JP6317212B2 - Novel transesterification catalyst and method for producing ester compound using the same - Google Patents

Description

  The present invention relates to a novel catalyst for transesterification comprising a zinc ate type complex and a method for producing an ester compound using the catalyst. More specifically, the present invention relates to a transesterification catalyst that can produce an ester compound in a high yield and high purity under mild conditions, and a method for producing an ester compound using the catalyst.

  The ester compound is a useful compound that is industrially used in the fields of paint resins, printing inks, molding resins, films, adhesives, medicines, and the like.

As a preparation method of the ester compound,
(1) Direct esterification by dehydration of carboxylic acid and alcohol in the presence of an acid catalyst
(2) A transesterification method using an ester compound and an alcohol is generally known. The method (1) has a problem that not only the treatment after the reaction between the excess carboxylic acid and the acid catalyst is complicated, but also a side reaction tends to occur. In order to avoid these problems, transesterification methods have been studied, but most of them generally require high-temperature conditions such as reaction under reflux of the solvent. When a reaction substrate having an optically active group is reacted under such conditions, there arises a problem that the optical activity due to racemization tends to be impaired.

Although there are few proposals of a novel catalyst for solving these problems, the following examples are given.
It has been reported that an organotin compound having a specific structure allows a transesterification reaction to proceed under mild reaction conditions of room temperature to give a reaction object in high yield and high purity (Patent Document 1). It has also been reported that the transesterification of ester and alcohol proceeds at room temperature when N-heterocyclic carbene is used. (Non-Patent Document 1)

Japanese Patent Laid-Open No. 11-285642 JP 2004-292328 A

J. Org. Chem., 68, 2812 (2003) (Polymer, Volume 53, August, 600 (2004)) T. Iwasaki et al., J. Org. Chem., 73, 5147 (2008)

  However, although the catalyst described in Patent Document 1 achieves higher activation than the conventional one, organotin compounds have concerns about toxicity, and are especially avoided when considering industrial applications. Is preferable. Further, when catalyst residues are mixed in the product, coloring may be caused.

  In addition, N-heterocyclic carbene in Non-Patent Document 1 is an excellent transesterification catalyst, but this compound is easy to form a complex with a metal with a strong base, and depending on the complex, it shows strong toxicity, so use with caution. Is the compound to be.

  Furthermore, since the above-described transesterification catalyst proceeds the transesterification reaction under a mild condition of room temperature, when reacting a reaction substrate having an optically active group, optical activity is higher than that of a conventional catalyst system that requires a high temperature reaction. It is hard to lose. However, a transesterification reaction at a lower temperature may be desired depending on the substrate, and it is difficult to say that the room temperature is sufficiently low.

  The problem to be solved by the present invention is to provide a catalyst that allows a transesterification reaction to proceed under mild conditions to give the desired product in a high reaction yield, and a method for producing an ester compound under mild conditions. It is to provide.

In order to solve the above problems, the present invention has been intensively studied.As a result, the dianion-type zinc ate complex t-Bu ₄ R _4-n ZnM _m having a bulky ligand is at a low temperature of room temperature or lower, and It has been found that it acts as a catalyst for a high transesterification reaction even in the presence of water and an amino group, and the present invention has been completed.

From here, it will be described how the present invention was found. Among zinc art complexes, dianion type zinc art complex t-Bu ₄ ZnLi ₂ (TBZL) having a bulky ligand has been reported to promote anionic polymerization of N-isopropylacrylamide without protecting acidic protons. Yes. (Non-Patent Document 2)

While investigating the anionic polymerization of 2-hydroxyethyl methacrylate (HEMA) with a TBZL catalyst, we have found that the HEMA polymer obtained in methanol solvent contains methyl methacrylate as a polymerization site. This means that 2-hydroxyethyl methacrylate and methanol transesterified. This discovery has never been reported before. It has also been found that insoluble polymers are formed in water. As a result of MALDI-TOFMS analysis of the obtained polymer, it was confirmed for the first time that an intramolecular transesterification reaction was in progress. That is, it was found that the insoluble polymer formed by HEMA polymerization in water had a cross-linked site formed in the polymer chain. This discovery has not been reported so far. Therefore, based on the new findings described herein, the utility as the transesterification catalyst dianion-type zinc ate complex _{t-Bu n R 4-n} ZnM m represented by the general formula (1), including TBZL In order to confirm, transesterification under various conditions was examined.

That is, are we, from the prior art information, the general formula (1) catalytic activity expression in transesterification of the dianion-type zinc ate complex _{t-Bu n R 4-n} ZnM m represented by was carried investigated in the hope Rather, they proceeded with the study based on their own small discoveries that were discovered by chance and completed the invention.

  The present invention for solving the above problems is as follows.

[1]
A method for producing an ester compound, comprising transesterifying an ester compound and an alcohol compound in the presence of a dianionic zinc art complex.
[2]
The production method according to [1], wherein the dianion type zinc art complex is a dianion type zinc art complex represented by the following general formula (1).
(In the formula, n is an integer of 1 to 4, and when n is 1 or 2, each R may be the same or different and is an alkyl group, alkenyl group, aryl group, or arylalkyl having 1 to 8 carbon atoms. Represents a group, M represents lithium or magnesium, and m represents 1 to 2.)
[3]
The production method according to [1] or [2], wherein the transesterification reaction is performed in a protic solvent.
[4]
The production method according to [1] or [2], wherein the transesterification reaction is performed in the absence of a solvent.
[5]
The production method according to any one of [1] to [4], wherein the transesterification reaction is performed at a temperature of 30 ° C or lower.
[6]
The production method according to any one of [1] to [5], wherein the dianion-type zinc ate complex is t-Bu ₄ ZnLi ₂ .
[7]
A catalyst for transesterification containing a dianionic zinc art complex.
[8]
The catalyst according to [7], wherein the dianion type zinc art complex is a dianion type zinc art complex represented by the following general formula (1).
(In the formula, n is an integer of 1 to 4, and when n is 1 or 2, each R may be the same or different and is an alkyl group, alkenyl group, aryl group, or arylalkyl having 1 to 8 carbon atoms. Represents a group, M represents lithium or magnesium, and m represents 1 to 2.)
[9]
The catalyst according to [7] or [8], wherein the transesterification reaction is performed in a protic solvent or in the absence of a solvent.
[10]
The catalyst according to any one of [7] to [9], wherein the transesterification reaction is performed at a temperature of 30 ° C or lower.
[11]
The catalyst according to any one of [7] to [10], wherein the dianion-type zinc ate complex is t-Bu ₄ ZnLi ₂ .

  When the ester exchange reaction catalyst of the present invention synthesizes an ester compound by transesterification, the reaction can proceed in a short time at a reaction temperature lower than room temperature. Further, the reaction proceeds even in an aqueous solvent, and the target ester compound can be obtained. Furthermore, the synthesis method using this catalyst is excellent in so-called “Chemoselectivity” in which transesterification selectively proceeds even in the presence of an amino group.

¹ shows a ¹ H-NMR chart used for calculating a conversion rate in an ester exchange reaction of ethyl acetate and benzyl alcohol (Example 1). The result of the transesterification reaction in Examples 2-4 is shown.

The catalyst used in the ester compound production method of the present invention and the transesterification catalyst of the present invention are dianionic zinc art complexes having at least one t-Bu group represented by the following general formula (1).

  Here, n is an integer of 1 to 4, and when n is 1 or 2, each R may be the same or different and is an alkyl group, alkenyl group, aryl group or arylalkyl group having 1 to 8 carbon atoms. is there. Specifically, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, sec-butyl group, n-pentyl group, n-hexyl group, vinyl group, phenyl group Examples thereof include a group and a benzyl group.

  M represents lithium or magnesium, m is 2 when M is lithium, and m is 1 when M is magnesium.

  The dianionic zinc art complex represented by the general formula (1) is described in Patent Document 2, and can be obtained by the method described in Patent Document 2. Specific examples of the dianion type zinc art complex represented by the general formula (1) include dilithium salts such as dilithium tetra-t-butylzinc zincate, dilithium trit-butylmethylzincate, dilithium trit-butylethylzincate, Di-lithium tri-t-butyl-n-propyl zincate, di-lithium tri-t-butyl-n-butyl zincate, di-lithium tri-t-butyl-i-butyl zincate, di-lithium tri-t-butyl-sec-butyl zincate, di-t -Butyldimethylzinc acid dilithium, di-t-butyldiethyl zinc acid dilithium, di-t-butyl di-n-propyl zinc acid dilithium, di-t-butyl di-n-butyl zinc acid zinc salt, di-t-butyl di-i-butyl zinc acid Dilithium, di-t-butyl di-sec-butyl dizinc zincate, t-butyltrimethylzinc zincate, t-butyltriethylzinc zincate, t-butyltri-n-propylzinc acid Lithium, t- butyltri -n- butyl zinc acid dilithium, t- butyltri -i--butyl zinc acid dilithium, t- butyltri -sec--butyl zinc acid dilithium, and the like. Magnesium salts include tetra-t-butyl magnesium zincate, magnesium tri-t-butylmethylzincate, magnesium tri-t-butylethylzincate, magnesium tri-t-butyl-n-propylzinc, tri-t-butyl-n- Magnesium butyl zincate, magnesium t-butyl-i-butyl zinc zincate, tri-t-butyl-sec-butyl magnesium zincate, magnesium di-t-butyldimethylzincate, magnesium di-t-butyldiethylzincate, di-t- Butyl di-n-propyl magnesium zincate, di-t-butyldi-n-butylmagnesium zincate, di-t-butyldi-i-butylmagnesium zincate, di-t-butyldi-sec-magnesium zincate, t-butyltrimethylzinc Magnesium oxide, magnesium t-butyltriethylzincate, magnesium t-butyltri-n-propylzinczate, t-butyltri-n-butyl Magnesium Le zincate, t-butyltri -i- magnesium butyl zincate, t-butyltri -sec- butyl zinc magnesium, and the like.

  The dianion-type zinc art complex described above may be used alone as a catalyst, or two or more kinds may be used in combination for the reaction.

  The reaction temperature in the transesterification reaction between the alcohol and the ester compound is not particularly limited, but can be appropriately selected from the range of -80 ° C to 200 ° C. When using a compound that may be modified by temperature, for example, an alcohol containing an optically active group, the reaction temperature can be selected in view of its instability and reaction rate. Considering the high transesterification ability of the catalyst at low temperature, it is preferably in the range of -80 ° C to 80 ° C, more preferably -50 ° C to 50 ° C. In particular, the catalyst of the present invention is effective as a catalyst for reactions at low temperatures, and is particularly effective when used at a temperature in the range of 30 ° C. or lower.

  The transesterification reaction between the alcohol and the ester compound may be carried out at normal pressure or under reduced pressure.

  The time required for the transesterification reaction between the alcohol and the ester compound may be adjusted so that the transesterification reaction is completed.

  When the transesterification reaction between the alcohol and the ester compound is performed, it is also possible to take a method of removing the by-produced alcohol by azeotropy with an organic solvent.

  By using the transesterification catalyst comprising the dianion-type zinc art catalyst of the present invention, transesterification can proceed efficiently at room temperature and normal pressure. However, there is no intention to exclude reactions at normal high temperature and pressure.

  The ester compound used as a raw material for the transesterification reaction in the present invention is not particularly limited, and specifically, a saturated or unsaturated aliphatic carboxylic acid or aromatic carboxylic acid which may have a substituent and a substituent. An ester compound with a saturated, unsaturated or aromatic alcohol which may have a functional group such as a hydroxyl group.

  Specific examples include methyl acetate, ethyl acetate, propyl acetate, n-butyl acetate, sec-butyl acetate, i-butyl acetate, t-butyl acetate, acetate esters, methyl acrylate, ethyl acrylate, propyl acrylate And (meth) acrylic acid esters such as butyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate and 2-hydroxyethyl methacrylate.

  The alcohol used as a raw material for the transesterification reaction in the present invention is not particularly limited, and specifically, it is a saturated, unsaturated or aromatic alcohol which may have a substituent, and a functional group such as a hydroxyl group. You may have.

  Specific examples include methanol, ethanol, propanol, n-butanol, i-butanol, 2-ethylhexanol, isodecyl alcohol, octanol, lauryl alcohol, stearyl alcohol, cyclohexanol, ethylene glycol, propylene glycol, neopentyl glycol, Saturated aliphatic alcohols such as butylene glycol, hexanediol, trimethylolpropane, pentaerythritol, ditrimethylolpropane, dipentaerythritol, vinyl alcohol, allyl alcohol, butenyl alcohol, octenyl alcohol, oleyl alcohol, linolyl alcohol, geraniol, Aliphatic unsaturated alcohols such as linalyl alcohol, phenol, benzyl alcohol, phenoxyethanol, Bruno carboxymethyl propanol, cresol, alpha-naphthol, beta-naphthol, catechol, hydroquinone, and aromatic substituted alcohols, such as bisphenol A and the like. Further examples include furfuryl alcohol, glucose, galactose, mannose, xylose, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, maltose, trehalose, lactose, sialic acid, glucuronic acid, iduronic acid, fucose, etc. It is done.

  The amount of the dianion type zinc art catalyst used in the transesterification reaction of the present invention is not particularly limited, but based on the lesser amount of the ester compound and alcohol compound used as raw materials, In general, it is in the range of 0.001 to 0.5 mol, preferably 0.001 to 0.1 mol, more preferably 0.005 to 0.05 mol. However, it is not intended to be limited to this range.

  The transesterification reaction in the present invention can be carried out in the absence of a solvent, but can also be carried out using a solvent inert to the reaction.

  Examples of solvents that can be used include water and ether solvents such as diethyl ether, dimethoxyethane, and tetrahydrofuran, aliphatic hydrocarbon solvents such as hexane, cyclohexane, and heptane, and aromatic hydrocarbon solvents such as benzene, toluene, and xylene. And so on.

[Preparation of _{t-Bu n R 4-n} ZnM m]
_{t-Bu n R 4-n} ZnM An example of _{m t-Bu 4 ZnLi 2 (} TBZL) can be mentioned. TBZL can be prepared according to the method described in Example 1 of JP-A-2004-292328 (Patent Document 2).

The conversion rate in the ester exchange reaction between the ester and the alcohol was calculated by ¹ H-NMR by the following method. Here, the transesterification reaction between ethyl acetate and benzyl alcohol (Example 1) is illustrated. A ¹ H-NMR chart used for calculation of the transesterification reaction is shown in FIG. In addition, the heavy solvent used for the measurement is deuterated chloroform.
Using the integral value by ¹ H-NMR of the methyl group (a) of ethyl acetate and the methyl group (e) of benzyl acetate after transesterification, it was determined by the following formula.
Reaction rate (%) = e / (a + e) * 100
FIG. 1 shows the assignment of each proton of ethyl acetate, benzyl alcohol, and the generated benzyl acetate.

  The following reaction was performed in a dry nitrogen gas atmosphere, and all solvents were dehydrated and degassed.

Example 1 Transesterification at 0 ° C with ethyl acetate and benzyl alcohol using TBZL In a glove box under a dry nitrogen atmosphere, 5 mmol of ethyl acetate and 5 mmol of benzyl alcohol were introduced into a one-necked eggplant flask containing a stirring bar. A three-way cock was attached. The eggplant flask was immersed in a bath set at 0 ° C. and cooled. To this, 0.1 mmol-TBZL of a THF solution of TBZL (prepared according to the method described in Example 1 of JP-A-2004-292328 (Patent Document 2)) manufactured by Tosoh Finechem Co. was added to initiate the reaction. A sample was partially taken at a reaction time of 60 minutes at 0 ° C., and the conversion rate in the transesterification reaction was determined by ¹ H-NMR to be 41%.

Example 2 Transesterification reaction at 0 ° C with ethyl acetate and methanol using TBZL In a glove box under a dry nitrogen atmosphere, 50 mmol ethyl acetate and 50 mmol methanol were introduced into a one-necked eggplant flask containing a stirrer, A three-way cock was attached. The eggplant flask was immersed in a bath set at 0 ° C. and cooled. To this was added 1 mmol-TBZL of TBZL manufactured by Tosoh Finechem, and the reaction was started. Samples were partially collected at 0 ° C. for reaction times of 5 minutes, 10 minutes, 20 minutes, 30 minutes, 60 minutes, and 120 minutes, and the conversion rates in the transesterification reaction were determined by ¹ H-NMR. The result is shown in figure 2. It was found that the conversion reached a maximum value in about 10 minutes at a reaction temperature of 0 ° C.

Example 3 Transesterification reaction at −20 ° C. with ethyl acetate and methanol using TBZL The transesterification reaction was carried out in the same manner as in Example 2 except that the reaction temperature was −20 ° C. The result is shown in figure 2. It was found that the reaction proceeded even at a reaction temperature of -20 ° C, and that the conversion reached the maximum value in about 60 minutes.

Example 4 Transesterification at -40 ° C with ethyl acetate and methanol using TBZL Same as Example 2 except that the reaction temperature was -40 ° C and additional sampling analysis was performed at 240 minutes The transesterification reaction was performed. The result is shown in figure 2. The reaction proceeded even at an extremely low reaction temperature of -40 ° C., and it was found that the conversion reached a maximum value in about 240 minutes.

Example 5 Transesterification reaction at 0 ° C. with ethyl acetate and isopropyl alcohol using TBZL A transesterification reaction was carried out in the same manner as in Example 1 except that isopropyl alcohol was used as the alcohol. The conversion rate in the transesterification reaction determined by ¹ H-NMR was 38%.

Example 6 Transesterification reaction at 0 ° C. with methyl phenylacetate and ethanol using TBZL A transesterification reaction was carried out in the same manner as in Example 1 except that methyl phenylacetate was used as an ester and ethanol was used as an alcohol. ^{When the} conversion rate in the transesterification was determined by ¹ H-NMR, it was 26%.

Example 7 Transesterification with TBZL using benzyl acetate and methanol at 0 ° C. Transesterification was performed in the same manner as in Example 1 except that benzyl acetate was used as the ester and methanol was used as the alcohol. The conversion rate in the transesterification reaction determined by ¹ H-NMR was 61%.

Example 8 Transesterification with TBZL using isopropyl acetate and methanol at 0 ° C. Transesterification was performed in the same manner as in Example 1 except that isopropyl acetate was used as the ester and methanol was used as the alcohol. The conversion rate in the transesterification reaction determined by ¹ H-NMR was 54%.

Example 9 Transesterification with TBZL using phenyl acetate and methanol at 0 ° C. Transesterification was carried out in the same manner as in Example 1 except that phenyl acetate was used as the ester and methanol was used as the alcohol. The conversion rate in the transesterification reaction determined by ¹ H-NMR was 52%.

Example 10 Transesterification Reaction at 0 ° C. in the Coexistence of Ethyl Acetate, Methanol and Triethylamine Using TBZL In a glove box under a dry nitrogen atmosphere, 5 mmol ethyl acetate, 5 mmol Methanol and 5 mmol triethylamine were introduced and a three-way cock was attached. The eggplant flask was immersed in a bath set at 0 ° C. and cooled. To this, 0.1 mmol-TBZL of a THF solution of TBZL manufactured by Tosoh Finechem was added to initiate the reaction. A sample was partially collected at a reaction time of 60 minutes at 0 ° C., and the conversion rate in the transesterification reaction was determined by ¹ H-NMR. As a result, it was 53%.

Example 11 Transesterification reaction at 0 ° C. in the presence of ethyl acetate, methanol and n-propylamine using TBZL In a glove box under a dry nitrogen atmosphere, 5 mmol of ethyl acetate was placed in a one-necked eggplant flask containing a stirrer. , 5 mmol methanol and 5 mmol n-propylamine were introduced and a three-way cock was attached. The eggplant flask was immersed in a bath set at 0 ° C. and cooled. To this, 0.1 mmol-TBZL of a THF solution of TBZL manufactured by Tosoh Finechem was added to initiate the reaction. A part of the sample was collected at a reaction time of 60 minutes at 0 ° C., and the conversion rate in the transesterification reaction was determined by ¹ H-NMR and found to be 51%.

Example 12 Transesterification at 0 ° C. in the Coexistence of Ethyl Acetate, Methanol, and Water Using TBZL In a glove box under a dry nitrogen atmosphere, 5 mmol ethyl acetate, 5 mmol Methanol and 5 mmol water were introduced and a three-way cock was attached. The eggplant flask was immersed in a bath set at 0 ° C. and cooled. To this, 0.1 mmol-TBZL of a THF solution of TBZL manufactured by Tosoh Finechem was added to initiate the reaction. A sample was partially taken at a reaction time of 60 minutes at 0 ° C., and the conversion rate in the transesterification reaction was determined by ¹ H-NMR, which was 47%.

Reference Example 1 Transesterification reaction at 0 ° C with ethyl acetate and methanol using a zinc tetranuclear cluster catalyst (Zn ₄ (OCOCF ₃ ) ₆ O) A mouthful of eggplant with a stirrer in a glove box under a dry nitrogen atmosphere 5 mmol ethyl acetate and 5 mmol methanol were introduced into the flask and a three-way cock was attached. The eggplant flask was immersed in a bath set at 0 ° C. and cooled. In addition, a zinc tetranuclear cluster catalyst (Zn ₄ (OCOCF ₃ ) ₆ O, Tokyo Chemical Industry Co., Ltd.) described in T. Iwasaki et al., J. Org. Chem., 73, 5147 (2008) (Non-patent Document 3). 0.1 mmol) (purchased from KK) was added to initiate the reaction. A sample was collected at a reaction time of 60 minutes at 0 ° C., and the conversion rate in the transesterification reaction was determined by ¹ H-NMR, and no progress of the reaction was observed. It was found that the zinc tetranuclear cluster catalyst (Zn ₄ (OCOCF ₃ ) ₆ O) does not proceed at 0 ℃.

Claims (9)

A method for producing an ester compound, comprising transesterifying an ester compound and an alcohol compound in the presence of a dianionic zinc art complex at a temperature of 30 ° C. or lower. The production method according to claim 1, wherein the dianion type zinc ate complex is a dianion type zinc ate complex represented by the following general formula (1).
(In the formula, n is an integer of 1 to 4, and when n is 1 or 2, each R may be the same or different and is an alkyl group, alkenyl group, aryl group, or arylalkyl having 1 to 8 carbon atoms. Represents a group, M represents lithium or magnesium, and m represents 1 to 2.) 3. The production method according to claim 1, wherein the transesterification reaction is performed in a protic solvent. 3. The production method according to claim 1, wherein the transesterification reaction is performed in the absence of a solvent. The dianion-type zinc art complex, t-Bu ₄ ZnLi ₂ a process according to any one of claims 1 to 4. A catalyst for transesterification performed at a temperature of 30 ° C. or lower , containing a dianionic zinc art complex. 7. The catalyst according to claim 6 , wherein the dianion type zinc ate complex is a dianion type zinc ate complex represented by the following general formula (1).
(In the formula, n is an integer of 1 to 4, and when n is 1 or 2, each R may be the same or different and is an alkyl group, alkenyl group, aryl group, or arylalkyl having 1 to 8 carbon atoms. Represents a group, M represents lithium or magnesium, and m represents 1 to 2.) The catalyst according to claim 6 or 7 wherein the transesterification is carried out in a protic solvent or without a solvent. The catalyst according to any one of claims 6 to 8 , wherein the dianion type zinc ate complex is t-Bu ₄ ZnLi ₂ .