Pyrimidine Fungicides - American Chemical Society

Chapter 23

Pyrimidine Fungicides: A New Class of Broad Spectrum Fungicides

Downloaded by CORNELL UNIV on June 19, 2012 | http://pubs.acs.org Publication Date: May 14, 1998 | doi: 10.1021/bk-1998-0686.ch023

Zen-Yu Chang, PamelaJ.Delaney, John O'Donoghue, and RuPing Wang Agricultural Products, Stine-Haskell Research Center, duPont and Company, Building 300, Newark, DE 19714

Broad spectrum fungicidal activities were shown by a class of pyrimidines substituted with nitrogen heterocycles. Biological data, synthesis, and structure-activity relationships are discussed The discovery of fungicidal activity of compounds 1, 2 (7) and 3 (Ferimzone®) (2) prompted us to undertake a major research program to explore the structure-activity of this class of chemistry. Based on the common structural features of these three compounds, we designed compounds represented by the general structure 4. We have focused our optimization effort in the Α-ring, B-ring and the aromatic or benzyl moieties shown in structure 4. Many of the compounds represented by 4 provided 100% control of economically important diseases such as wheat foot rot, wheat glum blotch, andriceblast in our discovery screens at a 200 PPM rate. Several compounds proved sufficiently active that they were evaluated in field tests to assess the potential for commercial development.

1 228

2

3

n = 0, 1 4

©1998 American Chemical Society

In Synthesis and Chemistry of Agrochemicals V; Baker, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1998.

229 Synthesis


Synthesis of different sub-classes of compounds of generic structure 4 will be discussed. The Α-ring and the aromatic moiety come primarilyfromcommercial sources and do not warrant much discussion. Rather, we will concentrate our discussion in the variation of B-ring. Pyrazolines 5 with a 5-membered Β-ring were prepared by condensation of the corresponding heterocyclic hydrazines with substituted 3-chloropropiophenones or 3-N,N-dimethylpropiophenones (Scheme 1). 3N, N-Dimethy lpropiophenones were prepared via the Mannich reaction (3).

5 Scheme 1 Tetrahydropyridazines 6 with a 6-membered B-ring were prepared by condensation of the hydrazines with substituted 4-chlorobutyrophenones. FriedelCrafts acylation of substituted benzenes with 4-chlorobutyrl chloride provided the requisite butyrophenones (Scheme 2).

Scheme 2 1,4-Dihydropyridazines 7 were prepared by condensation of the pyrimidinylhydrazines with benzoylpropionic acids to give pyridazinones. Reduction with one equivalent of lithium aluminum hydride (4) gave the intermediate aminal. Subsequent treatment with methanesulfonyl chloride in pyridine afforded the desired 1,4dihydropyridazines 7 (Scheme 3).



230

Scheme 3 The synthesis of 1,6-dihydropyridazines is shown in Scheme 4. Condensation of the pyrimidinylhydrazines with α,β-diketones gave the corresponding hydrazones as mixtures of E/Z isomers. Treatment of the mixtures with sodium hydride followed by addition of vinyltriphenylphosphonium bromide (5) provided the 1,6-dihydro pyridazines 8. The latter cyclization reaction did not work when the R group was 2pyridyl or 2-furanyl.

Bf Scheme 4


231


For the synthesis of 7-membered B-rings tetrahydrodiazepines 9, condensation of the pyrimidinylhydrazines with substituted 5-chlorovalerophenones was followed by treatment with sodium hydride (Scheme 5).

Scheme 5 The preparation of pyrazolines 5 in which the phenyl group is replaced by a benzyl group is shown in Scheme 6. The requisite chloroketones were prepared by coupling reactions between benzyl bromide and 3-chloropropionyl chloride catalyzed by a palladium reagent and zinc powder (

Pyrimidine Fungicides - American Chemical Society

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