WO2004094397A1 - Procede de production de derive de sulfonate de glycidyle - Google Patents

Procede de production de derive de sulfonate de glycidyle Download PDF

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Publication number
WO2004094397A1
WO2004094397A1 PCT/JP2004/005224 JP2004005224W WO2004094397A1 WO 2004094397 A1 WO2004094397 A1 WO 2004094397A1 JP 2004005224 W JP2004005224 W JP 2004005224W WO 2004094397 A1 WO2004094397 A1 WO 2004094397A1
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base
glycidol
reaction
solvent
derivative
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PCT/JP2004/005224
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English (en)
Japanese (ja)
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Takeshi Kondo
Natsuki Mori
Naoaki Taoka
Noboru Ueyama
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Kaneka Corporation
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D301/00—Preparation of oxiranes
    • C07D301/02—Synthesis of the oxirane ring
    • C07D301/24—Synthesis of the oxirane ring by splitting off HAL—Y from compounds containing the radical HAL—C—C—OY
    • C07D301/26—Y being hydrogen

Definitions

  • the present invention relates to a method for producing a glycidyl sulfonate derivative, which is important as a raw material for pharmaceuticals and agricultural chemicals.
  • the following method is known as a conventional method for producing a glycidyl sulfonate derivative.
  • 3-chloro-1,2-propanediol is reacted with at least a species selected from alkali metal carbonates, bicarbonates, and alkaline earth metal carbonates, and then p —A method of reacting with toluenesulfonyl chloride, tertiary amine and 4-dimethylaminopyridine (Japanese Patent No. 3250350).
  • Glycidol is dissolved in an organic solvent / water two-phase system solvent at least one inorganic base selected from hydroxides, carbonates or bicarbonates of alkali metal or alkaline earth metal and tertiary.
  • a method of reacting with a sulfonyl chloride derivative in the presence of a base consisting of a combination of an amine or a pyridine derivative Japanese Patent No. 3253634.
  • Japanese Patent No. 3253634 Japanese Patent No. 3253634
  • glycidol which has been isolated in advance is used.
  • the necessity of the isolation step is industrially disadvantageous, and in addition, glycidol is unstable and decomposes at the time of isolation or storage, and has the problem of reduced yield and quality. This is a problematic method for industrial adoption.
  • the solution viscosity increases during the reaction with an organic solvent other than a halogen-based organic solvent that has a large environmental load, and the solution is not suitable for practical use. Difficult and, in addition, the speed of the reaction is slow. As a result, a side reaction proceeds, and a large amount of impurities are contained. As a result, the obtained glycidyl p-toluenesulfonate has a problem that the quality is not sufficient, and crystallization must be performed twice, which is a problematic method for industrial adoption.
  • the method of (3) requires a step of extracting glycidol obtained as an intermediate in an organic solvent with water.
  • the increase in the number of processes is industrially disadvantageous, and in addition, there is a problem that the quality of the obtained glycidyl dinitrobenzenesulfonate is not sufficient. It is.
  • An object of the present invention is to provide a method for producing a glycidyl sulfonate derivative which is efficient, economical, and industrially suitable in view of the above situation. Disclosure of the invention
  • the inventors of the present invention have conducted various studies to solve such problems. As a result, the number of steps is small, the operation is simple, the amount of waste is small, and the quality is high.
  • the present inventors have found a method for producing a glycidyl acid derivative, and have completed the present invention. That is, the first invention relates to a method for producing a glycidyl sulfonate derivative, which comprises reacting 3-chloro-1,2-propanediol and a sulfonyl halide derivative in the presence of a base.
  • the second invention is to produce glycidol by reacting 3-chloro-1,2-propanediol in an organic solvent in the presence of an alkali metal hydroxide or an alkaline earth metal hydroxide.
  • a method for producing a glycidyl sulfonate derivative which comprises producing a glycidyl sulfonate derivative without isolating glycidol, followed by reacting with a sulfonyl halide derivative in the presence of a base group.
  • a third invention is a method for producing glycidyl nitrobenzenesulfonate by reacting glycidol and nitrobenzene sulfuryl halide in the presence of a base, wherein the method comprises using only an inorganic base as the base.
  • the present invention relates to a method for producing glycidyl sulfonate.
  • BEST MODE FOR CARRYING OUT THE INVENTION hereinafter, the present invention will be described in detail.
  • ammonia (NH 3 ) hydrogen atoms substituted with one atom other than hydrogen are replaced with primary amines, those substituted with two atoms with secondary amines, those substituted with three atoms Defined as tertiary amine. If the nitrogen atom has an unsaturated bond, calculate for each bond.
  • pyridine is a tertiary amine.
  • a method for producing a glycidyl sulfonate derivative which comprises reacting 3-chloro-1,2-propanepandiol and a sulfonylno, lide derivative in the presence of a base. Is done.
  • a compound in which the sulfonyl halide derivative is bonded only to the terminal hydroxyl group of the two hydroxyl groups of 3-chloro-1,2-propanediol is preferred. It is surprising that the compound obtained earlier and bonded to two hydroxyl groups or the compound bonded only to the 2-position hydroxyl group has less by-product.
  • any of a racemic form and an optically active form can be used. It is preferable to use an optically active substance because the desired glycidyl sulfonate derivative can be directly obtained as an optically active substance.
  • the sulfonyl halide derivative to be used is not particularly limited, and alkylsulfonyl halide having 1 to 20 carbon atoms, aryl alkylsulfonyl halide having 7 to 20 carbon atoms, and aryl having 6 to 20 carbon atoms. And sulfuryl halide in which one or more of these hydrogens are substituted with another functional group such as a halogen, a nitro group, a cyano group, and the like.
  • methanesnorefoylk mouth ride methanesnorefoylk mouth ride, ethanesulfoyurk mouth ride, benzylsulfonylchloride, phenethylsnorefoninolechloride, benzenesulfjork mouth ride, one toluenesulfjork mouth ride, dodecylbenzenesulfuride Elk mouth ride, naphthene snorehonyle / chloride, trifrenoleolomethanes honolehoninolechloride, 2-black benzene snolehoninolechloride, 2-bromobenzene snolehoninolechloride, 3—black benzene snolehonolechloride Henolechloride, 3-Bromobenzenes-nolehoninolechloride, 4-methylbenz
  • the amount is less than 0.7 equivalents, the yield is reduced due to the insufficient amount of the sulfonyl halide derivative. If the amount exceeds 2 equivalents, an excess amount of the sulfonyl halide derivative remains in the reaction solution, and when the target product is isolated, the yield decreases. It is not preferable because it lowers the quality or lowers the quality.
  • the base used in the reaction is not particularly limited, and only an organic base may be used, or only an inorganic base may be used. In addition, an organic base or an inorganic base can also be used. From the viewpoint of suppressing side reactions and allowing the target reaction to proceed preferentially, it is preferable to use only an inorganic base, or an organic base and an inorganic base.
  • organic base examples include primary amine, secondary amine, and tertiary amine.
  • monoalkylamines such as t-butylamine, dialkylamines such as di-t-butylamine, aromatic secondary amines such as imidazole, trimethylamine, triethylamine, tripropylamine, diisopropylethylamine, and dicycloamine.
  • Examples thereof include pyridine derivatives having 5 to 18 carbon atoms, aromatic amines having 4 to 18 carbon atoms such as pyrazine, pyrimidine, pyridazine, and quinoline. These can be used alone or in combination. When used as a mixture, the mixing ratio is not particularly limited. Among them, pyridine derivatives are preferable, and 4-dimethylaminopyridine is more preferable, from the viewpoint that the effect is exhibited by using a small amount.
  • the inorganic base examples include oxides, hydroxides, carbonates, bicarbonates, and potassium hydroxides, alkali metal hydrides, alkali metal or alkaline earth metals. Sulfate and the like.
  • sodium hydroxide, potassium hydroxide, sodium carbonate and carbonated lime are preferred from the viewpoint of low cost and easy handling, and sodium hydroxide and hydroxylated lime are preferred from the viewpoint of increasing the reaction rate. More preferred.
  • the amount of the base used is 1.5 to 11 equivalents, preferably 2 to 5 with respect to 3-chloro-1,2-propanediol. Is equivalent. If the amount is less than 1.5 equivalents, the reaction is not completed and the yield decreases. If the amount exceeds 11 equivalents, side reactions such as decomposition of glycidol are not preferred.
  • the mixing ratio of the organic base and the inorganic base is not particularly limited, but the ratio of the organic base to 3-chloro-1,2-propanediol is 0.00. 1 to 4 equivalents, preferably 0.01 to 0.5 equivalents, more preferably 0.01 to 0.1 equivalents, when the inorganic base is 0.5 to 50 equivalents based on 3-chloro-1,2-propanediol. 11 equivalents, preferably 2 to 5 equivalents. If the amount of the organic base used is less than 0.001 equivalent, the addition effect does not appear, and the reaction rate is slow.If the amount exceeds 4 equivalents, the excess organic base remains in the reaction solution and the target product is isolated.
  • the yield is lowered and the quality is deteriorated, which is not preferable. If the amount of the inorganic base used is less than 0.5 equivalent, the reaction is not completed and the yield is reduced, and if it exceeds 11 equivalents, side reactions such as decomposition of glycidol are not preferred.
  • These bases may be added in the entire amount at the start of the reaction, or may be added in portions during the reaction.
  • the diameter of the particles is preferably 5 mm or less, and the diameter is preferably 3 mm or less from the viewpoint of increasing the surface area and increasing the reaction rate. More preferably, the diameter is 1 mm or less.
  • the solvent is not particularly limited as long as it does not inhibit the reaction, and the reaction can be carried out in a mixed solvent of an organic solvent / water or an organic solvent. From the viewpoint of suppressing the hydrolysis of the sulfonyl halide derivative during the reaction, the reaction is preferably carried out in a two-phase solvent of an organic solvent / water or an organic solvent, suppressing side reactions and giving priority to the intended reaction. From the viewpoint of progressing to a second phase, an organic solvent / water two-phase solvent is more preferable.
  • the organic solvent used is not particularly limited as long as it does not hinder the reaction, and is an organic solvent that forms a two-phase with water at the start of the reaction.
  • Aliphatic hydrocarbon solvents such as hexane, heptane, cyclohexane, and petroleum ether; ester solvents such as ethyl acetate, methyl acetate, propyl acetate, and methyl propionate; and aromatic carbons such as toluene, benzene, and xylene Hydrogenated solvents, ether solvents such as t-butyl methyl ether, methyl ether, diisopropyl ether, etc., ketone solvents such as methyl ethyl ketone, diisopropyl ketone, methyl isobutyl ketone, methylene chloride, chloroform, 1 , 2 Dichloroethane, 1,1-dichloroethane, carbon
  • organic solvents may be used alone or in combination of two or more.
  • aromatic hydrocarbon solvents methyl ethyl ketone, methyl isobutyl ketone, methylene chloride, or a mixture of two or more of them are used.
  • Organic solvents are preferred, and benzene and toluene are more preferred.
  • the mixing ratio is not particularly limited.
  • the mixing ratio of the organic solvent Z water is not particularly limited, it is preferably 10: 1 to 1/10 (by volume), more preferably 5/1 to 1/5 (by volume).
  • the organic solvent used is not particularly limited as long as it does not inhibit the reaction, and examples thereof include aliphatic carbons such as pentane, hexane, heptane, cyclohexane, and petroleum ether.
  • Hydrogen solvents, ester solvents such as ethyl acetate, methyl acetate, propyl acetate, and methyl propionate; aromatic hydrocarbon solvents such as toluene, benzene, and xylene; t-butyl methyl ether; ⁇
  • Ethenolate solvents such as ethenoleate, diisopropynoleate, THF, and dioxane; ketone solvents such as acetone, methylethylketone, diisopropylketone, and methylisobutinoleketone; methylene chloride, chlorophonolem, 1,2- Halogenated hydrocarbon solvents such as dichloroethane, 1,1-dichloroethane, carbon tetrachloride, and chlorobenzene; nitrile solvents such as acetonitrile and propionitrile; and highly polar aprotic solvents such as DMF and DMSO. No.
  • organic solvents may be used alone or as a mixture of two or more.
  • the mixing ratio is not particularly limited.
  • the concept of an organic solvent includes that water does not form a two-phase phase and does not hinder the reaction.
  • toluene, benzene, acetone, methyl ethyl ketone, methyl isobutyl ketone, methylene chloride, or a mixture of two or more of these are considered from the viewpoint of low cost, easy handling, and solubility of the sulfonyl halide derivative.
  • Organic solvents are preferable, and acetone, methyl ketone, methyl isobutyl ketone, or an organic solvent obtained by mixing two or more thereof is more preferable.
  • the amount of the solvent to be used is preferably llOO vo lZw t times (1- to LO Oml) for 3-chloro-1,2-propanediol, and 3 to 30 V o 1 / wt times. More preferred. If the amount of solvent used is less than 1 Vo 1 t, the yield will decrease or handling will be difficult due to precipitation of insolubles or increase in solution viscosity, and if it exceeds 100 V o 1 / wt, It is not preferable because the reaction rate decreases or the productivity decreases.
  • the reaction can be carried out at a temperature of usually from 30 to 60 ° C, preferably from 110 to 30 ° C. If the temperature is lower than 30 ° C, the progress of the reaction is slow or the solvent solidifies, which is not preferable. If the temperature is higher than 60 ° C, decomposition and side reactions increase, which is not preferable. The reaction is usually completed in 2 to 24 hours.
  • the method of addition and the order of addition at the time of the reaction are not particularly limited.
  • (1) 3-chloro-1,2-propanediol or a mixture thereof with a sulfonyl halide derivative or a solvent thereof may be used.
  • a method of adding a base or a mixture thereof with a solvent after adding the mixture (2) a sulfonyl halide derivative or a mixture thereof.
  • a method in which 3-chloro-1,2-propanediol or a mixture with the solvent is added to the mixture with the solvent, and then a base or a mixture with the solvent is added.
  • 3-chloro-1 A method of adding a base or a mixture thereof with a solvent to 2-propanediol or a mixture thereof with a solvent, and then adding a sulfonyl halide derivative or a mixture thereof with the solvent; (4) 3-chloro-1, Examples thereof include a method in which a sulfonyl halide derivative or a mixture with the solvent and a base or a mixture with the solvent are simultaneously added to 2-propanediol or a mixture with the solvent. Among them, the method (1), (2) or (4) is preferable from the viewpoint of suppressing side reactions and allowing the target reaction to proceed preferentially.
  • the post-treatment method of the reaction solution is not particularly limited, and examples thereof include the following methods.
  • (1) In the case of an organic solvent system in which no solid is precipitated from the reaction solution, no special post-treatment is required, and in the case of a two-phase system of an organic solvent z water in which no solid is precipitated from the reaction solution By removing the aqueous phase, a solvent mixture of the target substance can be obtained.
  • the target solid When only the target solid is precipitated from the reaction solution, the target solid can be obtained by filtration.
  • a solvent mixture of the target can be obtained by removing the solid by filtration.
  • non-target solids inorganic salts, etc.
  • a solvent mixture can also be obtained.
  • a solid of the target substance and a solid that is not the target substance are precipitated from the reaction solution, add a solvent that dissolves the target substance, or add a solid that is not the target substance (such as an inorganic salt).
  • a solvent that dissolves for example, water, etc., and dissolving either one preferentially, and then performing operation (2) or (3), or performing operation (1) after dissolving both. By doing so, you can obtain the desired object.
  • the operations (1) to (4) may be performed in combination.
  • an organic solvent and / or water may be added, if necessary, or the reaction solution may be concentrated. Or may be heated or cooled.
  • the temperature is preferably adjusted to 10 to 60 ° C. If the temperature is lower than 10 ° C, the liquid-liquid separation property is not sufficient, which is not preferable. If the temperature is higher than 60 ° C, decomposition and side reactions are not preferable. Additives (acidic substances, basic substances, salts, etc.) may be added as long as they do not affect the quality of the target product.
  • the following operation may be further performed on the obtained solvent mixture of the target substance, if necessary.
  • water is added to the solvent mixture of the target substance, if water forms an organic solvent / water two-phase system, water and / or an acidic aqueous solution such as citric acid, hydrochloric acid, or sulfuric acid, and Z or baking soda or water It may be washed with an alkaline aqueous solution such as sodium oxide or potassium hydroxide. If two phases of organic solvent / water are not formed, washing may be performed after replacing with an organic solvent that forms two phases with water. At the time of washing, the temperature is preferably adjusted to 10 to 60 ° C. from the viewpoint of improving liquid-liquid separation properties.
  • the temperature is lower than 10 ° C, the liquid-liquid separation property is not sufficient, which is not preferable. If the temperature is higher than 60 ° C, decomposition and side reactions are not preferable. Thereafter, high-purity glycidyl sulfonate derivatives can be easily isolated by ordinary operations such as concentration and crystallization.
  • glycidol is reacted by reacting 3-chloro-1,2-propanediol in an organic solvent in the presence of an alkali metal and / or alkaline earth metal hydroxide.
  • the present invention provides a process for producing a glycidyl sulfonate derivative, which comprises producing the glycidyl sulfonate derivative without isolating the glycidol and subsequently reacting the sulfonyl halide derivative in the presence of a base.
  • alkali metal and hydroxide of alkaline metal or alkaline earth metal are used in the reaction of 3-chloro-1,2-propanediol, so that it can be practically used without using a halogenated solvent. It is surprising that there is no problematic increase in solution viscosity and, in addition, the speed of the reaction is high. Furthermore, in this method, water is produced in an equimolar amount to glycidol during the production of glycidol, but a compound in which the sulfonyl halide derivative binds to the glycidol hydroxyl group over the hydroxyl group of water is obtained preferentially. The point is surprising.
  • any of a racemic substance and an optically active substance can be used. It is preferable to use an optically active substance because the desired glycidyl sulfonate derivative can be directly obtained as an optically active substance.
  • alkali metal or alkaline earth metal hydroxide used as the base examples include lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, and calcium hydroxide. These can be used alone or in combination, and the mixing ratio is not particularly limited. Of these, sodium hydroxide and potassium hydroxide are preferred from the viewpoint of low cost and ease of handling.
  • the amount of the base to be used is 0.5 to 10 equivalents, preferably 1 to 4 equivalents, relative to 3-chloro-1,2-propanediol. If the amount is less than 0.5 equivalent, the reaction is not completed and the yield decreases, and if it exceeds 10 equivalents, side reactions such as decomposition of glycidol increase, which is not preferable.
  • the diameter of the particles is preferably 5 mm or less. It is more preferably at most 3 mm, particularly preferably at most l mm.
  • the organic solvent to be used is not particularly limited as long as it does not inhibit the reaction, and examples thereof include aliphatic hydrocarbon solvents such as pentane, hexane, heptane, cyclohexane, petroleum ether, ethyl acetate, and the like.
  • Estenole solvents such as methyl acetate, propyl acetate, and methyl propionate; aromatic hydrocarbon solvents such as tonolenene, benzene, and xylene; t-butyl methyl ether, getyl ether, diisopropyl ether, THF, and dioxane Solvents, ketone solvents such as acetone, methyl ethyl ketone, diisopropyl ketone, and methyl isobutyl ketone; salts; halogens such as methylene chloride, chlorophonolem, 1,2-dichloroethane, 1,1-dichloroethane, carbon tetrachloride, and chlorobenzene Hydrocarbon solvent, acetonitrile And tolyl solvents such as propionitrile, and highly polar nonproton solvents such as DMF and DMSO.
  • aromatic hydrocarbon solvents such as tonolenene, benz
  • organic solvents may be used alone or as a mixture of two or more. When using mixed organic solvents, the mixing ratio is particularly limited There is no.
  • organic solvent includes the inclusion of water that does not inhibit the reaction without forming two phases. Among these, ketone solvents, THF, acetonitrile, methylene chloride, and the like, from the viewpoint of low cost, easy handling, solubility of 3-chloro-1,2-propanediol, and dispersibility of bases and inorganic salts during the reaction. Alternatively, an organic solvent obtained by mixing two or more thereof is preferable.
  • ketones are preferred from the viewpoint that the reaction proceeds promptly in the same organic solvent without changing the kind of the organic solvent.
  • a system solvent is preferable, and acetone, methyl ethyl ketone, methyl isobutyl ketone, or an organic solvent obtained by mixing two or more thereof is more preferable.
  • the amount of the solvent used is preferably 1 to: LOO vo 1 / wt (1-to 1 g: LO Oml) based on 3-chloro-1,2-propanediol, and 3 to 30 V o. 1 / wt times is more preferred. If the amount of the solvent used is less than 1 Vo 1 t, the yield becomes lower or the handling becomes difficult due to the precipitation of insolubles or the increase in the solution viscosity, and if it exceeds 100 V o 1 / wt, However, it is not preferable because the reaction rate decreases or the productivity decreases.
  • the reaction can be carried out at a temperature of usually 30 to 50 ° C, preferably 120 to 30 ° C, more preferably 110 to 20 ° C.
  • a temperature usually 30 to 50 ° C, preferably 120 to 30 ° C, more preferably 110 to 20 ° C.
  • the temperature is lower than 30 ° C, the reaction progresses slowly or the organic solvent solidifies, which is not preferable.
  • side reactions such as decomposition of daricidol increase, which is not preferable.
  • the reaction is usually completed in 30 minutes to 5 hours.
  • the method of addition and the order of addition during the reaction are not particularly limited.
  • a method of adding 3-chloro-1,2-propanediol or a mixture thereof with an organic solvent to the mixture is exemplified.
  • the glycidol obtained as an intermediate can be reacted with a sulfonyl halide derivative in the presence of a base without isolation to produce a glycidyl sulfonate derivative.
  • a non-target solid inorganic salt, etc.
  • remove the solid by filtration obtain a glycidol solvent mixture, and then continue with the sulfonyl halide derivative. May be reacted.
  • the sulfonyl halide derivative to be used is not particularly limited, and the alkylsulfonyl halide having 1 to 20 carbon atoms, the arylsulfonyl halide having 7 to 20 carbon atoms, and the arylsulfonyl halide having 6 to 20 carbon atoms Halides, and sulfonyl halides in which one or more of these hydrogens are substituted with another functional group such as a halogen, a dinitro group, a cyano group, and the like.
  • methanes-norefoninochloride methanes-norefoninochloride, ethanes-norefole-chloride, penzinoles-norefonolechloride, phenethylsulfoylurk, benzenesulfoyluku, p-toluenesulfonyl chloride , Dodecylbenzenesulfonyl chloride, naphthylene selenoinochloride, trifnorolenomethane snorefoninochloride, 2-chlorobenzene snoleshonolinochloride, 2-bromobenzenesnolehoninochloride Benzene, snolephoninolechloride, 3-bromobenzenes / lehoninolechloride, 4-bromobenzenes / lehoninolechloride, 4-
  • the amount of the sulfonyl halide derivative to be used is 0.7 to 2 equivalents, preferably 0.8 to 1.5 equivalents, relative to 3-chloro-1,2-propanediol.
  • the amount is less than 0.7 equivalents, the yield decreases due to the insufficient amount of the sulfonyl halide derivative, and if it exceeds 2 equivalents, an excess amount of the sulfohalide derivative remains in the reaction solution, and the yield decreases when isolating the target product. It is not preferable because the quality deteriorates.
  • the base used is not particularly limited, and may be an organic base alone, an inorganic base alone, or an organic base and an inorganic base.
  • examples of the organic base include primary amine, secondary amine, and tertiary amine.
  • monoalkylamines such as t-butylamine, dialkylamines such as di-t-butylamine, aromatic secondary amines such as imidazole, trimethylamine, triethylamine, tripropylamine, diisopropylethylamine, Dicyclohexylmethylamine, N, N, ⁇ ', ⁇ '-tetramethylethylenediamine ⁇ , ⁇ -dimethylalanine ester and other trialkylamine derivatives with 3 to 18 carbon atoms, ⁇ , ⁇ -dimethyla Dilinolequinolepheninoleamine or monoa / req ⁇ diphene / reamine, triarylamines such as triphenylamine, phenylmethylpyrrolidine, ⁇ -methylpyrrolidine, etc.
  • aromatic secondary amines such as imidazole, trimethylamine, triethylamine, tripropylamine, diisopropylethylamine, Dicyclohex
  • Total carbon such as methylpiperidine, ⁇ -methylmorpholine, ⁇ -ethylmorpholine, DBU, DABC 0, quinuclidine 3 to 18 cyclic amines, such as pyridine, picoline, lutidine, collidine, 2-methoxypyridine, 2-dimethylaminopyridine, 3-dimethyl ⁇ aminoviridine, 4-dimethylaminopyridine, and 4-ethylaminopyridine Examples thereof include pyridine derivatives having 5 to 18 carbon atoms, aromatic amines having 4 to 18 carbon atoms such as pyrazine, pyrimidine, pyridazine, and quinoline. These can be used alone or in combination.
  • triethylamine, diisopropylethylamine, and pyridine derivatives are preferable from the viewpoint of low cost and ease of handling. Further, from the viewpoint that the effect is exhibited by using a small amount, a pyridine derivative is preferable, and 4-dimethylaminopyridine is particularly preferable.
  • the inorganic base include an alkali metal, an alkali metal hydride, an alkali metal or an alkaline earth metal, an oxide, a hydroxide, a carbonate, a hydrogen carbonate or a borate.
  • sodium hydroxide, potassium hydroxide, sodium carbonate, and carbonated carbonate are preferred from the viewpoint of low cost and ease of handling, and sodium hydroxide and potassium hydroxide are more preferred from the viewpoint of increasing the reaction rate.
  • the amount of the base to be used is 0.5 to 10 equivalents, preferably 1 to 4 equivalents, to dalicidol. If the amount is less than 0.5 equivalent, the reaction is not completed and the yield is reduced. If the amount exceeds 10 equivalents, side reactions such as decomposition of dalicidol are undesirably increased.
  • the mixing ratio of the organic base and the inorganic base is not particularly limited, but the organic base is preferably used in an amount of 0.001 to 3 equivalents, preferably 0.00, based on dalicidol.
  • the amount is from 1 to 0.5 equivalent, more preferably from 0.01 to 0.1 equivalent, and the amount of the inorganic base is from 0.5 to 10 equivalent, preferably from 1 to 4 equivalent to glycidol. If the amount of the organic base used is less than 0.001 equivalent, the addition effect does not appear, and the reaction rate is slow.If the amount exceeds 3 equivalents, an excessive amount of the organic base remains in the reaction solution and the desired product is isolated.
  • the yield is reduced and the quality is deteriorated, which is not preferable. If the amount of the inorganic base is less than 0.5 equivalent, the reaction is not completed and the yield is lowered. If it exceeds 10 equivalents, side reactions such as decomposition of daricidol increase, which is not preferable.
  • the diameter of the particles is preferably 5 mm or less, and the diameter of the particles is 3 mm. The following is more preferable, and the diameter is preferably 1 mm or less.
  • the necessary inorganic base may be added in advance when synthesizing glycidol, if necessary.
  • the solvent is not particularly limited as long as it does not inhibit the reaction, and the organic solvent described in the section of glycidol synthesis or a mixed solvent of the organic solvent and water may be used alone or as a mixture of two or more. Can be used. From the viewpoint of suppressing the hydrolysis of the sulfonyl halide derivative during the reaction, the reaction is preferably carried out in a two-phase solvent of an organic solvent / water or an organic solvent.
  • the concept of an organic solvent includes the presence of water that does not inhibit the reaction without forming two phases.
  • the amount of the solvent is not particularly limited, but the total amount of the solvent is 1 to glycidol.
  • the ratio be up to 100 V o 1 / wt (1 to 100 g / g).
  • the reaction can be carried out at a temperature of usually from 130 to 60 ° C, preferably from 10 to 30 ° C. If the temperature is lower than 30 ° C., the progress of the reaction is slow or the solvent solidifies, which is not preferable. If the temperature is higher than 60 ° C., decomposition and side reactions increase, which is not preferable. The reaction is usually completed in 2 to 24 hours.
  • the method of addition and the order of addition during the reaction are not particularly limited.
  • (1) After adding a sulfonyl halide derivative or a mixture of the solvent to a mixture of glycidol and a solvent, the base or the solvent is added.
  • (2) a method of adding a mixture of glycidol and a solvent to a sulfonyl halide derivative or a mixture of the solvent, and then adding a base or a mixture of the solvent and the solvent;
  • (4) A method of simultaneously adding a sulfonyl halide derivative or a mixture of the solvent and a base or a mixture of the solvent to a mixture of the glycidol and the solvent.
  • the post-treatment method of the reaction solution is not particularly limited, and examples thereof include the following methods.
  • (1) In the case of an organic solvent system in which no solid is precipitated from the reaction solution, no special post-treatment is required, and in the case of a two-phase system of organic solvent / water in which no solid is precipitated from the reaction solution By removing the aqueous phase, a solvent mixture of the target substance can be obtained.
  • (2) When only the target solid is precipitated from the reaction solution, the target solid can be obtained by filtration.
  • a solvent mixture of the target substance can be obtained by filtering to remove the solid.
  • non-target solids inorganic salts, etc.
  • a solvent mixture can also be obtained.
  • a solid of the target substance and a solid that is not the target substance are precipitated from the reaction solution, add a solvent that dissolves the target substance, or add a solid that is not the target substance (such as an inorganic salt).
  • a solvent such as water, etc., and either one is preferentially dissolved, and then the operation of (2) or (3) is performed, or the operation of (1) is performed after dissolving both. By doing so, you can obtain the desired object.
  • the operations (1) to (4) may be performed in combination.
  • an organic solvent and z or water are added, and the reaction solution is concentrated. Or may be heated or cooled.
  • the temperature is preferably adjusted to 10 to 60 ° C. from the viewpoint of improving liquid-liquid separability. If the temperature is lower than 10 ° C, the liquid-liquid separation property is not sufficient, so that it is not preferable.
  • Additives may be added as long as they do not affect the quality of the target product.
  • the organic solvent z water When water is added to the target solvent mixture, the organic solvent z water When forming a two-phase system, wash with water and / or an acidic aqueous solution such as citric acid, hydrochloric acid, or sulfuric acid, and / or an alkaline aqueous solution such as baking soda, sodium hydroxide, or potassium hydroxide. May be. If two phases of organic solvent / water are not formed, washing may be performed after replacing with an organic solvent that forms two phases with water. At the time of washing, the temperature is preferably adjusted to 10 to 60 ° C from the viewpoint of improving the liquid-liquid separation property.
  • the temperature is lower than 10 ° C, the liquid-liquid separation property is not sufficient, so that it is not preferable. Thereafter, high-purity glycidyl sulfonate derivatives can be easily isolated by ordinary operations such as concentration and crystallization.
  • a method for producing glycidyl nitrobenzenesulfonate by reacting glycidol with nitrobenzenesulfonyl halide in the presence of a base, wherein only an inorganic base is used as the base
  • a process for producing glycidyl nitrobenzenesulfonate is provided.
  • Glycidol used in the present invention can be either racemic or optically active. It is preferable to use an optically active substance since the target glycidyl ditrobenzenesulfonate can be directly obtained as an optically active substance.
  • any of a racemic form and an optically active form can be used. It is preferable to use an optically active substance because the target glycidyl nitrobenzenesulfonate can be directly obtained as an optically active substance.
  • the base used is not particularly limited, and may be an organic base alone, an inorganic base alone, or an organic base or an inorganic base.
  • the organic base include primary amine, secondary amine, and tertiary amine.
  • monoalkylamines such as t-butylamine, dialkylamines such as di-t-butylamine, aromatic secondary amines such as imidazole, and trimethylamine , Triethylamine, tripropylamine, diisopropylethylamine, dihexylmethylamine, N, N, N ', N'-tetramethylethylenediamine, N, N-dimethylalanine ester, etc.
  • examples thereof include pyridine derivatives having a total number of carbon atoms of 5 to 18 such as methylamino pyridine and 4-getylaminopyridine, and aromatic amines having a total number of carbon atoms of 4 to 18 such as pyrazine, pyrimidine, pyridazine and quinoline. These can be used alone or in combination.
  • triethylamine, diisopropylethylamine, and pyridine derivatives are preferable from the viewpoint of low cost and ease of handling.
  • Examples of the inorganic base used include an alkali metal, an alkali metal hydride, an oxide, a hydroxide, a carbonate, a hydrogen carbonate or a borate of an alkali metal or an alkaline earth metal.
  • an alkali metal an alkali metal hydride, an oxide, a hydroxide, a carbonate, a hydrogen carbonate or a borate of an alkali metal or an alkaline earth metal.
  • hydroxides, carbonates or bicarbonates of alkali metals or alkaline earth metals are preferred from the viewpoint of inexpensiveness and ease of handling, and sodium hydroxide, potassium hydroxide, sodium carbonate, Potassium carbonate is more preferred.
  • inorganic bases that do not adversely affect the subsequent reaction of glycidol with utrobenzenesulfonyl halide are preferred over organic bases. Guri If the organic base remains after the synthesis of cidol, the reaction between glycidol and nitrobenzenesulfonyl halide can be carried out without problems by eliminating the organic base by an operation such as neutralization with an acid.
  • the total amount of these bases used is 0.5 to 10 equivalents based on 3-chloro-1,2-propanediol. It is preferably 1 to 4 equivalents. If the amount is less than 0.5 equivalent, the reaction is not completed and the yield is lowered.
  • the diameter of the particles is preferably 5 mm or less, and 3 mm in diameter, from the viewpoint of increasing the surface area and increasing the reaction rate. The following is more preferred, and the diameter is particularly preferably 1 mm or less.
  • the solvent used examples include water, an organic solvent, and an organic solvent Z water mixed solvent.
  • an organic solvent / water mixed solvent both a one-phase system and a two-phase system are suitably carried out.
  • the organic solvent used is not particularly limited as long as it is an organic solvent that does not inhibit the reaction, and examples thereof include pentane, hexane, heptane, and cyclohexane.
  • Aliphatic hydrocarbon solvents such as xane and petroleum ether; ester solvents such as ethyl acetate, methyl acetate, propyl acetate, and methyl propionate; alcohol solvents such as methanol, ethanol, and isopropanol; toluene, benzene, xylene, etc.
  • Aromatic hydrocarbon solvents such as t-butyl methyl ether, getyl ether, diisopropyl ether, THF, and dioxane; ketone solvents such as acetone, methyl ethyl ketone, diisopropyl ketone, and methyl isobutyl ketone , Methylene chloride, black mouth form, 1, Examples include halogenated hydrocarbon solvents such as 2-dichloroethane, 1,1-dichloroethane, carbon tetrachloride, and chlorobenzene; nitrile solvents such as acetonitrile and propionitrile; and highly polar aprotic solvents such as DMF and DMSO.
  • ether solvents such as t-butyl methyl ether, getyl ether, diisopropyl ether, THF, and dioxane
  • ketone solvents such as acetone, methyl ethyl ketone, di
  • the mixing ratio is not particularly limited. Among these, THF, acetone, methyl ethyl ketone, methyl isobutyl ketone, acetonitrile, methylene chloride, or, from the viewpoint of low cost, easy handling, and solubility of 3-chloro-1,2-propanediol Organic solvents in which two or more of them are mixed are preferred.
  • the mixing ratio of the organic solvent is not particularly limited, but is preferably 10/1 to 1 ⁇ 10 (volume ratio), and more preferably 5Zl to 1/5 (volume ratio).
  • the amount of the solvent to be used is preferably 1 to: L O O v o 1 / wt relative to 3-chloro-1,2-propanediol (1 to 100 m 1 per 1 g).
  • the reaction can be carried out at a temperature of usually from 130 to 120 ° C, preferably from 0 to 100 ° C. If the temperature is lower than 30 ° C, the reaction progresses slowly or the solvent solidifies, which is not preferable. If the temperature exceeds 120 ° C, side reactions such as decomposition of glycidol increase, which is not preferable. The reaction is usually completed in 30 minutes to 24 hours.
  • the method of addition and the order of addition during the reaction are not particularly limited.
  • -Chloro-1,2-propanediol or a method of adding a mixture thereof with a solvent can be used.
  • the glycidol obtained as an intermediate can be subsequently reacted with trobenzenesulfonyl halide in the presence of an inorganic base to produce glycidyl ditrobenzenesulfonate.
  • Glycidol may be isolated by evaporation of the solvent, distillation, or the like, or may be used in the next step as it is as a mixed solvent containing glycidol. Non-isolation is preferred because of high reaction efficiency and high yield and quality.
  • the nitrobenzenesulfonyl halide to be used only needs to have at least one nitro group on the benzene ring.
  • 2-nitrobenzenesulfonyl- Norechloride, 3—Nitrobenzenesnolehoninolechloride, 4 12-Trobenzene snorehoninolek mouth light, 4—1-chloro-3—2-tooth benzene snorehoninolek mouth light, 2-Methyl-5,12-nitrobenzenesulfo Examples include Juruku's mouth, 2-Methoxy-5-2 Trovenzens / Lefoninolechloride, and 2,4-dinitrobenzenesnolehoninolechloride.
  • Nitrobenzenesulfonyl chloride is preferred. Nitrobenzenesulfonyl halide is used in an amount of 0.7 to 2 equivalents, preferably 0.8 to 1.0, based on glycidol.
  • Examples of the inorganic base used include alkali metal, alkali metal hydride, alkali metal or alkaline earth metal oxides, hydroxides, carbonates, hydrogen carbonates and borates.
  • alkali metal alkali metal hydride, alkali metal or alkaline earth metal oxides
  • hydroxides carbonates, hydrogen carbonates and borates.
  • sodium, sodium hydride, magnesium oxide, calcium oxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, hydrogen carbonate Lithium, sodium hydrogencarbonate, potassium hydrogencarbonate, calcium hydrogencarbonate and the like can be mentioned. These can be used alone or in combination.
  • the amount of the inorganic base to be used is 0.5 to 10 equivalents, preferably 1 to 4 equivalents, relative to glycidol. If the amount is less than 0.5 equivalent, the reaction is not completed and the yield decreases, and if it exceeds 10 equivalents, side reactions such as decomposition of glycidol increase, which is not preferable.
  • There is no particular limitation on the method of adding these inorganic bases and they may be added in the entire amount at the start of the reaction or may be added in portions during the reaction.
  • an inorganic base necessary for producing a derivative of glycidyl nitrobenzenesulfonate from glycidol may be added in advance when synthesizing glycidol. These are the synthesis of glycidol The total amount may be added at the beginning of the reaction, or may be added in portions during the reaction. When adding the entire amount of the inorganic base required for the synthesis of daricidyl nitrobenzenesulfonate when synthesizing glycidol, the inorganic base should be 10 equivalents or less based on 3-chloro-1,2-propanediol so as not to inhibit glycidol synthesis. So that
  • the diameter of the particles is preferably 5 mm or less, and 3 mm in diameter, from the viewpoint of increasing the surface area and increasing the reaction rate. The following is more preferred, and the diameter is particularly preferably 1 mm or less.
  • the solvent is not particularly limited as long as it does not inhibit the reaction, and the organic solvent mentioned in the section of glycidol synthesis or the organic solvent / water mixed solvent can be used alone or as a mixture of two or more.
  • the reaction is preferably carried out in a two-phase solvent of the organic solvent Z water or an organic solvent.
  • the concept of an organic solvent includes the presence of water to such an extent that the reaction does not hinder the reaction without forming two phases.
  • the amount of the solvent is not particularly limited, but the total amount of the solvent should be 1 to: L 0 V o 1 / wt times for glycidol (1 to 100 ml for 1 g). Is preferred.
  • the reaction can be carried out at a temperature of usually from 130 to 60 ° C, preferably from 110 to 30 ° C. If the temperature is lower than 30 ° C., the progress of the reaction is slow or the solvent solidifies, which is not preferable. If the temperature is higher than 60 ° C., side reactions such as decomposition of glycidol are not preferable. The reaction is usually completed in 30 minutes to 24 hours.
  • the method of addition and the order of addition during the reaction are not particularly limited.
  • the post-treatment method of the reaction solution is not particularly limited, and examples thereof include the following methods.
  • (1) In the case of an organic solvent system in which no solid is precipitated from the reaction solution, no special post-treatment is required, and in the case of a two-phase system of an organic solvent in which no solid is precipitated from the reaction solution and water By removing the aqueous phase, a solvent mixture of the target substance can be obtained.
  • (2) When only the target solid is precipitated from the reaction solution, the target solid can be obtained by filtration.
  • a solvent mixture of the target substance can be obtained by filtering to remove the solid.
  • non-target solids inorganic salts, etc.
  • a solvent mixture can also be obtained.
  • a solid of the target substance and a solid that is not the target substance are precipitated from the reaction solution, add a solvent that dissolves the target substance, or add a solid that is not the target substance (such as an inorganic salt).
  • a solvent such as water, etc., and either one is preferentially dissolved, and then the operation of (2) or (3) is performed, or the operation of (1) is performed after dissolving both. By doing so, you can obtain the desired object.
  • the operations (1) to (4) may be performed in combination.
  • an organic solvent and water or water are added, or the reaction solution is concentrated. Or may be heated or cooled.
  • the temperature is preferably adjusted to 10 to 60 ° C. from the viewpoint of improving liquid-liquid separability. If the temperature is lower than 10 ° C, the liquid-liquid separation property is not sufficient, so that it is not preferable.
  • Additives may be added as long as they do not affect the quality of the target product.
  • the following operation may be further performed on the obtained solvent mixture of the target substance, if necessary.
  • the organic solvent / water If a two-phase system is formed, wash with water and / or an acidic aqueous solution such as citric acid, hydrochloric acid, or sulfuric acid, and an alkaline aqueous solution such as Z or baking soda, sodium hydroxide, or potassium hydroxide. Is also good.
  • an acidic aqueous solution such as citric acid, hydrochloric acid, or sulfuric acid
  • an alkaline aqueous solution such as Z or baking soda, sodium hydroxide, or potassium hydroxide.
  • the temperature is preferably adjusted to 10 to 60 ° C from the viewpoint of improving the liquid-liquid separation property.
  • the temperature is lower than 10 ° C, the liquid-liquid separation property is not sufficient, which is not preferable. If the temperature is higher than 60 ° C, decomposition and side reactions increase, which is not preferable. Thereafter, high-purity glycidyl ditrobenzenesulfonate can be easily isolated by ordinary operations such as concentration and crystallization.
  • optical purity was analyzed by high performance liquid chromatography under the following conditions.
  • HPLC purity was defined as the following formula, and analyzed by high performance liquid chromatography under the following conditions.
  • HPLC purity (%) Glycidyl nitrobenzenesulfonate area (total area-solvent area-nitrobenzenesulfonyl chloride area)
  • XI 00 Analytical column: YMC Pack ODS-AA-303 (manufactured by YMC)
  • Wavelength 210 nm.
  • the mixture was stirred at 0 to 7 ° C for 7 hours to synthesize the desired product.
  • crystals of the target substance had precipitated, and were heated to 35 ° C. to dissolve.
  • the solution separated into two phases with good liquid-liquid separation properties, and the toluene solution of the target product was obtained by removing the lower layer (aqueous phase). Thereafter, this toluene solution was washed with about 10% aqueous citric acid (4 Oml) at about 35 ° C., and further washed with 5% aqueous sodium bicarbonate (25 ml). During the washing, the liquid-liquid separation property was good.
  • the yield of glycidyl (S) -p-toluenesulfonate was 15.7 g (pure), the yield was 76%, and the optical purity was 98%.
  • pandiol 98% ee optical purity
  • Glycidol was synthesized by reacting at about 10 ° C for 1 hour. During the reaction, the slurry was in a good slurry state with sufficient agitation, and no increase in solution viscosity that would cause a problem in practice was observed. Then, with stirring, at about o ° C, in a slurry state in which a solid that was not the target substance was precipitated, 10.1 g (99.5 benzyl) of triethylamine, and 172 mg of 4-dimethylaminoviridine ( 1.4 Image 1) was added.
  • Example 6 Synthesis of optically active glycidyl 3-nitrobenzenesulfonate Sodium hydroxide (shape: plate-like, diameter of about 3 to 5 mm) under nitrogen atmosphere at about 20 ° C while stirring 3.04 g (76.0 thighs) ol) was added to and dispersed in 70 ml of methyl isobutyl ketone (MI BK, water content 761 pm), and (R) -3-chloro-1,2-propanediol (optical purity 98% ee), 7.00 g ( 63.3 mmol). Glycidol was synthesized by reacting at 20 to 25 ° C for 1.5 hours.
  • MI BK methyl isobutyl ketone
  • sodium hydroxide (shape: granular, about lmm in diameter) 2.66 g (66 .5 mmol) was added to and dispersed in 7 Om1 of methyl ethyl ketone (MEK, water content 78 ppm), and (R) -3-chloro-1,2-propanediol (optical purity 98% ee), 7.00 g (63.3 mmol) was added.
  • Glycidol was synthesized by reacting at about 10 ° C for 1 hour. During the reaction, the slurry was in a good slurry state with sufficient agitation, and no increase in solution viscosity that would pose a practical problem was observed. After that, at a temperature of about o ° c with stirring, with the slurry in which the non-target substance precipitated
  • Example 8 Synthesis of Optically Active Dalicidyl 3-Nitrobenzenesulfonate Under a nitrogen atmosphere, (R) -3-chloro-1,2-propanediol (optical purity 98% ee), 7.00 g (63. ol), 10.5 g (76.0 mmol) of potassium carbonate and 70 ml of acetone were added, and the mixture was heated under reflux for 3 hours to synthesize glycidol. In a slurry state in which a solid that was not the target substance was precipitated, 14.0 g (63.3 t ol) of 3-nitrobenzenesulfyurokulide was added at 18 ° C. with stirring.
  • the solution Upon standing, the solution was separated into two phases with good liquid-liquid separation properties, and the toluene solution of the target product was obtained by removing the lower layer (aqueous phase). Thereafter, this toluene solution was washed with 40 ml of 10% aqueous citric acid at about 30 ° C., and further washed with 30 ml of 5% aqueous sodium bicarbonate. During the washing, the liquid-liquid separation property was good. Thereafter, the mixture was concentrated under reduced pressure to 19 g using an evaporator. At this stage, a part of the concentrate was withdrawn and subjected to quantitative analysis. As a result, the yield of glycidyl (S) -3-dinitrobenzenesulfonate was 7 T / JP2004 / 005224
  • This glycidol aqueous solution is stirred for about 5 minutes.
  • a solution of 39.5 g (178.4 mmo 1) of 3-2-nitrobenzenesulfouric-mouth chloride in 174 g of toluene was added.
  • 39.2 g (196.2 mmo 1) of a 20% aqueous sodium hydroxide solution was added.
  • the mixture was stirred at 15 ° C for 16 hours to synthesize the desired product.
  • crystals of the target substance had precipitated, so the mixture was heated to 35 ° C and dissolved.
  • the solution Upon standing, the solution was separated into two layers with good liquid separation properties, and the lower layer (aqueous layer) was removed to obtain the target toluene solution. Thereafter, the toluene solution was washed at about 35 ° C. with 72 g of water. During the washing, the liquid-liquid separation property was good. Thereafter, the mixture was concentrated under reduced pressure to 85.6 g (about 40 wt%) using an evaporator. At this stage, a part of the concentrate was sampled and quantitative analysis was performed. As a result, the yield of glycidyl (S) -3-nitrobenzenesulfonate was 74%, and the optical purity was 97.5% ee.
  • Example 11 14.0 g (63.3 mmol) of 3-nitrobenzenesulfonyl chloride was added to one of the aqueous glycidol solutions obtained by dividing into three at a temperature of about 0 ° C with stirring in toluene. A solution dissolved in 63 ml was added. Subsequently, 6.4 g (63.3 mmol) of triethylamine were added. The mixture was stirred at 0 to 5 ° C for 9 hours to synthesize the desired product. Thereafter, the mixture is heated to 30 ° C with stirring, and then left standing.
  • the lower layer (aqueous phase) is removed, and washed at about 30 ° C with 40 ml of 10% aqueous citric acid and 30 ml of 5% aqueous sodium bicarbonate. Thereafter, the solvent was distilled off under reduced pressure. As a result of analyzing this concentrate, the HPLC purity of glycidyl 3-nitrobenzenesulfonate was 51.0%. 05224
  • Example 1 14.0 g (63.3 mmol) of 3-nitrobenzenesulfoyl cucumide was dissolved in 63 ml of toluene under stirring at about 0 ° C. in one of the glycidol aqueous solutions obtained by dividing into three parts. The allowed solution was added. Subsequently, dimethylaminopyridine, 0.12 g (0.95 thigh.1), 30% aqueous sodium hydroxide, and 9.3 g (69.7) were added. The mixture was stirred at 0 to 5 ° C for 9 hours to synthesize the desired product. After that, the mixture was heated to 30 ° C under agitation, allowed to stand, and the lower layer (aqueous phase) was removed.
  • the present invention relates to (1) reacting 3-chloro-1,2-propanediol and a sulfonyl halide derivative in the presence of a base, or (2) reacting an alkali metal or alkaline earth in an organic solvent.
  • a method for producing glycidyl sulfonate derivatives which comprises producing glycidol from 3-chloro-1,2-propanediol in the presence of glycidol and then reacting it with nitrobenzenesulfonyl halide using only an inorganic base as a base. Since the number of processes is small and the operation is simple, the amount of waste is small, and the quality is high, it can be industrially suitably carried out.

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Abstract

Dérivé de sulfonate de glycidyle de haute qualité utile en tant qu'intermédiaire pour des médicaments, qui peut être produit selon un procédé simple comportant un petit nombre d'étapes, sans produire de grandes quantités de déchets. Ledit procédé consiste (1) à mettre en réaction du 3-chloro-1,2-propanediol avec un dérivé d'halogénure de sulfonyle en présence d'une base pour produire un dérivé de sulfonate de glycidyle ou (2) à produire du glycidol à partir de 3-chloro-1,2-propanediol dans un solvant organique en présence d'un hydroxyde de métal alcalin et / ou de métal alcalino-terreux, puis à faire réagir le glycidol avec un dérivé d'halogénure de sulfonyle en présence d'une base pour produire un dérivé de sulfonate de glycidyle, ou (3) à produire du glycidol à partir de 3-chloro-1,2-propanediol en présence d'une base, puis à faire réagir le glycidol avec un halogénure de nitrobenzènesulfonyle, une base inorganique étant utilisée comme seule base pour produire un dérivé de sulfonate de glycidyle.
PCT/JP2004/005224 2003-04-21 2004-04-12 Procede de production de derive de sulfonate de glycidyle WO2004094397A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57163372A (en) * 1981-03-30 1982-10-07 Otsuka Pharmaceut Co Ltd 2,3-epoxy-2,6-dimethyl-5-heptene derivative
JPH06184129A (ja) * 1992-12-17 1994-07-05 Mitsui Toatsu Chem Inc グリシジルアリールスルホナート類の製造方法
JP2000086645A (ja) * 1998-09-17 2000-03-28 Sumitomo Chem Co Ltd エポキシ誘導体およびその製造法
JP3250350B2 (ja) * 1993-12-09 2002-01-28 ダイソー株式会社 光学活性グリシジルトシレートの製法
JP3253634B2 (ja) * 1996-01-19 2002-02-04 ダイソー株式会社 グリシジルスルホナート誘導体の製造法

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JPS57163372A (en) * 1981-03-30 1982-10-07 Otsuka Pharmaceut Co Ltd 2,3-epoxy-2,6-dimethyl-5-heptene derivative
JPH06184129A (ja) * 1992-12-17 1994-07-05 Mitsui Toatsu Chem Inc グリシジルアリールスルホナート類の製造方法
JP3250350B2 (ja) * 1993-12-09 2002-01-28 ダイソー株式会社 光学活性グリシジルトシレートの製法
JP3253634B2 (ja) * 1996-01-19 2002-02-04 ダイソー株式会社 グリシジルスルホナート誘導体の製造法
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