Synthesis And Herbicidal Activity Of Nitrogen-Containing Derivatives Evolving From P-Menthane-Skeleton

The p-menthane compounds derived from natural essential oils have diverse structures and properties,which are often used in medicine,daily necessities,food,materials and other fields,but there are few studies on herbicidal activity and insufficient research.In this study,on the basis of the existing results,the skeleton structure of p-menthane was modified by substitution,ring opening,de-isopropylation,etc.,and a series of derivatives of p-menthane and its evolved-structures were synthesized,and their herbicidal activities were evaluated.The structure-activity relationship between the structure evolution of p-menthane and herbicidal activity was studied to provide guidance for the development of new botanical herbicides,which is great significant to the high value-added utilization of forest resource.The main conclusions are as follows:1.Using turpentine derivatives as raw materials,164 compounds of nitrogenous derivatives of p-menthane and their evolved structures were synthesized as 4 categories,including sec-p-menthane-1-amines,N-p-menth-3-en-1-yl sulfamides,sec-p-menthane-7-amines,tetrahydrolinalyl Schiff base,sec-tetrahydrolinalyl amines,tetrahydrolinalyl amides,1-methylcyclohexyl Schiff base and sec-1-methylcyclohexyl amines,their structures were identified by FTIR,¹H NMR,¹³C NMR and HRMS methods.2.The results showed that sec-p-menthane-1-amines and sec-p-menthane-7-amines compounds had certain herbicidal activities against the growth of barnyard grass and rape.The IC₅₀ value of compound A14 against the root and shoot growth of barnyard grass were 0.0056 and 0.0298 mmol/L,respectively,which were 692.9%and 451.0%higher than that of glyphosate,and the IC₅₀ value against rape stem growth was 0.0419 mmol/L,and the inhibitory activity was 1350.6%higher than that of glyphosate.The IC₅₀ values of compound C21 against the root and shoot growth of barnyard grass were 0.0088 and 0.0662mmol/L,respectively,and the herbicidal activity was 404.5%and 148.0%higher than that of glyphosate.The herbicidal activities of N-p-menth-3-en-1-yl sulfamides on barnyard grass was weaker than that of glyphosate.The tetrahydrolinalyl Schiff base and secondary amine had certain herbicidal activity against ryegrass and barnyard grass.The IC₅₀values of compound E24 against the root and shoot growth of barnyard grass were 0.0167 and 0.1348 mmol/L,respectively,which were 165.9%and 21.8%higher than that of glyphosate.Among sec-1-methylcyclohexyl amines,The IC₅₀ values of compounds H5 and H8against ryegrass root growth were 0.0163 and 0.0134 mmol/L,respectively,and their herbicidal activity were 139.9%and 191.8%higher than that of glyphosate,and the inhibitory effect against shoot was weaker than glyphosate.The IC₅₀ values of compounds H12 and H13 against barnyard grass shoot growth were 0.1223 and 0.1216 mmol/L,respectively,and their herbicidal activities were 34.3%and 35.0%higher than that of glyphosate.3.The study of structure-activity relationship showed that the p-menthane skeleton was necessary to herbicidal activity,and opening of the ring or removing the isopropyl group would lead to serious decline in herbicidal activity,as well as the conversion of amino group to sulfonamide and amide.The order of herbicidal activity is as follows:sec-p-menthane-1-amines>sec-p-menthane-7-amines>sec-tetrahydrolinalyl amines>sec-1-methylcyclohexyl amines>1-methylcyclohexyl Schiff base>tetrahydrolinalyl Schiff base>tetrahydrolinalyl amides>N-p-menth-3-en-1-yl sulfamides.The 3D-QSAR model among the sec-p-menthane-1-amines was established by Co MFA method,with r² of 0.85and q² of 0.58.The 3D-contour map of the model shows that the introduction of strong electron-withdrawing groups in the ortho-position of the benzene ring is beneficial to increase the activity,whereas the introduction of bulky groups in the para-position of the benzene ring is not conducive to the activity,the results have guiding significance for the design of herbicidal active substances.4.The safety evaluation results show that some compounds showed slight growth inhibitory effects on wheat,sorghum and other crops,but have strong inhibitory effects on cucumber and radish;most of the compounds showed no inhibitory effects on BALB/c 3T3 and HUVEC-C cells.