JPS62195390A - Fluorine containing phosphoric acid ester - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I (R' represents H or methyl; Rf represents 1-36C fluoroalkyl with >=1 F substituting H; M represents H or salt of alkali metal, ammonium, alkylamine or alkanolamine). EXAMPLE:Sodium heptadecafluorodecyl 2-hydroxy-3-methacryloyloxypropyl phosphate. USE:Useful in areas of engineering, medical science, etc., since having surface activity, self-constructive ability and polymerizabiity. PREPARATION:For example, a mono-alkali metal salt of mono- fluoroalkylphosphoric acid expressed by formula II (M' represents alkali metal) is reacted with glycidyl methacrylate or glycidyl acrylate expressed by formula III to produce a fluorine-containing phosphoric acid ester expressed by formula IV, if necessary, followed by acidification and further neutralization with a base.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel phosphoric acid ester, and more particularly to a fluorine-containing phosphoric acid ester having surface activity, self-assembly properties, and polymerizability.

[Problems to be solved by the prior art and the invention] A cell is the smallest unit of a living organism, and is covered by a cell membrane. This cell membrane is responsible for cell partition and compartment formation, cell movement,
It has various functions such as material transport and information transmission, and is the source of life activities.

On the other hand, in the field of polymer chemistry, research has been actively conducted in recent years to create artificial polymer membranes that have the functions possessed by cell membranes9 and to apply them to a wide range of fields such as engineering, medicine, and pharmacy. I'm bored.

For example, research is being conducted on polymer separation membranes with mass transport functions, and artificial polymer membranes are widely used in the field of engineering as ion exchange membranes, dialysis membranes, ultrafiltration membranes, reverse osmosis membranes, and gas separation membranes. etc. are widely used industrially. In addition, in the field of medicine, solute-permeable blood purification membranes found in artificial kidneys,
BACKGROUND OF THE INVENTION Research is being actively conducted on gas-permeable blood purification membranes found in heart-lung machines.

Research has also been conducted on microcapsules with a compartmental protection function, and artificial polymer membranes have been applied to microencapsulation of liquids, such as fragrances, and copy paper with microencapsulation of ink. Furthermore, research is being conducted on applications of microcapsules that also have a permeability function, such as sustained release drug formulation systems, microencapsulation of enzymes, and artificial red blood cells.

Furthermore, it has become clear that cell membranes have a bilayer structure of phospholipids, and bilayer membrane vesicles (liposomes) similar to cell membranes have been made using natural phospholipids (natural liposomes), and biomembrane It is used as a model material to elucidate various phenomena in biological membranes. Biological membranes are oriented in an orderly manner due to the physical properties of phospholipid molecules, which are characteristic of amphiphilic compounds with hydrophobic and hydrophilic groups (self-assembly), and form bilayer membranes. forming a structure. Therefore, conventional artificial polymer membranes have a completely different structure from biological membranes.

However, in recent years, not only natural phospholipids but also synthetic compounds have been discovered that have self-assembly properties and can form bilayer membrane structures, and it has become possible to create artificial liposomes using synthetic compounds. Furthermore, research into polymeric liposomes that stabilize the membrane by polymerizing this bilayer membrane structure has become active, and compounds with polymerizable groups in the hydrophobic or hydrophilic groups used as monomers are becoming more active. For example, a compound represented by the following formula (1v) has been synthesized by Regan et al. [Journal of the American Chemical Society (J, Amer.

Chem, Soc, ), 105. 2975 (1
983)).

(■) The forms of natural, artificial, and polymeric liposomes obtained in this way can be considered as a type of microcapsule, and are expected to be applied in engineering, medicine, etc. in the future. Therefore, when considering monomers as materials used in membranes, they not only have chemical properties but also physical properties such as surfactant ability and self-organizing ability.
And when considering future applications in medicine and medical polymers,
A substance with good compatibility with living organisms is desired. Phospholipids have exactly these desirable functions such as surface activity, self-assembly, and biocompatibility, and compounds in which polymerizable groups are introduced into phospholipids are attracting increasing attention.

[Problem that the invention seeks to solve]

However, there are limits to its application because phospholipids are difficult to obtain in high purity and are expensive.
It has been desired to develop a phosphate ester monomer that can be easily produced industrially, has surface activity, self-assembly properties, and polymerizability, and is highly safe for the human body.

[Means for solving problems]

Under these circumstances, the inventors of the present invention conducted extensive research and found that the following general formula (Vn) (wherein R' is a hydrogen atom or a methyl group, R is a carbon number 1
~36 linear or branched alkyl group, M represents a hydrogen atom, an alkali metal, ammonium, or a salt of an alkylamine or an alkanolamine) Phosphate esters have surfactant ability, self-assembly ability and It was discovered that it has polymerizability, and a patent application was previously filed (Japanese Patent Application No. 57025-1982).

The inventor conducted further research and found that the formula (Vl
l) A new fluorine-containing phosphoric acid ester in which a fluorine-containing alkyl group is introduced into the middle R has excellent surface activity, self-assembly ability, and polymerizability, and is easily produced from inexpensive and easily available raw materials. The present invention was completed based on the discovery that it can be synthesized with high purity and high yield through manipulation.

That is, the present invention relates to the following general formula (I) (in the formula, R' is hydrogen or a methyl group, and Rf has 1 to 1 carbon atoms.
36 linear or branched fluoroalkyl groups in which at least one hydrogen atom is substituted with 7 atoms,
M represents a hydrogen atom or a salt of an alkali metal, ammonium, alkylamine or alkanolamine. ) The present invention provides a fluorine-containing phosphate ester represented by

The fluorine-containing phosphoric acid ester represented by the formula (I) of the present invention can be prepared by converting the monoalkali metal salt of the monofluoroalkyl phosphoric acid represented by the formula (II) into the formula ([
) is reacted with glycidyl methacrylate or glycidyl acrylate, and a heptad-containing phosphate ester (!
It can be easily produced by producing a), acidifying it if necessary, and further neutralizing it with a base.

(II) ([) (In the formula, M' represents an alkali metal, and Rf and R/ are the same as above.) In the heptad-containing phosphate ester represented by formula (I),
Examples of the linear or branched fluoroalkyl group having 1 to 36 carbon atoms in which at least one hydrogen atom is substituted with a fluorine atom represented by Rf include tridecafluorooctyl, heptadecafluorododecyl, and heneicosa. Fluorododecyl, pentacosafluorotetradecyl, nonaco f7 fluorohexadecyl, tritriacontafluorooctadecyl, 2-pentafluoroethylpentafluorohexyl, 2-tridecafluorohexyltridecafluorodecyl, 2-hebutadecafluoro Examples include octylhebutadecafluorododecyl, 2-heneicosafluorodecylheneicosafluorotetradecyl, 2-pentacosafluorododecylpentacosafluorohexadecyl, 2-nonacosafluorotetradecyl nonacosafluorooctadecyl group, etc. , especially surfactant ability,
Those having 8 to 36 carbon atoms are preferred in terms of self-assembly ability.

Particularly preferred examples include tridecafluorooctyl,
Examples include heptadecafluorodecyl, heneicosafluorododecyl, and 2-tridecafluorohexyltridecafluorodecyl groups.

The group represented by R' is preferably a methyl group.

In the above reaction formula, the monofluoroalkyl phosphate represented by formula (II) is obtained by adding phosphorus pentoxide, phosphorus oxychloride,
It can be obtained by reacting a phosphorylating agent such as polyphosphoric acid to obtain a monofluoroalkyl phosphoric acid and then neutralizing it, and it may be obtained by any of these methods, but the fluorine-containing material of the present invention The monofluoroalkyl phosphate (It) used in the production of the phosphoric acid ester ([) is preferably of high purity. If the purity of the monofluoroalkyl phosphate is low and it is contaminated with many by-product impurities, the following problems will occur. In other words, when phosphorus pentoxide or phosphorus oxychloride is used as a phosphorylating agent, the presence of difluoroalkyl phosphates, which are by-products, reduces or eliminates the surfactant ability and self-assembly ability of monofluoroalkyl phosphates, and furthermore, The purity of the target compound decreases in the reaction with the epoxy compound, and purification to obtain a highly pure target compound becomes difficult. In addition, orthophosphoric acid, which is produced as a by-product when polyphosphoric acid is used as a phosphorylating agent, also reduces the yield of the desired reaction in the reaction with the epoxy compound, and further reduces the purity of the desired compound, making it difficult to obtain a highly pure desired compound. This makes purification difficult.

Therefore, it is preferable to use monofluoroalkyl phosphate (II) with a purity of 90% by weight or more.

In the above reaction, the amount of glycidyl methacrylate or glycidyl acrylate (1) is 1 to 10% per mole of monoalkali metal salt of monofluoroalkyl phosphoric acid (■)
It is preferable to react in moles, especially 3 to 5 moles.

If this reaction is carried out without converting monofluoroalkyl phosphoric acid into a monoalkali metal salt, not only the desired compound but also
Another 1 mole of the compound represented by formula (1) reacts to produce phosphoric acid triester, and at the end of the reaction, the ester bond is easily hydrolyzed due to the acidity of the system, resulting in the formation of the target compound. This is undesirable as it reduces the yield. Therefore, when carrying out this reaction, it is necessary to use monofluoroalkyl phosphoric acid in the form of a monoalkali metal salt.

The solvent used in the reaction includes inert polar solvents such as water, methyl alcohol, and ethyl alcohol, with water being particularly preferred.

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

Furthermore, polymerization inhibitors or polymerization inhibitors may be added during the reaction, such as hydroquinone monomethyl ether, hydroquinone, 2,2'-methylenebis(4
-ethyl-6-t-butylphenol) etc. is preferably added in an amount of 50 to 110,000 pp relative to glycidyl methacrylate.

In addition to the target compound, the fluorine-containing phosphate ester (I), the reaction solution thus obtained contains an unreacted compound represented by formula (1) or an epoxy moiety of the compound represented by formula (1). Contains hydrolyzed glyceryl methacrylate. Depending on the purpose of use, the reaction product may be used!
However, this product can be further purified to obtain a highly purified product. For example, sodium heptadecafluorodecyl 2-hydroxy-3-methacryloyloxyprobyl phosphate [in the compound of formula (I) R1 = CH,, Rf = C, H, C, F, , M
= Na, hereinafter referred to as compound (v)], the aqueous solution of sodium hebutadecafluorodecyl phosphate was reacted with glycidyl methacrylate, and then acetone was added to the reaction solution and cooled. Sodium heptadecafluorodecyl 2-hydroxy-3-methacryloyloxyglobyl phosphate is precipitated and separated from the acetone-soluble glycidyl methacrylate hydrolyzate to obtain the desired product with good purity. Acid form of hebutadecafluorodecyl 2-hydroxy-3-methacryloyloxyglobyl phosphate [formula (1) compound K OiteR'=
CHa, Rf = C, H4C, F,.

M=H) can be obtained by making the aqueous solution of Na salt obtained as described above acidic with an acid, such as hydrochloric acid, and extracting with a solvent such as ethyl ether.

In addition, in this reaction, depending on the reaction conditions, the following formula (VI)
A small amount of the compound shown may be produced.

0 (■) 0=P-ORf 0M (Rf, R', and M in the formula are the same as above.) [Operation] The fact that the compound (1) of the present invention exhibits excellent surface activity means that the surface of its aqueous solution This occurs because the tension decreases. As shown in Table 1, in particular, the general formula (
■) The compound is also excellent.

Below is a blank table 1 (*Surface tension method, 25℃, #Value at critical micelle concentration, 25℃) In Table 1, compound (V) is the same as above, A is formula (Vll), R'=CH, R=C,H,,,
M=Na (Q compound, B is R'= in formula (■)
CH3, R=C, 2f(2!l, M=Na compound, C ha formula (%'l[) K OiteR/=C)I, ,
Indicates a compound where R=C,, f(85, M=Na).

In addition, the fact that the compound shown in the present invention has polymerizability means that, for example, adding a photopolymerization initiator or a general water-based polymerization initiator to the above-mentioned aqueous solution of compound (V) gives light or heat. This can also be seen from the fact that these polymers have film-forming ability.

〔Effect of the invention〕

The fluorine-containing phosphate ester of the present invention has surfactant ability, self-assembly ability, and polymerizability, is highly safe for the human body, and can be produced industrially with great advantage. Therefore, it can be widely used in fields such as engineering and medicine.

〔Example〕

Next, the present invention will be explained with reference to Examples.

Example 1 A reactor was charged with 95.5 P of 97% pure hebutadecafluorodecyl phosphate (0.19 mol, but the AV of this sample
I (Number of η of KOH required to neutralize sample 1? of the present phosphoric acid monoester to the broom-equivalence point, the same applies below) = 10
8.9, AV2 (~number of KO)l required to neutralize sample 1? of this phosphoric acid monoester to the second equivalence point, the same applies hereafter) = 217.0) was added. , 1N hydroxide) Add 185L/l of IJum aqueous solution and stir.
The temperature was raised to 70'C to make it uniform. At this time, the acid value of the reaction system (
Sample 1? The number of KOH glues required to neutralize (hereinafter the same) was 36.8. Next, while maintaining the reaction system at 70'C, 104.5 P of glycidyl methacrylate was added.
(0.74 mol) was gradually added to the solution and stirred at this temperature for 9 hours. At this time, the acid value of the reaction system became approximately O, indicating that the reaction was completed. In addition, the sample at this time was subjected to HPLC
When analyzed by high performance liquid chromatography (the same applies hereinafter), a peak of unreacted glycidyl methacrylate was observed. After further stirring and reaction for a total of 20 hours, glycidyl methacrylate was no longer completely hydrolyzed, and peaks of glyceryl methacrylate and the target compound, in which the epoxy moiety of glycidyl methacrylate was hydrolyzed, were observed. Next, the reaction solution was cooled to room temperature, acetone 201' was added, and the mixture was cooled to -5°C to obtain 92 units of sodium heptadecafluorodecyl 2-hydroxy-3-methacryloyloxybrobyl phosphate (yield: 70 units). Ta.

IHNMR.

δ2. Oppm (a, 3H,CH,=C-C!!,
) δZ6 ppm (t t, 2H, -P-C)C:
HtC%CFt)sn''CNMR (standard sample: st(C)13)4)
δ (Ppm): a18.5. i33.4. h58.7.
e66.5. g67.6° f69.9. b126.5.
c137.6. d168.9 As a result of HPLC analysis,
Purity was 98-99%.

Test Example 1 S, O, was added as a polymerization initiator to about 101 aqueous solution of sodium heptadecafluorodecyl 2-hydroxy-3-methacryloyloxybrobyl phosphate [compound (V)] obtained in Example 1. Compound (v) added 1%, 60-70
When heated for 4 to 5 hours at °C, a colorless and transparent high viscosity aqueous solution was obtained, and furthermore, when this polymer was placed on a slide glass and left to stand, a colorless and transparent film-like substance was obtained.

Moreover, this high viscosity aqueous solution had anisotropic properties and had an organized liquid crystal structure.

Example 2 92% purity 2-tridecafluorohexyltridecafluorodecyl phosphate 205F-(0,025 mol, just 7)Ii [0AV1=70.1, Av2=1
39.8) with 1N hydroxide) IJium aqueous solution 24.
Dispersed in 8 ml, the acid value of the reaction system at this time was 31.1
), glycidyl methacrylate at 70°C 14.2
P (0.10 mol) was gradually added and at this temperature 30
Stir for hours. It can be seen that the acid value of the reaction system at this time was approximately 0 and the reaction rate of monoalkyl phosphoric acid was 100%. When the reaction solution was analyzed by HPLC, peaks of a hydrolyzate of glycidyl methacrylate and a new product were observed. The product was separated by HPLC and the solvent was distilled off under reduced pressure to obtain 2-tridecafluorohexyltridecafluorodecyl 2-hydroxy-3-methacryloyloxyzolobilurin mf thorium. (Yield 89
%) obtained.

Elemental analysis) As a result of IPLC analysis, the purity was 98-99%.

Written amendment to the above procedure (voluntary) April 8, 1985 1. Indication of the case: 1985 Patent Application No. 36988 2. Name of the invention: Fluorine-containing phosphate ester 3. Person making the amendment: Relationship to the case: Name of the applicant Name (091) Kao Corporation 4, agent name (7756) Patent attorney Toshio Takano;
6. “Claims” and “Detailed Description of the Invention” of the specification subject to amendment
Column 76 Contents of the amendment (The scope of claims in the 11th specification is amended as shown in the attached sheet.

(2) In the specification, in the third line from the bottom of page 6, the phrase [hydrogen or methyl group] is corrected to read "hydrogen atom or methyl group."

(3) Same, page 7, line 8, page 9, line 10, page 9, bottom line, page 10, lines 13-14, @10 negative line 17, and page 11, lines 4-5. Correct "monofluoroalkyl phosphoric acid" to "monofluoroalkyl phosphoric acid" (4) Same, page 9, lines 6-7, page 9, lines 13-14,
Page 9, line 15 and page 10, lines 9-10, “monofluoroalkyl phosphate” is replaced with “monofluoroalkyl phosphate”.
Fluoroalkyl phosphate”.

(5) Same, page 9, line 19, “difluoroalkyl phosphate” should be corrected to “zofluoroalkyl phosphate” (6) Same, page 11, line 16, “glycisol methacrylate” Correct the statement "(meth)acrylic acid glycisol" to "(meth)acrylic acid glycisol" 0 (7) Same, page 16, line 9, "has ceased to be hydrolyzed" has been replaced with "has ceased to be hydrolyzed," ” he corrected.

Claim 1, General formula (■), OHOM (R' in the formula is a hydrogen atom or a methyl group, Rf is a linear or branched chain with 1 to 360 carbon atoms, at least one hydrogen atom is a fluorine atom) fluoroalkyl group substituted with M is a hydrogen atom or an alkali metal, ammonium,
Indicates that it is an alkylamine or alkanolamine salt. ) A fluorine-containing phosphate ester.

Claims (1)

[Claims] 1. General formula (I), ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) (R' in the formula is hydrogen or a methyl group, Rf is a carbon number of 1 to
36 linear or branched fluoroalkyl groups in which at least one hydrogen atom is substituted with a fluorine atom,
M represents a hydrogen atom or a salt of an alkali metal, ammonium, alkylamine or alkanolamine. ) Fluorine-containing phosphate ester.