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

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

• 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

• through a conventional mechanism of nucleophilic aromatic substitution (SNAr). On the other hand, conversion of the second nitro group, as well as a similar transformation of compound 10b, can possibly be explained in terms of the radical-nucleophilic aromatic substitution (SRN1), since no other electron

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

Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene

• Javier Ajenjo,
• Martin Greenhall,
• Camillo Zarantonello and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 192–197, doi:10.3762/bjoc.12.21

• . The title compound was subjected to a nucleophilic aromatic substitution of the fluorine atom with oxygen, sulfur and nitrogen nucleophiles affording novel (pentafluorosulfanyl)benzenes with 3,5-disubstitution pattern. Vicarious nucleophilic substitution of the title compound with carbon, oxygen, and

• nitrogen nucleophiles provided 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzenes substituted in position four. Keywords: direct fluorination; fluorine; nucleophilic aromatic substitution; pentafluorosulfanyl group; vicarious nucleophilic substitution; Introduction Organic compounds with a

• fluorodenitration of known 3,5-dinitro-1-(pentafluorosulfanyl)benzene (5) [10][28]. The reaction with TBAF hydrate resulted in clean substitution of only one nitro group for the fluorine atom (Scheme 4). Nucleophilic aromatic substitution of fluorine leading to compounds 3 was investigated (Table 1). With low

Star-shaped tetrathiafulvalene oligomers towards the construction of conducting supramolecular assembly

• Masahiko Iyoda and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2015, 11, 1596–1613, doi:10.3762/bjoc.11.175

• 30 is estimated to be ca. 1000 times higher than that of the neutral fiber (before doping: σrt 3 × 10−6 S cm−1, after doping: σrt 3 × 10−3 S cm−1) [68]. Star-shaped pyrrole-fused TTF oligomers 38–43 were synthesized by nucleophilic aromatic substitution (SNAr) reactions of fluorinated benzenes with

Mechanical stability of bivalent transition metal complexes analyzed by single-molecule force spectroscopy

• Manuel Gensler,
• Christian Eidamshaus,
• Maurice Taszarek,
• Hans-Ulrich Reissig and
• Jürgen P. Rabe

Beilstein J. Org. Chem. 2015, 11, 817–827, doi:10.3762/bjoc.11.91

• – the ligand of coordination complex 2b. The synthesis of compound 10 – the ligand of coordination complex 2c – started by nucleophilic aromatic substitution of fluorinated pyridine 7 with compound 6 to receive a mixture of products 8 and 9 (Scheme 2). Purified compound 8 was then coupled with

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• aromatic substitution by using 2-fluoro-5-nitrobenzaldehyde (11b) to give rac-5 containing a tertiary arylamine nitrogen in 71% yield. With the 2-chloro-5-nitrobenzaldehyde reagent, only 3% yield for rac-5 could be achieved. Subsequently rac-5 was reacted with 1,3-dimethylbarbituric acid (12), Meldrum’s

• out according to the procedure of Litkey and Patonay [18] affording the racemic 3,4-dihydro-2-phenyl-1,4-benzoxazepine-5-one (rac-9) with high regioselectivity, which was reduced to (rac)-10 with LAH in dry THF. In the following step, the N-arylation of rac-10 was performed through a nucleophilic

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• inhibitor library generation programme. Results and Discussion Our retrosynthetic approach introduces the diversity point at a late stage and takes advantage of the heterocyclic lactam present in PreQ0 after activation and subsequent nucleophilic aromatic substitution. This convergent synthesis allowed us

• ] (Figure 3). The resulting pivalamide 8 proved to be more soluble than 1 and the subsequent halogenation step was accomplished in the presence of a phase transfer catalyst, affording the desired chloro-intermediate 9 in fair yield. In our hands, nucleophilic aromatic substitution on 9 using amines of

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• ester is utilised as a building block for the synthesis of 2-fluoro-2-arylacetic acid and fluorooxindole derivatives by a strategy involving nucleophilic aromatic substitution reactions with ortho-fluoronitrobenzene substrates followed by decarboxylation, esterification and reductive cyclisation

• elemental fluorine for the key construction of the carbon–fluorine bond by complementary direct selective direct fluorination [41][42][43][44], continuous flow [45][46][47][48][49] and building block [50] strategies, in this paper, we describe nucleophilic aromatic substitution reactions of carbanions

• -fluoronitrobenzene (2a) led to the efficient displacement of fluorine by a nucleophilic aromatic substitution process to provide diester 3 in good yield (Scheme 1). Displacement of fluorine from ortho-fluoronitrobenzene was quantitative as measured by 19F NMR spectroscopy of the crude reaction mixture and the

From porphyrin benzylphosphoramidate conjugates to the catalytic hydrogenation of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin

• Marcos C. de Souza,
• Leandro F. Pedrosa,
• Géssica S. Cazagrande,
• Vitor F. Ferreira,
• Maria G. P. M. S. Neves and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2014, 10, 628–633, doi:10.3762/bjoc.10.54

• , Portugal 10.3762/bjoc.10.54 Abstract Three new porphyrin aminoalkyl dibenzylphosphoramidates were synthesized by nucleophilic aromatic substitution of one p-fluorine atom of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (TPPF20) by primary aminoalkyl dibenzylphosphoramidates. The nucleophilic aromatic

• investigate the direct hydrogenation of TPPF20 with H2 in the presence of 10% Pd/C. Results and Discussion Synthesis of porphyrin dibenzylphosphoramidates 1 The method [4] for the nucleophilic aromatic substitution of the p-fluorine atoms of TPPF20 under reflux in toluene/triethylamine did not work in

• substitution was promoted by microwave irradiation in N-methyl-2-pyrrolidinone. Attempts to remove the benzyl groups of the phosphoramidate moiety by hydrogenolysis with 10% Pd/C led to the cleavage of the P–N bond and the reduction of the macrocycle to hydroporphyrin-type derivatives. The extent of the effect

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• tripeptide byproduct. Nucleophilic aromatic substitution (SNAr) chemistry contributes to creating useful materials. In 2005, Comer and Organ reported SNAr reactions of 2-fluoronitrobenzene using a flow microreactor system with microwave irradiation (Scheme 9) [69]. Toward making compound-libraries, Schwalbe

• , followed by two kinds of library diversification involving 1) Michael addition of a set of primary amines and the subsequent nucleophilic ring closure to give the difluoroquinolone system, 2) intermolecular nucleophilic aromatic substitution with various amines and hydrolysis of ester moieties to afford a

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• from the bacterial cell. Due to the elaborate substitution pattern of the parent quinolone ring systems these compounds are usually prepared via a linear consecutive sequence. In the case of moxifloxacin, an intramolecular base catalysed nucleophilic aromatic substitution is used to prepare the

• pyrimidines form very tight hydrogen-bonding arrays as seen in DNA and RNA. Synthetically, the electron-poor nature of pyrimidines accounts for the manifold functionalisation pathways using nucleophilic aromatic substitution chemistry. Electrophilic aromatic substitution reactions are more common during the

The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• , nucleophilic aromatic substitution reactions of halopyrimidines are smooth and high-yielding, especially when an electron-withdrawing group is present in this heterocycle. It is noteworthy that in the case of non-activated dihalopyrimidines, the first nucleophilic displacement reaction deactivates the

Synthesis of the calcilytic ligand NPS 2143

• Henrik Johansson,
• Thomas Cailly,
• Alex Rojas Bie Thomsen,
• Hans Bräuner-Osborne and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 1383–1387, doi:10.3762/bjoc.9.154

• optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature. Keywords: epoxides; GPCR; NPS 2143; nucleophilic aromatic substitution; pyrylium chemistry; Introduction The first G-protein-coupled receptors

• ). Previously, 4 has been synthesised by nucleophilic aromatic substitution on commercially available aryl fluoride 13 using crown ether and potassium acetate in acetonitrile [14]. Unfortunately, we found it difficult to drive the reaction to completion using the published method, obtaining only low yields of

Total synthesis of ochnaflavone

• Monica M. Ndoile and
• Fanie R. van Heerden

Beilstein J. Org. Chem. 2013, 9, 1346–1351, doi:10.3762/bjoc.9.152

• the oxidative cyclization to form ochnaflavone were established. Keywords: biflavone; diaryl ether; natural products; nucleophilic aromatic substitution; ochnaflavone; tetrahydroochnaflavone; Introduction Biflavonoids are a class of compounds that are receiving increasing attention because of their

Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides

• Magnus Liljenberg,
• Tore Brinck,
• Tobias Rein and
• Mats Svensson

Beilstein J. Org. Chem. 2013, 9, 791–799, doi:10.3762/bjoc.9.90

• functional theory to compute the energies of the possible σ-complex reaction intermediates, the “σ-complex approach”, has been shown to be very useful in predicting regioselectivity, in electrophilic as well as nucleophilic aromatic substitution. In this article we give a short overview of the background for

• structure of the σ-complex resembles the rate-limiting transition state and that this provides a rationale for the observed correlations between the SS and the reaction rate. Keywords: computational; DFT; nucleophilic aromatic substitution; reactivity; substrate selectivity; reactive intermediates

• of different substituents on the reactivity of one model substance. The first dealt with the Newman–Kwart rearrangement of an aromatic thionocarbamate by intramolecular nucleophilic aromatic substitution [20], the second applied semiempirical methods to study the reaction between methoxide anion and

Polymerization of novel methacrylated anthraquinone dyes

• Christian Dollendorf,
• Susanne Katharina Kreth,
• Soo Whan Choi and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 453–459, doi:10.3762/bjoc.9.48

• anthraquinone dyes has been synthesized by nucleophilic aromatic substitution reactions and subsequent methacrylation. Thereby, green 5,8-bis(4-(2-methacryloxyethyl)phenylamino)-1,4-dihydroxyanthraquinone (2), blue 1,4-bis(4-((2-methacryloxyethyl)oxy)phenylamino)anthraquinone (6) and red 1-((2-methacryloxy-1,1

• materials used for iris implants or other medical applications. Conclusion In conclusion, a series of novel anthraquinone based polymerizable dyes has been synthesized by nucleophilic aromatic substitution reactions of anthraquinone derivatives with several amino alcohols. Depending on the moieties that

Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

• Rajendra Surasani,
• Dipak Kalita,
• A. V. Dhanunjaya Rao and
• K. B. Chandrasekhar

Beilstein J. Org. Chem. 2012, 8, 2004–2018, doi:10.3762/bjoc.8.227

• 7-azaindole scaffolds appear in various pharmaceutically important molecules (Figure 1), which are very challenging and lengthy to prepare by the traditional methods [40][41]. In general, nucleophilic aromatic substitution (SNAr) reaction of a halo-precursor of 7-azaindole with a large excess of

Exploring chemical diversity via a modular reaction pairing strategy

• Joanna K. Loh,
• Sun Young Yoon,
• Thiwanka B. Samarakoon,
• Alan Rolfe,
• Patrick Porubsky,
• Benjamin Neuenswander,
• Gerald H. Lushington and
• Paul R. Hanson

Beilstein J. Org. Chem. 2012, 8, 1293–1302, doi:10.3762/bjoc.8.147

• nucleophilic aromatic substitution (SNAr) diversification pathway is reported. Eight benzofused sultam cores were generated by means of a sulfonylation/SNAr/Mitsunobu reaction pairing protocol, and subsequently diversified by intermolecular SNAr with ten chiral, non-racemic amine/amino alcohol building blocks

• . Computational analyses were employed to explore and evaluate the chemical diversity of the library. Keywords: benzoxathiazocine 1,1-dioxides; chemical diversity; informatics; nucleophilic aromatic substitution (SNAr); sultams; Introduction The demand for functionally diverse chemical libraries has emerged, as

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

• Nicola Otto and
• Till Opatz

Beilstein J. Org. Chem. 2012, 8, 1105–1111, doi:10.3762/bjoc.8.122

• formation; diaryl ethers; nucleophilic aromatic substitution; Ullmann-type coupling; Introduction The diaryl ether linkage is a common structural motif encountered in numerous classes of natural products. Moreover, various diaryl ethers have been shown to possess antibacterial, anti-inflammatory

Multistep organic synthesis of modular photosystems

• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2012, 8, 897–904, doi:10.3762/bjoc.8.102

• crude dibromo cNDA 32. Microwave-assisted reaction [15] with amines 14 and 15 gave the mixed cNDI 44 together with the symmetric side products. The obtained mixture of 2,6- and 3,7-regioisomers was not separated throughout the entire synthesis of photosystem 1. Nucleophilic aromatic substitution with

Directed aromatic functionalization

• Victor Snieckus

Beilstein J. Org. Chem. 2011, 7, 1215–1218, doi:10.3762/bjoc.7.141

• extent, nucleophilic aromatic substitution (SNAr) [2][6][7] reactions as taught to many generations of students in their first organic chemistry courses [8] (Figure 1). Being less steeped in history, radical nucleophilic substitution (SRN1) [9] and vicarious nucleophilic substitution (VNS) [10][11][12

Unusual behavior in the reactivity of 5-substituted-1H-tetrazoles in a resistively heated microreactor

• Bernhard Gutmann,
• Toma N. Glasnov,
• Tahseen Razzaq,
• Walter Goessler,
• Dominique M. Roberge and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2011, 7, 503–517, doi:10.3762/bjoc.7.59

• in a 3 μL fused-silica capillary, albeit not under continuous flow conditions, is the nucleophilic aromatic substitution reaction of 4-fluoro-1-nitrobenzene (15) with pyrrolidine (16) in THF (ΔV≠ = −58 cm3/mol) (Scheme 5) [71]. In order to confirm that these pressure enhancements can also be

• , significant corrosion of the reactor material can result, leading to unwanted side reactions. In addition, in specific cases reaction pressure can influence reaction rates as evidenced by the nucleophilic aromatic substitution reaction of 1-fluoro-4-nitrobenzene with pyrrolidine in the 60–180 bar pressure

• fresh 100 mL portions of KCN/m-nitrobenzenesulfinic acid sodium salt in water mixture before the reactor was finally washed with distilled water for 30 min to remove any remaining residues of the KCN/m-nitrobenzenesulfinic acid sodium salt in water mixture. Pressure dependence of nucleophilic aromatic

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• group unmasks the aniline which undergoes nucleophilic aromatic substitution to introduce the pyrimidine system with the formation of 253. Methylation of the secondary amine function with methyl iodide prior to a second SNAr reaction with a sulfonamide-derived aniline affords pazopanib (Scheme 50) [76

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• that aniline (B) is not derived from either chloro- (A) and iodo- (C)-sulfides, and iodo-product (C) is not formed from chlorosulfide (A). It is known [164] that photochemical nucleophilic aromatic substitution is promoted by electron-donating groups. Therefore, it appears most likely that the sulfides