Imide arylation with aryl(TMP)iodonium tosylates

• Souradeep Basu,
• Alexander H. Sandtorv and
• David R. Stuart

Beilstein J. Org. Chem. 2018, 14, 1034–1038, doi:10.3762/bjoc.14.90

• approach to N-aryl imides is to employ aniline starting materials (Scheme 1b, left), as was done in the synthesis of pentoxazone and related herbicides [2]. The alternative aromatic substitution approach with imide anions (Scheme 1b, right) is hampered by their low nucleophilicity [3]. Therefore

• ” surrogate, and the products depicted in Scheme 2 may be deprotected to yield aniline derivatives. In a specific example, 1a is reacted under modified conditions to yield 2a. In this one-pot procedure, hydrazine in aqueous ethanol is added directly to the reaction mixture and aniline 3 is isolated in 63

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• desired products have been obtained in good to excellent yields. The nature and the position of the aniline substituent at the aromatic ring influenced the outcome of the couplings. 2-Amino-13α-estrone was also synthesized in a two-step protocol including an amination of 2-bromo-13α-estrone 3-benzyl ether

• -bromo-13α-estrone 3-methyl (1 or 3) as well as 3-benzyl ethers (2 or 4) with aniline or substituted anilines as reagents. To the best of our knowledge, there are no literature reports concerning the Pd-catalyzed 2- or 4-amination of the estrane core. Results and Discussion Based on recent literature

• results [18][20], we started to optimize the reaction conditions for the transformation of 2-bromo-13α-estrone 3-methyl ether (1) with aniline (Table 1). Since the Pd source has been shown to be crucial in the amination step, two Pd catalysts were investigated. Namely, Pd(OAc)2 and Pd2(dba)3 were used in

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• '-pyrrole]-2,5'(1'H)-diones. We propose that the acid-mediated Boc deprotection in the Ugi intermediate 5 leads to aniline intermediate I which can simultaneously undergo a CIC cyclization through an intramolecular transamidation process giving compound 6 and, in the process, extrude methylamine as a

• )benzaldehyde (1a), aniline (2a), tetrolic acid (3a), and methyl isocyanide (4) in methanol at room temperature to generate adduct 5a; confirmed using mass spectroscopic analysis (Scheme 3). Intermediate 5a, which was not purified, was prone to undergo an intramolecular transamidation when 50% TFA was used to

• Table 1, entry 8 were used. To further explore the utility of our methodology, we examined similar reaction conditions for the synthesis of spiro[indoline-3,2'-pyrrolidine]-2,5'-dione scaffolds (Scheme 5). For this reaction we used 2-(Boc-amino)benzaldehyde 1c, aniline (2a), 3-chloropropanoic acid (3e

An uracil-linked hydroxyflavone probe for the recognition of ATP

• Márton Bojtár,
• Péter Zoltán Janzsó-Berend,
• Dávid Mester,
• Dóra Hessz,
• Mihály Kállay,
• Miklós Kubinyi and
• István Bitter

Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63

• ’-ArH, aniline), 7.97 (d, J = 8,8 Hz, 1H, ArH, 5-chromone), 7.72 (s 1H, 6-uracil), 7.39 (s, 1H, ArH, 8-chromone), 7.07 (d, J = 9,3 Hz, 1H, ArH, 6-chromone), 6.85 (d, J = 8.6 Hz, 2H, 3’-ArH, aniline), 5.30 (s, 2H, CH2), 5.19 (s, 2H, CH2), 3.02 (s, 6H, CH3); 13C NMR (126 MHz, DMSO) δ 171.46 (C=Ochromone

• ), 163.64 (C=O6-uracill), 161.90 (CAr-O), 155.98 (CAr-O), 151.16 (C=O2-uracil), 150.85 (C4’-Ar, aniline), 146.17 (CAr-O), 142.98 (CHAr, triazole), 141.70 (CH4-uracil), 136.82 (C-OHchromone), 128.64 (2CH2’-Ar, aniline), 125.96 (CHAr, chromone), 124.83 (CHAr, triazole), 118.06 (CAr, chromone), 115.42 (CAr

• , chromone), 114.46 (CHAr, chromone), 111.37 (2CH3’-Ar, aniline), 106.18 (C5-uracil), 101.15 (CHAr, chromone), 61.75 (CH2-O), 45.90 (CH2-N), 40.02 (CH3); HRMS calcd. for [M + H+]: 503.1679; found: 503.1675. Fluorescence measurements All the spectroscopic experiments were carried out at 25 °C. In all

Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• yield of 3fa is not clear yet. Steric factors seem to play an important role in the electrochemical CDC reaction of N-arylglycine esters with 2a. When the methyl group was situated at 2- or 3-position of the aniline, instead of in the 4-position, the corresponding products 3ga and 3ha were afforded in

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• -rich anisole type 5a and simple phenyl type 6a, which altered their electronic and steric properties [37]. First, pentafluoro-(2-iodophenyl)-λ6-sulfane (7) was synthesized from commercially available 2-(pentafluoro-λ6-sulfanyl)aniline (8), by completing a Sandmeyer reaction (Scheme 1). Fluoroboric acid

• procedure in the literature [67]. To 4 mL of HBF4 in a round bottomed flask, 1.1 g of 2-(pentafluoro-λ6-sulfanyl)aniline was added and heated until a clear solution formed. The solution was cooled to 0 °C and a cold solution of NaNO2 (380 mg in 2.5 mL distilled water) was added dropwise. The reaction was

Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

• Imane Nekkaa,
• Márta Palkó,
• István M. Mándity and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2018, 14, 318–324, doi:10.3762/bjoc.14.20

• of our results, tricyclic 15b was also prepared alternately: the mixture of 3-aminobicyclo[2.2.2]oct-5-ene-carboxylic acid, triethylorthoformate, aniline and acetic acid was subjected to microwave irradiation at 120 W at 80 °C for 20 min. After completion of the reaction, as monitored by TLC, 20

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -pyrazolo[3,4-d]pyrimidin-6-yl)aniline 214 by NO2 group reduction with H2, Pd/C followed by Boc protection, coupling with tributyl(3,6-dihydro-2H-pyran-4-yl)stannane (213) and subsequent Boc deprotection with TFA in DCM. Pyrazolo[3,4-d]pyrimidinylaniline 214 was used to synthesize pyrazolo[3,4-d

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• + X− generated in situ from the corresponding aniline. It was found that t-BuONO and aromatic amines decomposed CuCF3. Acid was added to make the diazonium substrate fully preformed prior to the reaction with CuCF3. Finally, they explored the possibility of reaction of hydrolysable CuCF3 reagent with

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• aniline which allows the cyclization. Standard Boc deprotection using TFA gave compound 33 in 96% over two steps. This was followed by p-toluoyl deprotection using sodium methoxide in methanol to afford 34 in 64% yield after isolation. Then, the material was protected with DMTr-Cl yielding the protected

• a more straightforward and versatile synthetic route. The Stille coupling was changed to a Suzuki–Miyaura coupling and the cyclization was performed directly starting from the free aniline nitrogen, as we found that Boc protection was required only for cyclization when using DBU and DABCO. To faster

• , 86%; d) DMTr-Cl, pyridine, 1.5 h, rt, 72%; e) AgNO3, TBDMS-Cl, pyridine, THF, 4 h, rt, 76%; f) 2-cyanoethyl-N,N-diisopropylchlorophosphoramidite, DIPEA, THF, 1 h, rt, 93%. Synthesis of protected deoxyribose qA [51]. a) N-(tert-Butoxycarbonyl)-2-(trimethylstannyl)aniline, (Ph3P)2PdCl2, DMF, 24 h, 60

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• mediator afforded high yields of the desired lignin derivatives. In 2014, Stephenson and co-workers developed a similar concept for the photocatalytic radical thiol–ene reaction (Scheme 5) [35]. Instead of using aniline derivatives as redox mediators for the activation of thiols, they generated the

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• substitution by reaction with NaN3 then resulted in AuNPs with mixed monolayers containing 52% N3- and 44% CH3-terminated alkanethiol ligands. A series of alkynes were synthesised, including derivatives of nitrobenzene (1), ferrocene (2), anthracene (3), pyrene (4), aniline (5), and polyethylene glycol (6) all

Quinone-catalyzed oxidative deformylation: synthesis of imines from amino alcohols

• Xinyun Liu,
• Johnny H. Phan,
• Benjamin J. Haugeberg,
• Shrikant S. Londhe and
• Michael D. Clift

Beilstein J. Org. Chem. 2017, 13, 2895–2901, doi:10.3762/bjoc.13.282

• (1a, Table 3). The reaction with aniline (6l, Table 3, entry 2, 68% yield) showed reduced reaction efficiency compared to that with para-anisidine (6a, Table 3, entry 1, 85% yield). When para-fluoroaniline (6m) was employed as the reaction partner, imine 7m was produced in a 77% yield (Table 3, entry

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• failed to give the expected product. With a substituent at the meta-position of the aniline ring, a mixture of regioisomers was obtained. Various alkenes with substituents (R3) were investigated and the oxindoles were obtained in moderate to high yields (Scheme 24). Simultaneously, Lei and co-workers

• obtained. For instance, from aniline, two isomers were obtained in 13% overall yield, and from 1,3-dimethoxybenzene, four products (regioisomers + bis-CF3 compounds) were obtained in 90% overall yield. For this transformation, a radical process was proposed: the trifluoromethyl radical CF3• was generated

• authors studied the effect of structural variations in the substrate (R1 = aryl, heteroaryl, alkyl; R2 = H, 6-OMe, 2-Me). Aniline amides gave no conversion nor did quinoline having an ester group at the 8 position instead of the 8-amino group. The chitosan-based copper catalyst was efficiently reused in

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• acetylenedicarboxylic acid diester with triphenylphosphine and aromatic amines such as aniline, p-toluidine, 4-acetylaniline, 4-bromoaniline, 4-nitroaniline, 1-naphthylamine, 2-aminopyridine, and 2-amino-5-bromopyridine in dichloromethane at room temperature in yields of 96–98% (Scheme 45). The resulting ylides 68 were

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• , Kashiwara, Osaka 582-8582, Japan 10.3762/bjoc.13.267 Abstract A series of aniline and m-phenylenediamine derivatives with electron-withdrawing 3,3,3-trifluoropropenyl substituents were synthesized as small and chemically stable fluorescent organic compounds. Their fluorescence performances were evaluated

• by converting 2,4-disubstituted aniline 1 to the non-fluorescent dipeptide analogue H-Gly-Pro-1 for the use as a fluorogenic substrate for dipeptidyl peptidase-4 (DPP-4). The progress of the enzymatic hydrolysis of H-Gly-Pro-1 with DPP-4 was monitored by fluorometric determination of 1 released into

• reactions of (E)-trimethyl-(3,3,3-trifluoroprop-1-enyl)silane and iodoanilines. This straightforward method is useful for TFPE introduction and a broad range of iodoanilines can be used without protection of the amino group. We used this approach to synthesize several aniline derivatives containing TFPE

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• aniline (3a) as model substrates (Scheme 3, Table 3). In dichloromethane at only slightly elevated temperatures imide 4a is not formed (Table 3, entry 1). Upon addition of N,N-dimethylformamide as a cosolvent at 80 °C the desired product 4a can be isolated in 15% yield (Table 3, entry 2). The yield of 4a

• can be increased to 47% upon raising the reaction temperature to 115 °C (Table 3, entry 3), however, higher temperatures, such as 160 °C, cause a significant drop in yield. Finally, at 115 °C with two equivalents of aniline the highest yield can be achieved (Table 3, entry 6). These imidation

• ]furan-1,3-diones 2 via in situ activation of arylpropiolic acids 1. Optimization of the synthesis of 2,4-diphenyl-1H-benzo[f]isoindole-1,3(2H)-dione (4a) by imidation of 4-phenylnaphtho[2,3-c]furan-1,3-dione (2a) with aniline (3a). Pseudo three-component synthesis of 4-aryl-1H-benzo[f]isoindole-1,3(2H

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• observed and the starting material was recovered intact. Therefore, in order to identify a suitable method converting 40a,b into 6a,b (Scheme 4), model studies was undertaken using the simplified substrate 41 (Table 2). Initially, attempts were made to reduce 41 into the corresponding aniline 42, with a

Main group mechanochemistry

• Agota A. Gečiauskaitė and
• Felipe García

Beilstein J. Org. Chem. 2017, 13, 2068–2077, doi:10.3762/bjoc.13.204

• by condensation reactions between acenaphthoquinone and the corresponding aniline derivative under acidic conditions, involving the use of transition-metal templates [85]. The acid-catalysed ball-milling of acenaphthoquinone with aniline derivatives in the presence of an organic catalyst was able to

• completion. A rare example of a one-pot multistep ball milling reaction is the case of an electron-rich aniline derivative that produced 4 in good yield without the need for ligand isolation. Previously reported examples typically employ “preformed” ligands and metal complexes [68][86], raising the

Solvent-free and room temperature synthesis of 3-arylquinolines from different anilines and styrene oxide in the presence of Al₂O₃/MeSO₃H

• Hashem Sharghi,
• Mahdi Aberi,
• Mohsen Khataminejad and
• Pezhman Shiri

Beilstein J. Org. Chem. 2017, 13, 1977–1981, doi:10.3762/bjoc.13.193

• MeSO3H has been previously used as an effective and mild reagent for organic transformations [14]. In continuation of our studies to develop new synthetic methods for heterocycles [15][16][17][18][19], herein, we disclose a novel route to the synthesis of 3-arylquinolines from aniline derivatives and

• . Column chromatography was carried out on short columns of silica gel 60 (70–230 mesh) in glass columns. General procedure for the synthesis of quinolines in the presence of Al2O3/MeSO3H Aniline (1.0 mmol) and styrene oxide (2.0 mmol) were added to a mixture of MeSO3H (0.3 mL) and Al2O3 (0.1 g). The

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• acetonitrile according to a previously published protocol (for more details see Supporting Information File 1) [40][41][42]. Surprisingly, the obtained 2-iodo-N-(4-methoxybenzyl)aniline (7a) turned out to be rather sluggish in its reaction with the sulfonyl chloride 2. Previously used conditions viz. carrying

• out the reaction in MeCN in the presence of pyridine at rt gave poor results [17][18][19][20]. Thus, in case of aniline 7a the desired sulfonamide 8a was obtained in only 7% yield. Employment of a stronger base such as triethylamine in various solvents (MeCN, DMF, CH2Cl2, THF) led to substantial

• sulfonyl chloride 2a should be performed in the presence of 2 equivalents of aniline without an additional base [21]. However, we figured out that the second equivalent of aniline could efficiently be replaced with an inexpensive weak base such as N,N-diethylaniline and under such conditions obtained the

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• mechanochemical Paal–Knorr pyrrole synthesis using a solid bio-sourced acid like citric acid. Using substituted aniline, benzyl or aliphatic amine and 1,4-diketo compounds in presence of 1 mol % citric acid under ball-milling afforded the desired N-substituted pyrrole with quantitative yield (Scheme 34) [142

Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• aforementioned aims, we envisaged that the synthesis set out in Scheme 2 could deliver access to substrates for the PFB reaction such as 9. After an initial, unfruitful, attempt to obtain the aminoacetals 9 from sequential condensation of aniline and alkyl and aryl halides, a double reductive alkylation that

• attributed to the poor solubility of the intermediate benzylated aniline. In addition, the reaction of 3,4-dimethoxyaniline under the same conditions did not afford 9q and instead 11 was the sole isolable reaction product (62% yield (Scheme 3)). The reaction was reproducible and proceeded even in the absence

• solution of benzaldehyde (1.0 mL, 10 mmol) and aniline (1.1 mL, 12 mmol) in CHCl3 (60 mL) and the mixture was stirred at room temperature (rt) for one hour (h). 2,2-Dimethoxyacetaldehyde (30 mmol) was then introduced into the reaction mixture followed by NaBH(OAc)3 (3.3 g, 15.0 mmol) and the resultant

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• organocatalyst design was first introduced by reacting 3,5-di(trifluoromethyl)phenyl isothiocyanate with 3,5-di(trifluoromethyl)aniline and 4-chloroaniline in a 1:1 ratio under LAG conditions using methanol as the grinding liquid. This led to quantitative formation of the Schreiner's catalyst 5 and thiourea 17

• equiv) for 40 minutes, followed by the click-coupling reaction of the second equivalent of an aniline with the intermediate isothiocyanate. In this way, non-symmetrical thioureas 25a–d were synthesized and isolated in high 87–94% yields. Instead of using thiophosgene and CS2 as corrosive and hazardous

• by the addition of the second equivalent of aniline, led to non-symmetrical thioureas 28e–g in ≥97% yields (Scheme 9). Treating p-pda with two equivalents of 26 gave 99% of bis-thiocarbamoyl benzotriazole 29, a masked 1,4-phenylene diisothiocyanate equivalent. In contrast, the analogous reaction of o

Sulfamide chemistry applied to the functionalization of self-assembled monolayers on gold surfaces

• Loïc Pantaine,
• Vincent Humblot,
• Vincent Coeffard and
• Anne Vallée

Beilstein J. Org. Chem. 2017, 13, 648–658, doi:10.3762/bjoc.13.64

• Surface, UMR CNRS 7197, 4 place Jussieu, 75005 Paris, France Université de Nantes, CNRS, CEISAM, UMR 6230, Faculté des Sciences et des Techniques, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France 10.3762/bjoc.13.64 Abstract Aniline-terminated self-assembled monolayers (SAMs) on gold surfaces

• have successfully reacted with ArSO2NHOSO2Ar (Ar = 4-MeC6H4 or 4-FC6H4) resulting in monolayers with sulfamide moieties and different end groups. Moreover, the sulfamide groups on the SAMs can be hydrolyzed showing the partial regeneration of the aniline surface. SAMs were characterized by water

• elaboration of the aniline terminated surface (SAM 4-ATP) is the first step in creating SAMs bearing a sulfamide group, see Figure 1. For this purpose, 4-amino-thiophenol (4-ATP) was first adsorbed on gold surfaces. The aniline-terminated surface obtained can then react with ArSO2NHOSO2Ar (Ar = 4-MeC6H4 and 4