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

• expected to give non-benzylated 1a. However, iodination of methyl indol-2-ylacetate led to polymerization reactions involving the CH2 protons. In order to investigate the general viability of this synthetic way, we performed iodination at position 3 of ethyl indole-2-carboxylate, which does not contain

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• intracellular ROS and includes inhibition of tubulin polymerization (Scheme 9). Semicarbazides and thiosemicarbazides are substances used to identify aldehydes and ketones, are very versatile in the synthesis of heterocycles, and have several applications in the preparation of important drugs. Nucleophilic

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• are acceptable although those with narrow molecular weight distribution are always desirable. These PEGs can be synthesized conveniently by polymerization of ethylene oxide under basic or acidic conditions [7]. The polymerization methods are inexpensive and PEGs with high molecular weight can be

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

• malignant tumors, including platelet-derived growth factor receptor beta (PDGFR-β), vessel epidermal growth factor receptor (VEGFR-2), and epidermal growth factor receptor (EGFR) [5][6]. In addition, these compounds may act as vascular disrupting agents and tubulin polymerization inhibitors, contributing to

• ). The EGFR inhibitor drugs bearing the 4-anilinoquinazoline moiety did not show potent cytotoxic activity against T98G cells (21.3 µM for erlotinib, and 37.8 µM for gefitinib). However, the tubulin polymerization inhibitor (verubulin), which contains 4-anilinoquinazoline in its chemical structure, was

Study on the interactions between melamine-cored Schiff bases with cucurbit[n]urils of different sizes and its application in detecting silver ions

• Jun-Xian Gou,
• Yang Luo,
• Xi-Nan Yang,
• Wei Zhang,
• Ji-Hong Lu,
• Zhu Tao and
• Xin Xiao

Beilstein J. Org. Chem. 2021, 17, 2950–2958, doi:10.3762/bjoc.17.204

• , are formed by polymerization of glycoluril, which contains rigid cavities for the study of host–guest chemistry and carbonyl groups for the study of coordination chemistry [16][17][18][19][20]. For the special methyl cucurbit[n]urils with abundant methyl groups, its high density of the

Polymer chemistry: fundamentals and applications

• Bernhard V. K. J. Schmidt

Beilstein J. Org. Chem. 2021, 17, 2922–2923, doi:10.3762/bjoc.17.200

• -healing materials are presented in this thematic issue. Finally, the use of polymerization-induced self-assembly for the synthesis of drug carriers is presented. The issue also shows the multidisciplinary character of polymer science, for example when supramolecular motifs, organic coupling reactions or

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• polymerization (ATRP) reactions and functional polymer synthesis [29][30][31][32][33][34]. Although α-bromo-γ-butyrolactone, which is a five-membered lactone, is easily accessible from the five-membered lactone by some bromination methods [35][36], the bromination method for the six-membered lactone, δ

• conditions. In sharp contrast, the corresponding six-membered α-bromo-δ-valerolactone has a more-distorted ring and is extremely unstable, even at room temperature [39][40][41]. In fact, it must be stored in a freezer because ring-opening polymerization and ring-contraction reactions occur readily at room

• in a dramatically lower yield of 3a (8%), most likely because 3a is unstable to base at room temperature and may decompose or polymerize (see Supporting Information File 1). To avoid decomposition or polymerization, 3a produced in situ by the intramolecular cyclization of 2a should be separated

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

• , Figure 1B) form via the polymerization of multiple glycoside units. The ports on both sides of these compounds are surrounded by carbonyl oxygen atoms, which form a hydrophobic cavity and two hydrophilic ports [20]. The outer surface of the cucurbit[n]uril is composed of a large number of nitrogen atoms

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

• photocatalysts have been successfully applied in both small- and large-scale synthesis such as organic reactions [16][17], free radical polymerization (FRP) [18][19][20], controlled radical polymerization (CRP) [21][22], CuAAC chemistry [23][24][25], and thiol–ene chemistry [26][27]. However, most of the

• [34][38][39][40]. The use of 2D materials for the photoinitiated electron transfer reactions with CuII catalysts for the photoinduced atom transfer radical polymerization (ATRP) and CuAAC reactions prompted us to develop a new photoredox system that works under NIR irradiation for the CuAAC reaction

• indicated that structurally diverse polymers formed by different polymerization mechanisms can readily be linked just by a simple NIR-induced CuAAC reaction. The macromolecular scope was further extended to the preparation of cross-linked materials. Thus, the formulations containing bisphenol A di(3-azido-2

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• more structural investigations are required to elucidate this. Keywords: micelle; mitochondria; phosphorylcholine; PISA; polymerization-induced self-assembly; Introduction Targeting mitochondria is a promising strategy for the development of new anticancer drugs [1]. Among them, organoarsenical drugs

• be taken into account that the drug can interfere with the block copolymer aggregation. Alternatively, the use of reactive polymers for the polymerization creates a functional anchor to enable post-functionalization of the PISA nanoparticles with drugs such as doxorubicin [35][36]. In a different

• strategy, drug conjugated monomers can be directly used in the polymerization, eliminating the post-modification step [28][37][38][39]. In order to use micelles, prepared by PISA or traditional techniques, for targeting specific receptors, it is necessary that these materials are low-fouling, thus repel

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• polymerization of azulene (1) by iodine or bromine to obtain polyazulene–iodine/bromine complexes (PAz-I2/PAz-Br2) (Scheme 1). The PAZ-I2 complex was found to be insoluble whereas PAZ-Br2 was sparingly soluble in most of the organic solvents. Although no structure was proposed for these polymer complexes, based

• of polymerization of ≈7) leaving speculation about a higher degree of polymerization for the THF-insoluble component of PAZ-Br2. The UV–vis spectrum of the chloroform-soluble fraction of PAZ-Br2 displayed absorption bands in the 190–330 nm region like the azulene monomer, and a long tail with a broad

• , Fukutomi, and Nakayama [19] reported the synthesis of what they described as ‘true polyazulene’ through a cationic polymerization reaction. Their protocol involved heating the trifluoroacetic acid (TFA) solution of azulene (1) followed by treatment with triethylamine to obtain a brown polymeric product

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• continuous development and improvement of polymerization techniques, more and more diverse copolymers can be synthesized. Very recently, Kertsomboon et al. succeeded in preparing a copolymer (poly(AAm-co-MDO)) of acrylamide and a degradable, hydrophobic monomer based on a ring opening polymerisation of

An initiator- and catalyst-free hydrogel coating process for 3D printed medical-grade poly(ε-caprolactone)

• Jochen Löblein,
• Thomas Lorson,
• Miriam Komma,
• Tobias Kielholz,
• Maike Windbergs,
• Paul D. Dalton and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2021, 17, 2095–2101, doi:10.3762/bjoc.17.136

• surface modification, we also observe bulk polymerization, which is expected for this method, and currently limits the controllability of this procedure. Keywords: additive manufacturing; light-induced polymerization; self-initiated photografting and photopolymerization; surface-initiated polymerization

• demonstrate this surface modification using a hydrogel, poly(2-hydroxyethyl methacrylate) (PHEMA) [19]. However, this approach should have broad utility for a spectrum of monomers and macromonomers susceptible to radical polymerization onto (almost) any surface featuring C–H bonds. This hydrogel coating is

• in proportion to the square of the distance, a larger working distance should result in less pronounced coating. Wang and Brown reported a polymerization conversion of 90% after 50 s for HEMA (0.30 mm ± 0.04 mm) [22] which is significantly faster than the values investigated in the present study

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• polymerization of acrylate/epoxy monomer blends) can also be carried out upon NIR light with the proposed systems. Keywords: cyanine; NIR light; photochemistry; Introduction Photopolymerization processes are well established due to the specific features and advantages. Indeed, the reaction is carried out at

• room temperature and with a high spatial resolution (the reaction only occurs in the light-irradiated areas). These latter photochemical processes are also very fast and efficient. However, energetic and unsafe UV light is usually used to ensure high polymerization rates and final reactive function

• conversions. To prevent the use of harmful UV light, different longer-wavelength photoinitiating systems (PISs) were proposed, e.g., blue light in dental materials [1][2]. Many PISs were developed for visible light, but much less studies are focused on the polymerization using near-Infrared (NIR) sources [3

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• 22, 14195 Berlin, Germany 10.3762/bjoc.17.129 Abstract The sequence, length and substitution of a polysaccharide influence its physical and biological properties. Thus, sequence controlled polysaccharides are important targets to establish structure–properties correlations. Polymerization techniques

• key to understanding polysaccharides’ function in nature and translate this knowledge into tailor-made materials. Synthesis (i.e., chemical, enzymatic, or through polymerization) offers the opportunity to access polysaccharides with well-defined composition, length, and substitution. These compounds

• glycosidic bond formation. Control over the polysaccharide length (degree of polymerization, DP) and regioselective insertion of modifications or branches are additional challenges. Three main approaches are available (Figure 1): A) enzymatic polymerization [10][11][12][13][14][15][16][17], B) chemical

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

• -catalyzed C–H activation Scandium is the first metal of the 3d metals row. It is relatively cheap compared to heavier transition metals, and it is commonly used on catalytic procedures, such as catalyzed polymerization [31][32] and C–C coupling reactions [33][34]. It is also an increasing metal option to

• this specific metal are highly desirable. Titanium is well known to be used as titanium dioxide, a powerful photocatalyst present in inks [61][62] and sunscreens [63][64]. As a catalyst, it can be used, for example, in polymerization methods to synthesize polypropylene [65]. With regard to C–H

• ] and batteries [174]. Due to its accessibility, it is well explored in catalysis for many fields, such as cycloaddition reactions [175], polymerization [176], and C–C cross-coupling methods [177]. Several biologically active compounds have been obtained through cobalt catalysis [178][179][180

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• on its own SM-gene-cluster [146][147][148]. The DHN-melanin of A. fumigatus is a heteropolymer formed through the polymerization of 1,8-dihydroxynaphtalene (1,8-DHN) monomers (10) and is responsible for the unique greyish-green colour of A. fumigatus conidia (Figure 5). The genetics and biochemistry

• to 1,8-dihydroxynaphthalene (1,8-DHN) (10) by Abr1, a multi-copper reductase. In a last step polymerization of 1,8-DHN monomers is facilitated by the laccase Abr2 [45][149][150][151][152]. Knock out mutants of either ayg1, arp2, or abr2 lead to different coloured conidia while loss of pksP aborts DHN

• predictions or artificial oxidative polymerization studies of 1,8-DHN monomers [144][153]. Next to offering the conidia protection from UV radiation, DHN-melanin was shown to be a key factor to survival during both predation and virulence. When preyed upon by fungivorous amoeba like P. aurantium melanised

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• dermatan sulfates. 10) Heparan sulfate extension: EXT1 and EXT2 both have GlcUA and GlcNAc transferase activities and are together responsible for HS chain polymerization. EXTL1–3 are additional enzymes with GlcNAc transferase activity that facilitate heparin sulfate biosynthesis. Additional enzymes that

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• Susanne M. Fischer Simon Renner A. Daniel Boese Christian Slugovc Institute for Chemistry and Technology of Materials, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria Christian Doppler Laboratory for Organocatalysis in Polymerization, Stremayrgasse 9, 8010 Graz, Austria

• stability of the phosphines was also evaluated and the most electron-rich TMTPP was found to be only slightly more sensitive to oxidation than TPP. Finally, the catalysts were employed in the oxa-Michael polymerization of 2-hydroxyethyl acrylate. With TMTPP polymers characterized by number average molar

• slightly lower than the activity of the methoxy-substituted congeners. As an example for acrylates as Michael acceptors, the performance of the catalysts in the oxa-Michael addition polymerization of 2-hydroxyethyl acrylate (HEA, 4) was investigated [27][28][29]. The catalyst loading was increased to 5 mol

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• polymerization. Extensive optimization led us to a set of conditions that routinely provided 4-nitro[2.2]paracyclophane (4) in good yields regardless of the scale of reaction (nitration has been performed on scales ranging from 0.5 g to 30 g). The 1H NMR of the crude reaction mixture invariably shows two other

• . Reaction of 1 with nitric acid alone led to a surprisingly clean, nitration, albeit by a very slow reaction. As stated earlier, nitration is normally a messy reaction. Presumably, the low concentration of nitronium ion present in equilibrium with the acid promotes a clean reaction without polymerization or

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• , ascorbic acid/hydrogen peroxide, respectively. The mixture was immediately placed in a Petri dish to complete the gelation via free radical polymerization under dark conditions. After 3 hours, the resulting hydrogel was purified with water to remove the unreacted species (monomers and redox mediators

• modification platform [49]. The as-prepared hydrogel network (HGCM) was immersed in various acrylic monomers. Following that, photoinduced free radical polymerization of employed monomers performed under visible light irradiation by taking advantage of embedded g-CN nanosheets in HGCM. According to literature

• , g-CN as an organic semiconductor is utilized in polymerization processes as a photoinitiator by generation of reactive radical species (O2−•, HO•, HO2•) under convenient light illumination. The ability of g-CN to initiate polymerization and act as a polymerization locus for a covalent polymer growth

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• [38][42]. The ratio of V-40/2a was important to depress the formation of self-polymerization of 2a (Table 1, entries 5–7). The results showed that the best amount of V-40 toward 2a was 10 mol %. Besides, the side product 3a’ is found up to 8% yield under photoirradiation. Considering that in our

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• deprotonated acetylacetone and diphenylmethane. Even there are reports on SNAr reactions of acetylacetone with purines and pyrimidines [56][80], in our hands only polymerization of acetylacetone was observed. On the other hand, the diphenylmethane anion (pKa 32; DMSO [81]) apparently is too basic and

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32