Plant protecting and regulating compositions – Plant growth regulating compositions – Organic active compound containing
Reexamination Certificate
2000-02-02
2001-10-02
Ramsuer, Robert W. (Department: 1626)
Plant protecting and regulating compositions
Plant growth regulating compositions
Organic active compound containing
C047S05810R
Reexamination Certificate
active
06297194
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to a method for the production of phosphonopyrazole compounds and related compositions and methods.
BACKGROUND OF THE INVENTION
Cross-fertilization of closely related plants can result in progeny that have a desirable combination of traits not possessed by either inbred parent. This phenomenon, known as heterosis or hybrid vigor has been identified in major crop species (Stuber,
Plant Breeding Rev
. 12:29-65, 1994). Hybrid plants often have substantially superior agronomic performance characteristics, including, for example, plant size, grain yield, disease resistance, herbicide tolerance, and climatic adaptation.
A major limitation in the production of hybrid seed for most crop species is the lack of simple, reliable and economical methods of generating male-sterility while leaving female gametes intact and accessible for cross-pollination by a suitable pollen donor. Gametocides, or chemical hybridizing agents (CHAs), are useful not only for producing hybrid plants but also for controlling gene flow from a genetically modified crop plant to related wild species.
In some plants, such as corn, physical removal of the organ containing male gametes is relatively straightforward because the organ is both exposed and spatially separated from the female gametes. However, most crop species have both functional male and female organs within the same flower, so that emasculation is neither simple nor straightforward, making this process labor intensive and expensive. Furthermore, it is difficult to ensure the complete absence of self-pollination through these approaches.
Several naturally occurring genetic mechanisms of male sterility have been exploited for the production of hybrid seed in some plant species, including various cytoplasmic male sterility (CMS) systems. A disadvantage of strategies involving CMS is that they require three distinct lines to produce a single crossed hybrid: the male-sterile female parent line; a maintainer line that is isogenic to the male-sterile line but contains fully functional mitochondria; and the male parent line. Many CMS types have unfavorable characteristics that eliminate or restrict their use, including undesirable linked or pleiotropic characteristics such as disease susceptibility, breakdown of sterility, and inconsistent and/or complexly inherited fertility restoration. Furthermore, CMS systems are unavailable in many important crop species.
Chemical gametocides have been described, including pyridines (EP 0 276 204), pyridones and pyridazines (U.S. Pat. Nos. 4,115,101 and 4,345,934), glyphosate (U.S. Pat. No. 4,735,649), 5-oxy- or amino-substituted cinnoline (U.S. Pat. No. 5,129,939), pyridazine (U.S. Pat. Nos. 5,062,880 and 4,345,934), diazabicycloctane (U.S. Pat. No. 4,925,477) and N-alkyl-4-oxonicotinate compounds (U.S. Pat. No. 4,714,492). One commercial male gametocide for wheat, Genesis® (Monsanto Company, St. Louis, Mo.; see U.S. Pat. No. 5,062,880), is an effective gametocide and is the standard for comparison and development of new gametocides for wheat. In addition, some phosphonyl-substituted pyrazoles, including some 3-hydroxy(alkoxy)-pyrazole-4-ylphosphonates, have systemic movement in plants and have been reported to be useful as insecticides in plants; however, this class of compounds was said to be nonphytotoxic and no gametocidal activity was reported (DE 4139849).
Few chemical hybridizing agents (CHAs) have been used for the commercial production of hybrid seed, primarily because of their lack of selectivity for gametes in general, and for male gametes in particular. Systemic movement and selective phytotoxic activity are necessary requirements for an effective gametocide. Many compounds destroy or impair male gametes of a plant but also kill female gametes and vegetative tissues. Compounds that selectively target the gametes to a greater extent than vegetative tissues are generally non-discriminating regarding the sex of the gametes destroyed. In addition, many chemical gametocides with good selectivity have toxicological issues or other environmental issues that limit the use of these compounds for production of commercial levels of hybrid seeds.
Genetic engineering has also resulted in strategies for causing male sterility, such as the use of protoxin (U.S. Pat. No. 5,254,801) and antisense (U.S. Pat. No. 5,728,926) technology.
Other desirable characteristics may be dictated by the plant to be treated. For example, in the case of wheat, male and female gametes are found inside the same flower, which remains closed until the male gametes release their pollen onto the female gametes. When the flower opens, self-fertilization is normally essentially complete. A useful wheat gametocide must kill the male gametes but not interfere with floral opening when the female gametes are ready to be fertilized, so that fertilization by pollen from other wheat plants can occur. The need for effective wheat gametocides or chemical hybridizing agents for wheat has been the subject of extensive research (Tschabold et al.,
Crop Science
28:583-588, 1988).
SUMMARY OF THE INVENTION
We have developed a novel process for production of phosphonopyrazole compounds by contacting an alkaline salt of 3-hydroxy-2-(dialkyl phosphono)acrylate and either a protonated hydrazine, a protonated alkyl hydrazine, or a protonated aryl hydrazine. In a preferred embodiment, the method involves addition of a base followed by acidification. This method has several advantages as compared with published cyclocondensation reactions. It is simpler as there is no purification step it and can be performed with an aqueous solvent (although organic solvents or combinations of aqueous and organic solvents can be employed). In addition, the intermediates are stable at room temperature indefinitely. Moreover, this method is more efficient and higher yielding. Examples of phosphonopyrazoles that can be used in such processes are dialkyl [1-aryl or alkyl-(3 or 5)-hydroxy-1H-pyrazole-4-yl]phosphonates, which can be used as reactants to produce dialkyl [1-aryl or aryl-(3 or 5)-hydroxy-1H-pyrazol-4-yl]phosphonates having gametocidal activity, for example.
According to one process of the invention, the alkaline salt of 3-hydroxy-2-(dialkyl phosphono)acrylate and the selected hydrazine are reacted in an aqueous medium. For ease of purification of the product of the process, the aqueous phase is washed with an organic solvent to remove impurities before acidification.
According to another aspect of the invention, the phosphonopyrazole employed in such a process is a compound of formula I or II:
wherein: R
1
is alkyl, aryl, heteroaryl, benzyl or C3-C8 cycloalkyl, preferably C3-C7 cycloalkyl; R
2
is hydrogen or an alkaline salt; R
3
is hydrogen, alkyl, aryl or heteroaryl; R
4
is hydrogen, alkyl, phenyl, or a salt; R
5
is hydrogen, alkyl, phenyl, or a salt; R
6
is alkyl, aryl or heteroaryl; alkyl is C1-C8, preferably C1-C4 branched or C1-C4 straight chains; aryl is phenyl or naphthyl optionally substituted with 1-5 groups, preferably 1-3 groups, selected from halogen, trihalomethyl, C1-C8 alkyl (straight or branched chain), C1-C8 alkoxy (straight or branched chain), nitro and cyano; benzyl is benzyl optionally substituted with 1-3 groups selected from halogen, trihalomethyl, C1-C8 alkyl (straight or branched chain), C1-C8, preferably C4 alkoxy (straight or branched chain), nitro and cyano; and heteroaryl is pyridyl optionally substituted with 1-4 groups selected from halogen, trihalomethyl, C1-C8 alkyl (straight or branched chain), C1-C8 alkoxy (straight or branched chain), nitro and cyano.
According to another aspect of the invention, compounds of formula I or II (as shown above) are provided wherein: R
1
is hydrogen, alkyl, aryl, heteroaryl, benzyl or C3-C8 cycloalkyl, preferably C3-C7 cycloalkyl; R
2
is hydrogen, alkyl, benzyl, C1-C8 alkenyl, preferably C1-C4 alkenyl, or a salt (preferably an agronomically acceptable salt such as an alkali metal salt or an amine salt, for example); R
3
is hydrogen, alkyl
Curtis Jane M.
Miller Paula C.
Molyneaux John M.
Owen Thomas J.
Monsanto Technology LLC
Ramsuer Robert W.
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