JP2018150243A - Method for producing xanthene derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing xanthene derivative having a high yield, and capable of supplying stably in comparison with a prior production method.SOLUTION: The method of producing a xanthene derivative includes; reacting a compound represented by the general formula (II) as set force in the specification with a compound represented by the general formula (III) in the presence of a Lewis acid having a magnesium element, and a solvent to obtain a xanthene derivative represented by the general formula (I); and reacting a compound represented by the general formula (II) with a compound represented by the general formula (IIIA) in the presence of a Lewis acid having a magnesium element, and a solvent, and reacting a reaction mixture obtained with a compound represented by the general formula (IV) to obtain a xanthene derivative represented by the general formula (IA).SELECTED DRAWING: None

Description

  The present invention relates to a method for producing a xanthene derivative.

  As a dye having a xanthene skeleton, commercially available Acid Red (AR) 52 or Acid Red (AR) 289 is used. In recent years, development has further progressed, and Patent Document 1 describes a method for producing a xanthene derivative in the presence of a raw material and zinc chloride.

Japanese Patent Laid-Open No. 2006-69655

However, in the conventional synthesis method, the yield is low, and there are many by-products in the synthesis, and purification by column chromatography is necessary, and it is difficult to stably supply the xanthene derivative.
In view of the above problems, there has been a demand for a method for producing a xanthene derivative that can be stably supplied with high yield and does not require purification by column chromatography.

  An object of this invention is to provide the manufacturing method of the xanthene derivative which has a high yield compared with the conventional manufacturing method and can be supplied stably.

  The present inventors diligently studied and found that the above problems can be solved by the following means.

[1]
By reacting a compound represented by the following general formula (II) and a compound represented by the following general formula (III) in the presence of a Lewis acid having a magnesium element and a solvent, the following general formula (I) A method for producing a xanthene derivative, wherein the xanthene derivative is obtained.

In general formula (II),
Ra represents a monovalent substituent.
na represents 0-4.
In general formula (III),
R ¹ and R ⁵ each independently represents a hydrogen atom or an alkyl group which may have a substituent.
R ² , R ³ , and R ⁴ each independently represent a hydrogen atom, an alkyl group that may have a substituent, or —SO ₃ M. M represents H or a counter cation. However, at least one of R ² , R ³ and R ⁴ represents —SO ₃ M.
In general formula (I),
Ra, na is the general formula (II) in Ra, it has the same meaning as ^na, R 1 to R ⁵ are the same meanings as ^R 1 to R ⁵ in the general formula (III).
[2]
The method for producing a xanthene derivative according to [1], wherein the total number of carbon atoms of the alkyl group represented by R ^{1 to} R ⁵ is 3 or more.
[3]
The method for producing a xanthene derivative according to [1] or [2], wherein the solvent is an alcohol solvent or an aprotic polar solvent.
[4]
In the said reaction, the manufacturing method of the xanthene derivative of any one of [1]-[3] which adds an organic base as an additive.
[5]
The method for producing a xanthene derivative according to any one of [1] to [4], wherein the reaction is performed at 60 to 200 ° C.
[6]
A compound represented by the following general formula (II) and a compound represented by the following general formula (IIIA) are reacted in the presence of a Lewis acid having a magnesium element and a solvent. The manufacturing method of the xanthene derivative which obtains the xanthene derivative represented by the following general formula (IA) by making the compound represented by Formula (IV) react.

In general formula (II),
Ra represents a monovalent substituent.
na represents 0-4.
In general formula (IIIA),
R ²¹ and R ²⁵ each independently represent a hydrogen atom or an alkyl group which may have a substituent.
R ²² , R ²³ , and R ²⁴ each independently represent a hydrogen atom, an alkyl group that may have a substituent, or —SO ₃ M. M represents H or a counter cation. However, at least one of R ²² , R ²³ and R ²⁴ represents —SO ₃ M.
In general formula (IV),
R ⁶ and R ¹⁰ each independently represents a hydrogen atom or an alkyl group which may have a substituent.
R ⁷ , R ⁸ and R ⁹ each independently represent a hydrogen atom, an alkyl group which may have a substituent, or —SO ₃ M. M represents H or a counter cation.
In general formula (IA),
Ra, na is the general formula (II) in Ra, has the same meaning as ^na, R 21 ^{to R 25} are respectively synonymous with ^R 21 ^{to R 25} in the general formula ^{(IIIA), R} 6 ~R ¹⁰ Are respectively synonymous with R < ⁶ > -R < ¹⁰ > in general formula (IV).
[7]
The method for producing a xanthene derivative according to [6], wherein the total number of carbon atoms of the alkyl group represented by R ^{21 to} R ²⁵ or the total number of carbon atoms of the alkyl group represented by R ^{6 to} R ¹⁰ is 3 or more.
[8]
The method for producing a xanthene derivative according to [6] or [7], wherein the solvent is an alcohol solvent or an aprotic polar solvent.
[9]
In the reaction of the compound represented by the general formula (II) and the compound represented by the general formula (IIIA), an organic base is added as an additive, any one of [6] to [8] The manufacturing method of the xanthene derivative of description.
[10]
The reaction between the compound represented by the general formula (II) and the compound represented by the general formula (IIIA), and the reaction of reacting the compound represented by the general formula (IV) with the reaction solution is performed in 60 to The method for producing a xanthene derivative according to any one of [6] to [9], which is performed at 200 ° C.

  ADVANTAGE OF THE INVENTION According to this invention, compared with the conventional manufacturing method, the manufacturing method of the xanthene derivative which has a high yield and can be supplied stably can be provided.

The manufacturing method of the xanthene derivative of the present invention has the following two aspects.
In the first production method, the compound represented by the general formula (II) and the compound represented by the general formula (III) are reacted in the presence of a Lewis acid having a magnesium element and a solvent, It is a manufacturing method of the xanthene derivative which obtains the xanthene derivative represented by the said general formula (I).
A second production method is obtained by reacting the compound represented by the general formula (II) with the compound represented by the general formula (IIIA) in the presence of a Lewis acid having a magnesium element and a solvent. It is the manufacturing method of the xanthene derivative which obtains the xanthene derivative represented by the said general formula (IA) by making the compound represented by the said general formula (IV) react with the obtained reaction liquid.

  In the first production method and the second production method of the present invention, a compound represented by the general formula (II) and a sulfonated aniline are reacted in the presence of a Lewis acid having a magnesium element to produce a xanthene derivative. Common in terms of gaining.

  In the first production method and the second production method, by using a Lewis acid having a magnesium element, the yield can be increased (for example, 80% or more) and stable compared to the conventional production method. Since a xanthene derivative can be supplied to this, it is an excellent manufacturing method.

The conventional synthesis route of the xanthene derivative represented by the general formula (I) or the general formula (IA) is a route in which aniline is introduced into the compound represented by the general formula (II) by a condensation reaction and then sulfonated. However, due to the low selectivity of sulfonation, low yield (about 30%) and stable supply were difficult (because there were many by-products and column purification was required). On the other hand, the synthesis route of the xanthene derivative represented by the general formula (I) or the general formula (IA) in the present invention is a sulfonated aniline (general formula (III) or general formula (IIIA)) (easily synthesized). In the compound represented by the general formula (II) by a condensation reaction. For this reason, it is not necessary to perform sulfonation with low selectivity. In the present invention, the Lewis acid containing magnesium element is a compound represented by the general formula (II) and aniline, or an intermediate (V) (generated by condensation of the general formula (II) and aniline) and aniline. It has been found that the condensation reaction is effectively accelerated. As a result, the reaction selectivity was dramatically improved, so that column purification after the reaction became unnecessary, and the xanthene derivative represented by the general formula (I) or the general formula (IA) could be stably produced.
The reason why the Lewis acid containing the magnesium element accelerates the above reaction is estimated as follows. That is, the magnesium element in the Lewis acid is strongly coordinated to the chlorine moiety of the general formula (II) or to the chlorine moiety of the intermediate (V) formed by condensation of the general formula (II) and aniline. It is believed to enhance and effectively accelerate the condensation reaction.

In the general formula (II-2), Ra has the same meaning as Ra in the general formula (II).
In the above intermediate ^(V), R 1 ~R ⁵ have the same meanings as ^R 1 to R ⁵ in formula (III).
Formula (II-2), the general formula (V), _{Mg-X 2} represents a Lewis acid having a magnesium element.

[First production method]
Hereinafter, first, the first manufacturing method will be described in more detail.
In the first production method of the present invention, a compound represented by the following general formula (II) and a compound represented by the following general formula (III) are reacted in the presence of a Lewis acid having a magnesium element and a solvent. By this, it is a manufacturing method of the xanthene derivative which obtains the xanthene derivative represented by the following general formula (I).

In general formula (II),
Ra represents a monovalent substituent.
na represents 0-4.
In general formula (III),
R ¹ and R ⁵ each independently represents a hydrogen atom or an alkyl group which may have a substituent.
R ² , R ³ , and R ⁴ each independently represent a hydrogen atom, an alkyl group that may have a substituent, or —SO ₃ M. M represents H or a counter cation. However, at least one of R ² , R ³ and R ⁴ represents —SO ₃ M.
In general formula (I),
Ra, na is the general formula (II) in Ra, it has the same meaning as ^na, R 1 to R ⁵ are the same meanings as ^R 1 to R ⁵ in the general formula (III).

[Compound represented by formula (II)]
The compound represented by formula (II) will be described.
In the general formula (II), as the monovalent substituent represented by Ra, for example, a substituent represented by the following substituent group A can be used, but preferably an alkyl group, a halogen atom, an alkoxy group. A group, more preferably a methyl group or a chlorine atom, still more preferably a chlorine atom.

  na represents 0 to 4, preferably 0, 1 or 4, more preferably 0 or 1, and particularly preferably 0.

[Compound represented by formula (III)]
The compound represented by formula (III) will be described.

In general formula (III), the alkyl group represented by R ¹ and R ⁵ is preferably an alkyl group having 1 to 12 carbon atoms, more preferably an alkyl group having 1 to 6 carbon atoms, and particularly preferably methyl. Group, ethyl group and isopropyl group.

R ² , R ³ , and R ⁴ each independently represent a hydrogen atom, an alkyl group that may have a substituent, or —SO ₃ M. M represents H or a counter cation.
R ² is preferably a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, more preferably a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and particularly preferably a hydrogen atom.
R ³ is preferably an alkyl group, —SO ₃ M, more preferably an alkyl group having 1 to 3 carbon atoms, —SO ₃ M, and particularly preferably a methyl group, —SO ₃ M. M represents H or a counter cation.
R ⁴ is preferably a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or —SO ₃ M, more preferably a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or —SO ₃ M, particularly preferably. hydrogen atom, an -SO ₃ M. M represents H or a counter cation.

  The alkyl group may further have a substituent. As a substituent which the said alkyl group may have, the substituent chosen from the following substituent group A is mentioned, for example, Specifically, an alkoxy group, a halogen atom, etc. are mentioned.

In the general formula (III), the total number of carbon atoms of the alkyl group represented by R ^{1 to} R ⁵ is preferably 2 or more, and more preferably 3 or more.
Note that the total number of carbon atoms of the alkyl group represented by R ¹ to R ⁵ described above, the alkyl group represented by R ¹ to R ⁵ is assumed not to include the number of carbon atoms of the substituent in the case having a substituent.

One of R ^{2, R 3} and ^{R 4} represents _-SO 3 M (M is H or a counter cation). M represents H or a counter cation.
Examples of the counter cation in M of —SO ₃ M include alkali metal ions (preferably lithium ions, sodium ions, or potassium ions), ammonium ions, and the like.

  The ratio between the amount of the compound represented by the general formula (II) and the amount of the compound represented by the general formula (III) is (the amount of the compound represented by the general formula (II)) / (general The amount of the compound represented by formula (III)) is preferably a molar ratio of 1/2 to 1/8, and more preferably 1/2 to 1/5.

More specifically, the reaction in the first production method of the present invention can be performed, for example, as follows. That is, a compound represented by the general formula (II), a compound represented by the general formula (III), a Lewis acid having a magnesium element, and a solvent are placed in a container such as a flask, and the container is heated, etc. It is preferable to react for a certain time. In addition, it does not specifically limit as a means to heat, For example, the method of using an oil bath etc. is mentioned. Further, the inside of the container may be stirred by a known means when performing the reaction.
The order and timing of adding the compound represented by the general formula (II), the compound represented by the general formula (III), the Lewis acid having a magnesium element, and the solvent are not particularly limited.
Moreover, you may add another component in a reaction system (reaction mixture) in the range which does not inhibit the said reaction. Examples of other components include organic bases.

[solvent]
In the first production method, the compound represented by the general formula (II) and the compound represented by the general formula (III) are reacted in the presence of a Lewis acid having a magnesium element and a solvent.
The solvent is not particularly limited as long as it can dissolve the compounds represented by the general formulas (II) and (III), and an alcohol solvent or an aprotic polar solvent is preferable.
Examples of alcohol solvents include ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, t-butanol, ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, 1,3. -Butanediol, 1,4-butanediol, 2-methyl-1,3-propanediol, diethylene glycol, dipropylene glycol, triethylene glycol, polyethylene glycol and the like.
Examples of the aprotic polar solvent include ethylene glycol monomethyl ether, propylene glycol monomethyl ether, diethylene glycol monomethyl ether, triethylene glycol monomethyl ether, polyethylene glycol monomethyl ether, dimethyl sulfone, diethyl sulfone, sulfolane, 2,4-dimethyl sulfolane, Examples thereof include dimethyl sulfoxide, dimethylformamide, dimethylacetamide, 1-methylpyrrolidin-2-one and the like.

  Among them, ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, 1,3-butanediol, 1,4-butanediol, 2-methyl-1,3-propanediol, diethylene glycol, dipropylene glycol, tri Ethylene glycol, sulfolane, 2,4-dimethylsulfolane, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, 1-methylpyrrolidin-2-one are preferred, ethylene glycol, sulfolane, 2,4-dimethylsulfolane, dimethylacetamide, 1-methyl Pyrrolidin-2-one is more preferable, and ethylene glycol and sulfolane are particularly preferable.

  The amount of the solvent used is preferably 1 to 100 times, more preferably 2 to 40 times, and further preferably 3 to 10 times the amount of the compound represented by the general formula (II). .

[Lewis acid containing magnesium element]
In the first production method, the compound represented by the general formula (II) and the compound represented by the general formula (III) are reacted in the presence of a Lewis acid having a magnesium element and a solvent. The Lewis acid having magnesium element is not particularly limited as long as it contains magnesium element and can be dissolved in a solvent. Magnesium chloride, magnesium chloride hexahydrate, magnesium bromide, magnesium iodide, magnesium oxide And magnesium triflate. Among these, magnesium chloride, magnesium bromide, and magnesium oxide are preferable, and magnesium chloride and magnesium bromide are more preferable.

  The amount of Lewis acid having magnesium element is preferably 0.1 to 10 times, more preferably 0.5 to 4 times, more preferably the amount of the compound represented by the general formula (II). 1 to 2 times.

[Organic base]
In the range which does not inhibit the reaction of reacting the compound represented by the general formula (II) and the compound represented by the general formula (III) in the presence of a Lewis acid having a magnesium element and a solvent, an organic base May be added. Addition of an organic base is preferable because it has an effect of trapping hydrochloric acid generated by the progress of the reaction and promoting the reaction.
The organic base is not particularly limited as long as it can be dissolved in a solvent, and is triethylamine, imidazole, pyridine, 2-methylpyridine, 3-methylpyridine, 2,6-lutidine, quinoline, isoquinoline, diazabicyclononene. And diazabicycloundecene. Among these, 2,6-lutidine, quinoline, isoquinoline, diazabicyclononene and diazabicycloundecene are preferable, and quinoline, isoquinoline and diazabicycloundecene are more preferable.
The amount of the organic base used is preferably 0.1 to 10 times, more preferably 0.2 to 5 times, still more preferably 0.5 to 2 times the amount of the compound represented by the general formula (III). Is double.

[Reaction temperature]
In the first production method of the present invention, the compound represented by the general formula (II) is reacted with the compound represented by the general formula (III) in the presence of a Lewis acid having a magnesium element and a solvent. From the viewpoint of the reaction rate, the reaction is preferably performed at 60 to 200 ° C, more preferably 100 to 200 ° C, and particularly preferably 120 to 200 ° C.

[Reaction time]
Although the time for performing the reaction is not particularly limited, the compound represented by the general formula (II), the compound represented by the general formula (III), the Lewis acid having a magnesium element, and the kind of the solvent, these Although it can adjust suitably by content etc., from a viewpoint of a by-product suppression, 24 hours or less are preferable, 18 hours or less are more preferable, and 12 hours or less are especially preferable.

〔atmosphere〕
The atmosphere in which the reaction is performed is not particularly limited. The reaction may be performed under an inert gas such as nitrogen or argon, or the reaction may be performed under the atmosphere.

〔pressure〕
The pressure at the time of performing the said reaction is not specifically limited. When the reaction is performed at a temperature higher than the boiling point of the compound represented by the general formula (II), the compound represented by the general formula (III), the Lewis acid having a magnesium element, and the solvent and other additives, The reaction may be performed under a pressure higher than 101325 Pa as necessary.

  After the reaction, the reaction solution is preferably cooled. There is no particular limitation on the cooling means, and for example, the heating device can be removed and cooling can be performed by cooling.

  The xanthene derivative represented by the general formula (I) obtained by the first production method of the present invention will be described below.

[Xanthene Derivatives Represented by General Formula (I)]

In general formula (I),
Ra, na is the general formula (II) in Ra, it has the same meaning as ^na, R 1 to R ⁵ are the same meanings as ^R 1 to R ⁵ in the general formula (III).

Ra and na in the general formula (I) have the same meanings as Ra and na in the general formula (II), respectively, and preferred ranges thereof are also the same.
R < ¹ > -R < ⁵ > in general formula (I) is synonymous with R < ¹ > -R < ⁵ > in general formula (III) respectively, and its preferable range is also the same.

  The xanthene derivative represented by the general formula (I) or a salt thereof is preferably 0.1 to 70% by mass and more preferably 0.2 to 50% by mass with respect to water at 25 ° C. Preferably, 0.3 to 25% by mass is dissolved.

The number of —SO ₃ M is preferably 1 to 9, and more preferably 1 to 3. Incidentally, -SO ₃ in the general Formulas (I) ^- also included in the number of -SO ₃ M.

[Second production method]
Next, the second manufacturing method. Further details will be described.
In the second production method of the present invention, a compound represented by the following general formula (II) and a compound represented by the following general formula (IIIA) are reacted in the presence of a Lewis acid having a magnesium element and a solvent. (This reaction is referred to as “first reaction”), and the resulting reaction solution is reacted with a compound represented by the following general formula (IV) (this reaction is referred to as “second reaction”). It is the manufacturing method of the xanthene derivative which obtains the xanthene derivative represented by (IA).

In general formula (II),
Ra represents a monovalent substituent.
na represents 0-4.
In general formula (IIIA),
R ²¹ and R ²⁵ each independently represent a hydrogen atom or an alkyl group which may have a substituent.
R ²² , R ²³ , and R ²⁴ each independently represent a hydrogen atom, an alkyl group that may have a substituent, or —SO ₃ M. M represents H or a counter cation. However, at least one of R ²² , R ²³ and R ²⁴ represents —SO ₃ M.
In general formula (IV),
R ⁶ and R ¹⁰ each independently represents a hydrogen atom or an alkyl group which may have a substituent.
R ⁷ , R ⁸ and R ⁹ each independently represent a hydrogen atom, an alkyl group which may have a substituent, or —SO ₃ M. M represents H or a counter cation.
In general formula (IA),
Ra, na is the general formula (II) in Ra, has the same meaning as ^na, R 21 ^{to R 25} are respectively synonymous with ^R 21 ^{to R 25} in the general formula ^{(IIIA), R} 6 ~R ¹⁰ Are respectively synonymous with R < ⁶ > -R < ¹⁰ > in general formula (IV).

  In the second production method of the present invention, a compound represented by the above general formula (IIIA), which is a sulfonated aniline, is first reacted with a compound represented by the general formula (II), and further aniline (sulfonated) is reacted. It is an embodiment in which the reaction may be performed or not.

  The said general formula (II) is synonymous with general formula (II) described with the said 1st manufacturing method, and its preferable range is also synonymous.

[Compound represented by formula (IIIA)]
The compound represented by formula (IIIA) will be described.

R < ²¹ > -R < ²⁵ > in general formula (IIIA) is synonymous with R < ¹ > -R < ⁵ > in general formula (III) respectively, and its preferable range is also the same.

  The ratio of the amount of the compound represented by the general formula (II) to the amount of the compound represented by the general formula (IIIA) is (the amount of the compound represented by the general formula (II)) / (general The amount of the compound represented by the formula (IIIA) is a molar ratio, preferably 1/1 to 1/4, more preferably 1/1 to 1/2, and particularly preferably 1/1 to 1 / 1.1. preferable.

[Compound represented by formula (IV)]
The compound represented by formula (IV) will be described.

In general formula (IV), as an alkyl group as R < ⁶ > and R < ¹⁰ >, Preferably it is a C1-C12 alkyl group, More preferably, it is a C1-C6 alkyl group, Most preferably, it is methyl. Group, ethyl group and isopropyl group.
R ⁷ , R ⁸ , and R ⁹ each independently represent a hydrogen atom, an alkyl group that may have a substituent, or —SO ₃ M. M represents H or a counter cation.
R ⁷ is preferably a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, more preferably a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and particularly preferably a hydrogen atom.
R ⁸ is preferably an alkyl group, —SO ₃ M, more preferably an alkyl group having 1 to 3 carbon atoms, —SO ₃ M, and particularly preferably a methyl group, —SO ₃ M. M represents H or a counter cation.
R ⁹ is preferably a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or —SO ₃ M, more preferably a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or —SO ₃ M, particularly preferably. hydrogen atom, an -SO ₃ M. M represents H or a counter cation.

The alkyl group may further have a substituent. Examples of the substituent that the alkyl group may have include a substituent selected from the following substituent group A, and specific examples include an alkoxy group, a halogen atom, and a cyano group.
Moreover, the said alkyl group may have group represented by following formula (1) as a substituent.

In the general formula (1),
L represents an alkylene group. R represents an alkyl group. n represents an integer of 1 to 5. A plurality of L may be the same or different.
Examples of the alkylene group for L include linear and branched alkylene groups having 1 to 3 carbon atoms.
Examples of the alkyl group for R include an alkyl group having 1 to 6 carbon atoms.

The counter cation at M of -SO ₃ M, in formula (III), is synonymous with the counter cation in M of -SO ₃ M.

The ratio between the amount of the compound represented by the general formula (II) and the amount of the compound represented by the general formula (IV) is (the amount of the compound represented by the general formula (II)) / (general The amount of the compound represented by the formula (IV)) is preferably 1/1 to 1/8, more preferably 1/2 to 1/5 in terms of molar ratio. "
The ratio of the amount of the compound represented by the general formula (III) to the amount of the compound represented by the general formula (IV) is (the amount of the compound represented by the general formula (III)) / (general The amount of the compound represented by the formula (IV)) is preferably 1/1 to 1/8, more preferably 1/2 to 1/5 in terms of molar ratio.

More specifically, the reaction in the second production method of the present invention can be performed, for example, as follows. That is, a compound represented by the above general formula (II), a compound represented by the above general formula (IIIA), a Lewis acid having a magnesium element, and a solvent are placed in a container such as a flask, and the container is heated. It is preferable to react for a certain time. In addition, it does not specifically limit as a means to heat, For example, the method of using an oil bath etc. is mentioned. Further, the inside of the container may be stirred by a known means when performing the reaction.
The order and timing of adding the compound represented by the general formula (II), the compound represented by the general formula (IIIA), the Lewis acid having a magnesium element, and the solvent are not particularly limited.
Thereafter, the compound represented by the general formula (IV) is added to the reaction solution to carry out the reaction.
Moreover, you may add another component in a reaction system (reaction mixture) in the range which does not inhibit said 1st reaction and 2nd reaction. Examples of other components include organic bases.

〔solvent〕
In the second production method, the compound represented by the general formula (II) is reacted with the compound represented by the general formula (IIIA) in the presence of a Lewis acid having a magnesium element and a solvent. The solvent is not particularly limited as long as it can dissolve the compounds represented by the general formulas (II) and (IIIA) and the compound represented by the general formula (IV). Protic polar solvents are preferred.
As an alcohol solvent or an aprotic polar solvent, it is synonymous with the above-mentioned alcohol solvent or aprotic polar solvent, and its preferable range is also synonymous.
In addition, it is preferable that the solvent remains in the second reaction.

[Lewis acid containing magnesium element]
In the second production method, the compound represented by the general formula (II) is reacted with the compound represented by the general formula (III) in the presence of a Lewis acid having a magnesium element and a solvent. As a Lewis acid which has a magnesium element, it is synonymous with the Lewis acid which has a magnesium element in a 1st manufacturing method, and its preferable range is also synonymous.

  The amount of Lewis acid having magnesium element in the first reaction is preferably 0.1 to 10 times, more preferably 0.55 to 4 times the amount of the compound represented by the general formula (II). Yes, more preferably 1 to 2 times.

  In addition, it is preferable that the Lewis acid which has a magnesium element remains in 2nd reaction.

[Organic base]
In the second production method, an organic base may be added within a range not inhibiting the first reaction and the second reaction. Addition of an organic base is preferable because it has an effect of trapping hydrochloric acid generated by the progress of the reaction and promoting the reaction.
As an organic base, it is synonymous with the organic base demonstrated by the 1st manufacturing method, and its preferable range is also synonymous.
The amount of the organic base used is preferably 1 to 10 times, more preferably 1 to 8 times, still more preferably 1 to 6 times the amount of the compound represented by the general formula (III).

  The organic base is preferably left in the second reaction.

[Reaction temperature]
In the second production method of the present invention, first, the compound represented by the general formula (II) and the compound represented by the general formula (IIIA) are reacted in the presence of a Lewis acid having a magnesium element and a solvent. (First reaction), from the viewpoint of the reaction rate, the reaction is preferably performed at 60 to 200 ° C, more preferably at 100 to 200 ° C, and particularly preferably at 120 to 200 ° C.
In the second production method of the present invention, the compound represented by the general formula (II) is reacted with the compound represented by the general formula (IIIA) in the presence of a Lewis acid having a magnesium element and a solvent. The reaction mixture is reacted with the compound represented by the general formula (IV) (second reaction), but the reaction mixture is reacted with the compound represented by the general formula (IV). From the viewpoint of the reaction rate, the reaction is preferably performed at 100 to 200 ° C, more preferably 120 to 200 ° C, and particularly preferably 150 to 200 ° C.
In addition, it is preferable that the reaction temperature of 1st reaction is higher than the reaction temperature of 2nd reaction.

[Reaction time]
Although the time of said 1st reaction is not specifically limited, The compound represented by the said general formula (II), the compound represented by the said general formula (IIIA), the Lewis acid which has a magnesium element, and the kind of solvent, these However, from the viewpoint of suppressing by-products, 12 hours or less is preferable, 8 hours or less is more preferable, and 4 hours or less is particularly preferable.
Further, the time of the second reaction is not particularly limited, but the compound represented by the general formula (II), the compound represented by the general formula (IIIA), the compound represented by the general formula (IV) The Lewis acid having magnesium element, the kind of the solvent, the content thereof, and the like can be appropriately adjusted. However, from the viewpoint of suppressing by-products, 24 hours or less is preferable, and 18 hours or less is more preferable. Particularly preferred is an hour or less.

〔atmosphere〕
The atmosphere in which the first reaction and the second reaction are performed is not particularly limited. The reaction may be performed under an inert gas such as nitrogen or argon, or the reaction may be performed under the atmosphere.

〔pressure〕
The pressure at the time of performing 1st reaction and 2nd reaction is not specifically limited. When the reaction is performed at a temperature higher than the boiling point of the compound represented by the general formula (II), the compound represented by the general formula (IIIA), the Lewis acid having magnesium element, and the solvent and other additives. If necessary, the reaction may be performed under a pressure higher than 101325 Pa.

  After the second reaction, it is preferable to cool the reaction solution. There is no particular limitation on the cooling means, and for example, the heating device can be removed and cooling can be performed by cooling.

  In the first production method and the second production method, the target product may be isolated from the reaction solution after cooling the reaction solution after the reaction. As a method for isolating the target product, it is possible to apply chemical engineering conventional means or production means represented by acid precipitation, crystallization, salting out and extraction.

  The xanthene derivative represented by the general formula (IA) obtained by the second production method of the present invention will be described below.

[Xanthene Derivatives Represented by General Formula (IA)]
The xanthene derivative represented by the general formula (IA) will be described.

In general formula (IA),
Ra, na is the general formula (II) in Ra, has the same meaning as ^na, R 21 ^{to R 25} are respectively synonymous with ^R 21 ^{to R 25} in the general formula ^{(IIIA), R} 6 ~R ¹⁰ Are respectively synonymous with R < ⁶ > -R < ¹⁰ > in general formula (IV).

Ra and na in the general formula (IA) have the same meanings as Ra and na in the general formula (II), respectively, and preferred ranges thereof are also the same.
R < ²¹ > -R < ²⁵ > in general formula (IA) is synonymous with R < ¹ > -R < ⁵ > in general formula (III) respectively, and its preferable range is also the same.
R < ⁶ > -R < ¹⁰ > in general formula (IA) is synonymous with R < ⁶ > -R < ¹⁰ > in general formula (IV), respectively, A preferable range is also the same.

However, in General Formula (IA), the total number of carbon atoms of the alkyl group represented by R ^{21 to} R ²⁵ or the total number of carbon atoms of the alkyl group represented by R ^{6 to} R ¹⁰ is preferably 2 or more, and more preferably 3 or more.
Note that the total number of carbon atoms of the alkyl group above R ²¹ to R ²⁵ represents an alkyl group represented by R ²¹ to R ²⁵ is assumed not to include the number of carbon atoms of the substituent in the case having a substituent.
Also, the total number of carbon atoms in the alkyl group above R ⁶ to R ¹⁰ represents an alkyl group represented by R ⁶ to R ¹⁰ are assumed not to include the number of carbon atoms of the substituent in the case having a substituent.

  The xanthene derivative represented by the general formula (IA) or a salt thereof is preferably 0.1 to 70% by mass, more preferably 0.2 to 50% by mass with respect to water at 25 ° C. It is preferable to dissolve 0.3 to 25% by mass.

The number of —SO ₃ M is preferably 1 to 9, and more preferably 1 to 3. Note that —SO ₃ ^— already present in the general formula (IA) is also included in the number of —SO ₃ M.

In the present invention, the substituent group A is a substituent represented by the following.
(Substituent group A)
In the present specification, the substituent group A includes a halogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, an aryl group, a heterocyclic group, a cyano group, a hydroxyl group, a nitro group, an alkoxy group, an aryloxy group, and a silyloxy group. Group, heterocyclic oxy group, acyloxy group, carbamoyloxy group, alkoxycarbonyloxy group, aryloxycarbonyloxy group, amino group, acylamino group, aminocarbonylamino group, alkoxycarbonylamino group, aryloxycarbonylamino group, sulfamoyl Amino group, alkyl or arylsulfonylamino group, mercapto group, alkylthio group, arylthio group, heterocyclic thio group, sulfamoyl group, alkyl or arylsulfinyl group, alkyl or arylsulfonyl group, acyl group Consists of aryloxycarbonyl group, alkoxycarbonyl group, carbamoyl group, aryl or heterocyclic azo group, imide group, phosphino group, phosphinyl group, phosphinyloxy group, phosphinylamino group, silyl group, ionic hydrophilic group It is a substituent group. These substituents may be further substituted, and examples of the further substituent include a group selected from the substituent group A described above.

  As a halogen atom, a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom is mentioned, for example.

Examples of the alkyl group include linear, branched, and cyclic substituted or unsubstituted alkyl groups, and include cycloalkyl groups, bicycloalkyl groups, and tricyclo structures having many ring structures. An alkyl group (for example, an alkyl group of an alkoxy group or an alkylthio group) in a substituent described below also represents such an alkyl group.
As the alkyl group, an alkyl group having 1 to 30 carbon atoms such as a methyl group, an ethyl group, an n-propyl group, an i-propyl group, a t-butyl group, an n-octyl group, an eicosyl group, 2- Examples thereof include a chloroethyl group, a 2-cyanoethyl group, a 2-ethylhexyl group, etc. The cycloalkyl group is preferably a substituted or unsubstituted cycloalkyl group having 3 to 30 carbon atoms, such as a cyclohexyl group, a cyclopentyl group, 4 -N-dodecylcyclohexyl group and the like, and the bicycloalkyl group is preferably a substituted or unsubstituted bicycloalkyl group having 5 to 30 carbon atoms, that is, one hydrogen atom from a bicycloalkane having 5 to 30 carbon atoms. Removed monovalent groups such as bicyclo [1,2,2] heptan-2-yl group, bicyclo [2,2 2] octan-3-yl group.

  Examples of the aralkyl group include a substituted or unsubstituted aralkyl group, and the substituted or unsubstituted aralkyl group is preferably an aralkyl group having 7 to 30 carbon atoms. For example, a benzyl group and a 2-phenethyl group can be mentioned.

Examples of the alkenyl group include linear, branched, and cyclic substituted or unsubstituted alkenyl groups, and include cycloalkenyl groups and bicycloalkenyl groups.
Preferred examples of the alkenyl group include substituted or unsubstituted alkenyl groups having 2 to 30 carbon atoms such as vinyl group, allyl group, prenyl group, geranyl group, and oleyl group. Preferred examples of the cycloalkenyl group include Is a substituted or unsubstituted cycloalkenyl group having 3 to 30 carbon atoms, that is, a monovalent group obtained by removing one hydrogen atom of a cycloalkene having 3 to 30 carbon atoms, such as a 2-cyclopenten-1-yl group, 2-cyclohexen-1-yl group and the like. As the bicycloalkenyl group, a substituted or unsubstituted bicycloalkenyl group, preferably a substituted or unsubstituted bicycloalkenyl group having 5 to 30 carbon atoms, that is, a double bond A monovalent group obtained by removing one hydrogen atom from a bicycloalkene having one of, for example, bicyclo [2,2,1] Hept-2-en-1-yl group, a bicyclo [2,2,2] oct-2-en-4-yl group and the like.

  The alkynyl group is preferably a substituted or unsubstituted alkynyl group having 2 to 30 carbon atoms such as an ethynyl group, a propargyl group, and a trimethylsilylethynyl group.

  The aryl group is preferably a substituted or unsubstituted aryl group having 6 to 30 carbon atoms, such as a phenyl group, a p-tolyl group, a naphthyl group, an m-chlorophenyl group, an o-hexadecanoylaminophenyl group, and the like. Can be mentioned.

  The heterocyclic group is preferably a monovalent group obtained by removing one hydrogen atom from a 5- or 6-membered substituted or unsubstituted aromatic or non-aromatic heterocyclic compound, and more preferably a carbon number. Examples thereof include 3 to 30 5- or 6-membered aromatic heterocyclic groups such as a 2-furyl group, a 2-thienyl group, a 2-pyrimidinyl group, and a 2-benzothiazolyl group. Examples of non-aromatic heterocyclic groups include morpholinyl groups.

  The alkoxy group is preferably a substituted or unsubstituted alkoxy group having 1 to 30 carbon atoms, such as a methoxy group, an ethoxy group, an isopropoxy group, a t-butoxy group, an n-octyloxy group, or a 2-methoxyethoxy group. Etc.

  The aryloxy group is preferably a substituted or unsubstituted aryloxy group having 6 to 30 carbon atoms, such as a phenoxy group, 2-methylphenoxy group, 4-t-butylphenoxy group, 3-nitrophenoxy group, 2 -Tetradecanoylaminophenoxy group etc. are mentioned.

  Preferred examples of the silyloxy group include substituted or unsubstituted silyloxy groups having 0 to 20 carbon atoms such as a trimethylsilyloxy group and a diphenylmethylsilyloxy group.

  Preferred examples of the heterocyclic oxy group include substituted or unsubstituted heterocyclic oxy groups having 2 to 30 carbon atoms, such as a 1-phenyltetrazole-5-oxy group and a 2-tetrahydropyranyloxy group.

  The acyloxy group is preferably a formyloxy group, a substituted or unsubstituted alkylcarbonyloxy group having 2 to 30 carbon atoms, a substituted or unsubstituted arylcarbonyloxy group having 6 to 30 carbon atoms, such as an acetyloxy group, Examples include a pivaloyloxy group, a stearoyloxy group, a benzoyloxy group, and a p-methoxyphenylcarbonyloxy group.

  The carbamoyloxy group is preferably a substituted or unsubstituted carbamoyloxy group having 1 to 30 carbon atoms, such as N, N-dimethylcarbamoyloxy group, N, N-diethylcarbamoyloxy group, morpholinocarbonyloxy group, N , N-di-n-octylaminocarbonyloxy group, Nn-octylcarbamoyloxy group and the like.

  The alkoxycarbonyloxy group is preferably a substituted or unsubstituted alkoxycarbonyloxy group having 2 to 30 carbon atoms, such as a methoxycarbonyloxy group, an ethoxycarbonyloxy group, a t-butoxycarbonyloxy group, or an n-octylcarbonyloxy group. Etc.

  The aryloxycarbonyloxy group is preferably a substituted or unsubstituted aryloxycarbonyloxy group having 7 to 30 carbon atoms, such as phenoxycarbonyloxy group, p-methoxyphenoxycarbonyloxy group, pn-hexadecyloxy. Examples include phenoxycarbonyloxy group.

  The amino group includes an alkylamino group, an arylamino group, and a heterocyclic amino group, preferably an amino group, a substituted or unsubstituted alkylamino group having 1 to 30 carbon atoms, a substituted or unsubstituted group having 6 to 30 carbon atoms. Examples of the substituted anilino group include a methylamino group, a dimethylamino group, an anilino group, an N-methyl-anilino group, a diphenylamino group, and a triazinylamino group.

  The acylamino group is preferably a formylamino group, a substituted or unsubstituted alkylcarbonylamino group having 1 to 30 carbon atoms, a substituted or unsubstituted arylcarbonylamino group having 6 to 30 carbon atoms, such as an acetylamino group, Examples include pivaloylamino group, lauroylamino group, benzoylamino group, 3,4,5-tri-n-octyloxyphenylcarbonylamino group, and the like.

  The aminocarbonylamino group is preferably a substituted or unsubstituted aminocarbonylamino group having 1 to 30 carbon atoms, such as a carbamoylamino group, N, N-dimethylaminocarbonylamino group, or N, N-diethylaminocarbonylamino group. And a morpholinocarbonylamino group.

  The alkoxycarbonylamino group is preferably a substituted or unsubstituted alkoxycarbonylamino group having 2 to 30 carbon atoms, such as methoxycarbonylamino group, ethoxycarbonylamino group, t-butoxycarbonylamino group, n-octadecyloxycarbonylamino. Group, N-methyl-methoxycarbonylamino group and the like.

  The aryloxycarbonylamino group is preferably a substituted or unsubstituted aryloxycarbonylamino group having 7 to 30 carbon atoms, such as phenoxycarbonylamino group, p-chlorophenoxycarbonylamino group, mn-octyloxyphenoxy. Examples thereof include a carbonylamino group.

  The sulfamoylamino group is preferably a substituted or unsubstituted sulfamoylamino group having 0 to 30 carbon atoms, such as a sulfamoylamino group, N, N-dimethylaminosulfonylamino group, Nn- Examples include octylaminosulfonylamino group.

The alkyl or arylsulfonylamino group is preferably a substituted or unsubstituted alkylsulfonylamino group having 1 to 30 carbon atoms, a substituted or unsubstituted arylsulfonylamino group having 6 to 30 carbon atoms, such as a methylsulfonylamino group. Butylsulfonylamino group, phenylsulfonylamino group, 2,3,5-trichlorophenylsulfonylamino group, p-methylphenylsulfonylamino group, and the like.
Preferred examples of the alkylthio group include substituted or unsubstituted alkylthio groups having 1 to 30 carbon atoms, such as a methylthio group, an ethylthio group, and an n-hexadecylthio group.

  Preferred examples of the arylthio group include substituted or unsubstituted arylthio groups having 6 to 30 carbon atoms such as a phenylthio group, a p-chlorophenylthio group, and an m-methoxyphenylthio group.

  Preferred examples of the heterocyclic thio group include substituted or unsubstituted heterocyclic thio groups having 2 to 30 carbon atoms, such as a 2-benzothiazolylthio group and a 1-phenyltetrazol-5-ylthio group.

  The sulfamoyl group is preferably a substituted or unsubstituted sulfamoyl group having 0 to 30 carbon atoms, such as N-ethylsulfamoyl group, N- (3-dodecyloxypropyl) sulfamoyl group, N, N-dimethylsulfuryl group. Examples include a famoyl group, an N-acetylsulfamoyl group, an N-benzoylsulfamoyl group, and an N- (N′-phenylcarbamoyl) sulfamoyl group.

  The alkyl or arylsulfinyl group is preferably a substituted or unsubstituted alkylsulfinyl group having 1 to 30 carbon atoms, a substituted or unsubstituted arylsulfinyl group having 6 to 30 carbon atoms, such as a methylsulfinyl group or an ethylsulfinyl group. , Phenylsulfinyl group, p-methylphenylsulfinyl group and the like.

  The alkyl or arylsulfonyl group is preferably a substituted or unsubstituted alkylsulfonyl group having 1 to 30 carbon atoms, a substituted or unsubstituted arylsulfonyl group having 6 to 30 carbon atoms, such as a methylsulfonyl group or an ethylsulfonyl group. , Phenylsulfonyl group, p-methylphenylsulfonyl group and the like.

  The acyl group is preferably a formyl group, a substituted or unsubstituted alkylcarbonyl group having 2 to 30 carbon atoms, a substituted or unsubstituted arylcarbonyl group having 7 to 30 carbon atoms, a substituted or unsubstituted group having 2 to 30 carbon atoms. Heterocyclic carbonyl groups bonded to carbonyl groups at substituted carbon atoms, such as acetyl, pivaloyl, 2-chloroacetyl, stearoyl, benzoyl, pn-octyloxyphenylcarbonyl, 2-pyridyl Examples thereof include a carbonyl group and a 2-furylcarbonyl group.

  The aryloxycarbonyl group is preferably a substituted or unsubstituted aryloxycarbonyl group having 7 to 30 carbon atoms, such as phenoxycarbonyl group, o-chlorophenoxycarbonyl group, m-nitrophenoxycarbonyl group, pt- A butylphenoxycarbonyl group etc. are mentioned.

  The alkoxycarbonyl group is preferably a substituted or unsubstituted alkoxycarbonyl group having 2 to 30 carbon atoms, such as a methoxycarbonyl group, an ethoxycarbonyl group, a t-butoxycarbonyl group, and an n-octadecyloxycarbonyl group.

  The carbamoyl group is preferably a substituted or unsubstituted carbamoyl group having 1 to 30 carbon atoms, such as a carbamoyl group, an N-methylcarbamoyl group, an N, N-dimethylcarbamoyl group, or an N, N-di-n-octyl group. Examples thereof include a carbamoyl group and an N- (methylsulfonyl) carbamoyl group.

  The aryl or heterocyclic azo group is preferably a substituted or unsubstituted arylazo group having 6 to 30 carbon atoms, a substituted or unsubstituted heterocyclic azo group having 3 to 30 carbon atoms, such as a phenylazo group or p-chlorophenylazo group. Group, 5-ethylthio-1,3,4-thiadiazol-2-ylazo group and the like.

  Preferred examples of the imide group include an N-succinimide group and an N-phthalimide group.

  The phosphino group is preferably a substituted or unsubstituted phosphino group having 0 to 30 carbon atoms, such as a dimethylphosphino group, a diphenylphosphino group, a methylphenoxyphosphino group, and the like.

  The phosphinyl group is preferably a substituted or unsubstituted phosphinyl group having 0 to 30 carbon atoms, such as a phosphinyl group, a dioctyloxyphosphinyl group, a diethoxyphosphinyl group, and the like.

  Preferred examples of the phosphinyloxy group include substituted or unsubstituted phosphinyloxy groups having 0 to 30 carbon atoms such as a diphenoxyphosphinyloxy group and a dioctyloxyphosphinyloxy group.

  The phosphinylamino group is preferably a substituted or unsubstituted phosphinylamino group having 0 to 30 carbon atoms, such as a dimethoxyphosphinylamino group or a dimethylaminophosphinylamino group.

  Preferred examples of the silyl group include substituted or unsubstituted silyl groups having 0 to 30 carbon atoms such as a trimethylsilyl group, a t-butyldimethylsilyl group, and a phenyldimethylsilyl group.

  Examples of the ionic hydrophilic group include a sulfo group, a carboxyl group, a thiocarboxyl group, a sulfino group, a phosphono group, a dihydroxyphosphino group, and a quaternary ammonium group. Particularly preferred are a sulfo group and a carboxyl group. The ionic hydrophilic group may contain a cation or an anion, and a state containing the cation or anion is called a salt state. The carboxyl group, phosphono group and sulfo group may be in the form of a salt. Examples of counter cations that form salts include ammonium ions, alkali metal ions (eg, lithium ions, sodium ions, potassium ions) and organic cations. (Eg, tetramethylammonium ion, tetramethylguanidinium ion, tetramethylphosphonium) are included, lithium salts, sodium salts, potassium salts, and ammonium salts are preferable, and mixed salts containing sodium salts or sodium salts as main components are included. More preferred is the sodium salt.

  The features of the present invention will be described more specifically with reference to examples and comparative examples. The materials, amounts used, ratios, processing details, processing procedures, and the like shown in the following examples can be changed as appropriate without departing from the spirit of the present invention. Therefore, the scope of the present invention should not be construed as being limited by the following examples.

[Example 1]

70.0 g of DCSF (dichlorosulfophthalein) (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred. 43.0 g of compound (IIIA-1), 16.5 g of magnesium chloride, diaza 27.6 g of bicycloundecene was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. 73.6g of compound (IV-1) was added to this reaction liquid. The internal temperature of this reaction solution was raised to 150 ° C., and then stirred at this temperature for 5 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, the filtrate was washed twice with 350 g of ethyl acetate, and dried for 1 day with a 50 ° C. blower dryer to obtain 112.2 g of compound (IA-1) (yield). 92%). Mass spectrum (MS) (m / z) = 683 ([M-Na + 2H] ⁺ , 100%).

[Example 2]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred. 68.7 g of compound (IIIA-2), 31.8 g of magnesium bromide, diazabicycloundecene 39. 5 g was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. To this reaction solution, 126.9 g of compound (IV-2) 2-2 was added. The internal temperature of the reaction solution was raised to 180 ° C., and then stirred at this temperature for 18 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the filtrate was washed twice with 350 g of ethyl acetate and dried for 1 day in a 50 ° C. blower dryer to obtain 115.8 g of Compound (IA-2) 2 ( Yield 88%). Mass spectrum (MS) (m / z) = 739 ([M-Na + 2H] ⁺ , 100%).

[Example 3]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred. 163.9 g of compound (III-1), 23.6 g of magnesium chloride, and 105.2 g of diazabicycloundecene were added thereto. Was added. The internal temperature of the reaction solution was raised to 150 ° C., and then stirred at this temperature for 10 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, the filtrate was washed twice with 350 g of ethyl acetate, and dried for 1 day in a 50 ° C. blower dryer to obtain 125.6 g of compound (I-1) (yield). Rate 90%). Mass spectrum (MS) (m / z) = 763 ([M-2Na + 3H] ⁺ , 100%).

[Example 4]

75.3 g of compound (II-2) was added to 437.5 g of ethylene glycol and stirred, and 43.0 g of compound (IIIA-1), 16.5 g of magnesium chloride and 27.6 g of diazabicycloundecene were added thereto. . The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. 73.6g of compound (IV-1) was added to this reaction liquid. The internal temperature of this reaction solution was raised to 150 ° C., and then stirred at this temperature for 5 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the filtrate was washed twice with 350 g of ethyl acetate and dried for 1 day in a 50 ° C. blower dryer to obtain 119.5 g of Compound (IA-3) (yield). 94%). Mass spectrum (MS) (m / z) = 713 ([M-Na + 2H] ⁺ , 100%).

[Example 5]

72.5 g of compound (II-3) was added to 437.5 g of ethylene glycol and stirred, and 68.7 g of compound (IIIA-2), 16.5 g of magnesium chloride, and 39.5 g of diazabicycloundecene were added thereto. . The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. 73.6g of compound (IV-1) was added to this reaction liquid. The internal temperature of the reaction solution was raised to 150 ° C., and then stirred at this temperature for 10 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, the filtrate was washed twice with 350 g of ethyl acetate, and dried for 1 day in a 50 ° C. blower dryer to obtain 115.8 g of compound (IA-4) (yield). Rate 88%). Mass spectrum (MS) (m / z) = 739 ([M-Na + 2H] ⁺ , 100%).

[Example 6]

93.9 g of compound (II-4) was added to 437.5 g of ethylene glycol and stirred, and 163.9 g of compound (III-1), 23.6 g of magnesium chloride, and 105.2 g of diazabicycloundecene were added thereto. . The internal temperature of the reaction solution was raised to 150 ° C., and then stirred at this temperature for 10 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the filtrate was washed twice with 350 g of ethyl acetate and dried for 1 day in a 50 ° C. blower dryer to obtain 140.6 g of compound (I-2) (yield). 86%). Mass spectrum (MS) (m / z) = 899 ([M-2Na + 3H] ⁺ , 100%).

[Example 7]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred. 72.3 g of compound (IIIA-3), 31.8 g of magnesium bromide, diazabicycloundecene 39. 5 g was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. To this reaction solution, 126.9 g of compound (IV-2) was added. The internal temperature of the reaction solution was raised to 180 ° C., and then stirred at this temperature for 18 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, the filtrate was washed twice with 350 g of ethyl acetate, and dried for 1 day in a 50 ° C. blower dryer to obtain 114.0 g of compound (IA-5) (yield). Rate 85%). Mass spectrum (MS) (m / z) = 753 ([M-Na + 2H] ⁺ , 100%).

[Example 8]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred. 163.9 g of compound (III-4), 23.6 g of magnesium chloride, and 105.2 g of diazabicycloundecene were added thereto. Was added. The internal temperature of the reaction solution was raised to 150 ° C., and then stirred at this temperature for 10 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the filtrate was washed twice with 350 g of ethyl acetate and dried in a blow dryer at 50 ° C. for 1 day to obtain 127.1 g of compound (I-3) (yield). 91%). Mass spectrum (MS) (m / z) = 763 ([M-2Na + 3H] ⁺ , 100%).

[Example 9]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred, and 84.5 g of compound (IIIA-5), 16.5 g of magnesium chloride, and 39.5 g of diazabicycloundecene were added thereto. Was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. To this reaction solution, 104.7 g of compound (IV-1) was added. The internal temperature of the reaction solution was raised to 150 ° C., and then stirred at this temperature for 8 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the filtrate was washed twice with 350 g of ethyl acetate and dried for 1 day in a 50 ° C. blower dryer to obtain 121.2 g of compound (IA-6) (yield). 92%). Mass spectrum (MS) (m / z) = 773 ([M-Na + 2H] ⁺ , 100%).

[Example 10]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred. 43.0 g of compound (IIIA-1), 16.5 g of magnesium chloride, and 27.6 g of diazabicycloundecene were added thereto. Was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. To this reaction solution, 126.9 g of compound (IV-3) was added. The internal temperature of this reaction solution was raised to 150 ° C., and then stirred at this temperature for 5 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the filtrate was washed twice with 350 g of ethyl acetate and dried for 1 day in a 50 ° C. blower dryer to obtain 115.8 g of compound (IA-7) (yield). 94%). Mass spectrum (MS) (m / z) = 694 ([M-Na + 2H] ⁺ , 100%).

[Example 11]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred, and 195.7 g of compound (III-6), 31.8 g of magnesium bromide, diazabicycloundecene 105. 2g was added. The internal temperature of the reaction solution was raised to 150 ° C. and then stirred at this temperature for 14 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, the filtrate was washed twice with 350 g of ethyl acetate, and dried for 1 day in a 50 ° C. blower dryer to obtain 135.4 g of Compound (I-4) (yield). Rate 87%). Mass spectrum (MS) (m / z) = 855 ([M-2Na + 3H] ⁺ , 100%).

[Example 12]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred. 43.0 g of compound (IIIA-1), 16.5 g of magnesium chloride, and 27.6 g of diazabicycloundecene were added thereto. Was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. 175.0g of compound (IV-4) was added to this reaction liquid. The internal temperature of the reaction solution was raised to 180 ° C., and then stirred at this temperature for 18 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the filtrate was washed twice with 350 g of ethyl acetate and dried for 1 day in a 50 ° C. blower dryer to obtain 124.0 g of compound (IA-8) (yield). Rate 90%). Mass spectrum (MS) (m / z) = 773 ([M-Na + 2H] ⁺ , 100%).

[Example 13]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred. 43.0 g of compound (IIIA-1), 16.5 g of magnesium chloride, and 27.6 g of diazabicycloundecene were added thereto. Was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. 98.6g of compound (IV-5) was added to this reaction liquid. The internal temperature of this reaction solution was raised to 150 ° C., and then stirred at this temperature for 5 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, the filtrate was washed twice with 350 g of ethyl acetate, and dried for 1 day in a 50 ° C. blower dryer to obtain 123.0 g of compound (IA-9) (yield). Rate 95%). Mass spectrum (MS) (m / z) = 729 ([M-Na + 2H] ⁺ , 100%).

[Example 14]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred, and 45.6 g of compound (IIIA-7), 16.5 g of magnesium chloride, and 27.6 g of diazabicycloundecene were added thereto. Was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. To this reaction solution, 87.2 g of compound (IV-6) was added. The internal temperature of this reaction solution was raised to 150 ° C., and then stirred at this temperature for 5 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the filtrate was washed twice with 350 g of ethyl acetate and dried for 1 day in a 50 ° C. blower dryer to obtain 119.5 g of Compound (IA-10) (yield). 93%). Mass spectrum (MS) (m / z) = 722 ([M-Na + 2H] ⁺ , 100%).

[Example 15]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred, and 184.7 g of compound (III-8), 31.8 g of magnesium bromide, diazabicycloundecene 105. 2g was added. The internal temperature of the reaction solution was raised to 150 ° C., and then stirred at this temperature for 10 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, the filtrate was washed twice with 350 g of ethyl acetate, and dried for 1 day in a 50 ° C. blower dryer to obtain 133.4 g of compound (I-5) (yield). Rate 89%). Mass spectrum (MS) (m / z) = 823 ([M-2Na + 3H] ⁺ , 100%).

[Example 16]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred. To this, 51.4 g of compound (IIIA-6), 16.5 g of magnesium chloride, 27.6 g of diazabicycloundecene were added. Was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. 130.2g of compound (IV-7) was added to this reaction liquid. The internal temperature of this reaction solution was raised to 150 ° C., and then stirred at this temperature for 5 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the residue was washed twice with 350 g of ethyl acetate and dried for 1 day in a 50 ° C. blower dryer to obtain 135.9 g of Compound (IA-11) (yield). 92%). Mass spectrum (MS) (m / z) = 833 ([M-Na + 2H] ⁺ , 100%).

[Example 17]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred, and 184.7 g of compound (III-9), 16.5 g of magnesium chloride, and 105.2 g of diazabicycloundecene were added thereto. Was added. The internal temperature of the reaction solution was raised to 150 ° C., and then stirred at this temperature for 10 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, the filtrate was washed twice with 350 g of ethyl acetate, and dried with a 50 ° C. blower dryer for 1 day to obtain 135.1 g of Compound (I-6) (yield). Rate 90%). Mass spectrum (MS) (m / z) = 823 ([M-2Na + 3H] ⁺ , 100%).

[Example 18]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol, followed by stirring. To this, 48.1 g of compound (IIIA-2), 55.7 g of magnesium trifluoromethanesulfonate, diazabicycloundecene was added. 27.6 g was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. 65.9g of compound (IV-8) was added to this reaction liquid. The internal temperature of this reaction solution was raised to 150 ° C., and then stirred at this temperature for 5 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the filtrate was washed twice with 350 g of ethyl acetate and dried for 1 day in a 50 ° C. blower dryer to obtain 116.6 g of compound (IA-12) (yield). 94%). Mass spectrum (MS) (m / z) = 697 ([M-Na + 2H] ⁺ , 100%).

[Example 19]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred. 40.5 g of compound (IIIA-10), 35.1 g of magnesium chloride hexahydrate, diazabicycloun 27.6 g of decene was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. 73.6g of compound (IV-1) was added to this reaction liquid. The internal temperature of the reaction solution was raised to 150 ° C., and then stirred at this temperature for 8 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the filtrate was washed twice with 350 g of ethyl acetate and dried in a blow dryer at 50 ° C. for 1 day to obtain 110.0 g of compound (IA-13) (yield). 92%). Mass spectrum (MS) (m / z) = 669 ([M-Na + 2H] ⁺ , 100%).

[Example 20]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred, and 40.5 g of compound (IIIA-10), 7.0 g of magnesium oxide, and 27.6 g of diazabicycloundecene were added thereto. Was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. 87.7g of compound (IV-9) was added to this reaction liquid. The internal temperature of the reaction solution was raised to 150 ° C., and then stirred at this temperature for 8 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, the filtrate was washed twice with 350 g of ethyl acetate, and dried for 1 day in a 50 ° C. blower dryer to obtain 112.7 g of compound (IA-14) (yield). 91%). Mass spectrum (MS) (m / z) = 695 ([M-Na + 2H] ⁺ , 100%).

[Example 21]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred, and 154.2 g of compound (III-10), 16.5 g of magnesium chloride, 105.2 g of diazabicycloundecene were added thereto. Was added. The internal temperature of the reaction solution was raised to 150 ° C., and then stirred at this temperature for 10 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, the filtrate was washed twice with 350 g of ethyl acetate, and dried for 1 day in a 50 ° C. blower dryer to obtain 120.9 g of Compound (I-7) (yield). Rate 90%). Mass spectrum (MS) (m / z) = 735 ([M-2Na + 3H] ⁺ , 100%).

[Example 22]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred. To this, 50.7 g of compound (IIIA-3), 16.5 g of magnesium chloride, 146.0 g of diazabicycloundecene were added. Was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 3 hours. 184.4g of compound (IV-10) was added to this reaction liquid. The internal temperature of the reaction solution was raised to 180 ° C., and then stirred at this temperature for 18 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the filtrate was washed twice with 350 g of ethyl acetate and dried in a blow dryer at 50 ° C. for 1 day to obtain 123.5 g of compound (IA-15) (yield). 84%). Mass spectrum (MS) (m / z) = 805 ([M-2Na + 3H] ⁺ , 100%).

[Example 23]

70.0 g of DCSF (compound (II-1)) was added to 437.5 g of ethylene glycol and stirred. 48.1 g of compound (IIIA-2), 31.8 g of magnesium bromide, 146. diazabicycloundecene. 0 g was added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 3 hours. 207.8g of compound (IV-11) was added to this reaction liquid. The internal temperature of the reaction solution was raised to 180 ° C., and then stirred at this temperature for 18 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the filtrate was washed twice with 350 g of ethyl acetate and dried for 1 day in a 50 ° C. blower dryer to obtain 128.5 g of compound (IA-16) (yield). 86%). Mass spectrum (MS) (m / z) = 821 ([M-2Na + 3H] ⁺ , 100%).

[Comparative Example 1]

To 240 g of sulfolane, 40.0 g of DCSF was added and stirred, and 60.1 g of compound 1-2 and 22.2 g of zinc chloride were added thereto. The internal temperature of the reaction solution was raised to 200 ° C. and then stirred at this temperature for 3 hours. The reaction solution was allowed to cool to 25 ° C. and then poured into 1.6 L of diluted hydrochloric acid. At that time, the precipitated crystals were separated by filtration and washed with 1.6 L of water. To the obtained wet cake, 800 mL of acetonitrile was added and stirred at 45 ° C. for 30 minutes. The crystals were collected by filtration, washed with 400 mL of acetonitrile, and dried for 1 day in a blow dryer at 50 ° C. to obtain 53.7 g of Intermediate 1-A (yield 90%). Mass spectrum (MS) (m / z) = 603 ([M + H] ⁺ , 100%).
18.0 g of Intermediate 1-A was added to 180 g of concentrated sulfuric acid (95%, manufactured by Wako Pure Chemical Industries, Ltd.) and stirred, and fuming sulfuric acid (25%, manufactured by Wako Pure Chemical Industries, Ltd.) 50 mL was maintained while maintaining the internal temperature at 0-8 ° C. Was added dropwise and stirred at an internal temperature of 5 ° C. for 2 hours. A 10% saline solution was prepared in another container, and the reaction solution was slowly poured therein so that the internal temperature was 30 ° C. or lower. The crystals precipitated at that time were filtered off. The obtained crystals are dissolved in 200 g of water and adjusted to pH 7.0 with dilute sodium hydroxide, and then column chromatography (filler: Sephadex LH-20 (Pharmacia), developing solvent: water / methanol) is used. Purified. Using a dialysis membrane (fractionated molecular weight 3500, Spectra / Por3 Dialysis Membrane (trade name, Spectrum = Laboratory)), the inorganic salt and residual organic solvent were removed, and the resulting aqueous solution was again diluted with dilute sodium hydroxide aqueous solution. The pH was adjusted to 7 by carrying out dust filtration with a membrane filter, and the resulting aqueous solution was concentrated to dryness with a rotary evaporator to obtain crystals of Exemplified Compound 1. Yield 6.6 g, 31% yield. Mass spectrum (MS) (m / z) = 683 ([M-Na + 2H] ⁺ , 100%).

[Comparative Example 2]

18.0 g of Intermediate 1-A was added to 180 g of concentrated sulfuric acid (95%, manufactured by Wako Pure Chemical Industries, Ltd.) and stirred, and 65 mL of fuming sulfuric acid (25%, manufactured by Wako Pure Chemical Industries, Ltd.) was maintained while maintaining the internal temperature at 0-8 ° C. Was added dropwise and stirred at an internal temperature of 5 ° C. for 48 hours. A 10% saline solution was prepared in another container, and the reaction solution was slowly poured therein so that the internal temperature was 30 ° C. or lower. The crystals precipitated at that time were filtered off. The obtained crystals are dissolved in 200 g of water and adjusted to pH 7.0 with dilute sodium hydroxide, and then column chromatography (filler: Sephadex LH-20 (Pharmacia), developing solvent: water / methanol) is used. Purified. Using a dialysis membrane (fractionated molecular weight 3500, Spectra / Por3 Dialysis Membrane (trade name, Spectrum = Laboratory)), the inorganic salt and residual organic solvent were removed, and the resulting aqueous solution was again diluted with dilute sodium hydroxide aqueous solution. The pH was adjusted to 7 by filtration, dust filtration was performed with a membrane filter, and the resulting aqueous solution was concentrated to dryness with a rotary evaporator to obtain crystals of Exemplified Compound 3. Yield 6.3 g, yield 26%. Mass spectrum (MS) (m / z) = 763 ([M-2Na + 3H] ⁺ , 100%).

[Comparative Example 3]

70.0 g of DCSF was added to 437.5 g of ethylene glycol and stirred. To this, 68.7 g of compound 2-1, 23.5 g of zinc chloride and 39.5 g of diazabicycloundecene were added. The internal temperature of the reaction solution was raised to 120 ° C., and then stirred at this temperature for 2 hours. To this reaction solution, 126.9 g of compound 2-2 was added. The internal temperature of the reaction solution was raised to 180 ° C., and then stirred at this temperature for 18 hours. The reaction solution was allowed to cool to 25 ° C., and 312 g of methanol was added. In another container, 1060 g of ethyl acetate was prepared, and the reaction solution was slowly poured therein. At that time, the precipitated crystals were separated by filtration, and the residue was washed twice with 350 g of ethyl acetate. The obtained crystals were dissolved in 400 g of methanol and purified by column chromatography (filler: Sephadex LH-20 (Pharmacia), developing solvent: methanol). The obtained methanol solution was concentrated to dryness with a rotary evaporator to obtain crystals of Exemplary Compound 2. Yield 15.9 g, 12% yield. Mass spectrum (MS) (m / z) = 763 ([M-2Na + 3H] ⁺ , 100%).

Claims (10)

By reacting a compound represented by the following general formula (II) and a compound represented by the following general formula (III) in the presence of a Lewis acid having a magnesium element and a solvent, the following general formula (I) A method for producing a xanthene derivative, wherein the xanthene derivative is obtained.

In general formula (II),
Ra represents a monovalent substituent.
na represents 0-4.
In general formula (III),
R ¹ and R ⁵ each independently represents a hydrogen atom or an alkyl group which may have a substituent.
R ² , R ³ , and R ⁴ each independently represent a hydrogen atom, an alkyl group that may have a substituent, or —SO ₃ M. M represents H or a counter cation. However, at least one of R ² , R ³ and R ⁴ represents —SO ₃ M.
In general formula (I),
Ra, na is the general formula (II) in Ra, it has the same meaning as ^na, R 1 to R ⁵ are the same meanings as ^R 1 to R ⁵ in the general formula (III). The total number of carbon atoms in the alkyl group represented by R ¹ to R ⁵ is 3 or more, a manufacturing method of a xanthene derivative according to claim 1.   The method for producing a xanthene derivative according to claim 1 or 2, wherein the solvent is an alcohol solvent or an aprotic polar solvent.   The method for producing a xanthene derivative according to any one of claims 1 to 3, wherein an organic base is added as an additive in the reaction.   The manufacturing method of the xanthene derivative of any one of Claims 1-4 which performs the said reaction at 60-200 degreeC. A compound represented by the following general formula (II) and a compound represented by the following general formula (IIIA) are reacted in the presence of a Lewis acid having a magnesium element and a solvent. The manufacturing method of the xanthene derivative which obtains the xanthene derivative represented by the following general formula (IA) by making the compound represented by Formula (IV) react.

In general formula (II),
Ra represents a monovalent substituent.
na represents 0-4.
In general formula (IIIA),
R ²¹ and R ²⁵ each independently represent a hydrogen atom or an alkyl group which may have a substituent.
R ²² , R ²³ , and R ²⁴ each independently represent a hydrogen atom, an alkyl group that may have a substituent, or —SO ₃ M. M represents H or a counter cation. However, at least one of R ²² , R ²³ and R ²⁴ represents —SO ₃ M.
In general formula (IV),
R ⁶ and R ¹⁰ each independently represents a hydrogen atom or an alkyl group which may have a substituent.
R ⁷ , R ⁸ and R ⁹ each independently represent a hydrogen atom, an alkyl group which may have a substituent, or —SO ₃ M. M represents H or a counter cation.
In general formula (IA),
Ra, na is the general formula (II) in Ra, has the same meaning as ^na, R 21 ^{to R 25} are respectively synonymous with ^R 21 ^{to R 25} in the general formula ^{(IIIA), R} 6 ~R ¹⁰ Are respectively synonymous with R < ⁶ > -R < ¹⁰ > in general formula (IV). The method for producing a xanthene derivative according to claim 6, wherein the total number of carbon atoms of the alkyl group represented by R ^{21 to} R ²⁵ or the total number of carbon atoms of the alkyl group represented by R ^{6 to} R ¹⁰ is 3 or more.   The method for producing a xanthene derivative according to claim 6 or 7, wherein the solvent is an alcohol solvent or an aprotic polar solvent.   The reaction according to any one of claims 6 to 8, wherein an organic base is added as an additive in the reaction between the compound represented by the general formula (II) and the compound represented by the general formula (IIIA). A method for producing a xanthene derivative.   The reaction between the compound represented by the general formula (II) and the compound represented by the general formula (IIIA), and the reaction of reacting the compound represented by the general formula (IV) with the reaction solution is performed in 60 to The manufacturing method of the xanthene derivative of any one of Claims 6-9 performed at 200 degreeC.