• 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 esters and can be used, in particular, in the preparation of C < - " C4-alkyl ester ", " chlorine " 3 '* C, -C4-alkoxy-2E- butenoic acid - intermediates for the synthesis of various substances The goal is to increase the yield and purity of the target product. ' Synthesis is carried out by the reaction of the chloroanhydride of the "»-chloroacetoacetic acid with 1, 4-2 equivalents of di-C ^ -C4 • a alkyl-sulfite (it is obtained in situ from thionyl chloride with the corresponding alcohol) and with the corresponding alcohol ~ C <; 'C4 with an increase in temperature from -10 to 60 Co. The obtained ketal ether is heated without separation at a temperature of 70-150 * C and a pressure of 50-500 mbar in the presence of a catalyst — sulfuric or methanesulfonic acid in an amount of 0.4-1 mol.%. alcohol - C ^ -C ^ -DL to form dialkyl sulfite and keta-ether in an amount of 5-20 moles per 1 mole of acid chloride. Words increase the yield of the target product ~ from 72-75 to 7 ^^ and its purity from 98 to 99.8 ^ .1 table (L
    公开号:SU1709903A3
    申请号:SU894614303
    申请日:1989-06-12
    公开日:1992-01-30
    发明作者:Дюк Лоран
    申请人:Лонца Аг (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to esters and can be used in the preparation of C (-C4 alkyl 4-chloro-3-C-C4-alkoxy-2E-butenoic acid ester of the general formula OR
    se

    OOR
    where R is an alkyl group of 1 to 4 atoms; mami carbon.
    These compounds are multipurpose components for numerous syntheses of biologically active
    substances for pharmaceuticals, chemicals for agriculture.
    A method of producing compounds of formula (I) is known by reacting a 4-chloroacetoacetic alkyl ester with
    (I) a trialkyl ester of o-formic acid in the presence of sulfuric acid, do-ketal ester and heating under vacuum.
    The disadvantage of this method is the low yield and purity of the target products (see table).
    The aim of the invention is to increase the yield and purity of the target products. The goal is achieved in that according to the method of producing compounds of formula (I), its acid chloride is used as a derivative of chloroacetoacetic acid, which is reacted with equivalents of dialkyl sulfite of the general formula (K0) L5 O where R has the indicated values, which is obtained in situ interactions thionyl chloride with the corresponding alcohol of the general formula where R has the indicated values, and with the corresponding alcohol of the general formula (III) with increasing temperature oY -10 up to 60 ° C, to obtain the ketal ether of the general formula where R has the indicated values, which, without isolation, is subjected to heating at 70-150 ° C and a pressure of SO 500 mbar in the presence of a catalyst of sulfuric acid or methanesulfonic acid in an amount of 0.4-1 mol to obtain the desired product, with the alcohol of the general formula (III) forming a dial Sulfite of general formula (II) and ketal ether of general formula (IV) is used in the amount of mole per 1 mo of 4-chloroacetic acid chloride. Example 1, 4 ™ chloro methyl ester 3 methoxybutene 2E of oic acid 206.6 g (0, -} 7 mol) mixture. -chloroacetyl chloride in methylene chloride is cooled to, 6 atmosphere of azo is added over a period of 30 minutes 102.5 g (3.2 mol) of methanol, then 83.3 g (0.7 mol) of thionyl chloride (dimethyl sulfite formation) is added over 30 minutes . Increase the temperature to room temperature. The solution is stirred for 3 m at 20-25 ° C. Excess methanol and methylene chloride are distilled off at a lower pressure. The residue (crude methyl ester 4-chloro 3,3 Dimetok of sibutanoic acid) is mixed with 0.21 g of methanesulfonic acid and heated at a pressure of 100 mbar at 125– 130 ° C. The resulting methanol and excess dimethyl sulfate are distilled. The residue (crude methyl ester of chloro-3-methoxy-butene-2E oic acid) was introduced into 110.2 g (120 ml) of toluene. The organic phase is washed with 69.8 g of aqueous 16% hydrochloric acid for 30 minutes; 32.1 g of an aqueous 10% solution of sodium chloride for 10 minutes, 13 g of an aqueous 10% solution of sodium hydroxide for 75 minutes and 32, 1 g of an aqueous solution of sodium chloride for 10 minutes. Toluene is evaporated. The residue is distilled at a pressure of 10 mbar and a temperature of 95-97 ° C. B1.7 g (80) of the expected product is obtained at a purity of 99.5 (GC). PRI mme R 2. Ethyl 4-chloro 3 -toxy-2E-2-oic acid. 2.06.6 (0, i (7 mol) 4; mixtures of chloroacetoacetyl chloride in methylene chloride) are cooled to -10 C. Then lt7.2 g (3.2 mol) of ethanol is added under a nitrogen atmosphere for 30 minutes, then 83s3 g (0, 7 mol) of thionyl chloride for 30 minutes (formation of diethyl sulfite). The temperature is raised from 55 to 60 ° C for I 4j and then further stirred at 55 to 60 C for 1 hour. At the same time, excess ethanol and methylene chloride are distilled off under reduced pressure. Residue (crude ethyl ether -Chlor-Z.Zdiztoksibutanovoy acid) is mixed with 0.27 g of methanesulfonic acid and heated at a pressure of 75 mbar at 125 130 ° C ethanol and excess diethyl sulfite are distilled off. The residue (crude ethyl ester chlorine 2 Ethoxybutene 2E-oic acid) is mixed with 110.2 g (120 ml) of toluene. The organic phase is washed with 63.8 g of aqueous hydrochloric acid for 10 minutes, 31 1 g of aqueous 10 A 10% solution of sodium chloride solution was 10 minutes, 13 g of an aqueous 10% solution of sodium hydroxide was 75 minutes and 32.1 g of an aqueous solution of sodium chloride was 10 minutes. Toluene was evaporated. The residue is distilled at a pressure of 2 mbar at 78–80 ° C., 8O, 6 g (88.5) of the desired product are obtained with a purity of 99.3 (GC), Example 3. Propyl ether A-chloro -3 Propoxibuten-2E ovic acid. 206.6 g (0.7 mol) of a mixture of 4-chloroacetoacetyl chloride in methylene chloride are cooled to. Then, under a nitrogen atmosphere, 192.3 g (3.2 mol) of propanol is added for 30 minutes and then 83.3 g (0.7 mol) of thionyl chloride in 30 minutes (formation of dipropylsulLitol). Raise the temperature to. The mixture is stirred at 1 ° C and at 30 ° C. Then, excess propanol and methylene chloride are distilled off under reduced pressure. The residue (crude propyl chloro-3,3 dipropoxybutanoic acid ester) is mixed with 0.21 g of methanesulfonic acid and heated to a pressure of 70 mbar up to 125– 130 ° C, and the formed prolanol is distilled off. The residue (crude propyl 4-chloro 3-propoxy-butene-2E oic acid and excess dipropylsulfite) is mixed with 110.2 g (120 ml) of toluene. The organic phase is washed with B9.8 g of aqueous 1B% hydrochloric acid 30. MI 32.1 g of aqueous 10% solution of sodium chloride for 10 minutes, 13 g of aqueous solution of sodium hydroxide for 75 minutes and 32.1 g of aqueous 10% - sodium chloride solution 10 min. Then the toluene is evaporated. The rest of the PB is distilled at a pressure of 0.05 mbar. Two fractions are obtained: dipropyl sulphate (21.2 g,.) And the target product (8k, kg (8P), then bp 73-75 ° purity (GC) 99 Example. Butyl ester 4- ° -chloro-3 butoxybutene-2E Odoxy acid 206.6 (0.47 mol) of a 35% mixture of chloroacetoacetyl chloride in methylene chloride is cooled to 10 ° C, then 244 g (3, 29 mol) butanol 30 min and then 83.3 g (0.7 mol) of thionyl chloride 30 min (formation of dibutylsulLit) Raise the temperature to -20 g at 25 ° C for 1 h, then stir further at 20-25 ° C for 1 h. Then excess butanol and methyl the enchloride is distilled off under reduced pressure. The residue (crude 4-chloro-3,3 ° d-butyl ester of dibutoxybutanoic acid) is mixed with 0.3 g of methanesulfonic acid and heated to 50 mbar at C. The resulting butanol is distilled off. The residue (not specified) 4-chloro-3-butoxy-butene-2E-oic acid butyl ester) and excess dibutyl sulfite are mixed with 110.2 g (120 ml) of toluene. The organic phase is washed with 69.8 g of aqueous hydrochloric acid for 30 minutes, 32.1 of aqueous chloride solution sodium 10 min, 134 g of aqueous 10% solution of sodium hydroxide 75 min and 32.1 zododyne 1O - sodium chloride sodium chloride 10 min. The toluene is then evaporated. The residue is distilled at a pressure of 0.1 mbar. Two fractions are obtained: dibutyl sulfite (37.7 g, bp. B2-80 C) and target product (g (80), bp. 99101 0), purity (GC) is 99.6%. Examples 10. The results of the analysis of the products obtained are given in the table. PRI me R 9 (prototype). A mixture of 4-chloro-Z-ethoxy-2E-butenoic acid ethyl ester, 33.4 g (0.2 mol) of 4-chloroacetic acid ethyl ester is mixed with 148.2 g (1.0 mol) of formic acid triethyl . Under stirring, 30.0 g of Amberlite-15 ion-exchange resin is added with stirring. With intense outgassing, the reaction temperature rises to 45 ° C. After stirring for 6 hours on a thin-layer chromatogram, no starting material was detected. The ion exchange resin is filtered off. The residue is distilled under a water jet vacuum. The distillate is mixed with 1.0 g of p-toluenesulfonic acid monohydrate and slowly heated to 155 s, and the ethanol is distilled off. Then the reaction mixture is distilled in a water jet vacuum. 23.6 g of a colorless liquid are obtained, tons of bales. 95 ° C (10 mm Hg). NMR (SBS1) 5, ppm: 5.16 (s. 1H), 4.67 (s, 2H), 3.73 (s, 6H). Exit 72,. HPLC purity The data on the yield and purity of the target products are given in the table. The proposed method allows to increase the yield to 78.0 and purity to 9.8. formula of the invention. Method for producing C-Cd-alkyl fir 4-chloro-3 C-C-alkoxy-2E-buenoic acid of general formula (I)
    where R is an alkyl group of 1 to k carbon atoms, using a derivative of chloroacetoacetic acid and elevated temperature, characterized in that, in order to increase the yield and purity of the target products, its acid chloride is used as a derivative of chloroacetoacetic acid, which is subjected to interaction with 1.4-2 equivalents of dialkyl sulfite of the general formula (II)
    (RO) 2S-O
    where R has the indicated values, which is obtained in situ by reacting thionyl chloride with the corresponding alcohol of the general formula (III) ROH, where R has the specified values, and with the corresponding alcohol of the general formula (III) with increasing temperature from to 6 ° C to produce the ketal ether Formula (IV)
    where R has the indicated values, which, without isolation, is subjected to heating at 70-150 ° C and a pressure of 40,500 mbar in the presence of a catalyst — sulfuric acid or methanesulfonic acid in an amount of 0, -1 mol; to obtain the desired product, the alcohol of general formula (III) for forming dialkyl sulfite of general formula (II) and ketal ester of general formula (IV) is used in an amount of 5-20 mol per 1 mol of acid chloride-chloroacetic acid.
    权利要求:
    Claims (1)
    [1]
    The claims 1 Method for the preparation of C {-Cd-alkyl ester 4 “Chlorine” 3 “C <-C | -alkoxy-2E-but55tenoic acid of the General formula (I)
    I
    I
    Cookie ε
    where R is an alkyl group of 1 to 4 carbon atoms, using a derivative of 4-chloroacetoacetic acid and an elevated temperature, about l and -, which, in order to increase the yield and purity of the target products, use 4-chloroacetoacetic acid as a derivative its acid chloride, which is subjected to * j interaction with 1.4-2 equivalents of dialkyl sulfite of the general formula (II) (R0) z S-0 where R has the indicated meanings, j which is obtained in situ by the interaction of thionyl chloride with the corresponding alcohol of the general formula (III ) ROH, where R has the specified z beginning, and with the corresponding alcohol of general formula (III) with increasing temperature from -10 ° C to 60 ° C to obtain a ketal ester of general formula (IV) where R has the indicated values, which without isolation is subjected to heating at 70-150 ° C and pressure 50t 500 mbar in the presence of a catalyst - sulfuric acid or methanesulfonic acid in an amount of 0.4-1 mol. ^ to obtain the target product, moreover, the alcohol of general formula (III) for the formation of dialkyl sulfite of the general formula (II) and the ketal ether of the general formula (IV) use in an amount of 5 ~ 20 mol per 1 mol of acid chloride 4 loracetacetic acid.
    Example R Image General Pressure Tempera- Sour Exit, Powerfallen if- nie tour, C one that % purityXia in honest mbarthe lucidityΌsitu in in, dial ROH mol.%. kil mole sulfite eq.
    1 sun 31, 48 b, 3 1 software 125-130 M 0.46 80 99.5 2 with 2 n 1.48. 6.8 75 125-130 m 0.6 88.5 99.8 3 • C n 71, 48 6.8 70 125-130 M 0.46 81 99.5 4 from 4 n 91.48 7 fifty 1 35-140 m 0.66 80 99,2 5 sun 32 20 100 125-130 and 1 79.5. 99 61.4 8 500 150 m 0.6 85.4 ' 99.5 7 sun 31,5 5 fifty 70 m 0.5 78 99 8 CzHj- 1.48 6.8 100 125-130 S 0.4 87.5 99.6 9 s r n 5- - -- - 72 97.5 10 sun 3 - - - - - 75 98 NOTE nie. M - Methanesulfonic acid, S - sulfuric acid.
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    同族专利:
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    法律状态:
    优先权:
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