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

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• ]. Hongtao and co-workers reported the synthesis of tetrakisindole species 13 through the coupling of aniline (12) and indole-2-boronic acid pinacol ester 11 using the Buchwald–Hartwig method (Scheme 3a) [42]. In a similar fashion, Han reported the syntheses of the symmetric and unsymmetric triaryl

• -substituted amines 15, 18, and 20 [43]. Taking aniline as the pivotal moiety, it was coupled with isomeric bromoindoles 14 and 16 for the synthesis of the targeted products (Scheme 3b). Ethers Hongtao and co-workers also studied the electroluminescence properties of the 3,3’-bis(indolyl) ether derivatives 23

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• aniline (Scheme 5) [40]. A one-pot and multicomponent route to 1,4,5-trisubstituted 1,2,3-triazoles 11 containing a carboxylic ester group on the triazole ring was reported by Zhao et al. This strategy generates desired products from the reaction of readily available primary amines 10, 1,3-dicarbonyl

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• approach starting from the corresponding aniline precursors. The Z→E photoconversion yields in acetonitrile are 80–85% and the thermal half-lives of the metastable E configurations are 31–74 min. Particularly, the high photoconversion yields (≈70%) of the water-soluble diazocines are noteworthy, which

• Fmoc chloride to accomplish an orthogonal protective group strategy. The removal of the Boc groups from compounds 5 with TFA gave the mixed aniline and nitro precursors 6. In previous approaches, the nitro groups were reduced to hydroxylamines with zinc and oxidized to the corresponding nitroso

• compounds with iron(III) to perform an intramolecular Baeyer–Mills reaction [15][21]. We found that a complete reduction of the nitro group to aniline 7 and oxidation with mCPBA is increasing the yield of the intramolecular cyclization from 39% to 62% (over two steps) for the unsubstituted diazocine 8c as

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• cycloisomerization/Pictet–Spengler cyclization of 2-(4-aminobut-1-yn-1-yl)aniline [16], the Ru and Rh-catalyzed [2 + 2 + 2] cycloadditions of yne-ynamides [17], and the Pd-catalyzed tandem coupling-cyclization [18] are significant works in the area (Scheme 1). However, the use of toxic and expensive metal catalysts

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• aprotic solvent, which led to moderate to good conversions after less than 30 minutes. Chen et al. were the first to show a significant acceleration of the reaction between cyanoguanidine and variously substituted aniline hydrochlorides under microwave irradiation (Scheme 7A) [22]. The reaction was

• and aromatic amines. Being free amines aliphatic amines reacted better with arylcyanoguanidine in the presence of excess copper(II) salts in aqueous ethanol, whereas aniline derivatives were more prompt to react as hydrochloride salts in a suitable high boiling point solvent. The reaction with copper

• Štrukil et al. who reported the addition of aniline hydrochloride to N1-cyano-N2,N3-diisopropylguanidine in water at 125 °C within 30 min [48]. In this case, the desired N1,N4,N5-trisubstituted product was obtained in gratifying 89% yield (Scheme 17B). The activation of the nitrile group of

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• unknown compounds 14–16 opens many synthetic possibilities for the preparation of novel fused derivatives of 1-aza-9-oxafluorene. The nitro compounds 14 and 15 were reduced to the corresponding aniline derivatives using hydrogen and Pd/C as a catalyst. The resulting aminophenols 17 and 18 were further

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• molecules of arylglyoxal 33 and amine 32 under microwave irradiation with p-TsOH as a catalyst for the generation of a library of pyrazolopyridines in good yields (Scheme 57). The methyl substitution at the C-4 position of the aniline (p-toluidine-32b) led to the formation of azepino[5,4,3-cd]indole

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• three-component reaction in the absence of light, which is of great significance for the later study of temperature-driven EDA complexes. In 2017, König and colleagues [42] discovered an EDA complex 75 formed by bromothiophene 72, aniline (73), and N,N-diisopropylethylamine (DIPEA) as organic base

• additive to give corresponding thiophene radical 76 and aniline radical cation under irradiation with light. Then, 76 reacted with 73, giving rise to corresponding radical 77. Finally, product 74 was given via hydrogen atom transfer (Scheme 26). In contrast to (hetero)aryl halides with indispensable

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• -azahexatriene system. Lastly, it was proposed that the carbodiimide 10 could be derived from urea 11. Therefore, we investigated the electrocyclization of a pyrrol-3-ylbenzene containing a carbodiimide moiety. First, 2-(pyrrol-3-yl)aniline 14 was synthesized by a Suzuki–Miyaura coupling reaction of 2

• , affording aniline 15 in 65% yield. Treatment of 15 with phenyl isocyanate in CH2Cl2 gave urea 16a in 54% yield. To obtain carbodiimide 17a, 16a was treated with carbon tetrabromide (CBr4), PPh3, and Et3N in CH2Cl2. The reaction was monitored by TLC, which confirmed the complete consumption of the starting

• reaction of 16a with CBr4, PPh3, and Et3N. Using the same procedure, carbodiimide 17b was then synthesized in 58% yield starting from aniline 14 via urea 16b. Then, the electrocyclization of 17b was attempted, but the cyclization did not proceed at all. As possible reason we considered a steric hindrance

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• using alkali salt promoters (Na2CO3, NaHCO3, Na2SO4 or K2SO4, Figure 4). PET wastes, including highly coloured and multilayered PET, could be used as substrate. More recently, it was demonstrated that the addition of a cosolvent for PET, such as dimethyl sulfoxide (DMSO), NMP, nitrobenzene or aniline to

• the conventional PET-insoluble EG system, greatly enhanced the depolymerisation kinetics, resulting in improved conversions (the solubility of PET at T > 130 °C was aniline > NMP > nitrobenzene > DMSO) [202]. For instance, the use of a DMSO/EG 2:1, w/w solvent mixture resulted in an increase of PET

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• obtained for the 3-(2-(dimethylamino)ethyl)aniline analogue 24j was due to the fact the 2-Cl-Py did not transform to the OAt ether in situ and the subsequent hydrolysis step was very sluggish. We postulate that the presence of the more basic N,N,-dimethylaminoethyl side chain (pKa ≈11) must prevent

• need for chromatography [19]. Amide coupling was best carried out under acidic coupling conditions by pre-activating 30 using EDCI, pentylfluorophenol (Pfp-OH) in the presence of one equivalent pyridine and adding aniline dropwise over a few minutes. Under basic coupling conditions (e.g., HATU, DIPEA

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• Iwasawa and co-workers in 2011 [18][66] (Scheme 10A). Treatment of Boc-protected aniline 139 and n-butyl vinyl ether (140) with a platinum(II) catalyst afforded tricyclic indole 141 in 83% yield. The authors suggested that this catalytic [3 + 2] cycloaddition reaction may involve an α,β-unsaturated

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• of 4-acetyl-1,2,3-triazole 5a–d with aniline followed by a Cornforth rearrangement of the 1,2,3-triazole ring [52]. Alkyl- (2a,b) and arylsulfonyl (2c–g) azides were prepared, respectively, from the corresponding sulfonyl chlorides and sodium azides according to published methods (Figure 3) [53]. We