CN109053510A - A kind of synthetic method for the sulphur ketenes derivative that the trifluoromethyl of visible light catalytic replaces - Google Patents
A kind of synthetic method for the sulphur ketenes derivative that the trifluoromethyl of visible light catalytic replaces Download PDFInfo
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- CN109053510A CN109053510A CN201810854295.7A CN201810854295A CN109053510A CN 109053510 A CN109053510 A CN 109053510A CN 201810854295 A CN201810854295 A CN 201810854295A CN 109053510 A CN109053510 A CN 109053510A
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- 239000005864 Sulphur Substances 0.000 title claims abstract description 11
- -1 sulphur ketenes Chemical class 0.000 title claims abstract description 11
- 230000003197 catalytic effect Effects 0.000 title claims abstract description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 title claims abstract description 5
- 238000010189 synthetic method Methods 0.000 title claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 18
- 239000012299 nitrogen atmosphere Substances 0.000 claims abstract description 16
- 239000003054 catalyst Substances 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 238000005286 illumination Methods 0.000 claims abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 50
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 26
- 239000003480 eluent Substances 0.000 claims description 15
- 239000001488 sodium phosphate Substances 0.000 claims description 15
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 15
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical group [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 15
- 239000003208 petroleum Substances 0.000 claims description 13
- 238000010898 silica gel chromatography Methods 0.000 claims description 13
- 238000003809 water extraction Methods 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical compound CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 claims description 7
- VQGHOUODWALEFC-UHFFFAOYSA-N 2-phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=CC=N1 VQGHOUODWALEFC-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- IICCLYANAQEHCI-UHFFFAOYSA-N 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 IICCLYANAQEHCI-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 238000013459 approach Methods 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 2
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 238000012805 post-processing Methods 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229930187593 rose bengal Natural products 0.000 claims description 2
- 229940081623 rose bengal Drugs 0.000 claims description 2
- STRXNPAVPKGJQR-UHFFFAOYSA-N rose bengal A Natural products O1C(=O)C(C(=CC=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 STRXNPAVPKGJQR-UHFFFAOYSA-N 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 239000012046 mixed solvent Substances 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 239000011574 phosphorus Substances 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 125000001424 substituent 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 14
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000006692 trifluoromethylation reaction Methods 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 101150009057 JAK2 gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000007146 photocatalysis Methods 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1815—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine with more than one complexing nitrogen atom, e.g. bipyridyl, 2-aminopyridine
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/30—Catalysts, in general, characterised by their form or physical properties characterised by their physical properties
- B01J35/39—Photocatalytic properties
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Inorganic Chemistry (AREA)
Abstract
The invention discloses the synthetic methods for the sulphur ketenes derivative that a kind of trifluoromethyl of visible light catalytic replaces, alpha-carbonyl dithio keteal shown in formula (I) or derivatives thereof, Umemoto reagent, alkaline matter and photochemical catalyst are added in organic solvent, 15-30h is stirred to react under nitrogen atmosphere, visible light illumination, normal temperature and pressure conditions, it is post-treated to obtain reaction solution, obtains sulphur ketenes trifluoromethyl derivative shown in formula (II)；Method reaction condition of the present invention is mild, easy to operate, and selectivity is high, and yield is good, and substituent group can be expanded；And visible light catalytic is used, have the characteristics that pollution-free, environmental-friendly, is a kind of very promising method.
Description
(1) technical field
The present invention relates to a kind of trifluoromethylation sides of carbonyl ortho position double bond using visible light catalytic sulphur ketenes derivative
Method.
(2) background technique
Alpha-carbonyl dithio keteal (as shown in Equation 1) refers to that β, the alpha, beta-unsaturated carbonyl that β -1,1-bialkyl sulphide replaces are closed
Object.Since Kelber in 1910 has synthesized 3,3- dimethyl sulphur-based -1- phenylpropen ketone (Ber.Dtsch.Chem.Ges, 1910,
43:1252-1259.), by the development in a nearly century, alpha-carbonyl dithio keteal is in synthesis, structural modification and organic
Greatly breaking through and developing using upper all achieve in synthesis, occupies an important position in organic synthesis.Its unique function
Unity structure imparts its great chemical activity, and carbonyl is connected with two alkylthio groups by alkene conjugation, and it is bis- to become 1,3-
With suitable parents' nucleome cyclization can occur for electrophilic body.According to hsab theory, due to β-carbon and soft base alkylthio group phase
Even and carbonyl is connected with hard base oxygen, therefore beta carbon and carbonyl carbon are regarded as soft, hard electrophilic center.So as to foundation
The needs of product preferentially carry out 1,2- or Isosorbide-5-Nitrae-conjugate addition reaction to select soft or hard nucleopilic reagent.
Alpha-carbonyl dithio keteal can be used as precursor synthesis arylpyrazoles compound for treating in pharmaceutical synthesis
Inflammation；It can also be used in the inhibitor for synthesizing JAK2 gene mutation simultaneously, to treat marrow appreciation tumour；Furthermore in vitamin
A and its efficiently synthesizing for derivative also have unique application.On the other hand, due to its powerful functional group's activity and electrophilic parent
The architectural characteristic of core is widely used in the building of cyclic compound and non-ring system in chemical synthesis.
However under so many advantage, synthesis is but extremely limited.Traditional sulphur ketenes trifluoromethyl is derivative
The synthesis of object is a certain amount of complex to be added under the catalysis of copper, while making alkali with KF class compound, is added certain
The AgCO of amount3As oxidant, synthesized under conditions of 100 DEG C.Maximum limitation is that reaction temperature is excessively high, dangerous；Simultaneously
Largely use Cu (OH)2A large amount of pollutions can be generated to environment, not environmentally.
Based on the above analysis, the new method for developing a kind of alpha-carbonyl dithio keteal trifluoromethyl derivative is that have weight
Want meaning.
(3) summary of the invention
Alpha-carbonyl dithio keteal carbonyl ortho position double bond is realized using visible light catalytic the object of the present invention is to provide a kind of
Trifluoromethylation method.
To achieve the above object, the present invention adopts the following technical scheme:
By alpha-carbonyl dithio keteal shown in formula (I) or derivatives thereof, Umemoto reagent, alkaline matter and photocatalysis
Agent is added in organic solvent, is stirred to react 15-30h under nitrogen atmosphere, visible light illumination, normal temperature and pressure conditions, is reacted
Liquid is post-treated, obtains sulphur ketenes trifluoromethyl derivative shown in formula (II)；The photochemical catalyst is selected from following compounds
One of: Eosin Y, Rose bengal, Ru (bpz)3(BF6)2、Ir(ppy)3、[Ir(ppy)2(dtbbpy)]PF6Or [Ir
(dFCF3ppy)2(dtbbpy)]PF6；Alpha-carbonyl dithio keteal shown in the formula (I) or derivatives thereof is tried with Umemoto
Agent, alkaline matter and photochemical catalyst the ratio between the amount for the substance that feeds intake for 1:1~2:1~4:0.005~0.01 (preferably 1:2:2:
0.005)；
Wherein, R1For C1~C4H on alkyl, phenyl or phenyl ring is by C1~C4Alkyl, fluorine, chlorine, bromine or methoxy substitution
Phenyl；R2For methyl or ethyl.
Further, the R1H preferably on methyl, isopropyl, phenyl or phenyl ring is taken by methoxyl group, isobutyl group, fluorine
The phenyl in generation.
In method of the present invention, the organic solvent is acetonitrile, methylene chloride, n,N-Dimethylformamide, two
Methyl sulfoxide, 1,2- dichloroethanes, benzene, toluene or N-Methyl pyrrolidone, further, preferably dimethyl sulfoxide.
Further, recommend the volumetric usage of organic solvent with raw material alpha-carbonyl dithio keteal shown in formula (I) or its derivative
The amount of the substance of object is calculated as 8~12mL/mmol.
Further, the alkaline matter is preferably sodium phosphate, dipotassium hydrogen phosphate or potassium phosphate.
Further, the alkaline matter is most preferably sodium phosphate.
Further, the photochemical catalyst is preferably Ir (ppy)3、[Ir(dF-CF3-ppy)2(dtbbpy)]PF6Or [Ir
(ppy)2(bpy)]PF6。
Further, the photochemical catalyst is most preferably Ir (ppy)3。
Further, the reaction time is preferably 25-30h.
Further, the light source is preferably one of following: 25~45W white light energy-saving lamp or 7W blue LED lamp.
Further, the light source is preferred are as follows: 7W blue LED lamp.
In general, the post-processing approach of the reaction solution are as follows: after reaction by reaction solution after methylene chloride and water extraction,
Organic phase is collected, silica gel column chromatography separation is then carried out, with the mixing of petroleum ether and ethyl acetate that volume ratio is 10~20:1
Solvent collects the eluent containing target product, obtains sulphur alkene shown in target product formula (II) through separating-purifying as eluant, eluent
Ketone trifluoromethyl derivative.
Compared with prior art, the beneficial effects of the present invention are:
The trifluoromethylation method of alpha-carbonyl dithio keteal carbonyl ortho position of the present invention double bond, reaction condition temperature
With it is easy to operate, selectivity is high, and yield is good, and substituent group can be expanded；And visible light catalytic is used, there is pollution-free, ring
The features such as border is friendly is a kind of very promising method.
(4) Detailed description of the invention
Fig. 1 is product 2a's1H NMR spectra.
Fig. 2 is product 2a's13C NMR spectra.
(5) specific embodiment
Below by specific embodiment to further illustrate the technical scheme of the present invention, but protection scope of the present invention is not
It is only limitted to this.Ir used in following embodiment (ppy)3、[Ir(dF-CF3-ppy)2(dtbbpy)]PF6、[Ir(ppy)2
(bpy)]PF6The structural formula of catalyst is as follows:
Catalyst described in the present embodiment and Umemoto reagent purchase from Shanghai Mike woods biochemical technology Co., Ltd or
Sigma-Aldrich company.
Embodiment 1
In Schlenk pipe, 1a (111mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), Ir are sequentially added
(ppy)3(3.27mg, 0.005mmol) sodium phosphate (164mg, 1mmol) and DMSO (5mL), connect nitrogen atmosphere, blue in 7W LED
30h is stirred at room temperature under light irradiation.After completion of the reaction, reaction solution is after methylene chloride and water extraction, with V petroleum ether: V ethyl acetate
=10~20:1 purifies to obtain faint yellow target product 2a, yield 91% by silica gel column chromatography as eluant, eluent.Product table
It is as follows to levy data:1H NMR(500MHz,CDCl3)δ7.97–7.90(m,2H),7.67–7.59(m,1H),7.52(m,2H),
2.47(s,3H),2.20(s,3H)。
Embodiment 2 (comparative example: solvent)
In Schlenk pipe, 1a (111mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), Ir are sequentially added
(ppy)3(3.27mg, 0.005mmol) sodium phosphate (164mg, 1mmol) and methylene chloride DCM (5mL), connect nitrogen atmosphere, in 7W
30h is stirred at room temperature under LED blue light illumination.After completion of the reaction, reaction solution is after methylene chloride and water extraction, with V petroleum ether: V second
Acetoacetic ester=10~20:1 purifies to obtain faint yellow target product 2a, yield 48% by silica gel column chromatography as eluant, eluent.
Embodiment 3 (comparative example: solvent)
In Schlenk pipe, 1a (111mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), Ir are sequentially added
(ppy)3(3.27mg, 0.005mmol) sodium phosphate (164mg, 1mmol) and DMF (5mL), connect nitrogen atmosphere, in 7W LED blue light
30h is stirred at room temperature under irradiation.After completion of the reaction, reaction solution is after methylene chloride and water extraction, with V petroleum ether: V ethyl acetate=
10~20:1 purifies to obtain faint yellow target product 2a, yield 40% by silica gel column chromatography as eluant, eluent.
Embodiment 4 (comparative example: solvent)
In Schlenk pipe, 1a (111mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), Ir are sequentially added
(ppy)3(3.27mg, 0.005mmol) sodium phosphate (164mg, 1mmol) and 1,2- dichloroethanes DCE (5mL), connects nitrogen atmosphere,
30h is stirred at room temperature under 7W LED blue light illumination.Reaction solution is after methylene chloride and water extraction, with V petroleum ether: V ethyl acetate
=10~20:1 purifies to obtain faint yellow target product 2a, yield 43% by silica gel column chromatography as eluant, eluent.
Embodiment 5 (comparative example: solvent)
In Schlenk pipe, 1a (111mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), Ir are sequentially added
(ppy)3(3.27mg, 0.005mmol) sodium phosphate (164mg, 1mmol) and NMP (5mL), connect nitrogen atmosphere, in 7W LED blue light
30h is stirred at room temperature under irradiation.After completion of the reaction, reaction solution is after methylene chloride and water extraction, with V petroleum ether: V ethyl acetate=
10~20:1 purifies to obtain faint yellow target product 2a, yield 50% by silica gel column chromatography as eluant, eluent.
Embodiment 6 (comparative example: without photochemical catalyst)
In Schlenk pipe, 1a (111mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), phosphoric acid are sequentially added
Sodium (164mg, 1mmol) and DMSO (5mL), connect nitrogen atmosphere, and 30h is stirred at room temperature under 7W LED blue light illumination.End of reaction
Afterwards, it can't detect the generation of product with TLC.
Embodiment 7 (comparative example: unglazed)
In Schlenk pipe, 1a (111mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), Ir are sequentially added
(ppy)3(3.27mg, 0.005mmol) sodium phosphate (164mg, 1mmol) and DMSO (5mL), connect nitrogen atmosphere, dark unglazed
30h is stirred at room temperature under irradiation.After completion of the reaction, it can't detect the generation of product with TLC.
Embodiment 8
In Schlenk pipe, 1b (127mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), Ir are sequentially added
(ppy)3(3.27mg, 0.005mmol) sodium phosphate (164mg, 1mmol) and DMSO (5mL), connect nitrogen atmosphere, blue in 7W LED
30h is stirred at room temperature under light irradiation.Reaction solution is after methylene chloride and water extraction, with V petroleum ether: ethyl acetate=10 V~20:1
As eluant, eluent, purify to obtain faint yellow target product 2b, yield 84% by silica gel column chromatography.Characterization of The Products data are such as
Under:1H NMR(500MHz,CDCl3)δ7.95–7.88(m,2H),7.03–6.96(m,2H),3.90(s,3H),2.47(s,3H),
2.23(s,3H)。
Embodiment 9
In Schlenk pipe, 1c (95mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), Ir are sequentially added
(ppy)3(3.27mg, 0.005mmol) sodium phosphate (164mg, 1mmol) and DMSO (5mL), connect nitrogen atmosphere, blue in 7W LED
30h is stirred at room temperature under light irradiation.After completion of the reaction, reaction solution is after methylene chloride and water extraction, with V petroleum ether: V ethyl acetate
=10~20:1 purifies to obtain faint yellow target product 2c, yield 90% by silica gel column chromatography as eluant, eluent.Product table
It is as follows to levy data:1H NMR(500MHz,CDCl3) δ 2.88 (q, J=7.3Hz, 3H), 2.45 (s, 2H), 1.30 (t, J=
7.4Hz,5H)。
Embodiment 10
In Schlenk pipe, 1d (95mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), Ir are sequentially added
(ppy)3(3.27mg, 0.005mmol) sodium phosphate (164mg, 1mmol) and DMSO (5mL), connect nitrogen atmosphere, blue in 7W LED
30h is stirred at room temperature under light irradiation.Reaction solution is after methylene chloride and water extraction, with V petroleum ether: ethyl acetate=10 V~20:1
As eluant, eluent, purify to obtain faint yellow target product 2d, yield 84% by silica gel column chromatography.Characterization of The Products data are such as
Under:1H NMR(500MHz,CDCl3) δ 2.98 (m, 1H), 2.40 (s, 6H), 1.19 (d, J=7.0Hz, 6H).
Embodiment 11
In Schlenk pipe, 1e (140mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), Ir are sequentially added
(ppy)3(3.27mg, 0.005mmol) sodium phosphate (164mg, 1mmol) and DMSO (5mL), connect nitrogen atmosphere, blue in 7W LED
30h is stirred at room temperature under light irradiation.After completion of the reaction, reaction solution is after methylene chloride and water extraction, with V petroleum ether: V ethyl acetate
=10~20:1 purifies to obtain faint yellow target product 2e, yield 81% by silica gel column chromatography as eluant, eluent.Product table
It is as follows to levy data:1H NMR(500MHz,CDCl3) δ 7.84 (d, J=8.2Hz, 2H), 7.39-7.17 (m, 2H), 2.56 (d, J=
7.2Hz, 2H), 2.47 (s, 3H), 2.20 (s, 3H), 2.00-1.87 (m, 1H), 0.93 (d, J=6.6Hz, 6H).
Embodiment 12
In Schlenk pipe, 1f (121mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), Ir are sequentially added
(ppy)3(3.27mg, 0.005mmol) sodium phosphate (164mg, 1mmol) and DMSO (5mL), connect nitrogen atmosphere, blue in 7W LED
30h is stirred at room temperature under light irradiation.After completion of the reaction, reaction solution is after methylene chloride and water extraction, with V petroleum ether: V ethyl acetate
=10~20:1 purifies to obtain faint yellow target product 2f, yield 92% by silica gel column chromatography as eluant, eluent.Product table
It is as follows to levy data:1H NMR(500MHz,CDCl3)δ7.99–7.93(m,2H),7.22–7.16(m,2H),2.48(s,3H),
2.22(s,3H)。
Embodiment 13
In Schlenk pipe, 1g (81mg, 0.5mmol), Umemoto reagent (340mg, 1mmol), Ir are sequentially added
(ppy)3(3.27mg, 0.005mmol) sodium phosphate (164mg, 1mmol) and DMSO (5mL), connect nitrogen atmosphere, blue in 7W LED
30h is stirred at room temperature under light irradiation.After completion of the reaction, reaction solution is after methylene chloride and water extraction, with V petroleum ether: V ethyl acetate
=10~20:1 purifies to obtain faint yellow target product 2g, yield 85% by silica gel column chromatography as eluant, eluent.Product table
It is as follows to levy data:1H NMR(500MHz,CDCl3)δ2.44(s,3H),2.42(s,6H)。
Claims (10)
1. the synthetic method for the sulphur ketenes derivative that a kind of trifluoromethyl of visible light catalytic replaces, it is characterised in that: described
Method specifically carries out in accordance with the following steps:
Alpha-carbonyl dithio keteal shown in formula (I) or derivatives thereof, Umemoto reagent, alkaline matter and photochemical catalyst are added
Enter in organic solvent, in a nitrogen atmosphere, under visible light illumination, is stirred to react 15-30h under normal temperature and pressure conditions, obtains
Reaction solution is post-treated, obtains sulphur ketenes trifluoromethyl derivative shown in formula (II)；The photochemical catalyst is selected from followingization
Close one of object: Eosin Y, Rose bengal, Ru (bpz)3(BF6)2、Ir(ppy)3、[Ir(ppy)2(dtbbpy)]PF6Or [Ir
(dFCF3ppy)2(dtbbpy)]PF6；Alpha-carbonyl dithio keteal shown in the formula (I) or derivatives thereof is tried with Umemoto
The ratio between agent, the amount for the substance that feeds intake of alkaline matter and photochemical catalyst are 1:1~2:1~4:0.005~0.01；
In formula (I) or formula (II), R1For C1~C4H on alkyl, phenyl or phenyl ring is by C1~C4Alkyl, fluorine, chlorine, bromine or first
The phenyl that oxygroup replaces；R2For methyl or ethyl.
2. the method as described in claim 1, it is characterised in that: the R1For the H on methyl, isopropyl, phenyl or phenyl ring
By methoxyl group, isobutyl group, fluorine-substituted phenyl.
3. the method as described in claim 1, it is characterised in that: the organic solvent is acetonitrile, methylene chloride, N, N- diformazan
Base formamide, dimethyl sulfoxide, 1,2- dichloroethanes, benzene, toluene or N-Methyl pyrrolidone.
4. the method as described in claim 1, it is characterised in that: the volumetric usage of the organic solvent is with original shown in formula (I)
The amount of the substance of material alpha-carbonyl dithio keteal or derivatives thereof is calculated as 8~12mL/mmol.
5. the method as described in claim 1, it is characterised in that: the alkaline matter is sodium phosphate, dipotassium hydrogen phosphate or phosphorus
Sour potassium.
6. the method as described in claim 1, it is characterised in that: the photochemical catalyst is Ir (ppy)3、[Ir(dF-CF3-
ppy)2(dtbbpy)]PF6Or [Ir (ppy)2(bpy)]PF6。
7. method as claimed in claim 6, it is characterised in that: the photochemical catalyst is Ir (ppy)3。
8. the method as described in claim 1, it is characterised in that: the reaction time is 25-30h.
9. the method as described in claim 1, it is characterised in that: the light source is 25~45W white light energy-saving lamp or 7W blue led
Lamp.
10. method described in claim 1, it is characterised in that: the post-processing approach of the reaction solution are as follows: after reaction, will
Reaction solution through methylene chloride and water extraction after, collect organic phase, then carry out silica gel column chromatography separation, with volume ratio be 10~
The petroleum ether of 20:1 and the mixed solvent of ethyl acetate collect the eluent containing target product, through separating-purifying as eluant, eluent
Obtain sulphur ketenes trifluoromethyl derivative shown in target product formula (II).
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Cited By (3)
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|---|---|---|---|---|
| CN114214646A (en) * | 2021-12-24 | 2022-03-22 | 南通大学 | Synthesis method for electrochemically oxidizing 2-trifluoromethyl-alpha-carbonyl dithio-ketene acetal compound |
| CN114890908A (en) * | 2022-05-26 | 2022-08-12 | 华中科技大学 | Gamma-position trifluoromethyl amino acid derivative and preparation method thereof |
| CN115745855A (en) * | 2022-12-06 | 2023-03-07 | 东北师范大学 | Trifluoromethyl polarized olefin compound and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114214646A (en) * | 2021-12-24 | 2022-03-22 | 南通大学 | Synthesis method for electrochemically oxidizing 2-trifluoromethyl-alpha-carbonyl dithio-ketene acetal compound |
| CN114214646B (en) * | 2021-12-24 | 2023-08-29 | 南通大学 | Synthesis method of electrochemical oxidation 2-trifluoromethyl-alpha-carbonyl dithio ketene compound |
| CN114890908A (en) * | 2022-05-26 | 2022-08-12 | 华中科技大学 | Gamma-position trifluoromethyl amino acid derivative and preparation method thereof |
| CN115745855A (en) * | 2022-12-06 | 2023-03-07 | 东北师范大学 | Trifluoromethyl polarized olefin compound and preparation method thereof |
| CN115745855B (en) * | 2022-12-06 | 2024-03-22 | 东北师范大学 | Trifluoromethyl polarized olefin compound and preparation method thereof |
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