CN111138432B - Method for preparing pyrrole [2,1,5-cd ] indolizine ring derivative through metal-free photocatalysis - Google Patents
Method for preparing pyrrole [2,1,5-cd ] indolizine ring derivative through metal-free photocatalysis Download PDFInfo
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Abstract
The invention discloses a method for preparing pyrrole [2,1,5-cd by metal-free photocatalysis]A method for preparing indolizine ring derivatives belongs to the technical field of organic synthetic chemistry, and relates to a novel metal-free photocatalysis method. The pyrrole [2,1,5-cd]The indolizine ring derivative is synthesized from base raw materials such as phenylpropargyl aldehyde, alkali, organic dye and the like. The method has the characteristics of easily obtained starting materials, wide substrate application range, economy, high efficiency, mild conditions and the like. By bis sp2A series of pyrrole [2,1,5-cd synthesized by hybrid C-H bond oxidation and electron-deficient alkyne addition]Indolizine ring derivatives. These compounds are widely used in pharmaceuticals or agrochemicals. Meanwhile, the fluorescent probe can be used as a fluorescent molecular probe in cell function research and can be used as an important fluorescent sensor and fluorescent material in material chemistry.
Description
Technical Field
The invention belongs to the technical field of organic synthetic chemistry, relates to a metal-free photocatalysis method, and particularly relates to a method for preparing pyrrole [2,1,5-cd ] indolizine ring derivatives through metal-free photocatalysis.
Background
Pyrrole [2,1,5-cd]The indolizine ring compounds are compounds with wide application, and some pyrrole [2,1,5-cd]The indolizine ring compound can be applied to medicines or agricultural chemicals, can also be used as a fluorescent molecular probe in cell function research, and can be used as an important fluorescent sensor and fluorescent material in material chemistry. During the past few decades, there have been many methods for the synthesis of fused endo-nitrides. In these processes, transition metal catalyzed reactions are considered to be one of the most valuable and powerful tools in basic and applied chemistry to produce higher value products. By using several metal catalysts: (1) pd salt as catalyst, (2) Cu salt as catalyst, (3) Ru salt as catalyst, many successful sp's were developed2And (3) activating and converting a hybridized C-H bond. Although numerous methods have been developed to meet the highly selective needs of nitrogen-containing compounds, these methods do not allow for the synthesis of fused endo-nitrides. There remains a long-standing need for innovative challenges in the direct route to improve its activity and extend the range of substrates. Therefore, the development of a metal-free photocatalytic oxidation system for constructing various organic pyrroles [2,1,5-cd ] is urgently needed]Indolizine rings.
CN107739378A discloses indolizine derivatives andthe application of the compound in medicine, wherein the preparation method of the indolizine derivative mainly comprises the step of firstly using R3The method comprises the following steps of performing alkylation reaction on a group-substituted acetoacetic ester raw material (I-0) under an alkaline condition to obtain an intermediate I-1, performing secondary substitution under the alkaline condition to obtain an intermediate I-2, reacting the intermediate I-2 with ammonium acetate under an acidic medium to generate a pyrrole intermediate I-3, performing three-step strong alkali hydrolysis to obtain carboxylic acid, reacting the carboxylic acid with HOBT and DCC to obtain HOBT activated ester, finally reacting the activated ester with sodium malonate to obtain a tricarbonyl intermediate I-4, performing alkali treatment on the tricarbonyl intermediate I-4 to obtain a ring-closing product I-5, and finally heating the I-5 and amino acid under the alkaline condition to obtain a final product I-X. The synthesis method has the advantages of more raw material components, complex process flow and complicated preparation steps.
CN109824667A discloses a method for synthesizing indoindoloprazinone compounds. The main synthesis steps of the compound comprise dissolving a 3-indolemethylamine compound and a 3-butynoic acid compound in an ionic liquid, heating and reacting for a certain time under the action of a catalyst acetylacetone metal complex, cooling to room temperature after the reaction is finished, adding a saturated sodium carbonate solution, adding ethyl acetate into the system for three times, washing twice with saturated salt water, drying with anhydrous sodium sulfate, evaporating the solvent under reduced pressure to obtain a solid, and finally recrystallizing by using 95% ethanol as the solvent to obtain a target product, wherein the yield is 80-92%. The method can synthesize the series of indoindoindolacenzone compounds in one step, and has the advantages of simple synthesis method, complex subsequent treatment work, long treatment time and large yield difference.
Photocatalytic conversion is considered to be an effective alternative to activating C-H bonds under mild conditions. It provides a unique direct access to molecular structures that are often difficult to synthesize using other reactions. The development of photocatalytic reactions is an attractive synthetic approach in synthetic chemistry. Compared with a transition metal catalyst, the used organic dye is more excellent due to low cost, nontoxicity and environmental friendliness, so that the research on constructing various organic pyrrole [2,1,5-cd ] indolizine ring derivatives by a metal-free photocatalytic oxidation system is of great significance.
Disclosure of Invention
In view of the above-mentioned deficiencies of the prior art, it is an object of the present invention to provide a class of pyrrole [2,1,5-cd ] indolizine ring derivatives having fluorescent activity.
The invention also aims to provide a rapid, convenient and mild method for preparing the pyrrole [2,1,5-cd ] indolizine ring derivative so as to overcome the defects of harsh conditions, narrow substrate application range and the like in the prior art for synthesizing the pyrrole [2,1,5-cd ] indolizine ring derivative.
In order to achieve the purpose, the technical scheme of the invention is as follows:
the invention relates to a method for preparing pyrrole [2,1,5-cd ] indolizine ring derivatives shown in formula 3 by metal-free photocatalysis, which has the following reaction formula:
wherein the radical R1、R2Is aryl, electron withdrawing group or alkyl; r3、R4Is aryl or alkyl.
The invention relates to a method for preparing pyrrole [2,1,5-cd ] indolizine ring derivatives shown in formula 5 by metal-free photocatalysis, which has the following reaction formula:
wherein the radical R1、R2Is aryl, electron withdrawing group or alkyl.
The invention relates to a method for preparing pyrrole [2,1,5-cd ] indolizine ring derivatives shown in formula 7 through metal-free photocatalysis, which has the following reaction formula:
wherein the radical R1、R2Is aryl, electron withdrawing group or alkyl; r3Is aryl or alkyl.
The invention relates to a method for preparing pyrrole [2,1,5-cd ] indolizine ring derivatives shown in formula 9 by metal-free photocatalysis, which has the following reaction formula:
wherein the radical R1、R2Is aryl, electron withdrawing group or alkyl.
Further, the molar ratio of the compound shown in the formula 2 to the 2-phenylindolizine shown in the formula 1 is 0.6-3: 1; the molar ratio of the 2-octanal shown in the formula 4 to the 2-phenylindolizine shown in the formula 1 is 0.6-3: 1; the molar ratio of the compound shown in the formula 6 to the 2-phenylindolizine shown in the formula 1 is 0.6-3: 1; the molar ratio of the 3- (thiophene-2-alkynyl) propionaldehyde shown in the formula 8 to the 2-phenylindolizine shown in the formula 1 is 0.6-3: 1. Preferably, the molar ratio of the compound shown in the formula 2 to the 2-phenylindolizine shown in the formula 1 is 1.1: 1; the molar ratio of the 2-octanal shown in the formula 4 to the 2-phenylindolizine shown in the formula 1 is 1.1: 1; the molar ratio of the compound shown in the formula 6 to the 2-phenylindolizine shown in the formula 1 is 1.1: 1; the molar ratio of the 3- (thiophene-2-alkynyl) propionaldehyde shown in the formula 8 to the 2-phenylindolizine shown in the formula 1 is 1.1: 1.
Further, the organic dye in the reaction formula includes, but is not limited to, one or more of rose bengal, eosin Y, eosin B, rhodamine 6G and fluorescein, preferably one or more of rose bengal, eosin Y and eosin B; the molar ratio of the organic dye to the compound shown in the formula 2 in the reaction formula is 0.001-3: 1; the molar ratio of the organic dye to the 2-octanal shown in the formula 4 in the reaction formula is 0.001-3: 1; the molar ratio of the organic dye to the compound shown in the formula 6 in the reaction formula is 0.001-3: 1; the molar ratio of the organic dye to the 3- (thiophene-2-alkynyl) propionaldehyde shown in the formula 8 in the reaction formula is 0.001-3: 1. Preferably, the molar ratio of the organic dye to the compound shown in the formula 2 in the reaction formula is 0.009: 1; the molar ratio of the organic dye to the 2-octanal shown in the formula 4 in the reaction formula is 0.009: 1; the molar ratio of the organic dye to the compound shown in the formula 6 in the reaction formula is 0.009: 1; the molar ratio of the organic dye to the 3- (thiophene-2-alkynyl) propionaldehyde shown in the formula 8 in the reaction formula is 0.009: 1.
Further, the base in the reaction formula includes but is not limited to potassium iodide, triethylene diamine, potassium tert-butoxide, sodium tert-butoxide, preferably potassium iodide; the molar ratio of the alkali to the compound shown in the formula 2 in the reaction formula is 0.01-3: 1; the molar ratio of the alkali to the 2-octanal shown in the formula 4 in the reaction formula is 0.01-3: 1; the molar ratio of the alkali to the compound shown in the formula 6 in the reaction formula is 0.01-3: 1; the molar ratio of the alkali to the 3- (thiophene-2-alkynyl) propionaldehyde shown in the formula 8 in the reaction formula is 0.01-3: 1. Preferably, the molar ratio of the base to the compound shown in formula 2 in the reaction formula is 0.91: 1; in the reaction formula, the molar ratio of the alkali to the 2-octanal shown in the formula 4 is 0.91: 1; the molar ratio of the alkali to the compound shown in the formula 6 in the reaction formula is 0.01-3: 1; the molar ratio of the base to the 3- (thiophene-2-alkynyl) propanal represented by formula 8 in the reaction formula is 0.91: 1.
Further, the organic solvent in the reaction formula includes, but is not limited to, dimethyl sulfoxide (DMSO), N-dimethylformamide, acetonitrile, dichloromethane, preferably dimethyl sulfoxide; the content of the organic solvent in the reaction formula is 0.5-1.5mL, and the stirring is carried out for 12-13h under the irradiation of the blue light LED in the reaction formula.
Further, the method for preparing the pyrrole [2,1,5-cd ] indolizine ring derivative comprises the steps of mixing 2-phenylindolizine, an organic dye and a base, adding dimethyl sulfoxide at room temperature, then respectively adding a compound shown as a formula 2, 2-octanal shown as a formula 4, a compound shown as a formula 6 and 3- (thiophene-2-alkynyl) propionaldehyde shown as a formula 8, stirring under blue light irradiation, spin-drying and then carrying out fast column chromatography to obtain a target product.
Compared with the prior art, the invention has the beneficial effects that:
(1) the invention provides a preparation method of pyrrole [2,1,5-cd ] indolizine ring derivatives with fluorescence activity, which is simple and easy to operate, does not contain metal participation, has wide reaction substrate application range, good regioselectivity and high yield, can efficiently synthesize various pyrrole [2,1,5-cd ] indolizine ring derivatives, and has wide application prospect in the aspects of agricultural chemicals, medicine preparation and fluorescent materials.
(2) The organic dye used in the invention has low cost, no toxicity and environmental friendliness.
(3) The invention develops effective methods for constructing the heterocycle, synthesizes the condensed indolizine through photocatalytic alkenylation cyclization, and the preparation method is simple and can obtain a target product easily.
(4) The preparation method disclosed by the invention realizes intermolecular [3+2] alkenylated cyclization under the action of catalytic amount of alkali (such as potassium iodide) and organic dye (such as rose bengal) and application of the cyclization in preparation of various pyrrole [2,1,5-cd ] indolizine ring derivatives.
Detailed Description
For a better understanding of the present invention, the present invention is further described in conjunction with the following specific examples, wherein the terminology used in the examples is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention. The raw materials used in the examples are all common commercial products, and therefore, the sources thereof need not be particularly limited.
Example 1
20.7mg (0.1mmol) of 2- (p-tolyl) indolizine, 1.1mg (0.001mmol) of rose bengal, and 16.6mg (0.1mmol) of potassium iodide were placed in a 25mL test tube equipped with a stirrer, and after 1mL of dimethyl sulfoxide was added at room temperature, 14.3mg (0.11mmol) of phenylpropargylaldehyde was further added, followed by stirring for 12 hours under blue light irradiation, and flash column chromatography was performed after spin-drying to obtain the objective product with a yield of 89%.
Pyrrole [2,1,5-cd]Of indolizine rings1H NMR，13C NMR and HR-ESI-MS spectrum data are respectively as follows:
1H NMR(400MHz,Chloroform-d)：δ10.11(s,1H),8.50(dd,J＝6.3,2.2Hz,1H),7.93(d,J＝6.3Hz,2H),7.53(dd,J＝8.0,1.4Hz,2H),7.48(t,J＝7.3Hz,1H),7.45–7.39(m,3H),7.29(d,J＝8.1Hz,2H),7.02(d,J＝7.9Hz,2H),2.35(s,3H).
13C NMR(101MHz,Chloroform-d)：δ187.63,138.68,138.21,138.12,132.28,131.62,131.43,130.50,129.33,129.07,129.04,128.71,128.34,126.26,123.41,120.57,114.87,113.46,111.84,21.23.
HR-ESI-MS：m/z calcd.for C23H15NO[M+Na]+:358.1201；found:358.1202.
example 2
The difference from example 1 is that the molar ratio of phenylpropargyl aldehyde to 2- (p-tolyl) indolizine was 0.6:1, the molar ratio of rose bengal to phenylpropargyl aldehyde was 0.001:1, the molar ratio of potassium iodide to phenylpropargyl aldehyde was 0.01:1, the content of dimethyl sulfoxide was 0.5mL, and stirring was carried out for 13h under irradiation of a blue LED. And (4) carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 80%.
Other sources and contents of raw materials and preparation method are the same as those of example 1.
1H NMR(400MHz,Chloroform-d)：δ10.11(s,1H),8.50(dd,J＝6.3,2.2Hz,1H),7.93(d,J＝6.3Hz,2H),7.53(dd,J＝8.0,1.4Hz,2H),7.48(t,J＝7.3Hz,1H),7.45–7.39(m,3H),7.29(d,J＝8.1Hz,2H),7.02(d,J＝7.9Hz,2H),2.35(s,3H).
13C NMR(101MHz,Chloroform-d)：δ187.63,138.68,138.21,138.12,132.28,131.62,131.43,130.50,129.33,129.07,129.04,128.71,128.34,126.26,123.41,120.57,114.87,113.46,111.84,21.23.
HR-ESI-MS：m/z calcd.for C23H15NO[M+Na]+:358.1201；found:358.1202.
Example 3
The difference from example 1 is that the molar ratio of phenylpropargyl aldehyde to 2- (p-tolyl) indolizine is 3:1, the molar ratio of rose bengal to phenylpropargyl aldehyde is 3:1, the molar ratio of potassium iodide to phenylpropargyl aldehyde is 3:1, the content of dimethyl sulfoxide is 1.5mL, and the mixture is stirred for 13h under the irradiation of a blue LED. And (4) carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 85%.
Other sources and contents of raw materials and preparation method are the same as those of example 1.
1H NMR(400MHz,Chloroform-d)：δ10.11(s,1H),8.50(dd,J＝6.3,2.2Hz,1H),7.93(d,J＝6.3Hz,2H),7.53(dd,J＝8.0,1.4Hz,2H),7.48(t,J＝7.3Hz,1H),7.45–7.39(m,3H),7.29(d,J＝8.1Hz,2H),7.02(d,J＝7.9Hz,2H),2.35(s,3H).
13C NMR(101MHz,Chloroform-d)：δ187.63,138.68,138.21,138.12,132.28,131.62,131.43,130.50,129.33,129.07,129.04,128.71,128.34,126.26,123.41,120.57,114.87,113.46,111.84,21.23.
HR-ESI-MS：m/z calcd.for C23H15NO[M+Na]+:358.1201；found:358.1202.
Example 4
19.3mg (0.1mmol) of 2-phenylindolizine, 1.1mg (0.001mmol) of rose bengal and 16.6mg (0.1mmol) of potassium iodide were placed in a 25mL test tube with a stirrer, 1mL of dimethyl sulfoxide was added thereto at room temperature, 13.6mg (0.11mmol) of 2-octanal was further added thereto, and the mixture was stirred for 12 hours under blue light irradiation, and flash column chromatography was performed after spin-drying to obtain the objective product with a yield of 61%.
Pyrrole [2,1,5-cd]Of indolizine rings1H NMR，13C NMR and HR-ESI-MS spectrum data are respectively as follows:
1H NMR(400MHz,Chloroform-d)：δ10.44(s,1H),8.33(dd,J＝5.1,3.4Hz,1H),7.89–7.85(m,2H),7.77(d,J＝7.0Hz,2H),7.54(t,J＝7.4Hz,2H),7.47(d,J＝7.4Hz,1H),7.35(s,1H),3.40–3.35(m,2H),1.76–1.70(m,2H),1.37–1.31(m,2H),1.28–1.24(m,2H),0.81(t,J＝7.2Hz,3H).
13C NMR(101MHz,Chloroform-d)：δ185.19,140.46,137.91,134.76,131.23,130.37,130.05,128.91,128.81,128.32,125.55,124.53,120.49,113.12,112.86,112.03,77.20,32.48,31.82,26.20,22.21,13.89.
HR-ESI-MS：m/z calcd.for C16H17OS[M+H]+:316.1695；found:316.1696.
example 5
The difference from example 4 is that the molar ratio of 2-octanal to 2- (p-tolyl) indolizine was 0.6:1, the molar ratio of rose bengal to 2-octanal was 0.001:1, the molar ratio of potassium iodide to 2-octanal was 0.01:1, the amount of dimethyl sulfoxide was 0.5mL, and stirring was carried out for 13h under blue LED irradiation. And (4) carrying out flash column chromatography after spin drying to obtain a target product, wherein the yield is 55%.
Other sources and contents of raw materials and preparation method are the same as those of example 4.
1H NMR(400MHz,Chloroform-d)：δ10.44(s,1H),8.33(dd,J＝5.1,3.4Hz,1H),7.89–7.85(m,2H),7.77(d,J＝7.0Hz,2H),7.54(t,J＝7.4Hz,2H),7.47(d,J＝7.4Hz,1H),7.35(s,1H),3.40–3.35(m,2H),1.76–1.70(m,2H),1.37–1.31(m,2H),1.28–1.24(m,2H),0.81(t,J＝7.2Hz,3H).
13C NMR(101MHz,Chloroform-d)：δ185.19,140.46,137.91,134.76,131.23,130.37,130.05,128.91,128.81,128.32,125.55,124.53,120.49,113.12,112.86,112.03,77.20,32.48,31.82,26.20,22.21,13.89.
HR-ESI-MS：m/z calcd.for C16H17OS[M+H]+:316.1695；found:316.1696.
Example 6
The difference from example 4 is that the molar ratio of 2-octanal to 2- (p-tolyl) indolizine was 3:1, the molar ratio of rose bengal to 2-octanal was 3:1, the molar ratio of potassium iodide to 2-octanal was 3:1, the content of dimethyl sulfoxide was 1.5mL, and stirring was carried out for 13h under blue LED irradiation. And carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 59%.
Other sources and contents of raw materials and preparation method are the same as those of example 4.
1H NMR(400MHz,Chloroform-d)：δ10.44(s,1H),8.33(dd,J＝5.1,3.4Hz,1H),7.89–7.85(m,2H),7.77(d,J＝7.0Hz,2H),7.54(t,J＝7.4Hz,2H),7.47(d,J＝7.4Hz,1H),7.35(s,1H),3.40–3.35(m,2H),1.76–1.70(m,2H),1.37–1.31(m,2H),1.28–1.24(m,2H),0.81(t,J＝7.2Hz,3H).
13C NMR(101MHz,Chloroform-d)：δ185.19,140.46,137.91,134.76,131.23,130.37,130.05,128.91,128.81,128.32,125.55,124.53,120.49,113.12,112.86,112.03,77.20,32.48,31.82,26.20,22.21,13.89.
HR-ESI-MS：m/z calcd.for C16H17OS[M+H]+:316.1695；found:316.1696.
Example 7
19.3mg (0.1mmol) of 2-phenylindolizine, 1.1mg (0.001mmol) of rose bengal and 16.6mg (0.1mmol) of potassium iodide are placed in a 25mL test tube with a stirrer, 1mL of dimethyl sulfoxide is added at room temperature, 7.5mg (0.11mmol) of methyl propiolate is added, the mixture is stirred for 12 hours under blue light irradiation, and flash column chromatography is performed after spin-drying to obtain the target product with the yield of 70%.
Pyrrole [2,1,5-cd]Of indolizine rings1H NMR，13C NMR and HR-ESI-MS spectrum data are respectively as follows:
1H NMR(400MHz,Chloroform-d)：δ8.34(d,J＝7.5Hz,1H),8.29(s,1H),8.02(d,J＝8.2Hz,2H),7.84(d,J＝12.5Hz,2H),7.55–7.49(m,3H),7.41(t,J＝7.4Hz,1H),4.03(s,3H).
13C NMR(101MHz,Chloroform-d)：δ165.51,135.66,134.05,131.96,129.83,129.11,128.46,127.58,124.43,124.38,119.57,114.77,114.03,113.05,109.10,51.41.
HR-ESI-MS：m/z calcd.for C23H24O2NS2[M+H]+:276.1019；found:276.1017.
example 8
The difference from example 7 is that the molar ratio of methyl propiolate to 2- (p-tolyl) indolizine was 0.6:1, the molar ratio of rose bengal to methyl propiolate was 0.001:1, the molar ratio of potassium iodide to methyl propiolate was 0.01:1, the content of dimethyl sulfoxide was 0.5mL, and stirring was carried out for 13h under blue LED irradiation. And (4) carrying out flash column chromatography after spin drying to obtain a target product, wherein the yield is 60%.
Other sources and contents of raw materials and preparation method are the same as those of example 7.
1H NMR(400MHz,Chloroform-d)：δ8.34(d,J＝7.5Hz,1H),8.29(s,1H),8.02(d,J＝8.2Hz,2H),7.84(d,J＝12.5Hz,2H),7.55–7.49(m,3H),7.41(t,J＝7.4Hz,1H),4.03(s,3H).
13C NMR(101MHz,Chloroform-d)：δ165.51,135.66,134.05,131.96,129.83,129.11,128.46,127.58,124.43,124.38,119.57,114.77,114.03,113.05,109.10,51.41.
HR-ESI-MS：m/z calcd.for C23H24O2NS2[M+H]+:276.1019；found:276.1017.
Example 9
The difference from example 7 is that the molar ratio of methyl propiolate to 2- (p-tolyl) indolizine was 3:1, the molar ratio of rose bengal to methyl propiolate was 3:1, the molar ratio of potassium iodide to methyl propiolate was 3:1, the content of dimethyl sulfoxide was 1.5mL, and stirring was carried out for 13h under blue LED irradiation. And (4) carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 67%.
Other sources and contents of raw materials and preparation method are the same as those of example 7.
1H NMR(400MHz,Chloroform-d)：δ8.34(d,J＝7.5Hz,1H),8.29(s,1H),8.02(d,J＝8.2Hz,2H),7.84(d,J＝12.5Hz,2H),7.55–7.49(m,3H),7.41(t,J＝7.4Hz,1H),4.03(s,3H).
13C NMR(101MHz,Chloroform-d)：δ165.51,135.66,134.05,131.96,129.83,129.11,128.46,127.58,124.43,124.38,119.57,114.77,114.03,113.05,109.10,51.41.
HR-ESI-MS：m/z calcd.for C23H24O2NS2[M+H]+:276.1019；found:276.1017.
Example 10
19.3mg (0.1mmol) of 2-phenylindolizine, 1.1mg (0.001mmol) of rose bengal and 16.6mg (0.1mmol) of potassium iodide are placed in a 25mL test tube with a stirrer, 1mL of dimethyl sulfoxide is added at room temperature, 15.0mg (0.11mmol) of 3- (thiophene-2-alkynyl) propanal is added, the mixture is stirred for 12 hours under blue light irradiation, and flash column chromatography is carried out after spin-drying to obtain the target product with the yield of 89%.
Pyrrole [2,1,5-cd]Of indolizine rings1H NMR，13C NMR and HR-ESI-MS spectrum data are respectively as follows:
1H NMR(400MHz,Chloroform-d)：δ10.32(s,1H),8.51(t,J＝4.2Hz,1H),7.93(d,J＝4.2Hz,2H),7.48(dd,J＝12.6,6.5Hz,3H),7.42(s,1H),7.35–7.29(m,3H),7.19(d,J＝3.5Hz,1H),7.12(dd,J＝5.1,3.6Hz,1H).
13C NMR(101MHz,Chloroform-d)：δ187.44,137.98,133.51,132.39,131.40,130.79,130.16,129.34,129.17,128.52,128.35,128.26,127.57,126.42,123.70,121.04,115.27,113.95,112.73.
HR-ESI-MS：m/z calcd.for C23H24O2NS2[M+H]+:328.0790；found:328.0790.
example 11
The difference from example 10 is that the molar ratio of 3- (thiophene-2-ynyl) propanal to 2- (p-tolyl) indolizine was 0.6:1, the molar ratio of rose bengal to 3- (thiophene-2-ynyl) propanal was 0.001:1, the molar ratio of potassium iodide to 3- (thiophene-2-ynyl) propanal was 0.01:1, the content of dimethyl sulfoxide was 0.5mL, and stirring was carried out for 13h under blue LED irradiation. And (4) carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 80%.
Other sources and contents of raw materials and preparation method are the same as those of example 10.
1H NMR(400MHz,Chloroform-d)：δ10.32(s,1H),8.51(t,J＝4.2Hz,1H),7.93(d,J＝4.2Hz,2H),7.48(dd,J＝12.6,6.5Hz,3H),7.42(s,1H),7.35–7.29(m,3H),7.19(d,J＝3.5Hz,1H),7.12(dd,J＝5.1,3.6Hz,1H).
13C NMR(101MHz,Chloroform-d)：δ187.44,137.98,133.51,132.39,131.40,130.79,130.16,129.34,129.17,128.52,128.35,128.26,127.57,126.42,123.70,121.04,115.27,113.95,112.73.
HR-ESI-MS：m/z calcd.for C23H24O2NS2[M+H]+:328.0790；found:328.0790.
Example 12
The difference from example 10 is that the molar ratio of 3- (thiophene-2-ynyl) propanal to 2- (p-tolyl) indolizine was 3:1, the molar ratio of rose bengal to 3- (thiophene-2-ynyl) propanal was 3:1, the molar ratio of potassium iodide to 3- (thiophene-2-ynyl) propanal was 3:1, the content of dimethyl sulfoxide was 1.5mL, and stirring was carried out for 13h under irradiation of a blue LED. And (4) carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 85%.
Other sources and contents of raw materials and preparation method are the same as those of example 10.
1H NMR(400MHz,Chloroform-d)：δ10.32(s,1H),8.51(t,J＝4.2Hz,1H),7.93(d,J＝4.2Hz,2H),7.48(dd,J＝12.6,6.5Hz,3H),7.42(s,1H),7.35–7.29(m,3H),7.19(d,J＝3.5Hz,1H),7.12(dd,J＝5.1,3.6Hz,1H).
13C NMR(101MHz,Chloroform-d)：δ187.44,137.98,133.51,132.39,131.40,130.79,130.16,129.34,129.17,128.52,128.35,128.26,127.57,126.42,123.70,121.04,115.27,113.95,112.73.
HR-ESI-MS：m/z calcd.for C23H24O2NS2[M+H]+:328.0790；found:328.0790.
Comparative example 1
The difference from example 1 is that the molar ratio of phenylpropargyl aldehyde to 2- (p-tolyl) indolizine was 0.4:1, the molar ratio of rose bengal to phenylpropargyl aldehyde was 0.001:1, the molar ratio of potassium iodide to phenylpropargyl aldehyde was 0.005:1, the content of dimethyl sulfoxide was 0.3mL, and stirring was carried out for 11h under irradiation of a blue LED. And carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 75%.
Other sources and contents of raw materials and preparation method are the same as those of example 1.
1H NMR(400MHz,Chloroform-d)：δ10.11(s,1H),8.50(dd,J＝6.3,2.2Hz,1H),7.93(d,J＝6.3Hz,2H),7.53(dd,J＝8.0,1.4Hz,2H),7.48(t,J＝7.3Hz,1H),7.45–7.39(m,3H),7.29(d,J＝8.1Hz,2H),7.02(d,J＝7.9Hz,2H),2.35(s,3H).
13C NMR(101MHz,Chloroform-d)：δ187.63,138.68,138.21,138.12,132.28,131.62,131.43,130.50,129.33,129.07,129.04,128.71,128.34,126.26,123.41,120.57,114.87,113.46,111.84,21.23.
HR-ESI-MS：m/z calcd.for C23H15NO[M+Na]+:358.1201；found:358.1202.
Comparative example 2
The difference from example 1 is that the molar ratio of phenylpropargyl aldehyde to 2- (p-tolyl) indolizine is 4:1, the molar ratio of rose bengal to phenylpropargyl aldehyde is 4:1, the molar ratio of potassium iodide to phenylpropargyl aldehyde is 4:1, the content of dimethyl sulfoxide is 1.8mL, and the mixture is stirred for 14h under the irradiation of a blue LED. And carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 79%.
Other sources and contents of raw materials and preparation method are the same as those of example 1.
1H NMR(400MHz,Chloroform-d)：δ10.11(s,1H),8.50(dd,J＝6.3,2.2Hz,1H),7.93(d,J＝6.3Hz,2H),7.53(dd,J＝8.0,1.4Hz,2H),7.48(t,J＝7.3Hz,1H),7.45–7.39(m,3H),7.29(d,J＝8.1Hz,2H),7.02(d,J＝7.9Hz,2H),2.35(s,3H).
13C NMR(101MHz,Chloroform-d)：δ187.63,138.68,138.21,138.12,132.28,131.62,131.43,130.50,129.33,129.07,129.04,128.71,128.34,126.26,123.41,120.57,114.87,113.46,111.84,21.23.
HR-ESI-MS：m/z calcd.for C23H15NO[M+Na]+:358.1201；found:358.1202.
Comparative example 3
The difference from example 4 is that the molar ratio of 2-octanal to 2- (p-tolyl) indolizine was 0.5:1, the molar ratio of rose bengal to 2-octanal was 0.001:1, the molar ratio of potassium iodide to 2-octanal was 0.05:1, the amount of dimethyl sulfoxide was 0.3mL, and stirring was carried out for 11h under blue LED irradiation. And (4) carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 50%.
Other sources and contents of raw materials and preparation method are the same as those of example 4.
1H NMR(400MHz,Chloroform-d)：δ10.44(s,1H),8.33(dd,J＝5.1,3.4Hz,1H),7.89–7.85(m,2H),7.77(d,J＝7.0Hz,2H),7.54(t,J＝7.4Hz,2H),7.47(d,J＝7.4Hz,1H),7.35(s,1H),3.40–3.35(m,2H),1.76–1.70(m,2H),1.37–1.31(m,2H),1.28–1.24(m,2H),0.81(t,J＝7.2Hz,3H).
13C NMR(101MHz,Chloroform-d)：δ185.19,140.46,137.91,134.76,131.23,130.37,130.05,128.91,128.81,128.32,125.55,124.53,120.49,113.12,112.86,112.03,77.20,32.48,31.82,26.20,22.21,13.89.
HR-ESI-MS：m/z calcd.for C16H17OS[M+H]+:316.1695；found:316.1696.
Comparative example 4
The difference from example 4 is that the molar ratio of 2-octanal to 2- (p-tolyl) indolizine was 4:1, the molar ratio of rose bengal to 2-octanal was 4:1, the molar ratio of potassium iodide to 2-octanal was 4:1, the content of dimethyl sulfoxide was 1.8mL, and the mixture was stirred for 14h under blue LED irradiation. And carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 54%.
Other sources and contents of raw materials and preparation method are the same as those of example 4.
1H NMR(400MHz,Chloroform-d)：δ10.44(s,1H),8.33(dd,J＝5.1,3.4Hz,1H),7.89–7.85(m,2H),7.77(d,J＝7.0Hz,2H),7.54(t,J＝7.4Hz,2H),7.47(d,J＝7.4Hz,1H),7.35(s,1H),3.40–3.35(m,2H),1.76–1.70(m,2H),1.37–1.31(m,2H),1.28–1.24(m,2H),0.81(t,J＝7.2Hz,3H).
13C NMR(101MHz,Chloroform-d)：δ185.19,140.46,137.91,134.76,131.23,130.37,130.05,128.91,128.81,128.32,125.55,124.53,120.49,113.12,112.86,112.03,77.20,32.48,31.82,26.20,22.21,13.89.
HR-ESI-MS：m/z calcd.for C16H17OS[M+H]+:316.1695；found:316.1696.
Comparative example 5
The difference from example 7 is that the molar ratio of methyl propiolate to 2- (p-tolyl) indolizine was 0.5:1, the molar ratio of rose bengal to methyl propiolate was 0.001:1, the molar ratio of potassium iodide to methyl propiolate was 0.005:1, the content of dimethyl sulfoxide was 0.3mL, and stirring was carried out for 11h under blue LED irradiation. And (4) carrying out flash column chromatography after spin drying to obtain a target product, wherein the yield is 55%.
Other sources and contents of raw materials and preparation method are the same as those of example 7.
1H NMR(400MHz,Chloroform-d)：δ8.34(d,J＝7.5Hz,1H),8.29(s,1H),8.02(d,J＝8.2Hz,2H),7.84(d,J＝12.5Hz,2H),7.55–7.49(m,3H),7.41(t,J＝7.4Hz,1H),4.03(s,3H).
13C NMR(101MHz,Chloroform-d)：δ165.51,135.66,134.05,131.96,129.83,129.11,128.46,127.58,124.43,124.38,119.57,114.77,114.03,113.05,109.10,51.41.
HR-ESI-MS：m/z calcd.for C23H24O2NS2[M+H]+:276.1019；found:276.1017.
Comparative example 6
The difference from example 7 is that the molar ratio of methyl propiolate to 2- (p-tolyl) indolizine was 4:1, the molar ratio of rose bengal to methyl propiolate was 4:1, the molar ratio of potassium iodide to methyl propiolate was 4:1, the content of dimethyl sulfoxide was 1.8mL, and the mixture was stirred for 14h under blue LED irradiation. And carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 59%.
Other sources and contents of raw materials and preparation method are the same as those of example 7.
1H NMR(400MHz,Chloroform-d)：δ8.34(d,J＝7.5Hz,1H),8.29(s,1H),8.02(d,J＝8.2Hz,2H),7.84(d,J＝12.5Hz,2H),7.55–7.49(m,3H),7.41(t,J＝7.4Hz,1H),4.03(s,3H).
13C NMR(101MHz,Chloroform-d)：δ165.51,135.66,134.05,131.96,129.83,129.11,128.46,127.58,124.43,124.38,119.57,114.77,114.03,113.05,109.10,51.41.
HR-ESI-MS：m/z calcd.for C23H24O2NS2[M+H]+:276.1019；found:276.1017.
Comparative example 7
The difference from example 10 is that the molar ratio of 3- (thiophene-2-ynyl) propanal to 2- (p-tolyl) indolizine was 0.5:1, the molar ratio of rose bengal to 3- (thiophene-2-ynyl) propanal was 0.001:1, the molar ratio of potassium iodide to 3- (thiophene-2-ynyl) propanal was 0.005:1, the content of dimethyl sulfoxide was 0.3mL, and stirring was carried out for 11h under blue LED irradiation. And carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 75%.
Other sources and contents of raw materials and preparation method are the same as those of example 10.
1H NMR(400MHz,Chloroform-d)：δ10.32(s,1H),8.51(t,J＝4.2Hz,1H),7.93(d,J＝4.2Hz,2H),7.48(dd,J＝12.6,6.5Hz,3H),7.42(s,1H),7.35–7.29(m,3H),7.19(d,J＝3.5Hz,1H),7.12(dd,J＝5.1,3.6Hz,1H).
13C NMR(101MHz,Chloroform-d)：δ187.44,137.98,133.51,132.39,131.40,130.79,130.16,129.34,129.17,128.52,128.35,128.26,127.57,126.42,123.70,121.04,115.27,113.95,112.73.
HR-ESI-MS：m/z calcd.for C23H24O2NS2[M+H]+:328.0790；found:328.0790.
Comparative example 8
The difference from example 10 is that the molar ratio of 3- (thiophen-2-ynyl) propanal to 2- (p-tolyl) indolizine was 4:1, the molar ratio of rose bengal to 3- (thiophen-2-ynyl) propanal was 4:1, the molar ratio of potassium iodide to 3- (thiophen-2-ynyl) propanal was 4:1, the content of dimethyl sulfoxide was 1.8mL, and stirring was carried out for 14h under irradiation of a blue LED. And carrying out flash column chromatography after spin-drying to obtain a target product, wherein the yield is 79%.
Other sources and contents of raw materials and preparation method are the same as those of example 10.
1H NMR(400MHz,Chloroform-d)：δ10.32(s,1H),8.51(t,J＝4.2Hz,1H),7.93(d,J＝4.2Hz,2H),7.48(dd,J＝12.6,6.5Hz,3H),7.42(s,1H),7.35–7.29(m,3H),7.19(d,J＝3.5Hz,1H),7.12(dd,J＝5.1,3.6Hz,1H).
13C NMR(101MHz,Chloroform-d)：δ187.44,137.98,133.51,132.39,131.40,130.79,130.16,129.34,129.17,128.52,128.35,128.26,127.57,126.42,123.70,121.04,115.27,113.95,112.73.
HR-ESI-MS：m/z calcd.for C23H24O2NS2[M+H]+:328.0790；found:328.0790.
In summary, when one of the raw materials in examples 1 to 3 is phenylpropargylaldehyde, the yield of the target product is 89%, 80% or 85% by performing flash column chromatography after spin-drying, when one of the raw materials is 2-octanal (examples 4 to 6), the yield of the target product is 61%, 55% or 59% by performing flash column chromatography after spin-drying, when one of the raw materials is methyl propiolate (examples 7 to 9), the yield of the target product is 70%, 60% or 67% by performing flash column chromatography after spin-drying, when one of the raw materials is 3- (thiophen-2-ynyl) propanal (examples 10 to 12), the yield of the target product is 89%, 80% or 85% by performing flash column chromatography after spin-drying, and the raw material ranges of comparative examples 1 to 8 are out of the scope of claims, it can be seen that the yields obtained by performing flash column chromatography on the target products respectively are lower than those obtained in the corresponding examples, and the highest yield of the target products can reach 89%. Therefore, the pyrrole [2,1,5-cd ] indolizine ring derivative prepared by the method of the invention has high yield.
Finally, it should be noted that the above-mentioned contents are only used for illustrating the technical solutions of the present invention, and not for limiting the protection scope of the present invention, and that the simple modifications or equivalent substitutions of the technical solutions of the present invention by those of ordinary skill in the art can be made without departing from the spirit and scope of the technical solutions of the present invention.
Claims (7)
1. A method for preparing pyrrole [2,1,5-cd ] indolizine ring derivatives shown in formula 3 by metal-free photocatalysis is disclosed, wherein the reaction formula is as follows:
wherein the radical R1、R2Is aryl or alkyl; r3、R4Is aryl or alkyl.
2. A method for preparing pyrrole [2,1,5-cd ] indolizine ring derivatives shown in formula 9 by metal-free photocatalysis is disclosed, wherein the reaction formula is as follows:
wherein the radical R1、R2Is aryl or alkyl.
3. The method according to any one of claims 1-2, wherein: the molar ratio of the compound shown in the formula 2 to the compound shown in the formula 1 is 0.6-3: 1; the molar ratio of the compound shown in the formula 8 to the compound shown in the formula 1 is 0.6-3: 1.
4. The method according to any one of claims 1-2, wherein: the molar ratio of the organic dye to the compound shown in the formula 2 in the reaction formula is 0.001-3: 1; the molar ratio of the organic dye to the compound shown in the formula 8 in the reaction formula is 0.001-3: 1.
5. The method according to any one of claims 1-2, wherein: the molar ratio of the alkali to the compound shown in the formula 2 in the reaction formula is 0.01-3: 1; the molar ratio of the alkali to the compound shown in the formula 8 in the reaction formula is 0.01-3: 1.
6. The method according to any one of claims 1-2, wherein: the reaction was stirred for 12-13h under blue LED illumination.
7. The method according to any one of claims 1 to 2, wherein the target product is obtained by mixing the compound represented by formula 1, the organic dye and the base, adding the solvent at room temperature, adding the compound represented by formula 2 or the compound represented by formula 8, stirring under the irradiation of a blue light LED, spin-drying, and performing flash column chromatography.
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| CN106045991A (en) * | 2016-05-30 | 2016-10-26 | 西南大学 | Application of chlorophyll serving as photosensitizer to visible light catalytic cyclization reaction based tetrahydroquinoline derivative synthesis |
| CN110078655A (en) * | 2019-06-05 | 2019-08-02 | 赣南师范大学 | A kind of method that photocatalysis prepares Benzazole compounds |
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| CN106045991A (en) * | 2016-05-30 | 2016-10-26 | 西南大学 | Application of chlorophyll serving as photosensitizer to visible light catalytic cyclization reaction based tetrahydroquinoline derivative synthesis |
| CN110078655A (en) * | 2019-06-05 | 2019-08-02 | 赣南师范大学 | A kind of method that photocatalysis prepares Benzazole compounds |
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| Title |
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| "A visible-light-induced intermolecular [3 + 2] alkenylation-cyclization strategy: metal-free construction of pyrrolo[2,1,5-cd]indolizine rings";Yaofeng Liang et al.;《Green Chemistry》;20190702;第21卷;第4025-4029页 * |
| "Visible-Light Induced Isoindoles Formation To Trigger Intermolecular Diels-Alder Reactions in the Presence of Air";Chao Lin et al.;《Organic Letters》;20150514;第17卷;第2684-2687页 * |
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