Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• -flow configurations demonstrate superior safety and efficiency. While the synthetic significance of nitration is underscored by the broad utility of nitro derivatives, persistent technical challenges including regioselectivity control, over-nitration phenomena, and substrate oxidation side reactions

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

• compounds are better leaving groups than diesters or nitro derivatives in this type of transformation. Another possible explanation is that Michael adducts other than 1,5-dicarbonyl compounds require more robust bases to shift the equilibrium toward the retro-Michael product. It is essential to highlight

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

• sunlight (especially on adsorbents), and basic dipolar solvents (DMSO, for example, causes rather rapid degradation) [23]. Note that nitro derivatives 10 or 11 are not formed when base 5 is kept in nitric acid (25 °C, excess of 65% HNO3, 24 h) which returns the starting compound unchanged. After that step

• -stacking of almost planar diazaarene fragments, leading to pronounced supramolecular aggregation. Although dipyridoacenaphthene does not undergo nucleophilic amination and dehydrogenation under a wide range of conditions, its 5(8)-nitro derivatives can be transformed under mild conditions into the

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• aromatic nitro derivatives 3 and 6 proceeds through the corresponding hydroxylamines, capable of intramolecular cyclization to products 4 or 7. Fortunately, under Zn/AcOH reductive conditions this was resolved by extending the duration of the reaction to 18–24 h, providing enough time for compounds 4/7 to

Synthesis, structure, and properties of switchable cross-conjugated 1,4-diaryl-1,3-butadiynes based on 1,8-bis(dimethylamino)naphthalene

• Semyon V. Tsybulin,
• Ekaterina A. Filatova,
• Alexander F. Pozharskii,
• Valery A. Ozeryanskii and
• Anna V. Gulevskaya

Beilstein J. Org. Chem. 2023, 19, 674–686, doi:10.3762/bjoc.19.49

• and 6b·HBF4. Since the UV–vis spectra of salts 11 are similar (even and especially in cases of methoxy and nitro derivatives 11e and 11b), it can be assumed that in all salts 11 the electron transfer from the terminal aryl to the central naphthalene rings takes place. Naturally, the more deficient the

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• solvent composition. In a very early 1927 study [4] of the solvolyses of benzenesulfonyl chloride (C6H5SO2Cl) and its p-methyl and m-nitro derivatives, solvolyzing in 50% acetone/50% water (v/v) at 25.0 °C, it was found that the differences in specific rates were quite small, at 0.0106 min−1 for the p

• % dioxane/70% water at 20 °C, we can, for the parent benzenesulfonyl chloride and for the p-methyl and p-nitro derivatives, abstract the specific rate data from Table 1 of the publication. The Hammett treatment using appropriate substituent constants leads to a Hammett ρ value of +0.35 with the p-methyl

• (1961–1971), Hambly and co-workers, published a series of eight papers (Solvolysis of Sulfonyl Halides, Parts I through VIII) [16][17][18][19][20][21][22][23]. In the initial study [16][17] of the solvolysis of the parent benzenesulfonyl chloride and the p-methyl, p-bromo-, and p-nitro derivatives in

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• reproducible protocol to isolate the product without the use of any organic solvent was established, and the recyclability of the DES mixture was successfully investigated. Keywords: alternative solvents; atom economy; DES; nitro derivatives; reduction; Introduction The search for alternative solvents, not

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• 5.7–6.4 (series 5), 5.3–5.9 (series 6), and 5.0–5.5 ppm (series 7), except for the nitro derivatives (R1: 5-NO2) where the nitro group always enhances the Ar–H4 chemical shift by about 0.7 ppm. Therefore, a 2D-NOESY experiment was performed for some representative 5-NO2 derivatives (5eb–ed) confirming

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• (Scheme 1). Exposing the standard substrate 1 to the general reaction conditions furnished the desired product 2 in a synthetically useful isolated yield of 60%. Introduction of para-substituents was tolerated enabling formation of the chloro, methoxy, and nitro derivatives 3–5 with up to 54% yield. The

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• asymmetric products 131 is mainly obtained, where the aromatic group coming from the boronic acid partner settles far from the carbonyl group. Methoxy, nitro, chloro and acetoxy groups of the aromatic moiety can be located at the ortho, meta and para positions, although 2-nitro derivatives gave low yields or

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• several aminated steroids in the literature, but the efficient generation of a C(sp2)–N bond on the aromatic ring A of estrone derivatives still remains a challenge. Aminoestrones substituted at C-2 or C-4 are mainly produced by the reduction or hydrogenation of the corresponding nitro derivatives [5

Electrochemical Corey–Winter reaction. Reduction of thiocarbonates in aqueous methanol media and application to the synthesis of a naturally occurring α-pyrone

• Ernesto Emmanuel López-López,
• José Alvano Pérez-Bautista,
• Fernando Sartillo-Piscil and
• Bernardo A. Frontana-Uribe

Beilstein J. Org. Chem. 2018, 14, 547–552, doi:10.3762/bjoc.14.41

• ]. With thiocarbonates 4 and 6 in our hands, their electrochemical behavior was studied in the MeOH/H2O media previously described (Figure 1). This mixture of solvents has been used for the electrochemical preparation of anilines, hydroxylamines and nitroso compounds via the reduction of aromatic nitro

• derivatives [32][33], showing a convenient electrochemical window with graphitic electrodes (−1.75 to 1.25 V vs Ag/AgCl) and giving good environmental compatibility. Cyclic voltammetry of thiocarbonates 4 and 6 using a vitreous carbon electrode, showed two irreversible reduction peaks located at −1.18 and

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

• nitrosoacetals 3 are not halocarbonyl compounds as in the case of oximes 1 and 2, but aliphatic nitro derivatives, which are readily transformed into enamines 3 by double silylation involving an internal redox process [19][20][21]. This allows the preparation of nitrosoalkenes, which are difficult to access by

Nitration of 5,11-dihydroindolo[3,2-b]carbazoles and synthetic applications of their nitro-substituted derivatives

• Roman A. Irgashev,
• Nikita A. Kazin,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2017, 13, 1396–1406, doi:10.3762/bjoc.13.136

• formation of mono-nitro derivatives (at C-2 or C-6) from the same indolo[3,2-b]carbazoles has also been observed in several cases. Reduction of 2-nitro and 2,8-dinitro derivatives with zinc powder and hydrochloric acid has afforded 2-amino- and 2,8-diamino-substituted indolo[3,2-b]carbazoles, while

• NMR spectra of nitro derivatives 9, while this singlet is observed at 8.01–8.04 ppm in the 1H NMR spectra of the starting aromatic compounds 8. We have demonstrated that mono C6-nitration of ICZ compounds 8a,b has afforded 6-nitro-ICZs 10a,b (Scheme 4). It has turned out that further nitration of 6,12

• [3,2-b]carbazoles has been obtained by using acetyl nitrate at a low temperature. Synthetic usefulness of the obtained nitro derivatives has been demonstrated by several examples. The nitro derivatives of the indolo[3,2-b]carbazole family can be considered as promising intermediates for further

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

• performed for the first time under continuous-flow conditions. Aromatic as well as aliphatic nitro derivatives were converted to the corresponding primary amines in high yields and very short reaction times with no need for purification. The methodology was also extended to the synthesis of two

• aromatic rings followed by reduction is the most classical entry for the preparation of anilines [1][2]. Lately, also aliphatic nitro derivatives have become more and more popular: a wide variety of highly functionalized and chiral aliphatic nitro compounds, precursors of the corresponding chiral amines

• tertiary amine generates in situ a dichlorosilylene species which is the actual reducing species [11]. Even though nitro derivatives are fundamental building blocks in organic synthesis, their application on a large scale is still quite limited because they are dangerous and potentially explosive chemicals

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• observed for all nitro derivatives due to the limited change of the piperazine chair conformation. Therefore, two coalescence points were determined and their resulting activation energy barriers were calculated using 1H NMR. To support this result, single crystals of 1-(4-nitrobenzoyl)piperazine (3a

• tosylate to yield compounds 5a,b in high yields of 87% and 81%, respectively. These derivatives can be utilized for both variants of the Staudinger ligation in addition to the classical and strain-promoted variants of the Huisgen-click reaction. For future radiolabeling procedures, nitro derivatives 4a and

• piperazines and to determine these energies, temperature-dependent NMR experiments [24] were performed for all nitro derivatives 3a, 4a, and 5a as well as for fluorine compound 3b. When monitoring compound 3a over a minimum range of 45 K, the four signals of the NCH2 groups gradually disappear and coalesce to

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• hypochlorite [58] or related electrophilic halogen precursors [59][60] may be used. However, most of these methods result in the formation of nitro derivatives along with the desired nitroso compounds. Relatively new methods for the conversion of nitroalkanes into geminal chloronitroso compounds involving

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38

• world production of nitric acid in 2012 is assumed to be close to 78 Mi TPA, of which 85% is used for the production of ammonium nitrate as fertilizer and 6% for production of nylon. The remaining 9% – that is about 8 Mi TPA – are used for the nitration of aromatics [7]. Nitro derivatives of aromatic

• the relevance of nitration for the dye and colorant industry covers more than a century. Nitro derivatives of the toluene diisocynate are employed in the manufacturing of flexible polyurethane foams, which are used in transformation, furniture, and carpet underlay. 2,4,6-Trinitrotoluene is a military

• and industrial explosive. Nitro derivatives of glycerine, urea and naphthalene also exhibit explosive properties. Some of the aniline based dyes were used for medical applications, too. The extension of the aniline based medicines led to hundreds of drugs [11], which were used for medication during

Easy and direct conversion of tosylates and mesylates into nitroalkanes

• Alessandro Palmieri,
• Serena Gabrielli and
• Roberto Ballini

Beilstein J. Org. Chem. 2013, 9, 533–536, doi:10.3762/bjoc.9.58

• transform the nitro group into other functionalities, the obtained adducts can be employed as strategic starting materials for the preparation of more complex structures [12][13]. In this context, primary nitroalkanes are the most used nitro derivatives [3][4][5][14][15][16][17], and thus, their

Discovery of practical production processes for arylsulfur pentafluorides and their higher homologues, bis- and tris(sulfur pentafluorides): Beginning of a new era of “super-trifluoromethyl” arene chemistry and its industry

• Teruo Umemoto,
• Lloyd M. Garrick and
• Norimichi Saito

Beilstein J. Org. Chem. 2012, 8, 461–471, doi:10.3762/bjoc.8.53

• ) is formed when a diaryl disulfide is treated with an excess of chlorine in the presence of an excess of the alkaline metal fluoride. Janzen et al. reported that cis- and trans-phenylsulfur chlorotetrafluoride and its p-methyl- and p-nitro-derivatives were formed by reaction of diaryl disulfide with

Laterally substituted symmetric and nonsymmetric salicylideneimine-based bent-core mesogens

• Sonja Findeisen-Tandel,
• Wolfgang Weissflog,
• Ute Baumeister,
• Gerhard Pelzl,
• H. N. Shreenivasa Murthy and
• Channabasaveshwar V. Yelamaggad

Beilstein J. Org. Chem. 2012, 8, 129–154, doi:10.3762/bjoc.8.15

• -crystalline behaviour was not observed for either of the nitro derivatives H 3c or OH 3c, probably because the 5-position of the nitro group, which is at the top of the bent molecules, is sterically unfavourable in most cases. Generally, melting temperatures and phase-transition temperatures of isophthalic

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• % aqueous sulfuric acid a rearrangement to furnish a mixture of the 3- and 5-nitro derivatives occurs, which unfortunately at this stage, could not be separated by crystallisation. However, when this mixture was subjected to catalytic hydrogenation with Raney nickel a separable mixture of the corresponding

Michael-type addition of azoles of broad-scale acidity to methyl acrylate

• Sławomir Boncel,
• Kinga Saletra,
• Barbara Hefczyc and
• Krzysztof Z. Walczak

Beilstein J. Org. Chem. 2011, 7, 173–178, doi:10.3762/bjoc.7.24

• of various azoles to α,β-unsaturated carbonyl and nitro derivatives has been frequently exploited in the synthesis of precursors of biologically active compounds [3][7][8][9][10][11][12][13][14][15]. This reaction, although structurally restricted to α,β-unsaturated carbonyl compounds and their

• (pKa range from 8.93 to 15.1) including imidazole and its 2- and 4(5)-methyl, 4(5)-nitro-, 2-methyl-4(5)-nitro- derivatives as well as with 1,2,4-triazole, there was no evidence for a regioselective course of the reactions. Furthermore, extremely high acidic azoles, which are substrates for many

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• ], unlike dialkyl disulfides [130][131] the yields generally do not exceed 40% (except for nitro derivatives 4-NO2 – 58%, 2-NO2 – 72%). The preliminary breaking of the S–S bond can be carried out very mildly and selectively [9], without affecting other functional groups (Scheme 39