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

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• influenced by the electronic effects induced by the substituents of the aniline unit (Table 1). Detailed information about characterization data for compounds 2a–l is given in Supporting Information File 1. X-ray crystallographic data In order to bring evidence of the geometry and arrangement of the

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• straightforward approach for accessing various N-(hetero)aryl-4,5-unsubstituted pyrroles, and some of the pyrrole products are not accessible with the methods reported hitherto. Results and Discussion Initially, a mixture of aniline (1a), α-bromoacetaldehyde acetal (2a), and ethyl acetoacetate (3a) was treated

• obtained for 4o and 4p were slightly inferior. Gratifyingly, a 3,5-dichloro-4-(1,1,2,2-tetrafluoroethoxy)aniline also participated smoothly in this reaction, and the expected product 4q can be obtained in 75% yield. This fluorinated substituent on the aniline ring has been identified as the key precursor

• with aniline (1a) or amantadine in the presence of HATU or EDCI to form the multisubstituted pyrrole-3-carboxamide derivatives 4x and 4y (Scheme 4). These skeletons have been proven to be promising inhibitors for the production of cytokines [47]. A plausible mechanism for the model reaction was

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• investigation, the LS-FAS-Cu was also found to be an efficient catalyst for the synthesis of aminonaphthalene derivatives (Table 5). The substituent effect of aniline was examined systematically, and the results showed that anilines bearing electron-donating groups such as Me, OMe and t-Bu at the para-position

• )acetophenone could react smoothly, generating the target products 10k–o in excellent yields. Unfortunately, aniline substituted with a strong electron-withdrawing group at the para-position and 2-(phenylethynyl)acetophenone substituted with an electron-donating group were reluctant to react under this

A heterobimetallic tetrahedron from a linear platinum(II)-bis(acetylide) metalloligand

• Matthias Hardy,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2020, 16, 2701–2708, doi:10.3762/bjoc.16.220

• employed the linear platinum(II)-bis(acetylide) metalloligand 3 that bears two 4-aniline moieties (Scheme 1). In order to synthesize this key compound, we followed known procedures to first isolate 4-ethynylaniline (1) [52] that was subsequently transformed into metalloligand 3 [53] upon treatment with

• trans-[Pt(PBu3)2Cl2] (2). The aniline moieties in 3 were further transformed into chelating pyridylimine binding sites in the following subcomponent self-assembly process when six equivalents of metalloligand 3 were reacted with twelve equivalents of pyridine-2-carbaldehyde and four equivalents of iron

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• Oxone™ (Wegner et al. [19][20][21], Scheme 1). Isolation of 3 was achieved, however, a one pot approach including a subsequent Baeyer–Mills reaction to yield 10 is preferred. 1-Iodo-3-nitrosobenzene (6) cannot be prepared by oxidation of the corresponding aniline because hypervalent iodine is formed [22

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• then reduce 3-nitrobenzoic acid to the corresponding aniline 25 to turn over the cobalt cycle. Simultaneously, 23 condenses with the chiral primary amine catalyst 26 to give enamine intermediate 27, which can be intercepted by 24 to generate imine intermediate 28, which is finally hydrolysed to turn

A proposed sustainability index for synthesis plans based on input provenance and output fate: application to academic and industrial synthesis plans for vanillin as a case study

• John Andraos

Beilstein J. Org. Chem. 2020, 16, 2346–2362, doi:10.3762/bjoc.16.196

• descending order of impact according to OSI values given in Table 1: benzene (12.000), aniline (10.350), toluene (10.150), nitrobenzene (10.130), cyclohexane (8.777), diethyl ether (8.421), acetic anhydride (8.309), petroleum ether (7.734), ethyl acetate (7.597), N,N-dimethyltoluidine (7.592), methyl tert

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• = 2.0 Hz, 1H) ppm, respectively. Crucially, it is apparent that using the photoredox conditions described in Scheme 3, the aniline nucleophile adds primarily at the α-position of the allenamide 15; this is in contrast to the archetypal electrophilic activation modes where comparable nucleophiles add to

• (32 to 35) in moderate to good isolated yields. 4-Bromo-2-fluoroaniline was also examined as a nucleophile, as we had previously shown this to be an effective aniline platform for developing linezolid analogues, and this delivered two N,N’-allylaminals 36 and 37, respectively. Masson had previously

• the conjugated N-acyliminium intermediate 14. Photoredox Ir-catalyzed intermolecular addition of bromide 18 and aniline 16 to allenamide 15. Reaction scope (a) allenamide; (b) arylamine nucleophile; (c) alcohol nucleophile. (a) Tentative mechanism for the photoredox-catalyzed formation of the

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• used for the photocatalytic generation of H2O2, the degradation of methylene blue dye, and the reduction of nitrobenzene to aniline. Although it was an interesting and novel approach to efficiently irradiating HPCats, the report did not address the potential concerns with the heat dissipation from the

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• ) [19], N-methyl-2-pyridone 7 (δ 139.5) [20], 2,4-dimethoxy-3-methylquinoline (8, δ 147.0) [21], and 2-methoxypyridine 9 (δ 147.2) [22] supported a 2-quinolone form 1 but not 2-quinolinol 2 (Figure 2, Table 1). The same structure was synthesized from diethyl malonate and aniline (see Supporting

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• approach was based on the one-electron reduction of diazonium salts (see the case of 13.3+ in Scheme 13), formed in situ by the reaction of the chosen 2-heteroaryl aniline (e.g., 13.1) with tert-butyl nitrite (1.5 equiv). Formation of the aryl radical 13.4· and following addition onto an alkyne moiety (e.g

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• ⋅LiCl solution, in the collection flask, away from a heat source. System scope: Bis(trimethylsilyl)amine (HMDS), diphenylamine (Ph2NH), aniline (PhNH2), and 2,2,6,6-tetramethylpiperidine (TMPH) were selected as substrates. Ph2NH, HMDS, and PhNH2 due to their lower pKa (25, 30, and 31, respectively, in

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions

• Shrikant D. Tambe,
• Kwan Hong Min,
• Naeem Iqbal and
• Eun Jin Cho

Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114

• unprecedented reductive coupling of N-benzylidene-[1,1'-biphenyl]-2-amines with an aliphatic amine. The presence of a phenyl substituent in the aniline moiety of the substrate was critical for the reactivity. The reaction proceeded via radical–radical cross-coupling of α-amino radicals generated by proton

• photocatalytic synthetic methods are mainly limited to aniline-based substrates and do not encompass aliphatic amines. We planned the synthesis of 1,2-diamine compounds having an aliphatic amine moiety by the intermolecular coupling of N-benzylidines with aliphatic amines that not only act as coupling partner

• 2p), did not have any significant impact on the reaction outcome. The heteroaryl ring-bearing substrates (2n and 2o) also underwent the transformation, and furnished the valuable vicinal diamine products. The modifications on the aniline moiety were also suitable, and substrates with both electron

The charge-assisted hydrogen-bonded organic framework (CAHOF) self-assembled from the conjugated acid of tetrakis(4-aminophenyl)methane and 2,6-naphthalenedisulfonate as a new class of recyclable Brønsted acid catalysts

• Svetlana A. Kuznetsova,
• Alexander S. Gak,
• Yulia V. Nelyubina,
• Vladimir A. Larionov,
• Han Li,
• Michael North,
• Vladimir P. Zhereb,
• Alexander F. Smol'yakov,
• Artem O. Dmitrienko,
• Michael G. Medvedev,
• Igor S. Gerasimov,
• Ashot S. Saghyan and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2020, 16, 1124–1134, doi:10.3762/bjoc.16.99

• crystals (Figure 5) reached a plateau at 160 °C after 5.9% of the mass was removed as water. The plateau was maintained until 340 °C, when the sample underwent an endothermic decomposition. The decomposition produced sulfur dioxide, naphthalene, and aniline, according to the infrared spectra of the

• Brønsted acid catalyst) cation exchange resin IR-120, which contains sulfonic acid functionalities, was mixed in its hydrogen form with aniline to give a model of F-1. An attempted use of the resulting compound with the same amount of ammonium groups as in F-1 for the conversion of the epoxide 2 into the