CN107311849B - Synthetic method of ring-bridged spiroindanone compound - Google Patents
Synthetic method of ring-bridged spiroindanone compound Download PDFInfo
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Abstract
A synthesis method of a ring-bridged spiro-indanone compound belongs to the technical field of organic synthesis, aromatic aldehyde and multi-molecule 1,3-indandione are subjected to domino reaction in the presence of a solvent and a catalyst, and after the reaction is finished, silica gel column chromatography is performed by using a mixed solvent of ethyl acetate and petroleum ether to obtain the ring-bridged spiro-indanone compound. Wherein the solvent is ethanol or methanol; the catalyst is triethylamine, piperidine, triethylene diamine or 1, 8-diazabicycloundec-7-ene. The invention has the advantages of wide substrate expansion range, easily obtained raw materials, simple operation and synthesis without transition metal catalyst.
Description
Technical Field
The invention belongs to the technical field of organic synthesis.
Background
1,3-Indandione has nucleophilic methylene and electrophilic carbonyl groups, and is susceptible to Condensation reactions with multiple molecules (Jacob, K.; Sigalov, M.; et al. Self-Condensation of 1,3-Indandione: A Reinforcement).[J].Eur. J. Org. Chem.2000, 2047-2055). The trimer of the 1,3-indandione has a large conjugated system, and has a plurality of applications in the field of photoelectric materials. In 2012, the Martini task group reported the synthesis of 1, 3-indanedione trimers and their derivatives as Bowl-shaped electron donors for use as photovoltaic materials for absorbing solar energy (Isla, H.; Martini, N.; et al, Bowl-shape electron donors with the same absorption of solar energy and the same summer-shaped electron assembly switch C)60[J].Chem. Sci., 2012,3, 498-508）。
Spiroindanone compounds are widely available in bioactive molecules such as natural products, medicines, pesticides and the like, and show outstanding physiological activities such as anti-tumor, anti-hypertension, anti-allergy and the like. The indeno-ring derivatives also exhibit multiple biogenesisSubstances and pharmacological activities, such as an alkaloid isolated from annona squamosa having an indanone pyridine skeleton, derivatives thereof found to have phosphodiesterase activity and adenosine A2a receptor binding inhibition, are useful for the treatment of neurodegenerative and inflammation-related diseases (Aran go, g.j.; cortex, d.; et al., azafluorogens from oxndra cf. major and dbogenetic compositions [ J].Phytochemistry, 1987,26, 2093-2098)。
The 1,3-indandione can be used for synthesizing spiroindanone compounds, but derivatization is relatively difficult due to the specificity of a 1,3-indandione substrate, and the methods reported in the literature have some problems to different degrees, such as use of strong acid and strong alkaline solvent, long reaction time, low yield, small substrate expansion range and the like. Therefore, the synthesis of the spiroindanone compound by using the 1,3-indandione and the derivatization to synthesize the cyclic bridged spiroindanone compound have important significance.
Disclosure of Invention
The technical problem to be solved by the invention is to overcome the problems and provide a compound of the ring-bridged spiro indanone which has the advantages of wide substrate expansion range, easily available raw materials, simple operation and no need of a transition metal catalyst.
The technical scheme of the invention is as follows: in the presence of a solvent and a catalyst, aromatic aldehyde and multi-molecule 1,3-indandione undergo a domino reaction, and after the reaction is finished, silica gel column chromatography is performed by using a mixed solvent of ethyl acetate and petroleum ether to obtain the ring-bridged spiroindanone compound. Wherein the solvent is ethanol or methanol; the catalyst is triethylamine, piperidine, triethylene diamine or 1, 8-diazabicycloundec-7-ene.
The general reaction formula is as follows:
wherein: r is C1～C4Alkyl-substituted phenyl, halophenyl, nitro-substituted phenyl, pyridyl or C1～C3Any one of the alkyl groups of (1).
The mechanism of the invention is as follows: the multi-molecular 1,3-indandione is condensed to generate an intermediate A, the intermediate A is subjected to electrocyclization to generate a B, and further [1,5] -H is transferred to form C,1, 3-indandione which is condensed with aldehyde to form E which is subjected to Diels-Alder reaction with the intermediate C to generate a final ring-bridged spiroindanone compound, wherein the reaction yield can reach 43% -74%.
The detailed process of the invention is as follows:
the invention takes easily obtained aromatic aldehyde and multi-molecule 1,3-indandione as raw materials, does not need anhydrous and anaerobic reaction conditions in the absence of a transition metal catalyst, does not need to add strong acid or strong base, and does not need to pre-treat the used raw materials, solvent and catalyst. The synthesis method is simple and convenient to operate, high in yield and environment-friendly.
Furthermore, R is any one of phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-nitrophenyl, 4-halophenyl, 3-methylphenyl, 3-methoxyphenyl, 3-nitrophenyl, 3-halophenyl, 2-methoxyphenyl, 2-halophenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, methyl, ethyl, propyl or butyl, and the synthetic yield can reach 43-76%.
More preferably, the aromatic aldehyde is benzaldehyde, m-methoxybenzaldehyde, m-chlorobenzaldehyde, m-methylbenzaldehyde, p-nitrobenzaldehyde, 4-pyridinecarboxaldehyde, m-fluorobenzaldehyde or p-bromobenzaldehyde. By adopting the specific substances to react the aromatic aldehyde and the multi-molecule 1,3-indandione, higher yield can be obtained.
The solvent is at least one of ethanol or methanol, and ethanol is preferred. When R is phenyl and ethanol is used as a solvent, the yield can reach 71 percent.
The catalyst is triethylamine, piperidine, triethylene Diamine (DABCO) or 1, 8-diazabicycloundecen-7-ene (DBU). Triethylamine or piperidine is preferred. When R is 2-methoxyphenyl and triethylamine is used as a solvent, the yield can reach 74 percent.
The feeding molar ratio of the aromatic aldehyde to the catalyst is 1: 1-4. The dosage of the catalyst is less than 1: 1, and the reaction is hardly carried out; over 4 times the amount, the product yield did not increase.
The feeding molar ratio of the aromatic aldehyde to the 1,3-indandione is 1: 4-5, and the reaction yield can reach 68-74% under the molar ratio.
The temperature condition of the domino reaction is 30-80 ℃. In view of the fact that the preferred solvent is ethanol, and more preferably, the reaction temperature is 78 deg.C, ethanol reflux (78 deg.C) is performed under normal pressure, the reaction time can be shortened to 5 hours. At this temperature, the reaction efficiency is highest. If the temperature is too high and the time is too long, the byproducts are increased; if the temperature is too low and the time is too short, the reaction is not complete. The highest reaction yield can reach 74 percent.
Detailed Description
The present invention will be described in further detail with reference to examples, but the scope of the present invention is not limited to these examples.
Example 1: preparation of 4b ' -hydroxy-17 ' -phenyl-4 b ',14c ' -dihydro-15 'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone:
a50 mL round-bottomed flask was charged with 0.053g (0.5mmol) of benzaldehyde, 0.321g (2.2mmol) of 1,3-indandione, and 20 mL of ethanol and 0.101g (1.0mmol) of triethylamine were added thereto to conduct a domino reaction under heating and refluxing (78 ℃ C.) for 5 hours.
After the reaction is finished, the solvent is evaporated and concentrated, and the mixture solvent of ethyl acetate and petroleum ether is used for silica gel column chromatography purification treatment, so that pure 4b '-hydroxy-17' -phenyl-4 b ',14c' -dihydro-15 'can be obtained'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone in an isolated yield of 71%.
The structural characterization data is as follows:
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.66 (d,J= 7.6 Hz, 1H, ArH), 8.13 (d,J= 7.6 Hz, 1H, ArH), 7.90 (t,J= 7.6 Hz, 1H, ArH), 7.81 (t,J= 6.8 Hz, 1H,ArH), 7.67-7.65 (m, 1H, ArH), 7.64-7.62 (m, 2H, ArH), 7.61-7.59 (m, 1H, ArH),7.43 (d,J= 7.6 Hz, 1H, ArH), 7.36 (d,J= 7.2 Hz, 1H, ArH), 7.32 (d,J=7.2 Hz, 1H, ArH), 7.29-7.24 (m, 2H, ArH), 7.20 (d,J= 7.6 Hz, 2H, ArH), 7.15(d,J= 8.0 Hz, 1H, ArH), 7.04 (d,J= 7.6 Hz, 1H, ArH), 6.90 (s, 1H, OH),6.86 (t,J= 7.6 Hz, 1H, ArH), 6.74 (t,J= 7.6 Hz, 2H, ArH), 6.47-6.44 (m,1H, ArH), 5.36 (s, 1H, CH), 4.43 (s, 1H, CH);13C NMR (150 MHz, DMSO-d 6 ) δ:201.7, 200.4, 199.0, 196.8, 188.2, 152.4, 146.0, 144.2, 142.3, 141.9, 141.4,140.7, 140.4, 137.1, 136.8, 136.6, 136.0, 135.2, 134.9, 134.7, 132.9, 129.6,129.1, 128.3, 127.7, 127.4, 127.1, 125.6, 125.2, 123.7, 123.2, 123.1, 122.3,121.8, 84.1, 65.5, 62.2, 58.3, 54.3, 52.2; IR (KBr) υ:3469, 3065, 2962, 1703,1656, 1592, 1459, 1251, 1067, 767, 701cm-1; MS (m/z): HRMS (ESI) C43H25O6([M+H]+) Theoretical 637.1464, found 637.1627.
Example 2: preparation of 4b ' -hydroxy-17 ' - (2-methoxyphenyl) -4b ',14c ' -dihydro-15 'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone:
a50 mL round-bottomed flask was charged with 0.068g (0.5mmol) of m-methoxybenzaldehyde, 0.365g (2.5mmol) of 1,3-indandione, 15 mL of methanol and 0.127g (1.5mmol) of triethylamine, and domino reaction was carried out at 50 ℃ for 8 hours.
After the reaction is finished, the solvent is evaporated and concentrated, and the mixture solvent of ethyl acetate and petroleum ether is used for silica gel column chromatography purification treatment, so that the 4b '-hydroxy-17' - (2-methoxyphenyl) -4b ',14c' -dihydro-1 can be obtained5'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone in an isolated yield of 74%.
The structural characterization data is as follows:
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.59 (d,J= 7.6 Hz, 1H, ArH), 8.12 (d,J= 7.6 Hz, 1H, ArH), 7.88 (t,J= 7.6 Hz, 1H, ArH), 7.77 (t,J= 8.0 Hz, 1H,ArH), 7.73 (d,J= 7.6 Hz, 1H, ArH), 7.65 (t,J= 7.2 Hz, 1H, ArH), 7.62-7.56(m, 2H, ArH), 7.44-7.40 (m, 1H, ArH), 7.34 (t,J= 7.6 Hz, 1H, ArH), 7.31-7.27 (m, 1H, ArH), 7.27-7.25 (m, 1H, ArH), 7.22-7.19 (m, 2H, ArH), 7.16 (d,J= 7.6 Hz, 1H, ArH), 7.00 (d,J= 7.6 Hz, 1H, ArH), 6.86-6.81 (m, 1H, ArH),6.80 (s, 1H, OH), 6.38 (d,J= 8.4 Hz, 1H, ArH), 6.30 (d,J= 7.6 Hz, 1H,ArH), 6.16-6.14 (m, 1H, ArH), 5.87 (s, 1H, CH), 4.52 (s, 1H, CH), 3.03 (s,3H, OCH3);13C NMR (150 MHz, DMSO-d 6 ) δ: 203.6, 202.2, 199.7, 196.1, 188.5,156.1, 151.4, 145.7, 144.2, 143.3, 142.6, 141.8, 141.5, 140.5, 137.6, 136.1,135.5, 135.3, 135.2, 135.0, 134.4, 132.2, 129.6, 129.4, 129.0, 128.6, 128.5,125.6, 124.7, 124.5, 123.9, 123.4, 123.0, 122.8, 122.4, 120.4, 109.6, 85.1,63.9, 62.3, 58.9, 55.1, 54.2, 44.4; IR (KBr) υ: 3390, 3066, 2930, 2834, 1708,1653, 1592, 1461, 1333, 1194, 1063, 760, 701 cm-1; MS (m/z): HRMS (ESI)C44H27O7([M+ H]+) Theoretical value is 667.1751, found 667.1753.
Example 3: preparation of 4b '-hydroxy-17' - (2-chlorophenyl) -4b ',14c' -dihydro-15 'of the formula'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone:
a50 mL round-bottomed flask was charged with 0.070g (0.5mmol) of m-chlorobenzaldehyde, 0.292g (2.0mmol) of 1,3-indandione, 15 mL of methanol, 0.127g (1.5mmol) of piperidine, and domino reaction was carried out at 40 ℃ for 10 hours.
After the reaction is finished, the solvent is evaporated and concentrated, and the mixture of ethyl acetate and petroleum ether is used for silica gel column chromatography purification treatment, so that 4b '-hydroxy-17' - (2-chlorphenyl) -4b ',14c' -dihydro-15 'can be obtained'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]1,3,5',10',15' -pentaketone in an isolated yield of 68%,
the structural characterization data is as follows:
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.63 (d,J= 8.0 Hz, 1H, ArH), 8.13 (d,J= 7.6 Hz, 1H, ArH), 7.91 (t,J= 7.6 Hz, 1H, ArH), 7.80 (t,J= 7.6 Hz, 1H,ArH), 7.71-7.69 (m, 1H, ArH), 7.67-7.64 (m, 3H, ArH), 7.42 (t,J= 7.2 Hz,1H, ArH), 7.37 (d,J= 7.2 Hz, 1H, ArH), 7.34-7.33 (m, 1H, ArH), 7.31-7.25(m, 2H, ArH), 7.23-7.15 (m, 3H, ArH), 7.13 (d,J= 7.6 Hz, 1H, ArH), 6.97-6.95 (m, 1H, ArH), 6.94 (s, 1H, OH), 6.82 (t,J= 8.0 Hz, 1H, ArH), 6.47-6.46(m, 1H, ArH), 5.35 (s, 1H, CH), 4.39 (s, 1H, CH);13C NMR (150 MHz, DMSO-d 6 )δ: 203.0, 202.1, 199.4, 195.9, 188.3, 151.4, 145.2, 143.6, 143.4, 142.8,141.6, 141.4, 140.1, 137.5, 136.5, 136.3, 136.1, 135.9, 135.3, 135.2, 134.4,133.7, 132.3, 130.4, 129.7, 129.2, 129.1, 128.6, 128.0, 125.7, 124.5, 124.2,123.5, 123.3, 123.2, 123.1, 84.6, 65.5, 62.4, 58.0, 55.4, 52.6; IR (KBr) υ:3364, 3066, 2961, 1703, 1659, 1590, 1464, 1194, 888, 762, 701cm-1; MS (m/z):HRMS (ESI) C43H24ClO6([M+H]+) Theoretical 671.1256, found 671.1237.
Example 4: preparation of 4b ' -hydroxy-17 ' - (3-methylphenyl) -4b ',14c ' -dihydro-15 'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone:
a50 mL round-bottomed flask was charged with 0.060g (0.5mmol) of m-tolualdehyde, 0.438g (3.0mmol) of 1,3-indandione, and then with 25 mL of methanol, 0.224g (2.0mmol) of triethylenediamine (DABCO) was added thereto, and domino reaction was carried out at 80 ℃ for 5 hours.
After the reaction is finished, the solvent is evaporated and concentrated, and the mixture of ethyl acetate and petroleum ether is used for silica gel column chromatography purification treatment, so that 4b '-hydroxy-17' - (3-methylphenyl) -4b ',14c' -dihydro-15 'can be obtained'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone in an isolated yield of 63%.
The structural characterization data is as follows:
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.65 (d,J= 7.6 Hz, 1H, ArH), 8.12 (d,J= 7.6 Hz, 1H, ArH), 7.89 (t,J= 7.6 Hz, 1H, ArH), 7.80 (t,J= 7.2 Hz, 1H,ArH), 7.69-7.61 (m, 4H, ArH), 7.44 (t,J= 7.2 Hz, 1H, ArH), 7.38-7.33 (m,2H, ArH), 7.32-7.25 (m, 2H, ArH), 7.22 (d,J= 8.0 Hz, 2H, ArH), 7.17 (d,J=7.6 Hz, 1H, ArH), 7.06 (d,J= 7.6 Hz, 1H, ArH), 6.90 (s, 1H, OH), 6.69-6.66(m, 1H, ArH), 6.64-6.61 (m, 1H, ArH), 6.24-6.17 (m, 1H, ArH), 5.32 (s, 1H,CH), 4.43 (s, 1H, CH), 1.72 (s, 3H, CH3);13C NMR (150 MHz, DMSO-d 6 ) δ: 203.3,202.4, 199.7, 196.1, 188.5, 151.6, 145.6, 143.8, 143.7, 143.0, 141.7, 141.4,140.3, 137.6, 137.4, 136.2, 136.0, 135.5, 135.3, 135.2, 134.4, 133.8, 132.1,129.6, 129.1, 128.5, 128.4, 127.7, 125.6, 124.4, 124.2, 123.4, 123.2, 123.0,122.9, 84.7, 65.8, 62.6, 58.1, 55.1, 53.4, 20.9; IR (KBr) υ:3512, 3067, 2922,1704, 1655, 1590, 1460, 1365, 1189, 1066, 771, 701 cm-1; MS (m/z): HRMS (ESI)C44H27O6([M+H]+) Theoretical 651.1789, found 651.1783.
Example 5: preparation of 4b ' -hydroxy-17 ' - (4-nitrophenyl) -4b ',14c '-dihydro-15'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone:
a50 mL round-bottomed flask was charged with 0.076g (0.5mmol) of p-nitrobenzaldehyde and 0.511g (3.5mmol) of 1,3-indandione, and then with 25 mL of ethanol and then with 0.056g (0.5mmol) of triethylenediamine (DABCO), and domino reaction was carried out at 78 ℃ for 5 hours.
After the reaction is finished, the solvent is evaporated and concentrated, and the mixture of ethyl acetate and petroleum ether is used for silica gel column chromatography purification treatment, so that 4b '-hydroxy-17' - (4-nitrophenyl) -4b ',14c' -dihydro-15 'can be obtained'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone in an isolated yield of 49%.
The structural characterization data is as follows:
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.63 (d,J= 7.6 Hz, 1H, ArH), 8.13 (d,J= 7.6 Hz, 1H, ArH), 7.92 (t,J= 7.2 Hz, 1H, ArH), 7.81 (t,J= 7.6 Hz, 1H,ArH), 7.70-7.67 (m, 3H, ArH), 7.65-7.63 (m, 3H, ArH), 7.43-7.41 (m, 1H, ArH),7.38 (d,J= 6.0 Hz, 1H, ArH), 7.35 (d,J= 7.6 Hz, 1H, ArH), 7.32-7.28 (m,2H, ArH), 7.24 (d,J= 7.2 Hz, 1H, ArH), 7.17-7.12 (m, 3H, ArH), 7.03 (s, 1H,OH), 6.83-6.75 (m, 1H, ArH), 5.54 (s, 1H, CH), 4.34 (s, 1H, CH);13C NMR (100MHz, DMSO-d 6 ) δ: 202.6, 201.7, 199.2, 195.9, 188.1, 151.1, 147.1, 144.8,143.4, 143.2, 142.4, 141.8, 141.4, 141.2, 139.9, 137.4, 136.7, 136.6, 136.2,135.3, 134.5, 132.6, 131.0, 129.8, 129.3, 128.6, 125.6, 124.6, 124.1, 123.6,123.4, 123.3, 123.2, 123.0, 84.6, 65.2, 62.4, 58.0, 55.6, 52.0; IR (KBr) υ:3469, 3061, 1702, 1653, 1588, 1462, 1249, 770, 701cm-1; MS (m/z): HRMS (ESI)C43H24NO8([M+H]+) Theoretical value 682.1496, found value 682.1485。
Example 6: preparation of 4b '-hydroxy-17' - (2-pyridine) -4b ',14c' -dihydro-15 'of formula'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone:
a50 mL round-bottomed flask was charged with 0.054g (0.5mmol) of 2-pyridinecarboxaldehyde and 0.511g (3.5mmol) of 1,3-indandione, and then with 25 mL of ethanol and then with 0.056g (0.5mmol) of triethylenediamine (DABCO), and domino reaction was carried out at 30 ℃ for 5 hours.
After the reaction is finished, the solvent is evaporated and concentrated, and the mixture of ethyl acetate and petroleum ether is used for silica gel column chromatography purification treatment, so that 4b '-hydroxy-17' - (2-pyridine) -4b ',14c' -dihydro-15 'can be obtained'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone in an isolated yield of 43%.
The structural characterization data is as follows:
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.52 (d,J= 7.2 Hz, 1H, ArH), 8.18 (d,J= 7.6 Hz, 1H, ArH), 7.94 (t,J= 7.6 Hz, 1H, ArH), 7.73-7.65 (m, 4H, ArH),7.63-7.56 (m, 2H, ArH), 7.34-7.28 (m, 3H, ArH), 7.25-7.18 (m, 4H, ArH), 7.12(d,J= 7.2 Hz, 1H, ArH), 7.09 (d,J= 7.6 Hz, 1H, ArH), 6.86-6.84 (m, 1H,ArH), 6.82 (s, 1H, OH), 6.42 (d,J= 8.0 Hz, 1H, ArH), 5.63 (s, 1H, CH), 4.26(s, 1H, CH);13C NMR (100 MHz, DMSO-d 6 ) δ: 202.2, 200.7, 200.1, 196.5, 188.4,156.1, 152.8, 148.4, 146.7, 145.8, 142.5, 142.3, 142.1, 141.6, 141.1, 137.3,137.2, 137.1, 136.5, 135.2, 135.1, 134.8, 132.9, 132.7, 129.9, 129.4, 127.4,126.2, 125.9, 124.0, 123.8, 123.0, 122.9, 122.6, 122.4, 122.1, 84.3, 64.2,61.4, 58.7, 55.1, 53.6; IR (KBr) υ:3427, 3056, 2923, 1705, 1661, 1592, 1465,1251, 778, 702 cm-1; MS (m/z): HRMS (ESI) C42H24NO6([M+H]+) Theoretical 638.1598, found 638.1620.
Example 7: preparation of 4b '-hydroxy-17' - (2-fluorophenyl) -4b ',14c' -dihydro-15 'of formula'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone:
a50 mL round-bottomed flask was charged with 0.062g (0.5mmol) of m-fluorobenzaldehyde, 0.511g (3.5mmol) of 1,3-indandione, 25 mL of ethanol, 0.152g (1.0mmol) of 1, 8-diazabicycloundecen-7-ene (DBU), and domino reaction was carried out at 78 ℃ for 5 hours.
After the reaction is finished, the solvent is evaporated and concentrated, and the mixture of ethyl acetate and petroleum ether is used for silica gel column chromatography purification treatment, so that 4b ' -hydroxy-17 ' - (2-fluorophenyl) -4b ',14c ' -dihydro-15 'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone in an isolated yield of 58%.
The structural characterization data is as follows:
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.63 (d,J= 7.6 Hz, 1H, ArH), 8.12 (d,J= 7.6 Hz, 1H, ArH), 7.90 (t,J= 7.6 Hz, 1H, ArH), 7.80 (t,J= 7.2 Hz, 1H,ArH), 7.70 (d,J= 7.2 Hz, 1H, ArH), 7.66-7.64 (m, 3H, ArH), 7.43 (t,J= 7.2Hz, 1H, ArH), 7.37 (d,J= 7.6 Hz, 1H, ArH), 7.33 (d,J= 6.8 Hz, 1H, ArH),7.31-7.21 (m, 3H, ArH), 7.20-7.15 (m, 2H, ArH), 7.12 (t,J= 8.0 Hz, 1H,ArH), 6.95 (s, 1H, OH), 6.87-6.81 (m, 1H, ArH), 6.76-6.71 (m, 1H, ArH), 6.38-6.37 (m, 1H, ArH), 5.37 (s, 1H, CH), 4.40 (s,1H, CH);13C NMR (100 MHz, DMSO-d 6 ) δ: 203.1, 202.1, 199.5, 196.0, 188.3, 161.9 (d,J= 246.0 Hz), 151.4,145.2, 143.6, 143.4, 142.8, 141.6, 141.4, 140.1, 137.5, 136.6 (d,J= 7.2Hz), 136.5, 136.3, 135.8, 135.3, 135.2, 134.5, 132.3, 129.7, 129.4 (d,J=8.1 Hz), 129.2, 128.6, 125.8, 125.6, 124.5, 124.2, 123.5, 123.3, 123.2,123.0, 117.2 (d,J= 25.6 Hz), 114.9 (d,J= 20.7 Hz), 84.7, 65.5, 62.5,58.0, 55.3, 52.7; IR (KBr) υ: 3471, 3072, 2922, 1703, 1658, 1591, 1459, 1255,955, 884, 773, 698 cm-1; MS (m/z): HRMS (ESI) C43H24FO6([M+H]+) Theoretical 655.1552, found 655.1551.
Example 8: preparation of 4b ' -hydroxy-17 ' - (4-bromophenyl) -4b ',14c ' -dihydro-15 'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone:
a50 mL round-bottomed flask was charged with 0.092g (0.5mmol) of p-bromobenzaldehyde, 0.511g (3.5mmol) of 1,3-indandione, and then with 25 mL of ethanol, and then with 0.152g (1.0mmol) of 1, 8-diazabicycloundecen-7-ene (DBU), and domino reaction was carried out at 78 ℃ for 5 hours.
After the reaction is finished, the solvent is evaporated and concentrated, and the mixture of ethyl acetate and petroleum ether is used for silica gel column chromatography purification treatment, so that 4b '-hydroxy-17' - (4-bromophenyl) -4b ',14c' -dihydro-15 'can be obtained'HSpiro [ indene-2, 16' - [4c,14b ]]Ethyl bis-indene [1,2-a:1',2'-c]Fluorene compounds]-1,3,5',10',15' -pentaketone in an isolated yield of 60%.
The structural characterization data is as follows:
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.64 (d,J= 7.6 Hz, 1H, ArH), 8.14 (d,J= 7.6 Hz, 1H, ArH), 7.95-7.91 (m, 1H, ArH), 7.83-7.80 (m, 1H, ArH), 7.73-7.69(m, 2H, ArH), 7.68-7.66 (m, 2H, ArH), 7.47-7.43 (m, 1H, ArH), 7.41-7.37 (m,1H, ArH), 7.36-7.33 (m, 1H, ArH), 7.32-7.27 (m, 2H, ArH), 7.25-7.17 (m, 4H,ArH), 7.03 (d,J= 8.8 Hz, 2H, ArH), 6.96 (s, 1H, OH), 6.49-6.43 (m, 1H,ArH), 5.38 (s, 1H, CH), 4.41 (s, 1H, CH);13C NMR (100 MHz, DMSO-d 6 ) δ: 203.1,202.0, 199.4, 196.1, 188.3, 151.3, 145.2, 143.5, 143.4, 142.7, 141.5, 141.3,140.0, 137.4, 136.4, 136.3, 135.8, 135.3, 135.2, 134.4, 133.1, 132.3, 131.7,131.0, 129.7, 129.2, 128.5, 125.5, 124.5, 124.1, 123.5, 123.3, 123.2, 123.1,122.0, 84.6, 65.4, 62.5, 58.0, 55.3, 52.4; IR (KBr) υ: 3478, 3071, 2956,1703, 1657, 1591, 1250, 827, 765, 704 cm-1; MS (m/z): HRMS (ESI) C43H24ClO6([M+H]+) Theoretical 715.0751, found 715.0719.
Claims (6)
1. A synthetic method of a ring-bridged spiro indanone compound is characterized by comprising the following steps: in the presence of a solvent and a catalyst, aromatic aldehyde and multi-molecule 1,3-indandione undergo a domino reaction, and after the reaction is finished, silica gel column chromatography is performed by using a mixed solvent of ethyl acetate and petroleum ether to obtain a ring-bridged spiroindanone compound;
the solvent is ethanol or methanol; the catalyst is triethylamine, piperidine, triethylene diamine or 1, 8-diazabicycloundec-7-ene;
the feeding molar ratio of the aromatic aldehyde to the 1,3-indandione is 1: 4-5; the temperature condition of the domino reaction is 30-80 ℃;
the general reaction formula is as follows:
wherein: r in aromatic aldehyde is C1～C4Alkyl-substituted phenyl, halophenyl, nitro-substituted phenyl or pyridyl.
2. The method for synthesizing the ring-bridged spiroindanone compound according to claim 1, which is characterized in that: r in the aromatic aldehyde is phenyl, 4-methylphenyl, 4-nitrophenyl, 4-halophenyl, 3-methylphenyl, 3-nitrophenyl, 3-halophenyl, 2-pyridyl, 3-pyridyl or 4-pyridyl.
3. The method for synthesizing the ring-bridged spiroindanone compound according to claim 2, which is characterized in that: the aromatic aldehyde is benzaldehyde, o-chlorobenzaldehyde, m-methylbenzaldehyde, p-nitrobenzaldehyde, 2-pyridylaldehyde, m-fluorobenzaldehyde or p-bromobenzaldehyde.
4. The method for synthesizing the ring-bridged spiroindanone compound according to claim 1, which is characterized in that: the solvent is ethanol.
5. The method for synthesizing the ring-bridged spiroindanone compound according to claim 1, which is characterized in that: the feeding molar ratio of the aromatic aldehyde to the catalyst is 1: 1-4.
6. The method for synthesizing the ring-bridged spiroindanone compound according to claim 5, which is characterized in that: the temperature condition of the domino reaction was 78 ℃.
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| CN105250260A (en) * | 2015-11-19 | 2016-01-20 | 成都中医药大学 | Anti-tumor application of 1,3-indandione spiro compound |
| CN106892921A (en) * | 2017-03-01 | 2017-06-27 | 扬州大学 | A kind of method for synthesizing spiral shell indenes pyrrolopyridines |
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| CN104557559A (en) * | 2015-01-14 | 2015-04-29 | 成都中医药大学 | Indanedione chiral cyclohexane spirocompound and preparation method and use thereof |
| CN105250260A (en) * | 2015-11-19 | 2016-01-20 | 成都中医药大学 | Anti-tumor application of 1,3-indandione spiro compound |
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