Linalool complexing modified compound and preparation method thereof

Abstract

The invention discloses a linalool complexing modified compound and a preparation method thereof. The structure of the linalool complex modified compound is shown as a formula (I), and the preparation method of the linalool complex modified compound comprises the following steps: adding linalool essential oil into a three-neck flask, starting stirring, and slowly heating to 30-60 DEG C; after the temperature is stable, dropwise adding tributyl phosphate, and continuously stirring to react for 1-5 hours; through a large number of experimental screening, tributyl phosphate is determined as a better choice. The complexing agent has good antibacterial activity and reaction activity with linalool, phosphoryl functional groups in the molecular structure of the complexing agent can chemically react with hydroxyl structures in linalool molecules under mild reaction conditions, stable covalent bond connection is formed, and the interaction mode of the complexing agent and bacteria is influenced. According to the invention, the problem of dissolution of linalool is also solved through a molecular complexing technology, and the solubility of a linalool modified product after complexing modification treatment in water is greatly improved. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the technical field of linalool modification, and particularly relates to a linalool complex modified compound and a preparation method thereof. Background Art

[0002] Linalool is a monoterpenol compound widely present in essential oils of various plants and has a fresh floral scent. In recent years, its bactericidal and disinfection functions have received increasing attention and shown great application potential in fields such as medicine, food preservation, and daily necessities. For example, in the medical field, linalool has a certain inhibitory effect on some common pathogenic bacteria such as Escherichia coli and Staphylococcus aureus; in food preservation, it can be used to prevent the growth of surface microorganisms on food and extend the shelf life of food.

[0003] However, the hydrophobicity of linalool severely limits its scope of application. In many practical application scenarios that require uniform dispersion and contact, such as in disinfectant formulations in aqueous systems, cosmetic emulsions and other products, linalool is difficult to fully dissolve and play its role. Traditional solubilization methods, such as using a large amount of organic solvents or surfactants, not only may affect the safety and stability of the product, but also increase costs and bring potential environmental problems.

[0004] Therefore, solving the dissolution problem of linalool and further improving its bactericidal and disinfection performance has become an urgent problem to be solved. Summary of the Invention

[0005] Object of the Invention: The object of the present invention is to provide a linalool complex modified compound to solve the problem of how to simultaneously improve the solubility and antibacterial performance of linalool. Another object of the present invention is to propose a preparation method of the linalool complex modified compound to solve the problem of how to prepare the linalool complex modified compound.

[0006] Technical Solution: A linalool complex modified compound described in the present invention has a structure shown in formula (I):

[0007]

[0008] Terpene group: The terpene group contains carbon-carbon double bonds. The carbon-carbon double bonds have high reactivity and can undergo addition, oxidation and other reactions with biological molecules in the bacterial cell membrane or inside the cell, destroying the bacterial cell membrane structure or interfering with the biochemical processes inside the cell, thereby playing a bactericidal role. In addition, the special structure and hydrophobicity of the terpene group may also make it easier to penetrate the bacterial cell membrane and enhance the interaction between the compound and the internal targets of the bacteria.

[0009] Preferably, the preparation method of the linalool complex modified compound includes the following steps:

[0010]

[0011] Reaction principle: Use tributyl phosphate and linalool as raw materials for ester exchange reaction. The butoxy group in tributyl phosphate is gradually replaced by chain terpene oxy groups to generate triterpene phosphate.

[0012] The modification of linalool by tributyl phosphate (TBP) forms a complex structure through intermolecular interactions, such as hydrogen bonds and van der Waals forces. The phosphorus atom in the molecule has an empty d orbital, which can accept the lone pair of electrons of the hydroxyl oxygen atom in the linalool molecule to form a coordination bond, thereby achieving the complex modification of linalool and improving its solubility and bactericidal and disinfectant properties. Selecting a suitable complexing agent can not only form a stable complex with the linalool molecule to improve its solubility, but also has active groups in its own structure that can be used to increase the bactericidal and disinfectant function. Under specific reaction conditions, linalool and the complexing agent undergo a complexation reaction, and the bactericidal and disinfectant groups are introduced into the molecular structure of linalool.

[0013] In the selection of complexing agents, after a large number of experimental screenings, tributyl phosphate (TBP) was determined as a better choice. This complexing agent has good antibacterial properties and reactivity with linalool. The -P=O (phosphoryl) functional group in its molecular structure can react chemically with the hydroxyl structure in the linalool molecule under mild reaction conditions to form a stable covalent bond connection, affecting its interaction with bacteria. After the reaction, a new structure is formed, which changes the distribution of the electron cloud. This new structure can achieve the bactericidal and disinfecting function by destroying the cell membrane of bacteria or viruses, or inhibiting the activity of key enzymes in their bodies. It also affects the potential of the bacterial cell membrane, cell depolarization, and then affects the production of ATP, and leads to metabolic abnormalities, which ultimately prevents bacteria from surviving and reproducing normally, thereby achieving the bactericidal and disinfecting function.

[0014] The reaction equation is: (C4H9O)3PO+3C 10 H 17 OH→(C 10 H 17 O)3PO+3C4H9OH.

[0015] Process flow: tributyl phosphate and linalool are added to a reactor in a certain proportion and reacted at an appropriate temperature and pressure. After the reaction is completed, the product is purified and refined to remove unreacted raw materials and impurities to obtain pure triterpene phosphate. The advantages of the transesterification method are that the reaction conditions are relatively mild, the byproduct methanol is easy to recycle, and the pollution to the environment is small.

[0016] Preferably, the molar ratio of linalool to tributyl phosphate is 1:2.9-5.0.

[0017] Preferably, the reaction temperature is 30 - 60 °C and the reaction time is 1 - 5 h. The reaction temperature is precisely controlled between 30 °C and 60 °C. This temperature range can not only ensure the smooth progress of the complexation reaction but also avoid side reactions caused by too high a temperature. The reaction time is set to 1 - 5 hours to ensure that linalool and the complexing agent react fully, achieving an ideal complexation degree and the introduction amount of bactericidal and disinfecting groups.

[0018] Preferably, the following purification steps are also included:

[0019] After the reaction ends, the reaction mixture cooled to room temperature is subjected to extraction and distillation to obtain a crude product; then the crude product is purified by column chromatography to obtain the linalool complex-modified compound.

[0020] Preferably, the extraction treatment method is: the reaction mixture cooled to room temperature is subjected to cyclic extraction with ethyl acetate. Compared with the traditional separatory funnel extraction, this method can make more full use of the extractant, improve the extraction efficiency, and reduce manual operation and the usage amount of the solvent.

[0021] Preferably, the distillation treatment method is: under vacuum conditions, the extract is subjected to molecular distillation at 80 - 120 °C. Under high vacuum conditions, the light components (mainly residual extractant and low-boiling impurities) volatilize from the heating surface, condense along the condensing surface, and are collected in the light component collection tank; while the heavy components (linalool complex-modified compound) flow along the heating surface into the heavy component collection tank. Molecular distillation can be carried out at a lower temperature, effectively avoiding side reactions such as decomposition and polymerization of the linalool complex-modified compound at high temperatures, and at the same time, the separation purity of the product is relatively high.

[0022] Preferably, the column chromatography purification method is:

[0023] The crude product is dissolved in an organic solvent to obtain a sample solution, the sample solution is added to a silica gel chromatography column, and then eluted with an eluent. According to the TLC detection results, the eluents containing the target product are combined; the eluent in the eluent is removed to obtain the linalool complex-modified compound.

[0024] Furthermore, the eluent is a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 10:0 - 100.

[0025] Beneficial effects: Compared with the prior art, the present invention has the following remarkable advantages:

[0026] Through the molecular complexation technology, the present invention successfully solves the solubility problem of linalool. The solubility of the linalool modified product after complexation modification in water and other solvents has increased significantly. For example, the solubility in water has increased by about 2 times compared with that before treatment. This enables linalool to be more evenly dispersed in various systems, which is conducive to the full play of its bactericidal and disinfecting functions.

[0027] Meanwhile, due to the significant increase in the number of bactericidal and disinfecting groups in the complexed molecules, the inhibitory ability of the linalool derivatives after complexation modification against specific bacteria (Pseudomonas syringae) is significantly enhanced. The application of this technology provides strong support for the wide application of linalool essential oil in the fields of medical and health, environmental protection, food processing, etc., and has significant economic and social benefits. Specific Embodiments

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

[0029] Example 1: A linalool complexation-modified compound, the structure of which is shown in formula (I):

[0030]

[0031] Its preparation method is as follows:

[0032]

[0033] Add 50 g of linalool essential oil with a purity of 95% into a three-necked flask, start stirring, and slowly heat up to 40°C. After the temperature stabilizes, dropwise add 30 g of tributyl phosphate (TBP), and continue stirring and reacting for 3 hours. During the reaction process, closely monitor the temperature change to ensure that the temperature fluctuation does not exceed ±2°C.

[0034] After the reaction is completed, transfer the reaction mixture cooled to room temperature to the flask of the continuous extraction device, and add ethyl acetate with a volume 1.5 times that of the reaction mixture. Connect the device well, and use the siphon principle to make ethyl acetate continuously circulate and extract in the reaction mixture. Heat the flask to 60°C to vaporize ethyl acetate, and the vapor is condensed by the condenser and then dripped into the reaction mixture for extraction. The extracted solution then flows back to the flask, and this is repeated for 2 - 3 hours.

[0035] After the extraction is completed, transfer the solution after continuous extraction treatment to the feed tank of the molecular distillation equipment. Set the operating pressure to be in a high vacuum state of 0.1 - 10 Pa. According to the difference in the molecular mean free path of the linalool complexation-modified compound and impurities, select the distillation temperature to be 120°C. The distillation temperature can be fine-tuned according to the product properties specifically. The rotation speed of the scraping film device is 200 r / min, and a crude product is obtained after molecular distillation.

[0036] Then, the crude product is purified by column chromatography. The method is as follows:

[0037] Column packing: Select a glass chromatography column with an appropriate inner diameter and length (if the crude product is 5 g, a chromatography column with a column volume of about 250 - 500 mL can be selected). Fill a layer of glass wool about 0.5 - 1 cm thick at the bottom of the column, and then add silica gel with a mesh size of 200 - 300 as the stationary phase into the column. While adding, gently tap the column body to make the silica gel packed tightly and evenly.

[0038] Sample loading: Dissolve the crude product in a small amount of chloroform to make a concentrated solution, and carefully add it slowly along the inner wall of the column to the surface of the silica gel, avoiding impacting the silica gel bed surface.

[0039] Elution: First, use petroleum ether as the eluent and elute at a flow rate of 50 - 100 μL / second, collecting the eluate. Detect the eluate by thin-layer chromatography (TLC). When petroleum ether can no longer elute impurities, gradually increase the proportion of ethyl acetate in the eluent (such as starting from petroleum ether:ethyl acetate = 10:1 and gradually adjusting), and continue elution. According to the TLC detection results, combine the eluates containing the target product.

[0040] Concentration: Place the combined eluates in a rotary evaporator and concentrate at 45°C under normal pressure to evaporate the eluent, obtaining the purified linalool complex modified compound. Silica gel column chromatography utilizes the difference in the adsorption ability of silica gel for different substances to achieve the separation and purification of mixtures.

[0041] The linalool complex modified compound is obtained after purification. The hydrogen spectrum data of this compound are as follows: The results of the nuclear magnetic resonance hydrogen spectrum of the product (at room temperature, 400 MHz, DMSO-d6) are:

[0042] 1 H NMR(400MHz,DMSO-d6)δ

[0043] 7.85(d,4H),7.76(d,6H),7.49(d,6H),7.36(d,6H),

[0044] 7.18(d,6H),6.77(d,6H),6.45(s,4H),6.39(s,4H),6.25(d,4H),2.44(s,10H)

[0045] Example 2: The rest are the same as in Example 1, except that:

[0046] The reaction raw materials are 80 g of linalool essential oil with a purity of 98% and 50 g of tributyl phosphate. The reaction temperature is 30°C, and the reaction time is 5 h.

[0047] Example 3: The rest are the same as in Example 1, except that:

[0048] The reaction raw materials are 100 g of linalool essential oil with a purity of 98% and 40 g of tributyl phosphate. The reaction temperature is 60 °C and the reaction time is 1 h.

[0049] Comparative Example 1: The rest are the same as in Example 1, except that:

[0050] Tributyl phosphate is replaced with an equimolar amount of monobutyl phosphate.

[0051] Comparative Example 2: The rest are the same as in Example 1, except that:

[0052] Tributyl phosphate is replaced with an equimolar amount of trimethyl phosphate.

[0053] Comparative Example 3: The rest are the same as in Example 1, except that:

[0054] Tributyl phosphate is replaced with an equimolar amount of sodium ethylene diamine tetra (methylene phosphonate).

[0055] Performance test: The final products prepared in Examples 1-3 and Comparative Examples 1-3 were subjected to a solubility test. An appropriate amount of the product was added to 100 mL of water, and after stirring evenly, the dissolution situation in water was observed. At the same time, a bactericidal performance test was carried out. According to the standard antibacterial experiment method, tests were conducted on Staphylococcus aureus, Escherichia coli, and Pseudomonas syringae pv. syringae. The results are as follows:

[0056] Table 1 Performance test results of different linalool modified products

[0057]

[0058] In the results of Table 1, the antibacterial effects of the modified products in Examples 1-3 on Staphylococcus aureus and Escherichia coli were not significantly improved compared with linalool, but the antibacterial effect on Pseudomonas syringae pv. syringae was significantly improved. Pseudomonas syringae pv. syringae was sensitive to the modified products in Examples 1-3, while it was not sensitive to unmodified linalool. The antibacterial effect of the modified product in Comparative Example 1 was not significantly improved compared with linalool. The main reason was that the modified molecule only contained one terpene group and one phosphoryl group, and there was no significant increase in antibacterial groups. The single phosphoryl group had a limited improvement on the overall antibacterial performance of the modified molecule. The antibacterial effects of the modified products in Comparative Examples 2 and 3 were significantly lower than that of linalool. The main reason was that inappropriate complexing agents could not efficiently complex with linalool to obtain the target product, and there were a large number of impurities and ineffective by-products in the reaction products, resulting in a significant reduction in the antibacterial performance of the modified products due to the failure of the modification reaction.

[0059] The complexing agents in Comparative Examples 1-3 could not significantly improve the solubility of linalool, while tributyl phosphate could effectively improve the solubility of linalool. The solubility of the modified products in Examples 1-3 in water was about three times that of linalool.

Claims

1. A linalool complex modified compound with the structure shown in formula (I):

2. The preparation method of the linalool complex modified compound according to claim 1, characterized in that, It includes the following steps:

3. The preparation method of the linalool complex modified compound according to claim 2, characterized in that, The molar ratio of linalool to tributyl phosphate is 1:2.9 - 5.

0.

4. The preparation method of the linalool complex modified compound according to claim 2, characterized in that The reaction temperature is 30 - 60 °C, and the reaction time is 1 - 5 h.

5. The preparation method of the linalool complex modified compound according to claim 2, characterized in that, It also includes the following steps: After the reaction is completed, the reaction mixture cooled to room temperature is subjected to extraction and distillation to obtain a crude product; then the crude product is purified by column chromatography to obtain the linalool complex modified compound.

6. The preparation method of the linalool complex modified compound according to claim 5, characterized in that, The extraction treatment method is: the reaction mixture cooled to room temperature is subjected to cyclic extraction with ethyl acetate.

7. The preparation method of the linalool complex modified compound according to claim 5, characterized in that, The distillation treatment method is: under vacuum conditions, the extract is subjected to molecular distillation at 80 - 120 °C.

8. The preparation method of the linalool complex modified compound according to claim 5, characterized in that, The column chromatography purification method is: the crude product is dissolved in an organic solvent to obtain a sample solution, the sample solution is added to a silica gel chromatography column, and then eluted with an eluent. According to the TLC detection results, the eluents containing the target product are combined; the eluent in the eluent is removed to obtain the linalool complex modified compound.

9. The preparation method of the linalool complex modified compound according to claim 8, characterized in that, The eluent is a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 10:0 - 100.

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