Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• -BuOK as the base in triglyme, and the desired trifluoromethyl ketone 2a was obtained in 29% yield (Table 1, entry 1). We next carried out the reaction in other solvents, THF (2a, 5%, Table 1, entry 2) and toluene (2a, 0%, Table 1, entry 3), and confirmed the advantage of the triglyme that was used

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• DMF (0.5 mL) was added and the reaction mixture was stirred for 15 min at rt, controlled by HPLC. Then toluene or ethyl acetate (25 mL) was added to the mixture and it was extracted with 5% LiCl solution (3 × 5 mL). The organic phase was dried over anhydrous Na2SO4, filtered and evaporated. Silica gel

• (toluene/MeCN; gradient 50% → 75%) gave product 5a as a slightly yellow amorphous solid, Rf = 0.17 (toluene/MeCN 1:1). Yield 103 mg, 87%. HPLC: tR = 6.33 min, purity 98%; IR (KBr) ν (cm−1): 3400, 2955, 2925, 2855, 2205, 2170, 1590, 1460, 1430, 1410, 1350, 1235, 1040; 1H NMR (300 MHz, CD3OD + D2O) δ 9.05 (s

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• times. The combined extracts were washed with brine and dried over Na2SO4. After removal of the solvent under reduced pressure, the residue was purified by silica gel column chromatography (toluene/EtOAc = 40:1) to give 4b (409 mg, 45%) as a white solid. 1H NMR (500 MHz, CDCl3) δ 2.36 (dd, J = 14.0, 6.1

• described above using 1,8-diiodonaphthalene (2b, 4.35 g, 11.4 mmol), boronate ester 3 (7.31 g, 25.2 mmol), Pd2(dba)3·CHCl3 (301 mg, 0.29 mmol), SPhos (239 mg, 0.58 mmol), K3PO4 (14.6 g, 68.7 mmol), DMF (38 mL), and H2O (19 mL) at 90 °C for 17 h. Purification by silica gel column chromatography (toluene

Mesoionic tetrazolium-5-aminides: Synthesis, molecular and crystal structures, UV–vis spectra, and DFT calculations

• Vladislav A. Budevich,
• Sergei V. Voitekhovich,
• Alexander V. Zuraev,
• Vadim E. Matulis,
• Vitaly E. Matulis,
• Alexander S. Lyakhov,
• Ludmila S. Ivashkevich and
• Oleg A. Ivashkevich

Beilstein J. Org. Chem. 2021, 17, 385–395, doi:10.3762/bjoc.17.34

• various organic solvents, such as alcohols, chloroform, dichloromethane, hexane, acetonitrile, toluene, and THF. They are also soluble in water. Remarkably, the solutions in organic solutions are yellow colored, whereas aqueous solutions are colorless. The UV–vis spectra of 8a were found to show

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• ) as the azide donor to facilitate the generation and immediate use of the intermediate acyl azide that would rearrange to an isocyanate upon heating. Toluene was chosen as a suitable solvent providing good solubility of the acid substrates (1 M) in the presence of triethylamine (1.0 equiv

• utilized as it is frequently used for esterification reactions [26][27][28]. CALB could convert benzyl alcohol in the presence of vinyl butyrate into benzyl butyrate and acetaldehyde. To demonstrate the feasibility, the flow process was adapted by mixing a stream of vinyl butyrate (4, 3 equiv in toluene

•  3. The telescoped approach provided the quantitative conversion of benzyl alcohol into benzyl butyrate which could be removed by crystallization (from heptanes) after evaporation of toluene and residual vinyl butyrate. The resulting telescoped flow approach thus enabled the facile generation and

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• tetralin derivatives 144a and 144b, respectively (Scheme 36). In addition, 144a could be further converted into 146 in the presence of aromatic nucleophiles (e.g., benzene or toluene). Similarly, derivatives 147a–c could also be converted into indanol derivatives 148a–c in high yields (Scheme 36) [95]. Ma

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• = 270.1892, suggesting that in methanol-d4 the reported [22] spectrum is not that of legonmycin A itself but that of the C(7a)-OCD3 derivative (21, Scheme 3; m/z calcd for C14H20D3N2O [M + H]+, 270.1892). A sample of the corresponding OCH3 derivative 22, containing a small amount of residual toluene from the

• , delivering the natural product in 56% yield (corrected for the presence of ≈10 wt % toluene) on a ≈2.0 mmol scale. The repetition of the process, using isocaproyl chloride instead of isovaleryl chloride, afforded legonmycin B in moderate yield from ≈0.5 mmol of intermediate 17. In a larger-scale reaction

• water bath, and stirring continued for 3.5 h. The mixture was concentrated, with azeotropic removal of ethanol and other volatiles with toluene, to afford the title compound as a caramel-colored solid (561 mg) that was used directly in the subsequent acylation and oxidation steps [the NMR spectra

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• generated from trifluoromethyl iodide (CF3I) and Zn dust (or ZnEt2) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) [65] and later isolated [66]. The reaction of Zn(CF3)2(DMPU)2 (2 equiv) with styrenes proceeded efficiently in toluene to provide the difluorocyclopropanes 56 in 53–93% yields

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• 10.3762/bjoc.17.24 Abstract We described herein a selective method to prepare α-organylthio esters and α-organylthio ketones by the reaction of β-keto esters with sodium S-benzyl sulfurothioate or sodium S-alkyl sulfurothioate (Bunte salts) under basic conditions in toluene as the solvent at 100 °C. When

• starting materials to establish the best reaction conditions under an air atmosphere (Table 1). In our preliminary experiment, a mixture of 1a (1.0 mmol) and 2a (0.5 mmol), using NaOH (2 equiv) as a base in toluene (3.0 mL), was stirred at 100 °C for 18 h. Under these reaction conditions, the products

• protic solvents gave a lower yield when compared to nonpolar and aprotic ones. Keeping toluene as the best solvent, we turned our attention to the amount of 1a and 2a (Table 1, entries 20 and 21). When the mixture of 1a (0.5 mmol) and 2a (1.0 mmol) reacted in the presence of NaOH (4 equiv), the product

Exploring the possibility of using fluorine-involved non-conjugated electron-withdrawing groups for thermally activated delayed fluorescence emitters by TD-DFT calculation

• Dongyang Chen and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 210–223, doi:10.3762/bjoc.17.21

• results showed that when the carbazoles were both located ortho to the cyano acceptor the molecule (2,6-2CzBN) possessed a highly twisted structure and a corresponding small ΔEST (0.27 eV in toluene). The ΔESTs increased to 0.41 (2,4-2CzBN) and 0.40 eV (3,5-2CzBN) in toluene when at least one of the

• energy gap (≈0.24 eV) between T2 and T1 [24]. In an analogous manner, 5CzTRZ showed very fast krISC of ≈1.5 × 107 s−1 in toluene, and the device based on 5CzTRZ exhibited superior EQEmax = 29% with λEL = 486 nm and very low efficiency roll-off with the EQE at 5,000 cd·m−2 remaining high at 27% [24

• ]. Huang et al. also adopted a multiple donor strategy in concert with the weak trifluoromethyl (CF3) acceptor group in their TADF emitter design. The blue-emitting TADF emitter 5CzCF3 possessed a miniscule measured ΔEST of 0.02 eV and ΦPL of 43% in oxygen-free toluene [25]. The solution-processed device

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• flow procedures involved acetonitrile, dichloromethane and acetone as solvents, however, incompatible with the utilization of reactive alkali organometals. An exception is made for toluene, used by Kirschning for the photoinduced azirine formation [27]. Therefore, we investigated the thermally induced

• cyclisation of 1-(1-azidovinyl)-4-methylbenzene (1a) in refluxing 2-MeTHF and cyclopentyl methyl ether (CPME) as green solvent candidates, and compared the results with the reaction conducted in toluene (Table 1). The reaction proceeded rapidly in CPME, while the use of 2-MeTHF resulted in longer reaction

• times if compared with toluene. We therefore selected CPME as the most suitable solvent for our purposes. Interestingly, besides being characterized by low toxicity, CPME has a very low affinity to water, making it suitable for moisture sensitive reactions, without previous distillation [31][32][33

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• toluene, MeCN, and DCM, and in the presence of 1–20 equiv of P(OEt)3, the formation of the desired phosphonates 4 was not observed (Scheme 6). We started an optimization of the reaction conditions using substrate 6d, and reactions in neat phosphite at various temperatures were tried (Table 2). The

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• D0 were obtained via extrapolation to zero scattering vector square and via Stokes–Einstein relation the hydrodynamic radii RH resulted. With the same setup static light scattering was measured. In static light scattering, the average sample, solvent (water), and standard (toluene) scattering

Supramolecular polymers with reversed viscosity/temperature profile for application in motor oils

• Jan-Erik Ostwaldt,
• Christoph Hirschhäuser,
• Stefan K. Maier,
• Carsten Schmuck and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2021, 17, 105–114, doi:10.3762/bjoc.17.11

• chloroform, toluene or motor oils. Yet, we were able to investigate the behavior of the ACP derivative 2 in chloroform and toluene (see Figure 5). For both solvents, screening for the optimum concentration range was repeated (see Supporting Information File 1, chapter 6.2). In both chloroform and toluene

• solution, an RVT effect occurred at a concentration of 60 mM, as found in DMSO. However, the RVT effect is significantly more pronounced in less polar solvents (Figure 5). Over the whole temperature range in chloroform (25–50 °C), we observed an increase of the specific viscosity. In toluene, a broader

• Figure 6 for compound 2 in toluene, see Supporting Information File 1, chapter 7 for compound 1 and other solvents). Here, an effect of the temperature on the hydrodynamic radius can be observed. We find two different peak areas, one with sizes of 10–40 nm and one with 100–700 nm. At 25 °C, the peak area

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• acid in toluene. After 5 minutes, 1.2 equiv of tributyltin fluoride was added to intermediate A, and at the end of the process, 63a and 63b were obtained after chromatographic purification with 81% yield for 63a and 74% yield for 63b. Finally, the alkenes were oxidized in the presence of osmium

• ) in 95% yield after 18 h (Scheme 12). Hydroxylamine (±)-104 was hydrolyzed in the presence of aqueous hydrochloric acid, and the resulting nitrone was heated in toluene to yield the homotropane (±)-105 in 57% yield over two steps. (±)-105 was alkylated with excess methyl iodide to form the

• ) amberlyst-15 resin, MeOH; iii) 1. n-BuLi; 2. TMSCl, 3. HCl aqueous, 76% over 3 steps; iv) oxalyl chloride, DMSO, Et3N, 80–90%; v) CH2=CHCH2MgBr, Et2O, 70–81%; vi) 1. CrO3, HOAc; 2. NH2OH·HCl, Py–EtOH, 58–66%; vii) NaCNBH3, MeOH, pH 3–4; viii) toluene, reflux, 9 h, 71–76%; ix) Raney-Ni, H2, 90 min, 93–96%; x

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• -dibromopyridine it was the only way for us to synthesize the target [4]helicenes [70]. Unfortunately, the coupling of 2,3-dichloroquinoxaline (3a) with 9-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole in the 5% Pd-C/PPh3/K2CO3/toluene/H2O catalytic system at 100 °C for 24 h (method A) gave the

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• p-nitrobenzaldehyde (2a) and 2,6-dimethylpyridine (1a) as model substrates. Our investigation started with the reaction of p-nitrobenzaldehyde (2a) and 2,6-dimethylpyridine (1a) in the presence of Hβ zeolite as a catalyst at 120 °C in toluene for 24 h in a sealed vial (Table 1, entry 1). However

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• ) [46]. The treatment of 11 with a catalytic amount of trifluoroacetic acid in toluene at 140 °C for 7 min led to the elimination of methanol and provided the 3-iodoenesulfonamide 12 in 77% yield [47]. To avoid the use of these harsh reaction conditions, we employed other methods, but both the

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• upon refluxing in toluene and subsequent epoxidation afforded 51 [32], which was converted to (−)-crinipelline A (15) in two steps. The synthesis of waihoensene (16) commenced with the conversion of aldehyde 52a to the corresponding hydrazone 52b, which was treated with sodium hydride under reflux to

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• reaction conditions [44]. Refluxing the reaction mixture of PPh3, DIAD, and toluene for two days provided the distally dialkylated calixarene 2 in 64% yield (Scheme 1). Compound 2 was regioselectively ipso-nitrated with 30 equiv of 65% aq HNO3 in an AcOH and CH2Cl2 mixture, making use of the higher

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• have found that 1-butyl-1,2,3-triazole-4-carbothioamide (1c) reacts well with benzenesulfonyl azide (2c) in various solvents to form the desired 1-butyl-1,2,3-N-sulfonyl amidine 3n in diverse solvents such as n-butanol, n-propanol, toluene, ethanol, water and even under solvent-free conditions (see

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• solvent on the model reaction was also examined. Anhydrous ethanol, acetonitrile, toluene, and DMSO did not bring any improvement with respect to the yield of 4a (Table 1, entries 8–11). The decrease of the catalyst loading from 10 to 5 mol % resulted in a slight decrease of the reaction yield (Table 1

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• sufficiently blue-shifting the UVRR spectrum away from the UV-excited autofluorescence [20][21]. This is illustrated in Figure 2 for the UVRR spectra of a 1 mM solution of toluene in acetonitrile acquired with 240, 258, and 266 nm laser excitation. The spectra are plotted as a function of the wavelength

• ). BA was chosen in order to test experimentally whether the UVRR at 244 nm laser excitation is free from UV-excited autofluorescence as expected from the initial results with toluene (Figure 2). RGD was chosen as a biologically relevant tripeptide sequence highly abundant in proteins of the

• solution of toluene in acetonitrile acquired with 240, 258, and 266 nm laser excitation, respectively. The UVRR spectra of a 200 µM solution of GCP ethyl amide in 6 mM BisTris buffer solution at pH 6 acquired with 266 nm (black curve) and 244 nm (magenta curve) laser excitation, respectively. The UVRR

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• . Interestingly, the fullerene C60 was not taken up as a guest by the tetramer (6)4 in chlorinated solvents. For a more defined self-sorting, the authors switched the solvent from CDCl3 to [d8]-toluene. Now, a 2-fold completive self-sorting delivered the homoleptic inclusion complexes [(5)4(C60)] and [(6)4(C60

• . e) A solvent change from CDCl3 to [d8]-toluene leads to a 2-fold completive self-sorting upon treatment with C60. (a) Two new Zn4L6-type cages. (b) The encapsulation of C70 induced distinct reconstitutions within a dynamic library of mixed ligand Zn4L6 cages. The formation of octahedral cages (a

Dirhamnolipid ester – formation of reverse wormlike micelles in a binary (primerless) system

• David Liese,
• Hans Henning Wenk,
• Xin Lu,
• Jochen Kleinen and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2020, 16, 2820–2830, doi:10.3762/bjoc.16.232

• and the ester alkyl chain length on the rheological properties of the reverse wormlike micelles in toluene was investigated in detail. Highly viscoelastic solutions were obtained even at a relatively low concentration of less than 1 wt %. The phase transition temperatures indicate that the formation

• polarity. An unusual behavior was observed when the dirhamnolipid esters were added to toluene. The more polar short chain length dirhamnolipid esters and 7 form a gel-like texture in toluene, indicating the formation of a network structure of the surfactant molecules. With increasing chain length of the

• dirhamnolipid esters, the ability to gel toluene vanishes. Rheological data Temperature sweep With this interesting observation we went on and performed rheological measurements to determine the viscoelastic properties of the dirhamnolipid ester/toluene gels. First, we performed temperature sweep measurements