Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• expensive diphenyl ether, which has a nauseating odor, at 0.01 molar dilution at reflux (259 °C) to effect the ring closure via electrophilic aromatic substitution; and (3) the aqueous work-up of this method which does not reliably produce a precipitate that can be filtered easily. Given the

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

A three-armed cryptand with triazine and pyridine units: synthesis, structure and complexation with polycyclic aromatic compounds

• Claudia Lar,
• Adrian Woiczechowski-Pop,
• Attila Bende,
• Ioana Georgeta Grosu,
• Natalia Miklášová,
• Elena Bogdan,
• Niculina Daniela Hădade,
• Anamaria Terec and
• Ion Grosu

Beilstein J. Org. Chem. 2018, 14, 1370–1377, doi:10.3762/bjoc.14.115

• complexes with various aromatic guests. Results and Discussion Cryptand 2 is accessible via nucleophilic aromatic substitution in good yields (42%, Scheme 1) by treating triphenol 3 [36] with the reactive and commercially available 2,6-dichloro-3,5-dicyanopyridine following a procedure previously elaborated

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• -guided electrophilic substitution (HIGES). Keywords: electrophilic aromatic substitution; hypernucleofugality; hypervalent iodine; iodonio-Claisen; transmetallation; Introduction Hypervalent iodine compounds have been known for over a hundred years, but it was not until their renaissance in the 1990’s

• ), product yields and selectivities based on appropriate solvents, temperatures, and Lewis acids [9][10][11]. A recent digest of RICR theorized an underlying mechanistic concept dubbed iodine-guided electrophilic aromatic substitution (IGEAS) [12]; the basis for which the work herein is titled. Other related

Imide arylation with aryl(TMP)iodonium tosylates

• Souradeep Basu,
• Alexander H. Sandtorv and
• David R. Stuart

Beilstein J. Org. Chem. 2018, 14, 1034–1038, doi:10.3762/bjoc.14.90

• approach to N-aryl imides is to employ aniline starting materials (Scheme 1b, left), as was done in the synthesis of pentoxazone and related herbicides [2]. The alternative aromatic substitution approach with imide anions (Scheme 1b, right) is hampered by their low nucleophilicity [3]. Therefore

Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• trifluoromethanesulfonamide group are reported. Novel derivatives of these types of acids were synthesized in good yields. The generated N-triflylbenzamides were further functionalized through cross-coupling and nucleophilic aromatic substitution reactions. All compounds were stable in dilute aqueous solutions. Studies of

• ) or trifluoroacetic acid (3) are not readily modified, and changing substituents on these acids will heavily impact their pKa value (Figure 1). In contrast, halogenated benzoic acid derivatives are easily functionalized through cross-coupling [4][5] or nucleophilic aromatic substitution reactions

• fluorine) may be generated in good yields and further functionalized through nucleophilic aromatic substitution or cross-coupling reactions. It was found that the products were stable in dilute aqueous solutions, but they slowly hydrolyzed in concentrated solutions or in the presence of other strong acids

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

• = tert-butyl) the reaction results in the formation of pyrazolo[1,5-a]pyrimidine derivative 90 as an additional product. The authors proposed that the bulky group had significantly slowed down the rate of electrophilic aromatic substitution at C-4 on 1H-pyrazol-5-amine due to which the aza-Michael

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• -iodoaniline 32 in 68% yield after isolation [52]. The cyclization was performed via nucleophilic aromatic substitution with DBU and DABCO. Presumably DABCO activates the chlorine and modifies it into a better leaving group allowing the sterically hindered base DBU to abstract a proton from the protected

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• arenes react well and substituted pyrroles and indoles give the corresponding sulfoxides in high yields. Less electron-rich thiophene or benzene derivatives gave low yields. Nevertheless, carbocyclic azulene afforded the respective sulfoxide in 88% yield. We propose an electrophilic aromatic substitution

• mechanism, where the sulfinamide is oxidized by ammonium persulfate to the respective sulfur-centred cationic intermediate. After electrophilic aromatic substitution, the amine moiety is cleaved and the corresponding sulfoxide is formed. The mechanistic proposal is supported by competition experiments using

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

• . coupled various 1,2-dihaloarenes with 2-mercaptobenzimidazole in a nucleophilic aromatic substitution reaction [53]. Zhu’s group used Cu salts as a promoter for the cycloaddition of isocyanides with benzothiazoles [54]. Benzo[d]imidazo[2,1-b]thiazoles have also been synthesized via coupling of 2

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• phosphinyl nitrosoalkenes NSA15 (derived from the corresponding α-bromooximes) with electron-rich nitrogen heterocycles to give adducts 69 is described and the comparison of electrophilic aromatic substitution (1) and cycloaddition (2) routes is discussed [59] (Scheme 24). Quantum-chemical calculations

The effect of milling frequency on a mechanochemical organic reaction monitored by in situ Raman spectroscopy

• Patrick A. Julien,
• Ivani Malvestiti and
• Tomislav Friščić

Beilstein J. Org. Chem. 2017, 13, 2160–2168, doi:10.3762/bjoc.13.216

• situ XRPD monitoring of the formation of glycinium oxalate salts from γ-glycine and oxalic acid dihydrate [42]. Other examples of explorations of the effect of milling frequency on mechanochemical reactivity include aromatic substitution reactions [43] and the synthesis of nitrogen-doped titania [44

Novel approach to hydroxy-group-containing porous organic polymers from bisphenol A

• Tao Wang,
• Yan-Chao Zhao,
• Li-Min Zhang,
• Yi Cui,
• Chang-Shan Zhang and
• Bao-Hang Han

Beilstein J. Org. Chem. 2017, 13, 2131–2137, doi:10.3762/bjoc.13.211

• one trialdehyde M3 [22] were employed to react with bisphenol A to produce phenolic-resin porous polymers PPOP-1–PPOP-3 (Scheme 1). It is well-known that the ortho- and para-position of phenol are activated with negative charge for the electrophilic aromatic substitution in consequence of the electron

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• [23][24]. However, this method is limited to sultams bearing a strong electron-withdrawing group on the aromatic ring. A similar approach utilizes a nucleophilic aromatic substitution and leads to benzo-γ-sultams, yet this reaction requires harsh conditions and has a limited scope with only few

Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• electrophilic aromatic substitution that is strongly impacted by the effects of the substituents on the electron density of the aromatic ring in intermediate 4. Given our established interest in exploring structural mimetics for the steroid nucleus we were drawn to explore whether the PFB reaction could be used

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

• both nitro groups, unlike potassium salts of indole or carbazole, which have caused substitution of only one nitro group. Keywords: electrophilic aromatic substitution; indolo[3,2-b]carbazole; N-heteroacenes; nitration; nucleophilic aromatic substitution; Introduction Organic π-conjugated compounds

• ], including elaboration of convenient synthetic ways to construction and modification of ICZ derivatives [34][35][36][37][38][39][40][41]. Taking into account the electron-donating character of the ICZ system, there is no doubt that electrophilic aromatic substitution (SEAr) reactions are the most attractive

• be unsuccessful, since we have obtained complicated mixtures of reaction products in those experiments. Further transformation of 6,12-dinitro-substituted ICZs can be realized through nucleophilic aromatic substitution, taking into account a mutual activation of the para-disposed nitro groups in

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• initial aromatic substitution step from 28 to 29 and the additional two reactions to 31, compared to the direct synthesis of both regioisomers depicted in Scheme 2. Results and Discussion A study to control the regioselectivity in the synthesis of 17d (ANTI) (Table 1) was motivated by our ongoing

Energy down converting organic fluorophore functionalized mesoporous silica hybrids for monolith-coated light emitting diodes

• Markus Börgardts and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 768–778, doi:10.3762/bjoc.13.76

• fluorophore derivatives 4 and 5 were accessible by Williamson ether synthesis [24]. The alkyne-functionalized green benzofurazane derivate 6 was obtained by nucleophilic aromatic substitution of 4-chloro-7-nitrobenzo[c][1,2,5]oxadiazole (3) with propargylamine. The alkyne-functionalized derivatives 4, 5 and 6

Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif

• Tetiana Bykova,
• Nawaf Al-Maharik,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72

• motif by the wider research community requires that a range of building blocks be prepared. It has proven relatively straightforward to prepare the phenyl derivative 2 and then subsequent elaboration to a range of functionalized analogues by standard electrophilic aromatic substitution reactions (Figure

Direct arylation catalysis with chloro[8-(dimesitylboryl)quinoline-κN]copper(I)

• Sem Raj Tamang and
• James D. Hoefelmeyer

Beilstein J. Org. Chem. 2016, 12, 2757–2762, doi:10.3762/bjoc.12.272

• SET mechanism [57], electron donation to ArI leads to a short-lived radical anion ArI•− that decomposes to I− and Ar•. The Ar radical undergoes homolytic aromatic substitution with benzene to form a biaryl radical, and deprotonation gives a biaryl radical anion that transfers one electron to ArI to

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

• the aromatic π-system, thus reducing the sp2 character of the nitrogen, and therefore lowering the reactivity of the system towards electrophilic aromatic substitution. An alternative, analogous synthesis was accordingly devised, in which the unsubstituted THQ 10 was targeted, as outlined in Scheme 4

One-pot synthesis of 4′-alkyl-4-cyanobiaryls on the basis of the terephthalonitrile dianion and neutral aromatic nitrile cross-coupling

• Roman Yu. Peshkov,
• Elena V. Panteleeva,
• Wang Chunyan,
• Evgeny V. Tretyakov and
• Vitalij D. Shteingarts

Beilstein J. Org. Chem. 2016, 12, 1577–1584, doi:10.3762/bjoc.12.153

• approach based on anionic forms of cyanoarenes as effective cross-coupling reagents toward neutral unactivated substrates [26][27], but also expand the knowledge about nucleophilic mechanisms such as aromatic substitution of a hydrogen atom (SNH) [28] and the vicarious substitution [29]. Results and

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

Palladium-catalyzed picolinamide-directed iodination of remote ortho-C−H bonds of arenes: Synthesis of tetrahydroquinolines

• William A. Nack,
• Xinmou Wang,
• Bo Wang,
• Gang He and
• Gong Chen

Beilstein J. Org. Chem. 2016, 12, 1243–1249, doi:10.3762/bjoc.12.119

• -arylpropylamines bearing strongly electron-donating or withdrawing substituents, complementing our previously reported PA-directed electrophilic aromatic substitution approach to this transformation. As demonstrated herein, a three step sequence of Pd-catalyzed γ-C(sp3)−H arylation, Pd-catalyzed ε-C(sp2)−H

• γ-arylpropylpicolinamides were then selectively iodinated at the remote ε-C(sp2)−H position via a rarely precedented PA-directed electrophilic aromatic substitution (SEAr) reaction (Scheme 1, reaction 2) [21][22]. Copper-catalyzed intramolecular C−N cyclization of these ortho-iodinated intermediates

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

• spectrum of biological and pharmacological properties and hence are very attractive as well as challenging synthetic targets [26]. Selected examples for the synthesis of 2-oxindole include an intramolecular homolytic aromatic substitution on the aryl ring by an amidyl radical formed by homolysis of a C–X