CN117756636A - Method for synthesizing polysubstituted naphthalene derivative - Google Patents
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- 150000002790 naphthalenes Chemical class 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title claims abstract description 18
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 45
- WQPDQJCBHQPNCZ-UHFFFAOYSA-N cyclohexa-2,4-dien-1-one Chemical class O=C1CC=CC=C1 WQPDQJCBHQPNCZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- -1 polysubstituted naphthalene compound Chemical class 0.000 claims abstract description 10
- 239000002841 Lewis acid Substances 0.000 claims abstract description 8
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 8
- 239000000758 substrate Substances 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 3
- 238000001308 synthesis method Methods 0.000 claims abstract 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 16
- 239000003480 eluent Substances 0.000 claims description 9
- 239000011968 lewis acid catalyst Substances 0.000 claims description 9
- 239000003208 petroleum Substances 0.000 claims description 9
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000007800 oxidant agent Substances 0.000 claims description 8
- 230000001590 oxidative effect Effects 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 4
- 239000000376 reactant Substances 0.000 claims description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 3
- 238000010189 synthetic method Methods 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 2
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 2
- 238000010828 elution Methods 0.000 claims description 2
- BZQRBEVTLZHKEA-UHFFFAOYSA-L magnesium;trifluoromethanesulfonate Chemical compound [Mg+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F BZQRBEVTLZHKEA-UHFFFAOYSA-L 0.000 claims description 2
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 claims description 2
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 2
- CITILBVTAYEWKR-UHFFFAOYSA-L zinc trifluoromethanesulfonate Chemical compound [Zn+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F CITILBVTAYEWKR-UHFFFAOYSA-L 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 238000000746 purification Methods 0.000 abstract description 8
- 125000000524 functional group Chemical group 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract 1
- 238000004440 column chromatography Methods 0.000 description 14
- 238000004090 dissolution Methods 0.000 description 7
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 7
- 239000007810 chemical reaction solvent Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
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- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 1
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- 230000002365 anti-tubercular Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
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- GPXLMGHLHQJAGZ-JTDSTZFVSA-N nafcillin Chemical compound C1=CC=CC2=C(C(=O)N[C@@H]3C(N4[C@H](C(C)(C)S[C@@H]43)C(O)=O)=O)C(OCC)=CC=C21 GPXLMGHLHQJAGZ-JTDSTZFVSA-N 0.000 description 1
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- FUSNMLFNXJSCDI-UHFFFAOYSA-N tolnaftate Chemical compound C=1C=C2C=CC=CC2=CC=1OC(=S)N(C)C1=CC=CC(C)=C1 FUSNMLFNXJSCDI-UHFFFAOYSA-N 0.000 description 1
- 229960004880 tolnaftate Drugs 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
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Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of organic synthesis, in particular to a synthesis method of a polysubstituted naphthalene derivative, which comprises the steps of preparation of a reaction substrate, main reaction and post-treatment. The invention uses Lewis acid as catalyst, the substrate cyclohexadienone derivative takes intramolecular cyclization reaction, and the polysubstituted naphthalene derivative is obtained by separation and purification. Compared with the traditional method, the method provided by the invention has the following advantages: simple operation, good tolerance of functional groups and mild reaction conditions, and is especially suitable for preparing related products in a large scale. The method also provides a new route for synthesizing the complex polysubstituted naphthalene compound, and has important application prospect in organic synthesis and industrial production.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing a polysubstituted naphthalene derivative.
Background
Naphthalene (napthalene) is the simplest condensed ring aromatic hydrocarbon and has a stable aromatic conjugated structure. Naphthalene derivatives have important biological functions, and oxidative metabolites of naphthalene derivatives can interact with cysteines in cell target proteins in a covalent bond mode, so that the proteins lose physiological activity and generate cytotoxicity. The polysubstituted naphthalene structure is widely used in natural products and artificially synthesized bioactive compounds, and also in medicine molecules, such as anticancer, antibacterial, antiinflammatory, antituberculosis, antiviral, and for treating nerve diseases and cardiovascular diseases. At present, clinical medicines containing polysubstituted naphthalene structures such as tolnaftate can effectively treat superficial skin fungus infection; nafcillin can be used for treating infections caused by gram positive bacteria, duloxetine for treating depressive disorder and generalized anxiety disorder, etc. Therefore, in recent years, the synthesis of polysubstituted naphthalene compounds has attracted widespread attention by synthetic chemists. Unfortunately, the current synthetic methods focus mainly on the construction of polysubstituted naphthalene structures by intermolecular transition metal catalyzed 6-endo-dig cyclization reactions (j. Org. Chem.2019,84, 12856-12870.) and tandem reactions of benzyl alkyne and α -cyano- β -methyleneketone (j. Org. Chem.2020,85, 14210-14218.), benzene cyclization reactions (org. Lett.2013,15, 898-901.), and the like, and are often accompanied by problems of harsh reaction conditions, high cost, low yields, poor substrate applicability, and the like. Therefore, the traditional method is difficult to meet the synthesis requirement of the polysubstituted naphthalene compounds, so that the synthesis route is simplified, the process cost is reduced, and the finding of a mild, efficient and universal synthesis strategy has important significance.
Disclosure of Invention
In view of the above-mentioned shortcomings in the prior art, the present invention aims to provide an economical, efficient and sustainable method for preparing polysubstituted naphthalene derivatives by using Lewis acid as a catalyst, and a series of polysubstituted naphthalene derivatives are synthesized by the method for pharmaceutical chemistry research.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
provided is a synthetic method of a polysubstituted naphthalene derivative, which comprises the steps of reaction substrate preparation, main reaction and post-treatment, and specifically comprises the following steps:
A. preparing a reaction system: dissolving a Lewis acid catalyst into an organic solvent, and stirring for 2-4 min to obtain a reaction system a;
B. the main reaction: sequentially adding a cyclohexadienone derivative, an oxidant and an organic solvent into the reaction system a, and stirring and reacting for 12-72 hours at the temperature of 15-25 ℃ to obtain a reactant b;
C. post-treatment: removing solvent substances in the reactant b, eluting, separating and purifying to obtain the target polysubstituted naphthalene compound.
Further, the molar ratio of the cyclohexadienone derivative, the Lewis acid and the oxidant is 1:0.1-0.4:1-3.
Further, the Lewis acid is any one of copper triflate, scandium triflate, magnesium triflate, zinc triflate, silver triflate, lithium chloride, triflic acid and tetrafluoroborate diethyl ether.
Further, the oxidant is any one of oxygen, copper acetate and silver nitrate, and 2, 3-dichloro-5, 6-dicyano-p-benzoquinone.
Further, the organic solvent is any one of methanol, ethanol, acetonitrile, tetrahydrofuran, 1, 4-dioxane, diethyl ether, dichloromethane, toluene, N-dimethylformamide and dimethyl sulfoxide.
Further, the elution is performed by using ethyl acetate and petroleum ether as the eluent.
Further, the resulting polysubstituted naphthalene compound is any of the following structural formula:
the beneficial effects of the invention are as follows:
1. the invention prepares the series of polysubstituted naphthalene compounds by using Lewis acid (Lewis acid) catalytic intramolecular cyclization strategy, thereby greatly reducing the production cost and having remarkable social and economic benefits.
2. The invention has the advantages of simplified synthetic route, simple and convenient operation and good functional group tolerance.
3. The synthesis of the invention can be applied to industrial scale, and breaks through the limitation of small scale of organic synthesis.
Detailed Description
The following description of the embodiments of the present invention is provided to facilitate understanding of the present invention by those skilled in the art, but it should be understood that the present invention is not limited to the scope of the embodiments, and all the inventions which make use of the inventive concept are protected by the spirit and scope of the present invention as defined and defined in the appended claims to those skilled in the art.
Example 1
In a glove box, a Lewis acid catalyst Cu (OTf) stored in a dark place 2 (0.02 mmol) was accurately weighed and charged into a Schlenk reaction tube with a stirrer, 1.0mL of tetrahydrofuran was added thereto for dissolution, and the mixture was stirred electromagnetically at room temperature for 2 minutes. Then the above cyclohexadienone derivative (0.20 mmol), the oxidant DDQ (0.20 mmol) was added, and finally 1mL tetrahydrofuran was added, and the glove box was removed by plugging. Stirring at ambient temperature (15-25 ℃). The progress of the reaction was monitored by TLC or GC-MS. After the reaction was completed, the reaction tube was opened and volatile matters were removed under reduced pressure using a rotary evaporator, and purified by column chromatography using ethyl acetate and petroleum ether as eluent. The reaction solvent was concentrated under reduced pressure, followed by column chromatography purification to give polysubstituted naphthalene compound 1 (90% yield). 1 H NMR(600MHz,CDCl 3 )δ12.04(s,1H),8.65(d,J＝12.0Hz,1H),7.74(d,J＝12.0Hz,1H),7.10-7.16(m,3H),4.10(s,3H).
Example 2
In a glove box, the Lewis acid catalyst AgOTf (0.02 mmol) stored in a dark place was accurately weighed and charged into a Schlenk reaction tube with a stirrer, after 1.0mL of tetrahydrofuran was added for dissolution, and stirred electromagnetically at room temperature for 2min. Then the above cyclohexadienone derivative (0.20 mmol) was added, and 1mL of tetrahydrofuran was added, and the glove box was removed by plugging. Oxygen was sparged to displace the three gases and stirred at ambient temperature (15-25 ℃). The progress of the reaction was monitored by TLC or GC-MS. After the reaction was completed, the reaction tube was opened and volatile matters were removed under reduced pressure using a rotary evaporator, and purified by column chromatography using ethyl acetate and petroleum ether as eluent. The reaction solvent was concentrated under reduced pressure, followed by column chromatography purification to give polysubstituted naphthalene compound 1 (90% yield). 1 H NMR(600MHz,CDCl 3 )δ12.04(s,1H),8.65(d,J＝12.0Hz,1H),7.74(d,J＝12.0Hz,1H),7.10-7.16(m,3H),4.10(s,3H).
Example 3
In a glove box, a Lewis acid catalyst Cu (OTf) stored in a dark place 2 (0.02 mmol) was accurately weighed and charged into a Schlenk reaction tube with a stirrer, 1.0mL of tetrahydrofuran was added thereto for dissolution, and the mixture was stirred electromagnetically at room temperature for 2 minutes. Then the above cyclohexadienone derivative (0.20 mmol), the oxidant DDQ (0.20 mmol) was added, and finally 1mL tetrahydrofuran was added, and the glove box was removed by plugging. Stirring at ambient temperature (15-25 ℃). The progress of the reaction was monitored by TLC or GC-MS. After the reaction was completed, the reaction tube was opened and volatile matters were removed under reduced pressure using a rotary evaporator, and purified by column chromatography using ethyl acetate and petroleum ether as eluent. The reaction solvent was concentrated under reduced pressure, followed by column chromatography purification to give polysubstituted naphthalene compound 2 (92% yield). 1 H NMR(600MHz,CDCl 3 )δ12.01(s,1H),8.67(d,J＝12.0Hz,1H),7.71(d,J＝12.0Hz,1H),7.12-7.14(m,3H),1.44(s,9H).
Example 4
In a glove box, the Lewis acid catalyst AgOTf (0.02 mmol) stored in a dark place was accurately weighed and charged into a Schlenk reaction tube with a stirrer, after 1.0mL of tetrahydrofuran was added for dissolution, and stirred electromagnetically at room temperature for 2min. Then the cyclohexadienone derivative (0.20 mmol) was added, and finally 1mL of tetrahydrofuran was added, and the glove box was removed by plugging. Oxygen was sparged to displace the three gases and stirred at ambient temperature (15-25 ℃). The progress of the reaction was monitored by TLC or GC-MS. After the reaction was completed, the reaction tube was opened and volatile matters were removed under reduced pressure using a rotary evaporator, and purified by column chromatography using ethyl acetate and petroleum ether as eluent. Will be reversedThe solvent was concentrated under reduced pressure, followed by column chromatography purification to give polysubstituted naphthalene compound 3 (88% yield). 1 H NMR(600MHz,CDCl 3 )δ12.01(s,1H),8.87(s,1H),7.73(d,J＝12.0Hz,1H),7.46(s,1H),6.62(s,1H),4.07(s,3H).
Example 5
In a glove box, the Lewis acid catalyst AgOTf (0.02 mmol) stored in a dark place was accurately weighed and charged into a Schlenk reaction tube with a stirrer, after 1.0mL of tetrahydrofuran was added for dissolution, and stirred electromagnetically at room temperature for 2min. Then the above cyclohexadienone derivative (0.20 mmol) was added, and finally 1.0mL tetrahydrofuran was added, and the glove box was removed by plugging. Oxygen was sparged to displace the three gases and stirred at ambient temperature (15-25 ℃). The progress of the reaction was monitored by TLC or GC-MS. After the reaction was completed, the reaction tube was opened and volatile matters were removed under reduced pressure using a rotary evaporator, and purified by column chromatography using ethyl acetate and petroleum ether as eluent. The reaction solvent was concentrated under reduced pressure, followed by column chromatography purification to give polysubstituted naphthalene compound 4 (93% yield). 1 H NMR(600MHz,CDCl 3 )δ12.03(s,1H),8.65(d,J＝12.0Hz,1H),7.90(d,J＝12.0Hz,1H),7.46(s,1H),6.81-7.01(m,2H),2.49(s,3H).
Example 6
In a glove box, the Lewis acid catalyst AgOTf (0.02 mmol) stored in a dark place was accurately weighed and charged into a Schlenk reaction tube with a stirrer, after 1.0mL of tetrahydrofuran was added for dissolution, and stirred electromagnetically at room temperature for 2min. Then the above cyclohexadienone derivative (0.20 mmol) was added, and finally 1.0mL tetrahydrofuran was added, and the glove box was removed by plugging. Oxygen was sparged to displace the three gases and stirred at ambient temperature (15-25 ℃). The progress of the reaction was monitored by TLC or GC-MS. Reaction junctionAfter the beam, the reaction tube was opened and the volatile matter was removed under reduced pressure using a rotary evaporator, and purified by column chromatography using ethyl acetate and petroleum ether as eluent. The reaction solvent was concentrated under reduced pressure, followed by column chromatography purification to give polysubstituted naphthalene compound 5 (88% yield). 1 H NMR(600MHz,CDCl 3 )δ12.07(s,1H),8.25(dd,J＝12.0Hz,1H),8.10(d,J＝12.0Hz,1H),7.80(d,J＝11.0Hz,2H),7.50-7.61(m,4H),6.90-7.04(m,2H).
Example 7
In a glove box, the Lewis acid catalyst AgOTf (0.02 mmol) stored in a dark place was accurately weighed and charged into a Schlenk reaction tube with a stirrer, after 1.0mL of tetrahydrofuran was added for dissolution, and stirred electromagnetically at room temperature for 2min. Then the above cyclohexadienone derivative (0.20 mmol) was added, and finally 1.0mL tetrahydrofuran was added, and the glove box was removed by plugging. Oxygen was sparged to displace the three gases and stirred at ambient temperature (15-25 ℃). The progress of the reaction was monitored by TLC or GC-MS. After the reaction was completed, the reaction tube was opened and volatile matters were removed under reduced pressure using a rotary evaporator, and purified by column chromatography using ethyl acetate and petroleum ether as eluent. The reaction solvent was concentrated under reduced pressure, followed by column chromatography purification to give polysubstituted naphthalene compound 6 (89% yield). 1 H NMR(600MHz,CDCl 3 )δ12.08(s,1H),8.23(dd,J＝12.0Hz,1H),8.12(d,J＝12.0Hz,1H),12.07(s,1H),8.25(dd,J＝12.0Hz,1H),8.10(d,J＝12.0Hz,1H),7.73(d,J＝10.3Hz,2H),7.51(s,1H),6.90-7.01(m,4H),3.81(s,3H).
Compared with the traditional method, the method provided by the invention has the following advantages: simple operation, good tolerance of functional groups and mild reaction conditions, and is especially suitable for preparing related products in a large scale. The method also provides a new route for synthesizing the complex polysubstituted naphthalene compound, and has important application prospect in organic synthesis and industrial production.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Furthermore, it should be understood that although the present disclosure describes embodiments, not every embodiment is provided with a separate embodiment, and that this description is provided for clarity only, and that the disclosure is not limited to the embodiments described in detail below, and that the embodiments described in the examples may be combined as appropriate to form other embodiments that will be apparent to those skilled in the art.
Claims (7)
1. The synthesis method of the polysubstituted naphthalene derivative is characterized by comprising the steps of preparation of a reaction substrate, main reaction and post-treatment, and specifically comprises the following steps:
A. preparing a reaction system: dissolving a Lewis acid catalyst into an organic solvent, and stirring for 2-4 min to obtain a reaction system a;
B. the main reaction: sequentially adding a cyclohexadienone derivative, an oxidant and an organic solvent into the reaction system a, and stirring and reacting for 12-72 hours at the temperature of 15-25 ℃ to obtain a reactant b;
C. post-treatment: removing solvent substances in the reactant b, eluting, separating and purifying to obtain the target polysubstituted naphthalene compound.
2. The method for synthesizing the polysubstituted naphthalene derivative according to claim 1, wherein the molar ratio of the cyclohexadienone derivative, the lewis acid and the oxidant is 1:0.1-0.4:1-3.
3. The method for synthesizing a polysubstituted naphthalene derivative according to claim 1, wherein the lewis acid is any one of copper triflate, scandium triflate, magnesium triflate, zinc triflate, silver triflate, lithium chloride, triflic acid, and diethyl tetrafluoroborate.
4. The method for synthesizing a polysubstituted naphthalene derivative according to claim 1, wherein the oxidizing agent is any one of oxygen, copper acetate, silver nitrate, 2, 3-dichloro-5, 6-dicyano-p-benzoquinone.
5. The method for synthesizing a polysubstituted naphthalene derivative according to claim 1, wherein the organic solvent is any one of methanol, ethanol, acetonitrile, tetrahydrofuran, 1, 4-dioxane, diethyl ether, dichloromethane, toluene, N-dimethylformamide, and dimethyl sulfoxide.
6. The method for synthesizing a polysubstituted naphthalene derivative according to claim 1, wherein the elution is performed using ethyl acetate and petroleum ether as the eluent.
7. A polysubstituted naphthalene derivative, characterized in that it is obtained by any of the synthetic methods according to claims 1-5, having the following structural formula:
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