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

• comprehensive reviews [18][19], but none is directly related to aromatic SNH reactions. The developed procedure was applied to the synthesis of compounds 4 and extended to arylamines with o-amino, o-hydroxy, and o-mercapto substituents, providing access to N-, O-, and S-containing heteropolycyclic structures

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• Fucα1-2Gal, likely due to steric clashes in the binding pocket. We thus conclude that the binding profile of CMA1 is distinct from that of the typical R-type lectin RCA1 and unusual for a R-type lectin in general. We also note that the flexibility of accommodated C2 substituents (from N-acetyl moieties

• to whole monosaccharides), could make CMA1 an interesting candidate for probing synthetically produced glycans with novel substituents. It is of course interesting to speculate about the physiological role of CMA1 in melons, yet this is hard to probe. It is noteworthy, however, that the glycan types

• no binding to unsubstituted galactose, we rather hypothesized the existence of specific interactions made with the C2-substituents, that did not exist in other R-type lectins such as RCA1. To determine this, we set out to resolve the detailed three-dimensional structure of CMA1 via X-ray

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• sulfur extrusion [44]. It appeared that thiepines carrying sterically demanding substituents on the sulfur α-positions as well as annelated analogues show substantially increased lifetimes, owing to steric and electronic effects [45]. With these criteria in mind, a variety of thermally-stable annelated

• , Yamada, Fukui, Shinokubo and co-workers tackled the synthesis of perylene bisimide (PBI), a valuable n-type semiconductor, via a “precursor approach” based on the late-stage extrusion of S-based fragments [57]. Dinaphthothiepine bisimides 3a and 3b, bearing octyl- and butylimide substituents respectively

• ), it was non-scalable and displayed low modularity. Indeed, the imide groups along with their substituents were introduced at a rather early stage of the synthesis, with the ultimate synthetic step being the formation of the thiepine ring via a two-fold nucleophilic aromatic substitution by sodium

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• spiropyridazine-benzosultams. The electronic effects of substituents and the influence of steric hindrance on the reaction were explored. The configuration of the product was determined by X-ray single crystal diffraction. This method has the advantages of mild reaction conditions, wide substrate scope, and high

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• (Me, t-Bu, OMe; 2c–e) and electron-withdrawing groups (Cl and CF3; 2f, and 2g) at the para-position of the aryl ring of thiophenols were well tolerated, furnishing the desired products (3ac–ag) in good yields. The reaction yield remains unaffected by the position of halogen substituents (2h–j), and

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

• , despite the presence of two pyridine nitrogen atoms, is extremely inert towards nucleophilic and oxidative amination reactions. Although molecule 5 does not explicitly contain deactivating electron-donating substituents such as alkoxy and dialkylamino (except for alkyl groups), the observed inertness may

• complexes due to the presence of 5(8) substituents, emerging from the plane of the π-system (see the previous section), and 3) acidification of the hydrogen atoms of the CH2 groups, which can facilitate their subsequent elimination. The analysis of the 1Н NMR spectrum not only confirmed the structure of

• structure of compound 15 was confirmed by a combination of spectral methods, in particular, the disappearance of a singlet from H-5,8 protons at 7.8–7.9 ppm in the starting material 5 during functionalization (nitration, bromination), unambiguously indicates the occurrence of substituents precisely in these

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• photochromic N,N'-diacyl derivatives of indigo, first examples of photochromic indigos containing aromatic N,N'-substituents 1984: first report on intra- and intermolecularly bridged photochromic N,N'-substituted indigos (follow-up studies in 1989, 2021) 1985: detailed kinetic studies of the thermal backward Z

• of H-bonded associates (Figure 2) [20][21][22]. As discussed above, the benzene rings play only a minor role in the formation of the color of indigo and its derivatives. However, electronic effects and especially the position of the substituents in the benzene rings have pronounced influence on the

• color of these dyes, as shown by the absorption maxima positions of the substituted indigo derivatives (Table 1) [23][24]. The introduction of the ED (electron-donating) substituents into the para (5,5')- or ortho (7,7')-positions to the electron-donating NH group results in a bathochromic shift of the

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• acid CPA-6 containing 2,4,6-triisopropylphenyl-substituents at the 3,3’-positions of the binaphthyl skeleton performed best giving the target product in 99% yield with 91% ee (Table 1, entry 6). This suggested, that the steric hindrance of the CPA catalyst at the 3,3’-position is important for

• aryl ring smoothly underwent this asymmetric reduction, affording the desired indolines in 95–99% yield and 90–96% ee within 3 hours. Replacing the 3,3-difluoro substituents by two methyl groups in the starting indole as well as the alkyne part by a phenyl group, the reaction still gave good results

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• –Lam/carbonylative cyclization After disclosing the optimal conditions for the Chan–Lam coupling, we screened different varieties of o-phenylenediamine derivatives. Overall, the o-phenylenene substrates bearing electron-donating substituents on the benzene ring proceeded smoothly under these conditions

• yields were observed in the case of electron-withdrawing substituents such as Cl and CF3 groups, which afforded the compounds 3e and 3f in 37% and 28% yields, respectively. The N-methylated precursor 1h was also tolerated by this system and afforded the desired compound 3h in 35% yield. Unfortunately

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• ][33][34][37][39][43][44][46]. During a study of a possible influence of remote acyl protective groups [23] on the sialylation outcome (which could become possible through participation in stabilization of glycosyl cation [24][47][48] in a conformation with all-axial substituents in the pyranose ring

• [49][50][51][52][53]), we needed to compare two different sialyl donors 1 [36] and 2 with trifluoroacetyl (TFA) and chloroacetyl (ClAc) groups at O-9, respectively, all other substituents being the same. Here, we report the unexpected problems encountered when comparing these glycosyl donors in the

• concerning their relative reactivity and selectivity. This prevented us from revealing a possible influence of remote acyl protective groups at O-9 on the sialylation outcome and their role in stabilization of glycosyl cation in a conformation with all-axial substituents in the pyranose ring. According to

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• ortho-methoxy substituents as previously observed by others [22][23], and demonstrating the high rotational barrier constraining the aryl substituent. This structure was unambiguously confirmed by X-ray crystallographic analysis (Figure 1). During this work we have been intrigued by the possible direct

• extend the scope of this tandem reaction sequence towards analogous skeletons, we explored the effect of various substituents on the aromatic cycles. The successive prenylation and then diversity-oriented benzylation (n = 1 for substrates 11a–n) of diethyl malonate (10) afforded a variety of new

• substrates to be submitted to the one-pot tandem transformation (Scheme 5). With only a few exceptions, the presence of ortho (R1), meta (R2), or para (R3) substituents on the benzyl moiety generally allowed the intramolecular Friedel–Crafts reaction, after the first intermolecular one in the presence of

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• tolerated, affording the desired products in excellent yields (92‒99%). These results indicated that the electronic effect of substituents affected the reaction only slightly. Products with substituents with derivatization feasibilities such as halogen (3ga–ia), acetyloxy (3ja), and ester groups (3ka) also

• substrates containing substituents on the quinoline ring. For example, the 6-OMe-substituted quinoline derivative N-(6-methoxyquinolin-8-yl)benzamide (4) underwent bromination at the C5 position to give 5 in nearly quantitative yield (Scheme 4, reaction 1). Subsequently, we attempted to apply this method to

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• chromophores, wherein both electron-donating and electron-accepting substituents are incorporated into a π-electron-conjugated system, exhibit exceptional optical and electronic properties. They hold significant promise for applications in diverse fields, particularly materials science (specifically in

• in the form of degraded fragments), affording the TCBD products. A distinguishing feature of the [2 + 2] CA–RE reaction involving electron-rich alkynes and DCFs is the alternation of regioselectivity, which is contingent upon the specific substituents incorporated onto the cyclopentadienyl moiety of

• -order kinetics, indicating a bimolecular process. Furthermore, their findings elucidated a compelling linear free-energy relationship between the rate constants and electronic characteristics of the para-substituents of the DCV electrophiles, implying a dipolar, zwitterionic mechanism. The researchers

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• of the substrates bearing substituents at the C5 position on the indole skeleton reacted well, furnishing the products in moderate to good yields from 53–79% (3e–i) except the 5-CHO-substituted substrate which afforded product 3j in 28% yield. Indoles with substituents at the C7 position of the

• short, this reaction tolerates different substituents on the indole ring, including electron-donating and electron-withdrawing groups, providing access to a diverse array of dihydropyrido[1,2-a]indolone derivatives. To gain insight into the reaction process, we performed a series of control experiments

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• binding constant reported for the 8,9-dimethoxybenzo[c]quinolizinium (Kb = 1.2 × 105 M−1) [20]. The slightly lower binding constants of derivatives 3c, 3e, and 3g as compared with the one of compound 3f, may be explained by the larger substituents of the former ligands, which cause more steric repulsion

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• with one of the exocyclic enediyne units removed) [17][18] is a particularly good electron acceptor as it gains 14π-aromaticity upon reduction. In this work, we also want to further explore pyrrolo-annelated IF-DTFs with different substituents on the nitrogen atom, and the functionalization at the

• could potentially after deprotonation be reacted with electrophiles as previously established [29] for the parent structure [30] without tert-butyl substituents. UV–vis absorption spectroscopy UV–vis absorption spectra of the known compound 4 [14] and new compounds 9–12 and 15 are depicted in Figure 3

• compound 17 is significantly blueshifted. This indicates that annelation of the dihydropyrrole ring to the DTF moiety does not change the absorption maximum significantly compared to the two SHex substituents, while annelation of a pyrrole ring results in an absorption maximum at significantly shorter

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• and 104.3(2)° in 2f (C18–P1–C24). A marginal shortening of about 0.02–0.03 Å of the bonds between P1 and the ipso-carbons of the aryl substituents in comparison to the parent phosphine 1 is observed. The alkyl groups attached to the phosphonium center do not show any special features. The distance

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

• -triazole-4-carbimidamides with alkyl, allyl, propargyl, benzyl, cycloalkyl, and indolyl substituents at the N1 position . Keywords: Cornforth rearrangement; cycloaddition reactions; 3,3-diaminoacrylonitriles; heterocyclic azides; 1,2,3-triazole; Introduction Heteroaryl amidines are widely used in the

• previously unknown 5-amino-1-substituted 1,2,3-triazole-N-heteroaryl-4-carboximidamides 3 bearing alkyl, allyl, propargyl, benzyl, cycloalkyl, and various heteroaryl substituents at the N1 postion of the carbimidamide group. Herein, we disclose our results on the cycloaddition reaction of 3,3

• of the substituents in azides 2 was observed. We assume the higher yield of pyrimidine containing triazoles 3a–k by their lower solubility in 1,4-dioxane compared with the solubility of azole containing compounds 3l–s in both 1,4-dioxane and ethanol. With regard to the scope of diaminoacrylonitriles

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• the robustness of this method. Substrates with multiple electron-withdrawing substituents such as trifluoromethyl and bromide gave good yields. The ethyl carbamate 2q proved to be a valid substrate for the reaction with a 74% yield. Phenylacetamide as the substrate resulted in the formation of 2r in

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• , MIC·CS2, and NHC·CS2 zwitterions displayed similar electronic properties and featured the same bite angle. Yet, their steric properties are liable to ample modifications by varying the exact nature of their cationic heterocycle and its substituents. Keywords: betaines; carbenes; ligand effects; nitrogen

• of MIC precursors [24][25][26][27][28]. By analogy with the archetypical NHCs bearing mesityl (Mes) or 2,6-diisopropylphenyl (Dipp) substituents on their nitrogen atoms, we have prepared three triazole derivatives with mixed Mes/Ph, Mes/Bu, or Dipp/Ph substituents on N1 and C4, respectively (Scheme 3

• ) depending on the nature of their aliphatic or aromatic substituents, and that the use of the stronger base KN(SiMe3)2 (pKa = 26) was not always mandatory [25][69][70]. Grubbs, Bertrand et al. also noticed that treating 1-benzyl-3-methyl-4-phenyl-1H-1,2,3-triazolium iodide with KOt-Bu did not afford the

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• -bromo-N-acetylhydrazones gave higher yields than the corresponding α-bromo-N-benzoylhydrazones. Also, substituents present in the MBH nitriles of isatins showed marginal effects on the yields. The obtained spiro[indoline-3,5'-[1,2]diazepines] 3a–m were fully characterized by various spectroscopic

• spiro[indoline-3,5'-[1,2]diazepine]-6'-carboxylates 5a–g in 63–77% yields (Scheme 3). The substituents on both substrates also showed little effect on the yields. The chemical structures were fully characterized by HRMS, IR, 1H and 13C NMR spectra. For demonstrating the synthetic value of this protocol

• -toluenesulfonylhydrazones 6 have a much higher reactivity compared to that of α-halogenated benzoylsulfonylhydrazones 1 in this reaction. The desired spiro[indoline-3,5'-[1,2]diazepines] 7a–n were obtained in satisfactory yields of 58–83% and the substituents in MBH nitriles of isatins showed only marginal effects on the

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• bibenzoimidazole portion of the molecules to the C6H4NMe2 Y substituents (see Figure 3d and Supporting Information File 1, Figure S11). Most of the above-mentioned substrates exhibit little or no absorption at 365 nm (see Supporting Information File 1, Figure S4 for comparison of spectra of the reductants and BnBr

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

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

• . These include the incorporation of heteroatoms within the acene backbone [7][8], stabilization of the acene core structure through the integration of diverse units [9][10], and the introduction of bulky substituents [11]. These approaches aim to maintain the desirable electronic properties of acenes

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

• conformations that contain dimethylacridan substituents [8]. OLEDs based on phenyl-substituted pyridine-3,5-dicarbonitrile showed very high EQEmax of 29.1% due to a high PLQY of 89% ascribed to the rigid acceptor geometry. In addition to the utilization of pyridine-3,5-dicarbonitriles in OLEDs, an example of

• /V∙s at the electric field of 8.1 × 105 V/cm (Figure 8). Conclusion Synthetically convenient protocols for the preparation of sophisticated pyridine-3,5-carbonitriles containing carbazole substituents in positions 2 and 6 were developed starting with 4-bromobenzaldehyde. The compounds were found to

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• ][25]. Regardless of the substituents (a–c) of benzyl bromide, 2, 3, 4, and 5 exhibited similar characteristic absorption features, respectively, supporting that the addition site of each isomer (e.g., 2a–c) are the same. We determined the addition sites of the single-bonded La@C2v-C82 derivatives, La