In the present work, 9fluorenone2carboxylic acid methyl ester 1 was prepared from 9fluorenone2carboxylic acid and then converted into the acid hydrazide 2. Journal of chemical and pharmaceutical research, 2012, 45. Recent advances in the synthesis of 1,2,4 and 1,3,4oxadiazoles. Recently, ajay kumar and coworkers reported the synthesis of 1,3,4oxadiazoles, in an attempt to synthesise alkenyl substituted oxadiazoles, they observed that.
In order to synthesize novel 1,3,4oxadiazole analogs containing. Various functionalized 1,3,4oxadiazoles were synthesized and it was found that the use of acetic acid. For example, raltegravir is an hiv drug which contains an 1,3,4oxadiazole ring. 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. This paper reports the synthesis and biological screening of some new 2,5. Onepot synthesis of 1, 2, 4oxadiazoles using carboxylic acid esters with amidoxime implementing potassium carbonate and eventually reflux for 612 hrs4. Pdf synthesis of oxadiazoles, thiadiazoles and triazoles. Chinese journal of chemistry 2017, 35 10, 16111618. Synthesized compounds are screened for microbial and cytotoxic activities. Synthesis of thiocarbohydrazides syntheses of carbohydrazide and thiocarbohydrazide of preparative value are exclusively variations of one basic reaction, viz. Apr 11, 2007 microwaveassisted as well as conventional synthesis of 5substituted22methyl4nitro1imidazomethyl1,3,4 oxadiazoles containing the nitroimidazole moiety is carried out and their antibacterial, antifungal and antiinflammatory activity is reported. A multistep protocol for the synthesis of 3,5disubstituted 1,2,4 oxadiazoles on dnachemical conjugates has been developed. A versatile continuousflow synthesis of highly functionalized 1,2,4 oxadiazoles starting from carboxylic acids is reported. Synthesis of oxadiazoles, thiadiazoles and triazoles derived from benzobthiophene.
Synthesis and optical properties of new 5arylsubstituted 2,5bis3decyl2,2bithiophen5yl1,3,4oxadiazoles anastasia s. The oxadiazoles have a wide range of applications such as antitussive, antiinflammatory, anaesthetic, vasodilator, anthelmintic, antiallergic, antiplatelet effects in vitro, antithrombotic properties in vivo, etc. A facile route towards the synthesis of 21hindol3ylacetamides using 1,1carbonyldiimidazole. Recent advances in the synthesis of 1,2,4 and 1,3,4. Solventfree microwaveassisted synthesis of oxadiazoles. Acylthiosemicarbazides prepared from the corresponding acylhydrazides undergo efficient cyclodesulfurization by phints in good yields. 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. Ptsazncl 2 is an efficient and mild catalyst for the synthesis of 3,5disubstituted1,2,4 oxadiazoles from amidoximes and organic nitriles. Firstly, the resinbound acylhydrazine is reacted with orthoesters to provide resinbound 1,3,4 oxadiazoles. Target compounds were docked into active site of pdf pdb code 1g2a using mvd version 5. Recent advances in the synthesis of 1,2,4 and 1,3,4oxadiazoles volume. The resultant reaction mixture was cooled and filtered. Faculty of pharmacy, university of ljubljana, askerceva 7, ljubljana, slovenia. This reaction is proposed to go through oxidative cleavage of csp.
T afforded 23chloro1benzobthiophen2yl5substituted phenyl1,3,4 oxadiazoles 5ah. The syntheses are based mostly on the use of primary amidoximes and acylating agents as the initial reactants. Pdf the synthesis of novel achiral and chiral amides incorporating 1,3,4 oxadiazole ring are reported. Other pharmaceutical drugs containing the 1,3,4oxadiazole ring include. Based on these previous findings, we report here the synthesis of a new series of 5substituted23,4,5trihydroxyphenyl1,3,4 oxadiazoles compounds 3nz with the objective to study the effect of changing the substitution at position 5 of the. Depending on the placement of the nitrogens in the ring, several isomers exist such as 1,2,4. Oxadiazoles two nitrogen and one oxygen atoms containing five membered cyclic derivatives are known as oxadiazoles, sequence varies with different structures of oxadiazoles. Synthesis and characterization of 1,3,4oxadiazoles derived. As part of our efforts to explore the utility of novel methods for the synthesis of heterocyclic compounds, 23 we report here a new method for the synthesis of 1,2,4 oxadiazoles via reaction of amidoximes with anhydrides under mild, catalystfree conditions in water. Additionally, it focuses on the emerging methodologies of microwaveassisted and solid phase synthesis, thus revealing the scope of influence that these methodologies have in the synthesis of 1,2,4 and 1,3,4 oxadiazoles.
The oxadiazoles prepared were extracted with chloroform, filtered it and washed precipitate 34 times with hot water and kept them in desiccator. T afforded 23chloro1benzobthiophen2yl5substituted phenyl1,3,4oxadiazoles 5ah. A straightforward and highyielding methodology for the synthesis of a high structural diversity of 1,2,4oxadiazoles from different chiral n protected. Synthesis of 2amino1,3,4oxadiazoles through elemental sulfur promoted cyclization of hydrazides with isocyanides. They can cause serious chronic illnesses, resulting in organ damage, cancer, and impaired growth and cognitive development in children. Schistosomiasis and hookworm are parasitic diseases responsible for significant mortality and morbidity in developing countries, together infecting more than 1 billion people worldwide. Synthesis of nheterocycles, synthesis of oheterocycles synthesis of 1,3,4 oxadiazoles.
Fourcomponent synthesis of sterically congested 1,3,4oxadiazole derivatives5 see table. Synthesis and screening of new 5substituted1,3,4oxadiazole. A convergent synthesis of 1,3,4oxadiazoles from acyl. 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. Oxadiazoles form a major class of compounds with a heterocyclic nucleus for drug development and were among. Based on these previous findings, we report here the synthesis of a new series of 5substituted23,4,5trihydroxyphenyl1,3,4oxadiazoles compounds 3nz with the objective to study the effect of changing the substitution at position 5 of the. The synthesis of 2aryl 1,3,4oxadiazoles can be accomplished using nisocyanoiminotriphenylphosphorane 172 with benzoic acid derivatives in a clean reaction under mild conditions. Synthesis and evaluation of some new 1,3,4oxadiazoles bearing. In this present investigations, we report the synthesis of 1,3,4oxadiazole derivatives starting from 2phenylethylamine and benzoic acid. Synthesis, characterization, oxadiazoles, thiadiazoles, derivatives introduction. Secondly, condensation of 1,3,4oxadiazoles resin with the corresponding arylamines hydrochloride to. Scheme 6 reaction scheme of onestep synthesis of 3amino4aryl1,2,5oxadiazoles. An external file that holds a picture, illustration, etc.
A versatile continuousflow synthesis of highly functionalized 1,2,4oxadiazoles starting from carboxylic acids is reported. A useful synthesis of 2acylamino1,3,4oxadiazoles from. Also 1,3,4oxadiazoles are suitable substrates in a new process in which tmp 2 zn. Wikimedia commons has media related to oxadiazoles. Pdf the synthesis of novel achiral and chiral amides incorporating 1,3,4oxadiazole ring are reported. 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.
The synthesis of novel achiral and chiral amides incorporating 1,3,4oxadiazole ring are reported. Westwell, design, synthesis and proapoptotic antitumor properties of indolebased 3,5 disubstituted oxadiazoles. Pdf various approaches for synthesis of oxadiazole derivatives. Synthesis of oxadiazole2oxide analogues as potential antischistosomal agents tetrahedron letters april 2009 identification of oxadiazoles as new drug leads for the control of schistosomiasis nature medicine april 2008. Synthesis and characterization of 1,3,4oxadiazoles derived from 9fluorenone rafidsaaddawood received 29, november, 2012 accepted 23, january, 20 abstract. In a direct annulation of hydrazides with methyl ketones for the synthesis of 1,3,4oxadiazoles, the use of k 2 co 3 as a base achieves an unexpected and highly efficient cc bond cleavage. Solid phase synthesis of 3,4,5trisubstituted1,2,4triazoles. Microwaveassisted as well as conventional synthesis of 5substituted22methyl4nitro1imidazomethyl1,3,4oxadiazoles containing the nitroimidazole moiety is carried out and their antibacterial, antifungal and antiinflammatory activity is reported. The 1,3,4oxadiazole is an aromatic heterocycle valued for its lowlipophilicity in drug development. Efficient and mild synthesis of substituted 2amino1,3,4. The pathway to another large group of 1,2,4oxadiazoles proceeding from a broad spectrum of reactants is via their reactions of 1,3dipolar cycloaddition, in particular, with. Synthesis of nheterocycles, synthesis of oheterocycles synthesis of 1,2,4 oxadiazoles. Pdf oxadiazole, a fivemembered heterocycle having two carbon atoms, two nitrogen atoms, one oxygen atom, and two double bonds, inclusive of inductive.
Mild synthesis of substituted 1,2,5oxadiazoles using 1,1. For the synthesis of 1,3,4oxadiazoles 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. A 100ml roundbottomed flask equipped with a magnetic stir bar was charged with the nitrile substrate 1. 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. Synthesis of chromene based oxadiazole derivatives 119. To the stirred mixture was added concentrated hcl 10. The alkylsubstituted1,3,4oxadiazoles are less encountered compared to their hetaryl counterparts. This document was downloaded for personal use only. The preparation of oxadiazoles from relevant oxidizole and hydrazones are shown in table 1. The extensive use of 1,3,4 oxadiazoles as a scaffold in medicinal chemistry, established this moiety as a member of the privileged. Development of oxadiazoles as treatment for schistosomiasis. 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.
This method could provide a facile shortcut to generate a series of 2acylamino1,3,4oxadiazoles in medicinal chemistry. Fourcomponent synthesis of 1,3,4oxadiazole derivatives. Synthesis of 2amino1,3,4oxadiazoles and 2amino1,3,4. Synthesis and characterization of 1,3,4oxadiazoles. In fact, the preparation of 2acylaminosubstituted 1,3,4oxadiazoles through. Recently, ajay kumar and coworkers reported the synthesis of 1,3,4 oxadiazoles, in an attempt to synthesise alkenyl substituted oxadiazoles, they observed that. We report the synthesis and biological assessment of 1,3,4oxadiazole substituted 24 derivatives as novel, potential antibacterial agents. Synthesis of 2, 5disubstituted 1, 3, 4oxadiazoles as. From the filtrate, excess of acetone was removed by distillation. R1 o o n r2 nh2 oh n o n r2 r1 r k 2co 3, toluene reflux, 612 hrs r me, et scheme2 parallel synthetic approach of 1, 2, 4oxadiazoles implementing cdi activation5 scheme3. Synthesis of 1,3,4 oxadiazoles 1a6d under conventional heating and under microwave irradiation. Thiocarbohydrazides in the synthesis of heterocycles 4.
Synthesis and antimicrobial properties of 1,3,4oxadiazole analogs. Fourcomponent synthesis of 1,3,4oxadiazole derivatives from. The synthesis of peptidomimetics is an area of research that has gained a lot of attention in recent years. Pages in category oxadiazoles the following 53 pages are in this category, out of 53 total. Nitro furan containing oxadiazole johan et al, 1972 have reported the synthesis of bis 1,2,4oxadiazole derivatives and their antimalarial activity 18. Nonspecific antispasmodic active oxadiazole derivatives later in 1969 breuer prepared a nitro furan containing oxadiazoles and studied the antimicrobial activity 17.
Synthesis and characterization of 1,3,4 oxadiazoles derived from 9fluorenone rafidsaaddawood received 29, november, 2012 accepted 23, january, 20 abstract. Design, synthesis, and biological evaluation of novel 5. Hence our prime target was to synthesize dimers of 2,5 disubstituted 1,3,4oxadiazoles. A simple and convenient onepot protocol for the synthesis of substituted 2amino1,3,4oxadiazoles mediated by tosyliminophenyl. This process was applied to the multistep synthesis of imidazo1,2apyridin2yl1,2,4oxadiazoles, using a three reactor, multistep continuousflow system without isolation of intermediates. Peptide deformylase pdf is a vital and extremely conserved enzyme. A set of six dnaconnected aryl nitriles were converted to corresponding amidoximes with hydroxylamine followed by the oacylation with a series of aryl and aliphatic carboxylic acids. This process was applied to the multistep synthesis of imidazo1,2apyridin2yl1,2,4 oxadiazoles, using a three reactor, multistep continuousflow system without isolation of intermediates. After cyclodehydration of the oacyl amidoximes by heating at 90 c in ph 9. A series of 1,2,4 oxadiazoles and 1,2,4thiadiazoles containing a 2,6ditertbutylphenol substituent were prepared and evaluated as dual inhibitors of 5lipoxygenase and cyclooxygenase in rat. A useful method for the synthesis of 2acylamino1,3,4 oxadiazoles was developed. This greener approach gives the desired products using acetonewater as solvent in very short reaction times.
The extensive use of 1,3,4oxadiazoles as a scaffold in medicinal chemistry, established this moiety as a member of the privileged. By far the most widespread method for the synthesis of the 1,3,4oxadiazole ring involves closure of a. Characterization of 1,3,4oxadiazoles oxadiazole o 1 form h 1 1 ethyl 7 methyl 3 5. The structures of the newly synthesized derivatives were established by the combined practice of uv, ir, 1 h nmr, c nmr, and mass spectrometry. A straightforward and highyielding synthesis of 1,2,4. Synthesis of 1,3,4oxadiazoles from 1,2diacylhydrazines. Synthesis of ethyl24bromophenylamino acetate i a mixture of pbromo aniline. The preparation of 1,3,4oxadiazoles from 1,2diacylhydrazines using xtalfluore et2nsf2bf4 as cyclodehydration reagent is described. Mild synthesis of substituted 1,2,5oxadiazoles using 1,1 carbonyldiimidazole as a dehydrating agent andrew j. Oxadiazoles heterocyclic building blocks sigmaaldrich. Synthesis of 1,3,4oxadiazoles 1a6d under conventional heating and under microwave irradiation.
Synthesis, characterization and biological activities of 1. Continuousflow synthesis of highly functionalized imidazo. Synthesis of nheterocycles, synthesis of oheterocycles synthesis of 1,3,4oxadiazoles. Substituents at the 2 andor 5positions can modulate the heterocycles electronic and hydrogen bondaccepting capability, while exploiting its use as a carbonyl bioisostere. An extension of our methodology on solidphase synthesis of 3,4,5trisubstituted1,2,4triazoles under mild conditions has been developed. Synthesis of chromen4oneoxadiazole substituted analogs as. The structures of newly synthesized compounds 4ah and.
The five membered ring heterocyclic compounds have been studied by many researchers because of chemical and variable biological effects1. Hydrazinecarbothioamide group in the synthesis of heterocycles. Files available from the acs website may be downloaded for personal use only. The individual variants of this general synthesis differ from one another in their. Synthesis, characterization and biological activities. This reaction is proposed to go through oxidative cleavage of csp 3 h bonds, followed by cyclization and deacylation. All the synthesized amides are characterized 1 h, c, ftir and elemental analysis techniques. Synthesis of 1,2,4oxadiazoles by tandem reaction of nitroalkenes. Oxadiazoles article about oxadiazoles by the free dictionary. Oxadiazoles form a major class of compounds with a heterocyclic nucleus for drug development and were among the first effective.
Oxadiazoles are fivemembered heterocyclic aromatic compounds consisting of one oxygen atom, two nitrogen atoms and two carbon atoms. Synthesis of nheterocycles, synthesis of oheterocycles synthesis of 1,2,4oxadiazoles. Synthesis of 1,3,4oxadiazoles organic chemistry portal. C, a wide range of 2acylamino1,3,4 oxadiazoles were afforded in moderate to excellent yields within two hours. Further these synthesized derivatives were subjected to antibacterial activity against all. Predicted data is generated using the us environmental protection agencys episuite. Synthesis of pyrazoles as previously mentioned, 1benzoyl2phenylacetylene 10a and 12thenoyl2phenylacetylene 10b reacted with thiocarbohydrazides to give 1carbothiohydrazinoyl5hydroxy3phenyl5r2pyrazolines 11 with yields of 6088% scheme 9. Secondly, condensation of 1,3,4 oxadiazoles resin with the corresponding arylamines hydrochloride to. A onepot synthesis of 3,5disubstituted 1,2,4oxadiazoles with two identical substituents directly from the reaction of nitriles and hydroxylamine hydrochloride in the presence of potassium.
Swift synthesis of 1, 2, 4 oxadiazoles employing polymersupported reagents in microwave heating. Oxadiazoles are fivemembered heterocyclic compounds with two nitrogen and one oxygen atoms. 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. This method could provide a facile shortcut to generate a series of 2acylamino1,3,4 oxadiazoles in medicinal chemistry. Synthesis and characterization of some oxadiazoles and. Ziga jakopin and marija sollner dolenc affiliation. One of such compound of 2,5disubstituted 1,3,4oxadiazole class a204197 had been proven useful for the treatment of neoplastic diseases inin vivo studies as an antimitotic agent51. Synthesis of 1,3,4oxadiazole derivatives from amino acid. The preparation of 1,3,4 oxadiazoles from 1,2diacylhydrazines using xtalfluore et2nsf2bf4 as cyclodehydration reagent is described. In an attempt to produce heterocyclic compounds based on. A useful method for the synthesis of 2acylamino1,3,4oxadiazoles was developed.
They are synthesized by ring condensation and rearrangement reactions. Oxadiazoles, cheminform on deepdyve, the largest online rental service for scholarly research with thousands. Ptsazncl 2 is an efficient and mild catalyst for the synthesis of 3,5disubstituted1,2,4oxadiazoles from amidoximes and organic nitriles. A series of 1,2,4oxadiazoles and 1,2,4thiadiazoles containing a 2,6ditertbutylphenol substituent were prepared and evaluated as dual inhibitors of 5lipoxygenase and cyclooxygenase in rat. Further these synthesized derivatives were subjected to antibacterial activity against all the. 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.