Automated synthesis of amidoximes 6, 7 and 1,2,4 oxadiazole 8. General procedure for the synthesis of 2,5disubstituted1,3,4oxadiazoles 1528 compounds 114 100 mg, 0. A new method for the separation of triphenylphosphine oxide from reaction products and an improved method for the synthesis of oxadiazoles in the presence of dbu were incorporated into the process to achieve its scalability. Synthesis and characterization of energetic 3nitro1,2,4 oxadiazoles zhanda fu, arui su,b yang wang, yaofeng wang, wei zeng, anan xiao, yukai wu, azhiming zhou, jun chen,b and fuxue chen in memory of professor haishan dong to reconcile the inherent contradiction of high energy and low sensitivity in energetic materials, the. Classic methods 8 for the synthesis of 2,5disubstitued 1. Preparation of 5substituted 2methyl1,3,4oxadiazoles.
Synthesis of various 3substituted 1,2,4 oxadiazole containing chiral. Some of the recent studies have shown that 1,3,4 oxadiazoles and its derivatives were reported to possess antimicrobial, 1 antiinflammatory, 2 antibacterial, 3 anticancer. Jul 24, 2014 the newly synthesized 1,3,4oxadiazoles derivatives were computationally designed and optimized to investigate the interactions between the target compounds and the amino acid residues of the e. Synthesis of 1,2,4oxadiazoles organic chemistry portal. Pyrroles are one of the most important classes of heteroaromatic compounds which are components of a structural fragment of. Substituents at the 2 andor 5positions can modulate the heterocycles electronic and hydrogen bond. I2mediated oxidative co bond formation for the synthesis of. Journal of the iranian chemical society 2015, 12 5, 801806. Synthesis of nitro, nitroso, azo, and azido derivatives of.
For the synthesis of 1,3,4 oxadiazoles using the amino acid derived from nprotected selenoamino acid 6, both methodologies allowed the preparation of the compounds with similar efficiency table 2, entries 6, 12, 18 and 24. All of the compounds were characterized well by spectroscopy analysis 1hnmr, cnmr, ftir and lcms. The most straightforward synthesis relies on the cyclization of. Oxadiazole is considered to be resultant from furan by replacement of two methane ch groups by two pyridine type nitrogen atoms n. Review of synthesis of 1,3,4 oxadiazole derivatives. The first step involved preparation of 3,4,5,6tetrachlorophthalimide via reaction of. Several methods have been reported in the literature for the synthesis of,oxadiazoles. High resolution image download ms powerpoint slide. Pages in category oxadiazoles the following 53 pages are in this category, out of 53 total. A convergent synthesis of 1,3,4oxadiazoles from acyl.
This reaction is proposed to go through oxidative cleavage of csp 3h bonds. Oxadiazoles article about oxadiazoles by the free dictionary. Heterocyclic compounds are highly important class of organic compounds due to large number of applications such as pharmaceutical, biological, agrochemical, industrial, biotechnology, and material chemistry. A useful method for the synthesis of 2acylamino1,3,4 oxadiazoles was developed. Substituents at the 2 andor 5positions can modulate the heterocycles electronic and hydrogen bondaccepting capability, while exploiting its use as a carbonyl bioisostere. Cheminform is a weekly abstracting service, delivering concise information at a glance that was extracted from about 200 leading journals. H bonds in the presence of i 2 and k 2 co 3 with o 2. The synthesis of 2aryl1,3,4 oxadiazoles can be accomplished using nisocyanoiminotriphenylphosphorane 172 with benzoic acid derivatives in a clean reaction under mild conditions. Synthesis and characterization of energetic 3nitro1,2,4. A robust and scalable synthesis was developed for the preparation of oxadiazole based s1p1 inhibitors. In this perspective, a study on the synthesis and bioassay of heterocyclic compounds has been taken up. Pdf synthesis and characterization of some new 1,3,4. Synthesis, characterization and biological activities.
Target compounds were docked into active site of pdf pdb code 1g2a using mvd version 5. A convergent synthesis of 1,3,4 oxadiazoles from acyl hydrazides under semiaqueous conditions kazuyuki tokumaru and je. Synthesis of 1,2,4oxadiazole, 1,3,4oxadiazole, and 1,2. Pdf synthesis of 3,5disubstituted 1,2,4oxadiazoles as. Depending on the placement of the nitrogens in the ring, several isomers exist such as 1,2,4. Various methods were reported in the literature for the synthesis of 1,3,4 oxadiazole and its derivatives wang et al. The preparation of 1,3,4 oxadiazoles from 1,2diacylhydrazines using xtalfluore et2nsf2bf4 as cyclodehydration reagent is described. In view of the reported activities of 1,3,4 oxadiazoles, these. A 3d qsar study was performed on 1,2,4 oxadiazole derivatives using the sw knn mfa, comfa, and comsia techniques. Oxadiazoles are fivemembered heterocyclic compounds with two nitrogen and one oxygen atoms. Ptsazncl 2 is an efficient and mild catalyst for the synthesis of 3,5disubstituted1,2,4 oxadiazoles from amidoximes and organic nitriles. Onepot synthesis of 1,2,4 oxadiazoles from carboxylic acids using 4dimethylaminopyridinium acetate as efficient, regenerable, and green catalyst with ionic liquid character.
Synthesis of fivemembered heteroaromatic compounds such as pyrazoles, isoxazoles and 1,2,4 oxadiazoles are important for pharmaceutical industry and material science due to their applications. Design, synthesis and antimicrobial evaluation of 1,3,4. Synthesis of nheterocycles, synthesis of oheterocycles synthesis of 1,2,4 oxadiazoles. Algwady department of chemistry college of science mosul university received 1262008. Development of a scalable synthesis of oxadiazole based. The epub format uses ebook readers, which have several ease of reading. Facile synthesis of 1,3,4oxadiazoles via iodine promoted. So in present work, we have developed rapid and efficient method for synthesis of 1,3,4 oxadiazoles by microwave irradiation using silica gel as solid support. Synthesis of novel 1,3,4oxadiazole derivatives and their. An analysis of the revealed structurepropertyfunction correlations in the llm compound series oxadiazole based heterocyclic energetics, bnff, bnff1, llm172, llm191, and llm. A facile synthesis of nzbocprotected 1,3,4oxadiazole. Synthesis and characterization of new 22thienyl5aryl1,3,4 oxadiazoles article pdf available in farmacia 663. Improved synthesis of oxadiazoles under microwave irradiation. Oxadiazoles are fivemembered heterocyclic aromatic compounds consisting of one oxygen atom, two nitrogen atoms and two carbon atoms.
A visiblelightinduced synthesis of 2,5disubstituted 1,3,4 oxadiazoles from simple diketones and hydrazides with the assistant of the photocatalyst eosin y catalyzed decarboxylation and cyclization under mild conditions has been discovered. Therefore, it was considered worthwhile to synthesize some new 34bromobenzoylpropionic acid derivatives by incorporating the oxadiazolyl moiety, hoping to get better antiinflammatory molecules. The most widely applicable route to the synthesis of 1,3,4 oxadiazole and its 2,5disubstituted derivatives is the thermal, acid and base catalyzed cyclization of their corresponding carbonylhydrazides. Silveri triflate agotf and and ytterbiumiii triflate ybotf 3 are suitable catalysts.
Amidoximes 1 reacted with isopropenyl acetate in presence of ksf under microwave irradiation and gave 1,2,4 oxadiazoles 2. Oxadiazole is a heterocyclic aromatic compound having molecular. Synthesis of 1,3,4 oxadiazoles 1a6d under conventional heating and under microwave irradiation. Oxadiazoles containing terminal amino acid moiety gezginci et al, 2001 have synthesised 1,2,4 oxadiazoles 179 isosteres of pyridine and pyrazinecarboxylic acids and tested for their antimycobacterial activity and found potency from 2 to 8 times higher than that of reference compound pyrazinamide 23. Synthesized compounds are screened for microbial and cytotoxic activities. This greener approach gives the desired products using acetonewater as solvent in very short reaction times. Rezki department of chemistry, college of science, almustansirya university, baghdad, iraq. These newly synthesized compounds were characterized by ftir, 1 h nmr, mass spectra, and also by elemental analysis.
Accepted 27102008 abstract a variety of 2amino5substituted 1,3,4thiadiazoles atda were prepared by. The heterocycles were obtained in good yields and in relatively short reaction times. For example, raltegravir is an hiv drug which contains an 1,3,4 oxadiazole ring. The content was stirred overnight and the progress of reaction was monitored by thin layer chromatography. C, a wide range of 2acylamino1,3,4 oxadiazoles were afforded in moderate to excellent yields within two hours. Synthesis of oxadiazoles, thiadiazoles and triazoles derived. Interestingly, this protocol could generate 1,3,4 oxadiazoles via oxidative cleavage of csp 2. The cyclization reaction proceeds smoothly with the assistance of cs 2 co 3, affording a variety of 1,3,4. I2mediated oxidative co bond formation for the synthesis. Easy to perform, functional group tolerant, and short syntheses of the privileged scaffold oxadiazole are highly desired. Recently, ajay kumar and coworkers reported the synthesis of 1,3,4 oxadiazoles, in an attempt to synthesise alkenyl substituted oxadiazoles, they observed that. The 1,2,3isomer is unstable and ringopens to form the diazo ketone tautomer. Synthesis and characterization of 1,3,4 oxadiazoles derived from 9fluorenone rafidsaaddawood received 29, november, 2012 accepted 23, january, 20 abstract.
Synthesis of 1,3,4oxadiazoles organic chemistry portal. Oxadiazoles two nitrogen and one oxygen atoms containing five membered cyclic derivatives are known as oxadiazoles, sequence varies with different structures of oxadiazoles. The syntheses are based mostly on the use of primary amidoximes and acylating agents as the initial reactants. Oxadiazoles form a major class of compounds with a heterocyclic nucleus for drug development and were among the first effective. This method could provide a facile shortcut to generate a series of 2acylamino1,3,4 oxadiazoles in medicinal chemistry. This study describes the synthesis of a series of novel oxadiazoles and indolizinecontaining compounds. This method has a broad substrate scope and a good tolerance for diverse functional groups. Johnston the 1,3,4 oxadiazole is an aromatic heterocycle valued for its lowlipophilicity in drug development.
The first step of the procedure was applied to 3nitrobenzonitrile, affording also in quantitative yield the corresponding 3nitrobenzamidoxime. Here in, we simply report the synthesis of 1, 3, 4 oxadiazole. Ammonolysis of this nitroisoxazolone afforded 2amino2hydroxyiminonmethylacetamide in excellent yield. A methodology to design novel energetic materials by means of a holistic approach that links synthesis, experimental characterization, quantumchemical modeling, and statistical empirical evaluation is proposed.
Download microwaveinduced synthesis of aromatic heterocycles. Oxadiazoles heterocyclic building blocks sigmaaldrich. Pdf oxadiazole, a fivemembered heterocycle having two carbon atoms, two nitrogen atoms, one oxygen atom, and. Optimization and scope and limitations of this short and general sequence are described. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. Other pharmaceutical drugs containing the 1,3,4 oxadiazole ring include. A facile route towards the synthesis of 21hindol3ylacetamides using 1,1carbonyldiimidazole. Synthesis of 1,3,4oxadiazole derivatives from amino acid. Pdf synthesis and characterization of new 22thienyl. Peptide deformylase pdf is a vital and extremely conserved enzyme. To access a cheminform abstract, please click on html or pdf.
Monosubstituted oxadiazoles were synthesized by the reaction of hydrazides with triethyl orthoformate. To the best of our knowledge, 1,3,4 oxadiazole bearing dipepti. Synthesis and characterization of 1,3,4oxadiazoles derived. Preparation of 5amino1,2,4oxadiazoles download pdf. Various functionalized 1,3,4 oxadiazoles were synthesized and it was found that the use of acetic acid as an additive generally improved the yields. Unlimited viewing of the articlechapter pdf and any associated supplements and figures.
Synthesis of oxadiazoles, thiadiazoles and triazoles derived from benzobthiophene. Also 1,3,4 oxadiazoles are suitable substrates in a new process in which tmp 2 zn. The newly synthesized 1,3,4 oxadiazoles derivatives were computationally designed and optimized to investigate the interactions between the target compounds and the amino acid residues of the e. Synthesis of substituted 1,3,4oxadiazole derivatives. Several new derivatives of 1,3,4 oxadiazoles and 1,2,4triazoles linked to 3,4,5,6 tetrachlorophthalimide moiety were synthesized through following multisteps.
Molecules free fulltext synthesis, in silico, and in. In fact, the preparation of 2acylaminosubstituted 1,3,4oxadiazoles. Synthesis of oxadiazoles, thiadiazoles and triazoles. Preparation of 5substituted 2methyl1,3,4 oxadiazoles from 5substituted tetrazoles and acetic anhydride. Synthesis and biological activity of 1,2,4oxadiazole. A practical and transitionmetalfree oxidative cyclization of acylhydrazones into 1,3,4 oxadiazoles has been developed by employing stoichiometric molecular iodine in the presence of potassium carbonate. On the basis of 3d qsar outcomes, new molecules were designed by substituting different substituents. The hydrazide prepared from carboxylic acid via an ester can be. The first bankruptcy of microwaveinduced synthesis of fragrant heterocycles is predicated on microwave idea, the newest advancements in instrumentation knowhow, and a number of the microwave applied sciences used for synthesis. The reaction also exhibits a broad substrate scope and good. Synthesis of 1,3,4oxadiazoles from 1,2diacylhydrazines. Synthesis of 2amino5substituted1,3,4thiadiazoles atda and their derivatives using conventional and microwave techniques moayed s. Synthesis and in vitro antimicrobial evaluation of new 1,3,4. In this paper, we have reported the synthesis of oxadiazole derivatives by the conventional.
They are synthesized by ring condensation and rearrangement reactions. Synthesis of macrocycles containing 1,3,4oxadiazole and. View the article pdf and any associated supplements and figures for a period of 48 hours. Comprehensive endtoend design of novel high energy. These designed compounds were synthesized and confirmed their synthesis by spectroscopic techniques.
Nonspecific antispasmodic active oxadiazole derivatives later in 1969 breuer prepared a nitro furan containing oxadiazoles and studied the antimicrobial activity 17. The 1,3,4 oxadiazole is an aromatic heterocycle valued for its lowlipophilicity in drug development. A useful synthesis of 2acylamino1,3,4oxadiazoles from. A mild and efficient method for the synthesis of unsymmetrical 2,5.
Due to the lack of approved vaccines against human leishmaniasis and the limitations of the current chemotherapy inducing side effects and drug resistance, development of new, effective chemotherapeutic agents is essential. Pdf various approaches for synthesis of oxadiazole derivatives. Synthesis of 1,2,4oxadiazoles by tandem reaction of nitroalkenes. Here, a metalfree protocol for mcrbased synthesis of 2,5disubstituted 1,3,4 oxadiazoles via a ugitetrazolehuisgen sequence was developed.
A range of 1,2,4oxadiazoles, having a carbamoyl group at the 3position, were synthesized from 2methyl4nitroisoxazolin52hone via three steps. Synthesis of nitro, nitroso, azo, and azido derivatives of 4. Synthesis, in silico, and in vitro evaluation of anti. The five membered ring heterocyclic compounds have been studied by many researchers because of chemical and variable biological effects1. Pdf the synthesis of novel achiral and chiral amides incorporating 1,3,4 oxadiazole ring are reported. Synthesis of nheterocycles, synthesis of oheterocycles synthesis of 1,3,4 oxadiazoles. Synthesis and characterization of 1,3,4oxadiazoles.
Examples of drugs containing 1,2,4oxadiazole structure. Synthesis of macrocycles containing 1,3,4 oxadiazole and pyridine moieties. Synthesis, characterization, oxadiazoles, thiadiazoles, derivatives introduction. The pathway to another large group of 1,2,4 oxadiazoles proceeding from a broad spectrum of reactants is via their reactions of 1,3dipolar cycloaddition, in particular, with primary amidoximes. A straightforward and highyielding synthesis of 1,2,4. Nitro furan containing oxadiazole johan et al, 1972 have reported the synthesis of bis 1,2,4 oxadiazole derivatives and their antimalarial activity 18. Interestingly, this protocol could generate 1,3,4oxadiazoles via oxidative cleavage of csp 2. The 1,3,4oxadiazole is an aromatic heterocycle valued for its lowlipophilicity in drug development. Westwell, design, synthesis and proapoptotic antitumor properties of indolebased 3,5 disubstituted oxadiazoles. Their reactions with benzoyl chloride gave benzoylcarbohydrazides, which under the action of thionyl chloride were cyclized to the respective 2,5disubstituted oxadiazoles. The compounds were screened in silico using an eiipaqvn filter.
Synthesis and characterization of some oxadiazoles and. The conditions of this cyclization reaction also work well with crude acylhydrazone substrates obtained from the condensation of aldehydes and hydrazides. The journal of organic chemistry 2003, 68 19, 73167321. In the present work, 9fluorenone2carboxylic acid methyl ester 1 was prepared from 9fluorenone2carboxylic acid and then converted into the acid hydrazide 2. Design and synthesis of a series of 2,4dinitro phenyl ring containing 1,3,4 oxadiazole and 1,2,4triazolo3,4b1,3,4thiadiazole derivatives. Download product flyer is to download pdf in new tab. In a direct annulation of hydrazides with methyl ketones for the synthesis of 1,3,4 oxadiazoles, the use of k 2 co 3 as a base achieves an unexpected and highly efficient cc bond cleavage.745 1153 1234 1352 979 80 593 116 1485 1337 664 332 840 66 375 512 1330 167 1248 521 318 1404 1213 665 815 461 848 1273 1066 1321 1384 1155