CN105017045A - Bis-quaternary ammonium salt with linking groups that contain diester groups and application thereof as bactericide - Google Patents

Abstract

The invention discloses a novel bis-quaternary ammonium salt compound containing a diester group in the linking group. The bis-quaternary ammonium salt compound containing a diester group in the linking group contains an ester group, which is environmentally friendly and easy to degrade, and has a simple preparation process; and Compared with the commonly used quaternary ammonium salt fungicides, the double quaternary ammonium salt with a diester group in the linking group of the present invention has high surface activity, higher bactericidal activity and less dosage. The structural general formula of described compound is as follows:

Description

A kind of double quaternary ammonium salt containing diester group in linking group and its application as fungicide

Technical field:

The invention belongs to the field of surfactants, and relates to a Gemini cationic surfactant and its preparation method and application. Specifically, the invention relates to a bis-quaternary ammonium salt with a diester group as a linker and its application in a fungicide Applications.

Background technique:

Quaternary ammonium salt surfactants have antibacterial and bactericidal functions, and have low toxicity and a wide range of applications. The research on them as fungicides has a long history. However, microorganisms are prone to produce drug resistance to quaternary ammonium salts. For example, dodecyl dimethyl benzyl ammonium chloride (1227) is a good quaternary ammonium salt fungicide, as shown in No. 802 Oil Production Plant No. 2 of Xinjiang Petroleum Administration Bureau Sewage was used as a sample to test its bactericidal effect. When the content of 1227 was 40% and the dosage was 80mg/L, the number of sulfate-reducing bacteria in oily sewage could only be reduced from 10 ⁴ /mL to 10 ³ per mL, while the number of iron bacteria remained unchanged at 10 ³ per mL (Oilfield Chemistry, 1994, 3:247).

Since the 1990s, a new type of surfactant—Gemini surfactant has attracted more and more attention from researchers. Different from the molecular structure of ordinary surfactants, Gemini surfactant molecules contain at least two hydrophilic groups and two hydrophobic groups, making this type of surfactant exhibit extremely high surface activity. Diquaternary ammonium compound belongs to cationic Gemini surfactant, which has high surface activity, good water solubility and stronger compound coordination effect, so it can be widely used in papermaking, mineral processing, coal washing, oil extraction, sewage treatment, food processing, etc. The industry has broad application prospects.

Diquaternary ammonium compounds have strong bactericidal activity. On the one hand, due to the existence of the linking group, the distance between the positively charged ion head groups in the Gemini surfactant molecule is shortened, and the positive charge density in a single surfactant molecule increases, thereby showing a higher bactericidal activity. On the other hand, Gemini surfactant has two hydrophobic alkane chains, which have stronger hydrophobic performance and stronger hydrophobic binding with cell lipid layer, which also leads to stronger bactericidal effect.

Mao Xueqiang and others studied the bactericidal performance of diquaternary ammonium salt Gemini surfactants (m-2-m, m=8, 10, 12, 14) with different hydrophobic chain lengths on oilfield sewage. The study found that, compared with the traditional fungicide 1227 Compared with, diquaternary ammonium salts have stronger bactericidal properties against sulfate-reducing bacteria, iron bacteria and saprophytic bacteria (Synthetic Chemistry, 2011, 19(2): 180). Tatsumi et al. synthesized a series of diquaternary ammonium Gemini surfactants with butylene, butenylene and butynylene as linking groups, and studied their bactericidal activity against Aspergillus niger and Candida albicans (J. Surf. Deterg., 2001, 4(3):271). Subsequently, Tatsumi et al. synthesized a double quaternary ammonium salt Gemini surfactant with butenylene as a linking group and an ester group in the hydrophobic chain, and studied its bactericidal activity against Gram-positive bacteria and Gram-negative bacteria (J. Oleo Sci., 2014, 63(2):137). Kuperkar studied the bactericidal activity of m-s-m type (m=12,16, s=2,4,6) diquaternary ammonium salt Gemini surfactant Gram-positive bacteria, Gram-negative bacteria and fungi (J.Surf.Deterg ., 2012, 15:107). CN103598186A discloses a double-base metronidazole-modified diquaternary ammonium salt fungicide and a preparation method thereof.

At present, the fungicide commonly used in oil field water and industrial circulating cooling water is still dodecyl dimethyl benzyl ammonium chloride (1227). Continuously increasing, production costs rise year by year, and cause environmental pollution.

Invention content:

The object of the present invention is to provide a kind of connecting base containing the double quaternary ammonium salt compound of diester group, can be used for sterilization, the structural general formula of the double quaternary ammonium salt compound containing diester group in the described connecting base is as follows:

Among them, Y is or n=5-13.

The synthetic method of the double quaternary ammonium salt compound containing diester group in the linker is as follows:

(1) Add an organic solvent and 1,4-tere-phenylenedimethanol or hydroquinone into the reaction kettle, then add an acid-binding agent, and finally add chloroacetyl chloride, keep the reaction for 3-5 hours, and the reaction will produce a brown precipitate; the reaction is over Finally, filter, and the filtrate is rotary evaporated to remove the solvent, washed with anhydrous methanol, and dried to obtain dichloroacetate.

The organic solvent described in step (1) is anhydrous dioxane or anhydrous tetrahydrofuran;

Described acid binding agent is triethylamine, sodium carbonate, sodium hydroxide or pyridine;

The molar ratio of the 1,4-tere-phenylenedimethanol or hydroquinone to chloroacetyl chloride is 1:2.5-3.

When the chloroacetyl chloride is added dropwise, the temperature is controlled at 0-10°C, and the reaction temperature after the dropwise addition is 30-45°C;

(2) The bischloroacetate obtained in step (1) reacts with the long carbon chain tertiary amine in an organic solvent, the reaction temperature is 80-110°C, and the reaction time is 30-48h. After the reaction is completed, filter and filter the cake with anhydrous Acetone recrystallization and drying can obtain the bis-quaternary ammonium salt compound containing the diester group in the linker;

The organic solvent described in step (2) is anhydrous dichloroethane, dioxane, acetonitrile or ethanol;

The molar ratio of the dichloroacetate to the long carbon chain tertiary amine is 1:2.2-3.

The general reaction formula is as follows:

Among them, Y is or n=5-13.

The present invention also provides the application of the bis-quaternary ammonium salt containing diester groups in the linking base in sterilization, and the concentration of the bis-quaternary ammonium salt containing diester groups in the linking base in water is 5-50 ppm.

Beneficial effect:

(1) The present invention discloses a new double quaternary ammonium salt structure containing a diester group, which is environmentally friendly and easy to degrade, and has a simple preparation process;

(2) Compared with the commonly used quaternary ammonium salt fungicides, the bis-quaternary ammonium salt with a diester group in the linking group of the present invention has good surface activity, higher bactericidal activity, and less dosage.

Description of drawings:

Fig. 1 is the infrared spectrogram of double quaternary ammonium salt (Ⅰ)

Figure 2 is the ¹ H NMR spectrum of the bisquaternary ammonium salt (Ⅰ)

Fig. 3 is the ESI-MS spectrogram of diquaternary ammonium salt (Ⅰ)

Fig. 4 is the infrared spectrogram of double quaternary ammonium salt (Ⅱ)

Figure 5 is the ¹ H NMR spectrum of bisquaternary ammonium salt (II)

Fig. 6 is the ESI-MS spectrogram of diquaternary ammonium salt (Ⅱ)

Fig. 7 is the infrared spectrogram of double quaternary ammonium salt (Ⅲ)

Figure 8 is the ¹ H NMR spectrum of the bisquaternary ammonium salt (Ⅲ)

Fig. 9 is the ESI-MS spectrogram of diquaternary ammonium salt (Ⅲ)

Fig. 10 is the infrared spectrogram of double quaternary ammonium salt (Ⅳ)

Fig. 11 is the ¹ H NMR spectrogram of diquaternary ammonium salt (Ⅳ)

Fig. 12 is the ESI-MS spectrogram of diquaternary ammonium salt (Ⅳ)

Fig. 13 is the surface tension to concentration graph of double quaternary ammonium salt

Detailed ways:

Example 1: the synthesis of two quaternary ammonium salts (Ⅰ)

1. Synthesis of p-phenylenedimethanol dichloroacetate

Add 11.10g (0.1mol) of terephthalmic alcohol and 100mL of anhydrous dioxane into a 250mL four-neck flask, and add 30.32g (0.3mol) of triethylamine to control the reaction temperature at 0-10°C in an ice-water bath , start stirring, and after all the substances are completely dissolved, slowly add 28.25g (0.25mol) of chloroacetyl chloride dropwise. After the reaction was completed, suction filtration was performed, and the filtrate was rotary evaporated to dryness of the solvent to obtain a brown solid. Wash the brown solid with 3×10 mL of anhydrous methanol, and filter with suction to obtain a white solid, ie, tere-xylylenedimethanol dichloroacetate.

2. Synthesis of double quaternary ammonium salt (I)

In a 100mL four-neck flask, add 2.93g (10mmol) of terephthalyl dimethanol dichloroacetate obtained in step 1, 40mL of anhydrous dioxane, stir, and heat up to reflux. After completely dissolving, add 5.34g (25mmol) ) Dimethyldodecyl tertiary amine, reacted for 48h under reflux conditions. After the reaction, the system was cooled to room temperature, filtered with suction, and the filter cake was washed with acetone to obtain a white solid, which was the diquaternary ammonium salt (I). The structure was characterized by infrared spectroscopy, hydrogen nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. The infrared spectrum is shown in Figure 1, the hydrogen nuclear magnetic resonance spectrum is shown in Figure 2, and the high-resolution mass spectrum is shown in Figure 3.

Infrared analysis results:

FT-IR (KBr, cm ⁻¹ ): 2917, 2850, 1747, 1517, 1465, 1241, 1191, 813, 719.

NMR: ¹ H NMR(CDCl ₃ ,ppm)0.874-0.916(t,6H,2CH ₃ ),1.269-1.341(m,36H,2CH ₃ (CH ₂ ) ₉ ),1.720(m,4H,2CH ₃ (CH ₂ ) ₉ CH ₂ ),3.545(m,12H,2N(CH ₃ ) ₂ ),3.838(m,4H,2CH ₃ (CH ₂ ) ₉ CH ₂ CH ₂ ),5.158(m,4H,2N(CH ₃ ) ₂ CH ₂ COO), 5.330 (m, 4H, CH ₂ ArCH ₂ ), 7.346 (m, 4H, ArH).

Mass spectrum: ESI-MS (positive): m/z 681.53569[M-Cl] ⁺ , 323.28080[M-2Cl] ²⁺ /2.

Example 2: the synthesis of two quaternary ammonium salts (Ⅱ)

1. Synthesis of hydroquinone dichloroacetate

Add 11.10g (0.1mol) of hydroquinone and 100mL of anhydrous tetrahydrofuran into a 250mL four-neck flask, control the reaction temperature in an ice-water bath at 0-10°C, add 19.78g (0.25mol) of pyridine, start stirring, wait After all the substances were completely dissolved, 28.25 g (0.25 mol) of chloroacetyl chloride was slowly added dropwise, and after the complete addition of chloroacetyl chloride, the temperature was raised to 40° C. for 4 hours. After the reaction was completed, suction filtration was performed, and the filtrate was rotary evaporated to dryness of the solvent to obtain a brown solid. Wash the brown solid with 3×10 mL of anhydrous methanol, and filter with suction to obtain a white solid, ie hydroquinone dichloroacetate.

2. Synthesis of double quaternary ammonium salt (Ⅱ)

In a 100mL four-neck flask, add 2.63g (10mmol) of hydroquinone dichloroacetate obtained in step 1, 40mL of anhydrous dichloroethane, stir, and heat up to reflux. After completely dissolving, add dropwise 6.76g (28mmol) ) Dimethyltetradecyl tertiary amine, reacted for 42h under reflux conditions. After the reaction, the system was cooled to room temperature, filtered with suction, and the filter cake was washed with acetone to obtain a white solid, which was the diquaternary ammonium salt (II). Structural characterization was carried out by infrared spectroscopy, hydrogen nuclear magnetic resonance spectroscopy and high-resolution mass spectroscopy. The infrared spectrum is shown in Figure 4, the hydrogen nuclear magnetic resonance spectrum is shown in Figure 5, and the high-resolution mass spectrum is shown in Figure 6.

Infrared analysis results:

FT-IR (KBr, cm ^-1 ): 2917, 2848, 1762, 1502, 1465, 1240, 1182, 1157, 835, 719.

NMR: ¹ H NMR(CDCl ₃ ,ppm)0.852-0.893(t,6H,2CH ₃ ),

1.248-1.349(m,44H,2CH ₃ (CH ₂ ) ₁₁ ),1.816(m,4H,2CH ₃ (CH ₂ ) ₁₁ CH ₂ ),

3.636(m,12H,2N(CH ₃ ) ₂ ),3.853(m,4H,2CH ₃ (CH ₂ ) ₁₁ CH ₂ CH ₂ ),

6.005 (m, 4H, 2N( _CH3 ) _2CH2COO ), _7.272 (m, 4H, ArH).

Mass spectrum: ESI-MS (positive): m/z 709.56539[M-Cl] ⁺ , 337.29789[M-2Cl] ²⁺ /2.

Example 3: Synthesis of two quaternary ammonium salts (Ⅲ)

1. Synthesis of p-phenylenedimethanol dichloroacetate

Add 11.10g (0.1mol) of terephthalmic alcohol and 100mL of anhydrous dioxane into a 250mL four-neck flask, and add 25.25g (0.25mol) of triethylamine under the conditions of controlling the reaction temperature at 0-10°C in an ice-water bath , start stirring, and after all the substances are completely dissolved, slowly add 33.90 g (0.30 mol) of chloroacetyl chloride dropwise, and after the dropwise addition of chloroacetyl chloride is complete, raise the temperature to 30° C. After the reaction was completed, suction filtration was performed, and the filtrate was rotary evaporated to dryness of the solvent to obtain a brown solid. Wash the brown solid with 3×10 mL of anhydrous methanol, and filter with suction to obtain a white solid, ie, tere-xylylenedimethanol dichloroacetate.

2. Synthesis of double quaternary ammonium salt (Ⅲ)

Add 2.93g (10mmol) of tere-phenylenedimethanol dichloroacetate obtained in step 1 into a 100mL four-neck flask, 40mL of anhydrous acetonitrile, stir, heat up to reflux, and after completely dissolving, add 6.03g (25mmol) of dimethyl Base tetradecyl tertiary amine, reacted under reflux conditions for 36h. After the reaction, the system was cooled to room temperature, filtered with suction, and the filter cake was washed with acetone to obtain a white solid, which was the diquaternary ammonium salt. Structural characterization was carried out by infrared spectroscopy, hydrogen nuclear magnetic resonance spectroscopy and high-resolution mass spectroscopy. The infrared spectrum is shown in Figure 7, the hydrogen nuclear magnetic resonance spectrum is shown in Figure 8, and the high-resolution mass spectrum is shown in Figure 9.

Infrared analysis results:

FT-IR (KBr, cm ⁻¹ ): 2915, 2848, 1747, 1519, 1467, 1243, 1189, 811, 719.

NMR: ¹ H NMR(CDCl ₃ ,ppm)0.852-0.891(t,6H,2CH ₃ ),

1.247-1.323(m,44H,2CH ₃ (CH ₂ ) ₁₁ ),1.719(m,4H,2CH ₃ (CH ₂ ) ₁₁ CH ₂ ),

3.531(m,12H,2N(CH ₃ ) ₂ ),3.814(m,4H,2CH ₃ (CH ₂ ) ₉ CH ₂ CH ₂ ),

5.125(m,4H,2N(CH ₃ ) ₂ CH ₂ COO),5.354(m,4H,CH ₂ ArCH ₂ ),

7.268-7.306 (m, 4H, ArH).

Mass spectrum: ESI-MS (positive): m/z 737.59819[M-Cl] ⁺ , 351.31347[M-2Cl] ²⁺ /2.

Example 4: the synthesis of (Ⅳ) of two quaternary ammonium salts

1. Synthesis of hydroquinone dichloroacetate

Add 11.10g (0.1mol) of hydroquinone and 100mL of anhydrous tetrahydrofuran into a 250mL four-neck flask, control the reaction temperature in an ice-water bath at 0-10°C, add 10.15g (0.25mol) of sodium hydroxide, and start stirring After all the substances are completely dissolved, slowly add 33.92g (0.30mol) of chloroacetyl chloride dropwise, and after the complete addition of chloroacetyl chloride, heat up to 40°C for 4 hours. After the reaction was completed, suction filtration was performed, and the filtrate was rotary evaporated to dryness of the solvent to obtain a brown solid. Wash the brown solid with 3×10 mL of anhydrous methanol, and filter with suction to obtain a white solid, ie hydroquinone dichloroacetate.

2, the synthesis of double quaternary ammonium salt (Ⅳ)

Add 2.63g (10mmol) hydroquinone dichloroacetate obtained in step 1 into a 100mL four-neck flask, 40mL absolute ethanol, stir, heat up to reflux, and after completely dissolving, add 6.42g (30mmol) dimethyl Base dodecyl tertiary amine, reacted under reflux conditions for 30h. After the reaction, the system was cooled to room temperature, filtered with suction, and the filter cake was washed with acetone to obtain a white solid, which was the diquaternary ammonium salt. Structural characterization was carried out by infrared spectroscopy, hydrogen nuclear magnetic resonance spectroscopy and high-resolution mass spectroscopy. The infrared spectrum is shown in Figure 10, the hydrogen nuclear magnetic resonance spectrum is shown in Figure 11, and the high-resolution mass spectrum is shown in Figure 12.

Infrared analysis results:

FT-IR (KBr, cm ^-1 ): 2917, 2848, 1766, 1502, 1463, 1243, 1180, 1155, 833, 719.

NMR: ¹ H NMR(CDCl ₃ ,ppm)0.865(t,6H,2CH ₃ ),

1.240-1.344(m,36H,2CH ₃ (CH ₂ ) ₉ ),1.817(m,4H,2CH ₃ (CH ₂ ) ₉ CH ₂ ),

3.625(m,12H,2N(CH ₃ ) ₂ ),3.846(m,4H,2CH ₃ (CH ₂ ) ₉ CH ₂ CH ₂ ),

5.977 (m, 4H, 2N( _{CH3 ) 2CH2COO} ), 6.849 (m, 4H, ArH).

Mass spectrum: ESI-MS (positive): m/z 653.50289[M-Cl] ⁺ , 309.26644[M-2Cl] ²⁺ /2.

Example 5: Surface Activity Determination of Diquaternary Ammonium Salts

The surface activity determination method of double quaternary ammonium salt is as follows:

When measuring the surface activity of this kind of Gemini surfactant, a series of surfactant solutions with different concentrations were prepared with ultrapure water, placed in a 100mL beaker, sealed with a safety film overnight, and the K100 automatic surface tensiometer was used to measure the surface activity using the platinum ring method. Equilibrium Surface Tension of Aqueous Active Agent Solutions. When testing, put the solution to be tested in a constant temperature water bath for a period of time, then remove the plastic wrap and gently place it on the test bench. After measuring a sample, the platinum ring should be washed with ultra-pure water, and then burnt with an alcohol lamp until it is reddish to ensure its absolute cleanliness. Figure 13 shows the relationship between surface tension and concentration of diquaternary ammonium salts I, II, III, and IV.

From Figure 13, the critical micelle concentrations of I, II, III, and IV of the four kinds of diquaternary ammonium salts prepared in the examples are 0.58, 0.10, 0,09, and 0.65 mmol/L, respectively, and under the same conditions, N, The critical micelle concentration of N-dimethylbenzyl ammonium chloride (1227) is 8.8mmol/L, and the prepared bis-quaternary ammonium salt with diester group in the linker has higher surface activity than 1227.

Embodiment 6: Bactericidal performance evaluation

1. Strain culture

Escherichia coli (E.coli) and Bacillus subtilis (B.subtilis) were cultured on slant for 72 hours. Culture medium preparation: add 15 grams of agar, add appropriate amount of distilled water and heat to dissolve, then add 10 grams of peptone, 3 grams of beef extract, 5 grams of sodium chloride in turn, and stir evenly, add distilled water to 1 liter, and use 1M HCl and 1M NaOH The pH of the solution was adjusted to about 7.2, dispensed while hot, and sterilized by high-pressure steam at 121°C for 30 minutes.

2. Bacteriostatic suspension

Transfer the inoculated and cultured strains to the Erlenmeyer flask with sterile normal saline, and shake fully to disperse the bacterial lawn in the normal saline. The number of colonies in each experimental bacterial suspension is 1×10 ⁷ ~1×10 ⁸ cfu /mL.

3. Bactericidal activity evaluation

Prepare a certain concentration of fungicide solution, take 10mL of bacterial suspension, add a certain amount of fungicide solution, place it on a shaking table at 34°C, and use 10-fold dilution method to dilute, and measure the number of colonies in the presence of different concentrations of fungicide. At the same time, make a blank sample and calculate the sterilization rate.

The formula for calculating the sterilization rate is as follows:

In the formula, I is the average number of colonies of the control sample, and II is the average number of colonies of the samples added with fungicide.

Table 1 has listed the bactericidal rate of the fungicides and fungicide 1227 described in Examples 1-4.

Table 1 Bactericidal effects of diquaternary ammonium salts Ⅰ, Ⅱ, Ⅲ, Ⅳ and "1227"

As can be seen from Table 1, whether it is a Gram-positive bacterium (Bacillus subtilis B.Subtilis) or a Gram-negative bacterium (Escherichia coli E.Coli), the prepared linker contains a diquaternary ammonium diester group Salt has a better bactericidal effect than 1227.

Claims (8)

1. connect the organic diammonium compound of base containing di-ester-base, it is characterized in that, described structural formula of compound is as follows:

Wherein, Y is or n=5-13.

2. a kind of preparation method connecting base and contain the organic diammonium compound of di-ester-base as claimed in claim 1, it is characterized in that, preparation method is as follows:

(1) add organic solvent and Isosorbide-5-Nitrae-terephthalyl alcohol or Resorcinol in a kettle., then add acid binding agent, finally add chloroacetyl chloride, maintain reaction 3 ~ 5h, reaction produces tan precipitate; After reaction terminates, filter, after filtrate revolving evaporates solvent, with anhydrous methanol washing, drying two chloracetate;

(2) two for step (1) gained chloracetate and Long carbon chain tertiary amine are reacted in organic solvent, temperature of reaction is at 80 ~ 110 DEG C, reaction times 30 ~ 48h, after reaction terminates, filter, filter cake anhydrous propanone recrystallization, drying can obtain the organic diammonium compound of described connection base containing di-ester-base.

3. a kind of preparation method connecting base and contain the organic diammonium compound of di-ester-base as claimed in claim 2, it is characterized in that, the organic solvent described in step (1) is anhydrous dioxane or anhydrous tetrahydro furan.

4. a kind of preparation method connecting base and contain the organic diammonium compound of di-ester-base as claimed in claim 2, it is characterized in that, described acid binding agent is triethylamine, sodium carbonate, sodium hydroxide or pyridine.

5. a kind of preparation method connecting base and contain the organic diammonium compound of di-ester-base as claimed in claim 2, it is characterized in that, the mol ratio of described Isosorbide-5-Nitrae-terephthalyl alcohol or Resorcinol and chloroacetyl chloride is 1:2.5 ~ 3.

6. a kind of preparation method connecting base and contain the organic diammonium compound of di-ester-base as claimed in claim 2, it is characterized in that, control temperature 0 ~ 10 DEG C when described chloroacetyl chloride drips, the temperature of reaction after being added dropwise to complete is 30 ~ 45 DEG C.

7. a kind of preparation method connecting base and contain the organic diammonium compound of di-ester-base as claimed in claim 2, it is characterized in that, described two chloracetate and the mol ratio of Long carbon chain tertiary amine are 1:2.2 ~ 3.

8. connect the organic diammonium compound application in sterilization of base containing di-ester-base as claimed in claim 1.