Green synthesis method of 2-amino-5-aryl-1, 3, 4-thiadiazole

Abstract

The invention discloses a green synthesis method of 2-amino-5-aryl-1, 3, 4-thiadiazole, and belongs to the technical field of chemical synthesis. The preparation method comprises the following specific steps: mixing aromatic aldehyde, thiosemicarbazide and ethanol, heating, precipitating a solid, carrying out suction filtration to obtain an intermediate compound, and carrying out a cyclization reaction on the intermediate compound and an ionic liquid to obtain 2-amino-5-aryl-1, 3, 4-thiadiazole with a yield of 96% or more. The method provided by the invention has the characteristics of high reaction efficiency, short reaction time, mild reaction conditions, recyclable catalyst, strong catalytic ability, greenness and energy conservation. The method solves the technical problems that in a traditional synthesis method, a catalyst cannot be recycled and is not high in catalytic capacity, a substrate is poor in adaptability in the synthesis process, and the yield and purity of a product are not high due to the fact that the chemical stability of a used compound is not high.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and particularly relates to a green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole. Background Art

[0002] The structure of 2-amino-5-aryl-1,3,4-thiadiazole contains an amino group (-NH2) and an aromatic group, which gives it certain biological activity and chemical properties. In the agricultural field, it can be used as a pesticide component to develop new insecticides or fungicides. In the pharmaceutical field, 2-amino-5-aryl-1,3,4-thiadiazole compounds often have biological activity and have application potential in the development of antibacterial, antitumor or anti-inflammatory drugs. In addition, it can also be used to synthesize new polymers or composite materials to enhance the heat resistance and mechanical strength of materials.

[0003] So far, a variety of routes have been studied for the synthesis of 2-amino-5-aryl-1,3,4-thiadiazole. However, most of them are synthesized under the catalysis of dehydrating agents such as concentrated sulfuric acid, concentrated hydrochloric acid, and polyphosphoric acid. Some are synthesized under the catalysis of phosphorus oxychloride and phosphorus oxychloride pentachloride. First, these substances are highly corrosive and have extremely high requirements for reaction equipment and operating environment. The slightest carelessness may cause equipment damage or safety accidents. Second, these dehydrating agents may produce harmful gases during operation. Compounds such as phosphorus oxychloride and phosphorus oxychloride pentachloride are highly toxic and pose a serious threat to the health of operators. Third, the use of these substances for catalysis usually requires higher reaction temperatures and pressures, which increases the difficulty of reaction control and energy consumption. Fourth, harsh reaction conditions may lead to an increase in side reactions and reduce the purity and yield of the target product. Chinese patent CN118255729A discloses a method for synthesizing 2-amino-5-substituted-1,3,4-thiadiazole. The catalyst in the synthesis method cannot be recycled and has weak catalytic ability. During the synthesis process, the substrate adaptability of the product is poor, and the chemical stability of the reactants is not high, resulting in low yield and purity of the product. Summary of the invention

[0004] In order to overcome the shortcomings of the above-mentioned prior art, the purpose of the present invention is to provide a green synthesis method for 2-amino-5-aryl-1,3,4-thiadiazole, so as to solve the technical problems that the catalyst in the traditional synthesis method cannot be recycled and the catalytic ability is not strong, the substrate adaptability is poor during the synthesis process, and the chemical stability of the used compounds is not high, resulting in low yield and purity of the product.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions:

[0006] The present invention discloses a green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole, which specifically comprises the following steps:

[0007] Step 1) Mix aromatic aldehyde, thiosemicarbazide and ethanol, then heat up and monitor by TLC until the reaction is complete. Pour the reaction solution into ice water to precipitate solid. Filter by suction and dry the filter cake to obtain a crude intermediate compound. The crude product is recrystallized from ethanol to obtain a pure intermediate compound.

[0008] The structural formula of the intermediate compound is as follows:

[0009]

[0010] Step 2) Take the intermediate compound generated in step (1), add ionic liquid, stir, and heat. Monitor the reaction progress by TLC until the reaction is complete; pour the reaction solution into ice water to precipitate solid. Filter by suction, and dry the filter cake to obtain a crude 2-amino-5-aryl-1,3,4-thiadiazole. The crude product is recrystallized from ethanol to obtain a pure 2-amino-5-aryl-1,3,4-thiadiazole.

[0011] The liquid phase reaction of step 1) is a typical condensation reaction, in which the carbonyl group of the aromatic aldehyde reacts with the amino group and the thiocarbonyl group of the thiosemicarbazide to form a new chemical bond. After the reaction is completed, the reaction solution is poured into ice water. Since the solubility of the product in cold water is small, solids will precipitate. The crude product of the intermediate compound is obtained by suction filtration and drying. In order to further improve the purity of the product, the crude product is recrystallized using ethanol to obtain a pure product of the intermediate compound.

[0012] In the above step 2), the intermediate compound undergoes a cyclization reaction under the catalysis of the ionic liquid to generate the target product 2-amino-5-aryl-1,3,4-thiadiazole. This reaction is a cyclization reaction, in which the amino group and the thiocarbonyl group of the intermediate compound react under the catalysis of the ionic liquid to form a thiadiazole ring. Similarly, after the reaction is completed, the reaction solution is poured into ice water to precipitate a solid. The crude product of the target product is obtained by suction filtration and drying. In order to further improve the purity of the product, the crude product is recrystallized again using ethanol.

[0013] Furthermore, in the steps, the reaction formula of the reaction is shown below:

[0014]

[0015] Further, the molar ratio of aromatic aldehyde, thiosemicarbazide and ethanol is 1.0:(1.0-1.2):

[0016] (0.5~1.0).

[0017] Further, in step 1), the aromatic aldehyde includes benzaldehyde, p-fluorobenzaldehyde, p-chlorobenzaldehyde, 2,4-dichlorobenzaldehyde, p-nitrobenzaldehyde, 3,5-dinitrobenzaldehyde and 4-pyridinecarboxaldehyde.

[0018] Furthermore, the temperature in step 1) is raised to 50-60°C.

[0019] In step 1), the condensation reaction of aromatic aldehyde and thiosemicarbazide in ethanol is mainly to generate an intermediate compound. This reaction requires a certain temperature to promote the molecular motion of the reactants, increase the collision frequency, and thus increase the reaction rate. At the same time, ethanol as a solvent has a low boiling point, so the reaction temperature cannot be too high, so as to avoid a large amount of ethanol volatilization affecting the reaction. Therefore, the temperature of step 1) is controlled at 50-60° C. This temperature range can both ensure the reaction rate and avoid a large amount of solvent volatilization.

[0020] Further, in step 2), the molar ratio of the intermediate compound to the ionic liquid is 1.0:

[0021] (0.5~2.0).

[0022] Furthermore, in the step 2), the ionic liquid catalyst used in the reaction is a 1-alkylimidazo[1,2-a]pyridinium salt ionic liquid, the structural formula of which is shown below:

[0023]

[0024] Furthermore, the temperature in step 2) is raised to 50-55°C.

[0025] Step 2) is a cyclization reaction of the intermediate compound with 1-alkyl imidazo[1,2-a]pyridinium salt ionic liquid to generate 2-amino-5-aryl-1,3,4-thiadiazole. This reaction requires higher energy to break certain chemical bonds and form new chemical bonds. However, too high a temperature can also lead to unfavorable factors such as decomposition of reactants or intermediates and increase in side reactions. Therefore, the temperature of step 2) is controlled at 50-55°C. This temperature range can both promote the cyclization reaction and avoid the occurrence of unfavorable factors.

[0026] Furthermore, the reactants in step 1) and step 2) are mixed and then monitored by TLC using petroleum ether and ethyl acetate in a volume ratio of 3:1 as a developing solvent.

[0027] Furthermore, ethanol with a mass fraction of 50%-75% is used.

[0028] Further, in step 1), aromatic aldehyde, thiosemicarbazide and ethanol are placed in a dry three-necked flask for mixing and reaction.

[0029] Further, the structural formula of 2-amino-5-aryl-1,3,4-thiadiazole is shown below:

[0030]

[0031]

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] The present invention provides a green synthesis method of 2-amino-5-aryl 1,3,4-thiadiazole. First, in an ethanol solution, aromatic aldehyde and thiosemicarbazide are used as reactants to obtain a pure intermediate compound through a liquid phase reaction. Since aromatic aldehyde is used as a reactant, aromatic aldehyde introduces an aromatic group, so that the pure intermediate compound has high chemical stability, thereby improving the chemical stability and substrate adaptability of the product; secondly, 1-alkyl imidazo [1,2-a] pyridinium salt ionic liquid is used to catalyze the self-cyclization reaction of the reaction intermediate, and high-yield and high-purity 2-amino-5-aryl 1,3,4-thiadiazole is obtained. Experiments show that the product obtained by the synthesis method not only has a yield of up to 96.7%, but also has the characteristics of a high melting point, indicating that the purity of the product is high. Among them, 1-alkyl imidazo[1,2-a]pyridinium salt ionic liquid is introduced into the crude intermediate compound. On the one hand, the ionic liquid can provide effective proton supply, promote the reaction, and improve the selectivity and yield of the product, so that the purity and yield of the product are higher; on the other hand, the reusability of the ionic liquid reduces the burden on the environment and reduces energy consumption; on the other hand, the ionic liquid can be recovered from the product by simple phase separation, which is convenient for the purification process. Experiments have shown that the ionic liquid used in this preparation method can still maintain high yield and high purity after continuous recovery and reuse. Finally, the reaction solution is poured into ice water to precipitate the solid, and then the product is purified by suction filtration and recrystallization. This method not only simplifies the complex post-processing process in traditional organic synthesis, such as extraction, washing, etc., but also improves the purity of the product.

[0034] Furthermore, in the synthesis method of the present invention, the aromatic aldehydes include benzaldehyde, p-fluorobenzaldehyde, p-chlorobenzaldehyde, 2,4-dichlorobenzaldehyde, p-nitrobenzaldehyde, 3,5-dinitrobenzaldehyde and 4-pyridinecarboxaldehyde, which greatly improves the substrate adaptability of the product. Experiments show that the yield of the product in the preparation method is still as high as 96.7% in the synthesis of different aromatic aldehyde substances. It can be seen that the product of the present invention has good substrate adaptability.

[0035] Furthermore, the synthesis method of the present invention is carried out at a relatively mild temperature, which saves energy and improves the selectivity of the product. Specifically, a lower reaction temperature means lower energy consumption, which is more in line with the principle of green chemistry, and mild conditions can reduce the occurrence of side reactions and improve the purity and yield of the target product.

[0036] Furthermore, the synthesis method of the present invention uses 50%-75% ethanol as a renewable green solvent, which can reduce pollution to the environment and conform to the concept of green chemistry. In addition, ethanol is easy to recycle and reuse, which helps to reduce production costs and environmental burden. In the recrystallization step, the use of 50%-75% ethanol helps to obtain a higher purity product. The moderate concentration of ethanol can dissolve impurities more effectively, thereby removing them during the crystallization process and improving the purity of the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 This is the IR spectrum of 2-amino-5-phenyl-1,3,4-thiadiazole;

[0038] Figure 2 This is the IR spectrum of 2-amino-5-p-fluorophenyl-1,3,4-thiadiazole;

[0039] Figure 3 This is the IR spectrum of 2-amino-5-p-chlorophenyl-1,3,4-thiadiazole;

[0040] Figure 4 This is the IR spectrum of 2-amino-5-(2,4-dichlorophenyl)-1,3,4-thiadiazole;

[0041] Figure 5 This is the IR spectrum of 2-amino-5-p-nitrophenyl-1,3,4-thiadiazole;

[0042] Figure 6 This is the IR spectrum of 2-amino-5-(3,5-dinitrophenyl)-1,3,4-thiadiazole;

[0043] Figure 7 This is the IR spectrum of 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole. DETAILED DESCRIPTION

[0044] In order to enable those skilled in the art to better understand the scheme of the present invention, the technical scheme in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention.

[0045] It should be noted that the terms "first", "second", etc. in the specification and claims of the present invention and the above-mentioned drawings are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the data used in this way can be interchanged where appropriate, so that the embodiments of the present invention described herein can be implemented in an order other than those illustrated or described herein. In addition, the terms "including" and "having" and any variations thereof are intended to cover non-exclusive inclusions, for example, a process, method, system, product or device that includes a series of steps or units is not necessarily limited to those steps or units that are clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or devices.

[0046] The present invention is further described in detail below in conjunction with specific examples of the present invention:

[0047] Example 1

[0048] (1) Add 0.1 mol benzaldehyde, 0.1 mol thiosemicarbazide and 0.1 mol 75% ethanol to a dry three-necked flask, then heat to 60°C for reaction and monitor by TLC until the reaction is complete. Pour the reaction solution into ice water to precipitate solid. Filter by suction and dry the filter cake to obtain a crude intermediate compound. Recrystallize the crude product from ethanol to obtain a pure intermediate compound.

[0049] (2) Take 0.1 mol of the intermediate compound generated in step (1), add 0.05 mol of 1-n-butylimidazo[1,2-a]pyridinium bromide ionic liquid ([C4impy][Br]), stir, and heat to 55°C for reaction. Monitor the progress of the reaction by TLC until the reaction is complete; pour the reaction solution into ice water to precipitate solid. Filter by suction, and dry the filter cake to obtain crude 2-amino-5-phenyl-1,3,4-thiadiazole. The crude product is recrystallized from ethanol to obtain pure 2-amino-5-phenyl-1,3,4-thiadiazole. White needle-shaped crystals, yield 92.4%, mp: 218.2-220.6°C. The structure of 2-amino-5-phenyl-1,3,4-thiadiazole is as follows:

[0050]

[0051] Example 2

[0052] (1) Add 0.1 mol benzaldehyde, 0.15 mol thiosemicarbazide and 0.1 mol 75% ethanol to a dry three-necked flask, then heat to 50°C for reaction and monitor by TLC until the reaction is complete. Pour the reaction solution into ice water to precipitate solid. Filter by suction and dry the filter cake to obtain a crude intermediate compound. The crude product is recrystallized from ethanol to obtain a pure intermediate compound;

[0053] (2) Take 0.1 mol of the intermediate compound generated in step (1), add 0.1 mol of 1-n-butylimidazo[1,2-a]pyridinium bromide ionic liquid ([C4impy][Br]), stir, and heat to 50°C for reaction. Monitor the reaction progress by TLC until the reaction is complete; pour the reaction solution into ice water to precipitate solid. Filter by suction, and dry the filter cake to obtain crude 2-amino-5-phenyl-1,3,4-thiadiazole. The crude product is recrystallized from ethanol to obtain pure 2-amino-5-phenyl-1,3,4-thiadiazole. White needle-shaped crystals, yield 96.3%, mp: 218.2-221.0°C.

[0054] Figure 1 The IR spectrum of 2-amino-5-phenyl-1,3,4-thiadiazole in Examples 1 and 2 is shown in Figure 1. The absorption peak at 3267 cm -1 , 2944cm -1 (νsN-H,s); 3039cm -1 (ν benzene ring CH, s); 1589cm -1 , 1505cm -1 ,1454cm -1 , (ν benzene ring C = C, s); 1671cm -1 ,1640cm -1 (νthiadiazole ring C=N,s); 1369cm -1 (m), 1245cm -1 (m) is (νC-N)+(δN-H); 1032cm -1 ,1002cm -1 ,482cm -1 (ν thiadiazole ring NCS, w); 742 cm -1 ,618cm -1 (δC-H in-plane bending vibration on the benzene ring), proving that the product is 2-amino-5-phenyl-1,3,4-thiadiazole.

[0055] Example 3

[0056] (1) Add 0.1 mol of p-fluorobenzaldehyde, 0.1 mol of thiosemicarbazide and 0.05 mol of 70% ethanol to a dry three-necked flask, then heat to 55°C for reaction and monitor by TLC until the reaction is complete. Pour the reaction solution into ice water to precipitate solids. Filter by suction and dry the filter cake to obtain a crude intermediate compound. The crude product is recrystallized from ethanol to obtain a pure intermediate compound.

[0057] (2) Take 0.1 mol of the intermediate compound generated in step (1), add 0.2 mol of 1-n-butylimidazo[1,2-a]pyridine bistrifluoromethanesulfonic acid imine salt ionic liquid ([C4impy][TFSI]), stir, and heat to 55°C for reaction. Monitor the reaction progress by TLC until the reaction is complete; pour the reaction solution into ice water to precipitate solid. Filter by suction, and dry the filter cake to obtain crude 2-amino-5-p-fluorophenyl-1,3,4-thiadiazole. After the crude product is recrystallized from ethanol, pure 2-amino-5-p-fluorophenyl-1,3,4-thiadiazole is obtained. White needle-shaped crystals, yield 92.7%, mp: 211.1-212.6°C.

[0058] Figure 2 The IR spectrum of 2-amino-5-p-fluorophenyl-1,3,4-thiadiazole in Example 3 shows the absorption peak at 3391 cm -1 ,3317cm -1 (νN-H,s); 3206cm -1 (ν benzene ring CH, s); 1602cm -1 (νthiadiazole ring C=N,s); 1176cm -1 (δ thiadiazole ring, m); 1414 cm -1 (νC-N,s); 802cm -1 (νC-SC,w), proving that the product is 2-amino-5-p-fluorophenyl-1,3,4-thiadiazole. The structure of 2-amino-5-p-fluorophenyl-1,3,4-thiadiazole is as follows:

[0059]

[0060] Example 4

[0061] (1) Add 0.1 mol of p-chlorobenzaldehyde, 0.12 mol of thiosemicarbazide and 0.1 mol of 75% ethanol to a dry three-necked flask, then heat to 55°C for reaction and monitor by TLC until the reaction is complete. Pour the reaction solution into ice water to precipitate solids. Filter by suction and dry the filter cake to obtain a crude intermediate compound. The crude product is recrystallized from ethanol to obtain a pure intermediate compound;

[0062] (2) Take 0.1 mol of the intermediate compound generated in step (1), add 0.2 mol of 1-n-hexyl imidazo[1,2-a]pyridine bistrifluoromethanesulfonic acid imine salt ionic liquid ([C6impy][TFSI]), stir, and heat to 50°C for reaction. Monitor the reaction progress by TLC until the reaction is complete; pour the reaction solution into ice water to precipitate solid. Filter by suction, and dry the filter cake to obtain crude 2-amino-5-p-chlorophenyl-1,3,4-thiadiazole. After the crude product is recrystallized from ethanol, pure 2-amino-5-p-chlorophenyl-1,3,4-thiadiazole is obtained. White needle-shaped crystals, yield 96.7%, mp: 225.9-227.6°C.

[0063] Figure 3 The IR spectrum of 2-amino-5-p-chlorophenyl-1,3,4-thiadiazole in Example 4 is shown by the absorption peak at 3261 cm -1 ,2962cm -1 (νsN-H,s); 3082cm -1 (ν benzene ring CH, s); 1633cm -1 (νthiadiazole ring C=N,s); 1383cm -1 (νC-N); 1261cm -1 (νN-H,s); 692cm -1 (νC-SC,w), proving that the product is 2-amino-5-p-chlorophenyl-1,3,4-thiadiazole. The structure of 2-amino-5-p-chlorophenyl-1,3,4-thiadiazole is as follows:

[0064]

[0065] Example 5

[0066] (1) Add 0.1 mol 2,4-dichlorobenzaldehyde, 0.1 mol thiosemicarbazide and 0.15 mol 60% ethanol to a dry three-necked flask, then heat to 60°C for reaction and monitor by TLC until the reaction is complete. Pour the reaction solution into ice water to precipitate solid. Filter by suction and dry the filter cake to obtain a crude intermediate compound. The crude product is recrystallized from ethanol to obtain a pure intermediate compound;

[0067] (2) Take 0.1 mol of the intermediate compound generated in step (1), add 0.2 mol of 1-n-butylimidazo[1,2-a]pyridinebisfluorosulfonic acid imide salt ionic liquid ([C4impy][FSI]), stir, and heat to 50°C for reaction. Monitor the reaction progress by TLC until the reaction is complete; pour the reaction solution into ice water to precipitate solid. Filter by suction, and dry the filter cake to obtain crude 2-amino-5-(2,4-dichlorophenyl)-1,3,4-thiadiazole. The crude product is recrystallized from ethanol to obtain pure 2-amino-5-(2,4-dichlorophenyl)-1,3,4-thiadiazole. White needle-shaped crystals, yield 95.4%, mp: 250.3-253.6°C.

[0068] Figure 4 The IR spectrum of 2-amino-5-(2,4-dichlorophenyl)-1,3,4-thiadiazole in Example 5, with the absorption peak at 3296 cm -1 ,3115cm -1 (νN-H,s); 1658cm -1 (νthiadiazole ring C=N,s); 1149cm -1 (δ thiadiazole ring, m); 1277 cm -1 (νC-N,s); 775cm -1 (νC-SC,w), proving that the product is 2-amino-5-(2,4-dichlorophenyl)-1,3,4-thiadiazole. The structure of 2-amino-5-(2,4-dichlorophenyl)-1,3,4-thiadiazole is as follows:

[0069]

[0070] Example 6

[0071] (1) Add 0.1 mol of p-nitrobenzaldehyde, 0.12 mol of thiosemicarbazide and 0.15 mol of 75% ethanol to a dry three-necked flask, then heat to 50°C for reaction and monitor by TLC until the reaction is complete. Pour the reaction solution into ice water to precipitate solid. Filter by suction and dry the filter cake to obtain a crude intermediate compound. The crude product is recrystallized from ethanol to obtain a pure intermediate compound;

[0072] (2) Take 0.1 mol of the intermediate compound generated in step (1), add 0.2 mol of 1-octyl imidazo[1,2-a]pyridine bisfluorosulfonic acid imide salt ionic liquid ([C8impy][FSI]), stir, and heat to 55°C for reaction. Monitor the reaction progress by TLC until the reaction is complete; pour the reaction solution into ice water to precipitate solid. Filter by suction, and dry the filter cake to obtain crude 2-amino-5-p-nitrophenyl-1,3,4-thiadiazole. After the crude product is recrystallized from ethanol, pure 2-amino-5-p-nitrophenyl-1,3,4-thiadiazole is obtained. White needle-shaped crystals, yield 95.4%, mp: 250.3-253.6°C.

[0073] Figure 5 The IR spectrum of 2-amino-5-p-nitrophenyl-1,3,4-thiadiazole in Example 6, with the absorption peak at 3423 cm -1 ,3285cm -1 (νsN-H,s); 3103cm -1 (v benzene ring CH, s); 1626cm -1 (νthiadiazole ring C=N,s); 1271cm -1 (νC-N,s); 715cm -1 (νC-SC,w), proving that the product is 2-amino-5-p-nitrophenyl-1,3,4-thiadiazole. The structure of 2-amino-5-p-nitrophenyl-1,3,4-thiadiazole is as follows:

[0074]

[0075] Example 7

[0076] (1) Add 0.1 mol 3,5-dinitrobenzaldehyde, 0.12 mol thiosemicarbazide and 0.15 mol 75% ethanol to a dry three-necked flask, then heat to 55°C for reaction and monitor by TLC until the reaction is complete. Pour the reaction solution into ice water to precipitate solid. Filter by suction and dry the filter cake to obtain a crude intermediate compound. The crude product is recrystallized from ethanol to obtain a pure intermediate compound;

[0077] (2) Take 0.1 mol of the intermediate compound generated in step (1), add 0.2 mol of 1-n-butylimidazo[1,2-a]pyridine dicyanoimide salt ionic liquid ([C4impy][N(CN)2]), stir, and heat to 55°C for reaction. Monitor the reaction progress by TLC until the reaction is complete; pour the reaction solution into ice water to precipitate solid. Filter by suction, and dry the filter cake to obtain crude 2-amino-5-(3,5-dinitrophenyl)-1,3,4-thiadiazole. After the crude product is recrystallized from ethanol, pure 2-amino-5-(3,5-dinitrophenyl)-1,3,4-thiadiazole is obtained. White needle-shaped crystals, yield 92.1%, mp: 248.6-251.7°C.

[0078] Figure 6 The IR spectrum of 2-amino-5-(3,5-dinitrophenyl)-1,3,4-thiadiazole in Example 7, with the absorption peak at 3425 cm -1 ,3266cm -1 (νN-H,s); 3085cm -1 (ν benzene ring CH, s); 1627cm -1 (νthiadiazole ring C=N,s); 1134cm -1 (δ thiadiazole ring, m); 1343 cm -1 (νC-N,s); 724cm -1 (νC-SC,w), proving that the product is 2-amino-5-(3,5-dinitrophenyl)-1,3,4-thiadiazole. The structure of 2-amino-5-(3,5-dinitrophenyl)-1,3,4-thiadiazole is as follows:

[0079]

[0080] Example 8

[0081] (1) Add 0.1 mol 4-pyridinecarboxaldehyde, 0.12 mol thiosemicarbazide and 0.15 mol 50% ethanol to a dry three-necked flask, then heat to 60°C for reaction and monitor by TLC until the reaction is complete. Pour the reaction solution into ice water to precipitate solid. Filter by suction and dry the filter cake to obtain a crude intermediate compound. The crude product is recrystallized from ethanol to obtain a pure intermediate compound;

[0082] (2) Take 0.1 mol of the intermediate compound generated in step (1), add 0.2 mol of 1-n-hexyl imidazo[1,2-a]pyridine dicyanoimide salt ionic liquid [C6impy][N(CN)2], stir, and heat to 50°C for reaction. Monitor the reaction progress by TLC until the reaction is complete; pour the reaction solution into ice water to precipitate solid. Filter by suction, and dry the filter cake to obtain crude 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole. The crude product is recrystallized from ethanol to obtain pure 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole. White needle-shaped crystals, yield 94.6%, mp: 210.3-212.9°C.

[0083] Figure 7 The IR spectrum of 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole in Example 8, with the absorption peak at 3298 cm -1 (νN-H,s); 3091cm -1 ,1510cm-1,685cm -1 (νpyridine, m); 1678cm -1 ,1620cm -1 (νthiadiazole ring C=N,s); 1193cm -1 (δ thiadiazole ring, m); 1023 cm -1 ,742cm -1 ,615cm -1 ,572cm -1 ,522cm -1 (ν thiadiazole ring NCS, w), it is proved that the product is 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole. The structure of 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole is as follows:

[0084]

[0085] Example 9

[0086] The 1-n-butylimidazo[1,2-a]pyridinium bromide ionic liquid ([C4impy][Br]) in Example 1 was used as a catalyst, which was continuously recovered and reused. When other conditions were unchanged, Example 1 was repeated 5 times. The results are shown in the following table:

[0087]

[0088] Example 10

[0089] The 1-n-hexyl imidazo[1,2-a]pyridine bistrifluoromethanesulfonic acid imide salt ionic liquid ([C6impy][TFSI]) in Example 4 was continuously recovered and reused. When other conditions were unchanged, Example 4 was repeated 5 times. The results are shown in the following table:

[0090]

[0091] In summary, in Example 9 and Example 10, when other conditions remain unchanged, the 1-n-butylimidazo[1,2-a]pyridinium bromide ionic liquid and the 1-n-hexylimidazo[1,2-a]pyridinium bistrifluoromethanesulfonic acid imide ionic liquid are continuously recovered and reused to participate in the synthesis reaction, and products with high yield and high melting point can still be obtained, indicating that the ionic liquid has excellent reusability.

[0092] Embodiment 11

[0093] Using 1-n-butylimidazo[1,2-a]pyridinium bromide ionic liquid ([C4impy][Br])[PPh3][TfOH] ionic liquid, concentrated sulfuric acid-concentrated phosphoric acid, concentrated sulfuric acid-phosphorus oxychloride, and concentrated sulfuric acid-phosphorus oxychloride as catalysts, respectively, and other conditions remain unchanged, Example 1 is carried out, and the results are as follows:

[0094]

[0095] It can be seen from the above chart that in the synthesis reaction of 2-amino-5-aryl-1,3,4-thiadiazole using different types of ionic liquids, it can be seen that the yield of the product synthesized by catalysis of 1-n-butylimidazo[1,2-a]pyridinium bromide ionic liquid ([C4impy][Br]) is higher, indicating that the catalytic ability of the ionic liquid used in the present invention is stronger.

[0096] The above contents are only for explaining the technical idea of ​​the present invention and cannot be used to limit the protection scope of the present invention. Any changes made on the basis of the technical solution in accordance with the technical idea proposed by the present invention shall fall within the protection scope of the claims of the present invention.

Claims

1. A green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole, characterized in that: The following steps are involved: Step 1) mixing aromatic aldehyde, thiosemicarbazide and ethanol, then heating, filtering after solid precipitation, to obtain an intermediate compound; The structural formula of the intermediate compound is as follows: Step 2) The intermediate compound and 1-alkylimidazo[1,2-a]pyridinium salt ionic liquid are mixed, and then the temperature is increased. After the solid is precipitated, it is filtered to obtain 2-amino-5-aryl-1,3,4-thiadiazole.

2. A green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole according to claim 1, characterized in that: In step (1), the molar ratio of aromatic aldehyde, thiosemicarbazide and ethanol is 1.0:(1.0-1.2):(0.5-1.0).

3. A green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole according to claim 1, characterized in that: In step 1), the aromatic aldehydes include benzaldehyde, p-fluorobenzaldehyde, p-chlorobenzaldehyde, 2,4-dichlorobenzaldehyde, p-nitrobenzaldehyde, 3,5-dinitrobenzaldehyde and 4-pyridinecarboxaldehyde.

4. A green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole according to claim 1, characterized in that: The temperature in step 1) is raised to 50-60°C.

5. A green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole according to claim 1, characterized in that: In step 2), the molar ratio of the intermediate compound to the 1-alkylimidazo[1,2-a]pyridinium salt ionic liquid is 1.0:(0.5-2.0).

6. A green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole according to claim 1, characterized in that: In step 2), the 1-alkylimidazo[1,2-a]pyridinium salt ionic liquid includes a substance having the following structural formula:

7. A green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole according to claim 1, characterized in that: The temperature in step 2) is raised to 50-55°C.

8. The green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole according to claim 1, characterized in that: The reactants in step 1) and step 2) are mixed and then monitored by TLC using petroleum ether and ethyl acetate as developing solvents.

9. A green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole according to claim 1, characterized in that: The ethanol with a mass fraction of 50%-75% is used.

10. A green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole according to claim 1, characterized in that: The structural formula of 2-amino-5-aryl-1,3,4-thiadiazole is as follows:

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