Studies of the New Herbicide KIH-6127. 4. Crystal Structure of KIH-6127 and Quantitative Structure−Activity Relationship of the Iminoxy Moiety of KIH-6127 Derivatives

Abstract

The crystal structure of the major isomer of KIH-6127 was investigated by X-ray crystallographic techniques. The solid state structure and its conformation were confirmed as the E form. Thus KIH-6127 is mainly consistent with methyl 2-[(4,6-dimethoxypyrimidin-2-yl)oxy]-6-[1-E-(methoxyimino)ethyl] benzoate (compound 1: Table ). Further modifications of the iminoxy moiety to introduce a variety of haloalkyl, haloalkenyl, and others were made, and the Z isomers of several derivatives were prepared. The physicochemical properties of these derivatives were measured, including their log P and K d values. We tested their herbicidal activity against barnyard grass and their phytotoxicity to transplanted rice in flooded paddy conditions. We also studied the role of the iminoxy moiety, on the basis of the hypothesis that the difference in the E/Z configurations of the iminoxy moiety determines their biological activity. However, clear differences in the herbicidal activities were not observed between these isomer groups. Each Z isomer was more hydrophilic than its E counterpart. To investigate this finding more intensively in a single E/Z pair, the surface area of each E/Z isomer of KIH-6127 was calculated from the X-ray data for the KIH-6127 E form. The Z conformation of the iminoxy moiety appears to take a more compact molecular conformation, resulting in the Z isomer having more hydrophilic surface area than the corresponding E isomer. QSAR studies focused on the iminoxy moiety. Both pre- and post-emergence activities of the compounds were well correlated with the square of the log P value for both configurations of the iminoxy moiety. In other words, these configurations merely contributed to the activity by way of their hydrophilicity. The difference between optimum log P values for pre- versus post-emergence indicated that the optimum compound is more lipophilic for pre- than for post-emergence activity. Phytotoxity against rice also correlated well with the K d value. Thus stronger soil adsorption of the compounds provides higher safety for rice. On the basis of those QSAR studies, compound 1 was selected as the optimal compound for development as a commercial herbicide. Keywords: Methyl 2-[(4,6-dimethoxypyrimidin-2-yl)oxy]-6-[1-E-(methoxyimino)ethyl] benzoate; KIH-6127; Pyriminobac-methyl; herbicide; barnyard grass; ALS; QSAR

Synthesis, crystal structure, and herbicidal activity of pyrimidinyl benzylamine analogues containing a phosphonyl group

“…These herbicides, which are known as inhibitors of branched chain amino acid (acetolactate or acetohydroxyacid) synthase, have attracted considerable attention from the field of pesticide scientists [1][2][3][4][5]. To date, several pyrimidyl carboxylic acid derivatives, such as Pyriminobacmethyl, have been used as commercially herbicides.…”

Synthesis and Herbicidal Activity of 2‐Aroxy‐propanamides Containing Pyrimidine and 1,3,4‐Thiadiazole Rings

“…Recently, pyrimidinyl salicylic acid derivatives, which acted as inhibitors of branched chain amino acids (acetolactate synthase (ALS) or acetohydroxyacid synthase (AHAS)) synthase, have been found to be effective herbicides against barnyard grass in different growth stages including preemergence treatment and excellent safety on transplanted rice crops, animals, fish, and so forth [1][2][3][4][5]. To date, several pyrimidyl carboxylic acid derivatives such as bispyribacsodium and pyriminobac-methyl, have been used as commercially herbicides (Figure 1), which are widely used in agriculture and plant protection around the world.…”

“…On the other hand, 1,3,4-thiadiazole derivatives possessed a wide range of pharmaceutical or agrochemical activities, such as anticancer [6], antiviral [7], antibacterial [8], antimicrobial, and anti-inflammatory activities [9]; some of them exhibited good fungicidal [10] and herbicidal activities [11]. To find novel lead compound with good herbicidal activity, we designed and synthesized a series of novel N-{5- [2-(4,6-dimethoxy-pyrimidin-2-yloxy)-phenyl]- [1,3,4]thiadiazol-2-yl} 2-aroxy-propanamides, according to the pesticide metabolism, which might be hydrolyzed to 2-(4,6-dimethoxy-pyrimidin-2yloxy)-benzoic acid and 2-aroxy propionic acid in plant tissues; both of them are effective herbicides. Their herbicidal activities against Brassica campestris L. and Echinochloa crus-galli (in vitro) were evaluated in this study.…”

“…A series of novel N-{5- [2-(4,6-dimethoxy-pyrimidin-2-yloxy)-phenyl]- [1,3,4]thiadiazol-2-yl}2-aroxypropanamides were designed and synthesized by the multistep reactions. 2-(4,6-Dimethoxy-pyrimidin-2yloxy)-benzaldehyde (1) reacted with aminothiourea to yield 2, which undergoes ring closure to give 5- [2-(4,6-dimethoxy-pyrimidin-2-yloxy)-phenyl]- [1,3,4]thiadiazol- 2-amine (3) in the presence of ferric chloride in refluxing ethanol. 3 reacted with 2-aroxy-propionyl chlorides to give the target compounds 4a-4i in moderate to good yields.…”

Synthesis and Biological Evaluation of Novel (Thio)Urea Derivatives as Potential Antitumor Agents

“…The pyrimidinyl group is a highly efficient pharmacophore and is widely used in pesticide [11] and drug [12] molecular design. We wanted to investigate whether there would be some new beneficial properties if the pyrimidinyl group was introduced in the urea derivatives.…”