Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• , Scheme 1A) belong to the 7-deazapurine family, which contain a pyrrolo[2,3-d]pyrimidine core. A rich pool of natural 7-deazapurine products has been identified, often (apparently) sharing a common biosynthetic pathway. Their functions are diverse; while some have been identified as having antifungal or

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• -d]pyrano[4,3-b]pyran-, furo[2',3':4,5]pyrano[3,2-c]chromene-, and furo[2,3-d]pyrimidine carboxylates were obtained from the reactions of alkyl 3-bromo-3-nitroacrylates with representatives of carbo- and heterocyclic CH-acids under simple conditions, without the use of organocatalysts. The structures

• furancarboxylates based on the interaction of alkyl 3-bromo-3-nitroacrylates [31] with carbo- and heterocyclic CH-acids of the naphthoquinone, pyran, and pyrimidine series. Results and Discussion We have proposed a synthesis of dihydronaphthofuran-3-carboxylates based on the interaction of alkyl 3-bromo-3

• 1a,b with pyrimidine-4,6-diols 2e–g. Supporting Information Supporting Information File 2: General synthetic procedures, characterization data and copies of IR spectra, 1H, 13C spectra of all synthesized compounds, as well as 1H-13C HMQC, 1H-13C HMBC spectra and the crystallographic data for

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• push–pull derivatives bearing electron-donating and electron-withdrawing groups at the para-position of the benzene rings are known to exhibit very fast thermal isomerizations [53]. Velasco and co-workers also reported that a pyrimidine-based azophenol exhibits thermal back reaction on the nanosecond

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• structure was obtained, revealing certain geometrical features. Keywords: 2-amino-substituted heterocycles; cyanoacetamide; Gewald reaction; multicomponent reaction (MCR); pyrimidine; Introduction The term “net-zero carbon” is becoming increasingly common as we consider a future marked by a rising global

• pyrimidine scaffold. Representative fluorescence spectrum of compounds 5b (λex = 330 nm) and 6e (λex = 430 nm) at 0.2 M in DMSO. Molecular geometry observed within the crystal structure of compound 7b (CCDC 2376493). Strategies towards targeted adducts: A) Niementowski quinazoline synthesis utilizing

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

• presence of catalytic amounts of Cu(OTf)2 lead to the formation of the products through formation of one C–C bond and three C–N bonds (Scheme 26) [44]. The same procedure allows a more general scope, giving access to imidazo[1,2-a]pyrimidine, imidazo[1,2-a]pyrazine and imidazo[2,1-b]thiazole derivatives

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• , Ankara 06800, Türkiye 10.3762/bjoc.20.273 Abstract Acenaphthylene-fused heteroarenes with a variety of five- and six-membered heterocycles such as thiophene, furan, benzofuran, pyrazole, pyridine and pyrimidine were synthesized via an efficient Pd-catalyzed reaction cascade in good to high yields (45–90

• (45%, Table 2, entry 7). The reaction with the symmetrical pyrimidine-5-ylboronic acid was observed to proceed smoothly to give acenaphthylene-fused pyrimidine 15i in 74% yield (Table 2, entry 8). After the completion of our studies on heterocyclic fluoranthene analogues, our next target was the

• pyrimidine derivatives, which were obtained in good to high yields (45–90%). Notably, we have shown that both boronic acid and a range of boronic esters could be utilized as reaction partners with comparable effectiveness in our methodology. The fluoranthene formation method was also applied to construct

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• reactivity compared to other alkynes, which typically require much shorter reaction times. Extending the reaction time provided a higher conversion to the product 14. Yields were observed to be greater for aryl azides (e.g., 4 vs 6). Heterocycles such as pyridine (1), pyrimidine (10), phenothiazine (11), and

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• Chemistry Department, RUDN University, 6 Miklukho-Maklaya St., 117198 Moscow, Russian Federation 10.3762/bjoc.20.236 Abstract The heterocyclic core of imidazo[1,2-a]pyrimidine was formed in satisfactory yields as a result of the interaction of the readily available 2-aminoimidazole with N-substituted

• in clinical use, suggest that they may possess antifungal activity against Candida albicans. Keywords: 2-aminoimidazole; antimycotic activity; imidazo[1,2-a]pyrimidine; molecular docking; N-arylitaconimides; N-substituted maleimides; recyclization; Introduction Nitrogen-containing heterocyclic

• (small-molecule concept) offer a distinctive advantage in the synthesis of new biologically active molecules, as they are synthetic bioisosters of purine bases. Imidazo[1,2-a]pyrimidine derivatives exhibit a wide range of pharmacological properties [4][5][6]. For example, this scaffold is a key

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• ). Solvents for extraction and column chromatography were distilled prior employment. Synthesis of 4a–i The synthesis of 4a–f has been previously reported. Novel derivatives 4g–i were prepared according to our previously reported procedure [65]. 1,3-Dimethyl-5-phenyl-6-(phenylethynyl)pyrimidine-2,4(1H,3H

• ; EIMS (70 eV) m/z (%): 352 (96, M+), 294 (28), 266 (67), 251 (14), 238 (30), 160 (100); HRESIMS-TOF(m/z): [M + H]+ calcd for C20H15F2N2O2, 353.1101; found, 353.1100. 5-(Benzo[b]thiophen-3-yl)-1,3-dimethyl-6-(p-tolylethynyl)pyrimidine-2,4(1H,3H)-dione (4i). Compound 4i was obtained as a brownish solid in

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

• 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

• -ammonium sulfate, probably due to the destruction of the pyrimidine ring. PcZn turned out to be the least active catalyst, resulting in a yield of MU-5-ammonium sulfate 2 of 72% (0.05 wt %). The catalysts’ activity decreased in the order of PcFe(II) > PcCo > PcFe(III) > PcMn > PcNi > PcZn. The catalytic

• pyrimidine ring destruction. The ideal oxidation of TMU (5) was achieved with the addition of 3.0–4.0 equiv H2O2 (Table 3). During the oxidation of pyridine (7) by the binary oxidation mixture APS/H2O2 at 45 °C, the yield of the reaction product – Py-sulfate 8 – increased gradually, reaching a maximum of 85

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• corresponding thiol [35][36][37][38], in the nucleophilic substitution reaction in the aromatic ring of catechol [39][40] or under electrochemical conditions [41][42][43]. An anodic activation of catechols in the presence of a thiol leads to S-functionalized catechols with triazole, triazine, pyrimidine

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• -4,6,7,8-tetrahydro-1H-thiopyrano[3,2-d]pyrimidine-2(3H)-one/thione/selenone 5,5-dioxides and some of their derivatives. Furthermore, this methodology was successfully applied for the synthesis of the SO2-containing analogue of the anticancer drug-candidate enastron (SO2 vs C=O), and we believe a multitude

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

• purification. Thus, it significantly improves existing approaches. Keywords: catalysis; deazaalloxazine; flavin; multicomponent approach; one-pot reaction; Introduction Heterocyclic compounds containing pyrimidine and quinoline motifs in their structure, both of natural and synthetic origin, find a wide set

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• efficiency, affording 3fa in 71% yield. Some heteroaryl chlorides including triazine, pyrimidine, and pyridazine skeletons were also effectively coupled with methyl acrylate to provide the desired products in good yields (3ga–ja). While unsubstituted chlorobenzene and bromobenzene were completely inert in

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• bacteria and fungi but not in mammalian cells, acts only on cytosine. Cytidine deaminase (CDA) as a key enzyme in the pyrimidine salvage pathway in mammals deaminates both cytidine and 2'-deoxycytidine. Members of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family, such as

• ][3][4][5]. Full inhibition of CDA leads to accumulation of toxic pyrimidine catabolism intermediates [6][7]. However, local and temporary inhibition of CDA in the liver provides a therapeutic benefit by allowing cytosine analogue-containing drugs to bypass the liver with an intact nucleobase

• against hCDA (Table 1), which might be a result of protonation of the pyrimidine ring in dZ (IIc). Some inhibition of hCDA by the β-anomer of Va was observed at pH 4.7, with a Ki value of 560 μM. At this pH value, less than 1 in 1,000 molecules of Va might be protonated, which could mean that protonated

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• the glycosidic bond using an organometallic purine or pyrimidine derivative and an electrophilic furanose derivative [23][25]. This process can result in anomeric mixtures, so 5 has potential applications in targeted synthesis, as the configuration of the pseudo-anomeric centre matches the common

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• conformational switching is di(hydroxyphenyl)pyrimidine which was developed by Osakada et al. [25] (Figure 5). By default, this moiety adopts a U-shaped conformation stabilized by OH···N hydrogen bonds. In this conformation, tweezers 4 with two 9-ethynylanthryl arms form a 1:1 complex with 2,4,7

• -trinitrofluorenone (TNF) with a good association constant of 2100 M−1. Upon protonation of the pyrimidine nitrogen atom the hydrogen bond is disturbed, which should result in a conformational change to an open W-shaped form. Even though an acid-mediated hydrogen bond disruption was expected, no clear experimental

• that binds to the OH groups instead of the pyrimidine nitrogen atoms. The group of Aprahamian has developed hydrazone-based molecular switches that can be controlled by photochemical or chemical stimuli such as pH [27]. They reported mesogenic tweezers-like compound 5 composed of a hydrazone switch

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• ] (Scheme 1A). A few years ago, we discovered that the replacement of enamines with 2-cyano-N,N-dialkylethanethioamides in this reaction [15] led to the formation of amidines containing two heterocycles: pyrimidine-2,4-dione and 1,2,3-thiadiazole (Scheme 1B). The idea came to our mind to construct a system

• comprising pyrimidine and 1,2,3-triazole rings connected with an amidine linker by the cycloaddition reaction of 3,3-diaminoacrylonitriles with 6-azidopyrimidine (Scheme 1C). Based on this idea, an efficient and novel method with wide scope has been developed which was then applied to obtain a variety of

• optimized reaction conditions to obtain the desired 5-amino-1,2,3-triazole-4-N-heteroarylcarbimidamides 3. In this way, 21 pyrimidine (3a–k), azolyl (3l–s), and chromenone (3t and 3u) derivatives were successfully prepared (Scheme 2 and Supporting Information File 1). Generally, the reaction proceeded in

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• the most electrophilic C2 carbon of the pyrimidine ring in 8 to give intermediate A. Cleavage of the C2–N3 bond in the latter followed by proton transfer in the formed zwitterion B affords bis-amidrazone C. Next, two molecules of bis-amidrazone C react with each other forming adduct D, which either

• to 1D and 2D NMR, and HRMS (ESI+) data, the product obtained was triazolo[1,5-c]pyrimidine 13 instead of the expected macrocycle 11. The structure 13 was unambiguously confirmed by its synthesis directly from pyrazolopyrimidine 8 (ethyl orthoformate, 1.3 equiv of HCOOH, reflux, 15 h). Analogously, no

• calculations was proposed. It involves nucleophilic attack of hydrazine on the C2 carbon of the pyrimidine ring followed by cleavage of the C2–N3 bond, dimerization of the bis-amidrazone formed, and macrocyclization of the dimer. The DFT calculations also showed that the hydrazine-promoted transformation of

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• -Tribromopyrimidine (6a), whose core pyrimidine structure can be found in many biologically active compounds, could be sequentially substituted with 1,3,5-trimethoxybenzene and N-methylpyrrole to give 8a. The protocol also enabled the selective reductive dehalogenation at the benzylic position of 9a with green light

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• systems with a pyrimidine-bridge fragment has been described in the literature [26][27][28]. Herein, we show that for pyrimidines 9 and 10 containing an allomaltol fragment the main direction of a phototransformation is also the cyclization of the triene system. In this case, condensed dihydropyranone

• and involves the condensation of 3-(dimethylamino)-1-phenylprop-2-en-1-one with cyanamide (14) in NMP in the presence of N-methylmorpholine [29]. However, this reaction led to a mixture of products and the yield of the target pyrimidine did not exceed 10%. It was assumed that the reported conditions

• of the process, as well as basic reagents and solvents to identify the optimal conditions and the best results are summarized in Table 1. At first, based on literature data we carried out the reaction in NMP at 100 °C for 16 h in the presence of N-methylmorpholine. In this case the target pyrimidine

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• structure 13 [37]. Draper’s group reported the pyrimidine-containing N-doped NGs (Scheme 3). Tri-pyrimidine precursors 21 and 23 were obtained by trimerization of 5-(phenylethynyl)pyrimidine in the presence of Co2(CO)8. Upon treatment of the tri-pyrimidine containing hexarylbenzene compounds 21 or 23 under

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• carbonyl component was proposed, but these aldehydes did not have the structure of imidazo[1,2-a]pyridine. Interestingly, in 2019 [1], the synthesis of the amine component using GBB-3CR and the modification of the imidazo-pyrimidine scaffold by a peptidomimetic chain was carried out using the Ugi reaction

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• ][1,2]oxaphosphocine 2-oxides 18 in good to excellent yields in DCM at room temperature for 4–8 h in the presence of the Grubbs 1st generation catalyst. Two naphthylene-fused (19 and 20), pyrimidine-2,4(1H,3H)-dione-fused (21), and 2H-chromen-2-one-fused (22) 1,2-oxaphosphocine 2-oxides were also

• refluxing acetonitrile for 6 h. It underwent a radical cyclization in refluxing benzene for 20 h to give rise to a nine-membered phostone thieno[2,3-d]pyrimidine-fused 2-hydroxy-1,2-oxaphosphonane 2-oxide 46 as a potential inhibitor after the deprotection of the benzyl group in the presence of DABCO in

• from 3-bromobut-3-en-1-yl ethenyl(phenyl)phosphinate and 2-bromophenylmethyl alk-1-enylphosphinates. Synthesis of thieno[2,3-d]pyrimidine-fused 2-hydroxy-1,2-oxaphosphonane 2-oxide from benzyl hydrogen allylphosphonate and 4-chloro-3-(chloromethyl)-2-(4-methylphenyl)benzo[b]thiophene. Synthesis of 3

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

• ,t and 4x,y). Lastly, we explored a few heterocycles that resemble imidazo[1,2-a]pyridine to vindicate the generality of this method. Gratifyingly, 6-phenylimidazo[2,1-b]thiazole, 2-phenylbenzo[d]imidazo[2,1-b]thiazole, and 2-phenylimidazo[1,2-a]pyrimidine participated well under the standard