Quaternary ammonium salt modified linalool derivative and preparation and application thereof

Abstract

The invention discloses a quaternary ammonium salt modified linalool derivative as well as preparation and application thereof. The structure of the quaternary ammonium salt modified linalool derivative is shown as a formula (I). The quaternary ammonium salt modified linalool derivative is prepared by carrying out nucleophilic substitution reaction on linalool and benzyltrimethylammonium chloride. The derivative can be applied to water-based disinfectants or antibacterial daily necessities. The derivative has good water solubility and bactericidal activity. Through the synergistic interaction of the quaternary ammonium salt group and the linalool mother nucleus, the disinfection and sterilization capacity of the linalool derivative is remarkably improved compared with that of independent quaternary ammonium salt or linalool, and the linalool derivative particularly has a better disinfection and killing effect on pathogens of a quaternary ammonium salt-resistant disinfectant. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to a linalool derivative and a preparation method thereof, and particularly to a quaternary ammonium salt modified linalool derivative and its preparation and application. Background Art

[0002] As a natural organic compound with a pleasant aroma, linalool has been attracting much attention in the fields of spices, medicine, cosmetics, etc. However, some inherent characteristics of linalool limit its wider and more efficient applications to a certain extent. The solubility of linalool is relatively poor, which poses challenges in application scenarios that require water as a medium. For example, when preparing water-based disinfectants, cleaners, or certain pharmaceutical preparations, its low water solubility makes it difficult to achieve the desired concentration and uniform dispersion, thus affecting the performance and effectiveness of the products. At the same time, although linalool itself has certain bactericidal and disinfectant capabilities, its effect is not strong enough when facing some stubborn bacteria and viruses. Therefore, improving its bactericidal and disinfectant performance has become an urgent need.

[0003] To improve the water solubility and bactericidal and disinfectant performance of linalool, the prior art simply physically mixes linalool with other water-soluble aids such as ethanol. Although the operation is simple, there are problems such as poor stability of the mixture and non-persistent bactericidal effect. In addition, the prior art also increases the water solubility of linalool through chemical modification methods such as introducing hydrophilic groups into linalool, but the bactericidal and disinfectant performance decreases while the water solubility is improved.

[0004] In industrial production and preparation, introducing other active functional groups into linalool, although theoretically promising, often faces many problems in actual operation, such as harsh reaction conditions, difficult product separation, difficult purity guarantee, and high cost. Therefore, developing an industrial production process that can simultaneously significantly improve the water solubility and bactericidal and disinfectant performance of linalool has become a technical problem to be solved urgently. Summary of the Invention

[0005] Object of the Invention: The object of the present invention is to provide a quaternary ammonium salt modified linalool derivative with good water solubility and bactericidal property. Another object of the present invention is to propose a preparation method of the quaternary ammonium salt modified linalool derivative to solve the problem of how to prepare the quaternary ammonium salt modified linalool derivative. The third object of the present invention is to propose the application of the quaternary ammonium salt modified linalool derivative in water-based disinfectants or antibacterial daily chemical products.

[0006] Technical Solution: A quaternary ammonium salt modified linalool derivative having a structure shown in formula (I) according to the present invention:

[0007]

[0008] The second aspect of the present invention discloses a preparation method of the above-mentioned quaternary ammonium salt-modified linalool derivative, which comprises the following reaction steps:

[0009]

[0010] The reaction process of linalool and benzyltrimethylammonium chloride can be understood as that linalool first reacts with a halogenated hydrocarbon to introduce a halogen atom, and then reacts with a tertiary amine to form a quaternary ammonium salt group.

[0011] The reaction mechanism is a nucleophilic substitution reaction: the hydroxyl group (-OH) of linalool is deprotonated under alkaline conditions to form an oxygen anion (-O-), and the oxygen anion attacks the chlorine atom (-Cl) in benzyltrimethylammonium chloride, substituting the chlorine atom and forming an ether bond (-O-CH2-), and the chlorine atom forms hydrogen chloride (HCl).

[0012] The oxygen atom of linalool attacks the carbon atom connected to chlorine in the benzyl group of benzyltrimethylammonium chloride, and the chlorine atom leaves to form the linalool quaternary ammonium salt product C 17 H 33 NO.

[0013] Preferably, the base is an inorganic strong base.

[0014] Further, the inorganic strong base is NaOH or KOH.

[0015] Creating an alkaline environment is one of the key steps. Under alkaline conditions, the hydroxyl group of linalool can be effectively deprotonated to form an oxygen anion with stronger nucleophilicity. This activation process lays the foundation for the subsequent reaction with the quaternary ammonium salt compound, greatly improving the reaction rate and efficiency.

[0016] Preferably, the heating temperature is 60-80 °C.

[0017] Appropriately increasing the temperature can increase the thermal motion energy of molecules, accelerate the collision and interaction between reactants, and thus promote the reaction. At the same time, the temperature control also needs to be accurately grasped to avoid side reactions or decomposition of products caused by too high a temperature.

[0018] Preferably, the molar ratio of linalool to benzyltrimethylammonium chloride is 1-1.5:1-1.5.

[0019] Preferably, it specifically comprises the following reaction steps: Dissolve linalool and benzyltrimethylammonium chloride in a solvent, slowly add an alkali solution dropwise until the pH value is greater than 9, and stir and heat to react to obtain the quaternary ammonium salt-modified linalool derivative.

[0020] Further, the solvent is water or ethanol.

[0021] Ethanol or water, as common solvents, can not only dissolve reactants well, providing a homogeneous reaction system, but also contribute to the separation and purification of products. Their polarity and solubility characteristics play a positive role in the reaction process, ensuring the smooth progress of the reaction and the quality of the products.

[0022] Furthermore, the pH value of the reaction system is 9 - 10, and the stirring and heating reaction time is 2 - 6 h.

[0023] The third aspect of the present invention discloses the application of the above-mentioned quaternary ammonium salt-modified linalool derivatives in the preparation of water-based disinfectants or antibacterial daily chemical products.

[0024] Beneficial effects: Compared with the prior art, the present invention has the following remarkable advantages:

[0025] 1. In terms of water solubility, due to the introduction of specific quaternary ammonium salt groups, the polarity and hydrophilicity of the molecule are greatly increased, enabling it to dissolve more easily in water and achieving a significant improvement in water solubility. This improvement creates favorable conditions for its wide application in water-based preparations, making it more convenient to prepare highly efficient water-based disinfectants, cleaners, and cosmetics, etc.

[0026] 2. In terms of bactericidal and disinfectant performance, the presence of specific quaternary ammonium salt groups enhances the cationic properties of the molecule and does not hinder the antibacterial activity of linalool. The modified linalool is more likely to adsorb on the surface of bacteria and viruses. Through interaction with the cell membrane, the integrity of the cell membrane is damaged, leading to the leakage of cell contents and cell death. Through the synergistic effect of the quaternary ammonium salt group and the linalool nucleus, the disinfection and sterilization ability of the linalool derivative is significantly improved compared with that of a single quaternary ammonium salt or linalool, especially having a better disinfection and killing effect on pathogens resistant to quaternary ammonium salt disinfectants.

[0027] 3. In terms of stability: The quaternary ammonium salt structure improves the chemical stability of linalool and reduces volatilization loss. Specific embodiments

[0028] The technical solutions of the present invention will be further described below.

[0029] Example 1: A quaternary ammonium salt-modified linalool derivative, whose structural formula is as follows:

[0030]

[0031] The preparation method of the above-mentioned quaternary ammonium salt-modified linalool derivative is as follows:

[0032]

[0033] 10 mmol of linalool and 12 mmol of benzyltrimethylammonium chloride were added to a three-necked flask containing 50 mL of ethanol. Subsequently, a 10% aqueous sodium hydroxide solution was slowly added dropwise to maintain the pH value of the reaction system between 9 and 10. The reaction system was heated to 60 °C in an oil bath and stirred at 300 rpm for 4 h.

[0034] After the reaction was completed, the reaction mixture was cooled to room temperature, and the insoluble impurities were removed by filtration. Then, ethanol and water were removed by distillation under reduced pressure to obtain a crude product. Further purification by column chromatography was carried out to obtain the final product, benzyltrimethylammonium linaloolate. The steps of column chromatography purification are as follows:

[0035] 1. Column packing

[0036] Stationary phase: silica gel (200 - 300 mesh) or alumina (selected according to the polarity of the product).

[0037] Column packing method: dry or wet packing, ensuring no air bubbles, and the ratio of column height to diameter is about 10:1.

[0038] 2. Sample loading

[0039] Sample treatment: Dissolve the crude product in a small amount of low-polarity solvent (such as dichloromethane or petroleum ether) to avoid band spreading caused by excessive solvent.

[0040] Sample loading method: Slowly add along the column wall with a dropper to avoid disturbing the stationary phase.

[0041] 3. Elution

[0042] Eluent: gradient elution (gradually increasing polarity), for example:

[0043] Start: petroleum ether / ethyl acetate (9:1) → gradually increase the proportion of ethyl acetate to (7:3).

[0044] If the product has high polarity: A small amount of methanol can be added (such as 95:5 DCM / MeOH).

[0045] Flow rate: 1 - 2 mL / min (manual pressure or using a pump).

[0046] 4. Collection and detection

[0047] TLC monitoring: Collect one tube every 10 - 15 mL and compare the Rf value of the target product by TLC (thin layer chromatography).

[0048] Color development method: UV 254 nm fluorescence quenching, or iodine vapor color development.

[0049] Combine the fractions: Combine the fractions containing the pure product and remove the solvent by rotary evaporation.

[0050] 5. Drying

[0051] Vacuum drying: The residual solvent was removed under reduced pressure at 40 °C to obtain a white to pale yellow solid, which is the final product.

[0052] The resulting final product was structurally characterized by scanning with an infrared spectrometer (IR) in the wavenumber range of 4000 - 400 cm -1 . The following results were obtained. The appearance of characteristic absorption peaks was observed, confirming the presence of ether bonds (-O-CH2-) and quaternary ammonium salt groups in the product. Meanwhile, the hydrogen spectrum (H-NMR) and carbon spectrum (C-NMR) were measured using a nuclear magnetic resonance spectrometer (NMR) respectively. Through the analysis of chemical shifts and peak integral areas, the chemical structure and composition of the product were further confirmed.

[0053] Infrared spectrum (IR)

[0054] Characteristic peak positions:

[0055] 3400 cm -1 (weak): Stretching vibration of residual hydroxyl (-OH).

[0056] 2850 - 3000 cm -1 : C-H stretching (methyl / methylene).

[0057] 1650 cm -1 (if any): C=C double bond (linalool skeleton).

[0058] 1100 - 1200 cm -1 : C-O-C ether bond (key peak, proving the formation of ether bond).

[0059] 900 - 1000 cm -1 : Vibration of quaternary ammonium salt (N + -CH3).

[0060] 1H-NMR

[0061] 1. Quaternary ammonium salt part:

[0062] 3.15 (s, 9H, N + (CH3)3)

[0063] 4.50 (s, 2H, Ph-CH2-N + )

[0064] 7.40 - 7.60 (m, 5H, benzyl benzene ring H)

[0065] 2. Linalool ether part:

[0066] 1.60 (s, 3H, CH3-C=C)

[0067] 1.70 (s, 3H, CH3-C=C)

[0068] 2.10 - 2.30 (m, 2H, -CH2-C=C)

[0069] 3.40 (t, J=6.8Hz, 2H, -O-CH2-)

[0070] 5.10 (t, J=6.8Hz, 1H, -CH=C)

[0071] 5.30 (t, J=6.8Hz, 1H, -CH=C)

[0072] 13C NMR

[0073] 1. Quaternary ammonium salt part:

[0074] 53.2 (N + (CH3)3)

[0075] 66.8 (Ph-CH2-N + )

[0076] 128.5 129.1 130.0 (Benzyl benzene ring C)

[0077] 134.5 (Benzyl benzene ring quaternary carbon)

[0078] 2. Linalool ether part:

[0079] 16.5 23.8 (CH3-C=C)

[0080] 25.7 (-CH2-C=C)

[0081] 62.3 (-O-CH2-)

[0082] 120.5 124.0 (-CH=C)

[0083] 139.8 142.0 (C=C quaternary carbon)

[0084] 3. Ether bond carbon:

[0085] 72.1 (-O-CH2-C)

[0086] Example 2: The quaternary ammonium salt modified linalool derivative was prepared as follows:

[0087] 15 mmol of linalool and 10 mmol of benzyltrimethylammonium chloride were added to a three-necked flask containing 60 mL of ethanol. Subsequently, an 8% aqueous sodium hydroxide solution was slowly added dropwise to maintain the pH value of the reaction system at 9 - 10. The reaction system was heated to 80 °C in an oil bath and stirred at 400 rpm for 2 h.

[0088] Example 3: The quaternary ammonium salt modified linalool derivative was prepared by the following method:

[0089] 10 mmol of linalool and 15 mmol of benzyltrimethylammonium chloride were added to a three-necked flask containing 70 mL of ethanol. Subsequently, a 12% aqueous sodium hydroxide solution was slowly added dropwise to maintain the pH value of the reaction system at 9 - 10. The reaction system was heated to 70 °C in an oil bath and stirred at 200 rpm for 6 h.

[0090] Example 4: The quaternary ammonium salt modified linalool derivative was prepared by the following method:

[0091] 12 mmol of linalool and 10 mmol of benzyltrimethylammonium chloride were added to a three-necked flask containing 50 mL of ethanol. Subsequently, a 10% aqueous sodium hydroxide solution was slowly added dropwise to maintain the pH value of the reaction system at 9 - 10. The reaction system was heated to 60 °C in an oil bath and stirred at 300 rpm for 6 h.

[0092] Comparative Example 1: The rest was the same as in Example 1, except that:

[0093] Benzyltrimethylammonium chloride was replaced with benzyltriethylammonium chloride.

[0094] The structure of the final product is as follows:

[0095]

[0096] 1. Linalool nucleus part

[0097] δ135.2 (-CH=, olefinic carbon)

[0098] δ115.3 (=CH2, terminal olefinic carbon)

[0099] δ70.5 (-O-CH2-, methylene linked by ether bond)

[0100] δ40.0–20.0 (aliphatic ring and -CH3)

[0101] 2. Quaternary ammonium salt part (introduced by benzyltriethylammonium chloride)

[0102] δ66.8 (-CH2-N + , benzyl carbon)

[0103] δ53.5 (-N + (CH2CH3)3, -CH2- of triethylammonium)

[0104] δ8.2 (-N + -CH2-CH3, -CH3 of ethyl)

[0105] Comparative Example 2: All other conditions were the same as in Example 1, except that:

[0106] benzyltrimethylammonium chloride was replaced with benzyldimethylethylammonium chloride.

[0107] The end product was a mixture of the following two compounds:

[0108]

[0109] 1. Linalool nucleus part (common to both products)

[0110] δ135.1 - 135.3 (-CH=, olefinic carbon)

[0111] δ115.1 - 115.4 (=CH2, terminal olefinic carbon)

[0112] δ70.3 - 70.6 (-O-CH2-, methylene group linked by ether bond)

[0113] δ40.0 - 20.0 (aliphatic ring and -CH3)

[0114] 2. Product 1: Linalool benzyldimethylethylammonium salt

[0115] δ66.5 (-CH2-N + , benzyl carbon)

[0116] δ54.8 (-N + (CH3)2, dimethylammonium carbon)

[0117] δ52.3 (-N + -CH2-CH3, -CH2- of ethyl)

[0118] δ8.5 (-N + -CH2-CH3, -CH3 of ethyl)

[0119] 3. Product 2: Linalool benzylmethyldiethylammonium salt

[0120] δ66.7 (-CH2-N + , benzyl carbon)

[0121] δ55.1 (-N + (CH3)(CH2CH3)2, methyl carbon)

[0122] δ53.0 (-N + -CH2-CH3, -CH2- of ethyl)

[0123] δ8.3 (-N + -CH2-CH3, -CH3 of ethyl)

[0124] Comparative Example 3: The rest is the same as in Example 1, except that:

[0125] benzyltrimethylammonium chloride was replaced with tolyltrimethylammonium, and the final product was:

[0126]

[0127] 1. Linalool nuclear part

[0128] δ135.0 (-CH=, olefin carbon)

[0129] δ115.1 (=CH2, terminal olefin carbon)

[0130] δ70.4 (-O-CH2-, methylene linked by ether bond)

[0131] δ40.0–20.0 (alicyclic ring and -CH3)

[0132] 2. Tolyltrimethylammonium part

[0133] δ140.2 (quaternary carbon of benzene ring, linked to -CH2-N + )

[0134] δ129.5, 128.3, 126.8 (other carbons of benzene ring)

[0135] δ65.3 (-CH2-N + , methylene carbon)

[0136] δ54.9 (-N + (CH3)3, trimethylammonium carbon)

[0137] δ21.5 (benzene ring -CH3)

[0138] The water solubility and bactericidal properties of the linalool derivatives prepared in Test Examples 1-4 and Comparative Examples 1-3 were tested as follows:

[0139] Water solubility test: Accurately weigh a certain amount of the linalool derivative sample, gradually add it to 100 mL of deionized water, stir and observe the dissolution situation. By measuring the mass of the linalool derivative dissolved at saturation under normal temperature and pressure, the solubility of the linalool derivative in water was calculated.

[0140] Bactericidal and disinfection performance test: Add 2 g of different linalool derivatives to 100 mL of Escherichia coli deionized water suspension (10,000 CFU / mL) respectively, mix evenly, and after culturing at 37 °C for 1 h, take the Escherichia coli suspension for viable cell counting. The blank control group did not add any bactericidal substances. The bactericidal rate calculation formula is as follows:

[0141] Bactericidal rate = (number of viable bacteria in the blank control group - number of viable bacteria in the experimental group) / number of viable bacteria in the blank control group × 100%;

[0142] The test results are as follows:

[0143] Table 1 Test results of bactericidal performance and water solubility of different linalool derivatives

[0144] Group Sterilization rate (%) Water solubility (g / 100mL) Example 1 92.3 5.11 Example 2 90.2 4.64 Example 3 88.6 5.06 Example 4 91.5 4.59 Comparative Example 1 49.7 4.48 Comparative Example 2 58.2 4.93 Comparative Example 3 55.1 3.87 Linalool 74.3 0.13 Benzyltrimethylammonium chloride 23.6 ＞40 Benzyl(dimethyl)ethylammonium chloride 37.8 ＞40 Tolyltrimethylammonium 29.6 ＞30

[0145] The results in Table 1 show that Escherichia coli exhibits strong resistance to quaternary ammonium salts, and the bactericidal rates of quaternary ammonium salts are all lower than 40%. It can be seen from Comparative Examples 1-3 that after modifying linalool with different quaternary ammonium salts as raw materials, although the water solubility of the derivatives is effectively improved, the bactericidal rate of the derivatives is significantly reduced compared with linalool. The reason may be that some substituents in the quaternary ammonium salt group shield the functional groups of the linalool nucleus, which instead limits the bactericidal function of the linalool nucleus. After screening, it was found that only the linalool derivative modified with benzyltrimethylammonium chloride has a bactericidal function significantly higher than that of linalool.

[0146] Example 5: Preparation of water-based disinfectant

[0147] Taking the linalool quaternary ammonium salt prepared in Example 1 as the main active ingredient, and mixing it with other auxiliaries in the following proportions to prepare a water-based disinfectant:

[0148] Linalool quaternary ammonium salt: 10% (w / w, mass fraction, the same below), as the main bactericidal component.

[0149] Surfactant: Tween-80, with an addition amount of 2%, which functions to reduce the surface tension and enhance the wetting and penetration ability of the disinfectant on the object surface.

[0150] Stabilizer: Ethylenediaminetetraacetic acid (EDTA), with an addition amount of 0.3%, used to chelate metal ions in water to prevent their influence on the stability of linalool quaternary ammonium salt.

[0151] pH regulator: Citric acid or sodium hydroxide, added appropriately to maintain the pH of the system at about 7 to ensure the stability and bactericidal activity of linalool quaternary ammonium salt.

[0152] Solvent: The balance is deionized water, used as a dilution and dissolution medium.

[0153] Example 6: Mix with other auxiliaries in the following proportions to prepare a water-based disinfectant:

[0154] Linalool quaternary ammonium salt prepared in Example 1: 5 wt%;

[0155] Surfactant: 1 wt% Tween-80;

[0156] Stabilizer: 0.1 wt% disodium EDTA;

[0157] pH regulator: citric acid or sodium hydroxide, add an appropriate amount to maintain the system pH at about 6;

[0158] Solvent: the balance is deionized water.

[0159] Example 7: Prepare a water-based disinfectant by mixing with other additives in the following proportions:

[0160] Linalool quaternary ammonium salt prepared in Example 1: 15 wt%;

[0161] Surfactant: 3 wt% Tween-80;

[0162] Stabilizer: 0.5 wt% disodium EDTA;

[0163] pH regulator: citric acid or sodium hydroxide, add an appropriate amount to maintain the system pH at about 8;

[0164] Solvent: the balance is deionized water.

Claims

1. A quaternary ammonium salt-modified linalool derivative with a structure shown in formula (I):

2. The preparation method of the quaternary ammonium salt modified linalool derivative according to claim 1, characterized in that, Comprising the following reaction steps:

3. The preparation method of the quaternary ammonium salt-modified linalool derivative according to claim 2, characterized in that, The base is an inorganic strong base.

4. The preparation method of the quaternary ammonium salt-modified linalool derivative according to claim 3, wherein, The inorganic strong base is NaOH or KOH.

5. The preparation method of the quaternary ammonium salt-modified linalool derivative according to claim 2, characterized in that, The temperature of the heating is 60 - 80 °C.

6. The preparation method of the quaternary ammonium salt modified linalool derivative according to claim 2, characterized in that, The molar ratio of linalool to benzyltrimethylammonium chloride is 1 - 1.5:1 - 1.

5.

7. The preparation method of the quaternary ammonium salt-modified linalool derivative according to claim 2, characterized in that, Comprising the following reaction steps: Dissolve linalool and benzyltrimethylammonium chloride in a solvent, slowly add an alkali solution dropwise until the pH value is greater than 9, and stir and heat to react to obtain a quaternary ammonium salt-modified linalool derivative.

8. The preparation method of the quaternary ammonium salt-modified linalool derivative according to claim 7, characterized in that, The solvent is water or ethanol.

9. The preparation method of the quaternary ammonium salt-modified linalool derivative according to claim 7, characterized in that, The pH value of the reaction system is 9 - 10, and the stirring and heating reaction time is 2 - 6 h.

10. Use of the quaternary ammonium salt-modified linalool derivative according to claim 1 in the preparation of a water-based disinfectant or an antibacterial daily chemical product.

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