JP2006206518A - Method for liquid phase oxidation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a safe and efficient method for liquid phase oxidation. <P>SOLUTION: The invention relates to the method for oxidation of an organic compound by bringing the compound into contact with a peroxide comprising use of a flow-through type micro reaction module comprising a micro heat-exchanger, a micro mixer and a micro heat retaining device, and the method comprises a process (1) of preheating a solution of the organic compound and a solution of the peroxide to a set temperature by using the micro heat-exchanger having 1-10,000 μm of equivalent diameter of inside diameter of a flowing pass, a process (2) of contact-mixing both of solutions passed the prescribed process by using the micro mixer having 1-10,000 μm of equivalent diameter of inside diameter of flowing pass, and a process (3) of performing oxidation reaction by keeping the temperature of the mixed solution passed the prescribed process by using the micro heat retaining device having 1-10,000 μm of equivalent diameter of inside diameter of flowing pass, wherein the residence time of the mixture in the process (3) in the micro heat retaining device is within 30 sec and the temperature of the mixture in the micro heat retaining device is regulated within ±2°C of the set temperature in the range of 70-150°C. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a method for oxidizing an organic compound in a liquid phase using a peroxide as an oxidizing agent.

  In general, the reaction proceeds faster the higher the temperature. Therefore, high temperature conditions are considered preferable for promoting the progress of the reaction. However, when oxidizing an organic compound in the liquid phase, increasing the temperature often promotes not only the desired reaction, but also unwanted side reactions. For example, the target product produced by the oxidation reaction is reduced due to excessive oxidation. Therefore, it has been difficult in the past to perform an efficient oxidation reaction at a high temperature.

  In addition, when peroxide is used as an oxidizing agent and an organic compound is oxidized in a liquid phase, there is often a problem of reaction heat generated as the reaction proceeds. When the temperature of the reaction solution rises due to reaction heat, decomposition of the peroxide used as the oxidizing agent is promoted. Furthermore, since the decomposition reaction of the peroxide is also an exothermic reaction, the undesirable decomposition reaction of the oxidant is accelerated. This not only lowers the yield and selectivity of the target oxidation reaction product, but can also cause safety problems in the operation of the reactor, such as runaway reaction. Therefore, in the conventional method, the reaction is carried out while maintaining the temperature of the reaction solution at a relatively low temperature.

  The rate of the oxidation reaction is greatly accelerated even when the concentration of the reactant is high. In order to prevent the reaction from proceeding explosively, a semi-batch type reaction operation such as gradually adding an oxidizing agent from a dropping device is often used.

  As described above, in the conventional method, the oxidation reaction in the liquid phase using peroxide as an oxidizing agent is often performed under a mild condition near room temperature using a low concentration oxidizing agent.

  Performing the oxidation reaction under such a mild condition is an effective means for stably carrying out the operation, but on the other hand, since the reaction takes a long time, The yield is low.

  In some types of oxidation reactions, an undesirable side reaction proceeds mainly under a relatively low temperature condition around room temperature, and a target reaction mainly proceeds under a high temperature condition. For example, in Non-Patent Document 1, a semi-batch reactor is used, and 2-methylnaphthalene and hydrogen peroxide are reacted in an acetic acid solvent in the presence of a strongly acidic ion exchange resin in which palladium is substituted as a catalyst. An example is given. In this case, the selectivity is low near room temperature, which is relatively low, and the selectivity is improved by raising the set temperature of the reactor to about 70 ° C., and the target product is efficiently obtained. However, in the conventional reaction method in which temperature control in the reactor cannot be precisely performed, when the set temperature is higher than 70 ° C., the selectivity is lowered.

  In the case of a semi-batch reactor, the residence time distribution in the reactor is widened, which may cause a reduction in the selectivity of the target reaction product.

  In recent years, research on chemical synthesis reactions using microchannels on the micrometer scale (several μm to several thousand μm) has become active. For example, Patent Document 1 describes a method of reacting an aromatic compound and a reactant (nitrating agent or sulfonating agent) in a liquid phase using a microreactor. In a chemical synthesis reaction using such a minute flow path, high heat exchange efficiency can be obtained, which is effective in a reaction with a large exotherm.

  Patent Document 2 describes a method of reacting an organic carbonyl compound and a peroxide in a liquid phase using an oxidation reaction apparatus comprising a quick mixer, a tubular reactor, and a micro heat exchanger. By using a micro heat exchanger with good heat exchange efficiency, a device for removing reaction heat generated by the oxidation reaction has been made. However, in this method, the tubular reactor portion is only insulated, and the temperature of the reaction liquid varies greatly between the inlet portion and the outlet portion of the reactor.

  Patent Document 3 describes a method of performing Bayer-Billiger oxidation in a liquid phase using a combination of a micro static mixer and a micro tubular reactor. However, this method is carried out under mild conditions around room temperature, and the residence time takes several hours.

S. Yamaguchi, et.al., Bull. Chem. Soc. Jpn., 59,2881-2884 (1986) JP-T-2001-521913 Japanese Patent Laid-Open No. 11-171857 Special Table 2003-527390

  An object of the present invention is to solve the above-mentioned problems in the prior art and to provide a safe and efficient liquid phase oxidation reaction method.

  As a result of intensive research on various oxidation reaction methods, the present inventors have determined that the temperature of the reaction solution in the reactor is set to a high temperature near the boiling point of the solution in the oxidation reaction using peroxide as an oxidizing agent. By setting and precisely controlling to a predetermined temperature during the residence time on the second scale, a safer and more efficient oxidation reaction method was found and the present invention was completed.

That is, the present invention is a flow reaction that performs an oxidation reaction by contacting an organic compound with a peroxide using a flow micro reaction module including a micro heat exchanger, a micro mixer, and a micro incubator,
(A) A step of preheating the organic compound solution and the peroxide solution to a set temperature using a micro heat exchanger having an equivalent inner diameter of the flow path of 1 to 10,000 μm;
(A) a step of contacting and mixing both solutions that have undergone the above-described step using a micromixer having an equivalent diameter of 1 to 10,000 μm of the inner diameter of the flow path; and
(C) a step of keeping the mixed solution having undergone the above step at a set temperature by using a micro incubator having an equivalent diameter of the flow path of 1 to 10000 μm and proceeding an oxidation reaction, the (c) step The residence time of the mixed solution in the micro incubator is within 30 seconds, and the temperature of the mixed solution in the micro incubator in the step (c) is within a range of 70 to 150 ° C. It is a flow-through oxidation method characterized by being controlled within a range of 2 ° C. The equivalent diameter is a value defined by (4 × S / L) in the cross-sectional area S and the cross-sectional perimeter L when the flow path is cut in a cross section perpendicular to the fluid traveling direction.

  According to the present invention, heat of reaction generated during the oxidation reaction can be efficiently removed. Therefore, precise temperature control becomes possible, decomposition of the oxidant due to high temperature can be suppressed, and utilization efficiency of the oxidant can be improved. The yield and selectivity of the target reaction product can be improved, and the stability and safety of the reaction operation are also increased.

  Further, according to the present invention, the reaction can be easily carried out even under severe reaction conditions at a relatively high temperature, which was difficult with the conventional method. Therefore, the reaction rate of the target oxidation reaction can be dramatically improved.

  Further, according to the present invention, it is possible to instantaneously mix a high concentration of reactants (oxidant, reaction substrate, catalyst, etc.) while maintaining safety. Therefore, the reaction time required for dropping the oxidizing agent can be shortened. Moreover, the fact that the concentration of the oxidizing agent, reaction substrate, catalyst, etc. can be set high leads to an improvement in the reaction rate.

  Further, according to the present invention, the reaction start operation and stop operation can be performed quickly. Thereby, since residence time can be controlled in a very short time, the loss | disappearance of the target reaction product by a sequential side reaction can be prevented. The reaction residence time distribution is relatively good, and the selectivity of the reaction product can be improved.

  In addition, according to the present invention, since the initial concentration of the reactant, reaction temperature, residence time, and the like can be precisely controlled, the reaction rate is uniquely determined, which is an effective means for test research such as reaction rate analysis in an oxidation reaction. It becomes.

  In the present invention, the oxidation reaction is carried out by continuously supplying and reacting a solution of an organic compound as a reaction substrate and a solution of a peroxide as an oxidizing agent to a flow-through microreaction module. .

The oxidation reaction step in the present invention includes:
(A) a step of preheating a solution of an organic compound as a reaction substrate and a solution of a peroxide as an oxidizing agent to a set temperature;
(B) A process in which both solutions preheated to a set temperature are contact-mixed to start an oxidation reaction
(C) a step of keeping the mixed reaction solution at a set temperature and proceeding an oxidation reaction;
Consists of.

  BEST MODE FOR CARRYING OUT THE INVENTION The best mode for carrying out the present invention will be described in detail below, but the present invention is not limited to the following embodiment, and various modifications may be made within the scope of the invention. Can do.

  The flow-type micro reaction module used in the present invention includes at least one or more heat exchangers used for the reaction substrate solution in step (a) and one or more micro heat exchangers used in the oxidant solution in step (a). (A) One or more micromixers used in the step, and (c) One or more reaction flow channel microreactors used in the step. It is preferable that the flow-through microreaction module further includes a separator for separating (d) an organic compound that is a reaction substrate and a peroxide that is an oxidizing agent, and terminating the oxidation reaction. In addition, the flow-type micro reaction module may additionally include devices such as a pump for feeding the reaction substrate solution and a pump for feeding the oxidant solution.

  In the present invention, as a flow-type microreaction module used in steps (a) to (c), a micro heat exchanger used in the oxidizing solution in step (a), a micromixer in step (a), and ( C) The flow-type microreactor of the step uses a flow-type reactor having an equivalent diameter of the flow path of 1 to 10000 μm, preferably an equivalent diameter of 20 to 2000 μm, and more preferably an equivalent diameter of 200 to 1000 μm. . The equivalent diameter is a value defined by (4 × S / L) in the cross-sectional area S and the cross-sectional perimeter L when the microreactor is cut in a cross section perpendicular to the traveling direction of the reaction fluid.

  In the present invention, the shape of the flow path of the flow-through microreaction module used in steps (a) to (c) is not limited as long as it is tubular, and the cross-sectional shape perpendicular to the flow direction is circular. It may be a quadrangle. In the present invention, a flow-type micro reaction module having a structure branched into two or more flow paths may be used, or a flow-type micro reaction module having a structure in which two or more flow paths are merged is used. Also good. Although there is no restriction | limiting in particular in the material of the flow-type micro reaction module used in this invention, The material with the corrosion resistance with respect to the reaction solution can be used, and a fluororesin and stainless steel are illustrated.

  In the present invention, a flow-through microreaction module having a micro static mixer as one of its components may be used in step (a) and / or (b) and / or (c). Good. The micro static mixer means a static mixer having a micro space on a micrometer scale (several μm to several thousand μm).

  In the present invention, a flow-type micro reaction module capable of temperature control is used. As a temperature control method, the flow-type micro reaction module may be immersed in a temperature-controlled medium tank such as an oil bath, or an electric heater or a heat medium flow path may be attached to the flow-type micro reaction module. In the present invention, the flow-type micro reaction module is temperature controlled to a set temperature within a range of 70 to 150 ° C, preferably within a range of 100 to 120 ° C. The flow-through microreaction module used in the steps (a) to (c) is preferably immersed in a temperature-controlled medium. Thereby, in (A) process, two types of solutions are heated up to the set temperature. Further, in the steps (a) and (c), the temperature of the reaction mixture in the microreactor is controlled within ± 2 ° C., particularly within ± 1 ° C. from the set temperature. If the reaction temperature is too low, the reaction rate of the target oxidation reaction becomes small, and a sufficient product yield cannot be obtained.

  In the present invention, (d) a separation operation used in the step of separating the organic compound as the reaction substrate and the peroxide as the oxidant and terminating the oxidation reaction, separates the reaction substrate and the product from the oxidant. There is no particular limitation as long as the operation is possible. For example, one substance can be phase-separated by putting the reaction solution into a poor solvent for either substance. A separation operation such as extraction can also be applied.

In the present invention, the time from the mixing operation in step (a) to the separation operation in step (d), that is, the residence time in step (c) is preferably within 30 seconds. If the residence time is too long, an undesirable sequential side reaction proceeds. The residence time is calculated by (reaction volume) ÷ (volume flow rate).

  In this reaction, the pressure condition is not particularly limited, but the inside of the microreactor can be kept at a high pressure in order to prevent vaporization of the solution due to a high temperature condition. As a pressure control method, a back pressure valve or the like may be used at the outlet of the microreactor.

  The oxidation reaction carried out in the present invention is an oxidation reaction in the liquid phase of an organic compound using a peroxide as an oxidizing agent. In the present invention, the organic compound used as a reaction substrate is not particularly limited, and examples thereof include aliphatic hydrocarbon compounds, aromatic hydrocarbon compounds, unsaturated bond compounds, oxygen-containing compounds, nitrogen-containing compounds, and sulfur-containing compounds. Of these, aromatic compounds and unsaturated bond compounds are preferred. In particular, an aromatic compound can be used as the organic compound and oxidized with a peroxide to produce a quinone compound. An example of the quinone compound is 2-methylnaphthalene.

  In the present invention, the peroxide used as the oxidizing agent is not particularly limited, and may be an organic peroxide or an inorganic peroxide. Examples of the organic peroxide include percarboxylic acid, percarboxylic acid ester, hydroperoxide, diacyl peroxide, and dialkyl peroxide. Examples of inorganic peroxides include hydrogen peroxide, sodium peroxide, ammonium peroxide, sodium percarbonate, peroxomonosulfuric acid, peroxodisulfate, and the like. Among these, an equilibrium percarboxylic acid solution is preferable. A plurality of peroxides may be contained in the solution as the oxidizing agent.

  The oxidation reaction in the present invention is performed in a liquid phase state. In this reaction, a solvent that dissolves the reaction substrate may be used, or the reaction substrate itself may be used in an amount of solvent. There is no restriction | limiting in particular as a solvent, Water, an organic solvent, etc. are used.

  In the present invention, a catalyst applicable to the liquid phase oxidation reaction can be used. Examples of the catalyst include an acid catalyst, a complex catalyst, a transition metal oxide catalyst, and a noble metal catalyst. The reaction may be carried out in a liquid phase homogeneous system using a homogeneous catalyst, or the reaction may be carried out in a solid / liquid phase heterogeneous system using a heterogeneous catalyst. Among these, acid catalysts and complex catalysts are preferable as the homogeneous catalyst. In addition, the heterogeneous catalyst is filled in a micro incubator. Further, the micromixer may be filled with a heterogeneous catalyst. As the catalyst, a palladium compound is particularly preferable.

  Next, the present invention will be described more specifically with reference to examples. However, the present invention is not limited by these examples.

Example 1
The apparatus shown in FIG. 1 was used as a flow-through microreaction module. Two preheating tubes 1a and 1b (inner diameter 1000 μm, length 1 m, material is stainless steel SUS-316), static micromixer 2 (Single Mixer manufactured by IMM, Germany, channel width is 30 μm) Connected to the entrance. In addition, one reaction tube 3 (inner diameter 1000 μm, length 1 m, material is stainless steel SUS-316) was connected to the outlet of the static micromixer. A back pressure valve 4 (manufactured by Upchurch, USA, 0.69 MPa) was attached to the outlet of the reaction tube 3. In the above micro reaction module, connectors for high performance liquid chromatography are used to connect each device, so it can be easily installed and removed, and tubes can be easily connected even when trouble such as blockage occurs. Can be exchanged.

  The reaction substrate solution and the oxidant solution were fed using two liquid feed pumps 5a and 5b for high performance liquid chromatography (LC-10Ai manufactured by Shimadzu Corporation) and introduced into the above-described micro reaction module. As the substrate solution, 2-methylnaphthalene was dissolved in glacial acetic acid and palladium acetate was dissolved as a catalyst (molar ratio of 2-methylnaphthalene, acetic acid and palladium acetate was 1: 35: 0.007, 2-methyl Naphthalene content 6.3% by weight) was fed to the reactor. As the oxidizer solution, 60% hydrogen peroxide solution, glacial acetic acid and concentrated sulfuric acid are mixed in advance (the molar ratio of hydrogen peroxide, acetic acid and sulfuric acid before mixing is 1: 12.6: 0.9). The equilibrated peracetic acid solution (the content of peracetic acid after equilibration was 8.6% by weight and the hydrogen peroxide content was 0.2% by weight) was used. The molar ratio of 2-methylnaphthalene and peracetic acid was 1: 3, and the flow rates of the two pumps 5a and 5b were set so that the residence time was 18 seconds.

  The above-described flow-type micro reaction module was immersed in an oil bath 8 (the inside of the oil bath was sufficiently stirred) with the reaction temperature set to 70 ° C. to carry out the reaction. When the liquid temperature in the reaction tube was measured, both the inlet and outlet of the reaction tube were within a temperature range of 70 ° C. to ± 1 ° C. or less in the thermostatic chamber. Moreover, when the behavior of the effluent from the outlet of the reaction tube was observed, no generation of gas was confirmed.

  A certain amount of the effluent from the reaction tube outlet was weighed into a glass container 7 in which cold water had been put in advance, and the reaction substrate and reaction product were precipitated as solids, and then extracted with benzene. When the extracted organic phase was analyzed using gas chromatography (GC-17A manufactured by Shimadzu Corporation), 2-methyl-1,4-naphthoquinone was obtained as a main product. In addition, 6-methyl-1,4-naphthoquinone was also detected as a by-product. Residual 2-methylnaphthalene and produced 2-methyl-1,4-naphthoquinone were quantified by an internal standard method. The results are shown in Table 1. The conversion rate of 2-methylnaphthalene was 24.5%, the yield of 2-methyl-1,4-naphthoquinone was 11.6%, and the selectivity of 2-methyl-1,4-naphthoquinone was 47.2%. It was.

The conversion rate, yield and selectivity were calculated from the number of moles of supplied 2-methylnaphthalene, remaining 2-methylnaphthalene and produced 2-methyl-1,4-naphthoquinone by the following formula.
Conversion (%) = {(supplied 2-methylnaphthalene)-(residual 2-methylnaphthalene)} / (supplied 2-methylnaphthalene) × 100
Yield (%) = (generated 2-methyl-1,4-naphthoquinone) / (2-methylnaphthalene supplied) × 100
Selectivity (%) = (generated 2-methyl-1,4-naphthoquinone) / {(supplied 2-methylnaphthalene)-(residual 2-methylnaphthalene)} × 100

Example 2
The same operation as in Example 1 was performed except that the reaction temperature was set to 100 ° C. and the residence time was set to 6 seconds. The results are shown in Table 1.

Example 3
The same operation as in Example 1 was performed except that the reaction temperature was set to 115 ° C. and the residence time was set to 3 seconds. The results are shown in Table 1.
Although the reaction was carried out by changing the reaction temperature to 70 ° C., 100 ° C., and 115 ° C., the selectivity did not decrease even when the high temperature state close to the boiling point of the solution was maintained.

Comparative Example 1
The same operation as in Example 1 was performed except that the reaction temperature was set to 30 ° C. and the residence time was set to 240 seconds. The results are shown in Table 1. The conversion rate of 2-methylnaphthalene was 25.8%, the yield of 2-methyl-1,4-naphthoquinone was 5.8%, and the selectivity of 2-methyl-1,4-naphthoquinone was 22.4%. It was. Compared with the residence time which shows the conversion rate equivalent to Examples 1-3, the yield and the selectivity fell.

1 shows a schematic diagram of a flow-through microreaction module suitable for use in the method of the present invention.

Explanation of symbols

1a Reaction substrate heat exchange tube 1b Oxidant heat exchange tube 2 Static micromixer 3 Reaction tube 4 Back pressure valve 5a Reaction substrate feed pump 5b Oxidant feed pump 6a Reaction substrate storage container 6b Oxidant storage Container 7 Reaction liquid separation container 8 Constant temperature bath

Claims (7)

Using a flow-type micro reaction module comprising a micro heat exchanger, a micro mixer, and a micro-heater, a flow-type reaction in which an organic compound is brought into contact with a peroxide to perform an oxidation reaction,
(A) A step of preheating the organic compound solution and the peroxide solution to a set temperature using a micro heat exchanger having an equivalent inner diameter of the flow path of 1 to 10,000 μm;
(A) a step of contacting and mixing both solutions that have undergone the above-described step using a micromixer having an equivalent diameter of 1 to 10,000 μm of the inner diameter of the flow path; and
(C) a step of keeping the mixed solution having undergone the above step at a set temperature by using a micro incubator having an equivalent diameter of the flow path of 1 to 10000 μm and proceeding an oxidation reaction, the (c) step The residence time of the mixed solution in the micro incubator is within 30 seconds, and the temperature of the mixed solution in the micro incubator in the step (c) is within a range of 70 to 150 ° C. A flow-through oxidation method characterized by being controlled within a range of 2 ° C.   The process according to claim 1, characterized in that the solution of peroxide is an equilibrium percarboxylic acid solution.   The method according to claim 1, wherein a palladium catalyst is used in (c).   The method according to claim 1, wherein an aromatic compound is used as the organic compound to produce a quinone compound.   The method according to claim 4, wherein 2-methylnaphthalene is used as the organic compound.   The method according to claim 1, wherein an equivalent diameter of an inner diameter of a flow path of the micro-incubator is 20 to 2000 μm.   The method according to claim 1, wherein the temperature of the mixed solution in the micro-incubator is controlled within a range of ± 2 ° C from a set temperature of 100 to 120 ° C.

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