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WO2018181672A1 - Chlorhydrate de 1,3-dicarbamoylthio-2-(n,n-diméthylamino)propane stable et son procédé de production - Google Patents

Chlorhydrate de 1,3-dicarbamoylthio-2-(n,n-diméthylamino)propane stable et son procédé de production Download PDF

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WO2018181672A1
WO2018181672A1 PCT/JP2018/013133 JP2018013133W WO2018181672A1 WO 2018181672 A1 WO2018181672 A1 WO 2018181672A1 JP 2018013133 W JP2018013133 W JP 2018013133W WO 2018181672 A1 WO2018181672 A1 WO 2018181672A1
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dimethylamino
dicarbamoylthio
propane hydrochloride
week
acid
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Japanese (ja)
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佐藤　誠
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Sumitomo Chemical Co Ltd
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Sumitomo Chemical Co Ltd
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Priority to CN201880022606.1A priority Critical patent/CN110461817B/zh
Priority to JP2019510108A priority patent/JP7118049B2/ja
Priority to BR112019020041-0A priority patent/BR112019020041B1/pt
Publication of WO2018181672A1 publication Critical patent/WO2018181672A1/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C333/00—Derivatives of thiocarbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C333/02—Monothiocarbamic acids; Derivatives thereof
    • C07C333/04—Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms

Definitions

  • the present invention relates to a stable 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride and a process for producing the same.
  • 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride is known to be useful as an insecticide.
  • methods for producing 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride methods described in Patent Documents 1 to 4 are known.
  • crystals of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride are obtained by filtering the reaction product.
  • the washing method of the crystal after filtration is a method of washing the crystal with methanol as described in Example 6 and Comparative Example 2 of Patent Document 1.
  • an object of the present invention is to provide 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride having storage stability and a method for producing the same.
  • 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride can be produced by the following method. Specifically, 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride is washed with an aqueous solution of a strongly acidic inorganic acid salt or an aqueous solution of a strongly acidic organic acid. It has been found that stable 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride can be produced.
  • 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride having the stability contains a strongly acidic inorganic acid salt or a strongly acidic organic acid.
  • Dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride in the form of an adduct of the strong acid inorganic acid salt or strong acid organic acid, the strong acid inorganic acid salt or strong acid In the range of 0.05 to 10% by weight based on the weight of the 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride adduct I also found out.
  • the present invention is as follows, but is not limited thereto.
  • 1,3-Dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride used in step (A) is Reacting 2- (N, N-dimethylamino) -1,3-dithiocyanate-propane hydrochloride with hydrogen chloride gas in methanol and an organic solvent that forms a two-layer system with methanol, or Reacting 2- (N, N-dimethylamino) -1,3-dithiocyanate-propane hydrochloride with hydrochloric acid in water and an organic solvent that forms a two-layer system with water;
  • the organic solvent that forms a two-layer system with methanol is one or a mixture of two or more selected from the group consisting of tol
  • Strongly acidic inorganic acid salt or strong acid organic acid content is 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride strongly acidic inorganic acid salt or strong acid 1,3-dicarbamoylthio-2- (N, N-dimethylamino)-described in the above item [6], in a range of 0.1 to 2% by weight based on the weight of the adduct of the organic acid Propane hydrochloride inorganic acid salt or organic acid adduct.
  • the strongly acidic inorganic acid salt or the strongly acidic organic acid is ammonium hydrogen sulfate, sodium hydrogen sulfate, potassium hydrogen sulfate, oxalic acid or citric acid.
  • stable 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride can be produced by an industrially feasible method.
  • the hydrochloride is excellent in thermal stability.
  • the present invention is a method for producing stable 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) by a method comprising the following step (A).
  • 1,3-Dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) used in the present invention is produced, for example, according to the methods described in the following production methods (1) to (3). be able to.
  • 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) (hereinafter sometimes referred to as “compound (I)”) is also referred to as cartap hydrochloride.
  • compound (I) is also referred to as cartap hydrochloride.
  • Examples of the organic solvent that forms a two-layer system with methanol include one or a mixture of two or more selected from the group consisting of toluene, xylene, 1,2-dichloroethane, chloroform, methylene chloride, and chlorobenzene.
  • the reaction can be carried out according to the method described in Patent Document 1 or Patent Document 3.
  • the washing treatment in the following step (A), step (B) and step (C) refers to 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride
  • crystals of I ie, crystals of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) containing filtrate (eg wet crystals)
  • the crystal is washed with an exemplified aqueous solution or alcohol (for example, the crystal is immersed in the exemplified aqueous solution or alcohol, or the exemplified aqueous solution or alcohol is sprayed on the crystal).
  • the crystal contains Replacement of part or all of the filtrate with an aqueous solution or alcohol.
  • step (A) After the step (A) is performed, the following step (B) and / or step (C) is further performed to obtain 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (The amount of strongly acidic inorganic acid salt or strongly acidic organic acid contained in I) can be adjusted.
  • step (B) and / or step (C) either step (B) or step (C) may be carried out, and both step (B) and step (C) may be carried out. Also good.
  • step (A) 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) is washed with an aqueous solution of a strongly acidic inorganic acid salt or an aqueous solution of a strongly acidic organic acid.
  • 1,3-Dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) used in step (A) is prepared according to the method described in the above production methods (1) to (3).
  • the prepared product, or the following step (B) (including step (B) after the following step (C)) or the following step (C) (including step (C) after the following step (B)) It may be any product prepared after treatment.
  • a product prepared according to the method described in the above production methods (1) to (3) is preferred.
  • Examples of strongly acidic inorganic acid salts include sulfates and nitrates, and specific examples of sulfates include ammonium hydrogen sulfate, sodium hydrogen sulfate, potassium hydrogen sulfate, and ammonium hydrogen sulfate.
  • Sodium bisulfate and potassium bisulfate can be produced by mixing sodium sulfate or potassium sulfate and concentrated hydrochloric acid, respectively. In this case, a mixture of sodium bisulfate and sodium chloride, and potassium bisulfate, respectively. A mixture of potassium chloride and potassium chloride can be used as it is.
  • Ammonium hydrogen sulfate may be prepared by mixing ammonium sulfate and concentrated hydrochloric acid, or one containing ammonium chloride may be used.
  • the strongly acidic inorganic acid salt include ammonium hydrogen sulfate and sodium hydrogen sulfate.
  • strongly acidic organic acids include organic acids such as oxalic acid, malonic acid, succinic acid, glutaric acid, glycolic acid, lactic acid, glyceric acid, tartaric acid, and citric acid.
  • strongly acidic organic acids include oxalic acid and citric acid.
  • an acid having low volatility that can remain during long-term storage for example, at a high temperature
  • a strongly acidic inorganic acid salt is more preferable.
  • An aqueous solution containing a strong acid inorganic acid salt or a strong acid organic acid is prepared by mixing the above strong acid inorganic acid salt or strong acid organic acid, or the acid or salt used to prepare them with water. By doing so, an aqueous solution can be prepared.
  • An aqueous solution of ammonium hydrogen sulfate is typically prepared by mixing concentrated sulfuric acid and aqueous ammonia. It can also be used as an aqueous solution of a mixture of ammonium hydrogen sulfate and ammonium chloride.
  • the aqueous solution of sodium hydrogensulfate is typically prepared by mixing concentrated sulfuric acid and sodium hydroxide, or by mixing concentrated sulfuric acid and aqueous sodium hydroxide.
  • aqueous solution of sodium hydrogen sulfate one prepared as an aqueous solution of a mixture of sodium hydrogen sulfate and sodium chloride may be used as it is.
  • the aqueous solution of potassium hydrogen sulfate is typically prepared by mixing concentrated sulfuric acid and potassium hydroxide, or by mixing concentrated sulfuric acid and aqueous potassium hydroxide solution.
  • the aqueous solution of potassium hydrogen sulfate one prepared as an aqueous solution of a mixture of potassium hydrogen sulfate and potassium chloride may be used.
  • the concentration of the inorganic acid salt or organic acid in the aqueous solution containing the strong acid inorganic acid salt or the strong acid organic acid is usually in the range of 0.5 to 30% by weight with respect to the weight of the aqueous solution, preferably 1 It is in the range of ⁇ 15% by weight.
  • the temperature of the aqueous solution containing a strongly acidic inorganic acid salt or strongly acidic organic acid used for washing is usually in the range of 0 to 30 ° C, preferably in the range of 0 to 10 ° C.
  • the amount of the aqueous solution containing a strongly acidic inorganic acid salt or a strongly acidic organic acid used for washing is usually in the range of 5 to 70% by weight, preferably 30 to 50% by weight, based on the weight of the wet crystals. It is a range.
  • Crude compositions containing 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I), including those with reduced content and / or with reduced quality ) Is made into a slurry solution with water, hydrochloric acid, an aqueous solution of a strong acid inorganic acid salt or an aqueous solution of a strong acid organic acid, filtered, and further, water, hydrochloric acid, an aqueous solution of a strong acid inorganic acid salt or a strong acid
  • a stable 1,3-dicarbamoylthio-2- (N, N-dimethylamino) is obtained by subjecting a solution obtained by heating and dissolving in an aqueous solution of a basic organic acid to cooling crystallization and then filtering to the production method of the present invention.
  • -Propane hydrochloride can be prepared.
  • 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) obtained in step (A) can be further prepared by the following steps (B) and / or ( You may use for C) and may adjust content of the strongly acidic inorganic acid salt or strong acid organic acid to contain.
  • Step (B) will be described.
  • 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) is washed with a weakly acidic aqueous inorganic salt solution.
  • the weakly acidic inorganic salt examples include ammonium chloride, sodium dihydrogen phosphate, and potassium dihydrogen phosphate, and preferably ammonium chloride.
  • the weakly acidic inorganic salt aqueous solution can be prepared by mixing a weakly acidic inorganic salt and water, and examples thereof include an ammonium chloride aqueous solution.
  • the concentration of the weakly acidic inorganic salt aqueous solution is usually in the range of 0.5 to 30% by weight, preferably in the range of 1 to 20% by weight, based on the weight of the aqueous solution.
  • the temperature of the weakly acidic inorganic salt aqueous solution used for washing is usually in the range of 0 to 30 ° C, preferably in the range of 0 to 10 ° C.
  • the amount of the weakly acidic inorganic salt aqueous solution used for washing is usually in the range of 5 to 60% by weight, preferably in the range of 10 to 30% by weight, based on the weight of the wet crystals.
  • Step (C) will be described.
  • 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride is washed with a lower alcohol.
  • it is preferably applied to the product obtained by the treatment of the step (A) or the step (B), more preferably applied to the product obtained by the treatment of the step (A).
  • the lower alcohol means an alcohol having 1 to 3 carbon atoms, and examples thereof include methanol, ethanol, and isopropyl alcohol, and methanol is preferable.
  • the temperature of the lower alcohol used for washing is usually in the range of 0 to 30 ° C, preferably in the range of 0 to 10 ° C.
  • the amount of the lower alcohol used for washing is usually in the range of 5 to 60% by weight, preferably in the range of 10 to 30% by weight, based on the weight of the wet crystals.
  • step (A) After the final step of step (A), step (B) or step (C), the desired 1,3-dicarbamoylthio-2- (N, N-dimethylamino) is obtained by passing through a drying step.
  • Propane hydrochloride (I) can be obtained.
  • All operations of the production method of the present invention can be performed at room temperature. However, in order to suppress the decrease of the target product in the cleaning liquid, it is preferable to perform cleaning using a cooled cleaning liquid.
  • Step (A) of the present invention comprises a composition comprising 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) having reduced content and / or reduced quality
  • 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) having reduced content and / or reduced quality
  • a stable 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) can also be prepared.
  • the salt of formula (I) having a reduced content and / or a reduced quality was slurried with water, hydrochloric acid, etc., filtered, and further heated and dissolved in water, hydrochloric acid, etc., and then cooled and crystallized. What is obtained by post-filtration may be subjected to step (A).
  • Compound (I) as an acid adduct It is contained in the strong acid inorganic acid salt or strong acid organic acid adduct of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride produced by the production method of the present invention.
  • the amount of the strongly acidic inorganic acid salt or the strongly acidic organic acid is 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride strongly acidic inorganic acid salt or strongly acidic acid.
  • Is usually in the range of 0.05 to 10% by weight, preferably in the range of 0.1 to 2% by weight, more preferably in the range of 0.1 to 1.5% by weight, based on the weight of the organic acid adduct. %, More preferably in the range of 0.1 to 1.1% by weight.
  • the pH of the aqueous solution of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride adduct is not more than 4.5, and usually not less than 3.0 and not more than 4.5 It is preferably 3.0 or more and 4.2 or less, more preferably 3.3 or more and 4.0 or less, still more preferably 3.7 or less, and still more preferably 3.
  • the pH of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) is a solution in which 1 g of the dry hydrochloride is dissolved in 100 ml of water (hereinafter referred to as “pH”). "1% aqueous solution”) was prepared, and the pH of this aqueous solution was measured.
  • the pH in a 1% aqueous solution is usually 3.0 to 4.5, but when 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) is decomposed, ammonia is dissolved.
  • the pH value is an important indicator for determining the presence or absence of decomposition as the content decreases. It is not preferred if the pH is greater than 4.5 (especially 3.7).
  • the stable 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) produced by the production method of the present invention is obtained by using 1,3-dicarbamoyl obtained by the conventional method.
  • thio-2- (N, N-dimethylamino) -propane hydrochloride (I) high purity and improved stability (eg thermal stability) enable long-term storage It is.
  • the produced 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) has a strong insecticidal action as described in Patent Document 3 and Patent Document 4, It can be used as an agricultural insecticidal composition.
  • Inorganic acid salt for example, NH 4 + contained in the inorganic acid salt or organic acid adduct of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) And SO 4 2 ⁇ ions
  • organic acid eg oxalic acid
  • HIC high-speed ion chromatograph
  • the content of sodium hydrogen sulfate was determined from the analytical value of sulfate ion (SO 4 2 ⁇ ) and the analytical value of sodium ion (Na + ) by the following calculation formula.
  • symbols represent the following meanings.
  • the pH of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) is a 1% aqueous solution of the dry hydrochloride. The pH of the aqueous solution is measured.
  • Example 1 138.0 g of 1,2-dichloroethane solution of 29.6 g (0.147 mol) of 2- (N, N-dimethylamino) -1,3-dithiocyanate-propane hydrochloride (II) (as the concentration of Compound II) 21.4%), 53.3 g of methanol was added, and 55 g (1.496 mol) of hydrogen chloride gas was blown in over 6 hours while cooling to 0 to 5 ° C. Thereafter, the mixture was stirred at 0 to 5 ° C. for 12 hours. The reaction solution was gradually heated to an internal temperature of 65 ° C., and after distilling off hydrogen chloride gas and methanol, 55 g of water was added.
  • II 2- (N, N-dimethylamino) -1,3-dithiocyanate-propane hydrochloride
  • Example 2 137.6 g of 1,2-dichloroethane solution of 29.6 g (0.147 mol) of 2- (N, N-dimethylamino) -1,3-dithiocyanate-propane hydrochloride (II) (concentration of compound (II))
  • II 2- (N, N-dimethylamino) -1,3-dithiocyanate-propane hydrochloride
  • 53.3 g of methanol was added to 21.5%, and 47 g (1.358 mol) of hydrogen chloride gas was blown in over 7 hours under cooling to 0 to 5 ° C. Thereafter, the mixture was stirred at 0 to 5 ° C. for 12 hours.
  • the reaction solution was gradually heated to an internal temperature of 65 ° C., and after distilling off hydrogen chloride gas and methanol, 55 g of water was added.
  • Example 3 137.6 g of 1,2-dichloroethane solution of 29.6 g (0.147 mol) of 2- (N, N-dimethylamino) -1,3-dithiocyanate-propane hydrochloride (II) (concentration of compound (II))
  • II 2- (N, N-dimethylamino) -1,3-dithiocyanate-propane hydrochloride
  • 53.3 g of methanol was added to 21.5%, and 47 g (1.358 mol) of hydrogen chloride gas was blown in over 7 hours under cooling to 0 to 5 ° C. Thereafter, the mixture was stirred at 0 to 5 ° C. for 12 hours.
  • the reaction solution was gradually heated to an internal temperature of 65 ° C., and after distilling off hydrogen chloride gas and methanol, 46 g of water was added.
  • the internal temperature was raised to 75 ° C., and 1,2-dichloroethane was distilled off azeotropically with water. 1,2-Dichloroethane was distilled off, and the mixture was gradually cooled to 5 ° C. or lower.
  • the precipitated crystals were filtered, and 8.9 g of a mixed aqueous solution of 5.2% NH 4 HSO 4 and 2.4% NH 4 Cl separately prepared. After washing with 12.4 g of methanol.
  • a mixed aqueous solution of 5.2% NH 4 HSO 4 and 2.4% NH 4 Cl was prepared by dissolving 4.5 g of (NH 4 ) 2 SO 4 with 73.1 g of water, and then adding 3.8 g of 35% hydrochloric acid.
  • Example 4 The same reaction and treatment as in Example 1 were carried out, and 542.26 g of a slurry solution of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) 5 After cooling to around 0 ° C., it was centrifuged with a desktop small centrifuge. The obtained wet crystals were washed with 37.28 g of a mixed aqueous solution of 10.7% NH 4 HSO 4 and 5.0% NH 4 Cl prepared from (NH 4 ) 2 SO 4 and 36% hydrochloric acid, and then methanol 84. Washed with 00 g.
  • the obtained wet crystals (226.74 g) were dried under reduced pressure at 75 ° C. for 2 hours to obtain 168.11 g (purity 97.5%) as a dried product.
  • the appearance was white crystals, and the pH of the 1% aqueous solution was 3.51.
  • As a result of measurement by ion chromatography analysis of the product it was found that NH 4 HSO 4 contained 0.35% and NH 4 Cl contained 0.19%.
  • an accelerated test at 60 ° C. was performed and the progress was observed.
  • the results of the 60 ° C. acceleration test were as follows.
  • Example 5 The same reaction and treatment as in Example 1 were carried out, and 532.66 g of a slurry solution of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) before filtration was added to 5 After cooling to around 0 ° C., it was centrifuged with a desktop small centrifuge. The obtained wet crystals were washed with 51.31 g of a mixed solution of 10.7% NH 4 HSO 4 and 5.0% NH 4 Cl prepared from (NH 4 ) 2 SO 4 and 36% hydrochloric acid, and then 20% NH. Washed with 69.32 g of 4 Cl.
  • I 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride
  • Example 6 40 g (0.146 mol) of reduced 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) (content: 95.8%, pH 5.20) After slurrying in 11.5% dilute hydrochloric acid (18.0 g of concentrated hydrochloric acid added to 28.0 g of water), the mixture was cooled to 5 ° C. or lower and stirred for 1 hour. Then, the mixture was washed with 9.4 g of a mixed aqueous solution of 7.1% NH 4 HSO 4 and 3.3% NH 4 Cl.
  • a mixed aqueous solution of 7.1% NH 4 HSO 4 and 2.4% NH 4 Cl was prepared by dissolving 0.79 g of (NH 4 ) 2 SO 4 with 78.0 g of water, and then adding 0.61 g of 35% hydrochloric acid.
  • the appearance was white crystals, and the pH of the 1% aqueous solution was 3.38.
  • Example 7 45.0 g of unwashed 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) wet crystals obtained by filtration after the same reaction and treatment as in Example 1 ( Content: 84.1%, 0.138 mol) was slurried in 11.5% dilute hydrochloric acid (28.0 g of water plus 13.1 g of concentrated hydrochloric acid), cooled to 5 ° C. or lower and stirred for 1 hour. Thereafter, the precipitated crystals were filtered and washed with 13.62 g of a 5.0% oxalic acid aqueous solution (0.68 g of oxalic acid dissolved in 12.94 g of water).
  • Example 8 45.0 g of unwashed 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) wet crystals obtained by filtration after the same reaction and treatment as in Example 1 ( Content: 84.1%, 0.138 mol) was slurried in 11.5% dilute hydrochloric acid (28.0 g of water plus 13.1 g of concentrated hydrochloric acid), cooled to 5 ° C. or lower and stirred for 1 hour. Thereafter, the precipitated crystals were filtered and washed with 13.62 g of a 5.0% aqueous citric acid solution (0.68 g of citric acid dissolved in 12.94 g of water).
  • Example 9 30 g (0.102 mol) (content: 93.1%, pH 5.00) of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) with reduced quality
  • slurrying in 2.0% dilute hydrochloric acid 33.0 g of water plus 1.9 g of concentrated hydrochloric acid
  • the mixture was heated to 70 ° C. and completely dissolved.
  • 9.0 g of 36% hydrochloric acid at the same temperature, the mixture was cooled to 55 ° C. and methanol 12.0 was added. After gradually cooling to 10 ° C.
  • a 3.0% NH 4 HSO 4 water / methanol mixed solution was prepared by dissolving 0.30 g of NH 4 HSO 4 with 5.1 g of water and adding 4.50 g of methanol. After drying under reduced pressure at 60 ° C. for 2 hours, 25.3 g of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) (purity 98.6%, recovery rate 90% .7%).
  • Example 10 The slurry obtained by carrying out the same reaction and treatment as in Example 1 was centrifuged and filtered to collect 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I ) About 35 parts by weight of wet crystals were sprinkled and washed with about 7 parts by weight of methanol on a centrifuge, and further about 8.5 parts by weight of NH 4 HSO 4 -water-methanol mixed solution of about 4% w / w ( NH 4 HSO 4 0.35 parts by weight, 2.8 parts by weight of water, and washed sprinkled with methanol 5.3 parts by weight).
  • I 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride
  • Example 11 45.0 g of unwashed 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) wet crystals obtained by filtration after the same reaction and treatment as in Example 1 ( Content: 84.1%, 0.138 mol) was slurried in 11.5% dilute hydrochloric acid (28.0 g of water plus 13.1 g of concentrated hydrochloric acid), cooled to 5 ° C. or lower and stirred for 1 hour.
  • dilute hydrochloric acid 28.0 g of water plus 13.1 g of concentrated hydrochloric acid
  • Comparative Example 1 133.4 g of 1,2-dichloroethane solution of 29.6 g (0.147 mol) of 2- (N, N-dimethylamino) -1,3-dithiocyanate-propane hydrochloride (II) 23.4%), 53.4 g of methanol was added, and 49.5 g (1.358 mol) of hydrogen chloride gas was blown in over 8 hours under cooling to 0 to 5 ° C. Thereafter, the mixture was stirred at 0 to 5 ° C. for 12 hours. The reaction solution was gradually heated to an internal temperature of 65 ° C., and after distilling off hydrogen chloride gas and methanol, 55 g of water was added.
  • II 2- (N, N-dimethylamino) -1,3-dithiocyanate-propane hydrochloride
  • the internal temperature was raised to 75 ° C., and 1,2-dichloroethane was distilled off azeotropically with water. After 1,2-dichloroethane was distilled off, the mixture was gradually cooled to 5 ° C. or lower, and the precipitated crystals were filtered and washed with 12.5 g of methanol. It was dried at 60 ° C. under reduced pressure for 2 hours, and 33.6 g of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) (purity 98.7%, yield 83) .2%).
  • Comparative Example 2 80 g (0.292 mol) of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) with reduced quality (content: 95.8%, pH 5.20) Slurried in 11.5% dilute hydrochloric acid (56.0 g of water plus 26.3 g of concentrated hydrochloric acid), cooled to 5 ° C. or lower, stirred for 1 hour, filtered the precipitated crystals, and filtered to 26.9 g of methanol. Washed with. After drying at 60 ° C.
  • Comparative Example 3 Unwashed wet crystal 224 of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) produced by the same method as in Comparative Example 1 except that methanol washing is not performed. .96 g was dried under reduced pressure at 75 ° C. for 2 hours to obtain 199.99 g (purity 98.0%) as a dried product. As a result of measurement by ion chromatography analysis of the product, NH 4 HSO 4 and NH 4 Cl were not detected. The appearance was white crystals, and the pH of the 1% aqueous solution was 3.95.
  • Comparative Example 4 Unwashed wet crystal 233 of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) produced by the same method as in Comparative Example 1 except that methanol washing is not performed. 0.000 g and the filtrate 233.00 g were mixed, and the reslurried solution was cooled to around 5 ° C. and then centrifuged with a desktop small centrifuge. The obtained wet crystals were washed while centrifuging with 64.0 g of methanol. 217.20 g of the obtained wet crystal was dried under reduced pressure at 75 ° C. for 2 hours to obtain 190.00 g (purity 98.0%) as a dried product.
  • Comparative Example 5 45.0 g of unwashed 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) wet crystals obtained by filtration after the same reaction and treatment as in Example 1 ( Content: 84.1%, 0.138 mol) was slurried in 11.5% dilute hydrochloric acid (28.0 g of water plus 13.1 g of concentrated hydrochloric acid), cooled to 5 ° C. or lower and stirred for 1 hour. Thereafter, the precipitated crystals were filtered and washed with 12.87 g of methanol. It was dried under reduced pressure at 60 ° C.
  • Comparative Example 6 30 g (0.102 mol) (content: 93.1%, pH 5.00) of 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) with reduced quality
  • 1.0% diluted hydrochloric acid 30.0 g of water plus 0.9 g of concentrated hydrochloric acid
  • the mixture was heated to 70 ° C. and completely dissolved.
  • After adding 10.5 g of 36% hydrochloric acid at the same temperature the mixture was cooled to 55 ° C. and methanol 12.0 was added. After slowly cooling to 10 ° C.
  • Degraded 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) is purified by recrystallization and is stable compared to conventional products (Padan (registered trademark)) The stability was improved, but the stability was poor as compared with that washed with a NH 4 HSO 4 water-containing methanol solution as in Example 9.
  • 1,3-dicarbamoylthio-2- (N, N-dimethylamino) -propane hydrochloride (I) having an excellent insecticidal action is considered to have good stability. It can be produced with good purity and yield.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne un procédé de production du chlorhydrate de 1,3-dicarbamoylthio-2-(N,N-diméthylamino)propane stable, le procédé comprenant une étape (A) dans laquelle le chlorhydrate de 1,3-dicarbamoylthio-2-(N,N-diméthylamino)propane est lavé avec une solution aqueuse d'un sel d'un acide fort inorganique ou avec une solution aqueuse d'un acide fort organique.
PCT/JP2018/013133 2017-03-30 2018-03-29 Chlorhydrate de 1,3-dicarbamoylthio-2-(n,n-diméthylamino)propane stable et son procédé de production Ceased WO2018181672A1 (fr)

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CN201880022606.1A CN110461817B (zh) 2017-03-30 2018-03-29 稳定的1，3-二(氨甲酰基硫基)-2-(n，n-二甲基氨基)-丙烷盐酸盐及其制造方法
JP2019510108A JP7118049B2 (ja) 2017-03-30 2018-03-29 安定な１，３－ジカルバモイルチオ－２－（ｎ，ｎ－ジメチルアミノ）－プロパン塩酸塩、およびその製造方法
BR112019020041-0A BR112019020041B1 (pt) 2017-03-30 2018-03-29 Cloridrato de 1,3-dicarbamoiltio-2-(n,n-dimetilamino)propano e método de produção do mesmo

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023148565A1 (fr) * 2022-02-01 2023-08-10 Gharda Chemicals Limited Procédé de préparation de chlorhydrate de cartap

Families Citing this family (1)

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CN113999150A (zh) * 2021-12-02 2022-02-01 湖南昊华化工股份有限公司 一种杀螟丹的制备方法

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Publication number Priority date Publication date Assignee Title
JPS491532B1 (fr) * 1969-03-08 1974-01-14
JPS4927857B1 (fr) * 1970-12-29 1974-07-22
JPS609482B2 (ja) * 1976-03-29 1985-03-11 武田薬品工業株式会社 粒状農薬の製造法
CN101103725A (zh) * 2007-07-23 2008-01-16 江苏天容集团股份有限公司 杀螟丹的环保型制备方法
CN101302179A (zh) * 2008-06-23 2008-11-12 江苏天容集团股份有限公司 杀螟丹合成的溶剂法工艺

Patent Citations (5)

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Publication number Priority date Publication date Assignee Title
JPS491532B1 (fr) * 1969-03-08 1974-01-14
JPS4927857B1 (fr) * 1970-12-29 1974-07-22
JPS609482B2 (ja) * 1976-03-29 1985-03-11 武田薬品工業株式会社 粒状農薬の製造法
CN101103725A (zh) * 2007-07-23 2008-01-16 江苏天容集团股份有限公司 杀螟丹的环保型制备方法
CN101302179A (zh) * 2008-06-23 2008-11-12 江苏天容集团股份有限公司 杀螟丹合成的溶剂法工艺

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023148565A1 (fr) * 2022-02-01 2023-08-10 Gharda Chemicals Limited Procédé de préparation de chlorhydrate de cartap

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CN110461817B (zh) 2021-11-23

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