JP2006182675A - Method for producing michael addition product - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method capable of producing a Michael addition product in a shorter time than those of conventional processes. <P>SOLUTION: This method for producing the Michael addition product in the shorter reaction time than those of the conventional methods is provided by continuously reacting a (meth)acrylic acid ester with a primary or secondary amine compound. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a method for producing a Michael addition compound suitable as various organic synthesis reagents.

  Various proposals have been made for producing Michael addition compounds by reaction of (meth) acrylic acid esters with primary or secondary amine compounds. For example, Patent Document 1 and Patent Document 2 disclose (meta) ) It is disclosed that the above reaction is performed in a batch (batch) reaction between an acrylate ester and a primary or secondary amine compound.

Japanese Patent Laid-Open No. 7-145122 (publication date: June 6, 1995) Japanese Patent Laid-Open No. 7-316111 (Publication date: December 5, 1995)

  In the method described in Patent Document 1, the reaction is carried out by a batch synthesis method. However, the batch synthesis method has a problem that the reaction time becomes long. In particular, since the reaction is an exothermic reaction, in order to prevent polymerization of (meth) acrylic acid esters due to an increase in the temperature of the reaction system, a method of dripping either substrate is advantageous, in which case the reaction time is longer. Become.

  The present invention has been made in view of the above-described conventional problems, and an object of the present invention is to provide a method by which a Michael addition compound can be produced in a shorter reaction time than a conventional reaction method. .

  In the present invention, “(meth) acrylic acid” includes acrylic acid and methacrylic acid, and “(meth) acrylate” includes acrylate and methacrylate.

  The inventor of the present application diligently studied a method for producing a Michael addition compound. As a result, by continuously reacting (meth) acrylic acid esters with a primary or secondary amine compound, a Michael addition compound can be produced in a shorter reaction time as compared with the conventional method. The inventors have found that this is possible and have completed the present invention.

  By continuously reacting a (meth) acrylic acid ester with a primary or secondary amine compound, the Michael addition compound can be produced in a shorter reaction time than in the conventional method.

  Furthermore, the unexpected effect that the Michael addition compound obtained by making the (meth) acrylic acid ester and primary or secondary amine compound react continuously is hardly colored was recognized.

  The method for producing a Michael addition compound of the present invention is a method in which a primary or secondary amine compound is continuously reacted with (meth) acrylic acid esters in the absence of a catalyst using a Michael addition reaction. Therefore, in the present invention, unlike the conventional batch (batch) production method, the reaction time is short.

  In order to realize the above-described continuous reaction, preferable conditions include a method of performing the reaction using a flow reactor that can continuously supply the raw materials and can continuously discharge the reaction liquid. This means that all raw materials are continuously fed to the flow reactor and reacted. For example, a microreactor can be used.

  The shape of the reactor used for the reaction is a flow type reactor in which a liquid flows, that is, a raw material can be continuously fed and a reaction liquid can be continuously discharged. Examples thereof include a reactor having a rectangular tube shape, a polygonal tube shape, an elliptic tube shape, a reactor containing a static mixing function, a reactor containing a driving type mixing function, and a micro / mini reactor. Two or more of these shapes may be combined, and a temperature control means for controlling the reaction temperature may be provided.

  The equivalent diameter of one flow path of the reactor is preferably 1 to 50,000 μm, more preferably 10 to 30,000 μm, and particularly preferably 50 to 10,000 μm. If it is 50,000 μm or more, a drift occurs, which is not preferable.

  Since the length and flow rate of the reaction channel are related to the reaction rate, they may be appropriately set according to the reaction rate. The flow rate in the reactor used for the above reaction is preferably 20 minutes or less, more preferably. May be set so that a residence time (reaction time) of 10 minutes or less is achieved.

  The material of the reactor is not affected by raw materials and solvents. For example, metal (iron, aluminum, titanium, nickel, stainless steel, various alloys), resin (fluororesin), glass (silicon, quartz), porcelain (Cordierite, ceramics) and the like.

The present invention also provides a compound represented by the general formula (1):
_{^{CH 2 = CR 1 -COOR 2 (}} 1)
(Wherein R ¹ represents a hydrogen atom or a methyl group, and R 2 represents an organic residue having 1 to 20 carbon atoms), and (meth) acrylic acid esters represented by the following general formula (2) :
R3-NH-R4 (2)
(Wherein R3 represents a hydrogen atom or an organic residue having 1 to 10 carbon atoms, and R4 represents an organic residue having 1 to 10 carbon atoms. R3 and R4 may be linked to form a cyclic structure. And a primary or secondary amine compound represented by the general formula (3)
_{^{R 3 R 4 N-CH 2}} -CHR 1 -COOR 2 (3)
(Wherein R ¹ , R ² , R ³ , and R ⁴ are as defined above) can be produced.

The organic residue represented by R ² in the general formula (1) is, for example, a linear, branched or cyclic saturated alkyl group having 1 to 20 carbon atoms, or a linear chain having 1 to 20 carbon atoms. , Branched or cyclic unsaturated alkyl group, linear having a C3-C20 ether bond, branched or cyclic saturated alkyl group, linear having a C3-C20 ether bond A branched or cyclic unsaturated alkyl group, a C2-C5 hydroxyalkyl group, a C6-C11 aromatic group, and the like. Of these, a saturated alkyl group having 1 to 4 carbon atoms and a saturated alkyl group having an ether bond having 3 to 4 carbon atoms are preferably used.

  Representative examples of the (meth) acrylic acid esters represented by the general formula (1) in the present invention include methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, and (meth) acrylic. Acid butyl, (meth) acrylic acid 2-ethylhexyl, (meth) acrylic acid cyclohexyl, (meth) acrylic acid methoxyethyl, (meth) acrylic acid methoxypolyethylene glycol, (meth) acrylic acid 2-hydroxyethyl, (meth) acrylic 3-hydroxypropyl acid, 2-hydroxypropyl (meth) acrylate, 4-hydroxybutyl (meth) acrylate, 4-hydroxycyclohexyl (meth) acrylate, 5-hydroxypentyl (meth) acrylate, (meth) acrylic Acid 6-hydroxyhexyl, (meth) acrylic acid 4-hydride Carboxymethyl cyclohexylmethyl, (meth) acrylic acid 2- (hydroxyethoxy) ethyl, (meth) acrylate, 2-vinyloxyethyl, and (meth) acrylic acid 2- (vinyloxy) ethyl and the like. Among these, acrylates are preferable, and methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, cyclohexyl acrylate, methoxyethyl acrylate, and the like are preferable.

The organic residue represented by R ³ and R ⁴ in the general formula (2) is, for example, a linear, branched or cyclic saturated alkyl group having 1 to 10 carbon atoms, 1 to 10 carbon atoms. A linear, branched or cyclic unsaturated alkyl group, a linear, branched or cyclic saturated alkyl group having a C3-10 ether bond, and a C3-10 ether bond Examples thereof include linear, branched or cyclic unsaturated alkyl groups, hydroxyalkyl groups having 2 to 5 carbon atoms, and aromatic groups having 6 to 10 carbon atoms. Of these, a saturated alkyl group having 1 to 4 carbon atoms and a saturated alkyl group having an ether bond having 3 to 4 carbon atoms are preferably used. R ³ and R ⁴ may be connected to form an alkylene group having 2 to 10 carbon atoms or an alkylene group having an ether bond having 2 to 6 carbon atoms.

  Representative examples of the primary amine compound represented by the general formula (2) in the present invention include methylamine, ethylamine, propylamine, butylamine, 2-ethylhexylamine, allylamine, 2-methoxyethylamine, 3-methoxypropylamine, Examples include 3-ethoxypropylamine, cyclohexylamine, benzylamine aniline, and the like. Among these, ethylamine, propylamine, butylamine, 3-methoxypropylamine, 3-ethoxypropylamine, cyclohexylamine and the like are preferable.

  Representative examples of the secondary amine compound represented by the general formula (2) in the present invention include dimethylamine, diethylamine, dipropylamine, dibutylamine, methylethylamine, methylpropylamine, diallylamine, di (3-methoxypropyl). Examples include amine, diphenylamine, pyrrolidine, piperidine, pyrrole, pyrroline, indole, indoline, morpholine and the like. Among these, diethylamine, dipropylamine, dibutylamine, pyrrolidine, piperidine, morpholine and the like are preferable.

  In the reaction of (meth) acrylic acid esters with primary or secondary amine compounds, the reaction molar ratio of (meth) acrylic acid esters and amine compounds may be appropriately selected depending on the post-reaction process and the purpose of use. However, the molar ratio of (meth) acrylic acid ester / amine compound is preferably 5/1 to 1/8, more preferably 3/1 to 1/6, further preferably 2/1 to 1/5, 1 / 1.1 to 1/4 is particularly preferable. The range of the molar ratio is preferable in terms of yield and economy.

  In the reaction system of the present invention, when a gas phase portion exists, the gas phase portion is preferably replaced with a molecular oxygen-containing gas. In addition, when there is no gas phase part, it is preferable to sufficiently dissolve oxygen by bubbling a molecular oxygen-containing gas before supplying the raw material (meth) acrylic acid ester to the reaction.

  Examples of the molecular oxygen-containing gas include a gas obtained by diluting pure oxygen or air with an inert gas such as nitrogen or helium. The concentration of molecular oxygen in the molecular oxygen-containing gas is preferably 0.1% by volume or more, more preferably 0.5% by volume or more, and particularly preferably 1% by volume or more. Moreover, 8 volume% or less is preferable and 7.5 volume% or less is more preferable. The range of the molecular oxygen concentration is preferable in terms of stable reaction and economy.

  The reaction temperature for the above reaction is preferably 0 ° C. or higher, more preferably 10 ° C. or higher, and particularly preferably 20 ° C. or higher. Moreover, it is preferable to set it as 120 degrees C or less, 100 degrees C is still more preferable, and 80 degrees C or less is especially preferable. The above temperature range is preferable in terms of yield and economy.

  In the present invention, it is preferable to add a polymerization inhibitor into the reaction system. Examples of the polymerization inhibitor include quinone polymerization inhibitors such as hydroquinone, methoxyhydroquinone, benzoquinone, and p-tert-butylcatechol, 2,6-di-tert-butylphenol, 2,4-di-tert-butylphenol, Alkylphenol polymerization inhibitors such as 2-tert-butyl-4,6-dimethylphenol, 2,6-di-tert-butyl-4-methylphenol, 2,4,6-tri-tert-butylphenol and alkylated diphenylamines N, N'-diphenyl-p-phenylenediamine, phenothiazine, 4-hydroxy-2,2,6,6-tetramethylpiperidine, 4-benzoyloxy-2,2,6,6-tetramethylpiperidine, 1, 4-dihydroxy-2,2,6,6-tetramethylpiperidine, Amine-based polymerization inhibitors such as -hydroxy-4-benzoyloxy-2,2,6,6-tetramethylpiperidine, 2,2,6,6-tetramethylpiperidine-N-oxyl, 4-hydroxy-2, Examples include N-oxyl polymerization inhibitors such as 2,6,6-tetramethylpiperidine-N-oxyl and 4-benzoyloxy-2,2,6,6-tetramethylpiperidine-N-oxyl. Among these, hydroquinone, methoxyhydroquinone, benzoquinone, p-tert-butylcatechol, phenothiazine, 2,2,6,6-tetramethylpiperidine-N-oxyl, 4-hydroxy-2,2,6,6-tetramethyl Piperidine-N-oxyl, 4-benzoyloxy-2,2,6,6-tetramethylpiperidine-N-oxyl and the like are preferable. These polymerization inhibitors may be used alone or in combination of two or more.

  The addition amount of the polymerization inhibitor is preferably 0.001% by mass or more, and 0.005% by mass with respect to the (meth) acrylic acid ester, although it depends on the type of (meth) acrylic acid ester used. The above is more preferable, and 0.01% by mass or more is particularly preferable. Moreover, 5 mass% or less is preferable, 1 mass% or less is more preferable, and 0.1 mass% or less is especially preferable. The range of the addition amount of the polymerization inhibitor is preferable from the viewpoint of yield, suppression of polymerization, and economical efficiency.

  In this reaction, it is not necessary to use a solvent, but any solvent that does not inhibit the reaction may be used. Examples of the solvent include aliphatic hydrocarbon solvents such as pentane, hexane, and heptane, alicyclic hydrocarbon solvents such as cyclopentane, cyclohexane, and methylcyclohexane, benzene, toluene, xylene, anisole, mesitylene, and the like. Aromatic hydrocarbon solvents, halogenated hydrocarbon solvents such as chloroform, dichloromethane, dichloroethane and chlorobenzene, ester solvents such as ethyl acetate, propyl acetate and butyl acetate, and alcohol solvents such as methanol and ethanol And acetonitrile, tetrahydrofuran, 1,4-dioxane and the like. These solvents may be used alone or in combination of two or more.

As the usage-amount of the said solvent, 0 mass% or more is preferable with respect to the total mass of (meth) acrylic acid esters and an amine compound. Moreover, 200 mass% or less is preferable, 100 mass% or less is more preferable, 75 mass% or less is further more preferable, and 50 mass% or less is especially preferable. The range of the amount of the organic solvent used is preferable in terms of yield and economy.
The Michael addition compound produced according to the present invention can be separated and purified as necessary after the reaction is completed. Examples of the separation / purification method include extraction methods, washing methods, column separation methods, evaporation methods, and distillation methods. These methods may be implemented in combination.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited at all by these.

[Example 1]
Connect an introduction tube of methyl acrylate and morpholine and a SUS316 tube (inner diameter 1 mmφ, length 5 m) as a reactor to a 1/16 inch 3-way union manufactured by Swagelok, and adjust the reactor to 25 ° C. Soaked in a water tank.

  Methyl acrylate containing 0.05% by weight of methoxyhydroquinone was introduced into the reactor using a metering pump at a rate of 0.088 g / min and morpholine at a rate of 0.107 g / min. At this time, the average residence time in the reactor was 5 minutes.

  The obtained reaction solution was colorless and transparent, and was analyzed by GC-1700 gas chromatography (manufactured by Shimadzu Corporation; hereinafter referred to as “GC”). As a result, it was found that methyl 3-morpholinopropionate, which is a Michael addition compound, was obtained. The yield was 96 mol%.

[Examples 2 to 6]
The same operation as in Example 1 was performed except that the reaction temperature was 40 ° C., 50 ° C., 60 ° C., 70 ° C., and 75 ° C., respectively.

  The obtained reaction solution was colorless and transparent, and was analyzed by GC. As a result, the yield of methyl 3-morpholinopropionate, which is a Michael addition compound, was 96 mol%, 95 mol%, 95 mol%, 95 mol%, 95 Mol%.

Example 7
The same operation as in Example 1 was carried out except that methyl acrylate containing 0.03% by mass of methoxyhydroquinone was introduced into the reaction system at a rate of 0.061 g / min and morpholine was introduced at a rate of 0.136 g / min. did. At this time, the average residence time in the reactor was 5 minutes.

  The obtained reaction solution was colorless and transparent, and was analyzed by GC. As a result, the yield of methyl 3-morpholinopropionate, which is a Michael addition compound, was 99 mol%.

[Examples 8 to 12]
The same operation as in Example 7 was performed except that the reaction temperature was 40 ° C, 50 ° C, 60 ° C, 70 ° C, and 75 ° C, respectively.

  The obtained reaction solution was colorless and transparent, and was analyzed by GC. As a result, the yield of methyl 3-morpholinopropionate, which is a Michael addition compound, was 99 mol%, 99 mol%, 99 mol%, 99 mol%, 99 mol, respectively. Mol%.

Example 13
The same operation as in Example 1 was carried out except that methyl acrylate containing 0.03% by mass of methoxyhydroquinone was introduced into the reaction system at a rate of 0.061 g / min and pyrrolidine was introduced at a rate of 0.160 g / min. did. At this time, the average residence time in the reactor was 5 minutes.

  The obtained reaction liquid was colorless and transparent, and was analyzed by GC. As a result, the yield of methyl 3-pyrrolidinopropionate, which is a Michael addition compound, was 99 mol%.

Example 14
The same operation as in Example 1 was carried out except that methyl acrylate containing 0.03% by mass of methoxyhydroquinone was introduced into the reaction system at a rate of 0.061 g / min and piperidine was introduced at a rate of 0.158 g / min. did. At this time, the average residence time in the reactor was 5 minutes.

  The obtained reaction liquid was colorless and transparent, and was analyzed by GC. As a result, the yield of methyl 3-piperidinopropionate, which is a Michael addition compound, was 99 mol%.

Example 15
The same operation as in Example 1 was carried out except that methyl acrylate containing 0.03% by mass of methoxyhydroquinone was introduced into the reaction system at a rate of 0.061 g / min and diethylamine was introduced at a rate of 0.192 g / min. did. At this time, the average residence time in the reactor was 5 minutes.

  The obtained reaction liquid was colorless and transparent, and was analyzed by GC. As a result, the yield of methyl 3-diethylaminopropionate, which is a Michael addition compound, was 99 mol%.

A Michael addition compound can be suitably produced, and can be applied to various organic synthesis reagents.

Claims (3)

  A method for producing a Michael addition compound, comprising continuously reacting (meth) acrylic acid esters with a primary or secondary amine compound.   The method for producing a Michael addition compound according to claim 1, wherein a flow reactor is used for the continuous reaction. The method for producing a Michael addition compound according to claim 2, wherein the flow path of the flow reactor has an equivalent diameter of 1 to 50,000 µm.