Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• reactions with mercaptoacetic acid and acetic anhydride leading to trifluoromethylated 1,3-thiazolidin-4-ones and 3-acetyl-2,3-dihydro-1,3,4-oxadiazoles, respectively. It was found that the C=N reactivity of the trifluoromethylated acylhydrazones is similar to that of other nitrogen-containing fluorinated

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

• Kian Donnelly Marcus Baumann School of Chemistry, University College Dublin, Science Centre South, Belfield, Dublin 4, Ireland 10.3762/bjoc.18.27 Abstract An efficient continuous flow process is reported for the synthesis of various 1,3,4-oxadiazoles via an iodine-mediated oxidative cyclisation

• significant development in continuous flow platforms, particularly in industry [16][17][18][19][20]. 1,3,4-Oxadiazoles are biologically relevant 5-membered heterocyclic compounds with various favourable pharmacokinetic properties and have been investigated as potential candidates for antiviral, antifungal and

• anticancer agents [21][22][23]. Previous reports of the synthesis of 1,3,4-oxadiazoles in continuous flow focused on the reaction between tetrazoles and carboxylic acids (Huisgen synthesis) [24][25]. Continuous flow technology has also been exploited for the further functionalisation of 1,3,4-oxadiazoles [26

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

• bond of these oxadiazoles quantitatively resulted in E/Z-vinyl triflates. The reactions of the cationic intermediates have been studied by DFT calculations and the reaction mechanisms are discussed. Keywords: acetylene-oxadiazoles; Friedel–Crafts reaction; hydroarylation; superelectrophilic activation

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 imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• ], benzimidazoles 6 [40][41], diazines 7 [42][43], or imidazolines 8 (Scheme 1) [44]. We have also shown that a nucleophilic attack on the phosphorylated nitronate species 2 can be carried out with the participation of N-acylhydrazides or thiosemicarbazides to afford the 1,3,4-oxadiazoles 9 [45] and the 1,3,4

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

• allowed a significant improvement of the reaction efficiency. The C–H coupling was compatible with a large panel of heteroaromatic substrates including benzoxazoles, oxazoles, thiazoles, and oxadiazoles, as well as non-aromatic oxazolines. Although the initial protocol necessitated the use of a

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

• exploited by providing very limited structural data [19]. Interestingly, increasing the reaction temperature to 100 °C yielded 1,2,4-oxadiazole-substituted propanes 4 as the major products which can only be interpreted via a decyanation pathway of cyanated oxadiazoles 3 (Figure 2). Up to date, various

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

• examples of drugs on the market containing such heteroaromatics (Figure 12). Yadav et al. reported the synthesis of 1,3,4-oxadiazoles from aldehyde semicarbazones, using CBr4, green LEDs and Eosin Y as the photocatalyst, at room temperature, in the presence of air (Scheme 18) [63]. This procedure offers a

• variation on the ligands of the aromatic ring covers a sensible range. The 4-pyridyl 18a example is particularly interesting, as is the hindered 2,6-disubstituted ring system 18b. Only the synthesis of 2-amino-1,3,4-oxadiazoles is reported, which although useful building blocks, are not extremely common in

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

• -oxadiazoles proceeded smoothly using TMSCF3 as a trifluoromethyl source and air as an oxidant to give the corresponding products in high yields. Various 1,3,4-oxadiazoles bearing electron-donating and electron-withdrawing groups at the para position on the aryl rings were well tolerated, although the latter

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

• , N4,C-diprotonated forms of oxadiazoles are the electrophilic intermediates in this reaction. Keywords: Friedel–Crafts reaction; hydroarylation; oxadiazoles; superelectrophilic activation; triflic acid; Introduction Oxadiazoles are an important class of heterocyclic compounds and great attention has

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• to structurally complex polycyclic ring systems [33]; an Ugi/aza-Wittig process allowed for the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles [34]; the Ugi/Pictet–Spengler sequence provided a rapid and efficient approach to polycyclic natural product-like alkaloids [35]. Accordingly, the

Isoxazole derivatives as new nitric oxide elicitors in plants

• Anca Oancea,
• Emilian Georgescu,
• Florentina Georgescu,
• Alina Nicolescu,
• Elena Iulia Oprita,
• Catalina Tudora,
• Lucian Vladulescu,
• Marius-Constantin Vladulescu,
• Florin Oancea and
• Calin Deleanu

Beilstein J. Org. Chem. 2017, 13, 659–664, doi:10.3762/bjoc.13.65

• known as reactive 1,3-dipoles involved in 1,3-dipolar cycloaddition reactions with various dipolarophiles generating five-membered heterocyclic compounds, such as isoxazoles, isoxazolines, oxadiazoles, oxadiazolines, dioxazolidines etc. [23][24][25]. Intermediate nitrile oxides are usually generated in

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

• ) molecules, namely 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles were prepared by palladium-catalyzed coupling from readily available compounds such as ethyl 3-decyl-2,2'-bithiophene-5-carboxylate and aryl halides. The obtained compounds feature increasing bathochromic shifts in

• the obtained diacylated hydrazines 14b–g were in the range of 58–74% (Scheme 3). Finally, heating the diacyl hydrazines 14b–g in phosphorus oxychloride led to the formation of the desired 1,3,4-oxadiazoles 15b–g. The product yields were between 65–94% after purification by column chromatography

• observed in D–A–D-type conjugated molecules [28]. DFT calculations To gain a deeper understanding of the electronic and photophysical properties of the synthesized 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles we have performed quantum-chemical calculations for four

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

• -oxadiazoles with different configurations have been reported [11][20][21][22] which exhibited the thermotropic liquid crystalline nematic (N), smectic and polar smectic (bent or banana) phase structures. Due to the presence of three heteroatoms in the ring structure of the oxadiazole, it possesses a high

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

• and Discussion Synthetic toolbox There are several approaches to the synthesis of 2,5-bis(2,2 '-bithiophen-5-yl)-1,3,4-oxadiazoles and 1,3,4-thiadiazoles. Transition metal-catalysed cross-coupling reactions, such as Stille, Suzuki etc. are typically used for the formation of thiophene–thiophene or

• 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

• ethyl 4-(hexyloxy)-2,2'-bithiophene-5-carboxylate (7). Hydrolysis and hydrazinolysis of esters 8–10. Synthesis of 2,5-bis(2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles 13 and 14 and 1,3,4-thiadiazole 15. Synthesis of 3,5-bis(3-decyl-2,2'-bithiophen-5-yl)-4-phenyl-4H-1,2,4-triazole (18). Absorption spectral

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• base and an oxidant. The reaction conditions had to be slightly customized for each class of substrates. The methodology was first developed for 2-substituted 1,3,4-oxadiazoles (Cu(OAc)2/1,10-phenanthroline/t-BuONa/NaOAc/air, Table 20), then extended to benzo[d]oxazoles, benzo[d]imidazoles, benzo[d

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

• -oxadiazoles are widely used in synthetic chemistry, e.g., in the search for antitumor agents. Cancer consists of more than one hundred different diseases, all of which are characterized by the uncontrolled growth and spread of abnormal cells. In this context, the identification of drugs acting as apoptosis

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

• analogue takes place inside an HPLC sample loop [43]. Diphenyl-1,2,4- and diphenyl-1,3,4-oxadiazoles The replacement of the stilbene ethylene linker with different heterocycles is a common strategy in medicinal chemistry used to improve the pharmacokinetics and/or pharmacodynamics of stilbenes (Scheme 5A

• ) [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

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

• →N migration of the glycosyl moiety in glycosylsulfanyloxadiazoles. (Benzylindolyl)glycosylsulfanyl-1,3,4-oxadiazoles could be thermally rearranged into the corresponding N-glycosides. These may either be converted into the corresponding (benzylindolyl)-2-N-(glycosyl)thiosemicarbazides (of type II

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

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

• method for the synthesis of 1,3,4-oxadiazoles [45][46]. In the NMP/AcOH/H2O solvent mixture, however, the formation of the oxadiazole 6 can scarcely compete with the intermolecular addition of water and oxadiazole 6 was therefore detectable only in minor amounts. Using NMP/AcOH as the solvent system, 2