CN102491886A - Method for synthetizing indanone compound - Google Patents
Method for synthetizing indanone compound Download PDFInfo
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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 cpds, especially relate to a kind of compound method of indanone compounds.
Background technology
Indanone compounds is the important source material of synthesis of polyolefins with metallocene catalyst, simultaneously medicine synthetic with fine chemicals in also be widely used.
The main compound method of the indanone compounds of document (like Organometallics 2006,25,1217-1229 and relevant document and support information, US2007/0135595 A1, US2002/0077507 A1 and CN 101337874A) report has at present:
1, with the substituted aroma hydrocarbon is the compound method of starting raw material
This method is to be starting raw material with the substituted aroma hydrocarbon, replaces propionyl chloride with 2-and under aluminum chloride catalysis, react, and generation substituted-phenyl replacement ethyl ketone obtains (US2002/0077507 A1) through bromination, aluminum chloride catalytic cyclization, hydrolysis etc. again.
2, the compound method that is raw material with substituted halogenation benzyl
This method is that raw material synthesizes with substituted halogenation benzyl such as benzyl chloride mainly; Halogenation benzyl and the reaction of substituted malonic ester generate substituted phenylpropionic acid compound; Under the sulfur oxychloride effect, be converted into corresponding chloride compounds then; Under the aluminum chloride effect, further indanone compounds (US2007/0135595A1) is synthesized in cyclisation again.
3, with the phenyl aldehyde be the compound method of raw material
This method is that raw material and the reaction of substituted malonic ester obtain 3-substituted-phenyl-2-substituting group vinylformic acid with substituted phenyl aldehyde; (Organometallics 2006 through the synthetic indanone compounds of multisteps such as hydrogenation, chloride, aluminum chloride or polyphosphoric acid catalyzed cyclization; 25,1217-1229).
4, be raw material with substituted halogenation benzyl, use the compound method of phosphorous acidic cpd
This method is that raw material synthesizes with substituted halogenation benzyl mainly, and halogenation benzyl and the reaction of substituted malonic ester generate substituted malonic ester compound, further synthesizes indanone compounds (CN 101337874A) with phosphorous acidic cpd reaction then.
In the method that above-mentioned document provides, all used a large amount of aluminum chlorides or phosphorous acidic cpd, operation has certain difficulty in the use, produces a large amount of acid waste liquids in the aftertreatment, and is seriously polluted.The compound method of developing simple, with low cost indanone compounds low in the pollution of the environment again is one of important goal of art technology worker.
Summary of the invention
The object of the invention is exactly to provide a kind of operation simple for the defective that overcomes above-mentioned prior art existence, and reaction conditions is easy to realize, produces the compound method of the few indanone compounds of waste liquid in the last handling process.
The object of the invention can be realized through following technical scheme:
A kind of compound method of indanone compounds may further comprise the steps:
(1) is raw material to replace isobenzofuran-1 (3H)-ketone compound, carries out conversion reaction, be converted into 1, the 3-dicarbonyl compound with the ester cpds that contains alpha-methylene;
(2) prepare 1, the 3-dicarbonyl compound carries out intramolecular cyclization, acidic conditions decarboxylic reaction under catalyst action, be converted into the replacement indanone compounds, is product.
The molecular formula of described replacement isobenzofuran-1 (3H)-ketone compound is:
The described molecular formula that contains the ester cpds of 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 H, Cl, Br, I, F, alkoxyl group, replacement or unsubstituted C respectively independently
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
18The straight or branched alkyl, preferred H, C
1-C
10The straight or branched alkyl.
R
2And R
3Represent H, Cl, Br, I, F, alkoxyl group, C respectively independently
1-C
18The straight or branched alkyl is at C
1-C
18In the straight or branched alkyl, preferred C
1-C
10The straight or branched alkyl.
R
1And R
2Perhaps R
2And R
3Perhaps R
3And R
4Between can be connected to C
3-C
12Cycloaliphatic ring or aromatic nucleus.
Step (1) specifically may further comprise the steps:
In anhydrous chemical solvents, add alkali; Under well-beaten condition in molar ratio for n: 1 (0.1≤n≤10) add ester compound that contains alpha-methylene and the mixture that replaces isobenzofuran-1 (3H)-ketone compound, under-30-150 ℃ condition stirring reaction 0.1-48 hour, add the deionized water diluted reaction mixture then; Use water-fast organic solvent extraction again; Water-fast organic solvent is fallen in redistillation, promptly obtains 1, the 3-dicarbonyl compound.
Described alkali comprises C
1-C
20Primary, sodium alkoxide, potassium alcoholate, the aluminium alcoholates of the second month in a season or the tertiary alcohol, sodium hydride, potassium hydride KH, trityl sodium, diisopropylamino lithium (LDA) or Grignard reagent, preferred C
1-C
6Primary, sodium alkoxide, potassium alcoholate, the aluminium alcoholates of the second month in a season or the 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 a normal hexane.
Step (2) specifically may further comprise the steps:
Be 1 in molar ratio in the organic chemistry solvent: (0.01-0.5) add 1; 3-dicarbonyl compound and catalyzer, control reaction temperature are 0-200 ℃, stirring reaction 0.1-48 hour; Filter then; Add hcl acidifying in the filtrating, reaction finishes the back standing demix, and the organic layer utilization is washed and distilled solvent and promptly obtains replacing the indone compound later on.
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, and 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 use operational difficultys that aluminum chloride or phosphorous acidic cpd brought in the present 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 that it is few to produce waste liquid in the last handling process, and the whole piece reaction process is low in the pollution of the environment, is easy to realize industriallization and Sustainable development.
Embodiment
Below in conjunction with specific embodiment the present invention is elaborated.
Embodiment 1
In the 2L reaction flask, adding 600ml DMSO, 1mol sodium hydride, drip 1mol ethyl propionate and 1mol isobenzofuran-1 (3H)-alcohol/ketone mixtures under the mechanical stirring condition, the maintenance temperature of reaction is-10-0 ℃; Dropwise, slowly be warmed up to room temperature and continue reaction 12 hours, add water 800ml dilution after reaction is accomplished; Use n-hexane extraction again; Distillation desolventizes, and gets 1,3-dicarbonyl compound 184.1g.
With the dissolving of 600ml ethylene dichloride, add 2% mol catalyst iodine again, mechanical stirring reaction 14 hours to above-mentioned 184.1g dicarbonyl compound; After-filtration is accomplished in reaction, and filtrating extracts with ethylene dichloride with after the concentrated hydrochloric acid acidifying; After which floor washing was once arranged, distillation desolventized, and got 2-methyl-2; 3-bihydrogen-1-indenone 111.6g, productive rate 76.3%.Spectral data is following:
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
With 4 of equimolar amount, 7-dimethyl--3-phenyl isobenzofuran-1 (3H)-ketone replaces the isobenzofuran among the embodiment 1-1 (3H)-ketone, and other conditions get 2,4,7-trimethylammonium-3-phenyl-2,3-bihydrogen-1-indenone 196.3g, productive rate 78.4% with embodiment 1.Spectral data is following:
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
With 5 of equimolar amount, 7-dimethyl-isobenzofuran-1 (3H)-ketone replaces the isobenzofuran among the embodiment 1-1 (3H)-ketone, and other reaction conditionss get 2,5,7-trimethylammonium-2,3-bihydrogen-1-indenone 138.5g, productive rate 79.5% with embodiment 1.Spectral data is following:
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
Replace the isobenzofuran among the embodiment 1-1 (3H)-ketone 7-(4-xenyl) isobenzofuran-1 (3H)-ketone with equimolar amount, other reaction conditionss get 7-(4-xenyl)-2-methyl-2,3-bihydrogen-1-indenone 231.2g, productive rate 77.5% with embodiment 1.Spectral data is following:
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
Replace the isobenzofuran among the embodiment 1-1 (3H)-ketone 4-chlorine isobenzofuran-1 (3H)-ketone with equimolar amount, other reaction conditionss get 4-chloro-2-methyl-2,3-bihydrogen-1-indenone 139.6g, productive rate 77.3% with embodiment 1.Spectral data is following:
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
Replace 4-(4-tert-butyl-phenyl)-isobenzofuran-1 (the 3H)-ketone of the isobenzofuran among the embodiment 1-1 (3H)-ketone with equimolar amount; Other operational conditions are with embodiment 1; Get 2-methyl-4-(4-tert-butyl-phenyl)-2,3-bihydrogen-1-indenone 169.8g, productive rate 61.0%.Spectral data is following:
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
With 5 of equimolar amount, 7-dimethyl-isobenzofuran-1 (3H)-ketone replaces the isobenzofuran among the embodiment 1-1 (3H)-ketone, and other operational conditions get 2,5,7-trimethylammonium-2,3-bihydrogen-1-indenone 110.5g, productive rate 63.4% with embodiment 1.Spectral data is following:
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
Replace the isobenzofuran among the embodiment 1-1 (3H)-ketone 4-phenyl isobenzofuran-1 (3H)-ketone with equimolar amount, other operational conditions get 2-methyl-4-phenyl-2,3-bihydrogen-1-indenone 158.3g, productive rate 71.2% with embodiment 1.Spectral data is following:
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
Replace 7-(3,5-difluoro) phenyl isobenzofuran-1 (the 3H)-ketone of the isobenzofuran among the embodiment 1-1 (3H)-ketone with equimolar amount, other operational conditions are with embodiment 1; Get 2-methyl-7-(3; The 5-difluoro) phenyl-2,3-bihydrogen-1-indenone 147.5g, productive rate 57.1%.Spectral data is following:
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
Replace the 3 Methylbutanoic acid ethyl ester of the ethyl propionate among the embodiment 1 with equimolar amount, other operational conditions get 2-sec.-propyl-2,3-bihydrogen-1-indenone 139.5g, productive rate 80.1% with embodiment 1.Spectral data is following:
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
The isobenzofuran among the embodiment 1-1 (3H)-ketone with 3,6,7 of equimolar amount, 8-tetrahydrochysene-1H-indeno [4; 5-c] furans-1-ketone replacement, other operational conditions get 2-methyl-2,3 with embodiment 1; 6,7-tetrahydrochysene-s-indacene-1 (5H)-ketone 135.2g, productive rate 72.6%.Spectral data is following:
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 the 2L reaction flask, adding 600ml DMSO, 1mol trityl sodium, drip 1mol 3 Methylbutanoic acid ethyl ester and 1mol 7-phenyl isobenzofuran-1 (3H)-alcohol/ketone mixtures under the mechanical stirring condition, the maintenance temperature of reaction is-10-0 ℃; Dropwise, slowly be warmed up to room temperature and continue reaction 12 hours, add water 800ml dilution after reaction is accomplished; Use n-hexane extraction again; Distillation desolventizes, and gets 1,3-dicarbonyl compound 290.5g.
With the dissolving of 600ml ethylene dichloride, add 3% mol catalyst iodine again, mechanical stirring reaction 14 hours to above-mentioned 290.5g dicarbonyl compound; After-filtration is accomplished in reaction, and filtrating extracts with ethylene dichloride with after the concentrated hydrochloric acid acidifying; After the organic layer washing once, distillation desolventizes, and gets 2-sec.-propyl-7-phenyl-2; 3-bihydrogen-1-indenone 196.3g, productive rate 78.4%.Spectral data is following:
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
Replace the NSC 8882 of the 3 Methylbutanoic acid ethyl ester among the embodiment 12 with equimolar amount, other operational conditions get 2-butyl-7-phenyl-2,3-bihydrogen-1-indenone 113.9g, productive rate 43.1% with embodiment 12.Spectral data is following:
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
Replace the 2-cyclohexyl acetic acid ethyl ester of the 3 Methylbutanoic acid ethyl ester among the embodiment 12 with equimolar amount, other operational conditions get 7-phenyl-2-cyclohexyl-2,3-bihydrogen-1-indenone 119.5g, productive rate 41.2% with embodiment 12.Spectral data is following:
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
Replace 4-bromine isobenzofuran-1 (the 3H)-ketone with equimolar amount of 7-phenyl isobenzofuran-1 (the 3H)-ketone among the embodiment 12, other operational conditions get 2-sec.-propyl-4-bromo-2,3-bihydrogen-1-indenone 152.9g, productive rate 81.2% with embodiment 12.Spectral data is following:
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
Replace 4-p-methoxy-phenyl isobenzofuran-1 (the 3H)-ketone of the isobenzofuran among the embodiment 12-1 (3H)-ketone with equimolar amount; Other operational conditions are with embodiment 12; Get 2-sec.-propyl-4-p-methoxy-phenyl-2,3-bihydrogen-1-indenone 207.7g, productive rate 74.1%.Spectral data is following:
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 the 2L reaction flask, adding 600ml DMSO, 1mol diisopropylamino lithium, drip 1mol ethyl n-butyrate and 1mol isobenzofuran-1 (3H)-alcohol/ketone mixtures under the mechanical stirring condition, the maintenance temperature of reaction is-10-0 ℃; Dropwise, slowly be warmed up to room temperature and continue reaction 12 hours, add water 800ml dilution after reaction is accomplished; Use n-hexane extraction again; Distillation desolventizes, and gets 1,3-dicarbonyl compound 200.8g.
With the dissolving of 600ml ethylene dichloride, add 5% mol catalyst iodine again, mechanical stirring reaction 14 hours to above-mentioned 200.8g dicarbonyl compound; After-filtration is accomplished in reaction, and filtrating extracts with ethylene dichloride with after the concentrated hydrochloric acid acidifying; After the organic layer washing once, distillation desolventizes, and gets 2-ethyl-2; 3-bihydrogen-1-indenone 111.0g, productive rate 69.3%.Spectral data is following:
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
Replace the isobenzofuran among the embodiment 17-1 (3H)-ketone 4-chlorine isobenzofuran-1 (3H)-ketone with equimolar amount, other operational conditions get 4-chloro-2-ethyl-2,3-bihydrogen-1-indenone 106.7g, productive rate 54.8% with embodiment 17.Spectral data is following:
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
The naphtho-[1 of the isobenzofuran among the embodiment 17-1 (3H)-ketone with equimolar amount; 2-c] furans-1 (3H)-ketone replacement; Ethyl n-butyrate replaces with the ethyl propionate of equimolar amount simultaneously, and other operational conditions get 2 with embodiment 17; 3-dihydro-2-methyl isophthalic acid H-benzo [e] 1-Indanone 137.4g, productive rate 70.0%.Spectral data is following:
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
Replace 6-fluorine isobenzofuran-1 (the 3H)-ketone of the isobenzofuran among the embodiment 17-1 (3H)-ketone with equimolar amount; Ethyl n-butyrate replaces with the ethyl propionate of equimolar amount simultaneously; Other operational conditions are with embodiment 17; Get 6-fluoro-2-methyl-2,3-bihydrogen-1-indenone 69.4g, productive rate 42.3%.Spectral data is following:
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 kind of compound method of indanone compounds may further comprise the steps:
(1) in ethanol, adds trityl sodium; Be the ester compound and the mixture that replaces isobenzofuran-1 (3H)-ketone compound that adding in 0.1: 1 contains alpha-methylene in molar ratio under well-beaten condition, stirring reaction is 48 hours under-30 ℃ condition, adds the deionized water diluted reaction mixture then; Extract with normal hexane again; Normal hexane is fallen in redistillation, promptly obtains 1, the 3-dicarbonyl compound.
Wherein, replace isobenzofuran-1 (3H)-ketone compound molecular formula, contain the ester cpds and 1 of alpha-methylene, the molecular formula of 3-dicarbonyl compound is respectively:
R
1, R
4Represent H, Cl, Br, I, F, alkoxyl group, replacement or unsubstituted C respectively independently
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
1Be Cl, R
4Be 1-base how.
R
5Represent H, Cl, Br, C
1-C
18The straight or branched alkyl, in the present embodiment, R
5Be C
4Straight chained alkyl.
R
2And R
3Represent H, Cl, Br, I, F, alkoxyl group, C respectively independently
1-C
18The straight or branched alkyl, in the present embodiment, R
2Be H, R
3Be C
5Branched-chain alkyl.
(2) be adding 1 in 1: 0.01 in molar ratio in organic chemistry solvent ethylene dichloride; 3-dicarbonyl compound and iron catalyst, control reaction temperature are 0 ℃, stirring reaction 48 hours; Filter then; Add hcl acidifying in the filtrating, reaction finishes the back standing demix, and the organic layer utilization is washed and distilled solvent and promptly obtains replacing the indone compound later on.
The molecular formula of the replacement indanone compounds for preparing is:
R
1, R
2, R
3, R
4, R
5With top identical.
Embodiment 22
A kind of compound method of indanone compounds may further comprise the steps:
(1) in methylene dichloride, adds sodium ethylate; Be the ester compound and the mixture that replaces isobenzofuran-1 (3H)-ketone compound that adding in 1: 1 contains alpha-methylene in molar ratio under well-beaten condition, stirring reaction is 36 hours under 10 ℃ condition, adds the deionized water diluted reaction mixture then; Extract with normal hexane again; Normal hexane is fallen in redistillation, promptly obtains 1, the 3-dicarbonyl compound.
Wherein, replace isobenzofuran-1 (3H)-ketone compound molecular formula, contain the ester cpds and 1 of alpha-methylene, the molecular formula of 3-dicarbonyl compound is respectively:
R
1, R
4Represent H, Cl, Br, I, F, alkoxyl group, replacement or unsubstituted C respectively independently
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
1Be 3-aminomethyl phenyl, R
4Be 3, the 5-3,5-dimethylphenyl.
R
5Represent H, C1, Br, C
1-C
18The straight or branched alkyl, in the present embodiment, R
5Be Cl.
R
2And R
3Represent H, Cl, Br, I, F, alkoxyl group, C respectively independently
1-C
18The straight or branched alkyl, in the present embodiment, R
2Be Cl, R
3Be C
6Straight chained alkyl.
(2) be adding 1 in 1: 0.1 in molar ratio in the organic chemistry methylene chloride; 3-dicarbonyl compound and aluminum trichloride catalyst, control reaction temperature are 30 ℃, stirring reaction 36 hours; Filter then; Add hcl acidifying in the filtrating, reaction finishes the back standing demix, and the organic layer utilization is washed and distilled solvent and promptly obtains replacing the indone compound later on.
The molecular formula of the replacement indanone compounds for preparing is:
R
1, R
2, R
3, R
4, R
5With top identical.
Embodiment 23
A kind of compound method of indanone compounds may further comprise the steps:
(1) in methylene dichloride, adds sodium ethylate; Be the ester compound and the mixture that replaces isobenzofuran-1 (3H)-ketone compound that adding in 5: 1 contains alpha-methylene in molar ratio under well-beaten condition, stirring reaction is 12 hours under 80 ℃ condition, adds the deionized water diluted reaction mixture then; Extract with normal hexane again; Normal hexane is fallen in redistillation, promptly obtains 1, the 3-dicarbonyl compound.
Wherein, replace isobenzofuran-1 (3H)-ketone compound molecular formula, contain the ester cpds and 1 of alpha-methylene, the molecular formula of 3-dicarbonyl compound is respectively:
R
1, R
4Represent H, Cl, Br, I, F, alkoxyl group, replacement or unsubstituted C respectively independently
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
1Be 4-tert-butyl-phenyl, R
4Be alkoxyl group.
R
5Represent H, Cl, Br, C
1-C
18The straight or branched alkyl, in the present embodiment, R
5Be C
6Branched-chain alkyl.
R
2And R
3Represent H, Cl, Br, I, F, alkoxyl group, C respectively independently
1-C
18The straight or branched alkyl, in the present embodiment, R
2Be Br, R
3Be C
5Straight chained alkyl.
(2) be adding 1 in 1: 0.3 in molar ratio in the organic chemistry methylene chloride; 3-dicarbonyl compound and polyphosphoric acid catalyzed dose, control reaction temperature is 100 ℃, stirring reaction 12 hours; Filter then; Add hcl acidifying in the filtrating, reaction finishes the back standing demix, and the organic layer utilization is washed and distilled solvent and promptly obtains replacing the indone compound later on.
The molecular formula of the replacement indanone compounds for preparing is:
R
1, R
2, R
3, R
4, R
5With top identical.
Embodiment 24
A kind of compound method of indanone compounds may further comprise the steps:
(1) in methylene dichloride, adds sodium ethylate; Be the ester compound and the mixture that replaces isobenzofuran-1 (3H)-ketone compound that adding in 5: 1 contains alpha-methylene in molar ratio under well-beaten condition, stirring reaction is 0.1 hour under 150 ℃ condition, adds the deionized water diluted reaction mixture then; Extract with normal hexane again; Normal hexane is fallen in redistillation, promptly obtains 1, the 3-dicarbonyl compound.
Wherein, replace isobenzofuran-1 (3H)-ketone compound molecular formula, contain the ester cpds and 1 of alpha-methylene, the molecular formula of 3-dicarbonyl compound is respectively:
R
1, R
4Represent H, Cl, Br, I, F, alkoxyl group, replacement or unsubstituted C respectively independently
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
1Be F, R
4Be 3,5-phenylbenzene phenyl.
R
5Represent H, Cl, Br, C
1-C
18The straight or branched alkyl, in the present embodiment, R
5Be H.
R
2And R
3Represent H, Cl, Br, I, F, alkoxyl group, C respectively independently
1-C
18The straight or branched alkyl, in the present embodiment, R
2Be H, R
3Be C
8Straight chained alkyl.
(2) be adding 1 in 1: 0.5 in molar ratio in organic chemistry solvent DMSO; 3-dicarbonyl compound and iodine catalyst, control reaction temperature are 200 ℃, stirring reaction 0.1 hour; Filter then; Add hcl acidifying in the filtrating, reaction finishes the back standing demix, and the organic layer utilization is washed and distilled solvent and promptly obtains replacing the indone compound later on.
The molecular formula of the replacement indanone compounds for preparing is:
R
1, R
2, R
3, R
4, R
5With top identical.
Claims (10)
1. the compound method of an indanone compounds is characterized in that, this method may further comprise the steps:
(1) is raw material to replace isobenzofuran-1 (3H)-ketone compound, reacts, be converted into 1, the 3-dicarbonyl compound with the ester cpds that contains alpha-methylene;
(2) prepare 1, the 3-dicarbonyl compound carries out intramolecular cyclization, acidic conditions decarboxylic reaction under catalyst action, be converted into the replacement indanone compounds, is product.
2. the compound method of a kind of indanone compounds according to claim 1 is characterized in that,
The molecular formula of described replacement isobenzofuran-1 (3H)-ketone compound is:
The described molecular formula that contains the ester cpds of alpha-methylene is:
Described 1, the molecular formula of 3-dicarbonyl compound is:
The molecular formula of described replacement indanone compounds is:
3. the compound method of a kind of indanone compounds according to claim 2 is characterized in that, R
1, R
4Represent H, Cl, Br, I, F, alkoxyl group, replacement or unsubstituted C respectively independently
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.
4. the compound method of a kind of indanone compounds according to claim 2 is characterized in that, R
5Represent H, Cl, Br, C
1-C
18The straight or branched alkyl, preferred H, C
1-C
10The straight or branched alkyl.
5. the compound method of a kind of indanone compounds according to claim 2 is characterized in that, R
2And R
3Represent H, Cl, Br, I, F, alkoxyl group, C respectively independently
1-C
18The straight or branched alkyl is at C
1-C
18In the straight or branched alkyl, preferred C
1-C
10The straight or branched alkyl.
6. the compound method of a kind of indanone compounds according to claim 2 is characterized in that, R
1And R
2Perhaps R
2And R
3Perhaps R
3And R
4Between can be connected to C
3-C
12Cycloaliphatic ring or aromatic nucleus.
7. the compound method of a kind of indanone compounds according to claim 1 is characterized in that, step (1) specifically may further comprise the steps:
In anhydrous chemical solvents, add alkali; Under well-beaten condition in molar ratio for (0.1-10): 1 adds ester compound that contains alpha-methylene and the mixture that replaces isobenzofuran-1 (3H)-ketone compound, under-30-150 ℃ condition stirring reaction 0.1-48 hour, adds the deionized water diluted reaction mixture then; Use water-fast organic solvent extraction again; Water-fast organic solvent is fallen in redistillation, promptly obtains 1, the 3-dicarbonyl compound.
8. the compound method of a kind of indanone compounds according to claim 7 is characterized in that, described alkali comprises C
1-C
20Primary, sodium alkoxide, potassium alcoholate, the aluminium alcoholates of the second month in a season or the tertiary alcohol, sodium hydride, potassium hydride KH, trityl sodium, diisopropylamino lithium (LDA) or Grignard reagent, preferred C
1-C
6Primary, sodium alkoxide, potassium alcoholate, the aluminium alcoholates of the second month in a season or the 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 a normal hexane.
9. the compound method of a kind of indanone compounds according to claim 1 is characterized in that, step (2) specifically may further comprise the steps:
Be 1 in molar ratio in the organic chemistry solvent: (0.01-0.5) add 1; 3-dicarbonyl compound and catalyzer, control reaction temperature are 0-200 ℃, stirring reaction 0.1-48 hour; Filter then; Add hcl acidifying in the filtrating, reaction finishes the back standing demix, and the organic layer utilization is washed and distilled solvent and promptly obtains replacing the indone compound later on.
10. the compound method of a kind of indanone compounds according to claim 9 is characterized in that, 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, and described metallic compound comprises aluminum chloride or palladium, and described nonmetallic compound comprises polyphosphoric acid or phosphorus oxide.
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| CN109053446A (en) * | 2018-09-13 | 2018-12-21 | 苏州大学张家港工业技术研究院 | Metal hydride/palladium compound system prepares the application in 1,3- dicarbonyl compound in Electron-poor olefin compound tandem reaction |
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