KR100316598B1 - Process for preparing n-alkylbenzyl morpholinium salts - Google Patents

Abstract

PURPOSE: A process for preparing N-alkylbenzyl morpholinium salts is provided, thereby rapidly preparing high purity N-alkylbenzyl morpholinium salts having strong biocidal effect on bacteria, fungi and yeasts and lower foam formation and less toxicity in higher yield. CONSTITUTION: A process for preparing N-alkylbenzyl morpholinium salts represented by formula(1) comprises reacting alkyl morpholine of formula(2) with benzyl halide in the presence of a solvent and alkali catalyst, wherein X is halogen; R1 is C8 to C18 straight or branched chain alkyl radical; R2 is selected from the group consisting of hydrogen, halogen, hydroxy and C1 to C4 alkyl radical; the solvent is selected from the group consisting of benzene, toluene, ethyl acetate, C1 to C4 straight or branched chain alkyl alcohol and a mixture thereof; and the alkali catalyst is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium sulfate and the mixture thereof.

Description

Method for preparing alkylbenzyl morpholine quaternary ammonium salt

[Industrial use]

The present invention relates to quaternary ammonium compounds, and more particularly, to a method for preparing N-alkylbenzyl morpholinium salts represented by the formula (1).

[Formula 1]

In Formula 1, X is a halogen atom, R ₁ is a linear or pulverized alkyl radical having 8 to 18 carbon atoms, and R ₂ is selected from the group consisting of hydrogen, a halogen atom, a hydroxyl group and an alkyl radical having 1 to 4 carbon atoms. .

[Prior art]

In general, quaternary ammonium compounds are widely used as household chemicals and industrial biocide because of their excellent bactericidal activity, low surface tension, low toxicity and low corrosiveness. In particular, quaternary ammonium compounds have excellent chemical stability under acid and alkali conditions, and are widely used as antiseptic agents for wood, paints, industrial water treatment agents, detergents, disinfectants, fibers, and antimicrobial polymers. For this reason, studies on these quaternary ammonium compounds have been actively conducted, and mainly, studies on N-alkylbenzyldimethyl quaternary ammonium compounds and N-dialkyldimethyl quaternary ammonium compounds have been reported. Reports of such quaternary ammonium compounds are well described in US Pat. Nos. 5,290,805, 5,399,762, 5,438,034, 5,561,187 and 5,567,372.

However, the quaternary ammonium compound is foamed a lot when used, and its use is limited where very strong sterilizing power is required. In addition, these quaternary ammonium compounds have good bactericidal activity against Gram-positive bacteria but are less likely to have bactericidal activity against Gram-negative bacteria, and some compounds have good sterilization effects against microorganisms but are difficult to commercialize due to high manufacturing costs.

In order to improve the problem of the quaternary ammonium compound, some researches were made in the 1940's for the manufacturing method of the morpholine quaternary ammonium compound, but there is a problem of low yield and low purity in the manufacturing method and commercialization since no application field has been found. Failed. In addition, in the 1980s, a new type of morpholine quaternary ammonium compound was reported in some fields in medicine or pesticides, but recently, there is little research activity in this field. Manufacturing methods and application fields for these morpholine quaternary ammonium compounds are US Patent Nos. 2,406,892, 2,437,833, 4,328,226, 5,232,686, Japanese Patent Nos. 54-80418, 57-164143, and 58 -180537, 59-20972, 61-206180, 62-63571, Gen. Physiol. Biophys., 1987, 6, 149-153 and Environment Protection Engineering, 1980, 6, 455-463.

Among the quaternary ammonium compounds, a method for preparing a morpholine quaternary ammonium compound is the most common method of reacting N-alkyl morpholine and benzyl halide to convert N-benzyl-N-alkyl morpholine quaternary ammonium compound. To manufacture. That is, N-alkyl morpholine, for example, N-octyl, N-decyl, N-lauryl, N-tetradecyl, N-cetyl, in which an alkyl radical having 8 to 18 carbon atoms is substituted for the nitrogen atom of morpholine. , Benzyl chloride or benzyl bromide is reacted with N-octadecyl morpholine to obtain the desired N-benzyl-N-alkyl morpholine quaternary ammonium compound. In the second method, N-benzyl morpholine having a boiling point of 260 to 261 ° C and an alkyl halide, that is, octyl, decyl, lauryl, tetradecyl, cetyl, octadecyl bromide or iodine, are reacted to react N-benzyl-N- There is a method of obtaining an alkyl morpholine quaternary ammonium compound. However, in the case of morpholine quaternary ammonium compounds, unlike the general quaternary ammonium compounds, the first method is generally used because benzyl is difficult to react with alkyl chloride due to steric hindrance due to the molecular structure. .

The method for preparing the morpholine quaternary ammonium compound described above does not use any solvent, and uses ethyl acetate as a recrystallized solvent while stirring at high temperature at a high temperature of 100 to 200 ° C. or higher to obtain a solid product after completion of the reaction. In this case, since the reaction time is 12 hours or more, and the starting material is always left, the yield and purity are low, and thus there is a disadvantage in that recrystallization is required to obtain a high purity morpholine quaternary ammonium compound. In addition, in the case of the substitution reaction of the benzyl-substituted morpholine and the alkyl halide having 8 to 18 carbon atoms, the reactivity of the alkyl halide is much lower than that of the benzyl halide. Difficult to remove phosphorus N-benzyl morpholine and alkyl halides had difficulty in commercialization.

The present invention is to solve the problems of the prior art as described above, the object of the present invention exhibits a strong biocidal effect (microbial effect) on microorganisms such as bacteria (fungi), yeast (yeast), The present invention provides a method for preparing N-alkylbenzyl morpholine quaternary ammonium compounds having very low foaming properties and high toxicity in a short time with high yield and high purity, thereby providing a method for commercialization.

[Means for solving the problem]

In order to achieve the above object of the present invention, the present invention provides a morpholine quaternary ammonium salt represented by the formula (1) comprising the step of reacting the alkyl morpholine and benzyl halide represented by the formula (2) in the presence of a solvent and an alkali catalyst. It provides a method of manufacturing.

[Formula 1]

[Formula 2]

In Chemical Formulas 1 and 2, X is a halogen atom, R ₁ is a linear or pulverized alkyl radical having 8 to 18 carbon atoms, and R ₂ is hydrogen, a halogen atom, a hydroxy group and an alkyl radical having 1 to 4 carbon atoms. Is selected.

The present invention is described in detail as follows.

In order to prepare N-alkylbenzyl morpholine quaternary ammonium salt of formula (1) in the process according to the present invention, N-alkyl morpholine (II) is prepared by alkylation with morpholine as starting material and N-alkyl N-alkylbenzyl morpholine halide (I) was prepared by secondary alkylation reaction of morpholine (II) with substituted benzyl halide (III). The method for preparing an N-alkylbenzyl morpholine halide (I) according to the present invention is shown in Scheme 1 below.

[Scheme 1]

In Scheme 1, X is a halogen atom, R ₁ is a linear or pulverized alkyl radical having 8 to 18 carbon atoms, and R ₂ is selected from the group consisting of hydrogen, a halogen atom, a hydroxy group and an alkyl radical having 1 to 4 carbon atoms. .

The present invention is described in more detail as follows.

As shown in Scheme 1, the morpholine is alkylated by refluxing the morpholine and the alkyl halide in the presence of an organic solvent and a catalyst at a ratio of 1: 0.4 to 0.5 for 1 to 24 hours at a temperature of 80 to 110 ° C, N-alkyl morpholine (II) is obtained in high yield by removing the resulting morpholine salt with a filter and then removing the organic solvent. In order to synthesize N-alkylbenzyl morpholine halide (I) from the intermediate N-alkyl morpholine (II), benzyl halide (III) was added in an amount of 0.9 to 1.1 equivalents of N-alkyl morpholine in the presence of an organic solvent and an alkali catalyst. It is added and reacted by heating for a certain time at a constant reaction temperature. After the reaction, filtration, removal of the organic solvent and recrystallization can yield N-alkylbenzyl morpholine halide (I) in high yield.

The organic solvent used in the reaction is selected from the group consisting of linear or pulverized alkyl alcohols having 1 to 4 carbon atoms such as benzene, toluene, ethyl acetate, methanol, ethanol, isopropanol, butanol, t-butanol, and mixtures thereof. do. The amount of the solvent is preferably used 0.1 to 3 times the alkyl halide in the production of N-alkyl morpholine, and about 0.1 to 5 times the weight of the N-alkyl morpholine in the preparation of N-alkylbenzyl morpholine halide. It is preferred to use, more preferably 0.2 to 3 times. If the amount of solvent is less than 0.1 times the weight of N-alkyl morpholine, the reaction yield is lowered to 50% or less, and if it is more than 5 times, the yield is increased, but the reaction time is longer than 24 hours, and the economical efficiency of the raw material is increased. Falls.

The catalyst used in the preparation of the N-alkyl morpholine is selected from the group consisting of sodium hydroxide, potassium hydroxide, soda ash, manganese (Na ₂ SO ₄ .10H ₂ O) and mixtures thereof, and 0.001 to 0.1 for alkyl halides. Preference is given to using 0.5 equivalents.

The alkali catalyst used in the preparation of the N-alkylbenzyl morpholine halide is selected from the group consisting of sodium hydroxide, potassium hydroxide, soda ash, manganese (Na ₂ SO ₄ 10H ₂ O) and mixtures thereof, and N- Preference is given to using 0.001 to 0.5 equivalents, more preferably 0.01 to 0.3 equivalents, relative to alkyl morpholine. When the amount of the catalyst used is less than 0.001 equivalent, the yield is lowered to 50% or less, and when the amount of the catalyst exceeds 0.5 equivalent, some of the catalyst remains in the crystallization process of the final product, thereby lowering the purity.

The reaction temperature and reaction time of the reaction is preferably about 1 hour to 24 hours in the range of 10 ℃ to 120 ℃. If the temperature is lower than the reaction temperature, the reaction time is long, and if the temperature is higher than the reaction temperature, there is a risk of explosion due to excessive reflux of the organic solvent.

EXAMPLE

Hereinafter, preferred examples and comparative examples of the present invention are described. However, the following examples are only examples of the present invention for the purpose of understanding the present invention, and the present invention is not limited to the following examples.

Example 1

Preparation of N-benzyl-N-tetradecyl-morpholinium chloride

A 1 L three-necked flask was equipped with a dropping funnel, a condenser and an agitator, and 192 g (2.2 mol) of morpholine and 11 g (0.1 mol) of soda ash were dissolved in 300 ml of ethyl acetate, followed by 1-chloro at room temperature. 233 g (1 mol) of tetradecane were added via dropping funnel. After the addition was completed, the reaction temperature was raised to 80 ° C. and heated for 12 hours. After the reaction, the produced morpholine salt and soda ash were removed by filtration, the filtrate was washed three times with 200 ml of water, and ethyl acetate was evaporated to give 270 g of N-tetradecyl morpholine. The yield of the resulting compound was 95%.

A 250 ml two-necked flask was equipped with a cooler, and 57 g (200 mmol) of N-tetradecyl morpholine and 2.1 g (20 mmol) of soda ash were dissolved in 30 ml of methanol, and 25 g (200 mmol) of benzyl chloride was added for 5 hours at a temperature of 80 ° C. Heated during. When the reaction solution turned brown, the filter was filtered to remove soda ash, the methanol in the product was evaporated, and about 10-fold hot ethyl acetate was added to form a uniform solution. The solution was cooled with gentle stirring to give 69 g of pure powdered N-benzyl-N-tetradecyl morpholinium chloride. The yield was 84% based on N-tetradecyl morpholine and 13% of unreacted N-tetradecyl morpholine. The molecular weight of C ₂₅ H ₄₄ NOCl was 410.08, the melting point was 130 to 132 ° C, and the measurement data by NMR were as follows.

¹ H-NMR (CDCl ₃ , 300 MHz) δ 0.86-0.91 (3H, t), 1.2-1.5 (22H, m), 1.78-1.9 (2H, brs), 3.6-4.2 (10H, m), 5.24 (2H , s), 7.4-7.5 (3H, m), 7.64-7.72 (2H, m)

¹³ C-NMR (CDCl ₃ , 300 MHz) δ 14.1, 22.2, 22.6, 26.4, 29.2, 29.3, 29.4 (2C), 29.5, 29.6 (2C), 31.9, 55.7, 56.9, 60.5, 64.8, 76.6, 77.0, 77.4 , 126.6, 129.3, 130.8, 133.5

Example 2

Preparation of N-benzyl-N-octadecyl-morpholinium chloride

A 1 L three-necked flask was equipped with a dropping funnel, a cooler, and a stirrer, and 192 g (2.2 mol) of morpholine and 11 g (0.1 mol) of soda ash were dissolved in 300 ml of ethyl acetate, followed by 289 g (1 mol) of 1-chlorooctadecane at room temperature. Add via dropping funnel. After the addition was completed, the reaction temperature was raised to 80 ° C. and heated for 12 hours. After the reaction, the resulting morpholine salt and soda ash were removed by filtration, the filtrate was washed three times with 200 ml of water, and ethyl acetate was evaporated to obtain 305 g of N-octadecyl morpholine. The yield of the resulting compound was 90%.

A 250 ml two-necked flask was equipped with a cooler, and 68 g (200 mmol) of N-octadecyl morpholine and 25 g (200 mmol) of benzyl chloride were dissolved in 30 ml of methanol, and 2.1 g (20 mmol) of soda ash was added for 5 hours at 80 ° C. Heated. When the reaction solution turned brown, soda ash was filtered off with a filter, methanol in the product was evaporated, and about 10-fold hot ethyl acetate was added to form a uniform solution. The solution was cooled with gentle stirring to afford 76 g of pure powdered N-benzyl-N-octadecyl morpholinium chloride. The yield was 82% based on N-octadecyl morpholine and 17% of unreacted N-octadecyl morpholine. The molecular weight of C ₂₉ H ₅₂ NOCl was 466.19, the melting point was 145 ° C, and the measurement data by NMR were as follows.

¹ H-NMR (CDCl ₃ , 300 MHz) δ 0.85-0.91 (3H, t), 1.1-1.42 (30H, m), 1.8-1.9 (2H, brs), 3.64-4.16 (10H, m), 5.22 (2H , s), 7.4-7.5 (3H, m), 7.6-7.74 (2H, m)

¹³ C-NMR (CDCl ₃ , 300 MHz) δ 14.0, 22.1, 22.6, 26.3, 29.1, 29.2, 29.3, 29.4, 29.5, 29.6 (2C), 29.8, 31.8, 55.8, 56.8, 60.4, 64.6, 76.6, 77.0, 77.4, 126.7, 129.2, 130.6, 133.4

Comparative Example 1

Preparation of N-benzyl-N-tetradecyl-morpholinium chloride

In the same manner as in Example 1, a 250 mL two-necked flask was equipped with a cooler, and 57 g (200 mmol) of N-tetradecyl morpholine was dissolved in 30 mL of methanol, and 25 g (200 mmol) of benzyl chloride were added thereto and heated at 80 ° C. for 10 hours. . When the reaction solution turned brown, the temperature was lowered, the methanol in the product was evaporated, and about 10-fold hot ethyl acetate was added to make a uniform solution. The solution was cooled slowly with stirring to afford 17 g of pure powdered N-benzyl-N-tetradecyl morpholinium chloride. Yield was 21% based on N-tetradecyl morpholine and 78% of unreacted N-tetradecyl morpholine.

Comparative Example 2

Preparation of N-benzyl-N-tetradecyl-morpholinium chloride

In the same manner as in Example 1, a 250 ml two-necked flask was equipped with a cooler, and 57 g (200 mmol) of benzyl chloride was added to 57 g (200 mmol) of N-tetradecyl morpholine and heated at a temperature of 80 ° C. for 74 hours. As the viscosity of the reactant increased, it was dissolved in about 5 ml of methanol, and about 10 times hot ethyl acetate was added to form a uniform solution. The solution was cooled slowly with stirring to afford 45 g of pure powdered N-benzyl-N-tetradecyl morpholinium chloride. At this time, the yield was 55% based on N-tetradecyl morpholine as a raw material and 44% of unreacted N-tetradecyl morpholine.

N-alkylbenzyl morpholine system having low foamability and low toxicity while showing strong bactericidal activity against microorganisms such as bacteria, fungi and yeast in a short time using high yield and high purity using a solvent and an alkali catalyst The quaternary ammonium compound can be prepared and the preparation method is very easy and commercialized.

Claims (5)

Alkyl morpholine and benzyl halide represented by the formula (2) are selected from the group consisting of benzene, toluene, ethyl acetate, linear or pulverized alkyl alcohols having 1 to 4 carbon atoms and mixtures thereof and sodium hydroxide, potassium hydroxide, soda ash Reacting in the presence of an alkali catalyst selected from the group consisting of manganese and mixtures thereof; Method for producing a morpholine quaternary ammonium salt represented by the following formula (1) comprising a. [Formula 1] [Formula 2] (In Formulas 1 and 2, X is a halogen atom, R ₁ is a linear or pulverized alkyl radical having 8 to 18 carbon atoms, R ₂ is a group consisting of hydrogen, a halogen atom, a hydroxy group and an alkyl radical having 1 to 4 carbon atoms. Is selected.) The method of claim 1, wherein the solvent uses about 0.1 to 5 times the weight of the alkyl morpholine. The method of claim 1, wherein the alkali catalyst uses 0.001 to 0.5 equivalents based on N-alkyl morpholine. The method of claim 1, wherein the reaction temperature is 10 to 120 ℃. The method of claim 1, wherein the alkyl morpholine is N-tetradecyl morpholine or N-octahesyl morpholine, the benzyl halide is benzyl chloride, and the morpholine quaternary ammonium salt is N-benzyl-N-tetra A process for producing decyl morpholinium chloride or N-benzyl-N-octadecyl morpholinium chloride.