Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• solvent composition. In a very early 1927 study [4] of the solvolyses of benzenesulfonyl chloride (C6H5SO2Cl) and its p-methyl and m-nitro derivatives, solvolyzing in 50% acetone/50% water (v/v) at 25.0 °C, it was found that the differences in specific rates were quite small, at 0.0106 min−1 for the p

• value of +0.82 for the para-methyl derivative and of +0.71 for the meta-nitro derivative. and, for the study in 47.5% ethanol/52.5% water the corresponding values are +0.22 and +0.38, respectively. These small reaction constant ρ values depend only on the type of reaction but not on the substituent used

• at least four orders of magnitude slower than the chloride as regards the solvolytic replacement of the halogen present in the benzenesulfonyl halide. For the reactions of the fluoride in 20% dioxane at 91 °C, the m-nitro derivative was shown to be subject to a strong nucleophilic catalysis by

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• [30], terminal blocking by acylation [29][31][32], formation of sugar ester [33], imine oxide [34], oxime [35], or functional group transformation into a hydroxy [33] or nitro group [35]. To the best of our knowledge, compounds 1–3 are the first to have a hydroxamic acid terminus. Similar to the

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

• 8b were reacted with 4-cyano- or 4-nitro-N-methylaniline (Table 1, entries 19–21). Given our interest in preparing 4-anilinoquinazolines 10g, 10h, 10q, and 10r, we decided to investigate a two-step strategy starting by N-arylation using o-methyl- and o-fluoro-substituted primary anilines, followed by

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• hemicucurbituril-based macrocycle, alternately consisting of amidobenzene and 2-imidazolidione moieties was designed and synthesized. Based on the fragment coupling strategy, nitrobenzene-containing hemicucurbituril was firstly prepared facilely under alkaline environment, and reduction of the nitro groups

• imidazolidinone components were observed at rt. This indicated that the formed macrocycle is highly symmetric in solution. After successful construction of macrocycle 9, the aminobenzene-containing hemicucurbituril 4 was obtained by reduction of the nitro groups in 9 with Fe powder in H2O/EtOH at 86 °C for 2 h

Host–guest interaction and properties of cucurbit[8]uril with chloramphenicol

• Lin Zhang,
• Jun Zheng,
• Guangyan Luo,
• Xiaoyue Li,
• Yunqian Zhang,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2021, 17, 2832–2839, doi:10.3762/bjoc.17.194

• peaks of the O–H bonds were observed at 1106 and 1066 cm−1. The nitro-symmetric tensile vibration peak observed at 1503 cm−1 and the nitro-asymmetric tensile vibration peak at 1320 cm−1 disappeared in the spectrum (d). At the same time, the fingerprint region peak of the benzene ring observed from 500

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• the series of compounds 3aa–fa and 3bb–be was carried out using chloroform (CHCl3), methanol (MeOH) or dimethyl sulfoxide (DMSO) solutions. As comparison, the UV–vis absorption spectra of compounds 3ea and 3be, which contain the nitro group in two different ring positions of the molecules recorded in

• shifting the emission maxima to lower energy values (Figure 4). Another possible comparison is between substituents with electron-donating and accepting properties in the same solvent media. Therefore, when the compounds containing a diethylamino group (3bb, R = Ph, R1 = 5-NEt2) and a nitro group (3be, R

• ; H, 2.99; N, 5.94; found: C, 58.04; H, 2.73; N, 6.26. (E)-4-Nitro-2-(((2-phenyl-4-(trifluoromethyl)quinolin-6-yl)imino)methyl)phenol (3be): Orange solid, yield 89%; mp 253–256 °C; 1H NMR (600 MHz, CDCl3) δ 14.01 (s, 1H, OH), 8.85 (s, 1H, CH=N), 8.48 (d, J = 2.7 Hz, 1H, 4-NO2C6H3OH), 8.35 (d, J = 9.0

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• good yields via metal- and additive-free TBHP-promoted cross-dehydrogenative coupling (CDC) of readily accessible N-methyl-2-(aminomethyl)biphenyls and 2-(aminomethyl)biphenyls. This methodology is compatible with numerous functional groups (methoxy, cyano, nitro, chloro, and SEM and TBS-protective

• % combined yield) and 10q1/2 (57% combined yield) further illustrates, how electron-withdrawing substituents negatively impact the yield of the reaction. As evident from Scheme 5, the cyclization protocol is compatible with several functional groups (chloro, nitro, cyano, trifluoromethyl). In contrast, the

• Suzuki cross-coupling reactions, followed by reduction or reductive amination. The oxidative cyclization conditions are compatible with many functional groups on the aromatic rings (methoxy, chloro, cyano, nitro, and phenol protecting groups like TBS and SEM – but not benzyl and methylenedioxy

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• reactions between 2-aminobenzaldehydes 42 and β-nitrostyrenes 43 to obtain chiral 3-nitro-1,2-dihydroquinolines 45 in good yields with up to 98% ee (Table 9) [43]. 1.4 Reactions catalyzed by chiral phase-transfer catalysts Chiral phase-transfer catalysts (PTC) have been recognized as versatile catalysts for

• to good yield of 53–99% with an ee of 74–93% [54]. Liu et al. accomplished a catalytic cascade aza-Michael–Henry-dehydration protocol for the preparation of chiral 3-nitro-1,2-dihydroquinolines 83 from the reaction of N-protected aminobenzaldehydes 80 with substituted nitroolefins 81 by using

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• % yield), para-alkoxy and para-halogen substituents (45–69%), ortho-methyl (74%), and meta-methyl (80% as a 65:35 mixture of regioisomers). Electron-withdrawing groups (nitro, cyano, and methyl ester) stopped at the ketone intermediate. Interestingly, another tandem sequence that exploits the relief of

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• the putative pyrrolizine product appears to be faster than the rate of cyclization of the enaminone. In particular, decomposition occurred during the attempted cyclization of the 2-nitrophenyl- and 2-iodophenylenaminones 15k and 15l even before all of the precursor had been consumed. In the 2-nitro

• and 4-nitro congeners in acetonitrile, followed by sulfide contraction of the resulting thioiminium ether salts with triethylamine and triethyl phosphite, afforded the (E)-enaminones 25a–c in yields of 86–89%. The E-geometry of 25a was again confirmed by NOESY NMR spectroscopy, which showed an

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• (such as n-propyl and n-hexyl) groups under the standard conditions. 2-En-4-ynyl azides 1 bearing electron-donating substituents (such as methyl and methoxy groups) obviously worked better than those with electron-withdrawing (such as nitro, cyano, acetyl, and trifluoromethyl) groups. Meanwhile, they

• previous studies on heterocycle synthesis, Punniyamurthy and co-workers designed the electrophilic iodocyclization of 2-nitro-1,3-enynes 34 for the synthesis of pyrrole derivatives. In 2013, they reported an efficient route to pentasubstituted pyrroles from 2-nitro-1,3-enynes 34, amines, and iodine under

• dibromopyrroles 38, respectively. Subsequently, Punniyamurthy and co-workers also described the copper-catalyzed cascade cyclization of 2-nitro-1,3-enynes 34 to tetrasubstituted pyrroles 39 (Scheme 14) [58]. Through screening the conditions, the Cu(OTf)2-promoted (5 mol %) annulation addition reaction of 2-nitro

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• corresponding aminal 3o exceeded 80%. Next, the effect of a strongly electron-withdrawing nitro group present on anthranilamide moiety was investigated. The reaction carried out in toluene did not reach a complete conversion even after a prolonged reaction time. When more polar THF was used as the solvent, the

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• and electron-withdrawing m-chloro and p-chloro substituents gave the products in good yields. However, the nitro-substituted chalcone gave the product 4h in a slightly lower yield. The structures of the pyrrolo[3,4-c]carbazoles 4a–l were established by various spectroscopy methods. Further, the single

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• , i.e., benzyl and ethyl, slightly decreased the yields of the products (see 4n and 4o). Regrettably, when a substrate 2 bearing a strong electron-withdrawing nitro or trifluoromethyl group on the phenyl ring was employed, the reaction gave very complex side products under the standard conditions, and

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• conditions A and B, highlights the steric influence of the halogen C-3 substituent. Furthermore, Bookser et al. have noted comparable regioselectivity with related C-3 bromo substituted N-containing heterocycles, under similar reaction conditions [24]. Marked N-1 regioselectivity was achieved with 3-nitro

• the corresponding N-2 regioisomer (Table 4, entries 1 and 2). This latter preference for N-2 alkylation is likely due to the proximal steric bulk of both the C-7 Me and Br substituents, respectively, to the N-1 position. The presence of a nitro or methyl carboxylate group at the C-7 position of the

• ) was extended to indazoles bearing a nitro (19) or carbonyl (21–24) functional group, the desired N-1 regioisomer was obtained with a very high degree of regioselectivity. In the case of C-3 substituted indazoles 9, 19 and 21–24 (those bearing a X=O α to the indazole C-3 position), we postulate that in

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• )-27-6. Enantioselective fluorinations of typical enolates were then performed (Scheme 63). The (R)-27-6 reagent gave up to 79% yield and 88% enantiomeric excess in the case of 2-benzyl-α-tetralone. 1-28. (R)- and (S)-N-fluoro-3-tert-butyl-7-nitro-benzothiazine 1,1-dioxides and spiro-type analogues In

• 2000, the Takeuchi group reported their second series of chiral N-fluorosultam reagents, (R)- and (S)-N-fluoro-3-tert-butyl-7-nitro-3,4-dihydro-2H-benzo[e][1,2]thiazine 1,1-dioxides 28-3 [93] (Scheme 64). Racemic 28-1 reacted with (+)-10-camphorsulfonyl chloride to give a mixture of the diastereomers

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• undoubtedly the result of the lengthy syntheses of these compounds. We report the simple synthesis of a rare example of a non-symmetric [2.2]metaparacyclophane. Treatment of [2.2]paracyclophane under standard nitration conditions gives a mixture of 4-nitro[2.2]paracyclophane, 4-hydroxy-5-nitro[2.2

• obviously presents one of the most direct routes to 4-amino[2.2]paracyclophanes so we returned to this venerable reaction. In this paper, we disclose a simple synthesis of 4-hydroxy-5-nitro[2.2]metaparacyclophane (5), a side-product from our nitration reactions. This chemistry offers a rapid route to non

• polymerization. Extensive optimization led us to a set of conditions that routinely provided 4-nitro[2.2]paracyclophane (4) in good yields regardless of the scale of reaction (nitration has been performed on scales ranging from 0.5 g to 30 g). The 1H NMR of the crude reaction mixture invariably shows two other

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• Fmoc chloride to accomplish an orthogonal protective group strategy. The removal of the Boc groups from compounds 5 with TFA gave the mixed aniline and nitro precursors 6. In previous approaches, the nitro groups were reduced to hydroxylamines with zinc and oxidized to the corresponding nitroso

• compounds with iron(III) to perform an intramolecular Baeyer–Mills reaction [15][21]. We found that a complete reduction of the nitro group to aniline 7 and oxidation with mCPBA is increasing the yield of the intramolecular cyclization from 39% to 62% (over two steps) for the unsubstituted diazocine 8c as

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• -vinylnaphthalen-2-yl)acetaldehyde (13h) was prepared from 1-bromo-2-naphthaldehyde in 48% yield over the three steps. It should be noted that the nitro-substituted intermediate 11d was prepared by nitration of 11a with nitric acid under the promotion of acetic anhydride. With the accessibility of the aromatic

• in 38–72% yield. To our gladness, aldehyde 13d, with an electron-deficient nitro group residing on the benzene ring reacted with veratrole under the standard conditions, delivering tetralin 14da in 55% yield. However, using furan as the nucleophile component, the reaction sequence with 13d failed to

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• ]. Herein, we report a better enantioselective version of the reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones (Scheme 1). Results and Discussion Initially a model reaction was examined between N-benzyl-4-benzylidenepyrrolidine-2,3-dione (1a) and 2-nitro-1-phenylethanone (2a) in the

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• direct C–C and C=C bond-forming tool which has been widely described in the literature to prepare a range of different valuable intermediates [127][128][129][130][131]. Applications in the F&F industry are sparse which is probably due to the unpredictable nature of some nitro intermediates. However, late

• in 1983, Ballini et al. represented the potentiality of the reaction for the synthesis of dihydrojasmone derivatives (Scheme 20) [132]. Flow chemistry embodies the safest conditions for handling hazardous chemicals, therefore opening new opportunities for nitro compounds to be industrially employed

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• reproducible protocol to isolate the product without the use of any organic solvent was established, and the recyclability of the DES mixture was successfully investigated. Keywords: alternative solvents; atom economy; DES; nitro derivatives; reduction; Introduction The search for alternative solvents, not

• , nitrocyclohexene was reduced in 60% yield in a ChCl/glycerol mixture, while 6c was obtained in similar yields in glycerol or DES B. Noteworthy, the reduction of nitrobutadiene 5d produced nitro derivative 6d in 63% yield in glycerol and 44% in DES B, with complete control of the chemoselectivity. Remarkably, the

• reduction of nitrodiene 5e, featuring an ester group, was also accomplished with complete chemoselectivity in 50% yield in DES B and in 60% yield in glycerol. The reduction of the nitro group to an amine, followed by cyclization would afford the unsaturated δ-lactam, a valuable precursor for further

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• , presumably caused by the nitro group that is known to be an efficient emission quencher. It was demonstrated with experiments in glycerol solution that the emission of 5a–d increases also upon suppression of conformational freedom of the molecule in media with high viscosity and limited free volume (Figure 2