Six novel chloro-containing 1-aryl-3-oxypyrazoles TMa-TMf with an oximino ester or an oximino amide moiety were prepared by the reaction of 1-aryl-1H-pyrazol-3-ols with benzyl bromide. Their structures were characterized by 1 H-NMR, 13 C-NMR, IR, MS, and elemental analysis. A preliminary in vitro bioassay indicated that compounds TMa, TMe and TMf displayed excellent fungicidal activity against Rhizoctonia solani and could be used as potential lead compounds for further development of novel fungicides.

A series of novel strobilurin analogues (1a-1f, 2a-2e, 3a-3e) containing arylpyrazole rings were synthesized and characterized by NMR spectroscopy. The structures of 1f, 2b and 3b were also determined by single crystal X-ray diffraction analysis. These analogues were collected together with other twenty-eight similar compounds 4a-4f, 5a-5h, 6a-6h and 7a-7f from our previous studies, for in vitro bioassays and thorough structure-activity relationships (SARs) studies. Most compounds exhibited excellent-to-good fungicidal activity against Rhizoctonia solani, especially 5c, 7a, 6c, and 3b with 98.94%, 83.40%, 71.40% and 65.87% inhibition rates at 0.1 μg mL−1, respectively, better than commercial pyraclostrobin. Comparative molecular field analysis (CoMFA) was employed to study three-dimensional quantitative structure-activity relationships (3D-QSARs). Density functional theory (DFT) calculation was also carried out to provide more information regarding SARs. The present work provided some hints for developing novel strobilurin fungicides.

Strobilurin fungicides [1][2][3] have attracted enormous attention because of their low toxicity toward mammalian cells, diverse bioactivities, and exceptional broad-spectrum and high activity. [4][5][6] It has been demonstrated that the (E)-β-methyl methoxyiminoacetate or isosteric (E)-β-methyl methoxyacrylate group is the essential pharmacophore of Strobilurin fungicides. 7 Linking the pharmacophore with a structurally diverse side chain is an effective way of obtaining new strobilurin derivatives. [8][9][10][11][12] For example, previous researchers have synthesised new strobilurins such as trifloxystrobin, metominostrobin and pyraclostrobin through modification of the structure of methoxyacrylate. 13,14 As a continuation of our research into fungicidal aryloxypyrazoles, the oxime ether pharmacophore of strobilurins were introduced into the 1-aryl-3-oxypyrazole structure of pyraclostrobin according to the principle of active parts combination, and a series of new aryloxypyrazole-based strobilurin analogues have been designed and synthesised (Fig. 1).We now report the design and synthesis of a series of 16 novel oxime ether derivatives containing 1-aryl-3-oxypyrazoles. The single crystal of one of them, the 4-chorophenyl heterocyclic ester 5c has been verified, which could help point the way to new structures with enhanced biological activities. The fungicidal activities against Rhizoctonia solani were evaluated and their preliminary structure-activity relationships were discussed. Furthermore, density functional theory (DFT) studies were carried out and their relationship with biological activities was investigated. Results and discussionIntermediates 1a-h and 4 were synthesised using reported pathways (Schemes 1 15 and 2 16 respectively). In a previous study, 16 we have prepared the 4-chorophenyl heterocyclic ester 5c and the corresponding N-methyl amide 6c. Using similar methods, we now report the synthesis of five more X-phenyl heterocyclic esters 5a-b, d-h and five more X-phenyl heterocyclic N-methyl amides 6a-b, d-h (Scheme 3). All the new products were characterised by their 1 H NMR and 13 C NMR spectra and by elemental analysis. X-ray crystallographyThe single X-ray crystallographic analysis of one of the title compounds, the 4-chlorophenylheterocyclic-ester 5c showed

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