N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• synthesis of indirubin-N-glycosides containing the carbohydrate moiety located at the amide-type nitrogen. Isatin-N-glycosides 16 were used as key building blocks. The reaction of ʟ-rhamnose (4c) with aniline afforded N-glycosyl aniline 4d which was acetylated to give 4e (Scheme 12) [22]. The AlCl3-mediated

• pivaloyl-protected N-glycosyl anilines also proved to be unsuccessful, which pointed to steric reasons. Therefore, we studied in our group the use of the less sterically hindered formyl instead of acetyl or pivaloyl protective groups. The reaction of glucose (22a) with aniline afforded anomerically pure N

• -glycosyl aniline β-22b which was formylated to give 22c in 74% yield (Scheme 16) [24]. Product 22c resides as a mixture of α- and β-anomers, because an anomeric equilibrium was activated during the acid-mediated formylation. The cyclization of 22c with oxalyl chloride, carried out under forcing conditions

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• , a secondary aniline only furnished traces of the expected product. Aliphatic aldehydes also failed to deliver the multicomponent adduct. Conclusion In conclusion, we have shown in this work that alkyl bromides can be used instead of alkyl iodides in a direct zincation–multicomponent organometallic

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• the presence of gaseous hydrogen sulfide, the aryl azide is reduced to an aniline functionality and luminescence is restored [11]. Drawing our previous findings and insights from the work of Hou, Wu, and co-workers [21], we postulate that gaseous H2S is interacting with the [Tb.1·3Cu]3+ complex as it

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• reacts with an isocyanide and an electron-rich aniline in a three-component Ugi-type reaction to give an α-aminoamidine. This compound might undergo an additional visible light-mediated oxidation to furnish a second iminium intermediate, which acts as electrophile in an intramolecular electrophilic

• , our plan provides: the oxidation of N-aryltetrahydroisoquinolines (N-Ar-THIQs) generating in situ the iminium ions 1, the 3C Ugi-type reaction of an electron-rich aniline, an isocyanide and 1; the subsequent oxidation of the Ugi-type product 2; and the final cyclization to give the spiro[indole-THIQs

• . However, the synthetic protocol presents some limitations: employing non-electron-rich anilines (such as aniline or p-methylaniline) the reaction was unsuccessful, and the desired spiro-compounds were not obtained. To deeply investigate this point, we carried out the synthetic procedure with p

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• aliphatic substituents at the ring nitrogen atom. Besides that, we managed to perform the investigated reaction using the corresponding aniline derivative 4r. It should be mentioned that in this case the considered recyclization proceeded in lower yield comparing with other amides and was accompanied by

Anion-dependent ion-pairing assemblies of triazatriangulenium cation that interferes with stacking structures

• Yohei Haketa,
• Takuma Matsuda and
• Hiromitsu Maeda

Beilstein J. Org. Chem. 2024, 20, 2567–2576, doi:10.3762/bjoc.20.215

• closure with aniline requires a base as reported by Laursen et al. [26], whereas 2,6-dimethylaniline in this study was reacted without the use of a base. This can be explained by the high nucleophilicity of 2,6-dimethylaniline, though it is sterically hindered. As counteranions affect ion-pairing

• -dimethylaniline (7.0 mL, 59 mmol) and tris(2,6-dimethoxyphenyl)methylium as a Cl− ion pair [22] (504 mg, 1.09 mmol). The Schlenk tube was placed in an oil bath and was heated from rt to reflux over a period of 30 min. The reaction mixture was allowed to reach rt, and then the aniline was removed by short silica

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• nitrogen-centered radical (Scheme 37). 1.3.4 Ru-assisted anodic oxidation. A ruthenium electrocatalyzed mono- and diacetoxylation of aniline derivatives via a C(sp2)–H functionalization was developed by Zhong and coworkers [51]. This transformation requires the presence of a removable directing group

• bonded to the nitrogen atom of the aniline substrate. The methodology showcases a broad scope for carboxylic acids and demonstrates multiple examples of LSF of pharmaceuticals and natural products. The proposed mechanism begins with the formation of Ru(II) diacetate through ligand exchange between the

• carboxylate substrate and [Ru(p-cymene)Cl2]2. Subsequently, the Ru complex coordinates with the aniline substrate, followed by C–H activation to form a six-membered Ru species. The final product is generated through reductive elimination, releasing Ru(0), which is then reoxidized on the anode to regenerate

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• ) demonstrates the synthetic utility of the developed method. Keywords: aniline; benzannulation; condensation; 1,3-diketone; Hammett constants; terphenyl; Introduction The aniline moiety is omnipresent in the synthetic chemistry with applications ranging from building blocks to catalysis [1][2][3][4]. Among

• amines with different nucleophilicity, namely benzylamine (primary alkylamine), morpholine (secondary alkylamine) and aniline (aromatic amine). We first examined the reaction of 1,2,4-oxadiazole-1,3-diketone 1a (σm/σp 0.463/0.575, which is quite close to the constants of the CO2Me group, so a successful

• reaction was expected, Figure 2) with morpholine under previously found conditions (Scheme 2). To our delight, the meta-1,2,4-oxadiazole aniline 3ab, formed by the sequence of aldol-type reactions, was isolated in 80% yield and its structure was confirmed by NMR and single crystal X-ray analysis (CCDC

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• ) [43]. In parallel, Sheng and Zhang et al. found that 2-(1,3,4-oxadiazol-2-yl)aniline derivatives 38 could be electrochemically synthesized from isatins 35 and acylhydrazine 36. The transformation was carried out in an undivided cell at high temperature in DMSO using potassium iodide as supporting

• 38. As such, the iodide electrolyte served as an electromediator to both promote the decarboxylation process and protect the aniline product from overoxidation. Importantly, a control experiment without electricity but in the presence of molecular iodine instead proceeded smoothly, thereby confirming

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

• first attached to carboxylic acid functionalized DNA headpiece 7a (first reverse amidation). Next, the ester was hydrolyzed to obtain acid 9, and finally, a second reverse amidation with aniline afforded 10. Both the reverse amidation and the ester hydrolysis were performed following literature

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• have been successfully synthesised through a one-pot, three-component reaction involving N,N-dimethylbarbituric acid, an aromatic aldehyde and aniline. By utilizing readily available reagents, this approach opens up the opportunity for the efficient formation of a variety of 5-aryldeazaalloxazines

• various anilines and aromatic aldehydes with electron-donating groups or electron-withdrawing halogen atoms. However, the reaction yield was affected by the nature of the substituent on the aniline moiety. The results suggest that substrates bearing electron-donating groups on anilines have higher

• were recorded on Agilent Cary 8454 spectrophotometer at 25 °C in analytical-grade DMF. Absorption spectra were processed by using Microsoft Excel and Origin 2018 (OriginLab). Typical procedure for the synthesis of 5-aryldeazaalloxazines 2: An equimolar mixture (3.0 mmol) of the corresponding aniline 3

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• of p-CF3-substituted aniline when synthesizing bisamide 6d. The yield of the amide 10c was about 8% and it was also the first to precipitate. In addition, it is worth mentioning that the corresponding amides 10 were observed in 1H NMR spectra and LC–MS analysis in many mother liquors after filtration

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• . Heating 5 with hexylamine or aniline in refluxing acetic acid successfully led to the formation of the targeted aromatic diimides bearing either N-hexyl (7-Hex) or N-phenyl (7-Ph) substitutions in good yields. The same strategy was employed to create the imide-capped anthracenes 8-Hex and 8-Ph

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• % by condensing unsaturated ketones 84 with aniline under refluxing ethanol. These intermediates were then subjected to a reaction with excess mercaptoacetic acid (also known as thioglycolic acid) in refluxing benzene, resulting in the formation of spiro 1,3-thiazolidin-4-one derivatives with good

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• desired product. Compound 6 [51] was subsequently reduced to the corresponding aniline derivative 4 [52] in the presence of H2 and Pd/C (Scheme 1). The synthesis of diethyl (4-hydroxyphenyl)methylphosphonate (7) [53] started from [4-(benzyloxy)phenyl]methanol (8). Compound 8 was submitted to a

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• cyanoarenes is a straightforward and powerful method for the synthesis of primary amines [5], and the reduction of nitroarenes is useful for the synthesis of aniline derivatives [6][7][8][9][10][11]. Nitrogen-containing aliphatic heterocycles, such as piperidines and tetrahydroquinolines, are key motifs in

• due to the oligomerization of the substrate. Reduction of nitroarenes to anilines Next, we reduced nitroarenes using a PEM reactor. First, the electrocatalyst and solvent were optimized (Table 3). While 6.0 F mol−1 of electricity should be required for the reduction of nitrobenzene (4a) to aniline (5a

• more π-extended aniline was easily obtained in a high yield. Reduction of quinolines to tetrahydroquinolines The electrochemical reduction of quinolines was performed using a PEM reactor. First, several different cathode catalyst were examined for the reduction of quinoline (6a) (Table 5). Because 4.0

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• -(trifluoromethyl)aniline in conjunction with external ligand 5 facilitated the formation of a series of fluorinated α-amino acids. Xu and co-workers also disclosed a palladium-catalysed protocol for the fluorination of simple benzylic substrates bearing a bidentate directing group (Figure 8) [42]. Yields varied

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• additive-free synthesis of 2-benzyl N-substituted anilines from (E)-2-arylidene-3-cyclohexenones and primary amines has been reported. The reaction proceeds smoothly through a sequential imine condensation–isoaromatization pathway, affording a series of synthetically useful aniline derivatives in

• acceptable to high yields. Mild reaction conditions, no requirement of metal catalysts, operational simplicity and the potential for scale-up production are some of the highlighted advantages of this transformation. Keywords: aniline; (E)-2-arylidene-3-cyclohexenone; imine condensation; isoaromatization

• ; primary amine; Introduction Aniline derivatives possessing arylmethyl substituents at the ortho position are an important class of amines. They have a wide variety of practical applications, ranging from anti-depression [1], being δ receptor stimulants in analgesic pharmaceuticals [2], to antioxidant

Synthesis and physical properties of tunable aryl alkyl ionic liquids based on 1-aryl-4,5-dimethylimidazolium cations

• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2024, 20, 1278–1285, doi:10.3762/bjoc.20.110

• scalability [38][39][40][41][42]. The substituted imidazoles 1–9 were synthesized using a condensation reaction between the corresponding aniline and diacetyl monoxime (Scheme 1), since the condensation using diacetyl was not successful for electron-poor aniline derivatives. This reaction leads to the

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• Vishnu Selladurai Selvakumar Karuthapandi Department of Chemistry, School of Advanced Sciences, VIT-AP University, Amaravati-522237, Andhra Pradesh, India 10.3762/bjoc.20.105 Abstract This article describes the detailed analysis of the reaction between arylamines, such as aniline, o-anisidine

• polymerization, and solvent oxidation. For aniline and o-anisidine, predominant oxidative polymerization occurred, leading to the formation of the respective polyaniline polymers as major products. For methyl anthranilate, the oxidative polymerization was suppressed due to the delocalization of amine lone pair

• ]. This reaction comprises four main steps: (i) iodide-mediated aryl transfer from boronic acid to selenium dioxide, (ii) reduction of arylseleninic acid to diaryl diselenide, (iii) oxidation of diaryl diselenide to aryl selenenyl iodide with iodine, and (iv) electrophilic substitution of aniline

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• -alkylation of aniline with secondary alcohols required a high temperature (100 °C) compared to substituted benzylic alcohols (60 °C). Interestingly, this protocol was used to synthesize the drug cinacalcet, via alkylating the challenging benzylamine substrate under non-optimized conditions. Later, Madsen’s

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• conditions (200 °C and 80 bar CO) for 5 hours in the presence of catalysts such as Fe(CO)5, Ru3(CO)12, or Rh6(CO)16 [21]. The process was not selective because aniline derivatives and other byproducts were also formed; moreover, the substrate conversion, in some cases, was not complete (Scheme 8). In

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• also compatible with these mild conditions (4y–aa, 51–72%). Additionally, the diazo derivative of epiandrosterone was reactive in this protocol, giving the product 4ab in 59% yield. Delightedly, this procedure was successfully applied to aromatic amine (N-methylaniline), primary amine (aniline) and

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• presented in Scheme 5. As can be seen, the yields of the target compounds 4 vary from good to moderate per two steps of synthesis. The introduction of acceptor substituents in both the aniline and arylidene moieties of the DAS molecule leads to a decrease in the yield of the final spirocycle. The structure