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

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• milling (Figure 1b and Figure S5 in Supporting Information File 1). Other substrates such as naphthalene and N-Boc-aniline proved unreactive under the milling conditions with NFSI. However, the more activated arene 2-naphthol underwent double fluorination affording 1,1-difluoronaphthalen-2(1H)-one as the

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• as the key intermediate. The third pathway (c) was centered around a ring-closure reaction via lactam-bond formation from a precursor that contains a carboxylic ester in position 2 and an o-aniline moiety in position 3 of the indole ring by Fischer indole synthesis from methyl 4-(2-nitrophenyl)-3

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• with reddish hues. The reaction with aniline forms the substitution product of the sulfonic group with a phenylamino group in a 90% yield. In his study, he proposed that the structure of the nucleophilic addition product was tautomer 19 (Scheme 1B). In search of a reagent that could form stable adducts

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• min) was necessary to obtain the desired products in good yield. Moreover, we did not observe any products when we used the 2-fluoro-substituted aniline 9i even at higher temperature and for longer reaction time (Table 1, entries 17 and 18). Furthermore, no aminated products were observed when 8a and

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• ) × 104 M−1, which was contrary to those of hemicucurbiturils. As observed by fluorescence titration experiments, macrocycle 4 showed weak interactions with selected anions. Results and Discussion Because of the relatively strong nucleophilicity of the amino group in aniline, the synthesis could become

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• literature to date. One of them is based on the construction of the central pyrimidine ring starting from ortho-disubstituted aromatic compounds 2 bearing a pyrrolidine moiety (see Scheme 1A). Examples include cyclocondensation of (2-pyrrolidin-1-yl)benzaldehyde and aniline occurring in the presence of TsOH

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• appropriate ester of benzoic acid in the presence of a base. After having the starting material in hand, we commenced our investigations for the synthesis of 1-aminoisoquinolines by treating 2-(2-oxo-2-phenylethyl)benzonitrile (3a) with aniline (4a) in the presence of different Lewis acids under varying

• steric effects of the substituents have influenced the yields of the reaction substantially. Comparably better yields were observed with electron donating substituents than the electron withdrawing halo groups on the aniline ring (Scheme 2, 5b–m). Importantly, the steric effects on the aniline ring have

• ) condenses with amine/aniline in the presence of Me3Al to afford imine intermediate A. Intermediate A then underdoes an intramolecular cyclisation to afford intermediate B. This intermediate B then undergoes an N-[1,3]-shift leading to the generation of intermediate C, which subsequently abstracts a proton

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• interactions with the substrates. Moreover, the SPA ligand loading of 1 mol % is effective for this reaction under mild conditions [50]. Moreover, Shi, Lin and co-workers reported the first Pd(II)-catalyzed directed atroposelective C–H allylation of 2-(naphthalen-1-yl)aniline derivatives 14 with methacrylates

• type of axially chiral indoles 27 (Scheme 10) bearing aniline groups by direct arylation and rearrangement in moderate to good yields with excellent enantioselectivities of mostly 99% ee (Scheme 9b) [59]. The electronic properties and position of the substituents on the azobenzene ring did not affect

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• derivatives, phase-transfer catalysts and bifunctional thiourea derivatives. 1.1 Reactions catalyzed by chiral cinchona alkaloid derivatives Cai et al. prepared and used a number of organocatalysts from Cinchona alkaloids for the aza-MR of aniline (1) with chalcone (2) to obtain the adducts 4 in poor to very

• formed Michael adduct (Scheme 1) [25]. The proposed catalytic cycle involved generation of the active complex through hydrogen bonding between catalyst and aniline followed by interaction with chalcone via π–π stacking of aromatic rings and hydrogen bonding leading to the Michael adduct. Likewise, Lee et

• bifunctional thiourea. Intramolecular aza-Michael addition reaction catalyzed by tertiary amine-thiourea. Intramolecular aza-Michael addition reaction catalyzed by chiral phosphoric acid. Asymmetric aza-Michael addition of aniline to β-nitrostyrenes. Intramolecular aza-Michael addition reaction catalyzed by

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• Serusi et al. in a tandem reaction to synthesize functionalized tryptamines from 2-hydroxycyclobutanones 107 with a primary aniline [30]. Notably, the α‑iminol rearrangement results in a ring contraction to give the 2-aminocyclopropyl ketone intermediate 109, which upon condensation with a second

• equivalent of aniline in the presence of a Brønsted acid undergoes a multistep rearrangement to form the indole group as part of the target tryptamine 110 (Figure 20). The one-pot conversions occurred successfully over a wide range of monosubstituted anilines, including various para-alkyl groups (65–72

• -ketol rearrangement is believed to give rise to 92 and 93, while a similar sequence at C1 is proposed to yield 94–96. R = Me or Et. α-Iminol rearrangements catalyzed by VANOL Zr (99). The rearrangement can be conducted with preformed iminol 97 or from a mixture of aldehyde 100 and aniline. α-Iminol

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• effectiveness of our strategy, the necessity of isolating the potentially hazardous diazonium salt may be seen as an important disadvantage. Arylating the quinone starting directly from the aniline in a one-pot procedure would effectively avoid the need for isolation of the potentially explosive salt and

• therefore greatly benefit our procedure. The in situ formation of the aryldiazonium salt from the corresponding aniline and tert-butyl nitrite in methanol and subsequent exposure to green light in the presence of 2,5-dichlorobenzoquinone (1) proved to generate the desired product in yields that were similar

• not alter the outcome. The diazonium salt derived from the electron-rich 4-anisidine (4j) proved to be less reactive, requiring 48 hours of reaction time. Compared to other substrates, reacting the chlorinated quinone with unsubstituted aniline (4l) resulted in substantially more side products