Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• Acetylene derivatives of 1,2,4-oxadiazoles, i.e., 5-(2-arylethynyl)-3-aryl-1,2,4-oxadiazoles, have been obtained, for the first time reported, from 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles by their bromination at the carbon–carbon double bond followed by di-dehydrobromination with NaNH2 in liquid NH3. The

• reaction of the acetylenyl-1,2,4-oxadiazoles with arenes in neat triflic acid TfOH (CF3SO3H) at room temperature for 1 h resulted in the formation of E/Z-5-(2,2-diarylethenyl)-3-aryl-1,2,4-oxadiazoles as products of regioselective hydroarylation of the acetylene bond. The addition of TfOH to the acetylene

• ; triflic acid; Introduction 1,2,4-Oxadiazoles have a great importance in chemistry, biology and medicine. Many drugs contain an 1,2,4-oxadiazole ring, such as butalamine [1], libexin [2], ataluren [3], oxolamine [4], and pleconaril [5]. Various oxadiazole derivatives show different kinds of activity

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

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• either 1,2,4-oxadiazoles 72 or quinazolinones 73 (Scheme 26), depending on the reaction conditions. The 1,2,4-oxadiazole ring was selectively obtained in DMF at 60 °С under oxygen atmosphere (1 atm) in the presence of an excess of K3PO4, whereas in DMSO at 100 °С under air and in the presence of Cs2CO3

• quinazolinones 73 were selectively synthesized. The authors proposed that 1,2,4-oxadiazoles were formed by a mechanism [117], analogous to the mechanism of the TEMPO-mediated oxidative oxime cyclization (Scheme 23 [114]). Apparently, both 1,2,4-oxadiazoles 72 and quinazolinones 73 are produced via the common

•  29). Later, DDQ-mediated oxidative cyclization of amidoximes with the formation of 1,2,4-oxadiazoles (analogous transformation with K3PO4/O2 system was shown above in Scheme 26) was realized without the addition of TsOH [120]. Isoxazolines 82 were synthesized by a one-pot sequence, which included the

Reactions of 3-(p-substituted-phenyl)-5-chloromethyl-1,2,4-oxadiazoles with KCN leading to acetonitriles and alkanes via a non-reductive decyanation pathway

• Akın Sağırlı and
• Yaşar Dürüst

Beilstein J. Org. Chem. 2018, 14, 3011–3017, doi:10.3762/bjoc.14.280

• Akin Sagirli Yasar Durust Department of Chemistry, Faculty of Arts & Sciences, Bolu Abant Izzet Baysal University, Bolu, TR14030, Turkey 10.3762/bjoc.14.280 Abstract The present work describes an unfamiliar reaction of 5-(chloromethyl)-3-substituted-phenyl-1,2,4-oxadiazoles with KCN affording

• structures, cyanation attempts of 5-(chloromethyl)-3-phenyl-1,2,4-oxadiazoles 1 with excess KCN at room temperature in CH3CN have been investigated leading to trisubstituted acetonitrile 3 instead of anticipated product 2. This result is in accord with a previous report where only one example (3a) has been

• the above considerations, we report here an unfamiliar example of non-reductive decyanation through the reaction of 5-(chloromethyl)-3-(substituted-phenyl)-1,2,4-oxadiazoles 1 with 2 equiv of KCN at 100 °C in a single step transformation. Results and Discussion In the first part of this work, 5

Metal-free hydroarylation of the side chain carbon–carbon double bond of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles in triflic acid

• Anna S. Zalivatskaya,
• Dmitry S. Ryabukhin,
• Marina V. Tarasenko,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya,
• Elena V. Grinenko,
• Ludmila V. Osetrova,
• Eugeniy R. Kofanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2017, 13, 883–894, doi:10.3762/bjoc.13.89

• University, Universitetskaya nab., 7/9, Saint Petersburg, 199034, Russia Institute of Synthetic Rubber, Gapsalskaya str., 1, Saint Petersburg, 198035, Russia 10.3762/bjoc.13.89 Abstract The metal-free reaction of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles with arenes in neat triflic acid (TfOH, CF3SO3H

• ), both under thermal and microwave conditions, leads to 5-(2,2-diarylethyl)-3-aryl-1,2,4-oxadiazoles. The products are formed through the regioselective hydroarylation of the side chain carbon–carbon double bond of the starting oxadiazoles in yields up to 97%. According to NMR data and DFT calculations

• and local anesthetic [15], and ataluren finds application for the treatment of fibrosis [16]. Often, oxadiazole derivatives act as inhibitors of bacterial phenylalanyl-tRNA-synthetase [17], phosphodiesterase 4B2 [18], y-secretase [19] and phenol-substituted 1,2,4-oxadiazoles exhibit powerful anti

Continuous-flow synthesis of highly functionalized imidazo-oxadiazoles facilitated by microfluidic extraction

• Ananda Herath and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2017, 13, 239–246, doi:10.3762/bjoc.13.26

• -oxadiazoles starting from carboxylic acids is reported. This process was applied to the multistep synthesis of imidazo[1,2-a]pyridin-2-yl-1,2,4-oxadiazoles, using a three reactor, multistep continuous-flow system without isolation of intermediates. This continuous-flow method was successfully combined with a

• follow-up confirmatory studies. We previously reported a method for the preparation of 1,2,4-oxadiazoles in an uninterrupted continuous-flow sequence using arylnitriles and acyl chloride precursors [9]. We also reported the flow synthesis of highly functionalized imidazo[1,2-a]heteroaryl derivatives from

• readily available starting materials in a single continuous process [7]. We now report an efficient continuous-flow procedure for the synthesis of 1,2,4-oxadiazoles directly from arylnitriles and carboxylic acid derivatives. We further demonstrate the incorporation of this procedure into a continuous

3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors

• Marion Donnier-Maréchal,
• David Goyard,
• Vincent Folliard,
• Tibor Docsa,
• Pal Gergely,
• Jean-Pierre Praly and
• Sébastien Vidal

Beilstein J. Org. Chem. 2015, 11, 499–503, doi:10.3762/bjoc.11.56

• catalytic site has been accomplished through various families of glucose-based derivatives such as oxadiazoles. Further elaboration of the oxadiazole aromatic aglycon moiety is now reported with 3-glucosyl-5-amino-1,2,4-oxadiazoles synthesized by condensation of a C-glucosyl amidoxime with N,N

• structure–activity relationship study with several isomeric oxadiazoles. The regioisomeric substitution around the 1,2,4-oxadiazoles (F [22][23] vs G [23][24]) plays a role in the inhibition observed with the glucosyl group at the 5-position of the 1,2,4-oxadiazole ring being preferred. Isomeric 1,3,4

• . The structure–activity relationship of 5-aryl-1,2,4-oxadiazoles F and G towards GP inhibition highlighted a set of interactions of the aryl moieties with the enzyme’s β-channel [22][23][24]. The amino acids present in this empty pocket are of mixed character and can accommodate hydrophobic groups such

Novel biphenyl-substituted 1,2,4-oxadiazole ferroelectric liquid crystals: synthesis and characterization

• Mahabaleshwara Subrao,
• Dakshina Murthy Potukuchi,
• Girish Sharada Ramachandra,
• Poornima Bhagavath,
• Sangeetha G. Bhat and
• Srinivasulu Maddasani

Beilstein J. Org. Chem. 2015, 11, 233–241, doi:10.3762/bjoc.11.26

• ) polarization switching. The mesomorphic thermal stabilities of these compounds are discussed in the domain of the symmetry and the flexibility of the alkyloxy end chain length attached to the chiral center. Keywords: 3,5-disubstituted-1,2,4-oxadiazoles; ferroelectric switching; mesomorphism; optical textures

• to their electroluminescent, non-linear optical, electron transport and liquid crystalline (LC) properties. Torgova et. al., have reported [16][17][18][19] 3,5-disubstituted-1,2,4-oxadiazoles with LC phase behavior for the first time in the literature. Subsequently, the derivatives of 1,2,4

• and characterize unsymmetrically substituted 1,2,4-oxadiazoles with a chiral substituted biphenyl moiety at C-5 position of the ring and two different moieties at C-3 position of the oxadiazole core, which are exhibiting the FELC phase structures. Results and Discussion Synthesis and characterization

A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime

• Raoni S. B. Gonçalves,
• Michael Dos Santos,
• Guillaume Bernadat,
• Danièle Bonnet-Delpon and
• Benoit Crousse

Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275

• revealed the presence of a side product and despite the total consumption of the aldoxime, a small amount of allylbenzene remained. It is known that nitrile oxides can dimerize or isomerize to yield different products, such as furoxans, isocyanates, 1,2,4-oxadiazoles and 1,4,2,5-dioxadiazines (Figure 2

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• starting from tert-butylamidoxime and 4-aminobenzoic acid or 4-nitrobenzonitrile. The structures of compounds 1, 2, 4, 5 and 6 were confirmed by X-ray crystallography. Keywords: antitumor activity; bioisosteres; maleimide; natural product analogs; 1,2,4-oxadiazoles; Introduction The five-membered

• heterocyclic 1,2,4-oxadiazole motif is of synthetic and pharmacological interest. It also forms an important constituent of biologically active compounds including natural products [1]. Sawyer et al. have described such compounds as bioisosteres for amides and esters [2], with the 1,2,4-oxadiazoles showing

• and recognizes the arginine–glycine–aspartic acid (RGD) sequence. Antagonists of this receptor are able to inhibit angiogenesis. 1,2,4-Oxadiazolebutanoic acids such as C were tested as non-peptidic analogs of αvβ3 antagonists [10]. Furthermore, substituted 1,2,4-oxadiazoles have been described as

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• ) [44][45][46]. In the case of Aβ probes, a series of 2,5-diphenyl-1,3,4-oxadiazoles 50a–f and 3,5-diphenyl-1,2,4-oxadiazoles 51a–e have been studied in this respect (Table 3 and Table 4). Among the 2,5-diphenyl-1,3,4-oxadiazoles, the dimethylamine analogue 50a (Ki = 20.1 ± 2.5 nM) and methoxy analogue

• -1,2,4-oxadiazole analogue 51c was more lipophilic than its 1,3,4 counterpart 50a (log P = 3.22 for 51c and 2.43 for 50a) [47]. In general, even though 3,5-diphenyl-1,2,4-oxadiazoles 51a–e show excellent affinity for Aβ aggregates in in vitro binding experiments (Ki = 4.3–47.1 nM), they show poorer brain

Liquid-crystalline heterodimesogens and ABA-heterotrimesogens comprising a bent 3,5-diphenyl-1,2,4-oxadiazole central unit

• Govindaswamy Shanker,
• Marko Prehm and
• Carsten Tschierske

Beilstein J. Org. Chem. 2012, 8, 472–485, doi:10.3762/bjoc.8.54

• crystals; 1,2,4-oxadiazoles; trimesogen; Introduction Liquid-crystalline (LC) dimers of low-molar-mass compounds formed by the coupling of two mesogenic segments are of contemporary interest [1][2][3][4]. These compounds exhibit fascinating properties, often different from the single mesogens, and they

• dimesogens only form tilted LC phases (SmC, NcybC), for Thia-Ox/5 with a relatively short spacer the tilt is significantly reduced (25°) compared to the related 2,5-diphenyl-1,2,4-oxadiazoles without an attached rod-like unit (40–50°) [64][65]. In the dimesogen Thia-Ox/10, in which the two mesogenic units

2-Arylhydrazononitriles as building blocks in heterocyclic synthesis: A novel route to 2-substituted- 1,2,3-triazoles and 1,2,3-triazolo[4,5-b]pyridines

• Saleh M. Al-Mousawi and
• Moustafa Sh. Moustafa

Beilstein J. Org. Chem. 2007, 3, No. 12, doi:10.1186/1860-5397-3-12

• that can be assigned as 1,2,4-oxadiazolylphenylhydrazone structure 4 or the isomeric acetylamino-1,2,3-triazole structure 6. Phenylhydrazono-1,2,4-oxadiazoles have been reported to rearrange thermally into acylamino-1,2,3-triazoles. [12] Compound 5 could be obtained via refluxing 3 in DMF in the