JPS6129774B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides a double layer composed of a novel surfactant or a multilayer structure film having a double layer as a basic skeleton,
and an endoplasmic reticulum consisting of the membrane. A feature of this novel surfactant-based bilayer or multilayer membrane and its endoplasmic reticulum is its ability to form stable structures at low concentrations. The stable structure referred to in the present invention is a stable, highly ordered, and strong structure that is different from the spherical micelles that general surfactants form in water or the loose lamellar micelles that soaps form in high concentration ranges. It has a layered structure, and its basic constituent unit is mainly a double layer structure. In recent years, the range of industrial applications of surfactants has been rapidly expanding. In other words, there are too many examples of applications ranging from conventional processing and finishing of detergents, emulsifiers, solubilizers, fibers, etc. to chemical reaction catalysts, catalyst carriers, microcapsules, selective adsorbents, and selectively permeable membranes. do not have. The present inventors have focused on the future prospects of new fields of development of surfactants, and as a result of intensive research, we have discovered that the secondary structure composed of a new type of surfactant as seen in the present invention. He found his body. The surfactant used in the present invention has the formula
It consists of a hydrophilic part X and a hydrophobic part linked to it as shown in (1) and (1'), and is represented by Ya-φ-Yb as a rigid part of 10 Å or more. Cn−Ya−φ−Yb−X …(1) Cn−Ya−φ−Yb−Cm−X …(1′) Here, Ya−φ−Yb is the joint portion Ya and
It means a bifunctional residue φ such that the bond axes bonded to Yb can maintain a substantially linear or parallel relationship, and the bonding portions Ya and Yb at both ends. In equations (1) and (1′), the rigid part is composed of
In Ya-φ-Yb, φ represents two aromatic rings connected via a direct bond or a carbon-carbon multiple bond, a carbon-nitrogen multiple bond, a nitrogen-nitrogen multiple bond, an ester bond, an amide bond, and 4 , has a bonding position at position 4'. An example of these is shown below.

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【formula】

【formula】

Y _a and Y _b are bonding atoms between the φ moiety and another hydrophobic moiety or hydrophilic moiety, and are -CH ₂ -, -CO-, -
Although it represents O-, -NH-, -S-, when bonding with a hydrophilic moiety, the atoms constituting the hydrophilic moiety may be shared as bonding atoms, and may be used as a direct bond type. In the present invention, defined in the rigid part,
Joint axis Y of φ that joins both end joints Y _a and Y _b
The limits of the linear state and parallel state in which _a -φ and φ-Y _b maintain a substantially linear or parallel relationship are defined as the following ranges. In other words, since it is difficult to actually measure these points beyond the length of the rigid part mentioned above, the bond axis Y _a −φ estimated by the molecular model estimation method, the potential energy estimation method, etc.
If the angle formed by φ-Y _b is less than 20 degrees, it can be considered parallel or straight. The length of the rigid portion of the present invention is the above-mentioned Y _a −φ
- In Y _b , the distance between the atomic centers of both end portions Y _a and Y _b is determined to be 10 Å or more, but it is difficult to actually measure the bond distance between arbitrary atoms by physical measurement of virtually all real molecules. Since this is impossible, in the present invention, we use analogical methods that are scientifically recognized and have established evaluations in the field, such as the accumulation method based on the average interatomic bond distance, approximation using a molecular model, and approximation using potential energy calculation. etc. shall be applied. C _o in formulas (1) and (1') is substantially an alkyl group with n carbon atoms, and the straight chain portion has 6 carbon atoms.
It is preferable that it is above. C _n is substantially a methylene chain (-CH ₂ )- _n , and the number m of chains is preferably 1 to 12. Further, the hydrophilic group X in formulas (1) and (1') is an ammonium salt, a phosphate, or a polyether, which are well known in general surfactants. Furthermore, in the present invention, formulas (1) and (1') can be extended, that is, the hydrophobic terminal C _o
Structures such as formulas (2) and (2') in which is shared between two molecules are also included within the scope of the present invention. Y′a, Y′b, C′m, and X′ are respectively Ya, Yb,
It corresponds to Cm and X, and may be the same or different. φ′ has the same meaning as φ, and
C′n is a methylene chain in which the number of carbon atoms in the straight chain portion is 6 or more. The characteristics of the stable structure in the low concentration range, which is characteristic of the present invention, will be described below. That is, the layered structure of the present invention differs from the unstable layered structure that is formed only in a concentrated state by a general surfactant, and the layered structure of the present invention can be formed in a concentration region (10 ^{- 2} ~ ^10-7M )
It forms and maintains a stable layered structure, a superimposed structure of these, or an endoplasmic reticulum disk-like structure, a string-like structure, etc. made of these, and furthermore, these are stable even in a concentrated state or even in a dry state. The layered structure of the present invention, which retains its structure and morphology, is different from single micelles formed by general surfactants with a CMC or higher, and is composed of a strong structure in which the constituent compounds are highly constrained. Furthermore, most of these layered structures constitute double-layer films or multilayer films having double-layer films as basic constituent units. The multilayer membrane structure and endoplasmic reticulum of the present invention may be in the form of a membrane, a multilayer structure, or a closed endoplasmic reticulum, depending on manufacturing conditions such as concentration, temperature, dissolution method, additives, and ionic strength of the system. It can exist. In its initial state of manufacture, it is generally a membranous or multilayered structure, but over time it changes to the form of an endoplasmic reticulum. When actively producing endoplasmic reticulum, it can be easily obtained by reducing the concentration of the compound of the present invention, increasing the temperature if necessary, and increasing stirring. Furthermore, a double layer or multilayer structure film can be obtained by coating a film-like material or multilayer structure on a support and drying it. Naturally, the characteristics of these layered structures have various effects on selective permeation and retention of substances, acceleration and deceleration of chemical reactions. Although it can be confirmed from various viewpoints that the structure of the present invention is stable and forms a strong layered structure or even a double layer film, it is known from a report already published by the present inventors. The most common method is direct observation using an electron microscope. (for example
T.Kunitake and Y.Okahata J.Am.Chem.Soc
99, 3860 (1977)) In other words, electron microscopy, which is the most direct morphological observation method, confirmed the existence of a layered structure with an interlayer spacing of 20 to 200 Å and a secondary structure of several hundred Å.
Moreover, these structures are stable even in solution and form strong structures with a high degree of constraint.
It is also confirmed by the broadening of the NMR spectrum absorption peak. The characteristics of these structures are based on the stability of the layered structure, and are utilized for various trapping actions, selective permeation of substances inside and outside the endoplasmic reticulum composed of the layered structure, or through the layered structure itself. The range of industrial utility value is extremely wide due to its application to reactions, substance separation, information recording, substance stabilization, substance absorption-release control, etc. And Chemical Abstracts Vol. 8 No. 26
Liposomes made of lecithin containing actinomycin D and having a double-layer membrane structure as described in 1975 are naturally occurring and are difficult to obtain in a pure form. Since suitable products can be designed using inexpensive raw materials and manufactured in large quantities, the range of applications is wide. The method for forming the structure of the present invention generally involves dissolving one or more surfactants having a rigid portion in a mixed system of an aqueous solvent or various solvents as well as organic compounds necessary for the application. , if necessary, use physical means such as ultrasound irradiation,
Layered structures, double layer structures, multilayer structures, endoplasmic reticulum, and string-like structures can be obtained, but depending on the case, up to 50% by weight of a commonly known surfactant may be added to the surfactant according to the present invention. It is also possible to obtain a structure by mixing. Specifically, for example, since the basic structural unit is a double-layer membrane that is stable at low concentrations, lipophilic substances that are dissolved in water in trace amounts are incorporated into the structure and removed from the system, and in some cases, It can be recovered. Examples 1 to 6 In this example, the compound expressed by formula (3), which synthesized a diphenylazomethine-based surfactant, was expressed by the abbreviation in formula (4), and the results are summarized in Table 1. C _o -BB-C _n -N ⁺ 3C ₁ ...(4) Compound (3) is an equimolar mixture of the corresponding p-alkylaniline and p(ω-trimethylammoniumalkyleneoxy)benzaldehyde bromide synthesized by the following method. After refluxing in ethanol for 0.5 to 1 hour in the presence of a small amount of acetic acid, the precipitate was recrystallized from ethanol 2 to 4 times. (Yield 50-80%) Production of p(ω-trimethylammonium butoxy)benzaldehyde bromide Dissolve 2.3 g of sodium metal in 200 ml of absolute ethanol, add 64.8 g of 1,4-dibromobutane and 12.4 g of p-hydroxybenzaldehyde at the same time,
The mixture was heated to reflux for an hour. After the reaction, the mixture was poured into ice water, and the precipitated oil was extracted with chloroform and then rectified. bp.145-147℃/0.01mmHg Yield 15g (58%)
15 g of p(ω-bromobutyloxy)benzaldehyde obtained here was dissolved in 80 ml of ethanol and reacted with 106 g of an aqueous trimethylamine solution (30%) in an ampoule at 100° C. for 38 hours. After the reaction, the solvent was distilled off and the precipitated solid was recrystallized from ethanol.
mp.201℃, yield 16g (86%) NMR spectrum ( _d6 in DMSO); δ3.1ppm (s) 9H, N ⁺ -
CH ₃ ; δ7.2(d), 7.9(d)4H, phenyl; δ10.0
(s) 1H, aldehyde. Other compounds were also produced in the same manner. Depending on the molecular weight of compound (3), add 180 to 260 mg to distilled water.
Suspend in 40 ml and disperse using an internal irradiation ultrasound generator (Branson Sonifier 185).
After 5-15 minutes a homogeneous 10mM aqueous solution is obtained. Mix 1 ml of this solution with 1 ml of 2% launyl acetate aqueous solution, stir with ultrasonic waves for about 20 seconds, cool in an ice bath for 30 minutes, place on a carbon membrane, dry under reduced pressure in a desiccator, and then use a Hitachi electron microscope H -500, an accelerating voltage of 75 to 100 kV, and a magnification of 50,000 to 300,000. Examples 7 to 12 In this example, the results of various conversions of X' in formula (5) for synthesizing a diphenyl surfactant were obtained by a method based on Example 1. Table 2 Compound (5) was produced according to the following formula. Add 55.8 g of 4,4'-dihydroxyphenyl and 24.9 g of dodecyl bromide to 4 g of sodium hydroxide in ethanol.
The mixture was heated under reflux with 300 ml for 5 hours. After the reaction, white crystals were precipitated when the mixture was cooled to room temperature. Recrystallized from ethyl acetate mp.110-135℃ Yield 22g (62%) 17.7 g of (6) and 32.4 g of 1,4-dibromobutane were heated under reflux for 6 hours together with 2 g of sodium hydroxide and 200 ml of ethanol. After the reaction, distilled water was added and the precipitated white solid was recrystallized from ethyl acetate. mp.95
~97℃ Yield 20g (82%) NMR spectrum ( _CDCl3 ); δ=0.9(s)
3H, −CH ₃ ; δ=1.3(s) 24H, −CH ₂ −; δ=
3.5 (m) 2H, Br-CH ₂ −; δ = 4.0 (m) 4H, −
O-CH ₂ ; δ = 6.9-7.5 (m) 8H aromatic H, In Example 7, (7) and trimethylamine were heated in a glass ampoule in ethanol at 100°C for 48 hours, and the resulting mixture was mixed with ethyl acetate and benzene-ethanol. Both were recrystallized. Yield: 63% NMR was consistent with the target structure. In Example 8, (7) and N-methylglucan were heated and refluxed together with sodium carbonate in ethanol for 50 hours.
The reaction product recrystallized from ethanol (yield 89%) was further reacted with methyl bromide in an ampoule at 100°C for 80 hours, and the desired product was obtained by recrystallization from ethanol. In Example 9, (7) and N.N-dimethylhydrazine were heated under reflux for 16 hours in an equal volume mixture of ethanol and benzene. Reactant (recrystallization yield from ethanol
80%) with acetyl chloride in benzene under reflux for 2 hours, and after distilling off the solvent, the residue was suspended in water and adjusted to pH 10-11 with a 10% aqueous sodium hydroxide solution, and the reaction was continued for 2 hours with stirring. and extract the reaction system with chloroform. After chloroform was distilled off, the white solid was recrystallized from ethanol to obtain the desired product. Yield: 67% In Examples 10 and 11, 4.0 g and 8.0 g of ethylene oxide were added to 2.8 g of (6), respectively, and the reaction was carried out in an autoclave at 120-160° in the presence of sodium hydroxide (2.5 hours). After purifying the product, we confirmed that it was a single product by Yatron synchrography, and calculated the added ethylene oxide unit by elemental analysis and NMR, and found agreement between the values of both methods. In Example 12, (6) and phosphorus oxytrichloride were heated under reflux in benzene for 3 hours to obtain an ethanol recrystallized product. Yield: 48% Examples 13-14 Electron micrographs of double-ended compounds having the following structures are shown in the drawings. Both form distinct structures. Example 13 Figure 14 Example 14 Figure 15 Example 15 Cholesterol-(α-triethylammonium) acetate bromide (melting point 110-113°C) was dispersed with an equal amount of cetyltrimethylammonium bromide, and electron microscopic observation of the resulting structure showed that it formed lamellae. .

【table】

[Table] Example 13 p-(ω-hydroxyhexyloxy)acetanilide (24 mmol) was dissolved in a 1:1 water-acetone solution (100 ml), concentrated HCl (10 ml) was added thereto, and NaNO ₂ (30 mmol) was added to this solution. ) was added with stirring in an ice-water bath.
Phenol (37m
mol), NaOH (35 mmol), NaCO ₃ , (57 mmol)
An aqueous solution (100 ml) containing was added, and the mixture was stirred at room temperature for 12 hours. This was neutralized with acetic acid, reprecipitated, and p-
(ω-Hydroxyhexyloxy)-p'-hydroxyazobenzene (mp 139-149°C, yellow powder) was obtained in a yield of 66%. This compound (95 mmol) and 1,4-dibromobutane (37 mmol) were refluxed and reacted in ethanol containing KOH (15 mmol), (mp106-114°C, yellow powder) was obtained in a yield of 23%. 4.5 mmol of this compound was reacted with propionyl chloride (6.5 mmol) in benzene in the presence of triethanolamine, (mp85-88°C) was obtained in 68% yield. This was placed in an ampoule and reacted with trimethylamine in an ethanol solution. (mp197-219°C, yellow plate shape) was obtained in a yield of 54%. Elemental analysis position (theoretical value) C 58.87 (58.63), H 7.45 (7.55), N 7.23 (7.33) The structure of this surfactant in water is as shown in Example 1.
It was an endoplasmic reticulum like ~6. Example 14 Coupling phenol to p-(dodecyloxy)aniline, I got it. Furthermore, 1,4-dibromobutane is reacted, (mp96−110°C) was obtained. This compound (2.7 mmol) was stirred in acetic acid (100 ml) containing 30% hydrogen peroxide (7.1 mmol) and
React for 48 hours at °C. (mp70-120°C, bluish yellow powder) was obtained in a yield of 50%. This was reacted with triethylamine in ethanol, (mp220-240℃, bluish yellow needle crystals)
was obtained in a yield of 51%. Elemental analysis value (theoretical value) C 61.68 (61.88) H 8.49 (8.54) N 6.80 (6.98) The structure of this surfactant in water is as shown in Example 1.
It was an endoplasmic reticulum like ~6. Example 15 is an intermediate product of Example 14 is reacted with trimethylamine in alcohol, I got it. Example 16 p-aniline-sulfonic acid (50 mmol) and
Dissolve NaOH (50 mmol) in 80 ml of water and add with acetic acid.
Adjust the pH to 4 and stir in an ice water bath.
Add 20 ml of aqueous solution containing NaNO ₂ (52 mmol),
A diazonium salt was obtained. Ethanol (150 ml) containing N-methyl-dodecylaniline (50 mmol) was added to this solution in an ice-water bath, and the mixture was further stirred at room temperature for 1 hour, and the pH was adjusted to 10 with an alkali. Recrystallize twice with ethanol, (mp300℃ or higher, orange color) was obtained in a yield of 56%. Elemental analysis values (theoretical values) C 62.82 (62.37), H 7.61 (7.48), N 8.62 (8.78) The structure of this surfactant in water is as shown in Example 1.
It was an endoplasmic reticulum like ~6. Example 17 20 ml of ethanol containing BaBH ₄ (10 mmol) was gradually added to ethanol containing p′-(ω-narimethylaminobutyl)-p-dodecylbenzylidene)aniline (9.8 mmol) with stirring, and
Reflux for an hour and acidify with hydrobromic acid. Remove the solvent, reprecipitate, (mp185−187℃, bluish yellow powder) yield
Got it at 85%. Elemental analysis values (theoretical values) C 50.00 (49.74), H 7.03 (7.03), N 3.64 (3.52) The structure of this surfactant in water was tube-shaped.

[Brief explanation of the drawing]

Figure 1 shows the NMR absorption spectra of the surfactants in Example 1, Example 2, and Reference Example 1;
Figures 1 to 15 are electron micrographs of surfactants in Examples 1 to 14.

Claims (1)

[Scope of Claims] 1. A double layer or a polycarbonate having a double layer as a basic skeleton composed of a surfactant represented by any of the following general formulas (1), (1'), (2), and (2'). Multilayer membrane. Cn−Ya−φ−Yb−X ……(1) Cn−Ya−φ−Yb−Cm−X ……(1′) [(i) Ya, Yb, Y′a, Y′b are −CH ₂ −, −CO−, −
Represents a bonding group selected from O-, -NH-, -S-, and _-SO2- . (ii) φ and φ′ represent two aromatic rings connected via a direct bond or a carbon-carbon multiple bond, a carbon-nitrogen multiple bond, a nitrogen-nitrogen multiple bond, an ester bond, an amide bond, and 4.4 has a bonding position of '. (iii) Cm and C'm represent a methylene chain of 1 to 12 carbon atoms. (iv) X and X' represent ammonium salts, phosphates or polyethers. (v) Cn represents an alkyl group having 6 or more carbon atoms in the straight chain portion. (vi) C′n represents a methylene chain in which the number of carbon atoms in the straight chain portion is 6 or more. ] 2 A double layer composed of a surfactant represented by any of the following general formulas (1), (1'), (2), or (2'), or a multilayer structure film with a double layer as its basic skeleton. Endoplasmic reticulum. Cn−Ya−φ−Yb−X ……(1) Cn−Ya−φ−Yb−Cm−X ……(1′) [(i) Ya, Yb, Y′a, Y′b are −CH ₂ −, −CO−, −
Represents a bonding group selected from O-, -NH-, -S-, and _-SO2- . (ii) φ and φ′ represent two aromatic rings connected via a direct bond or a carbon-carbon multiple bond, a carbon-nitrogen multiple bond, a nitrogen-nitrogen multiple bond, an ester bond, an amide bond, and 4.4 ' is the bonding position of the position. (iii) Cm and C'm represent a methylene chain having 1 to 12 carbon atoms. (iv) X and X' represent ammonium salts, phosphates or polyethers. (v) Cn represents an alkyl group having 6 or more carbon atoms in the straight chain portion. (vi) C′n represents a methylene chain in which the number of carbon atoms in the straight chain portion is 6 or more. ]