Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• substituted hydrazones obviated their generation in situ, and as ethanol was identified as a better solvent in the initial coupling step, no solvent exchange was necessary in the fragmentation step of the hydrazide intermediate. The addition of triethylamine and heating the reaction to 80 °C for 1 hour were

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• intermediate 4. Reaction conditions: a) i) TFAA, collidine, 0 °C, 30 min; ii) K2CO3, rt, 30 min, 99%; b) benzylamine, DCE, THF, sodium triacetoxyborohydride, N2, rt, 24 h, 60%; c) ethanol, 10% Pd/C, H2, rt, 24 h, 84%; d) Boc anhydride, DMAP, THF, rt, overnight, 100%; e) Na, NH3, THF, -60 °C, 1 h, 81

• %. Synthesis of ent-pavettamine as the TFA salt 28. Reaction conditions: a) IBX, DMSO, rt, overnight, quantitative yield; b) TsCl, DMAP, DCM, rt, 24 h, 83%; c) NaN3, DMF, 80 °C, 3 h, 75% yield; d) 10% Pd/C, H2, ethanol, rt, 12 h, quantitative yield; e) sodium triacetoxyborohydride, 1,2-DCE, THF, rt, 24 h, 95

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• industrialized total synthesis of a nontrivial natural product. The original experimental protocol was recently improved by replacing the inorganic base (KOH, NaOH) with the amidine base diazobicycloundecane (DBU) as well as ethanol with n-propanol [49]. The type-III Guareschi reaction is a three-component

• of the imide slowly forms. After stirring for 24–36 h, the precipitate is filtered, and the filtrate, after washing with ethanol or diethyl ether, is acidified to precipitate the imide. In the course of the work-up, Guareschi noticed the formation of copious gas, bubbling from the solution of the

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• also Supporting Information File 1 for details). The reaction of 5,7-dimethylimidazo[4,5-e]triazine-3-thione (3a) with DEAD proceeded in alcohols with moderate regioselectivity and isomer 5 predominated in the filtered precipitates (Table 1, entries 1–3). The use of absolute or 95% ethanol as a solvent

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• -catalyzed hydrogenolysis in ethanol/acetic anhydride appeared to be a logical deprotection step [26], the desired fluoro sugars were contaminated with varying quantities of unidentified byproducts. However, clean debenzylation was achieved by first converting the azide to an acetamide on reaction with

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• free amine. The first example from Smolka and Friedreich involved the preparation of unsubstituted biguanide by reacting cyanoguanidine with ammonium chloride in boiling ethanol [14]. Then, they used high-pressure autoclave conditions to increase the temperature. Ethylbiguanide and phenylbiguanide were

• prepared in this way from the corresponding ammonium chlorides (Scheme 4). Later, in 1911, Cohn proposed an upgrade of these methods for the synthesis of a series of arylbiguanides by replacing the use of ethanol in the autoclave with boiling water [19]. Interestingly, the authors improved the work-up of

• ). It is interesting to note that heterocyclic nitrogen atoms can also react with cyanoguanidine. For example, Zeng et al. reported the conversion of 1,2,4-triazole derivatives into their related biguanide products in good 70% yield by simple reflux heating in ethanol (Scheme 10). The resulting

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• ,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (DLin-MC3-DMA, >98%) was purchased from D&C Chemicals (China), DSPC and cholesterol were purchased from Echelon Biosciences, Inc. (USA), and DMG-PEG 2000 was purchased from Avanti Polar Lipids, Inc. (USA). Ethanol (BioUltra

• under vacuum. The lipid film was dissolved in ethanol (20.3 mg/mL) and added dropwise to stirring 50 mM citrate buffer at pH 4.0 and preheated to 35 °C to get a final lipid concentration of 6.1 mg/mL. The lipid solution was stirred for an additional 20 min at 35 °C, after which the lipid solution was

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• -fused tetrahydrodibenzoacridinones 9 using phenanthren-9-amine 8, aldehydes 5, and cyclic 1,3-diketones 6 as structural units in ethanol under microwave irradiation to result in the targeted products in excellent yields. A conventional heating used for the same protocol delivered the desired products in

• -alkenyloxindole 43 were considered to be the building blocks united in ethanol as solvent (Scheme 15). The notable highlights of the described methodology are diastereoselective C–C and C–N bond formation, high yields, non-toxic product, and cost-effectiveness along with a greener approach. The synthetic strategy

• . One such demonstration was reported by Padmini and co-workers [64] wherein a four-component reaction between substituted aldehydes 5, phenanthroline (63), malononitrile (51) and isocyanides 21 afforded pyrrolo[1,10]-phenanthrolines 64 in ethanol as a solvent with excellent yields. The conventional

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• Ke Wu Yichen Ling An Ding Liqun Jin Nan Sun Baoxiang Hu Zhenlu Shen Xinquan Hu College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032, P.R. China 10.3762/bjoc.17.69 Abstract After completing the thio-substitution with Lawesson’s reagent, ethanol was found to be

• scaling up the preparation of two pincer-type thioamides, we have successfully developed a convenient process with ethylene glycol to replace ethanol during the workup, including a traditional phase separation, extraction, and recrystallization. The newly developed chromatography-free procedure did not

• drawback for reactions at a larger scale. All attempts to isolate the desired product from the reaction mixture after ethanol treatment, e.g., by solvent extraction/phase separation using solvents of various polarity or even with an aqueous workup failed and showed that compound C1 was well distributed in

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• reaction time (Table 1, entries 11–24) as variables. Reactions in such solvents as ethanol and glycerol resulted in almost no conversion. The treatment in water led to a mixture of the product with the starting material where low conversion can be explained by solubility issues. To overcome this, the

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• developed, using a solvent or molecular hydrogen as cleaving agents [81]. The main solvolytic process include: hydrolysis (water) alcoholysis (methanol, ethanol, 1-butanol, 2-ethyl-1-hexanol, phenol) glycolysis (ethylene glycol (EG), 1,2-propanediol (PD), 1,3- and 1,4-butanediol (BD)), diethylene glycol

•  4, bottom). No details of byproducts were provided. Ethanol and butanol were much less reactive under identical reaction conditions. The as-prepared DMT could be used for the production of hydrocarbon jet fuels by catalytic hydrogenation. Metal-catalysed methanolysis of PET was described in previous

• compounds, with the notable exception of calcium oxide, which gave ʟ,ʟ-lactide from PLLA in ≈98% yield at 250 °C [263]. Alcoholysis. The solvolytic depolymerisation of PLA was mostly reported using zinc-based catalysts, ethanol or methanol agents, wherein a higher reactivity of the latter was ascribed to

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

• ) Acetyl chloride (300 μL, 4.22 mmol) was added dropwise to ethanol (2 mL) stirring at −78 °C under N2. The mixture was briefly warmed to rt (5 min) then re-cooled to −78 °C. A solution of crude cyanoketone 16 (1.0 g, 85% purity, 3.37 mmol) in ethanol (1 mL) was added, the cooling bath replaced with a rt

• 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

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• 0.1% (w/v) orcinol solution containing a sulfuric acid/ethanol/water 3:72.5:22.5, v/v/v mixture, followed by charring. Purification by column chromatography was performed using a Reveleris® flash chromatography automated system (Büchi) equipped with prepacked irregular silica gel 40–63 μm cartridges

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

• was then dissolved in acetic acid/ethanol 1:1 and treated with ten equivalents of ammonium acetate, stirred overnight at a temperature of 75 °C. Work-up followed by chromatographic column purification of the reaction mixture furnished (+)-euphococcinine (2) in 91% yield. This single step procedure

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

• alternating enantiomers form a screw along the a axis. Optical properties All helicenes 10 are well soluble in dichloromethane and chloroform. Solubility in other common solvents such as acetonitrile, DMSO, tetrahydrofuran, ethanol and hexane is markedly lower. Carbazole-based [6]helicene 12 was described as

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

• synthesis of 1-phenyl-2-(2-pyridyl)ethanol and 1-phenyl-2-(2-pyridyl)ethene under catalyst- and solvent-free conditions. Despite the low yield of the product of around 4%, this work described crystallographic data and the influence of reaction conditions such as the temperature and the reaction time on the

• stability of 1-phenyl-2-(2-pyridyl)ethanol [32]. Different catalysts such as ionic liquids [33], CuFe2O4 [34], and Ca(OTf)2 [35] were also utilized. Due to the abundant importance of these products, several different approaches were reported (Scheme 1 and Scheme 2). These higher azaarene products were also

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah’s reagent under solvent-free conditions

• Yumeng Liang,
• Akihito Taya,
• Zhengyu Zhao,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254

• sealed and the reaction mixture stirred at 70 °C for 24 h. Then the mixture was cooled to room temperature and ethanol (3.0 mL) was added to the mixture while stirring for an additional 30 min at room temperature. The mixture was then added to 1 M aqueous NaHCO3 (3 mL) at 0 °C, extracted with Et2O (3 × 5

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

• the nitro groups or (ii) concomitant reduction of the nitro groups and the allyl moieties. Thus, the reaction of 4a with SnCl2∙2H2O in ethanol gave the corresponding amine 5 in 57% yield after column chromatography on alumina. On the other hand, the four-day stirring of 4a with Pd/C under a H2

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

• azide (2c) neither in water, ethanol nor in the absence of a solvent, conditions that were successfully used in the synthesis of 1-alkyl-1,2,3-triazole-4-N-sulfonylimidamides 3a–s (Scheme 2). On the other hand, we have found the formation of a new product 3t in low yield together with the starting

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

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• flasks equipped with reflux condensers and magnetic stir bars. All reactions were followed by thin-layer chromatography (TLC) using Silufol UV-254 plates, which were visualized under UV light (254 nm), with acetone, hexane/acetone, or hexane/ethanol/acetone mixtures as eluent. Polyphosphoric acid (87

• (3.01 g, 10 mmol) in DMF (16 mL) was added potassium phthalimide (1.85 g, 10 mmol) in portions. The mixture was stirred at room temperature for 5 h. Then, water (30 mL) was added, and the formed precipitate was collected by filtration and washed with water. Recrystallization from ethanol afforded

• colorless crystals of intermediate 2-((6-bromoquinolin-2-yl)methyl)isoindoline-1,3-dione. This material (3.05 g, 8.3 mmol) was suspended in ethanol, and hydrazine hydrate (50%, 1.0 g, 10 mmol) was added. The reaction mixture was refluxed for 5 h and then cooled down to 0 °C. The precipitated phthalyl

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• –formaldehyde condensation reaction, and therefore equips the generated polymeric support with more sulfonic groups. The heterogeneous Cu catalyst (LS-FAS-Cu) was finally obtained through refluxing of LS-FAS with Cu(OTf)2 in ethanol, and the loading capacity of Cu was confirmed to be 0.92 mmol/g by means of ICP