CN109400611B - Synthesis method of 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound - Google Patents
Synthesis method of 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound Download PDFInfo
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Abstract
The invention discloses a novel method for synthesizing 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline derivatives, which comprises the following steps: adding aniline compounds substituted by para-pyrrole, terminal aryne and gold (I) hexafluoroantimonate into anhydrous toluene, heating to 100 ℃, reacting for 24 hours, and performing post-treatment and separation to obtain the 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline derivative. The invention provides a new method for synthesizing 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline derivatives by an aniline compound substituted by ortho-position pyrrole and an aryl terminal alkyne compound. The method has the advantages of simple and convenient operation, mild conditions, good substrate functional group compatibility, high product yield, easy separation of the catalyst and the product and the like, has potential biological activity, and can be used for screening the medicines by subsequently testing the medicinal activity of the medicines.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a synthesis method of a 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound.
Background
Quinoxaline compounds are very important heterocyclic compounds, wherein 4, 5-dihydropyrrole [1,2-a ] quinoxaline compounds and analogues thereof are important structural units for forming a plurality of natural product molecules and drug molecules with biological activity, and have wide application prospects in the field of pharmaceutical chemistry research, for example, a 6FQXP structure shown in a formula (10) has a drug effect of resisting HIV virus, and a CB1 receptor antagonist shown in a formula (11) can be used for treating obesity.
4, 5-dihydropyrrole [1,2-a ] quinoxaline compounds have important pharmacological action, thus attracting the extensive attention of chemists and developing various methods for synthesizing the compounds. The current synthesis method of 4, 5-dihydropyrrole [1,2-a ] quinoxaline compounds mainly comprises the Pictet-Spengler reaction catalyzed by protonic acid and Lewis acid, which takes aniline and aldehyde substituted by ortho-position pyrrole as raw materials (Eur.J.Org.chem.2011, 6998-7010.; adv.Syn.Cat.2018,360,1334-1339.) and transition metal catalyzed method which takes aniline and alkyne substituted by ortho-position pyrrole as raw materials (J.Am.chem.Soc.,2005, 12717000-17006). Although the method is a general method for synthesizing the 4, 5-dihydropyrrole [1,2-a ] quinoxaline compound at present, the method has harsh conditions and needs additional additives for reaction, and more importantly, the method can not carry out functional group reaction on pyrrole ring through one-step reaction. According to the invention, aniline and alkyne substituted by ortho-position pyrrole are used as raw materials, and a gold complex is used as a catalyst, so that a product different from other methods is obtained, the reaction with two molecules of alkyne is realized, and the multi-functionalized 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound is efficiently constructed.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides a synthesis method of a 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound with good yield.
In order to solve the technical problems, the invention provides the following technical scheme: the invention relates to a synthesis method of a 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound, which comprises the steps of taking an aniline compound substituted by ortho-position pyrrole shown in a formula (2) and aryl terminal alkyne shown in a formula (3) as raw materials under the action of a gold catalyst, reacting in a solvent under the action of the gold catalyst, carrying out thin-plate chromatography tracking reaction until the reaction is complete to obtain a reaction mixture, and carrying out post-treatment on the reaction mixture to obtain the 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound shown in the formula (1); the chemical reaction formula is shown as follows:
in the formula (2) or the formula (1), R is hydrogen, methyl, aryl or halogen; in formula (3) or formula (1), Ar is phenyl, naphthyl, heterocyclic ring (including but not limited to furan ring, thiophene ring, pyridine ring, etc.), substituted heterocyclic ring, or phenyl substituted by methyl, methoxy, halogen.
Further, the solvent is any one of dichloroethane, nitromethane, toluene, tetrahydrofuran, acetonitrile or chlorobenzene.
Further, the solvent is toluene.
Further, the gold catalyst is one of the gold catalysts shown below;
furthermore, the quantity ratio of the ortho-pyrrole substituted aniline compound to the aryl terminal alkyne is 1:2-1: 5.
Furthermore, the ratio of the amount of the gold catalyst to the amount of the ortho-pyrrole substituted aniline compound substance is 0.01-0.2.
Furthermore, the reaction temperature is 25-100 ℃, and the reaction time is 1-24 hours.
Further, the reaction post-treatment method comprises the following steps: after the reaction, the reaction mixture was concentrated by rotary evaporation and separated by silica gel column chromatography using petroleum ether: gradient elution is carried out by using mixed solution of ethyl acetate with the volume ratio of 20:1-5:1 as eluent to obtain the 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound shown in the formula (1).
Has the advantages that: the synthesis method has the advantages of good regioselectivity, wide range of reaction substrates, simple post-treatment and better yield (68-88%).
(1) The synthesis method takes a gold complex as a catalyst, takes methylbenzene as a solvent, carries out reaction under the condition of heating at 100 ℃, and then carries out post-treatment and separation to obtain the 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound, wherein the product has potential biological activity, and can be subjected to subsequent test on the pharmaceutical activity to carry out drug screening. Can also be used as an important organic intermediate to be applied to the fields of medicines, pesticides and the like.
(2) The 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline derivative prepared by the invention has potential bioactivity, and can be used for screening medicaments by subsequently testing the medicinal activity of the derivative. Can also be used as an important organic intermediate to be applied to the fields of medicines, pesticides and the like.
(3) The invention provides a new method for efficiently synthesizing a 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound by an aniline compound substituted by critical pyrrole and terminal aryne under the action of a gold catalyst. The whole reaction has the advantages of simple and convenient operation, mild condition, good substrate functional group compatibility, high product yield, easy separation of the catalyst and the product and the like.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without inventive labor; wherein:
FIG. 1 is a single crystal diffractogram of the compound 4- (4-bromophenyl) -1- (1- (4-bromophenyl) vinyl) -4-methyl) -4, 5-dihydropyrrolo [1,2-a ] quinoxaline (1 ae).
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with examples are described in detail below.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.
Furthermore, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
Example 1
The reaction formula is as follows:
to a 25mL round-bottomed flask, 2- (1H-1-pyrrolyl) aniline 2a (0.2mmol), phenylacetylene 3a (0.5mmol), toluene 2mL, gold catalyst (4) (acetonitrile) [ (2-biphenyl) di-t-butylphosphine ] gold (I) hexafluoroantimonate (0.01mmol) were added in this order, and the mixture was stirred at 100 ℃ for 24 hours. TLC monitoring reaction, after the reaction, rotary evaporation to remove solvent, the crude product through 280 mesh silica gel column chromatography, using petroleum ether and ethyl acetate (volume ratio is 10:1) mixed solvent as eluent to carry out gradient elution, collecting eluent and rotary evaporation to remove solvent, and the target product 1aa is obtained as white solid (yield is 78%).
1H NMR(400MHz,CDCl3):δ7.32-7.13(m,10H),6.71(t,J＝7.24Hz,1H),6.62(d,J＝6.92Hz,1H),6.39(t,J＝7.26Hz,1H),6.32(s,1H),6.08(s,1H),5.69(s,1H),5.51(s,1H),4.29(s,1H),1.88(s,1H).
13C NMR(100MHz,CDCl3):δ145.9,142.6,139.9,136.2,136.1,130.2,128.3,128.2,127.8,126.9,126.7,126.0,125.9,124.3,118.9,118.7,115.8,113.6,103.7,57.8,29.2.
Example 2
The reaction formula is as follows:
to a 25mL round-bottomed flask, 2- (1H-1-pyrrolyl) aniline 2a (0.2mmol), 4-methylphenylacetylene 3b (0.5mmol), toluene 2mL, gold catalyst (4) (acetonitrile) [ (2-biphenyl) di-t-butylphosphine ] gold (I) hexafluoroantimonate (0.01mmol) were added in this order, and the mixture was stirred at 100 ℃ for 24 hours. TLC monitoring reaction, after the reaction, rotary evaporation to remove solvent, the crude product through 300 mesh silica gel column chromatography, using petroleum ether and ethyl acetate (volume ratio of 20: 1) mixed solvent as eluent to carry out gradient elution, collecting eluent and rotary evaporation to remove solvent, and obtaining the target product 1ab as white solid (yield 85%).
1H NMR(400MHz,CDCl3):δ7.26-7.13(m,5H),7.01(q,J＝8.00Hz,4H),6.71(t,J＝7.56Hz,1H),6.60(d,J＝7.72Hz,1H),6.40(t,J＝7.70Hz),6.28(d,J＝3.44Hz,1H),6.05(d,J＝3.4Hz,1H),5.65(s,1H),5.42(s,1H),4.24(br,s,1H),2.24(s,6H),1.85(s,3H).
13C NMR(100MHz,CDCl3):δ143.1,142.5,137.6,137.3,136.2,136.1,130.3,129.0,128.9,126.5,126.1,125.9,124.2,118.9,118.7,115.9,115.1,113.4,103.6,57.5,29.2,21.2,21.0.
Example 3
The reaction formula is as follows:
to a 25mL round-bottomed flask, 2- (1H-1-pyrrolyl) aniline 2a (0.2mmol), 4-pentylphenylacetylene 3c (0.5mmol), toluene 2mL, gold catalyst (4) (acetonitrile) [ (2-biphenyl) di-t-butylphosphine ] gold (I) hexafluoroantimonate (0.01mmol) were added in this order, and the mixture was stirred at 100 ℃ for 24 hours. TLC is used for monitoring the reaction, after the reaction is finished, the solvent is removed through rotary evaporation, the crude product is subjected to 200-mesh silica gel column chromatography, gradient elution is carried out by taking a mixed solvent of petroleum ether and ethyl acetate (the volume ratio is 15:1) as an eluent, the eluent is collected, and the solvent is removed through rotary evaporation, so that the target product 1ac is obtained as a white solid (the yield is 88%).
1H NMR(400MHz,CDCl3):δ7.25-7.15(m,5H),7.05-6.98(m,4H),6.71(t,J＝7.51Hz,1H),6.61(d,J＝7.64Hz,1H),6.40(t,J＝7.66Hz,1H),6.28(d,J＝3.44Hz,1H),6.02(d,J＝3.40Hz,1H),5.66(s,1H),5.43(s,1H),4.24(s,1H),2.52-2.48(m,4H),1.85(s,3H),1.58-1.50(m,5H),1.33-1.19(m,9H),0.90-0.83(m,7H).
13C NMR(100MHz,CDCl3):δ143.2,142.6,142.5,141.5,137.3,136.3,136.1,130.3,128.4,128.2,126.6,126.0,125.9,124.2,118.8,115.8,115.0,113.4,103.6,57.5,35.6,35.5,31.6,31.4,31.03,30.98,29.2,22.6,14.1.
Example 4
The reaction formula is as follows:
to a 25mL round-bottomed flask, 2- (1H-1-pyrrolyl) aniline 2a (0.2mmol), 4-chlorophenylacetylene 3c (0.5mmol), toluene 2mL, gold catalyst (4) (acetonitrile) [ (2-biphenyl) di-t-butylphosphine ] gold (I) hexafluoroantimonate (0.01mmol) were added in this order, and the mixture was stirred at 100 ℃ for 24 hours. And (3) monitoring the reaction by TLC, after the reaction is finished, rotationally evaporating to remove the solvent, performing column chromatography on the crude product through 200-300-mesh silica gel, performing gradient elution by using a mixed solvent of petroleum ether and ethyl acetate (the volume ratio is 20: 1-10:1) as an eluent, collecting the eluent, and rotationally evaporating to remove the solvent to obtain the target product 1ad which is a light yellow solid (the yield is 68%).
1H NMR(400MHz,CDCl3):δ7.24-7.13(m,9H),6.74(t,J＝7.54Hz,1H),6.63(d,J＝7.64Hz,1H),6.42(t,J＝7.60Hz,1H),6.32(d,J＝3.48Hz,1H),6.07(d,J＝3.40Hz,1H),5.66(s,1H),5.53(s,1H),4.25(s,1H),1.85(s,3H).
13C NMR(100MHz,CDCl3):δ144.4,141.5,138.4,135.9,135.8,133.6,132.8,129.7,128.5,128.3,127.9,127.4,125.8,124.6,119.2,118.6,116.4,116.0,113.8,103.8,57.5,29.0.
Example 5
The reaction formula is as follows:
to a 25mL round-bottomed flask, 2- (1H-1-pyrrolyl) aniline 2a (0.2mmol), 4-bromophenylacetylene 3c (0.5mmol), toluene 2mL, gold catalyst (4) (acetonitrile) [ (2-biphenyl) di-t-butylphosphine ] gold (I) hexafluoroantimonate (0.01mmol) were added in this order, and the mixture was stirred at 100 ℃ for 24 hours. And (3) monitoring the reaction by TLC, after the reaction is finished, rotationally evaporating to remove the solvent, performing column chromatography on the crude product through 200-300-mesh silica gel, performing gradient elution by using a mixed solvent of petroleum ether and ethyl acetate (the volume ratio is 20: 1-10:1) as an eluent, collecting the eluent, and rotationally evaporating to remove the solvent to obtain a target product 1ae which is a light yellow solid (the yield is 71%).
1H NMR(400MHz,CDCl3):δ7.35-7.25(m,5H),7.17-7.15(m,3H),7.07(d,J＝8.16Hz,2H),6.75(t,J＝7.50Hz,1H),6.64(d,J＝7.72Hz,1H),6.43(t,J＝7.64Hz,1H),6.32(d,J＝3.12Hz,1H),6.08(s,1H),5.68(s,1H),5.54(s,1H),4.26(s,1H),1.85(s,3H).
13C NMR(100MHz,CDCl3):δ144.9,141.6,138.8,135.8,135.7,131.4,131.3,129.7,128.2,127.8,125.8,124.7,121.9,121.0,119.3,118.5,116.5,116.1,113.9,103.8,57.5,29.0.
Example 6
The reaction formula is as follows:
under the protection of argon, a 25mL round-bottom flask was taken, and 2a (0.2mmol), 6-methoxy-2-naphthylyne 3f (0.5mmol), 2mL of toluene, (acetonitrile) [ (2-biphenyl) di-tert-butylphosphine ] gold (I) hexafluoroantimonate (0.01mmol) were added in this order, and the mixture was stirred at 400rpm for 24 hours at 100 ℃. TLC monitoring reaction, after the reaction, using Heidolph rotary evaporator rotary evaporation, its speed of rotation is 200rpm, the temperature is 40 degrees C, the vacuum degree is 0.06Mpa, the processing time is 10 min. And performing 200-300 mesh silica gel column chromatography, wherein an eluent is ethyl acetate: petroleum ether 7:100, isolated to yield the desired product 1af (80% yield).
1H NMR(400MHz,CDCl3):δ7.65-7.53(m,7H),7.46(d,J＝8.60Hz,1H),7.31(d,J＝8.16Hz,1H),7.23(s,1H),7.10-7.02(m,4H),6.67-6.60(m,2H),6.37-6.32(m,2H),6.10(d,J＝3.16Hz,1H),5.80(s,1H),5.54(s,1H),4.33(s,1H),3.86(s,3H),3.84(s,3H),1.96(s,3H).
13C NMR(100MHz,CDCl3):δ157.8,157.7,142.5,141.1,136.3,136.1,135.3,134.2,133.5,130.4,129.9,129.7,128.8,128.4,126.9,126.8,126.0,125.9,125.2,125.1,124.5,124.4,118.9,118.8,118.7,118.6,115.9,115.8,113.6,105.6,105.5,104.0,57.8,55.34,55.28,28.9.
Example 7
The reaction formula is as follows:
a25 mL round-bottom flask was charged with 2a (0.2mmol),3g (0.5mmol) and 2mL of toluene, (acetonitrile) [ (2-biphenyl) di-t-butylphosphine ] gold (I) hexafluoroantimonate (0.01mmol) in this order under an argon atmosphere, and the mixture was stirred at 400rpm for 24 hours at 100 ℃. TLC monitoring reaction, after the reaction, using Heidolph rotary evaporator rotary evaporation, its speed of rotation is 200rpm, the temperature is 40 degrees C, the vacuum degree is 0.06Mpa, the processing time is 10 min. And performing 200-300 mesh silica gel column chromatography, wherein an eluent is ethyl acetate: petroleum ether 6:100, the desired product 1ag was isolated (yield 76%).
1H NMR(400MHz,CDCl3):δ7.28(t,J＝7.80Hz,2H),7.21-7.05(m,3H),6.97(s,1H),6.89(s,1H),6.80(t,J＝6.50Hz,1H),6.67(d,J＝7.72Hz,1H),6.50(t,J＝7.74Hz,1H),6.29(d,J＝3.44Hz,1H),6.00(d,J＝3.4Hz,1H),5.68(s,1H),5.42(s,1H),4.15(s,1H),1.90(s,3H).
13C NMR(100MHz,CDCl3):δ147.9,141.9,137.3,136.2,135.9,130.3,126.3,125.9,125.80,125.77,125,6,124.4,123.0,120.8,119.1,118.5,115.7,114.7,112.9,102.9,55.7,28.7.
Example 8
The reaction formula is as follows:
under the protection of argon, a 25mL round-bottom flask was taken, 4-methyl-2- (1H-1-pyrrolyl) aniline 2b (0.2mmol), phenylacetylene 3a (0.5mmol), toluene 2mL, (acetonitrile) [ (2-biphenyl) di-tert-butylphosphine ] gold (I) hexafluoroantimonate (0.01mmol) were added in this order, and the mixture was stirred at 400rpm for 24 hours at 100 ℃. TLC monitoring reaction, after the reaction, using Heidolph rotary evaporator rotary evaporation, its speed of rotation is 200rpm, the temperature is 40 degrees C, the vacuum degree is 0.06Mpa, the processing time is 10 min. And performing 200-300 mesh silica gel column chromatography, wherein an eluent is ethyl acetate: petroleum ether 5:100, isolated to yield the target product 1ba (77% yield).
1H NMR(300MHz,CDCl3):δ7.37-7.10(m,10H),δ6.97(s,1H),δ6.47(t,J＝8.73Hz,2H),δ6.33(d,J＝3.45Hz,1H),δ6.06(d,J＝3.39Hz,1H),δ5.61(d,J＝1.53Hz,1H),δ5.52(d,J＝1.44Hz,1H),δ1.90(s,3H),δ1.83(s,3H).
13C NMR(75MHz,CDCl3):δ146.0,143.0,140.2,136.2,133.5,130.2,128.2,127.7,126.8,126.7,125.9,125.8,124.6,119.6,115.7,115.6,113.6,103.6,57.7,29.2,20.6.
Example 9
The reaction formula is as follows:
under the protection of argon, a 25mL round-bottom flask was taken, 4-chloro-2- (1H-1-pyrrolyl) aniline 2c (0.2mmol), phenylacetylene 3a (0.5mmol), toluene 2mL, (acetonitrile) [ (2-biphenyl) di-tert-butylphosphine ] gold (I) hexafluoroantimonate (0.01mmol) were added in this order, and the mixture was stirred at 400rpm for 24 hours at 100 ℃. TLC monitoring reaction, after the reaction, using Heidolph rotary evaporator rotary evaporation, its speed of rotation is 200rpm, the temperature is 40 degrees C, the vacuum degree is 0.06Mpa, the processing time is 10 min. And performing 200-300 mesh silica gel column chromatography, wherein an eluent is ethyl acetate: petroleum ether 7:100, isolated to yield the desired product 1ca (76% yield).
1H NMR(500MHz,CDCl3):δ7.23-7.15(m,12H),6.62(d,J＝6.65Hz,1H),6.49(d,J＝8.35Hz,1H),6.38(d,J＝3.25Hz,1H),6.10(s,1H),5.67(s,1H),5.55(s,1H),4.40(br,s,1H),1.86(s,3H).
13C NMR(125MHz,CDCl3):δ145.5,142.5,139.8,135.9,134.6,130.4,128.4,128.3,128.0,127.1,126.8,126.5,125.8,123.9,123.5,119.0,116.5,116.4,114.0,104.1,57.8,29.1.
Example 10
The reaction formula is as follows:
under the protection of argon, a 25mL round-bottom flask was taken, 4-chloro-2- (1H-1-pyrrolyl) aniline 2c (0.2mmol),3b (0.5mmol), toluene 2mL, (acetonitrile) [ (2-biphenyl) di-tert-butylphosphine ] gold (I) hexafluoroantimonate (0.01mmol) were added in this order, and the mixture was stirred at 400rpm for 24 hours at 100 ℃. TLC monitoring reaction, after the reaction, using Heidolph rotary evaporator rotary evaporation, its speed of rotation is 200rpm, the temperature is 40 degrees C, the vacuum degree is 0.06Mpa, the processing time is 10 min. And performing 200-300 mesh silica gel column chromatography, wherein an eluent is ethyl acetate: petroleum ether 7:100, the desired product 1cb was isolated (yield 68%).
1H NMR(500MHz,CDCl3):δ7.29(d,J＝1.85Hz,1H),7.16(t,J＝8.50Hz,4H),7.08-7.04(m,4H),6.68(dd,J＝1.90,8.25Hz,1H),6.53(d,J＝8.30Hz,1H),6.89(d,J＝3.35Hz,1H),6.12(s,1H),5.68(d,J＝1.40Hz,1H),5.52(s,1H),2.29(s,3H),2.28(s,3H),1.89(s,3H).
13C NMR(125MHz,CDCl3):δ142.6,142.4,137.8,137.0,136.7,136.0,134.7,130.6,129.1,129.0,126.6,125.7,123.9,123.5,118.9,116.5,115.7,113.9,104.0,57.6,29.2,21.2,21.0.
Example 11
The invention relates to a synthesis method of a 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound, which comprises the steps of taking an aniline compound substituted by ortho-position pyrrole shown in a formula (2) and aryl terminal alkyne shown in a formula (3) as raw materials under the action of a gold catalyst, reacting in a solvent under the action of the gold catalyst, carrying out thin-plate chromatography tracking reaction until the reaction is complete to obtain a reaction mixture, and carrying out post-treatment on the reaction mixture to obtain the 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound shown in the formula (1); the chemical reaction formula is shown as follows:
in the formula (2) or the formula (1), R is hydrogen, methyl, aryl or halogen; in formula (3) or formula (1), Ar is phenyl, naphthyl, heterocyclic ring (including but not limited to furan ring, thiophene ring, pyridine ring, etc.), substituted heterocyclic ring, or phenyl substituted by methyl, methoxy, halogen.
The solvent is dichloroethane.
The gold catalyst is one of the following gold catalysts;
the quantity ratio of the aniline compound substituted by the ortho-position pyrrole to the aryl terminal alkyne is 1: 2.
The ratio of the amount of the gold catalyst to the amount of the ortho-pyrrole substituted aniline compound substance is 0.01.
The reaction temperature is 25 ℃, and the reaction time is 20 hours.
Example 12
The invention relates to a synthesis method of a 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound, which comprises the steps of taking an aniline compound substituted by ortho-position pyrrole shown in a formula (2) and aryl terminal alkyne shown in a formula (3) as raw materials under the action of a gold catalyst, reacting in a solvent under the action of the gold catalyst, carrying out thin-plate chromatography tracking reaction until the reaction is complete to obtain a reaction mixture, and carrying out post-treatment on the reaction mixture to obtain the 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound shown in the formula (1); the chemical reaction formula is shown as follows:
in the formula (2) or the formula (1), R is hydrogen, methyl, aryl or halogen; in formula (3) or formula (1), Ar is phenyl, naphthyl, heterocyclic ring (including but not limited to furan ring, thiophene ring, pyridine ring, etc.), substituted heterocyclic ring, or phenyl substituted by methyl, methoxy, halogen.
The solvent is nitromethane.
The gold catalyst is one of the following gold catalysts;
the quantity ratio of the aniline compound substituted by the ortho-position pyrrole to the aryl terminal alkyne is 1: 5.
The ratio of the amount of the gold catalyst to the amount of the ortho-pyrrole substituted aniline compound substance is 0.2.
The reaction temperature is 80 ℃, and the reaction time is 1 hour.
Example 13
The invention relates to a synthesis method of a 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound, which comprises the steps of taking an aniline compound substituted by ortho-position pyrrole shown in a formula (2) and aryl terminal alkyne shown in a formula (3) as raw materials under the action of a gold catalyst, reacting in a solvent under the action of the gold catalyst, carrying out thin-plate chromatography tracking reaction until the reaction is complete to obtain a reaction mixture, and carrying out post-treatment on the reaction mixture to obtain the 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound shown in the formula (1); the chemical reaction formula is shown as follows:
in the formula (2) or the formula (1), R is hydrogen, methyl, aryl or halogen; in formula (3) or formula (1), Ar is phenyl, naphthyl, heterocyclic ring (including but not limited to furan ring, thiophene ring, pyridine ring, etc.), substituted heterocyclic ring, or phenyl substituted by methyl, methoxy, halogen.
The solvent is any one of tetrahydrofuran, acetonitrile or chlorobenzene.
The gold catalyst is one of the following gold catalysts;
the quantity ratio of the aniline compound substituted by the ortho-position pyrrole to the aryl terminal alkyne is 1: 3.
The ratio of the amount of the gold catalyst to the amount of the ortho-pyrrole substituted aniline compound substance is 0.1.
The reaction temperature is 25-100 ℃, and the reaction time is 24 hours.
It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.
Claims (4)
1. A synthetic method of 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compounds is characterized by comprising the following steps: under the action of a gold catalyst, taking an aniline compound substituted by critical pyrrole shown in a formula (2) and an alkyne compound shown in a formula (3) as raw materials, reacting in a solvent under the action of the gold catalyst, carrying out thin-plate chromatography tracking reaction until the reaction is complete to obtain a reaction mixture, and carrying out post-treatment on the reaction mixture to obtain a 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound shown in the formula (1); the chemical reaction formula is shown as follows:
in the formula (2) or the formula (1), R is hydrogen, methyl, aryl or halogen; in the formula (3) or the formula (1), Ar is phenyl, naphthyl, heterocyclic group, substituted heterocyclic group, or phenyl substituted by methyl, methoxy or halogen;
the solvent is toluene; the gold catalyst is a gold catalyst shown as the following formula:
the mass ratio of the aniline compound substituted by the ortho-position pyrrole to the alkyne compound is 1:2-1: 5.
2. The method for synthesizing 1-vinyl-4, 5-dihydropyrrolo [1,2-a ] quinoxaline compound according to claim 1, wherein: the ratio of the amount of the gold catalyst to the amount of the ortho-pyrrole substituted aniline compound substance is 0.01-0.2.
3. The method for synthesizing 1-vinyl-4, 5-dihydropyrrolo [1,2-a ] quinoxaline compound according to claim 1, wherein: the reaction temperature is 25-100 ℃, and the reaction time is 1-24 hours.
4. The method for synthesizing 1-vinyl-4, 5-dihydropyrrolo [1,2-a ] quinoxaline compound according to claim 1, wherein: the reaction post-treatment method comprises the following steps: after the reaction, the reaction mixture was concentrated by rotary evaporation and separated by silica gel column chromatography using petroleum ether: gradient elution is carried out by using mixed solution of ethyl acetate with the volume ratio of 20:1-5:1 as eluent to obtain the 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound shown in the formula (1).
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