Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• , Leninskii prosp., 31, 119991, Moscow, Russia Institute of Inorganic Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany 10.3762/bjoc.20.202 Abstract A series of new RS−, RS−CH2− and R2N−CH2-functionalized сatechols with heterocyclic fragments such as 1,3,4-oxadiazole, 1,2,4

• corresponding thiols. The starting reagents such as substituted 1,3,4-oxadiazole-2-thiols and 4H-triazole-3-thiols are characterized by thiol–thione tautomerism, therefore their reactions with 3,5-di-tert-butyl-6-methoxymethylcatechol can proceed at the sulfur or nitrogen atom. In the case of mercapto

• -derivatives of thiazole or pyridine, this process leads to the formation of the corresponding thioethers with a methylene linker. At the same time, thiolated 1,3,4-oxadiazole or 1,2,4-triazole undergo alkylation at the nitrogen atom in the reaction with 3,5-di-tert-butyl-6-methoxymethylcatechol to form the

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• diketone 1b, bearing the less electron-withdrawing 1,3,4-oxadiazole moiety (σm/σp 0.335/0.443), with alkylamines proceeded well (73–74% yields), but required the addition of CHCl3 as co-solvent due to the low solubility of the starting 1,3-diketone 1b. On the other hand, the reaction of 1,3-diketone 1b

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• -derived NH-acylhydrazones to build 1,3,4-oxadiazole derivatives in good yields. The electrolysis was conducted under galvanostatic conditions in methanol using a carbon graphite anode and a platinum cathode. From a mechanistic point of view, in situ condensation of acylhydrazines 28 with α-keto acids 27

• 30. Importantly, a control experiment using benzaldehyde-derived N-benzoylhydrazone delivered the corresponding 1,3,4-oxadiazole in only 25% yield. This result indicates that benzaldehyde-derived hydrazone is a less probable reaction intermediate, thereby supporting the proposed mechanism (Scheme 7

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• and co-workers [41] also tested 1,3,4-oxadiazole 108 and 1,2,4-oxadiazole 109 histamine congeners towards carbonic anhydrase isoforms, finding moderate potencies among them, with 109 3 times more potent than histamine in CA type VII (Scheme 16). Oxolamine (110, Scheme 16) is a cough suppressant

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• the development of multidrug resistant bacteria due to excessive use of antibiotics [2][4]. Heterocyclic compounds are the key components for drug design and synthesis. Among them, 1,3,4-oxadiazole derivatives are attractive and have been investigated for decades. This is due to their promising

• MCF7) [13]. In 2008, Muhi-eldeen et al, synthesized a hybrid compound with 1,3,4-oxadiazole moiety and pyrrolidine connected with propargylic moiety showed antibacterial activity against Staphylococcus aureus and E. coli [14]. On the other hand, the coupling of piperazine with heterocyclic compounds

• , and the product showed antiviral activity (Figure 1) [23]. In continuation of our ongoing research on designing compounds with potential biological activities, we herein report the design, synthesis, and antimicrobial assessment of novel cholyl 1,3,4-oxadiazole moieties (Figure 1). For developing new

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• prove useful for accessing small quantities of medicinally interesting BCP-1,3,4-oxadiazole compounds for biological testing. Additionally, the reaction of 1,3-substituted isoxazole 1m under these conditions was investigated. Despite high degrees of decomposition, it was possible to isolate the desired

• ]. Various other methods to access this heterocyclic moiety have been reported in the literature, with many focusing on either cyclodehydration or cyclodesulphurisation (Scheme 1) [27]. However, in recent years, there have been a number of oxidative cyclisation protocols reported to access the same 1,3,4

• -oxadiazole unit [28][29][30][31][32][33]. In 2012, Guin and co-workers described the iodine-mediated cyclodesulphurisation of thiosemicarbazides, yielding the corresponding 1,3,4-oxadiazoles [32]. Subsequently, Yu and co-workers reported the iodine-mediated oxidative cyclisation of acyl hydrazones to form

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• ], 6,7-dihydro-6-oxo-5H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazine [17], 1,2,4-triazino[5,6-b]indole [18], 1,3,4-thiadiazoline [19], 1,3,4-oxadiazoline [19], 1,2,4-triazoline [19], 3-mercapto-1H-1,2,4-triazole [20], 1,3,4-oxadiazole-2(3H)-thione [20], 4-amino-5-mercapto-4H-1,2,4-triazole [20], and 1,2,4

Synthesis, liquid crystalline behaviour and structure–property relationships of 1,3-bis(5-substituted-1,3,4-oxadiazol-2-yl)benzenes

• Afef Mabrouki,
• Malek Fouzai,
• Armand Soldera,
• Abdelkader Kriaa and
• Ahmed Hedhli

Beilstein J. Org. Chem. 2020, 16, 149–158, doi:10.3762/bjoc.16.17

• , while their hydrocarbon counterparts are non-mesomorphic [20]. On the other hand, many heterocyclic-based liquid crystals have been designed and then synthesised due to their large scope of applications [21]. In this context, the 1,3,4-oxadiazole group was of a particular interest from a synthetic

• viewpoint, considering the numerous ways to introduce this group into a molecule [22][23]. So, it was established that the introduction of a 1,3,4-oxadiazole ring as terminal group on a biphenyl provides liquid crystalline materials [24][25]. However, when the oxadiazole unit is incorporated in the aromatic

• interaction between them. Rigid-core With three electronegative heteroatoms and only two carbons, the 1,3,4-oxadiazole core has a great electron deficient character. Nevertheless, when incorporated in the rigid-core, the two oxadiazole rings exhibit a slight difference in their electron deficiency. We

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

Recent advances in phosphorescent platinum complexes for organic light-emitting diodes

• Cristina Cebrián and
• Matteo Mauro

Beilstein J. Org. Chem. 2018, 14, 1459–1481, doi:10.3762/bjoc.14.124

• value dropping to 2% at a practical brightness of 500 cd m−2. Nevertheless, this work opens the door for a novel design of highly efficient deep-blue phosphors. More complex structures based on dinuclear platinum(II) complexes have also been recently described [20]. Upon using two 1,3,4-oxadiazole-2

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• ; cyclopropanations Dimethoxycarbene (6), generated in situ by thermal decomposition of 2,2-dimethoxy-2,5-dihydro-1,3,4-oxadiazole 7, reacts with E-1b yielding a mixture of the trans-configured tetramethoxycyclobutane 8 and 2,3-dihydrofuran 9 [21][22] (Scheme 3). The latter reacts further with dimethoxycarbene and

• , and in both cases pyrazol-3-ones 68 were obtained in ca. 35% yield (Scheme 22). The heterocyclization leading to 68 occurs in the intermediate enehydrazide 69 through the nucleophilic attack of the N-atom onto the ester group. The second product was postulated either as a 2,3-dihydro-1,3,4-oxadiazole

Synthesis and optical properties of new 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles

• Anastasia S. Kostyuchenko,
• Tatyana Yu. Zheleznova,
• Anton J. Stasyuk,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2017, 13, 313–322, doi:10.3762/bjoc.13.34

• by quantum chemical DFT/TDDFT calculations carried out for these new molecules. Keywords: bithiophene; donor–acceptor; luminescence; 1,3,4-oxadiazole; palladium-catalyzed coupling; Introduction π-Conjugated donor–acceptor (D-A) compounds are of significant scientific interest because they

• enables the preparation of linear D–A–D compounds with one or two 1,3,4-oxadiazole [16][17][18][19], 1,3,4-thiadiazole [16][18][19][20][21][22] or 1,2,4-triazole [16][18] central rings symmetrically disubstituted with alkylbithiophene 1, 2 as well as star-shaped molecules with D–A arms 3 (Figure 1) [23

• after which time all 7a had been consumed as judged by TLC. The other products 7e–g could be isolated in 42–60% yield after purification by column chromatography (Table 1). With the building blocks 7b–g at hand, we next turned towards the synthesis of 1,3,4-oxadiazole derivatives 15b–g with anticipated

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• and 2-phenyl-1,3,4-oxadiazole were smoothly iodinated to provide iodoheteroarenes 18 (Scheme 10) [45]. As typical electron-enriched arenes, phenols and analogous arenes tend to undergo a single-electron transfer process [46], the property of these arenes also resulted in sound attention to their C–H

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

• functionality between the 1,3,4-oxadiazole core and glucose [26] (I) or aromatic [27] (J) groups was recently investigated (Figure 1). The present study reports on the introduction of such amino groups between the oxadiazole and aromatic cores. Two synthetic strategies were used to obtain such scaffolds based

• ]. These poor inhibitory properties could be due to limited interactions of alkyl groups in the β-channel of GP in comparison to aromatic moieties. This lack of GP inhibition for a 5-aminooxadiazole can be correlated with the lack of inhibition of compound J in the 1,3,4-oxadiazole series (Figure 1). While

• the introduction of an NH moiety between the anomeric carbon atom and the heteroaryl group was actually beneficial (compare H to I in Figure 1), the same NH moiety at the 5-position of the 1,3,4-oxadiazole ring was highly detrimental (compare I to J in Figure 1). Conclusion In conclusion, we have

Synthesis of new, highly luminescent bis(2,2’-bithiophen-5-yl) substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole

• Anastasia S. Kostyuchenko,
• Vyacheslav L.Yurpalov,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2014, 10, 1596–1602, doi:10.3762/bjoc.10.165

• functionalised oligothiophenes, coupled to other heteroaromatic cores. Keywords: bithiophene; donor–acceptor; luminescence; 1,3,4-oxadiazole; 1,3,4-thiadiazole; 4H-1,2,4-triazole; Introduction In the past two decades oligo- and polythiophenes gained a significant research interest due to their wide application

• quinquethiophene by 1,3,4-oxadiazole leads to a substantial increase of the fluorescence quantum yield and a hypsochromic shift of the emission band [14], both features being technologically advantageous. They are, however, difficult to solution process due to strong intermolecular interactions, associated with

• that 1,3,4-oxadiazoles [26], 1,3,4-thiadiazole [27] and 1,2,4-triazoles [28][29][30] can be obtained from diacylhydrazines. Thus, 11 and 12 were converted to 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazole (13) and 2,5-bis[4-(hexyloxy)-2,2'-bithiophen-5-yl]-1,3,4-oxadiazole (14) by the reaction

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

• (9) and diphenyl-1,3,4-oxadiazole (10); and thioflavin-T analogues such as benzothiazole (11), benzoxazole (12), benzofuran (13), imidazopyridine (14), and benzimidazole (15); as well as quinoline (16) and naphthalene (17) derivatives (Figure 1B). In this review, we provide an overview of these AD

• kinetics [47]. Representative syntheses of radioiodinated oxadiazoles 50a and 51c are shown (Scheme 5B and C). The 1,3,4-oxadiazole core of [125I]50a was obtained from the reaction between 4-iodobenzhydrazide (52) and 4-dimethylaminobenzaldehyde (23) in the presence of ceric ammonium nitrate (CAN) followed

A new synthetic access to 2-N-(glycosyl)thiosemicarbazides from 3-N-(glycosyl)oxadiazolinethiones and the regioselectivity of the glycosylation of their oxadiazolinethione precursors

• El Sayed H. El Ashry,
• El Sayed H. El Tamany,
• Mohy El Din Abdel Fattah,
• Mohamed R. E. Aly,
• Ahmed T. A. Boraei and
• Axel Duerkop

Beilstein J. Org. Chem. 2013, 9, 135–146, doi:10.3762/bjoc.9.16

• respective thiosemicarbazides. Surprisingly, the formation of the galactosyl-1,2,4-triazoline-3-thione from the galactosyl-1,3,4-oxadiazole-2(3H)-thione was discovered for the first time. This is a new method for the conversion of an 1,3,4-oxadiazole-2(3H)-thione ring into a 1,2,4-triazoline-3-thione

• representative glucopyranosylsulfanyl-1,3,4-oxadiazole and glucopyranosylthiosemicarbazide, each. Results and Discussion The regiospecificity of glycosylations of 1,3,4-oxadiazolinethiones was tested by reacting 5-(1H-indol-2-yl)-1,3,4-oxadiazoline-2(3H)-thione (1) with a set of α-D-glycosyl halides 2–4 under

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• of the base, the role of MgCl2 is to increase its reactivity and the role of zinc is essential since it confers to this base an exceptional chemoselectivity (Scheme 8). Thus, the 1,3,4-oxadiazole 43 is readily converted to the zinc reagent 44 by the reaction with TMP2Zn·2MgCl2·2LiCl (42, 0.55 equiv

Unusual behavior in the reactivity of 5-substituted-1H-tetrazoles in a resistively heated microreactor

• Bernhard Gutmann,
• Toma N. Glasnov,
• Tahseen Razzaq,
• Walter Goessler,
• Dominique M. Roberge and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2011, 7, 503–517, doi:10.3762/bjoc.7.59

• -benzhydryl-5-methyl-1,3,4-oxadiazole (6) became one of the major products in the flow reactor under these reaction conditions. The resulting hydrazide 7 can be expected to have a weak N–N bond, however, the products obtained from the decomposition of diacylhydrazides are generally considered to arise via