A green synthetic process of 2-amino-5-aryl-1,3,4-thiadiazoles

Abstract

The application discloses a green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole and belongs to the technical field of chemical synthesis. The specific steps comprise the following steps: mixing aryl aldehyde, thiosemicarbazide and ethanol, then performing solid separation after temperature rising, performing suction filtration to obtain an intermediate compound, and then performing cyclization reaction on the intermediate compound and ionic liquid to obtain 2-amino-5-aryl-1,3,4-thiadiazole, and the yield can reach more than 96%. The application has the characteristics of high reaction efficiency, short reaction time, mild reaction condition, recyclable catalyst, strong catalytic capacity and green energy saving. The application solves the technical problems that the catalyst cannot be recycled and has weak catalytic capacity in the traditional synthesis method, the substrate has poor adaptability in the synthesis process, and the chemical stability of the used compound is not high, so that the yield and purity of the product are not high.

Description

TECHNICAL FIELD

[0001] The present application 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

[0002] The structure of 2-amino-5-aryl-1,3,4-thiadiazole contains an amino group (-NH2) and an aryl group, which makes it have certain biological activity and chemical properties. In the field of agriculture, it can be used as a pesticide ingredient for developing new insecticides or fungicides. In the field of medicine, 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 as a material that can be used to synthesize new polymers or composite materials, enhancing the heat resistance and mechanical strength of the material.

[0003] So far, various routes have been developed for the synthesis of 2-amino-5-aryl-1,3,4-thiadiazole. However, most of them use concentrated sulfuric acid, concentrated hydrochloric acid, polyphosphoric acid and other dehydrating agents to catalyze the synthesis, and some use phosphorus oxychloride and phosphorus pentachloride to catalyze the synthesis. First, these substances have strong corrosive properties, and the reaction equipment and operating environment require extremely high requirements. Any slight negligence may cause equipment damage or safety accidents. Second, these dehydrating agents may produce harmful gases during operation, and compounds such as phosphorus oxychloride and phosphorus pentachloride have high toxicity, which poses a serious threat to the health of operators. Third, the use of these substances usually requires high reaction temperature and pressure, which increases the difficulty of reaction control and energy consumption. Fourth, harsh reaction conditions can lead to an increase in side reactions, reducing 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 this synthesis method cannot be recycled and has weak catalytic ability. The substrate adaptability of the product is poor during the synthesis process, and the chemical stability of the reactants is not high, resulting in low yield and purity of the product. SUMMARY

[0004] In order to overcome the shortcomings of the prior art, the purpose of the present application is to provide a green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole, which solves the technical problems of the catalyst in the traditional synthesis method that cannot be recycled and has weak catalytic ability, poor substrate adaptability during the synthesis process, and low chemical stability of the compounds used, resulting in low yield and purity of the product.

[0005] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows:

[0006] The application discloses a green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole, and specifically comprises the following steps.

[0007] Step 1) mixing an aromatic aldehyde, a thiosemicarbazide and ethanol, then heating, and monitoring the reaction completion through TLC; pouring the reaction solution into ice water to precipitate a solid; performing suction filtration on the filter cake, and drying the filter cake to obtain a crude intermediate compound; and recrystallizing the crude intermediate compound in ethanol to obtain a pure intermediate compound;

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

[0009]

[0010] Step 2) adding an ionic liquid to the intermediate compound obtained in step 1), stirring and heating; monitoring the reaction progress through TLC until the reaction is completed; pouring the reaction solution into ice water to precipitate a solid; performing suction filtration on the filter cake, and drying the filter cake to obtain a crude 2-amino-5-aryl-1,3,4-thiadiazole; and recrystallizing the crude 2-amino-5-aryl-1,3,4-thiadiazole in ethanol to obtain a pure 2-amino-5-aryl-1,3,4-thiadiazole.

[0011] The liquid-phase reaction in 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 new chemical bonds. After the reaction is completed, the reaction solution is poured into ice water, and the product precipitates due to its low solubility in cold water. The crude intermediate compound is obtained through suction filtration and drying. In order to further improve the purity of the product, the crude product is recrystallized in ethanol to obtain the pure intermediate compound.

[0012] In 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, and the product precipitates. The crude target product is obtained through suction filtration and drying. In order to further improve the purity of the product, the crude product is recrystallized in ethanol again.

[0013] Further, the reaction formula of the reaction in the step is as shown in the following formula:

[0014]

[0015] Further, the molar ratio of the aromatic aldehyde, the thiosemicarbazide and the 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-pyridine carboxaldehyde.

[0018] Further, in step 1), the temperature is raised to 50-60℃.

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

[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] Further, in step 2), the ionic liquid catalyst used in the reaction is 1-alkyl imidazo[1,2-a]pyridine salt ionic liquid, the structure of which is shown as follows:

[0023]

[0024] Further, in step 2), the temperature is raised to 50-55℃.

[0025] Step 2) is the cyclization reaction of the intermediate compound and 1-alkyl imidazo[1,2-a]pyridine salt ionic liquid to generate 2-amino-5-aryl-1,3,4-thiadiazole. This reaction requires higher energy to break some chemical bonds and form new chemical bonds. However, too high a temperature will also cause the decomposition of the reactants or intermediates, increase the side reactions, and other adverse factors. Therefore, the temperature of step 2) is controlled at 50-55℃, which can promote the cyclization reaction and avoid the occurrence of adverse factors.

[0026] Further, after mixing the reactants in steps 1) and 2), petroleum ether and ethyl acetate with a volume ratio of 3:1 are used as the developing agent for TLC monitoring.

[0027] Further, 50%-75% ethanol by mass fraction is used.

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

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

[0030]

[0031]

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

[0033] The present application provides a green synthesis method of 2-amino-5-aryl-1,3,4-thiadiazole, first, in the ethanol solution, with aromatic aldehyde and thiosemicarbazide as reactants, through liquid phase reaction, the intermediate compound pure product is obtained, because the aromatic aldehyde is used as the reactant, the aromatic aldehyde introduces the aryl group, so that the intermediate compound pure product has high chemical stability, and further improve the chemical stability of the product and the substrate adaptability, second, the 1-alkyl imidazo[1,2-a] pyridine salt ionic liquid is used to catalyze the self-cyclization reaction of the intermediate, and the high yield and high purity 2-amino-5-aryl-1,3,4-thiadiazole is prepared. Experiments show that the product prepared by the synthesis method has a yield of 96.7%, and has the characteristics of high melting point, which indicates that the product has high purity. Among them, the 1-alkyl imidazo[1,2-a] pyridine salt ionic liquid is introduced into the intermediate compound crude product, first, 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, second, the reusability of the ionic liquid reduces the burden on the environment and reduces energy consumption, third, the ionic liquid can be recovered from the product by simple phase separation, which is convenient for the purification process. Experiments show that the ionic liquid used in the preparation method can maintain high yield and high purity after continuous recovery and repeated use. Finally, the reaction liquid is poured into ice water to precipitate the solid, and then the product is purified by suction filtration and recrystallization, which 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] Further, in the synthesis method of the present application, the aromatic aldehyde includes benzaldehyde, p-fluorobenzaldehyde, p-chlorobenzaldehyde, 2,4-dichlorobenzaldehyde, p-nitrobenzaldehyde, 3,5-dinitrobenzaldehyde and 4-pyridine formaldehyde, which greatly improves the substrate adaptability of the product. Experiments show that the product in the preparation method has a yield of 96.7% in the synthesis of different aromatic aldehyde substances, which shows that the product of the present application has good substrate adaptability.

[0035] Further, the synthetic method of the present application is carried out at relatively mild temperature, which is energy saving and improves the selectivity of the product. Specifically, lower reaction temperature means lower energy consumption, which is more in line with the principles of green chemistry. Mild conditions can reduce the occurrence of side reactions, improve the purity and yield of the target product.

[0036] Further, the synthetic method of the present application uses 50%-75% ethanol as a renewable green solvent, which can reduce environmental pollution and meet 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 product with higher purity. The moderate concentration of ethanol can more effectively dissolve impurities, thereby removing them during the crystallization process and improving the purity of the product. BRIEF DESCRIPTION OF DRAWINGS

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

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

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

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

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

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

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

[0044] In order for those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be described clearly and completely below in conjunction with the accompanying drawings of the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor should be within the scope of protection of the present application.

[0045] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments of the application only and is not intended to be limiting of the present application. For example, unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the present disclosure, and will not be interpreted in an overly literal or overly formal sense unless expressly so defined herein.

[0046] The present application is further described in detail by reference to specific examples of the application.

[0047] Example 1

[0048] (1) Into a dry three-necked flask, 0.1 mol of benzaldehyde, 0.1 mol of thiosemicarbazide and 0.1 mol of 75% ethanol were added, and then the reaction was carried out at 60°C, and the reaction was monitored by TLC until the reaction was completed. The reaction solution was poured into ice water to precipitate a solid. The solid was filtered and dried to obtain an intermediate compound in a crude form. The crude product was recrystallized from ethanol to obtain an intermediate compound in a pure form.

[0049] (2) 0.1 mol of the intermediate compound obtained in the step (1) was added with 0.05 mol of 1-n-butylimidazo[1,2-a]pyridine bromide ionic liquid ([C4impy][Br]), and then the reaction was carried out at 55°C. The reaction was monitored by TLC until the reaction was completed. The reaction solution was poured into ice water to precipitate a solid. The solid was filtered and dried to obtain 2-amino-5-phenyl-1,3,4-thiadiazole in a crude form. The crude product was recrystallized from ethanol to obtain 2-amino-5-phenyl-1,3,4-thiadiazole in a pure form. White needle-like crystal, yield 92.4%, m.p.: 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) Into a dry three-necked flask, 0.1 mol of benzaldehyde, 0.15 mol of thiosemicarbazide and 0.1 mol of 75% ethanol were added, and then the reaction was carried out at 50°C, and the reaction was monitored by TLC until the reaction was completed. The reaction solution was poured into ice water to precipitate a solid. The solid was filtered and dried to obtain an intermediate compound in a crude form. The crude product was recrystallized from ethanol to obtain an intermediate compound in a pure form.

[0053] (2) Take the intermediate compound generated in step (1) 0.1 mol, add 0.1 mol 1-n-butyl imidazo [1,2-a] pyridine bromide salt ionic liquid ([C4impy] [Br]), stirring, warming to 50 °C reaction. TLC monitoring reaction progress, until the reaction is complete; pour the reaction into ice water, precipitate solid. Filter, filter cake drying, get 2-amino-5-phenyl-1,3,4-thiadiazole crude product. Crude product recrystallized from ethanol, 2-amino-5-phenyl-1,3,4-thiadiazole pure product; white needle-like crystals, yield 96.3%, m.p.: 218.2-221.0 °C.

[0054] Figure 1 For example 1, 2, 2-amino-5-phenyl-1,3,4-thiadiazole IR spectrum, by the absorption peak 3267 cm -1 , 2944 cm -1 (νsN-H, s); 3039 cm -1 (νbenzene ring C-H, s); 1589 cm -1 , 1505 cm -1 , 1454 cm -1 , (νbenzene ring C = C, s); 1671 cm -1 , 1640 cm -1 (νthiadiazole ring C = N, s); 1369 cm -1 (m), 1245 cm -1 (m) is (νC-N) + (δN-H); 1032 cm -1 , 1002 cm -1 , 482 cm -1 (νthiadiazole ring N-C-S, w); 742 cm -1 , 618 cm -1 (δC-H in-plane bending vibration on the benzene ring), to prove the product is 2-amino-5-phenyl-1,3,4-thiadiazole.

[0055] Example 3

[0056] (1) To a dry three-necked flask, add 0.1 mol of p-fluorobenzaldehyde, 0.1 mol of thiosemicarbazide and 0.05 mol of 70% ethanol, then warm to 55 °C reaction, TLC monitoring until the reaction is complete. Pour the reaction into ice water, precipitate solid. Filter, filter cake drying, get intermediate compound crude product. Crude product recrystallized from ethanol, intermediate compound pure product;

[0057] (2) Take the intermediate compound generated in step (1) 0.1 mol, add 0.2 mol 1-n-butyl imidazo [1,2-a] pyridine bis trifluoromethanesulfonate imidazolium salt ionic liquid ([C4impy] [TFSI]), stirring, warming to 55°C reaction. TLC monitoring reaction progress, until the reaction is complete; pour the reaction into ice water, precipitate solid. Filter, filter cake drying, get 2-amino-5-p-fluorophenyl-1,3,4-thiadiazole crude product. Crude product recrystallized from ethanol, get 2-amino-5-p-fluorophenyl-1,3,4-thiadiazole pure product. White needle-like crystals, yield 92.7%, m.p.: 211.1-212.6°C.

[0058] Figure 2 For the IR spectrum of 2-amino-5-p-fluorophenyl-1,3,4-thiadiazole in Example 3, from the absorption peak: 3391 cm -1 ,3317cm -1 (νN-H,s); 3206 cm -1 (νphenyl ring C-H,s); 1602 cm -1 (νthiadiazole ring C=N,s); 1176 cm -1 (δthiadiazole ring, m); 1414 cm -1 (νC-N,s); 802 cm -1 (νC-S-C,w), prove that the product is 2-amino-5-p-fluorophenyl-1,3,4-thiadiazole. 2-amino-5-p-fluorophenyl-1,3,4-thiadiazole structure as follows:

[0059]

[0060] Example 4

[0061] (1) To a dry three-necked flask, add 0.1 mol p-chlorobenzaldehyde, 0.12 mol thiosemicarbazide and 0.1 mol 75% ethanol, then warming to 55°C reaction, TLC monitoring until the reaction is complete. Pour the reaction into ice water, precipitate solid. Filter, filter cake drying, get intermediate compound crude product. Crude product recrystallized from ethanol, get intermediate compound pure product;

[0062] (2) Take the intermediate compound generated in step (1) 0.1 mol, add 0.2 mol 1-n-hexyl imidazo[1,2-a]pyridine bis-trifluoromethanesulfonate imidazolium ionic liquid ([C6impy][TFSI]), stir, and heat to 50°C to react. Monitor the reaction progress by TLC until the reaction is complete; pour the reaction liquid into ice water to precipitate a solid. Filter, dry the filter cake, and obtain 2-amino-5-p-chlorophenyl-1,3,4-thiadiazole crude product. Recrystallize the crude product from ethanol to obtain 2-amino-5-p-chlorophenyl-1,3,4-thiadiazole pure product. White needle-like crystals, yield 96.7%, m.p.: 225.9-227.6°C.

[0063] Figure 3 For the IR spectrum of 2-amino-5-p-chlorophenyl-1,3,4-thiadiazole in Example 4, the absorption peaks at: 3261 cm -1 -1, 2962 cm -1 (νsN-H,s); 3082 cm -1 (νbenzene ring C-H,s); 1633 cm -1 (νthiadiazole ring C=N,s); 1383 cm -1 is (νC-N); 1261 cm -1 (νN-H,s); 692 cm -1 (νC-S-C,w) prove 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 to react, and monitor by TLC until the reaction is complete. Pour the reaction liquid into ice water to precipitate a solid. Filter, dry the filter cake, and obtain the intermediate compound crude product. Recrystallize the crude product from ethanol to obtain the intermediate compound pure product;

[0067] (2) Take the intermediate compound generated in step (1) 0.1 mol, add 0.2 mol 1-n-butyl imidazo[1,2-a]pyridine bisfluorosulfonate imidazolium salt ionic liquid ([C4impy][FSI]), stir, and warm to 50°C for reaction. Monitor the reaction progress by TLC until the reaction is complete; pour the reaction liquid into ice water to precipitate a solid. Filter, dry the filter cake, and obtain 2-amino-5-(2,4-dichlorophenyl)-1,3,4-thiadiazole crude product. Recrystallize the crude product from ethanol to obtain 2-amino-5-(2,4-dichlorophenyl)-1,3,4-thiadiazole pure product. White needle-like crystals, yield 95.4%, m.p.: 250.3-253.6°C.

[0068] Figure 4 For the IR spectrum of 2-amino-5-(2,4-dichlorophenyl)-1,3,4-thiadiazole in Example 5, the absorption peaks at 3296 cm -1 , 3115 cm -1 (νN-H, s); 1658 cm -1 (νthiadiazole ring C=N, s); 1149 cm -1 (δthiadiazole ring, m); 1277 cm -1 (νC-N, s); 775 cm -1 (νC-S-C, w) prove 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) Into a dry three-necked flask, add 0.1 mol of p-nitrobenzaldehyde, 0.12 mol of thiosemicarbazide, and 0.15 mol of 75% ethanol, then warm to 50°C for reaction, and monitor by TLC until the reaction is complete. Pour the reaction liquid into ice water to precipitate a solid. Filter, dry the filter cake, and obtain the intermediate compound crude product. Recrystallize the crude product from ethanol to obtain the intermediate compound pure product;

[0072] (2) Take the intermediate compound generated in step (1) 0.1 mol, add 0.2 mol 1-n-octyl imidazo[1,2-a]pyridine bisfluorosulfonate imidazolium ionic liquid ([C8impy][FSI]), stir, and warm to 55°C for reaction. Monitor the reaction progress by TLC until the reaction is complete; pour the reaction liquid into ice water to precipitate a solid. Filter, dry the filter cake, and obtain 2-amino-5-p-nitrophenyl-1,3,4-thiadiazole crude product. Recrystallize the crude product from ethanol to obtain 2-amino-5-p-nitrophenyl-1,3,4-thiadiazole pure product. White needle-like crystals, yield 95.4%, m.p.: 250.3-253.6°C.

[0073] Figure 5 For the IR spectrum of 2-amino-5-p-nitrophenyl-1,3,4-thiadiazole in Example 6, the absorption peaks at 3423 cm -1 , 3285 cm -1 (νsN-H,s); 3103 cm -1 (v benzene ring C-H,s); 1626 cm -1 (νthiadiazole ring C=N,s); 1271 cm -1 is (νC-N,s); 715 cm -1 (νC-S-C,w) prove 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) Into a dry three-necked flask, add 0.1 mol 3,5-dinitrobenzaldehyde, 0.12 mol thiosemicarbazide, and 0.15 mol 75% ethanol, then warm to 55°C for reaction, and monitor by TLC until the reaction is complete. Pour the reaction liquid into ice water to precipitate a solid. Filter, dry the filter cake, and obtain the intermediate compound crude product. Recrystallize the crude product from ethanol to obtain the intermediate compound pure product;

[0077] (2) Take the intermediate compound generated in step (1) 0.1 mol, add 0.2 mol 1-n-butyl imidazo[1,2-a]pyridine dicyano imine salt ionic liquid ([C4impy][N(CN)2]), stir, and warm to 55°C to react. Monitor the reaction progress by TLC until the reaction is complete; pour the reaction liquid into ice water to precipitate a solid. Filter, dry the filter cake, and obtain 2-amino-5-(3,5-dinitrophenyl)-1,3,4-thiadiazole crude product. Recrystallize the crude product from ethanol to obtain 2-amino-5-(3,5-dinitrophenyl)-1,3,4-thiadiazole pure product. White needle-like crystals, yield 92.1%, m.p.: 248.6-251.7°C.

[0078] Figure 6 For the IR spectrum of 2-amino-5-(3,5-dinitrophenyl)-1,3,4-thiadiazole in Example 7, the product is proved to be 2-amino-5-(3,5-dinitrophenyl)-1,3,4-thiadiazole by absorption peaks: 3425 cm -1 ,3266 cm -1 (νN-H,s); 3085 cm -1 (νbenzene ring C-H,s); 1627 cm -1 (νthiadiazole ring C=N,s); 1134 cm -1 (δthiadiazole ring,m); 1343 cm -1 (νC-N,s); 724 cm -1 (νC-S-C,w). 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-pyridine carboxaldehyde, 0.12 mol thiosemicarbazide, and 0.15 mol 50% ethanol to a dry three-necked flask, then warm to 60°C to react, and monitor by TLC until the reaction is complete. Pour the reaction liquid into ice water to precipitate a solid. Filter, dry the filter cake, and obtain intermediate compound crude product. Recrystallize the crude product from ethanol to obtain intermediate compound pure product;

[0082] (2) Take the intermediate compound 0.1 mol generated in step (1), add 0.2 mol of 1-n-hexyl imidazo[1,2-a]pyridine dicyano imine 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 liquid into ice water to precipitate a solid. Filter the solid, dry the filter cake, and obtain 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole crude product. Recrystallize the crude product from ethanol to obtain 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole pure product. White needle-like crystals, yield 94.6%, m.p.: 210.3-212.9°C.

[0083] Figure 7 For the IR spectrum of 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole in Example 8, the absorption peaks are: 3298 cm -1 (νN-H, s); 3091 cm -1 , 1510 cm-1, 685 cm -1 (νpyridine, m); 1678 cm -1 , 1620 cm -1 (νthiadiazole ring C=N, s); 1193 cm -1 (δthiadiazole ring, m); 1023 cm -1 , 742 cm -1 , 615 cm -1 , 572 cm -1 , 522 cm -1 (νthiadiazole ring N-C-S, w), which proves 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] Example 1 is repeated 5 times with the 1-n-butyl imidazo[1,2-a]pyridine bromide salt ionic liquid ([C4impy][Br]) as catalyst, which is continuously recovered and reused without changing other conditions. The results are as follows:

[0087]

[0088] Example 10

[0089] Example 4 was repeated 5 times with the 1-n-hexyl imidazo[1,2-a]pyridine bis-trifluoromethanesulfonimide salt ionic liquid ([C6impy][TFSI]) recovered and reused continuously and other conditions unchanged, and the results are as follows:

[0090]

[0091] In summary, Example 9 and Example 10 show that the 1-n-butyl imidazo[1,2-a]pyridine bromide salt ionic liquid and the 1-n-hexyl imidazo[1,2-a]pyridine bis-trifluoromethanesulfonimide salt ionic liquid were recovered and reused continuously in the synthesis reaction with other conditions unchanged, and high yield and high melting point products were still obtained, indicating that the ionic liquid has excellent reusability.

[0092] Example 11

[0093] Example 1 was carried out with the 1-n-butyl imidazo[1,2-a]pyridine bromide salt ionic liquid ([C4impy][Br]), [PPh3][TfOH] ionic liquid, concentrated sulfuric acid-concentrated phosphoric acid, concentrated sulfuric acid-phosphorus oxychloride, and concentrated sulfuric acid-pentachlorophosphorus as catalysts, respectively, with other conditions unchanged, and the results are as follows:

[0094]

[0095] As can be seen from the above table, 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 product yield catalyzed by the 1-n-butyl imidazo[1,2-a]pyridine bromide salt ionic liquid ([C4impy][Br]) is higher, indicating that the ionic liquid used in the present application has stronger catalytic ability.

[0096] The above content only illustrates the technical idea of the present application and cannot limit the protection scope of the present application. Any modification made according to the technical idea of the present application on the basis of the technical solution falls within the protection scope of the claims of the present application.

Claims

1. A green synthesis of 2-amino-5-aryl-l,3,4-thiadiazoles, characterized by, The method comprises the following steps: Step 1) mixing aromatic aldehyde, thiosemicarbazide and ethanol with a mass fraction of 50-75%, then heating, and after the solid is precipitated, performing suction filtration to obtain an intermediate compound; the structural formula of the intermediate compound is as follows: ； Step 2) mixing the intermediate compound and 1-alkyl imidazo[1,2-a]pyridine salt ionic liquid, then heating, and after the solid is precipitated, performing suction filtration to obtain 2-amino-5-aryl-1,3,4-thiadiazole; the structural formula of the ionic liquid is as follows: ； In the step, the reaction formula of the reaction is as follows: 。 2. The method of claim 1, wherein, In step 1), the molar ratio of aromatic aldehyde, thiosemicarbazide and ethanol is 1.0: (1.0-1.2): (0.5-1.0).

3. The method of claim 1, wherein, In step 1), the aromatic aldehyde includes benzaldehyde, p-fluorobenzaldehyde, p-chlorobenzaldehyde, 2,4-dichlorobenzaldehyde, p-nitrobenzaldehyde, 3,5-dinitrobenzaldehyde and 4-pyridine carboxaldehyde.

4. The method of claim 1, wherein, In step 1), the temperature is heated to 50-60 DEG C.

5. The method of claim 1, wherein, In step 2), the molar ratio of the intermediate compound and the ionic liquid is 1.0: (0.5-2.0).

6. The method of claim 1, wherein, In step 2), the 1-alkyl imidazo[1,2-a]pyridine salt ionic liquid is selected from 1-n-butyl imidazo[1,2-a]pyridine bromide salt, 1-n-butyl imidazo[1,2-a]pyridine bis-trifluoromethanesulfonimide salt, 1-n-hexyl imidazo[1,2-a]pyridine bis-trifluoromethanesulfonimide salt, 1-n-butyl imidazo[1,2-a]pyridine bis-fluorosulfonimide salt, 1-n-octyl imidazo[1,2-a]pyridine bis-fluorosulfonimide salt, 1-n-butyl imidazo[1,2-a]pyridine bis-cyanimide salt or 1-n-hexyl imidazo[1,2-a]pyridine bis-cyanimide salt.

7. The method of claim 1, wherein, In step 2), the temperature is heated to 50-55 DEG C.

8. The method of claim 1, wherein, After the reactants in step 1) and step 2) are mixed, TLC monitoring is performed by using petroleum ether and ethyl acetate as developing agents.

9. The method of claim 1, wherein, The structural formula of 2-amino-5-aryl-1,3,4-thiadiazole is as follows: 。 10. The method of claim 9, wherein, The specific structure of the 2-amino-5-aryl-1,3,4-thiadiazole is as follows: 。

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