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

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• , MG, Brazil 10.3762/bjoc.17.66 Abstract Desulfonylative alkylation of N-tosyl-1,2,3-triazoles under metal-free conditions leading to β-triazolylenones is reported here. The present study encompasses the synthesis of triazoles with a new substitution pattern in a single step from cyclic 1,3-dicarbonyl

• efficient synthesis of triazoles with different substitution pattern. One important methodology developed by the Sakai group involved the reaction of α,α-dichloroketone, tosyl hydrazide and primary amine [20]. However, in this case, the unstable α,α-dichlorohydrazone intermediate had to be isolated which

• paved the way for further modification of the protocol (Scheme 1c). Direct functionalization of triazoles is an alternative strategy to access triazoles with the desired substitution pattern. However, such approaches are complicated by a low energy barrier between the N1 and N2 tautomers in solution

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• analysis. This is similar to the previously observed substitution pattern in SNAr reactions of 2,6-bistriazolylpurine derivatives with simple N- and S-nucleophiles. Experimental General information Commercially available reagents were used as received. The reactions and the purity of the synthesized

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• 42% yield along with the corresponding dehydrated alkenylpyridine compound 6d in 16% yield (Table 3, entry 3). Different from the 2,6-substitution pattern, 3,5-dimethylpyridine (1e) was also tested under standard reaction conditions upon increasing the reaction time to 48 h, which did not furnish the

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

• , optical, and biological properties upon a careful selection of the substitution pattern [9], continually encouraged the scientific community to search for new powerful representatives and to elaborate advantageous synthetic protocols. Under chemical, biochemical, or electrochemical conditions the

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• the presence of AgNO3 the 3’-O-TBDMS derivative was always obtained in excess over the 2’-isomer. The differences in the reactivity of the 2’- and 3’-OH groups mirror the impact of the sugar conformation, which is dependent on the substitution pattern. Ribonucleosides favor the 3’-endo conformation

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• -phenyl migration have been found to be subtly dependent on the substitution pattern. For instance, the rate of 1,2-AS in 3b has been found to be much faster than the one of 3e. It is probably due to the extra hindrance of gem-dimethyl substituents at C-7 position in the latter. Moreover, only 1,2-AS

Synthesis of 6,13-difluoropentacene

• Matthias W. Tripp and
• Ulrich Koert

Beilstein J. Org. Chem. 2020, 16, 2136–2140, doi:10.3762/bjoc.16.181

• -positions resulted in a larger HOMO–LUMO gap compared to PEN, while PFP showed a smaller gap than PEN. Another example for a partially fluorinated pentacene is the F6PEN 4 [9]. Its unilateral substitution pattern leads to a disctinct electronic structure and a criss-cross packing motif, unlike the

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

• excellent yields. Remarkably, a high functional group tolerance was observed, including heterocyclic substrates. In contrast, the N-substitution pattern clearly impacted the efficiency of the reaction. Indeed, exchanging the N-sulfonyl or N-acetyl protecting group with other functionalities, such as

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• cyclopentenone ring in all cases (Scheme 32). This was expected for terminal alkyne 58a, since this is the substitution pattern always found (see Scheme 4). On the other hand, for alkynes bearing substituents of similar steric bulk, the electron withdrawing group is expected to occupy the β-position. However

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

• ), ethers (2e), halogens (2i and 2l) [48][49][50], the medicinally important CF3 group (2m), and acetals (2p) were tolerated under these mild reaction conditions. The substitution pattern of the aryl groups, such as ortho (2c, 2e, and 2k), meta (2m and 2p), and para substitution (2b–2d, 2g, 2i, 2l, 2o, and

• electron density or position of the substituent on the benzylidene moiety. Interestingly, the homocoupling process was highly stereoselective, resulting in the formation of only one diastereomer, probably due to the bulky substitution pattern of the substrates. The structure of the homocoupled 1,2-diamine

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• porphyrin [75] and rhodamine 6G (OD14) [76]. Aryl radicals from aryl halides. Aryl halides are generally more difficult to reduce than aryl diazonium salts (Ered < −1.2 V) [77][78]. However, they are more available and bench-stable. Their reduction potential is dependent on the substitution pattern and on

• fragmentation. N-aminopyridinium salts are also emerging starting materials. Iminyl radical generation Hydroxylamines have emerged as key precursors for iminyl radical generation [128]. Their redox properties can be easily tuned through the substitution pattern of the electrophore. They can be subjected to

• SET. After the reduction, a fragmentation affords the desired amidyl radicals together with the corresponding pyridines. The reduction potential of such species was around −0.75 V vs Ag/Ag+, depending on the substitution pattern. This scaffold was employed recently by the Hong group to achieve an

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• the phenol substrate substitution pattern, and it is therefore difficult to develop general methods for this transformation. This substrate–control bias was successfully outmaneuvered by the development of a copper-based catalytic system operating under aerobic conditions and allowing selective access

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• substituents on the P-heterocyclic core influence the outcome of the isomerization. Methyl group(s) in positon 3 and 4 represents a typical substitution pattern. Thus, the isomerization of 1-phenyl-3-phospholene oxide (5) and 1-phenyl-3,4-dimethyl-3-phospholene oxide (8) was investigated under the optimized

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• last hundred years [1][2][3][4]. Their substitution pattern easily facilitates shift of the absorption from the ultra violet part into the near infrared region while they exhibit huge extinction coefficients [3]. The connection of two nitrogens with an odd number of methine groups results in a positive

Synthesis and circularly polarized luminescence properties of BINOL-derived bisbenzofuro[2,3-b:3’,2’-e]pyridines (BBZFPys)

• Ryo Takishima,
• Yuji Nishii,
• Tomoaki Hinoue,
• Yoshitane Imai and
• Masahiro Miura

Beilstein J. Org. Chem. 2020, 16, 325–336, doi:10.3762/bjoc.16.32

• the solid state [50][51][52][53][54]. Conclusion In summary, we have achieved the synthesis of a series of CPL-active polyheteroaromatic compounds from readily available chiral BINOLs via the O-arylation and subsequent palladium-catalyzed C–H/C–H coupling reaction. The substitution pattern on the

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• because of the S/CH2 replacement, we assumed that "mapping" the substitution pattern of indanocine onto a hemithioindigo core should result in a lead structure for tubulin-binding (Z)-HTIs, namely the class of HITubs. The para-hydroxy substitution of indanocine suggested that HTI might be a more desirable

Synthesis and characterization of bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives

• David Martínez-López,
• Amirhossein Babalhavaeji,
• Diego Sampedro and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2019, 15, 3000–3008, doi:10.3762/bjoc.15.296

• populated at 20 °C (see Supporting Information File 1). Calculating the effect of the substitution pattern on the pKa value is problematic [18] and was not attempted here. Figure 2 shows calculated structures and spectra of the neutral forms of simplified models of 4 and 5, with either a pyrollidino or

• (i.e., a 2-bromo-6-methoxy substitution pattern) was found to lower the pKa of the azonium ion such that it fell outside the normal physiological range. The neutral version of this compound nevertheless underwent trans-to-cis photoisomerization in the presence of blue-green light and exhibited slow

Two new aromatic polyketides from a sponge-derived Fusarium

• Mada Triandala Sibero,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Ocky K. Karna Radjasa,
• Agus Sabdono,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2941–2947, doi:10.3762/bjoc.15.289

• . HMBC correlations from an exchangeable proton at δH 12.57 (4-OH) to C3, C4, and C4a were also supportive of the substitution pattern in this benzene ring. Strong correlations from H6 to C8 and C10a implied the meta-relationship of C8 and C10a to C6, and similarly the ortho-relationship of C5 and C7 to

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• changes of the substitution pattern allow for a modification of the selectivity and activity of these compounds to these enzymes. Docking studies of h-ENPP1 inhibitors Molecular docking of the most potent compounds 5c and 6a (for ENPP1) and for 6e (exhibiting dual inhibition for both isozymes) were

Design, synthesis and investigation of water-soluble hemi-indigo photoswitches for bioapplications

• Daria V. Berdnikova

Beilstein J. Org. Chem. 2019, 15, 2822–2829, doi:10.3762/bjoc.15.275

• shifted relative to the one of the Z-isomer. Depending on the substitution pattern, the thermal lifetimes of metastable E-isomers at 25 °C vary from hours to days and sometimes even years [12][13][14]. Remarkably, for sterically hindered hemi-indigo derivatives, thermal lifetimes of the metastable states

• high importance for biological applications. Herein, the synthesis and adjustment of the substitution pattern of hemi-indigo derivatives for the efficient photoswitching in aqueous medium are described. Detailed characterization of the photoinduced isomerization of hemi-indigo derivatives in water is

• in the presence of the co-solvent. The comparison with the reported data on Z-1a [13] and related hemi-indigo derivatives containing a 4-amino group in the phenyl ring [13] allowed to conclude that this substitution pattern is unfavorable for photoswitching in aqueous medium. Thus, a higher content

Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• well as on the electronic substitution pattern of the alkynone. While electron-donating groups furnish α-pyrones as main products, electron-withdrawing groups predominantly give the corresponding 1H-pyridines. Both heterocycle classes fluoresce in solution and in the solid state. In particular

• in solution and in the solid state. While the absorption behavior is not affected by the substitution pattern the emission maxima are shifted bathochromically with increasing acceptor strength. The same trend manifests for the solid-state emission. For α-pyrones the photophysical properties are

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• substitution pattern of this biaryl moiety, a broad spectrum of efficacies for CXCR3 can be obtained, i.e., from antagonists to partial agonists and full agonists (Figure 1C) [24]. Meta and para-substitution yields antagonists (exemplified by 1a,b), while ortho-substitution with halogen atoms provides agonists

• atom of 1e. These calculations indicate that CXCR3 agonism is more likely to be associated with the cis-isomer than with the trans-isomer in our designed azobenzenes. Synthesis of azobenzene analogues and exploration of substitution pattern on the outer aromatic ring In addition to unsubstituted

• azobenzene analogue 2a, we explored the substitution pattern of the outer aromatic ring with chlorine atoms in the ortho, meta and para-position (compounds 2b–d, respectively) to also assess the possibility of agonism provided by a halogen bond. Compound 2e, which contains a bromine atom in the ortho

Mono- and bithiophene-substituted diarylethene photoswitches with emissive open or closed forms

• A. Lennart Schleper,
• Mariano L. Bossi,
• Vladimir N. Belov and
• Stefan W. Hell

Beilstein J. Org. Chem. 2019, 15, 2344–2354, doi:10.3762/bjoc.15.227

• compounds were nonemissive. The Stokes shift of the OFs of nonoxidized DAEs was always ca. 6000 cm−1, independent of the substitution pattern. For comparison, this value was much lower than the Stokes shift of the OF of compound 6 (10,700 cm−1) [4]. The Stokes shift of the CFs of oxidized DAEs varied

Click chemistry towards thermally reversible photochromic 4,5-bisthiazolyl-1,2,3-triazoles

• Chenxia Zhang,
• Kaori Morinaka,
• Mahmut Kose,
• Takashi Ubukata and
• Yasushi Yokoyama

Beilstein J. Org. Chem. 2019, 15, 2161–2169, doi:10.3762/bjoc.15.213

• the terminal phenyl groups on the photochromic properties, compounds with methoxy groups or cyano groups at the para-position of the phenyl groups were also synthesized. To avoid the generation of isomers with a substitution pattern by Huisgen cyclization, the same substituents were introduced to both