Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• extend the scope of this tandem reaction sequence towards analogous skeletons, we explored the effect of various substituents on the aromatic cycles. The successive prenylation and then diversity-oriented benzylation (n = 1 for substrates 11a–n) of diethyl malonate (10) afforded a variety of new

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• ) halogenation, and 3) ring closure (Scheme 2). β-Nitrostyrene 2 serves as an appropriate acceptor for conjugate addition by diethyl malonate (3a) to afford adduct 4a, in which the methine group flanked by two carbonyl groups is readily halogenated, and the subsequent intramolecular nucleophilic substitution by

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• each on the pyridine ring. Moreover, IPs with a non-aromatic C-2 substituent like an ester group were also included (4r). We also explored bromo analogues of other active methylenes such as ethyl cyanoacetate, ethyl acetoacetate, dimethyl, and diisopropyl malonates, as extension of diethyl malonate (4s

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

• yields of the reactions with β-ketoesters and β-ketoamides were comparable with those obtained with 1,3-diketones. We also explored the reactions between 4-fluorophenyl hydroximoyl chloride (1a), which was the phenyl hydroximoyl chloride that gave the best yield, and diethyl malonate (2j) or dibenzyl

• mmol of 2, and 3 equivalents of DIPEA in 15 mL of 95% water, 5% methanol at room temperature for 2 hours. The yields were calculated after the isolation and purification of products. Reactions between 4-fluorophenyl hydroximoyl chloride (1a) and diethyl malonate (2j) or dibenzyl malonate (2k) did not

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• modify the triazolo[1,5-b][1,2,4,5]tetrazine ring system with a variety of structural fragments, thus enabling to vary their biological activity. The reactions of new triazolo[1,5-b][1,2,4,5]tetrazines with some CH-active compounds, such as malononitrile, ethyl cyanoacetate and diethyl malonate, have

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• the alkylating reagent on both efficiency and selectivity, we decided to perform a quick optimization study. As a model reaction, we evaluated the influence of various parameters on the reaction between diethyl malonate (1b) and iodobutane (2d) or bromobutane (2d') in the presence of a stoichiometric

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• to form 2-fluoro-2-nitropropane in a 40% yield (Scheme 1). The reaction with sodium diethyl malonate was also reported to produce the difluoromalonate, but in a very low yield of ca. 5%. N-F amine 1-1 is very volatile (bp 49.5 °C), and could only be prepared in 7.5% or 13% yield by electrochemical

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

• silica are suggested to play a key role in the water elimination step. Furthermore, the primary amine function on the silica shows better outcomes compared to a tertiary amine. Different products were prepared in moderate to excellent yields, however, with the less acidic diethyl malonate the catalyst

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• presence of a catalytic amount of piperidine afforded pyridopsoralen 22 in 46% yield. Analogously, pyridopsoralen 23 was prepared from 16 by Knoevenagel condensation with diethyl malonate and subsequent lactonization with 62% yield (Scheme 4) [13]. To the best of our understanding, the scaffolds 21–23 are

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

• first time reported a microwave-assisted four-component domino reaction involving acyclic 1,3-diketones 54, amines 32, diethyl malonate (126) and triethyl orthoformate (111) for the synthesis of substituted pyridone derivatives 127 at 120 °C under catalyst- and solvent-free conditions. The reaction

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

• transformation into a C–C bond. Compounds containing electron-withdrawing groups such as malonitrile, dimedone, ethyl cyanoacetate and diethyl malonate were used as C-nucleophiles. Transformations were performed in DMF in the presence of NaH and the products were obtained in high yields (Scheme 6). The lower

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• third bands in between the spectra in water and in those with the conjugate Dex-1b solution [37]. The I1/I3 of pyrene was 1.1 in water, while in the conjugated dextran solution it was 1.5, a value which is comparable with solvents like diethyl malonate, dioxane, or dimethoxyethane, all organic solvents

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

• Ilya V. Taydakov and
• Mikhail A. Kiskin

Beilstein J. Org. Chem. 2020, 16, 1863–1868, doi:10.3762/bjoc.16.153

• General and Inorganic Chemistry, Russian Academy of Sciences, Leninskiy prospect, 31, Moscow, GSP-1, 119991, Russian Federation 10.3762/bjoc.16.153 Abstract Diethyl 2-(perfluorophenyl)malonate was synthesized in 47% isolated yield by the reaction of sodium diethyl malonate and hexafluorobenzene. The

• readily accessible compound. Diethyl 2-phenylmalonate (4) is usually obtained (Scheme 1) by condensation of ethyl phenylacetate (5) and diethyl carbonate under basic conditions [22] because of the low reactivity of bromobenzene in noncatalytic nucleophilic reactions with sodium salts of diethyl malonate

• literature [25]. The target compound was obtained by the reaction of diethyl malonate, NaH and C6F6 in DMF for 5 h under reflux. This method was modified by Vlasov et al. [26], then NaH was replaced [27] by anhydrous K2CO3 and the reaction temperature was decreased [28] to 60 °C (Scheme 2). Although the

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• ) [19], N-methyl-2-pyridone 7 (δ 139.5) [20], 2,4-dimethoxy-3-methylquinoline (8, δ 147.0) [21], and 2-methoxypyridine 9 (δ 147.2) [22] supported a 2-quinolone form 1 but not 2-quinolinol 2 (Figure 2, Table 1). The same structure was synthesized from diethyl malonate and aniline (see Supporting

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• between diethyl malonate and nitrostyrene to afford only one of the two (S)-11 and (R)-11 enantiomers, depending on the redox state of the copper center. The reaction was run with a 5 mol % catalyst loading and a base (Et3N) and was compatible with different solvents (THF, MeCN, CH2Cl2 and hexane

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• monochloroacetic acid have been published. The production of basic building blocks like glycine [5] (>600 000 tons/year in China in 2015) and diethyl malonate from monochloroacetic acid show the value of this compound as a starting material. Many reactions with monochloroacetic acid, including the synthesis of

• glycine and diethyl malonate, are based on nucleophilic substitution of the chlorine [6][7][8][9][10]. In an attempt to find new synthetic applications of monochloroacetic acid we turned our attention to photoredox catalysis. We were inspired by the rebirth of visible light photoredox catalysis, induced

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• (25%) were obtained (Table 2). In pure CH2Cl2 as solvent there was only a small conversion, but no product 14 detectable. Only the debrominated diethyl malonate was identified as side product. This makes conclusively clear that the solvent DMF is needed for this type of photoredox reaction. The

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• oxidative conditions has been developed. The employment of Mn(OAc)3·2H2O or KMnO4 as stoichiometric oxidants allowed the use of a wide range of nucleophiles, such as nitromethane, (aza)indoles, pyrroles, phenols, pyrazole, indazole and diethyl malonate. The formation of the target compounds presumably

• diethyl malonate, providing compounds 14a–c in 40–58% yields. To conclusively reveal the scope of the reaction, we exploited N-cyanomethyl quaternary salts of fused thieno[2,3-c]pyridine 15 and 1-methyl-6-azaindole 16 in this transformation. Therefore, annulated chromenoimidazoles 17–20 were effectively

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

• Scientifique, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France Université Paris Descartes, Sorbonne Paris Cité, 12 rue de l'École de Médecine, 75006 Paris, France 10.3762/bjoc.14.264 Abstract We have explored here the scope of the age-old diethyl malonate-based accesses to α-amino esters involving Knoevenagel

• condensations of diethyl malonate on aldehydes, reductions of the resulting alkylidenemalonates, the preparation of the corresponding α-hydroxyimino esters and their final reduction. This synthetic pathway turned out to be general although some unexpected limitations were encountered. The synthetic

• led us to require a large variety of α-amino esters as starting material. In view of the limitations we encountered in the use of ethyl nitroacetate to reach such variety [2], we have focused here on diethyl malonate-based methods as an alternative. Indeed, as we reviewed recently [3], this approach

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

• al. [102] reported a protocol for the efficient synthesis of pyrazolo[1,5-a]pyrimidine-5,7-dione (150) by the reaction of 5-aminopyrazole (126) with diethyl malonate (149). Pyrazolo[1,5-a]pyrimidine-5,7-dione (150) was chlorinated to give 5,7-dichloropyrazolo[1,5-a]pyrimidine (151) which subsequently

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• ), C12–O3 1.3386(18), C11–C12 1.3687(19), C11–C14 1.450(2) Å) clearly indicate the enolic form of the compound. The reaction of 1 with less acidic diethyl malonate required the addition of 1 equivalent of Et3N. In this case product 13 was isolated in 78% yield (Table 1, entry 8). Again, due to the

• without added base while in case of diethyl malonate (pKa(H2O) 13.3) and TNT (pKa(H2O) 13.6) the addition of one equivalent of Et3N is required. In the latter case the formation of the adducts proceeds through the attack of the anion on C7. All other CH acids used exist mainly in enol form in polar

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• Stabilized enolates and their equivalents are the most studied C-nucleophiles in Michael addition reactions with nitrosoalkenes. A first systematic study in this area was done by Ohno and co-authors [13][23], who reported the addition of diethyl malonate and acetylacetone anions to cyclic nitrosoalkenes

• NSA1a–c generated from the corresponding α-chloroketones (2-chlorocyclohexanone oxime (1a), 2-chlorocyclooctanone oxime (1b) and 12-chloro-сyclododeca-4,8-dien-1-one oxime (1c)) upon the action of an excess of nucleophile (Scheme 2). It was found that oximes 1b and 1c react both with diethyl malonate

Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane

• Riccardo Porta,
• Alessandra Puglisi,
• Giacomo Colombo,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2016, 12, 2614–2619, doi:10.3762/bjoc.12.257

• obtained in quantitative yield as a clean product with no need for purification. We also investigated the continuous-flow reduction of nitro ester 5, which can be conveniently prepared in one step through the organocatalyzed addition of diethyl malonate to trans-β-nitrostyrene promoted by a chiral thiourea

Et₃B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

• Ahlem Abidi,
• Yosra Oueslati and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2402–2409, doi:10.3762/bjoc.12.234

• further used as synthetic intermediates in numerous synthetic routes to heterocyclic compounds and molecules of biological interest [41][42]. Results and Discussion We first investigated the allylation of diethyl malonate (2a) with the allylic alcohol 1a in DMF in the presence of Pd(OAc)2 (10 mol %), PPh3

• , carried out in DMF at 80 °C, gave a better result (30% yield in 12 h), using, in addition to NaH (0.5 equiv), 1 equiv of Et3B (Table 1, entry 3). Moreover, a remarkable improvement in yield (60% in 6 h) was also observed for the allylation of diethyl malonate (2a) with the MBH alcohol 1a using an excess

• of Et3B (3 equiv) and 1 equiv of NaH (Table 1, entry 4). Mechanistic considerations Scheme 1 illustrates the most probable catalytic cycle for the allylation of diethyl malonate (2a) with allyl alcohol 1a. We assume that there is first an activation of 1a through its conversion into I1 using Et3B [29

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• first tested in the reaction of trans-nitrostyrene (1a) with diethyl malonate (2a), leading to the enantioenriched addition product 4aa with a single stereocenter. In order to the creation of two tertiary-quaternary contiguous stereocenters (5aa) we also used ethyl 2-oxocyclopentanecarboxylate (3a) as

• of nucleophile and 10 mol % of catalysts (entries 1–4 and 9–11 in Table 1). As a general trend, the reactions were faster, and much more stereoselective for ketoester 3a than for diethyl malonate 2a, and that the difference was specially remarkable when supported ethylenediamine-derived thioureas II

• next consider the reaction of some 4-substituted nitrostyrenes (1b–d) with diethyl malonate (2a), and the addition of a range of β-functionalized nucleophiles 2b–g to 1a promoted by supported catalysts IV (5 mol %) and V (2 mol %), respectively (Scheme 2 and Table 2). The results obtained in the