JP2566828B2 - Novel quaternary ammonium salt, method for producing the same, and fungicide containing the same - Google Patents

Description

The present invention relates to a novel quaternary ammonium salt, more specifically 3-[(cyanoethyl) (1-oxoalkyl) useful as a mild bactericide. The present invention relates to an amino] -N, N, N-trialkyl-1-propanaminium salt, a method for producing the same, and a fungicide containing the same.

[Prior Art and its Problems] Conventionally, a quaternary ammonium salt has been widely used as a bactericide having surface activity in various industrial fields such as medicine and household products.

However, a quaternary ammonium salt having only an alkyl group and an arylalkyl group as an N-substituent is known to have strong skin irritation, and has a drawback that biodegradability is poor. There is. Furthermore, in recent years, resistant bacteria to such quaternary ammonium salts have begun to appear, which has become a serious problem.

[Means for solving the problem]

Under such circumstances, as a result of intensive studies conducted by the present inventors, the novel quaternary ammonium salt represented by the following general formula (I) exhibits excellent bactericidal activity and does not exhibit skin irritation. Further, it has been found that it can be produced in high purity and high yield by an easy operation from an easily obtainable intermediate while giving good foaming power with good degradability.
The present invention has been completed.

 That is, the present invention provides the following general formula (I)(Where R¹Is an alkyl group or alkenyl having 1 to 21 carbon atoms
Represents a group, R²And R³Are the same or different and have 1 to 6 carbon atoms
Represents an alkyl group, R^FourIs an alkyl group having 1 to 22 carbon atoms or
Represents an arylalkyl group, X Represents an anion] 3-[(cyanoethyl) (1-oxoal
Kill) amino] -N, N, N-trialkyl-1-propana
Minium salt, method for producing the same, and sterilization containing the same
The agent is provided.

 In the compound (I) of the present inventionAs the group, an acetyl group, a propionyl group, a butyryl group,
Isobutyryl group, valeryl group, isovaleryl group, hexa
Noyl group, octanoyl group, decanoyl group, lauroyl
Group, myristoyl group, palmitoyl group, stearoyl group
Group, arachidinoyl group, behenoyl group, oleoyl group,
Linoleoyl group, Isostearoyl group, 2-Ethyl-
Xanoyl group, 2-octyl-decanoyl group, neodeca
Examples thereof include a noyl group. R²And R³As methyl
Group, ethyl group, propyl group, isopropyl group, butyl
Group, isobutyl group, pentyl group, hexyl group, etc.
Can be R^FourAs a methyl group, an ethyl group, a propyl group,
Isopropyl group, butyl group, isobutyl group, pentyl
Group, neopentyl group, hexyl group, cyclohexyl group,
Benzyl group, octyl group, decyl group, dodecyl group, tet
Radecyl group, hexadecyl group, octadecyl group, eico
Examples thereof include a syl group and a docosyl group. Furthermore, X age
Fluorine ion, chlorine ion, bromine ion, iodine ion
Halogen ions such as on, sulfonate ions, and sulfate ions
ON, carboxylate ion, phosphate ion, nitrate ion
Which can be mentioned.

The compound (I) of the present invention comprises 3- [N-acyl-N- (dialkylaminopropyl) amino] propionitrile (II) and an alkyl halide in water, methanol, ethanol, isopropanol, etc., according to the reaction formula shown below. The compound (II) can be easily produced by quaternizing the compound (II) by heating in the solvent in the presence of a deoxidizer in the presence of a deoxidizing agent.

(Where R¹, R², R³, R^FourAnd X Has the same meaning as above
The alkyl halide used in this reaction includes
Tyl chloride, ethyl chloride, propyl chloride
De, isopropyl chloride, butyl chloride, iso
Butyl chloride, pentyl chloride, neopentyl
Chloride, hexyl chloride, cyclohexyl chloride
Ride, benzyl chloride, substituted benzyl chloride
, Methyl bromide, methyl iodide, ethyl
Romide, ethyl iodide, octyl chloride,
Decyl bromide, dodecyl bromide, tetradecyl
Bromide, hexadecyl bromide, octadecyl
Romide, eicosyl bromide, docosyl bromide
And the like. The amount of alkyl halide used is
0.8 to 5 mol, and further 0.9 to 2 mol per 1 mol of the compound (II).
And especially 1 to 1.1 mol.

Examples of the deoxidizing agent include sodium carbonate and the like, and the amount thereof is 1 to 5 mol% of the compound (II), especially 2
~ 41 mol% is preferred.

The reaction temperature in the reaction of the present invention is 20 to 150 ° C, and further 40 to 1
30 ℃, especially 60 ~ 110 ℃ is preferable, the reaction time is (I
Although it depends on the reactivity of I), the reaction is usually completed in 4 to 48 hours.

After completion of the reaction, the mixture is cooled, then the insoluble matter is filtered off, the solvent is removed, and the product is purified by recrystallization or column chromatography to obtain the compound (I) of the present invention.

Further, in the present invention, ion exchange may be carried out if necessary, and in this case, after completion of the reaction, cooling is carried out, and then an insoluble matter is filtered off and the obtained filtrate is filled with an ion exchange resin such as an anion exchange resin. Pass it through the column.

The thus-obtained compound (I) of the present invention is extremely hypoallergenic and exhibits excellent bactericidal activity against various bacteria. Therefore, it can be used as a bactericide in various industrial fields, medical applications, household applications, etc. It can be used for various purposes. For example, the compound (I) of the present invention is soluble in water, alcohols and the like, and also has a surface-active ability, so that it can be used in the form of a liquid preparation. In this case, additives can be added as needed. In addition to the liquid formulation, it can be used in the form of powder or ointment, and can be formulated into a formulation such as an aerosol or a spray.

The compounding amount of the compound (I) of the present invention in the bactericidal agent varies depending on its dosage form and use. For example, in the case of a bactericidal solution for skin used for fingers and the like, 0.01 to 10% by weight of the total composition ( Hereinafter, it is simply indicated by%), and particularly preferably 0.1 to 5%.

Further, the bactericide of the present invention may be used in combination with a conventionally known bactericide other than the compound (I) of the present invention which is an active ingredient, and if necessary, an additive usually used in the bactericide may be added. be able to.

Since the compound (I) of the present invention, which is an active ingredient, has an amide group, the bactericide of the present invention is far more excellent in biodegradability than conventional quaternary ammonium salt type compounds.

〔The invention's effect〕

The 3-[(cyanoethyl) (1-oxoalkyl) amino] -N, N, N-trialkyl-1-propanaminium salt (I) of the present invention is a novel compound having a nitrile group and an amide group in the molecule. It is a quaternary ammonium salt, and also acts as a surfactant. Further, since it has excellent characteristics that it is less irritating to the skin, has excellent foaming power, and has extremely good biodegradability and solubility in water, it can be widely used in various fields as an active ingredient of a bactericide. it can.

〔Example〕

Next, examples will be described, but the present invention is not limited thereto.

Example 1 Synthesis of 3-[(cyanoethyl) (1-oxododecyl) amino] -N, N, N-trimethyl-1-propanaminium chloride (Ia): 3- [N-lauroyl-in a 500 ml autoclave. N
-(3'-Dimethylaminopropyl) amino] propionitrile (IIa) 150g (0.444mol), isopropyl alcohol 39.1g, water 18.4g, sodium carbonate 5.7g (0.0533mo
l) and 26.9 g (0.533 mol) of methyl chloride were charged, reacted at 100 ° C. for 7 hours and then cooled, and salt by-produced was removed by filtration (the reaction rate of amine was 98.4%).
%). The solvent was evaporated under reduced pressure to give 138.6 g of a solid product (crude yield 80.4%). Recrystallize from 8-fold amount of acetone to give 3-[(cyanoethyl) (1-oxododecyl)
Amino] -N, N, N-trimethyl-1-propanaminium chloride (Ia) 100.52 g was obtained (yield 58.3%).

mp: 99-100 ° C HPLC: Purity 99.0% Elemental analysis (%): Analytical value Calculated value C 64.95 65.00 H 10.99 10.91 N 10.76 10.83 O 4.23 4.12 Cl 9.35 9.14 IR (KBr, cm ^-1 ): 3450,3000,2920 , 2840,2250,1650,1470,
1420,1385,1330,1295,1270,1240,1200,1180,1140,1080,
1060,1035,965,910,870,820,765,715 NMR (CDCl ₃ , δppm): 0.66 to 2.00 (23H, m), 2.00 to 2.60
(2H, m), 2.90 (2H, t, J = 6.0Hz), 3.43 (9H, s), 3.30 ~
4.05 (6H, m) Example 2 Synthesis of 3-[(cyanoethyl) (1-oxododecyl) amino] -N, N-dimethyl-N-benzyl-1-propanaminium chloride (Ib): 300 ml of 4 3- [N-lauroyl-N
-(3'-Dimethylaminopropyl) amino [propionitrile (IIa) 63.5 g (0.188 mol), isopropyl alcohol 19 g, water 6.5 g, sodium carbonate 0.6 g (0.00566mo)
l) and benzyl chloride (25 g, 0.197 mol) were charged, and the mixture was refluxed and stirred at 80 ° C. for 6 hours to cool the reaction,
Further, insoluble matter was removed by filtration. The solvent was evaporated under reduced pressure to obtain 86.09 g of a pale yellow viscous liquid (reaction rate of amine: 98.9%). 30 g of this was purified by silica gel column chromatography (developing solvent: chloroform / methanol = 8/2) to give 3-[(cyanoethyl) (1-oxododecyl) amino]-as a pale yellow viscous oily substance. 26.31 g of N, N-dimethyl-N-benzyl-1-propanaminium chloride (Ib) was obtained (yield 86.5
%).

HPLC: Purity 96.2% Elemental analysis (%): Analytical value Calculated value C 69.61 69.87 H 10.29 9.99 N 8.89 9.05 O 3.63 3.45 Cl 7.34 7.64 IR (NEAT, cm ^-1 ): 3406,2926,2860,2254,1644,1464 , 142
5,1383,1240,1220,1197,1074,1032,999,897,729,708,61
8 NMR (CDCl ₃ , δppm): 0.67 to 2.20 (23H, m), 2.20 to 2.57
(2H, m), 2.87 (2H, t, J = 6.0Hz), 3.20 (6H, s), 3.28〜
3.97 (6H, m), 4.89 (2H, d, J = 9.0Hz), 7.30 ~ 7.90 (5H,
m) Example 3 Synthesis of 3-[(cyanoethyl) (1-oxododecyl) amino] -N, N-dimethyl-N-hexadecyl-1-propanaminium bromide (Ic): In a 100 ml four neck flask. 3- [N-lauroyl-N
-(3'-Dimethylaminopropyl) amino] propionitrile (IIa) 5.0 g (0.0148 mol), isopropyl alcohol 20 ml, water 0.5 g, sodium carbonate 0.05 g (0.47 mmo
l), cetyl bromide 4.8g (0.0156mol) was charged, 80
The mixture was refluxed with stirring at 48 ° C. for 48 hours for reaction, cooled, and insoluble materials were removed by filtration. The solvent was evaporated under reduced pressure to obtain 9.92 g of a gel substance. Hexane / acetone 2
Recrystallization from 00 ml gave 3-[(cyanoethyl) (1-oxododecyl) amino] -N, N-dimethyl-N-hexadecyl-1-propanaminium bromide (Ic) 5.96 g as a colorless crystalline substance. (Yield 62.7%).

mp: 55-56 ℃ HPLC: Purity 98.5% Elemental analysis (%): Analytical value Calculated value C 67.55 67.26 H 11.40 11.29 N 6.49 6.54 O 2.43 2.49 Br 12.17 12.43 IR (KBr, cm ^-1 ): 3450,2910,2845 , 2245,1630,1465,1425,
1380,1340,1290,1250,1180,1140,1095,1040,980,910,89
0,820,745,720,610 NMR (CDCl ₃ , δppm): 0.66 to 2.21 (54H, m), 2.21 to 2.64
(2H, m), 2.93 (2H, t, J = 6.0Hz), 3.38 (6H, s), 3.47〜
4.07 (8H, m) Example 4 Synthesis of 3-[(cyanoethyl) (1-oxo-2-octyldecyl) amino] -N, N, N-trimethyl-1-propanaminium chloride (Id): 500 ml In an autoclave of 3- [N- (2-octyldecanoyl) -N- (3'-dimethylaminopropyl)
Amino] propionitrile (II b) 60.0 g (0.142 mo
l), ethanol 50.0g, water 7.2g, sodium carbonate 1.81g
(0.017mol), and methyl chloride 10.1g (0.200mo
l) was added and reacted at 100 ° C for 5 hours, then cooled,
Further, insoluble matter was removed by filtration (the reaction rate of amino was 97.5
%). The solvent was evaporated under reduced pressure to give 67.1% viscous material. The mixture was heated with 10 volumes of n-hexane and shaken to extract impurities into the n-hexane layer. The same operation was carried out four times in total to completely evaporate the volatile matter, and then purified 3-[(cyanoethyl) (1-oxo-2-octyldecyl) amino] -N, N, N-trimethyl-1-propana 53.14 g of minium chloride (Id) was obtained (yield 79.
1%).

HPLC: Purity 98.6% Elemental analysis (%): Analytical value Calculated value C 68.51 68.68 H 11.62 11.53 N 8.69 8.90 O 3.57 3.39 Cl 7.53 7.51 IR (NEAT, cm ^-1 ): 3400,3020,2935,2860,2250,1645 , 155
5,1490,1470,1435,1385,1250,1200,1140,1090,1040,97
0,920,730 NMR (CDCl ₃ , δppm): 0.61 ~ 2.00 (35H, m), 2.27 ~ 2.63
(2H, m), 2.84 (2H, t, J = 5.0Hz), 3.43 (9H, d, J = 4.0H
z), 3.51 to 4.13 (6H, m) Test Example 1 Antibacterial test by agar diffusion method (disk method): 40% 5% aqueous solution of each test compound was applied to a disk having a diameter of 8 mm.
μ impregnated with 0.1 ml of cell suspension (10 ⁵ cells / m
It was placed on an SCD agar medium (manufactured by Daigo Nutrition) of the following composition smeared with 1) and cultured at 30 ° C. for 2 days, and the diameter of the inhibition circle was measured. Here, the larger the numerical value of the diameter of the inhibition circle, the greater the bactericidal activity. A commercially available water-soluble antibacterial agent was used as a comparative compound. The results are shown in Table 1.

SCD agar medium composition Polypeptone 15g Polypeptone S 5g Sodium chloride 5g Agar 15g Ion-exchanged water 1 (pH 7.1-7.5) As is clear from Table 1, the compounds of the present invention have been often used conventionally. It has a bactericidal activity comparable to that of Sanizol C, and higher bactericidal activity than Tego 51, which is well known as a mild bactericide, and methylparaben used for cosmetics and medicines.

Test Example 2 Foaming power test: For the compound of the present invention and the comparative compound, the flat propeller was inverted every 6 seconds at a rotation speed of 1000 rpm, and each test compound solution was stirred in the cylinder for 5 minutes. The foaming force was measured by the so-called reversal stirring method for measuring the amount. The foaming power was represented by a relative value when the amount of foam was 1.00 when monolauryl phosphate triethanolamine salt was used as a test compound. The results are shown in Table 2.

As is clear from Table 2, the compound of the present invention has a high foaming power comparable to that of sodium lauryl sulfate which is said to be very excellent in terms of foaming power, and monolauryl phosphate triethanolamine salt and It showed much higher foaming power compared to mild surfactants such as lauroyl-N-methyl-β-alanine triethanolamine salt. Thus, the compound of the present invention has excellent foaming power.

Test Example 3 Skin irritation test: The skin irritation of the compound of the present invention and the comparative compound was evaluated by the 24-hour closed patch method using guinea pigs (1 group: 5 animals) and no skin irritation was observed 48 hours after patch removal.
Points, 1 point for slight erythema, 2 points for erythema, 3 points for obvious erythema, 4 points for erythema with drop, and the average value. Was determined as the skin irritation reaction strength. Table 3 shows the results of evaluation of the test compounds diluted with distilled water to obtain 30% concentration, 10% concentration, 5% concentration, 2.5% concentration and 1% concentration.

As is clear from Table 3, the compound of the present invention has the same or lower level of irritation as that of the comparative compound, which is well known as a hypoallergenic surfactant. It turned out to be extremely useful.

Example 5 Distilled water was added to 10 parts by weight of the compound (Ia) of the present invention (hereinafter, simply referred to as “part”) to make 100 parts by weight to obtain an aqueous bactericide solution.

A 50-fold dilution of this bactericide aqueous solution was sprayed onto the wall of the bathroom for 10 seconds at a rate of once a week, while Tego 51 was used as a control for comparison with the bactericide of the present invention. As a 0.2 wt% aqueous solution, it was similarly sprayed once a week for 10 seconds. As a result of continuing this operation for half a year and observing the wall surface, no mold was found when the fungicide of the present invention was used, but mold was found when the comparative fungicide was used.

Claims (3)

(57) [Claims] 1. The following general formula (I):(Where R¹Is an alkyl group or alkenyl having 1 to 21 carbon atoms
Represents a group, R²And R³Are the same or different and have 1 to 6 carbon atoms
Represents an alkyl group, R^FourIs an alkyl group having 1 to 22 carbon atoms or
Represents an arylalkyl group, X Represents an anion] 3-[(cyanoethyl) (1-oxoal
Kill) amino] -N, N, N-trialkyl-1-propana
Minium salt. 2. The following general formula (II) [In the formula, R ¹ represents an alkyl group or an alkenyl group having ¹ to 21 carbon atoms, and R ² and R ³ are the same or different and represent an alkyl group having 1 to 6 carbon atoms] 3- [N- Acyl-N- (dialkylaminopropyl) amino] propionitrile is quaternized with an alkyl halide and 3-[(cyanoethyl) (1-oxoalkyl) amino] -N according to claim 1. A method for producing an N, N-trialkyl-1-propanaminium salt. 3. The method according to claim 1, wherein the active ingredient is 3-
[(Cyanoethyl) (1-oxoalkyl) amino]-
A disinfectant comprising one or more N, N, N-trialkyl-1-propanaminium salts.