Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• a reversible acidochromic behavior [30]. Zhao et al. demonstrated a three-component transition-metal-free aerobic method using a KI/DMSO/O2 system for the facile generation of iminobenzo-1,4-thiazines in moderate to good yield [31]. 3,4-Dihydro-2H-benzo-1,4-thiazine derivatives 6 were also

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• electrolysis of complex 3 can be protonated using acetic acid (pKa in DMSO = 12.3 [53]), in contrast to their counterparts formed from complex 4. In the latter case, a stronger protonating agent is required, e.g., PhNEt2·HCl (pKa in DMSO = 2.45 for PhN+HMe2 [53]). The pKa value of 6 determined in DMSO solution

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• , growth control (no inhibitor), SC, sterile control (no bacteria), DMSO, culture medium supplemented with 1% DMSO, reflecting the DMSO concentrations in the hangtaimycin-containing samples. Structures of hangtaimycin (1) and its co-metabolites. First synthetic route towards TDD (4). Second synthetic route

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• compounds 4a–c in DMSO-d6 showed peaks of aromatic protons in the chemical shift region of 6.97–7.59 ppm, a singlet at 6.00–6.06 ppm for the proton at the 5-position of the 3-pyrrroline-2-one moiety. In addition, along with peaks of carbons at the 2,5-positions of the N-containing heterocyclic ring and

• signals of the aromatic carbons, the 13C NMR spectra of these compounds in DMSO-d6 also exhibited broad peaks at around 30 ppm and 191 ppm. The NMR spectra of the 2-pyrrolidinone derivative 4c were also recorded in CDCl3 and its 1H NMR spectrum is similar to the one observed in DMSO-d6. However, the 13C

• 4a–c in DMSO [46], a hydrogen-bond accepting solvent (Scheme 3). To clarify further this statement, DFT calculations were performed at the B3LYP/6-311++G(2d,2p)//B3LYP/6-31+G(d,p) level of theory as given in Table 2 and Table 3. The theoretical results show that structure 4a is more stable than 4a

Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

• Wei-Hsin Hsu,
• Susanne Reischauer,
• Peter H. Seeberger,
• Bartholomäus Pieber and
• Dario Cambié

Beilstein J. Org. Chem. 2022, 18, 1123–1130, doi:10.3762/bjoc.18.115

• a narrower residence time distribution and higher yields (see Table 2). C–O coupling reaction Finally, we evaluated the use of the capillary-based reactor for the related C–O coupling of 4-iodobenzotrifluoride and N-(Boc)-proline with N-tert-butylisopropylamine (BIPA) in dimethyl sulfoxide (DMSO

• micro-batch reactors (SMBR), b) rotor-stator spinning disk reactors, c) slurry with pulsator, d) packed bed. Light-mediated carbon–heteroatom cross-couplings. The yields reported are the NMR yields obtained in flow with the optimized conditions described later. DMAc = dimethylacetamide, DMSO = dimethyl

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• reaction compound 2 was obtained in 40% yield (Table 1, entry 3). The use of DMSO instead of DMF resulted in <22% yield of 2 (Table 1, entry 4). However, when MeOH was used 2 could not be obtained at all (Table 1, entry 5). Reactions with Bu4NCl, Bu4NI, and Bu4NBF4 instead of Bu4NBr produced the

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• experiments Feeding experiments were performed in 500 mL flasks each containing 100 mL of ISP-2 liquid medium and 10 mg daidzein (4, as 1 mL DMSO solution added after autoclave) by 1% inoculation from the above seed culture. On the 5th day, 2 mL of medium from each sample was taken and freeze-dried. Then, 1

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• . Melting points were determined with a PMF-II MS Tecnopon melting point apparatus using open capillaries. 1H (300 or 500 MHz) and 13C (75 or 126 MHz) NMR spectra were recorded at 25 °C with a Bruker Avance III HD or Ascend 500 spectrometer, respectively. The samples were dissolved in CDCl3/TMS or DMSO-d6

• . Chemical shifts (δ) were recorded in ppm. 1H NMR spectra recorded in CDCl3/TMS were calibrated using the TMS peak, and those recorded in DMSO-d6 were calibrated using the DMSO-d5 peak. 13C NMR spectra recorded in CDCl3/TMS and DMSO-d6 were calibrated using the CDCl3 and DMSO-d6 peak, respectively. The

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• decided to use 1 F/mol and a lower amount of methanol at the anode, in order to minimize the formation of byproduct 3a; the same amount of 2a was obtained, but the yield of the trans diastereoisomer increased from 24% to 32% (Table 2, entry 2 vs entry 4). Finally, changing methanol with DMSO in the

Introducing a new 7-ring fused diindenone-dithieno[3,2-b:2',3'-d]thiophene unit as a promising component for organic semiconductor materials

• Valentin H. K. Fell,
• Joseph Cameron,
• Alexander L. Kanibolotsky,
• Eman J. Hussien and
• Peter J. Skabara

Beilstein J. Org. Chem. 2022, 18, 944–955, doi:10.3762/bjoc.18.94

• which oxalyl chloride was added at room temperature, and then reacted with aluminium trichloride at 0 °C. The resulting material was not soluble in cold dichloromethane/chloroform, but was found to be sufficiently soluble in hot chlorinated solvents. NMR spectroscopy in deuterated DMSO indicated that

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• {1,1} (0.08 g, 3%) and then compound 3{1,1} (1.86 g, 76%) both as white powders. 3-Methyl-5-phenylpyrazin-2-ol (3{1,1}): NMR data were identical with those observed for the substance obtained via aromatization of 3-methyl-6-phenylpiperazin-2-one [34]. 1H NMR (DMSO-d6) δ 12.28 (br s, 1H), 7.85 (m, 3H

• ), 7.40 (m, 2H), 7.28 (m, 1H), 2.37 (s, 3H); 13C NMR (DMSO-d6) δ 156.3, 155.8, 136.5, 131.3, 129.0, 127.6, 124.9, 122.2, 20.9. 3-Methyl-6-phenylpyrazin-2-ol (4{1,1}): HRMS (m/z): [M + H]+ calcd for C11H11N2O, 187.0866; found, 187.0864; 1H NMR (CD3COOD) δ 7.85 (s, 1H), 7.80–7.77 (m, 2H), 7.58–7.54 (m, 3H

• } (1.71 g, 66%) both as white powders. 3-Benzyl-5-phenylpyrazin-2-ol (3{1,2}): NMR data were identical with those reported [29]. 3-Benzyl-6-phenylpyrazin-2-ol (4{1,2}): HRMS (m/z): [M + H]+ calcd for C17H15N2O, 263.1178; found, 263.1179. 1H NMR (DMSO-d6) δ 12.27 (br s, 1H), 7.82 (m, 3H), 7.48 (m, 3H

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• % CO2. RAW264.7 cells (1.6 × 105/well) were seeded in a 24-well plate overnight for cell adherence. Cells were treated with LPS alone (100 ng/mL, dissolved in DMSO) or with compounds at the indicated concentrations for 24 h. Total RNA was harvested from cells using TRIzolTM reagent (Invitrogen, USA

• -stimulated RAW264.7 macrophages. Data were normalized by DMSO group and are presented as means ± standard errors of the mean (n = 3). ###p < 0.001 vs the control group; ***p < 0.001 vs the DMSO group. Proposed cyclization pathway of terpene intermediates and plausible post-modifications of compounds 1–7. 1H

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• phenylacetylene (3a) was used as a model reaction to determine a suitable base and an equivalent number of reagents (Table 1). The key intermediate 2a was prepared in situ from 1a (0.5 mmol) and Se powder (0.5 mmol) in the presence of 10 mol % of CuI and 1,10-phenanthroline at 130 °C in DMSO under aerobic

• . Experimental General procedure for the synthesis of alkynyl imidazopyridinyl selenides A solution of 2-phenylimidazo[1,2-a]pyridine (1a, 1.0 mmol), selenium powder (79 mg, 1.0 mmol, 1 equiv), CuI (14 mg, 0.1 mmol, 10 mol %) and 1,10-phenanthoroline (18 mg, 0.1 mmol, 10 mol %) in DMSO (3 mL) was heated at 130

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• ]. Conformational analysis and self-assembling properties The 1H NMR analysis of monomer 1 in various solvents including CDCl3, CD3CN, C6D6, CD3OD, D2O, and DMSO-d6 showed two sets of resonances in proportions varying from 75:25 to 90:10 (Table 3). These two sets of signals were characterized as the backbone cis

• and trans-amide rotamers using NOESY experiments (Figure 4 and Supporting Information File 1). Specifically, in DMSO-d6, the predominant rotamer of monomer 1 is characterized by a NOE cross-peak between the acetyl methyl group and side chain methyl group, indicative of a trans-amide bond geometry. A

• of trimer 3, tetramer 4, pentamer 5, and hexamer 6, we were able, for example, to establish that the majority rotamer is present at 70%, 84%, 80%, and 86%, respectively in DMSO-d6, based on the integration of the backbone methylene signals. Overall, DMSO seems to be the most structuring solvent for

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• To a suspension of compound 5 (0.274 g, 1 mmol) in dry DMSO (0.3 mL) the corresponding amine (2 mmol; in the case of 8 – the solution of dimethylamine in DMSO) was added. The reaction mixture was stirred at 50–70 °C for 0.5 h, then cooled to room temperature, and poured into ice water (10 mL). The

• resultant precipitate was collected by filtration, washed with water, dried, and recrystallized from hexane. 6-Methyluracil (10) Method A. To a suspension of compound 5 (0.274 g, 1 mmol) in DMSO (0.3 mL) H2O (0.036 g, 2 mmol) was added. The reaction mixture was stirred at 100 °C for 0.5 h, then cooled to

• Na2SO4, and evaporated under reduced pressure. The residue was purified by column chromatography. FDA-approved HDAC inhibitors with a hydroxamic acid moiety. The conformational and tautomeric forms of hydroxamic acids according to [36]. Fragment of the 1H NMR spectrum in DMSO-d6 of compound 12. Synthesis

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• of 22 diverse compounds. Briefly, the alkyne 3 was treated with formaldehyde, a secondary amine, and CuI as catalyst in DMSO (Scheme 3). The three components were stirred at room temperature for 3 h to furnish the desired compounds 4a–v in moderate to excellent yields [14][34]. By this route, diverse

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• -bonding, which would lead to catalytic quenching, a unique design strategy was applied. Instead of using a cis-blocked palladium(II) unit for self-assembly, Pd(NO3)2 was employed along with the triazole-based 0° clip 13. In a one-pot reaction, 12 and 13 in DMSO were treated with Pd(NO3)2 in a 1:1:1 ratio

A study of the photochemical behavior of terarylenes containing allomaltol and pyrazole fragments

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61

• in a solution of DMSO-d6. UV irradiation at a wavelength of 365 nm for 48 h in an NMR tube did not lead to any transformations of the starting pyrazole 16. Our attempts to carry out the photocyclization of pyrazole 16 in various solvents (DMF, acetonitrile, toluene, ethanol, methylene chloride

• ). The phototransformation of compound 12a was studied using NMR monitoring. UV irradiation was carried out at a wavelength of 365 nm in a solution of DMSO-d6 (Figure 1). It should be noted that after UV irradiation for 8 h of the studied sample the NMR spectrum contained signals of protons of the

• solvents excluding acetic acid, DMSO and DMF. Initially, UV irradiation of compound 12a was carried out at a wavelength of 365 nm in a solution of DMSO in common glassware for 24 h. However, subsequent water treatment did not allow the isolation of the target product 14a. Due to the fact that aqueous

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• was collected by suction filtration, washed, and dried to obtain compound 2 as a yellow solid (3.76 g, 73%). Mp 104.8–106.6 °C; 1H NMR (400 MHz, DMSO-d6, 25 °C) δ 8.18 (s, 6H), 7.36 (s, 6H), 5.36 (s, 12H), 5.21, 5.17 (ABq, J = 12.4 Hz, 12H), 4.21 (s, 3H), 4.15 (q, J = 7.1 Hz, 12H), 1.58 (s, 3H), 1.19

• (t, J = 7.1 Hz, 18H); 13C NMR (100 MHz, DMSO-d6, 25 °C) δ 167.20, 147.89, 143.15, 137.57, 126.07, 110.42, 62.61, 62.55, 62.15, 61.50, 50.38, 27.48, 13.93; (+)-ESI-HRMS (m/z): [M + H]+ calcd for C65H73N18O18, 1393.5345; found, 1393.5354 (Δ = +0.7 ppm). Synthesis of compound 3. To a methanol solution

• was collected by suction filtration, and washed sequentially with water, dichloromethane, and acetone to give compound 3 as a colorless solid (0.37 g, 85%). Mp 59.6–60.7 °C; 1H NMR (400 MHz, DMSO-d6, 25 °C) δ 8.19 (br s, 6H), 7.38 (br s, 6H), 5.26 (br s, 12H), 5.21 (br s, 12H), 4.23 (s, 3H), 1.60 (s

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

• spectrometer using CDCl3, methanol-d4, or DMSO-d6 as the solvent. Chemical shifts (δ) were recorded in parts per million and referenced to CDCl3 (7.24 ppm for 1H NMR and 77.23 ppm for 13C NMR), methanol-d4 (3.31 ppm for 1H NMR and 49.15 ppm for 13C NMR), or DMSO-d6 (2.50 ppm for 1H NMR and 39.52 ppm for 13C

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

• triple bond is a minor direction for the reaction of bromopropargylic alcohols and phenol in the presence of Cs2CO3/DMF, which was completely suppressed by addition of water. When DMF was replaced by DMSO (Table 1, entry 13), the preparative yield of reaction products decreased possibly due to product

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

• -naphthoquinone (18) were obtained in 80% yield with a 75:25 ratio, respectively (Scheme 2, method A). In the methylation reaction using methyl radicals generated by the redox decomposition of H2O2 in DMSO solution, compounds 10 and 18 were obtained in an overall yield of 80–90% with a 77:23 ratio, respectively

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• dilution of compounds 1–6 dissolved in DMSO) were added to every well. EDTA was used as a reference and dissolved in water. The microtiter plate was gently shaken for 4 h at room temperature. After this incubation period the remaining CAS–Fe3+ complex in each well was quantified by measuring the absorbance

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

• . DMSO was introduced as a co-solvent to promote the SN2-type reaction, and the dibromide 49 was smoothly hydrolyzed site-selectively to the monohydroxy product 50, which was fixed in an unsymmetrical manner in the cavitand. The bromide terminal was hence protected deep within the cavity of the cavitand

• host E from further hydrolysis, despite the addition of 10 equivalents DMSO after 2 days or even after one month. The experiment without the cavitand host produced a mixture of different products, and the dibromide was fully converted to the dihydroxy product after prolonging the reaction time or

• increasing DMSO concentration, without the detection of any monohydrolyzed product. This work further demonstrated the striking ability of the water-soluble cavitand to mediate site-selective reactions. Conclusion To summarize, we have reviewed various site-selective reactions mediated by molecular

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• (Scheme 25) [38]. The coupling products by reaction of phenylacetylene and various aryl halides were obtained in moderate to good yields in the presence of this green catalyst with 4 equivalents of KOH as the base in DMSO at 140 °C. Without any decrease in the catalytic activity, the catalyst could be