A method for synthesizing 2-mercaptobenzothiazole derivatives

Abstract

The invention discloses a method for synthesizing 2-mercaptobenzothiazole derivatives, and belongs to the technical field of synthesizing 2-mercaptobenzothiazole derivatives. The method comprises: using o-amino aromatic disulfide and carbon disulfide as raw materials, dissolving in a solvent, under the action of sodium selenide, the o-amino aromatic disulfide breaks the S-S bond, and the carbon disulfide is activated, and a cyclization reaction is performed to obtain 2-mercaptobenzothiazole derivatives. The present invention utilizes sodium selenide activator to develop a method for synthesizing 2-mercaptobenzothiazole derivatives based on Se-S dynamic chemistry, achieving the advantages of low activator dosage, good substituent tolerance, and high yield.

Description

Technical Field

[0001] The invention relates to the technical field of synthesis of 2-mercaptobenzothiazole derivatives, and in particular to a method for synthesizing 2-mercaptobenzothiazole derivatives. Background Art

[0002] 2-Mercaptobenzothiazole derivatives, or MBTs, were first prepared by Woltersdorf et al. in 1887 and have been extensively studied in medicine and industry. In medical research, MBTs are often used to prepare antibacterial, anti-inflammatory, anthelmintic and anti-tuberculosis drugs. In industrial applications, MBTs are used as accelerators for rubber vulcanization and can also be used as ligands for luminescent metal complexes. Therefore, the study of the synthesis methods of MBTs remains one of the most attractive areas in synthetic chemistry.

[0003] Disulfide is an important starting material and intermediate for preparing sulfur-containing compounds. When using disulfide as the starting material for MBTs, the breaking of the SS bond is a key step. In existing studies, dynamic exchange reactions of thiol-disulfide bonds such as J. Comb. Chem. 2010, 12, 531 and dynamic exchange reactions of metal sulfide-disulfide bonds such as Green Chem., 2017, 19, 1102 have been used to break disulfide bonds to prepare MBTs. Based on this, the present invention uses sodium selenide as an activator for breaking disulfide bonds, and provides a method for synthesizing 2-mercaptobenzothiazole derivatives. Summary of the invention

[0004] The present invention provides a method for synthesizing 2-mercaptobenzothiazole derivatives. The method is based on Se-S dynamic chemistry and has the advantages of small amount of activator, i.e., 0.1 equiv., good tolerance to substituents, high yield, etc. Meanwhile, an environmentally friendly method for synthesizing 2-mercaptobenzothiazole derivatives is provided.

[0005] The present invention solves the above technical problems through the following technical solutions.

[0006] The object of the present invention is to provide a method for synthesizing 2-mercaptobenzothiazole derivatives, comprising the following steps:

[0007] Taking o-amino aromatic disulfide and carbon disulfide as raw materials, they are dissolved in a solvent. Under the action of sodium selenide activator, the SS bond of o-amino aromatic disulfide is broken, and the carbon disulfide is activated at the same time, and a cyclization reaction is carried out to obtain 2-mercaptobenzothiazole derivatives.

[0008] The reaction process of 2-mercaptobenzothiazole derivatives is as follows:

[0009]

[0010] According to the method of the present invention, after the reaction is completed, the product is generally obtained by filtering and washing with water, and sometimes it is necessary to obtain the product through extraction, concentration and purification processes. The concentration process adopts methods such as atmospheric distillation and reduced pressure distillation, such as vacuum concentration using a rotary evaporator. The purification process refers to column chromatography or recrystallization separation and purification technology.

[0011] As a preferred embodiment, the molar ratio of the sodium selenide to the o-amino aromatic disulfide is 1:1-10.

[0012] As a preferred embodiment, the molar ratio of the o-amino aromatic disulfide to carbon disulfide is 1:2-4.

[0013] As a preferred embodiment, the solvent is at least one of ethanol, N,N-dimethylformamide and acetonitrile.

[0014] As a preferred embodiment, the cyclization reaction is carried out at a temperature of 60 to 70° C. and for a time of 4 to 10 hours.

[0015] As a preferred embodiment, the structural formula of the o-amino aromatic disulfide is as follows:

[0016]

[0017] Wherein, R is selected from one of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, amine, trifluoromethyl, methanesulfonyl, cyano and nitro.

[0018] As a preferred embodiment, R is selected from one of hydrogen, C1-C2 alkyl, C1-C2 alkoxy, fluorine, chlorine, bromine, trifluoromethyl, amino, cyano and nitro.

[0019] As a preferred embodiment, R is selected from one of hydrogen, methyl, methoxy, fluorine, chlorine and bromine.

[0020] As a preferred embodiment, the o-amino aromatic disulfide is selected from one of 2,2'-dithiodiphenylamine, 4,4'-dichloro-2,2'-dithiodiphenylamine, 4,4'-dibromo-2,2'-dithiodiphenylamine, 4,4'-dimethoxy-2,2'-dithiodiphenylamine, 5,5'-dichloro-2,2'-dithiodiphenylamine, 6,6'-dimethyl-2,2'-dithiodiphenylamine and 6,6'-difluoro-2,2'-dithiodiphenylamine.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] The invention provides a method for synthesizing 2-mercaptobenzothiazole derivatives. Ortho-amino aromatic disulfide and carbon disulfide are used as raw materials and dissolved in a solvent. Under the action of sodium selenide, the ortho-amino aromatic disulfide breaks the SS bond to generate ortho-aminobenzenethiol anion, and the carbon disulfide is activated to sodium selenothiocarbonate. Then the two undergo a cyclization reaction to obtain the 2-mercaptobenzothiazole derivatives.

[0023] Based on Se-S dynamic chemistry, a class of 2-mercaptobenzothiazole derivatives were synthesized with the advantages of small amount of activator, i.e. 0.1 equiv., good tolerance to substituents and high yield. The reaction process is simple and will not affect the environment. DETAILED DESCRIPTION

[0024] In order to enable those skilled in the art to better understand the technical solution of the present invention and implement it, the present invention is further described below in conjunction with specific examples, but the examples are not intended to limit the present invention. The following test methods and detection methods, unless otherwise specified, are conventional methods; the reagents and raw materials, unless otherwise specified, are commercially available.

[0025] In the present invention, selenium, i.e., Se, is a chalcogen element having chemical and physical properties similar to those of sulfur. However, due to the larger radius, lower electronegativity, and higher polarizability of the selenium atom, Se 2- Species such as Se 2- 、R-Se - ,HSe - Than S 2- The corresponding substance has better nucleophilicity, see Nat. Synth 2024, 3, 477. In addition, the bond energy of Se-S bond is 203 kJ mol -1 Much smaller than the bond energy of a disulfide bond, 240 kJ mol -1 , see Acta Polymerica Sinica, 2020, 51, 1190, making it more dynamically reversible. 2- Species ratio S 2- The corresponding substances such as thiols and metal sulfides are more likely to attack disulfide bonds, and the formed Se-S bonds are more likely to undergo dynamic exchange reactions than disulfide bonds. Based on this, the present invention provides a method for synthesizing 2-mercaptobenzothiazole derivatives, comprising the following steps:

[0026] Take o-amino aromatic disulfide and carbon disulfide as raw materials, dissolve them in a solvent, and under the action of sodium selenide activator, o-amino aromatic disulfide breaks the SS bond to generate o-aminobenzenethiophenol anion, and carbon disulfide is activated to sodium selenothiocarbonate, and then the two undergo cyclization reaction to obtain 2-mercaptobenzothiazole derivatives. The reaction mechanism is as follows:

[0027]

[0028] The present invention is based on Se-S dynamic chemistry, and exhibits the advantages of small amount of activator 0.1 equiv., i.e. 0.1 equiv., good tolerance to substituents, high yield, etc., and synthesizes a class of 2-mercaptobenzothiazole derivatives, with a simple reaction process and no impact on the environment.

[0029] The present invention will now be further described with reference to specific embodiments.

[0030] 1. The synthesis process of the 2-mercaptobenzothiazole derivatives of the present invention comprises the following steps:

[0031] Place sodium selenide of o-amino aromatic disulfide in a reaction tube, evacuate, and introduce argon, repeat this operation 3-5 times, then use a syringe to add a reaction solvent, then add carbon disulfide, stir and react at 60°C for 10 hours, plate chromatography detection shows that the disulfide raw material reacts completely, cool to room temperature, extract with ethyl acetate, and then use a rotary evaporator to remove the solvent under reduced pressure to obtain a crude product. The crude product is separated by 200-300 mesh silica gel column chromatography using dichloromethane as an eluent and gradient elution to obtain a 2-mercaptobenzothiazole derivative.

[0032] In a specific embodiment, the molar ratio of sodium selenide to o-amino aromatic disulfide is 1:1 to 10. In the present invention, the molar ratio of sodium selenide to o-amino aromatic disulfide can be any ratio between 1:1 and 10, such as 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10, but is not limited to the listed values, and other unlisted values ​​within the above numerical range are also applicable, which will not be repeated here.

[0033] In a specific embodiment, the molar ratio of the o-amino aromatic disulfide to carbon disulfide is 1:2 to 4. In the present invention, the molar ratio of the o-amino aromatic disulfide to carbon disulfide can be any ratio between 1:2 and 4, such as 1:2, 1:3 or 1:4, but is not limited to the listed values, and other unlisted values ​​within the above numerical range are also applicable, which will not be repeated here.

[0034] In a specific embodiment, the solvent is at least one of ethanol, N,N-dimethylformamide, and acetonitrile.

[0035] In a specific embodiment, the temperature of the cyclization reaction is 60-70°C, and the time is 4-10h. In the present invention, the temperature of the cyclization reaction can be any specific value between 60-70°C, such as 60°C, 61°C, 62°C, 63°C, 64°C, 65°C, 66°C, 67°C, 68°C, 69°C or 70°C, etc., and the reaction time can be any specific value between 4-10h, such as 4h, 5h, 6h, 7h, 8h, 9h or 10h, etc., but is not limited to the listed values, and other unlisted values ​​within the above numerical range are also applicable, so they will not be repeated here.

[0036] The reaction process of 2-mercaptobenzothiazole derivatives is as follows:

[0037]

[0038] Wherein, R is selected from one of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, amine, trifluoromethyl, methanesulfonyl, cyano and nitro.

[0039] 2. The present invention synthesized the following 7 2-mercaptobenzothiazole derivatives:

[0040] The specific structural formulas of the seven derivatives of Examples 1 to 9 are shown in Table 1.

[0041] Table 1 Specific structural formulas of 7 derivatives

[0042]

[0043] Example 1

[0044] The synthesis method of mercaptobenzothiazole, wherein the molar ratio of 2,2'-dithiodiphenylamine:Na2Se:carbon disulfide=1:0.04:4, the solvent: ethanol, i.e., EtOH, comprises the following steps:

[0045] Add 99 mg, i.e. 0.40 mmol, of 2,2'-dithiodiphenylamine and 5 mg, i.e. 0.04 mmol, of Na2Se to a Shrek tube, then use a double-row tube to evacuate the mixture and introduce argon gas, repeat this operation three times, then use a syringe to add 2.5 mL of EtOH as a reaction solvent, then add 97 μL, i.e. 1.6 mmol of carbon disulfide, stir and react at 60°C for 10 hours, and plate chromatography detection shows that the disulfide raw material reacts completely, cool to room temperature, extract with ethyl acetate, and then use a rotary evaporator to remove the solvent under reduced pressure to obtain a crude product. The crude product is eluted with dichloromethane, gradient eluted, and separated by 200-300 mesh silica gel column chromatography to obtain 132 mg of white powder 2-mercaptobenzothiazole with a purity greater than 99%, an isolation yield of 99%, and a melting point of 182-183°C. Its structural formula is:

[0046]

[0047] Example 2

[0048] The synthesis method of mercaptobenzothiazole, wherein the molar ratio of 2,2'-dithiodiphenylamine:Na2Se:carbon disulfide=1:0.04:4, the solvent is N,N-dimethylformamide, i.e. DMF, comprises the following steps:

[0049] Add 99 mg, i.e. 0.40 mmol, of 2,2'-dithiodiphenylamine and 5 mg, i.e. 0.04 mmol, of Na2Se to the Shrek tube, then use a double-row tube to evacuate the tube and introduce argon. Repeat this operation three times, then use a syringe to add 2.5 mL of DMF as the reaction solvent, and then add 97 μL, i.e. 1.6 mmol of carbon disulfide. After stirring and reacting at 60°C for 10 hours, plate chromatography detection shows that the disulfide raw material has reacted completely, and the mixture is cooled to room temperature, extracted with ethyl acetate, and then the solvent is removed by a rotary evaporator under reduced pressure to obtain a crude product. The crude product is eluented with dichloromethane, gradient elution is used, and separation is performed on a 200-300 mesh silica gel column to obtain 123 mg of white powder 2-mercaptobenzothiazole with a purity greater than 99%, an isolation yield of 91%, and a melting point of 182-183°C. Its structural formula is

[0050]

[0051] Example 3

[0052] The synthesis method of mercaptobenzothiazole, wherein the molar ratio of 2,2'-dithiodiphenylamine:Na2Se:carbon disulfide=1:0.04:4, the solvent is acetonitrile, i.e. CH3CN, comprises the following steps:

[0053] Add 99 mg, i.e. 0.40 mmol, of 2,2'-dithiodiphenylamine and 5 mg, i.e. 0.04 mmol, of Na2Se to the Shrek tube, then use a double-row tube to evacuate and introduce argon, repeat this operation three times, then use a syringe to add 2.5 mL of CH3CN as the reaction solvent, then add 97 μL, i.e. 1.6 mmol of carbon disulfide, stir and react at 60°C for 10 hours, and plate chromatography detection shows that the disulfide raw material reacts completely, cool to room temperature, extract with ethyl acetate, and then use a rotary evaporator to remove the solvent under reduced pressure to obtain a crude product. The crude product is eluented with dichloromethane, gradient elution, and separation by 200-300 mesh silica gel column chromatography to obtain 129 mg of white powder 2-mercaptobenzothiazole with a purity greater than 99%, an isolation yield of 96%, and a melting point of 182-183°C. Its structural formula is:

[0054]

[0055] The data characterization of 2-mercaptobenzothiazole prepared in Examples 1-3 is as follows:

[0056] 1 H NMR (500MHz, DMSO-d6, TMS): δ13.75 (brs, 1H), 7.69 (d, 1H, J = 9.0Hz), 7.41-7.38 (m, 1H), 7.32-7.27 (m, 2H).

[0057] 13 C NMR (125MHz, DMSO-d6, TMS): δ189.7, 141.1, 129.2, 127.0, 124.1, 121.7, 112.3.

[0058] MS: EIMS calcd for C7H5NS2167.0,found 167.1[Μ + ].

[0059] Example 4

[0060] A method for synthesizing 6-chloro-2-mercaptobenzothiazole, wherein the molar ratio of 4,4'-dichloro-2,2'-dithiodiphenylamine:Na2Se:carbon disulfide=1:0.04:4, and the solvent is EtOH, comprising the following steps:

[0061] Add 127mg, i.e. 0.40mmol, of 4,4'-dichloro-2,2'-dithiodiphenylamine and 5mg, i.e. 0.04mmol, of Na2Se to the Shrek tube, then use a double-row tube to evacuate and introduce argon, repeat this operation three times, then use a syringe to add 2.5mL of EtOH as the reaction solvent, then add 97μL, i.e. 1.6mmol of carbon disulfide, stir and react at 60°C for 10h, plate chromatography detection shows that the disulfide raw material reacts completely, cool to room temperature, extract with ethyl acetate, and then use a rotary evaporator to remove the solvent under reduced pressure to obtain a crude product. The crude product is eluented with dichloromethane, gradient elution, and separation by 200-300 mesh silica gel column chromatography to obtain 146.8mg of white powder 6-chloro-2-mercaptobenzothiazole with a purity greater than 99%, a nuclear magnetic yield of 91.1%, and a melting point of 239-241°C. Its structural formula is:

[0062]

[0063] The data characterization of 6-chloro-2-mercaptobenzothiazole prepared in Example 4 is as follows:

[0064] 1H NMR (500MHz, DMSO-d6, TMS): δ13.86 (brs, 1H), 7.86 (d, 1H, J = 2.0Hz), 7.44 (dd, 1H, J1 = 8.5Hz, J2 = 2.0Hz), 7.28 (d, 1H, J = 8.5Hz).

[0065] 13 C NMR (125MHz, DMSO-d6, TMS): δ190.1, 140.1, 130.9, 128.5, 127.2, 121.3, 113.4.

[0066] MS: EIMS calcd for C7H4ClNS2201.0,found 200.9[Μ + ].

[0067] Example 5

[0068] The synthesis method of mercaptobenzothiazole, wherein the molar ratio of 4,4'-dibromo-2,2'-dithiodiphenylamine:Na2Se:carbon disulfide=1:0.04:4, the solvent: EtOH, comprises the following steps:

[0069] Add 163mg, i.e. 0.40mmol, of 4,4'-dibromo-2,2'-dithiodiphenylamine and 5mg, i.e. 0.04mmol, of Na2Se to the Shrek tube, then use a double-row tube to evacuate and introduce argon, repeat this operation three times, then use a syringe to add 2.5mL of EtOH as the reaction solvent, then add 97μL, i.e. 1.6mmol of carbon disulfide, stir and react at 60°C for 10h, plate chromatography detection shows that the disulfide raw material reacts completely, cool to room temperature, extract with ethyl acetate, and then use a rotary evaporator to remove the solvent under reduced pressure to obtain a crude product. The crude product is eluented with dichloromethane, gradient elution, and separation by 200-300 mesh silica gel column chromatography to obtain 177.4mg of white powder 6-bromo-2-mercaptobenzothiazole with a purity greater than 99%, a nuclear magnetic yield of 90.1%, and a melting point of 265-266°C. Its structural formula is:

[0070]

[0071] The data characterization of 6-bromo-2-mercaptobenzothiazole prepared in Example 5 is as follows:

[0072] 1H NMR (500MHz, DMSO-d6, TMS): δl3.86 (brs, lH), 7.98 (1,1H, J = 2.0Hz), 7.56 (dd, 1H, J1 = 8.5Hz, J2 = 2.0Hz), 7.22 (d, 1H, J = 8.5Hz).

[0073] 13 C NMR (125MHz, DMS0-d6, TMS): δl89.9, 140.6, 131.4, 129.9, 124.0, 116.2, 113.8.

[0074] MS: EIMS calcd for C7H4BrNS2244.9 found 246.8[M + ].

[0075] Example 6

[0076] A method for synthesizing 6-methoxy-2-mercaptobenzothiazole, wherein the molar ratio of 4,4'-dimethoxy-2,2'-dithiodiphenylamine:Na2Se:carbon disulfide=1:0.04:4, and the solvent is EtOH, comprising the following steps:

[0077] Add 123 mg, i.e. 0.40 mmol, of 4,4'-dimethoxy-2,2'-dithiodiphenylamine and 5 mg (0.04 mmol) of Na2Se to the Shrek tube, then use a double-row tube to evacuate and introduce argon, repeat this operation three times, then use a syringe to add 2.5 mL of EtOH as the reaction solvent, then add 97 μL, i.e. 1.6 mmol of carbon disulfide, stir and react at 60°C for 10 hours, and plate chromatography detection shows that the disulfide raw material reacts completely, cool to room temperature, extract with ethyl acetate, and then use a rotary evaporator to remove the solvent under reduced pressure to obtain a crude product. The crude product is eluented with dichloromethane, gradient elution, and separation by 200-300 mesh silica gel column chromatography to obtain 190.4 mg of white powder 6-methoxy-2-mercaptobenzothiazole with a purity greater than 99%, with an isolation yield of 96.5% and a melting point of 203-204°C. Its structural formula is:

[0078]

[0079] The data characterization of 6-methoxy-2-mercaptobenzothiazole prepared in Example 6 is as follows:

[0080] 1H NMR (500MHz, DMSO-d6, TMS): δl3.61 (brs, 1H), 7.35 (d, 1H, J = 2.5Hz), 7.22 (d, 1H, J = 9.0Hz), 6.99 (dd, 1H, J1 = 8.5Hz, J2 = 2.5Hz), 3.77 (s, 3H).

[0081] 13 C NMR (125MHz, DMS0-d6, TMS): δl88.2, 156.5, 135.1, 130.6, 114.7, 113.0, 105.8, 55.6.

[0082] Mass spectral data: EIMS calcd for C8H7NOS2197.0, found 197.0 [M + ].

[0083] Example 7

[0084] A method for synthesizing 5-chloro-2-mercaptobenzothiazole, wherein the molar ratio of 5,5'-dichloro-2,2'-dithiodiphenylamine:Na2Se:carbon disulfide=1:0.04:4, solvent: EtOH, comprises the following steps:

[0085] Add 127mg, i.e. 0.40mmol, of 5,5'-dichloro-2,2'-dithiodiphenylamine and 5mg, i.e. 0.04mmol, of Na2Se to the Shrek tube, then use a double-row tube to evacuate and introduce argon, repeat this operation three times, then use a syringe to add 2.5mL of EtOH as the reaction solvent, then add 97μL, i.e. 1.6mmol of carbon disulfide, stir and react at 60°C for 10h, plate chromatography detection shows that the disulfide raw material reacts completely, cool to room temperature, extract with ethyl acetate, and then use a rotary evaporator to remove the solvent under reduced pressure to obtain a crude product. The crude product is eluented with dichloromethane, gradient elution, and separation by 200-300 mesh silica gel column chromatography to obtain 156mg of white powder 5-chloro-2-mercaptobenzothiazole with a purity greater than 99%, an isolation yield of 96.7%, and a melting point of 199-200°C. Its structural formula is:

[0086]

[0087] The data characterization of 5-chloro-2-mercaptobenzothiazole prepared in Example 7 is as follows:

[0088] 1HNMR (500MHz, DMSO-d6, TMS): δ13.84 (brs, 1H), 7.72 (d, 1H, J = 8.5Hz), 7.35 (dd, 1H, J1 = 8.5Hz, J2 = 2.0Hz), 7.28 (d, 1H, J = 2.0Hz).

[0089] 13 C NMR (125MHz, DMSO-d6, TMSO): δ190.8, 142.1, 131.7, 128.2, 124.0, 123.1, 111.8.

[0090] MS: EIMS calcd for C7H4ClNS2201.0,found 200.9[M + ].

[0091] Example 8

[0092] A method for synthesizing 4-methyl-2-mercaptobenzothiazole, wherein the molar ratio of 6,6'-dimethyl-2,2'-dithiodiphenylamine:Na2Se:carbon disulfide=1:0.04:4, and the solvent is EtOH, comprising the following steps:

[0093] Add 111 mg, i.e. 0.40 mmol, of 6,6'-dimethyl-2,2'-dithiodiphenylamine and 5 mg, i.e. 0.04 mmol, of Na2Se to the Shrek tube, then use a double-row tube to evacuate and introduce argon, repeat this operation three times, then use a syringe to add 2.5 mL of EtOH as the reaction solvent, then add 97 μL, i.e. 1.6 mmol of carbon disulfide, stir and react at 60°C for 10 hours, and plate chromatography detection shows that the disulfide raw material reacts completely, cool to room temperature, extract with ethyl acetate, and then use a rotary evaporator to remove the solvent under reduced pressure to obtain a crude product. The crude product is eluented with dichloromethane, gradient elution, and separation by 200-300 mesh silica gel column chromatography to obtain 139.4 mg of white powder 4-methyl-2-mercaptobenzothiazole with a purity greater than 99%, an isolation yield of 96.1%, and a melting point of 191-193°C. Its structural formula is:

[0094]

[0095] The data characterization of 4-methyl-2-mercaptobenzothiazole prepared in Example 8 is as follows:

[0096] 1 HNMR (500MHz, DMSO-d6, TMS): δ13.57(brs,1H),7.51-7.48(m,1H),7.20(s,1H),7.19(s,1H),2.45(s,3H).

[0097] 13 C NMR (125MHz, DMSO-d6, TMS): δ190.0,140.1,128.9,128.1,124.1,122,5,118.9,17.4.

[0098] MS: EIMS calcd forC8H7NS2181.0,found 181.1[M + ].

[0099] Example 9

[0100] A method for synthesizing 4-fluoro-2-mercaptobenzothiazole, wherein the molar ratio of 6,6'-difluoro-2,2'-dithiodiphenylamine:Na2Se:carbon disulfide=1:0.04:4, and the solvent is EtOH, comprising the following steps:

[0101] Add 122mg, i.e. 0.40mmol, of 6,6'-difluoro-2,2'-dithiodiphenylamine and 5mg, i.e. 0.04mmol, of Na2Se to the Shrek tube, then use a double-row tube to evacuate and introduce argon, repeat this operation three times, then use a syringe to add 2.5mL of EtOH as the reaction solvent, then add 97μL, i.e. 1.6mmol of carbon disulfide, stir and react at 60°C for 10h, plate chromatography detection shows that the disulfide raw material reacts completely, cool to room temperature, extract with ethyl acetate, and then use a rotary evaporator to remove the solvent under reduced pressure to obtain a crude product. The crude product is eluented with dichloromethane, gradient elution, and separation by 200-300 mesh silica gel column chromatography to obtain 145.5mg of white powder 4-fluoro-2-mercaptobenzothiazole with a purity greater than 99%, with an isolation yield of 98.2% and a melting point of 190-192°C. Its structural formula is:

[0102]

[0103] Example 9 The data for preparing 4-fluoro-2-mercaptobenzothiazole are as follows:

[0104] 1 H NMR (500MHz, DMSO-d6, TMS): δ14.22(brs,1H),7.53-7.52(m,1H),7.20(s,1H),7.31-7.24(m,2H)).

[0105] 13C NMR (125MHz, DMSO-d6, TMS): δ190.6, 146.8 (d, 1C, J = 247Hz), 131.6 (d, 1C, J = 12Hz), 129. 5(d,1C,J=60Hz), 12.5(d,1C,J=25.5Hz), 117.67(d,1C,J=15Hz), 113.1(d,1C,J=66Hz).

[0106] MS: EIMS calcd for C7H4FNS2185.2, found 184.9[Μ + ].

[0107] Although the preferred embodiments of the present invention have been described, those skilled in the art may make other changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

[0108] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A method for synthesizing 2-mercaptobenzothiazole derivatives, characterized in that: The following steps are involved: Taking o-amino aromatic disulfide and carbon disulfide as raw materials, they are dissolved in a solvent, and under the action of sodium selenide activator, the o-amino aromatic disulfide breaks the SS bond, and the carbon disulfide is activated, and a cyclization reaction is carried out to obtain 2-mercaptobenzothiazole derivatives; The molar ratio of o-amino aromatic disulfide, sodium selenide and carbon disulfide is 1:0.04:4; The structural formula of the o-amino aromatic disulfide is as follows: Wherein, R is selected from at least one of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, amine, trifluoromethyl, methanesulfonyl, cyano and nitro.

2. The method for synthesizing 2-mercaptobenzothiazole derivatives according to claim 1, characterized in that: The solvent is at least one of ethanol, N,N-dimethylformamide and acetonitrile.

3. The method for synthesizing 2-mercaptobenzothiazole derivatives according to claim 1, characterized in that: The temperature of the cyclization reaction is 60-70° C. and the time is 4-10 hours.

4. The method for synthesizing 2-mercaptobenzothiazole derivatives according to claim 1, characterized in that: The R is selected from at least one of hydrogen, C1-C2 alkyl, C1-C2 alkoxy, fluorine, chlorine, bromine, trifluoromethyl, amine, cyano and nitro.

5. The method for synthesizing 2-mercaptobenzothiazole derivatives according to claim 4, characterized in that: The R is selected from at least one of hydrogen, methyl, methoxy, fluorine, chlorine and bromine.

6. The method for synthesizing 2-mercaptobenzothiazole derivatives according to claim 5, characterized in that: The o-amino aromatic disulfide is selected from one of 2,2'-dithiodiphenylamine, 4,4'-dichloro-2,2'-dithiodiphenylamine, 4,4'-dibromo-2,2'-dithiodiphenylamine, 4,4'-dimethoxy-2,2'-dithiodiphenylamine, 5,5'-dichloro-2,2'-dithiodiphenylamine, 6,6'-dimethyl-2,2'-dithiodiphenylamine and 6,6'-difluoro-2,2'-dithiodiphenylamine.

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