Synthesis And Antibacterial/Antifungal Activity Of 3-Cyanothiophenes Based On Cyanoalkynes

As a sulfur-containing aromatic compound,thiophene and its derivatives are abundantly present in natural products and artificially synthesized products,and have a large number of applications in the fields of agrochemicals,medicine,material synthesis,and nanoscience.As an important thiophene derivative,3-cyanothiophene is traditionally synthesized from cyanation of thiophene,but this method suffers from relatively low atom efficiency.As a new type of synthon,alkynylnitriles can construct various heterocyclic compounds containing cyano groups with higher atom efficiency.In this paper,a simple and efficient method for the construction of thiophene ring directly from acetylonitrile was reported,and the antibacterial and antifungal activity of the obtained 3-cyanothiophene and its derivatives were studied.In the first part of this study,Cu(OAc)2·H2O was used as the additive,and DMAc(N,Ndimethylacetamide)as the solvent to realize the [2+2+1] cyclization reaction of alkynonitrile and Na2S·9H2O.Meanwhile a molecule of the cyano group was eliminated to give the 2,5-diary-3-cyanothiophene and its derivatives.This method has a broad substrates scope and multiple functional groups can be tolerated.Compared with the traditional method of preparing thiophene,this study uses a cheap inorganic sulfur source,with less cost and higher atom efficiency compared with organic sulfur sources such as mercaptans,thiourea,and Lawesson reagent.Also,this reaction can be carried out under room temperature and air atmosphere,and can introduce one cyano group at the 3-position of thiophene,without the addition of extra cyanide.The method provides a new route for synthesizing cyanothiophenes,and has the advantages of mild reaction conditions,simple operation,and more environmental friendliness.In the second part of this study,four species including of Rhizoctonia solani,Pseudopestalotiopsis theae,Staphyloccocus aureus Rosenbach,and Bacillus coli communis Escherich were selected,and antibacterial and antifungi activity of up to ten 2,5-diaryl-3-cyanothiophene compounds were tested towards these four species.The results showed that under the concentration of 100 mg/L,most of these compounds have an inhibitory effect on Staphyloccocus aureus,and the highest inhibitory effect can reach up to 66.49%;the inhibitory effect on another bacterium,Bacillus coli communis Escherich,is moderate;it has no effect on the Rhizoctonia solani.The inhibitory effect towards germs is also moderate.Although most of these compounds have average inhibitory effects on the fungus Pseudopestalotiopsis theae,the inhibitory rates of 2,5-diphenyl-3-cyanothiophene and 2,5-dithienyl-3-cyanothiophene could reach to 78.16%and 73.85%,respectively,showing good to excellent inhibitory effects.In addition,2,5-bis(4-methoxyphenyl)-3-cyanothiophene exhibits a certain inhibitory effect on the growth of these four species,and it is expected to be developed into lead compound to provide new ideas for synthesis pharmaceuticals and pesticides.