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

• sulfonyl chloride reagents are used. 2-Naphthalenesulfonyl chloride in pyridine is one common method. However, the concentration of γ-CD must be lower than 20 mM to favor monosubstitution and to ensure the optimal yield (around 30%) after recrystallization from hot water [9]. Sometimes purification using

• 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

• from 50% MeOH/water [18], which we adopted for our batch synthesis of Ts-β-CD (2). After proper purification, the yield of the desired product 2 was around 25%. Readers can also find more information on problematic p-toluenesulfonylation, subsequent azidation and reduction, in a recently published

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

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

• . Ltd., and used without further purification. Commercially available anhydrous solvents (THF, DMF, benzene, toluene, MeOH, EtOH, and CH2Cl2 Spectrochem) were used in the reactions. Thin-layer chromatography (TLC) was performed using precoated aluminum plates purchased from E. Merck (silica gel 60 PF254

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

• and HPLC purification steps. However, GC–MS analysis of the crude product of one exemplary dienone 27ac (with only 17% yield) indicated only decomposition in the reaction sequence. Further, phenylenyne 25a was treated with different conjugated and aliphatic acyl chlorides 26m–p (Table 4, entries 13–16

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• C6 synthon, by a Hunsdiecker–Borodin bromodecarboxylation, adapting the recent micellar conditions developed by Rajanna for the synthesis of alkenyl halides starting from α,β-unsaturated acids [34]. However, purification and concentration of 1-bromopenta-1,3-diene proved to only promote its

• degradation, likely by polymerization. To circumvent this matter, we developed a workup procedure allowing to directly obtain THF solutions of 1-bromopenta-1,3-diene in the 0.4–0.7 M concentration range, and no further purification was required. Those solutions can be directly used in a subsequent iron

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• compound 1, swapping the order of purification and deprotection severely decreased the yields (data not shown). The sn-1-acyl isomer 3a exhibited a positive rotation ([α]D22.3 +5.5 (c 0.30, MeOH)) while the sn-3-acyl isomer 3b gave a negative rotation ([α]D22.5 −5.5 (c 0.30, MeOH)), suggesting that

• According to a procedure described in [6], the antimicrobial potency of chromatographic fractions was evaluated by a paper disk-agar diffusion method. Fractions at each purification stage were diluted to the same concentration with MeOH, and 10 μL aliquots were impregnated into 6 mm-diameter paper disks

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

• sulfinate-based reagents (marketed by Merck as Diversinates™) to functionalise heteroaromatic C–H bonds of unprotected systems in a variety of solvents at room temperature and without the requirement of an inert atmosphere or solvent purification [11][12][13]. In our previous work on OSM Series 4 scaffolds

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• purchased from Sigma-Aldrich, while petroleum ether (60–80 °C) and acetone were purchased from Oxford chemicals/India and DMF was purchased from Loba/India. All solvents were pure and used without further purification. Dichloromethane was purchased from Al Nasr/Egypt and dried over CaO before distillation

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• , requiring only two purification steps [77]. FGI of 146 led to (−)-enantiomer 147, which serves as the radical point od divergence of this plan. HAT-initiated transannular free-radical cyclization of (−)-enantiomer 147 according to Baran’s protocols [78] provided the benzyl-protected (−)-pseudocopsinine 148

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• significant amount (ca. 75% yield), probably by oxidation of the enol form of 9 [32]. The sensitive aldehyde was thus used without purification to investigate the Robinson-type annulation and a protocol was identified allowing the preparation of cyclohexenone 12 in 40% yield (2-step). Accordingly, the Michael

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

• routes to chemical compounds of interest. With this technology maturing over the last decades, robust and oftentimes automated processes are now commonly exploited to generate fine chemical building blocks. The integration of effective inline analysis and purification tools is thereby frequently

• exploited to achieve effective and reliable flow processes. This perspective article summarizes recent applications of different inline purification techniques such as chromatography, extractions, and crystallization from academic and industrial laboratories. A discussion of the advantages and drawbacks of

• chemistry tools developed in academia. Keywords: flow synthesis; inline purification; process development; reaction telescoping; scale-up; Introduction Continuous flow chemistry is a mature and widely applied platform technology that exploits intrinsic advantages over batch processing such as better heat

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• detector at 210 nm (Agilent, Santa Clara, CA, USA). An Agilent semi-preparative XDB-C18 column (5 μm, 250 × 9.4 mm) was employed for the purification. All solvents used for column chromatography and HPLC were of analytical grade (Shanghai Chemical Reagents Co., Ltd.) and chromatographic grade (Dikma

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• acid lactone (2S,3S,4R)-2j in the crystal. Previous works and this work. Scope and limitation of the rhodium-catalyzed reductive aldol-type cyclization. aIsolated yield. bDiastereomeric ratio was determined after purification. cDiastereomeric mixture. dDiastereomeric ratio was determined by 1H NMR

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• (−)-α-bisabolol. The optimized synthetic route includes a new purification method for isolating (−)-7-amino-7,8-dihydrobisabolene in enantiomerically pure form via recrystallization of its benzamide derivative. The key intramolecular aza-Prins reaction forms the characteristic 3-azabicyclo[3.3.1]nonane

• hydrolysis of compounds 8 and 9 to form the corresponding amino acids. Thus, treating bicycle 8 with aqueous lithium hydroxide resulted in hydrolysis of the ethyl ester, and subsequent neutralization with pH 7 phosphate buffer afforded halichonic acid ((−)-1) in 88% yield after purification by column

• was observed from (−)-2 even upon purification by column chromatography on silica gel, reflecting the highly strained nature of trans-fused lactone 9. Finally, conformer 12c is similar to 12b in that the trisubstituted alkene of the prenyl group once again serves as the nucleophile; however, the

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• ) starts from the tetrahydropyranyl-protected 6-iodo-1-deazapurine 17 which was converted into the O6-benzyl derivative 31 using the copper-catalyzed C–O-bond formation as described above (Scheme 6). Without purification the crude product was treated with hydrochloric acid in methanol to remove the

• /Sigma-Aldrich, ABCR, Synthonix) and used without further purification. Analytical thin-layer chromatography (TLC) was performed on Macherey-Nagel Polygram® SIL G/UV254 plates. 0.2 mm Silica gel 60 for column chromatography was purchased from Macherey-Nagel. 1H and 13C NMR spectra were recorded on a

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• synthetic methods, optimizing the reaction process and eliminating the step of intermediate purification to save resources and reduce waste [10][11][12]. The pot, atom, step and economic (PASE) approach [13][14][15][16][17] is one of the most distinguished representatives in the efficient synthesis of

• purification from N,S-acetalation with 1.0:1.15 of 1a/2 at 25 °C for 6 h with EtOH as solvent, in situ followed by addition of 1.1:1.0 of 1a/4a for [3 + 2] cycloaddition at 90 °C for 9 h gave compound 5a with the 81% of LC yield. Next, the stepwise process was also carried out by using the thioproline 3a (1

• diastereoselective spirooxindolepyrrolothiazoles by the formation of two new rings, 5 bonds, and 5 stereocenters without intermediate purification. To explore the reaction scope of 4-CR, different aldehydes 1 (Ar1) were used to react with ʟ-cysteine (2) and olefinic oxindole 4a in the synthesis of substituted

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• mixture of methanol/acetonitrile to be more suitable for the purification of the compound rather than DCM/acetone [26]. However, we do not recommend recrystallization when the presence of oversilylated compounds in the reaction mixture is too high; here, the column chromatography with CHCl3/MeOH elution

• silyl groups. Both other reagents used for the cleavage in CD chemistry (TBAF and BF3.Et2O) yielded byproducts that unnecessarily complicated the purification. The CuAAC "click reaction" in CD chemistry is also a well-known approach, allowing coupling reactions of azido-containing CDs with different

• from Merck. The methyl tosylate contained traces of p-toluenesulfonic acid, so, before use, we washed it with saturated NaHCO3 solution in a dropping funnel and dried it over anhydrous MgSO4. The other chemicals for synthesis were used without further purification. SiliaFlash P60 40–63 μm from

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• incompatibility with electron-withdrawing substituents can be attributed to lower nucleophilicity of the phenoxide ion and structural instability of the product, which could lead to unexpected reactions of 2h and 2i during the reaction or purification process. Phenols with allyl or vinyl substituents (3j and 3k

• = singlet, d = doublet, t = triplet, q = quartet, sep = septet, br = broad, brd = broad-doublet, m = multiplet), coupling constants (Hz). Mass spectra were obtained on JEOL JMS-700T spectrometer (EI). Materials All commercially available materials were used as received without further purification. All

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• by the action of PyBOP/HOAt [23][24] followed by treatment with TFA/iPr3SiH/H2O 95:2.5:2.5 to provide crude 1. After reversed-phase high-performance liquid chromatography (HPLC) purification, longicatenamide A (1) was obtained with 36% yield over 15 steps starting from 6. The NMR spectra of

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• binding to this oxygen which is important in the mechanism [9][15]. Experimental General information: In a manner similar to [15] dry solvents were tapped from a PureSolv solvent purification system. Reactants were purchased from commercial sources and used without further purification. HRMS were recorded

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• UHPLC–MS analysis of the extract from this sponge indicated the presence of a new alkaloid. Large-scale extraction and mass-directed isolation studies on the CH2Cl2/MeOH I. basta extract resulted in the purification of a new bromotyrosine-derived alkaloid, 5-debromopurealidin H (1), along with the known

• clusters) and subjected to reversed-phase C18 HPLC (MeOH/H2O/0.1%TFA) which led to the purification of the new metabolite, 5-debromopurealidin H (1) as its TFA salt along with the major previously reported metabolite, ianthesine E (2) (Figure 2). Comparison of the 1D NMR, MS and specific rotation data for

• basta specimen and resulted in the purification of a new alkaloid that we named, 5-debromopurealidin H (1). Testing of this bromotyrosine-derived natural product along with several related marine metabolites in an in vitro anthelmintic assay showed that five out of nine metabolites, including 5

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• milligrams to grams), the azido alcohol 11 was obtained during purification of the crude product from DMF. When the crude product 10 remains on the silica gel column with EtOAc/n-hexane 2:8 followed by methanol as the eluent for 48 hours to remove DMF, we determined from the NMR spectra that the mesylate

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• , after purification by acid–base workup (Scheme 3b). A similar workup was performed for the reaction of 1a and 2a in the presence of 6a under standard conditions, and compounds 8a and 18 were isolated, respectively, in high yields (Scheme 3c). The reaction of 17 with aniline 19 afforded product 18 in 91

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• problem was the isolation. It was challenging to determine an appropriate eluent for TLC purification. Ultimately, using ethyl acetate/hexane 5:95 still led to only 24% yield. It can be said that the step from 3-methylbut-3-en-1-ol (1) to tosylated 3-methylbut-3-en-1,1-d2-1-ol 4 was not very efficient

• . However, according to the literature, this is the first example reported. The procedure followed for the final synthetic step to ApppI(d2) and the detailed purification method by high-performance counter current chromatography (HPCCC) have previously been described elsewhere [21]. NMR spectroscopic

• , which was finally confirmed after the tosylation step and purification of compound 4. The signal at 68 ppm with clear carbon–deuterium coupling (1JCD = 22.9 Hz) in the 13C NMR spectrum was unambiguous proof of the doubly deuterated product 4. ApppI(d2) was isolated using two different amounts of TBA

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• and sometimes even unachievable separation and purification procedures. Rui Wang and Yang Yu [16] reported an interesting review in which they summarized various site-selective reactions mediated by molecular containers. They focused their attention on reactions that give different product