CN114230545A - Synthetic method of isocoumarin compound - Google Patents

Synthetic method of isocoumarin compound Download PDF

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CN114230545A
CN114230545A CN202111485872.8A CN202111485872A CN114230545A CN 114230545 A CN114230545 A CN 114230545A CN 202111485872 A CN202111485872 A CN 202111485872A CN 114230545 A CN114230545 A CN 114230545A
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余小春
王勤
金辉乐
王舜
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Wenzhou University
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Abstract

The invention belongs to the field of organic chemical synthesis, and particularly relates to a synthetic method of isocoumarin compounds. (A) Reacting the compound shown in the formula (A) with the compound shown in the formula (B) in a solvent under the action of a noble metal catalyst and a first additive to obtain a compound shown in the formula (C); the noble metal catalyst is one or more of dodecacarbonyltriruthenium, dichlorophenyl ruthenium (II) dimer and dichlorobis (4-methyl isopropylphenyl) ruthenium (II); the first additive is one or more of silver tetrafluoroborate, silver hexafluoroantimonate, copper acetate, zinc acetate, silver trifluoromethanesulfonate, copper trifluoromethanesulfonate and zinc trifluoromethanesulfonate. The invention provides a simple and effective method for constructing lactone compounds, and the method can be used for constructing isocoumarin compounds with self-cyclization and cross-cyclization of sulfoylide without adding additives with guiding effect.

Description

Synthetic method of isocoumarin compound
Technical Field
The invention belongs to the field of organic chemical synthesis, and particularly relates to a synthetic method of isocoumarin compounds.
Background
The lactone compound, coumarin, is widely distributed in higher plants. The coumarin can generate blue fluorescence in the presence of ultraviolet light, visible light and concentrated sulfuric acid, and has various biological activities of regulating plant growth, resisting bacteria and virus, resisting blood coagulation, relaxing smooth muscle, absorbing ultraviolet ray and resisting radiation. To date, many coumarins have not been isolated from citrus plants of the family rutaceae, and synthetic methods and performance studies of coumarins and their derivatives, particularly 3-substituted isocoumarins, have not been stopped.
At present, the synthesis methods of 3-substituted isocoumarin mainly comprise the following methods:
1) 2-chlorobenzoic acid and 2, 4-diketone-pentane are used as raw materials to synthesize the 3-substituted isocoumarin under the catalysis of Cu nano particles.
2) Cu (i) catalyzed coupling of halogenated aromatic carboxylic acids with alkynes.
3) And (3) internal cyclization of alkynyl aryl ester.
4) The newly reported aromatic amide, aromatic formic acid and sulfur ylide are cyclized under the catalysis of [ Rh ] and [ Ru ].
In particular, the following documents are mentioned:
the Xiaoquan Yao subject group (Wang, X.W.; Wu, C.L.; Sun, Y.W.; Yao, X.Q.Copper nanoparticles catalyzed econic synthesis of 3-substistuted isocoumarins from 2-chlorobenzoic acids/amides and 1, 3-diketenes [ J ]. Tetrahedron Lett.2017,58, 3164-. The reaction process is that 2-chlorobenzoic acid and 2, 4-diketone-pentane react for 2 hours at 100 ℃ in the atmosphere of auxiliary potassium carbonate and nitrogen by taking 10 mol% copper nanoparticles with higher catalytic activity as catalysts, and 3-substituted isocoumarin is obtained with excellent yield;
Figure BDA0003397505930000021
manojit Pal subject group (Chary, R.G.; Reddy, R.; Ganesh, Y.S.S.; Prasad, K.V.; Chandra, S.K.P.; Mukherjee, S.; Pal, M.Cu-catalyzed coupling-cyclization in PEG 400 end ultrasounds: a high hly selected and green adapter cement catalysts [ J. ]]RSC adv.2013,3, 9641-9644.) at CuI/K2CO3The coupling cyclization of o-iodobenzoic acid and terminal alkyne is promoted in a PEG reaction system under the action of ultrasonic waves, and a more green and practical approach is provided for 3-substituted isocoumarin with remarkable regioselectivity. However, the defects are that the universality of the substrate is not high, and the applicable range of the substrate is narrow;
Figure BDA0003397505930000022
sunwoo Lee topic group (Kumar, M.R.; Irudayananathan, F.M.; Moon, J.H.; Lee, S.W. Regioselective one-pot synthesis of isocoumarins and silanes from 2-iodobenzoic acids and aldehydes by thermal control [ J ]. adv.Synth.C. 2013,355, 3221-3230.) copper catalyzed coupling of 2-iodobenzoic acid with alkynes (terminal acetylene, alkynylcarboxylic acid, and trimethylsilylacetylene) in the presence of cesium carbonate and dimethyl sulfoxide selectively synthesizes isocoumarins. Wherein the selectivity of the 3-phenyl isocoumarin is 85%, but the selectivity of other substrates is poor, and the yield is generally low;
Figure BDA0003397505930000023
gilson Zeni topic group (Speransa, A.; Godoi, B.; Pinton, S.; Back, D.F.; Menezes, P.H.; Zeni, G.Regiospectic synthesis of isochromenones by Iron (III)/PhSeph mediated cyclization of 2-alkylarylesters [ J. ]]Chem.2011,76, 6789-6797.) by FeCl3The mediated alkynyl aryl ester can be used for synthesizing a series of 3-substituted isocoumarins at room temperature under the atmospheric atmosphere by taking cheap and environment-friendly iron salt as a metal source;
Figure BDA0003397505930000031
the Lutz Ackermann topic group (Liang, Y.F.; Yang, L.; Rogge, T.; Ackermann, L.Ruthenium (IV) intermedia in C-H activation/association by way of a beam o-cordination [ J. ]].Chem.Eur.J2018,24, 16548-16552) use of ruthenium complexes ([ RuCl ] with ortho-C-H activation effect2(p-cymene)]2) Catalyzing a cyclized benzoic acid compound and a sulfur ylide to synthesize different substituted isocoumarins with a wide substrate range;
Figure BDA0003397505930000032
xingwei Li topic group (Liang, Y.F.; Yang, L.; Rogge, T.; Ackermann, L.Rhodium (III) -catalyzed chemical reactions and anions beta N-methoxy benzamides and sulfoxonium amides via C-H activation [ J.]Chem.commu.2018, 54,670-673.) by rh (iii) ([ RhCp Cl2]2) Catalyzing C-H activation to realize chemical modification between N-methoxybenzamide and thioylide and neutral cyclization of oxidation reduction, wherein the thioylide is used as a carbene precursor, and is subjected to coupling cyclization under acid regulation to selectively generate 3-substituted isocoumarin;
Figure BDA0003397505930000033
the methods have the disadvantages that the method needs an additional equivalent of an auxiliary agent besides the necessary catalyst, the economy is not high, other guide groups are needed to be added, the substrate range is limited, the product yield is required to be improved, and the like.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a synthetic method of an isocoumarin compound.
The technical scheme adopted by the invention is as follows: a synthetic method of isocoumarin compounds has the following chemical reaction formula:
Figure BDA0003397505930000041
in the chemical reaction formula, the compound shown in (A) and the compound shown in (B) react in a solvent under the action of a noble metal catalyst and a first additive to obtain a compound shown in (C);
the noble metal catalyst is one or more of dodecacarbonyltriruthenium, dichlorophenyl ruthenium (II) dimer and dichlorobis (4-methyl isopropylphenyl) ruthenium (II);
the first additive is one or more of silver tetrafluoroborate, silver hexafluoroantimonate, copper acetate, zinc acetate, silver trifluoromethanesulfonate, copper trifluoromethanesulfonate and zinc trifluoromethanesulfonate.
The noble metal catalyst is dichlorobis (4-methyl isopropylphenyl) ruthenium (II).
The amount of dichlorobis (4-methylisopropylphenyl) ruthenium (II) added was 5 mol%.
The first additive is zinc trifluoromethanesulfonate.
And a second additive is also added in the reaction, and the second additive is one or more of benzoic acid, pivalic acid, phenylmethanesulfonic acid, polyphosphoric acid and glacial acetic acid.
The second additive is pivalic acid.
The amount of the compound represented by (A) is 1eq, and the amount of pivalic acid added is 0.1-1 eq.
The solvent is one or more of acetonitrile, toluene, styrene and dimethylformamide.
The solvent is styrene.
The invention has the following beneficial effects: the invention provides a simple and effective method for constructing lactone compounds, and the method can be used for constructing isocoumarin compounds with self-cyclization and cross-cyclization of sulfoylide without adding additives with guiding effect.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is within the scope of the present invention for those skilled in the art to obtain other drawings based on the drawings without inventive exercise.
FIG. 1 is a chemical reaction scheme of the present invention;
FIG. 2 is an X-ray diffraction single crystal structure obtained by X-ray single crystal diffraction analysis of the product prepared in example 45.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in further detail with reference to the accompanying drawings. The following description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the scope of the present invention, which is defined by the appended claims.
The invention provides a method for synthesizing isocoumarin compounds, which has the following chemical reaction formula:
Figure BDA0003397505930000051
in the chemical reaction formula, the compound shown in (A) and the compound shown in (B) react in a solvent under the action of a noble metal catalyst and a first additive to obtain a compound shown in (C);
the noble metal catalyst is one or more of dodecacarbonyltriruthenium, dichlorophenyl ruthenium (II) dimer and dichlorobis (4-methyl isopropylphenyl) ruthenium (II);
the first additive is one or more of silver tetrafluoroborate, silver hexafluoroantimonate, copper acetate, zinc acetate, silver trifluoromethanesulfonate, copper trifluoromethanesulfonate and zinc trifluoromethanesulfonate.
In some examples of the invention and comparative examples, triruthenium dodecacarbonyl (C) was used12O12Ru3) Ruthenium (C) chloride (1, 5-cyclooctadiene) (pentamethylcyclopentadiene)18H27ClRu 5), bis (triphenylphosphine) cyclopentadienyl ruthenium (II) chloride (C)41H35ClP2Ru), dichlorophenyl ruthenium (II) dimer (C)12H12Cl4Ru2) Bis (4-methylisopropylphenyl) ruthenium dichloride(II)(C20H28Cl4Ru2) Dimeric rhodium acetate (C)8H12O8Rh2) (1, 5-cyclooctadiene) chlororhodium (I) dimer (C)16H24Cl2Rh2) Bis (1, 5-cyclooctadiene) -rhodium trifluoromethanesulfonate (C)17H24F3O3RhS), bis (acetonitrile) (1, 5-cyclooctadiene) rhodium tetrafluoride (C)12H18BF4N2Rh), (1, 5-cyclooctadiene) iridium (I) chloride dimer (C)16H24Cl2Ir2) Tris (2-phenylpyridine) -iridium (C)33H24IrN3) And carrying out the reaction without adding a catalyst. Dodecacarbonyltriruthenium (C)12O12Ru3) Has good catalytic effect on the generation of 2a in a reaction system, and the (1, 5-cyclooctadiene) (pentamethylcyclopentadiene) ruthenium chloride (C)18H27ClRu5 and bis (triphenylphosphine) cyclopentadienyl ruthenium (II) chloride (C)41H35ClP2Ru) has no catalytic action on the reaction system; in the presence of dichlorophenylruthenium (II) dimer and dichlorobis (4-methyl isopropylphenyl) ruthenium (II) catalyst, a certain amount of product can be obtained; dimeric rhodium acetate (C)8H12O8Rh2) (1, 5-cyclooctadiene) chlororhodium (I) dimer (C)16H24Cl2Rh2) Bis (1, 5-cyclooctadiene) -rhodium trifluoromethanesulfonate (C)17H24F3O3RhS), bis (acetonitrile) (1, 5-cyclooctadiene) rhodium tetrafluoride (C)12H18BF4N2Rh), (1, 5-cyclooctadiene) iridium (I) chloride dimer (C)16H24Cl2Ir2) Tris (2-phenylpyridine) -iridium (C)33H24IrN3) Addition of (b) does not produce a product. The most preferred catalyst is dichlorobis (4-methylisopropylphenyl) ruthenium (II).
In some examples of the present invention and comparative examples, the reaction was carried out without adding and adding Lewis acid additives such as silver tetrafluoroborate, silver hexafluoroantimonate, copper acetate, zinc acetate, silver trifluoromethanesulfonate, copper trifluoromethanesulfonate, zinc trifluoromethanesulfonate, etc., respectively. When no Lewis acid additive is added and silver acetate is added in the reaction system, only trace amount of the target product is detected; when other materials such as silver tetrafluoroborate and silver hexafluoroantimonate are added, the reaction has better yield; when the silver trifluoromethanesulfonate, the copper trifluoromethanesulfonate and the zinc trifluoromethanesulfonate are added, the yield is high, and the zinc trifluoromethanesulfonate is the best.
In some embodiments of the invention, benzoic acid (PhCOOH), p-toluenesulfonic acid (TsOH), trifluoroacetic acid (CF) are not added, respectively3COOH), polyphosphoric acid (PPA), pivalic acid (PivOH), and glacial acetic acid (AcOH). When trifluoroacetic acid is added into the reaction system, only trace amount of the target product is detected; a small amount of product can be obtained without adding; when benzoic acid, p-toluenesulfonic acid, polyphosphoric acid, glacial acetic acid and pivalic acid are added, the addition is obviously improved compared with the case of no acid; pivalic acid is an advantageous additive for the reaction and promotes the formation of the desired product.
In some embodiments of the present invention, 0.1eq, 0.2eq, 0.6eq, 1.0eq of pivalic acid (PivOH) are used, respectively, and the reaction effect is best when 0.2eq of pivalic acid is used.
In some embodiments of the present invention, 0.05eq, 0.10eq, 0.15eq, 0.20eq, 0.25eq, 0.30eq of zinc trifluoromethanesulfonate is used for reaction, and the optimal amount of zinc trifluoromethanesulfonate is 0.2 eq.
In some embodiments of the present invention, 1 mol%, 3 mol%, 5 mol%, 8 mol% dichlorobis (4-methylisopropylphenyl) ruthenium (II) is used for the reaction, and the optimal dosage of dichlorobis (4-methylisopropylphenyl) ruthenium (II) is 5%, and the yield of the reaction is not significantly affected by increasing the dosage of the catalyst.
In some embodiments of the invention, the reaction is carried out at room temperature, 60 ℃, 80 ℃, 100 ℃ and 120 ℃ for 12-36h, the reaction can be carried out smoothly even at room temperature for 24 hours, but the yield is not high, and the yield can be improved by increasing the reaction temperature in the same time. The optimal reaction temperature and time of the reaction system are 120 ℃ and 24 hours.
In some embodiments of the invention, acetonitrile (CH) is employed separately3CN), toluene (PhCH)3) Dimethyl sulfoxide (DMSO), styrene (DCE), Dimethylformamide (DMF), the yields of which are low when acetonitrile is used as solvent; moderate yield is obtained when DMF is chosen; considerable yield is obtained when a non-polar solvent toluene is used; however, when DMSO is selected as a solvent, only a trace amount of product is obtained in the reaction system due to the solvent effect, and it is suspected that dimethyl sulfoxide is generated in the reaction process, while DMSO is used as a solvent to be unfavorable for the reaction; the good solvent of the reaction is DCE, and the corresponding target product has higher yield.
In some embodiments of the present invention, nitrogen, oxygen, and air are used as the reaction atmosphere, respectively, and the yield is not very different, so the reaction is performed in air.
In some embodiments of the present invention, a certain amount of product can be obtained by performing reactions with substrates with different substituents, which proves that the present invention is compatible with various functional groups.
The following are some specific examples of the present invention.
The specific operation process is as follows:
the operation steps of the sulfur ylide synthesis are as follows:
Figure BDA0003397505930000071
the general operation steps are as follows: potassium tert-butoxide (3.0g, 27.2mmol) and THF (30mL) were added to a dry 50mL round-bottom flask, and after stirring at room temperature for 10 minutes, trimethyl sulfoxide iodide (5.0g, 20.6mmol) was added and the resulting mixture was stirred at reflux for 2 h. Subsequently, the reaction was cooled to 0 ℃ and the acid chloride (7mmol) was added dropwise to the reaction mixture. The reaction was carried out at room temperature and stirred for 3 h. After completion of the reaction, the solvent was evaporated under vacuum and extracted with water and ethyl acetate to obtain a mixed solution. The separated organic layer was washed with saturated brine and then with anhydrous Na2SO4And (5) drying. After evaporation of the solvent, the crude product was purified using a silica gel column chromatography with EtOAc/MeOH (95: 5) to afford the corresponding thioylide product.
Figure BDA0003397505930000081
[ Ru ] catalyzing the sulfur ylide to synthesize isocoumarin through self-cyclization, comprising the following steps:
the general operation steps are as follows: to a dry Schlenk tube were added aromatic thioylide 1a (0.2mmol), [ Ru (p-cymene) Cl2]2(5mol％)，PivOH(0.2eq)，Zn(OTf)2(0.2eq), DCE (1.0 mL). Then, the reaction mixture is put into an oil bath kettle at 120 ℃ and stirred for 24 hours, after the reaction is finished, TLC or GC-MS is used for detecting the reaction condition, the mixture is cooled to room temperature, a proper amount of ethyl acetate is added for washing, the organic phase is subjected to reduced pressure distillation by a rotary evaporator, silica gel with the size of 100 plus 200 meshes is used for mixing samples, silica gel with the size of 200 plus 300 meshes or 300 plus 400 meshes is used for column chromatography, and the sample is loaded by a dry method, wherein the ethyl acetate: petroleum ether is 1: 30 leaching and concentrating to obtain the target product 3 a.
[ Ru ] catalyzing the operation steps of synthesizing isocoumarin by sulfoylide cross cyclization:
the general operation steps are as follows: to a dry Schlenk tube were added aromatic thioylide 1a (0.2mmol), [ Ru (p-cymene) Cl2]2(5mol％)，PivOH(0.2eq)，Zn(OTf)2(0.2eq), DCE (0.6 mL). Then, the reaction mixture is put into an oil bath kettle at 120 ℃ for stirring, then, the fatty sulfur ylide 2a (0.2mmol) is taken and dissolved in 0.4mL of DCE, the mixture is transferred into a 1mL injector after being fully dissolved, the mixture is slowly dripped into the previous reaction tube, the addition is completed within 5 minutes, the reaction is continued to 24 hours, after the reaction is completed, TLC or GC-MS is used for detecting the reaction condition, the mixture is cooled to room temperature, a proper amount of ethyl acetate is added for washing, the organic phase is subjected to reduced pressure distillation by a rotary evaporator, silica gel with 200 meshes is used for mixing samples, silica gel with 300 meshes or 300 meshes is used for column chromatography, dry sampling is carried out, and ethyl acetate: petroleum ether is 1: and (50) leaching and concentrating to obtain the target product 3 a.
The following examples and comparative examples were investigated for the conditions of the catalyst using compound 1a as a substrate.
Figure BDA0003397505930000091
The reaction conditions were as follows: 0.2mml of thioylide 1a is used as an initial substrate of the reaction, 5mol percent of catalyst, 1.0eq of pivalic acid is used as a second additive and 0.1eq of silver hexafluoroantimonate is used as a first additive, and the reaction is carried out in 1mL of 1, 2-dichloroethane solvent at 120 ℃ for 24 hours under the nitrogen atmosphere. The yields in the table were obtained by detecting the product concentration by GC-MS and then calculating based on the compound 1 a.
Figure BDA0003397505930000092
The following examples and comparative examples were investigated for the conditions of the second additive using compound 1a as a substrate.
Figure BDA0003397505930000093
The reaction conditions were as follows: 0.2mml of sulphur ylide 1a is used as initial substrate for the reaction, 5 mol% of catalyst C20H28Cl4Ru21.0eq of the second additive and 0.1eq of silver hexafluoroantimonate as the first additive were reacted in 1mL of 1, 2-dichloroethane solvent at 120 ℃ under a nitrogen atmosphere for 24 hours. The yields in the table were obtained by detecting the product concentration by GC-MS and then calculating based on the compound 1 a.
Figure BDA0003397505930000101
The following examples and comparative examples were investigated for the amount of PivOH added using Compound 1a as a substrate.
Figure BDA0003397505930000102
The reaction conditions were as follows: 0.2mml of sulphur ylide 1a is used as initial substrate for the reaction, 5 mol% of catalyst C20H28Cl4Ru2PivOH (X eq, X ═ 1.0, 0.6, 0.2, 0.1, 0) as the second additive and 0.1eq of silver hexafluoroantimonate as the first additiveThe additive was reacted in 1mL of 1, 2-dichloroethane solvent at 120 ℃ under a nitrogen atmosphere for 24 hours. The yields in the table were obtained by detecting the product concentration by GC-MS and then calculating based on the compound 1 a.
Figure BDA0003397505930000103
Figure BDA0003397505930000111
The following examples and comparative examples were investigated for the conditions of the first additive using compound 1a as a substrate.
Figure BDA0003397505930000112
The reaction conditions were as follows: 0.2mml of sulphur ylide 1a is used as initial substrate for the reaction, 5 mol% of catalyst C20H28Cl4Ru20.2eq of PivOH as the second additive and 0.1eq of the first additive were reacted in 1mL of 1, 2-dichloroethane solvent at 120 ℃ under a nitrogen atmosphere for 24 hours. The yields in the table were obtained by detecting the product concentration by GC-MS and then calculating based on the compound 1 a.
Figure BDA0003397505930000113
The following examples and comparative examples are given with Compound 1a as substrate pair Zn (OTf)2The amount of (A) is determined.
Figure BDA0003397505930000114
The reaction conditions were as follows: 0.2mml of sulphur ylide 1a is used as initial substrate for the reaction, 5 mol% of catalyst C20H28Cl4Ru20.2eq PivOH as second additive and Zn (OTf)2(X eq，X＝0.05、0.10、0.15, 0.20, 0.25, 0.30) as a first additive, in 1mL of 1, 2-dichloroethane solvent at 120 ℃ under a nitrogen atmosphere for 24 hours. The yields in the table were obtained by detecting the product concentration by GC-MS and then calculating based on the compound 1 a.
Figure BDA0003397505930000121
The following examples and comparative examples are the pair C with Compound 1a as the substrate20H28Cl4Ru2The amount of (A) is determined.
Figure BDA0003397505930000122
The reaction conditions were as follows: 0.2mml of sulphur ylide 1a is used as initial substrate of the reaction, Xmol% of catalyst C20H28Cl4Ru20.2eq PivOH as second additive and 0.2eq Zn (OTf)2As a first additive, the reaction was carried out in 1mL of 1, 2-dichloroethane solvent at 120 ℃ under a nitrogen atmosphere for 24 hours. The yields in the table were obtained by detecting the product concentration by GC-MS and then calculating based on the compound 1 a.
Figure BDA0003397505930000123
Figure BDA0003397505930000131
The following examples and comparative examples were obtained by searching for reaction temperature and time using compound 1a as a substrate.
Figure BDA0003397505930000132
The reaction conditions were as follows: 0.2mml of sulphur ylide 1a is used as initial substrate for the reaction, 5 mol% of catalyst C20H28Cl4Ru20.2eq PivOH as second additive and 0.2eq Zn (OTf)2As a first additive, the reaction was carried out in 1mL of 1, 2-dichloroethane solvent. The yields in the table were obtained by detecting the product concentration by GC-MS and then calculating based on the compound 1 a.
Figure BDA0003397505930000133
The following examples and comparative examples were prepared by probing a solvent with compound 1a as a substrate.
Figure BDA0003397505930000141
The reaction conditions were as follows: 0.2mml of sulphur ylide 1a is used as initial substrate for the reaction, 5 mol% of catalyst C20H28Cl4Ru20.2eq PivOH as second additive and 0.2eq Zn (OTf)2As a first additive, the reaction was carried out in 1mL of a solvent at 120 ℃ under a nitrogen atmosphere for 24 hours. The yields in the table were obtained by detecting the product concentration by GC-MS and then calculating based on the compound 1 a.
Figure BDA0003397505930000142
The following examples and comparative examples were investigated for gas atmosphere using compound 1a as a substrate.
Figure BDA0003397505930000143
The reaction conditions were as follows: 0.2mml of sulphur ylide 1a is used as initial substrate for the reaction, 5 mol% of catalyst C20H28Cl4Ru20.2eq PivOH as second additive and 0.2eq Zn (OTf)2As a first additive, the reaction was carried out in 1mL of 1, 2-dichloroethane solvent at 120 ℃ for 24 hours. The yields in the table were obtained by detecting the product concentration by GC-MS and then calculating based on the compound 1 a.
Figure BDA0003397505930000144
Figure BDA0003397505930000151
The following examples show that different substrates can be used for reaction to obtain different substituted products, whether the products are self-cyclization of sulfur ylides under the catalysis of dichlorobis (4-methylisopropyl) ruthenium (II) or cross-cyclization between two different substituted sulfur ylides, the substrate universality is wide, and the products can be compatible with sulfur ylides with different functional groups. We found that the yield of the target product of the sulfur ylide self-cyclization reaction is high, the sulfur ylide is compatible with functional groups (3aa-3ai) such as methyl, methoxy, halogen, trifluoromethyl and the like, the steric hindrance effect has little influence on the reaction system, and the yield of the corresponding product of the sulfur ylide with ortho-substitution such as methoxy, fluorine and chlorine is high (3ac, 3ae, 3ag and 3 ai). The electronic effect has larger influence on a reaction system, and sulfur ylides containing strong electron-withdrawing substituent groups such as cyano-group and ester group and nitro group do not detect corresponding target products in the reaction system. Subsequently, for the cross-cyclization between two differently substituted sulfur ylides, the corresponding desired product was obtained in moderately higher yields, with excellent substrate compatibility (3aj-3 an).
Figure BDA0003397505930000152
The reaction conditions were as follows: 0.2mml of each of the sulfur ylides with different substituents is used as the starting substrate for the reaction, 5 mol% of catalyst C20H28Cl4Ru20.2eq PivOH as second additive and 0.2eq Zn (OTf)2As a first additive, the reaction was carried out in 1mL of 1, 2-dichloroethane solvent at 120 ℃ for 24 hours. The yields in the table were obtained by detecting the product concentration by GC-MS and then calculating based on the compound 1 a.
Figure BDA0003397505930000153
Figure BDA0003397505930000161
According to the invention, a series of transition metal catalysts are screened, so that dichlorobis (4-methyl isopropylphenyl) ruthenium (II) has a good effect on the C-H activated cyclization at the ortho position of the sulfur ylide, and then systematic screening is carried out according to the amount of the catalyst, the amount of an auxiliary agent and an adjuvant, the reaction temperature, the solvent, the reaction time and the gas atmosphere in the system, so that the reaction conditions are finally obtained, and then the application range of the substrate is widened under the optimal reaction conditions. Therefore, a simple and effective method is developed to construct lactone compounds, and the specific method is to take 1.0eq of sulfoylide with different substituents as a reaction substrate, 5 mol% of dichlorobis (4-methylisoprophenyl) ruthenium (II) as a catalyst, 0.2eq of pivalic acid and zinc trifluoromethanesulfonate as additives, and 1, 2-dichloroethane as a solvent, react for 24 hours at 120 ℃, so that the self-cyclization and cross-cyclization of the sulfoylide can be realized at the same time. In order to reduce the cost of the reaction and improve the industrial applicability of the reaction, we will continue to explore a more safe, green, and efficient method for synthesizing isocoumarins by using a cheap and practical catalyst for the reaction.
The following is a data characterisation of the product prepared in the above example:
Figure BDA0003397505930000171
Compound 3aa 3-phenyl-1H-isochromen-1-one.White solid.1H NMR(500MHz,CDCl3):δ8.30(d,J＝8.0Hz,1H),7.87(d,J＝7.0Hz,2H),7.70(t,J＝8.0Hz,1H),7.49-7.40(m,5H),6.94(s,1H).13C NMR(125MHz,CDCl3):δ162.4,153.8,137.6,135.0,132.1,130.1,129.8,128.9,128.3,126.1,125.4,120.7,101.9.This compound is known:Xu,Y.W.；Zheng,G.F.；Yang,X.F.；Li,X.W.Chem.Commun.,2018,54,670—673.
Figure BDA0003397505930000172
Compound 3ab 6-methyl-3-(p-tolyl)-1H-isochromen-1-one.White solid.1H NMR(500MHz,CDCl3):δ8.16(d,J＝8.0Hz,1H),7.76(d,J＝8.2Hz,2H),7.31-7.25(m,4H),6.84(s,1H),2.47(s,3H),2.40(s,3H).13C NMR(125MHz,CDCl3):δ162.5,153.8,145.9,140.1,137.8,129.5,129.5,129.3,129.2,125.8,125.1,118.0,101.0,22.0,21.4.This compound is known:Wen,S.；Chen,Y.H.；Zhao,Z.M.；Ba,D.；Lv,W.W.；Cheng,G.L.J.Org.Chem.2020,85,1216-1223.
Figure BDA0003397505930000173
Compound 3ac 8-methoxy-3-(2-methoxyphenyl)-1H-isochromen-1-one.Brown solid.1H NMR(500MHz,CDCl3):δ7.98(dd,J＝7.5,3.5Hz,1H),7.60(t,J＝8.0,1H),7.36(td,J＝8.5,1.5Hz,1H),7.29(s,1H),4.01(s,3H),3.95(s,3H).13C NMR(125 MHz,CDCl3):δ161.7,159.4,157.4,150.9,141.2,135.6,130.9,129.1,121.0,120.8,118.6,111.5,109.8,109.6,107.1,56.4,55.8.This compound is known:Wen,S.；Chen,Y.H.；Zhao,Z.M.；Ba,D.；Lv,W.W.；Cheng,G.L.J.Org.Chem.2020,85,1216-1223.
Figure BDA0003397505930000181
Compound 3ad 6-methoxy-3-(4-methoxyphenyl)-1H-isochromen-1-one.Yellow soild.1H NMR(500MHz,CDCl3):δ8.20(d,J＝8.8Hz,1H),7.85-7.78(m,2H),7.02-6.97(m,1H),6.97-6.95(m,2H),6.84(d,J＝2.4Hz,1H),6.76(s,1H),3.92(s,3H),3.88(s,3H).13CNMR(125MHz,CDCl3):δ164.7,162.3,161.0,154.2,140.2,131.8,126.8,124.5,116.1,114.2,113.3,107.6,100.3,55.6,55.4.Thiscompound is known:Wen,S.；Chen,Y.H.；Zhao,Z.M.；Ba,D.；Lv,W.W.；Cheng,G.L.J.Org.Chem.2020,85,1216-1223.
Figure BDA0003397505930000182
Compound 3ae 8-fluoro-3-(2-fluorophenyl)-1H-isochromen-1-one.White solid.1H NMR(500MHz,CDCl3):δ8.03-7.98(m,1H),7.71-7.68(m,1H),7.44-7.38(m,1H),7.33-7.26(m,2H),7.22-7.16(m,3H).13C NMR(125MHz,CDCl3):δ162.8(d,J＝266.8Hz),160.1(d,J＝253.3Hz),157.5(d,J＝5.4Hz),149.0(d,J＝5.2Hz),139.9,136.2(d,J＝10.2Hz),131.5(d,J＝9.0Hz),128.5(d,J＝1.7Hz),124.6(d,J＝3.6Hz),122.3(d,J＝4.4Hz),119.6(d,J＝9.8Hz),116.4(d,J＝22.8Hz),115.6(d,J＝21.3Hz),109.5(d,J＝7.2Hz),106.50(dd,J＝16.0,3.0Hz).This compound is known:Wen,S.；Chen,Y.H.；Zhao,Z.M.；Ba,D.；Lv,W.W.；Cheng,G.L.J.Org.Chem.2020,85,1216-1223.
Figure BDA0003397505930000191
Compound 3af 6-fluoro-3-(4-fluorophenyl)-1H-isochromen-1-one.White solid.1H NMR(400MHz,CDCl3):δ8.31(dd,J＝8.8,5.6Hz,1H),7.91–7.85(m,2H),7.21–7.13(m,4H),6.85(s,1H).13C NMR(100MHz,CDCl3):δ166.8(d,J＝255.2Hz),164.0(d,J＝250.1Hz),161.2,154.0,140.1(d,J＝10.8Hz),133.1(d,J＝10.4Hz),127.8(d,J＝3.3Hz),127.5(d,J＝8.6Hz),116.8(d,J＝2.2Hz),116.5(d,J＝23.1Hz),116.1(d,J＝21.9Hz),111.5(d,J＝22.4Hz),101.0(dd,J＝2.7,1.7Hz).This compound is known:Zhou,M.D.；Peng,Z.；Wang,H.；Wang,Z.H.；Hao,D.J.；Li,L.Adv.Synth.Catal.2019,361,5191–5197.
Figure BDA0003397505930000192
Compound 3ag 8-chloro-3-(2-chlorophenyl)-1H-isochromen-1-one.Canary yellow.1H NMR(500 MHz,CDCl3):δ7.74-7.71(m,1H),7.61(t,J＝7.7 Hz,1H),7.59-7.56(m,1H),7.52-7.47(m,1H),7.41-7.36(m,3H),6.97(s,1H).13C NMR(125 MHz,CDCl3):δ158.8,152.0,140.0,137.2,134.6,132.3,131.4,131.0,130.9,130.7,130.6,127.1,125.2,117.7,107.4.This compound is known:Wen,S.；Chen,Y.H.；Zhao,Z.M.；Ba,D.；Lv,W.W.；Cheng,G.L.J.Org.Chem.2020,85,1216-1223.
Figure BDA0003397505930000193
Compound 3ah 6-chloro-3-(4-chlorophenyl)-1H-isochromen-1-one.White solid.1H NMR(500MHz,CDCl3):δ8.22(d,J＝8.4Hz,1H),7.82(d,J＝8.4Hz,2H),7.48–7.45(m,4H),6.86(s,1H).13C NMR(100MHz,CDCl3):δ161.3,153.9,141.7,138.7,136.5,131.4,130.0,129.2,128.9,126.7,125.5,118.8,101.1.This compound is known:Zhou,M.D.；Peng,Z.；Wang,H.；Wang,Z.H.；Hao,D.J.；Li,L.Adv.Synth.Catal.2019,361,5191–5197.
Figure BDA0003397505930000201
Compound 3ai 6-(trifluoromethyl)-3-(4-(trifluoromethyl)phenyl)-1H-isochrom-en-1-one.White solid.1H NMR(500MHz,CDCl3):δ8.45(d,J＝8.2Hz,1H),8.01(d,J＝8.2Hz,2H),7.83(s,1H),7.76(t,J＝7.7Hz,3H),7.11(s,1H).13C NMR(125MHz,CDCl3):δ160.6,153.3,137.3,136.7(q,J＝33.0Hz),134.6,132.2(q,J＝32.9Hz),130.8,126.7(q,J＝68.0Hz),126.1(q,J＝3.8Hz),125.7,125.0(q,J＝3.5Hz),123.7(q,J＝272.4Hz),123.4(q,J＝4.0Hz),123.2(q,J＝273.4Hz),102.6.This compound is known:Wen,S.；Chen,Y.H.；Zhao,Z.M.；Ba,D.；Lv,W.W.；Cheng,G.L.J.Org.Chem.2020,85,1216-1223.
Figure BDA0003397505930000202
Compound 3aj 3-isopropyl-8-methoxy-1H-isochromen-1-one.White solid.1H NMR(500MHz,CDCl3):δ7.56-7.53(m,1H),6.91-6.86(m,1H),6.13(d,J＝5.5Hz,1H),3.97(d,J＝5.5Hz,3H),1.25(t,J＝6.5Hz,6H).13C NMR(125MHz,CDCl3):δ163.6,161.7,159.9,140.8,135.7,117.4,109.4,109.2,100.6,56.3,32.1,20.2.This compound is known:Xu,Y.W.；Zheng,G.F.；Yang,X.F.；Li,X.W.Chem.Commun.2018,54,670—673.
Figure BDA0003397505930000203
Compound 3ak 8-chloro-3-isopropyl-1H-isochromen-1-one.White solid.1H NMR(500MHz,CDCl3):δ7.50(t,J＝7.5Hz,1H),7.43(d,J＝7.5Hz,1H),7.23(d,J＝7.5Hz,1H),6.19(s,1H),2.76-2.72(m,1H),1.26(d,J＝7.0Hz,6H).13C NMR(125MHz,CDCl3):δ163.9,159.6,140.8,137.0,134.5,130.5,124.4,117.4,100.6,32.24,20.16.This compound is known:Wen,S.；Chen,Y.H.；Zhao,Z.M.；Ba,D.；Lv,W.W.；Cheng,G.L.J.Org.Chem.2020,85,1216-1223.
Figure BDA0003397505930000211
Compound 3al 3-isopropyl-6-(trifluoromethyl)-1H-isochromen-1-one.White solid.1H NMR(500MHz,CDCl3):δ8.35(d,J＝8.0Hz,1H),7.65(d,J＝8.0Hz,2H),6.32(s,1H),2.82-2.78(m,1H),1.30(d,J＝7.0Hz,6H).13C NMR(125MHz,CDCl3):δ164.87,161.9,138.1,130.6,123.9,123.9,122.8,122.6,122.6,100.3,32.6,20.7.This compound is known:Xu,Y.W.；Zheng,G.F.；Yang,X.F.；Li,X.W.Chem.Commun.2018,54,670—673.
Figure BDA0003397505930000212
Compound 3am 3-((3r,5r,7r)-adamantan-1-yl)-1H-isochromen-1-one.White solid.1H NMR(400MHz,CDCl3):δ8.22(d,J＝7.9Hz,1H),7.63(t,J＝7.6Hz,1H),7.42(t,J＝7.6Hz,1H),7.35(d,J＝7.9Hz,1H),6.20(s,1H),2.08(s,3H),1.93-1.95(m,6H),1.78-1.71(m,6H).13C NMR(100MHz,CDCl3):δ165.1,163.1,137.8,134.5,129.3,127.4,125.4,120.2,99.6,39.6,37.2,36.5,28.0.This compound is known:Xu,Y.W.；Zheng,G.F.；Yang,X.F.；Li,X.W.Chem.Commun.2018,54,670—673.
Figure BDA0003397505930000213
Compound 3an 3-cyclohexyl-1H-isochromen-1-one.White solid.1H NMR(400MHz,CDCl3):δ8.21(d,J＝7.9Hz,1H),7.63(t,J＝7.6Hz,1H),7.42(t,J＝7.6Hz,1H),7.35(d,J＝7.8Hz,1H),6.21(s,1H),2.41(t,J＝11.4Hz,1H),2.02-1.99(m,2H),1.86-1.81(m,2H),1.47-1.22(m,6H).13C NMR(100MHz,CDCl3):δ163.1,162.3,137.7,134.6,129.3,127.4,125.2,120.2,100.8,41.8,30.5,25.9,25.8.This compound is known:Fei,X.D.；Ge,Z.Y.；Tang,T.；Zhu,Y.M.；Ji,S.J.J.Org.Chem.2012,77,10321-10328.

Claims (9)

1. a synthetic method of isocoumarin compounds is characterized in that: the chemical reaction formula is as follows:
Figure FDA0003397505920000011
in the chemical reaction formula, the compound shown in (A) and the compound shown in (B) react in a solvent under the action of a noble metal catalyst and a first additive to obtain a compound shown in (C);
the noble metal catalyst is one or more of dodecacarbonyltriruthenium, dichlorophenyl ruthenium (II) dimer and dichlorobis (4-methyl isopropylphenyl) ruthenium (II);
the first additive is one or more of silver tetrafluoroborate, silver hexafluoroantimonate, copper acetate, zinc acetate, silver trifluoromethanesulfonate, copper trifluoromethanesulfonate and zinc trifluoromethanesulfonate.
2. The method for synthesizing isocoumarins compound according to claim 1, wherein: the noble metal catalyst is dichlorobis (4-methyl isopropylphenyl) ruthenium (II).
3. The method for synthesizing isocoumarins compound according to claim 2, wherein: the amount of dichlorobis (4-methylisopropylphenyl) ruthenium (II) added was 5 mol%.
4. The method for synthesizing isocoumarins compound according to claim 1, wherein: the first additive is zinc trifluoromethanesulfonate.
5. The method for synthesizing isocoumarins compound according to claim 1, wherein: and a second additive is also added in the reaction, and the second additive is one or more of benzoic acid, pivalic acid, phenylmethanesulfonic acid, polyphosphoric acid and glacial acetic acid.
6. The method for synthesizing isocoumarin compounds according to claim 5, wherein: the second additive is pivalic acid.
7. The method for synthesizing isocoumarin compounds according to claim 6, wherein: the amount of the compound represented by (A) is 1eq, and the amount of pivalic acid added is 0.1-1 eq.
8. The method for synthesizing isocoumarins compound according to claim 1, wherein: the solvent is one or more of acetonitrile, toluene, styrene and dimethylformamide.
9. The method for synthesizing isocoumarins compound according to claim 8, wherein: the solvent is styrene.
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