WO2014146581A1 - 一种丙烯酸酯类化合物的制备方法 - Google Patents

一种丙烯酸酯类化合物的制备方法 Download PDF

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WO2014146581A1
WO2014146581A1 PCT/CN2014/073732 CN2014073732W WO2014146581A1 WO 2014146581 A1 WO2014146581 A1 WO 2014146581A1 CN 2014073732 W CN2014073732 W CN 2014073732W WO 2014146581 A1 WO2014146581 A1 WO 2014146581A1
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compound
reaction
general formula
group
preparation
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PCT/CN2014/073732
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English (en)
French (fr)
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邓旭芳
王文军
陈建伟
赵永长
池剑鸿
王龙
游华南
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北京颖泰嘉和生物科技有限公司
上虞颖泰精细化工有限公司
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Priority to EP14770470.4A priority Critical patent/EP2977371B1/en
Priority to BR112015024260-0A priority patent/BR112015024260B1/pt
Priority to US14/778,336 priority patent/US9556128B2/en
Priority to AU2014234835A priority patent/AU2014234835B2/en
Publication of WO2014146581A1 publication Critical patent/WO2014146581A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
    • C07C67/327—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups by elimination of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/34—One oxygen atom

Definitions

  • the present invention relates to a process for the preparation of an acrylate compound. Background technique
  • Acrylate fungicides represented by azoxystrobin and picoxystrobin are a new class of fungicides discovered and developed by the company, and can be represented by the general formula (I).
  • the compound of the structure represented by the formula (I) can usually be obtained by removing one molecule of methanol from a compound of the formula (?).
  • the compound of the formula (III) is one of acrylate compounds which can be obtained by conversion of the compound of the formula (IV).
  • a process for carrying out the above conversion process is disclosed in WO9208703A1, which comprises reacting potassium hydrogen sulfate as a catalyst at 250 ° C to obtain a structural compound of the formula (III). With such a conversion method, the conversion and selectivity of the reaction are not sufficiently high.
  • US Pat. No. 6,612,916 A discloses the completion of a compound of the formula (IV) to a formula (III) in the presence of an acid anhydride, an acid chloride or a 2-acetoxybenzonitrile using an acidic catalyst at a temperature of from 70 to 110 °C. Conversion of the indicated compounds.
  • the inventors of the present invention have found that methanol is formed during the reaction of converting a compound of the formula (?) into a compound of the formula (I), and as the reaction progresses, the amount of methanol gradually increases.
  • the reaction proceeds to a certain extent and the amount of methanol formed in the reaction system is large, the presence of methanol affects the conversion and selectivity of the above reaction process.
  • it is usually necessary to add an acid anhydride to the reaction system to react a methanol and an acid anhydride produced by the reaction to form a carboxylic acid to remove methanol.
  • the carboxylic acid formed by the reaction is further reacted with methanol to produce water, and the compound represented by the formula (I) is unstable in an aqueous acidic environment, and further hydrolysis occurs to form an aldehyde, resulting in a significant decrease in conversion and selectivity of the reaction.
  • the acid anhydride is highly irritating and corrosive, and it also harms the production environment while damaging the reaction device.
  • the conventional method for producing an acrylate compound of the structure represented by the formula (I) is usually carried out in the presence of a solvent which is a solvent which does not participate in the reaction.
  • the solvent generally has a boiling point of 70-140 ° C and is usually selected from aromatic hydrocarbons (such as toluene, chlorobenzene, o-xylene, m-xylene, etc.), alcohols (such as methanol, ethanol, etc.) and ketones (such as methyl isobutyl ketone). At least one of the others.
  • the reaction is carried out in the presence of a solvent, on the one hand, the cost of preparing the acrylate compound is increased, and on the other hand, the reaction mixture obtained after the end of the reaction is subjected to an additional operation to remove the solvent in the reaction mixture. While increasing the difficulty of the reaction operation, complicated operation steps may cause some products to be removed in the solvent removal operation, thereby affecting the yield and selectivity of the reaction; in addition, it is worth noting that some solvents such as aromatic hydrocarbons will be produced. Environmental and personnel health have certain adverse effects, which are not conducive to environmental protection, and have also increased investment in environmental protection costs.
  • An object of the present invention is to provide a novel process for producing an acrylate compound in order to overcome the following drawbacks of the prior art process for preparing an acrylate compound of the structure represented by the formula (I).
  • the anhydride reacts with methanol in the system to form a carboxylic acid, and the carboxylic acid reacts further with methanol.
  • Water should be produced, and the compound represented by formula (I) is unstable in an acidic acidic environment, and further hydrolysis can be carried out to form an aldehyde, resulting in a significant decrease in the conversion and selectivity of the reaction.
  • the acid anhydride and the carboxylic acid have strong stimulation. Sex, not only has a great impact on the health of the staff, the resulting three wastes will also cause harm to the environment;
  • the acid anhydride has strong corrosiveness, damages the reaction device, and increases investment costs.
  • the present invention provides a process for producing an acrylate compound having a structure represented by the formula (I), which comprises passing a compound of the structure represented by the formula (II) a mixture of a compound of the formula (I) and the structure of the formula (II) is subjected to a contact reaction with a catalyst in the absence of an acid anhydride, and the produced methanol is removed by vacuum distillation during the contact reaction;
  • R is selected from a decyloxy group having 1 to 5 carbon atoms, a phenoxy group having a substituent having 6 to 20 carbon atoms, and a heteroaryloxy group having a substituent having 4 to 20 carbon atoms; a substituent-containing heteroaryloxymethyl group having 4 to 20 carbon atoms, a substituted group-containing phenoxymethyl group having 5 to 20 carbon atoms, and a substituent having 2 to 20 carbon atoms
  • One of the scorpions of the regiment is selected from a decyloxy group having 1 to 5 carbon atoms, a phenoxy group having a substituent having 6 to 20 carbon atoms, and a heteroaryloxy group having a substituent having 4 to 20 carbon atoms; a substituent-containing heteroaryloxymethyl group having 4 to 20 carbon atoms, a substituted group-containing phenoxymethyl group having 5 to 20 carbon atoms, and a substituent having 2 to 20 carbon atoms
  • the conversion of the compound of the structure represented by the formula ( ⁇ ) and the reaction selectivity of the compound of the structure of the formula (I) can be remarkably improved, generally according to the present invention.
  • the conversion and selectivity obtained by the method can be as high as 99% or more.
  • the reason may be: in the method provided by the present invention, during the reaction of converting a compound of the formula ( ⁇ ) into a compound of the structure represented by the formula (I), the produced methanol is removed by distillation under reduced pressure (also That is, a part of the reaction product is removed, so that the above reaction process can always proceed in the intended direction; and no acid anhydride is added during the above reaction, and the conversion and selectivity are lowered due to the introduction of the acid anhydride.
  • Example 1 and Comparative Example 1 it can be seen that the implementation In Example 1, solvent and acid anhydride were not used and methanol formed during the reaction was removed by distillation under reduced pressure, and an acid anhydride was used in Comparative Example 1 and carried out under normal pressure.
  • the reaction conversion rate obtained in Example 1 and The selectivity was as high as 99.6% and 99.5%, respectively, which was significantly higher than that of Comparative Example 1.
  • Example 1 when the method of the present invention is carried out in the absence of a solvent, the conversion and selectivity of the reaction are higher.
  • the method provided by the invention simplifies the reaction step, reduces the cost input, avoids the environmental impact of the solvent use, and avoids environmental pollution and corrosion of the production equipment because no need to add an acid anhydride during the reaction, and the conventional routine is avoided.
  • the environmental and equipment hazards due to the use of anhydrides in the process. Therefore, the method of the present invention is more suitable for industrial scale production applications and is suitable for the preparation of 2-substituted phenyl-3-methoxymethyl acrylate fungicides such as azoxystrobin and picoxystrobin intermediates.
  • the present invention provides a process for producing an acrylate compound having a structure represented by the formula (I), which comprises a compound of the formula (II) or a formula (I) and a mixture of a compound of the formula ( ⁇ ) and a catalyst are subjected to a contact reaction in the absence of an acid anhydride, and the produced methanol is removed by vacuum distillation during the contact reaction;
  • R is selected from a decyloxy group having 1 to 5 carbon atoms, a phenoxy group having a substituent having 6 to 20 carbon atoms, and a heteroaryloxy group having a substituent having 4 to 20 carbon atoms;
  • Base carbon number is 4-20 One of the substituent-containing heteroaryloxymethyl group, the substituted group-containing phenoxymethyl group having 5 to 20 carbon atoms, and the substituent-containing fluorenyl group having 2 to 20 carbon atoms.
  • the heteroaryloxy group may be a pyridine having a substituent or a pyrimidine having a substituent.
  • R is 6-chloropyrimidin-4-oxy, 6-(2-cyanophenoxy)pyrimidin-4-oxy, chloromethyl or 2-((6-(trifluoromethyl) Pyridin-2-yl)oxy)methyl; most preferably, R is 6-chloropyrimidine
  • the production method according to the present invention wherein when the mixture contains a structural compound represented by the formula (I), the structural compound represented by the formula (I) and the structure represented by the formula (II) in the mixture
  • the molar ratio of the compound may be 1:1.5-4.
  • the molar ratio of the structural compound represented by the general formula (I) to the structural compound represented by the general formula (?) in the mixture may be 1: 2-3.5.
  • the catalyst may be selected from at least one of a sulfate ester and a sulfonic acid compound.
  • the catalyst is selected from at least one of dimethyl sulfate, diethyl sulfate, p-toluenesulfonic acid and methanesulfonic acid.
  • the catalyst in order to save the input and ensure the smooth progress of the reaction, it is preferred that the catalyst is used in an amount of 0.005 to 0.2 moles per mole of the compound of the structure represented by the formula (().
  • the catalyst is used in an amount of from 0.02 to 0.1 mol, but the invention is not limited thereto.
  • the temperature and time conditions for the contact reaction of the compound of the structure represented by the formula (?) or the compound containing the structure of the formula (I) and (II) with the catalyst are not particularly limited,
  • the reaction conditions of the compound of the structure represented by the above formula (I) can be appropriately determined according to a conventional compound having a structure represented by the above formula (II).
  • the temperature of the reaction is from 90 to 145 ° C, more preferably from 100 to 120 ° C; and the duration of the reaction is from 60 to 240 min, more preferably from 90 to 120 min.
  • the method provided by the invention further comprises controlling the reaction during the reaction.
  • the pressure of the system is a negative pressure, whereby the methanol formed during the contact reaction is continuously removed by a vacuum distillation method.
  • the pressure of the reaction may be 100 kPa or less, preferably 20 to 80 kPa. In the present invention, the pressure refers to the absolute pressure.
  • the reactants can be stirred to achieve sufficient contact between the components in the mixture and to improve heat transfer and mass transfer.
  • the agitation may be carried out by a conventional agitation method in the art, and may be, for example, anchor, slurry or propulsion.
  • the progress of the reaction can be measured by liquid chromatography. After the reaction was completed, the stirring was stopped and the reaction system was cooled to 20-30 °C.
  • the reaction process of converting a compound of the structure represented by the formula (?) into a compound of the structure represented by the formula (I) is preferably carried out without a solvent.
  • the cost of preparing the acrylate compound can be saved, and on the other hand, since the reaction does not require removal of the solvent in the reaction mixture, it is not necessary to carry out additional reaction on the obtained reaction mixture after the reaction is completed.
  • the solvent removal operation can avoid the difficulty of the reaction operation while avoiding the loss of part of the reaction product which may be caused by the complicated solvent removal operation step, thereby improving the conversion rate and selectivity of the reaction, and also avoiding part of the reaction solvent. Adverse effects on the production environment and personnel health.
  • the method in order to obtain a compound of the structure represented by the formula (I), the method may further comprise, after the reaction is completed, subjecting the product obtained by the contact reaction to a post-treatment step of cooling, washing with water, crystallization, and the like. .
  • Conversion rate (molar amount of raw material input - molar amount of raw material remaining in the product) / molar amount of raw material input ⁇ 100%
  • Examples 1-11 are used to illustrate the preparation of the acrylate compound provided by the present invention. Table 1
  • the acrylate compound was prepared according to the conditions in Table 1, respectively, in the following steps:
  • the reaction mixture was added to a dry flask equipped with a condenser. Stirring the mixture thoroughly and heating the reaction system to the corresponding reaction temperature, under continuous stirring and corresponding negative pressure
  • the methanol produced during the reaction was continuously removed by distillation under reduced pressure during the reaction.
  • the reaction mixture was cooled to a temperature of 25 ° C under nitrogen, and then ethyl acetate and water were added to the mixture and washed with water. After separation, the organic phase was concentrated to dryness. Recrystallization was carried out, the target product was obtained by filtration, and the conversion and selectivity of the reaction were measured. The results are shown in Table 2.
  • An acrylate compound was prepared according to the method of Example 1, except that 0.14 mol of toluene was added as a solvent to the reaction mixture. After the reaction was completed, the solvent was first removed by vacuum distillation, and then ethyl acetate and water were added for washing with water. Thereafter, the organic phase was concentrated to dryness, and the product was recrystallized by adding methanol to the residue, followed by filtration to obtain the desired product, and the reaction conversion and selectivity were measured. The results are shown in Table 2.
  • This comparative example is used to explain the preparation method of the prior art acrylate compound.
  • the compound of the formula (III) was prepared according to the method of Example 1, except that 1 mol of acetic anhydride was added to the reaction mixture, and the pressure of the reaction system was controlled to be normal pressure. After the reaction was completed, the product was separated and the conversion rate of the reaction was measured. Selectivity, the results are listed in Table 2.
  • Example 2 99.5 99.3 Example 3 99.3 99.3 Example 4 99.1 99.2
  • Example 12 99.1 98.4
  • the process for producing an acrylate-based compound according to the present invention can attain higher reaction conversion and selectivity.
  • the conversion and selectivity of the reaction are superior to the addition of acetic anhydride in Comparative Example 1. Preparation method.
  • Example 12 By comparing the results of Example 1 and Example 12, it can be seen that when the process for preparing the acrylate compound is carried out in the absence of a solvent, higher reaction conversion and selectivity can be obtained.
  • the process for preparing the acrylate compound is in a more preferable condition (i.e., the compound of the formula (I) in the reaction mixture: Formula (II)
  • the molar ratio of the compound shown is 1: 2-3.5
  • the molar ratio of the compound represented by the formula (II) to the catalyst is 1: 0.02-0.1
  • the reaction temperature is 100-120 ° C
  • the pressure is 20-80 kPa
  • the reaction time is Higher reaction conversion and selectivity can be obtained when carried out under 90-120 min).

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  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

本发明涉及一种丙烯酸酯类化合物的制备方法，该丙烯酸酯类化合物具有通式(Ⅰ)所示结构，该方法包括将通式(Ⅱ)所示结构的化合物或者通式(Ⅰ) 和通式(Ⅱ)所示结构的化合物的混合物与催化剂在没有酸酐存在的条件下进行接触反应，并在接触反应过程中通过减压蒸馏脱除生成的甲醇；其中，R 选自碳原子数为1-5的烷氧基、碳原子数为6-20的含取代基团的苯氧基、碳原子数为4-20的含取代基团的杂芳氧基、碳原子数为4-20的含取代基团的杂芳氧甲基、碳原子数为5-20的含取代基团的苯氧甲基和碳原子数为2-20 的含取代基团的烷基中的一种。根据本发明提供的所述丙烯酸酯类化合物的制备方法，能够显著提高反应的转化率和选择性。

Description

一种丙烯酸酯类化合物的制备方法 技术领域
本发明涉及一种丙烯酸酯类化合物的制备方法。 背景技术
以嘧菌酯和啶氧菌酯为代表的丙烯酸酯类杀菌剂是捷利康公司发现并 开发的一类新型的杀菌剂， 该类杀菌剂可用通式（ I )来表示。 而通式（I )所 示结构的化合物通常可由式 ( Π )所示结构的化合物脱去一分子甲醇得到。
Figure imgf000003_0001
(I) (II)
式 (III)所示化合物为丙烯酸酯类化合物中的一种， 其可由式 (IV)所示化 合物转化得到。
Figure imgf000003_0002
WO9208703A1中公开了一种完成上述转化过程的方法，该方法包括在 250°C下以硫酸氢钾为催化剂反应获得通式 (III)所示结构化合物。 利用此种 转化方法， 反应的转化率和选择性不够高。
US6162916A 中公开了在酸酐、 酰基氯或 2-乙酰氧基苄腈存在的条件 下， 利用酸性催化剂， 在 70-110°C的温度条件下完成通式 (IV)所示化合物到 通式 (III)所示化合物的转化。
CN102070538A中公开了将式 (IV)所示化合物与酸酐反应，采用硫酸二 甲酯为催化剂生成式 (III)所示化合物。 发明内容
本发明的发明人发现， 在由式 ( Π )所示结构的化合物转化为式（ I )所示 结构的化合物的反应过程中会生成甲醇， 随着反应的进行， 甲醇的量逐渐 增大， 当反应进行到一定程度并且反应体系中生成的甲醇的量较大时， 甲 醇的存在会影响上述反应过程的转化率和选择性。 为了克服这个问题， 通 常需要向反应体系中加入酸酐， 使反应产生的甲醇和酸酐反应生成羧酸， 以脱除甲醇。 然而， 反应生成的羧酸会和甲醇进一步反应产生水， 式（I ) 所示的化合物在含水的酸性环境中不稳定， 会发生进一步水解生成醛， 导 致反应的转化率和选择性显著下降。 另外， 酸酐有较强的刺激性和腐蚀性， 在损害反应装置的同时也会对生产环境造成危害。
此外，现有的制备式（ I )所示结构的丙烯酸酯类化合物的方法通常需要 在有溶剂存在的情况下进行， 所述溶剂为不参与反应的溶剂。 溶剂的沸点 一般为 70-140°C， 通常选自芳烃 （例如甲苯、 氯苯、 邻二甲苯、 间-二甲苯 等）、 醇 （例如甲醇、 乙醇等） 和酮 （例如甲基异丁酮等） 中的至少一种。 反应在有溶剂的条件下进行， 一方面增加了制备丙烯酸脂类化合物所需的 成本投入， 另一方面需要对反应结束后获得的反应混合物进行额外的操作 以脱除反应混合物中的溶剂， 在增加了反应操作难度的同时， 复杂的操作 步骤可能导致部分产物在脱溶剂操作中被移除， 从而影响反应的产率和选 择性； 另外， 值得注意的是部分溶剂如芳烃等会对生产的环境和人员的健 康造成一定的不良影响， 不利于环境的保护， 也增加了环保成本的投入。
本发明的目的是为了克服现有的制备式（ I )所示结构的丙烯酸酯类化 合物的方法中存在的下述缺陷， 提供一种新的制备丙烯酸酯类化合物的方 法。
首先， 酸酐和体系中的甲醇反应生成羧酸， 而羧酸会和甲醇进一步反 应产生水， 式（ I )所示的化合物在含水的酸性环境中不稳定， 会发生进一步 水解生成醛， 导致反应的转化率和选择性显著下降； 其次， 酸酐、 羧酸具 有较强的刺激性， 不仅对工作人员健康有很大影响， 产生的三废对环境也 会造成危害； 另外， 酸酐有较强的腐蚀性， 损害反应装置， 增加投资成本。
为了实现上述目的， 本发明提供了一种丙烯酸酯类化合物的制备方法， 该丙烯酸酯类化合物具有通式（ I )所示结构， 该方法包括将通式 ( II )所示结 构的化合物或者通式（ I )和通式 ( II )所示结构的化合物的混合物与催化剂在 在没有酸酐存在的条件下进行接触反应， 并在接触反应过程中通过减压蒸 馏脱除生成的甲醇；
Figure imgf000005_0001
(I) (II)
其中， R选自碳原子数为 1-5的垸氧基、 碳原子数为 6-20的含取代基 团的苯氧基、 碳原子数为 4-20的含取代基团的杂芳氧基、 碳原子数为 4-20 的含取代基团的杂芳氧甲基、 碳原子数为 5-20的含取代基团的苯氧甲基和 碳原子数为 2-20的含取代基团的垸基中的一种。
根据本发明提供的所述丙烯酸酯类化合物的制备方法， 能够显著提高 式（Π )所示结构的化合物的转化率和式（ I )所示结构的化合物的反应选择 性， 通常根据本发明的方法获得的转化率和选择性均可以高达 99%以上。 其原因可能是： 在本发明提供的方法中， 由式 (Π )所示结构的化合物转化为 式（I )所示结构的化合物的反应过程中， 通过减压蒸馏脱除生成的甲醇（也 即脱除部分反应产物）， 使得上述反应过程始终能够向着预期的方向进行； 并且上述反应过程中无需加入酸酐， 避免了由于引入酸酐而导致转化率和 选择性降低。 具体地， 根据实施例 1 以及对比例 1的结果可以看出， 实施 例 1 中未使用溶剂和酸酐并采用减压蒸馏的方式移除反应过程中生成的甲 醇， 而对比例 1 中使用了酸酐并且在常压下进行， 结果， 实施例 1获得的 反应转化率和选择性分别高达 99.6%和 99.5%， 明显高于对比例 1。
此外， 通过将实施例 1和实施例 12进行对比可以看出， 当本发明的所 述方法在没有溶剂存在的条件下进行时， 反应的转化率和选择性更高。
本发明所提供的方法简化了反应步骤、 减少了成本投入、 避免了溶剂 使用对环境的影响； 并且由于反应过程中无需加入酸酐， 不会对环境造成 污染和对生产设备造成腐蚀， 避免了常规方法中由于使用酸酐而对环境和 设备带来的危害。 因此， 本发明的所述方法更适用于工业化规模的生产应 用， 适用于 2-取代苯基 -3-甲氧基丙烯酸甲酯类杀菌剂如嘧菌酯及啶氧菌酯 中间体的制备。 具体实施方式
以下对本发明的具体实施方式进行详细说明。 应当理解的是， 此处所 描述的具体实施方式仅用于说明和解释本发明， 并不用于限制本发明。
本发明提供了一种丙烯酸酯类化合物的制备方法， 该丙烯酸酯类化合 物具有通式（ I )所示结构， 该方法包括将通式 ( II )所示结构的化合物或者通 式（ I )和通式 (Π )所示结构的化合物的混合物与催化剂在没有酸酐存在的条 件下进行接触反应， 并在接触反应过程中通过减压蒸馏脱除生成的甲醇；
Figure imgf000006_0001
其中， R选自碳原子数为 1-5的垸氧基、 碳原子数为 6-20的含取代基 团的苯氧基、 碳原子数为 4-20的含取代基团的杂芳氧基、 碳原子数为 4-20 的含取代基团的杂芳氧甲基、 碳原子数为 5-20的含取代基团的苯氧甲基和 碳原子数为 2-20的含取代基团的垸基中的一种。
所述杂芳氧基可以为含有取代基团的吡啶或含有取代基团的嘧啶。 优选的情况下， R为 6-氯嘧啶 -4-氧基、 6-(2-氰基苯氧基)嘧啶 -4-氧基、 氯甲基或 2-((6- (三氟甲基)吡啶 -2-基)氧)甲基； 最为优选地， R为 6-氯嘧啶
-4-氧基。
根据本发明所述的制备方法， 其中， 当所述混合物中含有通式（I )所示 结构化合物时， 所述混合物中通式（ I )所示结构化合物与通式 ( II )所示结构 化合物的摩尔比可以为 1 : 1.5- 4， 优选的， 所述混合物中通式（ I )所示结构 化合物与通式 ( Π )所示结构化合物的摩尔比可以为 1 : 2-3.5。
根据本发明所述的制备方法， 所述催化剂可以选自硫酸酯和磺酸类化 合物中的至少一种。
优选情况下， 所述催化剂选自硫酸二甲酯、 硫酸二乙酯、 对甲苯磺酸 和甲磺酸中的至少一种。
本发明提供的制备方法中， 为了节省投入和保证反应的顺利进行， 优 选情况下， 相对于 1摩尔的通式 ( Π )所示结构的化合物， 所述催化剂的用量 为 0.005-0.2摩尔， 最为优选的， 所述催化剂的用量为 0.02-0.1摩尔， 但本 发明并非仅限于此。
本发明提供的制备方法中， 通式 ( Π )所示结构的化合物或者含有通式 ( I )和（ II )所示结构的化合物的混合物与催化剂接触反应的温度和时间条件 没有特别的限定，可以根据常规的由上述式( II )所示结构的化合物制备上述 式（I )所示结构的化合物的反应条件适当地确定。优选情况下， 所述反应的 温度为 90-145°C，更优选为 100-120°C ;所述反应持续的时间为 60-240 min， 更优选为 90-120 min。
为了利于反应向产物生成的方向进行， 以进一步提高反应转化率、 选 择性以及反应效率， 本发明提供的方法还包括在反应进行过程中， 控制反 应体系的压力为负压， 从而通过减压蒸馏方法连续脱除所述接触反应的过 程中生成的甲醇。 反应的压力可以为 lOOkPa以下， 优选为 20-80kPa。 在本 发明中， 压力是指绝对压力。
本发明的反应过程中可以通过对反应物进行搅拌来达到使混合物中各 组分充分接触和改善传热、 传质的效果。 所述搅拌可以采用本领域常规的 搅拌方法， 例如可以为锚式、 浆式或推进式搅拌等。
在本发明提供的制备方法中， 反应进行的情况可以通过液相色谱进行 测定。 待反应完全后， 停止搅拌并使反应体系降温至 20-30°C。
在本发明提供的制备方法中， 由式 ( Π )所示结构的化合物转化为式（ I ) 所示结构的化合物的反应过程优选在没有溶剂的情况下进行。 在这种情况 下， 一方面可以节省制备丙烯酸脂类化合物所需的成本投入， 另一方面由 于反应不需要脱除反应混合物中的溶剂， 所以反应结束后不需要对获得的 反应混合物进行额外的脱除溶剂的操作， 从而能够在减小反应操作的难度 的同时避免复杂的脱溶剂操作步骤可能导致的部分反应产物的流失， 进而 提高反应的转化率和选择性， 并且也避免了部分反应溶剂对生产环境和人 员健康造成的不良影响。
在本发明提供的所述方法中， 为了获得式（I )所示结构的化合物， 所述 方法还可以包括， 在反应结束之后， 将接触反应得到的产物进行冷却、 水 洗、 结晶等后处理步骤。
以下将通过实施例对本发明进行详细描述。
以下实施例中反应物和产物的量通过液相色谱 （Agilent 1200) 测得。 以下实施例中， 反应的转化率和选择性通过以下公式计算：
转化率 = (原料投入摩尔量-产物中残留的原料摩尔量) /原料投入摩尔量 χ100%
选择性 =目标产物的实际摩尔量 /目标产物的理论摩尔量 Xl00% 实施例 1-11
实施例 1-11用于说明本发明提供的丙烯酸脂类化合物的制备方法。 表 1
Figure imgf000009_0001
分别按照表 1中的条件制备丙烯酸酯类化合物， 制备的步骤为： 在配有冷凝器的干燥烧瓶中加入反应混合物。 搅拌使混合物充分混合 并将反应体系加热至相应的反应温度， 在持续搅拌和相应的负压下反应相 应的时间， 并且在反应的过程中通过减压蒸馏连续移除反应过程中生成的 甲醇。 待反应完全后， 将反应混合物在氮气保护下降温至 25°C， 再在反应 混合物中加入乙酸乙酯和水进行水洗， 分层后将有机相浓缩至干， 在残留 物中加入甲醇对产物进行重结晶， 过滤得到目标产物， 测定反应的转化率 和选择性， 结果列于表 2。
实施例 12
按照实施例 1 的方法制备丙烯酸酯类化合物， 不同的是反应混合物中 添加 0.14mol甲苯作为溶剂，反应完全后， 首先通过真空蒸馏的方法去除溶 剂， 然后加入乙酸乙酯和水进行水洗， 分层后将有机相浓缩至干， 在残留 物中加入甲醇对产物进行重结晶， 过滤得到目标产物， 测定反应转化率及 选择性。 结果见表 2。
对比例 1
本对比例用于说明现有技术的丙烯酸脂类化合物的制备方法。
按照实施例 1的方法制备通式 (III)所示化合物，不同的是反应混合物中 添加 lmol 的醋酸酐， 并且控制反应体系的压力为常压， 反应完全后分离 产物并测定反应的转化率及选择性， 结果列于表 2。
表 2
编号 转化率 （％) 选择性 （％) 实施例 1 99.6 99.5
对比例 1 99.1 97.9
实施例 2 99.5 99.3 实施例 3 99.3 99.3 实施例 4 99.1 99.2
实施例 5 99.2 99.1
实施例 6 99.4 99.4
实施例 7 99.5 98.5
实施例 8 99.6 98.8
实施例 9 99.3 99.2
实施例 10 99.2 99.1
实施例 11 99.5 99.4
实施例 12 99.1 98.4 由上述表 2 的数据可以看出， 根据本发明所述的制备丙烯酸酯类化合 物的方法可以获得较高的反应转化率和选择性。具体地， 通过对比实施例 1 与对比例 1 的结果可以看出， 在采用本发明的方法制备丙烯酸酯类化合物 的过程中， 反应的转化率和选择性均优于对比例 1 中添加醋酸酐的制备方 法。
而且， 通过对比实施例 1与实施例 12的结果可以看出， 当制备丙烯酸 酯类化合物的过程在没有溶剂存在的条件下进行时， 可以获得更高的反应 转化率和选择性。
另外， 通过对比实施例 1-3与实施例 4-5的结果可以看出， 当制备丙烯 酸酯类化合物的过程在较优选的条件 （即反应混合物中式（ I )所示化合物： 式 ( II )所示化合物的摩尔比为 1 : 2-3.5， 式 ( II )所示化合物与催化剂的摩尔 比为 1： 0.02-0.1、 反应温度为 100-120 °C、 压力为 20-80kPa、 反应时间为 90-120min) 下进行时， 可以获得更高的反应转化率和选择性。 以上详细描述了本发明的优选实施方式， 但是， 本发明并不限于上述 实施方式中的具体细节， 在本发明的技术构思范围内， 可以对本发明的技 术方案进行多种简单变型， 这些简单变型均属于本发明的保护范围。
另外需要说明的是， 在上述具体实施方式中所描述的各个具体技术特 征， 在不矛盾的情况下， 可以通过任何合适的方式进行组合， 为了避免不 必要的重复， 本发明对各种可能的组合方式不再另行说明。
此外， 本发明的各种不同的实施方式之间也可以进行任意组合， 只要 其不违背本发明的思想， 其同样应当视为本发明所公开的内容。

Claims

权利要求
1、 一种丙烯酸酯类化合物的制备方法， 该丙烯酸酯类化合物具有通式
( I )所示结构， 该方法包括将通式 ( II )所示结构的化合物或者通式（ I )和通式
(II )所示结构的化合物的混合物与催化剂在没有酸酐存在的条件下进行接触 反应， 并在接触反应过程中通过减压蒸馏脱除生成的甲醇，
Figure imgf000013_0001
(I) (II)
其中， R选自碳原子数为 1-5的垸氧基、碳原子数为 6-20的含取代基团 的苯氧基、 碳原子数为 4-20的含取代基团的杂芳氧基、 碳原子数为 4-20的 含取代基团的杂芳氧甲基、 碳原子数为 5-20 的含取代基团的苯氧甲基和碳 原子数为 2-20的含取代基团的垸基中的一种。
2、根据权利要求 1所述的制备方法，其中， R为 6-氯嘧啶 -4-氧基、 6-(2- 氰基苯氧基)嘧啶 -4-氧基、 氯甲基或 2-((6- (三氟甲基)吡啶 -2-基)氧)甲基。
3、 根据权利要求 1或 2所述的制备方法， 其中， 通式（ I )所示结构的化 合物与通式 ( II )所示结构的化合物的摩尔比为 1 : 1.5-4。
4、 根据权利要求 1所述的制备方法， 其中， 相对于 1摩尔的通式 (II ) 所示结构的化合物， 所述催化剂的用量为 0.005-0.2摩尔。
5、 根据权利要求 1或 4所述的制备方法， 其中， 所述催化剂选自硫酸 酯和磺酸类化合物中的至少一种。
6、 根据权利要求 5所述的制备方法， 其中， 所述催化剂选自硫酸二甲 酯、 硫酸二乙酯、 对甲苯磺酸和甲磺酸中的至少一种。
7、 根据权利要求 1或 2所述的制备方法， 其中， 所述接触反应的条件 包括： 温度为 90-145°C， 时间为 60-240min， 压力为 lOOkPa以下。
8、 根据权利要求 1或 2所述的制备方法， 其中， 所述接触反应在不使 用溶剂的条件下进行。
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