Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• , pharmaceuticals, agrochemicals, and advanced materials [10][11][12][13][14]. The ubiquity of halogen atoms in these synthetic building blocks urges the development of efficient, sustainable, and mild methods for aromatic halogenation. The century-old classical method of using hazardous and corrosive reagents X2

• ) affording high yields of the corresponding monobrominated products. The reaction of halogen-substituted phenols also showed higher yields with no exchange of halogen atoms during the course of the reaction (products 2g–j, Scheme 3). As expected, exclusive ortho-bromination to the phenolic hydroxy group was

• Representative examples of important halogen-containing aryl derivatives. Strategies for halogenation of aromatic compounds using NXS. General scheme of PEG-400-assisted halogenation of phenols and anilines in an automated grinder using NXS. Monohalogenation of phenols and anilines by automated grinding with NXS

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• halogen groups at the 6-position of the imidazopyridine ring were tested and gave the desired products 4ba–ea in fair to good yields (Table 2, entries 8–11). Conversely, imidazopyridine 1f with an electron-withdrawing trifluoromethyl group did not yield the corresponding product 4fa, because the

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• using N-halosuccinimides as the halogen source under neat grinding or liquid-assisted grinding conditions in a ball mill has been described. Depending on the azobenzene substrate used, halogenation of the C–H bonds occurs in the absence or only in the presence of PdII catalysts. Insight into the

• -halosuccinimide (NXS, X = Br, I) as halogen source [47]. Two years later in 2017, Eslami's group applied a ball-milling method to synthesize aryl bromides and α-bromoketones with N-bromosuccinimide (NBS) and MCM-41-SO3H catalyst and no liquid additives [48]. In 2018, Wang and co-workers developed the ball-milling

• azobenzenes is strongly influenced by the nature of the azobenzene substituents. Conclusion We have applied a mechanochemical protocol for the halogenation of 4,4’-functionalized azobenzenes in a ball mill under NG or LAG conditions, using NXS (X = Cl, Br, and I) as the halogen source. Halogenation of

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• % yield. At the same time, arenes containing electron-withdrawing groups (such as halogen and trifluoromethyl) also give the corresponding products 3e–h in moderate yields with the meta substituted isomers as the major products. Interestingly, only the meta product was detected when (trifluoromethyl

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• -workers, with a strong focus on using rotaxanes with halogen-bond (XB) donors that act as binding sites for anionic guest molecules [23]. In 2017, Beer and co-workers reported the synthesis of the BINOL-containing chiral [2]rotaxanes 64 and their application for enantioselective anion recognition [63

• to slightly better stereodiscrimation of the guest molecules (see Figure 17). Subsequently, Beer and co-workers reported the first example of a chiral halogen-bonding [3]rotaxane for the recognition and sensing of dicarboxylate anions [64]. The [3]rotaxane (S)-68 was prepared in a two-fold clipping

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• derivatives may be metalated in a Li–halogen exchange reaction [27]. In another versatile approach, arylation and alkenylation reactions of the norbornadiene may be accomplished with a Suzuki–Miyaura coupling reaction. In this case, halogenated norbornadienes react with arylboronic acids or their esters to

• with Pd2(dba)3/(t-Bu)3PHBF4 as catalytic system and CsF as additive in THF at room temperature, because these conditions have been shown to be well-suitable for Suzuki–Miyaura reactions of halogen-substituted norbornadiene derivatives with arylboronic acids [28]. However, under these conditions the

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• anions of imine 1 with the terminal dihaloalkane is also considered to be an important factor in the formation of the desired product 3a. Therefore, a model reaction was conducted using dihaloalkanes with different types of terminal halogens (Cl, Br, and I) (Table 7). When the terminal halogen of the

• other hand, the yield of 3a decreased even when the terminal halogen of the dihaloalkane was changed to iodine (Table 7, entry 3). LSV measurements showed that the reduction potential of 1,4-diiodobutane (2c) was almost the same as that of the substrate imine 1 (Supporting Information File 1, Figure S12

• ); therefore, the competition between the reduction of 2c and that of the imine 1 may have caused the low yield of 3a. A large amount (50%) of unreacted 1 was recovered in this case. Therefore, it can be stated that Br is appropriate as the terminal halogen of the dihaloalkane in this cyclization reaction. A

A Se···O bonding catalysis approach to the synthesis of calix[4]pyrroles

• Qingzhe Tong,
• Zhiguo Zhao and
• Yao Wang

Beilstein J. Org. Chem. 2022, 18, 325–330, doi:10.3762/bjoc.18.36

• noncovalent forces, hydrogen bonding interactions play a central role in noncovalent catalysis [2] while halogen bonding interactions have lately been exploited as a new tool to catalyze a diverse array of reactions [3][4][5]. In addition, nonclassical interactions such as anion–π [6][7][8][9][10][11] as well

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• giving the best yield (2a–c). N-Methylisatin ketimines with various R2 residues were also evaluated. In the presence of substituents at the C5 or C6 position on the oxindole aromatic ring, such as electron-donating groups (6-OMe, 2d and 5-Me, 2e) and halogen substituents (6-Cl, 2f), good yields of the

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• transformations using chiral Brønsted acids, Brønsted base, and hydrogen bond donors. Recently noncovalent activation continues to expand into other types of weak attractive interactions such as halogen and chalcogen bonds. Not surprisingly, all activation modes allow further expansion and diversification via a

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

• derivative 7 was generated in 79% yield by treatment of amine 6 with chloroacetyl chloride. Next, the aminoacetyl group in 7 was benzyl-protected to give 8 in 88% yield. Halogen exchange reaction using excess sodium iodide in acetone gave the desired iodo-alkyl derivative 9 in 79% yield. Lastly, our attempt

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

• and Scott showed [9] that in 50% acetone/50% water at 0.5 °C, a hydroxide ion was about 106 times more reactive than a water molecule towards benzenesulfonyl chloride. Also, for the same solvent, at 25.0 °C, they found [10] that the fluoride, with a considerably stronger carbon–halogen bond, reacted

• 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

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

• the halogen substituents present in the anilines affected the N-arylation reactions. When we used 3-bromo-N-methylaniline (9f), we isolated derivatives 10k and 10l in 72 and 73% yields, respectively (Table 1, entries 11 and 12). Similarly, the reactions using 4-fluoro- or 3-fluoro-N-methylaniline (9g

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• -rich phenols, as well as those bearing halogen substituents, were suitable substrates under these reaction conditions. In Lei’s report, the reaction shuts down in the presence of TEMPO and in the absence of DDQ; thus, the formation of a phenoxy radical was proposed. In 2018, Zhong and co-workers

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• -withdrawing groups and halogen substituents in the meta or para position of the phenyl ring reacted smoothly and furnished the desired products 3a–k in good to excellent yields (71.5–92%) and enantioselectivities (76–97.5% ee). The β-silylenone with a strong electron-withdrawing group (cyano) attached to the

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

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• allylic alkylation were studied. As depicted in Scheme 3, a wide range of MBH carbonates 2 could proceed the allylation reaction with 2-picoline (1a). The MBH carbonates 2 containing electron-withdrawing groups on the phenyl ring, such as -NO2, -CO2Me, and halogen etc., were examined and were found to be

In-depth characterization of self-healing polymers based on π–π interactions

• Josefine Meurer,
• Julian Hniopek,
• Johannes Ahner,
• Michael Schmitt,
• Jürgen Popp,
• Stefan Zechel,
• Kalina Peneva and
• Martin D. Hager

Beilstein J. Org. Chem. 2021, 17, 2496–2504, doi:10.3762/bjoc.17.166

• previous studies, several of these interactions were already applied such as metal–ligand interactions [13][14], hydrogen bonds [15][16] or halogen bonds [17]. Furthermore, π–π interactions also feature a reversible behavior and were therefore utilized for the design of different self-healing polymers [18

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• the NMR tube. The reaction tube was irradiated by using a Philips 150 W PAR38E E27 halogen pressure glass type bulb with strong IR-A (NIR) emission. The light intensity inside the reaction tube was ≈200 mW·cm−2. The light bulb was attached to the top of a photoreactor setup equipped with a large air

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

• disclosed the application of N-fluorobenzenesulfonimide (NFSI) and NBS (N-bromosuccinimide), respectively, as the halogen sources, with diazoacetamide under catalyst-free conditions via a carbene pathway, which constructed 3-fluorooxindoles and 3-bromooxindoles (Scheme 1, reaction 1) [20][21]. Then, the

• proton at the C-3-position of 3-monohalooxindoles gave diagnostic singlets (5.25–5.93 Hz) instead of double peaks due to the absence of coupling with the phosphorus atom in the 1H NMR experiment. This indicated that the methylene moiety adjacent to the phosphate group had been displaced by a halogen atom

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• -trifluorophenyl-type catalysts [45]. Additionally, the first asymmetric systems involving purely halogen bond donor catalysis have recently been developed by the groups of Huber [46] and García Mancheño [47]. Moreover, though chloride as halide counter-anion still being particularly prominent, the application of

• catalyst 77, the catalyst loading could be decreased from 10 to only 0.1 mol % without significant loss of enantioselectivity (96% yield, 92% ee). Ultimately, this work gave a tremendous insight and a myriad of applications of such bis-thiourea catalysts with halogen counter-anions and phosphates [73][74

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

• ]. The presence of a halogen atom (I, Br, or Cl) at the C-3 position of the indazole scaffold (16–18) revealed no significant trend in regioselectivity (Table 2, entries 5–7). The latter observed preference for the formation of the corresponding N-1 regioisomer (33, 35, and 37, respectively), under both

• 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

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• ⋅PhMe in DCE at 60 °C. A series of o-alkynylated p-quinone methides containing electron-donating, electron-withdrawing, halogen, and alkyl groups was treated with Me3SiN3 under the optimized reaction conditions and produced the desired fused 1,2,3-triazole derivatives (Scheme 31) [57]. Two mechanisms

• electron-rich, electron-deficient, and halogen moieties were good partners in these reactions as well, affording the 5-arylated triazoles with good to excellent yield (Scheme 33) [58]. A probable mechanism for this transformation is illustrated in Scheme 34. A copper acetylide intermediate 113 is first

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• , hydrazides 1 with electron-donating or electron-withdrawing substituents were efficiently converted in the C–H/N–H activation annulation process. Notably, a wide range of valuable electrophilic functional groups, such as halogen, methylthio, cyano, amino, and ester groups, were well compatible, which should