Chapter 9
3-Benzyl-1-methyl-6-trifluoromethyluracils: A New Class of Protox Inhibitors
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Marvin J.Konz,Harvey R. Wendt, Thomas G. Cullen, KarenL.Tenhuisen, and OlgaM.Fryszman Agricultural Products Group,FMCCorporation, P.O. Box 8, Princeton,NJ08543
3-Benzyl-1-methyl-6-trifluoromethyluracils, as a new class of herbicides, were developed from a weakly active Protox inhibitor, N-[(4-chlorophenyl)methyl]glutarimide. In preemergent applications, 3-[(2,3,5-trichlorophenyl)methyl]-6-trifluoromethyl-1-methylpyrimidine-2,4-dione controlled broadleafs and grasses at rates of 10-30 g/ha in greenhouse evaluations and at rates of 60-120 g/ha in field trials with corn as the most tolerant crop. The historical background of this discovery, structure -activity relationships and the synthesis of 3-benzyluracils is discussed.
N-[(4-Chlorophenyl)methyl]glutarimide (1) was screened in the excised cucumber (/) and algae assay (2) for intrinsic herbicidal activity. The biodata indicated 1 to be a weak Protox inhibitor. On greenhouse testing, the glutarimide was active in pre- and postemergent applications but only at a rate of 8 kg/ha. ,0
Ο 1 Weak PPO Inhibitor • Excised Cucumber : pl 4.1 • Algae: ρϊ ο4.7 50
5
©1998 American Chemical Society
In Synthesis and Chemistry of Agrochemicals V; Baker, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1998.
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Although 1 was not very active, the structural comparison to two herbicide classes, 5-benzyloxy-l,3-dioxanes (2) (3,4) and 2-benzylisoxazolidine-3,5-diones (3) (5), was extremely interesting. The former is a mitotic inhibitor (Plummer, M . J., FMC Corporation, unpublished data) with grass toxicant properties whereas the latter is a carotenoid biosynthesis inhibitor with broadleaf and grass activity. It is quite unusual to observe a change in the mechanism of action which could be attributed to a change in the heterocyclicringportion of the molecule. For this reason and the absence of reported herbicidal activity of N-benzylglutarimides, it was decided to prepare additional analogs for testing.
2
3
N-Benzylglutarimides As the first approach, a chlorine probe strategy was employed to determine what positions of substitution in the aromatic ring would contribute to activity. For this purpose, ten compounds were prepared as shown in Scheme 1. The set of com pounds were evaluated in both the excised cucumber and algae assays. The data is summarized in Table I. The algae assay data was chosen for the Free-Wilson analysis as it met the criteria that the data should have a minimum spread of two orders of magnitude. The results of this analysis are shown in Table II. The conclusion was that substitution at the 3- and 5-positions had a significant contribution to activity whereas substitution at the 2- and 4-positions had a negligible effect. This is in contrast to other Protox inhibitors where substitution at the 2,4,5-positions of the aromaticringis a criterion for biological activity. χ
Ο
Ο
Scheme 1. Synthesis of N-Benzylglutarimides
In Synthesis and Chemistry of Agrochemicals V; Baker, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1998.
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Table L Intrinsic Assay Data: N-Benzylglutarimides Excised Cucumber Algae Compound No. X Pho pho 1 4.7 4.1 4-C1 4
