CN111018807B - Method for synthesizing 1,2, 4-thiadiazole derivative - Google Patents
Method for synthesizing 1,2, 4-thiadiazole derivative Download PDFInfo
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- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/08—1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
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Abstract
The invention relates to a method for synthesizing a 1,2, 4-thiadiazole derivative, and belongs to the technical field of chemical preparation. The phenylacetic acid compound and benzamidine hydrochloride compound are taken according to the mass ratio of 1-2: 1 is dissolved in an organic solvent, a catalyst, an oxidant and an alkaline medium are added, and the mixture is stirred for 18 to 24 hours at the temperature of between 130 and 140 ℃ to react to obtain the 1,2, 4-thiadiazole derivative. Cooling, extracting, drying, decompressing, evaporating to remove solvent and performing column chromatography to obtain a pure product. The method for synthesizing the thiadiazole has the following beneficial effects: (1) The reaction condition is milder, the product selectivity is high, and the substrate expansion range is wide. (2) The raw materials used are low in price, low in cost, simple in reaction operation, safe and convenient.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a method for synthesizing a 1,2, 4-thiadiazole derivative.
Background
Thiadiazole compounds belong to nitrogen heterocyclic compounds, are five-membered nitrogen heterocyclic compounds, contain two nitrogen atoms and one sulfur atom, and have various material functions and medical values. In fact, 1,3, 4-thiadiazoles having a symmetrical structure are the most used in industrial production and pharmaceutical treatment, and there is relatively little research on 1,2, 4-thiadiazoles, which are also widely pharmacologically active and industrially valuable as isomers of 1,3, 4-thiadiazoles having an asymmetric five-membered ring structure. As early as 1968, haruki Eiichi et al synthesized 3, 5-diphenyl-1, 2, 4-thiadiazole from N-chlorobenzamidine and phenylthioamide, but this method had the disadvantage that the substrate had to be synthesized in advance. (Bulletin of the Chemical Society of Japan 1968 41:6, 1361-1367)
In recent years, there have been many reports on methods for synthesizing 1,2, 4-thiadiazole derivatives: for example, the Xu group uses thioamides and aliphatic nitriles as raw materials, and elemental iodine as an oxidant to obtain 1,2, 4-thiadiazole by intramolecular oxidative coupling, with moderate to good yields (org. Biomol. Chem.,2017,15,8410-8417). However, this method has a disadvantage of complicated operation. The method is characterized in that the method takes benzyl bromide, benzamidine hydrochloride and elemental sulfur as initial raw materials and lithium tert-butoxide as auxiliary alkali to synthesize the asymmetric 1,2, 4-thiadiazole. This reaction is very versatile, but the use of lithium t-butoxide is at risk (Tetrahedron Letters,2017, 58 (26), 2571-2573).
Although there are many reports about the synthesis of 1,2, 4-thiadiazole at present, the above methods have some defects, and require expensive substrate raw materials, so that the reaction steps are complicated, the conditions are severe, the yield is low, the post-treatment is difficult, toxic solvents are used, and the high price, the strong toxicity and the dependence on the highly toxic solvents limit the industrial application of the method in many fields.
Disclosure of Invention
The invention aims to provide a method for synthesizing a 1,2, 4-thiadiazole derivative, which provides more choices for industrial production thereof. The method has the advantages of cheap and easily available initial raw materials and wide substrate applicability.
The technical scheme adopted by the invention is as follows: the method comprises the following specific steps: the phenylacetic acid compound and benzamidine hydrochloride compound are taken according to the mass ratio of 1-2: 1 is dissolved in an organic solvent, a catalyst, an oxidant and an alkaline medium are added, and the mixture is stirred for 18 to 24 hours at the temperature of between 130 and 140 ℃ to react to obtain the 1,2, 4-thiadiazole derivative.
The reaction process is as follows:
preferably, the benzamidine hydrochloride compound has the following structural formula
Wherein R is 1 Is one of hydrogen and methyl.
Benzamidine hydrochloride compounds are: benzamidine hydrochloride
4-methylbenzidine hydrochloride
Preferably, the phenylacetic acid compound has the following structural formula:
The oxidant is preferably sulfur powder; the mass ratio of the sulfur powder to the benzamidine hydrochloride compound is 4-6: 1.
the alkaline medium is preferably Na 2 CO 3 The method comprises the steps of carrying out a first treatment on the surface of the The ratio of the amount of the alkaline medium to the amount of the substance of the benzamidine hydrochloride compound is 2-3: 1.
the catalyst is preferably CuI, cuBr or Cu (OAc) 2 The method comprises the steps of carrying out a first treatment on the surface of the The ratio of the catalyst to the benzamidine hydrochloride compound is 0.1-0.2: 1.
the solvent is preferably dimethyl sulfoxide (DMSO); the solvent is added in an amount to dissolve the reaction raw materials.
In the technical proposal, the mixture is stirred for 18 to 24 hours at the temperature of 130 to 140 ℃ and then the product is obtained by cooling, extracting, drying and column chromatography separation of the system.
Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages:
1. the reaction condition is simple and mild, the reaction yield is high, and the highest yield can reach 82 percent.
2. Sodium carbonate is used as an alkaline medium, the catalyst is low-cost copper salt, the use amount of the catalyst is only 20% of the amount of benzamidine hydrochloride compound substances, the target product can be obtained by only adding an organic solvent into a reaction system, the increase of the economic cost of the final product is solved, the use amount of the catalyst is small, and the pollution to the environment is reduced; the product is cooled, extracted, dried, decompressed, distilled to remove the solvent and subjected to column chromatography to finish the post-treatment, and the post-treatment is simple and convenient.
3. The established catalytic system has wide applicability, high substrate conversion rate and high product yield, and expands industrial application in various fields.
Detailed Description
The invention is further described below in connection with examples, which are not intended to limit the invention in any way:
example 1:
this example shows the synthesis of 3, 5-diphenyl-1, 2, 4-thiadiazole as benzamidineHydrochloride, phenylacetic acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol phenylacetic acid, 3.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.1mmol of CuI was added with 2mL of dimethyl sulfoxide and stirred at 130℃for 24 hours, and the reaction was completed by TLC plate, resulting in the formation of a product.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
The yield is 65 percent, and the melting point of the 3, 5-diphenyl-1, 2, 4-thiadiazole is 86 to 88 ℃; nuclear magnetic hydrogen spectrum (500 MHz, CDCl) 3 )：8.41(d,J＝6.5Hz,2H),8.05(d,J＝6.5Hz,2H),7.57-7.46(m,6H).
Example 2:
this example shows the synthesis of 3, 5-diphenyl-1, 2, 4-thiadiazole using benzamidine hydrochloride, phenylacetic acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 0.5mmol phenylacetic acid, 2.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.1mmol of CuI was added with 2mL of dimethyl sulfoxide and stirred at 130℃for 24 hours, and the reaction was completed by TLC plate, resulting in the formation of a product.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
The yield is 52%, and the melting point of the 3, 5-diphenyl-1, 2, 4-thiadiazole is 86-88 ℃; nuclear magnetic hydrogen spectrum (500 MHz, CDCl) 3 )：8.41(d,J＝6.5Hz,2H),8.05(d,J＝6.5Hz,2H),7.57-7.46(m,6H).
Example 3:
this example shows the synthesis of 3, 5-diphenyl-1, 2, 4-thiadiazole using benzamidine hydrochloride, phenylacetic acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol phenylacetic acid, 3.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.1mmol of CuI was added with 2mL of dimethyl sulfoxide and stirred at 140℃for 24 hours, and the reaction was completed by TLC plate, resulting in the formation of a product.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
The yield is 60 percent, and the melting point of the 3, 5-diphenyl-1, 2, 4-thiadiazole is 86-88 ℃; nuclear magnetic hydrogen spectrum (500 MHz, CDCl) 3 )：8.41(d,J＝6.5Hz,2H),8.05(d,J＝6.5Hz,2H),7.57-7.46(m,6H).
Example 4:
this example shows the synthesis of 3, 5-diphenyl-1, 2, 4-thiadiazole using benzamidine hydrochloride, phenylacetic acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol phenylacetic acid, 3.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.1mmol of CuI was added with 2mL of dimethyl sulfoxide and stirred at 130℃for 18 hours, and the reaction was completed by TLC plate, resulting in the formation of a product.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
The yield is 51%, and the melting point of the 3, 5-diphenyl-1, 2, 4-thiadiazole is 86-88 ℃; nuclear magnetic hydrogen spectrum (500 MHz, CDCl) 3 )：8.41(d,J＝6.5Hz,2H),8.05(d,J＝6.5Hz,2H),7.57-7.46(m,6H).
Example 5:
this example shows the synthesis of 3, 5-diphenyl-1, 2, 4-thiadiazole using benzamidine hydrochloride, phenylacetic acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol phenylacetic acid, 2.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.1mmol of CuI was added with 2mL of dimethyl sulfoxide and stirred at 130℃for 24 hours, and the reaction was completed by TLC plate, resulting in the formation of a product.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
The yield is 55%, and the melting point of the 3, 5-diphenyl-1, 2, 4-thiadiazole is 86-88 ℃; nuclear magnetic hydrogen spectrum (500 MHz, CDCl) 3 )：8.41(d,J＝6.5Hz,2H),8.05(d,J＝6.5Hz,2H),7.57-7.46(m,6H).
Example 6:
this example shows the synthesis of 3, 5-diphenyl-1, 2, 4-thiadiazole using benzamidine hydrochloride, phenylacetic acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol phenylacetic acid, 3.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.05mmol of CuI, 2mL of dimethyl sulfoxide was added thereto, and the mixture was stirred at 130℃for 24 hours, whereupon the reaction was completed by TLC plate, and a product was formed.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
Yield 57%, of 3, 5-diphenyl-)The melting point of the 1,2, 4-thiadiazole is 86-88 ℃; nuclear magnetic hydrogen spectrum (500 MHz, CDCl) 3 )：8.41(d,J＝6.5Hz,2H),8.05(d,J＝6.5Hz,2H),7.57-7.46(m,6H).
Example 7:
this example shows the synthesis of 3, 5-diphenyl-1, 2, 4-thiadiazole using benzamidine hydrochloride, phenylacetic acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol phenylacetic acid, 3.0mmol sulfur powder, 1.5mmol Na 2 CO 3 0.1mmol of CuI was added with 2mL of dimethyl sulfoxide and stirred at 130℃for 24 hours, and the reaction was completed by TLC plate, resulting in the formation of a product.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
The yield is 59 percent, and the melting point of the 3, 5-diphenyl-1, 2, 4-thiadiazole is 86-88 ℃; nuclear magnetic hydrogen spectrum (500 MHz, CDCl) 3 )：8.41(d,J＝6.5Hz,2H),8.05(d,J＝6.5Hz,2H),7.57-7.46(m,6H).
Example 8:
this example shows the synthesis of 3, 5-diphenyl-1, 2, 4-thiadiazole using benzamidine hydrochloride, phenylacetic acid, sulfur powder, na 2 CO 3 The reaction formulas of the raw materials of CuBr and dimethyl sulfoxide are as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol phenylacetic acid, 3.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.1mmol of CuBr, 2mL of dimethyl sulfoxide was added thereto, and the mixture was stirred at 130℃for 24 hours, whereupon the reaction was completed by TLC plate, and a product was formed.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
The yield is 63%, and the melting point of the 3, 5-diphenyl-1, 2, 4-thiadiazole is 86-88 ℃; nuclear magnetic hydrogen spectrum (500 MHz, CDCl) 3 )：8.41(d,J＝6.5Hz,2H),8.05(d,J＝6.5Hz,2H),7.57-7.46(m,6H).
Example 9:
this example shows the synthesis of 3, 5-diphenyl-1, 2, 4-thiadiazole using benzamidine hydrochloride, phenylacetic acid, sulfur powder, na 2 CO 3 、Cu(OAc) 2 Dimethyl sulfoxide is used as a raw material, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol phenylacetic acid, 3.0mmol sulfur powder, 1.0mmol Na 2 CO 3 ，0.1mmol Cu(OAc) 2 2mL of dimethyl sulfoxide was added thereto, and the mixture was stirred at 130℃for 24 hours, whereupon completion of the reaction was detected by TLC plate, and a product was formed.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
The yield is 64 percent, and the melting point of the 3, 5-diphenyl-1, 2, 4-thiadiazole is 86-88 ℃; nuclear magnetic hydrogen spectrum (500 MHz, CDCl) 3 )：8.41(d,J＝6.5Hz,2H),8.05(d,J＝6.5Hz,2H),7.57-7.46(m,6H).
Example 10:
this example shows the synthesis of 3-phenyl-5- (m-tolyl) -1,2, 4-thiadiazole using benzamidine hydrochloride, 3-methylphenylacetic acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol 3-methylphenylacetic acid, 3.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.1mmol of CuI, 2mL of dimethyl sulfoxide was added thereto, and the mixture was stirred at 130℃for 24 hoursThe reaction was complete as detected by TLC plates with product formation.
The reaction solution was cooled, extracted, dried, distilled under reduced pressure to remove the solvent, and filtered to give a yellow oil.
Yield 50%, nuclear magnetic hydrogen spectrum (500 MHz, CDCl) of the 3-phenyl-5- (m-tolyl) -1,2, 4-thiadiazole 3 )：δ8.40(d,J＝6.3Hz,2H),7.88(s,1H),7.84(d,J＝7.1Hz,1H),7.50(d,J＝ 6.8Hz,3H),7.43–7.33(m,2H),2.47(s,3H).
Example 11:
this example shows the synthesis of 3-phenyl-5- (p-tolyl) -1,2, 4-thiadiazole using benzamidine hydrochloride, 4-methylphenylacetic acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol 4-methylphenylacetic acid, 3.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.1mmol of CuI was added with 2mL of dimethyl sulfoxide and stirred at 130℃for 24 hours, and the reaction was completed by TLC plate, resulting in the formation of a product.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
The yield is 61%, and the melting point of the 3-phenyl-5- (p-tolyl) -1,2, 4-thiadiazole is 115-116 ℃; nuclear magnetic hydrogen spectrum (300 mhz, cdcl 3): δ8.45-8.34 (m, 2H), 7.95 (d, j=8.0 hz, 2H), 7.50 (d, j=5.5 hz, 3H), 7.32 (d, j=7.9 hz, 2H), 2.44 (s, 3H).
Example 12:
this example shows the synthesis of 3-phenyl-5- (3- (trifluoromethyl) phenyl) -1,2, 4-thiadiazole in the form of benzamidine hydrochloride, 3-trifluoromethylphenylacetic acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube were charged 0.5mmol benzamidine hydrochloride, 1.0mmol 3-trifluoromethylphenylacetic acid, 3.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.1mmol of CuI was added with 2mL of dimethyl sulfoxide and stirred at 130℃for 24 hours, and the reaction was completed by TLC plate, resulting in the formation of a product.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
Yield 82%, nuclear magnetic hydrogen spectrum (500 mhz, cdcl 3) of the 3-phenyl-5- (3- (trifluoromethyl) phenyl) -1,2, 4-thiadiazole: δ8.41 (d, j=6.3 hz, 2H), 8.34 (s, 1H), 8.22 (d, j=7.8 hz, 1H), 7.81 (d, j=7.8 hz, 1H), 7.67 (t, j=7.8 hz, 1H), 7.52 (d, j=6.5 hz, 3H).
Example 13:
this example shows the synthesis of 5- (3-methoxyphenyl) -3-phenyl-1, 2, 4-thiadiazole in the form of benzamidine hydrochloride, 3-methoxyphenylacetic acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol 3-methoxyphenylacetic acid, 3.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.1mmol of CuI was added with 2mL of dimethyl sulfoxide and stirred at 130℃for 24 hours, and the reaction was completed by TLC plate, resulting in the formation of a product.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
Yield 69%, nuclear magnetic hydrogen spectrum (500 MHz, CDCl 3) of the 5- (3-methoxyphenyl) -3-phenyl-1, 2, 4-thiadiazole: δ8.40 (d, j=7.2 hz, 2H), 7.64-7.58 (m, 2H), 7.50 (d, j=7.2 hz, 3H), 7.43 (t, j=7.9 hz, 1H), 7.09 (d, j=9.7 hz, 1H), 3.93 (s, 3H).
Example 14:
this example shows the synthesis of 5- (4-methoxyphenyl) -3-phenyl-1, 2, 4-thiadiazole as benzamidine hydrochloride, 4-methoxyPhenylacetic acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol 4-methoxyphenylacetic acid, 3.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.1mmol of CuI was added with 2mL of dimethyl sulfoxide and stirred at 130℃for 24 hours, and the reaction was completed by TLC plate, resulting in the formation of a product.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
Yield 50%, nuclear magnetic hydrogen spectrum (500 MHz, CDCl 3) of the 5- (4-methoxyphenyl) -3-phenyl-1, 2, 4-thiadiazole: δ8.38 (d, j=6.6 hz, 2H), 8.00 (d, j=8.7 hz, 2H), 7.49 (d, j=7.6 hz, 3H), 7.02 (d, j=8.7 hz, 2H), 3.90 (s, 3H).
Example 15:
this example shows the synthesis of 5- (naphthalen-2-yl) -3-phenyl-1, 2, 4-thiadiazole in the form of benzamidine hydrochloride, 2-naphthyridine acid, sulfur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol benzamidine hydrochloride, 1.0mmol 2-naphthylacetic acid, 3.0mmol sulfur powder, 1.0mmol Na 2 CO 3 0.1mmol of CuI was added with 2mL of dimethyl sulfoxide and stirred at 130℃for 24 hours, and the reaction was completed by TLC plate, resulting in the formation of a product.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
Yield 77%, melting point of this 5- (naphthalen-2-yl) -3-phenyl-1, 2, 4-thiadiazole is 125-126 ℃; nuclear magnetic hydrogen spectrum (500 mhz, cdcl 3): δ8.58 (s, 1H), 8.44 (d, j=6.8 Hz, 2H), 8.11 (d, j=8.4 Hz, 1H), 7.99 (t, j=7.3 Hz, 2H), 7.90 (d, j=6.1 Hz, 1H), 7.56 (dd, j=35.5, 6.1Hz, 5H).
Example 16:
this example shows the synthesis of 5-phenyl-3- (p-tolyl) -1,2, 4-thiadiazole in the form of 4-methylbenzamidine hydrochloride, phenylacetic acid, sulphur powder, na 2 CO 3 CuI and dimethyl sulfoxide are used as raw materials, and the reaction formula is as follows:
the preparation method comprises the following steps: into a 25mL pressure-resistant tube was charged 0.5mmol of 4-methylbenzamidine hydrochloride, 1.0mmol of phenylacetic acid, 3.0mmol of sulfur powder, 1.0mmol of Na 2 CO 3 0.1mmol of CuI was added with 2mL of dimethyl sulfoxide and stirred at 130℃for 24 hours, and the reaction was completed by TLC plate, resulting in the formation of a product.
The reaction solution is cooled, extracted, dried, decompressed, distilled to remove the solvent, and filtered to obtain white solid.
Yield 63%, nuclear magnetic hydrogen spectrum (500 MHz, CDCl) of the 5-phenyl-3- (p-tolyl) -1,2, 4-thiadiazole 3 )：δ8.30(d,J＝8.0Hz,2H),8.05(d,J＝7.6Hz,2H),7.52(d,J＝7.1Hz,3H), 7.31(d,J＝7.8Hz,2H),2.44(s,3H)。
Claims (3)
1. A method for synthesizing 1,2, 4-thiadiazole derivatives comprises the following specific steps: the phenylacetic acid compound and benzamidine hydrochloride compound are taken according to the mass ratio of 1-2: 1, dissolving in an organic solvent, adding a catalyst, an oxidant and an alkaline medium, and stirring at 130-140 ℃ for 18-24 hours to react to obtain a 1,2, 4-thiadiazole derivative; wherein the organic solvent is dimethyl sulfoxide; the oxidant is sulfur powder; the molar ratio of the oxidant to the benzamidine hydrochloride compound is 4-6:1; the alkaline medium is Na 2 CO 3 The method comprises the steps of carrying out a first treatment on the surface of the The molar ratio of the alkaline medium to the benzamidine hydrochloride compound is 2-3:1; the catalyst is CuI, cuBr or Cu (OAc) 2 The method comprises the steps of carrying out a first treatment on the surface of the The mol ratio of the catalyst to the benzamidine hydrochloride compound is 0.1-0.2:1.
2. The method according to claim 1, characterized in that: the structural formula of the benzamidine hydrochloride compound is as follows:
wherein R is 1 Is one of hydrogen or methyl.
3. The method according to claim 1, characterized in that: the structural formula of the phenylacetic acid compound is as follows:
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