Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes

• Zhensheng Zhao and
• Graham K. Murphy

Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67

• . Experimental evidence suggests that a radical mechanism is involved. Keywords: allene; chlorination; hypervalent iodine; synthetic methods; vinyl chloride; Introduction Organochlorine compounds are vital as polymer precursors [1], as pharmaceuticals [2][3] and agrochemicals [4][5][6] and as functional

• vicinal-dichlorination of phenylallenes; however, no such chlorination reaction has yet been achieved [29][30][31][32][33][34]. Recent reports of reactions between hypervalent iodine reagents and phenylallenes have highlighted the possible product outcomes achievable through ionic and radical reaction

• ][44][45], there is potential for the selective generation of diverse, poly-chlorinated scaffolds. Reported here are the results of these investigations, and while indiscriminate chlorination of 2 was observed with 1a, 1b reacted chemo- and regioselectively to give 2,3-dichlorides (3) or chlorodienes

Palladium-catalyzed ortho-halogenations of acetanilides with N-halosuccinimides via direct sp² C–H bond activation in ball mills

• Zi Liu,
• Hui Xu and
• Guan-Wu Wang

Beilstein J. Org. Chem. 2018, 14, 430–435, doi:10.3762/bjoc.14.31

• ], we have independently investigated the solvent-free ortho-iodination of acetanilides under ball-milling conditions [45]. In addition, the current reaction can be extended to ortho-bromination and ortho-chlorination by using the corresponding N-halosuccinimides. Herein, we report these regioselective

• N-halosuccinimides. The influence of the milling frequency on the reaction of 1a with NIS. Palladium-catalyzed ortho-iodination of 1a in toluene. Plausible mechanism. Palladium-catalyzed ortho-bromination and chlorination of 1a in a ball mill. Optimization of the reaction conditions.a Substrate

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

•  41. 7-Chloropyrazolo[1,5-a]pyrimidines 140 obtained by 4-H/cyano/carboxylate-5-aminopyrazoles 126 (X = H, Y = R) and β-ketoesters 81 followed by chlorination with POCl3, were converted to 7-aminopyrazolo[1,5-a]pyrimidines 142 and 7-methoxy/thiomethoxypyrazolo[1,5-a]pyrimidines 143 on treatment of NIS

• -amines 198 possessing 4-(1H-benzimidazol-2-yl)phenylamine moiety at C4 position and primary as well as secondary amines at C6 position starting from 5-aminopyrazole-4-carboxamide (194). Compound 194 was treated with urea to give 1H-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione (195) followed by chlorination

• . Chlorination of pyrazolo[3,4-d]pyrimidine derivative 211 with phosphorus oxychloride afforded 4-chloro-1H-pyrazolo[3,4-d]pyrimidine derivative 212. The chloro and nitro groups were manipulated to introduce a 3,6-dihydropyran group at position-4 by Stille reaction which provided 4-(4-(3,6-dihydropyran-4-yl)-1H

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• that CF3SO2Cl reacts under reductive conditions while CF3SO2Na requires oxidative conditions. Electrophilic chlorination is obviously the exclusive preserve of CF3SO2Cl that has been exploited with emphasis in enantioselective chlorination. Keywords: chlorination; fluorine; sulfur

• trifluoromethylsulfonylation reactions. We now focused this second part of the review on the similarly diverse uses of trifluoromethanesulfonyl chloride plus chlorination. This review appears in two parts that are published back-to-back. We encourage the readers to refer to Part 1 for a general introduction in the field [1

• the presence of Eosin Y under visible light irradiation (Scheme 2) [9]. Acetophenone derivatives with various substitution patterns as well as aliphatic or heteroaromatic ketones were equally well tolerated. This methodology offered the advantage of minimising the chlorination side reaction

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• reactions, the versatility of these two reagents is presented in other reactions such as sulfonylation and chlorination. This first part is dedicated to sodium trifluoromethanesulfinate. Keywords: fluorine; sulfur; trifluoromethylation; trifluoromethylsulfenylation; trifluoromethylsulfonylation

Syntheses, structures, and stabilities of aliphatic and aromatic fluorous iodine(I) and iodine(III) compounds: the role of iodine Lewis basicity

• Tathagata Mukherjee,
• Soumik Biswas,
• Andreas Ehnbom,
• Subrata K. Ghosh,
• Ibrahim El-Zoghbi,
• Nattamai Bhuvanesh,
• Hassan S. Bazzi and
• John A. Gladysz

Beilstein J. Org. Chem. 2017, 13, 2486–2501, doi:10.3762/bjoc.13.246

• probed by DFT calculations. Keywords: chlorination; copper mediated perfluoroalkylation; crystal structure; DFT calculations; fluorous; hypervalent iodine; nucleophilic substitution; polar space group; Introduction A number of fluorous alkyl iodides, usually of the formula RfnCH2CH2I or RfnI (Rfn = CF3

• methylene group, RfnCH2ICl2, have been isolated for n = 8 and 10 as depicted in Scheme 1 [17][20]. Although partition coefficients are not available for the iodide Rf8CH2I (the byproduct that would form in most chlorination reactions), they would fall between those of Rf8I (88.5:11.5 for CF3C6F11/toluene

• starting material. Attempted syntheses of RfnICl2. Prior to the efforts described in the previous sections, iodine(III) dichlorides derived from perfluoroalkyl iodides RfnI were considered as targets. Since these lack sp3 carbon–hydrogen bonds, they are not susceptible to possible chlorination or other

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

• (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

• ) under solvent-free ball milling condition [88]. Aryl rings containing electron donating groups worked efficiently to yield 70–98% of mono or dibromo derivatives within 2 h. Similarly, NIS led to aryl iodination in near quantitative yield and NCS failed to produce any chlorination product (Scheme 25

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

• most important field of application of this catalytic principle. Based on several highly spectacular recent reports, we thus wish to discuss some of the most important achievements in this field within the context of this review. Keywords: amination; chlorination; fluorination; hydroxylation

• conditions [90]. Key to success in this spectacular report was the use of the systematically optimized sulfonamide-containing phosphonium salt J1. With this catalyst, they were able to achieve high selectivities in the α-chlorination of 1 with N-chlorophthalimide (13) as the Cl-source under H2O-rich

• -chlorination of β-ketoesters 1, by using N-chlorosuccinimide (14) as the Cl-transfer agent [76]. In continuation of our efforts to develop bifunctional ammonium salts D for asymmetric catalysis we have also recently investigated the asymmetric synthesis of α-chloroketoesters 12 [92]. We found that catalyst

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

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

• 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

Mechanochemistry-assisted synthesis of hierarchical porous carbons applied as supercapacitors

• Desirée Leistenschneider,
• Nicolas Jäckel,
• Felix Hippauf,
• Volker Presser and
• Lars Borchardt

Beilstein J. Org. Chem. 2017, 13, 1332–1341, doi:10.3762/bjoc.13.130

• of 0.20 cm3 g−1 and a surface area of 291 m2 g−1. Indeed, the high temperature chlorination reaction is essential to obtain the full porosity of the desired carbon. However, when we conducted the mechanochemical polymerization in the presence of small amounts of ethanol (liquid-assisted grinding, LA

Characterization of non-heme iron aliphatic halogenase WelO5* from Hapalosiphon welwitschii IC-52-3: Identification of a minimal protein sequence motif that confers enzymatic chlorination specificity in the biosynthesis of welwitindolelinones

• Qin Zhu and
• Xinyu Liu

Beilstein J. Org. Chem. 2017, 13, 1168–1173, doi:10.3762/bjoc.13.115

• natural products [1][2] and chlorination is the most common functionalization of this type [1][2]. Among other effects, chlorination enhances the electrophilicity of the modified carbon and alters the biological activities of drug(-like) molecules [3][4]. As aliphatic C–H groups are ubiquitous in organic

• previously characterized WelO5, it showed enhanced chlorination activity towards 1, distinct from WelO5. This study, along with the recent characterizations of WelU1 and WelU3 enzymes in H. welwitschii IC-52-3 [16], collectively provides the molecular basis for the altered structural diversity between the

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• evaluated as chiral organocatalysts in the enantioselective α-chlorination of β-ketoesters, with excellent results obtained after optimisation of the organocatalyst structure [12]. In an effort to identify new, easily accessible and tuneable organocatalysts with the privileged pyrrolidine motif from the

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• the chlorination and other C–H functionalization of (2-pyridyl)arenes. Together with this work, some other work on C–H acyloxylation provided an indirect pathway for the synthesis of phenols from arenes [54]. In 2014, Shi and co-workers designed a removable bidentate functional group, which could

A novel method for heterocyclic amide–thioamide transformations

• Walid Fathalla,
• Ibrahim A. I. Ali and
• Pavel Pazdera

Beilstein J. Org. Chem. 2017, 13, 174–181, doi:10.3762/bjoc.13.20

• chlorination of the heterocyclic amides to afford the corresponding chloroheterocycles. Secondly, the chloroherocycles and N-cyclohexyl dithiocarbamate cyclohexylammonium salt were heated in chloroform for 12 h at 61 °C to afford heteocyclic thioamides in excellent yields. Keywords: heterocyclic amides

• heterocyclic amides attracted our attention: as a first step, we applied a chlorination of heterocyclic amides, followed by thiation via reaction with thiourea on the basis of reagent-promoted desulfurylation of isothiourea under strong basic conditions [8][9]. Aiming to continue our reseach work on the

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• -specific cholesterol-lowering agent. The schematic representation of the synthesis of multi-Lac-β-CD (5) is shown in Figure 1. Briefly, per-NH2-β-CD (4) was synthesized by chlorination (per-chloro-β-CD (2)) and azidation (per-azido-β-CD (3)) of primary hydroxy groups of β-CD 1, as reported previously [17

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

• Olga C. Dennehy,
• Valérie M. Y. Cacheux,
• Benjamin J. Deadman,
• Denis Lynch,
• Stuart G. Collins,
• Humphrey A. Moynihan and
• Anita R. Maguire

Beilstein J. Org. Chem. 2016, 12, 2511–2522, doi:10.3762/bjoc.12.246

• first chlorination step, leading to a reaction mixture which contained acrylamide 4 as the main product formed (entry 5, Table 2). This ability to halt the cascade at the acrylamide intermediate 4 or push through to the α-thio-β-chloroacrylamide Z-3 highlights the enhanced control of reaction

• intermediates 4 and 5 as product impurities [3]. The stoichiometry of NCS used for the continuous process was also further optimized (Table 5). It was found that, at 130 °C, 2 equivalents of NCS resulted in the lowest levels of the impurities arising from reaction intermediates and over-chlorination byproducts

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

• on the benzene ring make parylene D superior to parylene N and parylene C. There are some creative strategies for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane (Figure 2), the precursor of parylene D [8]. Theoretically, direct chlorination of [2.2]paracyclophane is an ideal route to

Synthesis of medronic acid monoesters and their purification by high-performance countercurrent chromatography or by hydroxyapatite

• Elina Puljula,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2016, 12, 2145–2149, doi:10.3762/bjoc.12.204

• esterified via chlorination of the triester [33] or directly by using alkylhalides. Many of these strategies are sensitive to moisture and require dry conditions, or alternatively lead to the formation of mixtures of different mixed tetraesters of medronic acid. Additionally, we encountered one previously

• unreported problem in the chlorination reaction of trimethyl methylene-BP with oxalyl chloride, i.e., we observed that the triester readily formed a dimer with itself during the chlorination reaction according to the 1H and 31P NMR spectra. Dimerization has been previously observed with clodronic acid

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• TiO2 nanoparticle assemblies using H2O2 [51]. Geminal chloronitroso compounds are synthesized or in situ generated from their corresponding oximes by chlorination. As halogen source elemental chlorine [52][53][54], nitrosyl chloride [55], alkyl hypochlorites [56], N-chlorourea [57], tert-butyl

Synthesis of pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones: Rearrangement of pyrrolo[1,2-d][1,3,4]oxadiazines and regioselective intramolecular cyclization of 1,2-biscarbamoyl-substituted 1H-pyrroles

• Kkonnip Son and
• Seong Jun Park

Beilstein J. Org. Chem. 2016, 12, 1780–1787, doi:10.3762/bjoc.12.168

• using a more convenient and facile approach than those that have been previously reported in the literature [9][10][11][12]. Results and Discussion Our studies started with the synthesis of aminopyrrolocarbamate 10. The preparation of compound 10, which is illustrated in Scheme 2, involved chlorination

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

• halogenation of tetraphenylene attracted our attention. The Wang group reported an efficient and mild protocol for a gold-catalyzed direct C–H halogenation of arenes with N-halosuccinimides [56][57]. Therefore, we initially investigated the chlorination of tetraphenylene by subjecting it to Wang’s conditions

• -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

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• compound 3f. This subsequent chlorination of picolinic acid chloride is known from the literature to proceed under enforced conditions [27][28]. On the other hand, a selective synthesis of 3a is possible in 73% yield by coupling of β-enaminoketone 2a with picolinic acid under assistance of BOP as reagent

• (see Supporting Information File 1). The in situ generation of the acid chloride with thionyl chloride was possible without the undesired chlorination with the more electron-deficient 6-methoxycarbonyl-substituted 2-pyridine carboxylic acid delivering with 2a the desired β-ketoenamide 3g with excellent

• the accidental chlorination of the picolinic acid precursor (Scheme 2) – offered the option to perform two subsequent coupling reactions in a controlled fashion. In the first step, the more reactive nonaflate moiety of 5g was efficiently substituted by a phenyl group under standard Suzuki reaction

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• of intermediates have been proposed to be the reactive intermediates in many reactions such as aldol, Michael, Mannich, and α-functionalization (α-chlorination, α-amination, α-fluorination) reactions. Proline-type organocatalysts are considered priviliged, because their corresponding enamines exist