JPS648634B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to novel phosphorus derivatives. More specifically, the present invention provides the formula represented by the formula, R ₁ is lower alkylene or hydroxy lower alkylene, R ₂ and R ₃ are lower alkyl, and A is straight chain or branched C ₁₂ - ₂₂ alkyl or the formula -R ₄ -NHCO -A compound represented by _R5 , in which _R4 is lower alkylene _{, R5} is _C12-22 alkyl, and X is halogen. Regarding. The novel compounds of the present invention can be prepared by several methods, including the following methods: Method A: Reaction of a hydroxyl group-containing quaternary ammonium compound with phosphorus oxychloride General formula NR ₂ R ₃ -A ( R ₂ , R ₃ , A are as above)
A tertiary amine represented by X--R ₁ --OH (R ₁ ,
(as described above) is quaternized using an appropriate solvent, reaction apparatus, and reaction conditions. More specifically, the quaternization reaction is carried out in a glass or glass-lined reactor equipped with a heater, an overhead stirrer, a thermometer and a reflux condenser to ensure good mixing and temperature control. It is carried out using solvents such as lower alcohols, water or mixtures thereof. The reaction temperature can range from about 70°C to 120°C, but is generally governed by the reflux temperature of the reaction mixture. The progress of the reaction is monitored by argentometric determination of the halogen ions formed during the quaternization. Diagrammatically, this reaction can be shown as follows: To isolate the quaternary ammonium compound, a portion of the solvent is distilled and the reaction mixture is
Add acetone while maintaining at °C. On cooling, a crystalline precipitate forms which is filtered off with suction and isolated by vacuum drying. The second step of this reaction can be shown diagrammatically as follows: The reaction of a hydroxyl-containing quaternary ammonium compound with phosphorus oxychloride generally involves dispersing the quaternary ammonium compound in a low boiling point, low polar solvent, such as methylene chloride, and adding the required phosphorus oxychloride, generally at room temperature. Implemented by. Once all the phosphorous oxychloride has been added, the temperature is raised to the boiling point of the reaction mixture and the mixture is refluxed for up to 18 hours. The solvent is recovered by distillation and the phosphoric triester is purified by recrystallization from hot acetone. Other methods found to be effective are as follows: Method B: Reaction of tertiary amine with halogenated phosphate ester The initial step, i.e. the phosphate ester intermediate, is schematically shown as follows: It can be shown that: where X is a halogen functional group and Y is 12
an alkylene group of up to carbon atoms, which alkylene group may be interrupted by up to 3 oxygen atoms and may be substituted with lower alkyl, alkoxy, hydroxy or hydroxyalkyl groups of up to 10 carbon atoms . The subsequent step, namely the reaction of the phosphate ester with the tertiary amine, can be illustrated schematically as follows: Generally, the reaction is carried out in a glass reactor equipped with an overhead stirrer, addition funnel, reflux condenser and external heating and cooling units. 3-part substituted oxirane,

[Formula] is placed in a reactor, and while stirring vigorously, 1 part of concentrated phosphoric acid is added dropwise. The rate of addition of phosphoric acid is adjusted to maintain the reaction temperature between 65 and 95°C, preferably between 85 and 90°C. A halogen-containing epibiphosphate intermediate is produced. Three parts of the appropriate tertiary amine are added in portions while maintaining the reaction temperature between 90-100°C. After complete addition of amine, reduce the reaction mixture to 100-120
Heat to 0.degree. C. until argentometric titration of an aliquot indicates completion of the reaction. After cooling, the reaction mixture is dissolved in hot methanol/acetone. The desired product is obtained by isolating and drying the precipitate formed by cooling the methanol/acetone solution. The novel phosphotriester compound of the present invention is
It is a cationic surfactant and can be easily sorbed onto hair or other negatively charged surfaces to reduce electrostatic interactions. R ₄ , R ₅ or R ₆ is 16
When hair has more carbon skeletons than carbon atoms, when such compounds are applied to hair, it causes the hair to “flow in the wind”.
is reduced and the combing in wet and dry conditions is very good. Generally, cationic quaternary ammonium salts are not readily compatible with a wide range of other surfactants. Surprisingly, the novel compounds of the present invention are compatible with a wide range of surfactants, such as anionic surfactants of the sodium lauryl sulfate type or sodium lauryl ether sulfate type; such as betaines, salteines and phosphobetaines. Amphoteric surfactants; readily compatible with nonionic surfactants such as ethoxylated sorbitan esters. Because of this unexpected compatibility, the compounds of the present invention can be easily incorporated into common shampoo and cream rinse formulations. The compounds of this invention can be used in amounts of about 0.1 to about 20% by weight, depending on the composition in which they are utilized. If more than 20% by weight is used, the resulting composition may have a poor texture and be irritating when used as a shampoo or cream rinse. Furthermore, in the formula (10 negative) of the novel phosphoric acid triester compound of the present invention, when A or R ₅ which is a constituent part of A has a carbon chain length of 8 to 14 carbon atoms,
These compounds exhibit significant bacteriostatic and bactericidal properties. Compounds having these properties can be used at about 0.1% to about 5.0% by weight of the total composition. If amounts less than about 0.1% are used, the desired properties may be obtained, and if amounts greater than about 5.0% are used, the resulting compositions may be harsh to the touch and may be irritating. The following examples illustrate the invention. Example 500ml with overhead stirrer, water-cooled condenser, dropping funnel, thermometer and heating mantle
46.53 g of epichlorohydrin is placed in a glass reactor. 19.0 g of 85.5% phosphoric acid is then added via the addition funnel with vigorous stirring, adjusting the addition rate to maintain the temperature between 80-85°C. When the exothermic reaction ceases, the reactor is heated and the reaction mixture is maintained at 80°C for 1 hour. then
Add 148 g of octadecyldimethylamine to the reactor and stir the mixture for 20 hours at 102°C. Completion of the reaction is confirmed by argentometric titration of the chlorine ions generated. After cooling to approximately 40 °C, the reaction mixture was diluted with 200 ml of ethanol and transferred to a 2 volume beaker.
Add 1000ml of acetone. A yellow and colored precipitate forms, which is isolated by suction filtration and recrystallized from an ethanol/acetone mixture to give a yellow and colored powder. Silver titration for chloride ions and saponification assays show this material to be 98.6% pure. This product contains a novel phosphotriester of the following structural formula: Examples Using the glass reactor described in Examples,
93.52 g of epichlorohydrin is reacted with 38 g of 85.5% phosphoric acid at 85-90° C. for 2 hours. 213.2 g of dodecyldimethylamine are then added over a period of 3 hours, maintaining the temperature at 85-90°C.
Heating for a further 72 hours at 100±5° C. gives an argentometric titration value for chloride ions indicating greater than 90% completion of the reaction. The reaction product is isolated according to the procedure of the example, resulting in a pale yellow, colored, free-flowing powder that is assayed to be 99.0% pure. This product contains a triester of phosphoric acid with the following structure: EXAMPLE Using the apparatus described in the example, 19.0 g of concentrated phosphoric acid is added dropwise to 46.53 g of epichlorohydrin while maintaining the reaction temperature at 85-90°C. 176.5 g of a molten 50/50 mixture of eicosyldimethylamine and docosyldimethylamine was added to the temperature
Add over 2 hours while keeping at 100℃. 100℃
After another 12 hours at
The temperature rises to 140℃. After cooling, the desired product is isolated by crystallization from hot ethanol, filtering off with suction and drying. According to argentometric titration, the activity is 94.6%. The structure is identical to that of the example except that the C ₁₂ H ₂₅ substituent is replaced with a mixed group of C ₂₀ H ₄₁ and C ₂₂ H ₄₅ in a 1:1 ratio. EXAMPLE Using two glass reactors equipped with an overhead stirrer and a reflux condenser, 140.28 g of epichlorohydrin is reacted with 57 g of 85.5% phosphoric acid and the reaction is stirred for 2 hours at 85-90°C. To this reaction product, 548.6 g of 3-oleamidopropyl dimethylamine was added and the temperature was increased to 95-95.
The temperature rises to 100℃. After 22 hours, argentometric titration shows that the reaction is nearing completion and the reaction mixture is cooled. After crystallization from ethanol/acetone, suction filtration and drying, a gray powder is obtained. This product contains a novel phosphotriester of the following structure: Example Using the reactor and reaction conditions described in the example,
112.2 g of epichlorohydrin is reacted with 45.6 g of 85.5% phosphoric acid. Then, 458.4 g of stearamide ethyl diethylamine is added to the reaction mixture and the reaction mixture is maintained at 95° C. for 20 hours. Completion of the reaction is estimated by argentometric titration and the reaction product contains a novel phosphotriester of the following structure: Example 297 g of octadecyldimethylamine and 80 g of ethylene chlorohydrin are dissolved in absolute ethanol to a total volume of 1500 ml. The mixture is then heated in a 2 volume round bottom flask equipped with a reflux condenser. After 6 days, titration of chloride ions shows that the reaction is 91% complete and the reaction is stopped. The desired stearyldimethyl-2-hydroxyethylammonium chloride is isolated by precipitation with acetone. After recrystallization from an ethanol/acetone mixture, filtration and drying under vacuum, a white powder is obtained which, when titrated for chloride ions, is determined to be 98.9% pure. 228.7 g of this steryl dimethyl-2-hydroxyethylammonium chloride is then placed in a 2 volume three-neck round bottom flask equipped with an overhead stirrer, addition funnel, and reflux condenser.
Add 1200 ml of methylene chloride and disperse the quaternary ammonium compound with vigorous stirring. 30.70
g of phosphorus oxychloride, POCl ₃ , are added dropwise over 1 hour. The reaction mixture is then refluxed for 18 hours, the methylene chloride is removed by distillation and the triester is purified by recrystallization from hot acetone. This product contains a novel phosphotriester of the following structure: Example 213.14 g of dodecyldimethylamine are dissolved in 1200 ml of absolute ethanol, 80 g of ethylene chlorohydrin are added and the resulting reaction mixture is stirred for 72 hours. Dodecyldimethyl-2-hydroxyethylammonium chloride is obtained in a yield of 84% after precipitation with acetone, recrystallization with ethanol/acetone, filtration and drying in vacuo. 175.9
g of dodecyldimethyl-2-hydroxyethylammonium chloride is reacted with 30.70 g of phosphorus oxychloride using the equipment and reaction conditions described in the Examples. This product contains a novel phosphotriester of the following structure: Example 305.6 g of stearamide ethyl diethylamine are dissolved in 2000 ml of absolute ethanol. then 64
g of ethylene chlorohydrin are added and the reaction mixture is refluxed for 120 hours. Approximately three quarters of the ethanol is then removed by flash evaporation, acetone is added at the boiling point to saturation and the reaction mixture is cooled to room temperature. The white precipitate that forms is isolated, dried in vacuo, and identified as stearamide ethyl diethyl-2-hydroxyethylammonium chloride. 277.2g of this stearamide ethyl diethyl
2-hydroxyethylammonium chloride
React with 30.7 g of phosphorus oxychloride using the equipment and reaction conditions described in the Examples. This product contains a novel phosphotriester with the following structure: EXAMPLE A hair care product is prepared as follows: Structure: 150 parts by weight of a 30% active solution of phosphobetaine, where R is a C ₁₁ -C ₁₃ mixed group in a ratio of 1:1,
Add 200 parts of distilled water at ambient temperature followed by 77 parts by weight of a 26% active solution of the cationic triphosphate ester of the example and mix the resulting solution until clear and homogeneous. It is then prepared by the method described in U.S. Pat. No. 2,970,160 and has the following formula: 150 parts by weight of a 30% active solution of an amphoteric substance of the formula are added, where R is a C ₁₁ -C ₁₃ mixed group in a ratio of 1:1. Then 200 parts of 72% polyoxyethylene (80) sorbitan monococoate are added, followed by 12 g of polyethylene glycol 6000 distearate and the resulting mixture is stirred at 70° C. for 20 minutes. The solution is cooled to 35°C and the pH is adjusted to 7.0±1 with 15% HCl solution. Add preservatives and fragrances
Add enough deionized water to bring the total to 1000 g. The final product is transparent and tested at 12 rpm using a #2 spindle on a Bruckfield viscometer at 25°C.
The viscosity measured at is 1225 cps. This product exhibits excellent foaming and cleaning properties,
Beauty Salon's half head
head) Shows conditioning effects on hair as confirmed by research. These studies involved separating each subject's hair into two sections, treating one section with a shampoo composition containing the novel compound of the invention, and treating the other section with the same composition without the novel compound. and grade the results subjectively according to the same guidelines. EXAMPLES The following detergent hair or skin cleansers are prepared according to the procedure outlined in the examples: Ingredients W/W % Cocoamidopropyl sultamine 5.00 Tridecyl ether(4) sulfate 5.00 Tris-stearylaminophosphate Ester 0.30 Propylene Glycol 1.00 Thickener 2.00 Preservative 0.10 Dye 0.02 Fragrance 0.20 Add deionized water to 100% Above pH was adjusted to 5.5 with dilute HCl. Examples Whitening agent 0.5 Fragrance 0.3 Deionized water was added to 100%.The pH above was adjusted to 7.0±1 with 15% HCl. The composition of Example XI is tested for cleaning power with two commercially available compositions using the following procedure: Test Fabrics.
The relative cleaning ability of certain compositions is evaluated using standard soiled woolen fabric foils obtained from Jnc. Terg-O-
Tometer) Model 7243 is used to simulate the cleaning action. The controlled conditions are as follows: 1 Washing time (5 minutes) 2 Washing speed (100 rpm) 3 Washing time (5 minutes) 4 Washing speed (100 rpm) 5 Washing and washing temperature (105〓, 40.6°C) Test The cloth is made from wool shari weave and rolled into 10 yard (9.14 m) rolls. A stain mixture consisting primarily of soot, oil and industrial solvents is applied to the fabric with a print roll so that only half of the 8 inch wide fabric is stained. This test cloth is 4 x 8 inches (10.16 x 20.32 cm)
Cut into strips so that half of each strip is soiled and half is clean. A Gardner colorimeter is used to obtain initial color values (whiteness) for both the soiled and clean portions of each strip. Three of these strips, along with three 4 x 8 inch (10.16 x 20.32 cm) cotton filler strips, were placed in a Targu Autometer beaker containing 1000 ml of a 10% aqueous solution of the test composition. Put it in. Before this, add the solution to 105%
Stir at (40.6℃) for 2 minutes to equilibrate. Stir the sample for 5 minutes, remove, squeeze, and
〓Return to stirred beaker containing 1000ml of tap water at (40.6℃). After stirring for 5 minutes, remove the strips, squeeze, and lay flat to dry. When dry, they are evaluated again with a colorimeter to determine the extent to which the stain has been removed as well as the extent to which the stain has adhered to the unsoiled areas of the fabric.
The relative cleaning effect is indicated by the spread between the initial and final whiteness measurements, characterized as 4R. We consider 2 units of 4R to be significant. The commercial composition was compared with the composition of Example XI and the following results were obtained: △R Commercial Composition 5.7 Commercial Composition 8.0 Composition of Example XI 8.4 Example -on) Prepare cream rinse: W/W % Phosphate triester of example 1.10 Ethyl dihydroxypropyl para-aminobenzoic acid 0.55 Benzyl alcohol 0.55 Stearyl alcohol 0.88 Isostearyl alcohol 0.33 Fragrance 0.11 Hydroxyethyl cellulose 0.83 Sodium hydroxide 0.21 100% with deionized water This composition exhibits excellent wet carding and conditioning properties. EXAMPLES To demonstrate the antimicrobial properties of the novel compounds of the present invention, the following standard minimum inhibitory concentration test was conducted to determine the minimum effective concentration that inhibits the growth of various test organisms. First, add 200 mg of each compound of Examples and 2.0 mg/kg to 100 ml of distilled water.
ml, then make 10 series of 2-fold dilutions.
Make a final concentration of 0.0038 mg/ml. thus,
Prepare a concentration range of 0.0038 mg/ml to 2.00 mg/ml. Separately, 1000 ml of standard antibiotic medium #3 was inoculated with 1 ml of a 24-hour broth culture of each test organism, and the resulting solution was divided into 2 ml portions 13 mm x
Place in a 100 mm test tube at 4°C. Prepare two test tubes for each test organism. 0.4 ml of each concentration of test compound is then placed in each test tube and they are then placed shaking at 35° C. for 18 hours. The end point of activity is determined by streaking using a graduated loop on trypticase soy agar to determine the last tube (concentration) to grow, and then the next maximum concentration to the minimum inhibition. Considered as concentration. The results are shown in the table below:

TABLE These results demonstrate that the novel compounds of the present invention exhibit bactericidal and bactericidal properties at relatively low concentrations when compared to reference bacteriostatic and/or bactericidal agents, such as cetylpyridinium chloride, and It is revealed that it is an excellent antimicrobial agent. Although the invention has been described and illustrated with respect to certain preferred embodiments, various modifications, changes, omissions and substitutions may be made by those skilled in the art without departing from the spirit of the invention. Accordingly, the invention is limited only by the scope of the claims.

Claims (1)

[Claims] 1 formula represented by the formula, R ₁ is lower alkylene or hydroxy lower alkylene, R ₂ and R ₃ are lower alkyl, and A is straight chain or branched C ₁₂ - ₂₂ alkyl or the formula -R ₄ -NHCO -A compound represented by _R5 , in which _R4 is lower alkylene _{, R5} is _C12-22 alkyl, and X is halogen. 2. A compound according to claim 1, wherein X is Cl or Br. 3. A compound according to claim 1, which has the formula compound. 4. A compound according to claim 1, which has the formula compound. 5. A compound according to claim 1, which has the formula A compound of the formula wherein Ra is a mixed group of _C20H41 and _C22H45 in _a ratio _of 1:1. 6. A compound according to claim 1, which has the formula compound. 7. A compound according to claim 1, which has the formula compound. 8. A compound according to claim 1, which has the formula compound. 9 A compound according to claim 1, which has the formula compound. 10 A compound according to claim 1, which has the formula compound. 11 formula represented by the formula, R ₁ is lower alkylene or hydroxy lower alkylene, R ₂ and R ₃ are lower alkyl, and A is straight chain or branched C ₁₂ - ₂₂ alkyl or the formula -R ₄ -NHCO - A method for producing a compound represented by R ₅ , in which R ₄ is lower alkylene, R ₅ is C ₁₂ - ₂₂ alkyl, and X is halogen, the compound having the general formula NR ₂ A tertiary amine represented by R ₃ —A (R ₂ , R ₃ , A are as above) is replaced by X—R ₁ —OH
(X, R ₁ are as above) to produce a hydroxyl group-containing quaternary ammonium compound, and b react this hydroxyl group-containing quaternary ammonium compound with phosphorus oxyhalide. A method consisting of letting. 12 formula In the formula, R ₁ is [Formula], R ₂ and R ₃ are lower alkyl, and A is a straight chain or branched C ₁₂ - ₂₂ alkyl or the formula -R ₄ -NHCO-R ₅ A method for producing a compound represented _by the general _formula [ _{Formula ]} (X As described above, an epihalohydroline represented by Y (lower alikylene) is reacted with phosphoric acid to produce a halogen-containing epihalohydrin phosphate intermediate, and b this halogen-containing epihalohydrin phosphate intermediate has the general formula NR ₂ R ₃ -A (R ₂ , R ₃ , A
is as described above).