Synthesis and Fungicidal Activity of (E)‐5‐[1‐(2‐Oxo‐1‐oxaspiro[4,5]dec/non‐3‐en‐3‐yl)ethylidene]‐2‐aminoimidazolin‐4‐one Derivatives

Abstract

The novel fungicidal agents, (E)-5- [1-(2-oxo-1-oxaspiro[4,5]dec/non-3-en-3-yl)ethylidene]-2-aminoimidazolin-4-one derivatives, were designed and synthesized in moderate to excellent yields in four steps using α-hydroxyketone and diketene as raw materials and characterized by HR-ESI-MS, 1 H NMR and X-ray diffraction. The preliminary bioassay showed that some of these compounds, such as 5e, 6a, 6e, and 7h exhibit 87.8%, 91.3%, 89.9% and 87.8% inhibition rates against Sclerotinia scleotiorum, 3b, 3c, 4c and 7h exhibit 96.4%, 92.5%, 90.3% and 76.9% inhibition rates against Phytophthora capsici at the concentration of 50 µg/mL, respectively. These compounds exhibited significant fungicidal activities against S. scleotiorum and P. capsici with EC 50 values of 2.56 -11.60 µg/mL, and compounds 6e and 7h exhibited weak inhibition against the spore germination of S. scleotiorum, while the spore germination of P. capsici was strongly inhibited by compound 7h solution. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observation indicated that compound 7h had a significant impact on the structure and function of the hyphal cell wall of P. capsici mycelium. Keywords(E)-5-[1-(2-oxo-1-oxaspiro[4.5]dec/non-3-en-3-yl)ethylidene]-2-aminoimidazolin-4-one, synthesis, fungicidal activities www.cjc.wiley-vch.de (E)-5-[1-(2-Oxo-1-oxaspiro[4,5]dec/non-3-en-3-yl)ethylidene]-2-aminoimidazolin-4-one Chin. 1135 15H); HR-ESI-MS calcd for C 24 H 30 N 3 O 4 [M＋H] ＋ (E)-5-[1 5]dec/non-3-en-3-yl)ethylidene]-2-aminoimidazolin-4-one Chin.

Synthesis and Fungicidal Activity of (E)-5-[1-(4-Phenyl-2-oxo-1-oxaspiro[4.5]dec-3-en-3-yl)ethylidene]-2-aminoimidazolin-4-one Derivatives

“…The 1 H NMR spectra of products 5a-s were similar to those compounds reported in the literature. 21,22,26 In the previous paper, 22 the configuration of the C=C double bond in this class of compounds was ascertained to be of E-configuration according to X-ray diffraction analysis, so the structures of compounds 5a-s should have the same E-configuration of the C=C double bond, being the same as those previously reported in the literature. 26,27 The parent skeleton of the imidazolinone moiety, i.e., 2-amino-1,5-dihydro-4H-imidazolin-4-one, was consistent with previously reported X-ray structures, 22 and with other similar compounds described in the literature.…”

“…demonstrated improved fungicidal activity. 22 We also tried to replace the 4-methyl moiety with a 4-methoxy group to synthesize new derivatives and obtain insights into the structure-activity relationships of this type of compound. However, this proved unsuccessful due to an unexpected Michael addition-elimination reaction during the preparation of a key intermediate using 3-acetyl-4-methoxybutenolide and thiohydantoin.…”

“…Instead, we paid attention to the synthesis and evaluation of the activity of the 4-phenyl analogues (Schemes 1 and 2). As shown in Scheme 2, the intermediate 2 was prepared in 98% yield following the literature procedures, [22][23][24][25] via the reaction of easily available (1hydroxycyclohexyl)(phenyl)methanone (1) with diketene. The yield was much higher than those of the 4-methyl and 4-methoxy analogues reported in the previous papers.…”

“…Finally, intermediate 4 was reacted with different anilines or arylalkylamines under reflux to produce the target compounds 5a-s in moderate to excellent yields. 21,22 In the 1 H NMR spectra, the chemical shifts of the methyl groups in compounds 2-4 were easily assigned, while complex resonances due to the methyl groups and broad NH proton signals were observed due to the existence of tautomers of the 2-aminoimidazolin-4-one moiety in solution after transformation into compounds 5a-s. The 1 H NMR spectra of products 5a-s were similar to those compounds reported in the literature.…”

“…The synthesis of the intermediate 3 was performed following the process in our previous papers 21, 22 by the reaction of 2 (13.4 g) with thiohydantoin (6.3 g). 3, 4 and 5a,b,d-f,h-k, 5-[1-(2-oxo-4-phenyl-1-oxaspiro[4.5]dec-3-en-3-yl)ethylidene]-1,5-dihydro-4H-imidazol-4-one (4) The synthesis of the intermediate 4 was performed according to the method in our previous papers 21, 22 by the reaction of 3 (7.4 g) with methyl iodide (1.4 mL).…”