MX2008010139A - Process for production of o-methyl-n-nitroisourea - Google Patents

Abstract

Disclosed is an industrially advantageous process for production of O-methyl-N-nitroisourea. O-methyl-N-nitroisourea of the formula (1) or a salt thereof can be produced in a high yield by performing the nitration of O-methylisourea of the formula (2) or a salt thereof with a nitrating agent in the presence of fuming sulfuric acid.

Description

PROCESS TO PRODUCE O-METHYL-N-NITROISOUREA Field of the Invention The present invention relates to an improved process for producing O-methyl-N-nitroisourea which is useful as a synthetic intermediate of an insecticide. Background of the Invention O-methyl-N-nitroisourea is represented by the following chemical formula (1).

O-methyl-N-nitroisourea is useful, for example, as a synthetic intermediate of guanidine derivatives, which are useful as an insecticide. As a process for producing O-methyl-N-nitroisourea, a process for reacting O-methylisourea with nitration agents has been known. In the process, after the nitration is carried out with nitric acid in sulfuric acid, the reaction mixture is poured into cold water, ice or ice water, and cooled to a temperature of about -15 degrees centigrade.

When the generated O-methyl-N-nitroisourea is collected by filtration, O-methyl-N-nitroisourea is obtained. only in a yield of about 75% by filtration (for example, it refers to the Non-Patent Document 1). Because O-methyl-N-nitroisourea is soluble water. In addition, by extracting O-methyl-N-nitroisourea from a filtrate after filtration, the yield is increased to approximately 90%. However, since the solubility of O-methyl-N-nitroisourea in a solvent can be used so that the extraction is not too high, a large amount of organic solvent is needed for extraction and the process becomes complicated. Therefore, the process is not industrially convenient (for example, it refers to Patent Document 2, Non-Patent Documents 1 and 2). In addition, since the isolation and effective purification of N-nitroisourea are difficult, N-nitroisourea is used for the next reaction without isolation (refer to Patent Document 1). Patent Document 1: WO01 / 42787. Patent Document 2: WO97 / 00867. Non-Patent Document 1: Recueil des Travaux Chimiques des Pays-Bas, Vol. 81, p.69 (1962) Non-Patent Document 2: Journal of Chemical Society, p. 3551 (1955). Brief Description of the Invention An object of the present invention is to provide a industrially excellent process for producing O-methyl-N-nitroisourea, which is an important intermediate for producing guanidine derivatives having insecticidal activity, overcoming the problems mentioned in the prior art. That is, it is an object of the present invention to provide a process in which the yield of the reaction of O-methyl-N-nitroisourea obtained by nitration of O-methylisourea is increased and in which the O-methyl-N-nitroisourea is easily isolated through an industrially available process. In order to achieve the above objects, the inventors of the present invention have carried out an extensive study of a process for producing O-methyl-N-nitroisourea or a salt thereof. As a result, the inventors of the present invention have discovered that O-methyl-N-nitroisourea represented by the following chemical formula (1) or a salt thereof, is obtained with a high yield, by reacting O-methylisourea represented by the following chemical formula (2) or a salt thereof with nitration agents in the presence of smoldering sulfuric acid. NH Even though it is assumed that there are by-products generated by nitration, the starting material and the large amount of sulfates and nitrates in the reaction mixture in the present invention are usually unexpected since the compound is represented by the chemical formula (1 ) or a salt thereof, is obtained with a high yield. The inventors of the present invention have carried out a detailed study of the nitration of the compound represented by the chemical formula (2), with nitration agents and as a result, have discovered that the water generated during the reaction has a great influence on the reaction, causing a clogging of the reaction and deterioration of the reaction yield. That is, nitration is a reversible reaction, and the water generated by the reaction reacts with O-methyl-N-nitroisourea to produce O-methylisourea. For this reason, the reaction does not proceed completely and the reaction yield of O-methyl-N-nitroisourea becomes low. In addition, when a large amount of sulfuric acid and nitric acid is used, the influence of the sub-produced water becomes smaller, since the reaction proceeds and the reaction yield is improved. Without However, since the crystallization yield is decreased, the isolation of O-methyl-N-nitroisourea becomes difficult to carry out, and at the same time a large amount of acid waste is generated. The inventors of the present invention have carried out an extensive study of the dehydration conditions to allow an easy and effective isolation process without the influence of a sulfuric acid and nitration agents, such as nitric acid in the reaction mixture. As a result, the inventors of the present invention have further discovered an optimum condition by employing smoking sulfuric acid as a dehydrating agent in the reaction. In the present invention, by removing a part of water or all the water generated in the reaction using smoking sulfuric acid, the reaction yield is greatly increased. In addition, using this reaction condition, the efficiency of the operating process can be greatly improved, although O-methyl-N-nitroisourea can be obtained in high yield through a simple isolation process. As described above, a process for producing O-methyl-N-nitroisourea of the present invention has been contemplated. That is, the present invention relates to a process for producing O-methyl-N-nitroisourea represented by following chemical formula (1) or a salt thereof, wherein the nitration of O-methylisourea represented by the following chemical formula (2) or a salt thereof is carried out with nitrating agents in the presence of smoking sulfuric acid.

According to the present invention, the reaction yield of O-methyl-N-nitroisourea is easily improved and O-methyl-N-nitroisourea is easily isolated through an industrially available process. In other words, according to the present invention, O-methyl-N-nitroisourea of the chemical formula (1) which is an intermediate necessary to produce nitroguanidine derivatives having insecticidal activity is produced economically and easily. Detailed Description of the Invention The production process of the present invention can be carried out, for example with the reaction conditions described below. According to the following production process, when a product is obtained As an isolated compound, the obtained compound can be converted into a salt, or when a product is obtained in the form of a salt, the product obtained can be converted into an isolated compound, according to a usual process. Likewise, similarly when the starting material may be a salt, it may not be used solely as an isolated compound, but also as a salt. Accordingly, the starting material that will be used for the next production process and its reaction product also includes a salt thereof. The acid that forms salt with O-methyl-N-nitroisourea represented by the chemical formula (1) above, O-methylisourea represented by the chemical formula (2) above, may be those permissible in terms of organic chemistry. Examples thereof include inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, sulfuric acid, perchloric acid and the like; and organic acids such as formic acid, acetic acid, tartaric acid, malic acid, citric acid, oxalic acid, succinic acid, benzoic acid, picric acid, methanesulfonic acid, p-toluenesulfonic acid and the like. Of these acids, those used preferably are hydrochloric acid and sulfuric acid. As a salt of O-methylisourea, those used in a particularly preferred form are sulfate, 1/2 sulfate and monomethyl sulfate.

By carrying out the nitration of the compound represented by the chemical formula (2) or a salt thereof with nitrating agents in the presence of smoking sulfuric acid, O-methyl-N-nitroisourea represented by the chemical formula can be obtained (1 ) or a salt thereof (after the reaction formula). At the end of the reaction, the reaction mixture was diluted with water in a suitable amount and the precipitate is filtered. Therefore, the compound represented by the chemical formula (1) or a salt thereof can be easily isolated.

In the present invention, as nitrating agents, nitric acid and smoky nitric acid of 60 to 100% are widely used. In addition, alkali metal nitrates such as sodium nitrate, potassium nitrate and the like can be used; alkyl ester nitrates such as ethyl nitrate, amyl nitrate and the like; nitronium tetrafluoroborate, nitronium tetrafluoromethanesulfonate and the like. Particularly used are nitric acid and smoking nitric acid. The nitration agents can be used in an amount of about 1.0 to 20 moles, based on 1 mole of the compound represented by the chemical formula (2) or a salt thereof, although preferably in an amount of about 1.5 to 10 moles when nitric acid is used. In addition, when smoky nitric acid is used, it is preferably used in an amount of about 1.0 to 3.0 moles. In the reaction according to the present invention, when using a smoking sulfuric acid, such as a dehydrating agent, the reaction yield was improved. In the form of the smoking sulfuric acid, smoking sulfuric acid with 5 to 50% by weight of sulfur trioxide contained therein can be used. However, smoking sulfuric acid of 20 to 30% by weight is preferred. The steaming sulfuric acid can be used in an amount of 0.5 to 50 times of the starting material on the basis of the weight of the starting material, but in particular, preferably in an amount of 0.5 to 10 times. In addition, it can be used as a solvent. The reaction can be carried out without using any solvent. However, the reaction is again carried out in the presence of an acid solvent such as sulfuric acid, acetic acid, acetic anhydride, trifluoroacetic anhydride, trifluoromethanesulfonic acid and the like. As desired, a solvent that does not adversely affect the reaction or a mixture thereof can be used. In addition to the above acid solvents can be used as a solvent, aromatic hydrocarbons such as chlorobenzene, dichlorobenzene and the like; halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane, carbon tetrachloride and the like; saturated hydrocarbons such as hexane, heptane, cyclohexane and the like; ethers such as diethyl meter, tetrahydrofuran, dioxane and the like; ketones such as acetone, methylethyl acetone and the like; sulfoxides such as dimethyl sulfoxide and the like; and alcohols such as methane, ethane, propanol, isopropanol and the like. These solvents can be used in simple form, or two or more types can be used in combination in a suitable ratio, for example in a ratio of about 1: 1 to 1:10 (volume ratio). When the reaction mixture is not homogeneous, the reaction can be carried out in the presence of phase transfer catalyst such as quaternary ammonium salt, such as triethylbenzylammonium chloride, tri-n-octylmethylammonium chloride, trimethyldiallylammonium chloride, tetramethylammonium bromide, cetylpyridinium bromide and the like; crown ethers or the like. As a solvent, sulfuric acid is particularly preferably used. The reaction temperature in the nitration according to the present invention is usually within the range of about -50 to 100 degrees centigrade and preferably within the range of about -20 to 30. degrees Celsius. The reaction time is within the range of about 10 minutes to 24 hours and preferably within the range of about 2 to 10 hours. At the end of the reaction, the reaction mixture is diluted with water, or ice, or ice water, so that a mixture containing O-methyl-N-nitroisourea represented by the chemical formula (1) or a come out of it Specifically, at the end of the reaction, the reaction mixture is poured into cold water or ice, or ice water, and then the precipitate is filtered. Therefore, a mixture containing O-methyl-N-nitroisourea represented by the chemical formula (1) or a salt thereof can be isolated. The reaction mixture can be filtered before dilution, if necessary. The amount of water that will be used to dilute the reaction mixture is 1.0 to 5.0 times, and preferably 2.0 to 3.0 times on the weight basis, of the sulfuric acid present in the reaction mixture. EXAMPLES The present invention is illustrated below in detail with reference to the examples. However, the present invention should not be limited in any way to these examples. Example 1 O-methylisourea · 1/2 sulfuric acid (100 g) was introduced into fuming sulfuric acid (100 g), which was cooled to a temperature of -10 degrees Celsius, while maintaining the temperature at no more than 0 degrees Celsius. Subsequently, mixed acid (a mixture of 150 g of sulfuric acid 60 g of smoking nitric acid having a specific gravity of 1.52) was added to the reaction mixture while maintaining the temperature at -10 to 0 degrees. centigrade Subsequently, the reaction mixture was stirred at a temperature of -5 degrees centigrade for 24 hours. The yield of the reaction was analyzed by high performance liquid chromatography, and as a result, 97% of the reaction yield was obtained.

The aforementioned reaction mixture was added in the form of drops to water (685 g) while maintaining a temperature not higher than 2 degrees centigrade. The mixture was stirred at a mixture of -10 degrees Celsius for 3 hours, and then the precipitate was filtered to obtain a desired O-methyl-N-nitroisourea (amount: 86.3 g, purity: 94%, yield: 84%). 1 H NMR (DMSO, ppm): 3.70 (3H, S), 8.90 (2H, br). Comparative Example 1 O-methylisourea | 1/2 sulfuric acid (20 g) was introduced into sulfuric acid (20 g), at a temperature of 15 to 20 degrees centigrade. Subsequently, mixed acid was added in the form of drops to the reaction mixture (a mixture of 30 g of sulfuric acid, 12 g of fuming nitric acid having a specific gravity of 1.52) at the same temperature. Subsequently, the reaction mixture was stirred at a temperature of 20 degrees centigrade for 24 hours. The reaction yield was analyzed by high performance liquid chromatography, and as a result, 82% of the reaction yield was obtained. The aforementioned reaction mixture was added dropwise to 196 g of water at a temperature of 0 degrees centigrade while maintaining the temperature. The same mixture was stirred at a temperature of 0 degrees centigrade for 1 hour, and subsequently an aqueous solution of 20% sodium hydroxide (75 g) was added dropwise thereto, while maintaining the same temperature. In addition, the reaction mixture was stirred for 1 hour and then the precipitate was filtered to obtain a desired O-methyl-N-nitroisourea (amount: 9.5 g, purity: 90%, yield: 44%). Comparative Example 2 The reaction was carried out in the same manner as in Example 1, except that anhydrous sodium sulfate was used instead of smoking sulfuric acid. As a result, the reaction yield was about 80% and no improvement in the reaction yield was recognized.

Claims (2)

1. CLAIMS 1. A process for producing O-methyl-N-nitroisourea represented by the following chemical formula (1) or a salt thereof, in which the nitration of O-methylisourea represented by the following chemical formula (2) or a salt thereof, was carried out with nitration agents in the presence of smoking sulfuric acid.
2. 2. The process for producing O-methyl-N-nitroisourea as described in claim 1, wherein the nitrating agents are nitric acid and smoking nitric acid.