JPH0660185B2 - Method for producing phosphate ester - Google Patents

Description

The present invention relates to a novel method for producing a phosphoric acid ester, and more specifically, to react a monoalkali metal salt of a phosphoric acid ester with an epoxy compound with good selectivity. More preferably, it relates to a method for producing phosphodiesters.

[Conventional technology and its problems]

It has become clear that phospholipids are deeply involved in the functions of cell compartment formation, substance transport, etc. as constituents of cell membranes in vivo and also play an important role in various biological activities. .

Phosphatidylglycerol, which is one of the phosphoric acid esters having a glyceryl group, is also a kind of phospholipid, and (IV)
It has a formula-like structure.

On the other hand, phosphoric acid esters of organic hydroxy compounds are detergents, fiber treatment agents, emulsifiers, rust inhibitors, liquid ion exchangers,
It is also used in a wide range of fields such as pharmaceuticals. For example, phosphoric acid monoester salts of long-chain alkyl alcohols have good foaming power, good detergency, low toxicity and less skin irritation, so conventional alkyl sulfates, polyoxyethylene alkyl ether sulfates, alkylbenzene sulfonates , Has excellent properties as a detergent alternative to α-olefin sulfonate.

However, in recent years, with the advancement of living standards, safety awareness has been raised, and it has become desirable to develop cosmetics and cosmetic raw materials having higher safety for the human body.
Studies have been conducted to produce compounds having a structure similar to that of phospholipids of biological origin, such as the compounds of the formula.

However, the production of a compound having a structure similar to a phospholipid requires a multistep complicated reaction, requires a raw material that is difficult to synthesize, or hardly separates a target product after the reaction. Therefore, it was difficult to obtain these compounds industrially.

[Means for solving problems]

In such an actual situation, as a result of intensive research conducted by the present inventors, a cheap and easily available raw material was used, and the following formula (III) was used with a simple operation. (In the formula, m is 0 or 1, and when m is 0, R ¹ is a linear or branched alkyl group or alkenyl group having 1 to 36 carbon atoms, or a linear or branched chain having 1 to 15 carbon atoms. Represents a phenyl group substituted with a chain alkyl group,
R ² represents an alkylene group having 2 to 3 carbon atoms, and n is 0 to 3
Indicates the number of zeros. When m is 1, n is 0 and l is 0 or 1, and when m is 1 and l is 0, R ¹ has ¹ to 10 carbon atoms.
22 represents a straight-chain alkyl group, wherein m is 1 and l is 1,
R ¹ represents a linear or branched alkyl group or alkenyl group having 1 to 36 carbon atoms. M represents a hydrogen atom or a salt of an alkali metal, an alkaline earth metal, an alkylamine, an alkanolamine or ammonium), and a method for producing a phosphoric acid ester was found, and the present invention was completed.

That is, the present invention is the following general formula (I) (In the formula, M ′ represents an alkali metal, and R ¹ , R ² , l, m
And n have the meanings given above. ) A monoalkali metal salt of a phosphoric acid ester represented by the following formula (II) Is a method for producing a phosphoric acid ester (III) by reacting glycidol represented by the formula (1) and further converting it to a free acid or converting it to another salt, if necessary.

The phosphoric acid monoester salt represented by the formula (I) used in the present invention, monoethyl phosphate, monobutyl phosphate, monooctyl phosphate, monododecyl phosphate,
Monohexadecyl phosphate, monooctadecyl phosphate, monotetracosyl phosphate, mono 2-ethylhexyl phosphate, mono 2-hexyl decyl phosphate, mono 2
-Octyldodecyl phosphate, mono 2-tetradecyl octadecyl phosphate, mono monomethyl branched isostearyl phosphate, monooctenyl phosphate, monodecenyl phosphate, monododecenyl phosphate, monohexadecenyl phosphorus Mono- or branched-chain alkyl or alkenyl phosphates such as acid salts, monooctadecenyl phosphate, monotetracocenyl phosphate, monotriacontenyl phosphate [in the formula (I), R ¹ is A linear or branched alkyl or alkenyl group having 1 to 36 carbon atoms, m is 0 and n is 0]; monoalkylphenyl phosphates such as monooctylphenyl phosphate and monononylphenyl phosphate salt [formula R ¹ in (I) is a straight-chain or branched substituted phenyl group with an alkyl group having 1 to 15 carbon atoms, m is 0, n is 0]; Monopoli Kishiechiren (3 mol) dodecyl ether phosphate, Monopoli oxypropylene (3
Mol) decyl ether phosphate, monopolyoxyethylene (8 mol) polyoxypropylene (3 mol) dodecyl ether phosphate, monopolyoxyethylene (4 mol)
Monopolyoxyalkylene alkyl ether phosphates such as octadecenyl ether phosphate or monopolyoxyalkylene alkenyl ether phosphates [in the formula (I), R ¹ is a linear or branched alkyl group having 1 to 36 carbon atoms or Alkenyl group, m is 0, n is a number greater than 0 and 30 or less]; monopolyoxyethylene (5 mol)
Monopolyoxyalkylene alkylphenyl ether phosphates such as nonylphenyl ether phosphate and monopolyoxypropylene (2 mol) octylphenyl ether phosphate [in the formula (I), R ¹ is a straight chain having 1 to 15 carbon atoms] A phenyl group substituted with a chain or branched chain alkyl group,
m is 0 and n is a number greater than 0 and 30 or less]; mono-2-hydroxyalkyl phosphates such as mono-2-hydroxydodecyl phosphate and mono-2-hydroxyhexadecyl phosphate [R in formula (I)] ¹ is a straight-chain alkyl group having 1 to 22 carbon atoms, m is 1 and n is 0]; mono 2-hydroxy-3-dodecyloxypropyl phosphate, mono 2-hydroxy-3
-Monomethyl-branched isostearyloxypropyl phosphate, mono-2-hydroxy-3-octadecenyloxypropyl phosphate or other mono-2-hydroxy-3-alkyloxypropyl phosphate or mono2-hydroxy-
3-Alkenyloxypropyl phosphate [In the formula (I), R ¹ is a linear or branched alkyl or alkenyl group having 1 to 36 carbon atoms, l is 1, m is 1, m is 0]
Etc. As the alkali metal salt, sodium and potassium salts are preferable.

The monoalkali metal salt of the phosphoric acid monoester represented by the general formula (I) used in the present invention has, for example, m of 0.
In the case of, the corresponding organic hydroxy compound is phosphorus pentoxide,
A phosphoric acid monoester is obtained by reacting with a phosphorylating agent such as phosphorus oxychloride or polyphosphoric acid, or 1 is 0 and m is 1
In the case of, for example, by reacting α-olefin epoxide having a corresponding hydrocarbon group with phosphoric acid, a phosphorylating agent such as polyphosphoric acid to obtain a phosphoric acid monoester having a 2-hydroxyalkyl group, or, Also, l is 1, m
When 1 is 1, the alkyl glycidyl ether or alkenyl glycidyl ether having the corresponding hydrocarbon group is reacted with a phosphorylating agent such as phosphoric acid or polyphosphoric acid to obtain a phosphoric acid monoester, which is then neutralized. Which can be obtained and obtained by any method, but the phosphoric acid monoester salt used in the present invention
(I) preferably has a high purity. That is, when a phosphoric acid diester salt, which is a by-product when phosphorus pentoxide or phosphorus oxychloride is used as a phosphorylating agent, is contained, the surfactant activity as a phosphoric acid monoester is reduced or disappears. In the reaction, the purity of the target compound is lowered, and purification for obtaining a highly pure target compound becomes difficult. Further, the orthophosphate produced as a by-product when polyphosphoric acid is used as a phosphorylating agent also reduces the yield of the intended reaction in the reaction with the epoxy compound,
Further, the purity of the target compound is lowered, and purification for obtaining a highly pure target compound becomes difficult. Therefore,
The purity of phosphoric acid monoester salt (I) is 90% by weight.
It is preferable to use one having the above-mentioned purity. As a method for industrially producing such a high-purity phosphoric acid monoester, a method developed by a part of the present inventor (Japanese Patent Application No.
9-138829, or JP-A-58-5229.
No. 5) and the like, and a method for removing orthophosphoric acid from a mixture of monopolyoxyethylene or polyoxypropylene alkyl ether phosphoric acid and orthophosphoric acid has been developed by a part of the present inventors (Japanese Patent Application No. Sho 5
9-251409).

In the production method of the present invention, the glycidol represented by the formula (II) is a monoalkali metal salt of phosphoric acid monoester (I) 1
It is preferable to react 1 to 10 moles, especially 3 to 5 moles, relative to the moles.

When the reaction is carried out without converting the phosphoric acid monoester into a monoalkali metal salt, not only the target compound but also another
Phosphoric acid triester reacted with moles of glycidol is by-produced to reduce the yield of the target compound, which is not preferable. Therefore, in carrying out this reaction, it is necessary to use the phosphoric acid monoester in the form of the monoalkali metal salt (I).

As the solvent used in the reaction, an inert polar solvent is preferable, and for example, water, methyl alcohol, ethyl alcohol and the like can be mentioned, and among them, water is preferable. The fact that water can be used as a solvent is extremely preferable in terms of safety when industrially manufactured.

The reaction temperature is preferably 30 to 100 ° C, particularly preferably 50 to 90 ° C.

In the obtained reaction solution, the desired phosphoric acid ester (II
Among I), unreacted glycidol or its hydrolyzate is contained in addition to the compound which is an alkali metal salt.
The reaction product thus obtained can be used as it is depending on the purpose of use, but can be made into a highly purified product by further purification. For example, sodium dodecyl glyceryl phosphate [in the formula (III), R ¹
= C ₁₂ H ₂₅ , m = 0, n = 0, M = Na],
Glycidol is added to an aqueous solution of sodium dodecylphosphate to cause a reaction, and then the reaction solution is crystallized and refined in acetone-water to obtain the desired product with high purity. Furthermore, this product can be converted to dodecyl glyceryl phosphate by acidifying the aqueous solution and extracting the organic matter into an organic solvent such as ethyl ether, and then removing ammonia, alkylamine, alkanolamine. It can be converted into another salt by neutralizing with a base such as.

In the present invention, depending on the reaction conditions, in addition to the phosphoric acid ester salt represented by the formula (III) of the present invention, a small amount of phosphoric acid ester salt represented by the following general formula (V) is produced. Sometimes.

(In the formula, R ¹ , R ² , 1, m, n, and M have the above-mentioned meanings.) [Effects of the Invention] According to the present invention, cosmetics having high safety to human body,
A phosphoric acid ester which can be widely used in the field of cosmetics can be produced industrially extremely advantageously.

Then, the phosphoric acid ester (I
II) has a surface activity equivalent to that of the corresponding phosphoric acid monoester salt, and has a lower Kraft point, which makes it extremely versatile as a raw material for cosmetics and cosmetics. It can be advantageously used as an agent, for example, 2-hydroxyoctadecylphosphoric acid [in the formula (III), m = 1, R ¹ = C ₁₆ H ₃₂ , n = 0, M
= H] can be used as a synthetic intermediate of a phosphatidygylglycerol (IV) analogue by acylating the 2-hydroxyl group, and the application is not limited to cosmetics and perfumes, but can be widely used.

[Examples] Next, examples, test examples, and comparative examples will be described.

Example 1 20.0 g of monododecylphosphoric acid having a purity of 97% [0.07]
3 mol, but AV1 of this sample (KO required to neutralize 1 g of this phosphoric acid monoester sample to the first equivalent point)
H mg (the same applies below) = 210.3, AV2 (mg of KOH necessary to neutralize 1 g of this phosphoric acid monoester sample to the second equivalent point, the same below) = 420.8] Then, 75.0 m of 1N aqueous sodium hydroxide solution was added and stirred, and the temperature was raised to 70 ° C. to make the mixture uniform. At this time, the acid value of the reaction system (mg of KOH necessary to neutralize 1 g of the sample,
The same applies below) was 42.9. Next, the reaction system is 70-80
While maintaining the temperature at ℃, 24.0 g of glycidol (the oxirane number of this product (the amount of hydrochloric acid consumed when the oxirane ring in 1 g of sample was chlorhydrinized with hydrochloric acid, expressed in mg of potassium hydroxide) was 683.7). It was ] Was gradually added, and the mixture was stirred at this temperature for 6 hours. At this time, the acid value of the reaction system became almost 0, indicating that the reaction was completed. Next, the reaction liquid was poured into 1000 g of acetone, and left to refrigerate at 5 ° C. for crystallization. One day later, the precipitated crystals were separated and washed with acetone to obtain 18.3 g (yield 69.2%) of white crystals of sodium dodecyl glyceryl phosphate.

δ (ppm) a; 14.6, b; 23.4, c; 26.5, d; 29.3,
e; 30.3, f; 30.4, g; 31.5, h; 32.7, i; 63.1,
j; 66.8 to 67.1, k; 71.7 IR (KBr) Fig. 1 Elemental analysis Test Example The foaming amount and Kraft point of the dodecyl sodium glyceryl phosphate obtained in Example 1 were measured.
1 is obtained, and it can be seen that, as compared with the corresponding sodium dodecylphosphate as a comparative product, the bubbles are almost the same and the craft point thereof is significantly low.

The measurement of the amount of foam was performed as follows. That is, an aqueous solution having an activator concentration of 5% is prepared, and 100 g of this solution is injected into a graduated cylinder. Then, a stirring blade is placed in the solution and stirred for 30 seconds. The volume of bubbles generated after standing for 10 seconds was measured. The rotation speed of the stirring blade is 1000 rpm,
It was inverted every 5 seconds. The temperature was measured at 40 ° C.

Example 2 10.0 g of monohexadecylphosphoric acid having a purity of 96% was placed in a reactor.
(0.030 mol, but AV1 = 173.6, AV2 of this sample
= 344.0), 10.9 sodium hydroxide aqueous solution (30.9 m) was added and stirred, and the temperature was raised to 70 ° C. to make the mixture uniform. At this time, the acid value of the reaction system was 40.3. Next, while maintaining the reaction system at 70 to 80 ° C, 9.8 g of glycidol
(The oxirane number of this product was 683.7) was gradually added, and the mixture was stirred at this temperature for 6 hours. At this time, the acid value of the reaction system became almost 0, indicating that the reaction was completed. Next, the reaction solution was poured into 300 g of acetone and left at refrigeration at 5 ° C. for crystallization. One day later, the precipitated crystals were separated and washed with acetone to obtain 8.2 g (yield 65.3%) of white crystals of sodium hexadecyl glyceryl phosphate.

Elemental analysis Example 3 20 g (0.2%) of mono-2-hexyldecylphosphoric acid having a purity of 92%
057 mol, but AV1 = 167.2, AV2 = 32 for this sample
9.8) was dispersed in 59.6 m of 1N aqueous sodium hydroxide solution (the acid value of the reaction system at this time was 39.5), and the temperature was 70 ° C.
Glycidol 14.0 g (The oxirane number of this product is 683.
7) was gradually added, and the mixture was stirred at this temperature for 8 hours. It can be seen that the acid value of the reaction system at this time is 0.7 and the reaction rate of the phosphoric acid monoester is about 98%. When the reaction solution was analyzed by HPLC (high performance liquid chromatography, the same applies to the following), a new product peak was observed. From this, the product was separated by HPLC, and the solvent was distilled off under reduced pressure to obtain 19.6 g of sodium 2-hexyldecyl glyceryl phosphate (yield
82.1%) was obtained.

Elemental analysis Example 4 In a reactor, 20 g (0.13%) of 99% pure monobutylphosphoric acid was added.
Mol, but for this sample AV1 = 360.6, AV2 = 721.
3) is charged and 1N sodium hydroxide aqueous solution 129m
Was added and stirred, and dissolved at 70 ° C. (the acid value of the reaction system at this time was 46.7). Next, while maintaining the reaction system at 70 ° C, 42.7 g of glycidol (the oxirane value of this product is 68
3.7) was gradually added dropwise, and the mixture was stirred at this temperature for 6 hours. It can be seen that the acid value of the reaction system at this time is almost 0 and the reaction rate of the phosphoric acid monoester is almost 100%. The product was separated by HPLC and the solvent was distilled off under reduced pressure to obtain 26.5 g (yield 81.5%) of sodium butylglycerylphosphate.

Elemental analysis Example 5 20 g of mono-2-hydroxydodecylphosphoric acid having a purity of 95%
(0.067 mol, but for this sample AV1 = 200.2, AV2
= 400.5) was dissolved in 71.4 m of 1N aqueous sodium hydroxide solution (the acid value of the reaction system at this time was 42.4). At 70 ° C., 22.0 g of glycidol (the oxirane number of which is 683.7) was gradually added, and the mixture was stirred at this temperature for 8 hours. It can be seen that the acid value of the reaction system at this time is almost 0 and the reaction rate of the phosphoric acid monoester is almost 100%. When the reaction solution was analyzed by HPLC, a new product peak was found. From this, the product was separated by HPLC and the solvent was distilled off under reduced pressure to obtain 20.8 g (yield 81.7%) of sodium 2-hydroxydodecyl glyceryl phosphate.

Elemental analysis Example 6 20 g (0.049 mol, but AV1 = 142.8, AV2 = 288.2 of this sample) of monotrioxyethylene dodecyl ether phosphoric acid having a purity of 98% was placed in a reactor, and 50.9 m of 1N aqueous potassium hydroxide solution was added. The mixture was stirred and dissolved at 70 ° C. (the acid value of the reaction system at this time was 39.5). Next, 16.1 g of glycidol (which has an oxirane number of 683.7) was gradually added dropwise while maintaining the reaction system at 70 ° C., and the mixture was stirred at this temperature for 6 hours. At this time, the acid value of the reaction system is almost 0.
It can be seen that the reaction rate of the phosphoric acid monoester is almost 100%. The product was separated by HPLC and the solvent was evaporated under reduced pressure to obtain 20.8 g (yield 83.4%) of potassium trioxyethylenedodecyl glyceryl phosphate.

Elemental analysis Example 7 In a reactor, 20 g (0.035 mol, but A of this sample) of monopolyoxyethylene nonylphenyl ether phosphoric acid (average ethylene oxide addition mol number = 5) having a purity of 90% was used.
(V1 = 97.1, AV2 = 194.1), 1N potassium hydroxide aqueous solution (34.6 m) was added, and the mixture was stirred and dissolved at 70 ° C. (the acid value of the reaction system at this time was 34.4). Next, 11.5 g of glycidol (the oxirane number of which is 683.7) was gradually added dropwise while maintaining the reaction system at 70 ° C., and the mixture was stirred at this temperature for 6 hours. It can be seen that the acid value of the reaction system at this time was almost 0, and the phosphoric acid monoester reacted almost 100%.

Example 8 20 g (0.050 mol, but the acid value of this sample = 139) of mono-2-hydroxy-3-dodecyloxypropyl phosphate monosodium having a purity of 90% was added and dissolved in 80 g of water (the acid of the reaction system at this time). The value was 27.8), 16.3 g of glycidol at 70 ° C (the oxirane value of this product is 683.
7) was gradually added, and the mixture was stirred at this temperature for 8 hours. It can be seen that the acid value of the reaction system at this time is almost 0 and the reaction rate of the phosphoric acid monoester is almost 100%. HPLC reaction solution
A new product peak was found when analyzed by.
The product was collected from this by HPLC and the solvent was distilled off under reduced pressure to obtain 18.0% (yield 82.5%) of sodium 2-hydroxy-3-dodecyloxypropyl glyceryl phosphate.

Elemental analysis Comparative Example 1 100.0 g (0.3%) of monododecylphosphoric acid having a purity of 97% was placed in a reactor.
6 mol, but AV1 = 210.3, AV2 = 420 for this sample.
8) and was dissolved in 337 mg of tetrahydrofuran. Next, while maintaining the reaction system at 60 ° C., 150 g of glycidol (the oxirane number of which is 683.7) was gradually added, and then the mixture was reacted at 70 ° C. for 2 hours. At this time, the reaction system was AV1 = 4.4, AV2 = 6.0, unreacted monododecyl phosphate was about 4.5 mol%, and phosphodiester dodecyl glyceryl phosphate was about 8.1 mol%.
It can be seen that about 87.4 mol% of dodecyl diglyceryl phosphate, which is a phosphoric acid triester, is produced.

Comparative Example 2 50.0 g (0.18%) of monododecylphosphoric acid having a purity of 97% was placed in a reactor.
2 moles, but AV1 = 210.3, AV2 = 420 for this sample.
8) and was dissolved in 67.7 g of tetrahydrofuran. Next, while maintaining the reaction system at 60 ° C, glycidol
36.9 g (the oxirane number of this product = 683.7) was gradually added, and then the mixture was reacted at 70 ° C. for 10 hours. At this time, the reaction system was AV1 = 39.6, AV2 = 57.3, about 27 mol% of unreacted monododecylphosphoric acid, about 33 mol% of phosphoric acid diester dodecylglycerylphosphoric acid, and phosphoric acid triester. It can be seen that about 40 mol% of dodecyl diglyceryl phosphate is produced.

[Brief description of drawings]

FIG. 1 is a drawing showing an infrared absorption spectrum of dodecyl sodium glyceryl phosphate obtained in Example 1.

Claims (1)

[Claims] 1. The following general formula (I) (In the formula, m is 0 or 1, and when m is 0, R ¹ is a linear or branched alkyl group or alkenyl group having 1 to 36 carbon atoms, or a linear or branched chain having 1 to 15 carbon atoms. Represents a phenyl group substituted with a chain alkyl group,
R ² represents an alkylene group having 2 to 3 carbon atoms, and n is 0 to 3
Indicates the number of zeros. When m is 1, n is 0 or 1 when 0, and when m is 1 and 0, R ¹ is 1 to ¹ carbon atoms.
22 represents a straight-chain alkyl group, and when m is 1 and is 1,
R ¹ represents a linear or branched alkyl group or alkenyl group having 1 to 36 carbon atoms. M'denotes an alkali metal), a monoalkali metal salt of a phosphoric acid ester represented by the following formula (II) The following general formula (III) is characterized in that glycidol represented by the formula (1) is reacted and, if necessary, converted into a free acid or converted into another salt. (In the formula, M represents a hydrogen atom, or a salt of an alkali metal, an alkaline earth metal, an alkylamine, an alkanolamine or ammonium, and R ¹ , R ² ,
m and n have the same meanings as described above).