Alkyl sulfonic acid guanidine salt and preparation method thereof
By reacting the product in an aqueous solution and precipitating it with dichloromethane, followed by freeze filtration and drying, the problems of low synthesis efficiency and cumbersome purification of alkyl sulfonate guanidine salts have been solved, enabling high-yield and low-cost industrial production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- LANDE (JIANGSU) NEW MATERIAL TECHNOLOGY CO LTD
- Filing Date
- 2026-01-23
- Publication Date
- 2026-05-12
AI Technical Summary
Existing alkyl sulfonate guanidine salts have low synthesis efficiency, complicated purification processes, and poor compatibility between raw materials and equipment, making industrial production difficult. Furthermore, the high temperature and high pressure conditions increase energy consumption and operational risks.
Sodium alkyl sulfonate and guanidine hydrochloride are used as raw materials. They are reacted in an aqueous solution, and dichloromethane is added to precipitate a paste. After freeze filtration and drying, the process is simplified, avoiding high temperature and high pressure and multiple recrystallization.
It improves product yield and purity, reduces equipment corrosion, simplifies operation procedures, is suitable for large-scale production, and reduces costs and energy consumption.
Smart Images
Figure CN122010786A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of organic synthesis technology, and in particular to an alkyl sulfonate guanidine salt and its preparation method. Background Technology
[0002] Guanidine salts are a class of functional salts with unique structures and properties. Leveraging the strong polarity and bioactivity of the guanidine group and the ionic properties of the sulfonate group, they exhibit significant application value in antibacterial, flame retardant, and ion exchange fields. Among them, alkyl sulfonate guanidine salts, due to the introduction of the alkyl chain, allow for flexible adjustment of the compound's hydrophilicity / hydrophobicity, interfacial activity, and compatibility with other materials. They combine the broad-spectrum antibacterial properties of the guanidine group, the stability of the sulfonate group, and the performance-regulating effect of the alkyl chain, demonstrating promising application potential in high-performance antibacterial materials, environmentally friendly flame retardant additives, and fine chemical separation media, thus attracting widespread attention.
[0003] The properties of guanidine sulfonate salts vary depending on their specific structures. Their main applications include the following: (1) The guanidine group has strong polarity and a positive charge, easily binding to the negative charges on the surface of microbial cell membranes (such as phospholipids and proteins), disrupting cell membrane structure and inhibiting metabolism. Therefore, guanidine sulfonate salts often exhibit broad-spectrum antibacterial activity; (2) Sulfonate (-SO3) - It has strong hydrophilicity and ion exchange capacity, while the guanidinyl group (-C(NH2)2) has strong hydrophilicity and ion exchange capacity. + (1) The guanidine group is a cationic group, which makes guanidine sulfonate salts usable as ion exchangers or separation media; (2) The guanidine group is a key active group in many drug molecules (such as antibacterial drugs and antihypertensive drugs). The sulfonate group can regulate the water solubility and stability of the compound. Therefore, guanidine sulfonate salts are often used as pharmaceutical intermediates; (3) Guanidine sulfonate salts can be used as additives in electroplating solutions. By adjusting the ion concentration and interfacial tension, they can improve the uniformity and adhesion of the coating. The application of guanidine sulfonate salts is closely related to the bioactivity and cationic characteristics of the guanidine group in its structure, as well as the hydrophilicity and ion exchange capacity of the sulfonate group. It has practical value in many industrial and scientific research fields.
[0004] Existing alkyl sulfonate guanidine salts present several challenges in synthesis. One method involves controlling the alkyl group length on the guanidine group, but this approach is difficult and yields low results. For example, hexylguanidine sulfate, using ethanol as a solvent, involves reaction at a specific temperature, followed by filtration and recrystallization, with a yield below 70%. Another method involves reacting guanidine carbonate solution with an acid to remove water and obtain the product. This method uses strong acids such as methanesulfonic acid, sulfuric acid, nitric acid, and trifluoromethanesulfonic acid, and requires high temperature and vacuum conditions for water removal after the reaction. Neither of these methods is suitable for industrial production.
[0005] Existing methods for preparing guanidine alkyl sulfonate salts suffer from the following main problems: First, the synthesis efficiency is low. Due to the complexity of the guanidine alkylation process, the product yield is generally below 70%, which is insufficient to meet the efficiency requirements of industrial production. Second, the purification process is cumbersome, requiring multiple filtrations and recrystallizations, which not only prolongs the production cycle but also further reduces the overall yield due to crystallization losses. Third, the raw materials and processes are incompatible. When strong acids (such as methanesulfonic acid and sulfuric acid) are used in the reaction, they can easily corrode the equipment, and subsequent high-temperature vacuum dehydration is required, increasing energy consumption and operational risks. Fourth, the industrial adaptability is insufficient. The complex process steps, harsh reaction conditions, and low yield make it difficult for existing methods to achieve large-scale production, limiting the widespread application of guanidine alkyl sulfonate salts in various fields.
[0006] Therefore, it is of great significance to provide an alkyl sulfonate guanidine salt with simple process, low corrosivity, and improved product yield and purity, as well as its preparation method. Summary of the Invention
[0007] The purpose of this invention is to provide an alkyl sulfonate guanidine salt and its preparation method, which solves the problems of high energy consumption and the use of strong acids as raw materials in the prior art.
[0008] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides an alkyl sulfonate guanidine salt, the structural formula of which is: or
[0009] Formula 1 Formula 2
[0010] Among them, R1, R2, R3, R4, and R5 are all alkyl groups.
[0011] This invention also provides a method for preparing alkyl sulfonate guanidine salts, comprising the following steps: 1) React sodium alkyl sulfonate solution and guanidine hydrochloride solution to obtain the reaction product; 2) The reaction product is mixed with an organic solvent to obtain a product containing a paste; the product is frozen and then post-processed to obtain alkyl sulfonate guanidine salt.
[0012] Preferably, the sodium alkyl sulfonate solution is an aqueous solution of sodium alkyl sulfonate, wherein the mass ratio of sodium alkyl sulfonate to water in the sodium alkyl sulfonate solution is 1:1~2; the guanidine hydrochloride solution is an aqueous solution of guanidine hydrochloride, wherein the mass ratio of guanidine hydrochloride to water in the guanidine hydrochloride solution is 1:1~1.5.
[0013] Preferably, the molar ratio of sodium alkyl sulfonate to guanidine hydrochloride is 1~1.5:1.
[0014] Preferably, the purity of sodium alkyl sulfonate is ≥98%, and the purity of guanidine hydrochloride is ≥98%.
[0015] Preferably, the reaction is carried out at room temperature for 3 to 5 hours.
[0016] Preferably, the organic solvent is dichloromethane and / or xylene, and the mass ratio of the reaction product to the organic solvent is 0.8~1.2:0.8~1.2.
[0017] Preferably, the freezing temperature is -20 to -10°C, and the freezing time is 1 to 5 hours.
[0018] Preferably, the post-processing involves sequentially filtering and drying the frozen product; the drying temperature is 60~70℃.
[0019] The beneficial effects of this invention are: 1) The synthesis process of the alkyl sulfonate guanidine salt of the present invention is simple. Sodium alkyl sulfonate and guanidine hydrochloride are used as raw materials. After water-soluble mixing and temperature-controlled stirring reaction, dichloromethane is added to induce the precipitation of a paste. The crude product is obtained by freeze filtration and then washed and dried to obtain the high-purity product.
[0020] 2) The raw materials of this invention are low-corrosive conventional chemicals, which reduces equipment requirements; water is used as the reaction medium, which reduces the use of organic solvents and is more environmentally friendly and economical; the reaction does not require high temperature and high pressure, and freeze filtration replaces multiple recrystallizations, making the process simple and efficient and conducive to improving yield; the product has high purity and good stability, which is suitable for high-precision applications. At the same time, the mild conditions and simplified steps greatly improve industrial adaptability, save costs, and enable large-scale production. Attached Figure Description
[0021] Figure 1 The images show physical pictures of the guanidine heptylsulfonate salts prepared in Examples 1 and 2, where the left image is from Example 2 and the right image is from Example 1. Figure 2 The ion chromatogram of guanidine heptylsulfonate salt prepared in Example 1 is shown below. Figure 3 The image shows the ICP curve of the guanidine heptylsulfonate salt prepared in Example 1. Figure 4 The ion chromatogram of the guanidine heptylsulfonate salt prepared in Example 2 is shown below. Figure 5 The ICP chromatogram of the guanidine heptylsulfonate salt prepared in Example 2 is shown below. Figure 6 The NMR spectrum is that of the guanidine heptylsulfonate salt prepared in Example 1. Detailed Implementation
[0022] This invention provides an alkyl sulfonate guanidine salt, the structural formula of which is: or
[0023] Formula 1 Formula 2
[0024] Among them, R1, R2, R3, R4, and R5 are all alkyl groups.
[0025] In this invention, in the structural formulas of Formula 1 and Formula 2, R1 to R5 are preferably alkyl groups with 1 to 5 carbon atoms, and more preferably R1 is heptyl, and R2, R3, R4, and R5 are methyl groups.
[0026] This invention also provides a method for preparing alkyl sulfonate guanidine salts, comprising the following steps: 1) React sodium alkyl sulfonate solution and guanidine hydrochloride solution to obtain the reaction product; 2) The reaction product is mixed with an organic solvent to obtain a product containing a paste; the product is frozen and then post-processed to obtain alkyl sulfonate guanidine salt.
[0027] In this invention, the sodium alkyl sulfonate solution is preferably an aqueous solution of sodium alkyl sulfonate, and the mass ratio of sodium alkyl sulfonate to water in the sodium alkyl sulfonate solution is preferably 1:1~2, more preferably 1:1.2~1.8, and even more preferably 1:1.5~1.6; the guanidine hydrochloride solution is preferably an aqueous solution of guanidine hydrochloride, and the mass ratio of guanidine hydrochloride to water in the guanidine hydrochloride solution is preferably 1:1~1.5, more preferably 1:1.1~1.4, and even more preferably 1:1.2~1.3.
[0028] In this invention, guanidine hydrochloride is preferably guanidine hydrochloride or tetramethylguanidine hydrochloride.
[0029] In this invention, the molar ratio of sodium alkyl sulfonate and guanidine hydrochloride is preferably 1 to 1.5:1, more preferably 1.1 to 1.4:1, and even more preferably 1.2 to 1.3:1.
[0030] In this invention, the purity of sodium alkyl sulfonate is preferably ≥98%, and the purity of guanidine hydrochloride is preferably ≥98%.
[0031] In this invention, sodium alkyl sulfonate is preferably sodium heptane sulfonate.
[0032] In this invention, the reaction temperature is preferably room temperature, and the reaction time is preferably 3-5 hours, more preferably 3.5-4.5 hours, and even more preferably 4 hours.
[0033] In this invention, the organic solvent is preferably dichloromethane and / or xylene, and the mass ratio of the reaction product to the organic solvent is preferably 0.8~1.2:0.8~1.2, more preferably 0.9~1.1:0.9~1.1, and even more preferably 1:1.
[0034] In this invention, the freezing temperature is preferably -20 to -10°C, more preferably -18 to -12°C, and even more preferably -16 to -15°C, and the freezing time is preferably 1 to 5 hours, more preferably 2 to 4 hours, and even more preferably 3 hours.
[0035] In this invention, the post-processing is preferably to sequentially filter and dry the frozen products; the drying temperature is preferably 60~70℃, more preferably 62~68℃, and even more preferably 65~66℃.
[0036] In this invention, the chemical equation for the preparation of alkyl sulfonate guanidine salts is as follows:
[0037] Among them, R1 to R5 are independent alkyl groups with 1 to 5 carbon atoms.
[0038] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.
[0039] In the examples, the purity of sodium heptanesulfonate was 99%, the purity of guanidine hydrochloride was 99%, and the purity of tetramethylguanidine hydrochloride was 99%.
[0040] Example 1
[0041] Guanidine hydrochloride (0.042 mol, 4 g) was dissolved in water (guanidine hydrochloride to water mass ratio 1:1) to obtain a guanidine hydrochloride solution. Sodium heptanesulfonate (0.046 mol, 9.3 g) was dissolved in water (sodium heptanesulfonate to water mass ratio 1:2) to obtain a sodium heptanesulfonate solution. The guanidine hydrochloride solution and the sodium heptanesulfonate solution were poured into a 250 mL single-necked flask and stirred at room temperature for 4 h to obtain the reaction product. Dichloromethane (dichloromethane and reaction product mass were the same) was added to the reaction product, and stirring was continued for 5 min to allow the dichloromethane and aqueous solution to mix thoroughly, precipitating a product containing a paste. The product was frozen at -15 °C for 1 h and then filtered to obtain a white solid. The white solid was dried in an oven at 65 °C to constant weight to obtain guanidine heptylsulfonate salt.
[0042] The mass of heptaylsulfonic acid guanidine salt in this embodiment was weighed, and the yield was calculated to be 74.4%.
[0043] Example 2
[0044] The dichloromethane in Example 1 was replaced with xylene, and the other process conditions were the same as in Example 1.
[0045] The structural formulas of the guanidine heptylsulfonate salts prepared in Examples 1 and 2 are shown in Formula 3:
[0046] Formula 3.
[0047] Example 3
[0048] Guanidine hydrochloride (0.042 mol, 4 g) was dissolved in water (guanidine hydrochloride to water mass ratio 1:1.2) to obtain a guanidine hydrochloride solution. Sodium heptanesulfonate (0.06 mol, 12.13 g) was dissolved in water (sodium heptanesulfonate to water mass ratio 1:1.5) to obtain a sodium heptanesulfonate solution. The guanidine hydrochloride solution and the sodium heptanesulfonate solution were poured into a 250 mL single-necked flask and stirred at room temperature for 3.5 h to obtain the reaction product. Dichloromethane (dichloromethane and reaction product mass were the same) was added to the reaction product, and stirring was continued for 5 min to allow the dichloromethane and aqueous solution to mix thoroughly, precipitating a product containing a paste. The product was frozen at -10 °C for 4 h and then filtered to obtain a white solid. The white solid was dried in an oven at 65 °C to constant weight to obtain guanidine heptylsulfonate salt.
[0049] Example 4
[0050] Guanidine hydrochloride (0.042 mol, 4 g) was dissolved in water (guanidine hydrochloride to water mass ratio 1:1.4) to obtain a guanidine hydrochloride solution. Sodium heptanesulfonate (0.052 mol, 10.53 g) was dissolved in water (sodium heptanesulfonate to water mass ratio 1:1.2) to obtain a sodium heptanesulfonate solution. The guanidine hydrochloride solution and sodium heptanesulfonate solution were poured into a 250 mL single-necked flask and stirred at room temperature for 4.5 h to obtain the reaction product. Dichloromethane (dichloromethane and reaction product mass were equal) was added to the reaction product, and stirring was continued for 5 min to allow the dichloromethane and aqueous solution to mix thoroughly, precipitating a product containing a paste. The product was frozen at -20 °C for 2 h and then filtered to obtain a white solid. The white solid was dried in an oven at 65 °C to constant weight to obtain guanidine heptylsulfonate salt.
[0051] Example 5
[0052] Tetramethylguanidine hydrochloride (0.042 mol, 6.4 g) was dissolved in water (the mass ratio of tetramethylguanidine hydrochloride to water was 1:1) to obtain a tetramethylguanidine hydrochloride solution. Sodium heptanesulfonate (0.046 mol, 9.3 g) was dissolved in water (the mass ratio of sodium heptanesulfonate to water was 1:2) to obtain a sodium heptanesulfonate solution. The tetramethylguanidine hydrochloride solution and the sodium heptanesulfonate solution were poured into a 250 mL single-necked flask and stirred at room temperature for 4 h to obtain the reaction product. Dichloromethane (the mass of dichloromethane and the reaction product were the same) was added to the reaction product, and stirring was continued for 5 min to allow the dichloromethane and aqueous solution to mix thoroughly, precipitating a product containing a paste. The product was frozen at -15 °C for 1 h and then filtered to obtain a white solid. The white solid was dried in an oven at 65 °C to constant weight to obtain guanidine heptylsulfonate salt.
[0053] The yield of the heptasulfonic acid guanidine salt in this embodiment was calculated to be 76.7%.
[0054] The structural formula of the heptaylsulfonate guanidine salt prepared in this embodiment is shown in Formula 4:
[0055] Formula 4.
[0056] Comparative Example 1
[0057] The solvents for guanidine hydrochloride and sodium heptane sulfonate in Example 1 were replaced with dichloromethane, ethyl acetate, methanol, tert-butyl methyl ether, acetonitrile, and xylene, respectively, while the other processes were the same as in Example 1.
[0058] As can be seen from Example 1 and Comparative Example 1, guanidine heptylsulfonate is soluble in water and methanol, but insoluble in other organic solvents.
[0059] Comparative Example 2
[0060] The solvents water for guanidine hydrochloride and sodium heptane sulfonate in Example 1, as well as the dichloromethane (water + dichloromethane as a composite solvent) added to the product, were replaced with water + ethyl acetate, water + tert-butyl methyl ether, methanol + acetonitrile, methanol + ethyl acetate, methanol + water, methanol + dichloromethane, methanol + xylene, and water + xylene, respectively. Other processes were the same as in Example 1.
[0061] The results show that at room temperature, guanidine heptylsulfonate precipitates as a solid in the composite solvents of water + dichloromethane and water + xylene. From the perspective of impurity removal, the byproduct sodium chloride has a higher solubility in water than in methanol. Using water as the reaction solvent makes it easier to remove the byproduct and obtain a high-purity product.
[0062] The physical images of the guanidine heptylsulfonate salts prepared in Examples 1 and 2 are shown below. Figure 1 As shown, the left figure is Example 2, and the right figure is Example 1; The ion chromatogram of the guanidine heptylsulfonate salt prepared in Example 1 is shown below. Figure 2 As shown; the ICP chromatogram of the guanidine heptylsulfonate salt prepared in Example 1 is shown below. Figure 3 As shown; the ion chromatogram of the guanidine heptylsulfonate salt prepared in Example 2 is shown below. Figure 4 As shown; the ICP chromatogram of the guanidine heptylsulfonate salt prepared in Example 2 is shown below. Figure 5 As shown.
[0063] Depend on Figure 2 As can be seen, after filtration and drying, the product precipitated by dichloromethane was sent for ion chromatography (D160) and the residual chloride ion content was detected to be 73.1 ppm. Figure 3It can be seen that after the product precipitated by dichloromethane was filtered and dried, ICP testing showed that the residual sodium ion content in the product was 51.3 ppm; Figure 4 It can be seen that after the product precipitated by xylene was filtered and dried, ion chromatography revealed that the residual chloride ion content in the product was 2.6%; Figure 5 It can be seen that after the product precipitated by xylene was filtered and dried, the ICP test showed that the residual sodium ion content in the product was 110.9 ppm.
[0064] Combination Figure 2 and Figure 4 It can be concluded that the chloride ion residue of the guanidine heptylsulfonate salt prepared in Example 1 is relatively low; combined with Figure 3 and Figure 5 It can be concluded that the sodium ion residue of the guanidine heptanesulfonate prepared in Example 1 is relatively low. Based on the above results, and considering the safety of dichloromethane and xylene, dichloromethane is a better organic solvent.
[0065] The NMR spectrum of the guanidine heptylsulfonate salt prepared in Example 1 is as follows: Figure 6 As shown.
[0066] 1H NMR ((CD3)2SO), δ=0.79~0.90ppm, δ=1.21~1.33ppm, δ=1.51~1.60ppm, δ=2.42~2.49ppm, δ=7.04ppm.
[0067] NMR data show that the synthesis of heptyl sulfonate guanidine salt by guanidine hydrochloride and sodium heptyl sulfonate is correct and feasible; δ = 3.3 ppm is the water peak, δ = 2.5 ppm is the solvent peak, and δ = 7.04 ppm is the peak on the guanidine group in the same environment, thus the structure of the heptyl sulfonate guanidine salt prepared in Example 1 can be determined.
[0068] This invention provides a method for preparing guanidine sulfonate salts using guanidine hydrochloride and sodium alkyl sulfonate as reaction raw materials, water as reaction solvent, and dichloromethane as precipitant. Compared with the prior art, the method of this invention has the advantages of being simple and easy to operate, having high safety, low cost, producing no waste gas, and requiring less solvent, which is beneficial for industrial production and application.
[0069] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A guanidine alkyl sulfonate salt, characterized in that, The structural formula of the alkyl sulfonate guanidine salt is: or Formula 1 Formula 2 Among them, R1, R2, R3, R4, and R5 are all alkyl groups.
2. The method for preparing the alkyl sulfonate guanidine salt according to claim 1, characterized in that, It includes the following steps: 1) React sodium alkyl sulfonate solution and guanidine hydrochloride solution to obtain the reaction product; 2) The reaction product is mixed with an organic solvent to obtain a product containing a paste; the product is frozen and then post-processed to obtain alkyl sulfonate guanidine salt.
3. The preparation method according to claim 2, characterized in that, The sodium alkyl sulfonate solution is an aqueous solution of sodium alkyl sulfonate, wherein the mass ratio of sodium alkyl sulfonate to water in the sodium alkyl sulfonate solution is 1:1~2; the guanidine hydrochloride solution is an aqueous solution of guanidine hydrochloride, wherein the mass ratio of guanidine hydrochloride to water in the guanidine hydrochloride solution is 1:1~1.
5.
4. The preparation method according to claim 2 or 3, characterized in that, The molar ratio of sodium alkyl sulfonate to guanidine hydrochloride is 1~1.5:
1.
5. The preparation method according to claim 4, characterized in that, Sodium alkyl sulfonate has a purity of ≥98%, and guanidine hydrochloride has a purity of ≥98%.
6. The preparation method according to claim 4, characterized in that, The reaction was carried out at room temperature for 3-5 hours.
7. The preparation method according to claim 5 or 6, characterized in that, The organic solvent is dichloromethane and / or xylene, and the mass ratio of the reaction product to the organic solvent is 0.8~1.2:0.8~1.
2.
8. The preparation method according to claim 7, characterized in that, The freezing temperature is -20 to -10°C, and the freezing time is 1 to 5 hours.
9. The preparation method according to claim 8, characterized in that, The post-processing involves sequentially filtering and drying the frozen products; the drying temperature is 60~70℃.