The mechanochemical synthesis of quinazolin-4(3H)-ones by controlling the reactivity of IBX

• Md Toufique Alam,
• Saikat Maiti and
• Prasenjit Mal

Beilstein J. Org. Chem. 2018, 14, 2396–2403, doi:10.3762/bjoc.14.216

• benzaldehydes, aniline and IBX under ball-milling conditions an explosion was observed (Figure 1a; Caution! see experimental section) [30][31] and similar observations were made with Dess–Martin periodinane (DMP). On the other hand, benzamide was found to be unreactive with IBX and no reaction was observed

• aniline derivative with moderate reactivity. Therefore, we anticipate that the controlled reactivity of IBX under mechano-milling conditions led to successful reaction with 2-aminobenzamide. Finally, a large scale synthesis was performed to prove the synthetic utility of this methodology. By taking

• ). Melting points (mp) of the compounds were determined using a digital melting point apparatus and are uncorrected. Caution. When aniline and IBX are mixed under solvent-free conditions or at maximum contact, immediate explosion was observed. However, no explosion could be observed under similar conditions

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• . 4n was smoothly converted to the corresponding aniline derivative 4s in 87% isolated yield, after exposure to a reductive environment using Fe powder and NH4Cl. Subsequent Sandmeyer reaction of 4s took place very nicely to afford the corresponding CF2CF2-substituted iodobenzene derivative 4t in 67

Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3-triazoles

• James T. Fletcher,
• Matthew D. Hanson,
• Joseph A. Christensen and
• Eric M. Villa

Beilstein J. Org. Chem. 2018, 14, 2098–2105, doi:10.3762/bjoc.14.184

• groups attached at the para-phenyl positions of both 1-phenyl-4-formyl-1,2,3-triazole and aniline reactants were used in the current investigation. Two reaction conditions were employed in this study. Low temperature conditions used a 1:1 CHCl3/MeOH solvent system at room temperature, identified as

• where an electron-rich triazole was paired with an electron-poor aniline generated significant populations of rearranged imine products (Table 2, entries 16, and 22–24). This stands as a cautionary observation informing the design of 1-substituted-4-imino-1,2,3-triazoles intended for exposure to high

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• electron-poor heterocycles under the current conditions. However, the aniline coupling partner opens up a huge variety of opportunities, as arylamines and heteroarylamines are widely available. Scaffolds such as 7b have lots of potential for further elaboration. In addition, the presence of electron-poor

Rational design of boron-dipyrromethene (BODIPY) reporter dyes for cucurbit[7]uril

• Mohammad A. Alnajjar,
• Jürgen Bartelmeß,
• Robert Hein,
• Pichandi Ashokkumar,
• Mohamed Nilam,
• Werner M. Nau,
• Knut Rurack and
• Andreas Hennig

Beilstein J. Org. Chem. 2018, 14, 1961–1971, doi:10.3762/bjoc.14.171

• -dipyrromethene (BODIPY) dyes as a new class of fluorophores for the design of reporter dyes for supramolecular host–guest complex formation with cucurbit[7]uril (CB7). The BODIPYs contain a protonatable aniline nitrogen in the meso-position of the BODIPY chromophore, which was functionalized with known binding

• motifs for CB7. The unprotonated dyes show low fluorescence due to photoinduced electron transfer (PET), whereas the protonated dyes are highly fluorescent. Encapsulation of the binding motif inside CB7 positions the aniline nitrogen at the carbonyl rim of CB7, which affects the pKa value, and leads to a

• (BODIPYs) with an aniline substituent in the meso-position as fluorescent dyes in this type of anchor approach (Figure 1). BODIPYs are a class of fluorescent dyes that are particularly suitable for applications in medical imaging, and as fluorescent labels in biology, biochemistry and related fields [29

A pyridinium/anilinium [2]catenane that operates as an acid–base driven optical switch

• Sarah J. Vella and
• Stephen J. Loeb

Beilstein J. Org. Chem. 2018, 14, 1908–1916, doi:10.3762/bjoc.14.165

• benzylanilinium, as well as a smaller DB24C8 ring was synthesized and characterized. 1H NMR spectroscopy showed that the DB24C8 ring can shuttle between the two recognition sites depending on the protonation state of the larger macrocycle. When the aniline group is neutral, the DB24C8 ring resides solely at the

• chemical shifts for protons a–d and I–L on the benzylaniline portion of the large ring of [8DB24C8]6+ do not shift significantly inferring that in the neutral aniline state the crown ether resides exclusively at the bis(pyridinium)ethane site of the [2]catenane. Table 1 summarizes the chemical shift

• protonation of the aniline nitrogen atom to give [8-HDB24C8]7+ and a second viable recognition site for the crown ether. Figure 4 shows a partial 1H NMR spectrum of protonated [8-HDB24C8]7+ in CD3CN at 298 K. The smaller DB24C8 ring can now reside at either of the bis(pyridinium)ethane or benzylanilinium

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• Background: 4-(n-Octyloxy)aniline is a known component in the elaboration of organic materials with mesogenic properties such as N-substituted Schiff bases, perylene bisimide assemblies with a number of 2-amino-4,6-bis[4-(n-octyloxy)phenylamino]-s-triazines, amphiphilic azobenzene-containing linear-dendritic

• block copolymers and G-0 monomeric or dimeric dendritic liquid crystals with photochromic azobenzene mesogens. The present ab initio study explores a previously unknown use of 4-(n-octyloxy)aniline in the synthesis, structure and supramolecular behaviour of new dendritic melamines. Results: Starting

• from 4-(n-octyloxy)aniline, seven G-2 melamine-based dendrimers were obtained in 29–79% overall yields. Their iterative convergent- and chemoselective synthesis consisted of SN2-Ar aminations of cyanuric chloride and final triple N-acylations and Williamson etherifications (→ G-2 covalent trimers) or

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• by the same group and its utility in the enantioselective ring-opening of cis-stilbene oxide with aniline and thiophenol was demonstrated. The reaction provided the corresponding β-hydroxy derivatives in good yields and excellent enantioselectivities (Scheme 15) [49]. Bipyridine as a scaffold in

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• reagents has been described only in 2017 by the group Greaney [77]. Except for anilines bearing strong electron-withdrawing substituents (p-NO2), the triarylated amines 84 can be obtained in moderate to good yields, irrespective of the substitution of the aniline and the diaryl-λ3-iodane (Scheme 38

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• bearing electronically different substituents at the ortho, meta and para-positions of the aniline moieties was compatible. The scope of this methodology could be extended to another type of enaminones, such as hydroxyfuran-2-one-derived ones 25, which afforded by reaction with N-Boc-isatin imines 3 the

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