A continuous flow synthesis method for chloromethylnaphthylquinoline quaternary ammonium salt

Abstract

This invention discloses a continuous flow synthesis method for chloromethylnaphthylquinoline quaternary ammonium salt, belonging to the fields of organic synthesis and oil and gas field chemicals. The method includes: dissolving quinoline and 1-chloromethylnaphthyl in an organic solvent at a molar ratio of 1:1.05-1.2; adding tetrabutylammonium bromide as a catalyst at 0.1-3% of the molar amount of quinoline to form a reaction solution; continuously passing the reaction solution into a microchannel reactor and reacting at 100-120°C for 8-20 minutes; collecting the effluent and post-processing to obtain 1-naphthylquinoline quaternary ammonium chloride. This invention shortens the traditional batch reaction time of over 5 hours to minutes, reducing the reaction time by more than 95%, achieving a product HPLC purity ≥84.3%, and a molar yield of over 91%, which is up to 9 percentage points higher than the traditional method, while significantly reducing energy consumption. This method is simple, easy to scale up, and environmentally friendly, showing good prospects for industrial application.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis and oil and gas field chemicals technology, specifically relating to a continuous flow synthesis method for chloromethylnaphthylquinoline quaternary ammonium salt. Background Technology

[0002] Acid fracturing is a crucial technique for enhancing oil and gas well production. It involves injecting acid (such as hydrochloric acid or argonic acid) into the formation to dissolve rock pores or fractures, thereby increasing oil and gas permeability. However, while dissolving the rock, the acid can also cause severe corrosion to downhole tubing and surface equipment. Therefore, adding highly effective corrosion inhibitors is an indispensable key technology in acid fracturing operations.

[0003] Quinoline quaternary ammonium salt corrosion inhibitors are widely used in high-temperature deep well acidizing operations due to their excellent high-temperature resistance and adsorption film-forming ability. Among them, chloromethylnaphthalenequinoline quaternary ammonium salt, due to its naphthalene ring structure, has a larger π-electron conjugated system, which enables it to be more strongly adsorbed onto metal surfaces, thus exhibiting superior corrosion inhibition performance.

[0004] Several methods for preparing quinoline quaternary ammonium salts have been disclosed in the prior art. Patent CN115449363A discloses a method for preparing a quaternary ammonium salt-type high-temperature acid corrosion inhibitor. It uses a traditional batch reactor to react quinoline and chloromethylnaphthalene in isopropanol at 85°C for 5 hours to obtain chloromethylnaphthalenequinoline quaternary ammonium salt, which is then compounded with auxiliaries such as hexamethylenetetramine and formic acid to obtain an acid corrosion inhibitor.

[0005] In addition, as disclosed in CN114380743A, similar naphthylquinoline quaternary ammonium salts (brominated type) are also synthesized using traditional batch reactors, which also suffer from problems such as long reaction time and low heat and mass transfer efficiency.

[0006] However, the above-mentioned traditional batch synthesis methods have the following common shortcomings: (1) long reaction time (more than 5 hours), high energy consumption, and low production efficiency; (2) uneven heat transfer in batch reactors, which can easily lead to local overheating and trigger side reactions (such as multiple substitution, polymerization, etc.), affecting product purity; (3) multiple batches are required for scale-up production, and the process reproducibility is poor; (4) complex post-processing, generating a lot of organic waste liquid, which does not meet the development requirements of green chemistry.

[0007] To address the common problems in the batch synthesis process of the aforementioned brominated / chlorinated naphthylquinoline quaternary ammonium salts, a highly efficient, green, and continuous method for preparing chloromethylnaphthylquinoline quaternary ammonium salts has been developed, which has significant industrial application value and economic benefits. Summary of the Invention This invention aims to solve the problems of long reaction time, high energy consumption, low purity, many side reactions, and difficulty in continuous production in the batch synthesis method of chloromethylnaphthylquinoline quaternary ammonium salt in the prior art, and to provide an efficient, green, and easily scaled-up continuous flow synthesis method.

[0008] To solve the above-mentioned technical problems, the present invention provides a continuous flow synthesis method for chloromethylnaphthylquinoline quaternary ammonium salt, comprising the following steps: (1) mixing quinoline and 1-chloromethylnaphthyl in an organic solvent, adding a catalyst to form a reaction solution; (2) continuously passing the reaction solution into a microchannel reactor and reacting under heating and back pressure conditions; (3) collecting the product from the outlet of the reaction solution and obtaining 1-naphthylquinoline quaternary ammonium chloride after post-treatment.

[0009] As a preferred embodiment of the above technical solution, the continuous flow synthesis method of chloromethylnaphthylquinoline quaternary ammonium salt provided by the present invention further includes some or all of the following technical features: As an improvement to the above technical solution, the molar ratio of quinoline to 1-chloromethylnaphthalene is 1:1.05-1.2.

[0010] As an improvement to the above technical solution, the molar ratio of quinoline to 1-chloromethylnaphthalene is 1:1.1.

[0011] As an improvement to the above technical solution, the reaction temperature is 100-120℃ and the residence time is 8-20 minutes.

[0012] As an improvement to the above technical solution, the reaction temperature is 105-115℃ and the residence time is 10-15 minutes.

[0013] More preferably, the reaction temperature is 110°C and the residence time is 15 minutes.

[0014] As an improvement to the above technical solution, the catalyst is tetrabutylammonium bromide, and the amount of tetrabutylammonium bromide is 0.1-3% of the molar amount of quinoline. More preferably, the catalyst is tetrabutylammonium bromide, and the amount of tetrabutylammonium bromide is 0.5% of the molar amount of quinoline.

[0015] As an improvement to the above technical solution, the organic solvent is a mixed solvent of acetonitrile and isopropanol, with a volume ratio of 1:1 to 4:1.

[0016] As an improvement to the above technical solution, the organic solvent is a mixed solvent of acetonitrile and isopropanol in a volume ratio of 3:1.

[0017] As an improvement to the above technical solution, the inner diameter of the microchannel reactor is 3.0-8.0 mm, and the material is Hastelloy or stainless steel. More preferably, the inner diameter of the microchannel reactor is 5.0 mm, and the material is Hastelloy. More preferably, the microchannel reactor is a microtube type or a microplate type.

[0018] As an improvement to the above technical solution, the reaction is carried out under back pressure conditions, with a back pressure of 3-10 bar. More preferably, the back pressure is 5 bar.

[0019] As an improvement to the above technical solution, the post-processing includes: vacuum distillation to recover the solvent, adding ethyl acetate to induce crystallization, filtration, washing, and drying.

[0020] The present invention also includes a chloromethylnaphthylquinoline quaternary ammonium salt prepared by any of the above methods, wherein the chloromethylnaphthylquinoline quaternary ammonium salt is 1-naphthylquinoline quaternary ammonium chloride and its high performance liquid chromatography purity is ≥86%.

[0021] Compared with the prior art, the technical solution of the present invention has the following beneficial effects: (1) The reaction time is greatly shortened: the traditional batch reaction time of more than 5 hours is shortened to minutes (10-20 minutes), and the reaction time can be shortened by more than 95%, which significantly improves production efficiency.

[0022] (2) Product purity and yield are significantly improved: the microchannel reactor has high heat and mass transfer efficiency, precise temperature control, and effectively suppresses side reactions. The HPLC purity of the product can reach more than 90.3%, and the yield is more than 5 percentage points higher than that of traditional methods, and can be increased by up to about 9 percentage points.

[0023] (3) Significantly reduced energy consumption: The continuous flow reaction heat utilization rate is high, and the energy consumption is reduced by more than 80%, which meets the requirements of green chemical industry and energy conservation and emission reduction.

[0024] (4) The process is easy to scale up: The microchannel reactor has the characteristic of linear scale-up, and can be directly scaled up from the laboratory scale to industrial production without the need to re-optimize the process parameters, which has good industrialization prospects.

[0025] (5) Environmentally friendly: continuous flow reaction has low liquid holding capacity and high safety; post-treatment is simple and the amount of organic waste liquid generated is small, making it a green synthesis method.

[0026] (6) Significant synergistic effect: The quaternization reaction of quinoline and chloromethylnaphthalene is a strongly exothermic reaction. In traditional batch reactors, the heat of reaction cannot be removed in time, which easily leads to local overheating and side reactions such as quaternary ammonium salt decomposition or polyalkyl substitution. This is the main reason for the low yield and purity of traditional methods. The present invention uses a microchannel reactor, whose micron-sized channels endow it with a large specific surface area and a very high heat transfer coefficient, which can instantly remove the heat of reaction and achieve precise control of the reaction temperature, fundamentally suppressing the occurrence of side reactions. Experimental data (see Comparative Example 1 and Example 1) show that, under the same raw material ratio, the method of the present invention increases the yield by about 9 percentage points compared with the traditional batch method, and the purity is significantly improved. This significant leap in product quality is an unexpected technical effect brought about by microreactor technology.

[0027] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it in accordance with the contents of the specification, and to make the above and other objects, features and advantages of the present invention more apparent and understandable, the following detailed description is provided in conjunction with preferred embodiments. Attached Figure Description

[0028] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings of the embodiments will be briefly described below.

[0029] Figure 1 It is the chemical synthesis equation for chloromethylnaphthylquinoline quaternary ammonium salt; Figure 2 Liquid phase spectrum of chloromethylnaphthylquinoline quaternary ammonium salt (Example 1). Detailed Implementation

[0030] The following detailed description of specific embodiments of the present invention is part of this specification. The principles of the present invention are illustrated through examples, and other aspects, features and advantages of the present invention will become apparent from this detailed description.

[0031] Yield calculation method: The yields mentioned in this patent application are all molar yields, calculated according to the following formula: Molar yield (%) = (actual number of moles of chloromethylnaphthylquinoline quaternary ammonium salt obtained / theoretical number of moles of product) × 100% Wherein, the theoretical number of moles of product is calculated based on the amount of quinoline fed, assuming that the quinoline is completely converted and there are no side reactions.

[0032] Purity calculation method: The purity mentioned in this patent application is the purity determined by high performance liquid chromatography (HPLC) peak area normalization method. The detection conditions are: chromatographic column C18, mobile phase acetonitrile:water = 70:30, flow rate 0.2 mL / min, and detection wavelength 220 nm.

[0033] Post-processing operation specifications: The post-processing steps described in this invention shall be performed according to the following specific operations: (1) Vacuum distillation: The collected reaction liquid is transferred into a rotary evaporator and vacuum distilled under the conditions of vacuum degree ≤ -0.095 MPa (absolute pressure about 5 kPa) and water bath temperature 50-60℃. The solvent is recovered until no obvious fraction flows out, and the crude product is obtained.

[0034] (2) Crystallization purification: Add ethyl acetate to the crude product above. The volume-to-mass ratio of ethyl acetate to crude product is 5-8 mL / g. Stir at 25-30℃ for 0.5 hours to allow the product to be fully precipitated.

[0035] (3) Filtration and washing: The above suspension was filtered by suction filtration, and the filter cake was washed with ethyl acetate pre-cooled to 0-5℃. The washing amount was 1-2 times (mL / g) of the crude product mass, and the washing was performed twice.

[0036] (4) Vacuum drying: The washed filter cake is transferred to a vacuum drying oven and dried to constant weight (usually 4-6 hours) at a temperature of 50℃ and a vacuum degree of ≤-0.095 MPa (absolute pressure of about 5 kPa) to obtain the chloromethylnaphthylquinoline quaternary ammonium salt product.

[0037] The following detailed description of specific embodiments of the present invention is part of this specification. The principles of the present invention are illustrated through examples, and other aspects, features and advantages of the present invention will become apparent from this detailed description.

[0038] Example 1 Add quinoline (0.5 mol, 64.5 g) and 1-chloromethylnaphthalene (0.55 mol, 97.4 g) to a 1 L reagent bottle, dissolve them in a mixed solvent of acetonitrile / isopropanol (volume ratio 3:1, total volume 300 mL), add tetrabutylammonium bromide (2.5 mmol, 0.8 g) as a catalyst, and mix thoroughly to form a reaction solution.

[0039] The reaction solution was continuously pumped into a microchannel reactor (channel inner diameter 5.0 mm, made of Hastelloy alloy) at a flow rate of 8 mL / min using a high-pressure pump. The reaction temperature was set at 110 °C and the system back pressure at 5 bar. The residence time of the reaction solution in the microchannel reactor was 15 minutes. After continuous operation for 2 hours, the outlet reaction solution was collected.

[0040] The collected reaction solutions were combined, and the solvent was recovered by vacuum distillation to obtain a dark red, viscous semi-solid. 500 mL of ethyl acetate was added to the solid, and the mixture was stirred for 0.5 hours to precipitate the product. The product was filtered, and the filter cake was washed twice with a small amount of cold ethyl acetate. It was then dried under vacuum at 50°C to constant weight to obtain solid chloromethylnaphthylquinoline quaternary ammonium salt. The yield was calculated by weighing, yielding 143.9 g of product, with a yield of 94.2%.

[0041] The product prepared in this example was analyzed by HPLC (using an Agilent ZORBAX Eclipse Plus C18 column (4.6 mm × 150 mm, 5 μm), column temperature 30 ℃, isocratic elution with acetonitrile-water (70:30 v / v) as the mobile phase, flow rate 1.0 mL / min, injection volume 10 μL, ultraviolet (UV) detector or diode array detector (DAD), detection wavelength 220 nm; the sample was dissolved and diluted with the mobile phase to a concentration of approximately 0.5 mg / mL, filtered through a 0.45 μm filter membrane before injection, and purity was calculated by peak area normalization). The HPLC chromatogram is shown below. Figure 2 As shown, the purity of chloromethylnaphthylquinoline was measured to be 90.3%. The relevant test data analysis is shown in Table 1 below.

[0042] Table 1

[0043] Example 2 Add quinoline (0.5 mol, 64.5 g) and 1-chloromethylnaphthalene (0.55 mol, 97.4 g) to a 1 L reagent bottle, dissolve them in a mixed solvent of acetonitrile / isopropanol (volume ratio 3:1, total volume 300 mL), add tetrabutylammonium bromide (2.5 mmol, 0.8 g) as a catalyst, and mix thoroughly to form a reaction solution.

[0044] The reaction solution was continuously pumped into a microchannel reactor (channel inner diameter 5.0 mm, made of Hastelloy alloy) at a flow rate of 8 mL / min using a high-pressure pump. The reaction temperature was set at 115℃ and the system back pressure at 5 bar. The residence time of the reaction solution in the microchannel reactor was 10 minutes. After continuous operation for 2 hours, the outlet reaction solution was collected.

[0045] The collected reaction solutions were combined, and the solvent was recovered by vacuum distillation to obtain a dark red, viscous semi-solid. 500 mL of ethyl acetate was added to the solid, and the mixture was stirred for 0.5 hours to precipitate the product. The product was filtered, and the filter cake was washed twice with a small amount of cold ethyl acetate. It was then dried under vacuum at 50°C to constant weight to obtain solid chloromethylnaphthylquinoline quaternary ammonium salt. The yield was calculated by weighing, and the purity was determined by HPLC.

[0046] Results: 144.6 g of product was obtained, with a yield of 94.6% and an HPLC purity of 86.8%.

[0047] Example 3 Add quinoline (0.5 mol, 64.5 g) and 1-chloromethylnaphthalene (0.55 mol, 97.4 g) to a 1 L reagent bottle, dissolve them in a mixed solvent of acetonitrile / isopropanol (volume ratio 3:1, total volume 300 mL), add tetrabutylammonium bromide (2.5 mmol, 0.8 g) as a catalyst, and mix thoroughly to form a reaction solution.

[0048] The reaction solution was continuously pumped into a microchannel reactor (channel inner diameter 5.0 mm, made of Hastelloy alloy) at a flow rate of 8 mL / min using a high-pressure pump. The reaction temperature was set at 100℃ and the system back pressure at 5 bar. The residence time of the reaction solution in the microchannel reactor was 20 minutes. After continuous operation for 2 hours, the outlet reaction solution was collected.

[0049] The collected reaction solutions were combined, and the solvent was recovered by vacuum distillation to obtain a dark red, viscous semi-solid. 500 mL of ethyl acetate was added to the solid, and the mixture was stirred for 0.5 hours to precipitate the product. The product was filtered, and the filter cake was washed twice with a small amount of cold ethyl acetate. It was then dried under vacuum at 50°C to constant weight to obtain solid chloromethylnaphthylquinoline quaternary ammonium salt. The yield was calculated by weighing, and the purity was determined by HPLC.

[0050] Results: 143.0 g of product was obtained, with a yield of 93.6% and an HPLC purity of 89.4%.

[0051] Example 4 Add quinoline (0.5 mol, 64.5 g) and 1-chloromethylnaphthalene (0.55 mol, 97.4 g) to a 1 L reagent bottle, dissolve them in a acetonitrile / isopropanol mixed solvent (volume ratio 1:1, total volume 300 mL), add tetrabutylammonium bromide (2.5 mmol, 0.8 g) as a catalyst, and mix thoroughly to form a reaction solution.

[0052] The reaction solution was continuously pumped into a microchannel reactor (channel inner diameter 5.0 mm, made of Hastelloy alloy) at a flow rate of 8 mL / min using a high-pressure pump. The reaction temperature was set at 110 °C and the system back pressure at 5 bar. The residence time of the reaction solution in the microchannel reactor was 15 minutes. After continuous operation for 2 hours, the outlet reaction solution was collected.

[0053] The collected reaction solutions were combined, and the solvent was recovered by vacuum distillation to obtain a dark red, viscous semi-solid. 500 mL of ethyl acetate was added to the solid, and the mixture was stirred for 0.5 hours to precipitate the product. The product was filtered, and the filter cake was washed twice with a small amount of cold ethyl acetate. It was then dried under vacuum at 50°C to constant weight to obtain solid chloromethylnaphthylquinoline quaternary ammonium salt. The yield was calculated by weighing, and the purity was determined by HPLC.

[0054] Results: 139.4 g of product was obtained, with a yield of 91.2% and an HPLC purity of 84.3%.

[0055] Comparative Example 1 The chloromethylnaphthalenequinoline quaternary ammonium salt was synthesized according to the method of Example 1 of patent CN115449363A. In order to ensure that the comparative results accurately reflect the influence of reactor type on the synthesis effect, this comparative example was carried out with the exact same raw material ratio (quinoline:chloromethylnaphthalene = 1:1.1) and solvent amount as the example of the present invention.

[0056] In a 2L three-necked flask equipped with a condenser and a mechanical stirrer, quinoline (0.5 mol, 64.5 g), 1-chloromethylnaphthalene (0.55 mol, 97.4 g), and isopropanol (300 mL) were added. Stirring was started, and the temperature was raised to 85°C and maintained at this temperature for 5 hours. After the reaction was complete, a dark red viscous liquid was obtained. The solvent was recovered by vacuum distillation, and after cooling, 500 mL of ethyl acetate was added to precipitate the product. The product was filtered, washed, and dried to obtain chloromethylnaphthalenequinoline quaternary ammonium salt.

[0057] Results: 130.8 g of product was obtained, with a yield of 85.6% and an HPLC purity of 88.6%.

[0058] All the raw materials listed in this invention, as well as the upper and lower limits and ranges of the raw materials and the upper and lower limits and ranges of the process parameters (such as temperature, time, etc.), can realize this invention. Examples are not listed one by one here.

[0059] The above description is merely a preferred embodiment of the present invention, and should not be construed as limiting the scope of the invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications are also considered to be within the scope of protection of the present invention.

Claims

1. A continuous flow synthesis method for chloromethylnaphthylquinoline quaternary ammonium salt, characterized in that... Includes the following steps: (1) Mix quinoline and 1-chloromethylnaphthalene in an organic solvent, add a catalyst to form a reaction solution; (2) continuously pass the reaction solution into a microchannel reactor and react under heating and back pressure conditions; (3) collect the product from the outlet of the reaction solution and obtain 1-naphthylquinoline quaternary ammonium chloride after post-treatment.

2. The continuous flow synthesis method of chloromethylnaphthylquinoline quaternary ammonium salt as described in claim 1, characterized in that: The molar ratio of quinoline to 1-chloromethylnaphthalene is 1:1.05-1.

2.

3. The continuous flow synthesis method of chloromethylnaphthylquinoline quaternary ammonium salt as described in claim 1, characterized in that: The reaction temperature is 100-120℃, and the residence time is 8-20 minutes.

4. The continuous flow synthesis method of chloromethylnaphthylquinoline quaternary ammonium salt as described in claim 1, characterized in that: The catalyst is tetrabutylammonium bromide, and the amount of tetrabutylammonium bromide used is 0.1-3% of the molar amount of quinoline.

5. The continuous flow synthesis method of chloromethylnaphthylquinoline quaternary ammonium salt as described in claim 1, characterized in that: The organic solvent is a mixture of acetonitrile and isopropanol, with a volume ratio of 1:1 to 4:

1.

6. The continuous flow synthesis method of chloromethylnaphthylquinoline quaternary ammonium salt as described in claim 1, characterized in that: The organic solvent is a mixture of acetonitrile and isopropanol in a volume ratio of 3:

1.

7. The continuous flow synthesis method of chloromethylnaphthylquinoline quaternary ammonium salt as described in claim 1, characterized in that: The microchannel reactor has an inner diameter of 3.0-8.0 mm and is made of Hastelloy or stainless steel.

8. The continuous flow synthesis method of chloromethylnaphthylquinoline quaternary ammonium salt as described in claim 1, characterized in that: The reaction is carried out under back pressure conditions of 3-10 bar.

9. The continuous flow synthesis method of chloromethylnaphthylquinoline quaternary ammonium salt as described in claim 1, characterized in that: The post-processing includes: solvent recovery by vacuum distillation, crystallization by adding ethyl acetate, filtration, washing, and drying.

10. A chloromethylnaphthylquinoline quaternary ammonium salt prepared by any one of claims 1-9, characterized in that: The chloromethylnaphthylquinoline quaternary ammonium salt is 1-naphthylquinoline quaternary ammonium chloride, and its high performance liquid chromatography purity is ≥84.3%.

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