Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• only 10 mol % of DIPEA (92% 19F NMR yield, Scheme 5b). This reaction could result from base-assisted nucleophilic attack of adventitious water present in the reaction mixture. In addition to addition/elimination of fluoride ions to thioesters 3, a second potential mechanistic pathway exists for the

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• additional ligand was used in the next attempts. Additionally, it was observed that by replacing the less polar solvent by a mixture of a more polar solvent and water in a 5:1 ratio, yields could be significantly improved. Therefore, sodium hydroxide was used as the water-soluble base, which also proved to

• glacial acetic acid (60 mL) and after 5 min acetic anhydride (3 mL) was added. The reaction mixture was stirred for 10 min. Then, bromine (1 equiv; 23.4 mmol; 1.2 mL) was slowly added dropwise. After 1 hour, the reaction was stopped by adding water (25 mL) and cooling to 4 °C for 30 minutes. The

• was complete. The reaction was neutralized with an HCl solution (1 M) and diluted with water (40 mL). The phases were separated, and the aqueous layer was extracted with dichloromethane (3 × 30 mL). The combined organic layers were dried over Na2SO4, concentrated under reduced pressure, and purified

(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

• -oxabicyclo[2.1.1]hexanes To further increase the water solubility of 1,5-BCHs, Mykhailiuk and co-workers proposed 1,5-disubsituted-3-oxabicyclo[2.1.1]hexanes (3-oxa-1,5-BCHs) as isosteres for ortho-benzenes, introducing an oxygen atom into the hydrocarbon scaffold (Figure 10) [45]. Exit vector analysis

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• isotope labeling experiments [6], followed by a 2,7-cyclization, afforded C6 cationic intermediate IM-3 with cyclopiane skeleton. Quench of the cation IM-3 with water would give 4, while upon two 1,2-alkyl shifts of IM-3, followed by deprotonation of cation IM-4, would give spiroviolene (1). On the other

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• solvents including dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), toluene, acetic acid (AcOH) and water (Table 1, entries 9–13) were carried out. However, polar solvents such as AcOH and H2O were proved to be unsuitable for this reaction. For catalysts, we found that Cu(OAc)2 gave the best results

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• was attributed to a manganese peroxidase, however, the mechanism of degradation is unclear. Linear nitramines, produced by carbon capture, were shown to be biodegraded in soil and water [19]. Nitramines with hydroxy groups were best degraded in this study, including diethylnitramine, 2-methyl-2

• purchased from Fisher Scientific or VWR. Stock dithionite concentrations were determined by UV–vis absorbance at 318 nm (ε318 = 8000 M−1cm−1). Water used for all solutions was of 18.2 MΩ·cm resistivity from a Barnstead Nanopure (Thermo Fisher Scientific). Solvents for LC–MS experiments were of at least HPLC

• , 4.6 × 150 mm) and connected to an Agilent 6230 TOF mass spectrometer with electrospray ionization (ESI). Analyses used an isocratic mixture containing 65% water, 25% acetonitrile, and 10% isopropanol at a flow rate of 0.5 mL/min. The mass spectrometer was run in the negative ion mode with a probe

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• during chromatography, and so an alternate method was developed to generate a single product by promoting the formation of the hemiacetal series 12a–f. Following the rearrangement reaction, chromatography of the chlorides using silica with 2% water added led to the isolation of 12a,c–f in good yield

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• chloride metal halide complexes are −6 kJ mol−1 for SnCl4, −8 kJ mol−1 for BiCl3, −9 kJ mol−1 for ZnCl2, −15 kJ mol−1 for CdCl2, −16 kJ mol−1 for FeCl3, and −41 kJ mol−1 for AlCl3. d) Addition of chloride-containing salts (e.g., LiCl) accelerate the reaction. e) Traces of water can increase the rate of the

• potential safety hazards, especially in large-scale reactions [53]. Instead of acetyl chlorides, various other reagents, including pivaloyl chloride, oxalyl chloride, SOCl2, and TMSCl, can be employed to generate HCl. Numerous proton donors, such as water, alcohol, phenol, or acidic C–H groups, have been

• of water. Under slightly more forcing conditions (5 equivalents of TMSCl and 5 equivalents of water), even 1-hexene and cyclohexene reacted successfully at room temperature to afford the corresponding products 56 and 57. Interestingly, Δ9,10-octaline gave exclusively the trans-product 32. The

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

• Yue Ma Lorenzo Persi Yoko Yamakoshi Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland 10.3762/bjoc.20.71 Abstract With the aim of developing biocompatible and water-soluble C60 derivatives, three types of C60–peptide conjugates consisting

• successfully provide C60–peptide conjugates with one C60 and two peptide anchors as water-soluble moieties. Among three C60–peptide conjugates prepared, C60–oligo-Lys was soluble in water at neutral pH, and C60–oligo-Glu was soluble in buffer with a higher pH value, but C60–oligo-Arg was insoluble in water and

• most other solvents. C60–oligo-Lys and C60–oligo-Glu were characterized by 1H and 13C NMR. Photoinduced 1O2 generation was observed in the most soluble C60–oligo-Lys conjugate under visible light irradiation (527 nm) to show the potential of this highly water-soluble molecule in biological systems, for

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

• Chinese Medicine, No. 10 Poyang Lake Road, Tuanbo New Town, Jinghai District, Tianjin 301617, China 10.3762/bjoc.20.68 Abstract Crocins are water-soluble apocarotenoids isolated from the flowers of crocus and gardenia. They exhibit various pharmacological effects, including neuroprotection, anti

• are highly soluble in hot water but slightly soluble in anhydrous ethanol and ether. The presence of multiple conjugated double bonds in crocins makes them susceptible to degradation when exposed to certain conditions, such as high temperature, the presence of metal ions or light, certain pH values

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

• mixture was obtained due to the presence of the photocatalyst. Further investigation revealed that Ru(bpy)3Cl2·6H2O is not soluble in DME (Scheme 2B). In contrast, when it is in the presence of alkynyl-BF3K it readily dissolves. The addition of a couple of water drops to a suspension of photocatalyst in

• DME also allowed solubilization. The solubilization due to residual water coming from the alkynyl-BF3K was ruled out by careful drying of 5a. We postulated that an ion exchange between Ru(bpy)3Cl2 and 5a can occur to afford a more soluble photocatalyst with the general formula 9 (Scheme 2C

• . Having already modified most of the reaction parameters available we decided to explore the effect of different additives. In most reactions, 10 resulting from water addition was observed to some extent (4–8%), the presence of 4 Å molecular sieves effectively suppressed the formation of 10 (Table 7

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• transporters to form the siderophore Fe(III) complex extracellularly [2][3]. Subsequently, the stable and water soluble siderophore Fe(III) complex is transported across the cell membrane into the cytoplasm, where the iron is released from the complex by reduction, generating free Fe(II) ions that are

• University. To stimulate siderophore production, H002 was grown in modified minimal medium containing casamino acids and glucose as nitrogen and carbon sources, respectively, in the presence of HP-20 resin. Upon cultivation for one week, the non-polar resin was collected and washed thoroughly with water to

• , which was packed into a column for chromatography. The packed resin was washed with water several times and then eluted with an excess of methanol. The collected methanol fraction was concentrated in vacuo to obtain a crude extract. Subsequently, the crude extract was subjected to Sephadex LH-20 column

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• % conversion when 1 equivalent of sulfinate was used. Products 8 exhibited instability in the presence of water, leading to the formation of hydrolysis product 9 [25] in the reaction mixture. This instability caused issues during the reaction work-up, and attempts for purification using column chromatography

• % purity) [26] provided a more selective reaction, no water-based work-up was needed and the pure product was obtained by simple recrystallization from ethanol in yields up to 88%. The oxidation step thiol → sulfoxide was fast and full conversion to the intermediate was achieved in one hour for most

Organic electron transport materials

• Joseph Cameron and
• Peter J. Skabara

Beilstein J. Org. Chem. 2024, 20, 672–674, doi:10.3762/bjoc.20.60

• orthogonal processing. One of the biggest challenges with n-type materials is air stability. This is explained by the redox potentials of water (−0.66 V vs standard calomel electrode (SCE)) and oxygen (+0.024 V vs SCE, +0.57 V vs SCE) [2][3]. Therefore, it has been observed that once the overpotential

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• amine and the traces amount of water in this reaction system may serve as proton sources for the formation of hybrid α-ester alkylpalladium radical. On the basis of above mechanistic studies and previous reports [47][48][49][50][52][58], the following plausible mechanisms are proposed for the palladium

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• much greener as compared to methanol, it was chosen as the solvent to study the reaction scope. The use of water or solvent-free conditions resulted in much lower reaction yields (Table 1, entries 14–16). Next, the scope of the reaction was investigated with a range of 2-aminopyridines/2-aminothiazoles

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• onto macroporous resin for 4 hours or left overnight. It was then eluted with deionized water and ethanol through a chromatography column. The ethanol eluate was concentrated to dryness using a rotary evaporator. Subsequently, the ethanol extract underwent a triple extraction with EtOAc. The combined

• ). Subfraction Fr.J7 (17 mg) was then subjected to RP-HPLC with an acetonitrile–water gradient, resulting in the isolation of compounds 1 (1.36 mg) and 2 (0.36 mg). Similarly, the EtOAc extract (9.3 g) from the fermentation broth of XISR III medium was fractionated by column chromatography on silica with PE–EA

• and EA–MeOH gradients to yield 22 fractions (Fr.1–Fr.22) based on TLC analysis. Fraction Fr.12 (200 mg) was purified using a PE–EtOAc gradient to produce seven subfractions (Fr.a–Fr.g). Subfraction Fr.e (23.19 mg) was processed using RP-HPLC with an acetonitrile–water gradient, leading to the

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• . Reactions for thin-layer chromatography analysis were carried out using the same general reaction conditions reported above. Six μL of each reaction were spotted on the TLC silica gel 60 F254 (Sigma) and run with a solvent system containing butanol/ethanol/water 5:4:3. The TLC was stained using a solution

Possible bi-stable structures of pyrenebutanoic acid-linked protein molecules adsorbed on graphene: theoretical study

• Yasuhiro Oishi,
• Motoharu Kitatani and
• Koichi Kusakabe

Beilstein J. Org. Chem. 2024, 20, 570–577, doi:10.3762/bjoc.20.49

• ]. Actually, the presence of solutes consisting of water and proteins improves the stability of conformation 2. This stabilization is explained partly by the formation of hydrogen bonds between water molecules and PASE. Conformation 2 increases the number of sites where hydrogen bonds can form with water

• PBA-linked molecule is used, the relative energy of conformation II to that of conformation I can be better suited using our strategy. This stabilization is explained partly by the formation of hydrogen bonds between water molecules and PASE. As in the case of PASE, the chain portion of the PBA-linked

• molecule turns upward, increasing the number of sites that can form hydrogen bonds with water molecules in conformation II. Therefore, the formation of hydrogen bonds can stabilize conformation II relatively more strongly than conformation I. The hydration effect also improves the stability of conformation

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

• (13b): To a stirred mixture of 6-bromopyridin-2-amine (8, 10.00 g, 56.88 mmol, 1.00 equiv), 2-fluorophenylboronic acid (9.52 g, 65.98 mmol, 1.16 equiv), and Na2CO3 (12.06 g, 113.8 mmol, 2.00 equiv) in a mixture of 1,4-dioxane (80 mL) and water (80 mL) at room temperature was added Pd(dppf)Cl2 (1.67 g

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• chemistry; Introduction The terminology “molecular tweezers” was first introduced by Chen and Whitlock in 1978 through a seminal paper [1], wherein they presented a water-soluble molecular receptor composed of two caffeine recognition units linked by a semi-rigid diyne spacer. This ingenious design enabled

• attached functional arms. The formation of new hydrogen bonds between -OMe groups and protonated pyridine stabilizes a "W"-shaped open conformation. The conformation switch can be easily followed by NMR spectroscopy in solution. Remarkably, the water-soluble tweezers 1, when functionalized with hydrophobic

• bonding with the two protonated [9]aneN3 units and two water molecules coordinated to the zinc center. More recently, terpyridine was also used by Crassous and co-workers to create a chiroptic switch (Figure 10) [49]. They synthesized tweezers 18 bearing helicene moieties as functional groups. The two

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• [16]. KR21-0001A (1) is a new analog of 2,3-DHBA connected to N-acetylcysteine (Figure 2b). 1 has a stronger antioxidant activity than trolox, which is a water-soluble analog of the free radical scavenger α-tocopherol [17][18]. 1 shows no antimicrobial activity against bacteria and fungi. Conclusion

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

• dependence on MeOH. A similar acceleration in 1a hydroamination is seen when water additive is combined with DCM solvent, but unexpectedly, subtle differences were observed depending upon the identity of the catalyst (Table 3, Figure 3). Early experiments used JPhosAuOTf (synthesized in our lab) and water as

• co-solvent, but the conditions were modified to use readily accessible commercial [JPhosAu(NCCH3)]SbF6 (5) and MeOH, since water posed miscibility problems at higher concentrations. Titrating increasing amounts of water into reactions with JPhosAuOTf (4d) led to an increase in rate, similar to that

• seen with MeOH and catalyst 5, albeit smaller in magnitude (Table 3, entries 1–4 show the increasing rate with increasing water up to a 5.3-fold increase at 3.2 M water, while entries 5–8 show the increasing rate with increasing methanol up to a 14.6-fold increase at only 1.9 M methanol). In contrast

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

• -diketones occurs rapidly because the substrates lie predominantly in their enol tautomeric forms. The resulting 2-difluoro-1,3-diketones, on the other hand, are formed in their keto-tautomeric forms. Thus, we found difluorination could only be achieved upon addition of water or a base to accelerate the

• Supporting Information File 1). To isolate the main difluorinated product 3a, the reaction vessel was purged with nitrogen and the product mixture was partitioned between water and DCM to remove HF and salt by-products. Purification of 3a by column chromatography gave 3a as a white crystalline solid in 65

• extraction. Indeed, attempts to grow a single crystal of 5e from a mixture of EtOH and water led to the isolation of the corresponding gem-diol (Figure 3). There are very few examples of organic structures containing a C(OH)2–CF2–C fragment in the CCDC and only three acyclic examples (CSD 5.43 (Nov. 2021

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• was complex, we focused our attention on carrying out the reaction with KOH. The best result was obtained by treatment of 1 equivalent of butane 2 with 1.3 equivalents of KOH in the presence of 5 mol % of Bu4NBr as an interfacial carrier in water at room temperature for 2 h (Table 1, entry 7). After

• completion of the reaction the mixture of isomers 3a,b was separated from the water phase and distilled at 55 °C. Further increase in the amount of KOH led to the elimination of the second mole of HBr with the formation of hexafluorobut-2-yne (4). By controlling the course of the reaction by the 19F NMR

• showed a mixture of stereoisomers with a 2:1 ratio. The dehydrohalogenation reaction of 2-chloro-3-iodo-1,1,1,4,4,4-hexafluorobutane (5) was studied. Like the dehydrobromination of alkane 2, the reaction of compound 5 with 1.3 equivalents of KOH in water in the presence of 5 mol % of Bu4NBr was carried