Synthesis And Antibacterial Activity Of N(O)-Heterocycles And Diphenyl Ether Triazole Sec-Butanol Derivatives

As an important class of heterocyclic compounds,Nitrogen(oxygen)heterocyclic compounds often appeared in the structural molecules of natural products and drug molecules.In addition,these heterocyclic compounds can be modified by introducing various functionalized groups to carry out a variety of structural modifications,so they have good application value in new drug synthesis,plant protection and industrial production.(aza-)Wittig reactions had the advantages of mild reaction conditions,variable product structure and simple operation.They were widely used in the synthesis of target heterocyclic backbone.In this paper,(aza-)Wittig reactions were connected in series with a series of other reactions,such as isonitrile-based multicomponent and nucleophilic substitution reactions to synthesize a series of new heterocyclic compounds.At the same time,new diphenyl ether triazole sec-butanol derivatives were synthesized through the intramolecular sequential substitution/reduction reaction of bromomethyl diphenyl ether and acetonyl triazole.A total of more than one hundred and fifty heterocyclic compounds have been synthesized.Some of the compounds showed good antibacterial biological activity against various strains.The specific content is as follows:1.The latest development and applications of multicomponent reactions,such as isocyanide based multicomponent reactions,Ugi reaction and oxidative Ugi reaction,Wittig reaction and aza-Wittig reaction triazole fungicides are reviewed.2.The reactions of 2-(triphenylphosphonyl)-succinic acid-1-ester Ⅱ-1 and acid chloride produced disubstituted 2-(3H)-furanone compounds Ⅱ-2 in the presence of DMAP by a sequential acylation/Wittig reaction.Moreover,the 2-(3H)-furanone can further undergo O-acylation with different acid chlorides to obtain trisubstituted furan compounds Ⅱ-3 under the condition of two equivalent of triethylamine.Through the confirmation of the spectral properties of the compound structure and(high-resolution)mass spectrometry,the specific structure of the compound was determined.Subsequently,we tested the bactericidal activity of 2-(3H)-furanone and furan compounds at the concentration of 50 ppm,and the results showed that compound Ⅱ-3c had fungicidal effects on Pythium aphanidermatum of 73%.The inhibitory activities of compounds Ⅱ-3b,Ⅱ-3c and Ⅱ-3h against Sclerotinia scleotiorum reached 78%,79%and 77%respectively.The inhibitory activities of compound Ⅱ-3k against Fusarium graminearum reached 70%.3.The one-pot reactions of functionalized isocyano(triphenylphosphoranylidene)acetates,carboxylic acids and N-aryl-1,2,3,4-tetrahydroisoquinolines produced new polysubstituted 2-(1,2,3,4-tetrahydroisoquinolin-1-yl)oxazolesⅢ-4 directly in good yields in the presence of DEAD.A new effecient DEAD-promoted oxidative Ugi/Wittig reaction for the preparation of 2-(1,2,3,4-tetrahydroisoquinolin-1-yl)oxazoles has been developed.Through the confirmation of the spectral properties of the compound structure and high-resolution mass spectrometry,the specific structure of the compound was determined.Subsequently,we tested the bactericidal activity of 2-(1,2,3,4-tetrahydroisoquinolin-1-yl)oxazolesⅢ-4 at the concentration of 50 ppm,and the results showed that compounds Ⅲ-4 had certain antibacterial activity on Sclerotinia scleotiorum and Fusarium graminearum.4.The one-pot reactions of odorless(N-isocyanimine)triphenylphosphorane,carboxylic acids and N-aryl-1,2,3,4-tetrahydroisoquinolines produced new polysubstituted 5-(1,2,3,4-tetrahydroisoquinolin-1-yl)-1,3,4-oxadiazoles N-4 directly in good yields in the presence of DEAD.A new effecient DEAD-promoted oxidative Ugi/Wittig reaction for the preparation of 2-(1,2,3,4-tetrahydroisoquinolin-1-yl)oxazoles has been developed.Through the confirmation of the spectral properties of the compound structure and high-resolution mass spectrometry,the specific structure of the compound was determined.Subsequently,we tested the bactericidal activity of 5-(l,2,3,4-tetrahydroisoquinolin-1-yl)-1,3,4-oxadiazoles Ⅳ-4 at the concentration of 50 ppm,and the results showed that the bactericidal effects of compound Ⅳ-4s against Fusarium graminearum and Sclerotinia scleotiorum reached 71%and 80%respectively.5.The one-pot reactions of dialkyl acetylenedicarboxylates,2-azidobenzoic acids,(or 2-azidobenzaldehydes)and isocyanides produced functionalized quinazolin-4(3H)-ones Ⅴ-10 or furo[3,2-c]quinolines Ⅴ-6 in moderate to good yields by a I-MCR/Staudinger/aza-Wittig sequence.In addition,unreported trifunctional furo[3,2-c]quinolines were synthesized using the tandem reaction strategy with operational simplicity.Through the confirmation of the spectral properties of the compound structure and high-resolution mass spectrometry,the specific structure of the compound was determined.Subsequently,we tested the bactericidal activity of quinazolin-4(3H)-ones Ⅴ-10 and furo[3,2-c]quinolines Ⅴ-6 at the concentration of 50 ppm,and the results showed that The bactericidal effects of compound Ⅴ-6p against Fusarium graminearum reached 70%respectively.The bactericidal effect of compound Ⅴ-10n against Sclerotinia scleotiorum reached 88%.CompoundⅤ-10m,Ⅴ-10n,Ⅴ-10o and Ⅴ-l0p had fungicidal effects on Magnaporthe grisea of 70%,74%,73%and 73%respectively.6.The one-pot reactions of tertiary amines,2-azidobenzoic acids and isocyanides produced polysubstituted quinazolin-4(3H)-ones Ⅵ-4 in moderate to good yields by a CuCl/TBHP-mediated oxidative Ugi/Staudinger/aza-Wittig reaction.Through the confirmation of the spectral properties of the compound structure and high-resolution mass spectrometry,the specific structure of the compound was determined.Subsequently,we tested the bactericidal activity of quinazolin-4(3H)-ones Ⅵ-4 at the concentration of 50 ppm,and the results showed that the compounds Ⅵ-4 had certain antibacterial activity on Sclerotinia scleotiorum and Fusarium graminearum.7.Using diphenyl ether and 1-(1H-1,2,4-triazol-1-yl)propan-2-one as starting materials,diphenyl ether triazole sec-butanol derivatives were obtained by a three-step reaction of NBS bromination/nucleophilic substitution/sodium borohydride reduction reaction.Through the confirmation of the spectral properties of the compound structure and high-resolution mass spectrometry,the specific structure of the compound was determined.Subsequently,we tested the bactericidal activity of compounds Ⅶ-7 at the concentration of 50 ppm,and the results showed that the inhibitory activity of the compound Ⅶ-7p-1 against Sclerotinia sclerotiorum was equivalent to that of the commercial triadimefon.The inhibitory activity of compounds Ⅶ-7g-1,Ⅶ-7m-1 and Ⅶ-7n-1 against Botryosphaeria dothidea were higher than that of commercial triadimefon.The inhibitory activity of compounds Ⅶ-7g-1,Ⅶ-71-1,Ⅶ-7m-1,Ⅶ-7n-1,Ⅶ-7o-1 and Ⅶ-7p-1 against Magnaporthe grisea were higher than that of the commercial triadimefon.