Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• ]. Additionally, another very common method involves the employment of a strong base, typically sodium ethoxide or methoxide, in combination with an alkyl nitrite to promote the incorporation of the oximino group (Scheme 5, middle) [60][61]. Furthermore, a widely adopted strategy involves the conversion of a

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• stoichiometric amounts of alkali metal hydroxides or other strong bases, commonly NaOH, KOH, Ba(OH)2·8H2O or sodium ethoxide, etc. [12][13][14][15][16][17][18]. Such harsh conditions and the competitive formation of undesired side products have been the major limiting factors for the Cannizzaro reaction in the

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• spectrum showed the presence of acenaphthylene 8 and quinoline 5 as the major species in proportionate quantities. The use of sodium ethoxide in EtOH allowed us to carry out the reaction with full conversion in 2 days. Unfortunately, the admixtures and tarring formed in sufficient quantity made it

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

• occurrence of modest amounts of isomer 4{1,2}. Of note is that the use of sodium ethoxide was not successful (Table 2, entry 13) whereas the use of 0.75 N tetrabutylammonium hydroxide either diluted in water or in methanol (Table 2, entries 14 and 15) had the biggest impact on the reaction yield

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• reactions, amino diesters 89 being isolated as single diastereoisomers (Scheme 27). Removal of the sulfinyl group under acidic conditions, and further treatment of the resulting ammonium salts with sodium ethoxide, yielded α-methylene-γ-butyrolactams 90, in a one-pot, two-step process [103]. A six-membered

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• reaction, using sodium ethoxide in ethanol, followed by the hydrolysis with concentrated sulfuric acid at a low temperature [56], leading to the corresponding new γ-diketones 5a–d in 61–87% yield (Scheme 2). Despite the efficiency of the Nef reaction, the diversity at the R1 position via this synthetic

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• environmentally unfriendly transition-metal-based reactions. Acylations of in situ-generated nitrile anions with esters to produce β-ketonitriles were first reported long ago, for example by using sodium methoxide [2], sodium ethoxide [3] or sodium amide [4][5]. The reaction was found to proceed more efficiently

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• isocyanide component under air. In the case of using other bases, such as caesium carbonate (Cs2CO3), diisopropylethylamine (DIPEA) or sodium ethoxide (NaOEt), only the isothiocyanate intermediate of the reaction was isolated (Table 1, entries 17, 18, and 20). However, using diazabicycloundecene (DBU) as the

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• could be conducted under ultrasound irradiation using sodium ethoxide as catalyst, thus generating steroid ring A-fused 3,4-dihydropyrimidinones and 3,4-dihydropyrimidinthiones 44 in very good yields. Mohamed et al. [44] reported a 4CR for the synthesis of pyridopyrimidines fused to ring D of

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• , 147.7, 149.1, 170.1, 170.7, 205.6, 206.1, 206.2, 210.7, 213.0; HRMS: [M + H]+ calcd for C32H38NaO14, 669.2159; found, 669.2154. epi-Scorzodihydrostilbene D (13): A mixture of 12 (18 mg, 0.03 mmol), methanol (1 mL) and sodium ethoxide (3 mg, 0.06 mmol) was stirred at 25 °C for 4 h. The mixture was

A convenient and practical synthesis of β-diketones bearing linear perfluorinated alkyl groups and a 2-thienyl moiety

• Ilya V. Taydakov,
• Yuliya M. Kreshchenova and
• Ekaterina P. Dolotova

Beilstein J. Org. Chem. 2018, 14, 3106–3111, doi:10.3762/bjoc.14.290

• reagents [26], spectrophotometric determination of NaOR with α-santonin [27], thermometric determination of alkoxides [28] and some other special techniques. Unfortunately, these methods are too laborious for a common synthetic laboratory. The effect of sodium ethoxide quality on the yields of a

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• the next step after a minimal work-up. Accordingly, they were dissolved in ethanol and treated first with sodium ethoxide followed by isoamyl nitrite (iAmONO) to give the corresponding α-hydroxyimino esters 2a–al. These resulting compounds were then purified and isolated in yields reported in Table 1

• using the previously reported methylmagnesium chloride 1,4-addition on diethyl furfurylidenemalonate (6ae) [6]. Quite unexpectedly, repeated attempts to obtain the α-hydroxyimino ester 35 from the resulting β-methylated derivative 34 failed. Trials were made not only with sodium ethoxide but also with

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• with diethyl oxalate and sodium ethoxide in ethanol [28]. Isatoic anhydride 9f was then added to the solid enolate and both were dissolved in DMA and warmed to 60 °C for 12 hours. Following the general work-up protocol as described for Scheme 4, a light tan solid was isolated in modest yield after

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• pyrrolo[1,2-a]indoles by sodium ethoxide-promoted cyclization. The three-component coupling also becomes viable through a Co(III)-catalyzed hydroarylation strategy as Ellman and co-workers demonstrated (Scheme 39) [99]. The reaction of arene 21 with vinyl ketones and aldehydes in the presence of [CoCp

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -carboxylate (126) with benzoylisothiocyanate or phenylisothiocyantes for the synthesis of N-thiocarbamoyl pyrazole derivatives 180 and 183 which gave pyrazolo[3,4-d]pyrimidine derivatives 181 and 184 on treatment with ethanolic sodium ethoxide. Pyrazolo[3,4-d]pyrimidine derivatives 181 were also obtained

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• the nucleophilic agents used in these reactions were usually prepared by reaction of sodium hydride or sodium ethoxide with a proper nucleophile, such as diethylamine, piperidine, pyrrole, ethanol, p-toluenesulfonamide, thiophenol and others. Depending on the reactants used, Z- or E-stereoisomers of

Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates

• Tyler M. M. Stack,
• William H. Johnson Jr. and
• Christian P. Whitman

Beilstein J. Org. Chem. 2017, 13, 1022–1031, doi:10.3762/bjoc.13.101

• ,d) The syntheses of the 4Z-isomers of 3c and 3d (5-bromo- and 5-fluoro-, respectively) were based on the synthesis of (4Z)-3b, which followed the procedure used to produce 2-hydroxymuconate (3a) [8][11]. Sodium ethoxide was generated by allowing sodium metal (1 equiv, 26.2 and 17.3 g for 3c and 3d

• , respectively) to react completely with ethanol (50 mL), followed by the addition of toluene (300 mL) to the stirring mixture. The resulting solution was distilled (to remove water and ethanol) under an argon atmosphere until the temperature climbed above 80 °C. The anhydrous sodium ethoxide was chilled in an

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• ketoesters 59. The base-mediated cyclization of the latter in the presence of sodium ethoxide led to the formation of the corresponding 1-indanone anions α to carbonyl, which next were alkylated to give 2-substituted 1-indanones 60 (Scheme 20). This one-pot process utilizing a multi-task palladium catalyst

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• -ketoesters 5 and 6 were done with amidines 8g,h. The reaction between 5 and 8g was tested to achieve the optimal conditions. The use of acetonitrile or ethanol as the solvent (at 25 °C or reflux) in the presence of bases such as potassium carbonate (K2CO3) or sodium ethoxide (CH3CH2ONa), and with reaction

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• methanol [17] and cyclization was achieved under basic conditions using sodium ethoxide; the lactam was prone to racemization under strongly basic conditions, this was avoided by short reaction times with sodium ethoxide, and by avoiding strongly basic reaction conditions in subsequent steps. A key

• and p-toluenesulfonic acid under dehydrating conditions [18]. Opening of the oxazolidinone with sodium ethoxide as nucleophile thus yielded ester 7a, while addition of ethylamine yielded amide 7b. Subsequent amide bond formation with lactam 4 using isobutyl chloroformate or HBTU as coupling reagents

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

• Olga C. Dennehy,
• Valérie M. Y. Cacheux,
• Benjamin J. Deadman,
• Denis Lynch,
• Stuart G. Collins,
• Humphrey A. Moynihan and
• Anita R. Maguire

Beilstein J. Org. Chem. 2016, 12, 2511–2522, doi:10.3762/bjoc.12.246

• requires significant external cooling, an undesirable feature for scale-up. The synthesis of the α-thioamide 2 involves prior generation of fresh sodium ethoxide from sodium metal. Furthermore, this α-thioamide protocol, at high pH, ordinarily does not go to completion, leaving unreacted starting material

• , with the resulting product typically ca. 94% pure by HPLC. It was also envisaged that the facility to superheat the solvent in a pressurised continuous platform could enable sodium ethoxide to be replaced by a weaker base, obviating the need for sodium metal. At an early stage of process development

• . Elevating the temperature to 90 °C and employing DBU, as a more basic alternative to triethylamine, did not increase the reactivity. Hence, the focus was instead directed on converting the existing batch process (Scheme 2), with sodium ethoxide as base, into a stand-alone continuous process. Initially

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations

• Adriana K. Slavova-Kazakova,
• Silvia E. Angelova,
• Timur L. Veprintsev,
• Petko Denev,
• Davide Fabbri,
• Maria Antonietta Dettori,
• Maria Kratchanova,
• Vladimir V. Naumov,
• Aleksei V. Trofimov,
• Rostislav F. Vasil’ev,
• Giovanna Delogu and
• Vessela D. Kancheva

Beilstein J. Org. Chem. 2015, 11, 1398–1411, doi:10.3762/bjoc.11.151

• -hydroxy-4-oxohexa-2,5-dienoate) (8) To a solution of sodium ethoxide (1.1 g, 15.7 mmol) in tetrahydrofuran (20 mL) was added dropwise a solution of 6 (1 g, 2.6 mmol) in THF (15 mL) at room temperature under an N2 atmosphere. The reaction mixture was stirred at room temperature for 10 min. Diethyl oxalate

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• /trans-Isomers of 4- and 5-oxazole derivatives (1, 2) were synthesized by Wittig reactions from the diphosphonium salt of α,α’-o-xylene dibromide, formaldehyde and oxazole-4- and 5-carbaldehydes (3, 4), respectively, in absolute ethanol with sodium ethoxide as a base (Scheme 1). The procedure of this

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• different anilines in ethanol at 0 °C to rt furnished (Z,E)-3-aryl-5-methylthiazolidinones 30–32. As an example, thiazolidinone 32 was reacted with 4-chlorothiophenol in the presence of sodium ethoxide to give 4-chlorophenylthio compound 33 (60%), again as a mixture of Z- and E-isomers, but this time in a 2

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50