• 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 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide, the alkali and alkaline earth salts of which are used as sweet substances in Food Industry. The goal is to increase the purity of the target product and simplify the process technology. The preparation is carried out by cyclization of tri (lower alkyl) ammonium acetoacetamide-N-sulfonate under the action of an excess of sulfuric anhydride in methylene chloride with cooling, hydrolysis of the resulting 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2 adduct , 2-dioxide with sulfuric anhydride. The process is followed by the distillation of methylene chloride from the reaction mixture and the target product is crystallized from the remaining aqueous sulfuric acid phase. 1 tab.
    公开号:SU1535380A3
    申请号:SU864028042
    申请日:1986-09-01
    公开日:1990-01-07
    发明作者:Ройшлинг Дитер；Линкис Адольф；Райманн Вальтер；Эрнст Швайкерт Отто；Эрнст Мак Карл
    申请人:Хехст Аг (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to heterocyclic compounds, in particular to the preparation of 6-methyl-3, 4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide, alkali and alkaline earth salts of which are used as sweet substances in the food industry.
    The aim of the invention is to increase -. improving the purity of the target product and simplifying the process technology.
    The goal is achieved by the fact that according to the method for preparing 6-methyl-3, 4-dihydro-1, 2, 3-oxathiazin-4-one-2,2-dioxide by cyclization of tri (lower alkyl) ammonium acetoacetamide-H-sulfonate under the action of sulfuric anhydride in methylene chloride with cooling followed by hydrolysis of the resulting adduct
    6-methyl-1,2,3-oxathiazin-4-one-2,2-α-dioxide with sulfuric anhydride to isolate the target product from the mixture formed after hydrolysis, the methylene chloride is distilled off and from the remaining aqueous sulfuric acid phase crystallizes. left 6-methyl-3, 4-digidro-1, 2,3-oxathiazin-4-one-2,2-dioxide.
    In examples 6-methyl-3, 4-digndro-1, 2, 3-oxathiazin-4-one-2.2-dioxide reduced is called ASH, and its potassium salt is ASK.
    Preparation of the starting acetoacetamide-N-sulfonates.
    In 250 ml of CHjCl j, 48.6 g (0.5 mol) of amidosulfonic acid is neutralized with 52.5 g (0.53 mol) of triethylamine while cooling, so that
    cl
    OE SP
    with
    00

    cm
    temperature + 30 ° С was not exceeded. 3 g of acetic acid are added. 0 ° C is added dropwise over 60 minutes to 46.3 g (0.55 mol) of diketene and stirred for 6 hours at a room temperature.
    Example 1a Loop closure and hydrolysis. 500 ml of CH, C12 are preliminarily placed in a reaction vessel and cooled to -30 ° C. At the same time, a solution of triethylammonium acetacetamide-S-sulfonate and 120 ml (2.8 mol) SOj was added dropwise as described above. The temperature in the reaction vessel does not exceed -30 ° C. Following this, stir for another 30 minutes at -30 ° C. 162 ml of water are then added dropwise at (-15 ° C) - (-10 ° C) and stirred for 1.5 hours at O C.
    The result of the reaction is
    phase mixture of phase СНгС1а, phase H2SO4 and solid ASH.
    16. Separation. From the reaction mixture is distilled off by distillation in vacuum at 500 mbar and a temperature of 24 ° C. At the same time, the maximum temperature in the bottom of the column does not exceed 40 ° C. The ASH slurry in sulfuric acid is cooled to 0 ° C and filtered off on a glass suction filter. Filter cake is suction washed with 50 ml of 30% Hg504 and filtered.
    ASH filter cake was analyzed by potentiometric titration. It contains 92% ASH and 2.5% H, jSO. The balance up to 100% is water. When analyzed by HPLC (high pressure liquid chromatography), no organically by-products are detected.
    The yield of ASH is 49.8 g (0.31 mol) 61% of theory with respect to the initially used amidosulfonic acid. Melting point 123 ° C.
    In order to convert the potassium salt, ASH is dissolved in 61 ml of water at 30 ° C and neutralized at 30 ° C with 50% KOH to pH 7. The suspension of the resulting ASK is cooled to 0 ° C and filtered. After drying in a vacuum oven at 200 Torr and 60 ° C, 52.3 g ASK are obtained, which corresponds to a yield of 52% of theory with respect to amidosulfonic acid, ASK — a white color product. Purity is determined by
    potentiometric titration and HPLC.
    ASK: 99.9%; 0.1%; KS1, 20 parts per million. It was impossible to detect organic by-products using HPLC.
    After recrystallization from a 0.8-fold amount of water, the K2SO4 content in the ASK is less than 100 ppm.
    NMR 1H, DAO G (rrga): 2.10-2.11 (d, 3H, CH5 group), 5.64-5.68 (g, 1H, CH).
    Example 2. From the reaction mixture obtained in Example 1a, the mixture was distilled off under normal pressure and. boiling point for pressure in I bar is 42 ° C. At the end of the distillation, the maximum temperature of the lower part of the column does not exceed 70 ° C. Upon cooling, crystals are separated from the sulfuric acid phase, which are filtered at 0 ° C and washed with 50 ml of 30% sulfuric acid. The filter cake contains 90% ASH and 3.5% HTS04.
    The yield is 54 g (0.33 mol) 66% of theory with respect to amidosulfonic acid.
    The neutralization is carried out analogously to example 16. ASK is obtained with a content of 99.8% ASK and 0.2% Cr 504
    The yield is 54 g (0.27 mol) of 54% of theory with respect to amid sulfonic acid.
    After recrystallization, the ASK content is 100%. No HPLC was detected by-product.
    Examples 3-6. The reaction mixture obtained in example 1a was separated analogously to example 2 and neutralized. After ASH is filtered off from the sulfuric acid phase and the ASH is washed with 30% sulfuric acid, the sulfuric acid phase is extracted twice with 250 ml of methylene chloride. The extract is combined with the reaction mixture of the following experiment. The mother plant formed during ASK recrystallization is used to dissolve ASH during neutralization in a subsequent run.
    The yield and purity of 6-methyl-3,4-dihydro-I, 2,3-oxathiazin-4-one-2,2-dioxide and its potassium salt in examples 3-6 are shown in the table.
    Example 7. Obtained according to example) and the reaction mixture is metered from the original vessel with stirring on a thin evaporator apparatus. The capacity and heat output are set so that the drain temperature is 60 ° C. ASH crystallizes out of the flowing sulfuric acid phase upon cooling. Including the extraction of ASH from the sulfuric acid stock solution and the return of the crystallization mother liquor, an ASH yield of 71% of theory is obtained. ASH filter bag contains 94% ASH and 2%
    The neutralization is carried out according to Example 1, the resulting ASK contains 99.6% ASK and 0.3% KZS04.
    Comparative example.
    From the reaction phase prepared in Example 1a of the present invention, the methylene chloride phase is separated from the sulfuric acid phase and the latter is extracted twice by shaking with 250 ml of CH-jCly. The combined methylene chloride phases are dried using sodium sulfate. After distillation of CH7Cl1, ASH is obtained as a light yellow oily residue.
    After dissolving in 60 ml of water, ASH is neutralized with 50% KOH to obtain ASK and dried under vacuum. Get
    ten
    J5
    53806
    light yellow ASK with 85% ASK and 5% potassium sulphate.
    The yield is 66 g (0.33 mol) 65% of the theory with respect to the amidosulfonic acid.
    Thus, the invention makes it possible to significantly increase the purity of the target product and simplify the technology of its isolation: the product itself crystallizes from the water-sulfuric acid phase.
    five
    0
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of obtaining 6-methyl-3,4-di-hydro-1,2,3-oxathiazin-4-one-2,2-dioxide by cyclization of tri (lower alkyl) ammonium acetoacetamide-N-sulfonate under the action of an excess of sulfuric anhydride in methylene chloride with cooling, hydrolysis of the resulting adduct 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide with sulfuric anhydride and subsequent isolation of the target product, characterized in that , in order to increase the purity of the target product and simplify the process technology, to isolate the target product from the mixture formed after hydrolysis, otgr of methylene chloride and the remaining aqueous sulfuric acid phase is crystallized target 6-methyl-3,4-dihydro-1,2,3 -oksatiaein-4-one-2,2-dioxide.
    类似技术:
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    BR8604202A|1987-04-28|
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    FI81792B|1990-08-31|
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    NO163774C|1990-07-18|
    CS262440B2|1989-03-14|
    ES2000616A6|1988-03-01|
    DK418086A|1987-03-04|
    NO863503L|1987-03-04|
    EP0215347B1|1990-01-24|
    FI863522A0|1986-09-01|
    NO863503D0|1986-09-02|
    DE3668455D1|1990-03-01|
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    DK168044B1|1994-01-24|
    NO163774B|1990-04-09|
    IE862343L|1987-03-03|
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    US4806639A|1989-02-21|
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3624104A|1969-10-27|1971-11-30|Searle & Co|Aralkanoyl derivatives of dibenzoxazepine-n-carboxylic acid hydrazides|
    US3992375A|1974-08-12|1976-11-16|G. D. Searle & Co.|Dibenzoxazepine N-carboxylic acid hydrazines and derivatives|
    FR2133022A5|1971-04-06|1972-11-24|Skm Sa|
    DE2327804C3|1973-06-01|1980-08-14|Hoechst Ag, 6000 Frankfurt|Process for the preparation of 3,4-dihydro-1,23-oxathiazin-4-ones|
    DE2453063A1|1974-11-08|1976-05-13|Hoechst Ag|METHOD FOR PRODUCING ACETOACETAMIDE-N-SULFOFLUORIDE|
    DE3410440A1|1984-03-22|1985-09-26|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|
    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)|
    DE3531358A1|1985-09-03|1987-03-12|Hoechst Ag|METHOD FOR PRODUCING THE NON-TOXIC SALTS OF 6-METHYL-3,4-DIHYDRO-1,2,3-OXATHIAZINE-4-ON-2,2-DIOXIDS|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|
    DE3527070A1|1985-07-29|1987-01-29|Hoechst Ag|METHOD FOR PRODUCING 6-METHYL-3,4-DIHYDRO-1,2,3-OXATHIAZINE-4-ON-2,2-DIOXIDE|
    DE3531358A1|1985-09-03|1987-03-12|Hoechst Ag|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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    JP2008037777A|2006-08-03|2008-02-21|Daicel Chem Ind Ltd|Method for producing potassium salt of 3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide compound|
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    法律状态:
    2007-09-20| REG| Reference to a code of a succession state|Ref country code: RU Ref legal event code: MM4A Effective date: 20040902 |
    优先权:
    申请号 | 申请日 | 专利标题
    DE19853531359|DE3531359A1|1985-09-03|1985-09-03|METHOD FOR PRODUCING 6-METHYL-3,4-DIHYDRO-1,2,3-OXATHIAZINE-4-ON-2,2-DIOXIDE AND ITS CLEANING THEREOF|
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