• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The invention relates to heterocyclic compounds, in particular to the preparation of the potassium salt of 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide, which is used in the food industry. The goal is to increase the purity of the target product. The preparation is carried out by cyclization of a solution of the ammonium salt acetoacetamide-N-sulfonic acid in an organic water-immiscible solvent (methylene chloride) sulfuric anhydride (excess). The resulting adduct is hydrolyzed, the organic phase is separated and the 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide dissolved in it is converted into its potassium salt by treating the organic phase with water, or the residue of evaporation of the organic phase with a solution of potassium hydroxide. After its separation, the organic phase is purified by extraction with water (0.05-0.2 of the volume of the organic phase). The method allows to obtain the target product with a purity of 99.9% (against 90% by a known method). 5 hp f-ly, 1 tab.
    公开号:SU1582988A3
    申请号:SU864028038
    申请日:1986-09-01
    公开日:1990-07-30
    发明作者:Ройшлинг Дитер；Линкис Адольф；Райманн Вальтер；Эрнст Швайкерт Отто；Эрнст Мак Карл；Эбертц Вольфганг
    申请人:Хехст Аг (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to methods for producing the potassium salt of 6-methyl-3, 4-β-dihydro-1,2,3-oxathiazin-4-one-2.2-β-dioxide (Acesulfame K), which has a sweet taste and is used in food industry .;
    The aim of the invention is to increase the purity of the target product.
    This goal is achieved by the fact that in the method of producing the potassium salt of 6-methyl-3, 4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide by cyclizing the solution of the ammonium salt acetoacetamide-M- sulfonic acids in a water-immiscible organic solvent, such as methylene chloride, under the action of an excess of sulfuric anhydride dissolved in the indicated solvent, by hydrolysis of the resulting 6-methyl-3 adduct, 4-dihydro-1,2,3-oxathiazine-4-one-2 , 2-dioxide with sulfuric anhydride, separation of the organic phase and before transferring 6-methyl-3, 4-di dissolved in it hydro-1,2,3-oxathiazin-4-one-2,2-dioxide in its potassium salt, the organic phase immediately after its separation is purified by extraction with water, taken in
    0.05-0.2 volume of the organic phase.
    The water used after purification of the organic phase can then be sent to the stage of hydrolysis of the 6-methyl-3,4-dihydro-1,2,3-oxathiazine-4-OH-2.2-dioxide adduct with sulfuric anhydride.
    The conversion of 6-methyl-3,4 dihydro-1,2,3 oxathiazin-4-one-2, 2-dioxide to its potassium salt can be accomplished by treating the purified organic phase with an aqueous solution of potassium hydroxide with stirring or by evaporation with purified the organic phase with simultaneous addition of water, followed by treatment of the residue by evaporation of the organic phase in the form of its solution in water with an aqueous solution of potassium hydroxide, or by evaporation of the purified organic phase with simultaneous addition of an aqueous solution of potassium hydroxide, and evaporating ue purified organic phase with simultaneous addition of water or an aqueous potassium hydroxide solution can be carried out in a thin-film evaporator,
    For extreme requirements, the purity can be recrystallized with acepsulfam K from water, and in the specific case in the presence of activated carbons.
    In examples 6-methyl-3,4-dihydro-1, 2, 5,3-oxathiazin-4-one-2, 2-dioxide. The abbreviated name is ASH, and its potassium salt is called ASK.
    Obtaining the original acetoacetamide-No. sulfonate "
    97.1 g (1.0 mol) of amidosulfonic acid are suspended in 1.0 l of methylene chloride. With stirring, 106 g (1.05 mol) of triethylamine are added, the amidosulfonic acid being added to the solution as a triethylammonium salt. After the addition of 6 g (0.1 mol) of glacial acetic acid, is added dropwise within 1 hour with stirring at an internal temperature of 15 ° C, 93.8 g (1.08 mol) of 97% diketene. According to HPLC (high pressure liquid chromatography) analysis, the yield of acetoacetamide K-sulfonate is 90%. The solution thus obtained is used directly for the subsequent reaction.
    Example and hydrolysis.
    1 „loop closure
    g 5 0 5
    five
    0
    five
    0
    five
    0
    400 ml of a 15% aqueous solution of S03 in CH2Cl2 at an internal temperature of -30 ° C (cooled with isopropanol / dry ice from -40 to -60 ° C) are pre-placed in a round flask with a nitrogen pad, added dropwise with stirring within 25 min 1850 ml of a solution of S03 in CH2Cl2 (15%) and at the same time a solution of acetocetamide-K-sulfonate in CH2 C12.
    For hydrolysis with strong external cooling, starting at -30 ° C, 500 ml of water is added dropwise within about 30 minutes. The temperature quickly rises from -30 to 0 ° C, and then it is kept at a level of up to + 5 ° C
    Preparation of ASH solution in methylene chloride.
    At 5 ° C, the organic phase is separated and the aqueous sulfuric acid phase is extracted twice more, each time with 1.0 liter of CH2Cl2. A solution of 132 g of ASH in 5.0 l of methylene chloride (1.9% solution) is obtained.
    Yield 81% (with respect to amido sulfonic acid).
    Getting ASK. 2.5 liters of ASH in methylene chloride solution is stirred for 2 hours with 250 ml of water. Then the organic phase is evaporated in vacuo. The residue is dissolved in the same weight amount of methanol and then brought to pH = 8-10 with 20% KOH in methanol (precipitation of KOH in methanol). After filtering and drying, 69.5 g of ASK are recovered (yield 85% with respect to 66 g of used ASH),
    Analysis%: ASK 99.6; K2S040.4.
    Comparison 2.5 g of the obtained 1.9% ASH solution in methylene chloride is evaporated without further purification operations in a vacuum. The residue is dissolved in the same weight amount of methanol and then brought to pH 8-10 with 20% COC in methanol. After filtering and drying, 96.5 g of crude ASK are isolated (yield 98% relative to 66 g of used ASH), consisting of 83% of ASK with a K2S04 content of 8.8% (relative to ASK),
    Example 2. The return of the aqueous phase formed during the extraction of the organic phase of ASH with water to the hydrolysis step. For the cycle closing reaction, 1/10 of the amount of products used is used respectively.
    as described in Example 1. The resulting ASH solution in methylene chloride (500 ml) is then mixed with 50 ml of water for 2 hours. The resulting aqueous phase is then used for hydrolysis in the following experiment. After 10 experiments with 9 returns of the aqueous phase using the precipitation of KOH in methanol as in Example 1, the ASK samples listed in the table are isolated,
    Determination of ASK content in the product is carried out titrimetrically using perchloric acid in glacial acetic acid with a relative error of about 0.5%. Determination of KjSO is carried out through the sulfate content by precipitation with an aqueous solution of BaC12 and reverse
    titration of excess BaC12 with a standardized complexing agent solution with a relative error of approximately ± 1%.
    The yield and purity of Acesulfame K,



    Example 3. Extractive neutralization of the ASH phase in methylene chloride with 7% potassium liquor, 5.0 liters of the 1.9% ASH solution in methylene chloride prepared in Example 1 was stirred for 2 hours with 500 ml of water. The organic phase (containing 112 g of ASH) is separated and stirred with 600 g of 7% potassium liquor for 1.5 hours. Thereafter, the aqueous phase is separated. From this solution, 490 g of water is distilled off under vacuum (60 mbar). After cooling the residue to 0 ° C, filtering and drying, 115.7 g ASK are exhausted.
    Output 84% (relative to 112 g ASH).
    Analysis,% ASK 99, K2SO “0.05.
    0
    five
    0
    After further evaporation of the crystallization mother liquor, another 13.0 g of ASK is recovered.
    Yield 9% (relative to 112 g ASH).
    Analysis%: ASK 99.8; K2S04 0.3.
    Example 4. Extractive. neutralizing the ASH phase in methylene chloride with 30% potassium liquor in a stirred flask.
    A 5.0 l solution of ASH in methylene chloride prepared according to Example 1 is stirred for 2 hours with 500 ml of water. The organic phase (112 g ASH) is separated and stirred for h with 144.0 g 30% KOH. Following this, the reaction mixture is filtered. After drying, 112.8 g of ASH are obtained.
    Yield 31.5% (relative to 112 g ASH).
    Analysis%: ASK 99.8; K2S04 0.1.
    Example 5. Extractive neutralization of the ASH phase in methylene chloride - 5 with 30% potassium liquor in a thin film reactor. The apparatus consists of a conventional laboratory thin-layer evaporator with an effective length of 22 cm and an effective surface of 160 cm2, which is used as a thin-film reactor. Within 1 h, 2.5 liters of a solution of ASH in methylene chloride treated analogously to example 4 and simultaneously 65.4 g of 30% KOH (the rotor speed is about 800 rpm) are pumped into this reactor within 1 hour. The resulting ASK is continuously filtered from the reaction mixture withdrawn from the reactor by means of a suction nut. After drying, 56.1 g ASK are obtained.
    Yield 81% (relative to 56 g ASH. 5 Analysis,%: ASK 99.7; K2S04 0.3.
    From the dead volume of the reactor and the volume flows of the products used, is obtained by calculating an average treatment time of 2.5 seconds. 0 Example 6. Distillation of CH2Cl2 in a thin layer evaporator. With the addition of water. The apparatus consists of a conventional laboratory thin-layer evaporator with an effective length of 22 cm and an effective surface of 160 cm2. When the temperature of the heating jacket is 115 ° C, the evaporator is injected with a stream of 5.0 l / h treated as in Example 3.
    five
    0
    through 500 in SN.S1. (112g
    715
    ml of water solution ASH
    ASH) and at the same time water 180 g / h. Approximately 60% ASH solution in water in the water after being cooled to room temperature is neutralized with 78.5 g of 50% potassium liquor with stirring. After cooling to 0 ° C, 110.7 g of ASK are separated.
    Output, .80% (relative to 112 g ASH).
    Analysis%: ASK 99.9; K2S04 0.2.
    After further evaporation of the crystallization mother liquor, 12 „Og ASK is extracted again.
    Yield 9% (relative to 112 g ASH).
    Analysis%: ASK 99.7; K2S04 0.3.
    Example 7. Distillation of a CH2C thin-layer evaporator apparatus with the addition of potassium liquor. In the same apparatus as in Example 6, at a temperature of 115 ° C of the heating medium, 5.0 l / h of the same ASH solution in CH2Cl2 as in Example 6 was introduced and 250 g 16% potassium liquor. A homogeneous ASK water solution flows out of the evaporator.
    at
    1. The method of obtaining the potassium salt of 6-methyl-3, 4-dihydro-1,2,3-oxathiazine-4-one-2,2-dioxide by cyclization of a solution of the ammonium salt of acetoacetamide-M-sulfonic acid in water-immiscible an organic solvent, such as methylene chloride, under the action of an excess of sulfuric anhydride dissolved in the indicated solvent, by hydrolysis of the resulting adduct 6 (temperature 105 ° C). After cooling 30-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2, 2-dioxide with sulfuric anhydride, separating the organic phase and transferring 6-methyl-3, 4-dihydro dissolved in it -1,2, 3-oxathiazin-4- 35-one-2,2-dioxide in its potassium salt by treating the organic phase or a mixture of the organic phase with water or the residue of evaporation of the organic phase with a solution of potassium hydroxide, about 1 t of this solution to O C Crystallized ASK is filtered off and dried in vacuo.
    The yield is 127.2 g (92% relative to 112 g ASH).
    Analysis%: ASK 99.9; 0.1.
    Example 8. Proceed analogously to example 1, however, upon receipt of ASK, 2.5 l of ASH solution in methylene chloride is mixed with 500 w of water. The organic phase is then separated and evaporated under reduced pressure. The resulting crude ASK is dissolved in the same weight amount of methanol and with
    In order to increase the purity of the target product, the organic phase after its separation is purified by extraction with water, taken in an amount of 0.05-0.2 of the volume, using a 20% methanol solution of potassium hydroxide, is brought to pH 8-10. The ASK potassium salt precipitates. After filtration and drying, 66.8 g of product was recovered (83% yield).

    It has an ASK content of 99.8%, with a K2S04 content of 0.2%.
    Example 9. Proceed as in example 8, however, a solution of ASH methylene chloride is stirred instead of 500 ml with 125 ml of water. After filtering and drying the precipitated product with a KOH solution in methanol, 70.8 g of product was isolated (yield 88%), which had an ASK content of 99.4% and
    eight
    five

    0
    five
    the content of K2SCK is 0.6%. The target product Acesulfame potassium, obtained in all examples 1-9, has the following spectral characteristics:
     H-PMP (D20), rf (ppm): 2.10-2.11 (doublet, 3N, CH3 group); 5.64-5.68 (quadruplet, 1H, CH-group).
    IR spectrum in Kg, max. (media): 1650, 1580, 1170.
    Thus, the proposed method allows to obtain Aphesulfam K with a purity of 99.9%, which greatly exceeds the capabilities of the known method, in which the purity of the product does not reach 90% before recrystallization;
    权利要求:
    Claims (5)
    [1]
    1. The method of obtaining the potassium salt of 6-methyl-3, 4-dihydro-1,2,3-oxathiazine-4-one-2,2-dioxide by cyclization of a solution of the ammonium salt of acetoacetamide-M-sulfonic acid in water-immiscible an organic solvent, such as methylene chloride, under the action of an excess of sulfuric anhydride dissolved in the indicated solvent, by hydrolysis of the resulting 60-methyl-3,4-dihydro-1,2,3-oxathiazynnine adduct,
    due to the fact that, in order to increase the purity of the target product, the organic phase after its separation is purified by extraction with water, taken in an amount of 0.05-0.2 of the volume of the organic phase,
    [2]
    2. A method according to claim 1, characterized in that the water used after purification of the organic phase is directed to the stage of hydrolysis of the 6-methyl-3 adduct, 4-dihydro-1,2,3-oxathiazin-4-och-2.2 adduct dioxide with sulfuric anhydride.
    [3]
    3. Method according to paragraphs. 1 and 2, characterized in that the conversion of 6-methyl-3, 4-dihydro-1,2,3-oxathiazine-4-one-2,2-dioxide to its potassium salt is treated by treating the purified organic phase with an aqueous solution of potassium hydroxide with stirring.
    9 158298810
    [4]
    4. Method according to paragraphs. 1 and 2, about tl i-6-methyl-3,4-dihydro-1,2,3-oxathiazine, due to the fact that the conversion of 4-one-2,2-dioxide to its potassium 6-methyl-3 , 4-dihydro-1,2,3-oxathiazine-salt is carried out by evaporation of the purified -4-one-2,2-dioxide in its potassium. Organic phase, while the salt is carried out by evaporation by the purified addition of an aqueous solution. hydrochloric organic phase with simultaneous potassium oxide.
    adding water with the subsequent obra-6. The method according to paragraphs. 4 and 5, and the residue is evaporated organic by the evaporation phase in the form of its solution in the water of the purified organic phase with one.
    an aqueous solution of potassium hydroxide. by the addition of water or water
    [5]
    5. Method according to paragraphs. 1 and 2, about 1 ml of a potassium hydroxide solution is obtained by transferring to a thin layer evaporator.
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    CS632386A2|1988-07-15|
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    NO863504D0|1986-09-02|
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    KR870003080A|1987-04-15|
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE2327804C3|1973-06-01|1980-08-14|Hoechst Ag, 6000 Frankfurt|Process for the preparation of 3,4-dihydro-1,23-oxathiazin-4-ones|
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    DE3410439A1|1984-03-22|1985-09-26|Hoechst Ag, 6230 Frankfurt|METHOD FOR THE PRODUCTION OF 6-METHYL-3,4-DIHYDRO-1,2,3-OXATHIAZINE-4-ON-2,2-DIOXIDE AND ITS NON-TOXIC SALTS AND THE ACETOACETAMONE-N-SULDE-N-SULES SALTS)|
    DE3531359A1|1985-09-03|1987-03-12|Hoechst Ag|METHOD FOR PRODUCING 6-METHYL-3,4-DIHYDRO-1,2,3-OXATHIAZINE-4-ON-2,2-DIOXIDE AND ITS CLEANING THEREOF|DE3429039A1|1984-08-07|1986-02-20|Hoechst Ag, 6230 Frankfurt|METHOD FOR PRODUCING 6-METHYL-3,4-DIHYDRO-1,2,3-OXATHIAZINE-4-ON-2,2-DIOXIDE AND ITS NON-TOXIC SALTS|
    DE3531359A1|1985-09-03|1987-03-12|Hoechst Ag|METHOD FOR PRODUCING 6-METHYL-3,4-DIHYDRO-1,2,3-OXATHIAZINE-4-ON-2,2-DIOXIDE AND ITS CLEANING THEREOF|
    TW223067B|1992-03-17|1994-05-01|Hoechst Ag|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19853531358|DE3531358A1|1985-09-03|1985-09-03|METHOD FOR PRODUCING THE NON-TOXIC SALTS OF 6-METHYL-3,4-DIHYDRO-1,2,3-OXATHIAZINE-4-ON-2,2-DIOXIDS|
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