Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• substituents were also well tolerated. Especially the para-bromo compound 8 was interesting, since the bromine provides a handle for further functionalization. The electron-withdrawing CF3 group gave a good yield of 10 (61%), whereas the electron-donating methoxy group led to a decrease in yield (11, 44%). The

One-pot synthesis of dicyclopenta-fused peropyrene via a fourfold alkyne annulation

• Ji Ma,
• Yubin Fu,
• Junzhi Liu and
• Xinliang Feng

Beilstein J. Org. Chem. 2020, 16, 791–797, doi:10.3762/bjoc.16.72

• selective bromination of 4 with 4.4 equiv of bromine in nitrobenzene solution at 120 °C afforded 1,3,6,8-tetrabromo-2,7-diphenylpyrene (5) in excellent yield (86%). Compared to insoluble 1,3,6,8-tetrabromopyrene [34], the diphenyl-substituted compound 5 exhibited excellent solubility in common organic

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• = 0:59:41, Table 1, entry 6). The comparison of entries 5 and 6 (Table 1) clearly indicates that compound 4 was formed due to a rearrangement of selenocyanate 5 rather than by the “classical” nucleophilic substitution of bromine in thiaselenole 1. The rearrangement of selenocyanate 5 to compound 4

• seleniranium intermediate 2 (Scheme 7). The formation of thiaselenole 4 was the result of two rearrangements, rather than a “classical” nucleophilic substitution of the bromine atom in thiaselenole 1. Similar rearrangements were found and studied in the reactions of thiaselenole 1 with mercaptobenzazoles [40

Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel–Crafts reaction

• Yafang Dong,
• Masahiko Sakai,
• Kazuto Fuji,
• Kohei Sekine and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2020, 16, 409–414, doi:10.3762/bjoc.16.39

• phenylsilane (2d), the phenoxasilin product 3d was formed in 59% yield using conditions B and in 63% yield under conditions A. Di(4-bromophenyl)dihydrosilane (2e) was transformed successfully into phenoxasilin 3e in 83% yield without loss of the bromine substituent. The reaction system was also applicable for

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• yield the monobrominated products in excellent yields via visible-light photoredox catalysis (Scheme 20) [159]. Earlier literature reports suffered from the use of hazardous compounds (e.g., bromine) and low selectivities [160]. The reactive radical intermediates in their study were detected via laser

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• tolerated several functional groups, including bromine and nitrile units, which provide ample scope for further manipulation of the products from the perspective of medicinal chemistry. The catalyst can be easily recovered and recycled in a colloidal solid form, enabling catalytic recycling and reusability

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• barrier in the oxidative addition step [26][27], we envisioned that the C8 carbon could be more electron rich than C6 and C7, possibly due to the proximity of the nitrogen atom N1. All the above reactions were run on bromine-substituted analogs. Analogs bearing a strong carbon–chlorine bond did not react

Synthesis and characterization of bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives

• David Martínez-López,
• Amirhossein Babalhavaeji,
• Diego Sampedro and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2019, 15, 3000–3008, doi:10.3762/bjoc.15.296

• first pKa value of substituted piperazines falls in the range ca. 4–6 (vs 9–10 for the second pKa value) [22]. In addition, the electron-withdrawing bromine atoms were also expected to lower the azonium ion’s pKa value (the pKa values of 2-bromobenzoic acid and unsubstituted benzoic acid are 2.85 and

• significantly lowered pKa value, made 5 unsuitable as an azonium photoswitch under physiological conditions. Despite this undesired effect on the pKa value, the steric bulk introduced by the bromine substituents did appear to slow thermal relaxation of the neutral (unprotonated) azo forms of these compounds

• performed for any of the species, the following calculations were performed: To ensure that the conformation shown in Figure 2 was the thermodynamically most stable arrangement around the azo moiety, free energies for two alternative arrangements – conformer 2: with both bromine atoms on the same side of

Influence of the cis/trans configuration on the supramolecular aggregation of aryltriazoles

• Sara Tejera,
• Giada Caniglia,
• Rosa L. Dorta,
• Andrea Favero,
• Javier González-Platas and
• Jesús T. Vázquez

Beilstein J. Org. Chem. 2019, 15, 2881–2888, doi:10.3762/bjoc.15.282

• stacking interactions, in addition to hydrogen bonding, with the aromatic rings adopting a high degree of parallelism, as seen in crystal packings and ECD data. Furthermore, π–bromine interactions between the bromine atom of the aryl substituents and the triazole units might also contribute to an overall

• and 8e point at the fact that the presence of either the phenyl groups or the bromine atoms are not strictly necessary for gelation, although both might contribute to an overall stabilization of the supramolecular aggregation. Optical micrographs of the xerogels formed from compounds 7f, 8f, 10, 12

• as between the triazole rings, and therefore the presence of multiple intermolecular π–π stacking and π–bromine [19] interactions. This compound precipitated in the presence of any amount of water and gelled only in DMSO at a low temperature. Compound 10 produced pseudo-crystals in DMSO/H2O (1:1, v/v

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• azobenzene analogue 2a, we explored the substitution pattern of the outer aromatic ring with chlorine atoms in the ortho, meta and para-position (compounds 2b–d, respectively) to also assess the possibility of agonism provided by a halogen bond. Compound 2e, which contains a bromine atom in the ortho

• explained by the effect of the Cl atom present in the 4 subseries, that may give a rise in electron density to the azobenzene necessary to increase the efficacy of the cis-isomer. In both subseries 3 and 4, a bromine atom on the ortho-position of the outer ring gives optimal results in providing CXCR3

• efficacy photoswitching (Figure 3). To confirm this for subseries 4, the analogues of 4d with the bromine on the meta and para position (5b and 5c, respectively) were also synthesized. The synthetic route (Scheme 1) utilized 10c and 3- and 4-bromonitrosobenzene (11k,l) to form azobenzenes 15b,c, which were

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• (pyridine numbering) group. Since the smaller 2’-fluorine substituent in 16 should lead to a decrease in quantum yield compared to 15, we aimed for a molecule with an additional bulky 4’-substituent such as bromine. The bromine should not only alter the HOMO energy level of 16 in a favourable way, it can

• at the bromine via a nucleophilic substitution, we explored also if the ester analogue tert-butyl 5-bromo-6-chloronicotinate could undergo a HD reaction with subsequent xanthone addition. The reaction did not lead to any product, neither with n-BuLi nor with t-BuLi. However, it is noteworthy that no

• rearrangement. By our optimized procedure, we have obtained the dye 15 at high yield and without the necessity of HPLC purification. The chlorine atom in 2’-position can potentially be used to introduce the PET radionuclide fluorine-18 while the bromine atom serves as a constraint against rotation around the

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• bromo substituent of the appropriate substrates 20a or 20b should converted into the respective organomagnesium product by bromine–magnesium exchange. In an expected subsequent Parham-type ring-closing reaction [33] the nucleophilic carbon at position 4 should trap the ester (or nitrile) group to lead

• . Reaction of 20a with 2.2 equiv iPrMgCl∙LiCl, which is a very mild reagent for bromine–magnesium exchange reactions in the presence of labile functional groups like esters [35], at 0 °C led, after aqueous work-up, to the formation of the expected pyridoacridone 22 in 28% yield (Scheme 5). Although starting

• material could not be recovered, another product 23, which is most likely the debrominated, not cyclized analogue of 20a, was observed in traces. The outcome of this experiment shows that the bromine–magnesium exchange reaction was most likely completed, but the intramolecular trapping of the ester group

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• (iodine, bromine) and chalcogens (selenium and tellurium) [18]. While there are several strategies for the synthesis of triazoles, the Cu(II)-catalyzed azide–alkyne cycloaddition reaction (CuAAC click reaction) is considered as one of the most efficient, simple and mild approaches towards the preparation

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• NDI 1 in 90% yield (Scheme 1) [54]. The synthetic module for cNDIs with two substituents at the core is the 2,6-dibromo anhydride derivative 8 that can be synthesized from 7 by elementary bromine, dibromoisocyanuric acid, or 1,3-dibromo-5,5-dimethylhydantoine (DBH) in concentrated sulfuric acid, or

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• reaction mechanisms for these syntheses have not been reported. Therefore, we carried out several control experiments to clarify the reaction mechanism (Scheme 2). However, the reaction of 1-phenylbenzimidazole (11) without bromine at the phenyl group with diphenyl diselenide (12a) did not afford the

• group having bromine to generate the tetracyclic target molecule. Conclusion Benzo[d]imidazo[2,1-b]benzoselenoazoles were prepared via Cs2CO3-mediated tandem cyclization followed by reaction of 1-(2-bromoaryl)benzimidazoles with Se powder without a transition metal catalyst. The molecular structure of

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• substitution of bromine from tert-butyl bromoacetate with 2,3,4,6-tetra-O-acetyl-α-ᴅ-mannopyranose (9) in the presence of potassium carbonate followed. Chemoselective removal of the tert-butyl ester group from compound 10 resulted with O-mannoside 11 with a free carboxy group available for coupling of the

A golden opportunity: benzofuranone modifications of aurones and their influence on optical properties, toxicity, and potential as dyes

• Joza Schmitt and
• Scott T. Handy

Beilstein J. Org. Chem. 2019, 15, 1781–1785, doi:10.3762/bjoc.15.171

• expected due to the lack of direct conjugation with the carbonyl as well as the only modest electronic effects of alkyl, chlorine, and bromine. In general, the substituent effects are all fairly modest and result in fairly moderate changes in the extinction coefficient (although hydroxy substitution does

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• , we have turned our attention to different benzylic alcohols that could be utilized to further examine the functional group tolerance of the reaction. Notably, chlorine, bromine and iodine substituents were compatible with the transformation, providing 3m, 3n, 3r and 3s in 81–89% yield. The nitrile

Diazocine-functionalized TATA platforms

• Roland Löw,
• Talina Rusch,
• Fynn Röhricht,
• Olaf Magnussen and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1485–1490, doi:10.3762/bjoc.15.150

• bromotoluene 3 with TMS-protected acetylene 4 (95%). The C–C bond formation of 5 and 6 to give dibenzoyl 7 was achieved with potassium butoxide and elemental bromine (9%) according to a literature procedure [27]. The para-ethynyldiazocine 8 was obtained by reduction of both nitro groups, followed by oxidation

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• was produced in a low 31% yield. Electron-withdrawing groups such as a fluorine, bromine, chlorine, trifluoromethyl and a nitro group as well as electron-donating groups such as a methoxy group at the para-position were found to be well tolerated, as indicated by aryl cyclopropyl sulfides 1h–m which

• were obtained in yields ranging from 72 to 95%. Moving the bromine from the para- to the meta-position resulted in a substantial reduction in the yield of the reaction, as shown by compound 1n. Compound 1o possessing a methyl ester at the ortho-position was prepared in 44%, a yield which is consistent

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• similar chemical shifts in binding energies, fragments of larger organic compounds are not easily distinguished. Labeling molecular entities with elements possessing large excitation cross sections like fluorine, chlorine, or bromine [40] represents an approach that can greatly simplify the detection of

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

• Camila B. Francisco,
• Cleverton S. Fernandes,
• Ulisses Z. de Melo,
• Roberto Rittner,
• Gisele F. Gauze and
• Ernani A. Basso

Beilstein J. Org. Chem. 2019, 15, 818–829, doi:10.3762/bjoc.15.79

• correspond to ae (H1ax and H2eq) and ea (H1eq and H2ax) conformers individually (Table 1). The values of 3JH–H, δ and W at −80 °C allow the assignment of the signals to the respective conformers, and by the integrals, determination the percentage of each in the equilibrium. In the case of the bromine

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials

• Widukind Moormann,
• Daniel Langbehn and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 727–732, doi:10.3762/bjoc.15.68

• coupling of nitrotoluenes and the reductive ring closure of the dinitro compounds (Scheme 1). We recently improved the yield of the C–C coupling through addition of bromine as an oxidizing agent [27]. The reaction times thus are reduced to several minutes as compared to several hours in previous procedures

• reducing conditions of the azo cyclization. Moreover, the tert-butyl group can be conveniently removed under acidic conditions. As described in [27] potassium butoxide is used as a non-nucleophilic base to remove the α-toluene protons of 9a and 9b. By addition of bromine as an oxidizing agent dimers 10a

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• bromine atom on the benzene ring may play the key functional role in the inhibitory activity. This study could thus provide a clue for the further biological study and structure modification of marine brominated laurane sesquiterpenoid derivatives towards new effective PTP1B and/or NF-κB inhibitors

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• -phenylbutyl acetate (3a) with a concomitant reduction of iodate to iodine. The nature of the H-atom abstraction catalyst was then varied in an effort to increase the yield of compound 3a upon oxidation of n-butylbenzene. The presence of moderate electron withdrawing or donating substituents (chlorine, bromine