Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• in 3d proceeded smoothly with acetyl chloride in the presence of sodium hydride to afford 5 in good yield. The structure of the product and the site of acetylation was confirmed by X-ray crystallography of a single crystal of 5 [71] (Figure 3). The methylated and benzylated derivatives 6 and 7 were

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• ), sodium hydride (0.105 g, 4.2 mmol), and dried THF (16 mL). The mixture was stirred at rt for 2 h, and then methyl iodide (0.61 g, 4.3 mmol) was added and the mixture stirred at rt for 6 h. Then, distilled water (12 mL) and diethyl ether (15 mL) were added, the organic phase was separated, dried, and

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• (1.5–2.4 equiv) and proceeded in <1 h. Sodium hydride was investigated as a heterogeneous alternative to potassium tert-butoxide, although a lower isolated yield of the final amine was obtained. All amines were formed in high NMR and LC–MS purity without the need for purification by column

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• [22] (Scheme 93). The reaction mechanism was proposed as following. The treatment of trimethyloxosulfonium iodide (424) with sodium hydride generated dimethyloxosulfonium methylide (426) as the one carbon-containing nucleophile with DMSO (379) as a good leaving group. The nucleophilic attack of 426 on

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• procedure reported in literature [27]. OLED fabrication and characterization was carried out according to the procedure reported earlier [28]. Materials 2-Aminobenzophenone, 3,5-difluorobenzaldehyde, ammonium acetate, phenothiazine, sodium hydride, sodium sulfate, tert-butyl chloride, zinc chloride

• compounds 1–3 were synthesized through nucleophilic substitution reactions between quinazoline derivative Q1 and the respective donor compound in the presence of sodium hydride in dry dimethylformamide (DMF). The reaction mixtures were refluxed for 24 h. After completion of the reactions, the reaction

• ): Quinazoline derivative (Q1, 0.25 g, 0.79 mmol), 3,6-di-tert-butylcarbazole (0.48 g, 1.7 mmol) and sodium hydride (0.50 g, 1.6 mmol) in dry dimethylformamide (DMF) were used for the nucleophilic substitution reaction. The title compound was obtained as yellowish crystals in a yield of 0.25 g, 37%; Tm = 181 °C

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• -(diphenylphosphine)ethyl)-4,5-diazafluorene ligand 47 which includes a cyclopropylated intermediate (45, Scheme 8). The ligand was prepared by an initial cyclopropanation of diazafluorene 44. For this, 44 was treated with a dibromomethane solution in THF in the presence of sodium hydride under reflux for four hours

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• hydride-mediated reaction of arylmethyl isocyanides with xanthate esters in DMF is reported. The products thus obtained were compared with the carbamothioates obtained by the sodium hydride-mediated condensation of the corresponding benzylamines and xanthate esters in DMF. To account for these unexpected

• reactions, a mechanism is proposed in which the key steps are supported by quantum chemical calculations. Keywords: benzylamines; carbamothioates; density functional theory; intrinsic reaction coordinate analysis; isocyanides; sodium hydride; xanthate esters; Introduction Carbamothioates (thiocarbamates

• reported the synthesis of thiazoles from xanthate esters [31]. In continuation of this ongoing work, we planned to synthesize 5-alkoxy-4-arylthiazoles 3 by the sodium hydride/DMF-mediated reaction of arylmethyl isocyanides 2 with S-alkyl xanthate esters 1 or O-aryl/O-alkyl dithiocarbonates. Unexpectedly

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• -arabinopyranoside (1), available in multigram amounts, was benzylated in 79% yield using benzyl bromide and sodium hydride in DMF, followed by hydrolysis of the anomeric aglycon of 2 with 5 M HCl and SrCl2 in acetic acid, which afforded the hemiacetal 3 as a 2:3 α/β anomeric mixture in 60% yield (Scheme 1

Complexation of 2,6-helic[6]arene and its derivatives with 1,1′-dimethyl-4,4′-bipyridinium salts and protonated 4,4'-bipyridinium salts: an acid–base controllable complexation

• Jing Li,
• Qiang Shi,
• Ying Han and
• Chuan-Feng Chen

Beilstein J. Org. Chem. 2019, 15, 1795–1804, doi:10.3762/bjoc.15.173

• presence of sodium hydride. Helic[6]arene derivative H5 was synthesized by treatment of H1 with methyl bromoacetate followed by reduction with lithium aluminium hydride (Scheme 1). The guests G1–3 were prepared according to previously reported procedures [37][38][39]. Guest G4 was synthesized through

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

• and HPLC–MS. Based on preliminary experiments in our laboratory, the reaction was performed in tetrahydrofuran (THF) at 40 °C for 1 h using a 1.5 equiv excess of sodium hydride as the base, S8 and the alcohol component (Table 1, entry 1) resulting in the desired thiocarbamate 3a in 58% yield. During

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• the poor solubility of 12 in acetonitrile, the compound was successfully converted to iodide 9 via a Finkelstein reaction. Unfortunately, subsequent alkylation of 10 with iodide 9 in the presence of sodium hydride furnished 6 in a poor yield of 21%. Formation of self-alkylation product 13 constituted

An efficient and concise access to 2-amino-4H-benzothiopyran-4-one derivatives

• Peng Li,
• Yongqi Wu,
• Tingting Zhang,
• Chen Ma,
• Ziyun Lin,
• Gang Li and
• Haihong Huang

Beilstein J. Org. Chem. 2019, 15, 703–709, doi:10.3762/bjoc.15.65

• from 2’-chloroacetophenone as the starting material through treatment with carbon disulfide in the presence of sodium hydride [23], followed by alkylation using iodoethane according to the literature procedures [13][16][17][19]. The oxidation of 1 with 1.2 or 5 equiv of H2O2 yielded ethyl sulfoxide 2

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• purified and characterized or, for further transformations, the crude products are directly converted into the corresponding nonaflates by deprotonation with sodium hydride and treatment with 1-nonafluorobutanesulfonyl fluoride (NfF). Scheme 13 shows two examples, PM52 and PM54 that are ready for palladium

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

• and a connection to a combined nitrogen-vacuum line, charged with sodium hydride (1.6 g; 60% in mineral oil, 40 mmol) and closed with a septum. n-Hexane (20 mL) was injected by syringe and the suspension was stirred for 10 min. Then, stirring was interrupted and the supernatant liquid was removed by

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• phthalimides 16 and 23 [29]. These intermediary compounds 16 and 23 also allowed an N-methylation of the azaindole moiety with sodium hydride (NaH) and methyl iodide (MeI) to yield 17 and 24. By ethanolic hydrazinolysis and microwave irradiation the phthalimides (16, 17, 23, and 24) were deprotected yielding

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• -4,6-O-benzylidene-β-D-glucopyranoside (9). Compound 9 was treated with benzyl bromide in the presence of sodium hydride [20] to give O-benzylated derivative 10 in 90% yield in two steps, which on de-O-allylation by treatment with palladium chloride [21] furnished 2-azidoethyl 2-O-benzyl-4,6-O

A simple and effective preparation of quercetin pentamethyl ether from quercetin

• Jin Tatsuzaki,
• Tomohiko Ohwada,
• Yuko Otani,
• Reiko Inagi and
• Tsutomu Ishikawa

Beilstein J. Org. Chem. 2018, 14, 3112–3121, doi:10.3762/bjoc.14.291

• solution [38] (run 2 in Table 1) and with Me2SO4 and K2CO3 in 0.023 M solution [39] (run 3 in Table 1) afforded 1 in 86% and 72% yields, respectively. In the remaining reaction the use of sodium hydride (NaH) as a base produced 1 in 84% yield [40] (run 4 in Table 1). We at first re-examined these reactions

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

• dispersion in native form [18][19][25], we have found that mineral oil should be removed before the synthesis. The results of the optimization experiments are summarized in Table 1. The safest way to remove oil is by washing sodium hydride by means of decantation directly in the reaction flask. This

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• -amino esters, we tried their preparation via a C-methylation of α-nitroester 6a in DMF using sodium hydride and methyl iodide. Upon purification, this gave 46% of the nitro compound 9 with 94% purity (as assessed by 1H NMR). Despite this modest yield, the ensuing reduction using zinc and hydrochloric

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

• synthesis method through the one-pot acylation of ethyl acetoacetate with isatoic anhydrides followed by dehydrative intramolecular cyclization to access the desired quinoline scaffold 10 [18]. We replaced sodium hydride as the base required to generate the enolate of ethyl acetoacetate with sodium

• hydroxide [19][20]. The use of sodium hydride is of particular concern upon reaction scale-up due to limited solubility in organic solvents and the production of flammable hydrogen gas [21][22]. Sodium hydroxide avoids the off-gassing of hydrogen and produces water instead, thereby avoiding the use of any

• (Scheme 4). This strategy achieved the replacement of sodium hydride with sodium hydroxide thereby obviating any special equipment requiring the capture or scrubbing of hydrogen gas evolved. The extension of the 3-position ethyl ester into the α-tert-butoxy acetic acid residue was also demonstrated via a

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• benzyl alcohol (1) in the presence of slight excess of tetrafluoroboric acid in diethyl ether (HBF4·Et2O) and tetrahydrothiophene (THT). Notably, the use of acetonitrile (MeCN) as a solvent was critical for maintaining a homogeneous reaction and a successful outcome. We also observed that sodium hydride

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• sodium hydride in tetrahydrofuran and subsequent deprotection of Boc groups afforded L-proline immobilized calix[4]arene magnetic nanoparticles (Calix-Pro-MN) 86 (Scheme 23). In 2016, three new lower rim functionalized calix[4]arene-based L-proline catalysts 87–89 containing ester, amide and acid units

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

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

• intramolecular Wittig reaction. The yields of the product ranged between 6 and 95% [13]. 2.2.3. Reactions with nitrogen nucleophiles: The reaction of vinylphosphonium salt with 2-pyrrolocarbaldehyde in the presence of sodium hydride as described by Schweizer et al. provided bicyclic pyrrole derivatives 47 in 25

• deprotonation of β-ketosulfonamides or β-ketoamides with sodium hydride. The generated ylides 49 were then cyclized in the intramolecular Wittig reaction to give 3-pyrroline derivatives 50 in yields of 55–90%. It is worth emphasizing that enantiomerically pure 3-pyrroline derivatives were produced from

An efficient synthesis of 1,6-anhydro-N-acetylmuramic acid from N-acetylglucosamine

• Matthew B. Calvert,
• Christoph Mayer and
• Alexander Titz

Beilstein J. Org. Chem. 2017, 13, 2631–2636, doi:10.3762/bjoc.13.261

• -Triphenylmethyl-1,6-anhydro-N-acetylmuramic acid (13) A solution of 12 (910 mg, 2.0 mmol) in dioxane (16 mL) was treated with sodium hydride (60% suspension in mineral oil, 540 mg, 13.5 mmol) at room temperature. The suspension was warmed to 45 °C for 10 minutes, then cooled to rt. (S)-2-Chloropropionic acid

• ) was treated with sodium hydride (60% suspension in mineral oil, 130 mg, 3.3 mmol) at room temperature. The suspension was warmed to 45 °C for 10 minutes, then cooled to rt. (±)-2-Chloropropionic acid (130 mg, 110 µL, 1.2 mmol) was added, and the suspension stirred at 90 °C for 3 hours. The reaction