Dimethoxypyrimidines as Novel Herbicides. Part 1. Synthesis and Herbicidal Activity of Dimethoxyphenoxyphenoxypyrimidines and Analogues

A number of 6-(4-phenoxyphenoxy)pyrimidines and triazines were synthesized and their herbicidal activity was measured. Compounds with the methoxy groups at the 2- and 4-positions on the pyrimidine and triazine rings exhibited high herbicidal activity. Introduction of a substituent into the 5-position of the pyrimidine ring diminished the activity. In the phenoxyphenoxy substructure at the 6-position, the central ether bond can be replaced by a methylene group without loss of activity. The optimum substituent on the terminal phenyl ring was 3-trifluoromethyl. The compounds showed a strong Hill reaction inhibition, but unfortunately showed poor selectivity between weeds and crops.     

6-氟-2-嘧啶氧基-N-取代苯基苄胺类化合物的合成及其除草活性

从起始原料引入氟原子,分别经亚胺化、硼氢化钠还原、嘧啶氧化,及嘧啶氧化、溴化、胺化两条路线合成了28个新型的6-氟-2-嘧啶氧基-N-取代苯基苄胺类化合物;同时测试了该类化合物在温室中对稗草Echinochloa crusgalli等3种禾本科杂草和反枝苋Amaranthus retroflexus等3种阔叶杂草芽前、芽后的抑制率,结果表明,有12种目标化合物在有效剂量75 g/hm2下其抑制率超过80%。     

Studies of the New Herbicide KIH-6127. Part III. Synthesis and Structure–Activity Studies of Analogues of KIH-6127 against Barnyard Grass (Echinochloa oryzicola)*

The previously evaluated prototype, methyl 6-acetyl-2-[(4,6-dimethoxypyrimidin-2-yl)oxy]benzoate, was modified by the introduction of an oximino group. Further extensive synthetic modifications were then made to the 6-alkyl moiety (R¹), the ester moiety (R²), the alkoxyimino moiety (R³), the bridge-atom (X) and the 4,6-disubstituted-pyrimidine moiety (A, B, Z). Structure–activity relationships of the synthesized compounds were studied by examining their herbicidal activity against Barnyard grass (Echinochloa oryzicola) in paddy rice at various growth stages, including pre-emergence. The novel herbicide methyl 2-[(4,6-dimethoxypyrimidin-2-yl)oxy]-6-[1-(methoxyimino)ethyl]benzoate, (KIH-6127) was found to be the most effective compound. The commercial development of this compound is currently in progress. © 1997 SCI.     

新型取代氨基(或芳氧)磺酰基苯氧丙酸酯的合成及其除草活性

由α-苯氧基丙酸酯出发,合成了取代氨基(或芳氧)磺酰基苯氧丙酸酯,并测定了它们的除草活性。所有的化合物均经1H NMR和元素分析确证,初步的生测结果表明上述化合物具有一定的除草活性。     

Studies of the New Herbicide KIH-6127. Part II. Synthesis and Herbicidal Activity of 6-Acyl Pyrimidin-2-yl Salicylates and Analogues against Barnyard Grass

The method reported previously (Part I) was employed to prepare a variety of novel 6-acylsalicylates as key intermediates. 6-Acylpyrimidin-2-yl salicylates (2-acyl-6-[(4,6-disubstituted pyrimidin-2-yl)oxy]benzoate derivatives: Type 1), the closely related phthalide compounds (3-alkyl-7-[(4,6-dimethoxypyrimidin-2-yl)oxy]phthalide derivatives: Type 2) and the ketal derivatives of 2-acyl-6-[(4,6-dimethoxypyrimidin-2-yl)oxy]benzoates (Type 3) were synthesized and their herbicidal activities measured. Methyl 2-acetyl-6-[(4,6-dimethoxypyrimidin-2-yl)oxy]benzoate gave excellent control of barnyard grass with a promising profile as a prototype rice herbicide.     

Activity,adsorption, mobility and field persistence of sulfosulfuron in soil

Petri dish bioassays, based on root response of corn grown in soil or in perlite, were used to study the activity, adsorption, mobility and field persistence of sulfosulfuron in a silty clay loam and a sandy loam soil. Both bioassays indicated that activity of sulfosulfuron increased with increasing herbicide concentration, and to a slightly greater degree in sandy loam soil than in silty clay loam soil. More sulfosulfuron was adsorbed on the sandy loam (not biologically available) than on the silty clay loam soil. Consequently, slightly greater amounts of sulfosulfuron were leached through the silty clay loam than through the sandy loam soil. Biologically available sulfosulfuron was not detected at depths below 40 cm after application in sandy loam, but this was not the case for the silty clay loam soil. In 2002, all sulfosulfuron rates showed field persistence of less than 5 months. On the other hand, in 2003, biologically available sulfosulfuron was detected in the 0–10-cm soil depth 150 days after application. http://www.phytoparasitica.org posting May 6, 2004.     

1,3,5-三芳基-2-吡唑啉类化合物的合成及其光活化除草活性

为了探讨具有光导性能的芳基吡唑啉类化合物的光活化除草作用,由α,β-不饱和酮与苯肼环化,合成了5个1,3,5-三芳基吡唑啉类化合物,其化学结构经IR、1H NMR、MS和元素分析确证,并讨论了其波谱性质。首次研究了这类化合物对稗草的光活化除草作用。结果表明,1-苯基-3,5-二噻吩吡唑啉(化合物 Ⅱ e )光照下对稗草根长的IC50值为4.46 μg/mL,光活化比为2.69,具有较好的光活化除草活性。     

2-(5,7-二甲基-1,2,4-三唑[1,5-a]嘧啶-2-硫代)乙酰胺类化合物的合成及除草活性

以芳胺或取代稠杂环胺、氯乙酰氯和2-巯基-5,7-二甲基-1,2,4-三唑[1,5a-]嘧啶为原料,合成了8个含稠杂环及芳环的三唑并嘧啶类新化合物,结构经1H NMR,M S和IR确证,初步测定了该类化合物在室温下对稗草等3种禾本科杂草和反枝苋等3种阔叶杂草芽前芽后的抑制率,结果表明:有6个化合物在有效剂量75g/hm2下的抑制率超过80%。     

棉田除草剂溴嘧氯草醚的中试合成及杂质鉴定

为研究棉田除草剂溴嘧氯草醚(开发代号SIOC0426,化学名称为N-[2-氯-6-(4,6-二甲氧基-2-嘧啶氧基)苄基]-4-溴苯胺)的中试合成工艺,以2-氟-6-氯苯甲醛为起始原料,通过水解、缩合、还原和亲核取代反应在公斤级规模上合成了溴嘧氯草醚,用高效液相色谱外标法测定了原药含量,通过三维高效液相色谱-质谱联用(HPLC-DAD-MS)技术对原药中的杂质结构进行了鉴定。结果表明,反应总收率高于80%,原药含量大于98%,主要杂质为未反应完全的中间体2-[(4-溴苯氨基)甲基]-3-氯苯酚和溴嘧氯草醚Smiles重排产物。该工艺反应条件温和,反应收率高,原药含量高,"三废"排放较少,较适合工业化放大生产。     

2-(5,7-二甲基-1,2,4-三唑[1,5-a]嘧啶-2-硫代)乙酰胺类化合物的合成及除草活性

以芳胺或取代稠杂环胺、氯乙酰氯和2-巯基-5,7-二甲基-1,2,4-三唑 嘧啶为原料,合成了8个含稠杂环及芳环的三唑并嘧啶类新化合物,结构经1H NMR, MS 和IR确证,初步测定了该类化合物在室温下对稗草等3种禾本科杂草和反枝苋等3种阔叶杂草芽前芽后的抑制率,结果表明:有6个化合物在有效剂量75 g/hm2下的抑制率超过80%。     

Studies of the New Herbicide KIH-6127. Part I. Novel Synthesis of Methyl 6-Acetylsalicylate as a Key Synthetic Intermediate for the Preparation of 6-Acetyl Pyrimidin-2-yl Salicylates and Analogues

A novel synthesis of methyl 6-acetylsalicylate as a key synthetic intermediate for methyl 2-[(4,6-dimethoxypyrimidin-2-yl)oxy]-6-[1-(methoxyimino)ethyl]benzoate (KIH-6127) was studied, and directed at 6-substituted pyrimidin-2-yl salicylate herbicides and their analogues. Three synthetic approaches were successful: a modification of the Sandmeyer reaction of 6-acetylanthranilate (Method A), a direct ring-opening reaction of 3-methylphthalide using potassium permangamate and magnesium nitrate (Method B), and a regioselective ortho-lithiation of the protected 3-hydroxyacetophenone (Method C). These methods were applicable for the synthesis of various 6-acyl salicylates.     

The Synthesis and Fungicidal Activity of 2-Substituted 1-Azol-1-ylmethyl-6-arylidenecyclohexanols

A number of substituted 2,2-dimethyl-6-arylidene-1-triazol-1-ylmethylcyclohexanols and 2,2-dimethyl-6-arylidene-1-imidazol-1-ylmethylcyclohexanols were prepared from 2-methylcyclohexanone in four steps: Claisen–Schmidt condensation with substituted benzaldehydes, methylation of the resulting 2-methyl-6-benzylidenecyclohexanones, conversion to the oxiranes by interaction with dimethylsulfonium methylide and reaction of the oxiranes with triazole or imidazole. The compounds obtained were tested for antifungal activity against five phytopathogenic fungi of different taxonomic classes. EC₅₀ values were determined for all compounds. Structure–activity relationships are discussed in broad terms. Some of triazolymethyl-substituted cyclohexanols obtained are more active than triadimenol. © 1997 SCI.     

2-(4-羟基苯氧基)-6-氯-喹喔啉的合成新方法

以2,6-二氯喹喔啉、对苯二酚、液碱为原料,优化操作过程,于三元体系中合成2-(4-羟基苯氧基)-6-氯喹喔啉,收率达到96％以上.     

含2-氯-5-亚甲基吡啶基团的硫脲化合物的合成及生物活性

合成了 10个结构新颖的 2 -氯 - 5 -亚甲基吡啶的硫脲化合物 ,用 IR、1H NMR及元素分析对其结构进行了确证。植物生长调节活性的初步测定结果表明 :在 5 mg/ L时对水稻幼苗根的促生长率都大于 90 %。     

2-[4-(对氟苯基)噻唑-2-基]-3-羟基-3-烃氧基丙烯腈的合成及杀菌活性

为了寻找生物活性良好的噻唑基丙烯腈类化合物,利用2-氰甲基-4-(对氟苯基)噻唑( 3 )与取代氯甲酸酯( 4 )在碱存在下反应,合成了15个未见文献报道的2- -3-羟基-3-烃氧基丙烯腈化合物( 5 ),其结构经核磁共振氢谱、质谱和元素分析表征。初步杀菌活性测试结果表明:所有化合物在试验浓度下均具有一定的抑菌活性,尤其对炭疽病菌Colletotrichum gossypii表现出较好的抑制活性,在质量浓度25 mg/L下,所有化合物的抑制率均在50%以上,其中化合物 5a、5e、5g、5k、5n和5o 的抑制率在80%以上。     

(4-亚甲基-5-羰基-3-四氢呋喃基)-苯甲酸甲酯衍生物的合成及其杀菌活性

为了探索天然产物Cedarmycins衍生物的结构与活性关系,以α-亚甲基-β-羟甲基-γ-丁内酯为起始原料,经过与不同取代的羧酸缩合,合成了19个新的(4-亚甲基-5-羰基-3-四氢呋喃基)-苯甲酸甲酯衍生物。杀菌活性测定结果表明,该类衍生物具有广谱的杀菌活性,尤其对水稻纹枯病菌Rhizoctonia solani和辣椒疫霉Phytophthora capsici显示出很强的杀菌活性,其中化合物2e(R=2,4-2Cl)对这2种病菌的EC50值约为1.6 mg/L。     

Spatial and temporal changes in acetolactate synthase activity as affected by new herbicide ZJ0273 in rapeseed, barley and water chickweed

Propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)benzoate (ZJ0273), derived from a precursor compound pesticide (a derivative of 2-pyrimidinyloxy-N-aryl benzoate), is a novel herbicide used in the rapeseed field. This paper studied the differential tolerance or susceptibility of four plant species viz. Brassica napus L. (rapeseed), Hordeum vulgare L. (barley), Malachium aquaticum (L.) Fries (water chickweed), and Alopecurus aequalis Sobol. (equal alopecurus), to various concentrations of ZJ0273, based on the rate of inhibition of acetolactate synthase (ALS) activity. Brassica napus was observed as the most tolerant among four species in which ALS activity in vivo was hardly affected by ZJ0273 at 100 mg/L (recommended dose in the rapeseed field). In contrast, H. vulgare was found to be more susceptible which was reflected in the relative decline of ALS activity and lower biomass production even under at a lower rate of 10 mg/L of ZJ0273. The two weed species exhibited moderate susceptibility as compared to H. vulgare. The present study confirmed that ZJ0273 at 100 mg/L is the optimal dose of herbicide for rapeseed field. Seedling stage was critical in determining the tolerance of crops and susceptibility of weeds which indicated that over seven leaf stage was much safer for rapeseed whereas the two leaf stage juvenile water chickweed was more susceptible to the same rate of ZJ0273. Spatial and temporal variations in ALS activity as affected by 100 mg/L ZJ0273 in water chickweed, rapeseed and barley also suggested that the synchronized sampling based on the tissue position and seedling stage was necessary to examine precisely, the special difference in tolerance or susceptibility to ALS-inhibiting herbicide. The uppermost younger leaf seemed to be the most appropriate sample for evaluation. Furthermore, the variant tendency of ALS activity from different parts of plants between monocotyledons and dicotyledons to ZJ0273 treatments showed differential response which revealed some possible mechanism related to the altered absorption and translocation of the herbicide.     

含4-正庚/正辛氧基苯基杂环化合物的设计、合成及生物活性

通过研究苯甲脒类抑制剂与酮醇酸还原异构酶(KARI)对接的结合模式,设计合成了一系列含正庚氧基及正辛氧基苯基的杂环化合物。用核磁共振氢谱、红外光谱、质谱及元素分析对26个目标产物(其中22个是新化合物)的结构进行了表征和确认。初步生物活性测试结果表明,目标化合物大多具有不同程度的水稻KARI酶抑制活性和除草活性,其中化合物 9a和9b 在200 μg/mL浓度下对KARI酶的抑制率分别为65.7%和71.1%,在100 μg/mL浓度下对双子叶植物油菜Brassica campestris的抑制率分别达78.6%和89.0%。     

Synthesis and Evaluation of New Ethyl 2,3- Dihydro-3-oxoisothiazolo[5,4-b]pyridine- 2-alkanoate Derivatives as Potential Herbicides

Several ethyl 2,3-dihydro-3-oxoisothiazolo[5,4-b]pyridine-2-alkanoate derivatives were synthesized as herbicides. Only 5-methyl derivatives inhibited both hypocotyl and root growth in the lettuce (Lactuca sativa L.) seedling test at 100 mg litre^-1. Only ethyl propionate and valerate derivatives showed significant inhibition at 0·1 mg litre^-1, whereas ethyl acetate or butyrate derivatives were inactive. Contrary to unoxidized derivatives, the inhibitory effect of 1-oxide and 1,1-dioxide derivatives was strongly dependent on concentration; ethyl 2,3-dihydro-5-methyl-3-oxoisothiazolo[5,4-b]pyridine-2-propionate 1,1-dioxide inhibited 100% of germination at 100 mg litre^-1 and 45% of lettuce seedling growth at 0·1 mg litre^-1. Quantitative structure–inhibition of growth relationship analysis carried out by adaptive least-squares (ALS) method gave a good correlation with small and hydrophobic 5-substituents as well as with odd carbon-chain ethyl alkanoates in position 2. Active compounds did not show auxin-like activity from 0·1 to 100 mg litre^-1. © 1997 SCI.     

Substituted alpha-(phenylhydrazono)phenylacetonitrile derivatives. Part 2: Synthesis and biological activity of pro-pesticides

Pro-pesticides of alpha-(2,6-dichloro-4-trifluoromethylphenylhydrazono)-4-nitrophenylacetonitrile have been prepared and tested against mite and insect pests. Variations in potency and spectrum were observed depending on the choice of cleavable pro-moiety. Cleavage of the pro-moiety was demonstrated in one case by measuring the rate of increase in the uncoupling activity using a mitochondrial preparation. Irradiation experiments have demonstrated a rapid isomerisation of the planar Z isomer to the E isomer, which is reversible.