Uracil derivatives, such as commercial herbicides butafenacil and benzfendizone, have been identified as inhibitors of protoporphyrinogen oxidase (Protox, EC 1.3.3.4), one of the most important action targets of herbicides. In order to search for novel Protox inhibitors with high efficacy, broad-spectrum activity, and safety to crops, commercially herbicide butafenacil was used as lead compound for further optimization; a series of title compounds 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h, 8i, 8j, 8k, 8l, 8m, 8n were designed and synthesized by introducing 1,3,4-thiadiazole moiety into the uracil skeleton. The preliminary bioassays (in vitro) indicated that most of the target compounds displayed better inhibition against Echinochloa crus-galli than Brassica campestris. The greenhouse bioassay results indicated that most of the compounds tested exhibited good-to-excellent herbicidal activities against B. campestris, A. retroflexus, E. crusgalli, and D. sanguinalis in pre-emergence treatment at a dose of 1500 g/ha, for example, compound 8d showed 100% inhibition against the four plants tested in pre-emergence treatment at a dose of 1500 g/ha. So, these types of skeletons can be used as valuable lead compounds for the development of a pre-emergent herbicide.

Diverse chromenones were synthesized through tunable phosphine-mediated cascade reactions between 3-acyl-2H-chromen-2-ones and Morita–Baylis–Hillman (MBH) derivatives. With different phosphine loadings and reaction temperatures, MBH derivatives act either as C₁ or C₃ synthons for the construction of potential biologically active 3-dihydrofuran-fused chromen-2-ones, 4-allyl-3-acyl-chromen-2-ones, or 6H-benzo[c]chromen-6-ones. This method has the advantages of mild conditions, simple workup, and wide substrate scope, which make it powerful for the synthesis of diverse chromenone derivatives.

To find new strobilurin analogs with high activity against resistant pathogens, twelve (E)-α-(methoxyimino)benzeneacetate derivatives containing 1,2,4-triazole Schiff base side chain 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l were designed and synthesized. Their structures were confirmed by IR, ¹H-NMR, EIMS, and elemental analyses. Bioassays indicated that most of the target compounds showed moderate to good fungicidal activities against Physalospora piricola Nose and Alternaria solani. For example, compounds 3d, 3e, and 3f possessed 99.5%, 100%, and 95.6% inhibition against Physalospora piricola Nose, whereas compounds 3d, 3f, and 3g exhibited 92%, 91%, and 92% inhibition against Alternaria solani at the concentration of 50 mg/L, respectively.

A series of novel N-{5-[2-(4,6-dimethoxy-pyrimidin-2-yloxy)-phenyl]-[1,3,4]thiadiazol-2-yl}2-aroxy-propanamides were designed and synthesized by the multistep reactions. 2-(4,6-Dimethoxy-pyrimidin-2-yloxy)-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, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i in moderate to good yields. Their structures were confirmed by IR, ¹H-NMR, EIMS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate to good selective herbicidal activity against Brassica campestris L. at the concentration of 100 mg/L. However, these compounds did not possess inhibitory activity against Echinochloa crus-galli at the tested concentrations.

In order to find novel bleaching herbicide lead compounds, a series of novel 3-aryl-4-substituted-5-[3-(trifluoromethyl)phenoxy]-1,2,4-triazoles were designed and synthesized by the multi-step reactions. N-(Arylformamido)phenylthioureas undergo ring closure in the presence of sodium hydroxide to generate 3-aryl-4-substituted-4H-[1,2,4]triazol-5-thiols 1, which reacted with methyl sulfate in the presence of K₂CO₃ to give 3-aryl-5-methylsulfanyl-4-substituted-4H-[1,2,4]triazoles 2. The target compounds 4 were synthesized by the oxidation of 2 in the presence of H₂O₂ and Na₂WO₄, followed by the substitution with 3-(trifluoromethyl)phenol in moderate to good yields. Their structures were confirmed by IR, ¹H NMR, EI–MS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate to good selective herbicidal activity against Brassica campestris L at the concentration of 100 µg/mL. Compounds 4c and 4i possessed 75.0% and 82.6% inhibition against Brassica campestris L at the concentration of 100 µg/mL. However, the target compounds 4 showed weak herbicidal activity against Echinochloa crus-galli at the concentration of 100 and 10 µg/mL.

In order to find novel bleaching herbicide lead compounds, a series of novel 3-(trifluoromethyl)-4-(arylimino)-5-[3-(trifluoromethyl)phenoxy]-1,2,4-triazoles were designed and synthesized by the multi-step reactions. Their structures were confirmed by IR, ¹H NMR, EI-MS and elemental analyses. The preliminary bioassay indicated that compounds 4b, 4f, and 4h possessed 69.4%, 72.6%, and 88.5% inhibition against Brassica campestris L at the concentration of 100 mg/L. Generally speaking, this type of compounds exhibited weak herbicidal activity and might be not suitable as herbicide lead compound for further optimization.

A series of novel muti-substituted pyrido[4,3-d]pyrimidin-4-one derivatives 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5l were designed and synthesized by the muti-step reaction. N,S-acetal 1 reacted with acetyl acetamide in the presence of zinc nitrate to obtain muti-substituted pyridine 2, which reacted with triethyl orthoformate to give 8-cyano-5-methyl-7-methylthio-pyrido[4,3-d]pyrimidin-4-one 3; the target compounds 5 were obtained in good yields by the oxidation of 3 with H₂O₂ in a catalytic amount of sodium tungstate then by the substitution with various substituted phenols. Their structures were confirmed by IR, ¹H NMR, EI-MS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate herbicidal activity against dicotyledonous weed Brassica campestris L. at the concentration of 100 mg/L. For example, compounds 5a, 5f, and 5g possessed 76.0%, 62.7%, and 60.2% inhibition against B. campestris at the concentration of 100 mg/L. Moreover, 5a exhibited 58.2% inhibition against B. campestris at the concentration of 10 mg/L.

A series of novel 5-alkyl(aryl)-3-[(3-trifluoromethyl)anilino]-4,5-dihydro-1H-pyrazolo[4,3-d]pyrimidin-4-imines were designed and synthesized by the multistep reactions. 1 reacted with 3-(trifluoromethyl)aniline to obtain N,S-acetals 2 in the presence of 10 mol% DBU. 2 reacted with hydrazine to form 5-amino-3-[(3-trifluoromethyl)anilino]-1H-pyrazol-4- nitrile 3, the target compounds 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5l, 5m were obtained by the reaction of 3 with triethyl orthoformate followed by the cyclization of 4 with various amines. Their structures were confirmed by IR, ¹H NMR, EI-MS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate herbicidal activity against dicotyledonous weed Brassica campestris L at the concentration of 100 mg/L. For example, compounds 5f, 5g, 5h, and 5j possessed 60.1%, 63.4%, 67.1%, and 61.3% inhibition against Brassica campestris L at the concentration of 100 mg/L.

Strobilurins are a class of important agricultural fungicides that are used widely in plant protection. To find new strobilurin analogues with high activity against resistant pathogens, a series of new strobilurin derivatives bearing 1,2,4-triazole oxime ether side chain 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h were designed and synthesized. Their structures were confirmed by IR, ¹H NMR, EIMS, and elemental analyses. Bioassays indicated that some of the compounds showed good fungicidal activities in the concentration of 50 mg/L. For example, compound 3f possessed 100%, 100%, and 95.5% inhibition against Fusarium omysporum, Physalospora piricola Nose, and Gibberella saubinetii at the concentration of 50 mg/L, respectively.

An unexpected FeCl₃-mediated three-component cascade reaction has been used to construct structurally diverse pyrrolo[1,2-c]quinazolinone derivatives with potential biological activities. This method has advantages of mild conditions, simple work-up, as well as wide substrate scope, which makes it a powerful approach to the synthesis of diverse pyrrolo[1,2-c]quinazolinones. This cascade reaction involves 1,3-dipolar cycloaddition between azomethine ylides and allenoates, followed by intramolecular nucleophilic addition in the presence of FeCl₃. The obtained products could be easily transformed into derivatives with the pyrrolo[2,3-c]quinazoline alkaloid skeleton.

To find novel bleaching herbicide lead compounds, a series of novel 2-alkyl(aryl)-4-amino-3-[alkyl(alkoxy)carbonyl]-5-cyano-6-[(3-trifluoromethyl)phenoxy]-pyridines was designed and synthesized by the multistep reactions. N,S-acetal 1 reacted with 2 to obtain multisubstituted pyridines 3 in the presence of zinc nitrate as the catalyst. The target compounds 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5l were formed by the oxidation of 3, followed by the substitution with 3-(trifluoromethyl)phenol in the presence of potassium carbonate. Their structures were confirmed by IR, ¹H NMR, EI-MS, and elemental analyses. The preliminary bioassays indicated that some of them displayed moderate herbicidal activity against dicotyledonous weed Brassica campestris L at the concentration of 100 mg/L.

Two series of novel 4-acyl-2,5-disubstituted-3-hydroxypyrazoles 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h and 4-arylcarbonyl-3-substitutedisoxazol-5-ones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h, 7i were synthesized by the Scotton–Baumann reaction of 2,5-disubstituted-2,4-dihydro-pyrazol-3-ones 1 or 3-substituted-4H-isoxazol-5-ones 6 and various acyl chlorides, followed by the Fries rearrangement in the presence of calcium hydroxide and calcium oxide as the catalyst. Their structures were confirmed by IR, ¹H NMR, mass spectroscopy, and elemental analyses. ¹H NMR indicated that compounds 3 existed in enol forms and compounds 7 in keto configurations. The results of preliminary bioassays showed that some of the title compounds 3 and 7 exhibited moderate to good herbicidal activities against Brassica campestris L. at the concentration of 100 mg/L. Isoxazole compounds 7 showed better herbicidal activity against B. campestris L. than pyrazole compounds 3 did at the concentration of 100 mg/L. Moreover, most of the isoxazole compounds displayed higher herbicidal activity against B. campestris L. than Echinochloa crus-galli. However, these compounds showed weak herbicidal activities at the concentration of 10 mg/L.

A series of novel 5-aryl-1-(aryloxyacetyl)-3-(tert-butyl or phenyl)-4-(1H-1,2,4-triazol-1-yl)-4,5-dihydropyrazole 3a–3n were synthesized by the annulation of 2-aryloxyacetohydrazides with 3-aryl-1-t-butyl (or phenyl)-2-(1H-1,2,4-triazol-1-yl)prop-2-en-1-ones (2) in the presence of a catalytic amount of acetic acid. Compounds 2 were obtained by the Knoevenagel reactions of 1-t-butyl (or phenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone (1) with aromatic aldehydes in the presence of piperidine. Their structures were confirmed by IR, ¹H-NMR, ESI-MS, and elemental analyses. The preliminary bioassay indicated that some compounds displayed moderate to excellent fungicidal activity. For example, compounds 3l, 3m, and 3n possessed 100% inhibition against Cercospora arachidicola Hori at the concentration of 50 mg/L.

A series of novel acylpyrazole derivatives containing 1,2,3-thiadiazole ring 3a–3m were synthesized by the condensations of 1-phenyl-3-methyl-4-(substituted benzal or 4-methyl-1,2,3-thiadiazole-5-carbonyl)-5-hydroxypyrazole 2 with 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride or substituted benzoyl chloride. Their structures were confirmed by IR, ¹H-NMR, mass spectroscopy, and elemental analyses. The results of preliminary bioassays showed that some of the title compounds 3 exhibited moderate to good herbicidal activities against dicotyledonous plants (Brassica campestris L.) at the concentration of 100 mg/L. For example, compounds 3e, 3f, 3g, and 3k possessed 74.6%, 72.2%, 70.3%, and 84.5% inhibition against B. campestris L., respectively, whereas commercially available herbicide Sulcotrione showed only 35.0% inhibition at the same concentration. Moreover, these compounds displayed higher herbicidal activity against B. campestris L. than Echinochloa crus-galli. However, these compounds showed weak activities at the concentration of 10 mg/L.

A series of novel (Z)-1-tert-butyl (or phenyl)-2-(1H-1,2,4-triazol-1-yl)-ethanone O-[2,4-dimethylthiazole (or 4-methyl-1,2,3-thiadiazole) −5-carbonyl] oximes 5a–5c and (1Z, 3Z)-4,4-dimethyl-1-substitutedphenyl-2-(1H-1,2,4-triazol-1-yl)-pent-1-en-3-one O-[2,4-dimethylthiazole (or 4-methyl-1,2,3-thiadiazole)-5-carbonyl] oximes 6a–6e were synthesized by the condensations of (Z)-1-tert-butyl (or phenyl)-2-(1H-1,2,4-triazol-1-yl)-ethanone oximes 3 or (1Z, 3Z)-4,4-dimethyl-1-substitutedphenyl-2-(1H-1,2,4-triazol-1-yl)-pent-1-en-3-one oximes 4 with 2,4-dimethylthiazole-5-carbonyl chloride or 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride in the basic condition. Their structures were confirmed by IR, ¹H NMR, mass spectroscopy, and elemental analyses. The results of preliminary bioassays showed the title compounds 5 and 6 exhibited moderate to good fungicidal activities. For example, compound 6c possessed 86.4% inhibition against Fusarium oxysporum, and compound 6b exhibited 86.4 and 100% inhibition against Fusarium oxysporum and Cercospora arachidicola Hori at the concentration of 50 mg/L, respectively.

2-Chloro-5-(chloromethyl)-pyridine reacted with 3,4-dihydropyrimidin-2(1H)-ones 1 to afford 1-[6-aryl-1-(6-chloropyridin-3-yl-methyl)-2-(6-chloropyridin-3-yl-methylthio)-4-methyl-1,6-dihydropyrimidin-5-yl] carboxylates or ethanones 2 in good yields. The structure of the target compounds 2 was confirmed by IR, ¹H NMR, EI-MS, and elemental analyses, and compound 2a was further characterized by single crystal X-ray diffraction. The preliminary bioassay indicated that some of the title compounds possess moderate insecticidal and fungicidal activities. J. Heterocyclic Chem., (2011).

A series of α-hydroxy phosphonate derivatives containing pyrimidine moiety were designed and synthesized. Their structures were characterized by IR, ¹H NMR, MS and elemental analysis. The results of preliminary herbicidal activities (in vitro) showed that some of the title compounds 2 exhibited moderate herbicidal activities against dicotyledonous weeds (Brassica campestris L), and most of compounds 2 showed better activity against dicotyledonous weeds than monocotyledonous weeds (Echinochloa crus-galli). Further bioassays (in vivo) indicated that some of the title compounds 2 possessed good and selective herbicidal activity against amaranth pigweed (A. retroflexus) in both pre- and post-emergence treatments at the dose of 1.5 kg/ha. For exmple, compounds 2a, 2b and 2e exhibited 100% inhibition against A. retroflexus in pre-emergence treatment, and 91.7%, 98.8% and 99.5% inhibition in post-emergence treatment at the dose of 1.5 kg/ha, respectively.

In order to find novel high activity and low toxicity agrochemicals, a series of novel thiophosphoryl oximates containing thiazole and 1,2,3-triazole rings 4 were synthesized by the reactions of 1-{1-[(2-chlorothiazol-5- yl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}ethanone oxime with various asymmetric thiophosphoryl chlorides. Their structures were confirmed by IR, ¹H NMR, ³¹P NMR, EI-MS and elemental analyses. The target compounds existed as E-configuration, which was deduced by NMR analysis and by comparison with their pyridyl analog determined by X-ray diffraction. The results of preliminary bioassay indicate that some of title compounds possess moderate insecticidal and fungicidal activities.

A series of novel 1,3-dissubstitutedpyridyl(thiazolyl)methyl-2-substituted-methylideneimidazolidine derivatives 2 and 4 were designed and synthesized via the N-alkylation of the disubstituted heterocyclic ketene aminal derivative 1. When 1 (R = CN, R' = COOC₂H₅) was used as the starting materials, mono N-alkylated reaction can take place in good yields owing to the presence of the intramolecular hydrogen bond. However, as for 1 (R = R' = CN), it is difficult to obtain pure mono N-alkylated product. The structures of the target compounds were confirmed by IR, ¹H NMR, EI-MS and elemental analyses, and, in the case of 2c, by single crystal X-ray diffraction. The preliminary bioassay indicated that some of the title compounds possess moderate fungicidal and insecticidal activity.

A series of 3-[(6-chloropyridin-3-yl)methyl]-6-substituted-6,7-dihydro-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-imines were designed and synthesized via a multi-step sequence using 2-chloro-5-(chloromethyl)-pyridine as the starting material. Various primary aliphatic amines, hydrazine and hydrazide reacted with 3 to obtain the cyclization products 4. Their structures were confirmed by ¹H NMR and elemental analyses, some of them were also confirmed by IR, ¹³C NMR, MS and single crystal X-ray diffraction. The preliminary bioassay indicated that some of the target compounds 4 displayed moderate to weak fungicidal activity and insecticidal activity.

A series of pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidine derivatives, bearing phosphonylbenzyl chain in position 7, were conveniently synthesized in an attempt to obtain potent and selective antagonists for the A_2A adenosine receptor or potent pesticide lead compounds. Diethyl[(5-amino-4-cyano-3-methylsulfanyl-pyrazol-1-yl)-benzyl]phospho-nate (3), which was prepared by the cyclization of diethyl 1-hydrazinobenzylphosphonate (1) with 2-[bis(methylthio)methylene]malononitrile (2), reacted with triethyl orthoformate to afford diethyl[(4-cyano-5-ethoxymethyleneamino-3-methylsulfanyl-pyrazol-1-yl)-benzyl]phosphonate (4), which reacted with various acyl hydrazines in refluxing 2-methoxyethanol to give the target compounds 5a–h in good yields. Their structures were confirmed by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis. The crystal structure of 5e was determined by single crystal X-ray diffraction © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:634–638, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20478