biomaterials since related in vitro bioassay systems require water solubility of the chemicals for testing. To overcome this important obstacle, over the past decades, a variety of water-soluble fullerenes have been reported [10]. General approaches towards enhancing the water solubility of fullerenes involve

• solubility [14][15]. As early examples of the latter approach in the 1990s, Wennerström and co-workers reported the study of supramolecular BiCAP complexation of C60 with γ-cyclodextrin (γ-CD) [16]. Shinkai and co-workers synthesized water-soluble calixarene derivatives to form water-soluble complexes with

• -soluble C60 and C70 derivatives by covalently attaching biocompatible water-soluble polymers, such as polyethylene glycol (PEG) [37][38] and PVP [39]. Although these C60– and C70–polymer conjugates revealed high water-solubility, it was found that they, especially the PEG conjugates, formed micelle-like

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• known to enhance the aqueous solubility and tumor selectivity of hydrophobic drugs through the enhanced permeability and retention effect [46]. It was also shown that porphyrin 6 undergoes reaction with taurine (2-aminoethanesulfonic acid, 25) which is an essential nutraceutical with diverse

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• that it was able to convert crocetin dialdehyde (8) into crocetin (1) in vitro [100]. BdALDH and CsALDH3I1 belong to the ALDH3 family, one of the most diverse groups of the ALDH superfamily. UGTs: Glycosylation of crocetin (1) improves the solubility significantly [101][102]. Moraga et al. cloned two

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• minimized diazide formation. Next, a solvent screening was performed as it can vastly influence reaction proceeding via a carbocation intermediate. Alkynyltrifluoroborates have a low solubility in chlorinated solvents but are well soluble in acetonitrile. Although this solvent has been used in similar

• solubility in DME, which might cause the low yield observed. Ynonetrifluoroborate 5d could not be introduced as nucleophile, probably due to its reduced reactivity caused by the electron-withdrawing acyl group. Unfortunately, although Molander previously reported the use of vinyl-trifluoroborate 11 to trap

• investigation of the photocatalyst solubility. n.o = not observed, PC = photocatalyst. aThe data were already published in the supporting information of ref. [45]. Selected scope entries of the azido-alkynylation. The data were already published in ref. [45]. Unsuccessful examples. The conditions used are the

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• thiazole moiety into a thiazoline unit had a measurable impact on several physicochemical parameters, such as LogP and water solubility. Whilst thiazolo[4,5-b]pyridine 5 afforded a moderate water solubility of 49 mg/L, paired with a LogP of 2.28 (pH 2.3), the corresponding 2,3-dihydro[1,3]thiazolo[4,5-b

• ]pyridine 7b had a higher water solubility of 173 mg/L and a lower LogP of 1.59 (pH 2.3). However, the lipophilicity of the new 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines was highly dependent on the substituents. For example, the brominated analogs 13b and 13c showed considerably higher LogP values of 2.88

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• concentrations of 1a, solutions became turbid as the substrate became less soluble, thus limiting the range of concentrations that could be used for relative rate plots. Switching to carbamate 1b alleviated the solubility problem, but the significantly slower reactions required switching to a more reactive

• and organic molecules [6]. Our results here are consistent, but the dynamics of mixed solvent systems are complex – water in DCM enhances rates, while water in MeOH nearly shuts them down. We presume these are consistent with the solubility effects proposed by Michon. In DCM, protic co-solvents were

• deviating from classic π-activation. Solvent effects that subtly impact solubility and proton transfer processes are likely to mask the impact of individual mechanistic steps involving gold and are not adequate to distinguish between the contrasting mechanisms under consideration here (Scheme 1 vs Scheme 2

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• effective base to facilitate the formation of 1a-enolate from 1a-enol and thus facilitate the initial monofluorination step by either fluorine or N-fluoroammonium ion 6. Carbonate ions are also expected to be highly basic in MeCN, however, their limited solubility is likely to inhibit their ability to act

• as an effective base for the formation of enolates of 1a and 2a, and this is reflected in the modest levels of formation of 3a (Scheme 4). Chloride ion, on the other hand, is less basic (pKa(MeCN) of HCl is 10.30 [60]), however, its greater solubility seemingly allows some level of deprotonation of