JPH085833B2 - Method for producing 2-chloropropionaldehyde - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial field of application) The present invention relates to the following reaction formula (1) CH ₂ = CHCl + CO + H ₂ → CH ₃ -CHCl-CHO (1), vinyl chloride, carbon monoxide and The present invention relates to a method for producing 2-chloropropionaldehyde using hydrogen as a raw material.

2-Chloropropionaldehyde can be used as a useful intermediate for chemicals and agricultural medicine.

(Problems to be Solved by Prior Art and Invention) Using vinyl chloride, carbon monoxide and hydrogen as raw materials 2-
Methods for producing chloropropionaldehyde are known, for example, French Patent No. 1,397,779 and HELVETICA CHIMICAACTA, Volume 48, No. 5, 1.
It is shown on pages 151-1157. All of these methods use cobalt carbonyl as a catalyst, and, for example, according to the above-mentioned French Patent No. 1,397,779, a reaction temperature of 110 ° C.,
The reaction was carried out for 90 minutes under the reaction pressure of 200 atm, and the reaction results of vinyl chloride conversion rate of 57.4% and 2-chloropropionaldehyde selectivity of 86.2% were obtained.
However, in the method of using these cobalt carbonyls as a catalyst, the catalytic activity per cobalt is extremely low. Therefore, a large amount of cobalt carbonyl and a high reaction pressure of 160 to 200 atm are required, and the reaction temperature of 75 to 125 ° C
The method is such that the reaction is carried out for 90 to 120 minutes under heat. The target product, 2-chloropropionaldehyde, is a thermally unstable substance, and in order to reduce the reaction yield by consuming a considerable proportion in the sequential reaction under such reaction temperature and reaction time, This method is not reproducible, and hydrogen chloride is by-produced by this sequential reaction or other side reaction, which corrodes the material of the reactor violently and reacts with the cobalt carbonyl catalyst to form cobalt chloride. It also has a problem that it hinders reuse of the catalyst.

The inventors of the present invention have disclosed, as an improvement method for these, in JP-A-61-12.
6046, JP-A-62-10038, JP-A-62-22738, JP-A-62-96444, etc., vinyl chloride, carbon monoxide and hydrogen in the presence of a rhodium compound and a base. We have found a way to react. According to this method, the reaction proceeds at a lower temperature and a lower pressure and sufficient selectivity to the desired product is obtained, as compared with the conventional method using a cobalt carbonyl catalyst. In these methods, in the presence or absence of water, a base represented by the general formula, P (R ¹ R ² R ³ )
(Wherein P represents a phosphorus atom, R ¹ , R ² and R ³ each represent an alkyl group, an aryl group, a cycloalkyl group, an alkoxy group, an aryloxy group or a cycloalkoxy group), and pKa A combination with a nitrogen-containing compound of 3 to 11 is preferably used. These pKa are 3-1
Among the nitrogen-containing compounds of 1, pyridine compounds, quinoline compounds, imidazole compounds, triazole compounds and morpholine compounds are particularly preferably used from the viewpoint of reaction results and the like, but these bases are all relatively expensive compounds. Therefore, in industrial use, it is necessary to provide such a recovery device in order to minimize the amount of loss. Further, since all of these are highly reactive compounds, they are gradually consumed when used for a long time. Therefore, the operation also needs to be performed so as to suppress these losses as much as possible.
The operating conditions do not necessarily match those favoring the synthesis of 2-chloropropionaldehyde. Therefore, there is a problem in that the consumption and the reaction at a place slightly out of the optimum synthesis condition have a considerable influence on the production cost of the target product, 2-chloropropionaldehyde. In addition, many of pyridine compounds, quinoline compounds, morpholine compounds, and the like have relatively low boiling points, and these are used when the reaction product 2-chloropropionaldehyde is separated from the reaction solution by distillation. When mixed in a small amount of 2-chloropropionaldehyde having a low boiling point, it not only causes a decrease in the purity of 2-chloropropionaldehyde in the product but also when 2-chloropropionic acid is produced by oxidizing 2-chloropropionaldehyde. It also has a problem that it significantly inhibits the oxidation reaction of

An object of the present invention is to provide a method for producing 2-chloropropionaldehyde, which solves the above problems of the prior art.

(Means and Actions for Solving Problems) The present inventors have conducted detailed research for solving these problems. As a result, vinyl chloride, carbon monoxide and hydrogen are reacted with each other in the presence of a rhodium compound and a trivalent organic phosphorus compound or an oxide of a trivalent organic phosphorus compound to produce 2
In the production of chloropropionaldehyde, it was found that if a buffer solution is allowed to coexist in the reaction system, the reaction proceeds efficiently and the problems of the catalyst composed of rhodium and a base as described above are solved. The invention was completed.

That is, according to the present invention, vinyl chloride, carbon monoxide and hydrogen are reacted in the presence of a rhodium compound and a trivalent organic phosphorus compound or an oxide of a trivalent organic phosphorus compound to react with 2
-A method for producing 2-chloropropionaldehyde, characterized in that the reaction is carried out in the presence of a buffer solution when producing chloropropionaldehyde.

The trivalent organic phosphorus compound or the oxide of the trivalent organic phosphorus compound used in the method of the present invention is exemplified as follows.

That is, as a trivalent organic phosphorus compound, a compound represented by the general formula P ((R ¹
R ² R ³ ) (wherein P represents a phosphorus atom, and R ¹ , R ² and R ³ each represent the same or different alkyl, aryl, cycloalkyl, alkoxy, aryloxy or cycloalkoxy group) Examples of the trivalent organic phosphorus compound include phosphines such as trimethylphosphine, triethylphosphine, tripropylphosphine, tributylphosphine, trioctylphosphine, triphenylphosphine, tricyclohexylphosphine, and tribenzylphosphine, and trimethylphosphine. Examples of phosphites such as phosphite, triethyl phosphite, tripropyl phosphite, tributyl phosphite, trioctyl phosphite, triphenyl phosphite, tricyclohexyl phosphite, and tribenzyl phosphite. Be done.

In addition to the compounds represented by the above general formula P ((R ¹ R ² R ³ ), special phosphines include diphosphines such as bisdiphenylphosphinomethane and bisdiphenylphosphinoethane, and crosslinked polystyrene. Bound phosphines and the like are also preferably used.

Further, as an oxide of a trivalent organic phosphorus compound, an alkylphosphine oxide such as triethylphosphine oxide, tributylphosphine oxide or trioctylphosphine oxide, an arylphosphine oxide such as triphenylphosphine oxide or tritolylphosphine oxide, or an alkyl group and an aryl Examples thereof include alkylarylphosphine oxide having a group. In addition to these, use alkyl or aryl phosphite oxides such as triethyl phosphite oxide, tributyl phosphite oxide, and triphenyl phosphite oxide, and alkylyl aryl phosphite oxides having both an alkyl group and an aryl group. You can Furthermore, oxides of polydentate phosphines such as bis-1,2-diphenylphosphinomethanedioxide can also be used.

Further, the buffer solution in the method of the present invention means a solution having a buffering capacity with respect to a factor of variation in pH value, usually an acid,
It is prepared by dissolving a suitable combination of a base and various salts in a solvent. For these buffers, it is necessary to select the types of acids and bases that make up the buffers, and their concentrations and mixing ratios, according to the target pH value. Buffer is prepared. Examples of these are hydrochloric acid-potassium chloride buffer (typical pH range: 1 to 2.2), potassium hydrogen phthalate-
Hydrochloric acid buffer (typical pH range: 2.2 to 4.0), potassium hydrogen phthalate-sodium hydroxide buffer (typical pH range: 4.1 to 5.9), potassium dihydrogen phosphate-sodium hydroxide buffer (typical PH range: 5.8 to 8), boric acid-sodium hydroxide buffer (typical pH range: 8 to 10.2), sodium bicarbonate-sodium hydroxide buffer (typical pH range: 9.6 to 11), phosphoric acid Disodium hydrogen-sodium hydroxide buffer (typical pH range: 10.9-12) and the like,
In addition to these, various buffer solutions in which the types of acids, bases or salts constituting these buffer solutions are changed can also be mentioned. The pH value of these buffers usually varies depending on the measurement temperature, but in the method of the present invention, the pH value at 25 ° C. is represented for convenience. In the method of the present invention, among these buffers, an aqueous buffer having a pH value in the range of 1 to 12.5 is preferably used. In the presence of such a buffer, the rhodium compound exhibits high activity for 2-chloropropionaldehyde synthesis from vinyl chloride and syngas in the presence of a trivalent organic phosphorus compound or an oxide of a trivalent organic neighbor compound. In addition, since 2-chloropropionaldehyde, which is a reaction product, dissolves in a buffer solution immediately after being formed in the reactor, vinyl chloride, rhodium, and trivalent organic phosphorus compounds or oxides of trivalent organic phosphorus compounds are used as raw materials. It is also possible to employ a method of separating the organic layer containing a by liquid-liquid separation. Further, in this case, it is possible to easily separate 2-chloropropionaldehyde from a buffer solution containing 2-chloropropionaldehyde separated from the raw material vinyl chloride and the catalyst by distillation operation under normal pressure or slightly reduced pressure. You can On the other hand, the buffer solution thus recovered can be reused by taking out a part thereof and removing foreign ions as reaction by-products or exchanging it with a newly prepared buffer solution,
Such a method is very preferable as an industrial method for producing 2-chloropropionaldehyde.

The buffer used in the method of the present invention has a pH value of 1
It is particularly preferable that it is in the range of -9. The buffer solution having such a pH range is industrially easy to handle and brings about higher catalytic activity. Examples of such a buffer solution include an aqueous solution containing an acid and a salt containing the acid and a strong base. As the acid, an acid having a pKa in the range of 0.5 to 11 is preferable, and a carboxylic acid is particularly preferable. Specific examples of these carboxylic acids include formic acid, acetic acid, propionic acid,
Butyric acid, isobutyric acid, heptanoic acid, acrylic acid, methacrylic acid, crotonic acid, oxalic acid, malonic acid, methylmalonic acid,
Succinic acid, adipic acid, maleic acid, fumaric acid, 1,2,3
An aliphatic saturated or unsaturated mono- or polycarboxylic acid such as propanetricarboxylic acid, benzoic acid, toluic acid, o-ethylbenzoic acid, 2,4-dimethylbenzoic acid, phthalic acid, isophthalic acid, terephthalic acid, 3 -Monophthalic acid, trimellitic acid, trimesic acid, pyromellitic acid, benzenepentacarboxylic acid, monovalent or polyvalent aromatic carboxylic acid such as meritic acid, and the like. In addition, halogens, amino groups, carboxylic acids having a substituent such as a hydroxyl group in the alkyl group or aryl group of these carboxylic acids are also preferable, and examples of these include monofluoroacetic acid, difluoroacetic acid, trifluoroacetic acid, monochloroacetic acid, Dichloroacetic acid, trichloroacetic acid, monobromoacetic acid, dibromoacetic acid, 2-chloropropionic acid, 3-chloropropionic acid, halogen-substituted aliphatic carboxylic acids such as 2,2-dichloropropionic acid, o-chlorobenzoic acid, m-chloro Benzoic acid, p-chlorobenzoic acid, halogen-substituted aromatic carboxylic acids such as o-fluorobenzoic acid, glycine, sarcosine, alanine, β-alanine, 4-aminobutyric acid, valine, serine, aspartic acid, amino acids such as glutamic acid, Glycolic acid, lactic acid, 2-hydroxybutyric acid, glyceric acid, Gore acid, tartaric acid, citric acid, p- hydroxybenzoic acid, salicylic acid, a hydroxycarboxylic acid such as 2,4-dihydroxybenzoic acid. In addition, carboxylic acids having a substituent other than the above, such as phenylacetic acid, pyruvic acid, anisic acid, o-nitrobenzoic acid, and cinnamic acid, are also preferred examples. Among these carboxylic acids, halogen-substituted aliphatic carboxylic acids and monovalent or polyvalent aromatic carboxylic acids are particularly preferably used in the method of the present invention. Further, in the method of the present invention, as the acid, phosphoric acid, phosphorous acid, various oxyacids of phosphorus, for example, phosphonic acids, phosphonous acids, phosphinic acids,
Alternatively, phosphinous acids are also preferably used. Examples of these include methylphosphonic acid, ethylphosphonic acid,
Examples thereof include phenylphosphonic acid, phenylphosphonous acid, dimethylphosphinic acid, diethylphosphinic acid, diphenylphosphinic acid and diphenylphosphinic acid.
Furthermore, boric acid, carbonic acid and the like are also included in the examples of preferable acids.

As the strong base, oxides or hydroxides of alkali metals or alkaline earth metals are preferably used, and examples of such strong bases include magnesium oxide, calcium oxide, strontium oxide, lithium hydroxide and sodium hydroxide. , Potassium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, barium hydroxide and the like. Guanidines are also preferable strong bases, and specifically, various substituted guanidines other than guanidine, for example, methylguanidine and 1,1-dimethylguanidine are exemplified. In addition to these, various ammonium hydroxides, particularly quaternary ammonium hydroxide are also mentioned as examples of preferable strong bases, and specific examples thereof include tetramethylammonium hydroxide, tetraethylammonium hydroxide and choline. .

Salts of these acids and strong bases can be obtained by mixing these, for example, by mixing an acid and a carbonate or bicarbonate of a strong base, or by mixing an ammonium salt of a strong base and an acid. Also included in the scope of the present invention is a method of obtaining the same product as obtained by mixing an acid and a strong base, by the method described above.

When a polyvalent acid such as phthalic acid or pyromellitic acid is used in the method of the present invention, part of the acid radical may be in the form of a salt with a strong base and the rest may be in the form of a free acid. And one of the preferable means for allowing the acid and the salt of a strong base to coexist. Examples of acids that can be used in such a method include phosphoric acid and phosphorous acid, in addition to the polyvalent carboxylic acids described above. In addition, although it is preferable to use an aqueous buffer solution in the method of the present invention, most of the aromatic polycarboxylic acids have low solubility in water. However, by adopting the method as described above, most of the aromatic polycarboxylic acid has good solubility in water, and it becomes possible to form a buffer solution suitable for the method of the present invention. Such examples include phthalic acid and pyromellitic acid, as well as isophthalic acid and mellitic acid. In addition to this, terephthalic acid, which was not included in the examples of the preferred acids described above, can also be used in this method. By the above, it is included as an example of a preferable acid.

The concentration of these buffers is also important in the method of the present invention. When a low-concentration buffer solution is used, reaction results similar to those of a high-concentration buffer solution are obtained in the initial stage, but usually,
The pH value of the buffer decreases as the reaction progresses,
Outside the preferred pH range, the catalytic activity is impaired. Therefore, it is generally preferable that the concentration of the buffer solution is high, but it is not preferable in terms of handling that the concentration is too high.
Usually, the concentration of the buffer solution is preferably in the range of 0.001 mol to 10 mol, and particularly preferably in the range of 0.01 mol to 1 mol, per liter of the buffer solution, respectively. The amount of the buffer solution used may be small if the buffer solution has a high concentration, and conversely it is preferably used in a large amount if the buffer solution has a low concentration. The concentration and amount of these buffers are
Usually, it is particularly preferable to select the pH value of the buffer solution after the reaction so as to be in the range of 1 to 12.5. Usually, the amount of the buffer is 0.01 or more by weight ratio to vinyl chloride supplied to the reactor as a raw material, preferably in the range of 1000 or less, particularly 0.1-100
Is more preferably used.

Examples of the rhodium compound used in the method of the present invention include rhodium oxide, mineral acid salt, organic acid salt, and rhodium complex compound. Preferable examples thereof include rhodium oxide, rhodium nitrate, rhodium sulfate, rhodium acetate, triacetylacetonato rhodium, dicarbonylacetylacetonato rhodium, dodecacarbonyl tetrarhodium, hexadecacarbonyl hexarhodium, and the like, and rhodium complex. In addition to these compounds, compounds in which a complex compound is formed with rhodium and a base are more preferably used. The base may be a trivalent organic phosphorus compound or an oxide of a trivalent organic phosphorus compound which is preferably used in the method of the present invention,
Other bases may be used. These include for example, hydridocarbonyl tristriphenylphosphine rhodium _{[RhH (CO) (PPh 3)} 3 ], nitro silt list Li triphenylphosphine rhodium _{[Rh (NO) (PPh 3)} 3 ], .eta. Shikuropentaji Examples thereof include enylbistriphenylphosphine rhodium [Rh (C ₅ H ₅ ) (PPh ₃ ) ₂ ].

In the method of the present invention, the rhodium compound has a rhodium atom content of 0.0001 to 1 per liter of liquid phase in the reaction system.
It is used in an amount corresponding to 1000 milligram atoms, preferably in the range of 0.001 to 100 milligram atoms. Further, the trivalent organic phosphorus compound or the oxide of the trivalent organic phosphorus compound used in the method of the present invention is used in an amount of 0.1 to 500 mol, preferably 0.5 to 100 mol, per 1 gram atom of rhodium. To be done.

In the method of the present invention, the reaction proceeds without using a reaction solvent, but the reaction is usually performed in the presence of the reaction solvent. Any reaction solvent can be used as long as it does not adversely affect the reaction. In the method of the present invention, it is particularly preferable to use a water-insoluble or sparingly soluble solvent as a reaction solvent. By using such a solvent, the buffer solution containing 2-chloropropionaldehyde as a product can be easily separated from the solvent layer containing the catalyst component after the reaction. The water-insoluble or sparingly-soluble solvent means a solvent having a solubility in water of 5% by volume or less under operating temperature conditions,
Particularly, a solvent of 0.5% by volume or less is preferable. Hydrocarbons are particularly preferable as such a solvent. More specifically, hexane, heptane, octane, nonane, saturated hydrocarbons such as decane and the like, benzene, toluene, aromatic hydrocarbons such as xylene are preferably used, and also as a mixture of hydrocarbons industrially Ligroin obtained,
Kerosene, light oil, diesel oil, etc. are also included in these examples. In addition to these, ethers such as dipropyl ether and dibutyl ether, ketones such as diisobutyl ketone and holone, and esters such as butyl butyrate and butyl benzoate are also exemplified as preferable solvents.

In carrying out the method of the present invention, the reaction system contains other components such as an additive for improving the stability of the rhodium catalyst and an additive for improving the activity and selectivity of the catalyst. However, there is no particular problem as long as the pH value of the buffer solution is not significantly changed so as not to deviate from the preferable range of the present invention.

The method of the present invention is usually carried out at a reaction temperature of 10 to 150 ° C. and a reaction stress of 10 to 300 kg / cm ² gage, preferably 30 to 150 kg / c.
It is done in the m ² gauge range. The reaction temperature is preferably as low as possible from the viewpoint of the thermal stability of the produced 2-chloropropionaldehyde, and for this reason, 20-80 ° C is a particularly preferred temperature range. The mixing molar ratio of carbon monoxide and hydrogen in the raw material is usually in the range of 10 to 0.1 in terms of the value of carbon monoxide / hydrogen, and preferably in the range of 4 to 0.2. Carbon monoxide and hydrogen may be any mixed gas containing both components in the above composition ratio, and water gas, a gas such as methane, a gas inert to the reaction such as nitrogen, or carbon dioxide was contained. Things are used. The other raw material, vinyl chloride, is used in the form of gas, liquid, or solution dissolved in the solvent used for the reaction. The method of the present invention is a batch method,
It can be carried out by either a semi-batch method or a continuous method. For example, in the case of the grammar, vinyl chloride is gasified in an autoclave charged with a rhodium compound, a trivalent organophosphorus compound or an oxide of a trivalent organophosphorus compound, a buffer solution, and optionally a reaction solvent. , A liquid, or a solution, and a gas containing carbon monoxide and hydrogen is introduced into the mixture to a predetermined pressure, and the mixture is heated preferably with stirring to proceed the reaction. Examples of the continuous method include rhodium compounds, trivalent organic phosphorus compounds or oxides of trivalent organic phosphorus compounds, buffer solutions, and reaction solvents, if necessary, and vinyl chloride, carbon monoxide as raw materials. And hydrogen are continuously supplied to one of the pressure-resistant reactors, and the reaction mixture, unreacted vinyl chloride, carbon monoxide and hydrogen are continuously extracted from the other under stirring conditions at the reaction temperature. The reaction is thereby carried out.

(Examples) Hereinafter, the method of the present invention will be described more specifically with reference to Examples.

Reference Example 1 Dipotassium phthalate 6.25 mmol and monopotassium phthalate 6.25 mmol were dissolved in 100 ml of demineralized water to prepare a buffer solution.

 This buffer had a pH value of 4.2 at 25 ° C.

Reference Example 2 6.25 mmol monopotassium phthalate and 6.25 phthalic acid
A buffer solution was prepared by dissolving millimoles in 100 ml of demineralized water.

 This buffer had a pH value of 2.8 at 25 ° C.

Reference Example 3 6.25 mmol of phthalic acid and 6.25 mmol of sodium hydroxide were dissolved in 100 ml of deionized water to prepare a buffer solution.

 This buffer had a pH value of 3.9 at 25 ° C.

Reference Example 4 An aqueous solution of dichloroacetic acid in which 1 mol of dichloroacetic acid was dissolved in 1 liter of demineralized water and an aqueous solution of sodium dichloroacetate in which 1 mol of sodium dichloroacetate was dissolved in 1 liter of demineralized water were prepared. PH values of 1.4, 3.5, and 5.6 by mixing appropriately in the range of: 100.
100 ml of each of the three types of buffer solutions were prepared.

Reference Example 5 About 11 ml of a 0.1 mol / liter aqueous solution of sodium hydroxide was added to 50 ml of a 0.05 mol / liter aqueous solution of disodium hydrogen phosphate to prepare a buffer solution having a pH value adjusted to 11.5.

Example 1 After replacing the inside of a stainless steel autoclave with an internal volume of 100 ml equipped with a stirrer with nitrogen gas, hexadecacarbonylhexarodium 36 mg (Rh 0.2 mg atom)
Then, 262 mg (1 mmol) of triphenylphosphine and 20 ml of the buffer solution of Reference Example 1 were added, and 20 ml of a toluene solution of vinyl chloride containing 1.88 g (30 mmol) of vinyl chloride was added thereto. A gas mixture of carbon monoxide and hydrogen in a molar ratio of 1: 2 was added to the autoclave at room temperature under a pressure of 100 kg.
/ Pressing until the gauge reaches ² cm, raise the temperature to 55 ° C and
Let react for minutes. After cooling the autoclave to room temperature, the unreacted raw material mixed gas was collected in a gas sampling bag, the autoclave was opened, and the reaction mixed solution containing the catalyst, the solvent and the reaction product was taken out. As a result of quantifying the gas and liquid by gas chromatography, the conversion rate of vinyl chloride was 28.8%, the amount of 2-chloropropionaldehyde produced was 7.5 mmol (selectivity based on the converted vinyl chloride was 8%).
6.8%).

Examples 2 to 5 The reaction was carried out by changing the reaction temperature, the reaction pressure, the molar ratio of carbon monoxide and hydrogen, and the reaction time in the method of Example 1. The results are shown in Table 1.

Examples 6 to 9 In the method of Example 1, the reaction temperature is 50 ° C., the reaction time is 60 minutes, and the types of the rhodium compound, the trivalent organic phosphorus compound or the oxide of the trivalent organic phosphorus compound and the buffer solution are changed. The reaction was carried out. The amount of the rhodium compound was set to such an amount that rhodium was 0.2 mg atom.
Table 2 shows the results.

Examples 10 to 12 In Example 1, the type of buffer solution was changed to the buffer solution according to the method of Reference Example 4, and the amount used was changed to carry out the reaction. The results are shown in Table 3.

(Effect of the Invention) According to the present invention, 2-chloropropionaldehyde can be produced from vinyl chloride, carbon monoxide and hydrogen as raw materials at a low temperature and a low pressure with a high selectivity. In particular, according to the method of the present invention, an apparatus for recovering a base or removing a base mixed in 2-chloropropionaldehyde as in the conventional method is required, or a condition for suppressing the loss of the base is selected as much as possible. Without using the simple apparatus, the reaction can be stably proceeded for a long time. Further, the method of the present invention makes it possible to separate the catalyst component and the reaction product by an industrially preferable method.

Claims (8)

[Claims] 1. In producing 2-chloropropionaldehyde by reacting vinyl chloride, carbon monoxide and hydrogen in the presence of a rhodium compound and a trivalent organic phosphorus compound or an oxide of a trivalent organic phosphorus compound, A method for producing 2-chloropropionaldehyde, which comprises carrying out the reaction in the presence of a buffer solution. 2. The method according to claim 1, wherein a buffer solution having a pH value in the range of 1 to 12.5 at 25 ° C. is used. 3. The method according to claim 1, wherein a buffer solution having a pH value in the range of 1 to 9 at 25 ° C. is used. 4. The pH value of the buffer solution after the reaction is 1 at 25 ° C.
A method as claimed in any one of claims 1 to 3 in which the concentration and amount of the buffer solution are in the range of -12.5. 5. The method according to claim 1, wherein the buffer solution is an aqueous solution containing an acid having a pKa in the range of 0.5 to 11 and a salt consisting of the acid and a strong base. Method. 6. The method according to claim 5, wherein the acid is a carboxylic acid.
The method described in the section. 7. The method according to claim 5, wherein the strong base is an oxide or hydroxide of an alkali metal or an alkaline earth metal. 8. The method according to any one of claims 1 to 7, wherein the reaction is carried out in the presence of a water-insoluble or sparingly soluble solvent.