Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

• Laszlo Jicsinszky,
• Marina Caporaso,
• Katia Martina,
• Emanuela Calcio Gaudino and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230

• the chloride has less affinity to the macrocycle. It was not possible to reproduce the literature method [14] for per-6-chloro-β-CD synthesis, but a protocol using p-toluenesulfonyl chloride under reaction conditions that were analogous to the iodination/bromination reaction resulted in the targeted

The weight of flash chromatography: A tool to predict its mass intensity from thin-layer chromatography

• Freddy Pessel,
• Jacques Augé,
• Isabelle Billault and
• Marie-Christine Scherrmann

Beilstein J. Org. Chem. 2016, 12, 2351–2357, doi:10.3762/bjoc.12.228

• (7:3) as the eluent. Also in this case, the calculated values were very close to the experimental ones (differences of 1, 3 or 6%). The crude mixture of reaction b, a bromination in alpha position of a ketone leading to 2 [17][18] in 54% yield, was chromatographed using AcOEt–MeOH (9:1) as the eluent

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

• Arne Klinkebiel,
• Ole Beyer,
• Barbara Malawko and
• Ulrich Lüning

Beilstein J. Org. Chem. 2016, 12, 2267–2273, doi:10.3762/bjoc.12.219

• ). In order to synthesize the respective methoxy compound 5c, commercially available 3-hydroxybenzoic acid (10) was used as starting material (Figure 6). Bromination introduced a bromine atom into the 4 position (11) [19], then the phenol was turned into its methyl ether. This methylation can be

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• %) according to GC–MS analysis, and the iodinated product 2 was difficult to isolate by chromatography. In light of these results, bromination was conducted with the aim of synthesising the corresponding aryl iodide 2 by halogen exchange (Scheme 3). After careful optimisation of the reaction conditions, the

• . Absorption spectrum was recorded at 10 μM. Emission spectrum was recorded at 100 nM, with excitation at 318 nm. Proposed retrosynthesis scheme to access N-isopropyl-THQ 2. Synthesis of THQ 3 by initial N-alkylations, followed by PPA-mediated cyclisation. Bromination of 3 and attempted halogen exchange of the

Synthesis of 2-substituted tetraphenylenes via transition-metal-catalyzed derivatization of tetraphenylene

• Shulei Pan,
• Hang Jiang,
• Yanghui Zhang,
• Yu Zhang and
• Dushen Chen

Beilstein J. Org. Chem. 2016, 12, 1302–1308, doi:10.3762/bjoc.12.122

• substituted ones. Although direct bromination [22], nitration [22], and acetylation [45] of tetraphenylene via electrophilic aromatic substitution have been reported, it is still desirable to develop new methods for the derivatization of tetraphenylenes. Herein we report several synthetic protocols for the

• the reaction was run for 24 hours (Table 2, entry 5). Finally, the optimal 94% yield was achieved using 2.0 equiv NCS (Table 2, entry 6). Subsequently, the bromination of tetraphenylene (1) was examined. The reaction yielded the desired brominated product 3c under Wang’s conditions in 64% yield (Table

• -catalyzed acetoxylation of tetraphenylene (1). The AuCl3-catalyzed chlorination of tetraphenylene (1). The AuCl3-catalyzed bromination of tetraphenylene (1). The AuCl3-catalyzed iodination of tetraphenylene (1). The Pd(OAc)2-catalyzed carbonylation of tetraphenylene (1). Supporting Information Supporting

Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene

• Rudolf Knorr,
• David S. Stephenson,
• Ernst Lattke,
• Petra Böhrer and
• Jakob Ruhdorfer

Beilstein J. Org. Chem. 2016, 12, 1178–1184, doi:10.3762/bjoc.12.113

• Information File 1) generated 1,1-dimethylindene (2), whose in situ bromination furnished 1 (ca. 1%) in a trans/cis ratio of ca. 3:2. Since both dibromides trans-1 and cis-1 were stable under the reaction conditions and would distil together with 7, they were destroyed through HBr elimination by KOt-Bu (or

• a most unusual, highly cis selective olefin bromination. What else may appear unusual with 1 and its congeners? Trans-1 and cis-1 undergo regiospecific HBr eliminations even in the absence of bases, cis-1 does so more rapidly than trans-1. The products 3 and 4, respectively, can serve as precursors

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• interesting due to its unique halogenated tetracyclic core structure. Its biosynthesis is postulated to be carried out by a type III-PKS. Pure PKS-derived compounds are rare in myxobacteria, which together with the new carbon skeleton and the high bromination level makes this structure even more fascinating

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• -trimethylpyridines The starting material in the synthetic sequence, 3,5-dibromo-2,4,6-trimethylpyridine (1), can be easily prepared by simple bromination of 2,4,6-trimethylpyridine in 60% oleum on a multigram scale according to the procedure published by Drzeniek and Tomasikl [37]. In order to optimize the

Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

• Joyeeta Roy,
• Tanushree Mal,
• Supriti Jana and
• Dipakranjan Mal

Beilstein J. Org. Chem. 2016, 12, 531–536, doi:10.3762/bjoc.12.52

• carboxyaldehyde 15. Employment of a Darzens condensation followed by bromination was considered for further elaboration of 15 to 16. For the synthesis of key synthon 12 (Scheme 2), we started from cyclohexenone 19, which was prepared by base-catalyzed condensation of methyl acetoacetate with methyl crotonate [24

• ][25][26][27][28][29][30]. It was then treated with bromine in AcOH to afford 3,5-dibromoorsellinate 20 in 81% yield [31][32][33]. Subsequent O-methylation of 20 (using CH3I, K2CO3), and benzylic bromination of 21 with NBS followed by lactonization of 22 in a refluxing mixture of dioxane and water

• afforded phthalide 23 in 61% yield. NBS bromination of 23 afforded the 3-bromophthalide [33], which on treatment with dioxane/water furnished phthalaldehydic acid 24 in 69% yield over two steps [34]. Treatment of 24 with KCN furnished 3-cyanophathalide 12 in 75% yield analogously as described in references

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• benzylic bromination followed by elongation of the C3 unit [22]. To this end, the ester group at the C1 position of 15 was reduced by lithium borohydride, and the resultant 1,3-diol protected to give acetal 16 [16]. After various experiments, selective bromination of the methyl group on the aromatic ring

• of 16, however, was found to be difficult due to competitive bromination of the electron-rich aromatic ring, and thus the desired bromide 17 was obtained in only 14% yield. We then investigated an alternative route from adduct 5, even though the enantiomeric excess of 5 (86% ee) was a little lower

Syntheses of 2-substituted 1-amino-4-bromoanthraquinones (bromaminic acid analogues) – precursors for dyes and drugs

• Enas M. Malik,
• Younis Baqi and
• Christa E. Müller

Beilstein J. Org. Chem. 2015, 11, 2326–2333, doi:10.3762/bjoc.11.253

• -substituted derivative which, under different reaction conditions, yielded the corresponding carbaldehyde, carboxylic acid, and nitrile derivatives. The latter was further reacted to obtain 1-amino-2-tetrazolylanthraquinone. Subsequent bromination using bromine in DMF led to the corresponding bromaminic acid

• inert solvent (e.g., nitrobenzene) to form 1-aminoanthraquinone-2-sulfonic acid (4), the salt of which is then brominated to give bromaminic acid sodium salt (2). Sulfonation of 3 (oleum method) is achieved by the use of oleum followed by bromination in a one-pot reaction. Therefore, the oleum method is

• formaldehyde under alkaline conditions to yield 1-amino-2-hydroxymethylanthraquinone (5) in good isolated yield [56] (Scheme 2). Compound 5 was subjected to bromination using bromine in N,N-dimethylformamide (DMF). The reaction proceeded smoothly at room temperature affording 1-amino-4-bromo-2

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

• Yury A. Sayapin,
• Inna O. Tupaeva,
• Alexandra A. Kolodina,
• Eugeny A. Gusakov,
• Vitaly N. Komissarov,
• Igor V. Dorogan,
• Nadezhda I. Makarova,
• Anatoly V. Metelitsa,
• Valery V. Tkachev,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2015, 11, 2179–2188, doi:10.3762/bjoc.11.236

• of 3,5-dimethylcycloheptatrienecarboxylic acid to 3,5-dimethoxycycloheptatriene, bromination of the latter in chloroform to give β-methoxytropone and its subsequent demethylation [13]. The more general approach to β-tropolone was based on the multistep transformation of 3,4,5-trimethoxybenzoic acid

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• halogenations. In 2006, Gusevskaya and Menini [47][48] reported a highly selective method for C–H chlorination and bromination of various phenols under aerobic, copper-catalyzed conditions. As displayed in Scheme 11, the reaction of phenols 19 with 2 equiv of LiCl in the prensence of O2 and 12.5 mol % CuCl2 in

• modified catalytic conditions (Scheme 11). However, it was found that the oxidative bromination of phenols exhibited generally lower para regioselectivity than the corresponding chlorination [49]. Mechanistic studies on these reactions indicated that the halogenation reactions proceeded via a free radical

• acquired as dibromoanilines via double C–H bromination process. On the other hand, the chlorination was found less effective due to the presence of the side transformation and formation of N-acetylated byproducts [50]. In 2009, Stahl et al. [51] reported a Cu-catalyzed aerobic C–H halogenation protocol of

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• , which is driven by releasing ring strain of the cyclobutyl ring. The resulting γ-keto radical J subsequently undergoes radical bromination to form 8e [59]. This result unambiguously supports the presence of the alkoxy radical intermediate during oxaspirocyclohexadienone formation in our mechanistic

[2.2]Paracyclophane derivatives containing tetrathiafulvalene moieties

• Laura G. Sarbu,
• Lucian G. Bahrin,
• Peter G. Jones,
• Lucian M. Birsa and
• Henning Hopf

Beilstein J. Org. Chem. 2015, 11, 1917–1921, doi:10.3762/bjoc.11.207

• -yl)-1,3-dithiol-2-thione in the presence of trimethylphosphite. The 1,3-dithiol-2-thione derivative was in turn synthesized by the regioselective bromination of 4-acetyl[2.2]paracyclophane, then through the corresponding dithiocarbamates and 1,3-dithiolium salts. Keywords: dithiocarbamates; 1,3

• -dithiolium salts; [2.2]paracyclophane; regioselective bromination; stereoisomers; tetrathiafulvalenes; Introduction Tetrathiafulvalene (TTF) and its derivatives have been extensively studied with respect to their applications as organic metals and superconductors [1][2]. These properties are a consequence

• to avoid the formation of side products during the bromination process [15], the synthesis of compound 2 has been accomplished using the molecular complex of bromine with dioxane [16]. However, although this reagent has often been employed in mild and selective bromination reactions [17], there are

Reaction of allene esters with Selectfluor/TMSX (X = I, Br, Cl) and Selectfluor/NH₄SCN: Competing oxidative/electrophilic dihalogenation and nucleophilic/conjugate addition

• A. Srinivas Reddy and
• Kenneth K. Laali

Beilstein J. Org. Chem. 2015, 11, 1641–1648, doi:10.3762/bjoc.11.180

• catalyst for oxidative functionalization is comparatively less explored [11]. Notable examples of oxidative functionalization by Selectfluor include in situ generation of electrophile equivalents Cl+, Br+, SCN+ and NO2+ and their reactions with aromatics [12], the bromination of representative alkenes with

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• alkenes, alkynes and aromatics [85][86][87]. Its formation can be explained by the reaction of the pyridinium tetrafluoroborate radical (Scheme 2), pyridine and I2 or iodine radical. Bromination of 3b with Br2 was attempted under conditions similar to iodination but the reaction was slow and inefficient

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

• Anna Kuźnik,
• Roman Mazurkiewicz,
• Mirosława Grymel,
• Katarzyna Zielińska,
• Jakub Adamek,
• Ewa Chmielewska,
• Marta Bochno and
• Sonia Kubica

Beilstein J. Org. Chem. 2015, 11, 1418–1424, doi:10.3762/bjoc.11.153

• -acylamino- and dialkoxyphosphonyl groups of 1-aminophosphonates 5, the electrophilicity of these compounds’ α-carbon is displayed only after functionalisation of the α-position with a nucleofuge group, e.g. by α-bromination of 1-aminophosphonates with N-bromosuccinimide [28][38][39][40][41] or by

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• corresponding dibromide followed by formylation (Scheme 13). In 2006, Rajkumar and co-workers [103] have published the synthesis of stilbenophane 85 via McMurry coupling as a key step (Scheme 14). Terphenyl derivative 82 was subjected to benzylic bromination in the presence of NBS to generate compound 83. Later

The chemical behavior of terminally tert-butylated polyolefins

• Dagmar Klein,
• Henning Hopf,
• Peter G. Jones,
• Ina Dix and
• Ralf Hänel

Beilstein J. Org. Chem. 2015, 11, 1246–1258, doi:10.3762/bjoc.11.139

• . Exploratory photochemical studies were carried out with tetraene 19 as the model compound. On irradiation this reacted with oxygen to the stable endo-peroxide 52. Keywords: bromination; Diels–Alder reactions; epoxidation; photochemistry; polyolefins; reactivity; hydrogenation; Introduction Several years ago

• could be formed from 19 either by two consecutive 1,4-bromine addition processes or by a 1,8-addition followed by trans-bromination of its central double bond. This bond should be favored for steric reasons over the two terminal double bonds of the triene intermediate 23. Since this dibromide was not

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• valves so that the second loop transfers the reagent, whilst the first one is being recharged. This concept was successfully applied to the flow synthesis of a 20-member library of casein kinase I inhibitors (38) that also demonstrate the selective mono-bromination, heterocycle formations and high

• also been employed in the flow synthesis of a carprofen analogue [69] as well as in the regioselective bromination towards a rosuvastatin precursor [70] showcasing how continuous flow photochemistry is receiving a significant level of interest. This is not least because of the perceived green reagent

A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

• Roman A. Irgashev,
• Arseny A. Karmatsky,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2015, 11, 1000–1007, doi:10.3762/bjoc.11.112

• acetophenone (8a) according to the synthetic procedure described above. Isatin 7c containing an n-hexyl substituent at the nitrogen atom has been applied to ensure a good solubility of the target product 12o, as well as of the intermediate 10o. It should be noted that bromination of 2-phenyl-substituted thieno

• [2,3-b]indole 12a led to a rather complicated mixture of compounds, and all attempts to reach bromination of compound 12a with an excess of Br-agent (e.g., Br2/1,4-dioxane, NBS/CHCl3) proved to be unsuccessful (Scheme 5). Conclusion In summary, we have developed a convenient and robust synthetic

Properties of PTFE tape as a semipermeable membrane in fluorous reactions

• Brendon A. Parsons,
• Olivia Lin Smith,
• Myeong Chae and
• Veljko Dragojlovic

Beilstein J. Org. Chem. 2015, 11, 980–993, doi:10.3762/bjoc.11.110

• compounds, which was affected by the presence of solvents. In this study, we attempted to establish general trends of permeability of PTFE tape to different compounds and to better describe the process of solvent transport in PV-PTFE bromination reactions. Though PTFE tape has been reported as impermeable

• trends of the permeability of PTFE to different compounds, to investigate whether organic solvents alter it, and to better describe the process of solvent transport in PV-PTFE bromination reactions. We also compared PTFE tape to bulk PTFE, which is typically encountered as an inert protective coating

• ). Variations were considerably greater in trials involving dichloromethane. Solvent transport in the course of PV-PTFE bromination of cyclohexene To examine the solvent transport effect in the course of a reaction, we performed the delivery of bromine to an equimolar amount of cyclohexene dissolved in a

Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions

• Hengshuai Wang,
• Shengchao Jiao,
• Kerong Chen,
• Xu Zhang,
• Linxiang Zhao,
• Dan Liu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 416–424, doi:10.3762/bjoc.11.47

• ), deoxyvasicinone was subjected to a free-radical bromination using NBS and the subsequent treatment with NaOAc/AcOH as an acetoxylation reagent [12]. However, for most of these synthetic strategies harsh reaction conditions are a necessity, produce unstable sulfonamide anhydride intermediates [2][13], which are

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• –73%). However, cholesterol produced a complex mixture of products under the same reaction conditions. The same authors also studied the electrochemical bromination of similar cholesterol derivatives 1a–c (Scheme 6) [41]. The electrolyses were performed in a divided cell with a platinum anode in

• the Gif system. Electrochemical oxidation of cholesteryl acetate (1a) with dioxygen and iron–picolinate complexes. Electrochemical chlorination of cholesterol catalyzed by FeCl3. Electrochemical chlorination of Δ5-steroids. Electrochemical bromination of Δ5-steroids in different solvents. Direct