Fungicidal compounds and their preparation processes

Abstract

The present invention relates to fungicidal sulfenylphthalimide compounds of formula (I) and compounds of formula (II), which are substantially free of undesired impurities. In particular, the present invention relates to a process for preparing compounds of formula (I) and (II), which are substantially free of undesired impurities. [Formula 1] TIFF2023526778000018.tif43137

Description

Technical Field

[0001] The present invention relates to a fungicidal compound represented by formula (I). More specifically, the present invention relates to a process for preparing a fungicidal sulfenylphthalimide compound of formula (I) that is substantially free of undesirable impurities.

Background Art

[0002] Sulfenylphthalimides, developed by Standard Oil in the 1950s, are one of the oldest groups of fungicides, being effective, safe, and persistent. Captan (N-(trichloromethylthio)-3a,4,7,7a-tetrahydrophthalimide), captan (N-[1,1,2,2-tetrachloroethylthio]-4-cyclohexene-1,2-dicarboximide), and folpet (N-[trichloromethylthio]phthalimide) are three sulfenylphthalimides having antifungal activity.

[0003] Phthalimide and N-substituted phthalimides are an important class of compounds due to their important biological activities, and the structural features that can identify their activities are a hydrophobic aryl ring, a hydrogen bonding domain, an electron donating group, and another distal hydrophobic site.

[0004] Several synthetic reactions for preparing the phthalimide moiety include: (1) Mathews' reaction, in which "drying" hydrolysis of a nitrile with phthalic acid or an amide with phthalic anhydride occurs to obtain the corresponding carboxylic acid and phthalimide; (2) a reaction of a dicarboxylic acid or its corresponding anhydride with a reagent having a reactive amino(-NH2) functional group, in which nucleophilic attack of the amino group on the anhydride moiety yields aromatic or aliphatic cyclic imides and their derivatives; and (3) a common synthetic route for synthesizing imides by direct condensation using cyclic anhydrides or their corresponding dicarboxylic acids to form amides, which are simple and readily available reagents. This method has the advantage that the particular reagent can also function as a solvent, especially for aliphatic imides. (4) A preferred method for preparing sulfenylphthalimide is the reaction of a metal salt of the imide with perchloromethyl mercaptan (CISCCl3) in an organic solvent. For example, the synthesis of sulfenylphthalimide compounds, such as captan, is readily possible by Diels-Alder cycloaddition of maleic anhydride with butadiene, which is then converted to tetrahydrophthalimide with ammonia. Finally, alkylating the imide nitrogen atom with perchloromethyl mercaptan yields captan.

[0005] Forpet and Kaputan are phthalimide-based agricultural fungicides that have been in use for 60 years. The active moiety of each parent chemical is the trichloromethylthio functional group, SCl3, which is a toxin group. The toxin group, CCl3-S-, is obtained from trichloromethanesulfenyl chloride, also known as perchloromethyl mercaptan. Both Forpet and Kaputan decompose into the reactive substance thiophosgene, along with their relatively stable ring structures. Forpet decomposes into phthalimide (PI) and thiophosgene (SCCl2), while Kaputan decomposes into 1,2,3,6-tetrahydrophthalimide (THPI) and thiophosgene. PI and THPI are relatively stable.

[0006] Kaptan is a non-systemic fungicide used to control diseases of many fruit, ornamental, and vegetable crops. It is used in agricultural production as well as in household pesticides. Kaptan can be used to control plant diseases such as black rot, summer blight and late blight, and downy mildew, among others. Kaptan works by coming into contact with fungi and disrupting the major processes of their life cycle. It can be toxic to many different fungal diseases. Kaptan is non-systemic, meaning it is not expected to travel through plants. It is applied to packing and transport boxes for fruits and vegetables. Kaptan is used as a preservative for coverings, fabrics, and leather, as well as in root dipping and seed treatments, and is incorporated into paints, wallpaper pastes, plastics, and leather products.

[0007] Forpet, a chloroalkylthio compound containing the broad-spectrum protective fungicidal N-(trichloromethylthio)phthalimide, has been used for the past several decades. Forpet is primarily used in the agricultural sector, along with other industrial applications today.

[0008] During the synthesis of sulfenylphthalimide compounds, the generation of impurities is important to consider if they are particularly undesirable due to their toxicological, ecotoxicological, or environmental properties. Of several known impurities, carbon tetrachloride (haloalkane impurity) is a major concern from a toxicological standpoint. According to the IARC (International Agency for Research on Cancer), carbon tetrachloride induces hepatocyte proliferation and unintended DNA synthesis. Carbon tetrachloride has mutagenic effects and induces aneuploidy in some in vitro systems. Carbon tetrachloride may be carcinogenic to humans (Group 2B). In conclusion, the EU (European Commission) considers carbon tetrachloride a significant impurity in kaputan technology and stipulates that it should not exceed a maximum level of 0.1 g / kg in technical materials.

[0009] Carbon tetrachloride is toxic to the central nervous system and the liver. It is particularly hepatotoxic after ingestion. Liver cell damage is clearly caused by free radicals generated during the initial dechlorination process. Kidney damage also occurs. Arrhythmias progressing to cardiac fibrillation can occur after inhalation or liquid ingestion of high concentrations of carbon tetrachloride. Carbon tetrachloride impairs NADPH-dependent oxidases in liver microsomes by causing irreversible damage to cytochrome P-450. It does not act as a competitive inhibitor. In the liver, carbon tetrachloride produces elevated levels of glutamate oxaloacetate transaminase and aldolase (commonly used to track the clinical course of human patients with compound poisoning). Central lobular necrosis of the liver is the most characteristic lesion of carbon tetrachloride poisoning. Necrosis progresses cell by cell. Electron microscopy shows vesicle formation in the rough endoplasmic reticulum, tangled, smooth membrane clumps, and Golgi vacuolation. It also shows polysome loss and fat accumulation. Clear tubular lesions, including tubular necrosis and calcium deposition, are regularly observed. Mitochondria, rather than the endoplasmic reticulum, are considered to be the primary intracellular site of carbon tetrachloride toxicity in the kidney.

[0010] Carbon tetrachloride also contributes to the depletion of the Earth's ozone layer, which protects us from harmful ultraviolet radiation. Carbon tetrachloride (CCl4) is an ozone-depleting substance, accounting for about 10% of the chlorine in the troposphere. Under the provisions of the Montreal Protocol, its production for decentralized use has been prohibited since 2010.

[0011] Therefore, in order to avoid exposure to agricultural workers handling kaputan technology and to avoid environmental hazards, it is important to minimize the level of carbon tetrachloride impurities as much as possible while synthesizing sulfenylphthalimide.

[0012] U.S. Patent No. 2,553,770 discloses the synthesis of sulfenylphthalimide compounds. This patent discloses the purification of sulfenylphthalimide compounds by crystallization in carbon tetrachloride as a solvent, following the reaction of the sulfenylphthalimide compound in a dioxane solvent.

[0013] U.S. Patent No. 2,553,771 discloses the synthesis of sulfenylphthalimide compounds, comprising dissolving a dicarboxylic acid imide in an alkaline aqueous solution of an alkali metal compound and reacting the resulting product with perchloromethyl mercaptan. In both of these patents, the addition of carbon tetrachloride further contributes to increasing the level of carbon tetrachloride impurities in the finally synthesized sulfenylphthalimide.

[0014] U.S. Patent No. 2,553,776 discloses the synthesis of kaputan in which water is used as the solvent in the final step. The patent also discloses the effect of adding sodium chloride and potassium chloride to improve the yield of the final product. However, the patent does not disclose any impurities in the final product or their amounts.

[0015] U.S. Patent No. 2,713,058 discloses an improved method for synthesizing N-trichloromethylthioimide, comprising carrying out the reaction of an alkali metal imide product dissolved in an aqueous medium with perchloromethyl mercaptan in the presence of a water-immiscible saturated organic solvent for perchloromethyl mercaptan. The latter is preferably added to a reaction system dissolved in an organic solvent (saturated C5-C9 hydrocarbon) to obtain a product of substantially increased purity. The N-trichloromethylthioimide obtained according to this invention has a purity of over 95%, but this patent does not disclose anything about haloalkane impurities in the synthesis of N-trichloromethylthioimide or the amount thereof handled.

[0016] U.S. Patent No. 3,314,969 discloses a method for preparing an N-trichloromethylthioimide compound, comprising the steps of: isolating the N-polyhaloethylthio compound from the aforementioned reaction mixture as a polar solvent dispersion; contacting the dispersion with a 6-10 carbon aromatic hydrocarbon solvent at a temperature in the range of about 50-100°C for a time sufficient to dissolve substantially all of the N-polyhaloethylthio compound; separating the polar solvent phase from the aromatic hydrocarbon solvent phase; and cooling the aromatic hydrocarbon phase to isolate the purified N-polyhaloethylthio compound therefrom. U.S. Patent No. 3,314,969 uses an alkali metal salt in the aqueous phase and adds trichloromethyl sulfenyl chloride, diluted in an aliphatic hydrocarbon solvent, to an aqueous solution of the imide. The prior art does not disclose how carbon tetrachloride was handled in the final product.

[0017] While attempts have been made to obtain substantially pure sulfenylphthalimide, there is still a need to develop a simple, efficient, and cost-effective process for obtaining sulfenylphthalimide with haloalkane impurities, particularly carbon tetrachloride impurities, below the minimum acceptable limit. [Overview of the project]

[0018] Problems that the invention aims to solve The objective of the present invention is to develop a fungicidal sulfenylphthalimide compound that is substantially free of undesirable haloalkane impurities.

[0019] The objective of the present invention is to develop sulfenyl compounds that are substantially free of haloalkane impurities.

[0020] Another object of the present invention is to develop a substantially carbon tetrachloride-free fungicidal sulfenylphthalimide compound using aromatic hydrocarbons that minimize haloalkane impurities in the fungicidal sulfenylphthalimide compound.

[0021] Another object of the present invention is to provide a simple process for preparing a sulfenyl phthalimide compound in high yield and high purity. This process is simple, easy, convenient to carry out, economical and efficient.

[0022] Yet another object of the present invention is to provide a process for preparing a fungicidal sulfenyl phthalimide compound substantially free of haloalkane impurities, which process is efficient, simple and cost-effective.

[0023] Yet another object of the present invention is to develop a method for obtaining a fungicidal sulfenyl phthalimide compound in high yield.

[0024] Summary of the Invention In one aspect, the present invention relates to the preparation of a fungicidal sulfenyl phthalimide compound represented by formula (I), which compound of formula (I) is substantially free of undesirable haloalkane impurities.

[0025] In another aspect, the present invention relates to the preparation of a fungicidal sulfenyl phthalimide compound represented by formula (I), which compound of formula (I) is substantially free of haloalkane impurities.

[0026] [Chemical formula] (Wherein, K together with two adjacent carbon atoms forms a fused 6-membered aromatic ring a or a fused cyclohexene ring.)

[0027] In another aspect, the present invention provides a process for preparing a compound represented by formula (I), wherein K together with two adjacent carbon atoms forms a fused cyclohexene ring substantially free of haloalkane impurities, and the compound of formula (I) is 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfenyl)phthalimide.

[0028] In another embodiment, the present invention provides a process for preparing a compound represented by formula (I), wherein K, together with two consecutive carbon atoms, forms a substantially haloalkane-free condensed aromatic ring, and the compound of formula (I) is N-(trichloromethanesulfenyl)phthalimide.

[0029] In another aspect, the present invention provides a process for preparing a compound represented by formula (II) that is substantially free of haloalkane impurities and used for preparing a compound represented by formula (I).

[0030] [ka]

[0031] Another aspect of the present invention relates to a synthesis process for a fungicidal sulfenylphthalimide compound represented by formula (I) that is substantially free of haloalkane impurities, (a) Reacting an organosulfur compound with chlorine yields formula (II): [ka] A step of forming a sulfenyl compound represented by, (b) A step of converting the sulfenyl compound of formula (II) into a fungicidal sulfenylphthalimide compound of formula (I) that is substantially free of haloalkane impurities, Includes.

[0032] In another aspect of the present invention, the synthesis process of a fungicidal sulfenylphthalimide compound represented by formula (I) is as follows: (a) A step of reacting an organosulfur compound with chlorine to form a sulfenyl compound, (b) A step of isolating a pure sulfenyl compound by treating the sulfenyl compound with an aromatic hydrocarbon to remove haloalkane impurities, (c) A step of reacting a sulfenyl compound of formula (II) with phthalimide or a phthalimide derivative to obtain a pure sulfenylphthalimide compound represented by formula (I), Includes.

[0033] In another aspect of the present invention, the synthesis process of a 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfenyl)phthalimide compound of formula (I) substantially free of haloalkane impurities is as follows: (a) A step of reacting an organosulfur compound with chlorine to form a sulfenyl compound, (b) A step of treating the sulfenyl compound from step (a) with an aromatic hydrocarbon to remove haloalkane impurities and obtain a pure sulfenyl compound of formula (II), (c) A step of reacting a sulfenyl compound of formula (II) with tetrahydrophthalimide to obtain a pure 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfenyl)phthalimide compound of formula (I), Includes.

[0034] Another aspect of the present invention is a synthesis process for an N-(trichloromethanesulfenyl)phthalimide compound of formula (I) that is substantially free of haloalkane impurities, the process being: (a) A step of reacting an organosulfur compound with chlorine to form a sulfenyl compound, (b) A step of treating the sulfenyl compound from step (a) with an aromatic hydrocarbon to remove haloalkane impurities and obtain a pure sulfenyl compound of formula (II), (c) A step of reacting a sulfenyl compound of formula (II) in an aromatic hydrocarbon with phthalimide to obtain a pure N-(trichloromethanesulfenyl)phthalimide compound of formula (I), Includes.

[0035] In one aspect of the present invention, the synthesis process of a sulfenyl compound of formula (II) that is substantially free of haloalkane impurities is: (a) A step of reacting an organosulfur compound with chlorine to form a sulfenyl compound, (b) A step of treating the sulfenyl compound from step (a) with an aromatic hydrocarbon to remove haloalkane impurities and obtain a pure sulfenyl compound of formula (II) that is substantially free of haloalkane impurities, Includes.

[0036] In another aspect of the present invention, a synthesis process for a fungicidal sulfphenylphthalimide compound of formula (I) that is substantially free of haloalkane impurities, the process comprising reacting a sulfphenyl compound of formula (II) in an aromatic hydrocarbon with a phthalimide or phthalimide derivative compound to obtain a fungicidal sulfphenylphthalimide compound of formula (I). [Modes for carrying out the invention]

[0037] While several embodiments of the present invention have been described and illustrated herein, those skilled in the art will readily conceive of various other means and / or structures for performing the function and / or obtaining the results and / or one or more advantages described herein, each of such variations and / or modifications is considered to be within the scope of the present invention.

[0038] Surprisingly, the inventors of the present invention have found that when a sulfenyl compound is prepared by chlorinating carbon disulfene, subsequently treating the resulting crude sulfenyl compound with aromatic hydrocarbons, reacting the sulfenyl compound with phthalimide or a phthalimide derivative, and further treating it with aromatic hydrocarbons to obtain a substantially pure sulfenylphthalimide compound, the fungicidal sulfenylphthalimide compound of formula (I) can be obtained in a substantially pure form, containing only negligible haloalkane impurities.

[0039] The aromatic hydrocarbon treatment used in the synthesis of both sulfenyl compounds and sulfenylphthalimide compounds helps reduce haloalkane impurities, ultimately resulting in substantially pure sulfenylphthalimide compounds.

[0040] Advantageously, the present invention achieves improvements in the production of sulfenylphthalimide compounds and derivative compounds, such as captan and forpet, through the use of aromatic hydrocarbons, which are thought to minimize the formation of undesirable haloalkane impurities.

[0041] In a broad sense, the present invention envisions a process for preparing substantially pure fungicidal sulfenylphthalimide compounds from haloalkane impurities, and for preparing substantially pure fungicidal sulfenylphthalimide compounds from haloalkane impurities using aromatic hydrocarbons. The process envisioned by the present invention is further described by the following reaction scheme.

[0042] Process I: [ka]

[0043] Process II: [ka]

[0044] According to the present invention, the fungicidal sulfenyphthalimide compound of formula (I) represents some preferred compounds, and the compound of formula (I) represented by the structure shown below is substantially free of haloalkane impurities.

[0045] [ka] (In the formula, K, together with two consecutive carbon atoms, forms a condensed six-membered aromatic ring a or a condensed cyclohexene ring.)

[0046] One embodiment of the present invention provides a compound of formula I substantially free of haloalkane impurities, wherein K combines with two consecutive carbon atoms to form a condensed cyclohexene ring, and a process for preparing the same, wherein the compound of formula (I) is 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfenyl)phthalimide, represented by the following formula.

[0047] [ka]

[0048] One embodiment of the present invention provides a compound of formula I substantially free of haloalkane impurities, wherein K forms a condensed aromatic ring with two consecutive carbon atoms, and a process for preparing the same, wherein the compound of formula (I) is N-(trichloromethanesulfenyl)phthalimide as shown below.

[0049] [ka]

[0050] According to one embodiment of the present invention, a compound of formula (II) that is substantially free of haloalkane impurities and a process for preparing the same are provided.

[0051] [ka]

[0052] According to the present invention, the compound of formula (II) is also known as trichloromethanesulfenyl chloride or perchloromethyl mercaptan (PCMM).

[0053] According to the present invention, the fungicidal sulfenylphthalimide compound of formula (I) is substantially free of haloalkane impurities.

[0054] According to the present invention, a fungicidal sulfenylphthalimide compound of formula (I) that is substantially free of haloalkane impurities refers to a compound of formula (I) in which the haloalkane impurity is less than 0.05%, preferably less than 0.01%, (as measured by gas chromatography).

[0055] According to the present invention, the sulfenyl compound of formula (II) is substantially free of haloalkane impurities.

[0056] According to the present invention, a sulfenyl compound of formula (II) that is substantially free of haloalkane impurities refers to a compound of formula (II) in which the haloalkane impurity is less than 0.10, preferably less than 0.08%, in gas chromatography.

[0057] According to one embodiment of the present invention, haloalkane impurities refer to undesirable impurities belonging to the group including carbon tetrachloride and dichloro(chlorosulfanyl)methanesulfonyl chloride or mixtures thereof, which are produced during the synthesis process of sulfenyl compounds or sulfenylphthalimide compounds.

[0058] Typically, according to a preferred embodiment of the present invention, the haloalkane impurity is carbon tetrachloride.

[0059] According to one embodiment of the present invention, the haloalkane impurities present in sulfenylphthalimide may be any impurities, including reaction by-products, intermediates, starting materials, and solvents.

[0060] According to one embodiment of the present invention, haloalkane impurities can be removed by azeotropic mixtures through vacuum distillation, heat, or low-pressure evaporation.

[0061] According to one embodiment of the present invention, haloalkane impurities are preferably removed by distillation.

[0062] According to one embodiment of the present invention, a synthesis process for a fungicidal sulfenylphthalimide compound of formula (I) that is substantially free of haloalkane impurities is provided, and the process is as follows: (a) A step of reacting an organic sulfur compound with chlorine to form a sulfenyl compound, treating the sulfenyl compound with an aromatic hydrocarbon to remove haloalkane impurities and obtain a pure sulfenyl compound of formula (II), (b) A step of reacting a sulfenyl compound of formula (II) in an aromatic hydrocarbon with phthalimide or a phthalimide derivative to obtain a pure sulfenylphthalimide compound of formula (I), Includes.

[0063] In one embodiment, step (a) is carried out in the presence of an aqueous acidic medium, and the sulfenyl compound is further treated with an aromatic hydrocarbon solvent to obtain a pure sulfenyl compound of formula (II) that is substantially free of haloalkane impurities.

[0064] In one embodiment, step b) is carried out in the presence of an aqueous alkaline medium, and the sulfenylphthalimide compound is further treated with an aromatic hydrocarbon to obtain a pure sulfenylphthalimide compound (I) that is substantially free of haloalkane impurities.

[0065] According to one embodiment of the present invention, a synthesis process for a fungicidal sulfenylphthalimide compound of formula (I) that is substantially free of haloalkane impurities is provided, and the process is as follows: (a) A step of reacting an organic sulfur compound with chlorine to obtain a crude sulfenyl compound, (b) A step of treating the crude sulfenyl compound from step (a) with an aromatic hydrocarbon to remove haloalkane impurities and obtain a sulfenyl compound of formula (II), (c) A step of reacting a sulfenyl compound of formula (II) with phthalimide or a phthalimide derivative to obtain a sulfenylphthalimide compound of formula (I), Includes.

[0066] According to one embodiment of the present invention, a synthesis process for a 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfenyl)phthalimide compound of formula (I) that is substantially free of haloalkane impurities, the process is as follows: (a) A step of reacting an organic sulfur compound with chlorine to obtain a crude sulfenyl compound, (b) A step of treating the crude sulfenyl compound from step (a) with an aromatic hydrocarbon to remove haloalkane impurities and obtain a sulfenyl compound of formula (II), (c) A step of reacting a sulfenyl compound of formula (II) with tetrahydrophthalimide in an aromatic hydrocarbon to obtain a 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfenyl)phthalimide compound of formula (I), Includes.

[0067] In step a), the organosulfur compound is carbon disulfide, and the sulfenyl compound is perchloromethyl mercaptan. Typically, step a) is carried out at 5-10°C. After the completion of the reaction in step a), the reaction mixture is treated with an aromatic hydrocarbon solvent. The aromatic hydrocarbon solvent used is selected from the group including toluene, chlorobenzene, ethylbenzene, propylbenzene, xylene, etc. The solution thus obtained is then subjected to distillation to remove unwanted impurities, and a pure sulfenyl compound is isolated that can be used directly for the preparation of the sulfenylphthalimide compound of formula (I) without further purification.

[0068] In step c), the pure sulfenyl compound obtained in step b) is reacted with tetrahydrophthalimide in an aqueous basic medium. Typically, the reaction is carried out at a low temperature of 1 to 5 hours, preferably about 1 to 2 hours, preferably 0 to 10°C, more preferably 0 to 5°C. Then, an aromatic hydrocarbon solvent is added to the reaction mass, and the mixture is heated to a temperature in the range of 50 to 100°C, preferably 70 to 80°C, to obtain a high purity and high yield, and preferably an undesirable result. Haloalkane impurities A pure sulfenylphthalimide compound, with its concentration reduced to less than 0.01%, is isolated from the mixture.

[0069] According to one embodiment of the present invention, a synthesis process for an N-(trichloromethanesulfenyl)phthalimide compound of formula (I) that is substantially free of haloalkane impurities, the process is as follows: (a) A step of reacting an organosulfur compound with chlorine to form a sulfenyl compound, (b) A step of treating the sulfenyl compound from step (a) with an aromatic hydrocarbon to remove haloalkane impurities and obtain a sulfenyl compound of formula (II), (c) A step of reacting a sulfenyl compound of formula (II) with phthalimide to obtain an N-(trichloromethanesulfenyl)phthalimide compound of formula (I), Includes.

[0070] According to one embodiment of the present invention, there is a synthesis process for a sulfenyl compound of formula (II) that is substantially free of haloalkane impurities, and the process is (a) A step of reacting an organic sulfur compound with chlorine to obtain a crude sulfenyl compound, (b) A step of treating the crude sulfenyl compound from step (a) with an aromatic hydrocarbon to remove haloalkane impurities and obtain a sulfenyl compound of formula (II) that is substantially free of haloalkane impurities, Includes.

[0071] Another aspect of the present invention is a synthesis process for a fungicidal sulfenylphthalimide compound of formula (I) that is substantially free of haloalkane impurities, the process being: The process includes a step of reacting a sulfenyl compound of formula (II) with phthalimide or a phthalimide derivative to obtain a fungicidal sulfenylphthalimide compound of formula (I).

[0072] According to one embodiment of the present invention, a synthesis process for a 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfenyl)phthalimide compound of formula (I) that is substantially free of haloalkane impurities, the process is as follows: The present invention includes a step of reacting a sulfenyl compound of formula (II) obtained according to the process of the present invention with tetrahydrophthalimide to obtain a pure 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfenyl)phthalimide compound of formula (II) that is substantially free of haloalkane impurities.

[0073] According to one embodiment of the present invention, the organosulfur compound is selected from the group including carbon disulfide, carbonyl sulfide, thiophosgene, and the like.

[0074] According to a preferred embodiment of the present invention, the organosulfur compound is carbon disulfide.

[0075] According to one embodiment of the present invention, the acid medium used in step (a) to form the sulfenyl compound of formula (II) is selected from the group including hydrochloric acid (HCl), phosphoric acid, and sulfuric acid.

[0076] According to a preferred embodiment of the present invention, the acid medium used in step (a) to form the sulfenyl compound of formula (II) is hydrochloric acid (HCl).

[0077] According to one embodiment of the present invention, the alkaline medium used in step (b) to form the sulfenylphthalimide compound of formula (I) is selected from the group including sodium hydroxide (NaOH), potassium hydroxide (KOH), lithium hydroxide (LiOH), potassium carbonate (K2CO3), and the like.

[0078] According to a preferred embodiment of the present invention, the alkaline medium used in step (b) to form the sulfenylphthalimide compound of formula (I) is sodium hydroxide (NaOH).

[0079] According to one embodiment of the present invention, the aromatic hydrocarbon used in the synthesis of the sulfenylphthalimide compound of formula (I) and the sulfenyl compound of formula (II) is selected from the group including toluene, chlorobenzene, ethylbenzene, propylbenzene, xylene, and the like.

[0080] According to a preferred embodiment of the present invention, the aromatic hydrocarbon used in the synthesis of the sulfenylphthalimide compound of formula (I) and the sulfenyl compound of formula (II) is toluene.

[0081] Therefore, the fungicidal sulfenylphthalimide compound of formula (I) obtained by the process of the present invention as described above is substantially free of haloalkane impurities.

[0082] Preferably, the 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfenyl)phthalimide obtained by the process of the present invention is substantially free of haloalkane impurities.

[0083] Preferably, the N-(trichloromethanesulfphenyl)phthalimide obtained by the process of the present invention is substantially free of haloalkane impurities.

[0084] In one embodiment, the process according to the present invention involves particle size distribution D 10 This provides fungicidal sulfenylphthalimide particles less than approximately 23.101 μm in size.

[0085] In one embodiment, the process according to the present invention involves particle size distribution D 50 This provides fungicidal sulfenylphthalimide with a particle size of less than approximately 72.223 μm.

[0086] In one embodiment, the process according to the present invention involves particle size distribution D 90 This provides fungicidal sulfenylphthalimide with a particle size of less than approximately 172.728 μm.

[0087] According to the present invention, the compound of formula (1) can be obtained in high yield and has a high purity of over 98.5%. The process is simple, easy, convenient to carry out, efficient, economical, and industrially and commercially feasible.

[0088] According to one embodiment of the present invention, a fungicidal sulfenylphthalimide compound may be used in any type of solid or liquid formulation for agricultural applications, together with other optional components including, but not limited to, surfactants, dispersants, wetting agents, defoamers, antimicrobial agents, antioxidants, buffers, dyes, fragrances, stabilizers, and water-soluble salts.

[0089] According to one embodiment of the present invention, the fungicidal sulfenylphthalimide compound can also be mixed with other pesticide-acceptable components, such as fertilizers, plant-harmful substances, plant growth regulators, toxicity mitigators, and insecticides, including ammonium nitrate, urea, potassium, and superphosphates.

[0090] According to one embodiment, the present invention provides a fungicidal composition comprising a fungicidal sulfenylphthalimide compound of formula (I) that is substantially free of haloalkane impurities, prepared according to the present process. In another embodiment, the present invention provides a method for treating a fungal infection by applying a fungicidal sulfenylphthalimide compound of formula (I) that is substantially free of haloalkane impurities, prepared according to the present process, to a gene locus.

[0091] It will be apparent to those skilled in the art that various modifications and changes can be made to the present invention without departing from the scope or spirit of the invention. Other embodiments of the present invention will be apparent to those skilled in the art by considering the specifications and practices of the invention disclosed herein. This specification and the examples are intended to be illustrative only to the true extent. The process for preparing sulfenylphthalimide compounds is shown in the following examples. [Examples]

[0092] Example 1: Synthesis of 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfphenyl)phthalimide Step 1: To 1664 g of water, 974 g (30%) aqueous HCl solution and 380 g of carbon disulfide were added at 5-10°C, and the mixture was purged with chlorine gas at the same temperature for 22-24 hours. After the reaction was complete, the layers were separated, the organic mass was recovered, toluene (210 g / m³) was added, and the further organic layer was washed twice with 250 g / m³ of water. 905 g of crude perchloromethyl mercaptan (PCMM) toluene solution was obtained. The crude PCMM toluene solution was distilled on a 3-foot packed column to remove carbon tetrachloride (CTC), a low-boiling substance and haloalkane impurity, along with the toluene under vacuum. The PCMM toluene solution thus obtained was further acquired for Step 2. Final sulfenyl compound (PCMM) specifications: Residual PCMM: (778.0 g). Yield: 77.0%, Purity: 92.61%, CTC - 0.07% (by GC).

[0093] Step 2: 44.60 g (48%) NaOH solution was added to 400 g of water, and then cooled to 10-15°C. 81.38 g of tetrahydrophthalimide was slowly added to the above solution over 10-15 minutes, and the mixture was stirred at the same temperature for a further 45 minutes. Once a clear solution was observed, the mixture was then cooled to 0-2°C to obtain a reaction mass. Separately, 100.4 g of PCMM solution obtained in Step 1 was added to the reaction mass. Once precipitation was observed during the addition, the mixture was stirred at the same temperature for 2.0 hours. As a post-treatment, toluene (323 g) was added, and the reaction mass was heated to 75-80°C while stirring for 30 minutes, then cooled to 20-25°C, filtered, and washed twice with toluene (85 g) and hot water (98 g) to finally obtain 133.4 g of isolated dry solid. Specifications of the final sulfenylphthalimide compound: Yield: 88.78%, Purity: 98.70%, 0.0092% CTC.

[0094] Example 2: Synthesis of 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfphenyl)phthalimide Step I: To 323.6 g of water, 188.8 g (30%) aqueous HCl solution and carbon disulfide (73.6 g) were added at 5-10°C, and the mixture was purged with chlorine gas at the same temperature for 22-24 hours. After the reaction was complete, the layers were separated. Chlorobenzene (48.4 g / m) was added to the organic mass and washed twice with 48.4 g / m of water. 192.0 g of crude perchloromethyl mercaptan (PCMM) chlorobenzene solution was obtained. The crude PCMM chlorobenzene solution was distilled on a 3-foot packed column to remove carbon tetrachloride (CCl4), a low-boiling substance and haloalkane impurity, along with the chlorobenzene under vacuum. The PCMM chlorobenzene solution thus obtained was further acquired for Step 2. Final sulfenyl compound (PCMM) specifications: Residual PCMM: (147.2 g). Yield: 72.0%, Purity: 88.10%, CTC: 0.06%.

[0095] Step 2: 33.72 g (48%) NaOH solution was added to 302.4 g of water, and then cooled to 10-15°C. 61.3 g of tetrahydrophthalimide was slowly added to the above solution over 10-15 minutes, and the mixture was stirred at the same temperature for a further 45 minutes. Once a clear solution was observed, the mixture was then cooled to 0-2°C to obtain a reaction mass. Separately, 79.8 g of PCMM solution obtained in Step 1 was added to the reaction mass. Once precipitation was observed during the addition, the mixture was stirred at the same temperature for 2.0 hours. As a post-treatment, chlorobenzene (244 g) was added, and the reaction mass was heated to 75-80°C while stirring for 30 minutes, cooled to 20-25°C, filtered, and washed twice with chlorobenzene (64.2 g) and hot water (74.1 g) to finally obtain 91.5 g of isolated dry solid. Specifications of the final sulfenylphthalimide compound: Yield: 80.54%, Purity: 97.80%, CTC-0.008%.

[0096] Example 3: Synthesis of 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfphenyl)phthalimide Step I: To 323.6 g of water, 188.8 g (30%) aqueous HCl solution and carbon disulfide (73.6 g) were added at 5-10°C, and the mixture was purged with chlorine gas at the same temperature for 22-24 hours. After the reaction was complete, the layers were separated. Xylene (48.4 g / m) was added to the organic mass and washed twice with 48.4 g / m of water. 194.0 g of crude perchloromethyl mercaptan (PCMM) xylene solution was obtained. The crude PCMM xylene solution was distilled on a 3-foot packed column to remove low-boiling substances and haloalkane impurities, such as carbon tetrachloride (CCl4), along with the xylene under vacuum. The PCMM xylene solution thus obtained was further acquired for Step 2. Final sulfenyl compound (PCMM) specifications: Residual PCMM: (143.0 g). Yield: 70.40%, Purity: 88.70%, CTC: 0.07%.

[0097] Step 2: 33.72 g (48%) NaOH solution was added to 302.4 g of water and then cooled to 10-15°C. 61.3 g of tetrahydrophthalimide was slowly added to the solution over 10-15 minutes, and the mixture was stirred at the same temperature for a further 45 minutes. Once a clear solution was observed, the mixture was cooled to 0-2°C to obtain a reaction mass. Separately, 79.3 g of PCMM solution obtained in Step 1 was added to the reaction mass. Once precipitation was observed during the addition, the mixture was stirred at the same temperature for 2.0 hours. As a post-treatment, xylene (244 g) was added, and the reaction mass was heated to 75-80°C while stirring for 30 minutes. The mixture was then cooled to 20-25°C, filtered, and washed twice with xylene (64.2 g) and hot water (74.1 g) to finally obtain 88.0 g of isolated dry solid. Specifications of the final sulfenylphthalimide compound: Yield: 77.46%, Purity: 97.71%, CTC-0.0084%.

[0098] Example 4: Synthesis of 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfphenyl)phthalimide Step I: To 323.6 g of water, 188.8 g (30%) aqueous HCl solution and carbon disulfide (73.6 g) were added at 5-10°C, and the mixture was purged with chlorine gas at the same temperature for 22-24 hours. After the reaction was complete, the layers were separated. Ethylbenzene (48.4 g / m) was added to the organic mass and washed twice with 48.4 g / m of water. 190.0 g of crude perchloromethyl mercaptan (PCMM) ethylbenzene solution was obtained. The crude PCMM ethylbenzene solution was distilled on a 3-foot packed column to remove carbon tetrachloride (CCl4), a low-boiling substance and haloalkane impurity, along with ethylbenzene under vacuum. The PCMM ethylbenzene solution thus obtained was further acquired for Step 2. Final sulfenyl compound (PCMM) specifications: Residual PCMM: (146.3 g). Yield: 71.80%, Purity: 88.40% w / w, CTC - 0.06%.

[0099] Step 2: 33.72 g (48%) NaOH solution was added to 302.4 g of water, and then cooled to 10-15°C. 61.3 g of tetrahydrophthalimide was slowly added to the above solution over 10-15 minutes, and the mixture was stirred at the same temperature for a further 45 minutes. Once a clear solution was observed, the mixture was then cooled to 0-2°C to obtain a reaction mass. Separately, 79.60 g of PCMM solution obtained in Step 1 was added to the reaction mass. Once precipitation was observed during the addition, the mixture was stirred at the same temperature for 2.0 hours. As a post-treatment, ethylbenzene (244 g) was added, and the reaction mass was heated to 75-80°C while stirring for 30 minutes, cooled to 20-25°C, filtered, and washed twice with ethylbenzene (64.2 g) and hot water (74.1 g) to finally obtain 95.0 g of isolated dry solid. Specifications of the final sulfenylphthalimide compound: Yield: 83.6%, Purity: 98.61%, CTC-0.0088%.

[0100] Example 5: Synthesis of perchloromethyl mercaptan (PCMM) To 1664 g of water, 974 g (30%) aqueous HCl solution and 380 g of carbon disulfide were added at 5-10°C, and the mixture was purged with chlorine gas at the same temperature for 22-24 hours. After the reaction was complete, the layers were separated, the organic mass was recovered, toluene (210 g / m³) was added, and the remaining organic layer was washed twice with 250 g / m³ of water. 905 g of crude perchloromethyl mercaptan (PCMM) toluene solution was obtained. The crude PCMM toluene solution was distilled on a 3-foot packed column to remove low-boiling substances and haloalkane impurities, such as carbon tetrachloride (CCl₄), along with the toluene under vacuum. Final sulfenyl compound (PCMM) specifications: Residual PCMM: (778.0 g). Yield: 77.0%, Purity: 92.61%, CTC: 0.07%.

[0101] Example 6: Synthesis of N-(trichloromethanesulfphenyl)phthalimide Step 1: 974 g (30%) aqueous HCl solution and 380 g carbon disulfide were charged to 1664 g of water at 5-10°C, and chlorine gas was purged at the same temperature for 22-24 hours. After the reaction was complete, the layers were separated, the organic mass was recovered, toluene (210 g / m³) was added, and the further organic layer was washed twice with 250 g / m³ of water. 905 g of crude perchloromethyl mercaptan (PCMM) toluene solution was obtained. Distillation of the crude PCMM toluene solution on a 3-foot packed column was performed to remove carbon tetrachloride (CCl₄), a low-boiling substance and haloalkane impurity, along with toluene under vacuum. The PCMM toluene solution thus obtained was further acquired for Step 2. Final sulfenyl compound (PCMM) specifications: Residual PCMM: (778.0 g). Yield: 77.0%, Purity: 92.61%, CTC: 0.07%.

[0102] Step 2: 24 g (48%) NaOH solution was added to 200 g of water and then cooled to 10-15°C. 40.3 g of phthalimide was slowly added to the solution over 10-15 minutes, and the mixture was stirred at the same temperature for a further 45 minutes. Once a clear solution was observed, the mixture was then cooled to 0-2°C to obtain a reaction mixture. Separately, 53.98 g of PCMM solution obtained in Step 1 was added to the reaction mixture. Once precipitation was observed during the addition, the mixture was stirred at the same temperature for 2.0 hours. As a work-up, toluene (174 g) was added, and the reaction mixture was heated to 75-80°C while stirring for 30 minutes, then cooled to 20-25°C, filtered, and washed twice with toluene (45.6 g) and hot water (52.6 g) to finally obtain 55.8 g of isolated dry solid. Specifications of the final sulfenylphthalimide compound: Yield: 70%, Purity: 96.0%.

[0103] Thus, we succeeded in preparing a fungicidal sulfenylphthalimide compound substantially free of haloalkane impurities using the process according to the present invention. Treatment of the crude sulfenyl compound with aromatic hydrocarbons yields a sulfenyl compound with fewer haloalkane impurities, and the resulting sulfenyl compound can be further used to synthesize a sulfenylphthalimide compound substantially free of haloalkane impurities. It should be understood that the present invention should not be limited to the details of the above embodiments described merely as examples.

Claims

1. Equation (I): 【Chemistry 1】 (In the formula, K, together with two consecutive carbon atoms, forms a six-membered condensed aromatic ring or a condensed cyclohexene ring.) A process for preparing a fungicidal sulfenylphthalimide compound represented by, The aforementioned process, (a) React an organosulfur compound with chlorine to produce formula (II): 【Chemistry 2】 A step of forming a sulfenyl compound represented by, (b) A step of converting the sulfenyl compound of formula (II) into a fungicidal sulfenylphthalimide compound of formula (I) that is substantially free of haloalkane impurities, wherein the haloalkane impurities are selected from carbon tetrachloride and dichloro(chlorosulfanyl)methanesulfonyl chloride or a mixture thereof, A process for preparing a fungicidal sulfenylphthalimide compound of formula (I), including the following:

2. The process according to claim 1, wherein step (a) is carried out in the presence of an aqueous acidic medium and in a temperature range of 5°C to 20°C, and the sulfenyl compound is further treated with an aromatic hydrocarbon to obtain a sulfenyl compound of formula (II) that is substantially free of haloalkane impurities.

3. The process according to claim 1, wherein step (b) includes reacting a sulfenyl compound of formula (II) with a phthalimide or phthalimide derivative compound in a temperature range of 0°C to 10°C to obtain a sulfenylphthalimide compound of formula (I) that is substantially free of haloalkane impurities. 【Transformation 3】

4. The process according to claim 3, wherein the process is carried out in the presence of an aqueous alkaline medium and an aromatic hydrocarbon to obtain a sulfenylphthalimide compound of formula (I) that is substantially free of haloalkane impurities selected from carbon tetrachloride and dichloro(chlorosulfanyl)methanesulfonyl chloride or a mixture thereof.

5. The process according to claim 1, wherein the organic sulfur compound is selected from carbon disulfide, carbonyl sulfide, and thiophosgene.

6. The process according to claim 2, wherein the acid used in the acidic solution is selected from hydrochloric acid, phosphoric acid, and sulfuric acid.

7. The process according to claim 4, wherein the alkali used in the alkaline medium is selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, and potassium carbonate.

8. The process according to claim 2 or 4, wherein the aromatic hydrocarbon is selected from toluene, chlorobenzene, ethylbenzene, propylbenzene, and xylene.

9. a) A step of reacting carbon disulfide with chlorine in an acidic aqueous solution to obtain perchloromethyl mercaptan, and treating the perchloromethyl mercaptan with an aromatic hydrocarbon to obtain perchloromethyl mercaptan substantially free of haloalkane impurities, 【Chemistry 4】 b) A step of reacting a compound of formula (II) in an aromatic hydrocarbon solvent with a phthalimide or phthalimide derivative compound in an aqueous alkaline medium to obtain a sulfenylphthalimide compound of formula (I) that is substantially free of haloalkane impurities, 【Transformation 5】 This includes preparing a sulfenylphthalimide compound of formula (I), The process according to claim 1, wherein the compound of formula (II) and the compound of formula (I) are substantially free of carbon tetrachloride impurities.

10. The process according to claim 9, wherein the carbon tetrachloride impurity is reduced to less than 0.05% in the process.

11. The process according to claim 1, wherein the obtained compound of formula (II) and compound of formula (I) have a purity of 98%.

12. The process according to claim 1, wherein the sulfenylphthalimide compound of formula (I) is selected from 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfenyl)phthalimide or N-(trichloromethanesulfenyl)phthalimide.

13. The 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfenyl)phthalimide compound is (a) A step of reacting an organic sulfur compound with chlorine in the presence of an acidic aqueous solution to obtain crude perchloromethyl mercaptan, (b) A step of isolating pure perchloromethyl mercaptan substantially free of haloalkane impurities by treating crude perchloromethyl mercaptan with aromatic hydrocarbons, (c) A step of reacting pure perchloromethyl mercaptan with tetrahydrophthalimide in the presence of an aqueous alkaline medium to obtain a 3a,4,7,7a-tetrahydro-N-(trichloromethanesulfenyl)phthalimide compound substantially free of haloalkane impurities, The process according to claim 12, which is prepared by...

14. The aforementioned N-(trichloromethanesulfenyl)phthalimide compound (a) A step of reacting carbon disulfide with chlorine in an acidic aqueous solution to obtain crude perchloromethyl mercaptan, (b) A step of isolating pure perchloromethyl mercaptan substantially free of haloalkane impurities by treating the crude perchloromethyl mercaptan obtained in step (a) with an aromatic hydrocarbon solvent, (c) A step of reacting pure perchloromethyl mercaptan in an aromatic hydrocarbon with a phthalimide compound in an aqueous alkaline medium to obtain an N-(trichloromethanesulfenyl)phthalimide compound substantially free of haloalkane impurities, The process according to claim 12, which is prepared by...

15. Formula (II): 【Transformation 6】 A process for preparing sulfenyl compounds represented by, (a) A step of reacting an organic sulfur compound with chlorine in an acidic aqueous solution to obtain a crude sulfenyl compound, (b) A step of treating a crude sulfenyl compound with an aromatic hydrocarbon solvent to isolate a sulfenyl compound of formula (II) that is substantially free of haloalkane impurities, A process for preparing sulfenyl compounds of formula (II), including the following.

16. The process according to claim 15, comprising the steps of reacting carbon disulfide with chlorine to obtain perchloromethyl mercaptan, and treating the perchloromethyl mercaptan with toluene to obtain perchloromethyl mercaptan substantially free of haloalkane impurities.

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