CN108863740A - A kind of preparation method of naphthalene ketone compounds - Google Patents
A kind of preparation method of naphthalene ketone compounds Download PDFInfo
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- C—CHEMISTRY; METALLURGY
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- 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
- C07C45/68—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 by increase in the number of carbon atoms
- C07C45/72—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 by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
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Abstract
The present invention provides a kind of simple process, the synthetic method at low cost, reaction substrate wide adaptation range for preparing naphthalene ketone compounds, this method is using 2- brom-acetophenone class compound as raw material, in copper catalyst, ligand, under alkali and organic solvent and inert atmosphere, heating reaction, easily and with excellent yield prepares naphthalene ketone compounds.
Description
Technical field
The application belongs to organic synthesis field, and in particular to a kind of preparation method of naphthalene ketone compounds.
Background technique
Naphthalene ketone compounds have extensively as important chemical products and intermediate in fields such as medicine, pesticide, dyestuffs
Application.It is used to produce insecticide, herbicide etc. on pesticide industry；It is used to produce anthraquinone dye on dye industry；Medical work
It is mainly used to produce pharmaceutical intermediate such as Sertraline etc. in industry.The method of synthesis naphthalene ketone compounds mainly passes through tetrahydro at present
Change oxidation, aromatic compound and the methods of the gamma-butyrolacton condensation, γ-benzene butyl chloride cyclisation method of naphthalene derivatives to be synthesized.
However, to still have substrate adaptation range narrow for these traditional methods, the deficiencies of environmental pollution.
Yu Shouyun etc. is then to report a kind of method for preparing polysubstituted naphthol derivative (referring to CN103467282A；
Org.Lett., Vol.15, No.18,2013), this method is original with 2- brom-acetophenone class compound and phenylacetylene class compound
Material, photocatalytically dehydrocyclization obtains polysubstituted naphthol derivative.
Inventor is by concentrating on studies, and in the present invention, we have proposed one kind with 2- brom-acetophenone class compound and benzene
Acetylene compound is reaction raw materials, under the conditions of existing for the cheap transition metal copper catalyst, is concatenated Cyclization
The new method of naphthalene ketone compounds.
Summary of the invention
The purpose of the present invention is to overcome the deficiency in the prior art, provides a kind of simple process, at low cost, reaction substrate adapts to
The wide synthetic method for preparing naphthalene ketone compounds of range, this method are catalyzed using 2- brom-acetophenone class compound as raw material in copper
Under agent, ligand, alkali and organic solvent and inert atmosphere, heating reaction easily and with excellent yield prepares naphthalenone class
Compound.
The preparation method of naphthalene ketone compounds provided by the invention, is prepared through the following steps：
2- brom-acetophenone class compound shown in Formulas I is added into Schlenk tube sealing reaction device, replaces second shown in Formula II
Alkine compounds, copper catalyst, ligand, alkali and organic solvent, under an inert atmosphere, heating stirring reaction has been reacted through TLC detection
Entirely, then post-treated target product shown in formula III is obtained.
In Formulas I and formula III, R1One or more substituent groups on the connected phenyl ring of expression, selected from selected from hydrogen, C1-C20
Alkyl, C1-C20Alkoxy, C2-C20Alkenyl, C1-C20Alkylthio group, C6-C20Aryl, C5-C20Heteroaryl, C3-
C20Naphthenic base, nitro, halogen ,-OH ,-SH ,-CN ,-COOR5、-COR6、-OCOR7、-NR8R9；Wherein, R5、R6、R7、R8、R9
It is each independently selected from hydrogen, C1-C20Alkyl, C6-C20Aryl, C5-C20Heteroaryl, C3-C20Naphthenic base in it is any
It is one or more.
Wherein, the alkyl in above-mentioned each substituent group, alkenyl, aryl, heteroaryl, cycloalkyl moiety optionally by one or
It is multiple to be selected from C1-C6Alkyl, C1-C6Alkoxy, C1-C6Acyl group, halogen ,-NO2、-CN、-OH、C6-C20Aryl, C3-
C6Naphthenic base replaced.
Preferably, the R1It indicates one or more substituent groups in institute's connection ring, is selected from hydrogen, C1-C6Alkyl, C1-C6
Alkoxy, C6-C14Aryl, C5-C12Heteroaryl, C3-C8Naphthenic base, nitro, halogen ,-OH ,-SH ,-CN ,-
COOR5、-COR6、-OCOR7、-NR8R9；Wherein, R5、R6、R7、R8、R9It is each independently selected from hydrogen, C1-C6Alkyl, C6-C12's
Aryl, C3-C12Heteroaryl, C3-C8Naphthenic base.And alkyl, aryl, heteroaryl, cycloalkyl moiety in above-mentioned each substituent group
C is optionally selected from by one or more1-C6Alkyl, C1-C6Alkoxy, C1-C6Acyl group, halogen ,-NO2、-CN、-
OH、C6-C12Aryl, C3-C6Naphthenic base replaced.
It is further preferred that the C1-C6Alkyl be selected from methyl, ethyl, propyl, isopropyl, butyl, normal-butyl, isobutyl
Base, tert-butyl, amyl, isopentyl, neopentyl；The C1-C6Alkoxy be selected from methoxyl group, ethyoxyl, propoxyl group, butoxy；
The C6-C12Aryl be selected from phenyl, naphthalene, anthryl；The C3-C12Heteroaryl be selected from thienyl, imidazole radicals, pyridine
Base；The C3-C8Naphthenic base be selected from cyclopropyl, cyclobutyl, cyclohexyl；Wherein above-mentioned each group can be optionally by one
Or it is multiple selected from C1-C6Alkyl, C1-C6Alkoxy, C1-C6Acyl group, halogen ,-NO2、-CN、-OH、C6-C12Aryl,
C3-C6Naphthenic base replaced.
Most preferably, R1Indicate institute's connection ring on one or more substituent groups, selected from hydrogen, methyl, methoxyl group, halogen,
Acetyl group, nitro ,-CN.
In above-mentioned Formula II and formula III, R indicates C1-C20Alkyl, C3-C20Cyclic hydrocarbon radical, C3-C20Heteroaryl.On wherein
Stating each group can be optionally by one or more selected from C1-C6Alkyl, C1-C6Alkoxy, C1-C6Acyl group, halogen ,-
NO2、-CN、-OH、C6-C12Aryl, C3-C6Naphthenic base replaced.
Preferably, the R is selected from C1-C10Alkyl, C3-C10Cyclic hydrocarbon radical, C3-C12Heteroaryl.Wherein above-mentioned each base
Group optionally can be selected from C by one or more1-C6Alkyl, C1-C6Alkoxy, C1-C6Acyl group, halogen ,-NO2、-
CN、-OH、C6-C12Aryl, C3-C6Naphthenic base replaced.
It is highly preferred that the C that the R is indicated1-C6Alkyl can selected from methyl, ethyl, propyl, isopropyl, butyl,
Normal-butyl, isobutyl group, tert-butyl, amyl, isopentyl, neopentyl；The C3-C10Cyclic hydrocarbon radical can selected from phenyl, naphthalene,
Anthryl, cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl, cyclohexenyl group, cyclopentenyl；The C3-C12Heteroaryl can select
From thienyl, imidazole radicals, pyridyl group；Wherein above-mentioned each group optionally can be selected from C by one or more1-C6Alkyl, C1-
C6Alkoxy, C1-C6Acyl group, halogen ,-NO2、-CN、-OH、C6-C12Aryl, C3-C6Naphthenic base replaced.
Most preferably, R is selected from phenyl, the C that butyl, phenyl, cyclopropyl, cyclohexenyl group, halogen replace1-C6Alkyl replace
Phenyl, C1-C6Alkoxy replace phenyl, thienyl.
Reaction above-mentioned according to the present invention, the copper catalyst are selected from Cu (MeCN)4PF6, copper halide, cuprous halide, vinegar
Any one in sour copper.Wherein it is preferred to which the copper catalyst is selected from Cu (MeCN)4PF6、CuI、CuCl、CuBr2In
Any one, most preferably Cu (MeCN)4PF6。
Reaction above-mentioned according to the present invention, the ligand are any one in 1,10- o-phenanthroline, 2,2- bipyridyl
Kind.In the present invention, although without using also can be carried out in the case where ligand in reaction, inventors have found that 1,10- neighbour's phenanthrene is coughed up
The use of quinoline, 2,2- bipyridine ligand has excellent facilitation to reaction.Preferably, the ligand is that 1,10- neighbour phenanthrene is coughed up
Quinoline.
Reaction above-mentioned according to the present invention, the alkali can selected from alkali carbonate, alkali metal hydrogencarbonate,
Ag2CO3In any one, it is preferable that the alkali be selected from K2CO3、Na2CO3、Ag2CO3In any one, most preferably,
The alkali is K2CO3.Inventors have found that the presence of alkali is one of necessary condition, it is being other types there is no alkali or alkali
When alkali such as triethylamine, reaction not can be carried out or can only determine by GC the target product of trace.
Reaction above-mentioned according to the present invention, the organic solvent appointing in toluene, acetonitrile, chlorobenzene, dioxane
The mixture for one or more of anticipating, most preferably, the organic solvent are toluene.The usage amount of solvent does not limit particularly
It is fixed, so that each reaction mass is fully dispersed.
Reaction above-mentioned according to the present invention, wherein the inert atmosphere refers to nitrogen atmosphere or argon atmosphere.
Reaction above-mentioned according to the present invention, wherein the temperature range of the heating stirring reaction is 100-140 DEG C, preferably
Temperature range be 110-130 DEG C, most preferably 120 DEG C.
Method above-mentioned according to the present invention, wherein the reaction time of heating stirring reaction can be tracked by TLC plate
Monitoring to determine, General reactions 12-24 hour can fully reacting, the reaction time preferably is 16 hours.
Method above-mentioned according to the present invention, wherein formula (I) compound represented, formula (II) compound represented, copper catalysis
Agent, ligand, alkali molar ratio be (2~3):1:(0.05~0.2):(0.1-0.3)：(1~3), most preferably, shown in formula (I)
Compound, formula (II) compound represented, copper catalyst, ligand, alkali molar ratio be 2:1:0.1:0.2:2.
Method above-mentioned according to the present invention, wherein the post-processing operation is as follows：By mixed liquor warp after the reaction was completed
Short column of silica gel filtering, ethyl acetate wash filter cake, are concentrated under reduced pressure to give residue, then with n-hexane and ethyl acetate is elution
Liquid, the target product through the isolated formula III of column plastic column chromatography.
Beneficial effects of the present invention are as follows：
1. the present invention is reported for the first time with 2- brom-acetophenone class compound shown in Formulas I, replaced acetylene shown in Formula II
Object, copper catalyst, ligand, alkali and organic solvent are closed, under an inert atmosphere, heating stirring reaction prepares shown in formula III
The synthetic strategy of naphthalenone compound, this method are not seen in prior art report.
2. method of the invention uses cheap copper catalyst, cost is significantly reduced.
3. method of the invention has reaction substrate wide adaptation range, easy to operate, the high advantage of target product yield.
Specific embodiment
Below in conjunction with specific embodiment, further detailed description is carried out to the present invention.
The test of embodiment 1-19 reaction condition optimization
Using phenylacetylene shown in 2- brom-acetophenone shown in Formulas I -1 and Formula II -1 as reaction raw materials, differential responses have been inquired into
Wherein representative embodiment 1-19 is selected in influence of the condition for optimization of synthesis result.As a result such as one institute of table
Show.
Wherein the operation of embodiment 1 is as follows：
2- brom-acetophenone (42.4mg, 0.2mmol) shown in Formulas I -1, Formula II -1 are added into Schlenk tube sealing reaction device
Shown in phenylacetylene (10.2mg, 0.1mmol), Cu (MeCN)4PF6(7.46mg, 10mol%), 1,10-phen (7.2mg,
20mol%), K2CO3(55.2mg, 2equiv) and toluene (2mL) are stirred to react at 120 DEG C, examine through TLC under the conditions of argon gas
It surveys fully reacting (about 16 hours), then filters reaction solution by short silicagel column, ethyl acetate rinse filter cake is concentrated under reduced pressure
To residue, by residue, by silica gel column chromatography, (n-hexane/ethyl acetate volume ratio is 100:1) isolated formula III -1
Target product.Yield 82%；D.r.=1.1:1；Colourless oil liquid；1H NMR(400MHz,CDCl3)δ:8.19 (d, J=
8.0Hz, 0.5H), 8.04 (d, J=7.6Hz, 1H), 7.98 (d, J=8.4Hz, 0.5H), 7.85 (d, J=8.4Hz, 1H),
7.53-7.30(m,11H),7.21-7.17(m,1H),6.54(s,0.43H),6.22(s,0.57H),4.41-4.33(m,1H),
1.40 (s, 1.59H), 1.37 (d, J=7.6Hz, 1.61H), 1.30 (s, 1.52H), 1.15 (d, J=6.8Hz, 1.42H)；13C
NMR(100MHz,CDCl3)δ:139.8,139.4,138.1,138.0,137.7,136.7,136.6,135.6,135.0,
134.3,133.9,133.2,132.7,129.3,129.2,128.9,128.7,128.5,128.5,128.4,128.3,
127.8,127.6,127.5,127.4,127.4,126.6,128.4,50.9,50.0,48.6,47.3,23.9,23.3,14.7,
12.3.HRMS m/z(ESI)calcd for C26H23O2([M+H]+)367.1693,found 367.1701.。
Table one：
Wherein, the concrete operations of embodiment 2-19 and parameter except variable listed by above-mentioned table one and embodiment 1 it is not identical it
Outside, remaining operation and parameter are same as Example 1.And wherein, the structure difference of ligand L 3, L4 is as follows：
Be added without ligand reaction it can be seen from embodiment 1-19 still and can obtain 61% target product yield it is (real
Apply example 2), 2,2 '-bipyridyl as ligand to reaction also have certain facilitation (embodiment 3), other ligands are for example
L3, L4 have adverse effect (embodiment 4-5) to reaction；For catalyst type replacement experiments have shown that, the catalysis of other copper
Agent such as CuI, CuCl, CuBr2 can obtain medium yield, but are not so good as but are obviously not so good as Cu (MeCN)4PF6(embodiment
6-8), Cu (MeCN)4PF6The dosage of ligand of influence with to(for) reaction is unobvious, and the inventory relative to phenylacetylene is respectively
10mmol% and 20mmol% is the most suitable (embodiment 9-10).Reaction must just can be carried out in the presence of base, with K2CO3Effect
Fruit is preferably (embodiment 11-14)；Organic solvent still is able to obtain substantially comparable when replacing with chlorobenzene, acetonitrile, dioxane
Target product yield, optimal temperature select 120 DEG C (embodiment 15-19).
Optimal reaction condition is the reaction condition of embodiment 1 it can be seen from above-described embodiment 1-19, i.e. catalyst selects
Select Cu (MeCN)4PF6, ligand select 1,10-phen, alkali to be potassium carbonate, there is Solvents Solvent to be toluene, reaction temperature is 120 DEG C.
On the basis of obtaining optimum reaction condition, inventor further under the optimum reaction condition, selects the anti-of different substituents
Raw material is answered to prepare the naphthalene ketone compounds of various formula IIIs.
Embodiment 20
2- brom-acetophenone (0.2mmol) shown in Formulas I -1 is added into Schlenk tube sealing reaction device, shown in Formula II -2
To methyl phenylacetylene (0.1mmol), Cu (MeCN)4PF6(10mol%), 1,10-phen (20mol%), K2CO3(2equiv) and
Toluene (2mL) is stirred to react under the conditions of argon gas at 120 DEG C, detects fully reacting (about 16 hours) through TLC, then will reaction
Liquid is filtered by short silicagel column, ethyl acetate rinse filter cake, is concentrated under reduced pressure to give residue, and residue is passed through silica gel column chromatography
The target product of isolated formula III -2.Yield 78%；D.r.=1:1；Colourless oil liquid；1H NMR(400MHz,CDCl3)
δ:8.17 (d, J=7.6Hz, 0.5H), 8.03 (d, J=8.0Hz, 1H), 7.97 (d, J=7.6Hz, 0.5H), 7.84 (d, J=
7.6Hz,1H),7.59-7.36(m,5H),7.30-7.20(m,5H),6.51(s,0.5H),6.19(s,0.5H),4.41-4.29
(m, 1H), 2.41 (s, 3H), 1.39 (s, 1.50H), 1.36 (d, J=7.2Hz, 1.50H), 1.29 (s, 1.50H), 1.14 (d, J
=6.8Hz, 1.50H)；13C NMR(100MHz,CDCl3)δ:203.3,202.7,202.6,202.4,138.3,138.2,
137.7,137.2,137.1,136.8,136.7,136.4,136.3,135.4,134.9,134.2,133.9,133.2,
132.7,129.2,129.2,129.0,129.0,129.0,128.7,128.5,128.4,127.7,127.5,127.3,
126.4,126.4,50.9,50.0,48.6,47.3,23.9,23.2,21.2,14.6,12.3.HRMS m/z(ESI)calcd
for C27H25O2([M+H]+)381.1849,found 381.1855.。
Embodiment 21
2- brom-acetophenone (0.2mmol) shown in Formulas I -1 is added into Schlenk tube sealing reaction device, shown in Formula II -3
To chlorobenzene acetylene (0.1mmol), Cu (MeCN)4PF6(10mol%), 1,10-phen (20mol%), K2CO3(2equiv) and first
Benzene (2mL) is stirred to react under the conditions of argon gas at 120 DEG C, fully reacting (about 16 hours) is detected through TLC, then by reaction solution
It is filtered by short silicagel column, ethyl acetate rinse filter cake is concentrated under reduced pressure to give residue, and residue is passed through silica gel column chromatography point
From obtaining the target product of formula III -3.Yield 75%；D.r.=1.5:1；White solid；1H NMR(400MHz,CDCl3)δ:
8.19 (d, J=7.6Hz, 0.41H), 8.04 (d, J=7.6Hz, 0.82H), 7.98 (d, J=7.6Hz, 0.66H), 7.85 (d, J
=7.6Hz, 1.28H), 7.52-7.32 (m, 9H), 7.14 (t, J=7.6Hz, 1H), 6.54 (s, 0.41H), 6.22 (s,
0.62H), 4.41-4.33 (m, 1H), 1.39 (s, 1.82H), 1.37 (d, J=6.8Hz, 1.87H), 1.30 (s, 1.21H),
1.13 (d, J=6.8Hz, 1.23H)；13C NMR(100MHz,CDCl3)δ:202.9,202.8,202.6,202.0,138.2,
137.8,137.8,137.6,137.6,137.0,136.6,136.0,135.6,134.3,134.0,133.5,133.4,
133.3,132.8,130.7,130.5,128.9,128.8,128.5,128.5,128.4,128.0,127.8,127.5,
126.3,126.1,51.0,50.1,48.6,47.3,23.9,23.3,14.7,12.3.HRMS m/z(ESI)calcd for
C26H22ClO2([M+H]+)401.1303,found 401.1322.。
Embodiment 22
2- brom-acetophenone (0.2mmol) shown in Formulas I -1 is added into Schlenk tube sealing reaction device, shown in Formula II -4
To acetylbenzene acetylene (0.1mmol), Cu (MeCN)4PF6(10mol%), 1,10-phen (20mol%), K2CO3(2equiv)
It is stirred to react under the conditions of argon gas at 120 DEG C with toluene (2mL), detects fully reacting (about 16 hours) through TLC, it then will be anti-
Liquid is answered to filter by short silicagel column, ethyl acetate rinse filter cake is concentrated under reduced pressure to give residue, and residue is passed through silica gel column layer
Analyse the target product of isolated formula III -4.Yield 54%；d.r.>20:1；Colourless oil liquid；1H NMR(400MHz,
CDCl3)δ:8.02 (t, J=8.4Hz, 3H), 7.86 (d, J=7.6Hz, 2H), 7.54-7.45 (m, 4H), 7.41 (t, J=
7.6Hz, 2H), 7.34 (t, J=7.6Hz, 1H), 7.13 (d, J=8.0Hz, 1H), 6.27 (s, 1H), 4.45-4.32 (m, 1H),
2.66 (s, 3H), 1.41 (s, 3H), 1.38 (d, J=6.8Hz, 3H)；13C NMR(100MHz,CDCl3)δ:202.8,202.8,
197.7,144.8,137.4,136.5,136.4,136.3,134.3,134.0,132.9,129.6,128.9,128.5,
128.4,127.9,127.6,126.1,50.1,48.6,26.7,23.3,12.3.HRMS m/z(ESI)calcd for
C28H25O3([M+H]+)409.1798,found 409.1808.。
Embodiment 23
2- brom-acetophenone (0.2mmol) shown in Formulas I -1 is added into Schlenk tube sealing reaction device, shown in Formula II -5
O-methyl-benzene acetylene (0.1mmol), Cu (MeCN)4PF6(10mol%), 1,10-phen (20mol%), K2CO3(2equiv) and
Toluene (2mL) is stirred to react under the conditions of argon gas at 120 DEG C, detects fully reacting (about 16 hours) through TLC, then will reaction
Liquid is filtered by short silicagel column, ethyl acetate rinse filter cake, is concentrated under reduced pressure to give residue, and residue is passed through silica gel column chromatography
The target product of isolated formula III -5.Yield 69%；D.r.=1:1；Colourless oil liquid；1H NMR(400MHz,CDCl3)
δ:8.03 (d, J=7.6Hz, 0.51H), 7.97 (d, J=7.6Hz, 0.50H), 7.88 (t, J=7.2Hz, 2H), 7.52-7.39
(m, 4H), 7.32-7.22 (m, 5H), 6.84 (d, J=7.6Hz, 0.53H), 6.79 (d, J=8.0Hz, 0.50H), 6.21 (s,
0.52H), 6.18 (s, 0.49H), 4.45-4.35 (m, 1H), 2.28 (s, 1.52H), 2.19 (s, 1.53H), 1.40 (d, J=
6.8Hz, 3H), 1.36 (d, J=6.8Hz, 3H)；13C NMR(100MHz,CDCl3)δ:203.5,203.3,202.9,202.7,
139.3,139.2,139.4,139.3,137.6,136.7,136.6,136.5,135.4,135.0,134.5,134.1,
134.1,132.8,132.7,130.2,130.1,130.0,129.8,128.6,128.5,128.4,127.7,127.7,
127.4,127.3,126.3,126.2,126.1,125.7,50.0,49.7,49.3,48.8,24.2,23.6,19.8,19.6,
12.4,12.3.HRMS m/z(ESI)calcd for C27H25O2([M+H]+)381.1849,found 381.1859.。
Embodiment 24
2- brom-acetophenone (0.2mmol) shown in Formulas I -1 is added into Schlenk tube sealing reaction device, shown in Formula II -6
2- thiophene acetylene (0.1mmol), Cu (MeCN)4PF6(10mol%), 1,10-phen (20mol%), K2CO3(2equiv) and first
Benzene (2mL) is stirred to react under the conditions of argon gas at 120 DEG C, fully reacting (about 16 hours) is detected through TLC, then by reaction solution
It is filtered by short silicagel column, ethyl acetate rinse filter cake is concentrated under reduced pressure to give residue, and residue is passed through silica gel column chromatography point
From obtaining the target product of formula III -6.Yield 74%；D.r.=1:1；Colourless oil liquid；1H NMR(400MHz,CDCl3)δ:
8.18 (d, J=7.6Hz, 0.52H), 8.04 (d, J=7.6Hz, 1H), 7.99 (d, J=8.0Hz, 0.55H), 7.85 (d, J=
7.6Hz, 1H), 7.57-7.29 (m, 8H), 7.14 (t, J=5.6Hz, 1H), 6.62 (s, 0.48H), 6.30 (s, 0.50H),
4.41-4.31 (m, 1H), 1.41-1.34 (m, 3H), 1.29 (s, 1.52H), 1.13 (d, J=6.8Hz, 1.50H)；13C NMR
(100MHz,CDCl3)δ:203.0,202.7,202.6,202.1,140.1,139.7,138.0,137.9,137.6,136.7,
135.7,134.4,134.0,133.2,132.8,131.5,130.0,129.2,128.8,128.9,128.7,128.6,
128.5,128.5,128.4,126.3,126.1,125.4,125.3,123.4,123.3,51.0,40.1,48.4,47.3,
23.9,23.1,14.6,12.3.HRMS m/z(ESI)calcd for C24H21O2S([M+H]+)373.1257,found
373.1266.。
Embodiment 25
2- brom-acetophenone (0.2mmol) shown in Formulas I -1 is added into Schlenk tube sealing reaction device, shown in Formula II -7
Cyclopropyl acethlene (0.1mmol), Cu (MeCN)4PF6(10mol%), 1,10-phen (20mol%), K2CO3(2equiv) and first
Benzene (2mL) is stirred to react under the conditions of argon gas at 120 DEG C, fully reacting (about 16 hours) is detected through TLC, then by reaction solution
It is filtered by short silicagel column, ethyl acetate rinse filter cake is concentrated under reduced pressure to give residue, and residue is passed through silica gel column chromatography point
From obtaining the target product of formula III -7.Yield 49%；d.r.>20:1；Colourless oil liquid；1H NMR(400MHz,CDCl3)δ:
7.92 (d, J=7.6Hz, 1H), 7.86 (d, J=8.0Hz, 1H), 7.80 (d, J=8.0Hz, 2H), 7.62 (t, J=7.6Hz,
1H), 7.47 (d, J=7.2Hz, 1H), 7.40-7.30 (m, 3H), 6.08 (s, 1H), 4.32-4.22 (m, 1H), 1.35 (d, J=
7.6Hz,3H),1.26(s,3H),0.88-0.81(m,2H),0.59-0.53(m,1H),0.52-0.45(m,1H)；13C NMR
(100MHz,CDCl3)δ:203.6,202.8,139.1,136.7,134.0,132.7,132.5,132.2,128.6,128.4,
128.4,127.3,127.0,124.4,49.5,48.4,23.4,13.4,12.3,5.4,5.1.HRMS m/z(ESI)calcd
for C23H23O2([M+H]+)331.1693,found 331.1702.。
Embodiment 26
2- brom-acetophenone (0.2mmol) shown in Formulas I -1 is added into Schlenk tube sealing reaction device, shown in Formula II -8
Cyclohexenyl group acetylene (0.1mmol), Cu (MeCN)4PF6(10mol%), 1,10-phen (20mol%), K2CO3(2equiv) and
Toluene (2mL) is stirred to react under the conditions of argon gas at 120 DEG C, detects fully reacting (about 16 hours) through TLC, then will reaction
Liquid is filtered by short silicagel column, ethyl acetate rinse filter cake, is concentrated under reduced pressure to give residue, and residue is passed through silica gel column chromatography
The target product of isolated formula III -8.Yield 58%；d.r.>20:1；Colourless oil liquid；1H NMR(400MHz,CDCl3)
δ:8.11 (d, J=7.6Hz, 1H), 8.05 (d, J=8.0Hz, 2H), 7.58 (t, J=7.2Hz, 2H), 7.49 (t, J=
7.6Hz,2H),7.39-7.31(m,2H),6.36(s,1H),5.70(s,1H),4.39-4.31(m,1H),2.12-2.14(m,
3H), 1.79-1.68 (m, 4H), 1.20 (s, 3H), 1.06 (d, J=6.8Hz, 3H)；13C NMR(100MHz,CDCl3)δ:
202.9,202.7,138.7,138.1,137.8,136.9,134.3,133.5,133.2,129.2,128.7,128.5,
127.4,127.3,126.7,126.0,50.6,46.9,29.7,25.3,24.0,22.9,22.2,14.6.HRMS m/z(ESI)
calcd for C26H27O2([M+H]+)371.2006,found 371.2013.。
Embodiment 27
2- brom-acetophenone (0.2mmol) shown in Formulas I -1 is added into Schlenk tube sealing reaction device, shown in Formula II -9
Butyl-acetylene (0.1mmol), Cu (MeCN)4PF6(10mol%), 1,10-phen (20mol%), K2CO3(2equiv) and toluene
(2mL) is stirred to react under the conditions of argon gas at 120 DEG C, is detected fully reacting (about 16 hours) through TLC, is then led to reaction solution
Too short silicagel column filtering, ethyl acetate rinse filter cake are concentrated under reduced pressure to give residue, and residue is separated by silica gel column chromatography
Obtain the target product of formula III -9.Yield 53%；d.r.>20:1；Colourless oil liquid；1H NMR(400MHz,CDCl3)δ:
8.14 (d, J=7.6Hz, 1H), 8.06 (d, J=7.6Hz, 2H), 7.65-7.55 (m, 2H), 7.52-7.44 (m, 3H), 7.37
(d, J=8.4Hz, 1H), 6.41 (s, 1H), 4.38-4.32 (m, 1H), 2.65-2.55 (m, 2H), 1.66-1.56 (m, 3H),
1.48-1.40 (m, 2H), 1.18 (s, 3H), 1.05 (d, J=6.8Hz, 3H), 0.95 (t, J=7.2Hz, 3H)；13C NMR
(100MHz,CDCl3)δ:203.0,202.9,138.3,137.8,134.4,133.6,133.2,133.0,129.2,128.7,
128.5,127.5,127.3,124.1,50.7,46.8,32.5,30.9,24.2,22.6,14.6,14.0.HRMS m/z(ESI)
calcd for C24H27O2([M+H]+)347.2006,found 347.2019。
Embodiment 28
The bromo- 1- of 2- (4- methoxyphenyl) propyl- 1- ketone shown in Formulas I -2 is added into Schlenk tube sealing reaction device
(0.2mmol), phenylacetylene (0.1mmol) shown in Formula II -1, Cu (MeCN)4PF6(10mol%), 1,10-phen
(20mol%), K2CO3(2equiv) and toluene (2mL) are stirred to react under the conditions of argon gas at 120 DEG C, are detected and are reacted through TLC
(about 16 hours) completely, are then filtered reaction solution by short silicagel column, and ethyl acetate rinse filter cake is concentrated under reduced pressure to give remnants
Residue is passed through the target product of the isolated formula III -10 of silica gel column chromatography by object.Yield 78%；D.r.=1:1；Colorless oil
Shape liquid；1H NMR(400MHz,CDCl3)δ:8.18 (d, J=8.4Hz, 1H), 8.06 (d, J=8.4Hz, 2H), 7.48-7.36
(m, 5H), 6.96 (d, J=7.6Hz, 2H), 6.90 (d, J=8.8Hz, 1H), 6.68 (s, 1H), 6.60 (s, 1H), 4.38-
4.30 (m, 1H), 3.88 (s, 3H), 3.76 (s, 3H), 1.26 (s, 3H), 1.08 (d, J=8.8Hz, 3H)；13C NMR
(100MHz,CDCl3)δ:201.2,201.0,164.4,163.7,140.5,139.4,138.0,136.3,130.9,130.9,
130.1,129.2,128.3,127.5,123.0,113.9,113.2,111.6,55.5,55.4,50.8,46.7,24.1,
14.7.HRMS m/z(ESI)calcd for C28H27O4([M+H]+)427.1904,found 427.1911.。
Colourless oil liquid；1H NMR(400MHz,CDCl3)δ:8.18 (d, J=8.4Hz, 1H), 8.06 (d, J=
8.4Hz, 2H), 7.48-7.36 (m, 5H), 6.96 (d, J=7.6Hz, 2H), 6.90 (d, J=8.8Hz, 1H), 6.68 (s, 1H),
6.60 (s, 1H), 4.38-4.30 (m, 1H), 3.88 (s, 3H), 3.76 (s, 3H), 1.26 (s, 3H), 1.08 (d, J=8.8Hz,
3H)；13C NMR(100MHz,CDCl3)δ:201.2,201.0,164.4,163.7,140.5,139.4,138.0,136.3,
130.9,130.9,130.1,129.2,128.3,127.5,123.0,113.9,113.2,111.6,55.5,55.4,50.8,
46.7,24.1,14.7.。
Embodiment 29
The bromo- 1- of 2- (4- aminomethyl phenyl) propyl- 1- ketone shown in Formulas I -3 is added into Schlenk tube sealing reaction device
(0.2mmol), phenylacetylene (0.1mmol) shown in Formula II -1, Cu (MeCN)4PF6(10mol%), 1,10-phen
(20mol%), K2CO3(2equiv) and toluene (2mL) are stirred to react under the conditions of argon gas at 120 DEG C, are detected and are reacted through TLC
(about 16 hours) completely, are then filtered reaction solution by short silicagel column, and ethyl acetate rinse filter cake is concentrated under reduced pressure to give remnants
Residue is passed through the target product of the isolated formula III -11 of silica gel column chromatography by object.Yield 75%；D.r.=1:1；Colorless oil
Shape liquid；1H NMR(400MHz,CDCl3)δ:8.09 (d, J=8.0Hz, 1H), 7.96 (d, J=8.0Hz, 2H), 7.44-7.34
(m, 5H), 7.29 (d, J=8.0Hz, 2H), 7.21 (d, J=8.0Hz, 1H), 6.99 (s, 1H), 6.53 (s, 1H), 4.40-
4.32 (m, 1H), 2.42 (s, 3H), 2.32 (s, 3H), 1.27 (s, 3H), 1.10 (d, J=6.8Hz, 3H)；13C NMR
(100MHz,CDCl3)δ:202.3,202.1,145.3,144.1,139.6,138.1,137.0,136.5,135.3,129.4,
129.2,128.7,128.4,127.6,127.5,127.0,127.0,20.9,47.1,24.0,22.0,21.6,14.7.HRMS
m/z(ESI)calcd for C28H27O2([M+H]+)395.2006,found 395.2014.。
Colourless oil liquid；1H NMR(400MHz,CDCl3)δ:1H NMR (400MHz, CDCl3) δ 8.09 (d, J=
8.0Hz, 1H), 7.96 (d, J=7.6Hz, 2H), 7.45-7.35 (m, 5H), 7.29 (d, J=8.0Hz, 2H), 7.21 (d, J=
8.0Hz,1H),6.99(s,1H),6.53(s,1H),4.39-4.33(m,1H),2.42(s,3H),2.32(s,3H),1.27(s,
3H), 1.10 (d, J=7.6Hz, 3H)；13C NMR(100MHz,CDCl3)δ:202.4,202.1,145.3,144.1,139.6,
138.1,137.0,136.5,135.3,129.4,129.2,128.7,128.4,127.6,127.5,127.0,20.9,47.1,
24.0,22.0,21.6,14.7.。
Embodiment 30
The bromo- 1- of 2- (4- aminomethyl phenyl) propyl- 1- ketone shown in Formulas I -3 is added into Schlenk tube sealing reaction device
(0.2mmol), 2- thiophene acetylene (0.1mmol) shown in Formula II -6, Cu (MeCN)4PF6(10mol%), 1,10-phen
(20mol%), K2CO3(2equiv) and toluene (2mL) are stirred to react under the conditions of argon gas at 120 DEG C, are detected and are reacted through TLC
(about 16 hours) completely, are then filtered reaction solution by short silicagel column, and ethyl acetate rinse filter cake is concentrated under reduced pressure to give remnants
Residue is passed through the target product of the isolated formula III -12 of silica gel column chromatography by object.Yield 76%；D.r.=1:1；Colorless oil
Shape liquid；1H NMR(400MHz,CDCl3)δ:8.08 (d, J=8.0Hz, 0.48H), 7.95 (d, J=8.0Hz, 0.59H),
7.89 (d, J=7.6Hz, 0.87H), 7.75 (d, J=7.6Hz, 1.1H), 7.38 (d, J=7.6Hz, 1H), 7.29-7.11 (m,
6H),6.62(s,0.45H),6.28(s,0.55H),4.38-4.26(m,1H),2.42(s,1.32H),2.37(s,1.69H),
2.36 (s, 1.32H), 2.33 (s, 1.70H), 1.37 (s, 1.66H), 1.35 (d, J=8.4Hz, 1.68H), 1.26 (s,
1.39H), 1.09 (d, J=6.8Hz, 1.34H)；13C NMR(100MHz,CDCl3)δ:202.6,202.3,201.9,145.4,
144.9,144.1,143.5,140.3,139.9,138.1,137.1,136.3,135.3,134.2,131.4,129.4,
129.1,128.8,128.7,128.6,128.5,127.6,126.7,126.5,125.3,125.2,123.4,123.3,51.0,
50.0,48.2,47.0,24.0,23.0,22.0,22.0,21.6,21.5,14.7,12.4.HRMS m/z(ESI)calcd for
C26H25O2S([M+H]+)401.5435,found 401.5444.。
Embodiment 31
The bromo- 1- of 2- (4- chlorphenyl) propyl- 1- ketone shown in Formulas I -4 is added into Schlenk tube sealing reaction device
(0.2mmol), phenylacetylene (0.1mmol) shown in Formula II -1, Cu (MeCN)4PF6(10mol%), 1,10-phen
(20mol%), K2CO3(2equiv) and toluene (2mL) are stirred to react under the conditions of argon gas at 120 DEG C, are detected and are reacted through TLC
(about 16 hours) completely, are then filtered reaction solution by short silicagel column, and ethyl acetate rinse filter cake is concentrated under reduced pressure to give remnants
Residue is passed through the target product of the isolated formula III -13 of silica gel column chromatography by object.Yield 69%；D.r.=1.2:1；It is colourless
Oily liquids；1H NMR(400MHz,CDCl3)δ:8.09 (d, J=8.4Hz, 1H), 7.99 (d, J=8.0Hz, 2H), 7.51-
7.35 (m, 8H), 7.16 (s, 1H), 6.53 (s, 1H), 4.36-4.25 (m, 1H), 1.29 (s, 3H), 1.15 (d, J=6.8Hz,
3H)；13C NMR(100MHz,CDCl3)δ:201.2,201.0,141.1,139.8,139.7,138.6,138.1,135.9,
135.7,129.9,129.1,129.0,128.6,128.2,127.9,127.6,126.5,50.9,47.9,24.0,
14.9.HRMS m/z(ESI)calcd for C26H21Cl2O2([M+H]+)435.0913,found 435.0922.。
Colourless oil liquid；1H NMR(400MHz,CDCl3)δ:7.91 (d, J=8.4Hz, 1H), 7.79 (d, J=
8.0Hz, 2H), 7.47-7.37 (m, 8H), 7.16 (d, J=7.6Hz, 1H), 6.28 (s, 1H), 4.34-4.28 (m, 1H), 1.38
(s, 3H), 1.36 (d, J=7.6Hz, 3H)；13C NMR(100MHz,CDCl3)δ:202.4,201.7,139.8,138.9,
136.9,135.2,134.2,131.8,130.8,130.0,129.7,129.3,129.1,128.6,128.1,127.8,
127.5,50.1,49.1,23.6,12.2.。
Embodiment 32
The bromo- 1- of 2- (4- bromophenyl) propyl- 1- ketone shown in Formulas I -5 is added into Schlenk tube sealing reaction device
(0.2mmol), phenylacetylene (0.1mmol) shown in Formula II -1, Cu (MeCN)4PF6(10mol%), 1,10-phen
(20mol%), K2CO3(2equiv) and toluene (2mL) are stirred to react under the conditions of argon gas at 120 DEG C, are detected and are reacted through TLC
(about 16 hours) completely, are then filtered reaction solution by short silicagel column, and ethyl acetate rinse filter cake is concentrated under reduced pressure to give remnants
Residue is passed through the target product of the isolated formula III -14 of silica gel column chromatography by object.Yield 74%；D.r.=1.2:1；It is colourless
Oily liquids；1H NMR(400MHz,CDCl3)δ:8.03 (d, J=8.0Hz, 1H), 7.88 (d, J=8.4Hz, 2H), 7.63 (d,
J=8.4Hz, 2H), 7.54 (d, J=8.4Hz, 1H), 7.47-7.40 (m, 4H), 7.31 (d, J=7.6Hz, 2H), 6.51 (s,
1H), 4.29-4.22 (m, 1H), 1.29 (s, 3H), 1.15 (d, J=6.8Hz, 3H)；13C NMR(100MHz,CDCl3)δ:
201.4,201.2,139.6,138.5,138.0,136.1,135.8,132.1,131.1,130.0,129.5,129.1,
129.0,128.6,127.9,50.8,47.7,23.9,14.6.HRMS m/z(ESI)calcd for C26H21Br2O2([M+H
]+)522.9903,found 522.9911.。
Colourless oil liquid；1H NMR(400MHz,CDCl3)δ:1H NMR(400MHz,CDCl3)δ:7.82 (d, J=
8.0Hz, 1H), 7.71 (d, J=8.0Hz, 2H), 7.55 (d, J=8.4Hz, 2H), 7.47-7.36 (m, 6H), 7.33 (s, 1H),
6.26 (s, 1H), 4.35-4.26 (m, 1H), 1.38 (s, 3H), 1.35 (d, J=6.8Hz, 3H)；13C NMR(100MHz,
CDCl3)δ:202.4,201.7,139.8,138.9,136.9,135.2,134.2,131.8,130.8,130.0,129.7,
129.3,129.1,128.6,128.1,127.8,127.5,50.1,49.1,23.6,12.2.。
Embodiment 33
The bromo- 1- of 2- (3- aminomethyl phenyl) propyl- 1- ketone shown in Formulas I -6 is added into Schlenk tube sealing reaction device
(0.2mmol), phenylacetylene (0.1mmol) shown in Formula II -1, Cu (MeCN)4PF6(10mol%), 1,10-phen
(20mol%), K2CO3(2equiv) and toluene (2mL) are stirred to react under the conditions of argon gas at 120 DEG C, are detected and are reacted through TLC
(about 16 hours) completely, are then filtered reaction solution by short silicagel column, and ethyl acetate rinse filter cake is concentrated under reduced pressure to give remnants
Residue is passed through the target product of the isolated formula III -15 of silica gel column chromatography by object.Yield 63%；D.r.=1:1；Colorless oil
Shape liquid；1H NMR(400MHz,CDCl3)δ:7.99-7.89 (m, 1H), 7.83 (d, J=7.2Hz, 1H), 7.78 (d, J=
8.4Hz, 1H), 7.39-7.26 (m, 8H), 7.10 (d, J=8.0Hz, 1H), 6.52 (s, 0.5H), 6.46 (s, 0.5H), 4.36-
4.24 (m, 1H), 2.42 (s, 3H), 2.41 (s, 3H), 1.30 (s, 1.50H), 1.26 (d, J=7.2Hz, 1.53H), 1.15-
1.10(m,3H).13C NMR(100MHz,CDCl3)δ:203.1,203.0,202.9,202.7,143.2,140.3,139.6,
138.5,138.3,137.8,137.6,136.4,135.7,135.6,135.0,133.9,129.2,129.0,128.9,
128.6,128.3,127.9,127.7,127.6,127.5,127.0,126.6,125.8,125.7,125.6,51.0,50.9,
47.6,45.9,24.7,23.9,23.4,23.2,21.4,21.2,14.9,14.6.HRMS m/z(ESI)calcd for
C28H27O2([M+H]+)395.2006,found 395.2014.。
Embodiment described above is merely a preferred embodiment of the present invention, and the simultaneously exhaustion of the feasible implementation of non-present invention.For
It is any apparent to made by it under the premise of without departing substantially from the principle of the invention and spirit for those skilled in the art
Change, should all be contemplated as falling within claims of the invention.
Claims (9)
1. a kind of synthetic method of naphthalene ketone compounds, which is characterized in that described method includes following steps：It is sealed to Schlenk
2- brom-acetophenone class compound shown in Formulas I is added in pipe reactor, replaced acetylene compound shown in Formula II, copper catalyst,
Ligand, alkali and organic solvent, under an inert atmosphere, heating stirring reaction detects fully reacting through TLC, then post-treated obtain
Naphthalene ketone compounds shown in formula III；
In Formulas I and formula III, R1One or more substituent groups on the connected phenyl ring of expression, selected from selected from hydrogen, C1-C20Alkane
Base, C1-C20Alkoxy, C2-C20Alkenyl, C1-C20Alkylthio group, C6-C20Aryl, C5-C20Heteroaryl, C3-C20's
Naphthenic base, nitro, halogen ,-OH ,-SH ,-CN ,-COOR5、-COR6、-OCOR7、-NR8R9；Wherein, R5、R6、R7、R8、R9Respectively
Independently selected from hydrogen, C1-C20Alkyl, C6-C20Aryl, C5-C20Heteroaryl, C3-C20Naphthenic base in any one
Or it is a variety of；And alkyl in above-mentioned each substituent group, alkenyl, aryl, heteroaryl, cycloalkyl moiety optionally by one or
It is multiple to be selected from C1-C6Alkyl, C1-C6Alkoxy, C1-C6Acyl group, halogen ,-NO2、-CN、-OH、C6-C20Aryl, C3-
C6Naphthenic base replaced；
In Formula II and formula III, R indicates C1-C20Alkyl, C3-C20Cyclic hydrocarbon radical, C3-C20Heteroaryl；Wherein above-mentioned each R base
Group optionally can be selected from C by one or more1-C6Alkyl, C1-C6Alkoxy, C1-C6Acyl group, halogen ,-NO2、-
CN、-OH、C6-C12Aryl, C3-C6Naphthenic base replaced；
Wherein, the copper catalyst is selected from Cu (MeCN)4PF6, copper halide, cuprous halide, any one in copper acetate；
Any one of the ligand in 1,10- o-phenanthroline, 2,2- bipyridyl；
The alkali can be selected from alkali carbonate, alkali metal hydrogencarbonate, Ag2CO3In any one.
2. the method according to claim 1, wherein the R1Indicate one or more substitutions in institute's connection ring
Base is selected from hydrogen, C1-C6Alkyl, C1-C6Alkoxy, C6-C14Aryl, C5-C12Heteroaryl, C3-C8Naphthenic base, nitre
Base, halogen ,-OH ,-SH ,-CN ,-COOR5、-COR6、-OCOR7、-NR8R9；Wherein, R5、R6、R7、R8、R9It is each independently selected from
Hydrogen, C1-C6Alkyl, C6-C12Aryl, C3-C12Heteroaryl, C3-C8Naphthenic base；Alkyl, virtue in above-mentioned each substituent group
Base, heteroaryl, cycloalkyl moiety are optionally selected from C by one or more1-C6Alkyl, C1-C6Alkoxy, C1-C6Acyl
Base, halogen ,-NO2、-CN、-OH、C6-C12Aryl, C3-C6Naphthenic base replaced；
And the R is selected from C1-C10Alkyl, C3-C10Cyclic hydrocarbon radical, C3-C12Heteroaryl；Wherein above-mentioned each R group can be with
C is optionally selected from by one or more1-C6Alkyl, C1-C6Alkoxy, C1-C6Acyl group, halogen ,-NO2、-CN、-OH、
C6-C12Aryl, C3-C6Naphthenic base replaced.
3. according to the method described in claim 2, it is characterized in that, the R1Indicate one or more substitutions in institute's connection ring
Base, selected from hydrogen, halogen, methyl, ethyl, propyl, isopropyl, butyl, normal-butyl, isobutyl group, tert-butyl, amyl, isopentyl, new
Amyl；Methoxyl group, ethyoxyl, propoxyl group, butoxy；Phenyl, naphthalene, anthryl；Thienyl, imidazole radicals, pyridyl group；Cyclopropyl,
Cyclobutyl, cyclohexyl；Wherein above-mentioned each group optionally can be selected from C by one or more1-C6Alkyl, C1-C6Alcoxyl
Base, C1-C6Acyl group, halogen ,-NO2、-CN、-OH、C6-C12Aryl, C3-C6Naphthenic base replaced；With,
R is selected from methyl, ethyl, propyl, isopropyl, butyl, normal-butyl, isobutyl group, tert-butyl, amyl, isopentyl, neopentyl；
Phenyl, naphthalene, anthryl, cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl, cyclohexenyl group, cyclopentenyl；Thienyl, imidazole radicals, pyrrole
Piperidinyl；Wherein above-mentioned each group optionally can be selected from C by one or more1-C6Alkyl, C1-C6Alkoxy, C1-C6's
Acyl group, halogen ,-NO2、-CN、-OH、C6-C12Aryl, C3-C6Naphthenic base replaced.
4. according to the method described in claim 3, it is characterized in that, the R1Indicate one or more substitutions in institute's connection ring
Base is selected from hydrogen, methyl, methoxyl group, halogen, acetyl group, nitro ,-CN；With,
R is selected from phenyl, the C that butyl, phenyl, cyclopropyl, cyclohexenyl group, halogen replace1-C6Alkyl-substituted phenyl, C1-C6's
Phenyl, the thienyl of alkoxy substitution.
5. method according to any of claims 1-4, which is characterized in that the copper catalyst is selected from Cu (MeCN)4PF6、CuI、CuCl、CuBr2In any one, most preferably Cu (MeCN)4PF6；The ligand is 1,10- o-phenanthroline；It is described
Alkali be selected from K2CO3、Na2CO3、Ag2CO3In any one, most preferably, the alkali be K2CO3。
6. method according to any of claims 1-4, which is characterized in that the organic solvent is selected from toluene, second
Nitrile, chlorobenzene, any one or a few the mixture in dioxane, preferably toluene；The temperature of the heating stirring reaction
Range is 110-130 DEG C, preferably 120 DEG C.
7. method according to any of claims 1-4, which is characterized in that formula (I) compound represented, formula (II) institute
The compound that shows, copper catalyst, ligand, alkali molar ratio be (2~3):1:(0.05~0.2):(0.1-0.3)：(1~3).
8. the method according to the description of claim 7 is characterized in that chemical combination shown in formula (I) compound represented, formula (II)
Object, copper catalyst, ligand, alkali molar ratio be 2:1:0.1:0.2:2.
9. method according to any of claims 1-4, which is characterized in that the post-processing operation is as follows：It will be anti-
Mixed liquor after the completion of answering is filtered through short column of silica gel, and ethyl acetate washs filter cake, and filtrate decompression is concentrated to get residue, then with just
Hexane and ethyl acetate are eluent, through naphthalene ketone compounds shown in the isolated formula III of column plastic column chromatography.
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| CN109456156A (en) * | 2018-11-05 | 2019-03-12 | 荆门医药工业技术研究院 | A method of preparing 3- ethyl -4- methylol acetophenone |
| CN111218696A (en) * | 2020-01-07 | 2020-06-02 | 南昌航空大学 | Convergent electrochemical synthesis method |
| CN112500255A (en) * | 2020-12-03 | 2021-03-16 | 温州大学 | Synthesis method of 1, 3-disubstituted indene compounds |
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| CN103467282A (en) * | 2013-08-29 | 2013-12-25 | 南京大学 | Synthesis method of polysubstitution naphthol and derivative of polysubstitution naphthol |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109456156A (en) * | 2018-11-05 | 2019-03-12 | 荆门医药工业技术研究院 | A method of preparing 3- ethyl -4- methylol acetophenone |
| CN111218696A (en) * | 2020-01-07 | 2020-06-02 | 南昌航空大学 | Convergent electrochemical synthesis method |
| CN111218696B (en) * | 2020-01-07 | 2021-04-23 | 南昌航空大学 | Convergent electrochemical synthesis method |
| CN112500255A (en) * | 2020-12-03 | 2021-03-16 | 温州大学 | Synthesis method of 1, 3-disubstituted indene compounds |
| CN112500255B (en) * | 2020-12-03 | 2022-09-20 | 温州大学 | Synthesis method of 1, 3-disubstituted indene compounds |
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