A method for preparing an iodoarene

Abstract

The application provides a preparation method of an iodinated aromatic hydrocarbon, which comprises the following steps: dissolving an aromatic amine compound in a solvent to obtain an aromatic amine solution; adding concentrated nitric acid to the aromatic amine solution, fully stirring, and then adding an iodination reagent to perform iodination reaction to obtain the iodinated aromatic hydrocarbon. The preparation method of the iodinated aromatic hydrocarbon provided by the application uses an aromatic amine as a raw material, and the iodinated aromatic hydrocarbon is prepared by one-pot method under the action of nitric acid and an iodination reagent, without needing to go through a diazonium salt intermediate, and has the advantages of mild conditions, safe operation, high reaction efficiency and high yield.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology and relates to a method for preparing iodoaromatic hydrocarbons. Background Technology

[0002] Iodoaromatics are an important class of organic compounds whose skeletons are widely found in bioactive molecules and organic synthesis intermediates. They also have broad applications in fields such as radiotherapy. However, compared to other common halogenated hydrocarbons, such as chloroaromatics and bromoaromatics, the synthesis of iodoaromatics is more difficult.

[0003] Traditional methods for synthesizing iodoaromatics include direct iodination, halogen exchange reactions, and the Sandmeyer reaction. Direct iodination requires metal catalysis and often necessitates the presence of a directing group, limiting its applicability. Halogen exchange reactions involve exchanging chlorinated or brominated hydrocarbons with sodium iodide in a solvent. The solvent can be chosen where sodium iodide is readily soluble, while sodium chloride or bromide is not, such as acetone. The sodium chloride or bromide produced in the exchange reaction is not easily dissolved in acetone, thus promoting the forward reaction. However, halogen exchange reactions have low conversion rates, are slow, and sometimes fail to react. The Sandmeyer reaction involves the reaction of a diazonium salt of an aromatic ring with a haloalkane under copper catalysis to generate aryl halogens. Compared to chlorination and bromination, iodination is more reactive and does not require copper catalysis; iodoaromatics can be obtained directly under the action of potassium iodide or sodium iodide. However, this method requires the conversion of aromatic amines into diazonium salts first. Diazonium salts are unstable and easily decompose under light or heat. Some diazonium salts can decompose rapidly and explode when heated or vibrated in a dry state. Furthermore, the diazotization reaction needs to be carried out at low temperatures, and the resulting diazonium salt solution must be used immediately and cannot be stored or dried. The reaction conditions are extremely demanding. In addition, side reactions such as decomposition, hydrolysis, and coupling are prone to occur during the reaction, generating large amounts of acidic wastewater and waste gas, which pollute the environment.

[0004] In summary, how to prepare iodoaromatics more efficiently and safely with high conversion rates remains a pressing technical problem to be solved in this field. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a method for preparing iodoaromatics. This method uses aromatic amines as raw materials and prepares iodoaromatics in a one-pot process under the action of nitric acid / iodochemical reagent. It has the advantages of mild conditions, safe operation, high reaction efficiency, and high yield.

[0006] This invention provides a method for preparing iodoaromatic hydrocarbons, comprising the following steps:

[0007] The aromatic amine compound is dissolved in a solvent to obtain an aromatic amine solution; concentrated nitric acid is added to the aromatic amine solution and stirred thoroughly, and then an iodination reagent is added to carry out an iodination reaction to obtain the iodinated aromatic hydrocarbon.

[0008] The inventors speculate that the above preparation method involves the following reaction process:

[0009] First, when concentrated nitric acid is added to an aromatic amine solution, it can convert the amino group in the aromatic amine into a nitramide group, forming an aromatic nitramide intermediate. At the same time, the iodide ion in the iodination reagent has strong nucleophilicity and can nucleophilically attack the carbocation attached to the nitramide group. The nitramide group leaves as a leaving group, and finally, iodoaromatic hydrocarbons are obtained.

[0010] Compared to the traditional method of first converting aromatic amines into diazonium salt intermediates and then preparing iodoaromatics via the Sandmeyer reaction, the preparation method provided by this invention eliminates the need for diazonium salt intermediates. Iodoaromatics can be prepared in a one-pot process by sequentially adding concentrated nitric acid and an iodination reagent. This method eliminates the need for intermediate purification, is safe and efficient, and can produce iodoaromatics in high yields.

[0011] When the above preparation method is carried out on a large scale, for example, when preparing gram-level iodoaromatics, a large amount of heat will be released when concentrated nitric acid is added. In order to avoid the occurrence of material spraying and side reactions caused by the large amount of heat release, concentrated nitric acid should be added in batches or added dropwise to the aromatic amine solution. If necessary, it can be carried out in an ice bath to control the temperature during the addition process.

[0012] After adding concentrated nitric acid, the mixture should be stirred for a certain period of time to allow the concentrated nitric acid and aromatic amine to fully form a salt. Specifically, it can be stirred for 5 to 10 minutes before adding the iodination reagent to carry out the iodination reaction.

[0013] The concentrated nitric acid used in this invention can be selected from commercially available concentrated nitric acid solutions with a mass fraction of 65% to 68%. Using concentrated nitric acid solution is beneficial for converting aromatic amines into nitramide salts, thereby facilitating subsequent reactions.

[0014] In one specific embodiment, the aromatic amine compound has the general formula shown in Formula 1:

[0015] Ar-NH2 formula I

[0016] In Formula I, Ar is selected from unsubstituted or substituent aryl or heteroaryl groups.

[0017] As is known in the art, an aryl group refers to an aromatic ring composed of carbon and hydrogen atoms, which can be a single aromatic ring or multiple aromatic rings fused together; a heteroaryl group refers to an aromatic ring in which at least one carbon atom is replaced by a heteroatom (such as O, N, S). For example, an aryl group can be phenyl, naphthyl, etc.; a heteroaryl group can be a five-membered heteroaryl group containing 1 to 4 heteroatoms or a six-membered heteroaryl group containing 1 to 5 heteroatoms.

[0018] Among them, a five-membered heteroaryl containing one heteroatom includes, but is not limited to, one of pyrrole, furanyl, or thiophene; a five-membered heteroaryl containing two heteroatoms includes, but is not limited to, one of imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, or isothiazolyl; a five-membered heteroaryl containing three heteroatoms includes, but is not limited to, one of triazolyl, oxadiazolyl, or thiadiazolyl; a five-membered heteroaryl containing four heteroatoms includes, but is not limited to, tetrazolyl; a six-membered heteroaryl containing one heteroatom includes, but is not limited to, pyridinyl or pyranyl; a six-membered heteroaryl containing two heteroatoms includes, but is not limited to, one of pyridazinyl, pyrimidinyl, or pyrazinyl; a six-membered heteroaryl containing three heteroatoms includes, but is not limited to, triazinyl; and a six-membered heteroaryl containing four heteroatoms includes, but is not limited to, tetraazinyl.

[0019] Furthermore, the aryl group is preferably derived from phenyl; and / or, the heteroaryl group is preferably derived from a five- or six-membered heteroaryl group containing 1 to 3 nitrogen atoms. The five- or six-membered heteroaryl group containing 1 to 3 nitrogen atoms can be pyridine, imidazole, pyrazole, thiazole, pyrimidine, pyrazine, thiadiazole, etc.

[0020] More preferably, when Ar is selected from phenyl, i.e., the substrate is an aniline compound, the reactivity is higher, and iodoaromatics can be prepared in higher yields.

[0021] In one specific embodiment, the substituent in the aryl or heteroaryl group containing the substituent is selected from one or more of C1-C6 alkyl, C1-C6 alkoxy, halogen, cyano, nitro, hydroxy, trifluoromethyl, and sulfonamide groups.

[0022] Alkyl refers to a saturated aliphatic hydrocarbon group. C1 to C6 alkyl refers to straight-chain alkyl and branched alkyl with 1 to 6 carbon atoms, including but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, n-hexyl, etc.

[0023] Alkoxy refers to a group composed of an alkyl group and an oxygen atom. C1 to C6 alkoxy refers to a straight-chain alkoxy or branched-chain alkoxy with 1 to 6 carbon atoms, including but not limited to methoxy, ethoxy, propoxy, butoxy, etc.

[0024] Ester group refers to a group with a -COOR1 structure, where R1 is selected from C1 to C3 alkyl groups, including but not limited to -COOCH3, -COOC2H5, etc.

[0025] Halogens refer to fluorine, chlorine, bromine, or iodine.

[0026] sulfonamide group refers to the group with To prevent the amino group in the sulfonamide from participating in the reaction, a protecting group (such as an acetyl group) can be used to protect the amino group. For example, when an acetyl group is used to protect the sulfonamide group, the structure of the substituent is as follows:

[0027] The present invention does not limit the number of the above-mentioned substituents contained in the aryl or heteroaryl group and the position of the substituents. It is understood that the aryl or heteroaryl group is connected to an amino group to form the aromatic amine compound of the present invention, and the above-mentioned substituents can be present in one or more at the ortho, para or meta position of the amino group.

[0028] The inventors discovered that when the substituents are selected from electron-withdrawing groups, such as nitro or cyano, the substrate has higher reactivity and can be prepared in higher yields of iodoaromatics.

[0029] In a preferred embodiment, the temperature of the iodination reaction is 50–100°C. For example, it can be 50°C, 55°C, 60°C, 65°C, 70°C, 80°C, 85°C, 90°C, 95°C, 100°C, or any combination of the above values.

[0030] In a preferred embodiment, the iodination reaction takes 1 to 3 hours. For example, it can be 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, or any combination of these values. The reaction progress can be monitored using conventional detection methods such as HPLC, TLC, and NMR. Monitoring shows that the iodination reaction is typically completed within 1 to 3 hours.

[0031] The present invention does not specifically limit the type of iodinated reagent, which may be selected from iodinated reagents commonly used in the art, including but not limited to one or more of potassium iodide, sodium iodide, cuprous iodide, copper iodide, elemental iodine, and trimethylsilyl iodide, preferably potassium iodide and / or sodium iodide.

[0032] In a preferred embodiment, the molar ratio of the aromatic amine compound to the nitric acid in the concentrated nitric acid solution is 1:(4-8). Exemplarily, the molar ratio of the aromatic amine compound to the nitric acid in the concentrated nitric acid solution is 1:4, 1:5, 1:6, 1:7, 1:8, or any combination thereof.

[0033] In a preferred embodiment, the molar ratio of the aromatic amine compound to the iodinated reagent is 1:(2-5). For example, the molar ratio of the aromatic amine compound to the iodinated reagent is a range consisting of 1:2, 1:3, 1:4, 1:5, or any two of the above.

[0034] The present invention does not specifically limit the reaction solvent, which can be selected from aprotic organic solvents commonly used in the art, including but not limited to one or more of dichloromethane, dichloroethane, dioxane, tetrahydrofuran, chloroform, and chlorobenzene, more preferably dichloroethane.

[0035] After the halogenation reaction is completed, in order to obtain pure aryl halides, a post-treatment process for the reaction solution is also included.

[0036] In one specific embodiment, the post-processing includes: adding saturated sodium bicarbonate solution and sodium thiosulfate solution to the reaction system to quench the reaction, followed by filtration, separation, and concentration to obtain a crude product; and then purifying the crude product by column chromatography to obtain iodoaromatics.

[0037] The saturated sodium bicarbonate solution can neutralize the concentrated nitric acid that is not consumed in the reaction, and sodium thiosulfate can reduce the residual oxidizing substances in the reaction system, such as nitrogen oxides. During quenching, ammonium nitrate may also be generated in the reaction system, so it needs to be removed by filtration. After separation, the organic phase is retained in the filtrate. After concentration to remove the solvent, the crude product can be obtained.

[0038] The implementation of this invention has at least the following beneficial effects:

[0039] Compared to the traditional method of first converting aromatic amines into diazonium salt intermediates and then preparing iodoaromatics via Sandmeyer reaction, the preparation method provided by this invention does not require diazonium salt intermediates. Iodoaromatics can be prepared in one pot by sequentially adding concentrated nitric acid and iodination reagent. This method does not require purification of intermediates, has mild reaction conditions, high operational safety and preparation efficiency, and can ultimately obtain iodoaromatics in high yield. Detailed Implementation

[0040] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions in the embodiments of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0041] The method for preparing aryl halides from aromatic amines according to the present invention will be described in detail below with reference to specific embodiments.

[0042] In the following embodiments, unless otherwise specified, all raw materials can be prepared by commercially available or literature-described conventional methods. Experimental methods without specific conditions shall be performed in accordance with conventional methods and conditions in the art, or according to the product instructions.

[0043] Example 1

[0044] This embodiment provides a method for preparing m-nitroiodobenzene, the structural formula of which is as follows:

[0045]

[0046] The preparation method includes the following steps:

[0047] 1) Add 70 mg (0.5 mmol, 1 equiv) of m-nitroaniline, 5 mL of dichloroethane and a magnetic stir bar to a 20 mL reaction flask. Stir at room temperature to fully dissolve the m-nitroaniline. Then add 210 μL (3 mmol, 6 equiv) of concentrated nitric acid solution. Stir at room temperature for 5–10 minutes. Then add 332 mg (2 mmol, 4 equiv) of potassium iodide to the reaction system. Heat and stir the mixture at 70 °C for 1 hour. The reaction is considered complete when the reaction is detected.

[0048] 2) Cool the reaction system to room temperature, dilute with dichloromethane, then quench the reaction with saturated sodium bicarbonate solution and sodium thiosulfate. The quenched reaction solution is then filtered, separated, and concentrated under vacuum to obtain the crude product. The crude product is separated by column chromatography (petroleum ether / dichloromethane (v:v) = 5 / 1 to 1 / 1) to obtain 102 mg (0.41 mmol) of white solid product, with a yield of 82%.

[0049] The product was characterized by proton and carbon NMR spectra, and the data are as follows:

[0050] 1 H NMR (400MHz, CDCl3) δ7.80 (d, J = 8.2Hz, 2H), 7.74 (d, J = 8.2Hz, 2H), 3.90 (s, 3H).

[0051] 13 C NMR (101MHz, CDCl3) δ166.75,137.86,131.17,129.74,100.86,52.43.

[0052] Examples 2-18

[0053] Examples 2 through 18 all provide a method for preparing m-nitroiodobenzene. The preparation steps are basically the same as those in Example 1. The differences from Example 1, as well as the key conditions and product yields, are listed in Table 1. For easy comparison, the conditions of Example 1 are also listed in Table 1.

[0054] Table 1

[0055]

[0056]

[0057] It should be noted that the amount of concentrated nitric acid added in Table 1 refers to the molar amount of nitric acid contained in the concentrated nitric acid solution.

[0058] Example 19

[0059] This embodiment provides a method for preparing methyl 4-iodobenzoate. The structural formula of methyl 4-iodobenzoate is as follows:

[0060]

[0061] The preparation method includes the following steps:

[0062] 1) Add 76 mg (0.5 mmol, 1 equiv) of methyl 4-aminobenzoate, 5 mL of dichloroethane and a magnetic stir bar to a 20 mL reaction flask. Stir at room temperature until the solid is completely dissolved. Then add 210 μL (3 mmol, 6 equiv) of nitric acid. Stir at room temperature for 5 to 10 minutes. Then add 332 mg (2 mmol, 4 equiv) of potassium iodide to the reaction system. Heat and stir the mixture at 70 °C for 1 hour. The reaction is considered complete when the reaction is detected.

[0063] 2) Cool the reaction system to room temperature, dilute with dichloromethane, then quench the reaction with saturated sodium bicarbonate solution and sodium thiosulfate. The quenched reaction solution is then filtered, separated, and concentrated under vacuum to obtain the crude product. The crude product is separated by column chromatography (petroleum ether / dichloromethane (v:v) = 5 / 1 to 1 / 1) to obtain 100 mg (0.385 mmol) of white solid product, with a yield of 77%.

[0064] The product was characterized by proton and carbon NMR spectra, and the data are as follows:

[0065] 1 H NMR (400MHz, CDCl3) δ7.80 (d, J = 8.2Hz, 2H), 7.74 (d, J = 8.2Hz, 2H), 3.90 (s, 3H).

[0066] 13C NMR (101MHz, CDCl3) δ166.75,137.86,131.17,129.74,100.86,52.43.

[0067] Example 20

[0068] This embodiment provides a method for preparing p-iodobenzonitrile, the structural formula of which is as follows:

[0069]

[0070] The preparation method includes the following steps:

[0071] 1) Add 60 mg (0.5 mmol, 1 equiv) of p-aminobenzonitrile, 5 mL of dichloroethane and a magnetic stir bar to a 20 mL reaction flask. Stir at room temperature to fully dissolve the p-aminobenzonitrile. Then add 210 μL (3 mmol, 6 equiv) of nitric acid. Stir at room temperature for 5–10 minutes. Then add 332 mg (2 mmol, 4 equiv) of potassium iodide to the reaction system. Heat and stir the mixture at 70 °C for 1 hour. The reaction is considered complete when the reaction is detected.

[0072] 2) Cool the reaction system to room temperature, dilute with dichloromethane, then quench the reaction with saturated sodium bicarbonate solution and sodium thiosulfate. The quenched reaction solution is then filtered, separated, and concentrated under vacuum to obtain the crude product. The crude product is separated by column chromatography (petroleum ether / dichloromethane (v:v) = 5 / 1 to 1 / 1) to obtain 99 mg (0.435 mmol) of white solid product, with a yield of 87%.

[0073] The product was characterized by proton and carbon NMR spectra, and the data are as follows:

[0074] 1 H NMR (400MHz, CDCl3) δ7.89–7.80(m,1H),7.41–7.33(m,1H).

[0075] 13 C NMR (101MHz, CDCl3) δ138.66,133.31,118.36,111.89,100.46.

[0076] Example 21

[0077] This embodiment provides a method for preparing N-(4-iodobenzenesulfonyl)acetamide. The structural formula of N-(4-iodobenzenesulfonyl)acetamide is as follows:

[0078]

[0079] The preparation method includes the following steps:

[0080] 1) Add 65 mg (0.3 mmol, 1 equiv) of sulfacetyl, 3 mL of dichloroethane and a magnetic stir bar to a 20 mL reaction flask. Stir at room temperature to fully dissolve sulfacetyl. Then add 210 μL (3 mmol, 6 equiv) of nitric acid. Stir at room temperature for 5-10 minutes. Then add 332 mg (2 mmol, 4 equiv) of potassium iodide to the reaction system. Heat and stir the mixture at 70 °C for 1 hour. The reaction is considered complete when detected.

[0081] 2) Cool the reaction system to room temperature, dilute with dichloromethane, then quench the reaction with saturated sodium bicarbonate solution and sodium thiosulfate. The quenched reaction solution is then filtered, separated, and concentrated under vacuum to obtain the crude product. The crude product is separated by column chromatography (petroleum ether / dichloromethane (v:v) = 5 / 1 to 1 / 1.5) to obtain 68 mg (0.21 mmol) of white solid product, with a yield of 70%.

[0082] The product was characterized by proton and carbon NMR spectra, and the data are as follows:

[0083] 1 H NMR (400MHz, Acetone-d6) δ8.02(d,J=8.3Hz,2H),7.77(d,J=8.3Hz,2H),2.02(s,3H).

[0084] 13 C NMR (101MHz, DMSO-d6) δ168.96,138.99,138.06,129.16,102.16,23.26.

[0085] Example 22

[0086] This embodiment provides a method for preparing p-tert-butyliodobenzene. The structural formula of p-tert-butyliodobenzene is as follows:

[0087]

[0088] The preparation method includes the following steps:

[0089] 1) Add 48 μL (0.3 mmol, 1 equiv) of p-tert-butylaniline, 3 mL of dichloroethane and a magnetic stir bar to a 20 mL reaction flask and stir at room temperature. Then add 84 μL (1.2 mmol, 4 equiv) of nitric acid and stir at room temperature for 5–10 minutes. Then add 100 mg (0.6 mmol, 2 equiv) of potassium iodide to the reaction system and heat and stir at 70 °C for 1 hour. The reaction is considered complete when the reaction is detected.

[0090] 2) Cool the reaction system to room temperature, dilute with dichloromethane, then add saturated sodium bicarbonate solution and sodium thiosulfate to quench the reaction. The quenched reaction solution is then filtered, separated, and concentrated under vacuum to obtain the crude product. The crude product is separated by reverse-phase column chromatography (water / acetonitrile) to obtain an oily product of 39 mg (0.15 mmol), with a yield of 50%.

[0091] The product was characterized by proton and carbon NMR spectra, and the data are as follows:

[0092] 1 H NMR (400MHz, CDCl3) δ7.98–7.93(m,2H),7.51–7.46(m,2H),1.64(s,9H).

[0093] 13 C NMR (101MHz, CDCl3) δ150.95,137.19,127.70,90.78,34.69,31.29.

[0094] Example 23

[0095] This embodiment provides a method for preparing 5-iodo-2-trifluoromethylpyridine, the structural formula of which is as follows:

[0096]

[0097] The preparation method includes the following steps:

[0098] 1) Add 82 mg (0.5 mmol, 1 equiv) of 5-amino-2-trifluoromethylpyridine, 5 mL of dichloroethane and a magnetic stir bar to a 20 mL reaction flask, stir at room temperature until the solid is completely dissolved, then add 210 μL (3 mmol, 6 equiv) of nitric acid, stir at room temperature for 5 to 10 minutes, then add 332 mg (2 mmol, 4 equiv) of potassium iodide to the reaction system, and heat and stir the mixture at 70 to 75 °C for 1 hour until the reaction is complete;

[0099] 2) Cool the reaction system to room temperature, dilute with dichloromethane, then quench the reaction with saturated sodium bicarbonate solution and sodium thiosulfate. The quenched reaction solution is then filtered, separated, and concentrated under vacuum to obtain the crude product. The crude product is separated by column chromatography (petroleum ether / dichloromethane (v:v) = 15 / 1 to 6 / 1) to obtain 79 mg (0.29 mmol) of white solid product, with a yield of 58%.

[0100] The product was characterized by proton, carbon, and fluorine NMR spectra, and the data are as follows:

[0101] 1 H NMR (400MHz, CDCl3) δ8.95 (s, 1H), 8.21 (d, J = 8.2Hz, 1H), 7.51–7.43 (m, 1H).

[0102] 19 F NMR (376MHz, CDCl3) δ -68.12.

[0103] 13 C NMR (101MHz, CDCl3) δ156.37,147.44,147.09,145.96,125.70,122.98,122.12,122.09,122.07,122.04,120.25,117.53,97.03.

[0104] Example 24

[0105] This embodiment provides a method for preparing 4-iodo-2,6-dichloropyridine. The structural formula of 4-iodo-2,6-dichloropyridine is as follows:

[0106]

[0107] The preparation method includes the following steps:

[0108] 1) Add 49 mg (0.3 mmol, 1 equiv) of 4-amino-2,6-dichloropyridine, 3 mL of dichloroethane and a magnetic stir bar to a 20 mL reaction flask. Stir at room temperature until the solid is completely dissolved. Then add 126 μL (1.8 mmol, 6 equiv) of nitric acid. Stir at room temperature for 5 to 10 minutes. Then add 199 mg (1.2 mmol, 4 equiv) of potassium iodide to the reaction system. Heat and stir the mixture at 70 to 75 °C for 1 hour. The reaction is considered complete when the reaction is detected.

[0109] 2) Cool the reaction system to room temperature, dilute with dichloromethane, then quench the reaction with saturated sodium bicarbonate solution and sodium thiosulfate. The quenched reaction solution is then filtered, separated, and concentrated under vacuum to obtain the crude product. The crude product is separated by column chromatography (petroleum ether / dichloromethane (v:v) = 1 / 0 to 10 / 1) to obtain 40 mg (0.147 mmol) of white solid product, with a yield of 49%.

[0110] The product was characterized by proton and carbon NMR spectra, and the data are as follows:

[0111] 1 H NMR (400MHz, CDCl3) δ7.65 (s, 2H).

[0112] 13C NMR (101MHz, CDCl3) δ150.80,131.63,107.71.

[0113] Example 25

[0114] This embodiment provides a method for preparing 2-iodo-5-methyl-1,3,4-thiadiazole. The structural formula of 2-iodo-5-methyl-1,3,4-thiadiazole is as follows:

[0115]

[0116] The preparation method includes the following steps:

[0117] 1) Add 35 mg (0.3 mmol, 1 equiv) of 2-amino-5-methyl-1,3,4-thiadiazole, 3 mL of dichloroethane and a magnetic stir bar to a 20 mL reaction flask. Stir at room temperature until the solid is completely dissolved. Then add 126 μL (1.8 mmol, 6 equiv) of nitric acid. Stir at room temperature for 5 to 10 minutes. Then add 199 mg (1.2 mmol, 4 equiv) of potassium iodide to the reaction system. Heat and stir the mixture at 70 to 75 °C for 1 hour. The reaction is considered complete when the reaction is detected.

[0118] 2) The reaction system was cooled to room temperature, diluted with dichloromethane, and then quenched with saturated sodium bicarbonate solution and sodium thiosulfate. The quenched reaction solution was then filtered, separated, and concentrated under vacuum to obtain the crude product. The crude product was separated by column chromatography (petroleum ether / dichloromethane (v:v) = 95 / 5 to 3 / 1) to obtain 37 mg (0.162 mmol) of yellow solid product, with a yield of 54%.

[0119] The product was characterized by proton and carbon NMR spectra, and the data are as follows:

[0120] 1 H NMR(400MHz, CDCl3)δ2.83–2.79(m,3H).

[0121] 13 C NMR (101MHz, CDCl3) δ170.87,104.78,15.47.

[0122] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing iodoaromatic hydrocarbons, characterized in that, Includes the following steps: Aromatic amine compounds are dissolved in a solvent to obtain aromatic amine solutions; Concentrated nitric acid was added to the aromatic amine solution and stirred thoroughly. Then, an iodination reagent was added to carry out an iodination reaction to obtain the iodinated aromatic hydrocarbon. The temperature of the iodination reaction was 50-100℃, and the reaction time was 1-3 hours. The aromatic amine compound has the structure shown in Formula I: Ar-NH2 Formula I In Formula I, Ar is selected from unsubstituted or substituent-containing aryl or heteroaryl groups; the aryl group is selected from phenyl groups; the heteroaryl group is selected from five- or six-membered heteroaryl groups containing 1 to 3 nitrogen atoms; the substituent in the aryl or heteroaryl group containing substituents is selected from one or more of C1 to C6 alkyl groups, C1 to C6 alkoxy groups, halogen groups, cyano groups, nitro groups, trifluoromethyl groups, ester groups, and sulfonamide groups protected by acetyl groups; wherein the ester group is a group having a -COOR1 structure, and R1 is selected from C1 to C3 alkyl groups; The iodinated reagent is selected from one or more of potassium iodide, sodium iodide, cuprous iodide, copper iodide, elemental iodine, and trimethylsilyliodide.

2. The preparation method according to claim 1, characterized in that, The molar ratio of the aromatic amine compound to the nitric acid in the concentrated nitric acid solution is 1:(4~8).

3. The preparation method according to claim 2, characterized in that, The molar ratio of the aromatic amine compound to the iodinated reagent is 1:(2~5).

4. The preparation method according to any one of claims 1-3, characterized in that, The solvent is selected from one or more of dichloromethane, dichloroethane, 1,4-dioxane, tetrahydrofuran, chloroform, and chlorobenzene.

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