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

• protecting groups and time-consuming purification steps, that provides preQ1 in 43% overall yield with a purity of >98% (Scheme 2). The approach is based on the cyclocondensation reaction between 2-chloro-3-cyanopropan-1-al (6) (itself obtained from chloroacetonitrile and methyl formate) and 2,6

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

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• ketene dithioacetals [67] or β-ethylthio-β-indolyl-substituted α,β-unsaturated ketones [68], the cyclocondensation reaction of β-ethylthio-β-indolyl-substituted α,β-unsaturated ketones with hydrazines/hydroxylamine [69][70][71] and the tandem [5C + 1C/1N]-cycloaromatization of α-alkenoyl ketene

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

• efficiency of these reactions. In particular, traditional multistep syntheses of pyrazoles have considerably been extended by MCR. Progress has been made in the cyclocondensation of 1,3-dielectrophiles that are generated in situ. Limitations in the regioselectivity of cyclocondensation with 1,3-dicarbonyls

• were overcome by the addition–cyclocondensation of α,β-unsaturated ketones. Embedding 1,3-dipolar cycloadditions into a one-pot process has additionally been developed for concise syntheses of pyrazoles. The MCR strategy also allows for concatenating classical condensation-based methodology with modern

• cross-coupling and radical chemistry, as well as providing versatile synthetic approaches to pyrazoles. This overview summarizes the most important MCR syntheses of pyrazoles based on ring-forming sequences in a flashlight fashion. Keywords: cycloaddition; cyclocondensation; multicomponent reaction

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• 83 was achieved through a Co-mediated alkyne trimerization process. Finally, the synthesis of the targeted boron-doped extended POA 84 was carried out with a yield of 61%, following a series of reactions including cyclocondensation with BBr3 and mesitylation. Since the "v" and "z"-shaped POAs could

Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions

• Karolis Leitonas,
• Brigita Vigante,
• Dmytro Volyniuk,
• Audrius Bucinskas,
• Pavels Dimitrijevs,
• Sindija Lapcinska,
• Pavel Arsenyan and
• Juozas Vidas Grazulevicius

Beilstein J. Org. Chem. 2023, 19, 1867–1880, doi:10.3762/bjoc.19.139

• pyridine-3,5-carbonitriles 6–9 were synthesized starting with 4-bromobenzaldehyde (1) (Scheme 1 and Scheme 2). Thus, piperidinium 3,5-dicyano-6-hydroxy-4-(4-bromophenyl)pyridin-2-olate (2) was prepared by cyclocondensation of 1 with cyanoacetamide in methanol in the presence of piperidine. The conversion

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

• , 2 h, rt. Alternative manipulations of intermediates 3, leading to either 2-alkyl-4-quinolones 8 (via enaminoketones 6) or 2-alkyl-4-quinolone-3-carboxamides 5 (by direct reduction/cyclocondensation). Reagents and conditions: iii) H3PO4, 60 °C, 90 min; iv) Zn/AcOH/CH2Cl2, rt, overnight; v) HCOONH4

Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives

• Valeriy O. Filimonov,
• Alexandra I. Topchiy,
• Vladimir G. Ilkin,
• Tetyana V. Beryozkina and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2023, 19, 1191–1197, doi:10.3762/bjoc.19.87

• potential of such compounds. The most common method for obtaining 3,5-disubstituted pyrazoles is the cyclocondensation of 1,3-bielectrophilic reagents with hydrazine, which acts as a 1,2-dinucleophile [15][16]. It is worthy to note that a small number of methods for the synthesis of 3,5-diaminopyrazoles are

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• construction of tetrahydrofuro[3,2-c]pyridines is based on a Bischler–Napieralski cyclocondensation followed by the C=N bond reduction (Scheme 1d) [36][37][38][39]. Despite the simplicity of the latter approach and availability of 2-(furan-2-yl)ethanamine, the instability of intermediate dihydrofuro[3,2-c

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• protocol is appropriate for both ketosulfonyl reagents and α-sulfonyl-substituted alkyl acetates providing the target quinoline derivatives in good to excellent yields. Keywords: aza-Wittig reaction; azides; cyclocondensation; quinolones; sulfonamides; Introduction The quinoline scaffold has a wide

• through a range of synthetic methodologies suggested recently. Cyclization strategies [35][36][37][38][39][40][41][42][43][44][45] as well as cycloaddition/cyclocondensation techniques [46][47][48][49][50][51] represent those with hetero-ring construction. Alternative approaches rely on a peripheral

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• formed in situ from the corresponding aminothiols [9][10][11][12][13]. Green chemistry methods for benzo-1,4-thiazine synthesis have also been described in the literature. 2,3-Disubstituted-1,4-benzothiazines were prepared in high yield (83–96%) by oxidative cyclocondensation of 2-aminobenzenethiols and

• significantly accelerated by ultrasonic irradiation [16]. Cyclocondensation of 1,3-dicarbonyl compounds with substituted diaryl disulfides in water in the presence of β-cyclodextrin gave 2,3-disubstituted benzo-1,4-thiazines in 70–91% yield in 50 min [17]. A highly efficient visible-light-mediated one-pot

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• conditions described in the literature [19][20]. It was soon established that room-temperature TfOH-promoted cyclocondensation (method A) [19] and AlCl3-promoted reaction conducted at elevated temperature (method B) can be employed interchangeably, with yields registered for 3(2H)-isoquinolones 11 mostly

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

• -dihydrobenzo[d][1,2]azaphosphole 2-oxide (62) in 34% yield via transmethylation and intramolecular cyclocondensation (Scheme 9) [29]. In 1983, Collins and co-workers prepared 2-phenyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-sulfide (59) following the similar procedure. They first oxidized 2-aminobenzyl(phenyl

• % yield via the acid-catalyzed addition to the cyano group and subsequent cyclocondensation, hydrolysis, and tautomerization. Alternatively, the reaction of (E)-2-cyano-N'-((4-oxo-4H-chromen-3-yl)methylene)acetohydrazide (220) and phosphorus tribromide in the presence of triethylamine in dioxane followed

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• at the C4 position allow versatile further functionalization and are biologically interesting DHPMs [17][18][19][20][21], we envisioned an environmentally benign cyclocondensation protocol using low melting mixtures as a green reaction medium. We have established low melting mixtures [28][29][30][31

• derivatives in good yields under environmentally benign conditions. Electron-rich as well as electron-deficient, highly functionalized β,γ-unsaturated ketoesters proved to be excellent substrates in this cyclocondensation reaction. The carboxylic ester substitution at C4 position provides the option for

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• that, the cyclocondensation [29] of the halogenated anthranilamides 6a,b with benzaldehyde followed by dehydrogenation promoted by iodine gave the corresponding quinazolin-4(3H)-ones 7a,b, which we used in the next step without purification. Finally, chlorination [31] of quinazolin-4(3H)-ones 7a,b by

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• on PIFA-initiated oxidative 5-exo-trig cyclization of 2-(3-butenyl)quinazolin-4(3Н)-ones, in turn prepared by thermal cyclocondensation of the corresponding 2-(pent-4-enamido)benzamides. The products obtained have a good natural product likeness (NPL) score and therefore can be useful for the design

• literature to date. One of them is based on the construction of the central pyrimidine ring starting from ortho-disubstituted aromatic compounds 2 bearing a pyrrolidine moiety (see Scheme 1A). Examples include cyclocondensation of (2-pyrrolidin-1-yl)benzaldehyde and aniline occurring in the presence of TsOH

• derivatives with 4-chloroketones or 4-oxocarboxylic acids in ionic liquids [20][21][22][23] or refluxing acetic acid [24][25]. An alternative approach involves cascade cyclization of anthranilamides with 4-chlorobutanoyl chloride [26][27]. Also, reductive cyclocondensation of 2-nitrobenzamides and

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• the synthesis of a new 2,5-substituted 1,3-oxathiolane intermediate (Scheme 10). The approach involved the cyclocondensation reaction of anhydrous 4-nitrobenzyl glyoxylate with mercaptoacetaldehyde diethyl acetal (3nb) at reflux temperature in toluene solvent. This led to the formation of a 5-ethoxy

• 45 (Scheme 12). Kraus [51] developed the cyclocondensation of 2-mercaptoacetaldehyde bis(2-methoxyethyl) acetal (3nc) with diethyl 3-phosphonoaldehyde (3i) to provide the novel oxathiolane intermediate 46 (Scheme 13). The reaction was carried out in the presence of p-TSA at reflux temperature in

• , cyclocondensation of 47 with 2-mercaptoacetaldehyde diethyl acetal (3nb) in the presence of p-TSA in benzene solvent afforded 1,3-oxathiolane intermediate (±)-2,2-bis(acetoxymethyl)-5-ethoxy-1,3-thioxalane (48). More recently, an approach developed by Snead et al. [53] at the Medicines for All Institute used lactic

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• ]acetamide) by trimethyloxonium tetrafluoroborate in apolar solvents resulted in the recovery of starting material only. Next, we tested a cyclocondensation reaction between 2-chloro-3-cyanopropan-1-al and 2,6-diamino-4-methoxypyrimidine [30], however, target compound 1 (m6preQ0) was obtained in yields of 21

• queuosine (Q), the natural products dapiramicin A and huimycin, as well as intermediates of queuosine biosynthesis (preQ1 and preQ0), and the major synthetic targets of this study, m6preQ0 (1) and m6preQ1 (2) (grey box). Synthesis of compound 1 (m6preQ0) by cyclocondensation using a 4-methoxypyrimidine

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• synthesize tetrahydrobenzo[a]xanthene-11-ones 184 and diazabenzo[a]anthracene-9,11-dione derivatives 185 in good yields via a multicomponent reaction (Scheme 42) [76]. This methodology was based on the cyclocondensation of aromatic aldehydes 180, β-naphthol (181), and cyclic 1,3-dicarbonyl compounds 182 or

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• rearrangement; cyclocondensation; heterocycles; thiazolidine-4-one; 1,2,4-triazine; Introduction The thiazolidin-4-one heterocyclic system is a well-known, accessible and, as a consequence, a widely used pharmacophore in the chemistry of biologically active compounds possessing antimicrobial [1

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• in position 2. 2,4-Diaminoquinazolines and 3-guanidinoarylo[e][1,3]diazepine-1,5-dione derivatives are other “biguanide-like” structures obtained respectively from the cyclocondensation of 2-cyanoanilines with cyanoguanidine [34], and by double condensation of biguanides with aryl orthodiesters

• [35] Another example is the cyclocondensation of anthranilic acid with cyanoguanidine which occurs under sulfuric acid conditions via dehydration leading to the corresponding 2-guanidinoquinazolinones (Scheme 13A) [36]. However, performing this reaction in acetonitrile in a closed microwave tube

• cyclocondensation toward the desired benzothiazinone in a 67% yield after 1 h refluxing in water, without requiring acidic activation of the cyanoguanidine (Scheme 13C) [37]. Reaction of amines with substituted cyanoguanidines: In 1946, Curd and Rose reported the first synthesis of biguanides by the reaction of

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

• B undergoes cyclocondensation to yield the spiro product 139, whereas for 139a intermediate B falls prey to intramolecular cyclo condensation (Scheme 54). The synthesis of regioselectively functionalized macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives 142 was demonstrated by Jiang and co

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• ; 1,4-benzothiazine; cyclocondensation; diversity-oriented synthesis; furan-2,3-dione; Introduction Enaminones fused to the 1,4-benzoxazine-2-one I or quinoxaline-2(1H)-one II moiety (Figure 1) represent an intensively investigated class of enamines. Undying interest in these compounds is due to the

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• cyclocondensation of N-(trifluorochloroethylidene) carbamates IV with β-amino crotonates V led only to 4-trifluoromethylpyrimidin-2(1H)-ones I bearing a 5-alkoxycarbonyl substituent (R3/6 = CO2Alk) due to the strong structural limitations of the nucleophilic enamine component (see Figure 1а, method В) [31]. The