Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• straightforward and efficient method for the N-arylation of primary arylamines and secondary amines with 1,3-cyclohexanedione-derived aryliodonium ylides in the presence of copper catalysts in water as a solvent. Results and Discussion To test our hypothesis, we commenced our studies by treatment of aniline (1a

• ) with iodonium ylide 2-(phenyl-λ3-iodaneylidene)cyclohexane-1,3-dione (2a) obtained from 1,3-cyclohexanedione in the presence of copper salts as catalysts. The detailed optimization studies are described in Table 1. Initially, we treated aniline (1a, 0.2 mmol) with iodonium ylide 2a (0.24 mmol) in the

• , CuCl2, CuBr2, and CuSO4·5H2O (Table 1, entries 4–7) with maintaining the same reaction conditions. Among these salts, CuSO4·5H2O afforded a relatively higher yield of the product diphenylamine (3a, Table 1, entry 4). Inspired by this observation, we carried out the N-arylation of aniline (1a) with

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• , without isolation of the intermediate 3-(2-oxopropyl)piperidin-4-one 5a, the reaction mixture after acid hydrolysis was treated with aniline and the desired tetrahydro-1H-pyrrolo[3,2-с]pyridine 6а was isolated in 19% yield only (Scheme 4). Finally, we studied some reactions of the obtained tetrahydrofuro

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• -pyrrolyl, trifluoromethyl and alkynyl as other three substituents (Scheme 15c) [42]. In 2020, a completely para-selective aza-Friedel–Crafts protocol with N-monosubstituted aniline derivatives 59 catalyzed by the chiral phosphoric acid P19 was disclosed by Zhu, Zhang and co-workers [43]. The electrophilic

• with π–π interactions between the catalyst’s aryl group and the aryl substituent at the nitrogen in the aniline 59 (Scheme 16a) [43]. Recently, Fan and co-workers reported a chiral phosphoric acid P20-assisted enantioselective aza-Friedel–Crafts reaction between α-naphthols 17 and isatin-derived

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• with electron‐donating groups (i.e., OMe, Me) reacted much faster than aniline and furnished the pyrroles in excellent yields. In addition, the reaction of more sterically hindered aniline with 2,5-dimethoxytetrahydrofuran gave moderate yields and less sterically hindered aniline gave good yields. This

• ). The function of squaric acid as a catalyst was not clear, but the authors suggested that the Brønsted acidity of squaric acid affects the reactivity and selectivity of this process. The tentative mechanism of this protocol was proposed (Scheme 13b), in which a reversible acid–base reaction of aniline

• 28 with squaric acid afforded anilinium squarate salt A. Further, a catalytic amount of squaric acid hydrolyzes 2,5-dimethoxytetrahydrofuran (2) to give a 1,4-dicarbonyl compound B in water. Finally, N-phenylpyrrole 29 was obtained by condensation of activated 1,4-dicarbonyl compound with aniline. In

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• (Scheme 6). This means that the cleavage of the amide group that evolves aniline (pKa = 4.6) occurred smoothly after the initial thiazole ring closure (through 12a’ in Scheme 6). The addition of a thiophile (trimethyl phosphite) does not turn the reaction toward ECR and only decreases the yield of 13

• group. The leaving abilities of "aniline" nitrogen (anilinium has a pKa = 4.60 in water) [22] in intermediate 16 (Scheme 7) and "phenethylamine" nitrogen (2-phenyl-2-propylammonium has a pKa = 10.38 in water) [34] in 7a (Scheme 3) must differ by several orders of magnitude, which makes the irreversible

• leaving aniline moiety, prefers cyclization to give 13 (Scheme 6). Another key factor for successful ECR concerns the acidity of C–H in particular α-thioiminium salts 6a,b, 10a,b, 12a, 15 (pKaC) or the ease of proton transfer between the carbon and nitrogen in imidothioate followed by formation of the

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• deliver N-arylsulfonylimines under mild reaction conditions is highly desirable. Previously, we reported a tandem oxidative intramolecular cyclization of N-aryl(benzyl)amines, having an internal nucleophile substituted at the ortho-position in the aniline ring, to nitrogen heterocycles using potassium

• persulfate (K2S2O8) as the exclusive reagent [14]. The mechanistic study revealed that an initial oxidation to an iminium ion could be the key intermediate in the intramolecular cyclization step. In sharp contrast, when N-aryl(benzyl)amines that do not have an ortho-substituted nucleophile in aniline ring

• of the intermediate product 2c and 2-aminobenzamide gave 2-(p-tolyl)quinazolin-4(3H)-one (4b) in 85% yield. Furthermore, when various other ortho-substituted aniline derivatives such as 2-aminobenzylamine, 2-aminothiophenol, and o-phenylenediamine are reacted with imine 2a in a similar manner, the

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• '-dibromostilbenes 61 by means of a double Buchwald–Hartwig amination gave yields between 62% and 96% using aniline as the amine reactant (Scheme 13). The reaction proved to be compatible with both aromatic and aliphatic amines and the reaction time varied between 11 and 24 hours. Fluoro, chloro, nitrile, alkyl, and

Synthesis, structure, and properties of switchable cross-conjugated 1,4-diaryl-1,3-butadiynes based on 1,8-bis(dimethylamino)naphthalene

• Semyon V. Tsybulin,
• Ekaterina A. Filatova,
• Alexander F. Pozharskii,
• Valery A. Ozeryanskii and
• Anna V. Gulevskaya

Beilstein J. Org. Chem. 2023, 19, 674–686, doi:10.3762/bjoc.19.49

• )benzonitrile and N,N-dimethyl-4-((4-nitrophenyl)ethynyl)aniline in chloroform solution are 373 and 416 nm, respectively [35]. In the same time, λmax for 2-((4-nitrophenyl)ethynyl)-1,8-bis(dimethylamino)naphthalene is 474 nm [36]. The red shift observed in the spectrum of this compound as well as in the spectra

• solution (chloroform and acetonitrile were tested). For comparison, N,N-dimethyl-4-((4-nitrophenyl)ethynyl)aniline demonstrates a weak fluorescence with an emission maximum at 550 nm (EtOH) [37]. The optical band gaps (Egopt), estimated from the onset point of the absorption spectra, ranged within 2.39 eV

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• . Such a change in the reaction selectivity could be explained by the influence of a higher nucleophilicity of the examined alkylamines in comparison with benzylamine. Then, we tried to involve less nucleophilic amines to the proposed approach. For these, we examined a reaction of APBTT 1a with aniline

• the model reaction of APBTT 1a and aniline (11a) were optimized. The best yield of PBTA 12aa was observed when butyl acetate was used as the solvent and heated at 130 °C for 3 h (entry 3, Table 3). Heating the reaction mixture in toluene (entry 7, Table 3) showed a good yield too. Since the product

• closed microreaction V-vial. Reaction of APBTT 1a with an excess of benzylamine. Reaction of APBTT 1a with morpholine. Reaction of APBTT 1a with aniline (11a). Derivatization of PBTA 12aa. Reaction of APBTTs 1a–h and arylamines 11a–d. Isolated yields are given; reaction scale: a mixture of 1 (0.45 mmol

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• 20% yield. Although yields were slightly diminished, unsymmetrical bridgehead-monosubstituted oxabenzonorbornadiene led solely to the 1,2,4-trisubstituted regioisomer (Scheme 7), similar to that observed by Gutierrez and Molander [39]. Selected substituents on the aniline motif were found to hamper

• photoexcitation of the photosensitizer 43 to form 44 which can oxidize aniline 36a to give radical cation 46 (Scheme 7). Deprotonation by DBU produces the radical 40. The radical anion photosensitizer 45 can reduce Ni(I) to Ni(0), closing the first catalytic cycle. The Ni(0) complex can undergo oxidative addition

• those with hydrocarbon, ether, acetal, and ester functionalities; although, aniline nucleophiles only resulted in the one step asymmetric ring-opening (ARO) product under the standard reaction conditions. Fortunately, the authors noted the addition of triethylamine allowed for aniline nucleophiles to

Friedel–Crafts acylation of benzene derivatives in tunable aryl alkyl ionic liquids (TAAILs)

• Swantje Lerch,
• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2023, 19, 212–216, doi:10.3762/bjoc.19.20

• proved to be a potent reaction medium in catalytic hydrosilylation [53], hydroamination and hydroarylation [54], as well as for the synthesis of nanoparticles [55][56]. Results and Discussion Ionic liquids 1–6 were synthesized via a three-step procedure starting from commercially available aniline

• derivatives (see Scheme 1). First, the arylimidazole is obtained through a ring closing reaction using an aniline derivative, glyoxal, formaldehyde and ammonium chloride. The following alkylation with hexyl bromide yields the bromido ionic liquid. TAAILs 1–6 are then formed by an anion exchange reaction using

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• ] which underwent aromatization with the loss of sulfur dioxide and N-Boc-aniline. The multicomponent character and the fairly large scope of this reaction allows to place pairwise reactive groups in the aldehyde and the amine components, which would set a scene for further elaboration of the product’s

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• two options for the generation of 4-ethoxy-2,3,6-triaminopyridine (9). One possibility comprised the deprotection of the dicarbamate 5 with potassium hydroxide giving the diamine 6, followed by azo coupling with the diazonium salt obtained from aniline and sodium nitrite to give azo compound 7

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• , after purification by acid–base workup (Scheme 3b). A similar workup was performed for the reaction of 1a and 2a in the presence of 6a under standard conditions, and compounds 8a and 18 were isolated, respectively, in high yields (Scheme 3c). The reaction of 17 with aniline 19 afforded product 18 in 91

• % yield (Scheme 3d). These results suggest that the generation of benzamidine 18 by-produces aniline (19). On the other hand, aniline generation was not confirmed in the reaction between 1a and 2a without an acid–base workup (Table 1, entry 1). Based on the above control experiments and the reaction under

• addition of Et3N resulted in lower yield because the hydrochloric acid was trapped by the base (Table 1, entry 18). This reaction required two equivalents of thioamide 2 and Ph3BiCl2 6a for aminophenol (Table 1, entries 1, 15–17). The produced aniline 19 reacts with an excessive amount of D to form

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• cross-coupling, and 2) immobilization on a solid support via reduction and reaction of the aniline with an electrophile such as polystyrene isocyanate. DOPO scaffold We previously reported the syntheses of both enantiomers of 8-phenyl DOPO 3 [38]. The syntheses proceed in only three steps (including the

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• aniline 94 in three steps (Scheme 16). Subsequent deprotection and condensation with dimethyl mesoxalate (90b) gave imidazolidine 95. With compound 95 at hands, five further steps gave (−)-aplaminal (96) in a good overall yield of 19%. Cladoniamide G The unsymmetrical mesoxalic acid amide 102 was used by

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• -acetyl-3-hydroxy-3-pyrroline-2-ones via multicomponent reactions of ethyl 2,4-dioxovalerate with aromatic aldehydes, and aniline in glacial acetic acid. These 2-pyrrolidinone derivatives were then reacted with aliphatic amines in ethanol to obtain a library of 1,4,5-trisubstituted pyrrolidine-2,3-dione

• ), aniline (2), and ethyl 2,4-dioxovalerate (3) in glacial acetic acid was used for optimization (Scheme 1). Reacting equimolar amounts of 1a, 2, and 3, 0.5 M in acetic acid as solvent at room temperature [39], resulted in the formation of 1,5-diphenyl-4-acetyl-3-hydroxy-3-pyrrolin-2-one (4a) in a yield of

• amounts of 2 and 3 unchanged. However, increasing the concentration of aniline (2) in acetic acid to 0.75 M while keeping the amounts of 1 and 3 constant at 0.5 M resulted in a slight decrease of the yield (67%) of 2-pyrrolidinone derivative 4a (Table 1). Therefore, the ratio 1.5:1:1 of reactants, the

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• just 2 min of grinding (products 2q and 2r, Scheme 3). Next, a series of aniline derivatives were taken as the substrates for this electrophilic bromination by NBS. To our delight, the corresponding bromo derivatives were formed in high yields (75–89%) within 5–15 min of grinding (products 2s–y, Scheme

• in good yields (product 2ai and 2aj, Scheme 3). It is worthy to note that PEG-400 as the grinding auxiliary not only expedited the reaction but also played a key role in availing better regioselectivity. A very high para-selectivity was observed for both phenols and aniline substrates with free o

• ). Presumably, PEG-400 with several -O- and terminal -OH functionalities helps to enhance the polarization of the N–X bond. Thus, the formation of the halonium ion (X+) in the reaction medium is faster and stabilized by solvation to offer an extra bit of time for the attack of phenol (or aniline) preferably

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• -arylaminopropyl(methyl)phosphinic acids 45 under reduced pressure. The reactions of 1,2-oxaphospholane 2-oxides 47/2-sulfides 50 and anilines 48 generated 1-aryl-2-methyl-1,2-azaphospholidine 2-oxides 49 and 46a as well, while the reaction of 1,2-thiaphospholane 2-sulfide (51) with aniline (48a) gave

• synthetic method showed very limited substrate scope. Only less bulky primary amines underwent the first aza-Michael addition and then intramolecular nucleophilic substitution. However, aromatic amines, aniline, 2,3-dihydro-1H-inden-4-amine, and the bulky aliphatic primary amine adamantylamine did not

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• reliable synthesis of symmetric ABs in high yields via a Cu-catalyzed oxidative coupling of aniline derivatives [17]. This synthesis can be also used for the formation of non-symmetric AB, however, only for a selected set of anilines. One of the most applied methods to access non-symmetric azobenzenes is

• the proposed mechanism, which involves nucleophilic attack of the aniline on the nitrosobenzene derivatives in acidic or basic media (Scheme 1) [18][19][20][21]. However, in order to use azobenzenes as functional materials, access to a large-scale process is necessary. In this context continuous flow

• reaction to generate unsubstituted AB (1a) was performed with freshly distilled aniline (2a) and commercially available nitrosobenzene (3), dissolved separately in acetic acid. Both starting materials had the same concentration and were pumped by a Vapourtec E-Series system (for details, see experimental

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• (25), formaldehyde (26), and aniline (27) and 10 mol % of the organocatalyst to yield β-aminoketone 28 in 85% yield (88% ee), in less than 1 h. Although a significantly higher yield was achieved compared to the batch experiment, a slight reduction in enantioselectivity was observed. The Petasis or

• heated flow system [65][66][67][68][69][70][71]. This is exemplified for the tandem synthesis of benzofuran 47 and phenylindole 48 (Scheme 10, case B) starting from phenol 44 and aniline derivative 46, respectively. The latter reaction was carried out in a glass reactor filled with MagSilicaTM [53

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• utilized, which consisted of alkylation of aniline 3 by methyl bromoacetate, followed by introduction of the Boc group into intermediate Int-17a, and final reduction of Int-17b with DIBAL-H (Scheme 1). For the study of the asymmetric Henry reaction aldehydes 15–20, nitromethane, and highly enantioselective

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• phenol (2a, 1 equiv Cs2CO3, DMF, 50–55 °C, 3 h) to afford the corresponding product 4a in 29% isolated yield (Scheme 4). We tested aniline and 2-naphthylamine as nucleophiles (DMF, 50–55 °C) in the reaction of bromopropargylic alcohol 1a (Scheme 5). But such a protocol turned out to be ineffective

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• ). Disappointingly, the reactions carried out by varying the α-substitution did not afford the desired product. In order to demonstrate the synthetic utility of the oxyaminated compounds, the reductive cleavage of the N–O bond was attempted under Zn/AcOH conditions. Pleasingly, the reaction afforded the aniline

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• calix[6]arene scaffold, we carried out the synthesis of three monomeric gold catalyst analogues A’,B’,C’(AuCl). The synthesis of these compounds was performed using the previously optimized protocol, starting from a 4-(octyloxy)aniline intermediate (Scheme 2). Subsequently, due to the general interest