CN107286085B - Pyridine derivative and synthetic method thereof - Google Patents
Pyridine derivative and synthetic method thereof Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
Abstract
The invention discloses a pyridine derivative shown in a formula (I) and a synthesis method thereof. The synthetic method has the advantages of good reaction universality, simple and easily obtained raw materials, simple and convenient post-treatment, no metal catalyst, environmental friendliness and the like.
Description
Technical Field
The invention belongs to the technical field of organic compounds and synthesis, and relates to pyridine derivatives and a synthesis method thereof.
Background
The pyridine ring is used as a six-membered heterocyclic ring containing a nitrogen atom, widely exists in natural products and drug molecules, has good use value, and is an important structural unit of organic chemical materials. Such as the insecticide chlorantraniliprole, which is capable of killing many pests; lansoprazole, which can treat esophagitis; in materials, it can be used in chemical sensors. The literature reports a number of synthetic methods for pyridine compounds, most of which are based on the construction of pyridine rings by noble metal catalysis, such as the synthesis of thiazine compounds under metal catalysis, for example: (1) hyster, t.k.; tomislav, r.chem.commun.2011,47,11846.(2) Martin, r.m.; bergman, r.g.; jonathana.ellman, j.a.j.org.chem.2012,77,2501.(3) Zhao, m.n.; hui, r.r.; ren, z.h.; wang, y.y.; guan, z.h.org.lett.2014,16,3082, however, these methods use metal catalysis and are somewhat environmentally polluting.
Disclosure of Invention
The invention aims to provide a pyridine derivative and a synthesis method thereof, and provides a method for synthesizing the pyridine derivative by using catalytic amount of base catalysis, low cost and environmental friendliness.
The invention provides a pyridine derivative, which has a structure shown in a formula (I):
wherein R is1Is halogen, hydrogen, nitro; r2Is methyl or ethyl; r3Is an electron donating group or hydrogen; wherein the electron-donating group is selected from an alkyl group and an alkoxy group.
Preferably, R1Is halogen, hydrogen, nitro; r2Is methyl or ethyl; r3Is C1-C20 alkyl, C1-C20 alkoxy or hydrogen.
Further preferably, R1Is halogen, hydrogen, nitro; r2Is methyl or ethyl; r3Is C1-C10 alkyl, C1-C10 alkoxy or hydrogen.
Further preferably, R1Chlorine, bromine, nitro and hydrogen; r2Is methyl or ethyl; r3Methoxy, tert-butyl, hydrogen and methyl.
Further preferably, the pyridine derivatives include:
the invention also provides a synthesis method of the pyridine derivative, which comprises the steps of adding a catalyst and a raw material of the thiobenzamide substituted enyne ester compound shown as the formula (II) into a solvent, and synthesizing the pyridine derivative shown as the formula (I) through the processes of intramolecular cyclization and desulfurization.
The reaction process is shown in the following reaction formula (III):
wherein R is1Is halogen, hydrogen, nitro; r2Is methyl or ethyl; r3Is an electron donating group or hydrogen; wherein the electron-donating group is selected from an alkyl group and an alkoxy group.
Preferably, R1Is halogen, hydrogen, nitro; r2Is methyl or ethyl; r3Is C1-C20 alkyl, C1-C20 alkoxy or hydrogen.
Further preferably, R1Is halogen, hydrogen, nitro; r2Is methyl or ethyl; r3Is C1-C10 alkyl, C1-C10 alkoxy or hydrogen.
Further preferably, R1Chlorine, bromine, nitro and hydrogen; r2Is methyl or ethyl; r3Methoxy, tert-butyl, hydrogen and methyl.
Wherein, the thiobenzamide substituted enyne ester compound shown in the formula (II) is acyl amine substituted enyne ester with an electron-withdrawing group connected on a benzene ring, and thioamide amine substituted enyne ester with an electron-donating group or hydrogen connected on a benzene ring.
Wherein, the reaction can be carried out under the condition of water or no water, thioamide substituted enyne ester compound, catalyst and H2The molar ratio of O is 1.0: (1.0-2.0): (0.0-20.0); preferably, 1.0: 1.5: 15.0.
wherein the catalyst is alkali, and is selected from one or more of potassium tert-butoxide, lithium tert-butoxide, potassium carbonate and the like; preferably potassium tert-butoxide t-BuOK.
Wherein, when the catalyst is t-BuOK, the thioamide substituted enyne ester compound shown in the formula (II), t-BuOK and H2The molar ratio of O is 1.0: 1.5: 15.0.
wherein the solvent is selected from dioxane, DMF, toluene, NMP; preferably NMP.
Wherein, when the amount of the thioamide substituted enyne ester compound of the formula (II) is 0.2mmol, the amount of the solvent is 1-3 ml; preferably, it is 2 ml.
Wherein the reaction temperature is 50-110 ℃; preferably 90 ℃ and 110 ℃.
Wherein the reaction time is 24-30 hours; preferably 24-26 hours.
Wherein, the reaction is preferably carried out under air conditions.
Wherein the yield of the synthesis method is 10-60%.
In a specific embodiment, the thioamide substituted enyne ester compound, t-BuOK, NMP and H are added in sequence under the air2And O, reacting at 90 ℃ for 24-26h, detecting the complete reaction of the raw materials by TLC, and purifying to obtain a light yellow liquid or a solid formula (1).
The pyridine derivative shown in the formula (I) has potential application value in chemical sensors, antiviral agents, pesticides and the like.
The method has the advantages that the raw materials adopted by the synthesis method are common chemical raw materials, the raw material thiobenzamide substituted enyne ester compound is simple and convenient to synthesize and easy to obtain, and the reaction has the advantages of good substrate universality, simplicity and convenience in post-treatment, low-cost and non-toxic catalyst, environmental friendliness and the like. The pyridine compound contains halogen and nitro, so that the pyridine is provided with possibility for synthesizing other substances as an intermediate, and has great potential utilization value.
Detailed Description
The present invention will be described in further detail with reference to the following specific examples, and procedures, conditions, reagents, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited.
In the synthetic method, the pyridine is synthesized by using the thiobenzoylamine enol ester compound under the catalysis of t-BuOK, as shown in formula (II), and under the air, the N-thiobenzoylamine enol ester compound, t-BuOK, NMP and H2And O, heating to 90 ℃, reacting for 24-26 hours, and separating and purifying to obtain the pyridine derivative shown in the formula (I):
wherein R is1Is halogen, hydrogen, nitro; r2Is methyl or ethyl; r3Is an electron donating group or hydrogen; wherein the electron-donating group is selected from an alkyl group and an alkoxy group.
Example 1: synthesis of ethyl 6- (4-chlorophenyl) -5- (4-methoxyphenyl) nicotinate
Thiobenzamido substituted enyne esters, catalysts, H2O and a solvent are respectively selected from: trans-2- ((4-chlorophenylthioamido) methylene) -4- (4-methoxyphenyl) but-3-ynoic acid, t-BuOK, H2O, NMP, the dosage of raw material is trans-2- ((4-chlorphenylthioamido) methylene) -4- (4-methoxyphenyl) butyl-3-alkynoic acid 0.2mmol, t-BuOK0.3mmol, H2O3mmol and NMP 2 ml. The reaction was carried out at 90 ℃ for 24 hours to give the desired product as a yellow liquid with an isolated yield of 60%.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ1.43(t,J＝6.8Hz,3H),3.83(s,3H),4.45(q,J＝7.2Hz,2H),6.86(d,J＝8.4Hz,2H),7.11(d,J＝8.8Hz,2H),7.24(br,1H),7.27(br,1H),7.35(d,J＝8.4Hz,2H),8.30(d,J＝2.0Hz,1H),9.22(d,J＝2.0Hz,1H)；13C NMR(100MHz,CDCl3)δ14.02,55.17,61.41,114.29,125.06,128.52,130.84,131.12,131.51,134.86,135.69,138.21,139.80,149.26,159.59,159.67,165.69；
high-resolution-ratio mass spectrometry data: HRMS (EI) calcd for C21H18ClNO3:367.0975,found368.1048.
Example 2: synthesis of ethyl 6- (4-chlorophenyl) -5- (4-methoxyphenyl) nicotinate
Thiobenzamido substituted enyne esters, catalysts, H2O and a solvent are respectively selected from: trans-2- ((4-chlorophenylthioamido) methylene) -4- (4-methoxyphenyl) but-3-ynoic acid, t-BuOK, H2O, NMP, the dosage of raw material is trans-2- ((4-chlorphenylthioamido) methylene) -4- (4-methoxyphenyl) butyl-3-alkynoic acid 0.2mmol, t-BuOK0.3mmol, H2O3mmol and NMP 2 ml. The reaction was carried out at 110 ℃ for 24 hours to give the desired product as a yellow liquid in an isolated yield of 50%.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ1.43(t,J＝6.8Hz,3H),3.83(s,3H),4.45(q,J＝7.2Hz,2H),6.86(d,J＝8.4Hz,2H),7.11(d,J＝8.8Hz,2H),7.24(br,1H),7.27(br,1H),7.35(d,J＝8.4Hz,2H),8.30(d,J＝2.0Hz,1H),9.22(d,J＝2.0Hz,1H)；13C NMR(100MHz,CDCl3)δ14.02,55.17,61.41,114.29,125.06,128.52,130.84,131.12,131.51,134.86,135.69,138.21,139.80,149.26,159.59,159.67,165.69；
high-resolution-ratio mass spectrometry data: HRMS (EI) calcd for C21H18ClNO3:367.0975,found 368.1048.
Example 3: synthesis of ethyl 6- (4-chlorophenyl) -5- (4-methoxyphenyl) nicotinate
Thiobenzamido substituted enyne esters, catalysts, H2O and a solvent are respectively selected from: trans-2- ((4-chlorophenylthioamido) methylene) -4- (4-methoxyphenyl) but-3-ynoic acid, K2CO3、H2O, NMP, the dosage of raw material is trans-2- ((4-chlorphenylthioamido) methylene) -4- (4-methoxyphenyl) butyl-3-alkynoic acid 0.2mmol, K2CO30.3mmol，H2O3mmol and NMP 2 ml. The reaction was carried out at 90 ℃ for 24 hours to give the desired product as a yellow liquid with an isolated yield of 35%.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ1.43(t,J＝6.8Hz,3H),3.83(s,3H),4.45(q,J＝7.2Hz,2H),6.86(d,J＝8.4Hz,2H),7.11(d,J＝8.8Hz,2H),7.24(br,1H),7.27(br,1H),7.35(d,J＝8.4Hz,2H),8.30(d,J＝2.0Hz,1H),9.22(d,J＝2.0Hz,1H)；13C NMR(100MHz,CDCl3)δ14.02,55.17,61.41,114.29,125.06,128.52,130.84,131.12,131.51,134.86,135.69,138.21,139.80,149.26,159.59,159.67,165.69；
high-resolution-ratio mass spectrometry data: HRMS (EI) calcd for C21H18ClNO3:367.0975,found 368.1048.
Example 4: synthesis of ethyl 6- (4-chlorophenyl) -5- (4-methoxyphenyl) nicotinate
The thiobenzamido substituted enyne ester, the catalyst and the solvent are respectively selected from the following components: trans-2- ((4-chlorophenylthioamido) methylene) -4- (4-methoxyphenyl) butan-3-ynoic acid, t-BuOK and NMP, wherein the raw material dosage is 0.2mmol of trans-2- ((4-chlorophenylthioamido) methylene) -4- (4-methoxyphenyl) butan-3-ynoic acid, 0.3mmol of t-BuOK and 2ml of NMP. The reaction was carried out at 90 ℃ for 24 hours to give the desired product as a yellow liquid in an isolated yield of 20%.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ1.43(t,J＝6.8Hz,3H),3.83(s,3H),4.45(q,J＝7.2Hz,2H),6.86(d,J＝8.4Hz,2H),7.11(d,J＝8.8Hz,2H),7.24(br,1H),7.27(br,1H),7.35(d,J＝8.4Hz,2H),8.30(d,J＝2.0Hz,1H),9.22(d,J＝2.0Hz,1H)；13C NMR(100MHz,CDCl3)δ14.02,55.17,61.41,114.29,125.06,128.52,130.84,131.12,131.51,134.86,135.69,138.21,139.80,149.26,159.59,159.67,165.69；
high-resolution-ratio mass spectrometry data: HRMS (EI) calcd for C21H18ClNO3:367.0975,found368.1048.
Example 5: synthesis of ethyl 6- (4-bromophenyl) -5-phenylnicotinate
Thiobenzamido substituted enyne esters, catalysts, H2O and a solvent are respectively selected from: trans-2- ((4-bromophenylsulfanylamido) methylene) -4-phenylbutan-3-ynoic acid ethyl ester, t-BuOK, H2O, NMP, the dosage of raw material is trans-2- ((4-bromophenylsulfonamido) methylene) -4-phenylbutan-3-alkynoic acid ethyl ester 0.2mmol, t-BuOK0.3mmol, H2O3mmol and NMP 2 ml. The reaction was carried out at 90 ℃ for 24 hours to give the desired product as a yellow liquid in an isolated yield of 39%.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ1.43(t,J＝6.8Hz,3H),4.50(q,J＝7.2Hz,2H),7.17-7.22(m,2H),7.27(d,J＝8.4Hz,1H),7.30-7.35(m,3H),7.39(d,J＝8.0Hz,2H),8.32(d,J＝1.2Hz,1H),9.25(s,1H)；13C NMR(100MHz,CDCl3)δ14.01,61.44,123.32,125.08,128.07,128.93,129.65,131.45,131.85,136.01,138.47,138.99,139.93,149.66,159.66,165.60；
high resolution mass spectral data: HRMS (EI) calcd for C20H16BrNO2:381.03645,found382.0437.
Example 6: synthesis of ethyl 6- (4-nitrophenyl) -5-phenylnicotinate
Thiobenzamido substituted enyne esters, catalysts, H2O and a solvent are respectively selected from: trans-2- ((4-Nitrophenylthio)Amido) methylene) -4-phenylbutan-3-ynoic acid ethyl ester, DABCO, t-BuOK, H2O, NMP, the dosage of raw material is trans-2- ((4-nitrobenzenesulfonylamido) methylene) -4-phenylbutan-3-acetylenic acid ethyl ester 0.2mmol, t-BuOK0.3mmol, H2O3mmol and NMP 2 ml. The reaction was carried out at 90 ℃ for 24 hours to obtain the desired product as a white solid in an isolated yield of 54%, mp 149-.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ1.45(t,J＝6.8Hz,3H),4.47(q,J＝6.8Hz,2H),7.19(d,J＝4.8Hz,2H),7.33-7.36(m,3H),7.58(d,J＝7.6Hz,2H),8.12(d,J＝7.6Hz,2H)8.38(s,1H),9.30(s,1H)；13C NMR(100MHz,CDCl3)δ14.00,61.64,123.40,125.88,128.49,129.12,129.64,131.20,136.66,138.30,140.06,145.95,147.89,149.77,158.31,165.31；
high resolution mass spectral data: HRMS (EI) calcd for C20H17ClN2O4:348.1110,found349.1183.
Example 7: synthesis of ethyl 5- (4- (tert-butyl) phenyl) -6- (4-nitrophenyl) nicotinate
Thiobenzamido substituted enyne esters, catalysts, H2O and a solvent are respectively selected from: trans-ethyl-4- (4- (tert-butyl) phenyl) -2- ((4-nitrophenylthioamido) methylene), t-BuOK, H2O, NMP, starting from trans-ethyl-4- (4- (tert-butyl) phenyl) -2- ((4-nitrophenylthioamido) methylene) 0.2mmol, t-BuOK0.3mmol, H2O3mmol and NMP 2 ml. The reaction was carried out at 90 ℃ for 24 hours to give the desired product as a white solid in an isolated yield of 51%, mp 100-.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ1.33(s,9H),1.44(t,J＝7.2Hz,3H),4.46(q,J＝7.2Hz,2H),7.11(d,J＝8.0Hz,2H),7.35(d,J＝7.6Hz,2H),7.59(d,J＝8.4Hz,2H),8.12(d,J＝8.4Hz,2H),8.38(s,1H),9.28(s,1H)；13C NMR(100MHz,CDCl3)δ14.00,31.03,34.44,61.59,123.38,125.85,126.03,129.30,131.18,135.21,136.60,140.15,146.17,147.88,149.53,151.87,158.25,165.38；
high resolution mass spectral data: HRMS (EI) calcd for C24H24N2O4:404.1736,found 405.1809.
Example 8: synthesis of ethyl 6- (4-nitrophenyl) -5- (p-tolyl) nicotinate
Thiobenzamido substituted enyne esters, catalysts, H2O and a solvent are respectively selected from: trans-ethyl-2- ((4-nitrophenylthioamido) methylene) -4- (p-tolyl) but-3-ynoic acid, t-BuOK, H2O, NMP starting from trans-ethyl-2- ((4-nitrophenylthioamido) methylene) -4- (p-tolyl) but-3-ynoic acid 0.2mmol, t-BuOK0.3mmol, H2O3mmol and NMP 2 ml. The reaction was carried out at 90 ℃ for 26 hours to give the desired product as a white solid, isolated in 40% yield, mp 79-80 ℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ1.44(t,J＝7.2Hz,3H),2.37(s,3H),4.47(q,J＝7.2Hz,2H),7.07(d,J＝8.0Hz,2H),7.14(d,J＝8.0Hz,2H),7.58(d,J＝8.4Hz,2H),8.13(d,J＝8.8Hz,2H),8.36(d,J＝1.6Hz,1H),9.27(d,J＝1.6Hz,1H)；13C NMR(100MHz,CDCl3)δ14.00,21.92,61.61,123.42,125.86,129.51,129.84,131.17,135.28,136.68,138.53,140.06,146.15,147.84,149.54,158.28,165.39；
high resolution mass spectral data: HRMS (EI) calcd for C21H18ClN2O4:362.1267,found363.1339.
Example 9: synthesis of 6- (4-chlorophenyl) -5- (4-methoxyphenyl) methyl nicotinate
Thiobenzamido substituted enyne esters, catalysts, H2O and a solvent are respectively selected from: trans-2- ((4-chlorophenylthioamido) methylene) -4- (4-methoxyphenyl) butan-3-alkynoic acid, t-BuOK, H2O, NMP, the dosage of raw material is trans-2- ((4-chlorphenylthioamido) methylene) -4- (4-methoxyphenyl) butyl-3-alkynoic acid 0.2mmol, t-BuOK0.3mmol, H2O3mmol and NMP 2 ml. The reaction was carried out at 90 ℃ for 26 hours to give the desired product as a white solid in an isolated yield of 45% and mp 126-.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ3.83(s,3H),3.99(s,3H),6.86(d,J＝8.4Hz,2H),7.11(d,J＝8.4Hz,2H),7.24(br,2H),7.36(d,J＝8.4Hz,2H),8.30(s,1H),9.21(s,1H)；13C NMR(100MHz,CDCl3)δ52.35,55.17,114.31,124.75,128.53,130.83,131.05,131.52,134.90,135.74,138.19,139.86,149.23,159.70,166.18；
high resolution mass spectral data: HRMS (EI) calcd for C20H17ClNO3:353.0819,found 354.0891.
The protection of the present invention is not limited to the above embodiments. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected.
Claims (7)
1. A method for synthesizing pyridine derivatives is characterized in that under the action of a catalyst and in the presence of water or no water, thioamide substituted enyne ester compounds in a formula (II) undergo intramolecular cyclization and desulfurization processes to synthesize the pyridine derivatives shown in a formula (I);
the reaction process is shown in the following reaction formula (III):
wherein R is1Is halogen, hydrogen, nitro; r2Is methyl or ethyl; r3Is an electron donating group or hydrogen; wherein the content of the first and second substances,
the electron-donating groups are selected from C1-C20 alkyl, C1-C20 alkoxy;
wherein the solvent is selected from dioxane, DMF, toluene, NMP;
the catalyst is alkali and is selected from one or more of potassium tert-butoxide, lithium tert-butoxide and potassium carbonate.
2. The synthetic method of claim 1 wherein R is1Chlorine, bromine, nitro and hydrogen; r2Is methyl or ethyl; r3Methoxy, tert-butyl, hydrogen and methyl.
3. The synthesis method of claim 1, wherein the reaction is carried out under the condition of water or no water, the thioamide substituted enyne ester compound of the formula (II), a catalyst and H2The molar ratio of O is 1.0: (1.0-2.0): (0.0-20.0).
4. The synthesis method of claim 1, wherein the solvent is used in an amount of 1 to 3ml when the amount of the thioamide-substituted enyne ester compound of formula (II) is 0.2 mmol.
5. The method of synthesis according to claim 1, wherein the solvent is selected from dioxane, DMF, toluene, NMP.
6. The method of synthesis according to claim 1, wherein the temperature of the reaction is between 50 ℃ and 110 ℃.
7. The method of synthesis according to claim 1, wherein the reaction time is 24 to 30 hours.
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