WO2014069668A1 - Procédé de production d'un composé - Google Patents

Procédé de production d'un composé Download PDF

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WO2014069668A1
WO2014069668A1 PCT/JP2013/080055 JP2013080055W WO2014069668A1 WO 2014069668 A1 WO2014069668 A1 WO 2014069668A1 JP 2013080055 W JP2013080055 W JP 2013080055W WO 2014069668 A1 WO2014069668 A1 WO 2014069668A1
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weight
formula
parts
salt
compound represented
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PCT/JP2013/080055
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遠山　芳伴
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住友化学株式会社
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Priority to JP2014544627A priority Critical patent/JP6217646B2/ja
Priority to CN201380056227.1A priority patent/CN104755476B/zh
Publication of WO2014069668A1 publication Critical patent/WO2014069668A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/28—Radicals substituted by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms

Definitions

  • the present invention relates to a method for producing a compound.
  • Patent Document 1 discloses the following formula (3) represented by 2-chloro-5- (aminomethyl) thiazole.
  • X 1 represents a hydrogen atom or a halogen atom.
  • the thiazole compound shown by these is a compound useful as an intermediate of a medicine and an agrochemical.
  • the following formula (1) (Wherein X 1 represents the same meaning as described above, and X 2 represents a halogen atom.)
  • a method of simultaneously mixing and reacting a compound represented by the following formula with ammonia and formaldehyde, followed by hydrolysis treatment is described.
  • X 1 represents the same meaning as described above.
  • the compound represented by is by-produced.
  • the present invention includes the following inventions.
  • [1] A reaction between ammonia and formaldehyde, and the formula (8) A mixture containing the compound represented by formula (8) was obtained, and the resulting mixture containing the compound represented by formula (8) and formula (1) (In formula (1), X 1 represents a hydrogen atom or a halogen atom. X 2 represents a halogen atom. ) Or a salt thereof in the presence of a base, the compound of formula (2) (In formula (2), X 1 represents the same meaning as described above.) Or a salt thereof.
  • [2] The production method according to [1], wherein the base is a bicarbonate.
  • [3] The production method according to [2], wherein the bicarbonate is sodium bicarbonate.
  • the thiazole compound represented by the formula (3) can be obtained with high yield, and the amount of by-products generated can be suppressed.
  • a step of obtaining a compound represented by formula (2) or a salt thereof hereinafter sometimes referred to as compound (2)
  • step of obtaining compound (2) hereinafter, sometimes referred to as “step of obtaining compound (2)”
  • an organic solvent solution of ammonia dissolved in an organic solvent capable of dissolving ammonia such as ammonia gas, liquid ammonia, aqueous ammonia, and methanol can be used, and an organic solvent solution of ammonia is preferably used.
  • formaldehyde gas can be used, but from the viewpoint of handling, it is preferable to use paraformaldehyde or formalin, and it is more preferable to use paraformaldehyde.
  • the amount of formaldehyde used is usually 1.0 to 1.4 mol, preferably 1.01 to 1.1 mol, per 1 mol of ammonia.
  • examples of the halogen atom include a chlorine atom, a bromine atom, and an iodine atom.
  • Compound (1) can be produced according to a known method described in, for example, JP-A-4-234864.
  • Compound (1) includes a salt of the compound represented by Formula (1), and the salt is, for example, an acid addition salt.
  • the acid of the acid addition salt include inorganic acids such as hydrogen chloride, hydrogen bromide, sulfuric acid, and perchloric acid, and organic acids such as acetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, and p-toluenesulfonic acid.
  • the compound (1) 5- (chloromethyl) thiazole, 2-chloro-5- (chloromethyl) thiazole, 2-chloro-5- (bromomethyl) thiazole, 2-bromo-5- (bromomethyl) thiazole, 2 -Chloro-5- (iodomethyl) thiazole, 2-bromo-5- (iodomethyl) thiazole, 2-iodo-5- (iodomethyl) thiazole and the like.
  • the salt of the said compound is mentioned.
  • the amount of compound (1) to be used is generally 0.2-1 mol, preferably 0.5-1 mol, more preferably 0.66-0.84 mol, per 1 mol of ammonia.
  • the amount of compound (1) to be used is generally 0.2 to 1 mol, preferably 0.5 to 1 mol, more preferably 0.5 to 0.77 mol, per 1 mol of formaldehyde.
  • the amount of the salt of the compound represented by the formula (1) may be determined in consideration of the acid in the acid addition salt.
  • the base does not contain ammonia.
  • Examples of the base include carbonates such as lithium carbonate, sodium carbonate and potassium carbonate; hydrogen carbonates such as lithium hydrogen carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate; and organic bases such as triethylamine and diisopropylethylamine. Is preferred, and sodium bicarbonate is more preferred.
  • the amount of the base to be used is generally 0.9 to 1.5 mol, preferably 1 to 1.2 mol, more preferably 1.05 to 1.15 mol, per 1 mol of compound (1).
  • the amount of the base used may be determined in consideration of the acid in the acid addition salt.
  • the reaction temperature in the step of reacting ammonia and formaldehyde is usually ⁇ 20 to 60 ° C., preferably ⁇ 20 to 50 ° C., more preferably 5 to 50 ° C., further preferably 5 to 25 ° C., and particularly preferably 5 ⁇ 15 ° C.
  • the step of reacting ammonia and formaldehyde may be performed in the presence of a base or compound (1).
  • the reaction temperature in the step of obtaining the compound (2) is usually 15 to 100 ° C., preferably 40 to 70 ° C.
  • the step of obtaining the compound (2) may be performed under normal pressure conditions, or may be performed under pressurized conditions of 0.5 MPa (gauge pressure) or less.
  • the step of reacting ammonia and formaldehyde and the step of obtaining compound (2) are preferably performed in a solvent inert to the reaction between the mixture containing compound (8) and compound (1).
  • Solvents include alcohols such as methanol, ethanol, n-propanol and isopropanol, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as chlorobenzene and dichlorobenzene, aliphatic hydrocarbons such as hexane, heptane and cyclohexane, Examples include ethers such as diethyl ether, tetrahydrofuran and dioxane, aprotic polar solvents such as acetonitrile, propionitrile, dimethyl sulfoxide, N, N-dimethylacetamide, and water, and a combination of two or more solvents.
  • the amount of the solvent to be used is generally 0.5 to 5 parts by weight, preferably 0.7 to 2.0 parts by weight, more preferably 0.95 to 1 part per 1 part by weight of the compound (1). .5 parts by weight.
  • quaternary ammonium such as triethylbenzylammonium chloride, tri-n-octylmethylammonium chloride, trimethyldecylammonium chloride, tetramethylammonium bromide, tetra-n-butylammonium bromide, if necessary.
  • the reaction may be carried out in the presence of a phase transfer catalyst such as a salt or a crown ether.
  • the reaction mixture containing the compound (2) can be obtained by mixing the mixture containing the compound (8) and the compound (1) in the presence of a base.
  • Compound (2) can be taken out by concentrating the reaction mixture as necessary. After concentrating the mixture containing the compound (2) as necessary, water and a hydrophobic organic solvent are mixed, extracted, and the resulting organic layer is concentrated to extract the compound (2).
  • hydrophobic organic solvent examples include halogenated hydrocarbon solvents such as chlorobenzene and dichlorobenzene, esters such as ethyl acetate and butyl acetate, ketones such as methyl ethyl ketone and methyl isobutyl ketone, and aromatic hydrocarbons such as toluene and xylene. Two or more solvents may be combined.
  • halogenated hydrocarbon solvents such as chlorobenzene and dichlorobenzene
  • esters such as ethyl acetate and butyl acetate
  • ketones such as methyl ethyl ketone and methyl isobutyl ketone
  • aromatic hydrocarbons such as toluene and xylene. Two or more solvents may be combined.
  • Compound (2) includes a salt of the compound represented by formula (2), and the salt is, for example, an acid addition salt.
  • the acid of the acid addition salt include the same as described above.
  • examples of the compound (2) include salts of the above compounds.
  • hydroxylamines include hydroxylamine salts such as hydroxylamine, hydroxylamine sulfate and hydroxylamine hydrochloride, preferably hydroxylamine sulfate or hydroxylamine hydrochloride.
  • hydroxylamines commercially available ones may be used as they are, or those in a solution state such as an aqueous solution may be used.
  • the amount of hydroxylamine to be used is generally 0.5 to 10 mol, preferably 0.5 to 5 mol, more preferably 0.5 to 2 mol, per 1 mol of compound (2).
  • the acid examples include inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, and nitric acid, and hydrochloric acid or sulfuric acid is preferable.
  • the acid may be used as an aqueous solution.
  • the amount of the acid to be used is generally 0.5 to 10 mol, preferably 0.5 to 5 mol, per 1 mol of compound (2).
  • hydroxylamines may be added to the mixture of compound (2) and acid, or acid may be added to the mixture of compound (2) and hydroxylamine.
  • acid or hydroxylamine may be added all at once, or it may be dropped continuously or intermittently, and it is preferably dropped continuously or intermittently.
  • the step of obtaining the compound (3) is preferably performed in the presence of a solvent.
  • a solvent it is preferable to use a mixed solvent of water and an organic solvent that does not affect the reaction for obtaining the compound (3) or water.
  • the amount of water used is usually 0.5 to 10 parts by weight, preferably 0.5 to 5 parts by weight, more preferably 0.5 to 2 parts by weight with respect to 1 part by weight of the compound (2).
  • organic solvent examples include aromatic hydrocarbons such as toluene, xylene and chlorobenzene, ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether and tetrahydrofuran, and alcohols such as methanol, ethanol and isopropanol, preferably toluene. It is.
  • the amount of the organic solvent to be used is generally 0.5 to 20 parts by weight, preferably 1 to 10 parts by weight, more preferably 2 to 6 parts by weight with respect to 1 part by weight of the compound (2).
  • the reaction temperature in the step of obtaining the compound (3) is usually 0 to 100 ° C., preferably 0 to 50 ° C.
  • the reaction time in this step is usually 0.5 to 24 hours.
  • the resulting reaction solution is adjusted to pH 8 to 14, preferably pH 10 to 14, with an aqueous alkali solution such as sodium hydroxide to liberate compound (3).
  • the compound (3) can be taken out by adding an organic solvent insoluble in water and performing an extraction treatment or filtration.
  • the organic layer containing the free form of the compound (3) and the aqueous solution containing formaldoxime are separated, and the obtained organic layer is concentrated to obtain the compound. (3) can be taken out.
  • the separated compound (3) may be further purified by ordinary purification means such as recrystallization, distillation, column chromatography and the like.
  • the organic layer obtained by the extraction treatment and the aqueous acid solution are mixed and then subjected to a liquid separation treatment, whereby the formula (3)
  • the salt of the compound shown by the chemical formula (3) can be taken out.
  • a poor solvent in which the salt of the compound represented by the formula (3) is difficult to dissolve is added to the aqueous solution containing the salt of the compound represented by the formula (3) to precipitate crystals of the salt of the compound represented by the formula (3). It can also be made.
  • An aqueous solution containing a salt of the compound represented by the formula (3) can also be used as a raw material for the next step as it is.
  • the acid include aqueous solutions of acids such as hydrochloric acid, sulfuric acid, acetic acid, and methanesulfonic acid.
  • the amount of acid used is an amount such that the pH of the aqueous layer during the extraction treatment is usually in the range of 2.5 to 5.5, and preferably in the range of 3 to 5.
  • the aqueous solution may be decolorized with a decoloring agent such as activated carbon.
  • Compound (3) includes a salt of the compound represented by formula (3), and the salt is, for example, an acid addition salt.
  • the acid of the acid addition salt include the same as described above.
  • examples of the compound (3) include 5- (aminomethyl) thiazole, 2-chloro-5- (aminomethyl) thiazole, 2-bromo-5- (aminomethyl) thiazole and the like.
  • examples of the compound (3) include salts of the above compounds.
  • the compound (3) obtained and the compound represented by the formula (5) are reacted to obtain a compound represented by the formula (6) or a salt thereof, and a compound represented by the formula (6) or a salt thereof, and amines
  • the step of obtaining a thiazole compound represented by the formula (7) or a salt thereof by reacting with the salt thereof can be performed according to a known method described in JP-A-10-120666.
  • Example 1 A reaction vessel was charged with 25.2 parts by weight of paraformaldehyde (content: 92% by weight) and 89.2 parts by weight of methanol, and 115 parts by weight of a 12% by weight ammonia / methanol solution at an internal temperature of 15 ° C. or less over 4.9 hours. And dripped. To the obtained mixture, 45.4 parts by weight of sodium hydrogen carbonate and 95.7 parts by weight of 2-chloro-5- (chloromethyl) thiazole (content: 94.9% by weight) were sequentially charged. The resulting mixture was stirred at an internal temperature of 50 ° C. for 7 hours, then at 60 ° C. for 1 hour, and further at 68 ° C. for 2 hours.
  • Example 2 To the obtained toluene layer, 8.8 parts by weight of toluene and 142 parts by weight of water are added, and 190 parts by weight of an aqueous solution of hydroxylamine sulfate (sulfate content: 24% by weight) is charged over 0.5 hours and mixed. A solution was obtained. To the obtained mixed solution, 56.8 parts by weight of 35% by weight hydrochloric acid was added over 0.5 hours while maintaining the internal temperature of 20 to 30 ° C. After stirring at the same temperature for 30 minutes, 284 parts by weight of a 27% by weight aqueous sodium hydroxide solution was added to adjust the pH to 13.4, followed by liquid separation.
  • aqueous solution of hydroxylamine sulfate sulfate content: 24% by weight
  • the toluene solution was washed by adding 15.0 parts by weight of water and 17.0 parts by weight of a 27% by weight aqueous sodium hydroxide solution. Further, 122 parts by weight of water and 49.7 parts by weight of 35% by weight hydrochloric acid were added to adjust the pH to 4.16. The solution was separated, and 251 parts by weight of an aqueous solution containing 2-chloro-5- (aminomethyl) thiazole hydrochloride (content: 36.8% by weight, yield: 92.6% (2-chloro-5- (chloromethyl ) Thiazole standard)). The yield of bis ⁇ (2-chlorothiazol-5-yl) methyl ⁇ amine in the aqueous solution was 0.04% (based on 2-chloro-5- (chloromethyl) thiazole).
  • Example 3 A reaction vessel was charged with 25.2 parts by weight of paraformaldehyde (content: 92% by weight), 88.9 parts by weight of methanol, and 47.7 parts by weight of sodium bicarbonate in order, and cooled to 5 ° C. or lower, and then 2-chloro-5 93.5 parts by weight of (chloromethyl) thiazole (content: 96.6% by weight) was charged. To the resulting mixture, 115 parts by weight of an 11 wt% ammonia / methanol solution was added dropwise over 5 hours at an internal temperature of 25 ° C. or lower. The resulting mixture was stirred at an internal temperature of 50 ° C. for 7 hours, then at 60 ° C. for 1 hour, and further at 68 ° C.
  • Example 4 142 parts by weight of water was added to the obtained toluene layer, and 190 parts by weight of a hydroxylamine sulfate aqueous solution (sulfate content: 24% by weight) was charged over 0.5 hours to obtain a mixed solution.
  • a hydroxylamine sulfate aqueous solution sulfate content: 24% by weight
  • hydrochloric acid was added over 0.5 hours while maintaining the internal temperature of 20 to 30 ° C.
  • 284 parts by weight of a 27% by weight aqueous sodium hydroxide solution was added to adjust the pH to 13.1, and the liquids were separated.
  • An organic layer and an aqueous layer were obtained, respectively, and the obtained aqueous layer was extracted three times with toluene.
  • the obtained toluene layer and the previously obtained organic layer were mixed, and 987 parts by weight of a toluene solution containing 2-chloro-5- (aminomethyl) thiazole (content in terms of hydrochloride: 9.1% by weight, yield: 90.6% (based on 2-chloro-5- (chloromethyl) thiazole)) was obtained.
  • the yield of bis ⁇ (2-chlorothiazol-5-yl) methyl ⁇ amine in the toluene solution was 2.9% (based on 2-chloro-5- (chloromethyl) thiazole).
  • the toluene solution was washed with 15.3 parts by weight of water and 17.5 parts by weight of a 27% by weight aqueous sodium hydroxide solution.
  • Example 5 A reaction vessel was charged with 25.2 parts by weight of paraformaldehyde (content: 92% by weight), 89.1 parts by weight of methanol, and 47.8 parts by weight of sodium bicarbonate in order, and cooled to 5 ° C. or lower, and then 2-chloro-5 93.5 parts by weight of (chloromethyl) thiazole (content: 96.6% by weight) was charged. To the obtained mixture, 115 parts by weight of an 11 wt% ammonia / methanol solution was added dropwise at an internal temperature of 20 ° C. or less over 5 hours. The resulting mixture was stirred at an internal temperature of 50 ° C. for 7 hours, then at 60 ° C. for 1 hour, and further at 68 ° C.
  • Example 6 142 parts by weight of water was added to the obtained toluene layer, and 190 parts by weight of a hydroxylamine sulfate aqueous solution (sulfate content: 24% by weight) was charged over 0.5 hours to obtain a mixed solution.
  • a hydroxylamine sulfate aqueous solution sulfate content: 24% by weight
  • hydrochloric acid was added over 0.5 hours while maintaining the internal temperature of 20 to 30 ° C.
  • 283 parts by weight of a 27% by weight aqueous sodium hydroxide solution was added to adjust the pH to 13.3, followed by liquid separation.
  • An organic layer and an aqueous layer were obtained, respectively, and the obtained aqueous layer was extracted three times with toluene.
  • the obtained toluene layer and the previously obtained organic layer were mixed and 981 parts by weight of a toluene solution containing 2-chloro-5- (aminomethyl) thiazole (content in terms of hydrochloride: 9.2% by weight, yield: 90.6% (based on 2-chloro-5- (chloromethyl) thiazole)) was obtained.
  • the yield of bis ⁇ (2-chlorothiazol-5-yl) methyl ⁇ amine in the toluene solution was 3.1% (based on 2-chloro-5- (chloromethyl) thiazole).
  • Example 7 A reaction vessel was charged with 25.2 parts by weight of paraformaldehyde (content: 92% by weight), 88.8 parts by weight of methanol, 47.7 parts by weight of sodium hydrogen carbonate, and 2-chloro-5- (chloromethyl) thiazole (content: 96). .6 wt%) 93.5 parts by weight were charged in order. To the resulting mixture, 115 parts by weight of an 11 wt% ammonia / methanol solution was added dropwise at an internal temperature of 50 ° C. or less over 5 hours. The resulting mixture was stirred at an internal temperature of 50 ° C. for 7 hours, then at 60 ° C. for 1 hour, and further at 68 ° C. for 2 hours.
  • Example 8 142 parts by weight of water was added to the obtained toluene layer, and 190 parts by weight of a hydroxylamine sulfate aqueous solution (sulfate content: 24% by weight) was charged over 0.5 hours to obtain a mixed solution.
  • a hydroxylamine sulfate aqueous solution sulfate content: 24% by weight
  • hydrochloric acid was added over 0.5 hours while maintaining the internal temperature of 20 to 30 ° C.
  • 283 parts by weight of a 27% by weight aqueous sodium hydroxide solution was added to adjust the pH to 13.2, and the liquids were separated.
  • An organic layer and an aqueous layer were obtained, respectively, and the obtained aqueous layer was extracted three times with toluene.
  • the obtained toluene layer and the previously obtained organic layer were mixed, and 990 parts by weight of a toluene solution containing 2-chloro-5- (aminomethyl) thiazole (content in terms of hydrochloride: 9.1% by weight, yield: 90.7% (based on 2-chloro-5- (chloromethyl) thiazole)) was obtained.
  • the yield of bis ⁇ (2-chlorothiazol-5-yl) methyl ⁇ amine in the toluene solution was 3.0% (based on 2-chloro-5- (chloromethyl) thiazole).
  • Example 9 A reaction vessel was charged with 4.0 parts by weight of paraformaldehyde (content: 92% by weight) and 14.0 parts by weight of methanol, and 17.1 parts by weight of an 11% by weight ammonia / methanol solution at an internal temperature of 15 ° C. or less over 4 hours. And dripped. To the obtained mixture, 7.1 parts by weight of sodium hydrogen carbonate and 14.8 parts by weight of 2-chloro-5- (chloromethyl) thiazole (content: 94.9% by weight) were sequentially charged. The resulting mixture was stirred at an internal temperature of 50 ° C. for 8 hours, then at 60 ° C. for 1 hour, and further at 68 ° C. for 2 hours.
  • Example 10 To the obtained toluene layer, 1.4 parts by weight of toluene and 22.1 parts by weight of water were added, and 29.6 parts by weight of a hydroxylamine sulfate aqueous solution (sulfate content: 24% by weight) was added for 0.5 hour. The mixed solution was obtained. To the obtained mixed solution, 8.8 parts by weight of 35% by weight hydrochloric acid was added over 0.5 hours while maintaining the internal temperature of 20 to 30 ° C. After stirring at the same temperature for 30 minutes, 44.4 parts by weight of a 27% by weight aqueous sodium hydroxide solution was added to adjust the pH to 13.3, followed by liquid separation.
  • a hydroxylamine sulfate aqueous solution sulfate content: 24% by weight
  • the obtained aqueous layer was extracted with toluene three times.
  • the obtained toluene layer and the previously obtained organic layer were mixed and 1318 parts by weight of a toluene solution containing 2-chloro-5- (aminomethyl) thiazole (content: 12.8% by weight, yield: 88.4). % (Based on 2-chloro-5- (chloromethyl) thiazole)).
  • the yield of bis ⁇ (2-chlorothiazol-5-yl) methyl ⁇ amine in the toluene solution was 4.8% (based on 2-chloro-5- (chloromethyl) thiazole).
  • the toluene solution was washed by adding 29.3 parts of water and 31.5 parts by weight of a 27 wt% aqueous sodium hydroxide solution. Further, 229 parts by weight of water and 93.2 parts by weight of 35% by weight hydrochloric acid were added to adjust the pH to 3.5 to 4.5. The solution was separated, and 455 parts by weight of an aqueous solution containing 2-chloro-5- (aminomethyl) thiazole hydrochloride (content: 36.0% by weight, yield: 85.8% (2-chloro-5- (chloromethyl ) Thiazole standard)). The yield of bis ⁇ (2-chlorothiazol-5-yl) methyl ⁇ amine in the aqueous solution was 0.53% (based on 2-chloro-5- (chloromethyl) thiazole).
  • Comparative Example 3 A reaction vessel was charged with 25.2 parts by weight of paraformaldehyde (content: 92% by weight) and 88.8 parts by weight of methanol, and 195 parts by weight of a 12% by weight ammonia / methanol solution was added dropwise at an internal temperature of 15 ° C. or less over 2 hours. . The resulting mixture was charged with 97.0 parts by weight of 2-chloro-5- (chloromethyl) thiazole (content: 94.5 wt%), and the internal temperature was 50 ° C. for 7 hours, then 60 ° C. for 1 hour, and further 68 Stir for 2 hours at ° C.
  • the toluene solution was washed by adding 15.4 parts by weight of water and 17.3 parts by weight of a 27% by weight aqueous sodium hydroxide solution. Further, 122 parts by weight of water and 52.9 parts by weight of 35% by weight hydrochloric acid were added to adjust the pH to 4.03. The solution was separated, and 248 parts by weight of an aqueous solution containing 2-chloro-5- (aminomethyl) thiazole hydrochloride (content: 34.0% by weight, yield: 83.5% (2-chloro-5- (chloromethyl ) Thiazole standard)). The yield of bis ⁇ (2-chlorothiazol-5-yl) methyl ⁇ amine in the aqueous solution was 0.67% (based on 2-chloro-5- (chloromethyl) thiazole).
  • Example 11 269 parts by weight of O-methyl-N-nitroisourea mixed acid mixture (content: 19.2%) was added dropwise to 185 parts by weight of water cooled to 7 ° C while maintaining the temperature at 10 ° C or lower. To the obtained mixture, 551 parts by weight of 27% aqueous sodium hydroxide solution was added dropwise at 20 ° C. or lower. After adding 199 parts by weight (content: 36.2% by weight) of an aqueous solution containing 2-chloro-5- (aminomethyl) thiazole hydrochloride, the mixture was kept at an internal temperature of 18 to 24 ° C. for 42 hours. The temperature was raised to 35 ° C., followed by filtration.
  • Example 12 To 256 g of water, 50 parts by weight (content 96.1%) of O-methyl- (2-chloro-5-thiazolylmethyl) -N′-nitroisourea was added. To the obtained mixture, 22.3 parts by weight of methylamine aqueous solution (content 40%) was added and kept at 15 ° C. for 3 hours. To the obtained mixture, 38 parts by weight of methyl isopropyl ketone and 57 parts by weight of a 27% aqueous sodium hydroxide solution were added in order, and the mixture was stirred at 15 ° C. for 1 hour. After the liquid separation operation, 7.7 parts by weight of methanol was added to the aqueous layer.
  • methylamine aqueous solution content 40%
  • the thiazole compound represented by the formula (3) can be obtained with high yield. Moreover, the production amount of a by-product can be suppressed.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé de production d'un composé représenté par la formule (2), ou de son sel, par réaction d'ammoniac avec du formaldéhyde de manière à obtenir un mélange qui contient un composé représenté par la formule (8) puis par mélange du mélange obtenu qui contient le composé représenté par la formule (8) avec un composé représenté par la formule (1), ou son sel, en présence d'une base.
PCT/JP2013/080055 2012-11-02 2013-10-30 Procédé de production d'un composé WO2014069668A1 (fr)

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Application Number Priority Date Filing Date Title
JP2014544627A JP6217646B2 (ja) 2012-11-02 2013-10-30 化合物の製造方法
CN201380056227.1A CN104755476B (zh) 2012-11-02 2013-10-30 化合物的制造方法

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JP2012242488 2012-11-02
JP2012-242488 2012-11-02

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WO2014069668A1 true WO2014069668A1 (fr) 2014-05-08

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CN (1) CN104755476B (fr)
TW (1) TW201422613A (fr)
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* Cited by examiner, † Cited by third party
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WO2017026298A1 (fr) * 2015-08-10 2017-02-16 住友化学株式会社 Composé amide d'oxalyle et son utilisation pour lutter contre les arthropodes nuisibles

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2675382A (en) * 1954-04-13 Aminoalkydhexahydbo-
US3000889A (en) * 1957-01-28 1961-09-19 Aerojet General Co Tris n-alkylenepolynitro hexahydro s-triazines
JPS6372662A (ja) * 1986-09-17 1988-04-02 Mitsubishi Gas Chem Co Inc メチレンイミン化合物の製造法
JPS63198654A (ja) * 1987-02-14 1988-08-17 Mitsubishi Gas Chem Co Inc メチレンイミン化合物の製造法
JPH10120666A (ja) * 1995-11-17 1998-05-12 Takeda Chem Ind Ltd グアニジン誘導体の製造方法
WO2000034211A1 (fr) * 1998-12-04 2000-06-15 Bp Chemicals Limited Procede d'oligomerisation
JP2003105357A (ja) * 2001-09-14 2003-04-09 Ethyl Corp 直接噴射ガソリンエンジン用燃料組成物
JP2006290758A (ja) * 2005-04-07 2006-10-26 Sumitomo Chemical Co Ltd チアゾール化合物の製造法
JP2006312617A (ja) * 2004-06-17 2006-11-16 Sumitomo Chemical Co Ltd チアゾール化合物の製造方法
WO2008027721A1 (fr) * 2006-09-01 2008-03-06 Baker Hughes Incorporated Agents d'élimination rapide et à haute capacité du sulfure d'hydrogène

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2148849A1 (fr) * 1994-06-23 1995-12-24 Kishan Bhatia Methode pour traiter des hydrocarbures gazeux et liquides acides
CN1072213C (zh) * 1995-06-23 2001-10-03 武田药品工业株式会社 胍衍生物的制备方法及其中间体

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2675382A (en) * 1954-04-13 Aminoalkydhexahydbo-
US3000889A (en) * 1957-01-28 1961-09-19 Aerojet General Co Tris n-alkylenepolynitro hexahydro s-triazines
JPS6372662A (ja) * 1986-09-17 1988-04-02 Mitsubishi Gas Chem Co Inc メチレンイミン化合物の製造法
JPS63198654A (ja) * 1987-02-14 1988-08-17 Mitsubishi Gas Chem Co Inc メチレンイミン化合物の製造法
JPH10120666A (ja) * 1995-11-17 1998-05-12 Takeda Chem Ind Ltd グアニジン誘導体の製造方法
WO2000034211A1 (fr) * 1998-12-04 2000-06-15 Bp Chemicals Limited Procede d'oligomerisation
JP2003105357A (ja) * 2001-09-14 2003-04-09 Ethyl Corp 直接噴射ガソリンエンジン用燃料組成物
JP2006312617A (ja) * 2004-06-17 2006-11-16 Sumitomo Chemical Co Ltd チアゾール化合物の製造方法
JP2006290758A (ja) * 2005-04-07 2006-10-26 Sumitomo Chemical Co Ltd チアゾール化合物の製造法
WO2008027721A1 (fr) * 2006-09-01 2008-03-06 Baker Hughes Incorporated Agents d'élimination rapide et à haute capacité du sulfure d'hydrogène

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017026298A1 (fr) * 2015-08-10 2017-02-16 住友化学株式会社 Composé amide d'oxalyle et son utilisation pour lutter contre les arthropodes nuisibles

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