JPH0310618B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing mononitrophenyl-β-hydroxyethyl sulfone.

More specifically, the present invention is directed to the following formula ( The present invention relates to a novel method for producing mononitrophenyl-β-hydroxyethyl sulfone, which is useful as an intermediate for aminophenyl-β-sulfatoethyl sulfone.

Conventionally, aminophenyl-β represented by the formula ()
- Sulfatoethyl sulfone is produced by treating aniline with acetic anhydride to form acetanilide, converting it into sulfonyl chloride in a large excess of chlorosulfonic acid to obtain acetylaminobenzenesulfonyl chloride, which is then reduced with sodium sulfite to form sulfinyl chloride. It is produced by reacting with an acid and then ethylene oxide or ethylene chlorohydrin to obtain acetylaminophenyl-β-hydroxyethyl sulfone, which is then hydrolyzed in sulfuric acid and esterified with sulfuric acid.

Alternatively, nitrobenzene can be converted into sulfonyl chloride in a large excess of chlorosulfonic acid to give m-nitrobenzenesulfonyl chloride, which can be reduced with sodium sulfite to give the corresponding sulfinic acid and then treated with ethylene oxide or ethylene chlorohydrin. It is produced by obtaining m-nitrophenyl-β-hydroxyethylsulfone, reducing it with iron powder to give m-aminophenyl-β-hydroxyethylsulfone, and then converting it into sulfuric acid ester.

However, in implementing any of the above-mentioned methods industrially, there are various problems listed below, and these methods cannot necessarily be said to be industrially advantageous.

Sulfonyl chloride in chlorosulfonic acid is essentially an equilibrium reaction, and a large excess of chlorosulfonic acid is required to suppress the by-product of acetylaminobenzenesulfonic acid.

It is difficult to recover the above-mentioned excess chlorosulfonic acid, and ultimately it is necessary to treat it as an acidic waste liquid.

Acetylaminobenzenesulfonyl chloride is unstable, which contributes to lower yields.

Reduction to sulfinic acid with sodium sulfite results in low stability of sulfinic acid and therefore low reaction yield.

When aniline is used as a starting material, the acetic acid released by hydrolysis of the acetyl group in the final step reacts with the hydroxyl group, resulting in acetic acid ester by-product, resulting in a decrease in purity. The acetic acid produced causes major problems such as corrosion of reaction equipment and problems with waste water.

In view of these circumstances, the present inventors developed the formula ()
We investigated an industrially advantageous method for producing the compound represented by, and reduced mononitrophenyl β-hydroxyethyl sulfone obtained by oxidizing mononitrophenyl β-hydroxyethyl sulfide.
We have discovered a new manufacturing method in which the obtained aminophenyl-β-hydroxyethylsulfone is esterified with sulfuric acid to form the desired compound of formula (), and we have made the oxidation step in this new manufacturing method more industrially advantageous. We discussed in detail how to do this.

The conventional oxidation method is to use hydrogen peroxide at a relatively high temperature in glacial acetic acid [Proc.Indian.
Acad.Sci.38 Vol. A.23-30 (1953)], a method carried out in an aqueous sodium bicarbonate solution using hydrogen peroxide (Tokuko Sho.
43-24661), and a method using sodium hypochlorite in an aqueous solution of an inorganic compound such as sodium hydroxide, sodium carbonate, or sodium bicarbonate (German Patent No. 944607).

However, each of these methods has the following drawbacks. That is, in the production method in which oxidation is performed using hydrogen peroxide in glacial acetic acid, an acetalized product is produced as a by-product, and as a result, the purity and yield of mononitrophenyl-β-hydroxyethyl sulfone are lowered.

Furthermore, it is extremely difficult to quantitatively recover glacial acetic acid by distillation. Also, the reaction temperature is 70~80℃
However, it takes 10 hours, which is not advantageous as an industrial manufacturing method.

In the method of oxidation using hydrogen peroxide in an aqueous sodium bicarbonate solution, the oxidation reaction does not proceed smoothly due to the heterogeneity of the reaction system, and a considerable amount of unreacted substances or intermediates are produced even after 10 hours of incubation. The product mononitrophenyl-β-hydroxyethyl sulfoxide remains. Further, at a reaction temperature exceeding 45° C., self-decomposition of hydrogen peroxide takes precedence over oxidation reaction, and the yield of the sulfone produced is low. Furthermore, due to the heterogeneity within the system, the phenomenon of incubation tubes is added, making it extremely difficult to complete the reaction.

In the production method of oxidizing basic inorganic compounds using hypochlorous acid in an aqueous solution, the oxidation reaction does not proceed smoothly at a reaction temperature of 25 to 30°C due to the heterogeneity of the reaction system, resulting in a considerable amount of unused material. Since the reactants remain, the purity and yield of the sulfone produced will be low. If the reaction temperature is set to 30 to 60°C, the oxidation reaction will be facilitated, but high melting point substances will be produced as by-products, which is not preferable.

The present inventors have conducted intensive studies on a method for producing mononitrophenyl-β-hydroxyethyl sulfone with high purity and high yield in an industrially advantageous manner by oxidizing mononitrophenyl-β-hydroxyethyl sulfide. They discovered that the object could be achieved by carrying out oxidation using hydrogen peroxide in a specific reaction medium, leading to the completion of the present invention.

That is, the present invention provides mononitrophenyl-β-hydroxyethyl sulfide, which is characterized by oxidizing mononitrophenyl-β-hydroxyethyl sulfide using hydrogen peroxide in an aqueous medium containing at least one nitrile and a basic compound. - A method for producing β-hydroxyethyl sulfone is provided.

The method of the present invention will be explained in detail below.

Mononitrophenyl-β-hydroxyethyl sulfide used as a starting material in the method of the present invention may be produced by any method, but for example, mononitrohalobenzene with an alcohol,
It is 2- or 4-nitrophenyl-β-hydroxyethyl sulfide obtained by reacting mercaptoethanol in an organic solvent such as N-alkyl substituted amide.

Nitriles used in the method of the present invention are:
Aliphatic and aromatic nitriles, specifically acetonitrile, propionitrile, butyronitrile, adiponitrile,
Examples of the aromatic nitrile include glutaronitrile and 2-methylglutaronitrile, and examples of the aromatic nitrile include benzonitrile and tolnitrile. Of course, mixtures of two or more nitriles can also be used. Among them, acetonitrile is preferably used.

These nitriles can be used in an amount of 0.5 to 10 times the weight of the raw material sulfide. Of course, there is no problem in using 10 times the amount or more, but it is inefficient in manufacturing on an industrial scale, and the space-time efficiency also deteriorates. The preferred amount is
The amount is 0.5 to 6 times, more preferably 1 to 4 times.

Basic compounds include, for example, alkali metal hydroxides such as sodium hydroxide, alkali metal carbonates such as sodium carbonate, alkali metal hydrogen carbonates such as sodium hydrogen carbonate, and alkali metal hydrogen carbonates such as sodium hydrogen carbonate. Alkali metal phosphates such as sodium, disodium hydrogen phosphate, tertiary aliphatic organic amines such as triethylamine, ammonia, etc. are used, and one or more of these may be used.

The amount of these basic compounds to be used is 0.01 to 2 moles, preferably 0.1 to 1 mole, relative to the raw material sulfide.
It is twice as many moles. If the amount exceeds 2 moles, the PH of the reaction system
This is undesirable as it increases the decomposition of raw material sulfide or the self-decomposition of hydrogen peroxide.

The aqueous medium in the method of the present invention is prepared from the above-described nitriles, basic compounds, and water, and the amount thereof is adjusted appropriately so that the amount is 2 to 10 times, preferably 3 to 8 times, the weight of the raw material sulfide. You can change the mixing ratio. If the amount is 10 times or more, productivity will decrease and it will not be efficient.

The amount of the aqueous solution of the basic compound in the aqueous medium is 0.5 times or more, preferably 6 times or less, and more preferably 1 to 4 times the weight of the raw material sulfide.

Further, the pH of the aqueous medium is preferably in the range of 7.5 to 10.5, and in the reaction at pH 10.5 or higher, the hydrolysis of the sulfide in the raw material is promoted, and nitrophenol and the like are produced as by-products.

Further, self-decomposition of hydrogen peroxide takes precedence over oxidation reaction, which is not preferable from the viewpoint of hydrogen peroxide utilization efficiency. In addition, in a reaction at pH 7.5 or lower, the oxidation reaction progresses slowly, and in particular, the reaction to the target product sulfone is extremely slow than the intermediate product sulfoxide.

In particular, the raw material sulfide is 2-nitrophenyl-β
-PH7.5 for hydroxyethyl sulfide
When 8.5 is 4-nitrophenyl-β-hydroxyethyl sulfide, the pH is preferably 8.5 to 10.

Further, the organic solvent used in the production of the sulfide, which is the starting material, may be mixed into this aqueous medium.

The amount of hydrogen peroxide used is 2.1 to 3.5 mol, more preferably 2.1 to 3.0 mol, per 1 mol of raw material sulfide.
It is a mole.

The reaction temperature is within the range of 30-65°C, preferably 35-55°C. The time required for dropping the hydrogen peroxide solution in this preferred reaction temperature range is 0.5 to 3 hours, and the reaction is completed by keeping the temperature for 0.5 to 6 hours after the dropwise addition is completed.

It is not necessarily advantageous to raise the reaction temperature more than necessary because it causes self-decomposition of hydrogen peroxide.

In an embodiment of the present invention, for example, a mixture of nitrile and an aqueous solution containing a predetermined amount of a basic inorganic compound is used as a reaction medium, and after adding the raw material sulfide, a predetermined amount of hydrogen peroxide solution is added dropwise at a desired temperature, and the mixture is further kept warm. Do this.

Alternatively, after dissolving the raw material sulfide in nitrile, a predetermined amount of hydrogen peroxide is added, and a predetermined amount of an aqueous solution of a basic inorganic compound is further added dropwise at a desired temperature for reaction.

Alternatively, in another embodiment of the present invention, for example, after adding the raw material sulfide to the aqueous nitrile solution, a predetermined amount of hydrogen peroxide solution is dropped at a desired temperature, and in parallel, the pH in the system is adjusted to a predetermined value. A basic compound is added to keep the pH at the specified value, and even after dropping the hydrogen peroxide solution, the mixture is kept warm while maintaining the pH at the specified value until the reaction is completed. In this case, the basic compound may be added as an aqueous solution.

Alternatively, after adding the raw material sulfide to the nitrile solvent, a predetermined amount of hydrogen peroxide solution is added dropwise at the desired temperature, and in parallel, the base previously dissolved in water so as to maintain the PH in the system at a predetermined value. Add the compound dropwise and keep warm until the reaction is completed.

Moreover, a continuous form can be taken as an embodiment of the present invention.

According to the method of the present invention, mononitrophenyl-β
-Hydroxyethyl sulfone can be obtained with high purity and high yield, so it can be applied industrially with great advantage.

The method of the present invention will be explained in detail below using Examples, but the present invention is not limited to these Examples. In the examples, parts and % represent parts by weight and % by weight, respectively.

Example 1 40 parts of 2-nitrophenyl-β-hydroxyethyl sulfide was added to a mixed solution of 120 parts of acetonitrile and 120 parts of a 6% aqueous sodium bicarbonate solution.
57 parts of 30% hydrogen peroxide solution (2.5 times the mole) at 40℃
It dripped over time. After the dropwise addition was completed, the reaction was further monitored while being kept at this temperature, and it was found that 100% of the desired sulfone was produced within 2 hours of keeping the temperature, and neither the raw material sulfide nor the intermediate product sulfoxide remained.

After removing acetonitrile from the reaction solution under reduced pressure,
It was further concentrated, cooled, and dried.

45 parts of white crystals of 2-nitrophenyl-β-hydroxyethylsulfone were obtained.

The yield was 96%.

Example 2 40 parts of 2-nitrophenyl-β-hydroxyethyl sulfide was added to a mixed solution of 80 parts of acetonitrile and 40 parts of a 6% aqueous sodium bicarbonate solution. 50
57 parts (2.5 moles) of 30% hydrogen peroxide solution was added dropwise over 1 hour at °C. After dropping, continue at this temperature for 5 minutes.
It was kept warm for hours. 100% of the desired sulfone is produced,
No sulfide as a raw material or sulfoxide as an intermediate product remained.

After removing acetonitrile from the reaction solution under reduced pressure,
It was further concentrated, cooled, and dried.

44 parts of white crystals of 2-nitrophenyl-β-hydroxyethylsulfone were obtained.

The yield was 95%.

Example 3 80 parts of 4-nitrophenyl-β-hydroxyethyl sulfide was added to a mixed solution of 240 parts of acetonitrile and 80 parts of water.

At 40°C, 114 parts (2.5 moles) of 30% hydrogen peroxide solution was added dropwise over 1 hour.

During that time, a 10% aqueous sodium carbonate solution was added to maintain the pH within the system at 9.0.

After the addition was completed, the system was kept at the same temperature for 3 hours while maintaining the pH in the system at 9.0.

During this period, 150 parts of a 10% aqueous sodium carbonate solution was required to maintain the pH.

100% of the desired sulfone was produced, and no sulfide as a raw material or sulfoxide as an intermediate product remained.

After removing acetonitrile from the reaction solution under reduced pressure,
It was further concentrated, cooled, and dried.

88 parts of white crystals of 4-nitrophenyl-β-hydroxyethylsulfone were obtained.

The yield was 95%.

Example 4 40 parts of 2-nitrophenyl-β-hydroxyethyl sulfide was added to a mixed solution of 120 parts of acetonitrile and 100 parts of water.

At 40°C, 57 parts (2.5 moles) of 30% hydrogen peroxide solution was added dropwise over 1 hour.

During this time, sodium carbonate was added to maintain the pH in the system at 8.3.

After the addition was completed, the system was kept at the same temperature for 2 hours while maintaining the pH in the system at 8.3.

Approximately 7 parts of sodium carbonate was required to maintain the pH during this period. 100% of the desired sulfone was produced, and no sulfide as a raw material or sulfoxide as an intermediate product remained.

After removing acetonitrile from the reaction solution under reduced pressure,
It was further concentrated, cooled, and dried.

45 parts of white crystals of 2-nitrophenyl-β-hydroxyethylsulfone were obtained.

The yield was 96%.

Example 5 20 parts of 4-nitrophenyl-β-hydroxyethyl sulfide were added to 80 parts of acetonitrile.
29 parts of 30% hydrogen peroxide solution (2.5 times the mole) at 45℃
It dripped over time.

During this time, a 6% aqueous sodium carbonate solution was added to maintain the pH in the system at 9.6.

After the addition was completed, the system was kept at the same temperature for 4 hours while maintaining the pH in the system at 9.6.

No sulfide as a raw material or sulfoxide as an intermediate product remained.

After distilling off acetonitrile from the reaction solution, it was further concentrated, cooled, and dried.

21 parts of white crystals of 4-nitrophenyl-β-hydroxyethylsulfone were obtained.

The yield was 93%.

Example 6 20 parts of 3-nitrophenyl-β-hydroxyethyl sulfide was added to a mixed solution of 80 parts of acetonitrile and 80 parts of 5% sodium carbonate. At 45°C, 29 parts (2.5 moles) of 30% hydrogen peroxide solution was added dropwise over 1 hour.

After the addition was completed, the mixture was kept at this temperature for an additional 4 hours.
No sulfide as a raw material or sulfoxide as an intermediate product remained.

After distilling off acetonitrile from the reaction solution, it was further concentrated, cooled, and dried.

21 parts of white crystals of 3-nitrophenyl-β-hydroxyethylsulfone were obtained.

The yield was 93%.

Example 7 Benzonitrile is used instead of acetonitrile in the method described in Example 1. After 3 hours of heating, 100% of the desired sulfone was produced, and no sulfide as a raw material or sulfoxide as an intermediate product remained.

Comparative Example 1 (In the absence of nitrile) 40 parts of 2-nitrophenyl-β-hydroxyethyl sulfide was added to a 6% aqueous sodium bicarbonate solution.
240 parts of the mixture was added to the mixture, and 68 parts of 30% hydrogen peroxide solution (3 times the mole) was added dropwise at 40° C. over 1 hour while stirring. After the dropwise addition was completed, the temperature was kept at this temperature for another 10 hours, but 70% of the raw material sulfide remained and only 30% of the intermediate product 2-nitrophenyl-β-hydroxyethyl sulfoxide was formed, resulting in the desired sulfone. No formation was observed.

Comparative Example 2 (In the absence of acetonitrile) Add 40 parts of 2-nitrophenyl-β-hydroxyethyl sulfide to 120 parts of water, and add while stirring.
At 40°C, 68 parts (3 moles) of 30% hydrogen peroxide solution was added dropwise over 1 hour.

During this time, a 10% aqueous sodium carbonate solution was added to maintain the pH in the system at 8.3.

After the dropwise addition was completed, the system was kept at the same temperature for 10 hours while maintaining the pH in the system at 8.3, but 70% of the raw material sulfide remained, and the intermediate product 2-nitrophenyl-β-hydroxyethyl sulfoxide remained. 30
The desired sulfone was not produced.

Comparative Example 2 (When no basic compound is present) 40 parts of 4-nitrophenyl-β-hydroxyethyl sulfide was added to 120 parts of acetonitrile, and further 80 parts of water were added.

At 50°C, 57 parts (2.5 moles) of 30% hydrogen peroxide solution was added dropwise over 1 hour. After the dropping was completed, the temperature was kept at this temperature for another 7 hours, but the sulfide content of the raw material was 80%.
However, no production of the desired sulfone was observed.

Claims (1)

[Scope of Claims] 1. Mononitrophenyl-β-hydroxyethyl sulfide is prepared using hydrogen peroxide, at least one nitrile, and an alkali metal hydroxide,
At least one selected from carbonates, hydrogen carbonates, phosphates, tertiary aliphatic organic amines, and ammonia
1. A method for producing mononitrophenyl-β-hydroxyethyl sulfone, which comprises oxidizing it in an aqueous medium containing a basic compound. 2. The method according to claim 1, wherein the oxidation is carried out at a pH in the range of 7.5 to 10.5.