A preparation method of 2-methylquinoline

Abstract

This proposal discloses a method for preparing 2-methylquinoline in the field of materials chemistry technology. 1,2,3,4-tetrahydro-2-methylquinoline shown in formula 1a is used as a substrate, hydroxyl carbon nanotubes (CNTs-OH) are used as a catalyst, and phosphate buffer, Tris-H2SO4 buffer or alkaline solution are used as a reaction solvent to synthesize 2-methylquinoline shown in formula 2a. The synthesis route is as follows: #imgabs0# The present invention proposes a new strategy for applying hydroxyl carbon nanotubes to the oxidative dehydrogenation of tetrahydroquinoline compounds. The oxidative dehydrogenation of tetrahydroquinoline compounds can be catalyzed at room temperature and in an aqueous phase. The method has simple post-processing, low pollution, and is suitable for large-scale industrial production, which provides a new approach for synthesizing quinoline compounds.

Description

Technical Field

[0001] The invention belongs to the technical field of material chemistry, and particularly relates to a preparation method of 2-methylquinoline. Background Art

[0002] Quinoline drugs are alkaloids containing a quinoline ring in their structure, and have pharmacological activities such as antimalarial and antitumor activities. The most representative are quinine drugs, which can be used to treat and prevent malaria and pyromaniac disease. 2-Methylquinoline is a type of quinoline drug, mainly used as a metal ion precipitant, and is also an important dye and pharmaceutical intermediate. Among the many synthetic methods of 2-methylquinoline, the oxidative dehydrogenation of tetrahydroquinoline compounds has been widely studied by scientists as an important synthetic strategy. Among them, research based on precious metal oxidative dehydrogenation is prevalent, dominated by single-electron Co catalysis and precious metal catalysis such as Pd and Ir.

[0003] With technological advancements, research using non-precious metal catalysts has been reported. Data show that the use of light and metal synergistic catalysis to oxidative dehydrogenation reactions can effectively avoid the harsh high-temperature reaction conditions, but it still requires expensive ruthenium as a photosensitizer or requires heating to above 50°C for the reaction. In recent years, the use of graphene oxide and reduced graphene oxide to catalyze the oxidative dehydrogenation of nitrogen heterocyclic compounds has been successfully reported. Carbon-based non-metal catalysis has attracted great attention from scientists due to its advantages of being green, environmentally friendly, low-cost and sustainable, and has become a new research hotspot. However, existing carbon-based non-metal catalysis for the oxidative dehydrogenation of nitrogen heterocyclic compounds still requires high temperatures of 130°C and the assistance of toxic solvents. Summary of the Invention

[0004] The present invention aims to provide a method for preparing 2-methylquinoline, which can catalyze the oxidative dehydrogenation of tetrahydroquinoline compounds at room temperature in an aqueous phase to obtain 2-methylquinoline.

[0005] A method for preparing 2-methylquinoline in this scheme comprises the following steps: using 1,2,3,4-tetrahydro-2-methylquinoline as shown in Formula 1a as a substrate, hydroxy carbon nanotubes (CNTs-OH) as a catalyst, and phosphate buffer, Tris-H2SO4 buffer or alkaline solution as a reaction solvent to synthesize 2-methylquinoline as shown in Formula 2a. The synthesis route is as follows:

[0006]

[0007] Furthermore, the ratio of the hydroxyl carbon nanotubes to 1,2,3,4-tetrahydro-2-methylquinoline is 30-150 mg:0.02-0.03 mmol. 30-150 mg:0.02-0.03 mmol means that for every 0.02-0.03 mmol of 1,2,3,4-tetrahydro-2-methylquinoline added, 30-150 mg of hydroxyl carbon nanotubes are added.

[0008] Furthermore, the usage ratio of the hydroxy carbon nanotubes to 1,2,3,4-tetrahydro-2-methylquinoline is 90 mg:0.025 mmol.

[0009] Furthermore, the alkaline solution is one of potassium phosphate solution, cesium carbonate solution, sodium phosphate solution, sodium carbonate solution, and potassium carbonate solution.

[0010] Furthermore, the concentration of the phosphate buffer is 10 to 100 mM, the pH is 5.0 to 9.0, and the ratio of the phosphate buffer to 1,2,3,4-tetrahydro-2-methylquinoline is 3 to 8 mL:0.02 to 0.03 mmol. 3 to 8 mL:0.02 to 0.03 mmol means that for every 0.02 to 0.03 mmol of 1,2,3,4-tetrahydro-2-methylquinoline added, 3 to 8 mL of phosphate buffer is required.

[0011] Furthermore, the concentration of the phosphate buffer is 50 mM.

[0012] Furthermore, the pH of the phosphate buffer is 7.5.

[0013] Furthermore, the atmosphere during synthesis is one of air, oxygen and argon; air is preferred to ensure yield while saving costs.

[0014] Furthermore, the synthesis temperature is 10-100°C and the synthesis time is 0-48 hours. A synthesis time of 0 hours means that after all reactants are added to the reaction system, the reaction is immediately terminated and the yield is analyzed. Furthermore, the synthesis temperature is 37°C and the synthesis time is 24 hours.

[0015] Compared with the prior art, the present invention develops a method for applying hydroxyl carbon nanotubes to the oxidative dehydrogenation of tetrahydroquinoline compounds, which effectively avoids the use of precious metals, light, electricity, and heat energy, greatly reduces costs, simplifies the operation steps, and can successfully obtain 2-methylquinoline with a yield of 62.6% under mild conditions. The method also has simple post-processing and low pollution, making it suitable for large-scale industrial production, thus providing a new approach for the synthesis of quinoline compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is the screening bar chart of CNTs-OH dosage;

[0017] Figure 2 is the screening histogram of PB buffer pH;

[0018] Figure 3 This is a histogram for screening different buffer types;

[0019] Figure 4 is a screening histogram of the reaction atmosphere;

[0020] Figure 5 is a screening histogram of reaction temperature;

[0021] Figure 6 is a screening histogram of reaction time;

[0022] Figure 7 It is a screening bar chart of sodium phosphate dosage;

[0023] Figure 8 It is a screening bar chart of the types of bases;

[0024] Figure 9 It is the infrared spectrum of CNTs-OH before and after the cycle. DETAILED DESCRIPTION

[0025] The following is further described in detail through specific implementation methods:

[0026] Example 1

[0027] 50mg CNTs-OH was placed in a 25mL reaction bottle, 5mL PB (50mM, pH=7.0) solution was added, and 36.1μL 1,2,3,4-tetrahydro-2-methylquinoline substrate stock solution (10-fold diluted DMSO stock solution) was added to the solution using a pipette. The reaction bottle was placed in a water bath constant temperature oscillator, the speed was set to 250rpm, and the reaction was carried out at 37°C for 12h as the initial reaction conditions. On this basis, different amounts of CNTs-OH (0, 30, 50, 70, 90, 100, 110, 130, 150mg) were first screened ( Figure 1), the results showed that when no catalyst was used, the yield of the product was almost 0%. When the amount of catalyst increased from 30 mg to 90 mg, the yield showed an upward trend. When the amount of catalyst increased from 90 mg to 110 mg, the yield stabilized and reached a maximum value of 56.2%. Further increasing the amount of catalyst, the yield decreased. It is worth noting that the reaction almost did not occur under the condition of no catalyst, indicating that the catalyst is a necessary condition for the oxidative dehydrogenation process to occur. As the amount of catalyst continued to increase, the yield showed an upward trend, indicating that increasing the amount of catalyst within a certain range helps the reaction proceed, but too much catalyst is not conducive to the reaction. We speculate that the reason for the decrease in yield when more catalyst is used is that the adsorption of substrates and products on the surface or inside of the excess catalyst makes it difficult for the substrates and products to be extracted into the organic phase in the catalyst. Taking all factors into consideration, 90 mg was selected as the optimal catalyst amount for the oxidative dehydrogenation reaction of 1,2,3,4-tetrahydro-2-methylquinoline catalyzed by CNTs-OH.

[0028] Example 2

[0029] Based on the amount of CNTs-OH used in Example 1, the pH values ​​of 50 mM PB (5.0, 6.0, 6.5, 7.0, 7.5, 8.0, 9.0) were screened ( Figure 2 The results showed that when the pH of the reaction system was 5.0, the yield was only 10.2%. As the pH value increased, the yield continued to increase, reaching a maximum of 58.8% at pH 7.5, before declining. Therefore, an acidic reaction system is not conducive to the oxidative dehydrogenation reaction, while a neutral to alkaline reaction is more conducive to the reaction.

[0030] Example 3

[0031] Based on the pH value of Example 2, different buffers (H2O, PB (10mM, pH = 7.5), PB (30mM, pH = 7.5), PB (50mM, pH = 7.5), PB (100mM, pH = 7.5), Tris-H2SO4 (50mM, pH = 7.5), Na2HPO4, KH2PO4) were screened ( Figure 3), the results showed that when the concentration of PB increased from 10mM to 50mM, the yield showed an upward trend, and it was speculated that phosphate played a vital role in the reaction. The PB concentration was further increased to 100mM, and the yield at this time did not change much compared to that at 50mM. Next, we tried to use other types of buffers: Tris-H2SO4 (50mM, pH=7.5) as the reaction solvent, but the yield at this time dropped significantly compared to when PB was used as a buffer, so PB is still the preferred buffer at present. Finally, we screened the two individual components in PB separately and found that when a base was used for the reaction, the target oxidation product could be obtained with a yield of 31.0%, but the yield was still low, and when an acid was used for the reaction, the reaction could hardly proceed. Therefore, we selected PB (50mM, pH=7.5) as the preferred solvent for the reaction.

[0032] Example 4

[0033] Based on the buffer solution of Example 3, different reaction atmospheres (air, oxygen, argon) were screened ( Figure 4 ). When the reaction atmosphere was oxygen, the yield reached 62.8%, a modest improvement over air (58.8%). When the reaction atmosphere was argon, the yield dropped significantly, to only 19.2%. This indicates that oxygen is the second most critical control factor in the reaction, in addition to the catalyst, and that the oxygen content in air is sufficient to achieve high yields for the oxidative dehydrogenation of nitrogen heterocyclic compounds. Taking all factors into consideration, air was selected as the optimal reaction atmosphere.

[0034] Example 5

[0035] Based on the reaction atmosphere of Example 4, the reaction temperatures (10, 30, 37, 60, 100°C) were screened ( Figure 5 As the temperature increased from 10°C to 37°C, the yield increased, reaching its peak at 37°C. This suggests that increasing the temperature decreases the activation energy of the reaction, making the oxidative dehydrogenation process more likely to occur. However, as the temperature increased further, the yield decreased. This is presumably because the excessively high temperature altered the surface properties of the catalyst, increasing adsorption of the product and making the extraction process more difficult, thus reducing the yield. Therefore, 37°C was selected as the optimal reaction temperature.

[0036] Example 6

[0037] Based on the reaction temperature of Example 5, the reaction time (0, 2, 4, 6, 8, 12, 24, 36, 48 h) was screened ( Figure 6). The results show that as the reaction time increases, the yield increases, reaching a peak of 62.6% at 24 hours, and then slightly decreases. This shows that as the reaction time continues to increase, the contact area between the substrate and the catalyst continues to increase, and the amount of product generated also increases. When the reaction time reaches 24 hours, a dynamic equilibrium state is reached, and the yield reaches its maximum value. Subsequently, excessively long reaction times cause the generated products to be more firmly adsorbed inside the catalyst, making the extraction process more difficult, resulting in a downward trend in yield. Therefore, we selected 24 hours as the optimal reaction time.

[0038] Example 7

[0039] Figure 7 This bar chart shows the results of the catalytic reaction when different equivalents of sodium phosphate (1, 2, 3, 4, 5, and 6 equivalents) were added to the solution using water as the reaction solvent. This study investigates whether the role of PB in the reaction is to provide an alkaline environment. The experimental results show that the addition of base to the reaction system can also successfully catalyze the oxidative dehydrogenation of 1a. The yield increases with increasing amounts of Na3PO4 equivalents, suggesting that alkaline conditions are more conducive to dehydrogenation. At 3 equivalents of base, the yield reaches 60.9% and then levels off.

[0040] Example 8

[0041] Figure 8 The bar chart shows the catalytic reactions when three equivalents of different bases (potassium phosphate, cesium carbonate, sodium phosphate, sodium carbonate, and potassium carbonate, in that order) were added to the solution using water as the reaction solvent. The results show that all five bases produced the target product in yields of 46.6-61.5%. This indicates that the reaction proceeded well regardless of whether phosphate or carbonate was used, and the influence of the cation was not significant. Therefore, we speculate that the addition of PB, like the addition of bases, provides an alkaline environment for the reaction system, which facilitates the oxidative dehydrogenation process.

[0042] Example 9

[0043] Figure 9 The infrared spectra of CNTs-OH before and after the cycle are shown. -1 A strong and broad absorption peak appears near 2925-2851 cm, which is mainly attributed to the stretching vibration of hydroxyl groups; -1 The absorption peaks near 1710 cm are mainly the stretching vibrations of -CH2 and -CH3; -1 and 1625cm -1 The absorption peak near 1389cm is the stretching vibration of -C=O; -1 The absorption peak near 1080cm is the bending vibration of -OH; -1The absorption peak near is the stretching vibration of -CO. Figure 9 It can be seen that CNTs-OH contains relatively rich -OH and -C=O functional groups, and after five cycles, CNTs-OH ( Figure 9 The -C=O peak in the red curve (CNTs-OH-Recycle five times) is significantly reduced. Therefore, we speculate that functional group transformation occurs during the catalytic reaction, suggesting that the -C=O may serve as an active site for catalytic reactions.

[0044] Example 10

[0045] Based on Example 6, different carbon-based non-metallic catalysts were substituted to obtain the corresponding products. The specific reaction process is as follows: The effect of different carbon-based non-metallic catalysts on the yield of target product 2a was primarily examined. Subsequently, the specific surface areas of different carbon-based non-metallic catalysts were tested. The specific results are shown in Table 1.

[0046]

[0047] Table 1 is a comparison of the catalytic results and specific surface areas of different carbon-based non-metallic catalysts

[0048]

[0049]

[0050] We screened the four different carbon-based non-metallic catalysts mentioned above (Table 1) and found that, in addition to CNTs-OH, graphene oxide (GO) also successfully catalyzed the oxidative dehydrogenation of 1a, while graphite powder and graphene exhibited poor catalytic performance. Given the rich functional groups found in both CNTs-OH and GO, as well as the differences in specific surface areas shown in Table 1, we hypothesized that the functional groups on the catalysts' surfaces, their large specific surface area, and their porous structure played a key role in the catalytic reaction.

[0051] The above is only an embodiment of the present invention, and the common knowledge such as the specific structure and characteristics of the scheme is not described in detail here. It should be pointed out that for those skilled in the art, without departing from the structure of the present invention, several variations and improvements can be made, which should also be regarded as the scope of protection of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. A method for preparing 2-methylquinoline, characterized in that: The following steps are involved: 1,2,3,4-tetrahydro-2-methylquinoline as shown in formula 1a is used as a substrate, hydroxy carbon nanotubes CNTs-OH is used as a catalyst, and phosphate buffer and Tris-H2SO4 buffer are used as reaction solvents to synthesize 2-methylquinoline as shown in formula 2a. The amount ratio of the hydroxy carbon nanotubes and 1,2,3,4-tetrahydro-2-methylquinoline is 30-150 mg: 0.02-0.03 mmol; the concentration of the phosphate buffer is 10-100 mM, the pH is 5.0-9.0, and the amount ratio of the phosphate buffer to 1,2,3,4-tetrahydro-2-methylquinoline is 3-8 mL: 0.02-0.03 mmol; the atmosphere during the synthesis is air or oxygen; and the synthesis temperature is 10-100 o C, the synthesis time is 0~48 h; the synthesis route is as follows: 。 2. A method for preparing 2-methylquinoline according to claim 1, wherein: The usage ratio of the hydroxy carbon nanotubes to 1,2,3,4-tetrahydro-2-methylquinoline is 90 mg:0.025 mmol.

3. A method for preparing 2-methylquinoline according to claim 2, wherein: The concentration of the phosphate buffer is 50 mM.

4. A method for preparing 2-methylquinoline according to claim 3, characterized in that: The pH of the phosphate buffer is 7.

5.

5. A method for preparing 2-methylquinoline according to claim 4, characterized in that: The synthesis temperature is 37 o C, the synthesis time is 24 h.

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