CN111592505A - Synthesis method of iodine-catalyzed 2-substituted benzoselenazole compound - Google Patents

Abstract

The invention discloses a method for synthesizing iodine-catalyzed 2-substituted benzoselenazole compounds. The synthesis method includes: adding N-substituted-2-aniline compound, inorganic selenium source, catalyst, oxidant and solvent into a reaction tube, stirring the reaction at 130-150° C., cooling to room temperature after the reaction, and separating the product Purification to obtain the 2-substituted benzoselenoazole compounds. The invention develops a method for synthesizing 2-substituted benzoselenazole compounds under the catalysis of iodine element, using N-substituted-2-aniline compound as substrate, selenium element as inorganic selenium source, DMSO as oxidant, and chlorobenzene as solvent method. The method avoids using organic selenium as a selenium source and a halogen-containing substrate as a reaction precursor, but utilizes readily available elemental selenium as an inorganic selenium source, and an N-substituted aromatic amine compound without halogen atoms as a substrate, An efficient and green synthesis method is provided for the synthesis of 2-substituted benzoselenazole compounds.

Description

A kind of synthetic method of iodine-catalyzed 2-substituted benzoselenazole compounds

technical field

The invention belongs to the field of 2-substituted benzoselenazole compounds, in particular to a method for synthesizing iodine-catalyzed 2-substituted benzoselenazole compounds.

Background technique

Selenium is a non-metallic element and one of the trace elements necessary for the development of the human body. Most organic compounds containing selenium have good biological activity and medicinal value. play an important role.

Benzoselenide nitrogen heterocyclic compound, as an important organic selenium compound, has good medicinal value. For example, ebselen has been used in clinical research as a drug, and has now entered the clinical research stage. Therefore, it is of certain significance to study the synthesis methods of benzoselenazoles.

The invention develops a method for catalyzing and synthesizing 2-substituted benzoselenazole compounds using N-substituted-2-aniline compounds as substrates, selenium element as inorganic selenium source, and iodine element. The method avoids using organic selenium reagents as selenium sources and halogen-containing substrates as reaction precursors, but uses readily available elemental selenium as inorganic selenium sources and N-substituted aromatic amine compounds without halogen atoms as substrates , an efficient and green method for synthesizing 2-substituted benzoselenazoles is provided.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a kind of synthetic method of iodine-catalyzed 2-substituted benzoselenazole compounds in view of the shortcomings and deficiencies of the prior art. The invention develops a method for catalyzing and synthesizing 2-substituted benzoselenazole compounds by using N-substituted-2-aniline compounds as substrates, selenium element as inorganic selenium source, and iodine element. The method avoids the use of organic selenium as the selenium source and the halogen-containing substrate as the reaction precursor, but uses the readily available elemental selenium as the inorganic selenium source, and the N-substituted aromatic amine compounds without halogen atoms as the substrate. An efficient and green method for synthesizing 2-substituted benzoselenazole compounds is provided.

The purpose of the present invention is achieved through the following technical solutions.

A synthetic method of iodine-catalyzed 2-substituted benzoselenazole compounds, comprising the steps:

In the reaction tube, add N-substituted-2-aniline compound, inorganic selenium source, catalyst, oxidant and solvent, stir the reaction at 130~150 °C, cool down to room temperature after the reaction, and separate and purify the product to obtain the 2-Substituted benzoselenoazoles.

Further, the chemical reaction equation of the synthesis process is as follows:

In the formula, R ₁ is selected from one or more of methyl, methoxy, and halogen groups; R ₂ is selected from unsubstituted C6-C10 aryl, methyl, methoxy, nitro, cyano, One or more of ester group and halogen group.

Further, the N-substituted-2-aniline substrates are N-(4-methylbenzyl)-2-naphthylamine, N-(4-methoxybenzyl)-2-naphthylamine, N- -(4-(Trifluoromethoxy)benzyl)-2-naphthylamine, N-(4-fluorobenzyl)-2-naphthylamine, N-(4-nitrobenzyl)-2-naphthylamine , N-(4-cyanobenzyl)-2-naphthylamine, N-(4-cyanobenzyl)-2-naphthylamine, N-(3-methylbenzyl)-2-naphthylamine, N -(3-Fluorobenzyl)-2-naphthylamine, N-(3-nitrobenzyl)-2-naphthylamine, N-(3,4,5-trimethoxybenzyl)-2-naphthylamine , N-benzyl-3,5-dimethylaniline, N-benzyl-3,5-dimethoxyaniline, N-benzyl-3,4,5-trimethoxyaniline.

Further, the inorganic selenium source is elemental selenium; the molar ratio of the added amount of elemental selenium to the N-substituted-2-aniline compound is 1 to 2:1, preferably 1:1.

Further, the catalyst is one of sodium iodide, potassium iodide, hydrogen iodide, iodobenzene acetate, N-iodosuccinamide, tetrabutylammonium iodide, and elemental iodine, preferably elemental iodine.

Further, the molar ratio of the added amount of the catalyst iodine to the N-substituted-2-aniline compound is 0.05 to 0.5:1, preferably 0.1:1.

Further, the molar ratio of the added amount of the oxidant to the N-substituted-2-aniline compound is 1 to 10:1; preferably 3:1.

Further, the solvent is one of N,N-dimethylamide, N-methylpyrrolidone, methyl cyanide, dimethylacetamide, toluene, 1,4-dioxane, tetrahydrofuran and chlorobenzene , preferably chlorobenzene.

Further, the stirring temperature is 130-150 °C, preferably 140 °C.

Further, the time of the stirring reaction is 9 to 15 hours, preferably 10 hours.

Further, the separation and purification operation is as follows: adding the reaction solution into ethyl acetate, washing and extracting twice with saturated NaCl solution, taking the upper organic phase solution, drying with anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and then passing through The 2-substituted benzoselenazole compounds are obtained by column chromatography separation and purification.

The present invention utilizes DMSO as oxidant, selenium as inorganic selenium source, under the catalysis of iodine element, takes N-substituted-2-aniline compound as substrate, through intramolecular C(sp ³ )-H and C(sp ² )-H selenylation/cyclization reaction to construct 2-substituted benzoselenazole compounds, which provides an efficient and green synthesis method for the synthesis of 2-substituted benzoselenazole compounds.

Compared with the prior art, the present invention has the following advantages and beneficial effects:

(1) The present invention avoids the use of organic selenium as a selenium source and a halogen-containing substrate as a reaction precursor, but uses readily available elemental selenium as an inorganic selenium source, and the N-substituted aromatic amine compounds that do not contain halogen atoms are As a substrate, 2-substituted benzoselenazoles are constructed through intramolecular C(sp ³ )-H and C(sp ² )-H selenization/cyclization reactions, which have the advantage of high atom economy.

(2) The present invention does not require transition metals, has simple reaction conditions, readily available raw materials, and has good functional group compatibility, so it is expected to be applied to actual industrial production and facilitate better application.

Description of drawings

Figure 1 and Figure 2 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 1, respectively.

Figure 3 and Figure 4 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 2, respectively.

Figure 5 and Figure 6 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 3, respectively.

Figure 7 and Figure 8 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 4, respectively.

Figure 9 and Figure 10 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 5, respectively.

Figure 11 and Figure 12 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 6, respectively.

Figure 13 and Figure 14 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 7, respectively.

Figure 15 and Figure 16 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 8, respectively.

17 and 18 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 9, respectively.

Figure 19 and Figure 20 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 10, respectively.

Figure 21 and Figure 22 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 11, respectively.

Figure 23 and Figure 24 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 12, respectively.

Figure 25 and Figure 26 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 13, respectively.

27 and 28 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 14, respectively.

Figure 29 and Figure 30 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 15, respectively.

Specific implementation method

The technical solutions of the present invention will be described in further detail below with reference to specific embodiments and accompanying drawings, but the protection scope and embodiments of the present invention are not limited thereto.

Example 1

N-benzyl-2-naphthylamine (0.2 mmol), elemental selenium (0.2 mmol), elemental iodine (0.02 mmol), chlorobenzene (2.0 mL), dimethyl sulfoxide ( 0.6 mmol), after the addition of the sample, vacuum with an oil pump and then inject nitrogen for gas replacement. After three replacements, the reaction was stopped after 10 hours at 140 °C, cooled to room temperature, and the reaction solution was added to ethyl acetate and saturated with ethyl acetate. The NaCl solution was washed and extracted twice, the upper organic phase solution was taken, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and separated and purified by column chromatography to obtain the target product with a yield of 86%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 1 and Figure 2, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 8.15 (d, J = 9.0 Hz, 1H), 8.08 - 8.06 (m, 2H), 7.95 - 7.94 (m, 1H), 7.88 (d, J = 8.5 Hz, 2H), 7.58-7.47 (m, 5H); ¹³ C NMR (CDCL ₃ , 125 MHz) Δ 172.09, 153.70, 137.45, 136.19, 130.89, 130.80, 130.57,129.06, 127.72, 127.30, 127.01, 126.00, 126.00 , 122.99.

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 2

In a dry Schlenk reaction tube, N-(4-methylbenzyl)-2-naphthylamine (0.2 mmol), selenium (0.2 mmol), iodine (0.02 mmol), chlorobenzene (2.0 mL), Dimethyl sulfoxide (0.6 mmol), after the sample was added, evacuated with an oil pump and injected with nitrogen for gas replacement. After three replacements, the reaction was stopped at 140 °C for 10 hours, cooled to room temperature, and the reaction solution was added with acetic acid The ethyl ester was washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product with a yield of 78%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 3 and Figure 4, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 8.13 (d, J = 8.5 Hz, 1H), 7.96 - 7.94 (m, 3H), 7.88 (d, J = 8.5 Hz, 2H), 7.58 - 7.51 (m, 2H), 7.29 (d, J = 8.0 Hz, 2H), 2.42(s, 3H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 172.29, 153.69, 141.31, 137.13, 133.57, 130.85, 130.61, 129.78, 128 , 127.67, 127.42, 127.24, 126.99, 125.91, 122.91, 21.50.

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 3

N-(4-methoxybenzyl)-2-naphthylamine (0.2 mmol), elemental selenium (0.2 mmol), elemental iodine (0.02 mmol), and chlorobenzene (2.0 mL) were sequentially added to a dry Schlenk reaction tube , dimethyl sulfoxide (0.6mmol), after the sample is added, vacuum with an oil pump and then inject nitrogen for gas replacement, after three replacements, stop the reaction after 10 hours of reaction at 140 ℃, cool to room temperature, add the reaction solution In ethyl acetate, washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product with a yield of 58%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 5 and Figure 6, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 8.11 (d, J = 9.0 Hz, 1H), 8.00 (d, J = 9.0 Hz, 2H), 7.94 (d, J = 8.0 Hz, 1H), 7.88 - 7.86 (m, 2H), 7.58 - 7.50 (m, 2H), 6.99 (d, J = 8.5 Hz, 2H), 3.88 (s, 3H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 171.81, 161.84,153.74 , 136.86, 130.77, 130.61, 129.29, 129.11, 128.81, 127.38, 127.20, 126.97, 125.79, 122.79, 114.0, 55.45.

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 4

N-(4-(trifluoromethoxy)benzyl)-2-naphthylamine (0.2 mmol), selenium (0.2 mmol), iodine (0.02 mmol) and chlorobenzene were added to a dry Schlenk reaction tube in sequence. (2.0 mL), dimethyl sulfoxide (0.6 mmol), after adding the sample, evacuated with an oil pump and then injected with nitrogen for gas replacement. After three replacements, the reaction was stopped at 140 °C for 10 hours, and cooled to room temperature. The reaction solution was added to ethyl acetate, washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product. The yield was 77%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 7 and Figure 8, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 8.13 (d, J = 8.5 Hz, 1H), 8.09 (d, J = 9.0 Hz, 2H), 7.96 (d, J = 7.5 Hz, 1H), 7.90 - 7.88 (m, 2H), 7.60 - 7.54 (m, 2H), 7.34(d, J = 8.5 Hz, 2H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 170.07, 153.67, 150.90, 137.81, 134.82, 131.02, 130.54, 129.20, 128.89, 127.56, 127.45, 127.19, 126.26, 123.02, 121.29, 120.37 (q, J = 257 Hz).

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 5

In a dry Schlenk reaction tube, N-(4-cyanobenzyl)-2-naphthylamine (0.2 mmol), selenium (0.2 mmol), iodine (0.02 mmol), chlorobenzene (2.0 mL), Dimethyl sulfoxide (0.6 mmol), after the sample was added, evacuated with an oil pump and injected with nitrogen for gas replacement. After three replacements, the reaction was stopped at 140 °C for 10 hours, cooled to room temperature, and the reaction solution was added with acetic acid The ethyl ester was washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product with a yield of 70%.

The hydrogen spectrum, carbon spectrum and fluorine spectrum of the obtained target product are shown in Figure 9 and Figure 10, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 8.14 (d, J = 8.5 Hz, 3H), 7.97 (d, J = 7.0 Hz, 1H), 7.93 - 7.90 (m, 2H), 7.77 (d, J = 8.5 Hz, 2H), 7.62 - 7.57 (d, J = 8.5Hz, 2H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 169.18, 153.66, 139.92, 138.51, 132.84, 131.16, 130.39, 128.903, 0128 , 127.50, 127.38, 126.67, 123.12, 118.39, 113.82.

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 6

In a dry Schlenk reaction tube, N-(3-methylbenzyl)-2-naphthylamine (0.2 mmol), selenium (0.2 mmol), iodine (0.02 mmol), chlorobenzene (2.0 mL), Dimethyl sulfoxide (0.6 mmol), after the sample was added, evacuated with an oil pump and injected with nitrogen for gas replacement. After three replacements, the reaction was stopped at 140 °C for 10 hours, cooled to room temperature, and the reaction solution was added with acetic acid The ethyl ester was washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product with a yield of 82%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 11 and Figure 12, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 8.15 (d, J = 8.5 Hz, 1H), 7.95 (d, J = 7.5 Hz, 1H), 7.92 - 7.88 (m, 3H), 7.84 (d, J = 7.5 Hz, 1H), 7.59 - 7.53 (m, 2H), 7.39(t, J = 7.5 Hz, 1H), 7.32 (d, J = 7.5 Hz, 1H), 2.48 (s, 3H); ¹³ C NMR ( CDCL ₃ , 125 MHz) Δ 172.47, 153.62, 138.93, 137.32, 136.04, 131.71, 130.86, 130.56,129.00, 128.82, 127.43, 127.04, 125.17, 122.94,21.33.

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 7

In a dry Schlenk reaction tube, N-(2-methylbenzyl)-2-naphthylamine (0.2 mmol), selenium (0.2 mmol), iodine (0.02 mmol), chlorobenzene (2.0 mL), Dimethyl sulfoxide (0.6 mmol), after the sample was added, evacuated with an oil pump and injected with nitrogen for gas replacement. After three replacements, the reaction was stopped at 140 °C for 10 hours, cooled to room temperature, and the reaction solution was added with acetic acid In the ethyl ester, washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product with a yield of 77%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 13 and Figure 14, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 8.18 (d, J = 8.5 Hz, 1H), 7.98 - 7.96 (m, 1H), 7.91 (t, J = 7.5 Hz, 2H), 7.90 (t, J = 7.5 Hz, 1H), 7.60 - 7.54 (m, 2H), 7.41- 7.32 (m, 3H), 2.72(s, 3H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 171.76, 153.23,138.43, 136.49, 135.52, 131.57, 130.80, 130.50, 129.77, 128.79, 127.60, 127.11, 126.99, 126.16, 126.01, 123.11, 21.47.

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 8

In a dry Schlenk reaction tube, N-(2-fluorobenzyl)-2-naphthylamine (0.2 mmol), selenium (0.2 mmol), iodine (0.02 mmol), chlorobenzene (2.0 mL), di Methyl sulfoxide (0.6 mmol), after adding the sample, evacuated with an oil pump and then injected with nitrogen for gas replacement. After three replacements, the reaction was stopped at 140 °C for 10 hours, cooled to room temperature, and the reaction solution was added with ethyl acetate The ester was washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product with a yield of 74%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 15 and Figure 16, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 8.47 (td, J = 8.0 Hz, J = 1.5 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H), 7.95 (t, J = 7.5 Hz, 2H) ), 7.89 (d, J = 9.0 Hz, 1H), 7.59 -7.53 (m, 2H), 7.49 - 7.44 (m, 1H), 7.31 (t, J = 7.5 Hz, 1H), 7.25 (t, J = 9.5Hz, 1H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 162.71 (d, J = 5.13 Hz), 160.50 (d, J =251.00 Hz), 152.01, 138.30 (d, J =11.13 Hz), 131.82 (d, J = 8.75 Hz), 130.86, 130.50, 128.83, 128.65 (d, J = 1.75 Hz), 127.33, 127.28, 127.02, 126.15, 124.71 (d, J = 3.25 Hz), 123.69 (d, J = 10.00 Hz), 122.99, 116.27 (d, J = 22.25 Hz).

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 9

In a dry Schlenk reaction tube, N-(2-nitrobenzyl)-2-naphthylamine (0.2 mmol), selenium (0.2 mmol), iodine (0.02 mmol), chlorobenzene (2.0 mL), Dimethyl sulfoxide (0.6 mmol), after the sample was added, evacuated with an oil pump and injected with nitrogen for gas replacement. After three replacements, the reaction was stopped at 140 °C for 10 hours, cooled to room temperature, and the reaction solution was added with acetic acid In the ethyl ester, washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product with a yield of 77%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 17 and Figure 18, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 8.11 (d, J = 8.5 Hz, 1H), 7.96 (d, J = 7.0 Hz, 1H), 7.89 - 7.88 (m, 3H), 7.80 (d, J = 7.5 Hz, 1H), 7.67 (t, J = 7.5 Hz, 1H), 7.62 - 7.55 (m, 3H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 165.46, 153.03, 148.21, 139.34, 132.30, 131.88, 131.04, 130.64, 130.35, 130.32, 128.86, 127.58, 127.43, 127.21, 126.50, 124.41, 123.23.

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 10

In a dry Schlenk reaction tube, N-(naphthalene-1-methyl)-2-naphthylamine (0.2 mmol), selenium (0.2 mmol), iodine (0.02 mmol), chlorobenzene (2.0 mL), Dimethyl sulfoxide (0.6 mmol), after the sample was added, evacuated with an oil pump and injected with nitrogen for gas replacement. After three replacements, the reaction was stopped at 140 °C for 10 hours, cooled to room temperature, and the reaction solution was added with acetic acid The ethyl ester was washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product with a yield of 87%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 19 and Figure 20, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 9.08 (d, J = 8.5 Hz, 1H), 8.29 (d, J = 9.0 Hz, 1H), 8.00 - 7.98 (m, 2H), 7.95 - 7.90 (m, 4H), 7.68 - 7.65 (m, 1H), 7.61 -7.54 (m, 4H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 171.51, 153.61, 138.42, 134.01, 133.26, 130.88, 130.82, 130.97, 129.75, 128.80, 128.28, 127.67, 127.59, 127.25, 127.02, 126.49, 126.09, 125.93, 125.04, 123.20.

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 11

In a dry Schlenk reaction tube, N-(naphthalene-2-methyl)-2-naphthylamine (0.2 mmol), selenium (0.2 mmol), iodine (0.02 mmol), chlorobenzene (2.0 mL), Dimethyl sulfoxide (0.6 mmol), after the sample was added, evacuated with an oil pump and injected with nitrogen for gas replacement. After three replacements, the reaction was stopped at 140 °C for 10 hours, cooled to room temperature, and the reaction solution was added with acetic acid The ethyl ester was washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product with a yield of 89%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 21 and Figure 22, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 8.53 (s, 1H), 8.18 (d, J = 8.5 Hz, 2H), 8.00 -7.87 (m, 6H), 7.61 - 7.54 (m, 4H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 172.19, 153.76,137.50, 134.54, 133.52, 133.26, 130.93, 130.58, 128.87, 128.79, 127.88,127.81, 127.48, 127.44, 127.41, 127.11, 126.93, 126.10, 124.64, 122.97。

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 12

N-(3,4,5-trimethoxybenzyl)-2-naphthylamine (0.2 mmol), selenium element (0.2 mmol), iodine element (0.02 mmol), chlorobenzene were sequentially added to a dry Schlenk reaction tube. (2.0 mL), dimethyl sulfoxide (0.6 mmol), after adding the sample, evacuated with an oil pump and then injected with nitrogen for gas replacement. After three replacements, the reaction was stopped at 140 °C for 10 hours, and cooled to room temperature. The reaction solution was added to ethyl acetate, washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product. The yield 66%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 23 and Figure 24, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 8.13 (d, J = 9.0 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.90 - 7.88 (m, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.55 (t, J = 7.5Hz, 1H), 7.31 (s, 2H), 4.01 (s, 6H), 3.94 (s, 3H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 171.80, 153.59, 140.48, 137.36, 131.67, 130.87, 130.53, 128.87, 127.40, 127.35, 127.12, 126.06, 122.87, 104.86, 60.99, 56.35.

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 13

N-benzyl-3,5-dimethylaniline (0.2 mmol), selenium element (0.2 mmol), iodine element (0.02 mmol), chlorobenzene (2.0 mL), dimethyl aniline (0.02 mmol), chlorobenzene (2.0 mL) and dimethyl aniline were added to a dry Schlenk reaction tube. base sulfoxide (0.6 mmol), after adding the sample, evacuated with oil pump and injected with nitrogen for gas replacement, after three replacements, the reaction was stopped after 10 hours at 140 °C, cooled to room temperature, and the reaction solution was added to ethyl acetate , washed and extracted twice with saturated NaCl solution, took the upper organic phase solution, dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product with a yield of 56%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 25 and Figure 26, respectively, and the NMR data are as follows:

1H NMR (CDCl ₃ , 500 MHz) δ 8.03 - 8.01 (m, 2H), 7.78 (s, 1H), 7.49-7.48 (m, 3H), 6.99 (s, 1H), 2.55 (s, 3H), 2.47 (s, 3H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 171.94, 155.86, 136.56, 136.28, 136.23, 133.79, 130.80, 128.97, 127.83, 126.76, 122.31, 23.76, 21.

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 14

In a dry Schlenk reaction tube, N-benzyl-3,5-dimethoxyaniline (0.2 mmol), selenium (0.2 mmol), iodine (0.02 mmol), chlorobenzene (2.0 mL), di Methyl sulfoxide (0.6 mmol), after adding the sample, evacuated with an oil pump and then injected with nitrogen for gas replacement. After three replacements, the reaction was stopped at 140 °C for 10 hours, cooled to room temperature, and the reaction solution was added with ethyl acetate The ester was washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product with a yield of 37%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 27 and Figure 28, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 7.96 - 7.94 (m, 2H), 7.61 (s, 1H), 7.46 - 7.45 (m, 3H), 7.36 (s, 1H), 3.98 (s, 3H), 3.97 (s, 3H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 170.77, 149.95, 149.22, 148.28, 136.32, 130.51, 129.76, 129.01, 127.47, 106.50, 105.78, 56.3.

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Example 15

In a dry Schlenk reaction tube, N-benzyl-3,4,5-trimethoxyaniline (0.2 mmol), selenium (0.2 mmol), iodine (0.02 mmol), chlorobenzene (2.0 mL), Dimethyl sulfoxide (0.6 mmol), after the sample was added, evacuated with an oil pump and injected with nitrogen for gas replacement. After three replacements, the reaction was stopped at 140 °C for 10 hours, cooled to room temperature, and the reaction solution was added with acetic acid The ethyl ester was washed and extracted twice with saturated NaCl solution, the upper organic phase solution was taken, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target product with a yield of 36%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 29 and Figure 30, respectively, and the NMR data are as follows:

¹ H NMR (CDCl ₃ , 500 MHz) δ 7.97 - 7.95 (m, 2H), 7.47 - 7.46 (m, 3H), 7.42 (s, 1H), 4.07 (s, 3H), 3.96 (s, 3H), 3.95 (s, 3H); ¹³ C NMR (CDCl ₃ , 125 MHz) δ 172.33, 153.91, 151.58, 148.87, 139.64, 136.17, 130.79, 129.04, 127.62, 122.95, 102.69, 562.3.

Based on the above data, it is inferred that the structure of the target product is as follows:

。

.

Claims (10)

1. a synthetic method of 2-substituted benzoselenazole compounds by iodine catalysis is characterized by comprising the following steps: adding an N-substituted-2-aniline compound, an inorganic selenium source, a catalyst, an oxidant and a solvent into a reaction tube, stirring and reacting at 130-150 ℃, cooling to room temperature after the reaction is finished, and separating and purifying a product to obtain the 2-substituted benzoselenazole compound.

2. The method of claim 1, wherein the chemical reaction equation of the synthesis process is as follows:

in the formula, R₁One or more selected from unsubstituted C6-C10 aryl, methyl and methoxy; r₂Is selected from one or more of methyl, methoxy, trifluoromethoxy, nitro, cyano, ester group and halogen group.

3. The method of claim 1 or 2, wherein the N-substituted-2-anilines are N- (4-methylbenzyl) -2-naphthylamine, N- (4-methoxybenzyl) -2-naphthylamine, N- [4- (trifluoromethoxy) benzyl ] -2-naphthylamine, N- (4-fluorobenzyl) -2-naphthylamine, N- (4-nitrobenzyl) -2-naphthylamine, N- (4-cyanobenzyl) -2-naphthylamine, N- (3-methylbenzyl) -2-naphthylamine, N- (3-fluorobenzyl) -2-naphthylamine, N- (3-nitrobenzyl) -2-naphthylamine, one of N- (3,4, 5-trimethoxybenzyl) -2-naphthylamine, N-benzyl-3, 5-dimethylaniline, N-benzyl-3, 5-dimethoxyaniline and N-benzyl-3, 4, 5-trimethoxyaniline.

4. The method of synthesis of claims 1-3, wherein the inorganic selenium source is elemental selenium; the molar ratio of the added selenium simple substance to the N-substituted-2-aniline compound is 1-2: 1.

5. The synthesis method of claims 1-3, wherein the catalyst is one or more of sodium iodide, potassium iodide, hydrogen iodide, iodobenzene acetate, N-iodobutanediamide, tetrabutylammonium iodide, and iodine; the molar ratio of the addition amount of the catalyst to the N-substituted-2-aniline compound is 0.05-0.7: 1.

6. A synthesis method according to claims 1-3, characterized in that the oxidant is dimethyl sulfoxide; the molar ratio of the addition amount of the oxidant to the N-substituted-2-aniline compound is 1-10: 1.

7. The method according to claims 1 to 3, wherein the solvent is one or more of N, N-dimethylformamide, N-methylpyrrolidone, dimethylacetamide, toluene, 1, 4-dioxane, tetrahydrofuran, and chlorobenzene.

8. The synthesis method according to claims 1 to 3, characterized in that the stirring temperature is 130 to 150 ℃.

9. The synthesis method according to claims 1 to 3, wherein the reaction time is 8 to 12 hours.

10. The synthesis method according to claims 1 to 3, characterized in that the separation and purification operations are: adding the reaction solution into ethyl acetate, washing and extracting twice by using a saturated NaCl solution, taking an upper layer organic phase solution, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by using column chromatography to obtain the 2-substituted benzoselenazole compound.

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