Compounds and processes related to flumetylsulforim

Abstract

The present subject matter relates to compound I selected from a group consisting of (1) 4- (Hydroxymethyl)benzene-1-sulfinic acid, (2) 5-fluoro-1-((4- (hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(1H)-one, (3) 2,4-Pyrimidinedione, 5-fluoro-3-methyl-1-[(4-methylphenyl)sulfonyl], (4) (E)-2-fluoro-3-Imino-3-(methylamino)-1-(p-tolylsulfonylamino)1-propene and (5) [p-(3- Methylureidosulfonyl)phenyl]methanol and uses thereof.

Description

COMPOUNDS AND PROCESSES RELATED TO FLUMETHYLSULFORIMThis application claims the benefit of U.S. Provisional Application No. 63 / 458,599, filed April 11, 2023, the contents of which are hereby incorporated by reference.Throughout this application various publications are referenced. The disclosures of these documents in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.FIELD OF THE INVENTIONThe present subject matter relates to compound I selected from a group consisting of (1) 4- (Hydroxymethyl)benzene-l-sulfinic acid, (2) 5-fluoro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl], (4) (E)-2-fluoro-3- Imino-3 -(methylamino)- l-(p-tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol and uses thereof.BACKGROUND AND SUMMARYFungicides are compounds of natural or synthetic origin, which act to protect plants against damage caused by fungi. Current methods of agriculture rely heavily on the use of fungicides. In fact, some crops cannot be grown usefully without the use of fungicides. Using fungicides allows a grower to increase the yield and the quality of the crop, and consequently, increase the value of the crop. In most situations, the increase in value of the crop is worth at least three times the cost of the use of the fungicide. Flumethylsulforim having the chemical name 5-Fluoro-4-imino-3-methyl-l-tosyl-3,4-dihydropyrimidin- 2(lH)-one|and the structure I.structure I is a compound which provides control of a variety of pathogens affecting economically important crops including, but not limited to, the causal agent of leaf blotch in wheat, Zymoseptoria tritici (SEPTTR) and fungi of the classes ascomycetes and basidiomycetes.Flumethylsulforim is related with formation of different compounds and there is a need for tools for analyzing Flumethylsulforim.SummaryThe present invention provides a compound I selected from a group consisting of (1) 4- (Hydroxymethyl)benzene-l-sulfinic acid, (2) 5-fluoro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl], (4) (E)-2-fluoro-3- Imino-3 -(methylamino)- l-(p-tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol.The present invention also provides a process for preparing the compound I as described in any one of schemes 1-5.The present invention provides use of at least one compound I as reference standard for determining purity and / or metabolite profile of Flumethylsulforim.The present invention provides use of at least one compound I as reference standard for determining the purity of a composition comprising FlumethylsulforimThe present invention provides use of at least one compound I as a reference standard to test for its presence and / or quantity in Flumethylsulforim.The present invention provides use of at least one compound I as a reference standard to test for its presence and / or quantity in a composition.In some embodiments, the composition is a composition comprising Flumethylsulforim.The present invention provides use of at least one compound I as reference standard to test for its presence and / or quantity at a locus where Flumethylsulforim was applied.The present invention provide use of at least one compound I as reference standard to test for its presence and / or quantity in a plant to which Flumethylsulforim was applied.BRIEF DESCRIPTION OF THE DRAWINGSFigure 1 :1H NMR spectrum of structure A.Figure 2: Mass spectrum of structure A.Figure 3: 'H NMR (CDCh, 300MHz) of structure B. Figure 4: Mass spectrum of structure BFigure 5: Mass spectrum of structure C.Figure 6: 'H NMR spectrum of structure D.Figure 7: Mass spectrum of structure DFigure 8: 'H NMR spectrum of structure E. Figure 9: Mass spectrum for structure EDetailedific Embodiments of The InventionDefinitionsPrior to setting forth the present subject matter in detail, it may be helpful to provide definitions of certain terms to be used herein. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this subject matter pertains.Throughout the application, descriptions of various embodiments use the term “comprising”; however, it will be understood by one of skill in the art, that in some specific instances, an embodiment can alternatively be described using the language “consisting essentially of’ or “consisting of.”All disclosed lists of optional ingredients etc., should be seen as a disclosure of both closed and open lists as two independently disclosed alternatives.The term “a” or “an” as used herein includes the singular and the plural, unless specifically stated otherwise. Therefore, the terms “a,” “an” or “at least one” can be used interchangeably in this application, to be clear that the use of terms “a,” or “an” does not intend to convey the absence of multiples unless the context requires it.The term “about” herein specifically includes ±10% from the indicated values in the range. In addition, the endpoints of all ranges directed to the same component or property herein are inclusive of the endpoints, are independently combinable, and include all intermediate points and ranges.It is understood that where a parameter range is provided, all integers within that range, and tenths thereof, are also provided by the invention as if the integers and tenths thereof are expressly described herein. For example, “5 g / ha to 120 g / ha” includes 5.0 g / ha, 5.1 g / ha, 5.2 g / ha, 5.3 g / ha, 5.4 g / ha, etc. up to 120 g / haAs used herein, the term "plant" includes reference to the whole plant, plant organ (e.g., leaves, stems, twigs, roots, trunks, limbs, shoots, fruits etc.), plant cells, and propagation material of the plant.As used herein the term "plant" includes reference to agricultural crops include field crops (soybean, maize, wheat, rice, etc.), vegetable crops (potatoes, cabbages, etc.) and fruits (peach, etc.).As used herein the term "propagation material" is to be understood to denote all the generative parts of the plant such as seeds and spores, seedlings, and vegetative structures such as bulbs, corms, tubers, rhizomes, roots stems, basal shoots, stolons and buds.It will be understood that when an element is referred to as being “on” another element, it may be directly in contact with the other element or intervening elements may be present therebetween. In contrast, when an element is referred to as being “directly on” another element, there are no intervening elements present that may create a barrier between them.It will be understood that, although the terms first, second, third, etc. may be used herein to describe various elements, components, regions, layers, and / or sections, these elements, components, regions, layers, and / or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer, or section from another element, component, region, layer, or section. Thus, a first element, component, region, layer, or section discussed below could be termed a second element, component, region, layer, or section without departing from the teachings of the present embodiments.The terminology used herein is for the purpose of describing or illustrating particular embodiments only and is not intended to be limiting. As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise.Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this general inventive concept belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the present disclosure, and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.I, preparation and uses thereofFlumethylsulforim is related with formation of compound I selected from a group consisting of (1) 4-(Hydroxymethyl)benzene- 1 -sulfinic acid, (2) 5-fluoro-l-((4- (hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl], (4) (E)-2-fluoro-3- Imino-3 -(methylamino)- l-(p-tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol.Analyzing Flumethylsulforim was found to be challenging. Identification and characterization of compound I using a standard provides efficient, fast and simple tool for determining purity and / or metabolite profile of Flumethylsulforim.Flumethylsulforim includes all solid forms thereof including, but not limited to, amorphous, crystalline, solvate or hydrate. Crystalline forms of Flumethylsulforim are disclosed in PCT International Application Publication No. WO 2019 / 038583 Al, published February 28, 2019, and WO 2022 / 234487, published November 10, 2022, the entire content of which is hereby incorporated by reference.Compound I is selected from group consisting of (1) 4-(Hydroxymethyl)benzene- 1 -sulfinic acid, (2) 5-fluoro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4- dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fhioro-3-methyl-l-[(4- methylphenyl)sulfonyl], (4) (E)-2-fluoro-3 -Imino-3 -(methylamino)- 1 -(p- tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol.In some embodiments, compound I is 4-(Hydroxymethyl)benzene-l -sulfinic acid.In some embodiments, compound I is 5-fhioro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4- imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one.In some embodiments, compound I is 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4- methylphenyl)sulfonyl] .In some embodiments, compound I is (E)-2-fluoro-3-Imino-3-(methylamino)-l-(p- tolylsulfonylamino) 1 -propene.In some embodiments, compound I is [p-(3-Methylureidosulfonyl)phenyl]methanol.4-(Hydroxymethyl)benzene-l-sulfinic acid has structure A shown below:structure A.4-(Hydroxymethyl)benzene-l-sulfinic acid has an NMR spectrum substantially in accordance with the spectrum as shown in figure 1.5-fluoro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4- dihydropyrimidin-2(lH)-one has structure B shown below:structure B.5-fluoro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4- dihydropyrimidin-2(lH)-one has an NMR spectrum substantially in accordance with the spectrum as shown in figure 3.2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl] has structure C shown below:structure C.2,4-Pyrimidinedione, 5 -fluoro-3 -methyl- l-[(4-methylphenyl)sulfonyl] has a mass spectrum substantially in accordance with the spectrum as shown in figure 5.Any one or any combination of the peaks fragments shown in figure 5 may be used to identify 2,4-Pyrimidinedione, 5-fhioro-3-methyl-l-[(4-methylphenyl)sulfonyl], 2,4- Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl] may be identified using one of the peaks fragments shown in figure 5. For example, 2,4-Pyrimidinedione, 5-fluoro- 3-methyl-l-[(4-methylphenyl)sulfonyl] has characteristic peak fragment in mass spectroscopy [M+H]+ 299 m / z. 2,4-Pyrimidinedione, 5-fhioro-3-methyl-l-[(4- methylphenyl)sulfonyl] may be identified using two of the peaks shown in figure 5. 2,4- Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl] may be identified using three of the peaks fragments shown in figure 5. 2,4-Pyrimidinedione, 5 -fluoro-3 -methyl- 1- [(4-methylphenyl)sulfonyl] may be identified using four of the peaks fragments shown in figure 5.For example, 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl] has characteristic peak fragment in mass spectroscopy [M+H]+ 299 m / z and at least one fragments and adduct of the molecule are in 113.0712 m / z (C5H9N2O), 145.0408 m / z (C5H6FN2O2) or 316.0761 m / z (C12H15FN3O4S, [M+NH4] + ).For example, 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl] has characteristic peak in mass spectroscopy [M+H]+ 299 m / z and at least one fragments and adduct of the molecule are in 113.0712 m / z (C5H9N2O), 145.0408 m / z (C5H6FN2O2) and 316.0761 m / z (C12H15FN3O4S, [M+NH4] + ).(E)-2-fluoro-3 -Imino-3 -(methylamino)- 1 -(p-tolylsulfonylamino) 1 -propene has structureD shown below:structure D.(E)-2-fluoro-3-Imino-3 -(methylamino)- l-(p-tolylsulfonylamino)l -propene has an NMR spectrum substantially in accordance with the spectrum in figure 6. [p-(3-Methylureidosulfonyl)phenyl]methanol has structure E shown below:structure E.[p-(3-Methylureidosulfonyl)phenyl]methanol has an NMR spectrum substantially in accordance with the spectrum of figure 8. In some embodiments, compound I is produced synthetically.In some embodiments, compound I is free of plant material and / or biological material (such as tissue).The present invention also provides a process for preparing the compound I as described in any one of schemes 1-5. Compound I may be present as impurities in a batch of flumethylsulforim or in a mixture of composition comprising flumethylsulforim. The identification of compounds I, including the compounds described above, allows each of these compounds to be used as a reference standard for quality control of batches of flumethylsulforim or mixtures or compositions of flumethylsulforim. In particular, the identification of compounds I,including the compounds described above, allows for the development of a reference standard profile, including but not limited to NMR profile. Any machine can be calibrated for the detection of these compounds to screen batches of flumethylsulforim or mixtures or compositions of flumethylsulforim for presence of these compounds and amounts thereof.The present invention provides use of at least one compound I as reference standard for determining purity and / or metabolite profile of Flumethylsulforim.The present invention provides use of at least one compound I as reference standard for determining purity of a composition comprising Flumethylsulforim.The present invention provides use of at least one compound I as a reference standard to test for its presence and / or quantity in Flumethylsulforim.The present invention provides use of at least one compound I as a reference standard to test for its presence and / or quantity in a composition.In some embodiments, the composition is a composition comprising FlumethylsulforimThe present invention provides use of at least one compound I as reference standard to test for its presence and / or quantity at a locus where Flumethylsulforim was applied.The present invention provide use of at least one compound I as reference standard to test for its presence and / or quantity in a plant to which Flumethylsulforim was applied.The present invention provides use of any one of compound I as reference standard for determining purity and / or metabolite profile of Flumethylsulforim.The present invention provides use of any one of compound I as reference standard for determining purity of a composition comprising Flumethylsulforim.The present invention provides use of any one of compound I as a reference standard to test for its presence and / or quantity in Flumethylsulforim.The present invention provides use of any one of compound I as a reference standard to test for its presence and / or quantity in a composition.In some embodiments, the composition is a composition comprising FlumethylsulforimThe present invention provides use of any one of compound I as reference standard to test for its presence and / or quantity at a locus where Flumethylsulforim was applied.The present invention provide use of any one of compound I as reference standard to test for its presence and / or quantity in a plant to which Flumethylsulforim was applied.The present invention provides use of at least one compound I as reference standard (1) for determining purity and / or metabolite profile of Flumethylsulforim, (2) for determining purity of a composition comprising Flumethylsulforim, (3) to test for its presence and / or quantity in Flumethylsulforim, (4) to test for its presence and / or quantity in a composition, (5) to test for its presence and / or quantity at a locus where Flumethylsulforim was applied and / or (6) to test for its presence and / or quantity in a plant to which Flumethylsulforim was applied.In some embodiments, the present invention provides a compound I having the structure AStructure AIn some embodiments, the chemical name of structure A is 4-(Hydroxymethyl)benzene-l- sulfinic acid.In some embodiments, the present invention provides the use of compound I having the structure A as a standard for analytical measurement.In some embodiments, the present invention provides the use of compound I having the structure A for analyzing Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure A as reference standard for determining purity and / or metabolite profile of Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure A as reference standard for determining purity of a composition comprising FlumethylsulforimIn some embodiments, the present invention provides the use of compound I having the structure A as a reference standard to test for its presence and / or quantity in Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure A as a reference standard to test for its presence and / or quantity in a composition.In some embodiments, the composition is a composition comprising FlumethylsulforimIn some embodiments, the present invention provides the use of compound I having the structure A as reference standard to test for its presence and / or quantity at a locus where Flumethylsulforim was applied.In some embodiments, the present invention provides the use of compound I having the structure A as reference standard to test for its presence and / or quantity in a plant to which Flumethylsulforim was applied.In some embodiments, the compound I having structure A may be prepared as disclosed in scheme 1.Scheme 1.The present invention also provides, a process for preparing compound I having structure A as disclosed in scheme 1.In some embodiments, the process is as described in example 1. Each step or a combination of steps in the example represents a separate embodiment.In some embodiments, the present invention provides a compound I having the structure Bstructure BIn some embodiments, the chemical name of structure B is 5 is 5-fluoro-l-((4- (hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one.In some embodiments, the present invention provides the use of compound I having the structure B as standard for analytical measurements.In some embodiments, the present invention provides the use of compound I having the structure B for analyzing Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure B as reference standard for determining purity and / or metabolite profile of Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure B as reference standard for determining purity of composition comprising FlumethylsulforimIn some embodiments, the present invention provides the use of compound I having the structure B as a reference standard to test for its presence and / or quantity in Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure B as a reference standard to test for its presence and / or quantity in a composition.In some embodiments, the composition is a composition comprising FlumethylsulforimIn some embodiments, the present invention provides the use of compound I having the structure B as reference standard to test for its presence and / or quantity at a locus where Flumethylsulforim was applied. In some embodiments, the present invention provides the use of compound I having the structure B as reference standard to test for its presence and / or quantity in a plant to which Flumethylsulforim was applied.In some embodiments, compound I having structure B may be prepared as disclosed in scheme 2.Scheme 2.The present invention also provides, a process for preparing compound I having structure B as disclosed in scheme 2.In some embodiments, the process is as described in example 2. Each step or a combination of steps in the example represents a separate embodiment.In some embodiments, the present invention provides a compound I having the structure Cstructure CIn some embodiments, the chemical name of structure C is 2,4-Pyrimidinedione, 5-fluoro- 3-methyl-l-[(4-methylphenyl)sulfonyl],In some embodiments, the present invention provides the use of compound I having the structure C as standard for analytical measurements.In some embodiments, the present invention provides the use of compound I having the structure C for analyzing Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure C as reference standard for determining purity and / or metabolite profile of Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure C as reference standard for determining purity of composition comprising FlumethylsulforimIn some embodiments, the present invention provides the use of compound I having the structure C as a reference standard to test for its presence and / or quantity in Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure C as a reference standard to test for its presence and / or quantity in a composition.In some embodiments, the composition is a composition comprising FlumethylsulforimIn some embodiments, the present invention provides the use of compound I having the structure C as reference standard to test for its presence and / or quantity at a locus where Flumethylsulforim was applied.In some embodiments, the present invention provides the use of compound I having the structure C as reference standard to test for its presence and / or quantity in a plant to which Flumethylsulforim was applied.In some embodiments, compound I having structure C may be prepared as disclosed in scheme 3.Scheme 3The present invention also provides, a process for preparing compound I having structure C as disclosed in scheme 3.In some embodiments, the process is as described in example 3. Each step or a combination of steps in the example represents a separate embodiment.In some embodiments, the present invention provides a compound I having the structure Dstructure DIn some embodiments, the chemical name of structure D is ((E)-2-fluoro-3-Imino-3- (methylamino)- 1 -(p-tolylsulfonylamino) 1 -propene.In some embodiments, the present invention provides the use of compound I having the structure D as standard for analytical measurement.In some embodiments, the present invention provides the use of compound I having the structure D for analyzing Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure D as reference standard for determining purity and / or metabolite profile of Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure D as reference standard for determining purity of composition comprising FlumethylsulforimIn some embodiments, the present invention provides the use of compound I having the structure D as a reference standard to test for its presence and / or quantity in Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure D as a reference standard to test for its presence and / or quantity in a composition.In some embodiments, the composition is a composition comprising FlumethylsulforimIn some embodiments, the present invention provides the use of compound I having the structure D as reference standard to test for its presence and / or quantity at a locus where Flumethylsulforim was applied.In some embodiments, the present invention provides the use of compound I having the structure D as reference standard to test for its presence and / or quantity in a plant to which Flumethylsulforim was applied.In some embodiments, compound I having structure D may be prepared as disclosed in scheme 4.Scheme 4The present invention also provides, a process for preparing compound I having structure D may as disclosed in scheme 4.In some embodiments, the process is as described in example 4. Each step or a combination of steps in the example represents a separate embodiment.In some embodiments, the present invention provides a compound I having the structure Estructure EIn some embodiments, the chemical name of structure E is [p-(3- Methylureidosulfonyl)phenyl]methanol.In some embodiments, the present invention provides the use of compound I having the structure E as standard for analytical measurement.In some embodiments, the present invention provides the use of compound I having the structure E for analyzing Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure E as reference standard for determining purity and / or metabolite profile of Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure E as reference standard for determining purity of composition comprising FlumethylsulforimIn some embodiments, the present invention provides the use of compound I having the structure E as a reference standard to test for its presence and / or quantity in Flumethylsulforim.In some embodiments, the present invention provides the use of compound I having the structure E as a reference standard to test for its presence and / or quantity in a composition.In some embodiments, the composition is a composition comprising FlumethylsulforimIn some embodiments, the present invention provides the use of compound I having the structure E as reference standard to test for its presence and / or quantity at a locus where Flumethylsulforim was applied.In some embodiments, the present invention provides the use of compound I having the structure E as reference standard to test for its presence and / or quantity in a plant to which Flumethylsulforim was applied. In some embodiments, compound I having structure E may be prepared as disclosed in scheme 5.Scheme 5.The present invention also provides, a process for preparing compound I having structure E as disclosed in scheme 5.In some embodiments, the process is as described in example 5. Each step or a combination of steps in the example represents a separate embodiment.In some embodiments, analyzing Flumethylsulforim refers to identifying the compound I in a mixture comprising Flumethylsulforim and compound I.In some embodiments, analyzing Flumethylsulforim refers to identifying the amount of compound I in a mixture comprising Flumethylsulforim and compound I.The compound I selected from a group consisting of (1) 4-(Hydroxymethyl)benzene-l- sulfinic acid, (2) 5-fhioro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4- dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fhioro-3-methyl-l-[(4- methylphenyl)sulfonyl], (4) (E)-2-fluoro-3 -Imino-3 -(methylamino)- 1 -(p- tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol, can be obtained using well-known chemical procedures. Intermediates not specifically mentioned in this disclosure are either commercially available, can be obtained using procedures disclosed in the literature or may be readily synthesized from commercial starting materials utilizing standard procedures.The present invention provides compound I selected from a group consisting of (1) 4- (Hydroxymethyl)benzene-l-sulfinic acid, (2) 5-fluoro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl], (4) (E)-2-fluoro-3- Imino-3 -(methylamino)- l-(p-tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol as (1) reference standard for determining purity and / or metabolite profile of Flumethylsulforim, (2) reference standard for determining purity of composition comprising Flumethylsulforim, (3) a reference standard to test for its presence and / or quantity in Flumethylsulforim, (4) a reference standard to test for its presence and / or quantity in a composition, (5) reference standard to test for its presence and / or quantity at a locus where Flumethylsulforim was applied and / or (6) reference standard to test for its presence and / or quantity in a plant to which Flumethylsulforim was applied.The present invention provides use of at least one compound I selected from a group consisting of (1) 4-(Hydroxymethyl)benzene- 1 -sulfinic acid, (2) 5-fluoro-l-((4- (hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl], (4) (E)-2-fluoro-3- Imino-3 -(methylamino)- l-(p-tolylsulfonylamino)! -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol as (1) reference standard for determining purity and / or metabolite profile of Flumethylsulforim, (2) reference standard for determining purity of composition comprising Flumethylsulforim, (3) a reference standard to test for its presence and / or quantity in Flumethylsulforim, (4) a reference standard to test for its presence and / or quantity in a composition, (5) reference standard to test for its presence and / or quantity at a locus where Flumethylsulforim was applied and / or (6) reference standard to test for its presence and / or quantity in a plant to which Flumethylsulforim was applied.The present invention provides compound I selected from a group consisting of (1) 4- (Hydroxymethyl)benzene-l-sulfinic acid, (2) 5-fluoro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl], (4) (E)-2-fluoro-3- Imino-3 -(methylamino)- l-(p-tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol as standard for analytical measurement.The present invention provides compound I selected from a group consisting of (1) 4- (Hydroxymethyl)benzene-l-sulfinic acid, (2) 5-fluoro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl], (4) (E)-2-fluoro-3- Imino-3 -(methylamino)- l-(p-tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol for analyzing Flumethylsulforim.The present invention provides a compound having the following structure:The present invention provides a compound having the following structure:The present invention provides a compound having the following structure:The present invention provides a compound having the following structure:The present invention provides a compound having the following structure:Each compound described herein can be used as a reference standard to test for their presence and / or quantity in a composition, such as a composition comprising Flumethylsulforim.Each compound described herein can also be used as a reference standard to test for their presence and / or quantity at a locus where Flumethylsulforim was applied.Each compound described herein can further be used as a reference standard to test for their presence and / or quantity in a plant to which Flumethylsulforim was applied.Each compound described herein can be used as reference standard for determining purity and / or metabolite profile of Flumethylsulforim.Each compound described herein can be used as reference standard for determining purity of composition comprising Flumethylsulforim.In some embodiments, the present invention provides compound I selected from a group consisting of (1) 4-(Hydroxymethyl)benzene- 1 -sulfinic acid, (2) 5-fluoro-l-((4- (hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl], (4) (E)-2-fluoro-3- Imino-3 -(methylamino)- l-(p-tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol as a reference standard.In some embodiments, the composition is a water extracted solution.In some embodiments, the composition is a solid composition.In some embodiments, the composition is a liquid composition.In some embodiments, composition comprises Flumethylsulforim and agricultural acceptable carrier such as water and / or organic solvent.The present invention also provides a Flumethylsulforim comprising at least one compound I selected from a group consisting of (1) 4-(Hydroxymethyl)benzene-l -sulfinic acid, (2) 5-fluoro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4- dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fhioro-3-methyl-l-[(4- methylphenyl)sulfonyl], (4) (E)-2-fluoro-3 -Imino-3 -(methylamino)- 1 -(p- tolylsulfonylamino)! -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol .In some embodiments, the flumethylsulforim comprising 2 or more of compound I selected from a group consisting of (1) 4-(Hydroxymethyl)benzene-l -sulfinic acid, (2) 5 -fluoro- 1- ((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one,(3) 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl], (4) (E)-2- fluoro-3-Imino-3 -(methylamino)- l-(p-tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol.The present invention also provides a composition comprising Flumethylsulforim and at least one compound I selected from a group consisting of (1) 4-(Hydroxymethyl)benzene- 1-sulfinic acid, (2) 5-fluoro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3.4-dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fhroro-3-methyl-l-[(4- methylphenyl)sulfonyl], (4) (E)-2-fluoro-3 -Imino-3 -(methylamino)- 1 -(p- tolylsulfonylamino)l -propene, (5) [p-(3-Methylureidosulfonyl)phenyl]methanol and (6) any combination of (1), (2), (3), (4) and (5).The present invention also provides a composition comprising Flumethylsulforim and at least one compound I, wherein compound I is selected from a group consisting of (1) 4- (Hydroxymethyl)benzene-l-sulfinic acid, (2) 5-fluoro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one, (3)2.4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl], (4) (E)-2-fluoro-3-Imino-3 -(methylamino)- l-(p-tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol and (6) any combination of (1), (2), (3), (4) and(5).The following examples are presented to illustrate the various aspects of the compounds of the present disclosure and should not be construed as limitations of the claims.sectionExample 1, characterization and synthesis of 4-(Hydroxymethyl)benzene-l-sulfinic acid (compound A) having the structure A.Structure AMolecular formula: C7H8SO3Molecular weight: 172.2 g / molScheme of synthesis route:S chemi.Procedure:Step A:Molecular Weight: 234,04Procedure 1. A solution of (4-Iodophenyl)methanol (10 g') and Trimethylamine (2 eq) in Dichloromethane (DCM, 100 ml, reagent grade) was cooled down to 10°C and treated dropwise with pivaloyl chloride (PivCI ) (1.1 eq) at 10-15°C (~15min). Resulted suspension was aged for Ih at RT (TLC: traces SM, eluent DCM) and poured into IM HC1 aq (150ml). Organic phase was separated and washed with saturated NaHCOs and brine. Organic extract was dried over MgSO4 and concentrated to dryness. Crude product (brown oil) was dissolved in DCM (50 ml) and filtered through a 200 g silica pad by washing with DCM. Fractions containing desired product were concentrated to dryness giving 13 g' of M

[0318] as colorless oil (Yield: 96%).Procedure 2. A solution of (4-Iodophenyl)methanol (10 g') and Trimethylamine (2 eq) in Dichloromethane (DCM, 100 ml, reagent grade) was cooled down to 10°C and treated dropwise with pivaloyl chloride (PivCI) (1.1 eq) at 10-15°C (~15min). Resultedsuspension was aged for Ih at RT and poured into IM HC1 aq (150ml). Organic phase was separated and washed with saturated NaHCO Organic extract was dried over MgSO4 and concentrated to dryness. Crude product filtered and dry to get pure compound M318.Step B:All operations were done under Ar atmosphere.Procedure 1. A solution of (4-Iodophenyl)methyl pivalate (13 g') in THF (105 ml, anhydrous) was cooled down to -5°C and treated dropwise with iPrMgCl (1.1 eq) at -5°C (~15 min) under positive pressure of Ar. Resulted clear, brown solution was aged for 10 min. at -5°C (TLC: full transformation into Grignard reagent, eluent DCM)-. A stream of dry SO2 was passed through reaction mixture for 10 min. Temperature raised to 25°C and color turned to bright yellow. Clear RM was stirred for additional 10 min. and quenched with IM HC1 (100 ml). Ethyl acetate (EA) was added (200 ml) and organic phase was separated, washed with sat. NaHCCh and dried over MgSO-i. Solvents were removed i.v. giving crude product as dense oil. A solution of NaOH (3.6 g') in water (30 ml) and MeOH (100 ml) was added to the crude product and reaction mixture was aged at RT for 16h. Then MeOH was removed i.v. and the residue was treated with cone. HC1 until pH=3-4. Product was extracted with EA (2x100 ml), extracts were concentrated to ~l / 4 of initial volume and solids were collected by filtration. Crude acid was dissolved in water (50 ml, DI) and kept at 5°C for 16h under Ar. Resulted crystals were collected and dried i.v. at 33°C to give 1 g' of Ml 7- 15 (yield 3%)..Procedure 2. A solution of (4-Iodophenyl)methyl pivalate (13 g') in THF (105 ml, anhydrous) was cooled down to -5°C and treated dropwise with iPrMgCl (1.1 eq) at -5°C (~15 min) under positive pressure of Ar. Resulted clear, brown solution was aged for 10 min. at -5°C -. A stream of dry SO2 was passed through reaction mixture for 10 min. Temperature raised to 25°C and color turned to bright yellow. Clear RM was stirred foradditional 10 min. and quenched with IM HC1 (100 ml). Ethyl acetate (EA) was added (200 ml) and organic phase was separated, washed with sat. the final material dried and crystalized by water.'H NMR (300 MHz, Methanol-d4) 57.77 - 7.65 (m, 2H), 7.63 - 7.52 (m, 2H), 4.71 (s, 2H) Analytical NMR and Mass spectrum data shown in figures 1 and 2.Ml 7- 15 (structure A) seem to be unstable compound and susceptible for oxidation, the compound should be stored under Ar at -20°C.Example 2, characterization and synthesis of 5 -fluoro- 1 -((4- (hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one having structure B.Scheme 2.Step 1 of scheme 2, preparation of (4-methanesulfinylphenyl)methanolRaw materials consumption on 24g scale.Procedure To a mixture of 4-(Methylthio)benzyl alcohol (24g, 0.156mol) in water (200ml) was added TBHP (solution 70% in water, 129.4ml, 0.935mol). The reaction mixture was stirred at room temperature overnight. The resulting solution was saturated with NaCl (solid, ca. 140g), diluted with water (ca. 100ml) and extracted with DCM (5x200ml). Combined extracts were dried over MgSO-i, filtered and concentrated to yellowish oil. Yield: Quantitative, ca. 31g. (theoretical yield: 26.49g). Crude product was used in next step without further purification.Step 2 of scheme 2, preparation of 4-(hydroxymethyl)benzenesulfonyl chloride.Raw Materials consumption on 10g scaleProcedureTo a solution of 4-(methanesulfinylphenyl)methanol (10.00g, 0.058mol) in dry DCM (100ml) was dropped tfiluoroacetic anhydride (32.8ml, 0.235mol) at room temperature and the mixture was heated at 40°C for 30 minutes. The volatiles were removed in vacuo and the residue was co-evaporated with toluene to remove residual trifluoroacetic acid and anhydride. The residual oil was dissolved in dry DCM (100ml), cooled to 0°C and treated with water at this temperature. After 30 minutes acetic acid wad dropped at 0°C and chlorine gas was introduced by means of a glass pipet for 40 minutes at 0°-8°C. Then, the reaction mixture was washed with cold water (250ml), aq. Satur. NaHCCh (300ml) and 10% NaiSO Organic layer was dried over MgSO4, filtered and concentrated to give 7g(57.7%) of yellowish oil. Product was used in next step without further purification.Step 3 of scheme 2, preparation of 5-fluoro-l-[4-(hydroxymethyl)benzenesulfonyl]-4- imino-3 -methylpyrimidin-2-one.Raw materials consumption on 6.95g scaleProcedure5-fluoro-3-methylcytosine (4.81g, 0.033mol) was suspended in acetonitrile (35ml) and N,O-Bis(trimethylsilyl)acetamide (9.1ml, 0.037mol) was added. The resulting mixture was heated at 75°C (internal) for 1.5 hour, then cooled to 5°C and 4- (hydroxymethyl)benzenesulfonyl chloride (6.95g, 0.033mol) was dropped and stirred at this temperature for 30 minutes. The reaction mixture was allowed to warm to room temperature and stirred for 3 days. Acetonitrile was evaporated and the residual solid was purified by column chromatography on silica gel (400g) using 100% ethyl acetate as eluant.Fractions containing product was concentrated and the residual white solid (ca.3g) was macerated with ethyl acetate for 30 minutes, filtered off and dried under high vacuum at 45°-50°C for 5 days. Yield: 1.78g, 16.9%.Analytical NMR and Mass spectrum data shown in figures 3 and 4.REQUIREMENTS FOR CHEMICALSExample 3, characterization and synthesis of 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l- l(4-methylphenyl)sulfonyl1 having the structure C (Compound 12981) >Structure CMolecular formula: C12H11FN2O4SMolecular weight: 298g / molScheme 3.Synthesis of 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl] in the amount of ca. 1g and purity > 98%.Procedure- Tosylation of

[0144] to

[0298] 5 1. Addition of 5-fhioro-3-methylpyrimidine-2,4(lH,3H)-dione

[0144] , Na2CO3 andDMA- stirring at r.t.2. Addition of pTsCl.3. Taking a sample.4. Addition of 150 gr water to the reaction mixture at r.t. 0 5. Filtrating.6. Drying in the oven at 65°C for overnight.7. 22 gr white solid was received.Analytical Mass spectrum data shown in figure 5.The ion m / z 299.0496 is identified as protonated molecule [M+H]+ that accords to nominal* molecular mass 298 and molecular formula C12H11FN2O4S. The significant fragments and adduct of the molecule are: m / z 113.0712 (C5H9N2O), 145.0408 (C5H6FN2O2) and 316.0761 (C12H15FN3O4S, [M+NH4] + ). Example 4, characterization and synthesis of (E)-2-fhioro-3-Imino-3 -(methylamino)- l-(p- tolylsulfonylamino)l -propene (also named as (E)-2-Fluoro-N-methyl-3-((4- methylphenyl)sulfonamido)acrylamide)Molecular formula: C11H13FN2O3S Molecular weight: 272.3 g / molScheme of synthesis route:Scheme 4Materials:Procedure:50 g' M283 were added to a flask with 160 g' CPME and 40 g' DMA. The mixture was heated to 40°C and 78 g' Dimethylsulfate and additional 340 g' of CPME were added.NaOH (15% solution) were added, and the mixture was stirred at RT overnight.The solid was filtered off (containing -12% desired product).The phases of mother liquor were separated. The interphase containing more product was collected separately.Water was added to the interphase and stirred for 1 hour at RT.The solid filtered off and slurried with methanol for 1 hour at RT.The product was filtered and dried in vacuum at 35°C for 2 hours.Analytical NMR and Mass spectrum data shown in figures 6 and 7.Example 5, characterization and synthesis of [p-(3-Methylureidosulfonyl)phenyl]methanol having the structure EStructure ESynthesisSynthesis was carried out following the scheme given below:Scheme 5Step A:Compound 1 (23 g’, 123 mmol) was dissolved in dry THF and to this solution were added TBDMS-C1 (Tert-butyldimethylsilyl chloride) (27.5 g’, 182 mmol), and solution of imidazole (17 g’, 250 mmol) in dry THF. The reaction mixture was stirred overnight at RT. Then it was concentrated under reduced pressure. The residue was diluted with EtOAc (600 mL), washed with water (2x600 mL), then with 5% solution of NaCl (600 mL). Separated organic layer was dried over Na2SO4 and concentrated to obtain 35 g’ of compound 2 (116 mmol, 95% yield).Step B:To the solution of compound 2 (35 g’, 116 mmol) in dry Dichloromethane (400 mL) was added Triethylamine (14 g’, 138 mmol). After cooling by water bath, to the reaction mixture was added dropwise the solution of Methylisocyanate (8 g’, 140 mmol) in dry Dichloromethane (20 mL) and it was left stirring for 15 h at RT. Then the reaction mixture was mixed with 5% aqueous solution of NaHSO4 (500 mL). Separated organic layer was dried over Na2SO4 and concentrated (at the bath temperature below 40°C) to obtain 39 g’ of compound 3 (109 mmol,94% yield).Step C:To the solution of compound 3 (35 g’, 97.6 mmol) in dry Dichloromethane (400 mL) was added TFA (120 mL) and it was stirred for 40 min at RT. Then the reaction mixture was concentrated in vacuum at bath 40°C. The residue was diluted with Dichloromethane (250 mL), and left crystalized during 1 day. Then occurred precipitate was filtered and dried in vacuum (at the bath temperature below 40°C) to give 10 g’ of compound Ml 8-66 (40.9 mmol, 42% yields).Analytical NMR and Mass spectrum data shown in figures 8 and 9

Claims

Claims1. A compound I selected from a group consisting of (1) 4-(Hydroxymethyl)benzene-l- sulfinic acid, (2) 5-fluoro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4- dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fhioro-3-methyl-l-[(4- methylphenyl)sulfonyl], (4) (E)-2-fluoro-3 -Imino-3 -(methylamino)- 1 -(p- tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol .

2. The compound of claim 1, wherein the compound I is 4-(Hydroxymethyl)benzene-l- sulfinic acid having the structure A3. The compound of claim 1, wherein the compound I is 5 -fluoro- 1 -((4- (hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one having the structure B4. The compound of claim 1, wherein the compound I is 2,4-Pyrimidinedione, 5-fluoro-3- methyl- l-[(4-methylphenyl)sulfonyl], having the structure C5. The compound of claim 1, wherein the compound I is (E)-2-fluoro-3-Imino-3- (methylamino)-l-(p-tolylsulfonylamino)! -propene having the structure D6. The compound of claim 1, wherein the compound I is [p-(3- Methylureidosulfonyl)phenyl]methanol having the structure E7. A compound having the following structure:

8. A compound having the following structure:

9. A compound having the following structure10. A compound having the following structure:

11. A compound having the following structure:

12. A process for preparing the compound for any one of claims 1-11, as described in schemes 1-5.

13. Use of the compound of any one of claims 1-11 as a reference standard to test for its presence and / or quantity in a composition.

14. The use of claim 7, wherein the composition is a composition comprisingFlumethylsulforim.

15. Use of the compound of any one of claims 1-11 as a reference standard to test for its presence and / or quantity at a locus where Flumethylsulforim was applied.

16. Use of the compound of any one of claims 1-11 as a reference standard to test for its presence and / or quantity in a plant to which Flumethylsulforim was applied.

17. Use of the compound of any one of claims 1-11 as reference standard for determining purity and / or metabolite profile of Flumethylsulforim.

18. Use of the compound of any one of claims 1-11 as reference standard for determining purity of composition comprising Flumethylsulforim19. Flumethylsulforim comprising at least one compound I selected from a group consisting of (1) 4-(Hydroxymethyl)benzene- 1 -sulfinic acid, (2) 5-fluoro-l-((4- (hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4-dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fluoro-3-methyl-l-[(4-methylphenyl)sulfonyl], (4) (E)-2-fluoro-3- Imino-3 -(methylamino)- l-(p-tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl]methanol.

20. A composition comprising Flumethylsulforim and at least one compound I, wherein compound I is selected from a group consisting of (1) 4-(Hydroxymethyl)benzene-l- sulfinic acid, (2) 5-fhioro-l-((4-(hydroxymethyl)phenyl)sulfonyl)-4-imino-3-methyl-3,4- dihydropyrimidin-2(lH)-one, (3) 2,4-Pyrimidinedione, 5-fhioro-3-methyl-l-[(4- methylphenyl)sulfonyl], (4) (E)-2-fluoro-3 -Imino-3 -(methylamino)- 1 -(p- tolylsulfonylamino)l -propene and (5) [p-(3-Methylureidosulfonyl)phenyl] methanol and (6) any combination of (1), (2), (3), (4) and (5).

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