CN108675921B

CN108675921B - Synthetic method of spiroindanone compound

Info

Publication number: CN108675921B
Application number: CN201810676624.3A
Authority: CN
Inventors: 郭灿城; 李慧; 郭欣
Original assignee: Yuanjiang Hualong Catalyst Technology Co ltd
Current assignee: Yuanjiang Hualong Catalyst Technology Co ltd
Priority date: 2018-06-27
Filing date: 2018-06-27
Publication date: 2021-05-25
Anticipated expiration: 2038-06-27
Also published as: CN108675921A

Abstract

The invention discloses a synthesis method of a spiroindanone compound, which comprises the steps of carrying out one-pot reaction on a 1-indanone compound and an alpha-methylstyrene compound in a dimethyl sulfoxide solution system containing alkali metal persulfate to obtain the spiroindanone compound; the synthesis method is realized by a one-pot method, has mild reaction conditions, does not need additional catalysts, has good selectivity and high yield, and is beneficial to industrial production.

Description

Synthetic method of spiroindanone compound

Technical Field

The invention relates to a synthesis method of a spiroindanone compound, and also relates to a method for constructing a spiroindanone structure by a 1-indanone compound, an alpha-methylstyrene compound and dimethyl sulfoxide, belonging to the field of organic synthesis.

Background

Spiro compounds are also widely found in bioactive molecules such as natural products, drugs, pesticides and the like (chem.Soc.Rev.2012,41, 1060-1074; Eur.J.Org.chem.2012, 1935-1944; Org.chem.Front.2015, 2849-2858; ACS Catal.2013,3,540-553), and many spiro compounds exhibit outstanding physiological activities such as anti-tumor, anti-hypertension, anti-allergy and the like, and are widely used in clinical applications (J.Med.chem.1996,39, 4044-4057; Med.chem.Lett.2007,17, 266-271; Synthesis-Stuttgart.2013,45, 1909-1930; Med.chem.2009,52, 6936-6940).

Spiroindanone compounds have been widely spotlighted because of their specific spiro backbone, which exhibits various biological and pharmacological activities. Early spiroindanone compounds were found in natural plants, and alkaloids isolated from annona squamosa were reported to have an indanone pyridine skeleton, and derivatives thereof were found to have phosphodiesterase activity and ability to inhibit adenosine A2a receptor binding, and are useful for treating neurodegenerative and inflammation-related diseases (Aran go, g.j.; cortex, d.; et al, azafluorogens from Oxandra cf. major and biochemical disorders [ J ]. Phytochemistry,1987,26, 2093-. Up to now, methods for synthesizing spiroindanone compounds have been reported in the prior art, such as the typical method that 1-indanone and formaldehyde are firstly subjected to condensation reaction and then reacted with acetyl allene to obtain spiro compounds containing 1-indanone skeleton (Tetrahedron Lett.2013,54, 4425-4428). As another example, starting from 1-indanone, spiro compounds containing 1-indanone skeleton can be synthesized by Michael condensation and Dikmann condensation with acrylic ester (Helv Chim Acta 1995,78, 857-one 865). However, these methods all have the disadvantages of long flow path, not easy to obtain raw materials, low total yield, complex post-treatment and the like. Chinese patent (CN108047007A) discloses a synthesis method of a spiro-compound containing 1-indanone skeleton, which takes aromatic carboxylic acid and alpha, beta-unsaturated ketone as raw materials, adopts catalysts such as cymene ruthenium dichloride dimer and the like and heavy metal additives such as manganese, zinc and the like, and synthesizes the spiro-compound containing 1-indanone skeleton through four-step reactions such as conjugate addition reaction of aromatic carboxylic acid ortho-position C-H bond and alpha, beta-unsaturated ketone, intramolecular dehydration cyclization, Michael addition with second molecule alpha, beta-unsaturated ketone, intramolecular aldol condensation and the like by one-step reaction (the reaction route is as follows).

Disclosure of Invention

Aiming at the defects of complex steps, high cost, environmental friendliness and the like of the existing method for constructing the spiroindanone structure, the invention aims to provide a method for constructing the spiroindanone structure by using a 1-indanone compound to provide alpha-carbon, a DMSO to provide methyl and an alpha-methylstyrene compound to provide propenyl.

In order to realize the technical purpose, the invention provides a synthesis method of a spiroindanone compound, which comprises the steps of carrying out one-pot reaction on a 1-indanone compound and an alpha-methylstyrene compound in a dimethyl sulfoxide solution system containing alkali metal persulfate to obtain the spiroindanone compound;

the spiroindanone compound has the structure of formula 1:

the 1-indanone compound has the structure of formula 2:

the alpha-methyl styrene compound has a structure of formula 3:

wherein the content of the first and second substances,

R₁selected from halogen substituents, alkyl or alkoxy;

R₂selected from halogen substituents or alkyl groups.

In a preferred scheme, the 1-indanone compound participates in the reaction at alpha carbon, and because a benzene ring can participate in conjugation with a carbonyl group, the alpha carbon can be obviously increasedThe activity is low, and various substituent groups on the benzene ring have no obvious influence on the electronic effect and the steric hindrance effect of the cyclization reaction. R on benzene ring of 1-indanone compound₁May contain conventional substituents such as halogen (fluorine, chlorine, bromine or iodine) or short-chain alkyl (typically having C atoms)₁～C₅Such as methyl, ethyl, propyl, etc., and may also be branched alkyl groups such as isopropyl, isobutyl, etc.), alkoxy groups (C)₁～C₅Alkoxy groups of (ii) and the like. The position of the substituent is not particularly limited, and may be ortho, para or meta with respect to the carbonyl group. If the compound is cyclic ketone or alkyl substituted cyclic ketone, the yield of the obtained spiroindanone compound is obviously reduced.

In the alpha-methylstyrene compound of the present invention, R₂Selected from halogen substituents or alkyl groups. Halogen substituents such as fluorine, chlorine, bromine, iodine, and the like. Alkyl is C₁～C₁₀Alkyl groups of (a); more preferably C₁～C₅The lower alkyl group of (2) such as methyl, ethyl, propyl, etc., may also be a branched alkyl group such as isopropyl, isobutyl, etc. The substituent position is preferably para (relative to the alkenyl). The choice of alpha-methylstyrene compounds is limited to the choice of the aryl substituents which provide a large conjugated system and enable the methyl groups on the alkenyl groups to be sufficiently active to participate in the cyclization. The aryl substituent can not be replaced by other substituent groups at will, and the target product can not be obtained by replacing aryl with aromatic heterocycle, alkyl and the like. And the substituent group can be a weak electron-pushing group such as alkyl and can also be a weak electron-pulling group such as halogen. However, it is difficult to obtain an ideal yield from a strongly electron-withdrawing group such as an amino group and an alkoxy group, and a strongly electron-withdrawing group such as a nitro group.

In a preferable scheme, the molar ratio of the alkali metal persulfate to the 1-indanone compound is 1-2: 1. More preferably 1.3 to 1.8: 1.

In a preferred embodiment, the molar ratio of the 1-indanone compound to the alpha-methylstyrene compound is 1: 1.5-2.5.

In a preferable scheme, the concentration of the 1-indanone compound in a dimethyl sulfoxide solution system is 0.1-0.5 mol/L. Dimethyl sulfoxide serves mainly as a benign solvent on the one hand, and as a reaction substrate, two methyl groups are provided by two dimethyl sulfoxides as two carbon atoms in the cyclohexene ring in the spiroindanone structure on the other hand.

In a more preferred embodiment, the reaction conditions are as follows: reacting for 18-30 h at 110-160 ℃ in a protective atmosphere. In a more preferred embodiment, the reaction conditions are as follows: and reacting for 22-28 h at 130-150 ℃ in a protective atmosphere. The protective atmosphere generally refers to nitrogen or an inert atmosphere or a mixed atmosphere of the two.

The invention explains the reaction mechanism by constructing a spiroindanone structure by 1-indanone, dimethyl sulfoxide and alpha-methylstyrene together. After reviewing and referring to relevant documents, a series of mechanism research experiments were designed, as shown in the following reaction equations (1) to (6). In order to prove whether the reaction goes through the reaction course of free radicals, reaction (1) is designed, 2.0 equivalent (relative to 1-indanone) of 2, 6-di-tert-butyl-p-cresol (BHT) is added under standard reaction conditions, and the reaction is carried out for 12 hours, so that the generation of the target product of the spiroindanone structure can still be successfully detected through GC-MS, which indicates that the reaction is not inhibited, and the reaction does not go through the reaction course of one free radical. To demonstrate the presence or absence of reaction intermediates in this reaction, 1-indanone was reacted with dimethyl sulfoxide and α -methylstyrene under standard reaction conditions for 12 hours, and the presence of compound B and compound C was detected in addition to the target spiro compound by detection in GC-MS. In order to prove whether the compounds B and C are intermediates in the construction process of the spiroindanone structure, the reaction (2) and the reaction (3) are designed, the compound B is used as a raw material to replace alpha-methylstyrene for reaction under standard conditions, and the compound C is used as a raw material to replace the compound 1-indanone. To further clarify the source of compound B, reaction (4) was further designed to react alpha-methylstyrene with dimethylsulfoxide directly under standard conditions, and the presence of compound B was detected by GC-MS, while compound a was also obtained. To further clarify the source of Compound C, reaction (5) was further designed and willThe alpha-methyl styrene and dimethyl sulfoxide are directly reacted under standard conditions, and the existence of the compound C is found through GC-MS detection, and the compound D is also obtained. To obtain a more accurate verification of whether dimethyl sulfoxide is involved in the generation of cyclohexene ring in the spiroindanone structure, reaction (6) was devised, replacing conventional dimethyl sulfoxide with isotopically labeled deuterated dimethyl sulfoxide and reacting under standard conditions, successfully detecting the presence of deuterium in the cyclohexene ring of the spiroindanone structure and detecting the presence of deuterium on two carbon atoms, indicating that two methyl groups are provided by dimethyl sulfoxide. Standard reaction conditions: in N₂Next, 1-indanone (0.5mmol), α -methylstyrene (0.75mmol) and DMSO (2mL) were reacted at 140 ℃ for 24 h.

Reaction formula (1):

reaction formula (2):

reaction formula (3):

reaction formula (4):

reaction formula (5):

reaction formula (6):

according to the experiment, the invention provides a reasonable mechanism for constructing the structure of the spiroindanone by the 1-indanone, the dimethyl sulfoxide and the alpha-methylstyrene: the following reaction equation. First, adopt K₂S₂O₈Activating DMSO to obtain DMSO-containing solutionThe alpha-methyl styrene releases hydrogen protons and is converted into alpha-methyl styrene anions, the 1-indanone also releases hydrogen protons and is converted into 1-indanone anions, the alpha-methyl styrene anions and the 1-indanone anions are easy to couple with the dimethyl sulfur anions to generate sulfur methyl ether compounds A and D, and the sulfur methyl ether compounds A and D are at K₂S₂O₈Under the action of oxidation, removing the micromolecule methyl mercaptan compound through a demethylation reaction to obtain compounds B and C, and carrying out Diels Alder reaction on the compound B and the compound C to finally obtain a target product.

Compared with the prior art, the technical scheme of the invention has the beneficial technical effects that:

1) the spiroindanone structure of the invention is composed of 1-indanone and cyclohexene, and can contain abundant substituent groups and modifiable groups, thereby providing an effective intermediate for the synthesis of drugs and the like taking the spiroindanone structure as a parent.

2) According to the invention, alpha carbon is provided by 1-indanone, allyl is provided by an alpha-methyl styrene compound, and methyl is provided by dimethyl sulfoxide to successfully construct the spiroindanone structure, so that a brand new synthesis idea is provided for the construction of the spiroindanone structure.

3) The synthesis process of the spiroindanone compound does not need to use a catalyst, and compared with the existing synthesis method, the synthesis method avoids using expensive and pollution-like catalysts and additives, and is beneficial to reducing the cost and protecting the environment.

4) In the synthesis process of the spiro indanone compound, the 1-indanone compound, the alpha-methylstyrene compound and the dimethyl sulfoxide are used as basic raw materials, which are conventional chemical raw materials, so that the synthesis process is low in cost and beneficial to industrial production.

5) The synthesis process of the spiroindanone compound adopts a one-pot reaction, and has mild reaction conditions and simple operation, thereby meeting the requirements of industrial production.

6) The synthesis process of the spiroindanone compound has high utilization rate of raw materials, and the product yield can reach more than 80%.

7) The spiro indanone compound has wide application range to substrate raw materials in the synthesis process, can construct spiro compounds with various substituent groups, and has strong substituent position selectivity.

Drawings

FIG. 1 is a nuclear magnetic carbon spectrum of 1- (4-fluorophenyl) spiro [ cyclohex [6] ene-4,2' -inden ] -1' (3' H) -one.

FIG. 2 is a nuclear magnetic hydrogen spectrum of 1- (4-fluorophenyl) spiro [ cyclohex [6] ene-4,2' -inden ] -1' (3' H) -one.

FIG. 3 is a nuclear magnetic carbon spectrum of 1-phenylspiro [ cyclohex [6] ene-4,2' -inden ] -1' (3' H) -one.

FIG. 4 is a nuclear magnetic hydrogen spectrum of 1-phenylspiro [ cyclohex [6] ene-4,2' -inden ] -1' (3' H) -one.

Detailed Description

The following examples are intended to further illustrate the present disclosure, but not to limit the scope of the claims.

All reactions were performed in Schlenk tubes unless otherwise noted.

All reaction starting solvents were obtained from commercial sources and used without further purification.

The product is separated by silica gel chromatographic column and silica gel (granularity is 300-400 meshes).

1H NMR (400MHz), 13C NMR (100MHz) and 19F NMR (376MHz) measurements were performed using a Bruker ADVANCE III spectrometer with CDCl₃As solvent, TMS as internal standard, chemical shifts in parts per million (ppm) and reference shifts of 0.0ppm tetramethylsilane. The following abbreviations (or combinations thereof) are used to explain the multiplicity: s is singlet, d is doublet, t is triplet, q is quartet, m is multiplet, br is broad. Coupling constant J is in Hertz (Hz). Chemical shifts are expressed in ppm, with the center line for the triplet state referenced to deuterated chloroform at 77.0ppm or the center line for the heptad state referenced to deuterated DMSO at 39.52 ppm.

The GC-MS adopts a GC-MS QP2010 device for detection, the HRMS adopts an Electron Ionization (EI) method for measurement, the type of the mass analyzer is TOF, and the EI is detected by an Esquire 3000plus instrument.

1. Condition optimization experiment:

the construction of the spiroindanone structure by 1-indanone, dimethyl sulfoxide and alpha-methylstyrene is taken as an example, and a plurality of influencing factors such as oxidant, dosage, reaction temperature, reaction solvent, additive and the like are discussed to seek the optimal reaction conditions.

The specific reaction process is as follows: 1-indanone, alpha-methyl styrene, oxidant, additive and DMSO in N₂And reacting for 24 hours under the atmosphere.

The reaction route is as follows:

table 1: yield of target product spiroindanone structure under different reaction conditions

1) Selection of additives

As shown in Table 1, the use of the additive has a great influence on the reaction, and a large number of experiments show that, as items 1-6 and 11 in Table 1, no benign additive which is beneficial to improving the reaction efficiency and increasing the yield, such as DABCO, DBU and K, is found in the reaction process of constructing the spiroindanone structure by 1-indanone, dimethyl sulfoxide and alpha-methylstyrene₂CO₃、Cs₂CO₃、Et₃When N or NaOAc and other alkaline substances are used as additives, the reaction is obviously inhibited, and the target product spiroindanone compound is basically not obtained.

3) Selection of oxidizing agent

The present invention contemplates several common oxidants in the art, such as items 9-16 in Table 1, oxidantsSuch as alkali metal persulfate, organic peroxide, inorganic hydrogen peroxide and the like, has a good reaction effect only when the persulfate is used as the oxidant, and when tert-butyl hydroperoxide (TBHP), DTBP or hydrogen peroxide (H) is used₂O₂) Since the target product is hardly obtained as the oxidizing agent, an alkali metal sulfate is selected as the most preferable oxidizing agent.

4) Selection of the quantity of oxidant

After determining potassium persulfate, sodium persulfate, etc. as the optimal oxidizing agents, the influence of different amounts of the oxidizing agents on the reaction was explored. As in items 11, 17 and 18 of table 1. When the amount of the oxidant is 0.5-0.75 equivalent, the conversion rate of the raw materials and the yield of the product are increased with the increase of the amount of the oxidant. And when the amount of the oxidizing agent is more than 0.75 equivalent, the yield is remarkably decreased. Therefore, 0.75 equivalent of persulfate is the optimum amount for the reaction.

5) Selection of reaction temperature

The reaction temperature is an important factor affecting the chemical reaction process, and in order to obtain the optimum reaction temperature, the yield of the reaction at different temperatures was investigated, as in items 7 to 11 in Table 1. The target product can not be obtained basically at the temperature of less than 100 ℃, the reaction yield is obviously improved when the temperature reaches more than 120 ℃, the reaction yield reaches the highest when the temperature is raised to 140 ℃, and the reaction side reaction is obvious when the temperature is higher than 140 ℃. Thus, 140 ℃ is the optimum temperature for the reaction.

6) Selection of reaction solvent

Since DMSO is used as a reaction substrate and a solvent in the process of synthesizing dihydropyran, the DMSO is not replaceable by other solvents. The solvent of the invention can adopt DMSO, and can also adopt a mixed solvent of DMSO and other solvents.

2. Selection range of reaction substrates:

after the optimal synthesis conditions of the spiroindanone structure are determined, the substrate range and the applicability of the reaction are researched, and the experimental results are shown in tables 2 and 3. Table 2 shows the results of the reaction of various 1-indanone compounds with alpha-methylstyrene and DMSO. As can be seen from Table 2, the 1-indanone compounds containing different substituents on the benzene ring can effectively synthesize corresponding spiroindanone structures with alpha-methylstyrene and DMSO under standard reaction conditions, and the yield of the target product is about 70%, and can reach more than 80% at most, and the yield is relatively ideal. Moreover, a large number of experiments show that the influence of the substituent group of the 1-indanone compound on the reaction is small, the carbonyl is connected to a conjugate system, the activity of the carbonyl alpha carbon can be obviously improved due to the participation of the carbonyl in the conjugation, hydrogen protons are easy to lose, the spiroindanone structure can be successfully constructed with alpha-methylstyrene and DMSO, and the yield is about 80%. If cyclopentanone is not connected with a benzene ring but is connected with other groups such as alkyl and the like, the yield of the spirocyclic ring constructed by the cyclic ketone, alpha-methyl styrene and DMSO is obviously reduced. Table 3 shows the reaction results of different alpha-methyl styrene compounds, 1-indanone and DMSO, and experimental results show that the substituent at the 2-position of propylene must be a group with a large conjugated system, such as phenyl or substituted phenyl, other aromatic heterocycles, alkyl and the like cannot meet the requirements, and the aryl of the large conjugated system is favorable for improving the activity of alpha-methyl. The substituent on the phenyl is also selected according to the requirement, and can not be a substituent group with stronger electron pushing or pulling capacity, such as nitro, alkoxy and the like, while a substituent group with weaker electron pushing or pulling capacity, such as halogen, alkyl and the like, can meet the requirement. The position of the substituent is preferably the para position.

(1) The reaction equation for different 1-indanone compounds with 2-methylstyrene and DMSO is as follows:

weighing potassium peroxodisulfate (K)₂S₂O₈) (202.5mg,0.75mmol), 1-indanone compound (0.5mmol) was placed in a 25ml Schlenk reaction tube, and dimethyl sulfoxide (DMSO, 2ml), α -methylstyrene (118mg, 1mmol) and purged with nitrogen were added thereto. Stirring was carried out at 140 ℃ for 24 hours. After completion of the reaction, it was cooled to room temperature, water (4ml) was added, and extraction was performed with ethyl acetate (3 x 5ml) and anhydrous Na₂SO₄Drying, distilling off the solvent under reduced pressure, and separating by a silica gel column (200-300 mesh) to obtainThe target product is spiro indanone structure.

TABLE 2 reaction results of different 1-indanone compounds with alpha-methylstyrene and DMSO

(2) The reaction equation of different alpha-methyl styrene compounds with 1-indanone and DMSO is as follows:

weighing potassium peroxodisulfate (K)₂S₂O₈) (202.5mg,0.75mmol), 1-indanone (0.5mmol) was placed in a 25ml Schlenk reaction tube, and dimethyl sulfoxide (DMSO, 2ml), α -methylstyrene compound (1mmol) were added thereto, and nitrogen gas was purged. Stirring was carried out at 140 ℃ for 24 hours. After completion of the reaction, it was cooled to room temperature, water (4ml) was added, and extraction was performed with ethyl acetate (3 x 5ml) and anhydrous Na₂SO₄Drying, distilling off the solvent under reduced pressure, and separating by a silica gel column (200-300 meshes) to obtain the target product spiro compound.

TABLE 3 results of reaction of various alpha-methylstyrene compounds with 1-indanone and DMSO

Molecular structural characterization of the partially spiro compound:

1-phenylspiro[cyclohex[6]ene-4,2'-inden]-1'(3'H)-one；

7.5Hz,2H),7.23(d,J＝6.7Hz,1H),6.20(d,J＝4.5Hz,1H),3.11(d,J＝17.3Hz,1H),2.96(d,J＝17.3Hz,1H),2.63(dd,J＝26.5,11.9Hz,3H),2.05(dt,J＝15.1,5.6Hz,2H),1.72–1.66(m,1H).

¹³C NMR(101MHz,CDCl₃)δ211.07,152.80,141.52,136.05,135.90,134.95,128.36,127.52,127.02,126.74,125.06,124.36,122.55,48.17,39.10,35.08,29.30,24.86.

5'-fluoro-1-phenylspiro[cyclohex[6]ene-4,2'-inden]-1'(3'H)-one；

2.96(d,J＝17.5Hz,1H),2.74–2.53(m,3H),2.15–1.98(m,2H),1.70(dd,J＝13.4,3.4Hz,1H).

¹³C NMR(101MHz,CDCl₃)δ209.12,168.70,155.66(d,J＝10.0Hz),141.40,136.08,132.25,128.38,127.09,126.64(d,J＝10.5Hz),125.05,122.32,115.86(d,J＝23.8Hz),113.32(d,J＝22.1Hz),48.54,39.00,35.04,29.27,24.76

5'-chloro-1-phenylspiro[cyclohex[6]ene-4,2'-inden]-1'(3'H)-one；

(d,J＝4.0Hz,1H),3.08(d,J＝17.5Hz,1H),2.93(d,J＝17.5Hz,1H),2.66(d,J＝16.8Hz,2H),2.61–2.48(m,1H),2.10–1.98(m,2H),1.68(dd,J＝12.2,4.3Hz,1H)..

¹³CNMR(101MHz,CDCl₃)δ209.53,154.25,141.43,141.35,136.08,134.34,128.40,128.37,127.11,126.93,125.48,125.05,122.26,48.46,38.82,35.03,29.28,24.75.

6'-bromo-1-phenylspiro[cyclohex[6]ene-4,2'-inden]-1'(3'H)-one；

6.0Hz,1H),6.18(d,J＝4.7Hz,1H),3.04(d,J＝17.4Hz,1H),2.90(d,J＝17.4Hz,1H),2.71–2.61(m,2H),2.60–2.39(m,1H),2.04(ddd,J＝21.2,10.7,5.3Hz,2H),1.68(dd,J＝13.8,4.4Hz,1H).

¹³C NMR(101MHz,CDCl₃)δ209.53,151.26,141.35,137.77,137.65,136.10,128.39,128.32,127.27,127.11,125.05,122.23,121.67,48.80,38.72,35.02,29.26,24.77.

4'-methyl-1-phenylspiro[cyclohex[6]ene-4,2'-inden]-1'(3'H)-one；

1H),2.67(t,J＝14.0Hz,3H),2.33(s,3H),2.14–2.00(m,2H),1.71(dd,J＝9.3,6.8Hz,1H).

¹³C NMR(101MHz,CDCl₃)δ211.40,151.78,141.45,136.00,135.90,135.67,135.39,128.38,127.75,127.05,125.03,122.63,121.74,48.03,37.97,35.22,29.34,24.87,17.91.

6'-methyl-1-phenylspiro[cyclohex[6]ene-4,2'-inden]-1'(3'H)-one；

1H),3.06(d,J＝17.2Hz,1H),2.91(d,J＝17.1Hz,1H),2.64(t,J＝16.4Hz,3H),2.41(s,3H),2.09–2.00(m,2H),1.68(dd,J＝12.9,2.9Hz,1H).

¹³C NMR(101MHz,CDCl₃)δ211.17,150.14,141.55,137.44,136.23,136.04,136.01,128.36,127.00,126.43,125.05,124.26,122.63,48.50,38.75,35.14,29.33,24.88,21.15.

5'-methoxy-1-phenylspiro[cyclohex[6]ene-4,2'-inden]-1'(3'H)-one；

3.89(s,3H),3.07(d,J＝17.3Hz,1H),2.92(d,J＝17.3Hz,1H),2.61(dt,J＝17.7,11.7Hz,3H),2.06(ddd,J＝25.3,16.2,5.7Hz,2H),1.72–1.65(m,1H).

¹³C NMR(101MHz,CDCl₃)δ209.15,165.56,155.66,141.58,135.99,129.07,128.34,126.96,126.02,125.03,122.70,115.45,109.86,55.65,48.31,39.17,35.16,29.38,24.87.

6'-methoxy-1-phenylspiro[cyclohex[6]ene-4,2'-inden]-1'(3'H)-one；

1H),3.83(s,3H),3.03(d,J＝16.9Hz,1H),2.88(d,J＝16.9Hz,1H),2.66(d,J＝17.6Hz,2H),2.59(d,J＝6.5Hz,1H),2.09–1.99(m,2H),1.69(dd,J＝12.8,3.5Hz,1H).

¹³C NMR(101MHz,CDCl₃)δ211.07,159.53,145.59,141.53,137.00,136.01,128.37,127.46,127.02,125.05,124.37,122.60,105.43,55.63,49.04,38.44,35.19,29.37,24.91.

9-phenylspiro[5.5]undec-8-en-1-one；

¹³C NMR(101MHz,CDCl₃)δ215.34,141.55,135.04,128.22,126.75,124.94,122.10,47.01,38.55,36.62,33.23,29.66,27.91,24.05,20.96.

1-(p-tolyl)spiro[cyclohex[6]ene-4,2'-inden]-1'(3'H)-one；

1H),7.34(d,J＝7.6Hz,2H),7.16(d,J＝7.7Hz,2H),6.18(d,J＝4.2Hz,1H),3.13(d,J＝17.3Hz,1H),2.98(d,J＝17.3Hz,1H),2.74–2.54(m,3H),2.36(s,3H),2.07(ddd,J＝23.3,14.9,5.1Hz,2H),1.70(dd,J＝12.7,4.3Hz,1H).

¹³C NMR(101MHz,CDCl₃)δ211.14,152.84,138.67,136.70,135.93,135.82,134.92,129.04,127.49,126.73,124.91,124.35,121.68,48.22,39.08,35.07,29.30,24.86,21.09.

1-(4-chlorophenyl)spiro[cyclohex[6]ene-4,2'-inden]-1'(3'H)-one；

Hz,1H),7.36(d,J＝8.5Hz,2H),7.30(d,J＝8.2Hz,2H),6.20(s,1H),3.12(d,J＝17.3Hz,1H),2.96(d,J＝17.2Hz,1H),2.73–2.51(m,3H),2.13–1.99(m,2H),1.70(dd,J＝13.2,2.5Hz,1H).

¹³C NMR(101MHz,CDCl₃)δ210.83,152.69,139.92,135.83,135.00,132.69,128.44,127.57,126.74,126.33,124.38,123.18,48.01,39.13,35.02,29.23,24.80.

1-(4-fluorophenyl)spiro[cyclohex[6]ene-4,2'-inden]-1'(3'H)-one；

3H),7.03(t,J＝8.3Hz,2H),6.15(d,J＝3.6Hz,1H),3.12(d,J＝17.3Hz,1H),2.97(d,J＝17.2Hz,1H),2.71–2.52(m,3H),2.11–2.00(m,2H),1.70(dd,J＝13.2,2.7Hz,1H).

¹³C NMR(101MHz,CDCl₃)δ210.92,162.04(d,J＝245.9Hz),152.72,137.63,135.86,135.14,134.97,127.55,126.72,126.57(d,J＝7.8Hz),124.38,122.45,115.10(d,J＝21.3Hz),48.05,39.12,35.00,29.26,25.02.

Claims

1. a synthesis method of a spiro indanone compound is characterized in that: the 1-indanone compound and the alpha-methylstyrene compound are reacted in a dimethyl sulfoxide solution system containing alkali metal persulfate by one pot to obtain a spiro-indanone compound;

the spiroindanone compound has the structure of formula 1:

the 1-indanone compound has the structure of formula 2:

the alpha-methyl styrene compound has a structure of formula 3:

wherein the content of the first and second substances,

R₁selected from halogen substituents, alkyl or alkoxy;

R₂selected from halogen substituents or alkyl groups.

2. The method for synthesizing the spiroindanone compound according to claim 1, characterized in that:

R₁when selected from halogen substituents, the halogen substituents are selected from fluorine, chlorine, bromine or iodine;

R₁when selected from alkyl, the alkyl is C₁～C₅Alkyl groups of (a);

R₁when selected from alkoxy, the alkoxy is C₁～C₅Alkoxy group of (2).

3. The method for synthesizing the spiroindanone compound according to claim 1, characterized in that:

R₂when selected from halogen substituents, the halogen substituents are selected from fluorine, chlorine, bromine or iodine;

R₂when selected from alkyl, the alkyl is C₁～C₅Alkyl group of (1).

4. The method for synthesizing the spiroindanone compound according to claim 3, characterized in that:

R₂is a para substituent.

5. The method for synthesizing the spiroindanone compound according to claim 3, characterized in that:

the molar ratio of the alkali metal persulfate to the 1-indanone compound is 1-2: 1.

6. The method for synthesizing the spiroindanone compound according to claim 3, characterized in that:

the molar ratio of the 1-indanone compound to the alpha-methylstyrene compound is 1: 1.5-2.5.

7. The method for synthesizing the spiroindanone compound according to claim 3, characterized in that:

the concentration of the 1-indanone compound in a dimethyl sulfoxide solution system is 0.1-0.5 mol/L.

8. The method for synthesizing the spiroindanone compound according to claim 5, characterized in that: the alkali metal persulfate is at least one selected from potassium persulfate, sodium persulfate, potassium hydrogen persulfate and sodium hydrogen persulfate.

9. A synthesis method of a spiroindanone compound according to any one of claims 1-8, characterized in that: the reaction conditions are as follows: reacting for 18-30 h at 110-160 ℃ in a protective atmosphere.

10. The method for synthesizing the spiroindanone compound according to claim 9, characterized in that: the reaction conditions are as follows: and reacting for 22-28 h at 130-150 ℃ in a protective atmosphere.