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WO2013089272A1 - Procédé de production d'un sel d'acide halogénhydrique d'alkylamine halogénée - Google Patents

Procédé de production d'un sel d'acide halogénhydrique d'alkylamine halogénée Download PDF

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Publication number
WO2013089272A1
WO2013089272A1 PCT/JP2012/082854 JP2012082854W WO2013089272A1 WO 2013089272 A1 WO2013089272 A1 WO 2013089272A1 JP 2012082854 W JP2012082854 W JP 2012082854W WO 2013089272 A1 WO2013089272 A1 WO 2013089272A1
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Prior art keywords
formula
compound
salt
hydrogen halide
thiosulfuric acid
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Japanese (ja)
Inventor
和真 松尾
哲雄 川田
オルハン オズトゥルク
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Sumitomo Chemical Co Ltd
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Sumitomo Chemical Co Ltd
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Priority to CN201280060868.XA priority Critical patent/CN103974929B/zh
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
    • C07C209/74—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
    • C07C381/02—Thiosulfates

Definitions

  • the present invention relates to a process for producing a halogenated alkylamine hydrohalide.
  • Halogenated alkylamines are useful as intermediates for additives for rubbers such as tires or anti-vibration rubbers.
  • Patent Document 1 Japanese Patent Laid-Open No. 2011-93851 describes a method of producing 3-chloropropylamine hydrochloride by reacting thionyl chloride with 3-amino-1-propanol.
  • the present invention includes the following inventions.
  • R 1 represents an alkoxy group having 1 to 8 carbon atoms.
  • R 2 and R 3 each independently represent a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or R 2 and R 3 are bonded to each other, and together with the nitrogen atom to which they are bonded, Form.
  • m represents an integer of 2 to 9.
  • X 1 represents a halogen atom.
  • R 2 , R 3 and m represent the same meaning as described above.
  • R 1 represents an alkoxy group having 1 to 8 carbon atoms.
  • R 2 and R 3 each independently represent a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or R 2 and R 3 are bonded to each other, and together with the nitrogen atom to which they are bonded, Form.
  • m represents an integer of 2 to 9.
  • X 1 represents a halogen atom.
  • R 2 , R 3 and m represent the same meaning as described above.
  • M n + represents H + or an n-valent metal ion.
  • n represents an integer of 1 or 2.
  • R 2 , R 3 and m represent the same meaning as described above.
  • Compound represented by Formula (1) (hereinafter sometimes referred to as “Compound (1)”)> R 1
  • the alkoxy group having 1 to 8 carbon atoms methoxy group, ethoxy group, n-propyloxy group, isopropyloxy group, n-butyloxy group, isobutyloxy group, sec-butyloxy group, tert-butyloxy group, n-pentyl group Examples thereof include an oxy group, an n-hexyloxy group, a cyclohexyloxy group, an n-heptyloxy group, an n-octyloxy group, and a 2-ethylhexyloxy group.
  • R 1 Is preferably an alkoxy group having 1 to 4 carbon atoms, more preferably a methoxy group.
  • R 2 And R 3 Examples of the alkyl group having 1 to 6 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, heptyl group, and hexyl group. Can be mentioned.
  • R 2 And R 3 Are bonded to each other to form a ring with the nitrogen atom to which they are bonded, 2 And R 3 And combine with each other to form a polymethylene group.
  • polymethylene group examples include an ethylene group (dimethylene group), a trimethylene group, a tetramethylene group, a pentamethylene group, and a hexamethylene group.
  • R 2 And R 3 Is preferably a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, more preferably a hydrogen atom.
  • m is 1-6
  • R 2 And R 3 Is preferably a hydrogen atom
  • m is 3
  • R 2 And R 3 A compound in which is a hydrogen atom is more preferred.
  • m is 3 and R 2 And R 3
  • the compound in which is a hydrogen atom include 3-methoxypropylamine, 3-ethoxypropylamine, 3-n-propyloxypropylamine, 3-isopropyloxypropylamine, 3-n-butyloxypropylamine, 3-isobutyloxy Propylamine, 3-sec-butyloxypropylamine, 3-tert-butyloxypropylamine, 3-n-pentyloxypropylamine, 3-n-hexyloxypropylamine, 3-n-heptyloxypropylamine, 3- Examples include n-octyloxypropylamine and 3- (2-ethylhexyloxy) propylamine, and 3-methoxypropylamine is more preferable.
  • compound (1) As a commercial item of compound (1), 3-methoxypropylamine (Tokyo Chemical Industry), 3-ethoxypropylamine (Tokyo Chemical Industry), 3-n-propyloxypropylamine (Tokyo Chemical Industry), 3-isopropyloxy Examples thereof include propylamine (Tokyo Kasei Kogyo), 3-n-butyloxypropylamine (Tokyo Kasei Kogyo), and 3- (2-ethylhexyloxy) propylamine (Tokyo Kasei Kogyo).
  • Compound (1) can be produced by the method shown in the following reaction formula. In this method, acrylonitrile is reduced with Raney nickel in a hydrogen atmosphere in alcohol to obtain an amino compound, and then -NH as necessary.
  • Hydrogen halide examples include hydrogen fluoride, hydrogen chloride, hydrogen bromide, and hydrogen iodide, preferably hydrogen chloride or hydrogen bromide, and more preferably hydrogen chloride.
  • halogenated salt of a compound represented by the formula (2) (hereinafter sometimes referred to as “compound (2)”) (hereinafter sometimes referred to as “salt (2)”)> X 1
  • halogen atom a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom are exemplified, and a chlorine atom is preferable.
  • Examples of the hydrogen halide that forms a salt with the compound (2) include hydrogen chloride and hydrogen bromide, and preferably hydrogen chloride.
  • the salt (2) can be produced by reacting the compound (1) with a hydrogen halide.
  • the amount of hydrogen halide to be used is generally 2 to 15 mol, preferably 3 to 10 mol, more preferably 3 to 9 mol, per 1 mol of compound (1).
  • the reaction of compound (1) and hydrogen halide can be carried out in the absence of an organic solvent or in the presence of a solvent inert to compound (1) and hydrogen halide. It is preferably carried out in the presence.
  • reaction between the compound (1) and the hydrogen halide can be confirmed by an analytical means such as NMR or high performance liquid chromatography.
  • an analytical means such as NMR or high performance liquid chromatography.
  • reaction of compound (1) and hydrogen halide is carried out in the absence of an organic solvent
  • the introduction of the hydrogen halide gas is preferably performed by blowing a hydrogen halide gas.
  • the reaction temperature in the reaction between the compound (1) and the hydrogen halide is preferably higher than the temperature at which the reaction mixture solidifies and not higher than the boiling point of the compound (1).
  • the reaction temperature is usually 180 ° C.
  • the reaction temperature in the first half of the two stages is preferably higher than the temperature at which the reaction mixture solidifies and lower than the boiling point of the compound (1).
  • the reaction temperature in the first half is usually 160 ° C. or lower, preferably 0 to 120 ° C., more preferably 25 to 120 ° C., and further preferably 25 to 100 ° C.
  • the reaction temperature in the latter half of the two stages is preferably a temperature at which the reaction mixture does not solidify.
  • the reaction temperature in the latter half is usually 180 ° C.
  • Examples of the method of blowing hydrogen halide gas include a method of blowing directly into the compound (1) and a method of blowing into the gas phase portion in the reaction vessel, and a method of blowing directly into the compound (1) is preferable.
  • hydrogen halide gas is blown into the gas phase portion in the reaction vessel, hydrogen halide is absorbed into the liquid phase from the liquid surface of compound (1), and compound (1) and hydrogen halide react.
  • the blowing rate of the hydrogen halide gas is usually 0.02 to 2 mol / hour, preferably 0.02 to 1.5 mol / hour, more preferably 0 to 1 mol of the compound (1). .02 to 1 mol / hour.
  • the solvent include aromatic hydrocarbon solvents such as toluene, xylene and ethylbenzene; tetrahydrofuran, 1,2-dimethoxyethane, 1,2 Ether solvents such as diethoxyethane and 1,4-dioxane; halogenated aromatic hydrocarbon solvents such as monochlorobenzene and o-dichlorobenzene; halogenated aliphatic hydrocarbon solvents such as dichloromethane, dichloroethane and trichloroethane; ethyl acetate, An ester solvent such as isopropyl acetate is preferable, and an aromatic hydrocarbon solvent, a halogenated aromatic hydrocarbon solvent, or a halogenated aliphatic hydrocarbon solvent is preferable, and o-
  • the solvent may be used alone or as a mixture.
  • the amount of the solvent to be used is preferably 0.5 mL to 3 mL, more preferably 1 mL to 2 mL, relative to 1 g of compound (1).
  • the reaction between the compound (1) and the hydrogen halide can be carried out by blowing hydrogen halide gas into the mixture of the compound (1) and the solvent, and the hydrogen halide gas is mixed with water, an alcohol solvent or A solution dissolved in an ether solvent can be added to the mixture of the compound (1) and the solvent.
  • the reaction of compound (1) and hydrogen halide is preferably carried out by blowing hydrogen halide gas into the mixture of compound (1) and solvent.
  • the reaction temperature in the reaction between the compound (1) and hydrogen halide is preferably a temperature at which the reaction mixture does not solidify, and is usually 180 ° C. or lower, preferably 0 to 160 ° C., more preferably 25 to 160. ° C, more preferably 25 to 130 ° C.
  • the introduction of the hydrogen halide gas is preferably carried out step by step in two steps.
  • the reaction temperature in the first half of the two stages is preferably higher than the temperature at which the reaction mixture solidifies and not higher than the boiling point of compound (1) or the boiling point of the solvent.
  • the reaction temperature in the first half is usually 160 ° C. or lower, preferably 0 to 120 ° C., more preferably 25 to 120 ° C., and further preferably 60 to 100 ° C.
  • the reaction temperature in the latter half of the two stages is usually 180 ° C. or lower, preferably 90 to 160 ° C., more preferably 105 to 130 ° C.
  • Examples of the method of blowing hydrogen halide gas include a method of blowing directly into the mixture of the compound (1) and the solvent, and a method of blowing into the gas phase portion in the reaction vessel, and a mixture of the compound (1) and the solvent. A method of blowing directly into the nozzle is preferred.
  • the blowing rate of the hydrogen halide gas is usually 0.02 to 2 mol / hour, preferably 0.04 to 1 mol / hour, more preferably 0.1 to 1 mol of the compound (1). ⁇ 0.5 mol / hour.
  • the mixture obtained after completion of the reaction between the compound (1) and hydrogen halide (hereinafter sometimes referred to as “mixture (1)”) contains the salt (2).
  • the hydrogen halide in the gas phase in the reaction system may or may not be replaced with nitrogen, but is preferably not replaced with nitrogen. This is because the freezing point of the mixture (1) rises.
  • the mixture (1) can be cooled under normal pressure to precipitate the salt (2).
  • the obtained salt (2) can be dissolved in a solvent and used as a solution of the salt (2) in the next step (“step of reacting salt (2) with a metal salt of thiosulfuric acid” described later).
  • the solvent include water or an organic solvent.
  • an inorganic acid such as sodium hydroxide, hydrofluoric acid, odorous acid, hydrochloric acid, sulfuric acid, phosphoric acid or boric acid; an organic acid such as acetic acid or paratoluenesulfonic acid;
  • the solution of the obtained salt (2) can be used in the next step as it is.
  • the solution of the salt (2) is usually pH 1 to pH 7, preferably pH 2 to pH 5, more preferably pH 2 to pH 3.5.
  • ⁇ Compound represented by formula (3) (hereinafter sometimes referred to as “compound (3)”)> M n + As H + , Lithium ion, sodium ion, potassium ion, cesium ion, magnesium ion, calcium ion, strontium ion, barium ion, mangaion ion, iron ion, copper ion, zinc ion, preferably H + Or an alkali metal ion, more preferably H + Or it is a sodium ion.
  • S- (aminoalkyl) thiosulfuric acid S- (aminoalkyl) thiosulfate, S- (N, N-dialkylaminoalkyl) thiosulfuric acid, S- (N, N-dialkylaminoalkyl) ) Thiosulfate, S- (N-monoalkylaminoalkyl) thiosulfate, S- (N-monoalkylaminoalkyl) thiosulfate, preferably S- (aminoalkyl) thiosulfate, S- (amino) Alkyl) thiosulfate.
  • S- (aminoalkyl) thiosulfuric acid examples include S- (aminoethyl) thiosulfuric acid, S- (aminopropyl) thiosulfuric acid, S- (aminobutyl) thiosulfuric acid, S- (aminopentyl) thiosulfuric acid, S- ( Aminohexyl) thiosulfuric acid, S- (aminoheptyl) thiosulfuric acid, S- (aminooctyl) thiosulfuric acid, S- (aminononyl) thiosulfuric acid Is mentioned.
  • S- (aminoalkyl) thiosulfate examples include sodium S- (aminoethyl) thiosulfate, sodium S- (aminopropyl) thiosulfate, sodium S- (aminobutyl) thiosulfate, and S- (aminopentyl) thiosulfate.
  • Examples include sodium, sodium S- (aminohexyl) thiosulfate, sodium S- (aminoheptyl) thiosulfate, sodium S- (aminooctyl) thiosulfate, and sodium S- (aminononyl) thiosulfate.
  • S- (N, N-dialkylaminoalkyl) thiosulfuric acid examples include S- (N, N-dimethylaminoethyl) thiosulfuric acid, S- (N, N-dimethylaminopropyl) thiosulfuric acid, S- (N, N -Dimethylaminobutyl) thiosulfuric acid, S- (N, N-dimethylaminopentyl) thiosulfuric acid, S- (N, N-dimethylaminohexyl) thiosulfuric acid, S- (N, N-dimethylaminoheptyl) thiosulfuric acid, Examples thereof include S- (N, N-dimethylaminooctyl) thiosulfuric acid and S- (N, N-dimethylaminononyl) thiosulfuric acid.
  • S- (N, N-dialkylaminoalkyl) thiosulfate examples include sodium S- (N, N-dimethylaminoethyl) thiosulfate, sodium S- (N, N-dimethylaminopropyl) thiosulfate, S- ( N, N-dimethylaminobutyl) sodium thiosulfate, S- (N, N-dimethylaminopentyl) sodium thiosulfate, S- (N, N-dimethylaminohexyl) sodium thiosulfate, S- (N, N-dimethyl) Aminoheptyl) sodium thiosulfate, S- (N, N-dimethylaminooctyl) sodium thiosulfate, S- (N, N-dimethylaminononyl) sodium thiosulfate.
  • S- (N-monoalkylaminoalkyl) thiosulfuric acid examples include S- (N-methylaminoethyl) thiosulfuric acid, S- (N-methylaminopropyl) thiosulfuric acid, S- (N-methylaminobutyl) thiosulfuric acid.
  • S- (N-monoalkylaminoalkyl) thiosulfate examples include sodium S- (N-methylaminoethyl) thiosulfate, sodium S- (N-methylaminopropyl) thiosulfate, and S- (N-methylaminobutyl).
  • Examples of the metal salt of thiosulfuric acid include sodium thiosulfate, potassium thiosulfate, and calcium thiosulfate, and preferably sodium thiosulfate.
  • the metal salt of thiosulfuric acid may be a hydrate.
  • the amount of the metal salt of thiosulfuric acid is preferably 80 to 500 mol, more preferably 90 to 200 mol, and still more preferably 100 to 110 mol, per 100 mol of the salt (2).
  • the reaction of the salt (2) with the metal salt of thiosulfuric acid is carried out in the absence of an organic solvent or in the presence of a solvent inert to the metal salt of the salt (2) and thiosulfuric acid.
  • the solvent is preferably a solvent that can dissolve the metal salt of thiosulfuric acid.
  • the solvent include alcohol having 1 to 4 carbon atoms, water, and a mixed solvent of alcohol having 1 to 4 carbon atoms and water, and preferably water or a mixture of alcohol having 1 to 4 carbon atoms and water.
  • a solvent more preferably water.
  • the amount of the solvent to be used is generally 0.5 mL to 40 mL, preferably 1 mL to 20 mL, more preferably 1.5 mL to 10 mL with respect to 1 g of the salt (2).
  • the reaction between the salt (2) and the metal salt of thiosulfuric acid is a method in which the metal salt of thiosulfuric acid is added to and mixed with the salt (2) in the presence or absence of a solvent; in the presence or absence of a solvent.
  • the method of adding the salt (2) to the metal salt of thiosulfuric acid and mixing, and the method of adding the metal salt of thiosulfuric acid to the salt (2) and mixing in the presence of a solvent is preferred.
  • the reaction between the salt (2) and the metal salt of thiosulfuric acid includes alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc.
  • a metal salt such as an alkali metal hydrogen carbonate.
  • a metal salt such as an alkali metal hydrogen carbonate.
  • the amount of hydrogen halide in the salt (2) does not exceed 1 mol per 1 mol of the compound (2), it is preferable to add a metal salt before taking out the compound (3).
  • the amount of hydrogen halide in the salt (2) exceeds 1 mol per 1 mol of the compound (2), it is preferable to add the metal salt before adding the metal salt of thiosulfuric acid.
  • the amount of the metal salt to be used is preferably 1 to 500 mol, more preferably 1 to 100 mol, per 100 mol of the salt (2).
  • the reaction temperature in the reaction between the salt (2) and the metal salt of thiosulfuric acid is preferably 20 ° C.
  • mixture (2) is represented by the formula (4) in addition to the compound (3).
  • Salt (hereinafter sometimes referred to as “salt (4)”) may be included as a by-product.
  • M n + (Cl ⁇ ) n (4) (In formula (4), M n + Is H + Or an n-valent metal ion is represented.
  • n an integer of 1 or 2.
  • Step of Extracting Compound (3) wherein is an n-valent Metal Ion> [Step of adding metal salt] The metal salt is added before the compound (3) is precipitated and taken out from the mixture (2), or the metal salt is added in the presence of a solvent after the compound (3) is precipitated and taken out from the mixture (2). Thus, it is preferable to purify the compound (3).
  • Metal salts include lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, magnesium hydroxide, calcium hydroxide, strontium hydroxide, barium hydroxide, manganese hydroxide, iron hydroxide, copper hydroxide, water Metal hydroxides such as zinc oxide, metal carbonates such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, magnesium carbonate, calcium carbonate, strontium carbonate, barium carbonate, manganese carbonate, iron carbonate, copper carbonate, zinc carbonate, Alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate, lithium chloride, sodium chloride, potassium chloride, cesium chloride, magnesium chloride, calcium chloride, strontium chloride, barium chloride, manganese chloride, iron chloride, copper chloride, zinc chloride Metal chlorides such as are mentioned and more preferred Is a metal hydroxide or metal chloride.
  • the amount of the metal salt added is preferably 1 to 500 mol, more preferably 1 to 100 mol, per 100 mol of the salt (2).
  • the amount is preferably 80 / n to 500 / n mol, more preferably 90 / n to 200 / n mol, and still more preferably 100 / n to 110 / n mol with respect to 100 mol of the salt (2). .
  • the solvent is preferably distilled off from the mixture (2). By distilling off the solvent, the salt (4) can be reduced.
  • the conditions for distilling off the solvent are preferably from room temperature to the boiling point of the solvent under normal pressure or reduced pressure, more preferably from room temperature to 80 ° C. under reduced pressure.
  • the compound (3) can be taken out by washing the mixture (2) or the concentrated mixture obtained in the concentration step (hereinafter sometimes referred to as “concentrated mixture”).
  • the cleaning liquid include alcohols such as methanol and ethanol, water, and a mixed solvent of alcohol having 1 to 4 carbon atoms and water, preferably water or a mixed solvent of methanol, methanol and water.
  • the amount of the cleaning liquid used is preferably 0.01 mL to 40 mL, more preferably 0.1 mL to 10 mL, with respect to 1 g of the mixture (2) or the concentrated mixture.
  • the washing temperature is preferably from room temperature to the boiling point of the washing liquid.
  • the washing time is preferably 1 minute to 24 hours.
  • the solution in which the compound (3) is dissolved is separated from the insoluble matter insoluble in the washing solution.
  • the separation means include solid-liquid separation means such as decantation and filtration, and filtration is preferred.
  • the temperature at the time of separation is preferably from room temperature to the boiling point of the washing liquid or reaction solvent.
  • the compound (3) can be taken out by precipitating the compound (3) from the solution in which the compound (3) from which insoluble matter has been removed is dissolved. Precipitation can be performed by a method of cooling the solution or a method of distilling the cleaning liquid and / or the reaction solvent from the solution.
  • Examples of means for taking out the compound (3) include solid-liquid separation means such as decantation and filtration, and filtration is preferred.
  • the temperature at the time of separation is preferably from ⁇ 20 ° C. to the boiling point of the cleaning liquid.
  • Examples of the cleaning liquid include alcohols such as methanol and ethanol, water, and a mixed solvent of alcohol having 1 to 4 carbon atoms and water, preferably water, methanol, or a mixed solvent of methanol and water.
  • the extracted compound (3) may be dried. The drying temperature is usually room temperature to 100 ° C. under normal pressure or reduced pressure.
  • the extracted compound (3) may be purified by a purification means such as recrystallization.
  • the solvent used for recrystallization is preferably water, methanol or ethanol, more preferably water.
  • the taken out compound (3) may be washed with methanol or ethanol as necessary, and then dissolved in water, and the resulting solution may be concentrated and dried.
  • the amount of methanol or ethanol contained in compound (3) can be reduced by dissolving the extracted compound (3) in water and concentrating and drying the resulting solution.
  • Example 1 Step of reacting compound (1) with hydrogen chloride gas> 100 parts (1.12 mol) of 3-methoxypropylamine was placed in a 500-mL reaction vessel purged with nitrogen, and kept at 60 to 80 ° C. in the absence of a solvent. While maintaining the temperature in the reaction vessel at 60 to 80 ° C., 20.9 parts of hydrogen chloride gas (1 mole per 1 mole of 3-methoxypropylamine, 1.12 moles) was added to 3-methoxypropylamine. Infused over time.
  • N-9-fluorenylmethyloxycarbonyl-3-chloropropylamine solution was obtained.
  • HPLC high performance liquid chromatography
  • the yield was calculated by an absolute calibration curve method using NMR or high performance liquid chromatography.
  • ⁇ Calculation by absolute calibration curve method> A 50 ml sample solution was prepared by diluting 0.2 part of an aqueous solution of the mixture (2) obtained by reacting the mixture (1) with a metal salt of thiosulfuric acid with water. Next, 2 mL of 0.01 M 9-fluorenylmethyl chloroformate and 2 mL of the sample solution were added to 1 mL of 0.1 M phosphate buffer (pH 8.0) prepared separately, and stirred to 5 mL. N-9-fluorenylmethyl-3-chloropropylamine was obtained.
  • the acquisition rate of S- (3-aminopropyl) thiosulfuric acid was 71.3%.
  • the acquisition rate of S- (3-aminopropyl) thiosulfuric acid is obtained by obtaining S- (3-aminopropyl) thiosulfuric acid as the acquisition amount of S- (3-aminopropyl) thiosulfuric acid obtained by subtracting the sodium chloride content from the crystal acquisition amount. It refers to the yield of 3-aminopropyl) thiosulfuric acid.
  • Comparative Example 1 ⁇ Step of reacting 3-amino-1-propanol with thionyl chloride> In a four-necked flask purged with nitrogen, 10.5 parts (0.088 mol) of thionyl chloride and 70 mL of 1,2-dimethoxyethane were charged to obtain a mixture. The resulting mixture was cooled with a water bath. After dropwise adding a solution (concentration 0.2 M) of 5.0 parts (0.067 mol) of 3-amino-1-propanol in 330 mL of 1,2-dimethoxyethane over 1.5 hours to the cooled mixture. The mixture was stirred at room temperature for 7 hours to obtain a reaction mixture.
  • a halogenated alkylamine hydrohalide can be produced in a high yield.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention a pour objet un procédé de production d'un sel d'acide halogénhydrique d'un composé représenté par la formule (2), dans lequel un composé représenté par la formule (1) et un halogénure d'hydrogène sont mis à réagir l'un avec l'autre. (Dans la formule (1), R1 représente un groupe alcoxy group comportant 1 à 8 atomes de carbone ; chacun de R2 et R3 représente indépendamment un atome d'hydrogène ou un groupe alkyle comportant 1 à 6 atomes de carbone, ou en variante R2 et R3 se combinent ensemble pour former un cycle conjointement avec un atome d'azote auquel R2 et R3 sont liés ; et m représente un nombre entier de 2 à 9.) (Dans la formule (2), X1 représente un atome d'halogène ; et R2, R3 et m sont tels que définis ci-dessus.)
PCT/JP2012/082854 2011-12-15 2012-12-12 Procédé de production d'un sel d'acide halogénhydrique d'alkylamine halogénée Ceased WO2013089272A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS56133247A (en) * 1980-03-21 1981-10-19 Teijin Ltd Production of 2-chloroethylamine hydrochloride
JPS5824544A (ja) * 1981-08-07 1983-02-14 Daicel Chem Ind Ltd 塩素化されたアルキルアミン塩酸塩の製造法
JPH08151351A (ja) * 1994-11-28 1996-06-11 Mitsui Toatsu Chem Inc クロロアルキルアミン塩酸塩の製造法
JP2011093851A (ja) * 2009-10-30 2011-05-12 Sumitomo Chemical Co Ltd Ｓ−（アミノアルキル）チオ硫酸塩の製造方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3769347A (en) * 1971-02-11 1973-10-30 American Cyanamid Co Production of d,d'-2,2'-(ethylenediimino) di-1-butanol hydrochloride
CN1206209C (zh) * 2001-11-29 2005-06-15 山西医科大学 单核甘氨酰异羟肟酸、丙氨酰异羟肟酸二烃基锡配合物及其合成

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS56133247A (en) * 1980-03-21 1981-10-19 Teijin Ltd Production of 2-chloroethylamine hydrochloride
JPS5824544A (ja) * 1981-08-07 1983-02-14 Daicel Chem Ind Ltd 塩素化されたアルキルアミン塩酸塩の製造法
JPH08151351A (ja) * 1994-11-28 1996-06-11 Mitsui Toatsu Chem Inc クロロアルキルアミン塩酸塩の製造法
JP2011093851A (ja) * 2009-10-30 2011-05-12 Sumitomo Chemical Co Ltd Ｓ−（アミノアルキル）チオ硫酸塩の製造方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
AMUNDSEN, L.H. ET AL.: "The preparation of amino ethers and diamines from chloromethylether and butadiene", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 73, 1951, pages 1834 - 5 *
ELDERFIELD, R.C. ET AL.: "Synthesis of 1-alkylamino-4-bromopentane derivatives and of other amino halides", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 68, 1946, pages 1579 - 84 *

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