WO2023045601A1

WO2023045601A1 - Method for preparing tricine

Info

Publication number: WO2023045601A1
Application number: PCT/CN2022/111366
Authority: WO
Inventors: 袁永坤; 朱胜恺
Original assignee: 苏州亚科科技股份有限公司
Priority date: 2021-09-26
Filing date: 2022-08-10
Publication date: 2023-03-30
Also published as: CN113861053A; CN113861053B

Abstract

The present application relates to the technical field of biological buffers, and discloses a method for preparing tricine. The method comprises the following preparation steps: reacting compound I with compound A to obtain compound II; carrying out at least one of a hydrolysis reaction, an oxidation reaction and an acid-base treatment reaction on compound II to obtain a tricine crude product; and purifying same to obtain a tricine refined product. The preparation method of the present application is low in cost of used raw materials, easy in operation and high in purity of the obtained product, and also increases the yield of the product and reduces the application cost of the product. The obtained product meets the requirements of the field of biological buffers regarding the purity, impurity content, cost, etc. thereof. Moreover, the method is suitable for industrial production, and is also suitable for application in the field of biological buffers.

Description

A kind of preparation method of three (hydroxymethyl) methylglycine

technical field

The embodiments of the present application relate to the technical field of biological buffers, for example, to a preparation method of tris(hydroxymethyl)methylglycine.

Background technique

Tris(hydroxymethyl)methylglycine, referred to as Tricine, CAS: 5704-04-1, is a zwitterionic buffer used in biochemistry and molecular biology. The pH buffer range of Tricine is 7.4-8.8, which is mainly used to replace glycine, and is used in combination with SDS (sodium dodecyl sulfate) in small molecule protein electrophoresis; in biochemical research, it is often used in biochemical diagnostic kits, DNA/RNA Extraction kits and PCR diagnostic kits.

Patent CN112194590A discloses a preparation method of tris(hydroxymethyl)methylglycine, which adopts sodium chloroacetate and trishydroxymethylaminomethane in methanol, controls the pH value to react in the range of 8-10, and then passes through cooling , adding concentrated sulfuric acid, crystallization, drying and other steps to obtain tris(hydroxymethyl)methylglycine. The above preparation method has the disadvantages of strict control of reaction conditions, cumbersome preparation process, low product purity and high product impurities. Therefore, it is urgent to provide a method for preparing tris(hydroxymethyl)methylglycine with simple production method and high product purity and high yield.

Contents of the invention

The following is an overview of the topics described in detail in this article. This summary is not intended to limit the scope of the claims.

The embodiment of the present application provides a preparation method of tris(hydroxymethyl)methylglycine. The cost of raw materials used in the preparation method is low, the operation is simple, and the yield of the prepared product is relatively high. The tris(hydroxymethyl)methylglycine obtained by the above preparation method is (Hydroxymethyl)methylglycine crude product is purified to obtain high-purity tris(hydroxymethyl)methylglycine, which meets the requirements of the biological buffer field for its purity, impurity content, and cost.

The embodiment of the present application adopts the following technical solutions to realize:

A preparation method for tris(hydroxymethyl)methylglycine, comprising the following preparation steps:

Preparation step S1: react compound I with compound A to obtain compound II;

Preparation step S2: subjecting the above-mentioned compound II to at least one of hydrolysis reaction, oxidation reaction, and acid-base treatment reaction to obtain tris(hydroxymethyl)methylglycine;

The above-mentioned acid-base treatment reaction includes at least one of acid treatment and alkali treatment;

Wherein, the compound I is trishydroxymethylaminomethane;

The compound A is

or its salt,

At least one of the above, the Y is a halogen, OH, SH, an ester corresponding to OH, or an ester corresponding to SH.

Preferably, the compound A is

At least one of the above, Y ₁ and Y ₂ are both halogen, OH, SH, esters corresponding to OH, and esters corresponding to SH;

Preferably, the compound A is bromoacetic acid, ester corresponding to bromoacetic acid, acid anhydride corresponding to bromoacetic acid, mixed acid anhydride corresponding to bromoacetic acid, bromoacetic acid salt, iodoacetic acid, ester corresponding to iodoacetic acid, anhydride corresponding to iodoacetic acid, At least one of mixed acid anhydride and iodoacetate corresponding to iodoacetic acid.

Preferably, the compound A is at least one of esters corresponding to chloroacetic acid, anhydrides corresponding to chloroacetic acid, and mixed anhydrides corresponding to chloroacetic acid.

Preferably, the compound A is at least one of formaldehyde, paraformaldehyde, hydrogen cyanide, and cyanide MCN, and the M is one of metal cations, inorganic ammonium cations, and organic amine cations.

The reaction equation of the preparation step S1 is as shown in the following formula (1):

The reaction equation of the preparation step S2 is as shown in the following formula (2):

Preferably, the ester mentioned in the compound A is at least one of carboxylate, sulfonate, sulfinate and inorganic acid ester.

Preferably, the salt mentioned in the compound A is at least one of metal salt, ammonium salt, and complex salt based on acid-base interaction.

Preferably, in the preparation step S2, the oxidizing reagent used for the oxidation reaction of compound II is peroxide, ozone, permanganic acid, permanganate, dichromic acid, dichromate, hypochlorous acid, hypochlorous acid, chlorite, chlorite, fluorine, fluorine-containing gas mixture, chlorine, bromine, iodine, manganese dioxide, nitric acid, m-chlorobenzoic acid, m-chlorobenzoate, sulfuric acid, peroxy Sulfuric acid, peroxymonosulfate, dithionic acid, dithionate, pyrosulfuric acid, pyrosulfate, oxygen, caroic acid, m-chloroperoxybenzoic acid, m-chloroperoxybenzoate, sulfur trioxide, di at least one of nitrogen oxides.

Preferably, in the preparation step S1, the molar ratio of compound I to compound A is 1: (0.1-10); in the preparation step S2, the molar ratio of compound II to the oxidizing agent is 1: (0.1-10).

Preferably, in the preparation step S1, the reaction temperature is -50°C to 200°C, the reaction pressure is -0.05MPa to 1MPa, and the reaction time is 0.1h to 72h; in the preparation step S2, the reaction temperature is -50°C to 200°C, The reaction pressure is -0.05MPa～1MPa, and the reaction time is 0.1h～72h.

Preferably, in the preparation step S1, compound I reacts with compound A in a reaction solvent A, the reaction solvent A is methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl carbonate, diethyl ether, At least one of acetonitrile, dioxane, N,N-dimethylformamide, water, and dimethyl sulfoxide; in the preparation step S2, compound II is reacted in a reaction solvent B, and the reaction solvent B is Methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl carbonate, diethyl ether, acetonitrile, dioxane, N,N-dimethylformamide, water, dimethyl sulfoxide at least one.

The preparation method of above-mentioned tris (hydroxymethyl) methylglycine also comprises following preparation steps:

Under dry conditions, use dry airtight equipment or under dry gas purging, dissolve the tris(hydroxymethyl)methylglycine of the crude product obtained in the preparation step S2 in the purification solvent, then recrystallize, and then recrystallize under low temperature conditions Carry out crystallization, filtration and drying to obtain refined tris(hydroxymethyl)methylglycine.

The purification solvent is methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl carbonate, ether, acetonitrile, dioxane, N,N-dimethylformamide, water, dimethyl At least one of the group sulfoxide,

Compared with related technologies, the beneficial effects of the embodiments of the present application are:

The raw material cost used in the preparation method in the embodiment of the present application is low, and operation is simple, and the product purity obtained is higher, has not only improved the productive rate of the product and reduced the application cost of the product, and the obtained product conforms to the requirement in the biological buffer field. The requirements of purity, impurity content, cost, etc., and the method is suitable for industrial production and is suitable for application in the field of biological buffers.

The preparation method in the embodiment of the present application reacts compound I with compound A, which is easy to obtain and low in cost, to generate compound II, and then performs reactions such as hydrolysis reaction, oxidation reaction, and acid-base treatment reaction of compound II to obtain tris(methylol) base) methylglycine, which optimizes the preparation process, reduces production costs, and improves yield, which is of great significance.

The product obtained by the preparation process in the examples of the present application is easy to purify and separate. For the by-products and impurities generated in the reaction process, the product reaches the high-purity application standard in the field of biological buffers and meets the requirements for large-scale production. various requirements.

The entire preparation process in the examples of the present application is simple and easy to control, which is beneficial to scale-up production, shortens the reaction production cycle, and can obtain tris(hydroxymethyl)methylglycine with high purity through conventional recrystallization purification, which can effectively increase the yield of the product.

Other aspects will become apparent after reading and understanding the detailed description.

Detailed ways

Hereinafter, the present application will be further described in conjunction with specific implementation methods. It should be noted that, on the premise of not conflicting, the various embodiments or technical features described below can be combined arbitrarily to form new embodiments. It should be noted that the terms used in the examples are for describing specific implementations and do not limit the protection scope of the present application. In addition, the raw materials used in this application are all common commercially available products, so there is no need to specifically limit their sources.

The pressure values mentioned in this application, unless otherwise specified, refer to gauge pressure, and gauge pressure refers to the amount by which the total absolute pressure exceeds the surrounding atmospheric pressure or the pressure at a certain point in the liquid that is higher than the atmospheric pressure.

The yield is the percentage ratio between the actual product quality and the theoretical product quality, and the theoretical product quality is calculated based on the non-excessive raw materials in the reaction equation.

In the following examples, test method: nuclear magnetic analysis test, using the AVANCE 400 mega-NMR spectrometer of Bruker (Bruker); the purity of the product is measured by an acid-base titrator.

Example 1

Preparation step S1:

Under stirring conditions, add 20g compound I trishydroxymethylaminomethane, compound A, reaction solvent ethanol in the dry reactor of 1L, the molar ratio of compound I, compound A is respectively 1:1, and reaction oil bath temperature is 60 °C, the reaction pressure is 0MPa (gauge pressure), and the reaction time is 4h.

After the reaction was completed, the temperature was lowered to normal temperature, the insoluble matter was filtered off, the filtrate was evaporated under reduced pressure to remove the solvent, concentrated, and the crude compound II was prepared;

Among them, compound A is

Y is Cl.

Preparation step S2:

Under stirring conditions, add 20 g of compound II, ethanol as a reaction solvent, and hydrogen peroxide as an oxidation reagent to a 1 L dry reactor. The molar ratio of compound II to the oxidation reagent is 1:3, and the temperature of the reaction oil bath is 65 ° C. The reaction pressure is 0MPa (gauge pressure), and the reaction time is 6h.

After the reaction was completed, the temperature was lowered to normal temperature, the insolubles were filtered off, the filtrate was evaporated under reduced pressure to remove the solvent, and concentrated to prepare a crude product of tris(hydroxymethyl)methylglycine with a yield of 90%.

Preparation step S3:

Under dry conditions, use dry airtight equipment to dissolve the tris(hydroxymethyl)methylglycine obtained in the preparation step S2 in the purification solvent ethanol, then recrystallize, and then crystallize, filter, and dry under low temperature conditions , to obtain refined tris(hydroxymethyl)methylglycine fine product, the fine product purity is 99.5%.

The NMR characterization data of this product are as follows:

¹ H NMR (400 MHz, D ₂ O) δ 3.8 ppm (6H), 3.7 ppm (2H).

Example 2

Preparation step S1:

Under stirring conditions, add 20g compound I trishydroxymethylaminomethane, compound A, reaction solvent methanol in the dry reactor of 1L, the molar ratio of compound I, compound A is respectively 1:1.05, and reaction oil bath temperature is 60 °C, the reaction pressure is 0.01MPa (gauge pressure), and the reaction time is 4h.

Among them, compound A is

Y is OH.

Preparation step S2:

Under stirring conditions, add 20g of compound II and methanol as a reaction solvent to a 1L dry reactor to undergo hydrolysis and acid-base treatment with water. The temperature of the reaction oil bath is 94°C, and the reaction pressure is 0.015MPa (gauge pressure). The time is 6h.

After the reaction was completed, the temperature was lowered to normal temperature, the insoluble matter was filtered off, the filtrate was evaporated under reduced pressure to remove the solvent, and concentrated to prepare a crude product of tris(hydroxymethyl)methylglycine with a yield of 93%.

Preparation step S3:

Under dry conditions, use dry airtight equipment to dissolve the tris(hydroxymethyl)methylglycine obtained in the preparation step S2 in the purification solvent ethanol, then recrystallize, and then crystallize, filter, and dry under low temperature conditions , to obtain refined tris(hydroxymethyl)methylglycine fine product, the fine product purity is 99.6%.

The NMR characterization data of this product are as follows:

¹ H NMR (400 MHz, D ₂ O) δ 3.8 ppm (6H), 3.7 ppm (2H).

Example 3

Preparation step S1:

Under stirring conditions, add 20g compound I trishydroxymethylaminomethane, compound A, reaction solvent acetonitrile in the dry reactor of 1L, the molar ratio of compound I, compound A is respectively 1:2, and reaction oil bath temperature is 60 °C, the reaction pressure is -0.01MPa (gauge pressure), and the reaction time is 4h.

Among them, compound A is

Y is Br.

Preparation step S2:

Under stirring conditions, add 20g of compound II and acetonitrile as a reaction solvent to a 1L dry reactor, add water, and undergo a hydrolysis reaction with water. The temperature of the reaction oil bath is 90°C, and the reaction pressure is 0.02MPa (gauge pressure). for 6h, and then acid-base treatment reaction.

After the reaction was completed, the temperature was lowered to normal temperature, the insoluble matter was filtered off, the filtrate was evaporated under reduced pressure to remove the solvent, and concentrated to prepare a crude product of tris(hydroxymethyl)methylglycine with a yield of 94%.

Preparation step S3:

Under dry conditions, using dry airtight equipment, dissolve the tris(hydroxymethyl)methylglycine of the crude product obtained in the preparation step S2 in the purification solvent acetonitrile, then recrystallize, and then crystallize, filter and dry under low temperature conditions , to obtain refined tris(hydroxymethyl)methylglycine fine product, the fine product purity is 99.7%.

The NMR characterization data of this product are as follows:

¹ H NMR (400 MHz, D ₂ O) δ 3.8 ppm (6H), 3.7 ppm (2H).

Example 4

Preparation step S1:

Under stirring condition, add the mixture of 20g compound I trishydroxymethylaminomethane, compound A, reaction solvent ethanol and water in the dry reactor of 1L, the molar ratio of compound I, compound A is respectively 1:4, reaction oil The bath temperature is 60° C., the reaction pressure is 0 MPa (gauge pressure), and the reaction time is 4 h.

Among them, compound A is

Both Y ₁ and Y ₂ are Cl.

Preparation step S2:

Under stirring condition, add 20g compound II, reaction solvent dichloromethane in the dry reactor of 1L, add oxidation reagent potassium permanganate, the mol ratio of compound II and oxidation reagent is respectively 1:3, and reaction oil bath temperature is 65°C, the reaction pressure is -0.01MPa (gauge pressure), and the reaction time is 6h.

After the reaction was completed, the temperature was lowered to normal temperature, the insoluble matter was filtered off, the filtrate was evaporated under reduced pressure to remove the solvent, and concentrated to prepare a crude product of tris(hydroxymethyl)methylglycine with a yield of 64%.

Preparation step S3:

Under dry conditions, using dry airtight equipment, the tris(hydroxymethyl)methylglycine obtained in the preparation step S2 is dissolved in the mixture of purification solvent ethanol and water, then recrystallized, and then crystallized under low temperature conditions , filtered, and dried to obtain the refined tris(hydroxymethyl)methylglycine boutique, with a purity of 99.5%.

The NMR characterization data of this product are as follows:

¹ H NMR (400 MHz, D ₂ O) δ 3.8 ppm (6H), 3.7 ppm (2H).

Example 5

Preparation step S1:

Under stirring condition, add the mixture of 20g compound I trishydroxymethylaminomethane, compound A, reaction solvent methanol and water in the dry reactor of 1L, the molar ratio of compound I, compound A is respectively 1:2, reaction oil The bath temperature is 60° C., the reaction pressure is 0 MPa (gauge pressure), and the reaction time is 4 h.

Wherein, compound A is sodium bromoacetate.

Preparation step S2:

Under stirring conditions, add 20g of compound II to a 1L dry reactor, after acid-base treatment, the sodium salt becomes the corresponding acid, the temperature of the reaction oil bath is 65°C, the reaction pressure is 0MPa (gauge pressure), and the reaction time for 6h.

Preparation step S3:

Under dry conditions, using a dry airtight device, the tris(hydroxymethyl)methylglycine obtained in the preparation step S2 is dissolved in a mixture of purification solvent methanol and water, and then recrystallized, and then crystallized under low temperature conditions , filtered, and dried to obtain the refined tris(hydroxymethyl)methylglycine boutique, with a purity of 99.6%.

The NMR characterization data of this product are as follows:

¹ H NMR (400 MHz, D ₂ O) δ 3.8 ppm (6H), 3.7 ppm (2H).

Example 6

Preparation step S1:

Under stirring conditions, add 20g compound I trishydroxymethylaminomethane, compound A, reaction solvent methanol in the dry reactor of 1L, the molar ratio of compound I, compound A is respectively 1:1, and reaction oil bath temperature is 60 °C, the reaction pressure is 0MPa (gauge pressure), and the reaction time is 4h.

Wherein, compound A is the corresponding ethyl ester of chloroacetic acid.

Preparation step S2:

Under stirring conditions, add 20g of compound II to a 1L dry reactor. After acid-base treatment, the ester becomes the corresponding acid. The reaction oil bath temperature is 65°C, the reaction pressure is 0MPa (gauge pressure), and the reaction time is 6h.

After the reaction was completed, the temperature was lowered to normal temperature, the insolubles were filtered off, the filtrate was evaporated under reduced pressure to remove the solvent, and concentrated to prepare a crude product of tris(hydroxymethyl)methylglycine with a yield of 92%.

Preparation step S3:

The NMR characterization data of this product are as follows:

¹ H NMR (400 MHz, D ₂ O) δ 3.8 ppm (6H), 3.7 ppm (2H).

Example 7

Preparation step S1:

Under stirring conditions, add 20g compound I trishydroxymethylaminomethane, compound A, reaction solvent ethanol in the dry reactor of 1L, the molar ratio of compound I, compound A is respectively 1:3, and reaction oil bath temperature is 60 °C, the reaction pressure is 0MPa (gauge pressure), and the reaction time is 4h.

Among them, compound A is the mixture of paraformaldehyde and cyanide NaCN.

Preparation step S2:

Under stirring condition, add 20g compound II, reaction solvent ethanol in 1L dry reactor, add water, hydrolysis reaction occurs with water, reaction oil bath temperature is 95 ℃, reaction pressure is 0MPa (gauge pressure), reaction time is 6h.

After the reaction was completed, the temperature was lowered to normal temperature, the insoluble matter was filtered off, the filtrate was evaporated under reduced pressure to remove the solvent, and concentrated to prepare a crude product of tris(hydroxymethyl)methylglycine with a yield of 52%.

Preparation step S3:

Under dry conditions, use dry airtight equipment to dissolve the tris(hydroxymethyl)methylglycine obtained in the preparation step S2 in the purification solvent ethanol, then recrystallize, and then crystallize, filter, and dry under low temperature conditions , to obtain refined tris(hydroxymethyl)methylglycine fine product, the fine product purity is 99.0%.

The NMR characterization data of this product are as follows:

¹ H NMR (400 MHz, D ₂ O) δ 3.8 ppm (6H), 3.7 ppm (2H).

It can be seen from the above experiments that the tris(hydroxymethyl)methylglycine prepared in the examples has high purity and less impurity content, the crude product yield can reach more than 94%, and the refined product purity reaches more than 99.5%, which can meet Application requirements for biological buffers.

The above-mentioned implementation mode is only the preferred implementation mode of the present application, which cannot limit the protection scope of the present application. Scope of protection claimed.

Claims

A preparation method of tris(hydroxymethyl)methylglycine, which comprises the following preparation steps:

Preparation step S1: react compound I with compound A to obtain compound II;

Preparation step S2: subjecting the above-mentioned compound II to at least one of hydrolysis reaction, oxidation reaction, and acid-base treatment reaction to obtain tris(hydroxymethyl)methylglycine;

Wherein, the compound I is trishydroxymethylaminomethane;

The compound A is
or its salt,
or its salt,
or its salt,
At least one of the above, the Y is a halogen, OH, SH, an ester corresponding to OH, or an ester corresponding to SH.
The preparation method of tris(hydroxymethyl)methylglycine according to claim 1, wherein, the compound A is
At least one of the Y 1 and Y 2 are halogens, OH, SH, esters corresponding to OH, and esters corresponding to SH.
The preparation method of tris(hydroxymethyl)methylglycine according to claim 1, wherein, said compound A is bromoacetic acid, ester corresponding to bromoacetic acid, acid anhydride corresponding to bromoacetic acid, mixed acid anhydride corresponding to bromoacetic acid, bromine At least one of acetate, iodoacetic acid, an ester corresponding to iodoacetic acid, an anhydride corresponding to iodoacetic acid, a mixed anhydride corresponding to iodoacetic acid, and an iodoacetic acid salt.
The preparation method of tris(hydroxymethyl)methylglycine according to claim 1, wherein, said compound A is at least one of esters corresponding to chloroacetic acid, anhydrides corresponding to chloroacetic acid, and mixed anhydrides corresponding to chloroacetic acid .
The preparation method of tris(hydroxymethyl)methylglycine according to claim 1, wherein, said compound A is at least one of formaldehyde, paraformaldehyde, hydrocyanic acid, cyanide MCN, and said M is One of metal cations, inorganic ammonium cations, and organic amine cations.
The preparation method of tris(hydroxymethyl)methylglycine according to any one of claims 1-4, wherein, the ester mentioned in the compound A is carboxylate, sulfonate, sulfinate , at least one of inorganic acid esters; the salt mentioned in the compound A is at least one of metal salts, ammonium salts, and complex salts based on acid-base interactions.
The preparation method of tris(hydroxymethyl)methylglycine according to claim 1, wherein, in the preparation step S2, the oxidation reagent used when the compound II is oxidized is peroxide, ozone, permanganate, permanganate, Manganate, dichromic acid, dichromate, hypochlorous acid, hypochlorite, chlorous acid, chlorite, fluorine gas, mixed gas containing fluorine gas, chlorine gas, bromine, iodine, manganese dioxide , nitric acid, m-chlorobenzoic acid, m-chlorobenzoate, sulfuric acid, peroxymonosulfuric acid, peroxymonosulfate, dithionic acid, dithionate, pyrosulfuric acid, pyrosulfate, oxygen, caroic acid, m-chloro At least one of peroxybenzoic acid, m-chloroperoxybenzoate, sulfur trioxide, and nitrogen dioxide.
The preparation method of tris(hydroxymethyl)methylglycine according to claim 1, wherein, in the preparation step S1, the molar ratio of compound I to compound A is 1: (0.1～10); in the preparation step S2, the compound The molar ratio of II to the oxidizing agent is 1: (0.1-10).
The preparation method of tris(hydroxymethyl)methylglycine according to claim 1, wherein, in the preparation step S1, the reaction temperature is -50°C to 200°C, the reaction pressure is -0.05MPa to 1MPa, and the reaction time is 0.1 h to 72 hours; in the preparation step S2, the reaction temperature is -50°C to 200°C, the reaction pressure is -0.05MPa to 1MPa, and the reaction time is 0.1h to 72h.
The preparation method of tris(hydroxymethyl)methylglycine according to claim 1, wherein, in preparation step S1, compound I reacts with compound A in reaction solvent A, and described reaction solvent A is methanol, ethanol, acetone , tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl carbonate, ether, acetonitrile, dioxane, N,N-dimethylformamide, water, dimethyl sulfoxide at least one; preparation In step S2, compound II is reacted in a reaction solvent B, and the reaction solvent B is methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl carbonate, ether, acetonitrile, dioxane, At least one of N,N-dimethylformamide, water, and dimethyl sulfoxide.
The preparation method of tris(hydroxymethyl)methylglycine according to any one of claims 1-10, wherein, also comprising the following preparation steps:

Under dry conditions, use dry airtight equipment or under dry gas purging, dissolve the tris(hydroxymethyl)methylglycine of the crude product obtained in the preparation step S2 in the purification solvent, then recrystallize, and then recrystallize under low temperature conditions Carrying out crystallization, filtering, and drying to obtain refined tris(hydroxymethyl)methylglycine;

The purification solvent is methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl carbonate, ether, acetonitrile, dioxane, N,N-dimethylformamide, water, dimethyl At least one of the group sulfoxides.