CN108689815B - Synthetic method of indanone compound - Google Patents
Synthetic method of indanone compound Download PDFInfo
- Publication number
- CN108689815B CN108689815B CN201810675285.7A CN201810675285A CN108689815B CN 108689815 B CN108689815 B CN 108689815B CN 201810675285 A CN201810675285 A CN 201810675285A CN 108689815 B CN108689815 B CN 108689815B
- Authority
- CN
- China
- Prior art keywords
- reaction
- catalyst
- formula
- compound
- solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper
- B01J23/72—Copper
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/54—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition of compounds containing doubly bound oxygen atoms, e.g. esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a synthesis method of an indanone compound, which comprises the steps of adding a catalyst and an oxidant into a reaction bottle respectively, then adding a compound shown in formula (2), then adding a solvent, reacting under the protection of argon, wherein the reaction temperature is 70-120 ℃, the reaction time is 2-6 hours, and reacting to obtain the indanone compound; wherein the catalyst is Cu (OAc)2、CuCl2、CuBr2、CuO、CuF2、Cu(OTf)2、Cu(OH)2、Cu(NO3)2、CuCl、CuBr、CuI、Cu2O, tert-butyl hydroperoxide as an oxidizing agent, and toluene as a solvent. The invention provides a new synthetic idea of indenone compounds, a copper catalyst is used, the price of copper is low, the reserve amount is rich, the copper catalyst is environment-friendly, and the copper-catalyzed hydrogenation acylation reaction meets the requirement of green chemistry.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing indanone compounds.
Background
Transition metal catalyzed hydrogenation and acylation reaction of aldehyde and unsaturated organic compounds (such as olefin, alkyne, ketone and the like) is an important reaction in organic synthesis, and a C-C bond is effectively constructed. At present, various transition metals including noble metals such as rhodium, cobalt, ruthenium, iridium and palladium can effectively catalyze the hydrogenation acylation reaction, but the metals are expensive and resource-exhausted, and in addition, the heavy metal residue of the product is caused.
The indenone compound is an important organic synthesis intermediate, and has wide application in the aspects of medicines, pesticides, dye synthesis, organic luminescent materials and the like. The indenone compound has high pharmacological activity. For example, compound 1 (Donepezil) is mainly used for the treatment of senile dementia and has been approved by the U.S. Food and Drug Administration (FDA), and other compounds having similar structures are being studied for anti-senile dementia. Compound 2 (Indinavir ) is a protease inhibitor, and is mainly used for treating HIV infection and AIDS. The compound with the structure of the compound 3 and the derivative thereof are the raticide with good effect. The compound with the structure of the compound 4 and the derivative thereof not only show good herbicidal activity, but also can reduce the harm to crops.
The synthesis of the indanone compound is carried out by catalyzing aldehyde and unsaturated organic compound hydrogenation acylation reaction with transition metal, and the catalyst used at present is noble metal such as rhodium, cobalt, ruthenium, iridium and palladium. Based on the above important application of indanone compounds, research on the synthesis method thereof is necessary in order to find a more economically applicable synthesis method.
Disclosure of Invention
The invention solves the technical problem of providing a synthetic method of indenone compounds, which uses a copper catalyst, does not need to use a noble metal catalyst, and has the advantages of cheap and easily obtained raw materials and simple production operation.
In order to solve the technical problems, the invention adopts the following technical scheme: a synthetic method of indanone compounds has the following reaction equation:
in the formula (I), the compound is shown in the specification,
n is 0 or 1 or 2, R is selected from hydrogen, halogen, C1-6Alkoxy and C1-6Alkyl groups of (a);
a method for synthesizing a compound represented by formula (I): respectively adding a catalyst, an oxidant, a compound shown as a formula (2) and a solvent into a reaction bottle, and reacting under the protection of argon at the temperature of 70-120 ℃ for 2-6 hours to obtain a compound shown as a formula (I);
the catalyst is as follows: cu (OAc)2、CuCl2、CuBr2、CuO、CuF2、Cu(OTf)2、Cu(OH)2、Cu(NO3)2、CuCl、CuBr、CuI、Cu2O, the catalyst is used in the following amount: the molar ratio of the compound represented by the formula (2) to the molar ratio of the catalyst is 100 to (1-10);
the oxidant is tert-butyl hydroperoxide, and the dosage of the oxidant is as follows: the mole number of the compound shown in the formula (2) and the mole number of the oxidant are 1: 3;
the solvent is as follows: toluene, mesitylene, chlorobenzene, trifluorotoluene, 1, 4-dioxane, and 1, 2-dichloroethane.
As a preferred embodiment, the catalyst is: CuO and CuF2、Cu(NO3)2Any one of the above.
As a preferred embodiment, the catalyst is used in the amount of: the molar ratio of the compound represented by the formula (2) to the molar ratio of the catalyst is 100 to (3-5).
As a more preferred embodiment, the catalyst is CuO.
As a more preferred embodiment, the catalyst is used in an amount of: the molar ratio of the compound represented by the formula (2) to the molar ratio of the catalyst is 100: 3.
As a more preferred embodiment, the solvent is toluene.
As a more preferred embodiment, the solvent is used in an amount of: 4ml of toluene was used per 1mmol of the compound represented by the formula (2).
In a preferred embodiment, the reaction temperature is 90-110 ℃ and the reaction time is 4-6 hours.
As a more preferred embodiment, the reaction temperature is 110 ℃ and the reaction time is 5 hours.
In the process of screening and optimizing reaction conditions, the optimal conditions of the synthesis method of the compound shown in the formula (I) are found as follows: the compound shown in the formula (2) reacts for 5 hours at 110 ℃ under the protection of argon by using CuO as a catalyst, tert-butyl hydroperoxide as an oxidant and toluene as a solvent to obtain the compound shown in the formula (I).
The invention has the beneficial effects that: the invention provides a new synthesis idea of indenone compounds, and the copper catalyst is used, so that the copper is low in price, abundant in reserve and environment-friendly, and the copper-catalyzed hydrogenation acylation reaction meets the requirement of green chemistry, thereby providing a more economic method for the synthesis of the indenone compounds.
The method has the advantages of cheap and easily obtained raw materials, simple production operation, no need of noble metals, environmental protection and safety. The copper catalyst is very cheap, the production cost is greatly reduced, and meanwhile, the experimental operation is simple, so that the copper catalyst can be developed into an industrial production method.
The invention carries out screening optimization on synthesis conditions and further improves the reaction yield.
Detailed Description
The technical solution of the present invention will be described in detail by examples.
Examples 1 to 12
The target compound 2-methyl-1-indanone has a structural formula as follows:
the reaction equation is:
synthesized by the following method:
after adding a copper catalyst (0.025mmol) and t-butyl hydroperoxide (450.00mg,1.50mmol) as an oxidant to a dry Schlenk tube containing magnetons, respectively, argon gas was replaced three times, and then weighed 2-allylbenzaldehyde (73.00mg,0.50mmol) and toluene (3mL) were put into the Schlenk tube, argon gas was replaced three times again, and the reaction was carried out under argon protection at a reaction temperature of 110 ℃ for 6 hours. After the reaction, the reaction was stopped, cooled to room temperature, filtered, washed with saturated brine three times, the aqueous phase was back-extracted with ethyl acetate twice, the organic phases were combined, dried over anhydrous sodium sulfate, and spin-dried. Separating by thin layer chromatography to obtain the target product 2-methyl-1-indanone, and calculating the separation yield.
Examples 1-12 each used a different copper catalyst, as shown in table 1.
TABLE 1
Various copper catalysts are screened, and as can be seen from Table 1, under the condition of copper catalysis, 2-methyl-1-indanone compounds are synthesized. Several cupric catalysts were first screened, and when copper oxide was used as the catalyst, the reaction yield was up to 62%. Then, the monovalent copper catalyst was screened again, and the reaction yield was on the lower side of the middle level. Therefore, a divalent copper catalyst is preferably used, and copper oxide is more preferably used as a catalyst for the reaction.
Next, the oxidizing agent was screened. From examples 1 to 12, it can be seen that the yield was up to 62% when tert-butyl hydroperoxide (TBHP) was used as the oxidizing agent. Comparative examples 1 to 3 used di-tert-butyl peroxide (DTBP) as the oxidizing agent and hydrogen peroxide, m-chloroperoxybenzoic acid (m-CPBA) as the oxidizing agent, respectively.
Synthetic methods of comparative examples 1-3: after adding CuO (0.025mmol) as a catalyst and 1.50mmol as an oxidizing agent to a dry Schlenk tube containing magnetons to replace argon gas three times, weighed 2-allylbenzaldehyde (73.00mg,0.50mmol) and toluene (3mL) were put into the Schlenk tube to replace argon gas three times, and the reaction was carried out under the protection of argon gas at a reaction temperature of 110 ℃ for 6 hours. After the reaction, the reaction was stopped, cooled to room temperature, filtered, washed with saturated brine three times, the aqueous phase was back-extracted with ethyl acetate twice, the organic phases were combined, dried over anhydrous sodium sulfate, and spin-dried. The separation was performed by thin layer chromatography, and the separation yield was calculated.
Comparative examples 1-3 used different oxidizing agents, as shown in table 2.
TABLE 2
| Comparative example | Oxidizing agent | Yield (%) |
| 1 | DTBP | 9 |
| 2 | H2O2 | Without product |
| 3 | m-CPBA | Without product |
When di-tert-butyl peroxide was used as the oxidizing agent, the yield was 9%. When hydrogen peroxide or m-chloroperoxybenzoic acid is used as the oxidizing agent, no target product is produced. Therefore, t-butyl hydroperoxide is used as the oxidizing agent for the reaction.
Examples 13 to 20
The target compound 2-methyl-1-indanone has a structural formula as follows:
the reaction equation is:
synthesized by the following method:
after a copper oxide catalyst (0.025mmol) and t-butyl hydroperoxide (450.00mg,1.50mmol) as an oxidant were added to a dry Schlenk tube containing magnetons to replace argon three times, weighed 2-allylbenzaldehyde (73.00mg,0.50mmol) and toluene (3mL) were put into the Schlenk tube to replace argon three times, and the reaction was carried out under argon protection, specifically, the reaction temperature and the reaction time were shown in table 3. After the reaction, the reaction was stopped, cooled to room temperature, filtered, washed with saturated brine three times, the aqueous phase was back-extracted with ethyl acetate twice, the organic phases were combined, dried over anhydrous sodium sulfate, and spin-dried. Separating by thin layer chromatography to obtain the target product 2-methyl-1-indanone, and calculating the separation yield.
Examples 13 to 20 were carried out at different reaction temperatures and different reaction times, as shown in Table 3.
TABLE 3
| Examples | Reaction temperature (. degree.C.) | Reaction time (h) | Yield (%) |
| 13 | 50 | 6 | 26 |
| 14 | 70 | 6 | 56 |
| 15 | 90 | 6 | 61 |
| 4 | 110 | 6 | 62 |
| 16 | 120 | 6 | 60 |
| 17 | 110 | 5 | 67 |
| 18 | 110 | 4 | 61 |
| 19 | 110 | 3 | 59 |
| 20 | 110 | 2 | 57 |
The reaction temperature was investigated, and the influence of 120 ℃, 110 ℃, 90 ℃, 70 ℃ and 50 ℃ on the reaction yield was examined. It was found that increasing the temperature was beneficial for the reaction. When the reaction temperature is increased to 110 ℃, the reaction yield is the highest and reaches 62%, the temperature is continuously increased to 120 ℃, and the yield is slightly reduced. Therefore, the reaction temperature is preferably 110 ℃.
Next, the reaction time was selected. When the reaction time was 5 hours, the reaction yield was up to 67%. When the reaction time was decreased or increased, the yield was not high when the reaction time was 5 hours. Therefore, the reaction time is preferably 5 hours.
Examples 21 to 25
The target compound 2-methyl-1-indanone has a structural formula as follows:
the reaction equation is:
synthesized by the following method:
after a copper oxide catalyst (0.025mmol) and t-butyl hydroperoxide (450.00mg,1.50mmol) as an oxidant were added to a dry Schlenk tube containing magnetons to replace argon three times, respectively, weighed 2-allylbenzaldehyde (73.00mg,0.50mmol) and a reaction solvent (3mL) were put into the Schlenk tube to replace argon three times again, and the reaction was carried out under argon protection at 110 ℃ for 5 hours. After the reaction, the reaction was stopped, cooled to room temperature, filtered, washed with saturated brine three times, the aqueous phase was back-extracted with ethyl acetate twice, the organic phases were combined, dried over anhydrous sodium sulfate, and spin-dried. Separating by thin layer chromatography to obtain the target product 2-methyl-1-indanone, and calculating the separation yield.
Examples 21 to 25 each used a different reaction solvent, as shown in Table 4.
TABLE 4
| Examples | Reaction temperature (. degree.C.) | Reaction solvent | Yield (%) |
| 21 | 110 | Mesitylene | 26 |
| 22 | 110 | Chlorobenzene | 56 |
| 23 | 110 | Trifluorotoluene | 61 |
| 24 | 110 | 1, 4-dioxane | 62 |
| 25 | 110 | 1, 2-dichloroethane | 60 |
| 17 | 110 | Toluene | 67 |
The influence of the solvent on the reaction yield was screened. When 1,3, 5-trimethylbenzene (mesitylene), chlorobenzene, benzotrifluoride, 1, 4-dioxane and 1, 2-dichloroethane are selected as solvents, the reaction yield is on the middle lower side; when toluene is selected as the solvent, the reaction yield is highest. Therefore, toluene is preferably used as the reaction solvent.
Examples 26 to 28
The amount of solvent used was then screened as seen in examples 26-28.
Examples 26-28 were synthesized by the following method:
after a copper oxide catalyst (0.025mmol) and an oxidant, i.e., t-butyl hydroperoxide (450.00mg,1.50mmol), were added to a dry Schlenk tube containing magnetons, argon gas was replaced three times, and weighed 2-allylbenzaldehyde (73.00mg,0.50mmol) and various amounts of toluene solvent were put into the Schlenk tube, argon gas was replaced three times again, and the reaction was carried out under argon gas protection at a reaction temperature of 110 ℃ for 5 hours. After the reaction, the reaction was stopped, cooled to room temperature, filtered, washed with saturated brine three times, the aqueous phase was back-extracted with ethyl acetate twice, the organic phases were combined, dried over anhydrous sodium sulfate, and spin-dried. Separating by thin layer chromatography to obtain the target product 2-methyl-1-indanone, and calculating the separation yield.
Examples 26-28 each used different amounts of the reaction solvent toluene, as shown in Table 5.
TABLE 5
| Examples | Reaction temperature (. degree.C.) | Reaction solvent | Amount of solvent (ml) | Yield (%) |
| 26 | 110 | Toluene | 1 | 50 |
| 27 | 110 | Toluene | 2 | 71 |
| 28 | 110 | Toluene | 4 | 68 |
When the amount of toluene is 2mL, the reaction yield reaches 71%, and when the amount of toluene is increased or decreased, the reaction yield is reduced. Therefore, 2mL of toluene is preferred as the solvent.
Examples 29 to 31
The amount of catalyst used has an important influence on the yield of the reaction. The amounts of catalyst used were screened by examples 29-31.
Examples 29-31 were synthesized by the following method:
after different amounts of copper oxide catalyst and tert-butyl hydroperoxide (450.00mg,1.50mmol) as oxidant were added to a dry Schlenk tube containing magnetons to displace argon three times, respectively, weighed 2-allylbenzaldehyde (73.00mg,0.50mmol) and toluene solvent (2ml) were put into the Schlenk tube to displace argon three times again, and the reaction was carried out under argon protection at 110 ℃ for 5 hours. After the reaction, the reaction was stopped, cooled to room temperature, filtered, washed with saturated brine three times, the aqueous phase was back-extracted with ethyl acetate twice, the organic phases were combined, dried over anhydrous sodium sulfate, and spin-dried. Separating by thin layer chromatography to obtain the target product 2-methyl-1-indanone, and calculating the separation yield.
Examples 29-31 each utilized different amounts of copper oxide, as shown in Table 6.
TABLE 6
| Examples | Reaction temperature (. degree.C.) | Copper oxide dosage (mmol) | Yield (%) |
| 29 | 110 | 0.05 | 62 |
| 27 | 110 | 0.025 | 71 |
| 30 | 110 | 0.015 | 79 |
| 31 | 110 | 0.005 | 68 |
The amount of catalyst was screened to find that when the equivalent weight of copper oxide was 0.015mmol, i.e. the molar ratio to 2-allylbenzaldehyde was: when the ratio of 2-allyl benzaldehyde to copper oxide is 100: 3, the reaction effect is best and the yield is highest; when the amount of copper oxide is increased or decreased, the reaction yield is decreased. Thus, the amount of copper oxide used was selected to be 0.015mmol, i.e. the molar ratio to 2-allylbenzaldehyde: 2-allylbenzaldehyde to copper oxide 100: 3.
The 2-allyl benzaldehyde is used as a substrate, and different reaction conditions such as catalysts, oxidants, solvents, temperature, time and the like are systematically screened, so that better reaction conditions are finally obtained. Under the condition, the synthesis of the 2-methyl-1-indanone is carried out, and the specific steps are as follows.
(1) Synthesis of catalyst
Palladium dichloride (1.77g,1mmol) was dissolved in tetrahydrofuran solution (180mL), argon was replaced, LiCl (0.85g,2mmol) was then added, stirring was performed at room temperature for 5 minutes, triphenylphosphine (5.24g,2mmol) was added to the mixed solution, replaced again with argon, and reacted at room temperature for 2 hours under an argon atmosphere (Scheme 3.2). After the reaction was completed, the reaction mixture was filtered and recrystallized from methyl tert-butyl ether to obtain bis-triphenylphosphine palladium dichloride (yellow solid, yield 95%) as a catalyst.
(2) Synthesis of 2-allylbenzaldehyde
Sodium carbonate (35.30g,333.00mmol) was weighed and dissolved in 333mL of water to prepare a 1mol/L sodium carbonate solution.
2-formylphenylboronic acid (25.00g,166.70mmol), 3-bromopropyl (30.00g,250.00mmol) and 2-formylphenylboronic acid (5.85g,8.34mmol) were weighed into a 500mL three-necked flask, 100mL of tetrahydrofuran was added thereto, and the mixture was replaced with argon three times and placed in an oil bath pan previously heated to 50 ℃ for reaction. The prepared sodium carbonate solution (1mol/L) was added dropwise to the mixed solution over 1 hour, the oil bath was heated to 85 ℃ and the reaction was refluxed for 4 hours (Scheme 3.3). After the reaction is finished, cooling to room temperature, adding water for quenching, separating out an organic phase, washing the organic phase with saturated salt water for three times, back-extracting the organic phase with ethyl acetate for two times, combining the organic phases, drying the organic phase with anhydrous sodium sulfate, performing rotary drying under reduced pressure, and purifying a crude product by column chromatography to obtain 2-allyl benzaldehyde (light yellow liquid, yield is 62%).
1H NMR(400MHz,CDCl3)δ10.25(s,1H),7.84(dd,J＝7.7,1.4Hz,1H),7.55-7.51(m,1H),7.41-7.37(m,1H),7.29(d,J＝1.6Hz,1H),6.08-5.98(m,1H),5.11-5.07(m,1H),5.00-4.95(m,1H),3.83-3.80(m,2H)；MS(ESI)(m/z):147.2[M+H]+。
(3) Synthesis of 2-methyl-1-indanone
Copper oxide (1.18mg,0.015mmol) and tert-butyl hydroperoxide (450.00mg,1.50mmol) were added to a dry Schlenk tube containing magnetons, respectively, argon gas was replaced three times, and then weighed 2-allylbenzaldehyde (73.00mg,0.50mmol) and toluene (2mL) were put into a Schlenk tube, argon gas was replaced three times again, the reaction was carried out under argon gas protection, the reaction temperature was 110 ℃, the reaction was stopped after 5 hours of reaction, cooling to room temperature, filtration, washing with saturated common salt three times, back-extracting the aqueous phase with ethyl acetate twice, combining the organic phases, drying with anhydrous sodium sulfate, and spin-drying. Separating by thin layer chromatography to obtain the target product 2-methyl-1-indanone as yellow liquid.
1H NMR(400MHz,CDCl3)δ7.75(d,J＝7.6Hz,1H),7.58(t,J＝7.2Hz,1H),7.45(d,J＝7.6Hz,1H),7.36(t,J＝7.4Hz,1H),3.43-3.37(m,1H),2.76-2.66(m,1H),1.31(d,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3)δ209.5,153.5,136.4,134.7,127.4,126.6,124.0,42.0,35.0,16.3；MS(ESI)(m/z):147.1[M+H]+。
Examples 32 to 36
According to the screened optimal reaction conditions, the reaction substrate 2-allyl benzaldehyde is changed, a series of indenone compounds are respectively synthesized, and the yield can reach more than a medium level. The specific compounds synthesized are shown in table 7.
TABLE 7
The above description is only an example of the present invention, and is not intended to limit the scope of the present invention, and all equivalent modifications made by the present invention in the specification or other related fields directly or indirectly are included in the scope of the present invention.
Claims (7)
1. A synthetic method of indanone compounds is characterized in that the reaction equation is as follows:
in the formula (I), the compound is shown in the specification,
n is 0 or 1 or 2, R is selected from hydrogen, halogen, C1-6Alkoxy and C1-6Alkyl groups of (a);
a method for synthesizing a compound represented by formula (I): respectively adding a catalyst, an oxidant, a compound shown in a formula (2) and a solvent into a reaction bottle, and reacting under the protection of argon at the temperature of 70-120 ℃ for 2-6 hours to obtain a compound shown in a formula (I);
the catalyst is CuO, and the dosage of the catalyst is as follows: the molar ratio of the compound represented by the formula (2) to the molar ratio of the catalyst is 100 to (1-10);
the oxidant is tert-butyl hydroperoxide, and the dosage of the oxidant is as follows: the mole number of the compound shown in the formula (2) and the mole number of the oxidant are 1: 3;
the solvent is as follows: toluene, mesitylene, chlorobenzene, trifluorotoluene, 1, 4-dioxane, and 1, 2-dichloroethane.
2. The method for synthesizing indanone compounds according to claim 1, wherein the amount of the catalyst is: the molar ratio of the compound represented by the formula (2) to the molar ratio of the catalyst is 100 to (3-5).
3. The method for synthesizing indanone compounds according to claim 2, wherein the amount of the catalyst is as follows: the molar ratio of the compound represented by the formula (2) to the molar ratio of the catalyst is 100: 3.
4. The method for synthesizing indanone compounds according to claim 1, wherein the solvent is toluene.
5. The method for synthesizing indanone compounds according to claim 4, wherein the solvent is used in an amount of: 4ml of toluene was used per 1mmol of the compound represented by the formula (2).
6. The method for synthesizing the indenone compound according to claim 1, wherein the reaction temperature is 90-110 ℃ and the reaction time is 4-6 hours.
7. The method for synthesizing indanone compounds according to claim 6, wherein the reaction temperature is 110 ℃ and the reaction time is 5 hours.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810588452 | 2018-06-08 | ||
| CN2018105884524 | 2018-06-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108689815A CN108689815A (en) | 2018-10-23 |
| CN108689815B true CN108689815B (en) | 2021-03-19 |
Family
ID=63848410
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810675285.7A Active CN108689815B (en) | 2018-06-08 | 2018-06-27 | Synthetic method of indanone compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108689815B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4380672A (en) * | 1980-08-28 | 1983-04-19 | The Standard Oil Company | Conversion of 2-phenyl propanal to 2-indanone |
| CN106380440A (en) * | 2016-08-30 | 2017-02-08 | 华东师范大学 | Indanone pyrrole derivative and synthetic method and application thereof |
| CN107641068A (en) * | 2016-07-29 | 2018-01-30 | 浙江工业大学 | A kind of preparation method of indone analog derivative |
-
2018
- 2018-06-27 CN CN201810675285.7A patent/CN108689815B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4380672A (en) * | 1980-08-28 | 1983-04-19 | The Standard Oil Company | Conversion of 2-phenyl propanal to 2-indanone |
| CN107641068A (en) * | 2016-07-29 | 2018-01-30 | 浙江工业大学 | A kind of preparation method of indone analog derivative |
| CN106380440A (en) * | 2016-08-30 | 2017-02-08 | 华东师范大学 | Indanone pyrrole derivative and synthetic method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108689815A (en) | 2018-10-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Hayashi et al. | Stereo-and regiochemistry in palladium-catalyzed nucleophilic substitution of optically active (E)-and (Z)-allyl acetates | |
| CN110818545B (en) | Method for preparing substituted aryl ketone by ketone arylation | |
| CN114436949B (en) | Tetradentate ligand, metal complex, and preparation methods and applications thereof | |
| CN114920640A (en) | Chlorocyclopentanone derivative and synthesis method thereof | |
| CN108689815B (en) | Synthetic method of indanone compound | |
| JP2007230963A (en) | Method for producing 2,4-disubstituted pyridine | |
| CN109776407B (en) | Preparation method of 2-methyl-4-hydroxymethyl quinoline and derivatives thereof | |
| CN107353256B (en) | Method for synthesizing 4-acetyl-1, 2, 3-triazole compound by one-pot method | |
| WO2020118597A1 (en) | Process for making 1- [ (3r, 4s) -4-cyanotetrahydropyran-3-yl] -3- [ (2-fluoro-6-methoxy-4-pyridyl) amino] pyrazole-4-carboxamide | |
| CN106349125B (en) | Utilize the method for manganese salt selectivity synthesis (E) vinyl sulfone compound | |
| CN115215814A (en) | Synthetic method of isoxazolidine compounds | |
| CN106966994A (en) | A kind of triazole of N sulfonyls 1,2,3 of new 4 allyl acetic acid ester group substitution and preparation method thereof | |
| CN113880798A (en) | Synthesis method of polysubstituted 3-hydroxy-2-pyrone | |
| CN109721523B (en) | Indoline derivative and preparation method thereof | |
| CN110563551B (en) | Method for synthesizing trans-2-alkene-4-alkyne-1-alcohol compound | |
| CN110372675B (en) | Selective preparation method of N-1 and N2-oxyalkyl substituted 1,2, 3-triazole compound | |
| CN106892866B (en) | 1, 2-disubstituted-4-quinolone and synthesis method thereof | |
| CN108558974B (en) | Preparation and application of sugar-derived nickel pyridine triazole catalyst | |
| CN111320547B (en) | Synthesis method of lumefantrine-D9 | |
| CN110872225A (en) | Preparation method of Barosavir intermediate | |
| CN108586331B (en) | Intermediate for synthesizing nitrogen-containing heterocyclic compound and preparation method thereof | |
| CN117720396B (en) | Preparation method of cis-bicyclo [3.1.0] hex-3-ol | |
| CN113754597B (en) | Benzhydryl piperazine compound containing linear olefin and preparation method thereof | |
| CN112961105B (en) | Alkylation method of nitrogen-containing heterocyclic compound | |
| CN110452213B (en) | Synthetic method of piperine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20210226 Address after: Room 1402-8, Changxing Taihu capital Plaza, 1278 Mingzhu Road, Changxing Economic Development Zone, Huzhou City, Zhejiang Province, 313100 Applicant after: Huzhou Derui Medical Technology Co.,Ltd. Address before: 450000 No.5, unit 1, building 25, No.75 College Road, Erqi District, Zhengzhou City, Henan Province Applicant before: ZHENGZHOU DERUI PHARMACEUTICAL TECHNOLOGY Co.,Ltd. |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |