2, 4, 4-trimethyl thiazolidine derivative and synthesis method thereof

Abstract

The invention relates to the field of synthesis of thiazole compounds, in particular to a 2, 4, 4-trimethyl thiazolidine derivative and a synthesis method thereof. According to the invention, in the presence of alkali, calcium carbide, hydrogen sulfide and propargyl amine compounds are used as main raw materials for reaction; calcium carbide is used as a solid alkyne source, acetylene gas is released by depolymerizing the calcium carbide through hydrogen sulfide, and the acetylene gas reacts with a propargyl amine compound, so that the 2, 4, 4-trimethyltetrahydrothiazole derivative is synthesized. According to the method, H2S is adopted to depolymerize calcium carbide to synthesize the 2, 4, 4-trimethyltetrahydrothiazole derivative, safe, stable and easily available calcium carbide is used as a raw material, transition metal catalysis and high-pressure-resistant equipment are not needed, and toxic and harmful H2S gas is reasonably utilized. The synthesis method provided by the invention has more outstanding advantages of atom economy and green chemistry.

Description

Technical Field

[0001] The present invention relates to the field of synthesis of thiazole compounds, and more particularly to a 2,4,4-trimethylthiazole derivative and a synthesis method thereof. Background Art

[0002] Thiazolidine (tetrahydrothiazole) is a multifunctional five-membered heterocyclic structure widely found in natural and biologically active compounds. The presence of sulfur significantly enhances the pharmacological properties of thiazolidine, making it an important carrier for the synthesis of valuable organic compounds. In addition, thiazolidine compounds are important intermediates for pesticides and medicines, and their synthesis research has been ongoing.

[0003] According to relevant literature reports, there are many methods for synthesizing thiazolidine heterocyclic compounds. Most of these methods use isothiocyanate, thiourea, carbon disulfide, and 1,4-dithio-2,5-diol as raw materials to synthesize thiazolidine compounds.

[0004] Methylthiazolidine derivatives are a class of thiazolidine compounds. Currently, there are relatively few types of methylthiazolidine derivatives disclosed. Moreover, there are relatively few methods for synthesizing methylthiazolidine compounds. Currently, there is only one method disclosed: synthesis by reaction of cysteamine hydrochloride with aldehydes or ketones. Among them, the product synthesized by reaction with aldehydes, such as acetaldehyde, is 2-methylthiazolidine, and the product synthesized by reaction with ketones, such as acetone, is 2,2-dimethylthiazolidine. The scope of the substrate cysteamine hydrochloride in this synthesis method is relatively limited. References: Tetrahedron 64 (2008) 3691-3700; Tetrahedron Letters 41 (2000) 3381–3384; Bulletin de la Societe Chimique de France (1967), 10, 3637-3639). Summary of the invention

[0005] In order to enrich the types of methylthiazolidine compounds, the present invention synthesizes 2,4,4-trimethylthiazolidine derivatives and provides a synthesis method of the 2,4,4-trimethylthiazolidine derivatives.

[0006] The present invention, in the presence of alkali, uses calcium carbide (CaC 2 ), hydrogen sulfide (H 2 S) and propargylamine compounds are used as main raw materials for reaction; calcium carbide is used as a solid alkyne source, acetylene gas is released by depolymerizing calcium carbide with hydrogen sulfide, and acetylene gas is reacted with propargylamine compounds to synthesize 2,4,4-trimethylthiazole derivatives.

[0007] One of the purposes of the present invention is to provide a 2,4,4-trimethylthiazolidine derivative.

[0008] The 2,4,4-trimethylthiazolidine derivative refers to a derivative containing 2,4,4-trimethylthiazolidine The structural formula of the 2,4,4-trimethylthiazolidine derivative is shown in formula (I).

[0009] (I) In formula (I), R 1 is selected from thienyl, pyridyl, naphthyl, phenyl, substituted phenyl; The substituted phenyl group is selected from halogen, trifluoromethyl, hydroxyl, C 1-8 Hydrocarbon, C 1-8 In one or more alkoxy groups, the number of substituents is one or more, and the position of the substituents is arbitrary. When the number of substituents is two, the position of the substituents can be ortho, meta or para.

[0010] R 1 In, C 1-8 Hydrocarbyl groups include but are not limited to C 1-8 Alkyl, phenyl, alkyl-substituted phenyl, and the like.

[0011] R 1 In, C 1-8 Alkyloxy includes but is not limited to C 1-8 Alkoxy, C 6-8 Aromatic alkyloxy.

[0012] The C 1-8 Alkyl, C 1-8 The alkyl involved in the alkoxy group is an alkyl group having 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms, and can be a straight-chain alkyl group or a branched-chain alkyl group; the present invention has no particular limitation.

[0013] According to the embodiments disclosed in the present invention, the 2,4,4-trimethylthiazolidine derivative may be: 5-benzylidene-2,4,4-trimethylthiazolidine, whose structural formula is , 2,4,4-trimethyl-5-(4-methylbenzylidene)thiazolidine, whose structural formula is , 2,4,4-trimethyl-5-(4-methoxybenzylidene)thiazolidine, whose structural formula is , 2,4,4-trimethyl-5-(4-chlorobenzylidene)thiazolidine, whose structural formula is , 2,4,4-trimethyl-5-(4-iodobenzylidene)thiazolidine, whose structural formula is , 2,4,4-trimethyl-5-(4-trifluoromethylbenzylidene)thiazolidine, whose structural formula is , 2,4,4-trimethyl-5-(1-naphthylmethylene)thiazolidine, whose structural formula is , 2,4,4-trimethyl-5-(2-pyridylmethylene)thiazolidine, whose structural formula is , 2,4,4-trimethyl-5-(3-thienylmethylene)thiazolidine, whose structural formula is .

[0014] The second object of the present invention is to provide a method for synthesizing the 2,4,4-trimethylthiazolidine derivatives described in the first object of the present invention.

[0015] A method for synthesizing 2,4,4-trimethylthiazolidine derivatives comprises: in a closed environment, in the presence of a base, calcium carbide, hydrogen sulfide and a propargylamine compound react in an organic solvent.

[0016] The propargylamine compound refers to a compound containing propargylamine The structural formula of the propargylamine compound is shown in formula (II).

[0017] (II) In formula (II), R 1 is selected from thienyl, pyridyl, naphthyl, phenyl, substituted phenyl; The substituted phenyl group is selected from halogen, trifluoromethyl, hydroxyl, C 1-8 Hydrocarbon, C 1-8 In one or more alkoxy groups, the number of substituents is one or more, and the position of the substituents is arbitrary. When the number of substituents is two, the position of the substituents can be ortho, meta or para.

[0018] R 1 In, C 1-8 Hydrocarbyl groups include but are not limited to C 1-8 Alkyl, phenyl, alkyl substituted phenyl, and the like.

[0019] R 1 In, C 1-8 Alkyloxy includes but is not limited to C 1-8 Alkoxy, C 6-8 Aromatic alkyloxy.

[0020] The C 1-8 Alkyl, C1-8 The alkyl involved in the alkoxy group is an alkyl group having 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms, and can be a straight-chain alkyl group or a branched-chain alkyl group; the present invention has no particular limitation.

[0021] R in formula (II) 1 With R in formula (I) 1 The same, R in formula (I) 1 From R in formula (II) 1 That is, different propargylamine compounds are used to obtain different 2,4,4-trimethylthiazolidine derivatives; and the 2,4,4-trimethylthiazolidine derivatives are determined by the propargylamine compounds used. Therefore, those skilled in the art can select appropriate propargylamine compounds according to the 2,4,4-trimethylthiazolidine derivatives to be prepared.

[0022] According to the embodiments disclosed in the present invention, the propargylamine compound is selected from: 2-methyl-4-phenyl-3-butyn-2-amine, the structural formula of which is ; 4-(4-methylphenyl)-2-methyl-3-butyn-2-amine, whose structural formula is ; 4-(4-methoxyphenyl)-2-methyl-3-butyn-2-amine, whose structural formula is ; 4-(4-chlorophenyl)-2-methyl-3-butyn-2-amine, whose structural formula is ; 4-(4-iodophenyl)-2-methyl-3-butyn-2-amine, whose structural formula is ; 4-(4-trifluoromethylphenyl)-2-methyl-3-butyn-2-amine, whose structural formula is ; 2-methyl-4-naphthyl-3-butyn-2-amine, whose structural formula is ; 2-methyl-4-(2-pyridyl)-3-butyn-2-amine, whose structural formula is ; 2-methyl-4-(3-thienyl)-3-butyn-2-amine, whose structural formula is .

[0023] At this time, the prepared 2,4,4-trimethylthiazolidine derivatives are corresponding to 5-benzylidene-2,4,4-trimethylthiazolidine, 2,4,4-trimethyl-5-(4-methylbenzylidene)thiazolidine, 2,4,4-trimethyl-5-(4-methoxybenzylidene)thiazolidine), 2,4,4-trimethyl-5-(4-chlorobenzylidene)thiazolidine, 2,4,4-trimethyl-5-(4-iodobenzylidene)thiazolidine, 2,4,4-trimethyl-5-(4-trifluoromethylbenzylidene)thiazolidine, 2,4,4-trimethyl-5-(1-naphthylmethylene)thiazolidine, 2,4,4-trimethyl-5-(2-pyridylmethylene)thiazolidine, and 2,4,4-trimethyl-5-(3-thienylmethylene)thiazolidine.

[0024] The propargyl amine compound can be prepared by an existing method. For example, reference can be made to: OrgLett. 2014, 16, 2430−2433.; ACS Sustainable Chem. Eng. 2022, 10, 3, 1214–1219). According to an embodiment disclosed in the present invention, one of the preparation methods of the propargyl amine compound comprises: reacting THF / Et 3 N solution (5 mL, THF and Et 3 N (volume ratio of 4:1) was added with CuI (0.20 mmol), PdCl 2 (PPh 3 ) 2 (0.10 mmol) and aryl iodide compounds (5.5 mmol), and then 2-methyl-3-butyn-2-amine (5.0 mmol) was added, and the mixture was stirred at room temperature overnight. After the reaction was completed, saturated NH 4 Cl aqueous solution, then Et 2 O was extracted three times. The combined organic layers were washed with saturated brine and washed with anhydrous Na 2 SO 4 Dry, filter, concentrate under reduced pressure, and the residue is purified by silica gel column chromatography (PE / EA / Et 3 N=2 / 1 / 1%), and finally the corresponding propargyl amine compounds were obtained.

[0025] The role of the base is to promote the reaction and improve the yield. The base can be selected from a wide range. As a preferred embodiment, the base can be selected from 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), cesium carbonate (Cs 2 CO 3 ), Potassium tert-butoxide ( t-BuOK), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), tetramethylguanidine (TMG), sodium hydroxide (NaOH), triethylamine (Et 3 N), more preferably TBD, Cs 2 CO 3 , t -At least one of BuOK.

[0026] The organic solvent can be selected in a wide range without particular limitation. The organic solvent commonly used in the field of organic synthesis can be selected. Specifically, the organic solvent can be a polar aprotic solvent. As a preferred embodiment, the organic solvent is selected from at least one of N-methylpyrrolidone (NMP), N,N-dimethylformamide (DMF), N, N-dimethylacetamide, dimethyl sulfoxide (DMSO), and 1,4-dioxane, and more preferably at least one of N-methylpyrrolidone (NMP) and dimethyl sulfoxide (DMSO).

[0027] The amount of the organic solvent can be selected in a wide range. As a preferred embodiment, the ratio of the organic solvent to the propargylamine compound is 0.5-15 mL:1 mmol; that is, relative to 0.2 mmol of the propargylamine compound, the amount of the organic solvent can be 0.1-3 mL.

[0028] The propargylamine compound is mixed with calcium carbide, H 2 The molar ratio of S can be selected in a wide range. As a preferred embodiment, the propargylamine compound and calcium carbide, H 2 The molar ratio of S may be 1:(1-6):(2-9), more preferably 1:(2-4):(2-6).

[0029] The molar ratio of the propargylamine compound to the base can be selected in a wide range. As a preferred embodiment, the molar ratio of the propargylamine compound to the base is 1:(0.25-2), preferably 1:(0.5-1), for example, it can be 1:0.3, 0.4, 0.5, and the ratio of any two values ​​or any interval between any two values.

[0030] The reaction temperature can be selected in a wide range. As a preferred embodiment, the reaction temperature is 80-150°C, preferably 110-120°C.

[0031] The reaction time can be selected in a wide range. As a preferred embodiment, the reaction time is 1-6 hours, preferably 3-5 hours.

[0032] The synthesis method of the 2,4,4-trimethylthiazolidine derivative may further include adding copper salt.

[0033] A method for synthesizing 2,4,4-trimethylthiazolidine derivatives comprises: in a closed environment, in the presence of a base and a copper salt, calcium carbide, hydrogen sulfide and a propargylamine compound react in an organic solvent.

[0034] The copper salt comprises a +1-valent copper salt or a +2-valent copper salt. The copper salt can be selected from a wide range. As a preferred embodiment, the copper salt is selected from CuI, CuCl, CuBr, Cu 2 O, CuCl 2 , CuO, such as CuI.

[0035] The molar ratio of the propargylamine compound to the copper salt can be selected in a wide range. As a preferred embodiment, the molar ratio of the propargylamine compound to the copper salt can be 1:(0.1-3), preferably 1:(1-3), for example 1:1.

[0036] The synthesis method of the 2,4,4-trimethylthiazolidine derivative may include the following steps: Add propargylamine compounds, alkali, solvent, ground calcium carbide, and optionally copper salt into the reaction kettle, seal the reaction kettle, and introduce H 2 S gas, heated to the reaction temperature, reacted under stirring conditions, after the reaction was completed, cooled to room temperature, extracted, washed, the organic layer was dried and the solvent was removed under reduced pressure to obtain a crude product, and the crude product was separated by column chromatography to obtain a 2,4,4-trimethylthiazole derivative.

[0037] According to an embodiment disclosed in the present invention, a method for synthesizing a 2,4,4-trimethylthiazolidine derivative represented by formula (I) comprises: adding a propargylamine compound represented by formula (II), a base, a solvent, and ground calcium carbide into a reaction kettle, optionally adding a copper salt, closing the reaction kettle, and introducing H 2 S gas, heated to 100-120°C, reacted for 3-5h under stirring, after the reaction was completed, cooled to room temperature, extracted with ethyl acetate, washed with saturated brine, dried the organic layer and removed the solvent under reduced pressure to obtain a crude product, the crude product was separated by column chromatography to obtain a 2,4,4-trimethylthiazole derivative represented by formula (I); the propargyl amine compound was reacted with calcium carbide, H 2 The molar ratio of S, base and copper salt is 1:(1-6):(2-9):(0.25-2):(0.1-3), preferably 1:(2-4):(2-6):(0.5-1):(1-3).

[0038] Compared with the prior art, the present invention has the following beneficial effects: 1. The synthesis method of the present invention uses safe, stable and readily available calcium carbide as a reaction raw material; H 2S depolymerizes calcium carbide, which can not only solve H 2 Environmental pollution caused by S can also be 2 Rational use of S can avoid waste of sulfur resources.

[0039] 2. The synthesis method of the present invention is carried out in a closed environment. Except for the pressure generated by the introduction of hydrogen sulfide and the pressure generated by the gas generated during the reaction, no additional pressurization is required, and no high-pressure resistant equipment is required, which effectively reduces the risk of explosion and can synthesize 2,4,4-trimethylthiazolidine derivatives under relatively mild conditions.

[0040] 3. The synthesis method of the present invention is simple. In addition to the reaction raw materials, no transition metal catalysis is required. The target compound can be synthesized in high yield only under the action of a base.

[0041] 4. The synthesis method of the present invention has strong substrate applicability for synthesizing 2,4,4-trimethylthiazolidine derivatives and has a high yield.

[0042] 5. The synthesis method of the present invention can adjust the yield of 2,4,4-trimethylthiazolidine derivatives by adjusting specific reaction conditions (dosage, molar ratio, temperature, time).

[0043] In summary, the present invention adopts H 2 S depolymerizes calcium carbide to synthesize 2,4,4-trimethylthiazole derivatives, wherein safe, stable and readily available calcium carbide is used as a raw material, without the need for transition metal catalysis and high-pressure resistant equipment, and the toxic and harmful H 2 The S gas is used reasonably. The synthesis method of the present invention has more prominent advantages of "atom economy" and "green chemistry". DETAILED DESCRIPTION

[0044] The present invention is described in detail below in conjunction with specific embodiments. It is necessary to point out that the following embodiments are only used to further illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made to the present invention by those skilled in the art based on the contents of the present invention still fall within the scope of protection of the present invention.

[0045] The reaction reagents involved in the examples are all commonly used commercially available products. The model of the nuclear magnetic resonance spectrometer used in the examples is Agilent 500 MHz DD2.

[0046] Examples 1 to 20 Synthesis of propargyl amine compounds: THF / Et 3 N solution (5 mL, THF and Et 3 N (volume ratio of 4:1) was added with CuI (0.20 mmol), PdCl2 (PPh 3 ) 2 (0.10 mmol) and aryl iodide compounds (5.5 mmol), and then 2-methyl-3-butyn-2-amine (5.0 mmol) was added, and the mixture was stirred at room temperature overnight. After the reaction was completed, saturated NH 4 Cl aqueous solution, then Et 2 O was extracted three times. The combined organic layers were washed with saturated brine and washed with anhydrous Na 2 SO 4 The residue was purified by silica gel column chromatography (PE / EA / Et 3 N=2 / 1 / 1%). Finally, the corresponding propargylamine compounds were obtained. The general reaction formula is as follows:

[0047] The aryl iodide compounds and the corresponding propargyl amine compounds prepared and their NMR characterization data are shown in Table 1.

[0048] Table 1

[0049] Synthesis of 5-benzylidene-2,4,4-trimethylthiazolidine: (1) Add 0.2 mmol of propargylamine compounds (2-methyl-4-phenyl-3-butyn-2-amine )、CaC 2 , a base and 2 mL of solvent, optionally a copper salt, then the reactor was closed and H 2 S gas. The stirrer speed of the reactor was adjusted to 800 rpm, and the reactor was reacted in a sand bath at a temperature of T℃ for a reaction time of t. After the reaction was stopped, the reactor was taken out of the sand bath, cooled at room temperature, the residual gas was released in a fume hood, and the reactor was unscrewed. It was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried and the solvent was removed under reduced pressure to obtain a crude product. The crude product was separated by column chromatography (200-300 mesh silica gel) to obtain a light yellow oily substance with a purity greater than 99%.

[0050] (2) NMR characterization data of the light yellow oily substance obtained in step (1): 1H NMR (500 MHz, CDCl3): δ 7.45 (d, J = 8.0 Hz, 2H), 7.34 (t, J = 7.5 Hz, 2H), 7.17 (t, J = 8.0 Hz, 1H), 6.32 (s, 1H), 4.83 (q, J = 6.0 Hz, 1H), 1.75 (br, 1H), 1.66 (d, J = 6.0Hz, 3H), 1.58 (s, 3H), 1.34 (s, 3H). 13 C NMR (126 MHz, CDCl3): δ 151.86,137.72, 128.27, 127.80, 125.99, 114.32, 70.74, 64.26, 27.63, 27.33, 20.59. (3) The light yellow oily substance obtained in step (1) is 5-benzylidene-2,4,4-trimethylthiazolidine, and its structural formula is .

[0051] In step (1), propargylamine compound, calcium carbide, H 2 The molar ratio of S (also referred to as feed ratio), solvent, base, copper salt and their amounts, reaction temperature and reaction time are shown in Table 2; the yield of the prepared 5-benzylidene-2,4,4-trimethylthiazolidine is shown in Table 2.

[0052] Table 2

[0053] According to Table 2, it can be concluded that: 2-methyl-4-phenyl-3-butyn-2-amine: CaC 2 :H 2 Under the conditions of S feed ratio of 0.2:0.6:0.9, 1 equivalent of TBD as base catalyst, reaction temperature of 110℃, reaction time of 4 h, and DMSO as solvent, the yield of 5-benzylidene-2,4,4-trimethylthiazolidine was 99%.

[0054] Examples 21 to 28 Synthesis of 2,4,4-trimethylthiazolidine derivatives: The synthesis method is carried out according to Examples 1-20, and the feed ratio, solvent, base, reaction temperature and reaction time are the same as those of Example 19. The structural formula of the reaction substrate propargylamine compound is shown in Table 3. The structural formula, NMR characterization data and yield of the obtained product 2,4,4-trimethylthiazolidine derivative are shown in Table 3.

[0055] The general reaction formula of Examples 21-28 is as follows: .

[0056] Among them, the product R 1 From the reaction substrate R 1。 Reaction substrate The substituent R 1 Types, substitution positions and products The uniform one-to-one correspondence.

[0057] Table 3

[0058] In Table 2-3, the yield is calculated based on propargyl amine compounds, and the calculation formula is: Yield = target product mass / theoretical mass) × %.

Claims

1. A 2,4,4-trimethylthiazolidine derivative, the structural formula of which is shown in formula (I); （Ⅰ） In formula (I), R1 is selected from thienyl, pyridyl, naphthyl, phenyl, substituted phenyl; The substituted phenyl group is selected from halogen, trifluoromethyl, hydroxyl, C 1-8 Hydrocarbon, C 1-8 One or more types of the hydrocarbyloxy groups may have one or more substituents, and the positions of the substituents may be arbitrary.

2. The 2,4,4-trimethylthiazolidine derivative according to claim 1, characterized in that The C 1-8 Hydrocarbon groups include C 1-8 Alkyl, phenyl, alkyl-substituted phenyl; or / and, The C 1-8 Hydroxyl groups include C 1-8 Alkoxy, C 6-8 Aromatic alkyloxy.

3. The 2,4,4-trimethylthiazolidine derivative according to claim 1, characterized in that The 2,4,4-trimethylthiazolidine derivative is: 5-benzylidene-2,4,4-trimethylthiazolidine, whose structural formula is ; 2,4,4-trimethyl-5-(4-methylbenzylidene)thiazolidine, whose structural formula is ; 2,4,4-trimethyl-5-(4-methoxybenzylidene)thiazolidine, whose structural formula is ; 2,4,4-trimethyl-5-(4-chlorobenzylidene)thiazolidine, whose structural formula is ; 2,4,4-trimethyl-5-(4-iodobenzylidene)thiazolidine, whose structural formula is ; 2,4,4-trimethyl-5-(4-trifluoromethylbenzylidene)thiazolidine, whose structural formula is ; 2,4,4-trimethyl-5-(1-naphthylmethylene)thiazolidine, whose structural formula is ; 2,4,4-trimethyl-5-(2-pyridylmethylene)thiazolidine, whose structural formula is ; 2,4,4-trimethyl-5-(3-thienylmethylene)thiazolidine, whose structural formula is .

4. A method for synthesizing the 2,4,4-trimethylthiazolidine derivative according to any one of claims 1 to 3, characterized in that: The synthesis method comprises: in a closed environment, in the presence of a base, calcium carbide, hydrogen sulfide and a propargylamine compound react in an organic solvent.

5. The synthesis method according to claim 4, characterized in that The structural formula of the propargylamine compound is shown in formula (II); （Ⅱ） In formula (II), R1 is selected from thienyl, pyridyl, naphthyl, phenyl, substituted phenyl; The substituted phenyl group is selected from halogen, trifluoromethyl, hydroxyl, C 1-8 Hydrocarbon, C 1-8 One or more types of the hydrocarbyloxy groups may have one or more substituents, and the positions of the substituents may be arbitrary.

6. The synthesis method according to claim 5, characterized in that The C 1-8 Hydrocarbon groups include C 1-8 Alkyl, phenyl, alkyl-substituted phenyl; or / and, The C 1-8 Hydroxyl groups include C 1-8 Alkoxy, C 6-8 Aromatic alkyloxy; or / and, R1 in formula (II) is the same as R1 in formula (I).

7. The synthesis method according to claim 4, characterized in that The propargylamine compound is selected from 2-methyl-4-phenyl-3-butyn-2-amine, 4-(4-methylphenyl)-2-methyl-3-butyn-2-amine, 4-(4-methoxyphenyl)-2-methyl-3-butyn-2-amine, 4-(4-chlorophenyl)-2-methyl-3-butyn-2-amine, 4-(4-iodophenyl)-2-methyl-3-butyn-2-amine, 4-(4-trifluoromethylphenyl)-2-methyl-3-butyn-2-amine, 2-methyl-4-naphthyl-3-butyn-2-amine, 2-methyl-4-(2-pyridyl)-3-butyn-2-amine, 2-methyl-4-(3-thienyl)-3-butyn-2-amine; or / and, The base is selected from at least one of 1,5,7-triazabicyclo[4.4.0]dec-5-ene, cesium carbonate, potassium tert-butoxide, 1,8-diazabicyclo[5.4.0]undec-7-ene, tetramethylguanidine, sodium hydroxide and triethylamine; or / and, The organic solvent is selected from at least one of N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide and 1,4-dioxane.

8. The synthesis method according to claim 4, characterized in that The ratio of the organic solvent to the propargylamine compound is 0.5-15 mL: 1 mmol; or / and, The molar ratio of the propargylamine compound to calcium carbide and H2S is 1:(1-6):(2-9); or / and, The molar ratio of the propargylamine compound to the base is 1:(0.25-2); or / and, The reaction temperature is 80-150°C; or / and, The reaction time is 1-6h.

9. The synthesis method according to claim 4, characterized in that The molar ratio of the propargylamine compound to calcium carbide and H2S is 1:(2-4):(2-6); or / and, The molar ratio of the propargylamine compound to the base is 1:(0.5-1); or / and, The reaction temperature is 110-120°C; or / and, The reaction time is 3-5h.

10. The synthesis method according to claim 4, characterized in that The reaction is carried out in the presence of a copper salt; The copper salt is selected from at least one of CuI, CuCl, CuBr, Cu2O, CuCl2, and CuO; The molar ratio of the propylamine compound to the copper salt is 1:(0.1-3).

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