Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• bromination of the α-carbon using CBrCl3 as the Br source. This in situ halogenation strategy has been employed for the synthesis of quinoxalines [23], oxazoles [24][25], pyrido[1,2-a]benzimidazoles [26], imidazo[1,2-a]pyridines [27][28][29][30], thiazoles [31][32] and benzothiazoles [33][34]. With weak

• bicarbonate bases, direct bromination of the α-carbon does not occur. Instead, the Br is shuttled to the α-carbon by its coupling partner. With this tandem bromination and cyclization strategy, there is no need to presynthesize substrates, thus reducing the number of synthetic steps, time, chemicals and

• wastes. Here we describe the extension of this α-bromination shuttle system to 2-aminobenzothiazoles as substrates to synthesize benzo[d]imidazo[2,1-b]thiazoles. The benzo[d]imidazo[2,1-b]thiazole backbone is found in many bioactive molecules and pharmaceutical compounds as evident by its use as

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• triphenylphosphine with 1-bromoethylbenzene. The resulting phosphonium salt 11 was then deprotonated to the corresponding ylide 12, which in the last step was subjected to bromination to give the expected α-bromoethylphosphonium bromide 13 [10]. 1.3. Peterson olefination of α-trimethylsilylphosphonium ylides with

Structure–property relationships and third-order nonlinearities in diketopyrrolopyrrole based D–π–A–π–D molecules

• Jan Podlesný,
• Lenka Dokládalová,
• Oldřich Pytela,
• Adam Urbanec,
• Milan Klikar,
• Numan Almonasy,
• Tomáš Mikysek,
• Jaroslav Jedryka,
• Iwan V. Kityk and
• Filip Bureš

Beilstein J. Org. Chem. 2017, 13, 2374–2384, doi:10.3762/bjoc.13.235

• significantly increased solubility [32]. It should be noted that other alkylating reagents, bases, and solvents provided the desired products with much lower yield and purity. Subsequent treatment of 7 with N-bromosuccinimide (NBS) smoothly afforded dibromo derivative 8 with a high yield of 93%. Bromination of

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• with acetic anhydride to give fully protected galactose 1 as an anomeric mixture. The α and β anomers (3:7 molar ratio) were identified by NMR. To synthesize bromide 2, we used TiBr4 as a bromination agent. Bromide 2 was obtained as a mixture of α and β anomers (1:4 molar ratio) and was used directly

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• PEG with tosyl, bromide, thiol, carboxylic acid or amine functionalities in good to quantitative yields and with no polymer chain oligomerization, proving the versatility of the method. Keywords: amination; bromination; carboxylation; mechanochemistry; poly(ethylene glycol); solid state; thiolation

• ). 2D-HSQC was performed to validate terminal bromo functionality showing a cross-peak at 1H, 13C = 3.45 ppm, 30.10 ppm (Figure S3, Supporting Information File 1). These results are exciting given that PEG bromination is often performed under harsh conditions either via radical intermediates or using

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• significant in organic synthesis because aryl halides are important synthons for the synthesis of many natural and non-natural products [93][94]. In 2005, Rahman and co-workers reported a pioneering solid state benzylic bromination of diquinoline derivatives via N-bromosuccinimide (NBS) [95]. In 2012, Wang

• and co-workers reported bromination of phenol derivatives, chalcones, 1,3-dicarbonyl compounds using NaBr as bromine source and oxone as oxidant under ball-milling conditions [96]. Within 1 h they could isolate more than 90% of mono or poly-brominated products of phenol and 1,3-dicarbonyl compounds

• (Scheme 23). α,β-Unsaturated carbonyl compounds could also undergo a trans-bromination reaction efficiently within 40 min. Following to Wang’s report, Stolle and co-workers also reported a similar method of aryl bromination and chlorination using NaBr and NaCl, respectively, in the presence of oxidizing

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• derivative D2 performs best for this purpose, even with rather low catalyst loadings, but it has to be admitted that in general the enantioselectivities are lower than in the two other case studies shown in Scheme 6 [92]. α-Bromination and α-iodination reactions Asymmetric α-bromination and α-iodination

• opinion this field still requires further improvements. By looking for example on the difficulties in achieving high selectivities for asymmetric α-bromination or α-iodination reactions, it becomes clear that new methods are urgently required. Another application that may become of future interest could

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• functional groups in a chiral molecular skeleton were applied to the enantioselective synthesis of axially chiral benzamides via aromatic electrophilic bromination. The results demonstrate the versatility of bifunctional organocatalysts for the enantioselective construction of axially chiral compounds

• axial chirality [36][37]. Thus, we assumed that this method could be further applied to the enantioselective synthesis of a range of axially chiral compounds. In this study, we present the enantioselective synthesis of 3-hydroxybenzamides via aromatic electrophilic bromination [28][29]. The 3

• material was recovered (see Supporting Information File 1 for details). These results imply that the first bromination, occurring at the ortho-position of the axis (probably at the 2-position), is the enantiodetermining step of the reaction. Moreover, once one of the ortho-positions is brominated

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• as readily available starting material. Keywords: antibiotic; bromination; BSC; C–H arylation; cross-coupling; Hantzsch synthesis; thiopeptide; Introduction Thiopeptide antibiotics are a class of peptide-derived macrocycles which contain many thiazole and thiazoline units, with almost 90 structures

• with a sophisticated tris-1,3-diazole, judiciously prepared through direct C–H arylation method, to synthesize the trithiazolylpyridine intermediate (Figure 1). The latter was then transformed to heterocycle core of GE2270 by adding a final bromination/Hantzsch sequence to build the last 2,4

• of GE2270 was achieved by adding a final bromination/Hantzsch thiazole synthesis to build the adequate 2,4’-bithiazole appendage. Results and Discussion Our first investigations were directed towards the 6-chloro-5-thiazolylpicolinate ester 4 in multi-gram amounts. We found that our previously

Nitration of 5,11-dihydroindolo[3,2-b]carbazoles and synthetic applications of their nitro-substituted derivatives

• Roman A. Irgashev,
• Nikita A. Kazin,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2017, 13, 1396–1406, doi:10.3762/bjoc.13.136

• reduction of 6,12-dinitro derivatives under similar reaction conditions has been accompanied by denitrohydrogenation of the latter compounds into 6,12-unsubstituted indolo[3,2-b]carbazoles. Formylation of 6,12-dinitro derivatives has proved to occur only at C-2, while bromination of these compounds has

• obtained 2,8-bis(RCO)-substituted derivatives as building blocks for the synthesis of more complicated ICZ-containing compounds [42][43][44]. In addition, other research groups have previously reported convenient methods for C12-formylation, azo-coupling, bromination and chlorination of 6-mono-substituted

• ICZs [37], as well as C2- and C2,8-bromination of 6,12-disubstituted ICZs [23][38]. Bromo-containing ICZ derivatives have also been involved in further lithiation and metal-catalyzed cross-coupling reactions. Herein, we describe an effective protocol for nitration of 5,11-dihydroindolo[3,2-b]carbazoles

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• has been reported that nitration and bromination of 2 take place at the 1-position (however, the bromine atom in 1-bromopyrene can migrate into the 4-position in the presence of AlCl3) [8][9], whereas Friedel–Crafts acylation and Vilsmeier formylation take place at the 4-position [10]. We recently

Molecular-level architectural design using benzothiadiazole-based polymers for photovoltaic applications

• Vinila N. Viswanathan,
• Arun D. Rao,
• Upendra K. Pandey,
• Arul Varman Kesavan and
• Praveen C. Ramamurthy

Beilstein J. Org. Chem. 2017, 13, 863–873, doi:10.3762/bjoc.13.87

• impurities and subsequently brominated using N-bromosuccinimide to produce the desired monomer M1. The synthesis of fluorinated monomer M2 started from 1,2-difluorobenzene. However, the direct bromination of this compound in the 1,4-position is hindered due to the electronegative fluorine substituents. Hence

• , 1,2-difluorobenzene was reacted with trimethylsilyl chloride in the presence of lithium diisopropylamide to afford the 1,4-disilylated intermediate 4 and bromination of the latter compound in neat bromine afforded the desired 1,4-dibromo-2,3-difluorobenzene (5). Nitration of 5 by treatment with fuming

• stannylated thiophene, followed by bromination using NBS. For the synthesis of monomer M3, the required thienothiophene substrate 10 was prepared by the butyllithium-mediated reaction of thieno[3,2-b]thiophene with chlorotrimethylstannane. The latter compound was then coupled with benzothiadiazole 2 affording

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• -workers developed the synthesis of 5-(dibromomethyl)thiazole derivatives 44 by treatment of N-propargyl thioamides 43 with bromine in an ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate). Mechanistically, the reaction involves: i) bromination of triple bond of thioamide 43 which resulted in a

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• in ethanol in the presence of NBS (Figure 1). The detailed description of the syntheses is reported in Supporting Information File 1. The synthesis of EoB (4) was performed in two steps: first, dibromofluorescein (3) was synthesized through partial bromination of 1 with NBS in acetic acid (Figure 1

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• phenyl group was proposed to introduce at the 3-position in substituted pyrazinone via regioselective bromination followed by Suzuki coupling with phenylboronic acid. Accordingly, the bromination of 10a was successfully carried out to furnish regioisomers 12a and 12b in 82% yield upon treatment with

Efficient access to β-vinylporphyrin derivatives via palladium cross coupling of β-bromoporphyrins with N-tosylhydrazones

• Vinicius R. Campos,
• Ana T. P. C. Gomes,
• Anna C. Cunha,
• Maria da Graça P. M. S. Neves,
• Vitor F. Ferreira and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2017, 13, 195–202, doi:10.3762/bjoc.13.22

• substrates were prepared by following literature procedures; the halide partner by controlled bromination of 5,10,15,20-tetraphenylporphyrin (TPP) with N-bromosuccinimide followed by metallation with Zn(AcO)2 [31][32] and the tosylhydrazones 2a–c by reaction of the adequate ketones with tosylhydrazines [33

A new protocol for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane

• Donghui Pan,
• Yanbin Wang and
• Guomin Xiao

Beilstein J. Org. Chem. 2016, 12, 2443–2449, doi:10.3762/bjoc.12.237

• precursor of parylene D, from 2,5-dichloro-p-xylene. In the first bromination step, with H2O2–HBr as a bromide source, this procedure becomes organic-waste-free and organic-solvent-free and can appropriately replace the existing bromination methods. The Winberg elimination–dimerization step, using aqueous

• sodium hydroxide solution instead of silver oxide for anion exchange, results in a significant improvement in product yield. Furthermore, four substituted [2.2]paracyclophanes were also prepared in this convenient way. Keywords: bromination; dimerization; H2O2–HBr system; paracyclophane; polymerization

• also adopted an improved bromination process to prepare 1-(bromomethyl)-2,5-dichloro-4-methylbenzene. Traditionally, there are several disadvantages when molecular bromine is used as a brominating reagent, such as toxicity, inconvenient handling and high reactivity, which lead to unsatisfactory results

Methylenelactide: vinyl polymerization and spatial reactivity effects

• Judita Britner and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 2378–2389, doi:10.3762/bjoc.12.232

• donating (“pushing”) oxygen atom. Monomers with such substitution patterns are defined as captodative or push–pull monomers [1]. MLA was first synthesized in 1969 by Scheibelhoffer et al. through a bromination of L-lactide followed by a basic HBr elimination [2]. In 2008, the first Diels–Alder reaction

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