Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• studies on naphthalene and the conversion of naphthalene to phthalides, a reaction that, two decades later, became of critical relevance for the industrial synthesis of indigo. It is surprising that, after spending only three years in Siena, Guareschi obtained, in 1879, the prestigious Chair of Medicinal

• of 47. In Turin, Guareschi pursued an amazing range of research topics. The one of ptomaines (alcaloidi cadaverici, cadaverous alkaloids) and the chemistry of naphthalene led to considerable fame for Guareschi because of both his original contributions and his comprehensive reviews of the area. Thus

• the chemistry of naphthalene. The last one dates from 1887 and deals with the formation of isomers in the electrophilic aromatic substitution of naphthalene with chlorine and bromine [32]. This work was done in collaboration with Pietro Biginelli (1860–1937), the only collaborator of Guareschi who

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• naphthalene, the reaction successfully provided the benzoindoline 3g in 56% yield. Substrates with an N-Boc group also worked well to deliver the corresponding indoline 3h in 77% yield. Moreover, a scale-up reaction of 1a (2 mmol) was conducted, affording the corresponding product 3a (0.28 g) in a yield of 62

• , delivering the corresponding regioisomers 8l and 8l’ in 62% with 1:1.6 ratio. Moreover, the naphthalene and tetrahydroisoquinoline-derived acrylamides were also compatible, giving the polycyclic products 8m and 8n in 77% and 70%, respectively. Additionally, protecting groups such as isopropyl, benzyl, or

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

Synthesis, structural characterization, and optical properties of benzo[f]naphtho[2,3-b]phosphoindoles

• Mio Matsumura,
• Takahiro Teramoto,
• Masato Kawakubo,
• Masatoshi Kawahata,
• Yuki Murata,
• Kentaro Yamaguchi,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2021, 17, 671–677, doi:10.3762/bjoc.17.56

• and IR). All the corresponding aromatic proton and carbon atoms on the two naphthalene rings were equivalent in the 1H and 13C NMR spectra of phospholes. These results show that all phosphole derivatives had a symmetric structure in solution. The 31P NMR spectra of these show the typical low-field

• recrystallization. The molecular structure of 2, determined through single-crystal X-ray diffraction analysis, is illustrated in Figure 2, and selected geometrical parameters are shown in Table 1. The results revealed that the naphthalene and fused phosphole rings are almost coplanar (mean deviation = 0.030 Å). The

• angle between each naphthalene ring containing ten carbon atoms is 1.64°, which is smaller than that for group 15 analogs (i.e., N-phenyldibenzo[b,h]carbazole: 4.47° or 2.57° [22], for crystal data, see Figure S2, Supporting Information File 1 and Sb-phenyldinaphtho[2,3-b:2′,3′-d]stibole: 8.05° [23

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

• %), olefins (22.5%) and naphthalene (4.1%) at total HDPE conversion at 350 °C [144]. In another example, hydrocracking of PE was performed over Pt NPs supported on SrTiO3 perovskite nanocuboids [145]. Virgin PE (Mw = 18000–420000 g⋅mol−1) or PE from single-use plastic bags (Mw = 115000 g⋅mol−1) was converted

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• respect, a bifunctional quinine-derived sulfonamide organocatalyst was developed to catalyze the asymmetric sulfa-Michael reaction of naphthalene-1-thiol with trans-chalcone derivatives. The target sulfa-Michael adducts were obtained with up to 96% ee under mild conditions and with a low (1 mol

• nucleophiles [27][28][29][30]. Thionaphthols, however, are overlooked in sulfa-Michael addition reactions. And to our best knowledge, no study is present concerned with SMAs with naphthalene-1-thiol as the nucleophile for the addition to enones. Encouraged by the good results obtained with enantioselective

• sulfa-Michael additions of thiols to chalcones with sulfonamide-type organocatalysts in the literature [30][31], in this study, a new quinine sulfonamide organocatalyst derivative was developed to catalyze the enantioselective SMA of naphthalene-1-thiol to trans-chalcones under mild conditions and with

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• %. Naphthalene 6h and 2-pyridine 6i were also successfully obtained, however, the reactions with the 3- and 4-pyridines 5j and 5k resulted in complex mixtures from which no desired product, nor starting material, could be observed. The scope of this chemistry also extends to substrates with a shorter

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• can be successfully applied to cyclization at multiple reaction sites. By using bisacetals bearing a naphthalene core (Ar2) as substrates, tandem cyclization achieved the efficient synthesis of several ortho-fused six-hexagon benzenoids [21]. On the basis of our work mentioned above, we assumed that

• , respectively. Thus, phenylboronic acid ester 3 bearing an acetal moiety functions as a reagent for fused naphthalene ring extension through our cross-coupling/cycloaromatization sequence [31][32][33][34][35]. Hetero[5]helicenes 12 were synthesized via tandem cycloaromatization using teraryl precursors, in

• silica gel column chromatography (hexane/EtOAc = 10:1) gave 1a (1.19 g, 80%). 1,8-Bis{2-[(1,3-dioxolan-2-yl)methyl]phenyl}naphthalene (4b) A DMF (6.7 mL) and H2O (3.3 mL) solution of 1,8-diiodonaphthalene (2b, 759 mg, 2.00 mmol), boronate ester 3 (1.28 g, 4.40 mmol), Pd2(dba)3·CHCl3 (52 mg, 50 μmol

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• isomerization [36]. Several nitrogen nucleophiles have been evaluated as catalysts to promote the difluorocarbene formation from TFDA in order to bring about the cyclopropanation of a 2-siloxybuta-1,3-diene derivative; 1,8-bis(dimethylamino)naphthalene (proton sponge) was found to be particularly effective [37

• reaction of 2-(2,2-difluorocyclopropyl)naphthalene (167) with sodium arylsulfinates 168 under palladium catalysis afforded the 2-fluoroallylic sulfones 166 in moderate to good yields with (Z)-selectivity. This method showed a good compatibility with a broad range of substrates and substituents. As

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• excimer (490 nm) to monomer emission (406 nm, Figure 3B). Thus, monitoring the relative fluorescence intensities at two wavelengths (F406/F490) allowed the ratiometric detection of nucleic acids. Schmuck et al. reported a similar cationic peptide beacon 3 coupled with a FRET pair, a naphthalene donor and

• a dansyl acceptor, for ratiometric detection of dsDNA (Figure 4 [33]. Compound 3 contains two Gly–Ser–Lys tripeptide arms attached via their C-terminus to a central lysine spacer (Figure 4A). Compound 3 is in unfolded form in unbound conditions as it exhibits the naphthalene emission at 383 nm upon

• arms attached through their C-terminus to a central lysine. Two heparin sensors 10 and 11 are developed by attaching the N-terminus of the peptide beacon with pyrenes and fluorescence resonance energy transfer (FRET) pair (naphthalene and dansyl), respectively for ratiometric detection of heparin

Naphthalonitriles featuring efficient emission in solution and in the solid state

• Sidharth Thulaseedharan Nair Sailaja,
• Iván Maisuls,
• Jutta Kösters,
• Alexander Hepp,
• Andreas Faust,
• Jens Voskuhl and
• Cristian A. Strassert

Beilstein J. Org. Chem. 2020, 16, 2960–2970, doi:10.3762/bjoc.16.246

• or rotational modes [34][35]. Secondly, a considerably distorted conformation is also needed to prevent detrimental exciton interactions in the solid state. Currently, 6,7-disubstituted naphthalene-2,3-dicarbonitrile derivatives represent an intensively investigated class of compounds, due to their

• reports on the DSE behavior of 6,7-disubstituted naphthalene-2,3-dicarbonitrile derivatives so far. Herein we have designed and synthesized donor–acceptor (D–A) naphthalonitriles (NCNs) symmetrically γ-disubstituted with two p-functionalized phenyl moieties and investigated their photophysical properties

• -disubstituted-6,7-diphenylnaphthalene derivatives with varying distal groups. B) Schematic depiction of the D–π–A system. Synthesis of p-phenyl-6,7-disubstituted naphthalene-2,3-dicarbonitrile. Photophysical properties of the samples in fluid at rt and 77 K. In all cases, the lifetimes were fitted mono

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• )] (Figure 4e). Equally, Schalley and Nitschke developed a guest-induced self-sorting based on two new Zn4L6 cages (Figure 5a) using the aldehyde 9 and the diamine subcomponents 7 and 8 that contained either the naphthalene diimide or zinc porphyrin moiety [51]. Both cages respond selectively to distinct

• chemical stimuli yielding different supramolecular products. The porphyrin ligands of the cage [Zn4(8')6]8+ interacted favorably with C70 as a guest, whereas an electron-rich aromatic crown-ether did thread onto the electron-deficient naphthalene diimides of cage [Zn4(7')6]8+ forming mechanically

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• synthetic molecular machines. Developing switchable and specifically designed crown ethers enables the implementation of function into molecular assemblies. Seven tailor-made redox-active crown ethers incorporating tetrathiafulvalene (TTF) or naphthalene diimide (NDI) as redox-switchable building blocks are

• motivated us to conduct the present study on the thermodynamic and electrochemical properties of seven redox-active crown ethers of different ring sizes in comparison to the unfunctionalized analogs DBC8 and BC7 (Figure 1). Crown ethers incorporating TTF, an extended TTF, and naphthalene diimide (NDI) as

• Information File 1). Slow diffusion of CH3CN into a concentrated solution of NDIC7 in CH2Cl2 yielded single crystals suitable for X-ray diffraction (Figure 2b). The macrocycle displays a folded conformation in the solid state due to the flexible linker, featuring an intramolecular NDI/naphthalene stacking

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• ), whereas host 1 and guest 3 would lead to a 75 backbone-atom trefoil (and unknotted macrocycle). Results and Discussion The synthesis of bis-macrocyclic host 1 began by breaking the symmetry of naphthalene-1,5-diol (4) by alkylation of one of the alcohols with 2-azidoethyl mesylate to yield azide 5 in 27

• % yield (Scheme 1). Alkylation of 5 with 1,2-dibromoethane provided key intermediate azido-bromide 6 in 60% yield. This two-step route to 6 is efficient, but the 16% overall yield was lower than desired. An alternate route began by converting diol 4 to bis(2-hydroxyethoxy)naphthalene 7 in 92% yield by

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• naphthalene diimde analogue (NDI) equipped at the imide positions with two guanidinio-carbonyl-pyrrole (GCP) pendant arms interacted significantly stronger with ds-DNA at pH 5 than at pH 7, due to reversible protonation of the GCP arms. This was consequence of a pH-switchable threading intercalation into ds

• the DNA/RNA conjugate NDI-GCP2 showed also aggregation along the ds-polynucleotide and AFM and DLS demonstrated that NDI-GCP2 has pronounced ds-DNA condensation ability. Keywords: AFM; circular dichroism; DNA/RNA recognition; fluorescence; guanidinio-carbonyl-pyrrole; naphthalene diimide

• attention to a less common DNA/RNA binding motif: threading intercalation. This sterically very demanding binding mode is characterised by a central large aromatic moiety, in this case the well-known naphthalene diimide (NDI), equipped at both sides of the long axis with large substituents, which have to

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• Chemistry (CNC), Universität Würzburg, Theodor-Boveri-Weg, 97074 Würzburg, Germany 10.3762/bjoc.16.170 Abstract Two novel unnatural amino acids, prepared by linking a dicationic purple-coloured and fluorescent naphthalene diimide (NDI) at core position to amino acid side chains of variable length, strongly

• the type of polynucleotide, thus the studied NDI dyes act as dual fluorimetric/ICD probes for sensing the difference between here used GC-DNA, AT-DNA and AU-RNA. Keywords: amino acid–fluorophore conjugate; circular dichroism; DNA/RNA recognition; fluorescence; intercalation; naphthalene diimide

• ][13][14][15][16]. These inspiring results encouraged us to broaden the palette of available amino acid (AA)–chromophore conjugates. Therefore, in this work we have chosen a naphthalene diimide (NDI) chromophore [17][18][19][20], a well-known DNA/RNA binding moiety, which differs from previously used

The biomimetic synthesis of balsaminone A and ellagic acid via oxidative dimerization

• Sharna-kay Daley and
• Nadale Downer-Riley

Beilstein J. Org. Chem. 2020, 16, 2026–2031, doi:10.3762/bjoc.16.169

• 16 in 29, 34, and 19% yields, respectively (Table 1). As anticipated, the reaction of naphthalene 17 with CAN under aqueous conditions resulted in preferential oxidative demethylation to give quinone 7, as opposed to oxidative dimerization. The elimination of water from the reaction posed a few

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• naphthalene ring. The transformation proceeded under either Cu/Ag co-catalysis or using the dual Ru/Cu photoredox system. In the latter case, the methodology was operative at room temperature within a short reaction time, affording the desired products in good to excellent yields. The described sulfonylation

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

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• synthesized through alkylation of the benzophenone imine of glycine ester 73, with perfluorinated benzylbromide 19c or 2,4-bis(trifluoromethyl)benzyl bromide (74) in the presence of 2,7-bis[O(9)-allylhydrocinchonidinium-N-methyl]naphthalene dibromide, to afford the fluorinated phenylalanine imines 75a,b with

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• -dichloro-1,1,3,3-tetraisopropyldisiloxane, TBSOTf = tert-butyldimethylsilyl trifluoromethanesulfonate, proton sponge = 1,8-bis(N,N-dimethylamino)naphthalene. Synthesis of (Z)-bromide 4 using a palladium-catalyzed, stereoselective dehalogenation [21][22][23][24]. TBSOTf = tert-butyldimethylsilyl

Copper-catalyzed remote C–H arylation of polycyclic aromatic hydrocarbons (PAHs)

• Anping Luo,
• Min Zhang,
• Zhangyi Fu,
• Jingbo Lan,
• Di Wu and
• Jingsong You

Beilstein J. Org. Chem. 2020, 16, 530–536, doi:10.3762/bjoc.16.49

• arylation; nonprecious metal catalyst; copper catalysis; polycyclic aromatic hydrocarbons (PAHs); regioselectivity; Introduction Polycyclic aromatic hydrocarbons (PAHs) with rigid planar structure, such as naphthalene, phenanthrene, pyrene and their derivatives, can usually emit relatively strong

• Pd(II) species to more electrophilic high-valent cationic Pd(IV). In addition, this protocol is not compatible with other PAHs except naphthalene, such as phenanthrene, pyrene and fluoranthene, and cannot tolerate some special functional groups, such as alkenyl and alkynyl groups. As a component part

• lower yield (Scheme 2, 3q). We next examined the scope of various naphthalene substrates (Scheme 3, 4a–l). The electronic effect of C4-substituents on N-(tert-butyl)-1-naphthamide was not obvious. The 4-substituted 1-naphthamide substrates, whether with electron-donating methyl and methoxy groups, or