CN112939753A - Synthesis method of 1-indanone compound - Google Patents
Synthesis method of 1-indanone compound Download PDFInfo
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- CN112939753A CN112939753A CN202010968342.8A CN202010968342A CN112939753A CN 112939753 A CN112939753 A CN 112939753A CN 202010968342 A CN202010968342 A CN 202010968342A CN 112939753 A CN112939753 A CN 112939753A
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- QNXSIUBBGPHDDE-UHFFFAOYSA-N alpha-indanone Natural products C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 title claims abstract description 32
- -1 1-indanone compound Chemical class 0.000 title claims abstract description 29
- 238000001308 synthesis method Methods 0.000 title abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 23
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000005711 Benzoic acid Substances 0.000 claims abstract description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 235000010233 benzoic acid Nutrition 0.000 claims abstract description 10
- 229930040373 Paraformaldehyde Natural products 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229920002866 paraformaldehyde Polymers 0.000 claims abstract description 7
- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 7
- 239000010948 rhodium Substances 0.000 claims abstract description 7
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 239000003513 alkali Substances 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical group FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 3
- QVLTVILSYOWFRM-UHFFFAOYSA-L CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C Chemical group CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C QVLTVILSYOWFRM-UHFFFAOYSA-L 0.000 claims description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 239000001632 sodium acetate Substances 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims 1
- 150000001559 benzoic acids Chemical class 0.000 claims 1
- 239000000758 substrate Substances 0.000 abstract description 5
- 125000000524 functional group Chemical group 0.000 abstract description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 50
- 238000001228 spectrum Methods 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 238000004440 column chromatography Methods 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 13
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- 239000001257 hydrogen Substances 0.000 description 13
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 11
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000002156 mixing Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- NYBCPEOJFAJPLJ-UHFFFAOYSA-N 2,3,6,7,8,9-hexahydrocyclopenta[a]naphthalen-1-one Chemical compound C1CCCC2=C3C(=O)CCC3=CC=C21 NYBCPEOJFAJPLJ-UHFFFAOYSA-N 0.000 description 2
- KQBXYYMELBQTFL-UHFFFAOYSA-N 2,3-dihydrocyclopenta[a]naphthalen-1-one Chemical compound C1=CC=CC2=C3C(=O)CCC3=CC=C21 KQBXYYMELBQTFL-UHFFFAOYSA-N 0.000 description 2
- NXOHUHPRFMGJSZ-UHFFFAOYSA-N 5,7-dimethyl-2,3-dihydroinden-1-one Chemical compound CC1=CC(C)=CC2=C1C(=O)CC2 NXOHUHPRFMGJSZ-UHFFFAOYSA-N 0.000 description 2
- LWUXXRGOGYBNHJ-UHFFFAOYSA-N 5-bromo-7-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC(Br)=CC2=C1C(=O)CC2 LWUXXRGOGYBNHJ-UHFFFAOYSA-N 0.000 description 2
- KTWVPXXMTRMYIM-UHFFFAOYSA-N 5-chloro-7-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC(Cl)=CC2=C1C(=O)CC2 KTWVPXXMTRMYIM-UHFFFAOYSA-N 0.000 description 2
- YUZJSMSRZDCHKC-UHFFFAOYSA-N 5-chloro-7-methyl-2,3-dihydroinden-1-one Chemical compound CC1=CC(Cl)=CC2=C1C(=O)CC2 YUZJSMSRZDCHKC-UHFFFAOYSA-N 0.000 description 2
- VFAXSVBTFNUTSW-UHFFFAOYSA-N 5-fluoro-7-methyl-2,3-dihydroinden-1-one Chemical compound CC1=CC(F)=CC2=C1C(=O)CC2 VFAXSVBTFNUTSW-UHFFFAOYSA-N 0.000 description 2
- UUUDFFGGORMLAR-UHFFFAOYSA-N 6,7-dimethoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=C2CCC(=O)C2=C1OC UUUDFFGGORMLAR-UHFFFAOYSA-N 0.000 description 2
- CZXBVBATQPHSSL-UHFFFAOYSA-N 7-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=CC2=C1C(=O)CC2 CZXBVBATQPHSSL-UHFFFAOYSA-N 0.000 description 2
- DOXALDISRDZGNV-UHFFFAOYSA-N 7-methyl-2,3-dihydroinden-1-one Chemical compound CC1=CC=CC2=C1C(=O)CC2 DOXALDISRDZGNV-UHFFFAOYSA-N 0.000 description 2
- HDEZOUNABYXYOB-UHFFFAOYSA-N O=C1CCC2=CC=CC(CC3=CC=CC=C3)=C12 Chemical compound O=C1CCC2=CC=CC(CC3=CC=CC=C3)=C12 HDEZOUNABYXYOB-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- NTFFVFPCZOKKOT-UHFFFAOYSA-N 3-chloro-1-(4-methoxyphenyl)prop-2-en-1-one Chemical compound COC1=CC=C(C(=O)C=CCl)C=C1 NTFFVFPCZOKKOT-UHFFFAOYSA-N 0.000 description 1
- PFLSDXYKTMMDEA-UHFFFAOYSA-N 4-cyclopropylbenzoyl chloride Chemical compound C1=CC(C(=O)Cl)=CC=C1C1CC1 PFLSDXYKTMMDEA-UHFFFAOYSA-N 0.000 description 1
- RWEVGLMABSFMKW-UHFFFAOYSA-N 8-bromo-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=C1C=CC=C2Br RWEVGLMABSFMKW-UHFFFAOYSA-N 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
- 238000006229 Nazarov cyclization reaction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- SISAYUDTHCIGLM-UHFFFAOYSA-N bromine dioxide Inorganic materials O=Br=O SISAYUDTHCIGLM-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000006452 multicomponent reaction Methods 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
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- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a synthesis method of a 1-indanone compound, which comprises the following steps: adding a benzoic acid compound, dimethyl malonate, paraformaldehyde, a rhodium catalyst and alkali into an organic solvent, heating under the condition of nitrogen for reaction, and after the reaction is completed, carrying out post-treatment to obtain the 1-indanone compound. The invention provides a method for synthesizing 1-indanone compounds, which has the advantages of simple and convenient operation, cheap and easily obtained substrate, wide universality and good functional group compatibility, and provides a simple and efficient method for synthesizing indanone derivatives with diversified structures.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of a 1-indanone compound.
Background
The 1-indanone compounds are very important and universal frameworks, widely exist in bioactive molecules and drug molecules, are important substrates for screening the activity of drug molecules, and are also important intermediates for pharmaceutical chemistry and organic synthesis. Chemists have developed many methods to build this important backbone, such as Friedel-Crafts acylation of aromatics, Nazarov cyclization. These methods generally require pre-functionalization of the substrate, lengthy reaction steps, and harsh reaction conditions. Therefore, it is necessary to develop a novel and efficient method for constructing the 1-indanone skeleton compounds.
The transition metal catalyzed C-H bond activation strategy assisted by a guide group provides an atom economical and step economical method for efficiently synthesizing complex molecules through decades of development. In recent years, methods for synthesizing 1-indanones by activating C-H bonds have been reported. Different directing groups have been used in these processes for the construction of indanones, such as amides and thioylide-type directing groups. However, these directing groups often require pre-installation, adding synthetic steps and limiting the synthetic applications of the method. Carboxyl groups are common functional groups widely present in organic molecules, while carboxylic acids are readily available starting materials in organic synthesis. Based on the availability of carboxylic acids that are inexpensive and can act as traceless directing groups, much attention has been focused on carboxylic acid-directed C-H activation reactions. Despite the tremendous advances made in this area, applications for the construction of complex molecules for carboxylic acid-directed multicomponent reactions have not been fully developed.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides a method for synthesizing 1-indanone compounds, which has the advantages of simple and convenient operation, cheap and easily-obtained substrate, wide universality and good functional group compatibility, and provides a simple and efficient method for synthesizing indanone derivatives with diversified structures.
A method for synthesizing 1-indanone compounds comprises the following steps: adding a benzoic acid compound, dimethyl malonate, paraformaldehyde, a rhodium catalyst and alkali into an organic solvent, heating under the condition of nitrogen for reaction, and after the reaction is completed, carrying out post-treatment to obtain the 1-indanone compound;
the specific reaction process is as follows:
wherein, R is one of benzyl, alkyl, methoxy and halogen, preferably one or more of benzyl, methyl, methoxy, F, Cl or Br.
Preferably, the chemical formula of the 1-indanone compound is one of the compounds shown in formula (I-1) to formula (I-12):
preferably, the organic solvent is Hexafluoroisopropanol (HFIP).
Preferably, the base is sodium acetate.
Preferably, the rhodium catalyst is pentamethylcyclopentadienylrhodium dichloride.
The reaction temperature under the nitrogen condition is preferably 150-160 ℃, and more preferably 150 ℃. The reaction time is preferably 12 to 18 hours, and more preferably 18 hours. .
Preferably, the molar ratio of the rhodium catalyst to the benzoic acid compound is (0.03-0.07): 1, more preferably 0.05: 1.
preferably, the molar ratio of the base to the benzoic acid compound is (0.8 to 1.2): 1, more preferably 1: 1.
preferably, the molar ratio of the benzoic acid compound, the dimethyl malonate, and the paraformaldehyde is 1: (1.5-2.5): (1.5-2.5), more preferably 1: 2: 2.
preferably, the post-treatment comprises cooling, suction filtration, silica gel sample mixing and column chromatography purification.
Compared with the prior art, the invention has the beneficial effects that:
(1) the 1-indanone compound is synthesized by a simple and easily-obtained raw material multi-component one-pot method, so that the conversion efficiency is high, and the economical efficiency of the steps is good;
(2) the synthetic method disclosed by the invention is simple to operate, high in reaction yield, and very good in substrate universality and functional group compatibility.
Drawings
FIG. 1 is a hydrogen spectrum and a carbon spectrum of a compound obtained in example 1 of the present invention;
FIG. 2 is a graph showing a hydrogen spectrum and a carbon spectrum of a compound obtained in example 2 of the present invention;
FIG. 3 shows a hydrogen spectrum and a carbon spectrum of a compound obtained in example 3 of the present invention;
FIG. 4 is a graph showing a hydrogen spectrum and a carbon spectrum of a compound obtained in example 4 of the present invention;
FIG. 5 shows a hydrogen spectrum and a carbon spectrum of a compound obtained in example 5 of the present invention;
FIG. 6 shows a hydrogen spectrum and a carbon spectrum of a compound obtained in example 6 of the present invention;
FIG. 7 shows a hydrogen spectrum and a carbon spectrum of a compound obtained in example 7 of the present invention;
FIG. 8 is a graph showing a hydrogen spectrum and a carbon spectrum of a compound obtained in example 8 of the present invention;
FIG. 9 shows a hydrogen spectrum and a carbon spectrum of a compound obtained in example 9 of the present invention;
FIG. 10 shows a hydrogen spectrum and a carbon spectrum of a compound obtained in example 10 of the present invention;
FIG. 11 is a graph showing a hydrogen spectrum and a carbon spectrum of a compound obtained in example 11 of the present invention;
FIG. 12 shows a hydrogen spectrum and a carbon spectrum of a compound obtained in example 12 of the present invention.
Detailed Description
The present invention will be further described with reference to specific examples, which are intended to be preferred embodiments of the invention.
Examples 1 to 12
Adding benzoic acid compound (0.3mmol), dimethyl malonate (0.6mmol), paraformaldehyde (0.6mmol), pentamethylcyclopentadienyl rhodium dichloride (0.015mmol), sodium acetate (0.3mmol) and 0.4ml of organic solvent into a test tube according to the raw material ratio shown in the table 1, uniformly mixing and stirring, respectively reacting according to the reaction conditions shown in the table 2 in the presence of nitrogen, cooling, performing suction filtration, mixing a sample with silica gel, and performing column chromatography purification to obtain corresponding 1-indanone compound (I);
the data of the 1-indanone compound (I) are represented in the figures 1-12, wherein a hydrogen spectrum is tested on a 400MHz nuclear magnetic instrument, and a carbon spectrum is tested on a 100MHz nuclear magnetic instrument; testing conditions are that tetramethylsilane is used as an internal standard at room temperature, and a sample is dissolved by deuterated chloroform;
the above reaction process is shown as the following formula:
TABLE 1 raw material ratios of examples 1 to 12
TABLE 2 reaction conditions and reaction results of examples 1 to 12
In tables 1 and 2, T is the reaction temperature, T is the reaction time, Bn is benzyl, 1-naphthyl is 1-substituted naphthyl, and 1-tetrahydronaphtyl is 1-substituted tetrahydronaphthyl.
The structures and related data of the partial compounds prepared in examples 1-12 are as follows:
7-methyl-2, 3-dihydro-1H-inden-1-one (I-1): purification by column chromatography (petroleum ether: EtOAc ═ 15: 1) gave a white solid (35.5mg, 81%) with a melting point of 48-49 ℃.
1H NMR(400MHz,CDCl3)δ7.42(t,J=7.6Hz,1H),7.27(d,J=7.6Hz,1H),7.09(d,J=7.6Hz,1H),3.08(t,J=6.0Hz,2H),2.67-2.65(m,2H),2.63(s,3H);13C NMR(100MHz,CDCl3)δ208.1,156.0,138.9,134.5,134.0,129.1,124.0,36.8,25.4,18.4.
7-benzyl-2, 3-dihydro-1H-inden-1-one (I-2): purification by column chromatography (petroleum ether: EtOAc ═ 15: 1) gave a white solid (46.7mg, 70%) with a melting point of 77-79 ℃.
1H NMR(400MHz,CDCl3)δ7.43(t,J=7.6Hz,1H),7.29(d,J=7.6Hz,1H),7.26-7.25(m,4H),7.20-7.15(m,1H),7.05(d,J=7.6Hz,1H),4.48(s,2H),3.08(t,J=6.4Hz,2H),2.68-2.66(m,2H);13C NMR(100MHz,CDCl3)δ207.7,156.2,141.8,140.5,134.2,133.9,129.3,128.7,128.4,126.0,124.6,36.9,36.6,25.3.HRMS(EI-TOF)calcd for C16H14O(M+):222.1045,found:222.1043.
7-methoxy-2, 3-dihydro-1H-inden-1-one (I-3): purification by column chromatography (petroleum ether: EtOAc ═ 3: 1) gave a pale yellow solid (41.8mg, 86%), mp 92-93 ℃.
1H NMR(400MHz,CDCl3)δ7.49(t,J=8.0Hz,1H),6.98(d,J=7.6Hz,1H),6.75(d,J=8.0Hz,1H),3.92(s,3H),3.05(t,J=6.4Hz,2H),2.65-2.62(m,2H);13C NMR(100MHz,CDCl3)δ204.9,158.1,158.0,136.4,125.2,118.4,108.8,55.7,36.8,25.6.
6-bromo-7-methyl-2, 3-dihydro-1H-indan-1-one (I-4): purification by column chromatography (petroleum ether: EtOAc ═ 20: 1) gave a yellow solid (27.0mg, 40%) m.p. 82-83 ℃.
1H NMR(400MHz,CDCl3)δ7.68(d,J=8.4Hz,1H),7.15(d,J=8.0Hz,1H),3.01(t,J=6.4Hz,2H),2.71(s,3H),2.70-2.68(m,2H);13C NMR(100MHz,CDCl3)δ206.8,155.1,138.6,137.6,135.8,125.3,125.0,37.1,24.7,17.0.HRMS(EI-TOF)calcd for C10H9BrO(M+):223.9837,found:223.9838.
6, 7-dimethoxy-2, 3-dihydro-1H-inden-1-one (I-5): purification by column chromatography (petroleum ether: EtOAc ═ 3: 1) gave a white solid (38.1mg, 66%) with a melting point of 41-42 ℃.
1H NMR(400MHz,CDCl3)δ7.17(d,J=8.4Hz,1H),7.09(d,J=8.0Hz,1H),3.99(s,3H),3.87(s,3H),3.02(t,J=6.4Hz,2H),2.70-2.67(m,2H);13C NMR(100MHz,CDCl3)δ204.6,151.2,148.1,147.2,129.6,121.2,120.3,61.9,57.0,37.7,24.8.
5, 7-dimethyl-2, 3-dihydro-1H-inden-1-one (I-6): purification by column chromatography (petroleum ether: EtOAc ═ 15: 1) gave a white solid (36.0mg, 75%) with a melting point of 75-76 ℃.
1H NMR(400MHz,CDCl3)δ7.07(s,1H),6.91(s,1H),3.02(t,J=6.4Hz,2H),2.65-2.62(m,2H),2.59(s,3H),2.38(s,3H);13C NMR(100MHz,CDCl3)δ207.5,156.5,145.0,138.6,132.3,130.3,124.4,37.0,25.2,21.8,18.2.
5-fluoro-7-methyl-2, 3-dihydro-1H-inden-1-one (I-7): purification by column chromatography (petroleum ether: EtOAc ═ 15: 1) gave a pale yellow solid (35.5mg, 72%) with a melting point of 49-50 ℃.
1H NMR(400MHz,CDCl3)δ6.92(d,J=8.4Hz,1H),6.80(d,J=9.6Hz,1H),3.06(t,J=6.4Hz,2H),2.69-2.66(m,2H),2.62(s,3H);13C NMR(100MHz,CDCl3)δ206.1,166.31(d,JC-F=253.0Hz),158.9(d,JC-F=11.0Hz),141.9(d,JC-F=11.0Hz),131.0,116.8(d,JC-F=23.0Hz),110.5(d,JC-F=22.0Hz),37.1,25.5(d,JC-F=3.0Hz),18.4.HRMS(EI-TOF)calcd for C10H9FO(M+):164.0637,found:164.0638.
5-chloro-7-methyl-2, 3-dihydro-1H-inden-1-one (I-8): purification by column chromatography (petroleum ether: EtOAc ═ 20: 1) gave a yellow solid (25.5mg, 47%) melting point 59-60 ℃.
1H NMR(400MHz,CDCl3)δ7.19(s,1H),7.02(s,1H),2.99(t,J=6.4Hz,2H),2.62-2.59(m,2H),2.53(s,3H);13C NMR(100MHz,CDCl3)δ206.5,157.4,140.4,140.2,133.0,129.5,124.1,36.9,25.2,18.1.HRMS(EI-TOF)calcd for C10H9ClO(M+):180.0342,found:180.0342.
5-chloro-7-methoxy-2, 3-dihydro-1H-inden-1-one (I-9): purification by column chromatography (petroleum ether: EtOAc ═ 3: 1) gave a white solid (45.4mg, 77%), mp 114-.
1H NMR(400MHz,CDCl3)δ6.98(s,1H),6.74(s,1H),3.91(s,3H),3.03(t,J=6.4Hz,2H),2.66-2.63(m,2H);13C NMR(100MHz,CDCl3)δ203.4,159.0,158.2,142.4,123.9,118.7,110.1,56.1,36.8,25.6.HRMS(EI-TOF)calcd for C10H9ClO2(M+):196.0291,found:196.0290.
5-bromo-7-methoxy-2, 3-dihydro-1H-inden-1-one (I-10): purification by column chromatography (petroleum ether: EtOAc ═ 3: 1) gave a white solid (44.8mg, 62%), mp 105-.
1H NMR(400MHz,CDCl3)δ7.17(s,1H),6.91(s,1H),3.92(s,3H),3.04(t,J=6.4Hz,2H),2.66-2.63(m,2H);13C NMR(100MHz,CDCl3)δ203.6,159.1,158.1,131.0,124.3,121.8,113.0,56.2,36.7,25.5.HRMS(EI-TOF)calcd for C10H9BrO2(M+):239.9786,found:239.9784.
2,3,6,7,8, 9-hexahydro-1H-cyclopenta [ a ] naphthalen-1-one (I-11): purification by column chromatography (petroleum ether: EtOAc ═ 15: 1) gave a yellow oil (33.5mg, 60%).
1H NMR(400MHz,CDCl3)δ7.24(d,J=8.0Hz,1H),7.16(d,J=8.0Hz,1H),3.19-3.18(m,2H),3.02(t,J=6.0Hz,2H),2.79-2.78(m,2H),2.65-2.62(m,2H),1.80-1.77(m,4H);13C NMR(100MHz,CDCl3)δ208.2,154.1,137.9,136.3,135.6,134.1,123.4,37.1,29.4,25.8,25.1,22.7,22.5.
2, 3-dihydro-1H-cyclopenta [ a ] naphthalen-1-one (I-12): purification by column chromatography (petroleum ether: EtOAc: 15: 1) gave a white solid (36.6mg, 67%), m.p. 101-.
1H NMR(400MHz,CDCl3)δ9.15(d,J=8.4Hz,1H),8.01(d,J=8.4Hz,1H),7.87(d,J=8.4Hz,1H),7.68-7.64(m,1H),7.56-7.52(m,1H),7.48(d,J=8.4Hz,1H),3.18(t,J=5.6Hz,2H),2.79-2.76(m,2H);13C NMR(100MHz,CDCl3)δ207.6,158.5,135.7,132.6,131.1,129.4,128.9,128.1,126.6,124.1,124.0,36.9,26.2。
Claims (10)
1. A method for synthesizing 1-indanone compounds is characterized by comprising the following steps: adding a benzoic acid compound, dimethyl malonate, paraformaldehyde, a rhodium catalyst and alkali into an organic solvent, heating under the condition of nitrogen for reaction, and after the reaction is completed, carrying out post-treatment to obtain the 1-indanone compound;
the structure of the benzoic acid compound is shown as the formula (II):
the structure of the dimethyl malonate is shown as the formula (III):
the structure of the paraformaldehyde is shown as a formula (IV):
HCHO (IV);
the structure of the 1-indanone compound is shown as the formula (I):
in the formulas (I) to (II), R is one or more of benzyl, alkyl, methoxy and halogen.
2. The method for synthesizing the 1-indanone compound according to claim 1, wherein R is one or more of benzyl, methyl, methoxy, F, Cl or Br.
4. the method for synthesizing 1-indanone compounds according to claim 1, wherein the organic solvent is hexafluoroisopropanol.
5. The method for synthesizing 1-indanone compounds according to claim 1, wherein the alkali is sodium acetate.
6. The method for synthesizing the 1-indanone compound according to claim 1, wherein the rhodium catalyst is pentamethylcyclopentadienyl rhodium dichloride.
7. The method for synthesizing the 1-indanone compound according to claim 1, wherein the reaction temperature is 150-160 ℃ and the reaction time is 12-18 hours under the nitrogen condition.
8. The method for synthesizing 1-indanone compounds according to claim 1, wherein the molar ratio of the rhodium catalyst to the benzoic acid compounds is (0.03-0.07): 1.
9. the method for synthesizing 1-indanone compounds according to claim 1, wherein the molar ratio of the base to the benzoic acid compound is (0.8-1.2): 1.
10. the method for synthesizing 1-indanone compounds according to claim 1, wherein the molar ratio of the benzoic acid compound, the dimethyl malonate, and the paraformaldehyde is 1: (1.5-2.5): (1.5-2.5).
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JP2013227271A (en) * | 2012-03-29 | 2013-11-07 | Japan Polyethylene Corp | Metallocene compound, olefin polymerization catalyst component and olefin polymerization catalyst including the same, and method of producing olefine polymer using the olefin polymerization catalyst |
US20180071412A1 (en) * | 2014-06-13 | 2018-03-15 | Merck Sharp & Dohme Corp. | Pyrrolo[2,3-c]pyridines as imaging agents for neurofibrilary tangles |
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US20080221083A1 (en) * | 2006-11-20 | 2008-09-11 | Matthias Hochgurtel | Heterobicyclic metalloprotease inhibitors |
CN101318887A (en) * | 2008-07-08 | 2008-12-10 | 上海化工研究院 | Method for preparing indene compounds |
JP2013227271A (en) * | 2012-03-29 | 2013-11-07 | Japan Polyethylene Corp | Metallocene compound, olefin polymerization catalyst component and olefin polymerization catalyst including the same, and method of producing olefine polymer using the olefin polymerization catalyst |
US20180071412A1 (en) * | 2014-06-13 | 2018-03-15 | Merck Sharp & Dohme Corp. | Pyrrolo[2,3-c]pyridines as imaging agents for neurofibrilary tangles |
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Publication number | Priority date | Publication date | Assignee | Title |
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CN115181014A (en) * | 2022-07-21 | 2022-10-14 | 四川大学 | Preparation method of 2-alkyl indan-1-ketone compound |
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