JP2005089440A - Method for producing ester - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an excellent method for producing an ester by using a catalyst without showing any corrosive property, capable of being recovered and recycled and having a high activity. <P>SOLUTION: This method for producing the ester is provided by performing the reaction of a carboxylic acid with an olefin in the presence of a solid catalyst consisting of a meso-porous material containing a sulfonic acid group. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a method for producing an ester, in which a carboxylic acid is reacted with another raw material in the presence of an acid catalyst.

  Esters are used as various chemical products and their intermediates, and various methods are used for their synthesis. In addition, when synthesizing intermediates for pharmaceuticals and agricultural chemicals, when reacting a compound having many functional groups, the carboxylic acid moiety is tertiary-butylated to form an ester, which is protected and selectively reacted. Also, esterification techniques are useful.

As a general example of the esterification method, a method of producing an ester by reacting a carboxylic acid and an alcohol in the presence of an acid catalyst is known.
In this case, a homogeneous catalyst such as sulfuric acid or paratoluenesulfonic acid is generally used as the acid catalyst. However, homogeneous catalysts have problems such as being unable to be recovered and being corrosive.

Therefore, although application of a solid acid catalyst has been attempted, for example, when zeolite or the like is used, since the pore diameter is as small as several angstroms, the substrates that can be reacted are extremely limited.
Therefore, an attempt has been made to introduce a sulfonic acid group, which is a homogeneous catalyst component, into mesoporous silica having a large pore diameter and use it as a solid catalyst. For example, Non-Patent Document 1 describes that mesoporous silica into which a sulfonic acid group is introduced is used when esterifying a carboxylic acid with an alcohol.

As another example of the esterification method, a method of producing an ester by reacting a carboxylic acid and an olefin in the presence of an acid catalyst is known.
In this case, a homogeneous catalyst such as sulfuric acid is generally used as the acid catalyst. For example, Non-Patent Document 2 describes a method of reacting a carboxylic acid with butene using sulfuric acid as a catalyst in the process of peptide synthesis to form an ester by tertiary butylation.

Journal of Catalysis, 182, 156 (1999) Journal of American Chemical Society, 82, 3359 (1960)

However, in the case of a method of reacting a carboxylic acid and an alcohol, mesoporous silica into which a sulfonic acid group described in Non-Patent Document 1 is introduced has a lower catalytic activity compared to paratoluenesulfonic acid or the like that is a homogeneous catalyst. There was a problem.
Further, in the technique of reacting a carboxylic acid and an olefin, the technique of Non-Patent Document 2 has problems such that the catalyst cannot be recovered and corrosive because a homogeneous sulfuric acid is used as a catalyst.

Therefore, there has been a demand for a catalyst that is used when producing an ester from a carboxylic acid as a raw material, has no corrosive properties, can be recovered and recycled, and has a high activity.
The present invention has been made in view of the above-described problems. That is, an object of the present invention is to provide an excellent method for producing an ester using a catalyst which is not corrosive, can be recovered and recycled, and has a high activity.

  As a result of intensive studies to solve the above problems, the present inventor used an olefin as a reaction substrate when esterifying a carboxylic acid and used a mesoporous material having a sulfonic acid group as a catalyst, rather than a homogeneous catalyst. The inventors found that high activity can be obtained and completed the present invention. This is a surprising finding because it has been conventionally believed that the activity decreases when a homogeneous catalyst is immobilized.

  That is, the gist of the present invention resides in a method for producing an ester, characterized in that an ester is produced by reacting a carboxylic acid with an olefin in the presence of a solid catalyst made of a mesoporous material having a sulfonic acid group (claim). Item 1).

At this time, the mesoporous material preferably contains at least mesoporous silica.
The molar ratio M / Si between the elements M and Si other than O and Si contained in the mesoporous silica is preferably 0.5 or less (Claim 3).

The sulfonic acid group is preferably bonded to the mesoporous material via a divalent hydrocarbon group (claim 4).
Moreover, it is preferable that content of the sulfonic acid group of this mesoporous material is 0.1 mmol / g or more and 5 mmol / g or less (Claim 5).

  According to the present invention, when an ester is produced using a carboxylic acid as a raw material, an olefin is used as a reaction substrate, and a mesoporous material having a sulfonic acid group is used as a catalyst, so that it is not corrosive and can be recovered and recycled. High activity can be obtained in the presence of a simple catalyst.

Hereinafter, the present invention will be described in more detail.
The ester production method of the present invention is characterized in that an ester is produced by reacting a carboxylic acid with an olefin in the presence of a solid catalyst made of a mesoporous material having a sulfonic acid group.

<Solid catalyst>
In the ester production method of the present invention, a solid catalyst made of a mesoporous material having a sulfonic acid group (hereinafter, appropriately referred to as “solid catalyst of the present invention”) is used.
The mesoporous material refers to a porous material having mesopores. A mesopore means a pore larger than a micropore and smaller than a macropore, specifically, a pore usually having a diameter of 2 nm or more and 50 nm or less.

Specific surface area The specific surface area of the mesoporous material according to the ester production method of the present invention (hereinafter referred to as the mesoporous material used in the present invention as appropriate) is not particularly limited, but is usually 400 m ² / g or more, preferably 500 m ² / g or more, More preferably, it is 600 m ² / g or more, and usually 2000 m ² / g or less. Since a large number of sulfonic acid groups can be introduced, a larger specific surface area is preferable. When the specific surface area is smaller than this range, a sufficient amount of sulfonic acid groups as a catalyst cannot be contained. On the other hand, if the specific surface area is larger than this range, sufficient strength as a solid catalyst cannot be obtained, and there is a possibility that recovery becomes difficult.
In addition, although the measuring method of a specific surface area is arbitrary, it can measure by BET method etc. by nitrogen gas adsorption / desorption, for example.

-Moderate pore diameter The mode pore diameter _Dmax of the mesoporous material used in the present invention is usually 2 nm or more, preferably 2.2 nm or more, more preferably 2.5 nm or more, and usually 50 nm or less, preferably 20 nm or less, More preferably, it is 10 nm or less. When the mode pore diameter D _max is smaller than the above range, a small substrate that can enter the pore can react, but a large substrate that cannot enter the pore cannot react, It cannot be an ester. Furthermore, when the pores are smaller than the above range, the pores are clogged by by-products such as oligomers generated by side reactions and the like, and the activity deterioration tends to become severe. Further, if the mode pore diameter _Dmax is larger than the above range, there is a possibility that a sufficiently wide reaction field cannot be secured.
In addition, although the measuring method of mode pore diameter _Dmax is arbitrary, for example, it can measure by BJH method etc. by nitrogen gas adsorption / desorption.

In addition, the mesoporous material used in the present invention usually has a pore volume having a diameter within a range of ± 20% of the value of the most frequent pore diameter _Dmax , with respect to a pore volume having a diameter of 1 nm or more. It is preferably 70% or more, preferably 75% or more, and more preferably 80% or more. This means that the diameters of the pores of the mesoporous material used in the present invention are uniform around the most frequent pore diameter D _max , that is, the pore diameter distribution is extremely narrow (sharp). The upper limit of the ratio value is not particularly limited, but is usually 99% or less. If the pore size distribution is small, the structure of the mesoporous material used in the present invention becomes uniform, and the space in the pores can be used effectively.

  In addition, when the mesoporous material used in the present invention contains mesoporous silica described later, regular mesopore spatial coordination occurs because the mesoporous silica has uniform pores, There can be no hydrophobicity. For the hydrophobicity thus generated, see, for example, Microporous Materials, 2, (1993), pages 17-26. The point that the mesoporous material used in the present invention preferably has hydrophobicity will be described later.

-Pore volume The pore volume of the mesoporous material used in the present invention is usually 0.3 ml / g or more, preferably 0.4 ml / g or more, more preferably 0.5 ml / g or more, and usually 1 ml / g or less. , Preferably 0.9 ml / g or less, more preferably 0.8 ml / g or less. If the pore volume is smaller than the above range, a sufficient reaction field may not be provided. On the other hand, if the pore volume is larger than the above range, the solid catalyst cannot have a sufficient strength, and there is a possibility that the recovery becomes difficult.

-Hydrophobicity The mesoporous material used in the present invention preferably has high hydrophobicity.
In the ester production method of the present invention, since the substrate is an organic substance, the substrate is adsorbed to the hydrophobic field (the hydrophobic portion of the solid catalyst). Therefore, when a mesoporous material having an acid point (that is, a sulfonic acid group) in a hydrophobic field is used as a catalyst, the reaction efficiency of the substrate is improved.
In addition, in a catalyst having low hydrophobicity such as silica, acid sites may be poisoned by water and the catalyst performance may be deteriorated. However, in a catalyst having high hydrophobicity, water is not brought close to acid sites as described above. There is no risk of poisoning.

  Specific examples of the mesoporous material used in the present invention include mesoporous silica and activated carbon. Among these, mesoporous silica is preferable because it satisfies the above-mentioned preferable characteristics in a well-balanced manner.

  Conventionally, catalysts with sulfonic acid groups immobilized on silica have been known. However, ordinary silica has a small amount of isolated hydroxyl groups on the surface, so surface reactivity is poor. For this reason, sulfonic acid groups are immobilized on silica. With the prepared catalyst, the amount of sulfonic acid groups introduced into silica was insufficient. On the other hand, mesoporous silica having a large amount of isolated hydroxyl groups on the surface and high surface reactivity can introduce sulfonic acid groups efficiently and exhibits sufficient activity as a catalyst.

-Mesoporous silica Mesoporous silica as a mesoporous material used in the present invention (hereinafter referred to as mesoporous silica used in the present invention as appropriate) is, for example, a mesoporous material described on page 13 of "Science and Engineering of Zeolite" (Kodansha 2000). This is mesoporous silica. That is, it refers to silica having a pore diameter intermediate between micropores and macropores and usually having pores having a pore diameter of 2 nm to 50 nm.
Further, in the present invention, silica refers to silicic anhydride and is represented by the chemical formula of SiO ₂ .

-Constituent element of mesoporous silica The mesoporous silica used for this invention may contain elements other than O and Si. However, when many elements other than O and Si are contained, the mesoporous silica used in the present invention usually becomes hydrophilic, so care must be taken.

  Specific examples of elements other than O and Si that may be contained in the mesoporous silica used in the present invention (hereinafter, this element is represented by “M”) include elements from group 4 to group 14 of the normal periodic table. Preferably, Al, B, Ga, Ti, Zn, V, Fe, Mn, Co, Zr, Nb, Sn, etc. are mentioned. More preferably, Al, B, Ga, Ti, Zn, Fe are included. Can be mentioned.

  Further, the molar ratio (M / Si) of M to Si of the mesoporous silica used in the present invention is usually 0 or more, usually 0.5 or less, preferably 0.3 or less, more preferably 0.1 or less. is there. A smaller M content is preferred because of higher hydrophobicity.

-Method for synthesizing mesoporous silica The method for synthesizing mesoporous silica used in the present invention is not particularly limited as long as it can produce mesoporous silica having the above-mentioned characteristics. Preferred examples include surfactant molecule assembly as a template. And a method of synthesizing using a mesostructure composed of a body and an inorganic species (silica) as a precursor. By this method, uniform pores are formed as described above, and regular spatial coordination of mesopores is generated, so that it can have hydrophobicity not found in ordinary silica.

Specific Examples of Mesoporous Silica Specific examples of mesoporous silica used in the present invention include mesoporous silica described in pages 17 to 26 of the above-mentioned Microporous Materials, 2, (1993), that is, FSM-16. MCM-41, MCM-48, MCM-50, SBA-1, SBA-2, SBA-3, HMS, MSU-1, MSU-2, SBA-11, SBA-12, MSU-V, MSU-3, SBA-15, SBA-16, etc. are mentioned.

· Mesoporous material used in the sulfonic acid groups present invention has a sulfonic acid group (-SO ₃ H).
The sulfonic acid group is not limited in any state as long as it is fixed to the mesoporous material used in the present invention, but is usually fixed to the mesoporous material via a divalent hydrocarbon group. It is preferable that That is, it is preferable that the sulfonic acid group is fixed as shown in the following general formula (1) to the mesoporous material used in the present invention.

Q-R-SO ₃ H ··· formula (1)
In the general formula (1), Q represents a mesoporous material used in the present invention, and R represents a divalent hydrocarbon group. By fixing the sulfonic acid group to the mesoporous material via the divalent hydrocarbon group R, the hydrophobicity of the mesoporous material used in the present invention can be increased.

Although there is no restriction | limiting in particular about bivalent hydrocarbon group R, Usually, an alkylene group or an arylene group is preferable.
The carbon number of the divalent hydrocarbon group R is usually 1 or more, preferably 3 or more, and usually 8 or less, preferably 7 or less.
In addition, the divalent hydrocarbon group R may be either one having a substituent or one having no substituent, but usually one having no substituent is used.
Specific examples of R include methylene group, ethylene group, propylene group, butylene group, hexylene group, heptylene group, and phenylene group.

-Content of sulfonic acid group The content of the sulfonic acid group of the mesoporous material used in the present invention is usually 0.1 mmol / g or more, preferably 0.5 mmol / g or more, more preferably 1 mmol / g or more, and usually 5 mmol / g or less. The higher the sulfonic acid group content, the higher the catalytic activity. Therefore, it is preferable that the amount of the sulfonic acid group is large.

-Method for introducing sulfonic acid group into mesoporous material The method for introducing a sulfonic acid group into the mesoporous material used in the present invention is not particularly limited and can be carried out by any known method. Those that can be introduced in large numbers are preferred.

Here, the example of the method of introduce | transducing a sulfonic acid group with respect to mesoporous silica is shown.
Introduction method example 1:
Mesoporous silica is placed in water to hydrate the mesoporous silica. Thereafter, toluene is added, heated, distilled off as an azeotrope, and dehydrated by repeating this operation.

Thereafter, a sulfonic acid source represented by the following general formula (2) is added, the mixture is heated to reflux, and then the produced alcohol is distilled off. Thereafter, the solid is filtered off and washed, and the resultant is put into a mixture of hydrogen peroxide and methanol, stirred, oxidized, filtered and washed to introduce sulfonic acid groups.
_{^{(R 1 O) n -Si (}} X) 3-n -R-SO 3 H ··· formula (2)
In the general formula (2), R represents the same as defined in the general formula (1). R ¹ O represents an alkoxy group having 1 to 5 carbon atoms or an aryloxy group, preferably a group selected from a methoxy group, an ethoxy group, a propoxy group, a butoxy group, and a phenoxy group, and more preferably a methoxy group Or represents an ethoxy group. X represents a hydrogen atom or a halogen atom, and preferably represents chlorine or bromine. N represents an integer of 1 to 3, and 3 is particularly preferable.

Specific examples of the sulfonic acid source represented by the general formula (2) include (CH ₃ O) ₃ —Si—CH ₂ CH ₂ —SO ₃ H, (C ₂ H ₅ O) ₃ —Si—CH ₂ CH _2. —SO ₃ H, (CH ₃ O) ₃ —Si—CH ₂ CH ₂ CH ₂ —SO ₃ H, (C ₂ H ₅ O) ₃ —Si—CH ₂ CH ₂ CH ₂ —SO ₃ H, (CH _{3 O) 3 -Si-CH 2 CH} 2 CH 2 CH 2 -SO 3 H, and the like _{(C 2 H 5 O) 3} -Si-CH 2 CH 2 CH 2 CH 2 -SO 3 H.

Introduction method 2:
Further, after dehydrating mesoporous silica in the same manner as in the introduction method 1 described above, instead of adding the sulfonic acid source represented by the general formula (2), a sulfonic acid source represented by the following general formula (3) is added, After introducing SH groups into mesoporous silica, the SH groups may be oxidized to form sulfonic acid groups.
_{^{(R 1 O) n -Si (}} X) 3-n -R-SH ··· formula (3)
In general formula (3), R represents the same as defined in general formula (1), and R ¹ O, X, and n represent the same as defined in general formula (2). .

Specific examples of the sulfonic acid source represented by the general formula (3) include (CH ₃ O) ₃ —Si—CH ₂ CH ₂ —SH, (C ₂ H ₅ O) ₃ —Si—CH ₂ CH ₂ —SH. _{, (CH 3 O) 3 -Si} -CH 2 CH 2 CH 2 -SH, (C 2 H 5 O) 3 -Si-CH 2 CH 2 CH 2 -SH, (CH 3 O) 3 -Si-CH 2 CH ₂ CH ₂ CH ₂ -SH, and the like _{(C 2 H 5 O) 3} -Si-CH 2 CH 2 CH 2 CH 2 -SH.

  In addition to immobilizing sulfonic acid groups on mesoporous silica using a sulfonic acid source as in the introduction methods 1 and 2 described above, at least one of the above general formula (2) and general formula (3) is shown. A mesoporous silica having a sulfonic acid group may be produced by using a sulfonic acid source as a raw material for the mesoporous silica used in the present invention.

<Esterification reaction substrate>
In the ester production method of the present invention, carboxylic acid and olefin are used as substrates, and these carboxylic acid and olefin are reacted to produce an ester. Hereinafter, each of carboxylic acid and olefin will be described.

-Carboxylic acid If the carboxylic acid used for this invention is an organic compound which has a carboxy group, there will be no restriction | limiting in particular in the kind, According to the kind of target ester, arbitrary things can be used.
Moreover, there is no restriction | limiting in particular about the property of carboxylic acid used for this invention, Solid or liquid may be sufficient. However, when a solvent is used for the reaction, it is preferably one that dissolves in the solvent.

Specifically, the molecular weight of the carboxylic acid used in the present invention is usually 500 or less, preferably 300 or less, more preferably 200 or less.
Moreover, carbon number of the carboxylic acid used for this invention is 50 or less normally, Preferably it is 30 or less, More preferably, it is 20 or less.
In addition, the number of carboxy groups in one molecule of the carboxylic acid used in the present invention is usually 3 or less, preferably 2 or less, and more preferably 1.

-Olefin Normally, alcohol etc. are used as a reaction substrate which esterifies carboxylic acid, but when alcohol is used, water will be generated with esterification. Further, the esterification reaction is an equilibrium reaction, and the generated water blocks the acid sites of the solid catalyst and causes catalyst poisoning. On the other hand, if olefin is used as a reaction substrate, no water is produced even if the esterification reaction proceeds. Therefore, in the present invention, olefin is used as a reaction substrate.

  The olefin used in the present invention is not particularly limited, and any olefin may be used as long as it has a molecular weight that contacts the acid sites inside the mesoporous material used in the present invention. However, considering the reactivity, those having a small number of carbon atoms are preferable.

The molecular weight of the olefin used in the present invention is usually 200 or less, preferably 150 or less, more preferably 100 or less.
The carbon number of the olefin used in the present invention is usually 10 or less, preferably 8 or less, more preferably 5, most preferably 4 or less.
The number of olefin double bonds used in the present invention is usually 2 or less, preferably 1.

  Specific examples of the olefin used in the present invention include ethylene, propylene, 1-butene, 2-butene, isobutene, 1-hexene, 2-ethyl-1-hexene, 1-octene, 2-methyl-1-butene, 2 -Ethyl-1-butene, cyclohexene, cyclooctene and the like can be mentioned, among which propylene, isobutene, 1-butene, 2-butene and the like are preferable, and isobutene is more preferable.

<Esterification reaction>
In the ester production method of the present invention, an ester is produced by reacting a carboxylic acid and an olefin in the presence of the above-described solid catalyst of the present invention.

-Reaction Phase and Method In the ester production method of the present invention, the esterification reaction may be carried out in any of a gas phase, a liquid phase, and a gas-liquid mixed phase, and may be appropriately selected according to the properties of the reaction substrate. The reaction is preferably carried out in the liquid phase. The reaction method is not particularly limited, and may be a batch method or a continuous method, and may be appropriately selected according to the properties of the reaction substrate. However, when the reaction is performed in a liquid phase, the reaction is performed in a batch method. Hereinafter, a case where the reaction is performed in a batch mode in the liquid phase will be described.

  The amount of the olefin used is a molar ratio with respect to the carboxylic acid and is usually 5 or more, preferably 10 or more, and usually 200 or less, preferably 100 or less. If the amount of olefin used is less than this range, the esterification reaction may not proceed sufficiently, such being undesirable. On the other hand, if the amount of olefin used exceeds this range, the ester yield reaches its peak, which is also not preferable.

  The amount of the solid catalyst used is a weight ratio with respect to the carboxylic acid, and is usually 10% by weight or more, preferably 20% by weight or more, and usually 300% by weight or less, preferably 200% by weight or less. If the amount of the solid catalyst used is less than this range, the esterification reaction may not proceed sufficiently, such being undesirable. On the other hand, if the amount of the solid catalyst used exceeds this range, the ester yield reaches its peak, which is not preferable.

-Solvent In the ester production method of the present invention, a solvent may or may not be used, but is preferably used when the reaction substrate is a solid.
When a solvent is used, it is necessary to select a solvent inert to the esterification reaction according to the substrate used. Moreover, it is preferable to select a solvent that dissolves the substrate to be used.

  Specific examples of the solvent used in the ester production method of the present invention include aromatic hydrocarbons such as benzene and toluene; aliphatic hydrocarbons such as tetralin and cyclohexane; ethers such as diethyl ether, tetrahydrofuran and dioxane; acetone Ketones such as methyl ethyl ketone; esters such as ethyl acetate and butyl adipate; aliphatic halogenated hydrocarbons such as dichloromethane; amides such as DMF and NMP; sulfones such as dimethyl sulfone and sulfolane; dimethyl sulfoxide and the like Sulfoxides; and nitriles such as acetonitrile, benzonitrile, adiponitrile, and the like. Among these, aromatic hydrocarbons, aliphatic hydrocarbons, and ethers are preferable, and ethers are more preferable.

  The amount of the solvent used is not particularly limited as long as the reaction substrate can be sufficiently dissolved, but is usually 0% by weight or more, preferably 100% by weight or more, and usually 10000% by weight in terms of the weight ratio to the carboxylic acid. Hereinafter, it is preferably 1000% by weight or less.

-Method of esterification reaction The reaction method may be a known method and is not particularly limited. However, since the vapor pressure of the olefin used may be high, the reaction is usually carried out using a pressure vessel. The solid catalyst, reaction substrate (carboxylic acid and olefin), and solvent are preferably dried before use so as not to absorb moisture. Further, when the vapor pressure of olefin is high, a method of introducing the reactor at a low temperature may be used.

  In the reactor, a reaction solution comprising a carboxylic acid and an olefin as reaction substrates and a solvent used as necessary is added, and the above-mentioned solid catalyst is added, and the reaction is carried out while stirring the reaction solution. The order of addition of the reaction substrate, solvent, and solid catalyst is not particularly limited, and may be added to the reactor in any order.

The temperature during the esterification reaction is usually 5 ° C. or higher, preferably 10 ° C. or higher, more preferably 20 ° C. or higher, and usually 150 ° C. or lower, preferably 100 ° C. or lower, more preferably 80 ° C. or lower.
The pressure during the reaction may be normal pressure, or may be performed under pressure by appropriately adjusting the pressure by adding an inert gas such as nitrogen.
Although depending on the temperature of the reaction, the reaction time is usually 10 minutes or more, preferably 1 hour or more, more preferably 3 hours or more, and usually 50 hours or less, preferably 40 hours or less, more preferably 30 hours or less. is there.

  After completion of the reaction, the reaction solution is cooled, the solid catalyst of the present invention is separated by a technique such as filtration, and a product is obtained by an operation such as distillation. When examining the reaction results, gas chromatography analysis may be performed by adding an internal standard in the presence of the solid catalyst of the present invention. The separated solid catalyst of the present invention can be dried and used repeatedly as necessary.

  Further, the yield of the ester by the above-described ester production method of the present invention varies depending on the reaction conditions, but is usually 30% or more, preferably 50% or more, more preferably 80% or more.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples unless it exceeds the gist.

I. When producing 3-phenylpropionic acid t-butyl ester [1. Synthesis of Mesoporous Silica Si-MCM41]
Solution A was prepared by gradually adding 19.00 g of n-hexadecyltrimethylammonium bromide to 56.92 g of distilled water at 50 ° C. while stirring with a stirrer.

Next, 21.92 g of water glass No. 3 (Na ₂ : 9.6 wt%, SiO ₂ : 29.4 wt%) (manufactured by Nippon Chemical Industry Co., Ltd.) was taken and stirred with a stirrer, diluted sulfuric acid (concentrated) 1.35 g of sulfuric acid diluted with distilled water to 46.65 g) was added, followed by stirring for 5 minutes. This was designated as Solution B.

  While adding Solution B little by little to Solution A, the mixture was stirred with a glass rod and further stirred for 15 minutes. Next, 22 g of distilled water was added and stirred until the bubbles disappeared. Here, the pH was adjusted to 9.70 using 1 mmol / l sulfuric acid. This solution was transferred to a 500 ml Teflon (registered trademark) container and placed in a constant temperature bath at 100 ° C. Ten days later, the product was taken out from the thermostatic chamber, allowed to cool at room temperature, and then filtered. The obtained solid was washed 11 times with 150 ml of distilled water at 50 ° C. and filtered. The white solid thus obtained was baked in air at 540 ° C. for 6 hours to obtain Si-MCM41.

From the results of nitrogen adsorption, the BET specific surface area was 1010 m ² / g (FIG. 1), and the most frequent pore diameter D _max determined by the BJH method was 29.0 mm (FIG. 2). Further, the volume of the pores having a diameter within the range of ± 20% of the value of the mode pore diameter D _max was 80% or more with respect to the volume of the pores having a diameter of 1 nm or more. 1 is a nitrogen adsorption curve measured for Si-MCM41, and FIG. 2 is a BJH plot measured for Si-MCM41.

[2. Synthesis of Mesoporous Silica Si-FSM16]
10 g of sodium δ-disilicate was dispersed in 100 ml of ion-exchanged water, and then mixed with 100 ml of 0.2 M aqueous solution of n-hexadecyltrimethylammonium bromide to prepare a solution. Then, this solution was heated and stirred at 70 ° C. for 3 hours, and then 2N hydrochloric acid was slowly added dropwise to adjust the pH of the solution to 8.5, followed by further stirring for 3 hours. Subsequently, the solution was allowed to cool to room temperature, and the resulting suspension was filtered, washed and dried to obtain a solid, which was calcined in air at 550 ° C. for 6 hours to obtain Si-FSM16. .

From the results of nitrogen adsorption, the BET specific surface area was 1060 m ² / g (FIG. 3), and the most frequent pore diameter D _max determined by the BJH method was 27.2 mm (FIG. 4). In addition, the volume of the pores having a diameter within the range of ± 20% of the value of the mode pore diameter D _max was 80% or more with respect to the volume of the pores having a diameter of 1 nm or more. 3 is a nitrogen adsorption curve measured for Si-FSM16, and FIG. 4 is a BJH plot measured for Si-FSM16.

[3. Introduction of sulfonic acid group (A)]
(Introduction of sulfopropyl group into hydrated mesoporous silica)
1 g of Si-MCM41 was suspended in 140 ml of distilled water, refluxed at 120 ° C. for 3 hours, and filtered. The obtained product was suspended in 85 ml of anhydrous toluene, and an azeotropic mixture of toluene and water was distilled off at 130 ° C. After 30 ml of this azeotrope was distilled off, 30 ml of anhydrous toluene was added. This operation was repeated a total of 3 times.

  Thereafter, (3-mercaptopropyl) trimethoxysilane ((3-Mercaptopropyl) trimethylsilane: hereinafter abbreviated as MPTS) 5.714 g (29.12 mmol) was added, and the mixture was refluxed at 130 ° C. for 3 hours. Was distilled off. This was filtered and washed with distilled water (150 ml) followed by diethyl ether (150 ml). The obtained product was suspended in a mixed solution of 3 g of 30% hydrogen peroxide water and 8.75 g of methanol, stirred for 24 hours at room temperature, and then filtered. After washing with 150 ml each of distilled water and ethanol, it was dried to introduce a sulfopropyl group. This is expressed as SP-MCM (A).

Moreover, the sulfopropyl group was introduce | transduced into Si-FSM16 by the method similar to this. This is expressed as SP-FSM (A).
About SP-MCM (A) and SP-FSM (A), each was alkali-melted using sodium carbonate and subjected to elemental analysis by ICP emission analysis to determine the amount of sulfonic acid groups.

[4. Introduction of sulfonic acid group (B)]
(Introduction of sulfopropyl group into vacuum-dried mesoporous silica)
After 0.944 g of Si-MCM41 was vacuum dried at 250 ° C. for 1 hour, it was suspended in 85 ml of anhydrous toluene. Thereafter, 2.115 g (10.8 mmol) of MPTS was added and refluxed at 130 ° C. for 3 hours, and then a trap was attached to distill off the produced alcohol. This was filtered and washed with 150 ml each of distilled water and diethyl ether. The obtained product was suspended in a mixed solution of 3 g of 30% hydrogen peroxide water and 8.75 g of methanol, stirred for 24 hours at room temperature, and then filtered. After washing with 150 ml each of distilled water and ethanol, it was dried to introduce a sulfopropyl group. This is expressed as SP-MCM (B).

Furthermore, this and Si-FSM16 a similar manner, and, in the amorphous silica (Davison # 57) sulfopropyl introduced respectively, each SP-FSM (B), and the SP-SiO _2. SP-MCM (B), SP-FSM (B), and SP-SiO ₂ were each alkali-melted using sodium carbonate and subjected to elemental analysis by ICP emission analysis to determine the amount of sulfonic acid groups.

[5. Production of ester]
<Example 1>
SP-MCM (A) was vacuum dried at 40 ° C. for 1 hour. To a pressure-resistant test tube, 150.1 mg (1 mmol) of 3-phenylpropionic acid and 100 mg of dried SP-MCM (A) were added, and 0.8 ml of 1,4-dioxane was added to dissolve 3-phenylpropionic acid. This pressure-resistant test tube was immersed in acetone-dry ice bath, and 40 mmol of isobutene was bubbled therein. Thereafter, the mixture was stirred at room temperature for 20 hours to carry out a synthesis reaction of 3-phenylpropionic acid t-butyl ester. After completion of the reaction, it was immersed in an ice bath, the lid was opened, the product was filtered, and diluted with 150 ml of toluene. N-Pentadecane was added to this as an internal standard, analyzed by gas chromatography, and the yield of the obtained 3-phenylpropionic acid t-butyl ester was calculated.

<Example 2>
A 3-phenylpropionic acid t-butyl ester was synthesized in the same manner as in Example 1 except that SP-MCM (B) was used instead of SP-MCM (A), and the yield was calculated.

<Example 3>
A 3-phenylpropionic acid t-butyl ester was synthesized in the same manner as in Example 1 except that SP-FSM (A) was used instead of SP-MCM (A), and the yield was calculated.

<Example 4>
A 3-phenylpropionic acid t-butyl ester was synthesized in the same manner as in Example 1 except that SP-FSM (B) was used instead of SP-MCM (A), and the yield was calculated.

<Comparative Example 1>
(Synthesis using silica that is not mesoporous silica as a catalyst)
A 3-phenylpropionic acid t-butyl ester was synthesized in the same manner as in Example 1 except that SP-SiO ₂ was used instead of SP-MCM (A), and the yield was calculated.

<Comparative example 2>
(Synthesis using homogeneous catalyst)
In a pressure test tube, 150.1 mg (1 mmol) of 3-phenylpropionic acid was taken. 49.6 mg (0.50 mmol) of concentrated sulfuric acid was dissolved in 0.8 ml of 1,4-dioxane and added to a pressure-resistant test tube. This pressure-resistant test tube was immersed in acetone-dry ice bath, and 40 mmol of isobutene was bubbled therein. Thereafter, the mixture was stirred at room temperature for 20 hours to carry out a synthesis reaction of 3-phenylpropionic acid t-butyl ester. After completion of the reaction, the mixture was immersed in an ice bath, the lid was opened, 105.0 mg of sodium carbonate dissolved in 1 ml of distilled water was added, and the product was filtered and diluted with 150 ml of toluene. N-Pentadecane was added to this as an internal standard, analyzed by gas chromatography, and the yield of the obtained 3-phenylpropionic acid t-butyl ester was calculated.

<Comparative Example 3>
(Synthesis using homogeneous catalyst)
In a pressure test tube, 150.1 mg (1 mmol) of 3-phenylpropionic acid was taken. 86 mg (0.50 mmol) of paratoluenesulfonic acid (p-TsOH) is dissolved in 0.8 ml of 1,4-dioxane and added to a pressure test tube. This pressure-resistant test tube was immersed in acetone-dry ice bath, and 40 mmol of isobutene was bubbled therein. Thereafter, the mixture was stirred at room temperature for 20 hours to carry out a synthesis reaction of 3-phenylpropionic acid t-butyl ester. After completion of the reaction, the mixture was immersed in an ice bath, the lid was opened, 105.0 mg of sodium carbonate dissolved in 1 ml of distilled water was added, and the product was filtered and diluted with 150 ml of toluene. N-Pentadecane was added to this as an internal standard, analyzed by gas chromatography, and the yield of the obtained 3-phenylpropionic acid t-butyl ester was calculated.

<Comparative example 4>
(Synthesis using polymer having sulfonic acid group as catalyst)
Weigh 310.8 mg (2.07 mmol) of 3-phenylpropionic acid and 1.25 g (1.0 mmol) of Nafion (registered trademark) NR50 (Aldrich) (0.8 mmol / g), and put them in a pressure test tube in this order. It was. Subsequently, 1.6 ml of 1,4-dioxane was added to dissolve 3-phenylpropionic acid. This pressure-resistant test tube was immersed in acetone-dry ice bath, and 7.4 ml (80 mmol) of isobutene was bubbled therein. Thereafter, the mixture was stirred at room temperature for 19 hours to carry out a synthesis reaction of a 3-phenylpropionic acid t-butyl ester. After completion of the reaction, it was immersed in an ice bath, the lid was opened, the product was filtered, and diluted with 150 ml of toluene. N-Pentadecane was added to this as an internal standard, analyzed by gas chromatography, and the yield of the obtained 3-phenylpropionic acid t-butyl ester was calculated.

<Comparative Example 5>
(Synthesis using ion exchange resin as catalyst)
Weigh 151.7 mg (1.01 mmol) of 3-phenylpropionic acid and 4.00 g (10.2 mmol) of ion exchange resin DIAION (registered trademark) PK228 (2.55 mmol / g), and put them in a pressure-resistant test tube in this order. It was. Subsequently, 1.6 ml of 1,4-dioxane was added to dissolve 3-phenylpropionic acid. This pressure-resistant test tube was immersed in acetone-dry ice bath, and 2.7 ml (34.9 mmol) of isobutene was bubbled therein. Thereafter, the mixture was stirred at room temperature for 14 hours to carry out a synthesis reaction of 3-phenylpropionic acid t-butyl ester. After completion of the reaction, it was immersed in an ice bath, the lid was opened, the product was filtered, and diluted with 150 ml of toluene. N-Pentadecane was added to this as an internal standard, analyzed by gas chromatography, and the yield of the obtained 3-phenylpropionic acid t-butyl ester was calculated.

  The results of Examples 1 to 4 and Comparative Examples 1 to 5 are shown in Table 1. In addition, TON is the molar ratio of the product (3-phenylpropionic acid t-butyl ester) / sulfonic acid group of the catalyst. The yield is (number of moles of product) / (number of moles of raw material) × 100 (%).

  From the results shown in Table 1, the ester production methods of Examples 1 to 4 using a solid catalyst in which a sulfonic acid group is introduced into mesoporous silica, which is a mesoporous material, are a homogeneous catalyst and a catalyst in which a sulfonic acid group is introduced into silica. It can be seen that the yield of the ester is substantially equal to or higher than that of the ester production methods of Comparative Examples 1 to 5 using Nafion, which is a resin containing a sulfonic acid group, and an ion exchange resin catalyst. Moreover, the manufacturing method of ester of Examples 1-4 has a high TON value compared with the manufacturing method of the ester of Comparative Examples 1-5, and it turns out that the activity per sulfonic acid group is excellent.

<Example 5>
(Repeated experiment)
The same procedure as in Example 3 except that the amount of 3-phenylpropionic acid used and the amount of catalyst {SP-FSM (A)} was changed by reusing the SP-FSM (A) used in Example 3. The experiment was repeated, and the synthesis reaction of 3-phenylpropionic acid t-butyl ester was carried out four times in total.
The amount of 3-phenylpropionic acid used, the amount of catalyst {SP-FSM (A)}, and the results are shown in Table 2.

  From the results in Table 2, it can be seen that no significant performance degradation has occurred due to repeated use. Therefore, it was confirmed that the solid catalyst in which a sulfonic acid group is introduced into mesoporous silica, which is a mesoporous material, can be repeatedly used by performing recovery.

II. When producing 3-benzoylpropionic acid t-butyl ester [Preparation of solid catalyst]
As described above [3. In the same manner as in the introduction of the sulfonic acid group (A)], [1. Synthesis of mesoporous silica Si-MCM41] and [2. Into the Si-FSM 16 synthesized in [Synthesis of Mesoporous Silica Si-FSM16], sulfonic acid groups were introduced, respectively. The catalyst into which the sulfonic acid group has been introduced is represented as SP-MCM (A2) and SP-FSM (A2), respectively.

In addition, the above-mentioned [4. [1. By introduction of sulfonic acid group (B)], [1. Synthesis of Mesoporous Silica Si-MCM41] [2. Synthesis of Mesoporous Silica Si-FSM16] was introduced into each of Si-FSM16 synthesized in the above and amorphous silica. The catalyst into which the sulfonic acid group is introduced is expressed as SP-MCM (B2), SP-FSM (B2), and SP-SiO ₂ (2), respectively.

<Example 6>
SP-MCM (A2) was used instead of SP-MCM (A) as the solid catalyst, 179 mg (1 mmol) of 3-benzoylpropionic acid and 42 mmol of isobutene were used instead of 3-phenylpropionic acid as the substrate, and the product was A t-butyl ester compound was synthesized in the same manner as in Example 1 except that a 3-benzoylpropionic acid t-butyl ester compound was obtained instead of the 3-phenylpropionic acid t-butyl ester compound. After completion of the reaction, the lid of the test tube was opened to vaporize isobutene. Thereafter, it was diluted with 200 ml of toluene and 50 ml of chloroform. N-Pentadecane was added to this as an internal standard, analyzed by gas chromatography, and the yield of the obtained 3-benzoylpropionic acid t-butyl ester was calculated.

<Example 7>
A 3-benzoylpropionic acid t-butyl ester was synthesized and the yield was calculated in the same manner as in Example 6 except that SP-MCM (B2) was used instead of SP-MCM (A2).

<Example 8>
A 3-benzoylpropionic acid t-butyl ester was synthesized and the yield was calculated in the same manner as in Example 6 except that SP-FSM (A2) was used instead of SP-MCM (A2).

<Example 9>
A 3-benzoylpropionic acid t-butyl ester was synthesized and the yield was calculated in the same manner as in Example 6 except that SP-FSM (B2) was used instead of SP-MCM (A2).

<Comparative Example 6>
(Synthesis using silica that is not mesoporous silica as a catalyst)
A 3-benzoylpropionic acid t-butyl ester was synthesized and the yield was calculated in the same manner as in Example 6 except that SP-SiO ₂ (2) was used instead of SP-MCM (A2).

<Comparative Example 7>
(Synthesis using homogeneous catalyst)
179 mg (1 mmol) of 3-benzoylpropionic acid was taken in a pressure test tube. 18.5 mg (0.19 mmol) of concentrated sulfuric acid was dissolved in 0.8 ml of 1,4-dioxane and added to a pressure-resistant test tube. This pressure-resistant test tube was immersed in acetone-dry ice bath, and 42 mmol of isobutene was bubbled therein. Then, it stirred at room temperature for 20 hours, and the t-butyl ester body synthesis reaction was performed. After completion of the reaction, it was immersed in an ice bath, the lid was opened, 8 ml of sodium carbonate dissolved in 1 ml of distilled water was added, the product was filtered, and diluted with 150 ml of toluene and 100 ml of distilled water. The organic phase was separated with a separatory funnel, washed with toluene and benzene, concentrated, transferred with chloroform, added with n-pentadecane as an internal standard, and analyzed by gas chromatography. The yield of 3-benzoylpropionic acid t-butyl ester was calculated.

<Comparative Example 8>
(Synthesis using homogeneous catalyst)
A 3-benzoylpropionic acid t-butyl ester was synthesized in the same manner as in Comparative Example 7 except that 30 mg (0.16 mmol) of paratoluenesulfonic acid (p-TsOH) was used instead of concentrated sulfuric acid as a catalyst. The rate was calculated.

<Comparative Example 9>
179 mg (1 mmol) of 3-benzoylpropionic acid and 0.1 g (0.08 mmol) of Nafion (registered trademark) NR50 (Aldrich) (0.8 mmol / g) were weighed and placed in a pressure test tube in this order. Subsequently, 0.8 ml of 1,4-dioxane was added to dissolve 3-benzoylpropionic acid. This pressure-resistant test tube was immersed in acetone-dry ice bath, and 4.0 ml (42 mmol) of isobutene was bubbled therein. Then, it stirred at room temperature for 20 hours, and the t-butyl ester body synthesis reaction was performed. After completion of the reaction, it was immersed in an ice bath, the lid was opened, the product was filtered, and diluted with 150 ml of toluene and 50 ml of chloroform. N-Pentadecane was added to this as an internal standard, analyzed by gas chromatography, and the yield of the obtained 3-benzoylpropionic acid t-butyl ester was calculated.

The results of Examples 6 to 9 and Comparative Examples 6 to 9 are shown in Table 3. In addition, TON is the molar ratio of the product (3-benzoylpropionic acid t-butyl ester) / sulfonic acid group of the catalyst.

  From the results in Table 3, the ester production methods of Examples 6 to 9 using a solid catalyst in which sulfonic acid groups are introduced into mesoporous silica, which is a mesoporous material, are homogeneous catalysts, catalysts in which sulfonic acid groups are introduced into silica. It can be seen that the yield of the ester is much higher than that of the esters of Comparative Examples 6 to 9 using Nafion, which is a resin containing sulfonic acid groups. Moreover, the manufacturing method of ester of Examples 6-9 has a high TON value compared with the manufacturing method of ester of Comparative Examples 6-9, and it turns out that the activity per sulfonic acid group is excellent.

III. When producing an ester from other reaction substrates <Example 10>
Instead of 179 mg (1 mmol) of 3-benzoylpropionic acid and 42 mmol of isobutene as reaction substrates, 251 mg (1 mmol) of isobenzone and 42 mmol of isobutene were used instead of 42 mmol of isobutene, and instead of 3-benzoylpropionic acid t-butyl ester as a product. A t-butyl ester compound was synthesized in the same manner as in Example 6 except that an N-Carbobenzoxy-L-proline t-butyl ester compound was obtained. After completion of the reaction, isobutene was vaporized, washed with toluene and chloroform, and concentrated under reduced pressure to obtain a candy-like substance. This was analyzed by proton NMR, and the yield of t-butyl ester was calculated to be 97%.
Moreover, when the solid catalyst after use was collect | recovered and the same synthetic reaction was performed, the yield of the t-butyl ester body obtained by another synthetic reaction was 92%.

<Example 11>
N-Carbobenzoxy-L-proline t-butyl ester was synthesized in the same manner as in Example 10 except that SP-FSM (A2) was used instead of SP-MCM (A2) as the solid catalyst, and the yield was calculated. did. The yield of t-butyl ester was 75%.

<Comparative Example 10>
N-Carbobenzoxy-L-proline t-butyl ester was synthesized in the same manner as in Example 10 except that concentrated sulfuric acid 18.9 mg (0.193 mmol) was used instead of SP-MCM (A2) as a catalyst. The rate was calculated. The yield of t-butyl ester was 23%.

As described above, the ester production methods of Examples 10 and 11 using a solid catalyst in which a sulfonic acid group is introduced into mesoporous silica, which is a mesoporous material, are the same as the ester production method of Comparative Example 10 using a homogeneous catalyst. It can be seen that the yield of the ester is much higher than
Further, from Example 10, it was confirmed that the solid catalyst in which a sulfonic acid group was introduced into mesoporous silica showed higher activity than before even when recovered and reused after use.

<Example 12>
(T-butyl esterification for protected amino acids)
N-Carbobenzoxy-L-phenylalanine t-butyl ester was synthesized in the same manner as in Example 11 except that 300 mg (1 mmol) of N-Carbonoxy-L-phenylalanine was used instead of N-Carbobenzoxy-L-proline as a substrate. The yield was calculated. The yield of t-butyl ester was 50%.

<Example 13>
(T-butyl esterification for protected amino acids)
An N-Carbobenzoxy-L-alanine t-butyl ester was synthesized in the same manner as in Example 11 except that 225 mg (1 mmol) of N-Carbonoxy-L-alanine was used instead of N-Carbobenzoxy-L-proline as a substrate. The yield was calculated. The yield of t-butyl ester was 57%.

  From Examples 12 and 13, it can be seen that the solid catalyst in which a sulfonic acid group is introduced into mesoporous silica, which is a mesoporous material, exhibits high activity even when t-butyl esterification is performed on a protected amino acid.

  The method for producing an ester of the present invention is not particularly limited as long as the ester is produced, and can be carried out in various cases. In particular, in the synthesis of a compound having many functional groups, the functional group is protected. It is useful to use as a method of esterification in the process. For example, it is suitably used for the protection of carboxylic acids by tertiary butylation in the process of protection or deprotection during the synthesis of fine chemicals such as peptides and saccharides including intermediates of pharmaceuticals and agricultural chemicals.

It is a nitrogen adsorption curve measured about Si-MCM41 synthesize | combined in the Example. It is a BJH plot measured about Si-MCM41 synthesize | combined in the Example. It is a nitrogen adsorption curve measured about Si-FSM16 synthesize | combined in the Example. It is a BJH plot measured about Si-FSM16 synthesize | combined in the Example.

Claims (5)

  A method for producing an ester, comprising producing an ester by reacting a carboxylic acid with an olefin in the presence of a solid catalyst comprising a mesoporous material having a sulfonic acid group.   The method for producing an ester according to claim 1, wherein the mesoporous material contains at least mesoporous silica.   The method for producing an ester according to claim 2, wherein the molar ratio M / Si between the elements M and Si other than O and Si contained in the mesoporous silica is 0.5 or less.   The method for producing an ester according to any one of claims 1 to 3, wherein a sulfonic acid group is bonded to the mesoporous material via a divalent hydrocarbon group.   The method for producing an ester according to any one of claims 1 to 4, wherein the content of the sulfonic acid group in the mesoporous material is 0.1 mmol / g or more and 5 mmol / g or less.

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