Extrusion – back to the future: Using an established technique to reform automated chemical synthesis

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 65–75, doi:10.3762/bjoc.13.9

• , the most common transformation, involves the constant growth of a polymer chain where the ability to terminate the reaction is removed [14]. Again, there are several types of transformation including ionic polymerisation, ring opening metathesis, free radical and growth polycondensations [15]. All of

• . It must be noted, however, that the reaction reported by Höcker involves the use of s-BuLi, making the process more difficult, but still a greater throughput rate is obtained than that predicted by Meyer [20]. Free radical polymerisation involving deactivation polymerisation, iniferter polymerisation

• and reversible addition fragmentation chain transfer (RAFT) polymerisation, amongst others [21], has been studied extensively by extrusion to produce, for example, branched polypropylene, polyethylene and polylactide polymers. The process involves the production of a free radical at the end of an

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• ]. This finding points to a free radical or its reversible adsorption at the electrode. However, the latter pathway was ruled out by experiments of Utley et al. [48][49], when comparing the coupling of unsaturated and saturated carboxylic acids and the effect of adsorption. Ester 30a has been cleaved with

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids

• Naganna Narra,
• Shiva Shanker Kaki,
• Rachapudi Badari Narayana Prasad,
• Sunil Misra,
• Koude Dhevendar,
• Venkateshwarlu Kontham and
• Padmaja V. Korlipara

Beilstein J. Org. Chem. 2017, 13, 26–32, doi:10.3762/bjoc.13.4

• of the prepared derivatives were studied by the well-established DPPH radical scavenging assay and also by studying the oxidation of linoleic acid using DSC. The DPPH radical is a commercially available stable free radical which is widely used to preliminarily determine the radical scavenging

• cinnamic acid derivative 3a. This could be due to the absence of a phenolic hydroxy group which is responsible for the anti-oxidant activity of most of the natural phytochemicals. Among all compounds, 3c was found to be the most efficient free radical scavenger which showed a value closest to the standard

• anti-oxidant, α-TP. Compounds 3d and 3e also showed free radical scavenging activity (FRSA) of 68% and 67%, respectively, whereas compound 3b showed only moderate activity with 30% FRSA. In another study, the ability of the prepared derivatives in inhibiting the oxidation of linoleic acid was studied

Radical polymerization by a supramolecular catalyst: cyclodextrin with a RAFT reagent

• Kohei Koyanagi,
• Yoshinori Takashima,
• Takashi Nakamura,
• Hiroyasu Yamaguchi and
• Akira Harada

Beilstein J. Org. Chem. 2016, 12, 2495–2502, doi:10.3762/bjoc.12.244

• permeation chromatography (GPC). The polymerization of DMA and AA mediated by α-CD-CTA gave polymers with similar molecular weights (12.8 and 14.8 kDa) and narrow distributions in good yields (85–88%) (Table 1, entries 2 and 5). In contrast, in the absence of α-CD-CTA, free radical polymerization with VA-044

• inhibiting the molecular recognition of α-CD, the inclusion complexation ratio between the monomer and α-CD-CTA was decreased, which lead to lower yields and higher molecular weight of the resulting polymers due to preceding free radical polymerization. In the reaction of AAm monomer, which has a low

• reaction, some of the polymer chains (Pn•) form dead chains through termination or irreversible chain transfer. However, the Mw/Mn of the polymer mediated by α-CD-CTA agents that the termination reaction is suppressed by α-CD-CTA compared to free radical polymerization. Conclusion We studied the radical

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

• bromides from substituted (4-methylbenzyl)bromides. Bromination of 2,5-dichloro-p-xylene (1) with H2O2–HBr. Visible-light induced free-radical bromination of substituted p-xylenes with H2O2–HBr. Synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane 16 from 11. Synthesis of substituted [2.2]paracyclophanes

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

• Judita Britner Helmut Ritter Institute of Organic Chemistry and Macromolecular Chemistry, Heinrich-Heine-University, Universitätsstraße 1, 40225 Düsseldorf, Germany 10.3762/bjoc.12.232 Abstract The first detailed study on free-radical polymerization, copolymerization and controlled radical

• employing MLA as dienophile was described [3][4][5][6]. In a recent NMR study we demonstrated that, poly(MLA) prepared via free radical polymerization contains mainly isotactic units. Furthermore, we found that the polymer attached lactide rings react like activated esters and thus readily undergo

• -Michael additions on MLA were reported [11][12]. In this paper, we wish to present a kinetic study of free radical and controlled/living radical polymerization of MLA. The latter reactions were conducted via a reversible addition fragmentation chain transfer (RAFT) mechanism. We also investigated the

New furoisocoumarins and isocoumarins from the mangrove endophytic fungus Aspergillus sp. 085242

• Ze’en Xiao,
• Senhua Chen,
• Runlin Cai,
• Shao’e Lin,
• Kui Hong and
• Zhigang She

Beilstein J. Org. Chem. 2016, 12, 2077–2085, doi:10.3762/bjoc.12.196

• epidermidis, Escherichia coli, Klebsiella pneumoniae, and Bacillus subtilis. None of the compounds was active at a concentration of 50 μg/mL. In the free radical scavenging assay using 2,2-diphenyl-1-picrylhydrazyl (DPPH), only compounds 1 and 3 exhibited weak activity with EC50 values of 125 and 130 μM

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• agents and initiators for free-radical reactions both in industry and in laboratory. These compounds are produced and involved in various natural and biological processes and were explored extensively as antimalarial agents, anthelmintics, and anticancer drugs. Organic peroxides, such as alkyl

• Baeyer−Villiger oxidation and it is one of the methods for the synthesis of commercially important caprolactone from cyclohexanone with peracetic acid [55][56]. Autoxidation processes with formation of hydroperoxides and their subsequent free-radical transformations with generation of carbon- and oxygen

• ][109][110][111][112][113]. Organic peroxides are widely used as oxidants in oxidative coupling processes [114][115][116][117][118][119][120]. Industrial-scale production of readily available and efficient initiators of free radical polymerization and effective biologically active compounds promotes the

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• equiv of NaOt-Bu [38][39]. In the same year, Taylor and co-workers independently reported synthesis of 2-oxindoles in the presence of Cu(OAc)2·H2O as oxidant (Scheme 1) [40][41][42][43][44]. Experimental evidence suggests involvement of a free-radical process in the addition of α-carbonylalkyl radicals

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• traditional Suzuki–Miyaura coupling. It is used to control a range of plant pathogens in broadacre and horticultural crops (Scheme 6) [207]. Felpin and co-workers have reported its synthesis starting from aryldiazonium salts [208], while the Heinrich group has employed a free-radical biaryl cross-coupling of

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• method, despite its relatively low yield and selectivity, does offer a rapid way to access potential drug metabolites or analogs for further biological evaluations. Free radical approach In 1994, Undheim and co-workers developed a radical relay strategy, using a progression from an aryl radical to an α

• , et al. in 2013 [67]. Free radical approach by Undheim et al. in 1994 [68]. Anodic oxidation approach by Nyberg et al. in 1976 [70]. Acknowledgements We thank the Purdue University for financial support.

Amino-functionalized (meth)acryl polymers by use of a solvent-polarity sensitive protecting group (Br-t-BOC)

• Helmut Ritter,
• Monir Tabatabai and
• Markus Herrmann

Beilstein J. Org. Chem. 2016, 12, 245–252, doi:10.3762/bjoc.12.26

• )-amino-protected monomers 2-((1-bromo-2-methylpropan-2-yl)oxycarbonylamino)ethyl (meth)acrylate 3a,b. For this purpose, 2-isocyanatoethyl (meth)acrylate 1a,b was reacted with 1-bromo-2-methylpropan-2-ol (2a). The free radical polymerization of (Br-t-BOC)-aminoethyl (meth)acrylates 3a,b yielded poly((Br-t

• , IR, GPC and DSC methods. The kinetics of the deprotection step was followed by 1H NMR spectroscopy. The solvent polarity and neighboring group effects on the kinetics of deprotection are discussed. Keywords: amino group protection; bromo-tert-butyloxycarbonyl; deprotection; free radical

• . Carpino [8][9][10] and a first practical application in peptide synthesis [11] this protecting group was quasi forgotten. In the present work we report new Br-t-Boc-protected (meth)acrylic monomers and their polymerization through free radical polymerization. The kinetics of Br-t-BOC solvolysis of the

Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol

• Miriana Kfoury,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2016, 12, 29–42, doi:10.3762/bjoc.12.5

• 2 are described as potent free-radical scavengers [29]. Moreover, it is well accepted that a wide variety of essential oils possess important antioxidant activities due to their high content in 1 and 2 [50]. In this work, the effect of encapsulation on the antioxidant activity of 1 and 2 was

Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines

• Brett N. Hemric and
• Qiu Wang

Beilstein J. Org. Chem. 2016, 12, 22–28, doi:10.3762/bjoc.12.4

• olefins with a tethered amino or oxygen functionality has been achieved for the construction of a variety of 1,2-oxyamino products, using palladium [19][20], platinum [21], gold [22], copper [23][24][25][26], free-radical initiators [27][28][29], hypervalent iodine [30], and electrochemical oxidation [31

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• beneficial biological properties, i.e., free radical scavenging activity [3], cardioprotective action [4], antibacterial and antiviral activities [5]. Two flavonoids in the class of flavanones, hesperetin and naringenin (chemical structures in Figure 1), can be extracted from citrus fruits such as lemon

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• mechanistically unclear, the authors suggested that either a free radical process or a photoinduced double bond isomerization (C9,C1 to C1,C2) followed by an [1,3]H shift might lead to the formation of 4-hydroxycrenulide (138). The total synthesis of (+)-acetoxycrenulide (151) commenced with preparation of

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

• ). Control experiments in the presence of TEMPO suggested that the reaction might proceed via a C-centered free radical provided by SET between the quinoline substrate and the cupric salt. In recent years, the formation of C–F chemical bonds received global research interest owing to the particular functions

• 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

• process (Scheme 12). In the presence of a Cu(II) catalyst, the one-electron oxidation to the phenol led to the occurrence of phenoxy radical 25 via the formation of phenoxyl copper(II) salt 24. The isomeric free radical species 26 then rapidly captured the halogen atom from LiX to give the target product

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

• interest in this functional group. Synthetic methods towards aliphatic SF5-containing compounds are based on free radical addition of SF5Cl or SF5Br to unsaturated compounds [7][8][9], whereas aromatic derivatives are available either by the Umemoto’s two-step synthesis from diaryl disulfides or

• unreactive (3g), presumably due to a large steric demand of B2pin2. The mechanism of this borylation reaction remains to be elucidated. Based on experimental results and literature precedent, we propose the following free-radical mechanism (Scheme 2). Aryldiazonium salt 3 reacts with pyridine to form

Probing multivalency in ligand–receptor-mediated adhesion of soft, biomimetic interfaces

• Stephan Schmidt,
• Hanqing Wang,
• Daniel Pussak,
• Simone Mosca and
• Laura Hartmann

Beilstein J. Org. Chem. 2015, 11, 720–729, doi:10.3762/bjoc.11.82

• cannot be homopolymerized through free radical polymerization, meaning that only single CA units will be attached to the PEG chains [14]. However, other phenomena may also affect the resulting grafting density such as different tendency of grafting from and grafting to between the different monomers

• case of CA it is generally believed that it cannot be homo polymerized via free radical polymerization [14]. CA contains a 1.2-disubstituted ethylene exhibiting high steric hindrance, which might explain the low reactivity compared to the MA and AA. Therefore, radicals at the β-carbon may not be able

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

Multicomponent versus domino reactions: One-pot free-radical synthesis of β-amino-ethers and β-amino-alcohols

• Bianca Rossi,
• Nadia Pastori,
• Simona Prosperini and
• Carlo Punta

Beilstein J. Org. Chem. 2015, 11, 66–73, doi:10.3762/bjoc.11.10

• : aminoalcohols; free-radical addition; imine; multicomponent reaction; titanium salts; Introduction Multicomponent reactions (MCRs) represent a green approach towards the synthesis of polyfunctionalized molecules by promoting multiple bond-forming mechanisms in a one-pot synthesis [1][2][3][4][5][6][7

• to the field clearly illustrate how the free-radical approach can be considered a valuable alternative to classical ionic protocols [16][17][18][19][20][21][22][23]. In this context, we succeeded in combining the advantages of the radical synthetic route with the high added value of a multicomponent

• reported optimized conditions for the selective free radical nucleophilic addition of ethers and alcohols to ketimines generated in situ under non-anhydrous conditions. The protocol consists of a three-component, one-pot reaction involving an aromatic amine, a ketone, and the source of the ketyl radical

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• (Scheme 1) [9], Bischler–Napieralski reactions [10], reduction of phenanthridones [11][12], free radical methodology, palladium/rhodium/iron-catalysed reactions, etc. One of the approaches to the large variety of 6-arylphenanthridine derivatives was the synthesis starting from benzotriazole derivatives of

Host–guest-driven color change in water: influence of cyclodextrin on the structure of a copper complex of poly((4-hydroxy-3-(pyridin-3-yldiazenyl)phenethyl)methacrylamide-co-dimethylacrylamide)

• Nils Retzmann,
• Gero Maatz and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 2480–2483, doi:10.3762/bjoc.10.259

• tyramine (1) was selectively methacrylated at room temperature followed by a diazotation coupling with 3-aminopyridine (4) leading to N-(4-hydroxy-3-(pyridin-3-yldiazenyl)phenethyl)methacrylamide (5). Subsequently, the azo dye containing polymer 7 was synthesized through free radical copolymerization of 5

Influence of cyclodextrin on the UCST- and LCST-behavior of poly(2-methacrylamido-caprolactam)-co-(N,N-dimethylacrylamide)

• Alexander Burkhart and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 1951–1958, doi:10.3762/bjoc.10.203

• synthesized from methacryloyl chloride (3) and racemic α-amino-ε-caprolactam (2). Copolymerization of 4 with N,N-dimethylacrylamide (5) was carried out by a free-radical mechanism using 2,2’-azobis(2-methylpropionitrile) (AIBN) as an initiator. The new copolymers show a lower critical solution temperature

• -amino-ε-caprolactam (2) was obtained according to literature via cyclocondensation of L-lysine (1) [15]. Through amidation of the primary amine (2) with methacryloyl chloride (3) the polymerizable 2-methacrylamido-caprolactam (4) was obtained (Scheme 1) [14]. Free radical copolymerization of 4 in

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• others, free radical polymerization of C-6 of the glucosamine residues with poly(ethylenglycol) acrylate [58]; free-radical polymerization of C-1 of glucosamine with mPEG [59] and 1,3-dipolar cycloaddition between the azide of an N-azidated chitosan and mPEG derivatives containing a triazolyl moiety [60