A method for synthesizing an n-alkylated pyrithione compound

Abstract

The application belongs to the technical field of organic synthesis, and discloses a synthesis method of N-alkylated pyrithione compounds, which comprises the following steps: taking 2,2-dithiodipyridine and a benzyl halide compound as substrates, and synthesizing the N-alkylated pyrithione compound under the condition of the presence or absence of a base; the reaction temperature is 60 DEG C, and the reaction time is 4-12 h; the benzyl halide compound has the following structural formula: R-X, wherein R is selected from a benzyl group, a benzyl group in which hydrogen on a benzene ring is substituted by halogen or a methyl group, and X is selected from bromine; the 2,2-dithiodipyridine and the benzyl halide compound are used as raw materials, and the N-alkylated pyrithione compound is synthesized by a one-step green method under the condition of no solvent and no catalyst.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis, and relates to a synthesis method of N-alkylated pyrithione compounds. BACKGROUND

[0002] N-alkyl heterocycle is a structural element commonly existing in natural products and pharmacologically active structures, and corresponding derivatives thereof are commonly present in many biologically active molecules, drugs, ligands, and natural products, such as common lupine alkaloids used for treating various central nervous system diseases and assisting in smoking cessation (Organic Letters. 2005, 7(20), 4459-4462; J. Org. Chem. 2008, 73, 6425-6428), so their synthesis has attracted much attention.

[0003] N-alkylated pyridone compounds have potential anticancer activity, and there are few reports on synthesis methods thereof. At present, the synthesis of such substances requires a multi-step reaction, that is, first, O-alkylated products are generated by a nucleophilic substitution reaction of 2-halogenated pyridine compounds and alcohol as raw materials under the promotion of a stoichiometric base, then the O-alkylated products are rearranged and converted into N-alkylated pyridone compounds under the catalysis of a transition metal or LiI, and finally, N-alkylated pyridone compounds are reacted with Lawesson's reagent to complete an oxygen-sulfur exchange process to generate N-alkylated pyrithione compounds. In 2007, Jacek G. reported a method for synthesizing N-alkylated 2-pyrithione compounds through a three-step method (Tetrahedron, 2007, 63, 11862-11877); due to the multi-step reaction, the method has the disadvantages of complex operation, use of a large amount of solvent and metal catalyst, or reaction at high temperature, and is not friendly to the environment. Therefore, it is necessary to develop a more economical and greener synthesis method. SUMMARY

[0004] The application aims at the above technical problems, and provides a synthesis method of N-alkylated pyrithione compounds, which is easy to obtain raw materials, has mild reaction conditions, and realizes one-step green synthesis of N-alkylated pyrithione compounds under the conditions of no solvent and no catalyst.

[0005] To achieve the above object, the application adopts the following technical scheme:

[0006] The application provides a synthesis method of N-alkylated pyrithione compounds, which comprises the following steps: taking 2,2-dithiobispyridine and a benzyl halide compound as substrates, and synthesizing N-alkylated pyrithione compounds under the condition of the presence or absence of a base; the reaction temperature is 60 DEG C, and the reaction time is 4-12 h; the benzyl halide compound has the following structural formula: R-X, wherein R is selected from a benzyl group, a benzyl group in which hydrogen on a benzene ring is substituted by halogen or a methyl group, and X is selected from bromine.

[0007] In one technical solution, the molar ratio of the 2,2-dithiodipyridine to the benzyl halide compound is 1:1-4.

[0008] In one technical solution, the benzyl halide compound is selected from one of benzyl bromide, 2-fluorobenzyl bromide, 3-fluorobenzyl bromide, 4-fluorobenzyl bromide, 2-chlorobenzyl bromide, 3-chlorobenzyl bromide, 4-chlorobenzyl bromide, 3-bromobenzyl bromide, or p-methylbenzyl bromide.

[0009] In one technical solution, the base is one of cesium carbonate (Cs2CO3), sodium bicarbonate (NaHCO3), sodium carbonate (Na2CO3), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 4-dimethylaminopyridine (DMAP), pyridine, or triethylamine (Et3N), and the amount of the base used is 10% of the moles of the 2,2-dithiodipyridine.

[0010] Compared with the prior art, the present application has the following beneficial effects:

[0011] The present application uses 2,2-dithiodipyridine and a benzyl halide compound as raw materials to realize the one-step green synthesis of N-alkylated pyridine thione compounds under the conditions of no solvent and no catalyst. Compared with the existing method, the present application uses cheap and readily available 2,2-dithiodipyridine as raw material, and the presence of a disulfide bond reduces the nucleophilicity of the sulfur atom, which plays a certain blocking effect on the sulfur nucleophilic site, and then through condition control, the synthesis of N-alkylated pyridine thione compounds is realized more efficiently, with the advantages of fewer steps, less waste, and the like.

[0012] Compared with the synthesis method in the prior art, the present application has the advantages of readily available raw materials, simple operation, mild reaction conditions, no need to use metal catalysts excessively, no need to use solvents, compliance with the requirements of green chemistry, and obvious advantages and practical value. DETAILED DESCRIPTION

[0013] The following examples are used to illustrate the present application, but are not used to limit the protection scope of the present application. If not specifically indicated, the technical means used in the examples is the conventional means known to those skilled in the art. The test methods in the following examples are conventional methods, unless otherwise specified.

[0014] Example 1: Synthesis of N-benzylthiopyridone

[0015]

[0016] Into a 10 mL reaction tube, 2,2'-dithiodipyridine (110.1 mg, 0.5 mmol), benzyl bromide (256.5 mg, 1.5 mmol), and cesium carbonate (16.3 mg, 0.05 mmol) were sequentially added. The reaction tube was tightly capped and stirred at 60 °C for 4 h. Upon completion of the reaction, the reaction solution was separated by column chromatography (eluent: methanol: petroleum ether = 0-1 / 20) to obtain the product: N-benzylthiopyridone, with a yield of 74%.

[0017] The NMR data of the product N-benzylthiopyridone are as follows: 1 H NMR (600 MHz, CDC13) δ 7.76 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.48 - 7.30 (m, 5H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 6.66 - 6.58 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 136.5, 135.2, 133.8, 129.2, 128.5, 113.7, 58.8.

[0018] Example Two Synthesis of N-benzylthiopyridone

[0019]

[0020] Into a 10 mL reaction tube, 2,2'-dithiodipyridine (110.1 mg, 0.5 mmol), benzyl bromide (256.5 mg, 1.5 mmol), and cesium carbonate (16.3 mg, 0.05 mmol) were sequentially added. The reaction tube was tightly capped and stirred at 60 °C for 4 h. Upon completion of the reaction, the reaction solution was separated by column chromatography (eluent: methanol: petroleum ether = 0-1 / 20) to obtain the product: N-benzylthiopyridone, with a yield of 74%.

[0021] The NMR data of the product N-benzylthiopyridone are as follows: 1 H NMR (600 MHz, CDC13) δ 7.76 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.48 - 7.30 (m, 5H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 6.66 - 6.58 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 136.5, 135.2, 133.8, 129.2, 128.5, 113.7, 58.8.

[0022] Example Three Synthesis of N-benzylthiopyridone

[0023]

[0024] To a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), benzyl bromide (256.5 mg, 1.5 mmol), sodium bicarbonate (4.2 mg, 0.05 mmol) were added sequentially, the cap of the reaction tube was tightened and placed in a 60 °C water bath for 4 h. Once the reaction was complete, the reaction was separated by column chromatography (eluent: methanol: petroleum ether = 0-1 / 20) to give the product: N-benzylthiopyridone, in 49% yield.

[0025] The NMR data for the product N-benzylthiopyridone are as follows: 1 H NMR (600 MHz, CDC13) δ 7.76 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.48 - 7.30 (m, 5H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 6.66 - 6.58 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 136.5, 135.2, 133.8, 129.2, 128.5, 113.7, 58.8.

[0026] Example Four Synthesis of N-benzylthiopyridone

[0027]

[0028] To a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), benzyl bromide (256.5 mg, 1.5 mmol), sodium bicarbonate (4.2 mg, 0.05 mmol) were added sequentially, the cap of the reaction tube was tightened and placed in a 60 °C water bath for 4 h. Once the reaction was complete, the reaction was separated by column chromatography (eluent: methanol: petroleum ether = 0-1 / 20) to give the product: N-benzylthiopyridone, in 49% yield.

[0029] The NMR data for the product N-benzylthiopyridone are as follows: 1 H NMR (600 MHz, CDC13) δ 7.76 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.48 - 7.30 (m, 5H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 6.66 - 6.58 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 136.5, 135.2, 133.8, 129.2, 128.5, 113.7, 58.8.

[0030] Example Five Synthesis of N-benzylthiopyridinone

[0031]

[0032] Into a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), benzyl bromide (256.5 mg, 1.5 mmol), DBU (7.6 mg, 0.05 mmol) were added in sequence, the cap of the reaction tube was tightened and the reaction was stirred at 60 °C for 4 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0~1 / 20) to obtain the product: N-benzylthiopyridinone, with a yield of 50%.

[0033] The nuclear magnetic resonance data of the product N-benzylthiopyridinone are as follows: 1 H NMR (600 MHz, CDC13) δ 7.76 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.48 - 7.30 (m, 5H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 6.66 - 6.58 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 136.5, 135.2, 133.8, 129.2, 128.5, 113.7, 58.8.

[0034] Example Five Synthesis of N-benzylthiopyridinone

[0035]

[0036] Into a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), benzyl bromide (256.5 mg, 1.5 mmol), 4-dimethylaminopyridine (6.1 mg, 0.05 mmol) were added in sequence, the cap of the reaction tube was tightened and the reaction was stirred at 60 °C for 4 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0~1 / 20) to obtain the product: N-benzylthiopyridinone, with a yield of 69%.

[0037] The nuclear magnetic resonance data of the product N-benzylthiopyridinone are as follows: 1H NMR (600 MHz, CDC13) δ 7.76 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.48 - 7.30 (m, 5H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 6.66 - 6.58 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 136.5, 135.2, 133.8, 129.2, 128.5, 113.7, 58.8.

[0038] Example Seven Synthesis of N-benzylthiopyridinone

[0039]

[0040] Into a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), benzyl bromide (256.5 mg, 1.5 mmol), pyridine (4.0 mg, 0.05 mmol) were added in sequence, the cap of the reaction tube was tightened and the reaction was stirred at 60 °C for 4 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0~1 / 20) to obtain the product: N-benzylthiopyridinone, with a yield of 73%.

[0041] The nuclear magnetic resonance data of the product N-benzylthiopyridinone are as follows: 1 H NMR (600 MHz, CDC13) δ 7.76 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.48 - 7.30 (m, 5H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 6.66 - 6.58 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 136.5, 135.2, 133.8, 129.2, 128.5, 113.7, 58.8.

[0042] Example Eight Synthesis of N-benzylthiopyridinone

[0043]

[0044] Into a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), benzyl bromide (256.5 mg, 1.5 mmol), triethylamine (5.1 mg, 0.05 mmol) were added in sequence, the cap of the reaction tube was tightened and the reaction was stirred at 60 °C for 4 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0~1 / 20) to obtain the product: N-benzylthiopyridinone, with a yield of 70%.

[0045] The NMR data of the product N-benzylthiopyridinone is as follows: 1 H NMR (600 MHz, CDC13) δ 7.76 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.48 - 7.30 (m, 5H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 6.66 - 6.58 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 136.5, 135.2, 133.8, 129.2, 128.5, 113.7, 58.8.

[0046] Example Nine Synthesis of N-(2-fluorobenzyl)thiopyridinone

[0047]

[0048] Into a 10 mL reaction tube was added 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), 2-fluorobenzyl bromide (283.5 mg, 1.5 mmol) sequentially, the reaction tube was tightly capped and stirred at 60 °C for 4 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0-1 / 20) to obtain the product: N-(2-fluorobenzyl)thiopyridinone, with a yield of 55%.

[0049] The NMR data of the product N-(2-fluorobenzyl)thiopyridinone is as follows: 1 H NMR (600 MHz, CDC13) δ 7.76 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.48 - 7.30 (m, 5H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 6.66 - 6.58 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 136.5, 135.2, 133.8, 129.2, 128.5, 113.7, 58.8.

[0050] Example Ten Synthesis of N-(3-fluorobenzyl)thiopyridinone

[0051]

[0052] Into a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), 3- fluorobenzyl bromide (189.0 mg, 1.0 mmol), cesium carbonate (16.3 mg, 0.05 mmol) were added successively, the reaction tube was tightly capped and stirred at 60 °C for 12 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0~1 / 20) to obtain the product: N-(3-fluorobenzyl)thiopyridinone, with a yield of 76%.

[0053] The nuclear magnetic resonance data of the product N-(3-fluorobenzyl)thiopyridinone are as follows: 1 H NMR (600 MHz, DMSO-d6) δ 8.26-8.13 (m, 1H), 7.53 (dd, J = 8.4, 0.6 Hz, 1H), 7.45-7.32 (m, 2H), 7.12 (dd, J = 9.0, 6.6 Hz, 3H), 6.89-6.80 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, DMSO-d6); δ 179.87 (s), 162.63 (d, J = 243.5 Hz), 142.75 (s), 139.48 (d, J = 7.5 Hz), 135.53 (d, J = 2.2 Hz), 131.10 (d, J = 8.3 Hz), 124.26 (d, J = 2.1 Hz), 115.11 (d, J = 19.1 Hz), 115.03 (s), 114.91 (s), 114.39 (s), 57.40 (s).

[0054] Example Eleven Synthesis of N-(4-fluorobenzyl)thiopyridinone

[0055]

[0056] Into a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), 3- fluorobenzyl bromide (189.0 mg, 1.0 mmol), cesium carbonate (16.3 mg, 0.05 mmol) were added successively, the reaction tube was tightly capped and stirred at 60 °C for 12 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0~1 / 20) to obtain the product: N-(3-fluorobenzyl)thiopyridinone, with a yield of 76%.

[0057] The nuclear magnetic resonance data of the product N-(3-fluorobenzyl)thiopyridinone are as follows: 1H NMR (600 MHz, CDC13) δ 7.74 (d, J = 8.4 Hz, 1H), 7.59 (dd, J = 6.6, 1.2 Hz, 1H), 7.38 - 7.31 (m, 2H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 7.10 - 6.97 (m, 2H), 6.67 - 6.59 (m, 1H), 5.78 (s, 2H);13C NMR (151 MHz, CDC13) δ 180.96 (s), 162.64 (d, J = 254.8 Hz), 139.90 (s), 136.59 (s), 133.90 (s), 131.07 (d, J = 2.8 Hz), 130.31 (d, J = 8.2 Hz), 116.06 (d, J = 21.7 Hz), 113.84 (s), 58.03 (s).

[0058] Example Twelve Synthesis of N-(2-chlorobenzyl)thiopyridinone

[0059]

[0060] Into a 10 mL reaction tube was added 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), 2-chlorobenzyl bromide (205.5 mg, 1.0 mmol) sequentially, the reaction tube was tightly capped and stirred at 60 °C for 4 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0-1 / 20) to obtain the product: N-(2-chlorobenzyl)thiopyridinone, with a yield of 59%.

[0061] The nuclear magnetic resonance data of the product N-(2-chlorobenzyl)thiopyridinone are as follows: 1 H NMR (600 MHz, CDC13) δ 7.74 (d, J = 8.4 Hz, 1H), 7.59 (dd, J = 6.6, 1.2 Hz, 1H), 7.38 - 7.31 (m, 2H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 7.10 - 6.97 (m, 2H), 6.67 - 6.59 (m, 1H), 5.78 (s, 2H);13C NMR (151 MHz, CDC13) δ 180.96 (s), 162.64 (d, J = 254.8 Hz), 139.90 (s), 136.59 (s), 133.90 (s), 131.07 (d, J = 2.8 Hz), 130.31 (d, J = 8.2 Hz), 116.06 (d, J = 21.7 Hz), 113.84 (s), 58.03 (s).

[0062] Example Thirteen Synthesis of N-(3-chlorobenzyl)thiopyridinone

[0063]

[0064] Into a 10 mL reaction tube, 2,2'-dithiobispyridine (110.1 mg, 0.5 mmol), 3- chlorobenzyl bromide (205.5 mg, 1.0 mmol) were added sequentially, the cap of the reaction tube was tightened and placed in a 60 °C water bath for 4 h. When the reaction was complete, the reaction was separated by column chromatography (eluent: methanol: petroleum ether = 0~1 / 20) to obtain the product: N-(3-chlorobenzyl)thiopyridinone, with a yield of 60%.

[0065] The NMR data of the product N-(3-chlorobenzyl)thiopyridinone are as follows: 1 H NMR (600 MHz, CDC13) δ 7.79 - 7.71 (m, 1H), 7.59 (dd, J = 6.6, 0.6 Hz, 1H), 7.34 - 7.28 (m, 3H), 7.25 - 7.15 (m, 2H), 6.69 - 6.61 (m, 1H), 5.81 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.1, 140.0, 137.2, 136.6, 134.9, 134.0, 130.4, 128.6, 128.2, 126.4, 113.9, 58.1.

[0066] Example Fourteen Synthesis of N-(4-chlorobenzyl)thiopyridinone

[0067]

[0068] Into a 10 mL reaction tube, 2,2'-dithiobispyridine (110.1 mg, 0.5 mmol), 3- chlorobenzyl bromide (205.5 mg, 1.0 mmol) were added sequentially, the cap of the reaction tube was tightened and placed in a 60 °C water bath for 4 h. When the reaction was complete, the reaction was separated by column chromatography (eluent: methanol: petroleum ether = 0~1 / 20) to obtain the product: N-(3-chlorobenzyl)thiopyridinone, with a yield of 60%.

[0069] The NMR data of the product N-(4-chlorobenzyl)thiopyridinone are as follows: 1 H NMR (600 MHz, CDC13) δ 7.79 - 7.71 (m, 1H), 7.59 (dd, J = 6.6, 0.6 Hz, 1H), 7.34 - 7.28 (m, 3H), 7.25 - 7.15 (m, 2H), 6.69 - 6.61 (m, 1H), 5.81 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.1, 140.0, 137.2, 136.6, 134.9, 134.0, 130.4, 128.6, 128.2, 126.4, 113.9, 58.1.

[0070] Example Fifteen Synthesis of N-(3-bromobenzyl)thiopyridinone

[0071]

[0072] Into a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), 3-bromobenzyl bromide (249.9 mg, 1.0 mmol), cesium carbonate (16.3 mg, 0.05 mmol) were added in sequence, the cap of the reaction tube was tightened and the reaction was stirred at 60 °C for 12 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0~1 / 20) to obtain the product: N-(3-bromobenzyl)thiopyridinone, with a yield of 60%.

[0073] The nuclear magnetic resonance data of the product N-(3-bromobenzyl)thiopyridinone are as follows: 1 H NMR (600 MHz, CDC13) δ 7.75 (d, J = 8.4 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.28 - 7.21 (m, 2H), 7.19 (ddd, J = 8.6, 6.6, 1.8 Hz, 1H), 6.69 - 6.60 (m, 1H), 5.80 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.2, 14.0, 137.4, 136.7, 134.0, 131.6, 131.1, 130.7, 127.0, 123.1, 113.9, 58.0.

[0074] Example Sixteen Synthesis of N-(p-methoxybenzyl)thiopyridinone

[0075]

[0076] Into a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), 3-bromobenzyl bromide (249.9 mg, 1.0 mmol), cesium carbonate (16.3 mg, 0.05 mmol) were added in sequence, the cap of the reaction tube was tightened and the reaction was stirred at 60 °C for 12 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0~1 / 20) to obtain the product: N-(3-bromobenzyl)thiopyridinone, with a yield of 60%.

[0077] The nuclear magnetic resonance data of the product N-(3-bromobenzyl)thiopyridinone are as follows: 1H NMR (600 MHz, CDC13) δ 7.77 (dd, J = 8.4, 0.6 Hz, 1H), 7.55 (dd, J = 6.6, 1.2 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.20 - 7.12 (m, 3H), 6.64 - 6.56 (m, 1H), 5.77 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 138.3, 136.5, 133.5, 131.9, 129.9, 128.6, 113.3, 58.5, 21.3.

[0078] Example Seventeen Synthesis of N-benzylthiopyridinone

[0079]

[0080] Into a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), benzyl bromide (85.5 mg, 0.5 mmol) were added successively, the cap of the reaction tube was tightened and it was stirred at 60 °C for 4 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0~1 / 20) to obtain the product: N-benzylthiopyridinone, with a yield of 61%.

[0081] The nuclear magnetic resonance data of the product N-benzylthiopyridinone are as follows: 1 H NMR (600 MHz, CDC13) δ 7.76 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.48 - 7.30 (m, 5H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 6.66 - 6.58 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 136.5, 135.2, 133.8, 129.2, 128.5, 113.7, 58.8.

[0082] Example Eighteen Synthesis of N-benzylthiopyridinone

[0083]

[0084] Into a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), benzyl bromide (171.0 mg, 1.0 mmol) were added successively, the cap of the reaction tube was tightened and it was stirred at 60 °C for 4 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0~1 / 20) to obtain the product: N-benzylthiopyridinone, with a yield of 65%.

[0085] The NMR data of the product N-benzylthiopyridone is as follows: 1 H NMR (600 MHz, CDC13) δ 7.76 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.48 - 7.30 (m, 5H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 6.66 - 6.58 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 136.5, 135.2, 133.8, 129.2, 128.5, 113.7, 58.8.

[0086] Example Nineteen Synthesis of N-benzylthiopyridone

[0087]

[0088] Into a 10 mL reaction tube, 2,2-dithiodipyridine (110.1 mg, 0.5 mmol), benzyl bromide (342.1 mg, 2.0 mmol) were added successively, the reaction tube was tightly capped and stirred at 60 °C for 4 h. After the reaction was completed, the reaction solution was separated by column chromatography (developing agent: methanol: petroleum ether = 0-1 / 20) to obtain the product: N-benzylthiopyridone, with a yield of 73%.

[0089] The NMR data of the product N-benzylthiopyridone is as follows: 1 H NMR (600 MHz, CDC13) δ 7.76 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 6.6, 1.2 Hz, 1H), 7.48 - 7.30 (m, 5H), 7.17 (ddd, J = 8.4, 6.6, 1.8 Hz, 1H), 6.66 - 6.58 (m, 1H), 5.82 (s, 2H);13C NMR (151 MHz, CDC13) δ 181.0, 140.0, 136.5, 135.2, 133.8, 129.2, 128.5, 113.7, 58.8.

[0090] The above-described embodiments are only preferred embodiments of the present application and are used to explain the present application, but not to limit the scope of the present application. Those skilled in the art can easily make other embodiments according to the disclosed technical contents in the specification by substitution or change, and any changes and improvements made on the principles of the present application shall be included in the scope of the patent application.

Claims

1. A method for synthesizing an N-alkylated pyrithione compound, characterized by, comprising the steps of: In the presence of a base or without a base, N-alkylated pyridine thione compounds are synthesized by using 2,2-dithiodipyridine and benzyl halide as substrates; the reaction temperature is 60 DEG C, and the reaction time is 4-12 h; the benzyl halide has the following structural formula: R-X, wherein R is selected from benzyl, benzyl in which hydrogen on a benzene ring is substituted by halogen or methyl, and X is selected from bromine; the N-alkylated pyridine thione compound has the following structural formula: .

2. The method for synthesizing an N-alkylated pyridinethione compound according to claim 1, characterized in that, a molar ratio of the 2,2-dithiodipyridine to the benzyl halide compound is 1:1~4.

3. The method for synthesizing an N-alkylated pyridinethione compound according to claim 1, characterized in that, the benzyl halide compound is selected from one of benzyl bromide, 2-fluorobenzyl bromide, 3-fluorobenzyl bromide, 4-fluorobenzyl bromide, 2-chlorobenzyl bromide, 3-chlorobenzyl bromide, 4-chlorobenzyl bromide, 3-bromobenzyl bromide, or p-methylbenzyl bromide.

4. The method for synthesizing an N-alkylated pyridinethione compound according to claim 1, characterized in that, the base is one of cesium carbonate, sodium bicarbonate, sodium carbonate, 1,8-diazabicyclo[5.4.0]undec-7-ene, 4-dimethylaminopyridine, pyridine, or triethylamine.

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