Research and development of a novel rice herbicide, pyrimisulfan^#

Introduction

Almost all Japanese rice farmers apply one-shot herbicides, which are now essential tools for weed control in paddy fields. Approximately 90% of one-shot herbicides contain 3 or 4 active ingredients. Through our research into developing a paddy rice herbicide, we found a new ALS herbicide, pyrimisulfan, with optimal physical and chemical properties for a one-shot paddy herbicide by exchanging the acidic group, the bridge, and the hydrophobic group of our PC herbicide. Furthermore, we developed Best Partner®, which is the first one-shot herbicide for rice containing only one a.i., with our original formulation technology, maximizing the herbicidal activity of pyrimisulfan under versatile environmental conditions. Pyrimisulfan is an ultimate herbicide that has realized the key words: “Food Safety and Security” and “Sustainable Agriculture.”

This paper describes the history of the discovery along with the synthesis, structure–activity relationship, biological properties, safety, and environmental fate of pyrimisulfan.

1. Discovery and synthesis

We have so far developed and commercialized our original Pyrimidinyl Carboxy (PC) herbicides. These compounds exhibit excellent herbicidal activities by specifically and strongly inhibiting ALS of plants. Because mammals lack the ALS enzyme, these herbicides are inherently safe to mammals, and, coupled with high activity with low use rates, PC herbicides are extensively used worldwide as environmentally friendly herbicides.

During the course of research on PC herbicides, we confirmed that to exhibit high ALS inhibitory activity and high herbicidal activity, a hydrophobic group, pyrimidine ring, and acidic group must be placed in a certain configuration via a suitable linkage group. PC herbicides have a carboxyl group, but because the carboxyl-group has comparable high acidity, they often have the problem of being susceptible to the effects of water movement and, consequently, having unstable herbicidal activity during preemergence application under flooded conditions.

Furthermore, because the oxy-bridge, which is characteristic of PC herbicides, is degraded by metabolism, attempts have been made to change the oxy-bridge to a carbon-bridge in order to secure adequate residual activity and also to change the acidic group to a sulfonamide group to provide a broader weed-control spectrum. As a result, a sulfonanilide with a pyrimidinyl-containing group at the 2′-position was redesigned and synthesized.

In pot tests of the herbicidal activity of chloromethanesulfonanilide under flooded conditions, the ED₉₀ values for Monochoria vaginalis and Schoenoplectus juncoides varied from 16 to 63 g a.i. ha⁻¹. Then, with the aim of further enhancing the herbicidal activity and expanding the weed-control spectrum, we made various modifications to the sulfonamide group, as well as at the bridge moiety, and also introduced various substituents on the phenyl ring. Among the compounds synthesized, pyrimisulfan showed the best broad-spectrum preemergence herbicidal activity against grass, sedge, and broadleaf weeds without injury to rice.

The key intermediate of pyrimisulfan was synthesized by reacting o-nitrophenyl-acetonitrile and 4,6-dimethoxy-2-methylsulfonylpyrimidine. Then, the intermediate was oxidized, dehydrocyanated, and reduced to make an aniline with a pyrimidinyl-containing group at the 2′-position. Pyrimisulfan was obtained by sulfonation of the aniline.

2. Structure-activity relationship

For the novel series of sulfonanilides with a pyrimidinyl-containing group at the 2′-position, structure-activity relationships were probed by substituting the sulfonyl group, the bridge, and the benzene ring. Among the sulfonamides, haloalkyl and cyanoalkyl compounds showed comparatively good herbicidal activity. Above all, the F₂CH compound showed high activity and a broad spectrum for controlling weeds, including Echinochloa oryzicola. The most preferable substitution position on the benzene ring was the 6-position, and the lower alkyl group showed high herbicidal activity and a broad spectrum of weed control. Among the compounds tested, the methoxymethyl group was the best. With respect to the bridge moiety, the hydroxyl group was the best.

3. Biological properties

Pyrimisulfan is a herbicide for controlling a wide range of weeds with selectivity in transplanted and water-seeded rice. The low application rate of 50–75 g a.i. ha⁻¹ has provided outstanding efficacy on major weeds of Japanese paddy fields, such as Echinochloa spp., Schoenoplectus juncoides, Monochoria vaginalis, and Lindernia spp., with only a single a.i. In addition, it can control other troublesome weeds, including Sagittaria trifolia, Scirpus nipponicus, Bolboschoenus maritimus, Eleocharis kuroguwai, and sulfonylurea-resistant weeds, which have presented serious problems in recent years. It has a wide application window from pre- to postemergence of the weed and is very easy to use. Pyrimisulfan has sufficient rice safety and residual activity. As is common to all herbicides, however, it could cause phytotoxicity and reduced efficacy depending on paddy field conditions. To optimize its performance, this compound has been incorporated in a new release control formulation technology. In Japan, pyrimisulfan alone is commercially available under the trade name Best Partner®. It is commercialized as My Way® in combination with oxaziclomefone, and as Yaiba® in combination with fentrazamide, whereas Muso® is the trade name for the mixture with mefenacet. Best Partner® is the first one-shot herbicide for rice containing only one a.i., and it has shown excellent preemergence herbicidal activity against broad-spectrum paddy weeds without injury to rice plants.