CN111704558A - Method for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis - Google Patents
Method for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis Download PDFInfo
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- CN111704558A CN111704558A CN202010571136.3A CN202010571136A CN111704558A CN 111704558 A CN111704558 A CN 111704558A CN 202010571136 A CN202010571136 A CN 202010571136A CN 111704558 A CN111704558 A CN 111704558A
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Abstract
The invention discloses a palladium-catalyzed preparation of phenyl-2- (2' -cyanophenyl) acetylene compounds shown in formula (IV)The preparation method of the compound comprises the following steps: the benzonitrile compound shown in the formula (I), the acetylene shown in the formula (II) and the iodobenzene compound shown in the formula (III) react fully under oxygen by taking palladium chloride as a catalyst, sodium carbonate as alkali and dimethyl sulfoxide as a solvent, and the reaction product is subjected to post-treatment to prepare the phenyl-2- (2' -cyanophenyl) acetylene compound. The method has high efficiency and meets the requirement of environmental protection; the catalytic system has wide adaptability and is suitable for the production of large-scale pharmaceutical and chemical intermediates.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical and chemical intermediate preparation, and particularly relates to a method for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis.
Background
Phenyl-2- (2' -cyanophenyl) acetylene compounds are a very important chemical raw material and synthetic intermediate, and are widely used for manufacturing medicines, synthetic fibers and plastics. Meanwhile, phenyl-2- (2' -cyanophenyl) acetylene compounds are commonly used in electroplating and mining industries (extraction of gold, silver, etc.), production of various resins and synthesis of nitrile compounds. Sometimes also used for fumigation of rats in warehouses and cabins. The most important property of the phenyl-2- (2' -cyanophenyl) acetylene compound is that it is stable in a weakly alkaline medium. Therefore, the product of soap, detergent, etc. can replace aldehydes to increase the stability of essence. The reported preparation method of the phenyl-2- (2' -cyanophenyl) acetylene compounds is mainly obtained by metal catalysis and multi-step-CN group substitution, and has the defects of more reaction steps, low reaction efficiency, easy generation of virulent hydrocyanic acid in the reaction process and the like. According to the method, palladium chloride with high catalytic efficiency is used as a catalyst, and the green preparation of the phenyl-2- (2' -cyanophenyl) acetylene compounds is realized by a multi-component one-pot method. Has the advantages of low cost, simple operation, safety, reliability, excellent yield and the like. Has important application prospect in the industrial field of the synthesis of the drug intermediate related to the phenyl-2- (2' -cyanophenyl) acetylene compounds.
Disclosure of Invention
In view of the problems in the prior art, the invention aims to provide a method for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis.
The invention is realized by the following technical scheme:
the method for preparing the phenyl-2- (2' -cyanophenyl) acetylene compounds shown in the formula (IV) by palladium catalysis is characterized by comprising the following steps: the method comprises the following steps of (1) sufficiently reacting a benzonitrile compound shown in a formula (I), acetylene shown in a formula (II) and an iodobenzene compound shown in a formula (III) under oxygen by taking metal salt as a catalyst, carbonate as alkali and an organic solvent as a medium to prepare a target reaction product, and carrying out post-treatment on the reaction product to prepare a phenyl-2- (2' -cyanophenyl) acetylene compound; the metal salt catalyst is palladium chloride, the carbonate is sodium carbonate, and the organic solvent is dimethyl sulfoxide;
in the reaction formula, R1Selected from one of the following: hydrogen, methyl, dimethyleneoxy; r2Selected from one of the following: hydrogen, methyl, methoxy, trifluoromethyl, dimethylamino, phenyl.
The method for preparing the phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis is characterized in that the proportion of the benzonitrile compounds, acetylene and iodobenzene compounds is 5 mmol: 6 mmol: 5 mmol.
The method for preparing the phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis is characterized in that the ratio of the benzonitrile compounds, acetylene and palladium chloride is 5 mmol: 6 mmol: 0.5 mmol.
The method for preparing the phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis is characterized in that the ratio of the benzonitrile compounds, acetylene and sodium carbonate is 5 mmol: 6 mmol: 10 mmol.
The method for preparing the phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis is characterized in that the ratio of the benzonitrile compounds, acetylene and solvent dimethyl sulfoxide is 5 mmol: 6 mmol: 15 mL.
The method for preparing the phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis is characterized in that the equivalent ratio of the benzonitrile compounds, acetylene and iodobenzene compounds is 1 (1-1.2): 1.
the method for preparing the phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis is characterized in that the reaction is carried out in an oxygen atmosphere, the reaction temperature is 100 ℃, and the reaction time is 10 hours.
The method for preparing the phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis is characterized by comprising the following steps:
1) and (3) extraction: after the reaction product is cooled to room temperature at normal temperature, 20mL of saturated sodium chloride aqueous solution is added into the reaction product, then ethyl acetate is used for extraction for 3 times, 20mL of the ethyl acetate is used for each time, and the extraction liquid is combined;
2) concentration: drying the extract with anhydrous sodium sulfate, and rotary drying with rotary evaporator to obtain concentrate;
3) adsorbing the obtained concentrate by using column chromatography silica gel, adding the concentrate into a 200-mesh 300-mesh chromatography silica gel column, and adding normal hexane: performing flash column chromatography with ethyl acetate according to a certain proportion, mixing eluates, spin-drying with a rotary evaporator, and pumping with an oil pump to obtain the product, namely the phenyl-2- (2' -cyanophenyl) acetylene compounds.
The method for preparing the phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis is characterized in that the drying time in the step 2) is 10 hours.
The method for preparing the phenyl-2- (2' -cyanophenyl) acetylene compounds under the catalysis of palladium is characterized in that the volume ratio of n-hexane to ethyl acetate in the step 3) is 4:1-1: 1.
Drawings
FIG. 1 is a drawing of product 4a of the present invention1H NMR spectrum;
FIG. 2 shows the product 4a of the present invention13C NMR spectrum;
FIG. 3 shows the product 4b of the present invention1H NMR spectrum;
FIG. 4 shows the product 4b of the present invention13C-NMR spectrum;
FIG. 5 shows the preparation of 4c according to the invention1H NMR spectrum;
FIG. 6 shows the preparation of 4c according to the invention13C-NMR spectrum;
FIG. 7 shows the product 4d of the present invention1H NMR spectrum;
FIG. 8 is a drawing showing the production of 4d in the present invention13C NMR spectrum;
FIG. 9 shows the preparation of 4e according to the invention1H NMR spectrum;
FIG. 10 shows the preparation of 4e according to the invention13C-NMR spectrum;
FIG. 11 shows the preparation of 4f of the present invention1H NMR spectrum;
FIG. 12 shows the preparation of 4f of the present invention13C NMR spectrum;
FIG. 13 shows 4g of the product of the present invention1H NMR spectrum;
FIG. 14 shows 4g of the product of the present invention13C-NMR spectrum;
FIG. 15 shows 4h of the product of the present invention1H NMR spectrum;
FIG. 16 shows 4h of the product of the present invention13C NMR spectrum;
Detailed Description
The present invention will be described in more detail with reference to specific examples.
According to the synthetic method, 5mmol of benzonitrile compound 1, 6mmol of acetylene 2 and 5mmol of iodobenzene compound 3 are sequentially added into a 25mL round-bottom flask, then 15mL of dimethyl sulfoxide, 0.5mmol of palladium chloride and 10mmol of sodium bicarbonate are sequentially added, and the mixture is reacted under oxygen and stirred at 100 ℃ for 10 hours. After cooling, 20mL of saturated sodium chloride aqueous solution is added into the system, extraction is carried out for 3 times by ethyl acetate, 20mL of saturated sodium chloride aqueous solution is carried out for each time, organic phases are combined, after drying by anhydrous sodium sulfate, solvent is evaporated, and the pure product of the phenyl-2- (2' -cyanophenyl) acetylene class compound 4 is obtained by 200-mesh silica gel column chromatography, wherein the yield is 75-93%.
Specific examples and characterization data are as follows.
Example 1: 4a preparation of the product
In a 25mL round bottom flask was added 5mmol benzonitrile, 6mmol acetylene and 5mmol 4-trifluoromethyliodobenzene sequentially followed by 15mL dimethyl sulfoxide, 0.5mmol palladium chloride and 10mmol sodium bicarbonate at room temperature and the reaction stirred under oxygen at 100 ℃ for 10 h. After cooling, 20mL of a saturated aqueous solution of sodium chloride was added to the system, and the mixture was extracted with ethyl acetate 3 times (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was distilled off, and the phenyl-2- (2' -cyanophenyl) acetylene compound 4a was obtained by 200-mesh 300-mesh silica gel column chromatography (1220mg, yield 90%, yellow powder). 4a1The H NMR spectrum is shown in figure 1,13the C NMR spectrum is shown in FIG. 2.
2-((4-(Trifluoromethyl)phenyl)ethynyl)benzonitrile(4a).Mp 105-106℃；1H NMR(400MHz,CDCl3)7.58-7.72(m,6H),7.40-7.48(m,2H)；13C NMR(100MHz,CDCl3)134.4,134.0,133.3,132.8,132.6,132.4,132.3,129.0,127.7,126.5,125.9,125.5(q,J＝3.89Hz,1C),122.5,117.5,117.2,115.9,115.6,94.2,87.8；
HRMS(ESI-TOF)[M+H]+Calcd for C16H9F3N 272.0687,found 272.0702.
Example 2: 4b preparation of the product
5mmol of benzonitrile, 6mmol of acetylene and 5mmol of 6-methoxy-2-iodonaphthalene are added successively at room temperature to a 25mL round-bottomed flask, then 15mL of dimethyl sulfoxide, 0.5mmol of palladium chloride and 10mmol of sodium bicarbonate are added successively, and the reaction is stirred under oxygen at 100 ℃ for 10 hours. After cooling, 20mL of a saturated aqueous solution of sodium chloride was added to the system, and the mixture was extracted with ethyl acetate 3 times (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was distilled off, and the phenyl-2- (2' -cyanophenyl) acetylene compound 4b was obtained by 200-mesh 300-mesh silica gel column chromatography (1302mg, yield 92%, yellow powder). 4b1The H NMR spectrum is shown in FIG. 3,13the C NMR spectrum is shown in FIG. 4.
2-((6-Methoxynaphthalen-2-yl)ethynyl)benzonitrile(4b).Mp113-114℃；
1H NMR(400MHz,CDCl3)8.06(s,1H),7.54-7.74(m,6H),7.39(td,J＝7.7,1.3Hz,1H),7.17(dd,J＝8.9,2.5Hz,1H),7.12(d,J＝2.5Hz,1H),3.92(s,3H)；
13C NMR(100MHz,CDCl3)158.8,134.8,132.8,132.5,132.2,132.1,129.7,129.0,128.5,128.1,127.6,127.1,119.7,117.8,116.9,115.3,105.9,96.9,85.5,55.5；
HRMS(ESI-TOF)[M+H]+Calcd for C20H14NO 284.1075,found 284.1071.
Example 3: preparation of 4c product
5mmol of benzonitrile, 6mmol of acetylene and 5mmol of 2-iodopyridine are added successively in a 25mL round-bottomed flask at room temperature, then 15mL of dimethyl sulfoxide, 0.5mmol of palladium chloride and 10mmol of sodium bicarbonate are added successively, and the reaction is stirred under oxygen at 100 ℃ for 10 hours. After cooling, 20mL of a saturated aqueous solution of sodium chloride was added to the system, and the mixture was extracted with ethyl acetate 3 times (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was distilled off, and the phenyl-2- (2' -cyanophenyl) acetylene compound 4c was obtained by 200-mesh 300-mesh silica gel column chromatography (908mg, 89% yield, yellow powder). 4c1The H NMR spectrum is shown in FIG. 5,13the C NMR spectrum is shown in FIG. 6.
2-(Pyridin-2-ylethynyl)benzonitrile(4c).Mp 116-117℃；
1H NMR(400MHz,CDCl3)8.63(d,J＝4.5Hz,1H),7.64-7.72(m,4H),7.57(td,J＝7.7,1.3Hz,1H),7.42-7.46(m,1H),7.25-7.29(m,1H)；13C NMR(100MHz,CDCl3)150.3,142.5,136.4,132.8,132.2,129.1,128.6,128.2,126.3,123.7,117.4,115.7,94.6,85.0；
HRMS(ESI-TOF)[M+H]+Calcd for C14H9N2205.0766,found 205.0775.
Example 4: preparation of 4d product
In a 25mL round-bottom flask at room temperature, 5mmol of benzonitrile, 6mmol of acetylene and 5mmol of 2-iodothiophene were added sequentially, then 15mL of dimethyl sulfoxide, 0.5mmol of palladium chloride and 10mmol of sodium bicarbonate were added sequentially and reacted in the presence of oxygenStirring for 10 hours at 100 ℃ under air. After cooling, 20mL of a saturated aqueous solution of sodium chloride was added to the system, and the mixture was extracted with ethyl acetate for 3 times (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was distilled off, and the phenyl-2- (2' -cyanophenyl) acetylene compound 4d (1045mg, yield 81%, yellow powder) was obtained by 200-mesh silica gel column chromatography. 4d1The H NMR spectrum is shown in FIG. 7,13the C NMR spectrum is shown in FIG. 8.
2-(Thiophen-3-ylethynyl)benzonitrile(4d).Mp 82-83℃；
1H NMR(400MHz CDCl3)7.52-7.65(m,4H),7.36-7.41(m,1H),7.30-7.32(m,1H),7.24(d,J＝4.9Hz,1H)；
13C NMR(100MHz,CDCl3)132.8,132.5,132.1,130.5,130.0,128.3,127.3,125.8,121.2,117.7,115.1,91.3,85.4；
HRMS(ESI-TOF)[M+H]+Calcd for C13H8NS 210.0377,found 210.0388.
Example 5: preparation of 4e product
5mmol of 3, 4-dioxymethylenebenzonitrile, 6mmol of acetylene and 5mmol of p-methoxyiodobenzene are added in succession at room temperature to a 25mL round-bottomed flask, then 15mL of dimethyl sulfoxide, 0.5mmol of palladium chloride and 10mmol of sodium hydrogencarbonate are added in succession and the reaction is stirred under oxygen at 100 ℃ for 10 hours. After cooling, 20mL of saturated aqueous sodium chloride solution was added to the system, and the mixture was extracted with ethyl acetate 3 times (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was distilled off, and the phenyl-2- (2' -cyanophenyl) acetylene compound 4e (1080mg, yield 78%, yellow powder) was obtained by 200-mesh silica gel column chromatography. 4e1The H NMR spectrum is shown in FIG. 9,13the C NMR spectrum is shown in FIG. 10.
6-((4-Methoxyphenyl)ethynyl)benzo[d][1,3]dioxole-5-carbonitrile(4e).Mp 102-103℃；
1H NMR(400MHz,CDCl3)7.51(d,J＝7.0Hz,2H),6.99(d,J＝13.7Hz,2H),6.87(d,J＝8.8Hz,2H),6.07(s,2H),3.82(s,3H)；
13C NMR(100MHz,CDCl3)160.3,151.3,147.6,133.5,132.4,123.6,117.9,114.2,113.8,111.6,108.4,102.7,95.0,84.6,55.4；
HRMS(ESI-TOF)[M+H]+Calcd for C17H12NO3278.0817,found 278.0824.
Example 6: preparation of 4f product
In a 25mL round bottom flask was added 5mmol of 3-indole carbonitrile, 6mmol of acetylene and 5mmol of iodobenzene sequentially at room temperature, followed by 15mL of dimethyl sulfoxide, 0.5mmol of palladium chloride and 10mmol of sodium bicarbonate, and the reaction was stirred under oxygen at 100 ℃ for 10 hours. After cooling, 20mL of a saturated aqueous solution of sodium chloride was added to the system, and the mixture was extracted with ethyl acetate 3 times (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was distilled off, and the phenyl-2- (2' -cyanophenyl) acetylene compound 4f (911mg, yield 75%, yellow powder) was obtained by 200-mesh silica gel column chromatography. 4f1The H NMR spectrum is shown in FIG. 11,13the C NMR spectrum is shown in FIG. 12.
2-(Phenylethynyl)benzofuran-3-carbonitrile(4f).Mp 95-96℃；1H NMR(400MHz,CDCl3)7.81(d,J＝7.8Hz,1H),7.62-7.64(m,2H),7.55(d,J＝3.6Hz,2H),7.38-7.46(m,4H)；
13C NMR(100MHz,CDCl3)155.3,132.1,129.7,129.2,129.0,128.7,126.3,125.0,121.9,121.7,116.4,112.4,111.3,100.9,76.0；
HRMS(ESI-TOF)[M+H]+Calcd for C17H10NO 244.0762,found 244.0760.
Example 7: preparation of 4g of product
In a 25mL round bottom flask was added 5mmol of 3-pyridinecarbonitrile, 6mmol of acetylene and 5mmol of iodobenzene sequentially at room temperature, followed by 15mL of dimethylsulfoxide, 0.5mmol of palladium chloride and 10mmol of sodium bicarbonate, and the reaction was stirred under oxygen at 100 ℃ for 10 hours. After cooling, 20mL of a saturated aqueous solution of sodium chloride was added to the system, and the mixture was extracted with ethyl acetate 3 times (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was distilled off, and 200-mesh 300-mesh silica gel column chromatography was performed to obtain 4g of phenyl-2- (2' -cyanophenyl) acetylene compounds (949mg, yield 93%, yellow powder). 4g1The H NMR spectrum is shown in FIG. 13,13the C NMR spectrum is shown in FIG. 14.
2-(Phenylethynyl)nicotinonitrile(4g).Mp 108-109℃；
1H NMR(400MHz,CDCl3)8.76(d,J＝4.1Hz,1H),7.97(d,J＝7.7Hz,1H),7.68(d,J＝7.0Hz,2H),7.32-7.44(m,4H)；
13C NMR(100MHz,CDCl3)153.0,146.0,140.0,132.6,130.0,128.7,122.2,121.0,116.1,112.9,96.2,85.8；
HRMS(ESI-TOF)[M+H]+Calcd for C14H9N2205.0766,found 205.0758.
Example 8: preparation of the 4h product
In a 25mL round bottom flask was added 5mmol of 3-quinolinecarbonitrile, 6mmol of acetylene and 5mmol of 4-dimethylaminoiodobenzene sequentially at room temperature followed by 15mL of dimethylsulfoxide, 0.5mmol of palladium chloride and 10mmol of sodium bicarbonate sequentially and the reaction was stirred under oxygen at 100 ℃ for 10 hours. After cooling, 20mL of saturated aqueous sodium chloride solution was added to the system, and the mixture was extracted with ethyl acetate 3 times (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was evaporated, and the phenyl-2- (2' -cyanophenyl) acetylene compounds were obtained by 200-mesh 300-mesh silica gel column chromatography for 4 hours (1233mg, yield 83%, yellow powder). 4h1The H NMR spectrum is shown in FIG. 15,13the C NMR spectrum is shown in FIG. 16.
2-((4-(Dimethylamino)phenyl)ethynyl)quinoline-3-carbonitrile(4h).Mp113-114℃；
1H NMR(400MHz,CDCl3)8.44(s,1H),8.08(d,J＝8.5Hz,1H),7.78-7.83(m,2H),7.56-7.61(m,3H),6.64(d,J＝8.8Hz,2H),3.00(s,6H)；
13C NMR(100MHz,CDCl3)151.2,148.8,143.7,142.0,134.2,133.1,129.3,128.1,124.6,116.8,111.6,109.4,107.2,99.0,85.9,40.1；HRMS(ESI-TOF)[M+H]+Calcd forC20H16N3298.1344,found 298.1357.
Claims (10)
1. A method for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds shown in a formula (IV) by palladium catalysis is characterized by comprising the following steps: the method comprises the following steps of (1) sufficiently reacting a benzonitrile compound shown in a formula (I), acetylene shown in a formula (II) and an iodobenzene compound shown in a formula (III) under oxygen by taking metal salt as a catalyst, carbonate as alkali and an organic solvent as a medium to prepare a reaction product, and carrying out post-treatment on the reaction product to prepare a phenyl-2- (2' -cyanophenyl) acetylene compound; the metal salt catalyst is palladium chloride, the carbonate is sodium carbonate, and the organic solvent is dimethyl sulfoxide;
in the reaction formula, R1Selected from one of the following: hydrogen, methyl, dimethyleneoxy; r2Selected from one of the following: hydrogen, methyl, methoxy, trifluoromethyl, dimethylamino, phenyl.
2. The method for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds according to claim 1, wherein the ratio of benzonitrile compound, acetylene and iodobenzene compound is 5 mmol: 6 mmol: 5 mmol.
3. The method for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds according to claim 1, wherein the ratio of benzonitrile compound, acetylene and palladium chloride is 5 mmol: 6 mmol: 0.5 mmol.
4. The method for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds according to claim 1, wherein the ratio of benzonitrile compound, acetylene and sodium carbonate is 5 mmol: 6 mmol: 10 mmol.
5. The method for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds according to claim 1, wherein the ratio of benzonitrile compound, acetylene and solvent dimethyl sulfoxide is 5 mmol: 6 mmol: 15 mL.
6. The method for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis according to claim 1, wherein the equivalent ratio of benzonitrile compound, acetylene and iodobenzene compound is 1 (1-1.2): 1.
7. the method for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds according to claim 1, wherein the reaction is carried out in oxygen atmosphere at 100 ℃ for 10 hours.
8. The palladium-catalyzed preparation method of phenyl-2- (2' -cyanophenyl) acetylene compounds according to claim 1, characterized in that the specific method of post-treatment consists of the following steps:
1) and (3) extraction: after the reaction product is cooled to room temperature at normal temperature, 20mL of saturated sodium chloride aqueous solution is added into the reaction product, then ethyl acetate is used for extraction for 3 times, 20mL of the ethyl acetate is used for each time, and the extraction liquid is combined;
2) concentration: drying the extract with anhydrous sodium sulfate, and rotary drying with rotary evaporator to obtain concentrate;
3) adsorbing the obtained concentrate by using column chromatography silica gel, adding the concentrate into a 200-mesh 300-mesh chromatography silica gel column, and adding normal hexane: performing flash column chromatography with ethyl acetate according to a certain proportion, mixing eluates, spin-drying with a rotary evaporator, and pumping with an oil pump to obtain the product, namely the phenyl-2- (2' -cyanophenyl) acetylene compounds.
9. The palladium-catalyzed process for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds according to claim 8, wherein the drying time in step 2) is 10 hours.
10. The method for preparing phenyl-2- (2' -cyanophenyl) acetylene compounds by palladium catalysis according to claim 8, wherein the volume ratio of n-hexane to ethyl acetate in step 3) is 4:1-1: 1.
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| CN103068947A (en) * | 2010-08-10 | 2013-04-24 | 日产化学工业株式会社 | Adhesive composition containing resin having carbon-carbon multiple bond |
| WO2014112798A1 (en) * | 2013-01-16 | 2014-07-24 | 주식회사유한양행 | Novel phenylethynyl benzamide glucokinase activator and method for preparing same |
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| WO2014112798A1 (en) * | 2013-01-16 | 2014-07-24 | 주식회사유한양행 | Novel phenylethynyl benzamide glucokinase activator and method for preparing same |
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