Electrochemical synthesis of 2-aminothiazole compounds

Abstract

The present invention relates to an electrochemical synthesis method of 2-aminothiazole compounds with the structural formula shown below: 1 =4‑Me‑, 3‑Me‑, 2‑Me‑, 4‑Et‑, 4‑MeO‑, 4‑OH‑, 4‑F‑, 4‑Cl‑, 3‑Cl‑, 2‑Cl‑.R 2 =H, Me, Et, Ph. The main process is: in a single-chamber electrolytic cell, ketone (0.589 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H 2 O (0.951g, 5mmol), DMSO (10ml), H 2 O (5ml). Both the cathode and the anode are inserted into graphite sheets, and the current density is 5mA / cm 2 The reaction temperature was 70°C and the current was 3F / mol. The corresponding 2-aminothiazole compound 3 was obtained with a yield of 38-72%.

Description

Technical Field

[0001] The invention relates to an electrochemical synthesis method of 2-aminothiazole compounds. Background Art

[0002] Thiazole compounds have broad application prospects in many fields such as medicine, pesticides, materials, and fragrances, so the synthesis methods of this type of compounds have always received close attention.

[0003] The traditional thiazole synthesis method mainly adopts a multi-step synthesis method to achieve synthesis through the transformation between functional groups. For example, the Hantzch method uses α-haloaldehyde or ketone to react with thioamide to prepare thiazole compounds. This method has a high yield, but the first step of the method requires the use of a chemical amount of chlorine, liquid bromine or elemental iodine to prepare α-haloaldehyde or ketone. In 2019, Evren et al. (Evren AE, Yurttas L., Ekselli B., Akali-Ciftcib G. Phosphorus, Sulfur and Silicon and the Related Elements, 2019, 194 (8): 820-828.) reported a method in which ketones were first prepared under Br2 / HBr / AcOH reaction conditions, and then reacted with thiourea at room temperature for 24 hours to prepare thiazole compounds. The main problems with this method are as follows:

[0004] (1) Liquid bromine is used as an oxidant and HBr / AcOH is used as a catalyst. A large amount of corrosive hydrohalic acid is produced during the reaction, which makes post-treatment complicated and causes serious environmental problems.

[0005] (2) The reaction steps are complicated;

[0006] (3) The reaction time is relatively long.

[0007] At present, there is no report on the electrochemical synthesis method of 2-aminothiazole compounds in domestic and foreign literature. Summary of the invention

[0008] The purpose of the present invention is to provide an electrochemical synthesis method of 2-aminothiazole compounds which is efficient, low-cost, simple to operate and relatively less polluting to the environment.

[0009] The electrochemical synthesis method of 2-aminothiazole compounds provided by the present invention comprises the following steps: in a single-chamber electrolytic cell, using compound 1 and thiourea 2 as raw materials, using dimethyl sulfoxide and water as solvents, using ammonium halide or alkali metal halide as both electrolyte and electrocatalyst, using graphite sheets as cathode and anode, reacting at a temperature of 50-90°C and a current density of 5 mA / cm 2After passing 3-6F / mol of electricity, the corresponding 2-aminothiazole compound 3 was obtained.

[0010]

[0011] R 1 =4-Me-, 3-Me-, 2-Me-, 4-Et-, 4-MeO-, 4-OH-, 4-F-, 4-Cl-, 3-Cl-, 2-Cl-.

[0012] R 2 =H, Me, Et, Ph.

[0013] The above solvent system is DMSO, DMF, methanol, ethanol, acetonitrile, DMSO:H2O=(2:1), DMSO:H2O=(1:1), DMSO:H2O=(1:2), preferably DMSO:H2O=(2:1).

[0014] The ammonium halide or alkali metal halide is ammonium iodide, tetraethylammonium iodide, tetrabutylammonium iodide, sodium iodide, sodium bromide, sodium chloride, potassium iodide, preferably ammonium iodide.

[0015] The electrolysis anode is a graphite electrode, and the cathode is a graphite electrode.

[0016] The above reaction temperature is 50-90°C, preferably 70°C.

[0017] The above current density is preferably 5 mA / cm 2 .

[0018] The amount of electricity passed is 3-6F / mol, preferably 1F / mol.

[0019] Compared with the existing methods, the method of the present invention has the following characteristics:

[0020] (1) This electrochemical method constructs the thiazole ring in one step without the need to separate the intermediate α-haloketone.

[0021] (2) The electrochemical method only requires a catalytic amount of halide, avoiding the use of stoichiometric, toxic halogen elements, thereby avoiding the generation of a large amount of corrosive hydrohalic acid;

[0022] (3) The device should be simple and the experimental operation should be convenient.

[0023] (4) A constant current electrolysis method is used. The equipment cost required by this method is low. At the same time, constant current electrolysis is more suitable for industrial production.

[0024] (5) The working electrode is a graphite electrode, which is cheap and readily available.

[0025] (6) The reaction temperature is mild.

[0026] The present invention relates to an electrochemical synthesis method of 2-aminothiazole compounds having the structural formula shown below:

[0027]

[0028] R 1 =4-Me-, 3-Me-, 2-Me-, 4-Et-, 4-MeO-, 4-OH-, 4-F-, 4-Cl-, 3-Cl-, 2-Cl-.

[0029] R 2 =H, Me, Et, Ph.

[0030] The main process is: in a single-chamber electrolytic cell, ketone 1 (0.589 g, 3 mmol), thiourea 2 (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), H2O (5 ml) are added in sequence. Graphite sheet electrodes are inserted into the cathode and anode, and the current density is 5 mA / cm 2 The reaction temperature was 70°C and the current was 3F / mol. The corresponding 2-aminothiazole compounds 3 were obtained with a yield of 38-72%.

[0031] The structures of the 2-aminothiazole compounds prepared electrochemically from ketone and thiourea as raw materials in the method of the present invention were confirmed by nuclear magnetic resonance. The analysis results are attached after the examples. DETAILED DESCRIPTION

[0032] Example 1: Electrochemical Synthesis of 2-Amino-4-phenyl-5-methylthiazole 3a

[0033] In a single-chamber electrolytic cell, phenylacetone (0.403 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70℃, and the electrolytic reaction begins. After 3F / mol of electricity is applied, the electricity is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove excess iodine, extracted with dichloromethane (20ml×3), filtered, and the organic phase is dried with anhydrous Mg2SO4, and concentrated by rotary evaporation to obtain a crude product. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3a with a yield of 61%. 1H NMR (300MHz, CDCl3): δ2.351 (s, 3H), 5.524 (br, 2H), 7.273 (t, J=6.9Hz, 1H), 7.372 (t, J=6.6Hz, 2H), 7.532 (d, J=6.3Hz, 2H). 13 CNMR (75MHz, CDCl3): δ12.23, 117.07, 127.04, 128.12, 128.24, 135.08, 145.84.

[0034]

[0035] Example 2: Electrochemical Synthesis of 2-Amino-4-phenylthiazole 3b

[0036] In a single-chamber electrolytic cell, acetophenone (0.360 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature was 70°C, and the electrolytic reaction was started. After 3F / mol of electricity was applied, the electricity was stopped and post-processing was performed. An appropriate amount of Na2S2O3 solution was added to remove the excess iodine, and dichloromethane (20 ml×3) was used for extraction, filtration, and the organic phase was dried with anhydrous Mg2SO4. The crude product was concentrated by rotary evaporation. The crude product was separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3b with a yield of 67%. 1 H NMR (300MHz, CDCl3): δ5.259 (br, 2H), 6.708 (s, 1H), 7.285 (t, J=7.2Hz, 1H), 7.376 (t, J=7.2Hz, 2H), 7.764 (d, J=7.5 Hz, 2H). 13 C NMR (75MHz, CDCl3): δ102.71, 125.97, 127.73, 128.58, 134.56, 151.14, 167.41.

[0037]

[0038] Example 3: Electrochemical Synthesis of 2-Amino-4-phenyl-5-ethylthiazole 3c

[0039] In a single-chamber electrolytic cell, phenylbutyrophenone (0.445 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70℃, and the electrolytic reaction begins. After 3F / mol of electricity is applied, the electricity is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove excess iodine, and dichloromethane (20ml×3) is used for extraction, filtration, and the organic phase is dried with anhydrous Mg2SO4, and the crude product is obtained after rotary evaporation and concentration. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3c with a yield of 38%. 1 H NMR (300MHz, CDCl3): δ1.226 (t, J=7.5Hz, 3H), 2.772 (q, J=7.5Hz, 2H), 5.570 (br, 2H), 7.278 (t, J=7.2Hz, 1H), 7.368 (t, J=7.2Hz, 2H), 7.496 (d, J=7.2Hz, 2H). 13 C NMR (75MHz, CDCl3): δ16.67, 20.45, 125.53, 127.16, 128.15, 128.33, 135.26, 145.06, 164.55.

[0040]

[0041] Example 4: Electrochemical Synthesis of 2-Amino-4,5-Diphenylthiazole 3d

[0042] In a single-chamber electrolytic cell, diphenylacetophenone (0.589 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70℃, and the electrolytic reaction begins. After 3F / mol of electricity is applied, the electricity is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove excess iodine, and dichloromethane (20ml×3) is used for extraction, filtration, and the organic phase is dried with anhydrous Mg2SO4, and the crude product is obtained after rotary evaporation and concentration. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3d with a yield of 72%. 1H NMR (300MHz, CDC13): δ5.219 (br, 2H), 7.240-7.263 (m, 8H), 7.438-7.470 (m, 2H). 13 C NMR (75MHz, CDCl3): δ 122.41, 127.32, 127.57, 128.19, 128.55, 128.86, 129.37, 132.45, 135.01, 145.49, 165.22.

[0043]

[0044] Example 5: Electrochemical Synthesis of 2-amino-4-(4-methylphenyl)-5-methylthiazole 3e

[0045] In a single-chamber electrolytic cell, p-methylpropiophenone (0.445 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70℃, and the electrolytic reaction begins. After 3F / mol of electricity is applied, the electricity is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove excess iodine, and dichloromethane (20ml×3) is used for extraction, filtration, and the organic phase is dried with anhydrous Mg2SO4, and the crude product is obtained after rotary evaporation and concentration. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3e with a yield of 54%. 1 H NMR (300MHz, CDCl3): δ2.369 (s, 6H), 5.116 (br, 2H), 7.197 (d, J=7.8Hz, 2H), 7.442 (d, J=8.1Hz, 2H). 13 C NMR (75MHz, CDCl3): δ12.35, 21.21, 94.02, 116.94, 128.20, 128.91, 132.18, 136.89, 145.97, 163.75.

[0046]

[0047] Example 6: Electrochemical Synthesis of 2-Amino-4-(3-methylphenyl)-5-methylthiazole 3f

[0048] In a single-chamber electrolytic cell, 3-methylpropiophenone (0.445 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70℃, and the electrolytic reaction begins. After 3F / mol of electricity is applied, the electricity is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove the excess iodine, and dichloromethane (20 ml×3) is used for extraction, filtration, and the organic phase is dried with anhydrous Mg2SO4, and the crude product is obtained after rotary evaporation and concentration. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3f with a yield of 58%. 1 H NMR (300MHz, CDCl3): δ2.349 (s, 3H), 2.364 (s, 3H), 5.372 (br, 2H), 7.093 (d, J=7.2Hz, 2H), 7.231-7.326 (m, 2H), 7.368 (s, 1H). 13 C NMR (75MHz, CDCl3): δ12.24, 21.37, 117.01, 125.32, 127.83, 127.97, 128.96, 134.97, 137.71, 145.98, 164.13.

[0049]

[0050] Example 7: Electrochemical Synthesis of 3 g of 2-amino-4-(2-methylphenyl)-5-methylthiazole

[0051] In a single-chamber electrolytic cell, 2-methylpropiophenone (0.445 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70℃, and the electrolytic reaction begins. After 3F / mol of electricity is applied, the electricity is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove excess iodine, extracted with dichloromethane (20ml×3), filtered, and the organic phase is dried with anhydrous Mg2SO4, and concentrated by rotary evaporation to obtain a crude product. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain 3g of the target compound with a yield of 46%. 1H NMR (300MHz, CDC13): δ1.997 (s, 3H), 2.150 (s, 3H), 5.467 (br, 2H), 7.076-7.140 (m, 4H). 13 C NMR (75MHz, CDC13): δ11.58, 19.69, 117.45, 125.23, 127.71, 129.96, 129.99, 134.52, 137.18, 146.23, 164.48.

[0052]

[0053] Example 8: Electrochemical Synthesis of 2-Amino-4-(4-ethylphenyl)-5-methylthiazole 3h

[0054] In a single-chamber electrolytic cell, 4-ethylpropiophenone (0.506 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70℃, and the electrolytic reaction begins. After 3F / mol of electricity is applied, the electricity is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove excess iodine, extracted with dichloromethane (20ml×3), filtered, and the organic phase is dried with anhydrous Mg2SO4, and concentrated by rotary evaporation to obtain a crude product. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3h with a yield of 47%. 1 H NMR (300MHz, CDC13): δ1.250 (t, J=7.5, 3H), 2.369 (s, 3H), 2.665 (q, J=7.5, 2H), 5.259 (br, 2H), 7.216 (d, J=8.1, 2H), 7.461 (d, J=8.1, 2H). 13 C NMR (75MHz, CDCl3): δ12.50, 15.61, 28.74, 117.01, 127.86, 128.43, 132.57, 143.39, 146.12, 149.87, 164.04.

[0055]

[0056] Example 9: Electrochemical Synthesis of 2-amino-4-(4-methoxyphenyl)-5-methylthiazole 3i

[0057] In a single-chamber electrolytic cell, 4-methoxypropiophenone (0.493, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70℃, and the electrolytic reaction begins. After 3F / mol of electricity is applied, the electricity is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove excess iodine, and dichloromethane (20ml×3) is used for extraction, filtration, and the organic phase is dried with anhydrous Mg2SO4, and the crude product is obtained after rotary evaporation and concentration. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3i with a yield of 54%. 1 H NMR (300MHz, CDCl3): δ2.326 (s, 3H), 3.803 (s, 3H), 5.596 (br, 2H), 6.907 (d, J=8.4, 2H), 7.463 (d, J=8.7, 2H). 13 C NMR (75 MHz, CDCl3): δ12.36, 55.30, 113.69, 115.86, 127.83, 129.59, 145.53, 158.74, 164.33.

[0058]

[0059] Example 10: Electrochemical Synthesis of 2-Amino-4-(4-hydroxyphenyl)-5-methylthiazole 3j

[0060] In a single-chamber electrolytic cell, 4-hydroxypropiophenone (0.451 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70℃, and the electrolytic reaction begins. After 3F / mol of electricity is applied, the electricity is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove excess iodine, extracted with dichloromethane (20ml×3), filtered, and the organic phase is dried with anhydrous Mg2SO4, and concentrated by rotary evaporation to obtain a crude product. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3j with a yield of 65%. 1H NMR (300MHz, CDC13): δ3.273 (s, 3H), 6.703 (s, 2H), 6.774 (d, J=8.4, 2H), 7.369 (d, J=8.4, 2H), 9.456 (br, 1H). 13 C NMR (75MHz, CDCl3): δ12.18, 112.32, 114.87, 126.59, 129.28, 145.16, 156.23, 163.99.

[0061]

[0062] Example 11: Electrochemical Synthesis of 2-Amino-4-(4-chlorophenyl)-5-methylthiazole 3k

[0063] In a single-chamber electrolytic cell, 4-chloropropiophenone (0.506 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70℃, and the electrolytic reaction begins. After the power is applied to 3F / mol, the power is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove the excess iodine, and the mixture is extracted with dichloromethane (20ml×3), filtered, and the organic phase is dried with anhydrous Mg2SO4, and concentrated by rotary evaporation to obtain a crude product. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3k with a yield of 46%. 1 H NMR (300MHz, CDC13): δ2.358 (s, 3H), 5.219 (br, 2H), 7.350 (d, J=8.4, 2H), 7.350 (d, J=8.4, 2H). 13 C NMR (75 MHz, CDCl3): δ12.33, 117.87, 128.37, 129.53, 132.87, 133.54, 144.81, 164.06.

[0064]

[0065] Example 12: Electrochemical Synthesis of 2-Amino-4-(3-chlorophenyl)-5-methylthiazole 31

[0066] In a single-chamber electrolytic cell, 3-chloropropiophenone (0.506 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70°C, and the electrolytic reaction begins. After 3F / mol of electricity is applied, the electricity is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove excess iodine, extracted with dichloromethane (20ml×3), filtered, and the organic phase is dried with anhydrous Mg2SO4, and concentrated by rotary evaporation to obtain a crude product. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3l with a yield of 52%. 1 H NMR (300MHz, CDCl3): 2.367 (s, 3H), 5.326 (br, 2H), 7.277-7.328 (m, 2H), 7.411-7.429 (m, 1H), 7.554 (s, 1H). 13 C NMR (75MHz, CDCl3): δ12.28, 118.35, 126.31, 127.13, 128.28, 129.41, 134.05, 136.84, 144.49, 164.20.

[0067]

[0068] Example 13: Electrochemical Synthesis of 2-Amino-4-(2-chlorophenyl)-5-methylthiazole 3m

[0069] In a single-chamber electrolytic cell, 2-chloropropiophenone (0.506 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70℃, and the electrolytic reaction begins. After 3F / mol of electricity is applied, the electricity is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove excess iodine, extracted with dichloromethane (20ml×3), filtered, and the organic phase is dried with anhydrous Mg2SO4, and concentrated by rotary evaporation to obtain a crude product. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3m with a yield of 38%. 1H NMR (300MHz, CDC13): δ2.150 (s, 3H), 5.043 (br, 2H), 7.249-7.305 (m, 2H), 7.340-7.384 (m, 1H), 7.406-7.462 (m, 1H). 13 C NMR (75MHz, CDCl3): δ11.88, 119.47, 126.39, 129.08, 129.57, 131.72, 134.04, 143.63, 164.58.

[0070]

[0071] Example 14: Electrochemical Synthesis of 2-amino-4-(4-fluorophenyl)-5-methylthiazole 3n

[0072] In a single-chamber electrolytic cell, 4-fluoropropiophenone (0.457 g, 3 mmol), thiourea (0.076 g, 1 mmol), anhydrous ammonium iodide (0.145 g, 1 mmol), TsOH·H2O (0.951 g, 5 mmol), DMSO (10 ml), and H2O (5 ml) were added in sequence. Graphite sheet electrodes were inserted into the cathode and anode, and the current density was 3 mA / cm 2 , the reaction temperature is 70℃, and the electrolytic reaction begins. After 3F / mol of electricity is applied, the electricity is stopped and post-processing is performed. An appropriate amount of Na2S2O3 solution is added to remove excess iodine, extracted with dichloromethane (20ml×3), filtered, and the organic phase is dried with anhydrous Mg2SO4, and concentrated by rotary evaporation to obtain a crude product. The crude product is separated by column chromatography using a 200-300 mesh silica gel column to obtain the target compound 3n with a yield of 56%. 1 H NMR (300MHz, CDCl3): δ2.327 (s, 3H), 5.497 (br, 2H), 7.026 (m, 2H), 7.471-7.519 (m, 2H). 13 C NMR (75MHz, CDCl3): δ12.15, 114.88and115.16 (d, J (C, F) = 21Hz), 116.88, 129.85 and 129.95 (d, J (C, F) = 7.5 Hz), 131.18and131.22(d, J(C, F)=3Hz), 144.90, 160.17and163.43(d, J(C, F)=244.5Hz), 164.30.

[0073] .

Claims

1. An electrochemical synthesis method of 2-aminothiazole compounds, the steps of which are: in a single-chamber electrolytic cell, using compound 1 and thiourea 2 as raw materials, dimethyl sulfoxide and water as solvents, ammonium halide or alkali metal halide as both electrolyte and electrocatalyst, graphite sheet as cathode and anode, in the presence of additives, reaction temperature 50-90 ° C, current density 5 mA / cm 2 After 3-6F / mol of electricity, the corresponding 2-aminothiazole compound 3 is obtained, and the reaction formula is as follows: R 1 =4-Me-,3-Me-,2-Me-,4-Et-,4-MeO-,4-OH-,4-F-,4-Cl-,3-Cl-,2-Cl- R 2 =H, Me, Et, Ph.

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