CN106810430B - A kind of 2- Trifluoromethyl-1, the preparation method of 4- naphthoquinone derivatives - Google Patents
A kind of 2- Trifluoromethyl-1, the preparation method of 4- naphthoquinone derivatives Download PDFInfo
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- FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-naphthoquinone Chemical class C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims abstract description 72
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims abstract description 36
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- 125000003118 aryl group Chemical group 0.000 claims abstract description 20
- 150000002576 ketones Chemical class 0.000 claims abstract description 20
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052802 copper Inorganic materials 0.000 claims abstract description 8
- 239000010949 copper Substances 0.000 claims abstract description 8
- HVAPLSNCVYXFDQ-UHFFFAOYSA-N 3,3-dimethyl-1-(trifluoromethyl)-1$l^{3},2-benziodoxole Chemical compound C1=CC=C2C(C)(C)OI(C(F)(F)F)C2=C1 HVAPLSNCVYXFDQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 5
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims abstract description 4
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims abstract description 4
- 238000004090 dissolution Methods 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- 238000012805 post-processing Methods 0.000 claims 1
- OBORPMPYHHKEFS-UHFFFAOYSA-N 2-(trifluoromethyl)naphthalene-1,4-dione Chemical class C1=CC=C2C(=O)C(C(F)(F)F)=CC(=O)C2=C1 OBORPMPYHHKEFS-UHFFFAOYSA-N 0.000 abstract description 7
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 4
- 125000000524 functional group Chemical group 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 96
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 16
- 238000004293 19F NMR spectroscopy Methods 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 238000011017 operating method Methods 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 10
- 239000007788 liquid Substances 0.000 description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
- -1 1,4-naphthoquinone class compound Chemical class 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 229910020323 ClF3 Inorganic materials 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 238000006692 trifluoromethylation reaction Methods 0.000 description 2
- 125000000182 1,4-naphthoquinonyl group Chemical group C1(C(=CC(C2=CC=CC=C12)=O)*)=O 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- 229930192627 Naphthoquinone Natural products 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 150000001723 carbon free-radicals Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 150000002791 naphthoquinones Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C46/00—Preparation of quinones
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a kind of 2- Trifluoromethyl-1s, the preparation method of 4- naphthoquinone derivatives, in organic solvent by the dissolution of copper catalyst, alkali and togni reagent, the compound of benzaldehyde category that aryl acetylenic ketone replaces is added and forms reaction system, reaction system is reacted 10 hours at 60 DEG C, it is post-treated to obtain 2- Trifluoromethyl-1,4- naphthoquinone derivatives.A step of the invention realizes 2- Trifluoromethyl-1, the synthesis of 4- naphthoquinone derivatives, and combined coefficient significantly improves, and reaction condition is mild, and easy to operate, wide application range of substrates, functional group compatibility is good, using cheap cuprous bromide as catalyst, has applications well prospect.
Description
Technical field
The invention belongs to organic synthesis fields, and in particular to a kind of 2- Trifluoromethyl-1, the preparation side of 4- naphthoquinone derivatives
Method.
Background technique
1,4-naphthoquinone class compound is widely present in nature, many natural with physiology or pharmacological activity and
All contain the segment in non-native molecules:
Meanwhile 1,4-naphthoquinone class compound is also a kind of important fine-chemical intermediate, has been widely used in doctor
The industries such as medicine, pesticide, plasticizer, fragrance, dyestuff, the study found that 1,4-naphthoquinone class compound has good anti-corrosion, sterilization, resists
Ultraviolet light, anti-inflammatory and anticancer activity.
On the other hand, due to trifluoromethyl (CF3) there are the strong characteristics such as electron-withdrawing, lipophilicity and stable C-F key, it will
It, which is introduced into organic compound, can significantly change its acidity, dipole moment, polarity, lipophilicity and chemistry and metabolic stability
Property, therefore, the introducing of trifluoromethyl is at one of organic chemistry in recent years and the hot spot of pharmaceutical chemistry research.However, in naphthoquinones
The upper report for introducing trifluoromethyl is actually rare.Traditional 2- Trifluoromethyl-1, the synthetic method of 4- naphthoquinones are needed through five steps
(reduction, hydroxyl protection, bromination, trifluoromethylation, oxidation) Lai Hecheng is reacted, this multistep synthetic route Atom economy is low,
Combined coefficient is relatively low, and this method needs 1,4-naphthoquinone as raw material, in fact, the 1,4-naphthoquinone type of commercialization is seldom,
Cause its substrate applicability not ideal enough.1 2- Trifluoromethyl-1, the prior synthesizing method of 4- naphthoquinones:
2013, Szab ó and Wang Jianbo et al. reported the fluoroform of the direct C-H activation of copper catalysis 1,4-naphthoquinone ring in succession
Glycosylation reaction realizes a kind of new 2- Trifluoromethyl-1, the synthetic method of 4- naphthoquinone compound:
However, it is raw material to design as above method that these reactions, which are all based on 1,4-naphthoquinone, equally by commodity
Change the few limitation of 1,4-naphthoquinone type, product structure diversity is relatively difficult to achieve.Therefore, development is not using 1,4-naphthoquinone as raw material
The one-step synthesis of 2- Trifluoromethyl-1,4- naphthoquinones is significant.
Summary of the invention
The present invention provides a kind of copper to be catalyzed CF3The trifluoromethylation for the benzaldehyde that free radical initiation aryl acetylenic ketone replaces/
It is cyclized tandem reaction, which only needs a step that can construct 2- Trifluoromethyl-1,4- naphthoquinones skeleton, furthermore, it is possible to pass through virtue
Ring substituents (R1And R2) change realize 2- Trifluoromethyl-1,4- naphthoquinone derivatives structure diversity synthesis, reaction yield
Well, easy to operate, for synthesizing 2- Trifluoromethyl-1,4- naphthoquinones class natural products or drug molecule have good using valence
Value.
The technical solution adopted by the present invention are as follows:
A kind of 2- Trifluoromethyl-1, the preparation method of 4- naphthoquinones include the following steps:
In organic solvent by the dissolution of togni reagent shown in copper catalyst, alkali and structural formula III, II institute of structural formula is added
The benzaldehyde that the aryl acetylenic ketone shown replaces forms reaction system, and reaction system is reacted 10 hours at 60 DEG C, post-treated to be tied
2- Trifluoromethyl-1 shown in structure formula I, 4- naphthoquinone derivatives；
The togni reagent is 1- (trifluoromethyl) -1,2- benzenesulfonyl -3 (1H) -one, and structure is as shown in formula III:
The benzaldehyde that the aryl acetylenic ketone replaces is as shown in formula II:
The 2- Trifluoromethyl-1,4- naphthoquinone derivatives structure is as shown in formula I:
In formula I and formula II, R1For hydrogen atom, chlorine or fluorine, R2Selected from hydrogen atom, 4- fluorine, 4- chlorine, 4- tert-butyl, 2- methyl,
One of 2- methoxyl group, 3- phenoxy group, 2,6- dimethyl, 3,4- dimethoxy, 3,4,5- trimethoxy；
The alkali is potassium carbonate, and the catalyst is cuprous bromide, and the organic solvent is acetonitrile.
The copper catalyst, alkali, togni reagent, II compound represented of structural formula molar ratio be 0.2:1:2:1.
The reaction is carried out in 60 DEG C of reactions, and the optimal reaction time is 10 hours.
The reaction route of optimum condition is as follows:
It is used after the fully reacting and adds the technologies such as water quenching goes out, extracts, organic phase is washed, dry and column chromatography for separation
It is post-processed, to obtain the product of high-purity.
Ethyl acetate can be used as extractant in the extraction.
Saturated common salt washing can be used in the washing.
The condition of the column chromatography for separation are as follows: silica gel 300-400 mesh, eluent: the volume ratio of petrol ether/ethyl acetate
It is 10/1.
Compared with the existing technology, the present invention has the advantage that 1, one step realizes 2- Trifluoromethyl-1,4- naphthoquinone derivatives
Synthesis, combined coefficient significantly improves, and atom and step economy are high；2, it does not use 1,4-naphthoquinone for raw material, virtue can be passed through
Ring substituents (R1And R2) change realize 2- Trifluoromethyl-1, the structure diversity synthesis of 4- naphthoquinone derivatives, substrate is applicable in model
It encloses and greatly improves；3, reaction condition is mild, easy to operate, wide application range of substrates, and functional group compatibility is good, with cheap bromination
Cuprous is catalyst, has applications well prospect；4, the reaction is the more rare capture carbon radicals synthesizing carbonyl of aldehyde radical
One of example of compound.Therefore the present invention has biggish theory innovation value and implementary value.
Specific embodiment
Embodiment 1
Take a dry reaction tube, be weighed into cuprous bromide (5.7mg, 0.04mmol), potassium carbonate (27.6mg, 0.2
Mmol), 1- (trifluoromethyl) -1,2- benzenesulfonyl -3 (1H) -one (126.4mg, 0.4mmol), vacuum and exchange nitrogen, displacement three
It is secondary, 2- (3- phenyl propyne acyl group) the benzaldehyde 1a (46.8mg, 0.2mmol) for being dissolved in the dry acetonitrile of 2mL is then added.Reaction exists
After stirring 10h at 60 DEG C, 10mL water quenching is added to go out, three times with ethyl acetate (10mL) extraction, with the edible water washing of saturation after merging
Organic phase, anhydrous sodium sulfate are dry.Organic phase concentration after with silica gel (300-400 mesh) column chromatography for separation (eluent: petroleum ether/
The volume ratio of ethyl acetate is 10/1) to obtain 33.2mg yellow liquid 3a, yield 55%.Product Spectrum Analysis1H NMR
(600MHz,CDCl3),δ:8.20(dd,J1=7.8Hz, J2=1.2Hz, 1H), 8.12 (dd, J1=7.8Hz, J2=1.2Hz,
1H),7.86-7.80(m,2H),7.50-7.45(m,3H),7.24-7.23 (m,2H)；13C NMR(151MHz,CDCl3),δ:
183.7,180.9,149.5,134.9,134.6,132.8 (q, J=27.2Hz), 131.9,131.4,131.3,129.8,
128.7 (q, J=1.6Hz), 128.0,127.2,126.8,121.7 (q, J=277.8Hz)；19F NMR(565MHz,
CDCl3),δ:-56.29；HRMS(ESI)(m/z):calcd for C17H9F3O2([M+H]+),303.0627；found
303.0626.
Reaction equation is as follows:
Embodiment 2
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1b replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 50%, yellow solid, and fusing point 103-
105 ℃；1H NMR(400MHz,CDCl3),δ:8.21(dd,J1=7.6Hz, J2=1.6Hz, 1H), 8.14 (dd, J1=
6.8Hz,J2=2.0Hz, 1H), 7.90-7.82 (m, 2H), 7.28-7.24 (m, 2H), 7.20-7.16 (m, 2H)；13C NMR
(151MHz,CDCl3), δ: 183.6,180.7,163.8 (d, J=250.7Hz), 148.5,135.0,134.7,133.1 (q, J
=27.2Hz), 131.9,131.3,131.0,127.1,126.9,121.6 (q, J=279.4Hz), 115.4,115.3；19F
NMR(565MHz,CDCl3),δ:-56.25,-110.69；HRMS(ESI) (m/z):calcd for C17H8F4O2([M+H]+),
321.0533；found 321.0531.
Reaction equation is as follows:
Embodiment 3
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1c replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 52%, yellow solid, and fusing point 69-71
℃；1H NMR(600MHz,CDCl3),δ:8.19(dd,J1=7.8Hz, J2=1.2Hz, 1H), 8.12 (dd, J1=7.2Hz, J2
=1.6Hz, 1H), 7.87-7.81 (m, 2H), 7.46-7.44 (m, 2H), 7.18-7.17 (m, 2H)；13C NMR(151MHz,
CDCl3), δ: 183.4,180.6,148.3,136.2,135.1,134.8,133.1 (q, J=27.2Hz), 131.8,131.2,
(130.2,129.6,128.4,127.2,126.9,121.6 q, J=279.4Hz)；19F NMR(565MHz,CDCl3),δ:-
56.24；HRMS(ESI)(m/z):calcd for C18H11F3O3 ([M+H]+),337.0238；found 337.0233.
Reaction equation is as follows:
Embodiment 4
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1d replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 60%, yellow liquid；1H NMR
(600MHz, CDCl3),δ:8.19(dd,J1=7.2Hz, J2=1.2Hz, 1H), 8.12 (dd, J1=7.2Hz, J2=1.2 Hz,
1H), 7.84-7.80 (m, 2H), 7.48 (d, J=8.4Hz, 2H), 7.19 (d, J=8.4Hz, 2H), 1.37 (s, 9H)；13C
NMR(151MHz,CDCl3), δ: 183.8,180.9,153.0,149.5,134.7,134.4,132.5 (q, J=27.2Hz),
(131.8,131.3,128.7 q, J=1.5Hz), 128.1,127.1,126.6,124.8,121.7 (q, J=279.4Hz),
34.9,31.2；19F NMR(565MHz,CDCl3),δ:56.20；HRMS (ESI)(m/z):calcd for C21H17F3O2([M+
H]+),359.1253；found 359.1253.
Reaction equation is as follows:
Embodiment 5
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1e replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 62%, yellow liquid；1H NMR
(600MHz, CDCl3),δ:8.23(dd,J1=7.2Hz, J2=0.6Hz 1H), 8.12 (dd, J1=7.8Hz, J2=1.2 Hz,
1H), 7.87-7.81 (m, 2H), 7.38-7.36 (m, 1H), 7.30-7.26 (m, 2H), 7.02 (d, J=7.2 Hz, 1H), 2.15
(s,3H)；13C NMR(151MHz,CDCl3), δ: 183.4,180.7,150.3,135.0 (q, J=1.5Hz), 134.9,
134.7,133.4 (q, J=27.2Hz), 132.0,131.8,131.4,130.0,129.5,127.5 (q, J=3.0Hz),
(127.2,127.0,125.5,121.6 q, J=277.8Hz), 20.1；19F NMR (565MHz,CDCl3),δ:-58.03；
HRMS(ESI)(m/z):calcd for C18H11F3O2([M+H]+),317.0784； found 317.0781.
Reaction equation is as follows:
Embodiment 6
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1f replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 63%, yellow solid, and fusing point 124-
126 ℃；1H NMR(600MHz,CDCl3),δ:8.20(dd,J1=7.2Hz, J2=1.2Hz, 1H), 8.12 (dd, J1=
7.2Hz,J2=1.2Hz 1H), 7.84-7.78 (m, 2H), 7.46-7.43 (m, 1H), 7.07-7.04 (m, 2H), 6.98 (d, J
=8.4Hz, 1H), 3.76 (s, 3H)；13C NMR(151MHz,CDCl3),δ:183.0, 180.8,156.4,147.7,134.6,
134.4,133.6 (q, J=27.2Hz), 132.0,131.7,131.2,129.4,127.1,126.8,121.7 (q, J=
277.8Hz),121.1,120.3,110.8,55.8；19F NMR (565MHz,CDCl3),δ:-58.56；HRMS(ESI)(m/
z):calcd for C18H11F3O3([M+H]+),333.0733； found 333.0734.
Reaction equation is as follows:
Embodiment 7
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1g replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 58%, yellow liquid；1H NMR
(600MHz, CDCl3),δ:8.18(dd,J1=7.8Hz, J2=1.8Hz, 1H), 8.12 (dd, J1=7.2Hz, J2=1.2 Hz,
1H), 7.86-7.80 (m, 2H), 7.42 (t, J=7.8Hz, 1H), 7.37-7.34 (m, 2H), 7.14-7.11 (m, 2H), 7.06
(d, J=7.8Hz, 2H), 6.95 (d, J=7.8Hz, 1H), 6.87 (t, J=1.8Hz, 1H)；13C NMR(151MHz,
CDCl3),δ:183.4,180.7,157.0,156.8,148.8,135.0,134.7, 133.1,132.8,131.8,131.3,
(130.0,129.5,127.2,126.9,123.8,123.4,121.6 q, J=277.8Hz), 119.9,119.3,119.0；19F
NMR(565MHz,CDCl3),δ:-56.42；HRMS(ESI) (m/z):calcd for C23H13F3O3([M+H]+),
395.0890；found 395.0887.
Reaction equation is as follows:
Embodiment 8
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1h replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 61%, yellow solid, and fusing point: 85-87
℃；1H NMR(600MHz,CDCl3),δ:8.27(dd,J1=7.8Hz, J2=1.2Hz, 1H), 8.16 (dd, J1=7.8Hz, J2
=1.2Hz, 1H), 7.90 (dt, J=1.8Hz, 1H), 7.86 (dt, J=1.8Hz, 1H), 7.28 (d, J=7.8Hz, 1H),
7.4 (d, J=7.8Hz, 2H), 2.12 (s, 6H)；13C NMR(151MHz, CDCl3),δ:183.2,180.4,150.1,
135.0,134.7,134.3,132.0,131.6,131.5,129.0, 127.5,127.3,127.2,127.0,121.6(q,J
=279.4Hz), 20.2；19F NMR(565MHz,CDCl3), δ:-59.93；HRMS(ESI)(m/z):calcd for
C19H13F3O2([M+H]+),331.0940；Found 331.0939. reaction equation is as follows:
Embodiment 9
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1i replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 55%, red liquid；1H NMR
(600MHz, CDCl3),δ:8.17(dd,J1=7.8Hz, J2=1.8Hz 1H), 8.11 (dd, J1=7.2Hz, J2=1.2 Hz,
1H), 7.84-7.78 (m, 2H), 6.94 (d, J=8.4Hz, 1H), 6.84 (dd, J1=8.4Hz, J2=2.4Hz, 1H), 6.79
(d, J=1.8Hz, 1H), 3.94 (s, 3H), 3.89 (s, 3H)；13C NMR(151MHz, CDCl3),δ:183.8,181.1,
150.7,148.5,134.8,134.5,132.5 (q, J=27.2Hz), 131.9,131.4,127.2,126.7,123.5,
(122.6,121.8 q, J=277.8Hz), 112.7,110.6,56.08,56.02；19F NMR(565MHz,CDCl3),δ:-
56.23；HRMS(ESI)(m/z):calcd for C19H13F3O4 ([M+H]+),363.0839；found 363.0837.
Reaction equation is as follows:
Embodiment 10
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1j replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 72%, red solid, and fusing point 126-
128 ℃；1H NMR(600MHz,CDCl3),δ:8.17(dd,J1=7.8Hz, J2=1.8Hz, 1H), 8.11 (dd, J1=
7.2Hz,J2=1.8Hz, 1H), 7.85-7.80 (m, 2H), 6.46 (s, 2H), 3.91 (s, 3H), 3.85 (s, 6H)；13C NMR
(151MHz,CDCl3), δ: 183.6,180.9,152.9,149.3,139.4,134.9,134.7,132.8 (q, J=
27.2Hz), 131.8,131.3,127.2,126.8,126.4,121.7 (q, J=277.8Hz), 106.6,61.1,56.3；19F
NMR(565MHz,CDCl3),δ:-56.43；HRMS(ESI)(m/z):calcd for C20H15F3O5([M+H]+),363.0944；
found 363.0941.
Reaction equation is as follows:
Embodiment 11
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1k replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 61%, yellow liquid；1H NMR
(400MHz, CDCl3), δ: 8.14 (d, J=8.4Hz, 1H), 8.07 (d, J=2.0Hz, 1H), 7.78 (dd, J1=8.4 Hz,
J2=2.4Hz, 1H), 7.48 (d, J=8.4Hz, 2H), 7.17 (d, J=8.4Hz, 2H), 1.37 (s, 9H)；13C NMR
(151MHz,CDCl3), δ: 183.0,180.1,153.4,149.6,141.7,134.9,132.7 (q, J=27.2Hz),
132.5,130.1,128.8,128.6,127.8,127.1,125.0,121.6 (q, J=277.8Hz), 35.0,31.3；19F
NMR(565MHz,CDCl3),δ:-56.19；HRMS(ESI)(m/z):calcd for C21H16ClF3O2([M+H]+),
393.0864；found 393.0831.
Reaction equation is as follows:
Embodiment 12
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1l replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 63%, yellow solid, and fusing point: 91-93
℃；1H NMR(600MHz,CDCl3),δ:8.16(dd,J1=8.4Hz, J2=0.6Hz, 1H), 8.07 (d, J=2.4Hz,
1H),7.80(dd,J1=8.4Hz, J2=1.8Hz, 1H), 7.38 (dt, J1=7.8Hz, J2=1.8Hz, 1H), 7.29 (m,
2H),7.01(dd,J1=7.2Hz, J2=1.2Hz, 1H), 2.14 (s, 3H)；13C NMR(151MHz,CDCl3),δ:182.1,
179.6,166.5 (d, J=258.8Hz), 156.4,147.9,134.2 (d, J=8.3Hz), 133.7 (q, J=28.1Hz),
182.4,179.7,150.2,141.8,135.0,133.5 (q, J=27.2Hz), 132.5,131.4,131.0,130.1,
(129.6,128.8,127.5,127.1,126.4,125.6,121.4 q, J=279.4Hz), 20.0；19F NMR(565MHz,
CDCl3),δ:-58.00； HRMS(ESI)(m/z):calcd for C18H10ClF3O2([M+H]+),351.0394；found
351.0391.
Reaction equation is as follows:
Embodiment 13
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1m replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 70%, red solid, and fusing point: 159-
160 ℃；1H NMR(600MHz,CDCl3), δ: 8.14 (d, J=8.4Hz, 1H), 8.08 (d, J=8.4Hz, 1H), 7.80
(dd,J1=8.4Hz, J2=1.8Hz, 1H), 6.45 (s, 2H), 3.93 (s, 3H), 3.66 (s, 6H)；13C NMR(151MHz,
CDCl3), δ: 182.8,180.0,153.0,149.3,141.8,139.7,135.1,132.9 (q, J=28.7Hz), 132.4,
130.1,128.6,127.1,126.0,121.6 (q, J=279.4 Hz), 106.7,61.4,56.4；19F NMR(565MHz,
CDCl3),δ:-56.41,-100.69；HRMS(ESI) (m/z):calcd for C20H14ClF3O5([M+H]+),427.0555；
found 427.0554.
Reaction equation is as follows:
Embodiment 14
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1n replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 58%, yellow solid, and fusing point 96-98
℃；1H NMR(400MHz,CDCl3),δ:8.24(dd,J1=8.8Hz, J2=5.2Hz, 1H), 7.76 (dd, J1=8.0Hz, J2
=2.4Hz, 1H), 7.51-7.47 (m, 3H), 7.17 (d, J=8.4Hz, 2H), 1.37 (s, 9H)；13C NMR(151MHz,
CDCl3), δ: 183.0,179.8,166.5 (d, J=259.7Hz), 153.4,149.7,133.9 (d, J=9.1Hz), 132.7
(q, J=28.7Hz), 130.2 (d, J=9.1Hz), 128.8 (q, J=1.5Hz), 128.5,127.9,125.0,122.2 (d,
), J=22.7Hz 121.7 (q, J=277.8Hz), 113.7 (d, J=22.7Hz), 35.0,31.3；19F NMR(565MHz,
CDCl3),δ:-56.15,-100.39； HRMS(ESI)(m/z):calcd for C21H16F4O2([M+H]+),377.1159；
found 377.1166.
Reaction equation is as follows:
Embodiment 15
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1o replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 61%, yellow solid, and fusing point 90-92
℃；1H NMR(400MHz,CDCl3),δ:8.30(dd,J1=8.4Hz, J2=4.8Hz, 1H), 7.78 (dd, J1=8.4Hz, J2
=2.8Hz, 1H), 7.54 (dt, J1=8.0Hz, J2=2.4Hz, 1H), 7.40 (dt, J1=7.6Hz, J2=0.8Hz, 1H),
7.33-7.28 (m, 2H), 7.04 (d, J=7.2Hz, 1H), 2.17 (s, 3H)；13C NMR(151MHz,CDCl3),δ:182.5,
179.4,166.6 (d, J=259.7Hz), 150.4,135.0,134.0 (d, J=7.6Hz), 133.5 (q, J=27.2Hz),
(131.4,130.5,130.4,130.1,129.6,128.5,127.5 q, J=1.5Hz), 125.6,122.3 (d, J=
22.6Hz), 121.5 (q, J=277.8 Hz), 113.8 (d, J=2.3Hz), 20.0；19F NMR(565MHz,CDCl3),δ:-
57.96,-100.11；HRMS (ESI)(m/z):calcd for C18H10F4O2([M+H]+),335.0690；found
335.0689.
Reaction equation is as follows:
Embodiment 16
Except the benzaldehyde that the aryl acetylenic ketone shown in structural formula 1p replaces replaces implementing 2- shown in structural formula 1a in example 1
Outside (3- phenyl propyne acyl group) benzaldehyde, remaining operating procedure is with embodiment 1, yield: 54%, yellow solid, and fusing point: 142-
144 ℃；1H NMR(400MHz,CDCl3),δ:8.16(dd,J1=8.8Hz, J2=5.2Hz, 1H), 7.83 (dd, J1=
8.4Hz,J2=2.4Hz, 1H), 7.49-7.43 (m, 2H), 7.08-7.04 (m, 2H), 6.98 (d, J=8.4Hz, 1H), 3.76
(s,3H)；13C NMR(151MHz,CDCl3), δ: 181.7,179.8,166.6 (d, J=259.7Hz), 156.4,148.0,
134.5 (d, J=7.6Hz), 133.8 (q, J=27.2Hz), 131.3,130.5 (d, J=9.1Hz), 129.4,128.3,
121.8 (d, J=22.7Hz), 121.5 (q, J=277.8 Hz), 120.8,120.3,113.5 (d, J=24.2Hz), 110.8,
55.8；19F NMR(565MHz,CDCl3), δ:-58.72,-100.20；HRMS(ESI)(m/z):calcd for C18H10F4O3
([M+H]+),351.0639；found 351.0638.
Reaction equation is as follows:
。
Claims (3)
1. a kind of 2- Trifluoromethyl-1, the preparation method of 4- naphthoquinone derivatives, it is characterised in that include the following steps:
In organic solvent by the dissolution of togni reagent shown in copper catalyst, alkali and structural formula III, it is added shown in structural formula II
The compound of benzaldehyde category that aryl acetylenic ketone replaces forms reaction system, and reaction system is reacted 10 hours at 60 DEG C, post-treated
To 2- Trifluoromethyl-1 shown in structural formula I, 4- naphthoquinone derivatives；
In formula I and formula II, R1For hydrogen atom, chlorine or fluorine, R2Selected from hydrogen atom, 4- fluorine, 4- chlorine, 4- tert-butyl, 2- methyl, 2- first
One of oxygroup, 3- phenoxy group, 2,6- dimethyl, 3,4- dimethoxy, 3,4,5- trimethoxy；The copper catalyst is
Cuprous bromide, the alkali are potassium carbonate, and the organic solvent is acetonitrile, and the togni reagent is 1- (trifluoromethyl)-
1,2- benzenesulfonyl -3 (1H) -one.
2. according to the method described in claim 1, it is characterized by: the copper catalyst, alkali, togni reagent, structural formula II
The molar ratio of compound represented is 0.2:1:2:1.
3. according to the method described in claim 1, it is characterized by: the post-processing includes being quenched, extracting, drying and column layer
Analysis.
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| WO2012041918A3 (en) * | 2010-09-28 | 2012-06-21 | Solvay Sa | Process for the manufacture of hydrogen peroxide |
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| CN102020598A (en) * | 2010-11-11 | 2011-04-20 | 中山大学 | Gronwell naphthaquinone derivative, preparation method of gronwell naphthaquinone derivative and application of gronwell naphthaquinone derivative serving as anticarcinoma drug |
| CN106008402A (en) * | 2016-05-23 | 2016-10-12 | 浙江师范大学 | Epsilon-trifluoromethyl substituted amide preparing method |
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