Series of novel furan/thiophene and piperazine-containing 1,2,4-triazole Mannich bases and bis(1,2,4-triazole) Mannich bases have been conveniently synthesized via Mannich reaction with triazole Schiff bases, various piperazine derivatives, and formaldehyde as intermediates in good yields. Their structures were characterized by melting points, ¹H NMR, ¹³C NMR, IR and elemental analysis. The preliminary bioassay showed that most compounds exhibited significant in vitro and in vivo fungicidal activity against several test plant fungi. Among 32 new compounds, the trifluoromethyl-containing compounds showed superior activity than the methyl-containing ones. Several compounds, such as F8, F9, F10, G5, H7, H8, I3 and I4, were comparable with some commercial fungicides against different fungi during the present study and could be further structurally optimized. Meanwhile, several compounds showed good herbicidal activity against Brassica campestris at 100 µg/mL and KARI inhibitory activity at 200 µg/mL. However, compounds exhibited poor insecticidal activity against oriental armyworm at 200 µg/mL in the preliminary studies. The research results will provide useful information for the design and discovery of new agrochemicals with novel heterocyclic structures.

The structure of osthole has been modified to improve its larvicidal activity against mosquitoes. A new efficient synthesis of osthole derivatives with Grignard reagents has been developed, which employs CuI and LiCl as promoters and covers a broad range of substrates to afford the corresponding products in mild to good yields (up to 83%). Bio-activity evaluation showed that several products exhibited better activities than osthole.

Due to a novel mode action, low toxicity to mammals and low residue characteristics, phthalic acid diamides have aroused considerable interests in agricultural chemistry. With introduction of N-cyano, N-trifluoroacetyl, N-carbamoylsulfiliminyl and sulfoximinyl substituents into phthalamides, 12 novel derivatives containing trifluoromethyl moiety were designed and synthesized. All title compounds were characterized by ¹H NMR and high-resolution mass spectrometry. The preliminary results of biological activity assessment indicated that some title compounds exhibited moderate to good insecticidal activities against oriental armyworm (Pseudaletia separata Walker). In particular, Va gave higher activity against oriental armyworm and diamondback moth. The present work reported that the new trifluoromethylated diamides incorporating N-trifluoroacetylsulfoximinyl moieties are potential lead compounds for further structure optimization, providing some insight into the relating structure-activity relationship.

In this article, we report the synthesis and herbicidal activities of sulfonylureas bearing the 1,3,4-thiadiazole moiety. The target compounds 9a, 9b, 9c, 9d, 9e, 9f, 9g, 9h, 9i, 9j, 9k, 9l were synthesized using 2-hydrazinocarbonyl benzenesulfonamide (4) and phenyl pyrimidinecarbamates as starting materials. The key intermediate, 2-(4,5-dihydro-5-thioxo-1,3,4-thiadiazol-2-yl)benzenesulfonamide (5), was prepared from 4 and CS₂ via a conventional method or an improved method. The improved method, in which sulfonamido group acts as a directing group for the cyclization reaction, is more concise and efficient. The structures of the target compounds were determined by IR, ¹H-NMR, ¹³C-NMR, MS, and elemental analysis. Their herbicidal activities were screened by Petri dish tests and pot tests. As the results, sulfonylureas 9h and 9j inhibited Brassica napus, Amaranthus retroflexus, and Echinochloa crusgalli at the 15 g/ha level, which is at the same level as azimsulfuron. Moreover, the safety tests showed that 9j was safe to wheat at dosage of 60 g/ha and might develop further into a herbicide in wheat field.

In order to discover novel insecticides with the new action mode on ryanodine receptor (RyR), a series of novel phthalic acid diamide derivatives were designed and synthesized. All compounds were characterized by ¹H NMR spectra and HRMS. The preliminary results of biological activity assessment indicated that some title compounds exhibited excellent insecticidal activities against Mythimna separata, Spodoptera exigua, and Plutella xylostella. The title compound 3-nitro-N-cyclopropyl-N′-[2-methyl-4-(perfluoropropan-2-yl)phenyl]phthalamide (4a) was more efficient against diamondback moths than the control (chlorantraniliprole). The effects of some title compounds on intracellular calcium of neurons from the Spodoptera exigua proved that the title compounds were RyR activators.

In search of environmentally benign compounds with high biological activity, low toxicity and low resistance, 8 novel benzoyl hydrazines containing pyrazole were designed and synthesized. All compounds were characterized by ¹H NMR spectra and HRMS. The preliminary results of biological activity assessment indicated that most of title compounds exhibited certain insecticidal activities against Mythimna separata Walker at 200 mg·L⁻¹ but excellent fungicidal activities against six fungus at 50 mg·L⁻¹, which were better than the control.

A series of novel N-pyridylpyrazole carbonyl thioureas were designed and synthesized. Their structures were characterized by melting points, ¹H NMR, IR and elemental analysis or HRMS. The bioassay tests indicated that some of these compounds exhibited moderate insecticidal activity against Mythimna separata Walker and Culex pipiens pallens. Among 17 compounds, 5n and 5p showed 100% larvicidal activity against Mythimna separata Walker at the test concentration of 100 mg/L.

Two series of novel anthranilic diamide insecticide containing trifluoroethyl ether were designed and synthesized, and their structures were characterized by ¹H NMR spectroscopy, elemental analysis and single crystal X-ray diffraction analysis. The insecticidal activities of the new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal activities. The insecticidal activities of compounds 19a, 19b, 19d, 19g, 19k and 19m against oriental armyworm at 2.5 mg·kg⁻¹ were 100%. The larvicidal activities of 19a, 19b, 19c, 19d, 19e, 19g and 19n against diamond-back moth were 100% at 0.1 mg·kg⁻¹. Surprisingly, most of them still exhibited perfect insecticidal activity against diamond-back moth when the concentration was reduced to 0.05 mg·kg⁻¹, which was higher than the commercialized Chlorantraniliprole.

A series of 3-thiazolidine acetic acid-2-(per-O-acetylglycosyl)-1′-imino-α-(substituted)-4-oxo ethyl ester derivatives (3a–t) were prepared via the reaction of substituted amino acid-N-[(per-O-acetylglycosylamino)thioxomethyl]-ethyl ester with ethyl bromoacetate. The crystal structure of 3-thiazolidine acetic acid-2-(2′,3′,4′,6′-tetra-O-acetyl-β-d-galactoyranosyl)-1′-imino-α-methyl-4-oxo ethyl ester 3g and ¹H-¹³C HMBC (2D NMR experiments) measurements of 3-thiazolidine acetic acid-2-(2′,3′,4′,6′-tetra-O-acetyl-β-d-galactopyranosyl)-1′-imino-α-(1-methylthio)ethyl-4-oxo ethyl ester 3j revealed the exclusive regioselectivity during the closure of these rings toward the N-2 position of the thiourea moiety. Furthermore, the crystal structure of compound 3g showed that the attack of N-1 was blocked by sugar ring owing to the steric effect. The bioactivity data suggested that compound 2e has mild anticancer activity.

In an attempt to search for potent antifungal agents, a series of novel 1-substituted phenyl-4-[N-[(2′-morpholinothoxy)phenyl]aminomethyl]-1H-1,2,3-triazoles 5a–m was designed and synthesized via Huisgen cycloaddition reaction between various (2-morpholinoethoxy)-N-(prop-2-ynyl)aniline and different azidobenzene. Their chemical structures were characterized by ¹H NMR and elemental analysis. A cleaner reaction with milder conditions and satisfactory yields was observed in the micorwave-assisted synthesis of 4a–c. The fungicidal activity of some target compounds were evaluated in vitro against Fusarium omysporum, Physalospora piricola, Alternaria solani, Cercospora arachidicola and Gibberella zeae at 50 μg/mL. The bioassay results indicated that some compounds exhibited moderate fungicidal activities. Furthermore, compound 5h displayed equal activity to the positive control compounds against Alternaria solani.

A series of novel Mannich bases with trifluoromethyl-1,2,4-triazole and substituted benzylpiperazine moieties were synthesized. Their structures were confirmed by IR, ¹H NMR and elemental analysis. The single crystal structure of compound 4r was also determined. The preliminary bioassays showed that most of the lead compounds had low herbicidal activity against Brassica campestris, Echinochloa crusgalli, and KARI enzyme. However, most of them exhibited significant fungicidal activity at the dosage of 50 μg/mL toward five test fungi. Among the 18 novel compounds, several showed superiority over the commercial fungicide Triadimefon against Cercospora arachidicola and Fusarium oxysporum f. sp. cucumerinum during this study. Meanwhile, some compounds displayed plant growth regulatory activity at the dosage of 10 μg/mL.

A series of new N,N′-diacylhydrazine derivatives were synthesized efficiently under microwave irradiation. Their structures were characterized by ¹H NMR, MS, and elemental analysis. Various biological activities of these compounds were tested. Most of them exhibited higher herbicidal activities against dicotyledonous weeds than monocotyledonous weeds. In addition, favorable in vivo fungicidal activities were also found of these compounds against Cladosporium cucumerinum, Corynespora cassiicola, Sclerotinia sclerotiorum(Lib.)de Bary, Erysiphe cichoracearum, and Colletotrichum orbiculare (Berk aLMont) Arx. All compounds displayed excellent plant growth regulatory activities: 100% inhibition was achieved against the radicle growth of cucumber. To further investigate the structure–activity relationship, comparative molecular field analysis was performed on the basis of herbicidal activity data, resulting in a statistically reliable model with good predictive power (r² = 0.913, q² = 0.556). Based on the calculation, five additional novel compounds were designed and synthesized. Satisfyingly, compound 4u displayed excellent herbicidal activity (94.7%) at 1500 g/ha, although it is less active than 2,4-D. Meanwhile, this compound also exhibited good fungicidal activity against C. orbiculare (Berk aLMont) Arx (82.16%).

In order to look for novel insecticides containing N-pyridylpyrazole, ten novel pyrazolecarboxamides containing different ortho-substituents in the aniline part were synthesized, and their structures were characterized by ¹H NMR, ¹³C NMR and HRMS. The single crystal structure of10bwas determined by X-ray diffraction. Their evaluated insecticidal activity against oriental armyworm (Mythimna separata) indicated that all the compounds exhibited moderate insecticidal activities.

A series of cycloadducts--pyrazoles via 1,3-dipolar cycloaddition reactions of generated nitrilimines with N-(4-chloro-2-fluorophenyl)maleimide were described. The novel compounds synthesized were characterized by ¹H NMR, MS, and elemental analysis. The fungicidal tests showed that most of the title compounds exhibit significant fungicidal activities against Corynespora cassiicola.

Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) catalyzes the second common step in branched-chain amino acid biosynthesis. This enzyme is an important target for drug design. Based on the crystal structure of ketol-acid reductoisomerase/N-hydroxy-N-isopropyloxamate (IpOHA) complex, we have carried out high throughput receptor-based virtual screening of the ZINC/drug like database (2 000 000 compounds) to look for novel inhibitors of KARI for the first time. Some novel compounds were found to inhibit rice KARI in vitro among 15 procured compounds. This method can provide useful information for further design and discovery of KARI inhibitors.

12 novel pyrazolecarboxamides containing cyano substituted N-pyridylpyrazole were synthesized, and their structures were characterized by ¹H NMR and HRMS techniques. Their evaluated insecticidal activities against oriental armyworm (Mythimna separata) indicated that the cyano-containing pyrazolecarboxamides exhibited moderate insecticidal activities. Compounds 6i and 6k showed comparable higher activity than corresponding anthranilic diamide 6m.

Ten novel neonicotinoid derivatives containing N-oxalyl groups were designed and synthesized, and their structures were characterized by ¹H NMR, MS, IR, elemental analysis and single crystal X-ray diffraction analysis. The insecticidal activities of the new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal activities.

A series of novel triazolinones were synthesized and their structures were characterized by ¹H NMR, elemental analysis and single-crystal X-ray diffraction analysis. The herbicidal activities were evaluated against Echinochloa crusgalli (L.) Beauv., Digitaria adscendens, Brassica napus and Amaranthus retroflexus. The herbicidal activity data indicated that the title compounds had higher activities with substituted benzyl group moieties than with other groups such as sulfonyl, alkyl, etc. To further investigate the structure–activity relationship, comparative molecular field analysis was performed on the basis of herbicidal activity data. Both the steric and electronic field distributions of comparative molecular field analysis are in good agreement in this work. The results showed that a bulky and electronegative group around the ortho- or para-positions of the benzene ring would possibly lead to higher activity. Based on the comparative molecular field analysis, compound I-23 was designed and synthesized, which display as good herbicidal activities as the commercial herbicide, carfentrazone-ethyl. The activity against Digitaria adscendens is 66.1% under pre-emergence at 300 g of a.i./ha.

In search of environmentally benign insecticides with high activity, low toxicity and low residual effects, a series of novel amides (sulfonamides) containing N-pyridylpyrazole were designed and synthesized. Their chemical structures were characterized by ¹H NMR, MS and elemental analysis or HRMS. The bioassay tests indicated that some of these compounds exhibited moderate insecticidal activities against Mythimna separata Walker and Culex pipiens pallens.

In search of environmentally benign insecticides with high activity, low toxicity and low residue, a novel series of anthranilic acid esters containing N-pyridylpyrazole were designed and synthesized. All of the compounds were characterized and confirmed by IR, ¹H NMR, MS and elemental analysis. The single crystal structure of 14d was determined by X-ray diffraction. The bioassay tests showed that the synthesized compounds exhibited good insecticidal activities against Mythimna separata Walker and Culex pipiens pallens.

A novel series of guanidine derivatives were designed, synthesized and confirmed by FTIR, MS, ¹H NMR and elemental analysis. The single crystal structure of 11b was determined by X-ray diffraction. Herbicidal activities of these guanidine derivatives were evaluated through barnyardgrass and rape cup tests, among which compounds 11a, 11b, and 11c against Brassica campestris reached 71.2%, 86.7%, and 86.9% at 100 µg·mL⁻¹ respectively. The preliminary ketol-acid reductoisomerase test showed that the synthesized compounds had weak activities.

Novel structures of bis-heterocyclic pyrrodiazole derivatives containing pyrazole were designed and synthesized. The title compounds were characterized by ¹H NMR, IR, MS, and elemental analysis. Biological activities of three intermediate compounds and 25 pyrrodiazole derivatives were tested in vivo and in vitro. Some of the title compounds exhibited certain herbicidal activities against barnyardgrass and rape. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:21–27, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20369