Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• . Quinazolinones 10 can be synthesized from substituted acetophenones and aromatic amines (Scheme 11) [44]. On the other hand, diarylpyridines 8, 9, and 11 can be obtained from acetophenones, but using aliphatic amines or ammonium formate as the nitrogen source [42][43]. In all these cases, the activation of DMSO

• ][73]. Hexamethylenetetramine In Ugi-type isocyanide-mediated reactions, the formation of an imine from the amine and the carbonyl component is a crucial step that, and when hampered, strongly affects the outcome of the entire process. In general, the imine readily forms when aliphatic or aromatic

• amines and carbonyl components are used. However, when ammonia and formaldehyde are employed, side reactions are favored leading to low yields or even to no Ugi product at all [81][82]. Rosalba et al. showed that HMTA (hexamethylene tetramine) can be used as a formaldehyde surrogate to generate

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

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

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• ). Apparently, for the realization of the presented condensation, the nucleophilicity of the aromatic amines is not sufficient. Wherein, the type of substituent in the aroyl fragment of furanone 1 doesn’t influence the result of this reaction. Thus, enamines 4 can be synthesized only using active aliphatic

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• conditions in hands, the scope of the reaction was investigated by using various MBH nitriles of isatins and aromatic amines in the reaction. The results are summarized in Scheme 1. All reactions proceeded smoothly to give the expected allylic SN2-substituted products 3a–i in satisfactory yields. Aromatic

• spectroscopy techniques. In order to show the universality of the substitution reaction, MBH maleimides of isatins 4 were also employed in the reaction. In the absence of any base as promoter, the reaction of MBH maleimides of isatins with various aromatic amines in toluene at 65 °C gave the expected

• amines with various substituents could be employed in the reaction to give the expected products. N-Methylaniline and n-butylamine were also successfully converted to the desired products 3h and 3i in 72% and 63% yields, respectively. The structures of compounds 3a–i were fully characterized by various

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• the product are accessible by adjusting the two distinct chiral catalysts. C–N Bond formation In 2018, Mei et al. developed the electrochemical C–H amination of arenes with amine electrophiles using copper catalysis, which provided a step-economical approach for the synthesis of aromatic amines by

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• , secondary aliphatic or aromatic amines and thiols in the presence of catalytic Cu(OTf)2 (1 mol %) in aqueous media was proven to be a sustainable procedure to access thioaminals 5, avoiding high temperatures and/or hazardous reagents required by classical conditions (Scheme 4) [18]. The 1,2

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• importance of hydrogen on the amino or hydroxy groups, supposedly through the bonding with the catalyst. Substitution of these groups or their hydrogens led to either halted reaction or significantly reduced enantiopurity of the products. Expanding the scope of available azodicarboxylates 77 and aromatic

• amines 76 in the C–H amination reaction with CPA C25, the authors were able to prepare axially chiral para-amination products 78 (Scheme 25) [49]. Such amination products 78 were prepared with high levels of yields and showed remarkable enantiomeric purities. Interestingly, when a phenyl substituent was

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• : oxidation; 6-methyluracil; peroxydisulfate; phthalocyanine catalysts; pyridine; Introduction The Elbs and Boyland–Sims peroxydisulfate oxidation reactions offer a convenient means of introducing the hydroxy function into phenols and aromatic amines [1]. The oxidation of phenol using peroxydisulfate was

• first demonstrated by Karl Elbs in 1893 [2], with E. Boyland later expanding this reaction to include aromatic amines [3]. Concurrently, the successful oxidation of several pyrimidine derivatives was also reported [4]. Since then, the reaction has been extensively researched on various classes of

• reactions was made. It has been suggested that a nucleophilic substitution of the peroxide oxygen atom occurs in peroxydisulfate [32]. Regarding phenols (Elbs reaction), there is also a nucleophilic substitution of the phenolate ion. For aromatic amines (Boyland–Sims reaction), a neutral nitrogen atom of

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

• regioselectivity, with 3,4-fused pyrazoles being accessible when cyclic β-oxodithioesters are employed as substrates. However, aromatic amines cannot be successfully employed in the sequence. Alkenoyl derivatives as key intermediates The Michael addition and cyclocondensation of hydrazines and α,β-unsaturated

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• aromatic amines (Scheme 34). The GBB-like multicomponent reaction was carried out under MW heating. The initial condensation of the three precursors was catalyzed by I2, providing electron deficient ketoimines 108. The intermediates 108 underwent intramolecular heterocyclization to furnish the fused

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

• , azomethines based on aromatic amines and substituted pyrrolecarbaldehyde [40] or pyrrolyl-β-chlorovinylaldehyde [39], contain several frequently encountered motifs in drugs and drug candidates – a pyrrole heterocycle and an azomethine C=N fragment (Figure 1) – and exhibit some biological activity. Thus, Ugi

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• strategy with aromatic amines [24], pyrrole-2-carboxylic acid and N-phenylglycine, and carried out their reactions with arylglyoxals, alkylamines and isocyanides (Scheme 5). As we expected, the cyclization product 9 was observed, although the complete cyclization of the Ugi adduct, found as the enol

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

• % yields. Finally, when we switched our attention to the generality of primary aromatic amines such as aniline or secondary amines such as dibenzylamine, it was found that only the starting materials were recovered after work-up of the reaction mixture. The structure of 2-benzyl N-substituted anilines 4

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• 2,5-furandicarboxylic acid (FDCA), a monomer used for biopolymer production [61]. Other modifications include the use of ortho-substituted aromatic amines as a base in the Cannizzaro reaction and others (Figure 2) [62]. The synthesis of several useful molecular entities [63][64] and synthons of

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

• generation of manganese PNP pincer complexes for the N-methylation of aromatic amines with methanol [35]. Various primary anilines were methylated selectively with good yields using Mn2 (2 mol %) and t-BuOK (0.5 equiv) as a base at 100 °C for 16 h (Scheme 4). Compared to their previous report, the N

• temperature [41]. The coupling of several aromatic amines with aliphatic and benzylic alcohols was studied with bis-NHC-manganese complex (Mn6). A catalyst loading of 1.5 mol % in the presence of t-BuOK (1 equiv) at room temperature produced the corresponding N-alkylated amines with 40–93% yield (Scheme 11

• loading (0.5 mol %) and mild reaction conditions (60–100 °C) were employed for this transformation. Aromatic amines gave good yields with benzyl alcohol at 60 °C, but 1,1-phenylethylamine, linear aliphatic amine and benzylamine required 100 °C to achieve the good yields (Scheme 12). Similarly, the N

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• probes, organic light-emitting diodes, and organic solar cells [2][7][8][9]. The principal way for the preparation of these heterocycles involves the coupling of 3H-phenoxazin-3-ones with variously functionalized aromatic amines. This is followed by the cyclization of the initially formed adducts [10][11

• formation [6]. In turn, without an acidic catalyst, it is driven by the distribution of the electron density (Figure 1), such that the nucleophilic attack occurs at the most electrophilic C(2) center. With this in mind, we presented a convenient procedure for the SNH reaction of aromatic amines with

• -di-tert-butyl-2-(arylamino)-3H-phenoxazin-3-ones 4. 6,8-Di-tert-butyl-2-(arylamino)-3H-phenoxazin-3-ones 4 prepared by the one-pot reaction between 6,8-di-tert-butyl-3H-phenoxazin-3-one (1) and aromatic amines 2b (the yield is given in parentheses). Synthesis of 14H-quinoxaline[2,3-b]phenoxazines 5

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• Cu···Cu distance of ca. 2.3 Å was detected in these complexes. In 2017, Romanov et al. synthesized a series of amido and (phenolato)Cu–NHC complexes from the reaction of (AdL)MCl (M = Cu, Au) with phenols, thiophenols, or aromatic amines in the presence of NaOt-Bu at rt in anhydrous THF (Scheme 30

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• ]. Further, a few reports are also available for the copper and palladium-catalyzed N-arylation of primary and secondary aliphatic as well as aromatic amines using diaryliodonium salts as aryl sources [33][34][35] (Scheme 1a). Similarly, iodonium ylides undergo a wide range of reactions through in situ

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• and co-workers [57] synthesized various N-substituted pyrrole derivatives 9 using the Clauson–Kaas reaction to study their structure–reactivity relationship (SRR). These compounds were synthesized in 15–90% yields from the reaction between various aliphatic and aromatic amines 8 and 2,5-DMTHF (2) in

• (P2O5) as a catalyst for the conversion of various aliphatic amines, aromatic amines, sulfonamides and primary amides into N-substituted pyrroles (Scheme 5). These pyrroles were synthesized in 46–100% yields by the modified Clauson–Kaas reaction between amines 10 and 2,5-DMTHF (2) in the presence of

• their expectation thus, they synthesized 13 derivatives of pyrroles in good yields in short reaction times (10–45 min). It has been observed that aromatic amines and amides take a longer time compared to the primary amines and sulfonamides. In another study, Rochais et al. [59] reported in 2004 the

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• unfavorable (DABCO, quinuclidine) and in the case of triarylamines containing no hydrogen atoms at carbon atoms connected to the cation radical center. Cation radicals of aromatic amines or N-heterocyclic cation radicals are usually involved in electron transfer processes due to their low affinity to hydrogen

• site-selectivity of CH-functionalization. Important advantages of this organocatalyst family are synthetic availability and activity tuning by variation of substituents. In contrast to the aliphatic amine cation radicals which typically abstract H-atoms, the cation radicals of aromatic amines are used

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• mechanochemical conditions are presented. The two methodologies exhibit complementary features as they enable the derivatization of aliphatic and aromatic amines. Keywords: acetamides; formamides; mechanochemistry; N-formylation; p-tosylimidazole; Introduction The preparation of N-formylated and N-acetylated

• hand, the methodology was successfully applied to the synthesis of several formamides starting from a series of aromatic amines (Scheme 1). The N-formyl derivative 3 was prepared in good yields as well as formanilides bearing halogen substituents, which were well tolerated (Scheme 1, products 4 and 5

• -formylation reaction of several aromatic amines. On the other side, p-Ts-Im, activated by the acid reagent, proved an efficient activating agent under mild mechanochemical conditions for the formylation and acylation of those amines with less marked or limited (see protonated aliphatic amines) reactivity

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• synthetic method showed very limited substrate scope. Only less bulky primary amines underwent the first aza-Michael addition and then intramolecular nucleophilic substitution. However, aromatic amines, aniline, 2,3-dihydro-1H-inden-4-amine, and the bulky aliphatic primary amine adamantylamine did not

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• constructing C–N bonds are in high demand in organic synthesis since nitrogen-containing organic compounds are widely used in biologically active substances [1], multifunctional materials [2][3], and metal ligands [4][5]. Among them, the synthesis of aromatic amines has been important to researchers in recent

• (reaction 3) [27]. Herein, we report a method for the construction of aromatic amines via the copper-catalyzed intermolecular radical amination of arenes with N-hydroxyphthalimide (NHPI) under air. Results and Discussion Initially, N-hydroxyphthalimide (NHPI, 2a) was reacted with benzene, catalyzed by CuBr

• envisaged that this work will provide a simple amination strategy for synthesizing aromatic amines. Experimental All new compounds were fully characterized. 1H NMR and 13C NMR spectra were obtained with Agilent Technologies AVANCE-400 MHz or 600 MHz spectrometers in CDCl3 as the solvent with TMS as an

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• acid. The next step of our investigation was the two-step synthesis of persubstituted aminopyrazoles 5 upon reaction of the benzotriazolyl derivative 2c with primary, secondary, aliphatic, or (het)aromatic amines (first step) and successive reaction of the obtained dienes 4 with 7-chloro-4

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• primary amines 1 afford an excellent yield. Ortho-, meta-, and para-substituted aromatic amines with both electron-donating and -withdrawing groups were used in this protocol. Aromatic amines with electron-donating groups offered a slightly higher yield compared to those with electron-withdrawing groups

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• addition, several authors concluded that this was a good method for analytically determining low levels of activated aromatic amines in drugs. This method continued to be used over the years and was subsequently optimized by a spectrophotometric determination technique coupled with continuous flow [55]. In

• highlights some important drugs containing primary or secondary amino groups in capsules, tablets, powders, formulations, formulations of associated drugs, injection formulations, and biological fluids [42][58][59][60][61][62][63][64][65][66][67][68][69]. β-NQS reacts with aliphatic and aromatic amines

• position C4 provides 26 (Scheme 4). The same group developed reaction conditions using different hydrophilic solvents to synthesize unsymmetrical 2-amino-4-imino compounds 28 from 27 in good yields by employing primary aromatic amines (Scheme 5) [78]. Ortiz and co-workers [79] performed several reactions