Design, Synthesis And Herbicidal Activity Of Acyl Thiourea And Their Cyclization Products Containing Isoxazole Moiety

Acetolactate synthase (ALS) inhibitors exhibit high biological activities, broad herbicidal spectrum and other features, and have become a major breakthrough in weed control technology. However, ALS inhibitor are facing more and more prominent drug-resistance problem. Therefore, targeting on acetolactate synthase, to find novel compounds with super-efficient, low toxicity, broad spectrum properties, has become focus in the field of chemical and pesticide.Pyrimidinyl acylthiourea and 2H-1,2,4-thiadiazolo[2,3-a]pyrimidine have been reported to form hydrogen bonds and hydrophobic interactions easily with amino acid residues of active center of ALS, activity of ALS is decreased or lost and biosynthesis of branch-chain amino acid is blocked. In view of this, two series of novel compounds targeting on ALS were designed and synthesized, and their herbicidal activities in vitro were screened. Main work and results were listed as follows:1. A series of novel heterocyclic pyrimidinyl acylthiourea: sixteen N-[5-methyl-3-substitu tedphenyl)isoxazolyl-4-yl]acyl-N'-(4,6-disubstitutedpyrimidin-2-yl) thioureas were synthesi zed from 2,4-chlorobenzaldehyde or 4-trifluoromethylbenzaldehyde (starting materials) in multi-steps; Another series of novel fused heterocyclic compound: sixteen 5,7-disubstituted -2-[5-methyl-3-substitutedphenylIsoxazolyl-4-formylimino]-2H-1,2,4- thiadiazolo [2, 3-a] pyrimidine were prepared from corresponding acyl thioureas by employing bromine as oxid ant. Structures of target compounds were confirmed by IR, 1H NMR and elemental analysis, their physical, chemical properties and spectral properties have also been analyzed and discu ssed.2. Preliminary herbicidal activities evaluation of target compound was performed accord ing to bioassay standard method, the culture dish method. Monocotyledon (Echinochloa crusgalli L, Digitaria ciliaris L), Dicotyledons (Chenopodium serotinum L, Brassica napus L) was employed as materials, fenoxaprop-p-ethyl as controlling herbicide. Results indicate d that two series of target compounds showed cartain inhibitory activity, inhibition of root length is greater than that of stalk length, and inhibi tion of dicotyledons is higher than that of monocotyledons in general; 5,7-disubstituted-2-[5-methyl-3- (4-trifluoromethylphenyl) Isoxazolyl-4-formylimino]-2H-1,2,4-thiadiazolo[2,3-a]pyrimidine 5i～5_p exhibited highest activity with inhibitory rate towards root length of Brassica napus L. more than 75 % at a higher dose of 100mg/L, 5,7-disubstituted-2-[5-methyl-3-(2,4-dichloro phenyl) Isoxazolyl-4-formylimino]-2H-1,2,4-thiadiazole [2,3-a] pyrimidine 5_a～5_h exhibited higher activity with inhibitory rate towards root length of Chenopodium serotinum L. in the range of 70 % to 75 % at a higher concentration of 100mg/ L, higher than the controling; N-[5-methyl-3-(4-trifluoromethyl phenyl)Isoxazolyl-4-yl]acyl-N'-(4,6-disubstitutedpyrimidin-2-yl) thioure as 4i～4_p and N-[5-methyl-3-(2,4-dichlorophenyl) Isoxazolyl-4-yl]acyl-N'-(4, 6-disubstitu ted pyrimidin-2-yl) thioureas 4_a～4h showed relatively high inhibitory activity at the conce ntration of 100 mg/L, inhibition rate towards root length of Brassica napus L. in the range of 50 % to 55 %, some of these compounds showed certain plant growth regulat ing activity, which can promote growth of root at low concentration (10 mg/L).3. Single crystal structure of 4i was determined from single crystal X-ray diffraction data. The crystal belongs to system with space group a = 7.351(6)(?), b = 10.373 (10)(?), c = 14.12 0 (12)(?),α= 72.222(14)°,β= 85.372(15)°,γ= 85.380 (14)°, V = 1020.1 (16) (?)3, Z = 2, Dcalcd.= 1.418 g·cm^-3,μ= 0.211mml, F(000) = 448. A six-membered ring comes into being between the nitrogen atom on thiourea linkage and the nitrogen atom on pyrimidine ring in the form of intermolecule hydrogen bond N-H…N.4. Preliminary relationships between structure and activity of target compounds were also analyzed and discussed. Bioassay results indicated it was necessary for improving herbicidal activity of target compounds that the moieties at ortho- and para- positions of phenyl were electron withdrawing groups, while 4,6- positions of pyrimidine ring were electron donor groups (i.g. methyl or methoxy).