阅读说明：本技术 氮杂环卡宾羧酸根双齿配体、双齿钌配合物和制备方法及其催化羧酸-炔烃加成的应用 (N-heterocyclic carbene carboxylate bidentate ligand, bidentate ruthenium complex, preparation methods and application of N-heterocyclic carbene carboxylate bidentate ligand and bidentate ruthenium com) 是由 郭帅 胡艳艳 崔柳 于 2020-07-02 设计创作，主要内容包括：本发明公开氮杂环卡宾羧酸根双齿配体和双齿钌配合物、制备方法及其催化羧酸-炔烃加成的应用,以咪唑及其衍生物和氯乙酸甲酯为原料,合成含咪唑鎓基的双齿配体,氮杂环卡宾螯合配体通过转移金属化,得到氮杂环卡宾羧酸根双齿钌配合物；以氮杂环卡宾羧酸根双齿钌配合物为催化剂,催化分子内或分子间的羧酸-炔烃加成反应。本发明所提供的配合物具有良好的羧酸-炔烃加成反应催化活性,尤其是分子内加成反应,温度更温和,催化产率更高。首次使用介离子型氮杂环卡宾-钌配合物来催化羧酸-炔烃的加成反应。(The invention discloses a nitrogen heterocyclic carbene carboxylate radical bidentate ligand and bidentate ruthenium complex, a preparation method and application thereof in catalyzing carboxylic acid-alkyne addition, wherein imidazole and derivatives thereof and methyl chloroacetate are used as raw materials to synthesize the bidentate ligand containing imidazolium radical, and the nitrogen heterocyclic carbene chelate ligand is subjected to transfer metallization to obtain the nitrogen heterocyclic carbene carboxylate radical bidentate ruthenium complex; the nitrogen heterocyclic carbene carboxylate bidentate ruthenium complex is used as a catalyst to catalyze the intramolecular or intermolecular carboxylic acid-alkyne addition reaction. The complex provided by the invention has good carboxylic acid-alkyne addition reaction catalytic activity, especially intramolecular addition reaction, milder temperature and higher catalytic yield. The first time, the mesoionic azacyclo-carbene-ruthenium complex is used for catalyzing the addition reaction of carboxylic acid-alkyne.)

1. The N-heterocyclic carbene carboxylate bidentate ligand is characterized by being a bidentate ligand containing imidazolium groups, and the structures of the bidentate ligand are shown as L1, L2, L3 and L4:

2. the N-heterocyclic carbene carboxylate bidentate ruthenium complex is characterized in that the structure is shown as Ru-L1, Ru-L2, Ru-L3 and Ru-L4:

3. the preparation method of the nitrogen heterocyclic carbene carboxylate bidentate ruthenium complex is characterized by comprising the following steps:

(1) synthesizing the imidazolium-group-containing bidentate ligand as claimed in claim 1 by using imidazole and derivatives thereof and methyl chloroacetate as raw materials;

(2) the N-heterocyclic carbene chelate ligand is metalated by transfer to obtain the N-heterocyclic carbene carboxylate bidentate ruthenium complex as claimed in claim 2.

4. The method for preparing the N-heterocyclic carbene carboxylate bidentate ruthenium complex according to claim 3, characterized in that, in the step (1),

the preparation method of the N-heterocyclic carbene carboxylate bidentate ligand L1 comprises the following steps: reacting 5mmol of 1-methylimidazole with 5.5mmol of methyl chloroacetate in 7mL of acetonitrile at 90 ℃ for 24 hours, draining the solvent, and washing with diethyl ether to obtain the compound;

the preparation method of the N-heterocyclic carbene carboxylate bidentate ligand L2 comprises the following steps: reacting 5mmol of 1-phenylimidazole and 5.5mmol of methyl chloroacetate in 7mL of acetonitrile at 90 ℃ for 24 hours, draining the solvent, and washing with diethyl ether to obtain the compound;

the preparation method of the N-heterocyclic carbene carboxylate bidentate ligand L3 comprises the following steps: the compound is prepared by reacting 5mmol of 1-methyl-2-phenylimidazole with 5.5mmol of methyl chloroacetate in 10mL of acetonitrile at 90 ℃ for 24 hours, draining the solvent, and washing with diethyl ether;

the preparation method of the N-heterocyclic carbene carboxylate bidentate ligand L4 comprises the following steps: obtained by reacting 5mmol of 1, 2-diphenylimidazole with 5.5mmol of methyl chloroacetate in 10mL of acetonitrile at 90 ℃ for 24 hours, draining the solvent and washing with diethyl ether.

5. The method of claim 3, wherein in step (2), the N-heterocyclic carbene carboxylate bidentate ligand and Ag are present₂Reacting O in dichloromethane at room temperature in the dark to obtain silver carbene, and adding [ RuCl₂(cym)]₂The dichloromethane solution is subjected to transfer metallization reaction at room temperature to obtain the N-heterocyclic carbene carboxylate bidentate ruthenium complex.

6. The preparation method of the N-heterocyclic carbene carboxylate bidentate ruthenium complex according to claim 4, characterized in that 0.5mmol of N-heterocyclic carbene carboxylate bidentate ligand and 0.66mmol of silver oxide are mixed in 10mL of dichloromethane, and reacted at room temperature in the dark for 24 hours, and the filtered silver carbene intermediate solution is dropwise added to the solution containing 0.25mmol of [ RuCl ]₂(cym)]₂And the mixture is subjected to a dark reaction for 24 hours in 5mL of dichloromethane solution, the filtrate is obtained by centrifugation, and is dried by pumping to obtain an orange red crude product, the mixture is purified by column chromatography to obtain the azacyclo-carbene carboxylate radical bidentate ruthenium complex, the filler of the chromatographic column is silica gel, the eluent is a mixed solution of dichloromethane and methanol, and the volume ratio is 10: 1.

7. the application of the nitrogen heterocyclic carbene carboxylate bidentate ruthenium complex in catalyzing addition of carboxylic acid and alkyne is characterized in that the nitrogen heterocyclic carbene carboxylate bidentate ruthenium complex is used as a catalyst to catalyze intramolecular or intermolecular addition reaction of carboxylic acid and alkyne, and the catalytic reaction temperature is less than 100 ℃.

8. The application of the azacyclo-carbene carboxylate bidentate ruthenium complex to catalysis of carboxylic acid-alkyne addition according to claim 7, wherein in the catalysis of intramolecular addition reaction, acetylenic acid is used as a reaction substrate, in deuterated chloroform, the loading amount of the catalyst is 1-2% of the amount of acetylenic acid substances, the reaction time is 2/3-24h, and the reaction temperature is 60 ℃.

9. The application of the N-heterocyclic carbene carboxylate bidentate ruthenium complex in catalyzing addition of carboxylic acid and alkyne in claim 7 is characterized in that in the catalysis of intermolecular carboxylic acid-alkyne addition reaction, terminal alkyne and benzoic acid derivative are used as reaction substrates, a catalyst and silver trifluoromethanesulfonate AgOTf are added, the loading amount of the catalyst is 1% of the amount of benzoic acid derivative substances, the adding amount of AgOTf is 1% of the amount of benzoic acid derivative substances, and the reaction is carried out for 16h in toluene at the reaction temperature of 70 ℃.

Technical Field

The invention relates to the technical field of synthesis of carbene ruthenium complexes. In particular to a nitrogen heterocyclic carbene carboxylate bidentate ligand and bidentate ruthenium complex, a preparation method and application thereof in catalyzing carboxylic acid-alkyne addition.

Background

Catalytic intramolecular and intermolecular carboxylic acid-alkyne addition is a method of building alkenoic acid esters (Hintermann, L., Top. Organomet. chem.,2010,31, 123. chem., Bruneau, C., Top. Organomet. chem.,2013,43, 203. cozone 230; Abbati, G.; Beccalli, E.M., Rossi, E.E., Top. Organomet. chem.,2013,43, 231. cozone 290; Javier F., Victorio C., Catalyss, 2017, 328.). Catalyzing intramolecular and intermolecular additions, unsaturated (endo) ester products are obtained, which are common building blocks in Natural and biologically active molecules, and are also valuable synthetic intermediates (Rao, Y.S., chem.Rev.,1976,76, 625-694; Laduwahetty, T., Contemp.Org.Synth.,1995,2, 133-149; Libiszewska, K., Biotechnol.food Sci.,2011,75, 45-53; Janecki, T. (Ed.) Natural Lactors and Lactams: Synthesis, Occurence and Iologic Activity; Wiley-VCH: Weinheim, Germany, 2013; ISBN 97528334148;N.,Lionel L.,Lionel D.,Albert D.,Aust.J.Chem.,2009,62,227-231；JanineJ.,Christian G.,Heinrich L.,J.Org.Chem.,2016,81,476-484；Bathoju C.C.,SunggakK.,J.Org.Chem.,2010,75,7928-7931.)。

the most common metals used to catalyze the above reaction include Pd, Au, Rh, and the like. Among these, Pd (N.Nebra, J.Monot, R.Shaw, B.Martin-Vaca, and D.Bourissouu, ACS Cat.2013, 3,2930; C.Lambert, K.Utimoto, H.Nozaki, Tetrahedron Lett.,1984,25, 5323; L.B.Wolf, K.C.M.F.Tjen, H.T.ten Brink, R.H.Blauw, H.Hihimema, H.E.Schoemaker, F.P.J.T.Rutjes, Adv.Synth.Cat.2002, 344, 70; F.Neatu, L.Protesescou, M.rea, V.I.Parvuleseses, C.M.Teorecuu, N.P.Apo.P.P.P.P.P.J.Tje.P.J.Tje.P.J.P.J.J.Chevel, C.C.C.C.Synth.C.C.C.C.C.C.C.C.C.C.C.D.C.C.C.C.E.C.C.C.C.C.C.C.C.C.C.E.C.C.C.E.C.C.C.C.E.C.E.C.C.C..

There are few reports on coordination systems of metallic Ru that catalyze such reactions, especially intramolecular carboxylic acid-alkyne addition reactions (t.opsal, f.verpoort, Tetrahedron lett.,2002,43, 9259; t.opsal, f.verpoort, Synlett,2003,3, 314; k.melis, f.verpoort, Journal of molecular catalysis a: Chemical, 2003, 194, 39-47; t.a.mitsudo, y.hori, y.yamakawa, y.watanabe, j.org.chem.1987,52,2230; e.musengimanana 1, c.fatakanwa1, j.iran.chem.soc.2016,13,253.). In addition, the reaction of the only metal ruthenium system for catalyzing the intramolecular carboxylic acid-alkyne addition reaction is mostly carried out at a higher temperature (>100 ℃), the reaction conditions are harsh, the operation is not facilitated, and the prepared metal ruthenium catalyst is poor in stability and short in service life.

Disclosure of Invention

Therefore, the technical problem to be solved by the invention is to provide the N-heterocyclic carbene carboxylate bidentate ligand and bidentate ruthenium complex, the preparation method and the application thereof in catalyzing carboxylic acid-alkyne addition reaction, wherein the N-heterocyclic carbene ruthenium complex catalyzes intramolecular and intermolecular carboxylic acid-alkyne addition reaction at a milder temperature and in a higher yield.

In order to solve the technical problems, the invention provides the following technical scheme:

the N-heterocyclic carbene carboxylate bidentate ligand is a bidentate ligand containing imidazolium groups, and the structures of the ligand are shown as L1, L2, L3 and L4:

the nitrogen heterocyclic carbene carboxylate bidentate ruthenium complex has the structure shown as Ru-L1, Ru-L2, Ru-L3 and Ru-L4:

the preparation method of the N-heterocyclic carbene carboxylate bidentate ruthenium complex comprises the following steps:

(1) synthesizing the imidazolium-group-containing bidentate ligand as claimed in claim 1 by using imidazole and derivatives thereof and methyl chloroacetate as raw materials;

(2) the N-heterocyclic carbene chelate ligand is metalated by transfer to obtain the N-heterocyclic carbene carboxylate bidentate ruthenium complex as claimed in claim 2.

In the preparation method of the nitrogen heterocyclic carbene carboxylate bidentate ruthenium complex, in the step (1),

the preparation method of the N-heterocyclic carbene carboxylate bidentate ligand L1 comprises the following steps: reacting 5mmol of 1-methylimidazole with 5.5mmol of methyl chloroacetate in 7mL of acetonitrile at 90 ℃ for 24 hours, draining the solvent, and washing with diethyl ether to obtain the compound;

the preparation method of the N-heterocyclic carbene carboxylate bidentate ligand L2 comprises the following steps: reacting 5mmol of 1-phenylimidazole and 5.5mmol of methyl chloroacetate in 7mL of acetonitrile at 90 ℃ for 24 hours, draining the solvent, and washing with diethyl ether to obtain the compound;

the preparation method of the N-heterocyclic carbene carboxylate bidentate ligand L3 comprises the following steps: the compound is prepared by reacting 5mmol of 1-methyl-2-phenylimidazole with 5.5mmol of methyl chloroacetate in 10mL of acetonitrile at 90 ℃ for 24 hours, draining the solvent, and washing with diethyl ether;

the preparation method of the N-heterocyclic carbene carboxylate bidentate ligand L4 comprises the following steps: obtained by reacting 5mmol of 1, 2-diphenylimidazole with 5.5mmol of methyl chloroacetate in 10mL of acetonitrile at 90 ℃ for 24 hours, draining the solvent and washing with diethyl ether.

In the preparation method of the N-heterocyclic carbene carboxylate radical bidentate ruthenium complex, in the step (2), the N-heterocyclic carbene carboxylate radical bidentate ligand and Ag₂Reacting O in dichloromethane at room temperature in the dark to obtain silver carbene, and adding [ RuCl₂(cym)]₂The dichloromethane solution is subjected to transfer metallization reaction at room temperature to obtain the N-heterocyclic carbene carboxylate bidentate ruthenium complex.

The preparation method of the N-heterocyclic carbene carboxylate radical bidentate ruthenium complex comprises the steps of mixing 0.5mmol of N-heterocyclic carbene carboxylate radical bidentate ligand and 0.66mmol of silver oxide in 10mL of dichloromethane, reacting for 24 hours in a dark place at room temperature, and dropwise adding the filtered silver carbene intermediate solution into 0.25mmol of [ RuCl ]₂(cym)]₂Reacting in dichloromethane solution 5mL for 24 hr in dark place, centrifuging to obtain filtrate, draining to obtain orange red crude product, and performing column chromatographySeparating and purifying to obtain the N-heterocyclic carbene carboxylate radical bidentate ruthenium complex, wherein the chromatographic column filler is silica gel, the eluent is mixed solution of dichloromethane and methanol, and the volume ratio is 10: 1.

the application of the nitrogen heterocyclic carbene carboxylate bidentate ruthenium complex in catalyzing the addition of carboxylic acid-alkyne is to use the nitrogen heterocyclic carbene carboxylate bidentate ruthenium complex as a catalyst to catalyze the intramolecular or intermolecular addition reaction of carboxylic acid-alkyne, and the catalytic reaction temperature is less than 100 ℃.

The application of the N-heterocyclic carbene carboxylate bidentate ruthenium complex in catalyzing carboxylic acid-alkyne addition reaction is characterized in that in catalytic intramolecular addition reaction, alkynoic acid is used as a reaction substrate, in deuterated chloroform, the loading amount of a catalyst is 1-2% of the amount of an alkynoic acid substance, the reaction time is 2/3-24h, and the reaction temperature is 60 ℃.

In the application of the nitrogen heterocyclic carbene carboxylate bidentate ruthenium complex in catalyzing carboxylic acid-alkyne addition reaction, terminal alkyne and benzoic acid derivative are used as reaction substrates, a catalyst and silver trifluoromethanesulfonate AgOTf are added, the loading amount of the catalyst is 1% of the amount of the benzoic acid derivative, the addition amount of the AgOTf is 1% of the amount of the benzoic acid derivative, the reaction is carried out in toluene for 16h, and the reaction temperature is 70 ℃.

The technical scheme of the invention achieves the following beneficial technical effects:

1. the divalent ruthenium complex catalyst is simple and efficient to synthesize, and does not need the strict conditions of water removal and oxygen removal.

2. The divalent ruthenium complex has high stability and is storage-resistant, the divalent ruthenium complex is stored for one month at room temperature, and nuclear magnetism shows no decomposition sign.

3. The mesoionic N-heterocyclic carbene-ruthenium complex is used for catalyzing the addition reaction of carboxylic acid-alkyne for the first time, and compared with other known catalytic systems, the catalytic system has good catalytic activity of the addition reaction of carboxylic acid-alkyne, catalyzes the addition reaction of carboxylic acid-alkyne in molecules and between molecules, particularly the addition reaction in molecules, and has the advantages of milder temperature (60-70 ℃) and higher catalytic yield.

Drawings

FIG. 1 is a scheme for the synthesis of N-heterocyclic carbene carboxylate bidentate ruthenium complexes L1, L2, L3 and L4;

FIG. 2 is a schematic diagram of a scheme for catalyzing intramolecular carboxylic acid-alkyne addition reaction with an azacyclo-carbene carboxylate bidentate ruthenium complex;

FIG. 3 is a schematic diagram of a scheme of a nitrogen heterocyclic carbene carboxylate bidentate ruthenium complex catalyzing an intermolecular carboxylic acid-alkyne addition reaction.

Detailed Description