On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• issue in this regard as a major portion of published data will have to be filtered out before such methods starts to make some tangible headways [57]. For instance, a recent “deep-learning” search for new antibiotics came out with the finding that halicin (1) depicted in Figure 1 was, as many nitro

• second original class of bacterial gyrases inhibitors. In 2004, the nitro-bearing derivative 11, resulting from a high-throughput phenotypic-based screening, was patented by Pharmacia/Pfizer for its antibacterial properties [122][123]. Even if this compound was also effective in vivo, many synthesis and

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• relies upon stoichiometric reagents or transition-metal catalysis. Herein, a borane-catalysed hydroboration of nitriles to give primary amines is reported. Good yields (48–95%) and chemoselectivity (e.g., ester, nitro, sulfone) were observed. DFT calculations and mechanistic studies support the proposal

• %), nitro (1r, 67%), and sulfone (1s, 48%). The 1H NMR spectra of the crude reaction mixtures displayed no reduction of these functional groups. Such functional group tolerance was not exhibited by the other non-metal and boron-based catalytic nitrile hydroboration systems [22][23][24][27]. It should be

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• the reaction scope was mainly limited to rather simple compounds containing methyl and phenyl substituents [32][33][34][35][36][37]. When discussing examples of reductive cyclopropane ring opening, one should refer to early publications concerning the carbonyl- and nitro-substituted compounds [38][39

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• reaction time was needed in order to increase the rather low yield observed after 24 h. In turn, to obtain the product 2g derived from 5-nitro-substituted arylhydrazone 1g, the reaction time had to be decreased. Aiming to expand the scope of 1H-indazoles synthetized by copper-catalyzed intramolecular N

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• functionalized 5-hydroxycyclopentenes 3a–l in good to excellent yields. The phenacylmalononitriles with electron-donating groups usually gave higher yields than that of substrates bearing an electron-donating chloro, bromo and nitro group. Both diethyl and dimethyl but-2-ynedioates can be successfully employed

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• a nitro-substituent. Moreover, some further cases of ortho-substituted anilines were unsuccessful, for which steric effects could serve as an explanation (see Supporting Information File 1 for details). In comparison with published batch syntheses, the herein reported continuous flow synthesis

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• . Benzimidazoles with a variety of aryl substituents (such as bromo, nitro, chloro, and 2,4,6-trimethyl) in the 2-position of the benzimidazole (2a–d,g) were obtained in good yields. Furthermore, the synthesis of the corresponding benzimidazoles with fused aromatic systems in the 2-position such as anthracenyl (2e

• corresponding products 6n and 6o with 79 and 82% yields, respectively. Nitro and fluoro-substituted aromatic aldehydes efficiently reacted with the chloro and fluoro-substituted anthranilamides and delivered the corresponding products 6q and 6r with good yields. To understand the reaction mechanism, we have

Syntheses of novel pyridine-based low-molecular-weight luminogens possessing aggregation-induced emission enhancement (AIEE) properties

• Masayori Hagimori,
• Tatsusada Yoshida,
• Yasuhisa Nishimura,
• Yukiko Ogawa and
• Keitaro Tanaka

Beilstein J. Org. Chem. 2022, 18, 580–587, doi:10.3762/bjoc.18.60

• 13C NMR spectroscopy (Figures S5 and S6 in Supporting Information File 1). Similarly, the reaction of 1 with 2-aminopyridine derivatives 2d–g bearing electron-withdrawing groups, except for the nitro-group containing substrate 2h, at position 5 of the pyridine ring, afforded N-methyl-4-((pyridin-2-yl

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

• -nitro-1H-pyrazoles bearing a dichloromethyl and an amino or thio moiety at C3 and C5 has been prepared in yields up to 72% from the reaction of 1,1-bisazolyl-, 1-azolyl-1-amino-, and 1-thioperchloro-2-nitrobuta-1,3-dienes with 7-chloro-4-hydrazinylquinoline. A new way for the formation of a pyrazole

• cycle from 3-methyl-2-(2,3,3-trichloro-1-nitroallylidene)oxazolidine (6) is also described. In addition, the antimalarial activity of the synthesized compounds has been evaluated in vitro against the protozoan malaria parasite Plasmodium falciparum. Notably, the 7-chloro-4-(5-(dichloromethyl)-4-nitro-3

• -(1H-1,2,4-triazol-1-yl)-1H-pyrazol-1-yl)quinoline (3b) and 7-chloro-4-(3-((4-chlorophenyl)thio)-5-(dichloromethyl)-4-nitro-1H-pyrazol-1-yl)quinoline (9e) inhibited the growth of the chloroquine-sensitive Plasmodium falciparum strain 3D7 with EC50 values of 0.2 ± 0.1 µM (85 ng/mL, 200 nM) and 0.2

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• reacted with two equiv 3-nitro-5-(trifluoromethyl)benzyl bromide (2) in the presence of a base to afford the dinitro compounds 3a–f in moderate to excellent yields (Scheme 1a). The diminished yield for product 3d was probably caused by the large steric hindrance of the 3-pentyl substituent. Reduction of

• the nitro groups by SnCl2 under acidic conditions gave the bisamine fragments 4a–f in 83–98% yields. The bisamine fragments were further converted to the bisisothiocyanates 5a–f by reaction with 1,1'-thiocarbonyldiimidazole in 66–89% yields. Having the bisamine and bisisothiocyanate fragments in hand

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• 26 were chosen. The reduction of the nitro groups in 24 and 26 via the hydrogenation procedure proceeded smoothly with almost quantitative yields; the amine intermediates were immediately used in the next step. Hence, the N-acylation reactions were performed by the action of the corresponding

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• recovered by applying an external magnet and reused for successive five runs. Functional groups including nitro, carbonyl, and methoxy on the aryl halide were compatible with the catalyst. Aryl iodides gave better yields when compared to aryl bromides. A good synergistic effect of the nanoparticles with the

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• -substituted system (2a and 2c vs 2b and 2d). Both electron-rich and electron-deficient acyl hydrazones afforded high yields, with a slight decrease observed with the presence of the electron-withdrawing CF3 group in the case of the electron poor nitro-substituted substrate 2g. The reaction was also

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• optimal reaction conditions, we proceeded to evaluate the generality of this nitroso aldol reaction with respect to the amide component of malonamate (Scheme 2). Pleasingly, our strategy was found to be operational with malonamates bearing electronically different substituents such as halo, nitro, acetyl

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• attempted starting from the known dioctyloxydinitro derivative DN (Scheme 1) [33]. Reduction of the nitro groups with hydrazine, in the presence of catalytic amounts of Pd/C (10 mol %) led to the corresponding diamino intermediate. This latter could be subsequently reacted with the desired phosphino benzoic

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• diastereomer, meaning vicinal hydrogens were in anti-configuration. In all previous experiments only E-isomers were used. In the case of the 3-nitro-substituted starting material 2q we managed to separate isomers and carried out the reaction with both the E- and Z-isomer. In these experiments, both isomers

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• led exclusively to the desired isomer 5 with the nitrophenyl group in position 3, most likely due to the steric effect. Then, the nitro group in 5 was reduced by hydrogenation under 4 bar using Pd/C as catalyst to yield the desired amine 6 in 78% yield. Subsequently, the desired chloroacetyl

• previous observations [38]. Reduction of the nitro group by palladium-catalyzed hydrogenation in dry methanol gave 2a in 92% yield. Interestingly compound 2a undergoes ring-closure reaction spontaneously at room temperature to give trace amounts of 3a (59 mg, 2%) after column chromatography, when a 3.1 g

• the nitro group but also to cyclization and the reductive elimination of bromine to afford 3a. The synthesis of 3b could be realized in 58% yield by using iron powder under acidic conditions. Reaction of methyl 5-(2-nitrophenyl)-4-oxopentanoate [44] and 1-benzyl-1-phenylhydrazine [36] hydrochloride in

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