C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• carbocyclization with diethyl malonate, yielding fluorinated pyrroloquinazolinones in acceptable to high yields [11]. The reaction was conducted in an undivided cell with a carbon cloth anode and a platinum (Pt) cathode, using K2CO3 (10 mol %) as the base, Ir(ppy)3 (3 mol %) as the photocatalyst, and an equivalent

• plausible mechanism for the electrochemical radical cyclization is proposed in Scheme 18. Initially, a diethyl malonate radical A is generated through a proton-coupled electron-transfer (PCET) process at the anode, with the aid of K2CO3. This radical then adds to the C=C bond, forming alkyl radical

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• reacted with deprotonated diethyl malonate to obtain compounds 36 and ent-36 in 95 and 92% yield, respectively, over two steps from 34 and ent-34. The diols 28 (85%) and ent-28 (90%) were isolated after reduction of their parent malonates 36 and ent-36 using LiAlH4 in ether. Following several experiments

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• enolate of diethyl malonate yielded (S)-2-(hex-5-en-2-yl)malonate ((S)-6), and realized a stereospecific inversion of chiral secondary tosylate (R)-5 [30][31]. The geminal ester (S)-6 was next treated with NaOH in methanol to afford (S)-2-(hex-5-en-2-yl)malonic acid ((S)-7) in 96% yield [32]. Then

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• with enals having an aliphatic substituent in the β-position (entries 8 and 9, Table 5). The resolution of Michael adducts 14 and 15 derived from dimethyl and diethyl malonate has also been studied (Table 5, entries 14 and 15). Unfortunately, the retro-Michael reaction did not take place under the

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• indicated DMSO as the best for the attainment of high yields and diastereoselectivity (entries 1–5 vs 6 in Table 4), we further examined bases in this solvent to find out that t-BuOK behaved nicely, and the reaction of 2b with 2.0 equiv of diethyl malonate for 0.5 h at room temperature furnished 93% yield

• , the isolated inseparable mixture of anti,syn-7a and -7b by the reaction of 2b and diethyl malonate was treated with an equimolar amount of DBU in DMSO (rt, 3 h) to furnish products which were identical to the ones obtained in entries 8 or 9 (Table 4). The relative stereochemistry of the isomerized

• of the active hydrogen in DMSO: 13.3 [52]), nitromethane (17.2 [53]), ethyl (diethylphosphono)acetate (18.6 [52]), malononitrile (11.1 [53]), ethyl 2-nitroacetate (9.1 [54]), ethyl 2-cyanoacetate (13.1 [55]), and diethyl malonate (16.4 [56]) all failed to afford the desired addition products. From

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• . Addition of relatively weak H-donors such as diethyl malonate significantly increases the reduction current of S3 and shifts the potential value for 30 mV toward positive potentials (Figure 1b). In the reverse scan, a new peak appears, corresponding to oxidation of the malonate anion [23]; the peak of the

• useful compounds with multiple functionalities that were poorly available previously. CV curves for salt S2 and corresponding amine A2 (left, Figure 1a) and salt S3 with and without diethyl malonate additives (right, Figure 1b). (Pt, MeCN, 0.1 M Bu4NBF4, 0.1 V/s, vs Ag/AgCl, KCl(sat.). CV curves for

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