JP2020011945A - Method for producing iodide ester compound - Google Patents

Abstract

To provide a method for producing an iodide ester compound that makes it possible to obtain a target iodide ester compound in high yield with high regioselectivity for iodine introduction.SOLUTION: A method for producing an iodide ester compound includes an iodide forming step in which: in the presence of a porous material, an ester compound represented by the following formula (2), iodine (I), and an iodine-based oxide are reacted with each other, an iodide ester compound represented by the following formula (3) is formed.SELECTED DRAWING: None

Description

  The present invention relates to a method for producing an iodide ester compound.

  An iodide of an aromatic ester compound in which iodine is introduced into a predetermined position of an aromatic ring (aromatic iodide ester compound) is widely used in, for example, pharmaceutical intermediates, agricultural chemical intermediates, and electronic material intermediates. Have been.

  Conventionally, an iodination reaction of an aromatic compound has been performed under conditions using, for example, sulfuric acid (for example, see Non-Patent Document 1).

Liebigs Ann. Chem., 634, 84 (1960)

  However, when such a reaction is applied to the production of an iodide of an aromatic ester compound, generally, a large number of products are produced by an unintended reaction other than the iodination reaction, and the selectivity of the iodine introduction position is reduced. The present inventor has found that there is a problem of being lowered. In addition, such a problem has occurred remarkably depending on the type of the aromatic ester compound (reaction substrate) as a raw material.

  An object of the present invention is to provide a method for producing an iodide ester compound, which has high regioselectivity at the position where iodine is introduced and can obtain a target iodide ester compound in a high yield.

（ただし、式（２）中、ｎは、１以上５以下の整数、Ｒは、炭素数が１以上３以下のアルキル基である。）

（ただし、式（３）中、ｎは、１以上５以下の整数、Ｒは、炭素数が１以上３以下のアルキル基である。） Such an object is achieved by the present invention described below.
In the method for producing an iodide ester compound of the present invention, an ester compound represented by the following formula (2) is reacted with iodine and an iodine-based oxide in the presence of a porous substance, and the reaction is carried out by the following formula (3). Characterized by having an iodination step of obtaining an iodinated ester compound.

(However, in the formula (2), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

(However, in the formula (3), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

（ただし、式（１）中、ｎは、１以上５以下の整数である。）

（ただし、式（２）中、ｎは、１以上５以下の整数、Ｒは、炭素数が１以上３以下のアルキル基である。）

（ただし、式（３）中、ｎは、１以上５以下の整数、Ｒは、炭素数が１以上３以下のアルキル基である。） The method for producing an iodide ester compound of the present invention comprises the step of esterifying an alcohol compound represented by the following formula (1) in a solution containing a carboxylic acid and an acid anhydride thereof to form an ester represented by the following formula (2) An esterification step of obtaining a compound,
An iodination step of reacting the ester compound, iodine, and an iodine-based oxide in the presence of a porous substance to obtain an iodide ester compound represented by the following formula (3) is provided.

(In the formula (1), n is an integer of 1 or more and 5 or less.)

(However, in the formula (2), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

(However, in the formula (3), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

（ただし、式（１）中、ｎは、１以上５以下の整数である。）

（ただし、式（２）中、ｎは、１以上５以下の整数、Ｒは、炭素数が１以上３以下のアルキル基である。）

（ただし、式（３）中、ｎは、１以上５以下の整数、Ｒは、炭素数が１以上３以下のアルキル基である。） The method for producing an iodide ester compound of the present invention comprises the step of esterifying an alcohol compound represented by the following formula (1) in a solution containing a carboxylic acid and an acid anhydride thereof to form an ester represented by the following formula (2) Perform an esterification step to obtain a compound, using the obtained reaction mixture,
An iodination step of reacting the ester compound with an iodine-based oxide to obtain an iodide ester compound represented by the following formula (3) is performed.

(In the formula (1), n is an integer of 1 or more and 5 or less.)

(However, in the formula (2), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

(However, in the formula (3), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

  In the method for producing an iodide ester compound of the present invention, the molar ratio of the acid anhydride to the carboxylic acid used in the esterification step is preferably 0.2 or more and 1.0 or less.

  In the method for producing an iodide ester compound of the present invention, the molar ratio of the acid anhydride to the alcohol compound used in the esterification step is preferably 1.2 or more and 5.0 or less.

  In the method for producing an iodide ester compound of the present invention, the esterification step is preferably performed in the presence of the porous substance.

  In the method for producing an iodide ester compound of the present invention, the esterification step is preferably performed in the presence of the iodine.

  In the method for producing an iodide ester compound of the present invention, it is preferable that the iodine-based oxide is at least one selected from iodic acid, periodic acid and salts thereof.

  In the method for producing an iodide ester compound of the present invention, the iodine-based oxide is preferably an acidic compound.

  In the method for producing an iodide ester compound of the present invention, it is preferable that the iodine-based oxide is supplied into the reaction system in a state of an aqueous solution.

  In the method for producing an iodide ester compound of the present invention, the iodination step may be performed in a dispersion in which the dispersoid containing the iodine-based oxide is dispersed using an organic solution containing a carboxylic acid as a dispersion medium. preferable.

  In the method for producing an iodide ester compound according to the present invention, it is preferable that the average pore diameter of the porous substance is not less than 5.0 ° and not more than 9.0 °.

  In the method for producing an iodide ester compound according to the present invention, the porous substance is preferably a zeolite.

In the method for producing an iodide ester compound of the present invention, the SiO ₂ / Al ₂ O ₃ ratio (molar ratio) in the zeolite is preferably 4 or more and 90 or less.

  ADVANTAGE OF THE INVENTION According to this invention, the manufacturing method of the iodide ester compound which can obtain the target iodide ester compound with high regioselectivity of the introduction position of iodine in a high yield can be provided.

  The iodide ester compound (p-monoiodide ester compound) produced using such an alcohol compound as a raw material is particularly useful in various uses such as a pharmaceutical intermediate, an agricultural chemical intermediate, and an electronic material intermediate. High compound.

FIG. 1 is a flowchart showing a preferred embodiment of the method for producing an iodide ester compound of the present invention.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.
[Method for producing iodide ester compound]
First, the method for producing the iodide ester compound of the present invention will be described.
FIG. 1 is a flowchart showing a preferred embodiment of the method for producing an iodide ester compound of the present invention.

  The method for producing an iodide ester compound according to the present invention comprises reacting an ester compound represented by the following formula (2) with an iodine-based oxide in the presence of a porous substance to obtain an iodide compound represented by the following formula (3) It is characterized by having an iodination step of obtaining an ester compound.

（ただし、式（２）中、ｎは、１以上５以下の整数、Ｒは、炭素数が１以上３以下のアルキル基である。）

(However, in the formula (2), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

（ただし、式（３）中、ｎは、１以上５以下の整数、Ｒは、炭素数が１以上３以下のアルキル基である。）

(However, in the formula (3), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

  With such a configuration, it is possible to provide a method for producing an iodide ester compound, which has a high regioselectivity of an iodine introduction position and can obtain a target iodide ester compound in a high yield.

  Such an excellent effect is obtained by combining a porous substance and an iodine-based oxide, and when at least one of these is not used or is replaced with another substance, , Satisfactory results cannot be obtained.

For example, when a porous substance is not used, the iodination reaction hardly proceeds.
When the iodine-based oxide is not used, the iodination reaction hardly proceeds.

  Further, when sulfuric acid is used instead of the porous substance, the selectivity (p-selectivity) of the iodine introduction position is significantly reduced.

  Further, when chloric acid or a salt of chloric acid is used instead of the iodine-based oxide, the conversion of the ester compound is reduced and the selectivity (p-selectivity) of the iodine introduction position is also significantly reduced. I do. In addition, when the content of chloric acid or a salt of chloric acid in the reaction system is increased, the production of the chlorinated product takes precedence over the production of the iodide ester compound.

  When perchloric acid or a salt of perchloric acid is used instead of the iodine-based oxide, the iodination reaction does not proceed.

  When sulfuric acid or persulfate is used instead of the iodine-based oxide, the iodination reaction does not proceed.

  Further, when nitric acid is used instead of the iodine-based oxide, the selectivity (p-selectivity) of the iodine introduction position is reduced, and a large amount of nitrated product is generated.

  Further, the iodine-based oxide is preferably an acidic compound. When iodic acid or periodic acid is used, the selectivity (p-selectivity) of the iodine introduction position is increased.

In particular, in the present embodiment, the ester compound is converted into a solution containing the carboxylic acid (RCOOH) and the acid anhydride ((RCO) ₂ O) corresponding to the acid component constituting the ester compound by the following formula (1) )) Is produced through an esterification step of esterifying an alcohol compound represented by the formula (1). In another aspect of the present invention, a method for producing an iodide ester compound comprises a solution containing a carboxylic acid (RCOOH) and an acid anhydride ((RCO) ₂ O) corresponding to an acid component constituting the ester compound. An esterification step of esterifying an alcohol compound represented by the following formula (1) to obtain an ester compound represented by the following formula (2); and an ester compound, iodine (I ₂ ) in the presence of a porous substance; The method includes an iodination step of reacting with an iodine-based oxide to obtain an iodide ester compound represented by the following formula (3).

（ただし、式（１）中、ｎは、１以上５以下の整数である。）

(In the formula (1), n is an integer of 1 or more and 5 or less.)

（ただし、式（２）中、ｎは、１以上５以下の整数、Ｒは、炭素数が１以上３以下のアルキル基である。）

(However, in the formula (2), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

（ただし、式（３）中、ｎは、１以上５以下の整数、Ｒは、炭素数が１以上３以下のアルキル基である。）

(However, in the formula (3), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

  With such a configuration, the desired esterification reaction can proceed efficiently, and the desired ester compound can be obtained in a high yield. In particular, in the reaction, there is substantially no by-product that causes a problem in a subsequent step or becomes a problem by being included in the final iodide ester compound. Can be omitted or simplified. Further, it is suitable for performing the iodination step described later in detail. Further, since the alcohol compound represented by the formula (1) is easily available and inexpensive compared to the ester compound represented by the formula (2), the production cost of the iodide ester compound represented by the formula (3) is reduced. From the viewpoint of suppression and stable supply, it is preferable to use the alcohol compound as a raw material. Further, the esterification step and the iodination step can be suitably performed as a one-pot reaction.

That is, an alcohol compound represented by the above formula (1) is esterified in a solution containing a carboxylic acid and an acid anhydride thereof in the presence of a porous substance to obtain an ester compound represented by the above formula (2). An esterification step is performed, and the ester compound is reacted with iodine (I ₂ ) and an iodine-based oxide using the obtained reaction mixture to obtain an iodide ester compound represented by the above formula (3). An iodination step can be performed.

  By performing the esterification step and the iodination step as a one-pot reaction, the productivity of the iodide ester compound can be further improved.

  Further, the common component can be effectively used in the esterification step and the iodination step, which can contribute to the reduction of the amount of material used, and is preferable from the viewpoint of resource saving and reduction of production cost. More specifically, for example, an acid anhydride can be used as an esterifying agent for a hydroxyl group in the esterification step, and can function as a dehydrating agent for removing water generated by the reaction in the iodination step. The reaction can proceed more suitably.

<Esterification step>
In the esterification step, the alcohol compound represented by the above formula (1) is esterified in a solution containing a carboxylic acid (RCOOH) and its acid anhydride ((RCO) ₂ O), and the above formula (2) Is obtained.

  The alcohol compound serving as a substrate is represented by the above formula (1). In the formula (1), n may be 1 or more and 5 or less, but is preferably 1 or more and 4 or less, and is preferably 2 or more. It is more preferably 4 or less, and still more preferably 3.

As a result, the conversion of the ester compound in the subsequent iodination step (the amount of the ester compound used as a raw material in this step is X _E [mol], and the amount of the ester compound remaining as an unreacted component at the end of this step) the _'when a _{[mol], [(X E} -X E' X E and) / _{X E]} × value represented by 100) and selectivity of the position of the introduction of iodine (p- selectivity) higher ones can do.

As the carboxylic acid (RCOOH) and its acid anhydride ((RCO) ₂ O), those having an alkyl group (R) corresponding to an acid component constituting an ester compound may be used.

Examples of the carboxylic acid (RCOOH) include acetic acid, propionic acid, and butyric acid.
Examples of the acid anhydride include acetic anhydride, propionic anhydride, and butyric anhydride.

Among them, the carboxylic acid, preferably acetic acid (R = CH _3), acetic anhydride as an acid anhydride (R = CH ₃₎ are preferred.

  Thereby, the conversion of the ester compound in the subsequent iodination step and the selectivity (p-selectivity) of the introduction position of iodine can be made higher. Further, the reaction rate in the iodination step becomes faster, and the productivity of the target iodide ester compound can be made more excellent. Acetic acid and acetic anhydride are inexpensive among various carboxylic acids and various acid anhydrides, and are easily available. Therefore, it is advantageous from the viewpoint of reducing the production cost of the iodide ester compound, stable production of the iodide ester compound, and the like.

In this step, the reaction of esterifying the alcohol compound may be performed in a solution containing carboxylic acid (RCOOH) and its anhydride ((RCO) ₂ O), and the amount of each component is not particularly limited. However, it is preferable to satisfy the following conditions.

That is, the molar ratio (amount of substance of carboxylic acid anhydrides for the carboxylic acid used in this step _X CA [mol], the substance of the acid anhydride of _X AA _{/ X CA} when the _X AA [mol] Value) is preferably 0.2 or more and 1.0 or less, more preferably 0.3 or more and 0.8 or less, and even more preferably 0.4 or more and 0.7 or less.

  Thereby, the carboxylic acid can more suitably function as a solvent, and the acid anhydride can more suitably function as an esterifying agent. As a result, the esterification reaction in this step is more preferably performed. Let it proceed. In addition, when the esterification step and the iodination step are performed as a one-pot reaction, an acid anhydride can be left in an appropriate ratio at the end of this step (esterification step), and the acid anhydride can be left in the iodination step. Can function more suitably as a dehydrating agent.

Further, the material of the molar ratio (alcohol compounds anhydride to alcohol compound used in the present process _X AC [mol], the substance of the acid anhydride _X AA [mol] and then the _X AA _{/ X AC} when the Value) is preferably 1.2 or more and 5.0 or less, more preferably 1.5 or more and 4.5 or less, and even more preferably 1.8 or more and 4.0 or less.

  This allows the acid anhydride to function more suitably as an esterifying agent, and allows the esterification reaction in this step to proceed more suitably. In addition, when the esterification step and the iodination step are performed as a one-pot reaction, an acid anhydride can be left in an appropriate ratio at the end of this step (esterification step), and the acid anhydride can be left in the iodination step. Can function more suitably as a dehydrating agent. In addition, since an acid anhydride is not used more than necessary, it is advantageous from the viewpoint of reducing the production cost of iodide ester compounds and saving resources.

  Further, this step is preferably performed in the presence of a porous substance (particularly, a porous substance used also in the iodination step).

In the iodination step, the reaction proceeds in the pores, so that the ester compound is sterically hindered, and the generation of by-products can be more effectively suppressed. When the porous material functions as a source of hydrogen ions (H ⁺ ) such as zeolite, in the esterification step, the porous material functions as a catalyst for the esterification reaction, and an acidic material is separately added. Even if not used, the esterification reaction can proceed more efficiently. When a porous substance (preferably zeolite) is used, the esterification step and the iodination step can be suitably performed as a one-pot reaction, and the productivity of the iodide ester compound can be further improved.
The porous substance will be described later in detail.

Further, the esterification step of the present invention can be performed in the presence of iodine (I _2, particularly iodine used also in the iodination step).

Thereby, the esterification step and the iodination step can be suitably performed as a one-pot reaction, and the productivity of the iodide ester compound can be further improved. In addition, iodine (I ₂ ) does not inhibit the esterification reaction and can be dissolved first, so that the dissolution time can be shortened and the productivity of the iodide ester compound as a whole can be further increased. It can be excellent. The esterification step may be performed, for example, in a state where most of the iodine (I ₂ ) in the system is not dissolved.

  The reaction temperature in this step is not particularly limited, but is preferably 5 ° C to 45 ° C, more preferably 10 ° C to 40 ° C, and even more preferably 15 ° C to 30 ° C.

  Thus, the esterification reaction can proceed more favorably while omitting or simplifying the temperature control such as heating and cooling, which is advantageous from the viewpoint of improving the productivity of the iodide ester compound.

  The treatment time (reaction time) in this step is not particularly limited, but is preferably 2 minutes or more and 120 minutes or less, more preferably 5 minutes or more and 90 minutes or less, and is 15 minutes or more and 60 minutes or less. Is more preferred.

  Thereby, the yield of the ester compound in this step can be further improved, and it is advantageous from the viewpoint of improving the productivity of the iodide ester compound.

<Iodination process>
In the iodination step, an ester compound represented by the formula (2) is reacted with iodine (I ₂ ) and an iodine-based oxide in the presence of a porous substance to form an iodide ester compound represented by the formula (3) (P-monoiodide ester compound) is obtained.

By using a porous substance, iodine (I ₂ ), and an iodine-based oxide, an iodination reaction of an ester compound can be efficiently advanced, and a target iodide ester compound can be obtained in a high yield. be able to.

  Further, the iodination reaction of the ester compound can proceed with high regioselectivity (that is, p-selectivity), and generation of isomers and the like can be efficiently prevented. Thus, the subsequent purification step can be performed under mild conditions, the purification step can be performed efficiently in a short time, and the final purity can be further increased.

In addition, the iodine-based oxide functions as an oxidizing agent in the iodination reaction and also functions as an iodine (I) source, so that the amount of iodine (I ₂ ) used can be reduced.

In this embodiment, after the esterification step, an iodine-based oxide is supplied into the reaction system.
By carrying out the reaction in two steps, excessive heat generation can be suppressed, so that decomposition of iodine-based oxides and generation of by-products can be suppressed, and the reaction can proceed more suitably.

  The iodine-based oxide may be supplied to the reaction system in a solid state, for example, but is preferably supplied to the reaction system in the form of an aqueous solution dissolved in water.

  Thus, an easily available aqueous solution (an aqueous solution of an iodine-based oxide) can be suitably used for the reaction, which is advantageous from the viewpoint of suppressing the production cost of the target iodide ester compound and improving the productivity. . In addition, solid iodine-based oxides have low solubility in carboxylic acid and the like as a solvent and are difficult to uniformly exist in the reaction system, but by using an aqueous solution, iodine-based oxide The oxide can be made to exist more uniformly, and the iodination reaction can suitably proceed.

After the esterification step, components other than the iodine-based oxide may be supplied into the reaction system. For example, at least one of a carboxylic acid, an acid anhydride, a porous substance, and iodine (I ₂ ) may be supplied into the reaction system after the esterification step. In this case, a mixture of a plurality of types of components may be supplied into the reaction system.

  This step is preferably performed in a dispersion in which a dispersoid containing an iodine-based oxide is dispersed in a dispersion medium composed of an organic solution containing a carboxylic acid.

  Since the iodine-based oxide has low solubility in carboxylic acid and the like as a solvent, by dispersing a dispersoid containing the iodine-based oxide, the iodine-based oxide can be more uniformly present in the reaction system. In addition, the iodination reaction can suitably proceed.

  The average particle size of the dispersoid is preferably 50 μm or more and 10000 μm or less, more preferably 80 μm or more and 5000 μm or less, and even more preferably 100 μm or more and 1000 μm or less.

  This allows the iodine-based oxide to be more uniformly present in the reaction system, and allows the iodination reaction to proceed more suitably.

  In the present specification, the average particle size refers to a volume-based average particle size unless otherwise specified. The average particle size can be determined, for example, by measurement using Microtrac UPA (manufactured by Nikkiso Co., Ltd.).

  Further, the iodine-based oxide may be dispersed in any method, but may be dispersed in the reaction system by a method of sequential addition or divisional addition, or a method of adding a dispersion in a solvent in advance. It is preferable that the dispersoid containing the iodine-based oxide be dispersed.

  This allows the iodine-based oxide to be more uniformly present in the reaction system, and allows the iodination reaction to proceed more suitably.

  As long as the iodine-based oxide is contained in the reaction system when the reaction of this step proceeds, it is added to the reaction system after the reaction system is heated after the esterification step. Is preferred.

Thereby, in the case of using the acid anhydride ((RCO) ₂ O), the dehydration by the acid anhydride proceeds more favorably, a fine dispersoid can be formed, and the iodine-based oxide is formed in the reaction system. It can be more uniformly present. As a result, the iodination reaction can proceed more suitably.

In this step, an ester compound represented by the formula (2), iodine (I ₂ ), and an iodine-based oxide may be reacted in the presence of a porous substance. Preferably, the reaction is performed in a solution containing a carboxylic acid (RCOOH) and an acid anhydride ((RCO) ₂ O) corresponding to the above.

  As a result, undesired transesterification and hydrolysis of the ester compound can be effectively prevented, and the generation of undesirable by-products can be more effectively prevented.

  When this step is performed in a solution containing a carboxylic acid and an acid anhydride, the content (molar ratio) of the acid anhydride to the content of the carboxylic acid in the solution used in this step is 0.05 or more and 0.8 or more. It is preferably at most 0.1, more preferably at least 0.1 and at most 0.6, even more preferably at least 0.2 and at most 0.5.

  Thereby, the carboxylic acid can more suitably function as a solvent, and the acid anhydride can more suitably function as a dehydrating agent.

  Further, the content (molar ratio) of the acid anhydride to the content of the ester compound in the solution used in this step is preferably 0.2 or more and 4.0 or less, and 0.5 or more and 3.5 or less. More preferably, it is more preferably 0.8 or more and 3.0 or less.

  This allows the acid anhydride to function more suitably as a dehydrating agent. In addition, since an acid anhydride is not used more than necessary, it is advantageous from the viewpoint of reducing the production cost of iodide ester compounds and saving resources.

The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in this step (X when the amount of the ester compound is X _E [mol] and the amount of the iodine (I ₂ ) is X _I [mol] the value of _I / _{X E)} is preferably from 0.1 to 1.0, and more preferably at 0.2 to 0.8, and even 0.3 to 0.6 More preferred.

As a result, iodine (I ₂ ) is not used more than necessary, which is more advantageous from the viewpoint of reducing the production cost of iodide ester compounds and saving resources.

The molar ratio of iodine oxide to an ester compound in the solution used in this step (the substance amount of the ester compound X _{E [mol],} when the amount of substance of iodine oxide and X _{A [mol]} X _A / the value of X _E) is preferably 0.05 or more and 1.0 or less, more preferably 0.10 to 0.7, even more preferably 0.20 to 0.5 .

  As a result, the iodine-based oxide is not used more than necessary, which is more advantageous from the viewpoint of reducing the production cost of the iodide ester compound and saving resources.

The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used in this step (the amount of iodine-based oxide was X _A [mol], and the amount of iodine (I ₂ ) was X _I [mol]. the value of _X I / _{X a} when the) is preferably 0.3 to 3.0, more preferably at 1.0 to 2.5, 1.2 to 2.0 Is more preferred.

As a result, iodine (I ₂ ) and iodine-based oxide are not used more than necessary, which is more advantageous from the viewpoint of reducing the production cost of iodide ester compounds and saving resources.

  Further, the content of the porous substance with respect to 100 parts by mass of the ester compound in the solution used in this step is preferably 5 parts by mass or more and 150 parts by mass or less, more preferably 10 parts by mass or more and 100 parts by mass or less. More preferably, the amount is 15 parts by mass or more and 70 parts by mass or less.

  Thereby, the iodination reaction proceeds more suitably, and while the conversion of the ester compound is made higher, after the completion of this step, the iodide ester compound remains in the pores of the porous substance, and the iodide ester The compound recovery can be more effectively prevented from lowering. Further, recovery of the iodide ester compound becomes easy.

  The reaction temperature in this step is not particularly limited, but is preferably 30 ° C or more and 80 ° C or less, more preferably 35 ° C or more and 75 ° C or less, and further preferably 40 ° C or more and 60 ° C or less.

  This makes it possible to increase the energy state of the reaction raw material while more effectively preventing the iodine-based oxide from being thermally decomposed, and to allow the iodination reaction to proceed more suitably.

  The treatment time (reaction time) in this step is not particularly limited, but is preferably 3 hours to 48 hours, more preferably 4 hours to 24 hours, and more preferably 5 hours to 12 hours. Is more preferred.

  Thereby, the yield of the iodide ester compound can be further improved, and it is advantageous from the viewpoint of improving the productivity of the iodide ester compound.

Hereinafter, the iodine-based oxide used in this step will be described.
The iodine-based oxide in the present invention is a compound containing an oxidized iodine atom, and includes iodine oxide, iodic acids and salts thereof. The iodine oxide includes a compound represented by I _x O _y (x and y are natural numbers). The iodic acids include hypoiodic acid, iodic acid and periodic acid. Sodium, potassium and the like salts of hypoiodic acid, iodic acid and periodate can also be used. The iodine-based oxide in the present invention is preferably iodic acids which are acidic compounds capable of generating hydrogen ions, and more preferably iodic acid and periodic acid.

Iodic acid is a compound represented by the composition formula of HIO ₃ .
Periodic acid includes two types of metaperiodic acid (HIO ₄ ) and orthoperiodic acid (H ₅ IO ₆ ). When the iodine-based oxide contains periodic acid, it may contain only one of metaperiodic acid (HIO ₄ ) and orthoperiodic acid (H ₅ IO ₆ ), or may contain both. Good.

  The iodine-based oxide in the present invention particularly preferably contains iodic acid, and contains iodic acid as a main component (for example, the content of iodic acid in all iodine-based oxides is 50% by mass or more. Is more preferable, and it is still more preferable that the film substantially consists of only iodic acid.

  Thereby, the conversion, the selectivity of the ester compound, and the selectivity (p-selectivity) of the iodine introduction position can be made higher.

Conversion of the ester compound in the end of this process (the substance amount of the ester compound used as the starting material in this step X _{E [mol],} the substance amount of the ester compound remaining as unreacted during the process ends X _{E 'when} the _{[mol], [(X E} -X E') / X E] value indicated by × 100) is preferably 100% or less 60% or more, 100% or more and 90% or less Is more preferable, and it is still more preferable that it is 95% or more and 100% or less.

  At the end of this step, the p-selectivity (position selectivity) of the iodine introduction position to the aromatic ring in all the iodide ester compounds as the reaction product is preferably 90% or more and 100% or less, and is preferably 94% or less. % Or more, and more preferably 96% or more and 100% or less.

  This not only improves the yield of the target iodide ester compound (p-monoiodide ester compound), but also allows, for example, when performing a subsequent purification step, the step to be performed under milder conditions. In addition, the purification step can be performed efficiently in a short time, and the final purity can be further increased.

<Purification process>
After the iodination step, a purification step of purifying the mixture containing the reaction product may be provided as necessary.

  Examples of the purification treatment include filtration, removal of a porous substance by decantation or the like, distillation of components such as a solvent using an evaporator or the like, liquid separation treatment, recrystallization, distillation, treatment by various types of chromatography, and the like. Can be

  In particular, in the present invention, the desired iodide ester compound (p-monoiodide ester compound) is preferably precipitated by cooling the composition after iodination step (composition in which the reaction product is dissolved). Can be.

  That is, as described above, according to the present invention, the target iodide ester compound (p-monoiodide ester compound) has high selectivity while suppressing the generation of undesired by-products in the iodination step. And at a high conversion rate, the content of the target iodide ester compound (p-monoiodide ester compound) is higher than the content of other isomers even before the purification treatment. The rate is particularly high.

  Thereby, the target iodide ester compound (p-monoiodide ester compound) can be easily and efficiently separated from other isomers and unreacted components (ester compound and alcohol compound) under relatively mild conditions. can do. More specifically, when the composition after the iodination step (the composition in which the reaction product is dissolved) is cooled, the target iodide ester compound can be selected without extremely lowering the cooling temperature. Can be efficiently and efficiently deposited.

  The cooling temperature at the time of precipitating the target iodide ester compound is, for example, preferably -25 ° C or higher and -1 ° C or lower, more preferably -15 ° C or higher and -2 ° C or lower, and -10 ° C. More preferably, the temperature is not higher than -3 ° C.

  When the target iodide ester compound is precipitated (when recrystallized), a recrystallization solvent (a poor solvent for the iodide ester compound) may be used.

  As the poor solvent for recrystallization, for example, hydrocarbon solvents such as n-heptane and n-hexane can be used.

<Porous substance>
Hereinafter, the porous substance used in the production method of the present invention will be described in detail.

  The porous substance used in the production method of the present invention may have any pores, and the average pore diameter of the porous substance is not particularly limited, but is preferably from 5.0 ° to 9.0 °, It is more preferably 5.5 ° or more and 6.8 ° or less, and still more preferably 5.9 ° or more and 6.5 ° or less.

  This makes it easier for the ester compound as a reaction substrate to penetrate into the pores of the porous substance in a predetermined direction, thereby improving the selectivity (p-selectivity) of the iodine introduction position and the target iodine. The reaction rate of the conversion reaction can be further increased. Further, deterioration of the porous material can be more effectively prevented, and for example, the porous material can be more suitably recycled.

  The porous substance may have pores enough to allow the reaction substrate to enter, and for example, zeolite, aluminum phosphate, crystalline silica titanium, a crystalline layered compound such as smectite and the like can be used, In particular, zeolite is preferred.

The zeolite not only has pores as a field where the ester compound reacts, but also functions as a supply source of hydrogen ions (H ⁺ ), so that the overall reaction efficiency can be further improved. In addition, zeolite is a porous material that is relatively inexpensive, easily and stably available, and is therefore advantageous from the viewpoint of stable production of iodide ester compounds and reduction in production cost of iodide ester compounds. It is.

The SiO ₂ / Al ₂ O ₃ ratio (molar ratio) in the zeolite is preferably 4 or more and 90 or less, more preferably 6 or more and 70 or less, and even more preferably 10 or more and 45 or less.
Thereby, the number of acid sites in the pores increases, and the reaction rate can be further increased.

  As the zeolite, for example, various types such as A type, L type, Y type, X type, β type, ferrierite, MCM-22, ZSM-5, and mordenite can be used. Is preferred.

  The preferred embodiments of the present invention have been described above, but the present invention is not limited to these.

  For example, the method for producing an iodide ester compound of the present invention may include steps other than the above-described steps (for example, a pretreatment step, an intermediate treatment step, a post-treatment step, and the like).

  Further, the method for producing an iodide ester compound of the present invention may have the above-mentioned iodination step, and other steps may be omitted. For example, when an ester compound (for example, a commercially available ester compound) is used as a raw material, the esterification step may be omitted. Further, the purification step after the iodination step may be omitted.

  Further, in the method for producing an iodide ester compound of the present invention, components other than those described above may be used. For example, a solvent component other than those described above may be used. In particular, an auxiliary solvent may be used together with the above-mentioned solvent. As such a co-solvent, for example, ethyl acetate or the like can be used.

  Hereinafter, the present invention will be described in detail based on specific examples, but the present invention is not limited thereto. In the processing and measurement in the following examples, those not showing the temperature conditions were performed at room temperature (23 ° C.).

[Examination of relationship between reaction substrate and reactivity]
(Example A1)
First, a commercially available alcohol compound represented by the following formula (4) (a compound in which n in the formula (1) is 3) was prepared.

Next, the alcohol compound, iodine (I ₂ ), acetic acid, zeolite, and acetic anhydride were put into an eggplant flask at a predetermined ratio, and the mixture was stirred at 25 ° C. for 30 minutes to advance the acetylation reaction (ester). Process). Here, the amounts of the alcohol compound, iodine (I ₂ ), acetic acid, and acetic anhydride used were 10: 4: 60: 30 in a molar ratio. The amount of zeolite used was 37 parts by mass with respect to 100 parts by mass of the alcohol compound. As the zeolite (porous substance), an H-β type zeolite having an average pore diameter of 6 ° and a SiO ₂ / Al ₂ O ₃ ratio (molar ratio) of 18 was used.
Thereafter, the mixture in the eggplant flask was heated to 60 ° C. while stirring.

Thereafter, a predetermined amount of a 70% by mass aqueous HIO ₃ solution was added to the eggplant-shaped flask, followed by stirring at 60 ° C. for 22 hours (iodination step). At this time, the HIO ₃ aqueous solution was added such that the molar ratio of HIO _{3 to} the ester compound (the same as the molar ratio to the alcohol compound) was 0.3. In addition, with the HIO ₃ aqueous solution added, the reaction system was in the state of a dispersion in which a dispersoid containing an iodine-based oxide (HIO ₃ ) was dispersed.

  The content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.3.

  The content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 2.0.

The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 0.4.

The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used in the iodination step was 1.3.

Immediately after the end of the iodination step, a part of the mixture was sampled from the eggplant flask and analyzed by gas chromatography, and the conversion and selectivity (X _{A ′} [ mol], and when the substance amount of all iodide ester compounds at the end of the iodination step (the introduction position of iodine is not limited, and includes o-form and m-form), X _IE [mol] is represented by (X _IE / X _{A ′} ) × 100), p-selectivity (X _PIE [mol] of the amount of the p-monoiodinated ester compound at the end of the iodination step, total iodide ester at the end of the iodination step) When the substance amount of the compound (however, the position where iodine is introduced is not limited and the o-form and the m-form are included) is defined as X _IE [mol], a value represented by (X _PIE / X _IE ) × 100) and And p-monoiodide ester compound selectivity (a value indicated by the product of selectivity and p-selectivity) was evaluated.

(Example A2)
Except that the alcohol compound was changed to a commercially available compound represented by the following formula (5) (compound in which n in the formula (1) is 1), the same treatment as in Example A1 was carried out. Was evaluated for conversion, selectivity, p-selectivity and p-monoiodide ester compound selectivity.

(Example A3)
Except that the alcohol compound was changed to a commercially available compound represented by the following formula (6) (compound in which n in the formula (1) is 2), the same treatment as in Example A1 was carried out. Was evaluated for conversion, selectivity, p-selectivity and p-monoiodide ester compound selectivity.

(Example A4)
Except that the alcohol compound was changed to a commercially available compound represented by the following formula (7) (compound in which n in the formula (1) is 4), the same treatment as in Example A1 was carried out. Was evaluated for conversion, selectivity, p-selectivity and p-monoiodide ester compound selectivity.

(Example A5)
Except that the alcohol compound was changed to a commercially available compound represented by the following formula (8) (compound where n in the formula (1) is 5), the same treatment as in the above-mentioned Example A1 was carried out. Was evaluated for conversion, selectivity, p-selectivity and p-monoiodide ester compound selectivity.

  These results are summarized in Table 1. In each of the examples, the yield of the ester compound from the alcohol compound was 100%.

In each of the above examples, the content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.2 or more. 0.3 or less, and the content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 2.0 to 2.2. The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 0.4 to 0.5, The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used for the above was 1.3 or more and 1.4 or less.

  As is clear from Table 1, in the present invention, the target iodide ester compound (p-monoiodide ester compound) could be obtained with a high conversion and a high selectivity for the p-monoiodide ester compound.

[Examination of relationship between porous material and reactivity]
(Example B1)
First, a commercially available alcohol compound represented by the following formula (4) (a compound in which n in the formula (1) is 3) was prepared.

Next, the alcohol compound, iodine (I ₂ ), acetic acid, zeolite and acetic anhydride were put into a eggplant flask at a predetermined ratio, and the mixture was stirred at 25 ° C. for 30 minutes to advance the acetylation reaction (ester). Process). Here, the amounts of the alcohol compound, iodine (I ₂ ), acetic acid, and acetic anhydride used were 10: 4: 60: 30 in a molar ratio. The amount of zeolite used was 38 parts by mass based on 100 parts by mass of the alcohol compound. As the zeolite (porous substance), an H-β type zeolite having an average pore diameter of 6 ° and a SiO ₂ / Al ₂ O ₃ ratio (molar ratio) of 18 was used.
Thereafter, the mixture in the eggplant flask was heated to 60 ° C. while stirring.

Thereafter, a predetermined amount of a 70% by mass aqueous HIO ₃ solution was added to the eggplant-shaped flask, followed by stirring at 60 ° C. for 22 hours (iodination step). At this time, the HIO ₃ aqueous solution was added such that the molar ratio of HIO _{3 to} the ester compound (the same as the molar ratio to the alcohol compound) was 0.25. In addition, with the HIO ₃ aqueous solution added, the reaction system was in the state of a dispersion in which a dispersoid containing an iodine-based oxide (HIO ₃ ) was dispersed.

  The content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.3.

  The content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 2.0.

The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 0.4.

The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used in the iodination step was 1.6.

Immediately after the end of the iodination step, a part of the mixture was sampled from the eggplant flask and analyzed by gas chromatography, and the conversion and selectivity (X _{A ′} [ mol], and when the substance amount of all iodide ester compounds at the end of the iodination step (the introduction position of iodine is not limited, and includes o-form and m-form), X _IE [mol] is represented by (X _IE / X _{A ′} ) × 100), p-selectivity (X _PIE [mol] of the amount of the p-monoiodinated ester compound at the end of the iodination step, total iodide ester at the end of the iodination step) When the substance amount of the compound (however, the position where iodine is introduced is not limited and the o-form and the m-form are included) is defined as X _IE [mol], a value represented by (X _PIE / X _IE ) × 100) and And p-monoiodide ester compound selectivity (a value indicated by the product of selectivity and p-selectivity) was evaluated.

(Examples B2 and B3)
As shown in Table 2, the same treatment as in Example B1 was performed, except that a zeolite having a different SiO ₂ / Al ₂ O ₃ ratio (molar ratio) as shown in Table 2 was used. Conversion, selectivity and p-selectivity were evaluated.

(Examples B4 to B6)
Except that H-ZSM-5 under the conditions shown in Table 2 was used as the zeolite, the same treatment as in Example B1 was carried out, and the conversion, selectivity, p-selectivity and The p-monoiodide ester compound selectivity was evaluated.

(Example B7)
Except that H-mordenite under the conditions shown in Table 2 was used as the zeolite, the same treatment as in Example B1 was performed, and the conversion, selectivity, p-selectivity and p-selectivity at the end of the iodination step were completed. The monoiodide ester compound selectivity was evaluated.

(Examples B8 to B10)
Except for using HY type zeolite under the conditions shown in Table 2, the same treatment as in Example B1 was performed, and the conversion, selectivity, and p-selectivity at the end of the iodination step were performed. And p-monoiodide ester compound selectivity was evaluated.

(Comparative Example B1)
The same treatment as in Example B1 was carried out except that zeolite was not used and sulfuric acid was used instead, and the conversion, selectivity, p-selectivity, and p-monoiodide ester compound selection at the end of the iodination step. Rate was evaluated. The amount of sulfuric acid used in this comparative example was 38 parts by mass with respect to 100 parts by mass of the alcohol compound.

  Table 2 summarizes the conditions and evaluation results of the porous substance (zeolite) for these examples and comparative examples. In each of the above Examples and Comparative Examples, the yield of the ester compound from the alcohol compound was 100%.

In each of the above examples, the content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.2 or more. 0.3 or less, and the content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 2.0 to 2.2. The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 0.4 to 0.5, The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used for the above was 1.4 or more and 1.6 or less.

As is clear from Table 2, in the present invention, the desired iodide ester compound (p-monoiodide ester compound) could be obtained with a high p-monoiodide ester compound selectivity. Particularly, excellent results were obtained by using a porous material (zeolite) under preferable conditions.
On the other hand, in the comparative example, a satisfactory result was not obtained.

[Examination of relationship between ratio of iodine and iodine-based oxide and reactivity]
(Example C1)
First, a commercially available alcohol compound represented by the following formula (4) (a compound in which n in the formula (1) is 3) was prepared.

Next, the alcohol compound, iodine (I ₂ ), acetic acid, zeolite, and acetic anhydride were put into an eggplant flask at a predetermined ratio, and the mixture was stirred at 25 ° C. for 30 minutes to advance the acetylation reaction (ester). Process). Here, the amounts of the alcohol compound, iodine (I ₂ ), acetic acid, and acetic anhydride used were 10: 4: 60: 30 in a molar ratio. The amount of zeolite used was 37 parts by mass with respect to 100 parts by mass of the alcohol compound. As the zeolite (porous substance), an H-β type zeolite having an average pore diameter of 6 ° and a SiO ₂ / Al ₂ O ₃ ratio (molar ratio) of 18 was used.
Thereafter, the mixture in the eggplant flask was heated to 60 ° C. while stirring.

Thereafter, a predetermined amount of a 70% by mass aqueous HIO ₃ solution was added to the eggplant-shaped flask, followed by stirring at 60 ° C. for 22 hours (iodination step). At this time, the HIO ₃ aqueous solution was added such that the molar ratio of HIO _{3 to} the ester compound (the same as the molar ratio to the alcohol compound) was 0.20. In addition, with the HIO ₃ aqueous solution added, the reaction system was in the state of a dispersion in which a dispersoid containing an iodine-based oxide (HIO ₃ ) was dispersed.

  The content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.3.

  The content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 2.0.

The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 0.4.

The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used in the iodination step was 2.0.

Immediately after the end of the iodination step, a part of the mixture was sampled from the eggplant flask and analyzed by gas chromatography, and the conversion and selectivity (X _{A ′} [ mol], and when the substance amount of all iodide ester compounds at the end of the iodination step (the introduction position of iodine is not limited, and includes o-form and m-form), X _IE [mol] is represented by (X _IE / X _{A ′} ) × 100), p-selectivity (X _PIE [mol] of the amount of the p-monoiodinated ester compound at the end of the iodination step, total iodide ester at the end of the iodination step) When the substance amount of the compound (however, the position where iodine is introduced is not limited and the o-form and the m-form are included) is defined as X _IE [mol], a value represented by (X _PIE / X _IE ) × 100) and And p-monoiodide ester compound selectivity (a value indicated by the product of selectivity and p-selectivity) was evaluated.

(Examples C2 to C7)
Except that the ratio of iodine (I ₂ ) and HIO ₃ (iodine-based oxide) to the alcohol compound was changed as shown in Table 3, the same treatment as in Example C1 was performed, and the conversion at the end of the iodination step was performed. The rate, selectivity, p-selectivity and p-monoiodide ester compound selectivity were evaluated.

(Comparative Example C1)
When iodine (I ₂ ) was not used and the ratio of HIO ₃ (iodine-based oxide) to the alcohol compound was changed as shown in Table 3, the same treatment as in Example C1 was performed. Was evaluated for conversion, selectivity, p-selectivity and p-monoiodide ester compound selectivity.

Table 3 shows the ratios of iodine (I ₂ ) and HIO ₃ (iodine-based oxide) to the alcohol compound and the evaluation results for these Examples and Comparative Examples. In each of the above Examples and Comparative Examples, the yield of the ester compound from the alcohol compound was 100%.

In each of the above examples, the content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.2 or more. 0.3 or less, and the content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 2.0 to 2.2. And the molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 0.4 or more and 1.0 or less. The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used for the above was 0.4 or more and 3.3 or less.

As is clear from Table 3, in the present invention, the desired iodide ester compound (p-monoiodide ester compound) could be obtained with a high conversion and a high selectivity for the p-monoiodide ester compound.
On the other hand, in the comparative example, a satisfactory result was not obtained.

[Examination of relationship between amount of porous material used and reactivity]
(Example D1)
First, a commercially available alcohol compound represented by the following formula (4) (a compound in which n in the formula (1) is 3) was prepared.

Next, the alcohol compound, iodine (I ₂ ), acetic acid, zeolite and acetic anhydride were put into a eggplant flask at a predetermined ratio, and the mixture was stirred at 25 ° C. for 30 minutes to advance the acetylation reaction (ester). Process). Here, the amounts of the alcohol compound, iodine (I ₂ ), acetic acid, and acetic anhydride used were 10: 4: 60: 30 in a molar ratio. The amount of zeolite used was 37 parts by mass with respect to 100 parts by mass of the alcohol compound. As the zeolite (porous substance), an H-β type zeolite having an average pore diameter of 6 ° and a SiO ₂ / Al ₂ O ₃ ratio (molar ratio) of 18 was used.
Thereafter, the mixture in the eggplant flask was heated to 60 ° C. while stirring.

Thereafter, a predetermined amount of a 70% by mass aqueous HIO ₃ solution was added to the eggplant-shaped flask, followed by stirring at 60 ° C. for 22 hours (iodination step). At this time, the HIO ₃ aqueous solution was added such that the molar ratio of HIO _{3 to} the ester compound (the same as the molar ratio to the alcohol compound) was 0.25. In addition, with the HIO ₃ aqueous solution added, the reaction system was in the state of a dispersion in which a dispersoid containing an iodine-based oxide (HIO ₃ ) was dispersed.

  The content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.3.

  The content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 2.0.

The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 0.4.

The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used in the iodination step was 1.6.

Immediately after the end of the iodination step, a part of the mixture was sampled from the eggplant flask and analyzed by gas chromatography, and the conversion and selectivity (X _{A ′} [ mol], and when the substance amount of all iodide ester compounds at the end of the iodination step (the introduction position of iodine is not limited, and includes o-form and m-form), X _IE [mol] is represented by (X _IE / X _{A ′} ) × 100), p-selectivity (X _PIE [mol] of the amount of the p-monoiodinated ester compound at the end of the iodination step, total iodide ester at the end of the iodination step) substance amount of the compound (provided that the position of the introduction of iodine is not limited, o bodies, m body including) when was the _X IE _[mol], our value represented by _{(X PIE / X IE) ×} 100) Beauty p- mono-iodinated ester compound selectivity (the value represented by the product of selectivity and p- selectivity) was assessed.

(Examples D2 to D4)
Except that the amount of zeolite (porous substance) used was changed as shown in Table 4, the same treatment as in Example D1 was performed, and the conversion, selectivity, p-selectivity and p at the end of the iodination step were completed. -The monoiodide ester compound selectivity was evaluated.

(Comparative Example D1)
Except that no zeolite (porous substance) was used, the same treatment as in Example D1 was performed, and the conversion, selectivity, p-selectivity, and p-monoiodide ester compound selectivity at the end of the iodination step were reduced. evaluated.

  Table 4 summarizes the amounts of zeolite used and the evaluation results with respect to the alcohol compound for these Examples and Comparative Examples. In each of the examples, the yield of the ester compound from the alcohol compound was 100%.

In each of the above examples, the content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.2 or more. 0.3 or less, and the content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 2.0 to 2.2. The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 0.4 to 0.5, The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used for the above was 1.3 or more and 1.6 or less.

As is clear from Table 4, in the present invention, the desired iodide ester compound (p-monoiodide ester compound) could be obtained with a high conversion and a high selectivity for the p-monoiodide ester compound.
On the other hand, in the comparative example, a satisfactory result was not obtained.

[Examination of the relationship between reaction temperature and reactivity in the iodination step]
(Example E1)
First, a commercially available alcohol compound represented by the following formula (4) (a compound in which n in the formula (1) is 3) was prepared.

Next, the alcohol compound, iodine (I ₂ ), acetic acid, zeolite and acetic anhydride were put into a eggplant flask at a predetermined ratio, and the mixture was stirred at 25 ° C. for 30 minutes to advance the acetylation reaction (ester). Process). Here, the amounts of the alcohol compound, iodine (I ₂ ), acetic acid, and acetic anhydride used were 10: 4: 60: 30 in a molar ratio. The amount of zeolite used was 37 parts by mass with respect to 100 parts by mass of the alcohol compound. As the zeolite (porous substance), an H-β type zeolite having an average pore diameter of 6 ° and a SiO ₂ / Al ₂ O ₃ ratio (molar ratio) of 18 was used.
Thereafter, the mixture in the eggplant flask was heated to 40 ° C. while stirring.

Thereafter, a predetermined amount of a 70% by mass aqueous HIO ₃ solution was added to the eggplant-shaped flask, followed by stirring at 40 ° C. for 22 hours (iodination step). At this time, the HIO ₃ aqueous solution was added such that the molar ratio of HIO _{3 to} the ester compound (the same as the molar ratio to the alcohol compound) was 0.25. In addition, with the HIO ₃ aqueous solution added, the reaction system was in the state of a dispersion in which a dispersoid containing an iodine-based oxide (HIO ₃ ) was dispersed.

  The content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.3.

  The content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 2.0.

The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 0.4.

The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used in the iodination step was 1.6.

Immediately after the end of the iodination step, a part of the mixture was sampled from the eggplant flask and analyzed by gas chromatography, and the conversion and selectivity (X _{A ′} [ mol], and when the substance amount of all iodide ester compounds at the end of the iodination step (the introduction position of iodine is not limited, and includes o-form and m-form), X _IE [mol] is represented by (X _IE / X _{A ′} ) × 100), p-selectivity (X _PIE [mol] of the amount of the p-monoiodinated ester compound at the end of the iodination step, total iodide ester at the end of the iodination step) substance amount of the compound (provided that the position of the introduction of iodine is not limited, o bodies, m body including) when was the _X IE _[mol], our value represented by _{(X PIE / X IE) ×} 100) Beauty p- mono-iodinated ester compound selectivity (the value represented by the product of selectivity and p- selectivity) was assessed.

(Examples E2 to E5)
Except that the treatment temperature (reaction temperature) in the iodination step was changed as shown in Table 5, the same treatment as in Example E1 was performed, and the conversion, selectivity, and p-selectivity at the end of the iodination step. And p-monoiodide ester compound selectivity was evaluated.

  Table 5 summarizes the processing temperatures (reaction temperatures) in the iodination step and the evaluation results for these examples. In each of the examples, the yield of the ester compound from the alcohol compound was 100%.

In each of the above examples, the content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.2 or more. 0.3 or less, and the content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 2.0 to 2.2. The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 0.4 to 0.5, The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used for the above was 1.3 or more and 1.6 or less.

  As is clear from Table 5, in the present invention, the target iodide ester compound (p-monoiodide ester compound) could be obtained with a high conversion and a high selectivity for the p-iodoester compound.

[Examination of relationship between other various conditions and reactivity]
(Example F1)
First, a commercially available alcohol compound represented by the following formula (4) (a compound in which n in the formula (1) is 3) was prepared.

Next, the alcohol compound, iodine (I ₂ ), acetic acid, zeolite and acetic anhydride were put into a eggplant flask at a predetermined ratio, and the mixture was stirred at 25 ° C. for 30 minutes to advance the acetylation reaction (ester). Process). Here, the amounts of the alcohol compound, iodine (I ₂ ), acetic acid, and acetic anhydride used were 10: 4: 60: 30 in a molar ratio. The amount of zeolite used was 37 parts by mass with respect to 100 parts by mass of the alcohol compound. As the zeolite (porous substance), an H-β type zeolite having an average pore diameter of 6 ° and a SiO ₂ / Al ₂ O ₃ ratio (molar ratio) of 18 was used.
Thereafter, the mixture in the eggplant flask was heated to 60 ° C. while stirring.

Thereafter, a predetermined amount of a 70% by mass aqueous HIO ₃ solution was added to the eggplant flask, and the mixture was stirred at 60 ° C. for 7 hours (iodination step). At this time, the HIO ₃ aqueous solution was added such that the molar ratio of HIO _{3 to} the ester compound (the same as the molar ratio to the alcohol compound) was 0.30. In addition, with the HIO ₃ aqueous solution added, the reaction system was in the state of a dispersion in which a dispersoid containing an iodine-based oxide (HIO ₃ ) was dispersed.

  The content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.3.

  The content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 2.0.

The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 0.4.

The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used in the iodination step was 1.3.

Immediately after the end of the iodination step, a part of the mixture was sampled from the eggplant flask and analyzed by gas chromatography, and the conversion and selectivity (X _{A ′} [ mol], and when the substance amount of all iodide ester compounds at the end of the iodination step (the introduction position of iodine is not limited, and includes o-form and m-form), X _IE [mol] is represented by (X _IE / X _{A ′} ) × 100), p-selectivity (X _PIE [mol] of the amount of the p-monoiodinated ester compound at the end of the iodination step, total iodide ester at the end of the iodination step) substance amount of the compound (provided that the position of the introduction of iodine is not limited, o bodies, m body including) when was the _X IE _[mol], our value represented by _{(X PIE / X IE) ×} 100) Beauty p- mono-iodinated ester compound selectivity (the value represented by the product of selectivity and p- selectivity) was assessed.

(Example F2)
A 30 mass% HIO ₃ aqueous solution was used instead of the 70 mass% HIO ₃ aqueous solution, the molar ratio of HIO _{3 to} the ester compound (the same as the molar ratio to the alcohol compound) was 0.3, and the reaction temperature in the iodination step was 40 ° C. Except for changing to above, the same treatment as in Example F1 was performed, and the conversion, selectivity, p-selectivity and p-monoiodide ester compound selectivity at the end of the iodination were evaluated.

(Example F3)
The HIO ₃ of solid (powder) used in place of 70 wt% HIO ₃ solution, except that the molar ratio of HIO ₃ for the ester compound (the same molar ratio to the alcohol compound) was 0.3, the Example The same treatment as in F1 was performed, and the conversion, selectivity, p-selectivity and p-monoiodide ester compound selectivity at the end of the iodination step were evaluated.

(Example F4)
Using a solid (powder) orthoperiodic acid (H ₅ IO ₆ ) instead of the 70% by mass HIO ₃ aqueous solution, the molar ratio of orthoperiodic acid to the ester compound (the same as the molar ratio to the alcohol compound) is set to 0. The same treatment as in Example F1 was performed, except that the conversion rate, selectivity, p-selectivity, and p-monoiodide ester compound selectivity at the end of the iodination step were evaluated.

(Example F5)
Instead of the 70 mass% HIO ₃ aqueous solution, solid (powder) sodium iodate (NaIO ₃ ) was used, and the molar ratio of sodium iodate to the ester compound (the same as the molar ratio to the alcohol compound) was set to 0.3. Except for the above, the same treatment as in Example F1 was performed, and the conversion, selectivity, p-selectivity, and p-monoiodide ester compound selectivity at the end of the iodination step were evaluated.

(Example F6)
Instead of the 70 mass% HIO ₃ aqueous solution, solid (powder) sodium iodate (NaIO ₃ ) was used, and the molar ratio of sodium iodate to the ester compound (the same as the molar ratio to the alcohol compound) was set to 1.0. Except for the above, the same treatment as in Example F1 was performed, and the conversion, selectivity, p-selectivity, and p-monoiodide ester compound selectivity at the end of the iodination step were evaluated.

(Example F7)
Solid (powder) sodium periodate (NaIO ₄ ) was used instead of the 70% by mass HIO ₃ aqueous solution, and the molar ratio of sodium periodate to the ester compound (same as the molar ratio to the alcohol compound) was 0.3. Except for the above, the same treatment as in Example F1 was performed, and the conversion, selectivity, p-selectivity, and p-monoiodide ester compound selectivity at the end of the iodination step were evaluated.

(Comparative Example F1)
The same treatment as in Example F1 except that the iodine-based oxide was not used and the amounts of the alcohol compound, iodine (I ₂ ), acetic acid, and acetic anhydride were changed to 10: 11: 60: 30 by molar ratio. The conversion, selectivity, p-selectivity and p-monoiodinated ester compound selectivity at the end of the iodination step were evaluated.

(Comparative Examples F2 to F9)
Except that the components shown in Table 6 were used in place of the iodine-based oxide, and the amounts (molar ratios) of the respective components were as shown in Table 6, the same treatment as in Example F1 was performed, and the iodination process was performed. At the end, the conversion, selectivity, p-selectivity and p-monoiodide ester compound selectivity were evaluated.

  Table 6 summarizes the conditions and evaluation results of the components (the components other than acetic acid, acetic anhydride, and the porous substance) used in the production of the iodide ester compound in these Examples and Comparative Examples. In each of the above Examples and Comparative Examples, the yield of the ester compound from the alcohol compound was 100%.

In each of the above examples, the content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.2 or more. 0.3 or less, and the content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 2.0 to 2.2. The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 0.4 to 0.5, The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used for the above was 0.4 or more and 1.4 or less.

As is clear from Table 6, in the present invention, the target iodide ester compound (p-monoiodide ester compound) could be obtained with a high p-monoiodide ester compound selectivity. Particularly, excellent results were obtained by using the iodine-based oxide under preferable conditions (composition, state at the time of addition, ratio of addition).
On the other hand, in the comparative example, a satisfactory result was not obtained.

[Examination of the ratio and reactivity of HIO ₃ and H ₅ IO _{6 in} the iodination step]
(Example G1)
First, a commercially available alcohol compound represented by the following formula (4) (a compound in which n in the formula (1) is 3) was prepared.

Next, the alcohol compound, iodine (I ₂ ), acetic acid, zeolite and acetic anhydride were put into a eggplant flask at a predetermined ratio, and the mixture was stirred at 25 ° C. for 30 minutes to advance the acetylation reaction (ester). Process). Here, the amounts of the alcohol compound, iodine (I ₂ ), acetic acid, and acetic anhydride used were 10: 4: 60: 30 in a molar ratio. The amount of zeolite used was 37 parts by mass with respect to 100 parts by mass of the alcohol compound. As the zeolite (porous substance), an H-β type zeolite having an average pore diameter of 6 ° and a SiO ₂ / Al ₂ O ₃ ratio (molar ratio) of 18 was used.

Thereafter, the mixture in the eggplant flask was heated to 60 ° C. while stirring.
Thereafter, a predetermined amount of a 70% by mass aqueous HIO ₃ solution and H ₅ IO ₆ were added to the eggplant flask, followed by stirring at 60 ° C. for 22 hours (iodination step). At this time, the amounts of the HIO ₃ aqueous solution and H ₅ IO ₆ added were 0.25 and 0.05, respectively, in a molar ratio to the ester compound (the same as the molar ratio to the alcohol compound). Further, with the HIO ₃ aqueous solution added, the reaction system was in a state of a dispersion in which a dispersoid containing iodine-based oxides (HIO ₃ and H ₅ IO ₆ ) was dispersed.

  The content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.3.

  The content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 2.0.

The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 0.4.

The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used in the iodination step was 1.3.

Immediately after the end of the iodination step, a part of the mixture was sampled from the eggplant flask and analyzed by gas chromatography, and the conversion and selectivity (X _{A ′} [ mol], and when the substance amount of all iodide ester compounds at the end of the iodination step (the introduction position of iodine is not limited, and includes o-form and m-form), X _IE [mol] is represented by (X _IE / X _{A ′} ) × 100), p-selectivity (X _PIE [mol] of the amount of the p-monoiodinated ester compound at the end of the iodination step, total iodide ester at the end of the iodination step) When the substance amount of the compound (however, the position where iodine is introduced is not limited and the o-form and the m-form are included) is defined as X _IE [mol], a value represented by (X _PIE / X _IE ) × 100) and And p-monoiodide ester compound selectivity (a value indicated by the product of selectivity and p-selectivity) was evaluated.

(Examples G2 and G3)
Except that the ratio of iodine (I ₂ ), HIO ₃ and H ₅ IO _{6 to} the alcohol compound was changed as shown in Table 7, the same treatment as in Example G1 was performed, and the conversion at the end of the iodination step was changed. , Selectivity, p-selectivity and p-monoiodide ester compound selectivity were evaluated.

  Table 7 shows the conditions and evaluation results of the components (the components other than acetic acid, acetic anhydride, and the porous substance) used in the production of the iodide ester compound for these examples. In each of the examples, the yield of the ester compound from the alcohol compound was 100%.

In each of the above examples, the content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.2 or more. 0.3 or less, and the content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 2.0 to 2.2. The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 0.4 to 0.5, The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used for the above was 1.3 or more and 1.4 or less.

  As is clear from Table 7, in the present invention, the desired iodide ester compound (p-monoiodide ester compound) could be obtained with a high conversion and a high selectivity for the p-monoiodide ester compound.

[Examination of ratio of acetic acid to acetic anhydride and reactivity]
(Example H1)
First, a commercially available alcohol compound represented by the following formula (4) (a compound in which n in the formula (1) is 3) was prepared.

Next, the alcohol compound, iodine (I ₂ ), acetic acid, zeolite and acetic anhydride were put into a eggplant flask at a predetermined ratio, and the mixture was stirred at 25 ° C. for 30 minutes to advance the acetylation reaction (ester). Process). Here, the amounts of the alcohol compound, iodine (I ₂ ), acetic acid, and acetic anhydride used were 10: 4: 150: 30 in a molar ratio. The amount of zeolite used was 37 parts by mass with respect to 100 parts by mass of the alcohol compound. As the zeolite (porous substance), an H-β type zeolite having an average pore diameter of 6 ° and a SiO ₂ / Al ₂ O ₃ ratio (molar ratio) of 18 was used.

Thereafter, the mixture in the eggplant flask was heated to 60 ° C. while stirring.
Thereafter, a predetermined amount of a 70% by mass aqueous HIO ₃ solution was added to the eggplant-shaped flask, followed by stirring at 60 ° C. for 22 hours (iodination step). At this time, the amount of the HIO ₃ aqueous solution added was 0.3 in a molar ratio to the ester compound (the same as the molar ratio to the alcohol compound). In addition, with the HIO ₃ aqueous solution added, the reaction system was in the state of a dispersion in which a dispersoid containing an iodine-based oxide (HIO ₃ ) was dispersed.

  The content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.1.

  The content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 2.0.

The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 0.4.

The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used in the iodination step was 1.3.

Immediately after the end of the iodination step, a part of the mixture was sampled from the eggplant flask and analyzed by gas chromatography, and the conversion and selectivity (X _{A ′} [ mol], and when the substance amount of all iodide ester compounds at the end of the iodination step (the introduction position of iodine is not limited, and includes o-form and m-form), X _IE [mol] is represented by (X _IE / X _{A ′} ) × 100), p-selectivity (X _PIE [mol] of the amount of the p-monoiodinated ester compound at the end of the iodination step, total iodide ester at the end of the iodination step) When the substance amount of the compound (however, the position where iodine is introduced is not limited and the o-form and the m-form are included) is defined as X _IE [mol], a value represented by (X _PIE / X _IE ) × 100) and And p-monoiodide ester compound selectivity (a value indicated by the product of selectivity and p-selectivity) was evaluated.

(Examples H2 to H5)
Except for changing the ratio of acetic acid and acetic anhydride to the alcohol compound as shown in Table 8, the same treatment as in Example H1 was performed, and the conversion, selectivity, p-selectivity and The p-monoiodide ester compound selectivity was evaluated.

(Example H6)
Except that acetic acid was not used, and the ratio of acetic anhydride to the alcohol compound was changed as shown in Table 8, the same treatment as in Example H1 was performed, and the conversion, selectivity, p-selection at the end of the iodination step Rate and p-monoiodide ester compound selectivity were evaluated.

(Example H7)
Except that acetic anhydride was not used and the ratio of acetic acid to the alcohol compound was changed as shown in Table 8, the same treatment as in Example H1 was performed, and the conversion, selectivity, p-selection at the end of the iodination step Rate and p-monoiodide ester compound selectivity were evaluated.

  Table 8 summarizes the conditions of the components (iodine, iodine-based oxide aqueous solution, and components other than the porous substance) used in the production of the iodide ester compound, and the evaluation results. In each of Examples H1 to H6, the yield of the ester compound from the alcohol compound was 100%. In Example H7, the yield of the ester compound from the alcohol compound was 57%.

In each of the above Examples, the content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0 or more. 6 or less, and the content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 0 or more and 4.0 or less; The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is from 0.4 to 0.5, and the solution used in the iodination step The molar ratio of iodine (I ₂ ) to iodine-based oxide in the mixture was 1.3 or more and 1.4 or less.

  As is clear from Table 8, in the present invention, the desired iodide ester compound (p-monoiodide ester compound) could be obtained at a high conversion and a high selectivity for the p-monoiodide ester compound. Particularly, excellent results were obtained by using preferable conditions.

[Examination of the relationship between the type of carboxylic acid and carboxylic anhydride and reactivity]
(Example I1)
First, a commercially available alcohol compound represented by the following formula (4) (a compound in which n in the formula (1) is 3) was prepared.

Next, the alcohol compound, iodine (I ₂ ), acetic acid, zeolite and acetic anhydride were put into a eggplant flask at a predetermined ratio, and the mixture was stirred at 25 ° C. for 30 minutes to advance the acetylation reaction (ester). Process). Here, the amounts of the alcohol compound, iodine (I ₂ ), acetic acid, and acetic anhydride used were 10: 4: 60: 30 in a molar ratio. The amount of zeolite used was 37 parts by mass with respect to 100 parts by mass of the alcohol compound. As the zeolite (porous substance), an H-β type zeolite having an average pore diameter of 6 ° and a SiO ₂ / Al ₂ O ₃ ratio (molar ratio) of 18 was used.

Thereafter, the mixture in the eggplant flask was heated to 60 ° C. while stirring.
Thereafter, a predetermined amount of a 70% by mass aqueous HIO ₃ solution was added to the eggplant-shaped flask, followed by stirring at 60 ° C. for 22 hours (iodination step). At this time, the amount of the HIO ₃ aqueous solution added was 0.25 in the molar ratio of HIO _{3 to} the ester compound (the same as the molar ratio to the alcohol compound). In addition, with the HIO ₃ aqueous solution added, the reaction system was in the state of a dispersion in which a dispersoid containing an iodine-based oxide (HIO ₃ ) was dispersed.

  The content (molar ratio) of acetic anhydride to the content of acetic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.3.

  The content (molar ratio) of acetic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 2.0.

The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) was 0.4.

The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used in the iodination step was 1.3.

Immediately after the end of the iodination step, a part of the mixture was sampled from the eggplant flask and analyzed by gas chromatography, and the conversion and selectivity (X _{A ′} [ mol], and when the substance amount of all iodide ester compounds at the end of the iodination step (the introduction position of iodine is not limited, and includes o-form and m-form), X _IE [mol] is represented by (X _IE / X _{A ′} ) × 100), p-selectivity (X _PIE [mol] of the amount of the p-monoiodinated ester compound at the end of the iodination step, total iodide ester at the end of the iodination step) When the substance amount of the compound (however, the position where iodine is introduced is not limited and the o-form and the m-form are included) is defined as X _IE [mol], a value represented by (X _PIE / X _IE ) × 100) and And p-monoiodide ester compound selectivity (a value indicated by the product of selectivity and p-selectivity) was evaluated.

(Example I2)
Except that propionic acid was used instead of acetic acid, and that propionic anhydride was used instead of acetic anhydride, the same treatment as in Example I1 was performed, and the conversion, selectivity, and p-selection at the end of the iodination were completed. Rate and p-monoiodide ester compound selectivity were evaluated.

(Example I3)
Using butyric acid instead of acetic acid, and performing the same treatment as in Example I1 except that butyric anhydride was used instead of acetic anhydride, and the conversion, selectivity, p-selectivity, and The p-monoiodide ester compound selectivity was evaluated.

  Table 9 summarizes the conditions of the alcohol compound, carboxylic acid, and acid anhydride used in the production of the iodide ester compound, and the evaluation results. In each of the examples, the yield of the ester compound from the alcohol compound was 100%.

In each of the above Examples, the content (molar ratio) of carboxylic anhydride to carboxylic acid in the solution used in the iodination step (the solution at the end of the esterification step) was 0.1%. 2 or more and 0.3 or less, and the content (molar ratio) of the carboxylic anhydride to the content of the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 2.0 or more. The molar ratio of iodine (I ₂ ) to the ester compound in the solution used in the iodination step (the solution at the end of the esterification step) is 0.4 or more and 0.5 or less; The molar ratio of iodine (I ₂ ) to iodine-based oxide in the solution used in the iodination step was 1.0 or more and 1.4 or less.

  As is clear from Table 9, in the present invention, the target iodide ester compound (p-monoiodide ester compound) could be obtained with a high p-monoiodide ester compound selectivity.

  In each of the above examples, the filtrate after the zeolite was separated by filtration was extracted with n-hexane, and the extract was cooled to −5 ° C. to obtain the desired product, iodide ester compound (p -Monoiodinated ester compound) could be selectively crystallized and purified with high purity.

The method for producing an iodide ester compound of the present invention comprises reacting an ester compound represented by the above formula (2), iodine (I ₂ ), and an iodine-based oxide in the presence of a porous substance, And an iodination step of obtaining an iodide ester compound represented by 3).

  The method for producing an iodide ester compound of the present invention has a high regioselectivity at the position of introduction of iodine, and can obtain a target iodide ester compound in a high yield. Have.

  The iodide ester compound (p-monoiodide ester compound) produced in the present invention is a compound having particularly high utility in various uses such as a pharmaceutical intermediate, an agricultural chemical intermediate, and an electronic material intermediate.

Claims (14)

An iodination step of reacting an ester compound represented by the following formula (2) with iodine and an iodine-based oxide in the presence of a porous substance to obtain an iodinated ester compound represented by the following formula (3) A method for producing an iodide ester compound, comprising:

(However, in the formula (2), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

(However, in the formula (3), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.) An esterification step of esterifying an alcohol compound represented by the following formula (1) in a solution containing a carboxylic acid and an acid anhydride thereof to obtain an ester compound represented by the following formula (2);
An iodination step of reacting the ester compound with iodine and an iodine-based oxide in the presence of a porous substance to obtain an iodide ester compound represented by the following formula (3): A method for producing an ester compound.

(In the formula (1), n is an integer of 1 or more and 5 or less.)

(However, in the formula (2), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

(However, in the formula (3), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.) An esterification step of esterifying an alcohol compound represented by the following formula (1) in a solution containing a carboxylic acid and an acid anhydride thereof to obtain an ester compound represented by the following formula (2) was performed. Using the reaction mixture,
A method for producing an iodide ester compound, comprising performing an iodination step of reacting the ester compound with an iodine-based oxide to obtain an iodide ester compound represented by the following formula (3).

(In the formula (1), n is an integer of 1 or more and 5 or less.)

(However, in the formula (2), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)

(However, in the formula (3), n is an integer of 1 to 5 and R is an alkyl group having 1 to 3 carbon atoms.)   The method for producing an iodide ester compound according to claim 2 or 3, wherein a molar ratio of the acid anhydride to the carboxylic acid used in the esterification step is 0.2 or more and 1.0 or less.   The method for producing an iodide ester compound according to any one of claims 2 to 4, wherein a molar ratio of the acid anhydride to the alcohol compound used in the esterification step is 1.2 or more and 5.0 or less.   The method for producing an iodide ester compound according to any one of claims 2 to 5, wherein the esterification step is performed in the presence of the porous substance.   The method for producing an iodinated ester compound according to any one of claims 2 to 6, wherein the esterification step is performed in the presence of the iodine.   The method for producing an iodinated ester compound according to any one of claims 1 to 7, wherein the iodine-based oxide is at least one selected from iodic acid, periodic acid and salts thereof.   The method for producing an iodide ester compound according to any one of claims 1 to 8, wherein the iodine-based oxide is an acidic compound.   The method for producing an iodide ester compound according to any one of claims 1 to 9, wherein the iodine-based oxide is supplied into the reaction system in a state of an aqueous solution.   11. The iodine according to claim 1, wherein the iodination step is performed in a dispersion in which the dispersoid containing the iodine-based oxide is dispersed using an organic solution containing a carboxylic acid as a dispersion medium. 12. For producing an esterified ester compound.   The method for producing an iodide ester compound according to any one of claims 1 to 11, wherein the porous material has an average pore diameter of 5.0 ° or more and 9.0 ° or less.   The method for producing an iodide ester compound according to any one of claims 1 to 12, wherein the porous substance is zeolite. 14. The method for producing an iodide ester compound according to claim 13, wherein a SiO ₂ / Al ₂ O ₃ ratio (molar ratio) in the zeolite is 4 or more and 90 or less.

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