CN102491886B - Method for synthetizing indanone compound - Google Patents
Method for synthetizing indanone compound Download PDFInfo
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- CN102491886B CN102491886B CN201110394293.2A CN201110394293A CN102491886B CN 102491886 B CN102491886 B CN 102491886B CN 201110394293 A CN201110394293 A CN 201110394293A CN 102491886 B CN102491886 B CN 102491886B
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Abstract
The invention relates to a method for a synthetizing indanone compound, which comprises the steps of using substituted isobenzofuran-1(3H)-ketone as a raw material, reacting the substituted isobenzofuran-1(3H)-ketone and an ester compound containing alpha-methylene to produce a 1,3-dicarbonyl compound, and further synthetizing the substituted indanone compound under the action of a catalyst. Compared with the prior art, the problems including difficult operation due to large usage of acid compounds containing phosphorus or aluminium trichloride and the like, large amounts of liquid waste due to after-treatment and the like by means of the existing indanone compound synthetizing technology are mainly solved, reaction operation is simple, reaction conditions are easy to achieve, produced liquid waste is little in the after-treatment process, the pollution of the entire reaction process environment is low, and industrialization and sustainable development are easy to achieve.
Description
Technical field
The present invention relates to the preparation method of organic compound, especially relate to a kind of synthetic method of indanone compounds.
Background technology
Indanone compounds is synthesis of polyolefins by the important source material of metallocene catalyst, is also widely used in and fine chemicals synthetic at medicine simultaneously.
Document is (as Organometallics 2006 at present, 25,1217-1229 and relevant document and support information, US2007/0135595 A1, US2002/0077507 A1 and CN 101337874A) the main synthetic method of indanone compounds of report has:
1, take the synthetic method that substituted aroma hydrocarbon is starting raw material
The method is to take substituted aroma hydrocarbon as starting raw material, replaces propionyl chloride react under Using Aluminium Trichloride as Catalyst with 2-, generates substituted-phenyl and replaces ethyl ketone, then obtain (US2002/0077507 A1) through bromination, Using Aluminium Trichloride as Catalyst cyclisation, hydrolysis etc.
2, take the synthetic method that the halogenation benzyl that replaces is raw material
The method mainly be take the halogenation benzyl that replaces and is synthesized as raw material as benzyl chloride, halogenation benzyl reacts with the malonic ester of replacement and generates the phenylpropionic acid compound replacing, then under sulfur oxychloride effect, be converted into corresponding chloride compounds, again under aluminum chloride effect, further Cyclization indanone compounds (US2007/0135595A1).
3, take the synthetic method that phenyl aldehyde is raw material
The method be take the phenyl aldehyde replacing and is obtained 3-substituted-phenyl-2-substituting group vinylformic acid as raw material reacts with the malonic ester of replacement, through the synthetic indanone compounds of the multisteps such as hydrogenation, chloride, aluminum chloride or polyphosphoric acid catalyzed cyclization, (Organometallics 2006,25,1217-1229).
4, take the halogenation benzyl replacing is raw material, uses the synthetic method of phosphorous acidic cpd
The method mainly be take the halogenation benzyl that replaces and is synthesized as raw material, and halogenation benzyl react the malonic ester compound that generates replacement with the malonic ester of replacement, then further react with phosphorous acidic cpd and synthesize indanone compounds (CN 101337874A).
In the method that above-mentioned document provides, all used a large amount of aluminum chlorides or phosphorous acidic cpd, in use procedure, operation has certain difficulty, produces a large amount of acid waste liquids in aftertreatment, seriously polluted.Developing the synthetic method of indanone compounds low in the pollution of the environment again simple, with low cost is one of important goal of art technology worker.
Summary of the invention
Object of the present invention is exactly to provide a kind of operation simple in order to overcome the defect of above-mentioned prior art existence, and reaction conditions is easy to realize, and produces the synthetic method of the indanone compounds that waste liquid is few in last handling process.
Object of the present invention can be achieved through the following technical solutions:
A synthetic method for indanone compounds, comprises the following steps:
(1) take that to replace isobenzofuran-1 (3H)-one compound be raw material, carry out conversion reaction with the ester cpds that contains alpha-methylene, be converted into 1,3-dicarbonyl compound;
(2) prepare 1,3-dicarbonyl compound carries out intramolecular cyclization, acidic conditions decarboxylic reaction under catalyst action, is converted into replacement indanone compounds, is product.
The molecular formula of described replacement isobenzofuran-1 (3H)-one compound is:
The molecular formula of the described ester cpds that contains alpha-methylene is:
Described 1, the molecular formula of 3-dicarbonyl compound is:
The molecular formula of described replacement indanone compounds is:
R
1, R
4represent independently respectively H, Cl, Br, I, F, alkoxyl group, replacement or unsubstituted C
6-C
18aryl, described C
6-C
18aryl comprises phenyl, 1-how base, phenanthryl, 3-tert-butyl-phenyl, 4-tert-butyl-phenyl, 3,5-di-tert-butyl-phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 3,5-3,5-dimethylphenyl, 4,4 '-xenyl or 3,5-phenylbenzene phenyl.
R
5represent H, Cl, Br, C
1-C
18straight or branched alkyl, preferably H, C
1-C
10straight or branched alkyl.
R
2and R
3represent independently respectively H, Cl, Br, I, F, alkoxyl group, C
1-C
18straight or branched alkyl, at C
1-C
18in straight or branched alkyl, preferred C
1-C
10straight or branched alkyl.
R
1and R
2or R
2and R
3or R
3and R
4between can be connected to C
3-C
12cycloaliphatic ring or aromatic nucleus.
Step (1) specifically comprises the following steps:
In anhydrous chemical solvents, add alkali, under well-beaten condition, be n in molar ratio: 1 (0.1≤n≤10) add the ester compound that contains alpha-methylene and the mixture that replaces isobenzofuran-1 (3H)-one compound, stirring reaction 0.1-48 hour under the condition of-30-150 ℃, then add deionized water diluted reaction mixture, use again water-fast organic solvent extraction, water-fast organic solvent is fallen in redistillation, obtains 1,3-dicarbonyl compound.
Described alkali comprises C
1-C
20sodium alkoxide, potassium alcoholate, the aluminium alcoholates of primary, secondary or tertiary alcohol, sodium hydride, potassium hydride KH, trityl sodium, diisopropylamino lithium (LDA) or Grignard reagent, preferably C
1-C
6sodium alkoxide, potassium alcoholate, the aluminium alcoholates of primary, secondary or tertiary alcohol, trityl sodium, sodium hydride, potassium hydride KH or diisopropylamino lithium (LDA); Described anhydrous chemical solvents comprises ethanol, DMF, second cyanogen, chlorobenzene, toluene, Benzene Chloride, ethylene dichloride, methylene dichloride or DMSO; Described water-fast organic solvent is normal hexane.
Step (2) specifically comprises the following steps:
In organic chemistry solvent, be 1 in molar ratio: (0.01-0.5) add 1,3-dicarbonyl compound and catalyzer, control temperature of reaction is 0-200 ℃, stirring reaction 0.1-48 hour, then filter, in filtrate, add hcl acidifying, reaction finishes rear stratification, and organic layer utilization is washed and distilled solvent and obtains replacing indone compound later.
Described organic chemistry solvent comprises second cyanogen, chlorobenzene, ethylene dichloride, methylene dichloride, toluene, Benzyl Chloride, Nitromethane 99Min., nitroethane or oil of mirbane; The preferred 30-100 ℃ of described temperature of reaction; Described catalyzer be can this reaction of catalysis metal or nonmetallic simple substance or compound, preferred non-metal simple-substance or nonmetallic compound, described metal simple-substance comprises iron or palladium, described non-metal simple-substance comprises iodine or sulphur, described metallic compound comprises aluminum chloride or palladium etc., and described nonmetallic compound comprises polyphosphoric acid or phosphorus oxide.
Compared with prior art, the invention solves a large amount of operational difficultys that use aluminum chloride or phosphorous acidic cpd to bring in current indanone compounds building-up process, and the shortcomings such as a large amount of waste liquids of aftertreatment generation.Simple simple substance catalyzer is used in this invention, and operation is simple, and reaction conditions is easy to realize, and produces waste liquid few in last handling process, and whole piece reaction process is low in the pollution of the environment, is easy to realize industrialization and Sustainable development.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in detail.
Embodiment 1
In 2L reaction flask, add 600ml DMSO, 1mol sodium hydride, under mechanical stirring condition, drip 1mol ethyl propionate and 1mol isobenzofuran-1 (3H)-one mixture, keep temperature of reaction to be-10-0 ℃, dropwise, be slowly warmed up to room temperature and continue reaction 12 hours, after having reacted, add water 800ml dilution, use again n-hexane extraction, distillation desolventizes, and obtains 1,3-dicarbonyl compound 184.1g.
Above-mentioned 184.1g dicarbonyl compound is dissolved with 600ml ethylene dichloride, add again 2% mol catalyst iodine, mechanical stirring reaction 14 hours, has reacted rear filtration, and filtrate is with after concentrated hydrochloric acid acidifying, with ethylene dichloride, extract, have after which floor washing once, distillation desolventizes, and obtains 2-methyl-2,3-bihydrogen-1-indenone 111.6g, productive rate 76.3%.Spectral data is as follows:
1h NMR (500MHz, CDCl
3): δ=1.30 (d, 3H), δ=2.54-2.76 (d, 2H), δ=3.34-3.46 (m, 1H), δ=7.31-7.40 (t, 1H), δ=7.42-7.47 (t, 1H), δ=7.50-7.60 (t, 1H), δ=7.75-7.82 (t, 1H).
Embodiment 2
4 of equimolar amount for the-one of isobenzofuran-1 in embodiment 1 (3H), 7-dimethyl-3-phenyl isobenzofuran-1 (3H)-one replaces, and other conditions are with embodiment 1, obtain 2,4,7-trimethylammonium-3-phenyl-2,3-bihydrogen-1-indenone 196.3g, productive rate 78.4%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=1.23 (d, 3H), δ=2.34 (s, 6H), δ=2.58-2.83 (dd, 2H), δ=3.55 (dd, 1H), δ=7.41-7.58 (m, 5H), δ=7.80 (s, 1H).
Embodiment 3
5 of equimolar amount for the-one of isobenzofuran-1 in embodiment 1 (3H), 7-dimethyl isobenzofuran-1 (3H)-one replaces, and other reaction conditionss, with embodiment 1, obtain 2,5,7-trimethylammonium-2,3-bihydrogen-1-indenone 138.5g, productive rate 79.5%.Spectral data is as follows:
1h NMR (400MHz, CDCl
3): δ=1.27 (d, 3H), δ=2.36 (s, 3H), δ=2.58 (s, 3H), δ=3.25 (dd, 1H), δ=6.90 (s, 1H), δ=7.04 (s, 1H).
Embodiment 4
Isobenzofuran-1 in embodiment 1 (3H)-one is replaced by 7-(4-xenyl) isobenzofuran-1 (3H)-one of equimolar amount, other reaction conditionss are with embodiment 1, obtain 7-(4-xenyl)-2-methyl-2,3-bihydrogen-1-indenone 231.2g, productive rate 77.5%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=1.30 (d, 3H), δ=2.67-2.80 (m, 2H), δ=3.37-3.49 (m, 1H), δ=7.14-7.67 (12H).
Embodiment 5
Isobenzofuran-1 in embodiment 1 (3H)-one is replaced by 4-chlorine isobenzofuran-1 (3H)-one of equimolar amount, and other reaction conditionss, with embodiment 1, obtain 4-chloro-2-methyl-2,3-bihydrogen-1-indenone 139.6g, productive rate 77.3%.Spectral data is as follows:
1h NMR (CDCl
3): δ=1.30 (d, 3H), δ=2.69 (m, 2H), δ=3.35 (m, 1H), δ=7.29 (m, 1H), δ=7.52 (dd, 1H), δ=7.60 (m, 1H).
Embodiment 6
Isobenzofuran-1 in embodiment 1 (3H)-one is replaced by 4-(4-tert-butyl-phenyl)-isobenzofuran-1 (3H)-one of equimolar amount, other operational conditions are with embodiment 1, obtain 2-methyl-4-(4-tert-butyl-phenyl)-2,3-bihydrogen-1-indenone 169.8g, productive rate 61.0%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=0.82 (d, 3H), δ=1.07 (d, 3H), δ=2.35-2.46 (m, 1H), δ=2.64-3.20 (m, 3H), δ=7.15-7.25 (m, 2H), δ=7.60-7.76 (t, 1H), δ=7.78-7.92 (d, 1H).
Embodiment 7
5 of equimolar amount for the-one of isobenzofuran-1 in embodiment 1 (3H), 7-dimethyl isobenzofuran-1 (3H)-one replaces, and other operational conditions, with embodiment 1, obtain 2,5,7-trimethylammonium-2,3-bihydrogen-1-indenone 110.5g, productive rate 63.4%.Spectral data is as follows:
1h NMR (400MHz, CDCl
3): δ=1.27 (d, 3H), δ=2.36 (s, 3H), δ=2.58 (s, 3H), δ=3.25 (dd, 1H), δ=6.90 (s, 1H), δ=7.04 (s, 1H).
Embodiment 8
Isobenzofuran-1 in embodiment 1 (3H)-one is replaced by 4-phenyl isobenzofuran-1 (3H)-one of equimolar amount, and other operational conditions, with embodiment 1, obtain 2-methyl 4-phenyl-2,3-bihydrogen-1-indenone 158.3g, productive rate 71.2%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=1.28 (d, 3H), δ=2.51-2.90 (m, 2H), δ=3.25-3.35 (dd, 1H), δ=7.2-7.9 (m, 8H, Aromatic).
Embodiment 9
7-(3 isobenzofuran-1 in embodiment 1 (3H)-one with equimolar amount, 5-difluoro) phenyl isobenzofuran-1 (3H)-one replaces, other operational conditions are with embodiment 1, obtain 2-methyl-7-(3,5-difluoro) phenyl-2,3-bihydrogen-1-indenone 147.5g, productive rate 57.1%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=1.29 (d, 3H), δ=2.6-2.8 (m, 2H), δ=3.43 (m, 1H), δ=7.62-7.31 (m, 6H).
Embodiment 10
Ethyl propionate in embodiment 1 is replaced with the 3 Methylbutanoic acid ethyl ester of equimolar amount, and other operational conditions, with embodiment 1, obtain 2-sec.-propyl-2,3-bihydrogen-1-indenone 139.5g, productive rate 80.1%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=0.82 (d, 3H), δ=1.07 (d, 3H), δ=3.35-3.46 (m, 1H), δ=2.64-3.20 (m, 3H), δ=7.15-7.25 (m, 2H), δ=7.60-7.76 (t, 1H), δ=7.78-7.92 (d, 1H).
Embodiment 11
3,6,7 of equimolar amount for the-one of isobenzofuran-1 in embodiment 1 (3H), 8-tetrahydrochysene-1H-indeno [4,5-c] replacement of furans-1-ketone, other operational conditions, with embodiment 1, obtain 2-methyl-2,3,6,7-tetrahydrochysene-s-indacene-1 (5H)-one 135.2g, productive rate 72.6%.Spectral data is as follows:
1h NMR (400MHz, CDCl
3): δ=1.29 (d, 3H), δ=1.85 (m, 4H), δ=2.50 (dd, 1H), δ=2.68 (m, 3H), δ=2.80 (m, 2H), δ=3.20 (dd, 1H), δ=7.08 (d, 1H), δ=7.48 (d, 1H).
Embodiment 12
In 2L reaction flask, add 600ml DMSO, 1mol trityl sodium, under mechanical stirring condition, drip 1mol 3 Methylbutanoic acid ethyl ester and 1mol 7-phenyl isobenzofuran-1 (3H)-one mixture, keep temperature of reaction to be-10-0 ℃, dropwise, be slowly warmed up to room temperature and continue reaction 12 hours, after having reacted, add water 800ml dilution, use again n-hexane extraction, distillation desolventizes, and obtains 1,3-dicarbonyl compound 290.5g.
Above-mentioned 290.5g dicarbonyl compound is dissolved with 600ml ethylene dichloride, add again 3% mol catalyst iodine, mechanical stirring reaction 14 hours, has reacted rear filtration, and filtrate is with after concentrated hydrochloric acid acidifying, with ethylene dichloride, extract, after organic layer washing once, distillation desolventizes, and obtains 2-sec.-propyl-7-phenyl-2,3-bihydrogen-1-indenone 196.3g, productive rate 78.4%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=0.91 (d, 6H), δ=2.36 (m, 2H), δ=2.58-2.83 (m, 2H), δ=7.33-8.24 (m, 8H, Aromatic).
Embodiment 13
3 Methylbutanoic acid ethyl ester in embodiment 12 is replaced with the ethyl hexanoate of equimolar amount, and other operational conditions, with embodiment 12, obtain 2-butyl-7-phenyl-2,3-bihydrogen-1-indenone 113.9g, productive rate 43.1%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=0.91 (t, 3H), δ=1.41 (m, 5H), δ=1.94 (m, 1H), δ=2.65 (m, 1H), δ=2.83 (dd, 1H), δ=3.34 (dd, 1H), δ=7.23-7.28 (1H), δ=7.35-7.47 (6H), δ=7.58 (t, 1H).
Embodiment 14
3 Methylbutanoic acid ethyl ester in embodiment 12 is replaced with the 2-cyclohexyl acetic acid ethyl ester of equimolar amount, and other operational conditions, with embodiment 12, obtain 7-phenyl-2-cyclohexyl-2,3-bihydrogen-1-indenone 119.5g, productive rate 41.2%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=1.0-1.46 (m, 6H), δ=1.60-1.80 (m, 4H), δ=1.98-2.10 (m, 1H), δ=2.65 (m, 1H), δ=2.92 (dd, 1H), δ=3.11 (dd, 1H), δ=7.20-7.92 (10H).
Embodiment 15
7-phenyl isobenzofuran-1 (3H)-one in embodiment 12 is replaced by 4-bromine isobenzofuran-1 (3H)-one of equimolar amount, other operational conditions are with embodiment 12,2-sec.-propyl-4-is bromo-2,3-bihydrogen-1-indenone 152.9g, productive rate 81.2%.Spectral data is as follows:
1h NMR (CDCl
3): δ=0.8 (d, 3H), δ=1.07 (d, 3H), δ=2.36-2.46 (m, 1H), δ=2.66 (dd, 1H), δ=2.66-2.72 (m, 1H), δ=3.09 (dd, 1H), δ=7.25 (t, 1H), δ=7.67 (d, 1H), δ=7.73 (d, 1H).
Embodiment 16
Isobenzofuran-1 in embodiment 12 (3H)-one is replaced by 4-p-methoxy-phenyl isobenzofuran-1 (3H)-one of equimolar amount, other operational conditions are with embodiment 12, obtain 2-sec.-propyl-4-p-methoxy-phenyl-2,3-bihydrogen-1-indenone 207.7g, productive rate 74.1%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=0.91 (d, 6H), δ=2.36 (m, 2H), δ=3.83 (m, 3H), δ=2.58-2.83 (m, 2H), δ=7.05-7.92 (m, 7H, Aromatic).
Embodiment 17
In 2L reaction flask, add 600ml DMSO, 1mol diisopropylamino lithium, under mechanical stirring condition, drip 1mol ethyl butyrate and 1mol isobenzofuran-1 (3H)-one mixture, keep temperature of reaction to be-10-0 ℃, dropwise, be slowly warmed up to room temperature and continue reaction 12 hours, after having reacted, add water 800ml dilution, use again n-hexane extraction, distillation desolventizes, and obtains 1,3-dicarbonyl compound 200.8g.
Above-mentioned 200.8g dicarbonyl compound is dissolved with 600ml ethylene dichloride, add again 5% mol catalyst iodine, mechanical stirring reaction 14 hours, has reacted rear filtration, and filtrate is with after concentrated hydrochloric acid acidifying, with ethylene dichloride, extract, after organic layer washing once, distillation desolventizes, and obtains 2-ethyl-2,3-bihydrogen-1-indenone 111.0g, productive rate 69.3%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=0.90 (t, 3H), δ=1.59-2.10 (m, 2H), δ=2.60-2.80 (m, 2H), δ=3.37 (m, 1H), δ=7.35-7.37 (m, 1H), δ=7.58 (d, 1H), δ=7.92 (d, 1H).
Embodiment 18
Isobenzofuran-1 in embodiment 17 (3H)-one is replaced by 4-chlorine isobenzofuran-1 (3H)-one of equimolar amount, and other operational conditions, with embodiment 17, obtain the chloro-2-of 4-ethyl-2,3-bihydrogen-1-indenone 106.7g, productive rate 54.8%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=0.95-1.06 (t, 3H), δ=1.50-2.10 (m, 2H), δ=2.60-2.80 (m, 2H), δ=3.30-3.41 (m, 1H), δ=7.30 (m, 1H), δ=7.52 (d, 1H), δ=7.65 (d, 1H).
Embodiment 19
Naphtho-[1 isobenzofuran-1 in embodiment 17 (3H)-one with equimolar amount, 2-c] replacement of furans-1 (3H)-one, ethyl butyrate replaces with the ethyl propionate of equimolar amount simultaneously, other operational conditions are with embodiment 17, obtain 2,3-dihydro-2-methyl isophthalic acid H-benzo [e] 1-Indanone 137.4g, productive rate 70.0%.Spectral data is as follows:
1h NMR (400MHz, CDCl
3): δ=1.37 (d, 3H), δ=2.80 (m, 4H), δ=3.45 (dd, 1H), δ=7.46 (d, 1H), δ=7.54 (t, 1H), δ=7.65 (t, 1H), δ=7.86 (d, 1H), δ=8.01 (d, 1H), δ=9.16 (d, 1H).
Embodiment 20
Isobenzofuran-1 in embodiment 17 (3H)-one is replaced by 6-fluorine isobenzofuran-1 (3H)-one of equimolar amount, ethyl butyrate replaces with the ethyl propionate of equimolar amount simultaneously, other operational conditions are with embodiment 17, obtain the fluoro-2-of 6-methyl-2,3-bihydrogen-1-indenone 69.4g, productive rate 42.3%.Spectral data is as follows:
1h NMR (300MHz, CDCl
3): δ=1.30 (d, 3H), δ=2.55-2.77 (d, 2H), δ=3.33-3.46 (m, 1H), δ=7.05-7.25 (m, 2H), δ=7.51-7.65 (d, 1H).
Embodiment 21
A synthetic method for indanone compounds, comprises the following steps:
(1) in ethanol, add trityl sodium, under well-beaten condition, be to add the ester compound that contains alpha-methylene and the mixture that replaces isobenzofuran-1 (3H)-one compound at 0.1: 1 in molar ratio, under the condition of-30 ℃, stirring reaction is 48 hours, then add deionized water diluted reaction mixture, with normal hexane, extract again, normal hexane is fallen in redistillation, obtains 1,3-dicarbonyl compound.
Wherein, the molecular formula of molecular formula, the ester cpds that contains alpha-methylene and 1, the 3-dicarbonyl compound of replacement isobenzofuran-1 (3H)-one compound is respectively:
R
1, R
4represent independently respectively H, Cl, Br, I, F, alkoxyl group, replacement or unsubstituted C
6-C
18aryl, C
6-C
18aryl comprises phenyl, 1-how base, phenanthryl, 3-tert-butyl-phenyl, 4-tert-butyl-phenyl, 3,5-di-tert-butyl-phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 3, and 5-3,5-dimethylphenyl, 4,4 '-xenyl or 3,5-phenylbenzene phenyl, in the present embodiment, R
1for Cl, R
4for 1-base how.
R
5represent H, Cl, Br, C
1-C
18straight or branched alkyl, in the present embodiment, R
5for C
4straight chained alkyl.
R
2and R
3represent independently respectively H, Cl, Br, I, F, alkoxyl group, C
1-C
18straight or branched alkyl, in the present embodiment, R
2for H, R
3for C
5branched-chain alkyl.
(2) in organic chemistry solvent ethylene dichloride, be to add 1 at 1: 0.01 in molar ratio, 3-dicarbonyl compound and iron catalyst, controlling temperature of reaction is 0 ℃, stirring reaction 48 hours, then filter, in filtrate, add hcl acidifying, reaction finishes rear stratification, and organic layer utilization is washed and distilled solvent and obtains replacing indone compound later.
The molecular formula of the replacement indanone compounds preparing is:
R
1, R
2, R
3, R
4, R
5identical with above.
Embodiment 22
A synthetic method for indanone compounds, comprises the following steps:
(1) in methylene dichloride, add sodium ethylate, under well-beaten condition, be to add the ester compound that contains alpha-methylene and the mixture that replaces isobenzofuran-1 (3H)-one compound at 1: 1 in molar ratio, under the condition of 10 ℃, stirring reaction is 36 hours, then add deionized water diluted reaction mixture, with normal hexane, extract again, normal hexane is fallen in redistillation, obtains 1,3-dicarbonyl compound.
Wherein, the molecular formula of molecular formula, the ester cpds that contains alpha-methylene and 1, the 3-dicarbonyl compound of replacement isobenzofuran-1 (3H)-one compound is respectively:
R
1, R
4represent independently respectively H, Cl, Br, I, F, alkoxyl group, replacement or unsubstituted C
6-C
18aryl, C
6-C
18aryl comprises phenyl, 1-how base, phenanthryl, 3-tert-butyl-phenyl, 4-tert-butyl-phenyl, 3,5-di-tert-butyl-phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 3, and 5-3,5-dimethylphenyl, 4,4 '-xenyl or 3,5-phenylbenzene phenyl, in the present embodiment, R
1for 3-aminomethyl phenyl, R
4it is 3,5-3,5-dimethylphenyl.
R
5represent H, C1, Br, C
1-C
18straight or branched alkyl, in the present embodiment, R
5for Cl.
R
2and R
3represent independently respectively H, Cl, Br, I, F, alkoxyl group, C
1-C
18straight or branched alkyl, in the present embodiment, R
2for Cl, R
3for C
6straight chained alkyl.
(2) in organic chemistry methylene chloride, be to add 1 at 1: 0.1 in molar ratio, 3-dicarbonyl compound and aluminum trichloride catalyst, controlling temperature of reaction is 30 ℃, stirring reaction 36 hours, then filter, in filtrate, add hcl acidifying, reaction finishes rear stratification, and organic layer utilization is washed and distilled solvent and obtains replacing indone compound later.
The molecular formula of the replacement indanone compounds preparing is:
R
1, R
2, R
3, R
4, R
5identical with above.
Embodiment 23
A synthetic method for indanone compounds, comprises the following steps:
(1) in methylene dichloride, add sodium ethylate, under well-beaten condition, be to add the ester compound that contains alpha-methylene and the mixture that replaces isobenzofuran-1 (3H)-one compound at 5: 1 in molar ratio, under the condition of 80 ℃, stirring reaction is 12 hours, then add deionized water diluted reaction mixture, with normal hexane, extract again, normal hexane is fallen in redistillation, obtains 1,3-dicarbonyl compound.
Wherein, the molecular formula of molecular formula, the ester cpds that contains alpha-methylene and 1, the 3-dicarbonyl compound of replacement isobenzofuran-1 (3H)-one compound is respectively:
R
1, R
4represent independently respectively H, Cl, Br, I, F, alkoxyl group, replacement or unsubstituted C
6-C
18aryl, C
6-C
18aryl comprises phenyl, 1-how base, phenanthryl, 3-tert-butyl-phenyl, 4-tert-butyl-phenyl, 3,5-di-tert-butyl-phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 3, and 5-3,5-dimethylphenyl, 4,4 '-xenyl or 3,5-phenylbenzene phenyl, in the present embodiment, R
1for 4-tert-butyl-phenyl, R
4for alkoxyl group.
R
5represent H, Cl, Br, C
1-C
18straight or branched alkyl, in the present embodiment, R
5for C
6branched-chain alkyl.
R
2and R
3represent independently respectively H, Cl, Br, I, F, alkoxyl group, C
1-C
18straight or branched alkyl, in the present embodiment, R
2for Br, R
3for C
5straight chained alkyl.
(2) in organic chemistry methylene chloride, be to add 1 at 1: 0.3 in molar ratio, 3-dicarbonyl compound and polyphosphoric acid catalyzed dose, controlling temperature of reaction is 100 ℃, stirring reaction 12 hours, then filter, in filtrate, add hcl acidifying, reaction finishes rear stratification, and organic layer utilization is washed and distilled solvent and obtains replacing indone compound later.
The molecular formula of the replacement indanone compounds preparing is:
R
1, R
2, R
3, R
4, R
5identical with above.
Embodiment 24
A synthetic method for indanone compounds, comprises the following steps:
(1) in methylene dichloride, add sodium ethylate, under well-beaten condition, be to add the ester compound that contains alpha-methylene and the mixture that replaces isobenzofuran-1 (3H)-one compound at 5: 1 in molar ratio, under the condition of 150 ℃, stirring reaction is 0.1 hour, then add deionized water diluted reaction mixture, with normal hexane, extract again, normal hexane is fallen in redistillation, obtains 1,3-dicarbonyl compound.
Wherein, the molecular formula of molecular formula, the ester cpds that contains alpha-methylene and 1, the 3-dicarbonyl compound of replacement isobenzofuran-1 (3H)-one compound is respectively:
R
1, R
4represent independently respectively H, Cl, Br, I, F, alkoxyl group, replacement or unsubstituted C
6-C
18aryl, C
6-C
18aryl comprises phenyl, 1-how base, phenanthryl, 3-tert-butyl-phenyl, 4-tert-butyl-phenyl, 3,5-di-tert-butyl-phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 3, and 5-3,5-dimethylphenyl, 4,4 '-xenyl or 3,5-phenylbenzene phenyl, in the present embodiment, R
1for F, R
4it is 3,5-phenylbenzene phenyl.
R
5represent H, Cl, Br, C
1-C
18straight or branched alkyl, in the present embodiment, R
5for H.
R
2and R
3represent independently respectively H, Cl, Br, I, F, alkoxyl group, C
1-C
18straight or branched alkyl, in the present embodiment, R
2for H, R
3for C
8straight chained alkyl.
(2) in organic chemistry solvent DMSO, be to add 1 at 1: 0.5 in molar ratio, 3-dicarbonyl compound and iodine catalyst, controlling temperature of reaction is 200 ℃, stirring reaction 0.1 hour, then filter, in filtrate, add hcl acidifying, reaction finishes rear stratification, and organic layer utilization is washed and distilled solvent and obtains replacing indone compound later.
The molecular formula of the replacement indanone compounds preparing is:
R
1, R
2, R
3, R
4, R
5identical with above.
Claims (5)
1. a synthetic method for indanone compounds, is characterized in that, the method adopts following steps:
(1) take and replace isobenzofuran-1(3H)-one compound is raw material, reacts with the ester cpds that contains alpha-methylene, is converted into 1,3-dicarbonyl compound;
(2) prepare 1,3-dicarbonyl compound carries out intramolecular cyclization, acidic conditions decarboxylic reaction under catalyst action, is converted into replacement indanone compounds, is product;
Described replacement isobenzofuran-1(3H) molecular formula of-one compound is:
The molecular formula of the described ester cpds that contains alpha-methylene is:
Described 1, the molecular formula of 3-dicarbonyl compound is:
The molecular formula of described replacement indanone compounds is:
R
1, R
4represent independently respectively H, Cl, Br, I, F, alkoxyl group, replacement or unsubstituted C
6-C
18aryl, described C
6-C
18aryl is phenyl, phenanthryl, 3-tert-butyl-phenyl, 4-tert-butyl-phenyl, 3,5-di-tert-butyl-phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 3,5-3,5-dimethylphenyl, 4,4 '-xenyl or 3,5-phenylbenzene phenyl;
R
5represent H, Cl, Br, C
1-C
18straight or branched alkyl;
R
2and R
3represent independently respectively H, Cl, Br, I, F, alkoxyl group, C
1-C
18straight or branched alkyl;
R
1and R
2or R
2and R
3or R
3and R
4between can be connected to C
3-C
12cycloaliphatic ring or aromatic nucleus;
Step (1) specifically adopts following steps:
In anhydrous chemical solvents, add alkali, under well-beaten condition, be the mixture of (0.1-10) ︰ 1 adds the ester compound that contains alpha-methylene and replaces isobenzofuran-1(3H)-one compound in molar ratio, stirring reaction 0.1-48 hour under the condition of-30-150 ℃, then add deionized water diluted reaction mixture, use again water-fast organic solvent extraction, water-fast organic solvent is fallen in redistillation, obtains 1,3-dicarbonyl compound;
Described alkali is C
1-C
20sodium alkoxide, potassium alcoholate, the aluminium alcoholates of primary, secondary or tertiary alcohol, sodium hydride, potassium hydride KH, trityl sodium, diisopropylamino lithium (LDA) or Grignard reagent; Described anhydrous chemical solvents is ethanol, DMF, second cyanogen, chlorobenzene, toluene, ethylene dichloride, methylene dichloride or DMSO; Described water-fast organic solvent is normal hexane;
Step (2) specifically adopts following steps:
In organic chemistry solvent, be that 1 ︰ (0.01-0.5) adds 1 in molar ratio, 3-dicarbonyl compound and catalyzer, control temperature of reaction is 0-200 ℃, stirring reaction 0.1-48 hour, then filter, in filtrate, add hcl acidifying, reaction finishes rear stratification, and organic layer utilization is washed and distilled solvent and obtains replacing indone compound later;
Described organic chemistry solvent is second cyanogen, chlorobenzene, ethylene dichloride, methylene dichloride, toluene, Benzyl Chloride, Nitromethane 99Min., nitroethane or oil of mirbane; Described catalyzer be can this reaction of catalysis metal or nonmetallic simple substance or compound, described metal simple-substance is iron or palladium, described non-metal simple-substance is iodine or sulphur, and described metallic compound is aluminum chloride or palladium, and described nonmetallic compound is polyphosphoric acid or phosphorus oxide.
2. the synthetic method of a kind of indanone compounds according to claim 1, is characterized in that,
R
5represent H, C
1-C
10straight or branched alkyl; R
2and R
3represent independently respectively C
1-C
10straight or branched alkyl.
3. the synthetic method of a kind of indanone compounds according to claim 1, is characterized in that, the alkali described in step (1) is C
1-C
6sodium alkoxide, potassium alcoholate, the aluminium alcoholates of primary, secondary or tertiary alcohol, trityl sodium, sodium hydride, potassium hydride KH or diisopropylamino lithium (LDA).
4. the synthetic method of a kind of indanone compounds according to claim 1, is characterized in that, the temperature of reaction described in step (2) is 30-100 ℃.
5. the synthetic method of a kind of indanone compounds according to claim 1, is characterized in that, the catalyzer described in step (2) is non-metal simple-substance or nonmetallic compound.
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| CN109053446B (en) * | 2018-09-13 | 2021-01-01 | 苏州大学张家港工业技术研究院 | Application of metal hydride/palladium compound system in preparation of 1, 3-dicarbonyl compound by series reaction of electron-deficient alkene compound |
| CN108976122B (en) * | 2018-09-13 | 2021-01-12 | 南通纺织丝绸产业技术研究院 | Method for producing 1, 3-dicarbonyl compounds based on metal hydride/palladium compound systems |
| WO2020056564A1 (en) * | 2018-09-17 | 2020-03-26 | 南通纺织丝绸产业技术研究院 | Method for preparing 1,3-dicarbonyl compound based on metal hydride/palladium compound system |
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| CN1403434A (en) * | 2002-09-20 | 2003-03-19 | 王明春 | Prepn process of 5-chloro-2,3-dihydro-1-indenone |
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| CN101318887A (en) * | 2008-07-08 | 2008-12-10 | 上海化工研究院 | Method for preparing indene compounds |
| CN101337874A (en) * | 2008-08-14 | 2009-01-07 | 上海化工研究院 | Method for preparing indanone compounds |
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| CN1403434A (en) * | 2002-09-20 | 2003-03-19 | 王明春 | Prepn process of 5-chloro-2,3-dihydro-1-indenone |
| CN101293820A (en) * | 2007-04-27 | 2008-10-29 | 天津药明康德新药开发有限公司 | Process for synthesizing 5-trifluoromethyl-1-indene ketone |
| CN101318887A (en) * | 2008-07-08 | 2008-12-10 | 上海化工研究院 | Method for preparing indene compounds |
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