New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• nucleophilic substitution using hydrobromic acid, as a 33% solution in acetic acid, to afford the corresponding bromide derivative 9 [54] (Scheme 2). Subsequently 1-(benzyloxy)-4-(bromomethyl)benzene (9) underwent Michaelis–Arbuzov reaction with triethyl phosphite to afford diethyl [4-(benzyloxy)phenyl

• , purification of the crude product by column chromatography led to the decomposition of compound TP7. Another strategy was devised to obtain the desired triazinephosphonate TP7: The first step was the nucleophilic substitution of the chlorine atoms of triazine 1 by 4-hydroxybenzaldehyde (12), followed by the

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• an ammonium hypoiodite species which first facilitates the α-iodination of the pronucleophile, followed by a phase-transfer-catalyzed nucleophilic substitution by the azide. Furthermore, we also show that an analogous α-nitration by using NaNO2 under otherwise identical conditions is possible as well

• first, which then facilitates the α-iodination of 1a (hereby either the formed benzoate or the hypoiodite itself may serve as a base). Intermediate 3 then undergoes a phase-transfer-catalyzed nucleophilic substitution with NaN3 thus delivering the final product 2a. With optimized conditions and a

• pronucleophile, followed by a phase-transfer-catalyzed nucleophilic substitution by the azide. Furthermore, we also obtained a first proof-of-concept for the conceptually analogous α-nitration by using NaNO2 under otherwise identical conditions. Experimental General details 1H, 13C and 19F NMR spectra were

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• followed by the addition of diisopropylamine, either in a one-pot synthesis or in two consecutive steps (Table 1). Subsequently, different aliphatic and aromatic substituents were attached to the pyrazole nitrogen by nucleophilic substitution with suitable organohalides 16 and cesium carbonate [3]. Due to

• 25 was carried out using the nucleophilic substitution procedure reported above with yields of 63–76%. The anticipated formation of a second regioisomer could not be confirmed due to the limited analytical methods available for compounds on solid supports. The cleavage to obtain azidopyrazole 19g was

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• interest [12][13]. The various approaches used for selenation of aromatic compounds include directed lithiation [14][15], copper-catalyzed selenation [16][17][18], and aromatic nucleophilic substitution reactions [19][20][21][22]. Electrophilic selenium reagents (e.g., phenylselenenyl bromide) have often

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• corresponding Ugi adduct 5aa in 42% yield (Scheme 2 and Figure 2). Interestingly, N-benzyl-2-(N-(1-benzyl-3,3-dimethoxy-2-oxoindolin-5-yl)acetamido)-3-hydroxy-2-methylpropanamide (5aa) was obtained rather than the predictable compound with a 3-chloro-2-methylpropanamide group. We believe that a nucleophilic

• substitution occurs due to the presence of acetic acid (2a) as reaction component. Aliphatic aldehydes with small chains (3b and 3c) were used successfully in the reaction approach, as expected. Also, aromatic 2-chlorobenzaldehyde (3d) was used and the desired compound 5ad was obtained in 36% yield (Scheme 2

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• the basis of readily available 2-chloro-3-nitropyridines via the intramolecular nucleophilic substitution of the nitro group as a key step. The previously unknown base-promoted Boulton–Katritzky rearrangement of isoxazolo[4,5-b]pyridine-3-carbaldehyde arylhydrazones into 3-hydroxy-2-(2-aryl[1,2,3

• ]triazol-4-yl)pyridines was observed. Keywords: aromatic nitro compounds; Boulton–Katritzky rearrangement; isoxazolo[4,5-b]pyridines; nucleophilic substitution; 1,2,3-triazoles; Introduction Nitrogen heterocycles represent a very important class of organic compounds that has found application in various

• shown in Scheme 1C. Since the key step of the synthesis is the intramolecular nucleophilic substitution of the aromatic nitro group, we assumed that the presence of an electron-withdrawing substituent at the pyridine ring would facilitate this transformation. Results and Discussion According to the

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• , deiodination at the bridgehead position, and nucleophilic substitution at the alkyl chloride. From 1,2-BCP (±)-4, a variety of 1,2-BCPs were prepared through basic chemical transformations (Scheme 1B) [26]. Selective deprotection gave access to free alcohol-containing 1,2-BCPs (±)-5 and (±)-8. Oxidation and

• ]propellane (129). Gassman reported the initial synthesis of [3.1.1]propellane (129) in 1980 [61], and this was recently optimised by Uchiyama (Scheme 13A) [47]. Cyclisation to the bridged structure 126 was achieved by enolate formation and intramolecular nucleophilic substitution of iodide diester 125. A

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• conjugates with functionalized linker groups suitable for bioconjugation or which may be efficient for PDT and BNCT improvement. Results and Discussion Synthesis Nucleophilic substitution reactions of the four p-fluorine atoms in 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (1) are well studied [15][16

• studied the nucleophilic substitution reactions of the p-fluorine atom in the pentafluorophenyl-containing porphyrin 6 with thiol-substituted compounds such as 2-mercaptoethanol (15), cysteamine hydrochloride (16), and 3-chloro-1-propanethiol (17) as shown in Scheme 5. The reactions proceeded readily in

• DMSO at room temperature for 10 min using anhydrous NaOAc as a base to afford the corresponding boronated porphyrin conjugates 18–20 in 80–87% yields. Exploring the reactivity of the p-fluorine atom similar nucleophilic substitution reactions of porphyrin 6 were carried out with 1,8-diamino-3,6

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• : aromatic nucleophilic substitution; azide–tetrazole equilibrium; 4-azido-2-sulfonylquinazolines; quinazolines; sulfonyl group dance; Introduction The quinazoline core is a privileged structure with a wide range of applications. Quinazoline derivatives exhibit a broad spectrum of biological activities

• efficiencies [5][6][7]. Consequently, ongoing efforts focus on advancing methodologies for synthesizing established quinazoline-based drugs and acquiring novel modified quinazoline derivatives for pharmaceutical or materials science purposes. Aromatic nucleophilic substitution [8] or metal-catalyzed reactions

• pharmaceutically active substances such as terazosin and prazosin, nucleophilic substitution at the C2 position was carried out with the corresponding amines – piperazin-1-yl(tetrahydrofuran-2-yl)methanone and furan-2-yl(piperazin-1-yl)methanone to give products 17e and 17f. Products 17e,f can be obtained through

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• crossover process [47][48][49][50]. However, activated alkyl halides are not suitable for these carboamination reactions due to the direct nucleophilic substitution of activated alkyl halides with nucleophilic reagents under the necessary alkaline conditions [51]. Recently, a Pd-catalyzed alkyl Heck

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• nucleophilic substitution takes place to afford products of the type 155 (Scheme 31B). Representative examples of the substrate scope are shown in Scheme 31C. The in situ-generated phthalimidyl anion (–Nphth) is a competent nucleophile and gives rise to primary protected amines such as 156. Additionally

• , fragmentation of 90 yields tert-butyl radical 64, which then adds to styrene 91 affording radical intermediate 92. At this stage, recombination of intermediates 89 and 92 may occur via SET followed by addition or through radical–radical coupling, affording benzylsulfonium intermediate 93. Finally, nucleophilic

• substitution with alcohol 94 in the presence of lithium phthalimide 95 leads to product 96 and turns over the catalytic cycle. Importantly, species 93 can be detected by high resolution mass spectrometry, when the reaction is carried out without nucleophile and using stoichiometric amounts of PTH1. H. Fu and

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• University, 1 Pushkin St., 355017, Stavropol, Russian Federation 10.3762/bjoc.20.34 Abstract A convenient method for the synthesis of a series of 2-(arylamino)-3H-phenoxazin-3-ones based on the nucleophilic substitution reaction between sterically crowded 3H-phenoxazin-3-one and arylamines performed by

• ][12]. At the first stage, this reaction follows one of three possible reaction pathways, including Schiff base formation (attack at the C(3) center), Michael addition at C(1), or nucleophilic substitution (SNH) at the C(2) center [13][14][15]. Most readily used is the pathway involving carbonyl–amine

• the crystalline samples, which is otherwise typical for solid-state reaction, was employed in this case. As seen in Scheme 2, the nucleophilic substitution reaction occured in good yield and with no restrictions in terms of amine basicity. The molecular structures of compounds 4c,d,f were determined

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• nucleophilic substitution of benzylic bromides with sodium azide and a subsequent copper(I)-catalyzed double click reaction in one pot [17]. In summary, these contributions by renowned experts demonstrate the broad diversity of impressive catalytic domino, tandem, and one-pot processes towards many valuable

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• quinolines, at the benzene ring, and the resulting nitro compounds could potentially be subjected to further transformations, including nucleophilic substitution of nitro groups. Indeed, under the action of a small excess of the nitrating mixture, dipyridoacenaphthene 5 undergoes double nitration at

• undergo a nucleophilic substitution. Indeed, upon boiling with an excess of sodium methoxide in methanol, the crude dinitration product 10(12) gives up to 6% of a new substance with low mobility on sorbents and blue luminescence under UV light. Its spectral analysis confirmed the symmetrical structure

• impurity in compound 10. The possibility of a double nucleophilic substitution without dehydrogenation was tested in a separate experiment with pure dinitro compound 12 taken as a starting material. Indeed, this variant produces the same dimethoxyacenaphthylene 14 in a noticeably higher yield (Scheme 6

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• -annelated IF-DTF 12 by removal of the tosyl (Ts) group under alkaline conditions, followed by nucleophilic substitution to incorporate the hexyl chain on the pyrrole. Furthermore, treatment of the IF-DTF ketone 4 with Lawesson’s reagent (using a recently established protocol [20]) yielded the large dimer 13

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• and proceeds through a by base-promoted annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates. The reaction mechanism of this formal [4 + 3] annulation includes the in situ generated allylic ylide, nucleophilic substitution, Michael additon, and elimination processes

• ylide B. Thirdly, the intermediate C is formed by the nucleophilic substitution of a halide ion in substrate 1 by the allylic ylide B. Then, Michael addition of the amino group to the C=C bond results in the cyclic intermediate D. Finally, the spiro[indoline-3,5'-[1,2]diazepine] 3 is produced by the

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• reaction is believed to occur via electron transfer, followed by the radical coupling of La@C2v-C82 and benzyl radicals, rather than by bimolecular nucleophilic substitution reaction of La@C2v-C82 anion with 1. Keywords: electron transfer; metallofullerene; radical; reduction; Introduction Fullerenes

• transfer, followed by bimolecular nucleophilic substitution (SN2) reaction [8]. Endohedral metallofullerenes, wherein one or more metal atoms are encapsulated inside a fullerene cage, have garnered research interest [12][13][14][15]. The encapsulation of metal atoms can result in electron transfer from the

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• overwhelmingly more common in the latter because there are other more selective and efficient solution chemistry methods for post-polymerization modification, such as nucleophilic substitution [94][96]. In this section, we discuss the radical chemistry used in both processes. 3.1 Post-polymerization modification

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• reductive elimination to yield ketone 78. In the acylthiolation cycle, the azaphilic ZnCl2 activated NTSE 1’’’ via N–Zn coordination to facilitate the leaving ability of succinimide. Then, nucleophilic substitution of arylmagnesium bromide 75 to intermediate IV provided thioester 79. In 2022, Gao and co

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• diaminocarbenes) Cu(I) hexamethyldisilazide complexes by using lithium hexamethyldisilazide as a base in 2017 (Scheme 15) [29]. The initially formed NHC–CuCl complexes 41, 44, and 47 reacted with another molecule of LiN(SiMe3)2 to undergo nucleophilic substitution of Cl by a bis(trisilyl)amino group to furnish

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• Hans-Ulrich Reissig Fei Yu Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, D-14195 Berlin, Germany Asymchem Boston Corporation, 10 Gill Street, Woburn, Massachusetts, 01801, USA 10.3762/bjoc.19.101 Abstract The nucleophilic substitution of benzylic bromides with sodium

• carbohydrate mimetics, but the reductive cleavage of the 1,2-oxazine rings to aminopyran moieties did not proceed cleanly with these compounds. Keywords: alkynes; azides; copper catalysis; nucleophilic substitution; 1,2-oxazines; Introduction The concept of click reactions [1][2], in particular, the

• . In this study we investigated the compatibility of the nucleophilic substitution of 1,2-, 1,3- or 1,4-bis(bromomethyl)benzene H with sodium azide and the copper-catalyzed alkyne–azide cycloadditions with compounds of type G to provide divalent compounds I (Scheme 1). These may serve as precursors of

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• mesylation produced 17.3. Then, the nucleophilic substitution (SN2) reaction of benzoate with 17.3 produced the benzoate ester 17.4 with an inversion of configuration. Then, the two protecting groups (ester and trityl) were removed to produce (S)-17.6. The modification of the sn-2 position is illustrated in

• mesylated to 29.2. Then, a bromine atom was introduced via a nucleophilic substitution with LiBr in acetone to form 29.3. Finally, the primary bromide was used to introduce different ammonium salts as illustrated with compound 29.4. A variation of this sequence consisted in placing an ether function in

Organic thermally activated delayed fluorescence material with strained benzoguanidine donor

• Alexander C. Brannan,
• Elvie F. P. Beaumont,
• Nguyen Le Phuoc,
• George F. S. Whitehead,
• Mikko Linnolahti and
• Alexander S. Romanov

Beilstein J. Org. Chem. 2023, 19, 1289–1298, doi:10.3762/bjoc.19.95

• containing a rigid benzoguanidine ligand in its molecular structure. Results and Discussion Synthesis and structure 4BGIPN was prepared in 70% yield by aromatic nucleophilic substitution reaction from 2,4,5,6-tetrafluoroisophthalonitrile and 5H-benzo[d]benzo[4,5]imidazo[1,2-a]imidazole (benzoguanidine) after

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• various nucleophiles, including C- and heteronucleophiles, such as compounds bearing –OH, –SH, and –NH groups [4][5][6][7]. Among them, the carbon–nitrogen bond formation through N-nucleophilic substitution reactions plays a central role for the synthesis of numerous compounds exhibiting various

• precursors in nucleophilic allylic substitution reactions with amines, presumably due to the perceived poor leaving group ability and low reactivity of the hydroxy group. Interestingly, the direct nucleophilic substitution of the corresponding alcohols has drawn much attention because of the availability of

• in the presence of imidazole (2a), as a powerful nucleophilic additive, affording, via competitive allylic nucleophilic substitution in toluene at reflux, a mixture of the corresponding N-substituted morpholine and N-substituted imidazole derivatives 6 [23]. In addition, a literature survey showed

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• ) halogenation, and 3) ring closure (Scheme 2). β-Nitrostyrene 2 serves as an appropriate acceptor for conjugate addition by diethyl malonate (3a) to afford adduct 4a, in which the methine group flanked by two carbonyl groups is readily halogenated, and the subsequent intramolecular nucleophilic substitution by