CN105111116A - Catalytic synthetic method for aryl sulfide compound - Google Patents
Catalytic synthetic method for aryl sulfide compound Download PDFInfo
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- CN105111116A CN105111116A CN201510507295.6A CN201510507295A CN105111116A CN 105111116 A CN105111116 A CN 105111116A CN 201510507295 A CN201510507295 A CN 201510507295A CN 105111116 A CN105111116 A CN 105111116A
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- -1 aryl sulfide compound Chemical class 0.000 title abstract description 5
- 238000010189 synthetic method Methods 0.000 title abstract description 5
- 230000003197 catalytic effect Effects 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 48
- 238000000034 method Methods 0.000 claims abstract description 45
- 239000003513 alkali Substances 0.000 claims abstract description 19
- 239000003960 organic solvent Substances 0.000 claims abstract description 15
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 230000008569 process Effects 0.000 claims description 33
- 238000007036 catalytic synthesis reaction Methods 0.000 claims description 32
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 27
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 11
- 229910052802 copper Inorganic materials 0.000 claims description 11
- 239000010949 copper Substances 0.000 claims description 11
- 150000004832 aryl thioethers Chemical class 0.000 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 claims description 9
- 150000002941 palladium compounds Chemical class 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 2
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- SLINHMUFWFWBMU-UHFFFAOYSA-N Triisopropanolamine Chemical compound CC(O)CN(CC(C)O)CC(C)O SLINHMUFWFWBMU-UHFFFAOYSA-N 0.000 claims description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 2
- 229960003511 macrogol Drugs 0.000 claims description 2
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 claims description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 26
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000011259 mixed solution Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 235000002639 sodium chloride Nutrition 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 4
- GPNDARIEYHPYAY-UHFFFAOYSA-N palladium(ii) nitrate Chemical compound [Pd+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O GPNDARIEYHPYAY-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- 101150003085 Pdcl gene Proteins 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- JKDRQYIYVJVOPF-FDGPNNRMSA-L palladium(ii) acetylacetonate Chemical compound [Pd+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O JKDRQYIYVJVOPF-FDGPNNRMSA-L 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 0 *B(c(cccc1)c1[Br+])O Chemical compound *B(c(cccc1)c1[Br+])O 0.000 description 1
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N C1CCCC1 Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- CVNQNVBPCYBPEP-UHFFFAOYSA-N C=CCCCSc(cccc1)c1Br Chemical compound C=CCCCSc(cccc1)c1Br CVNQNVBPCYBPEP-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- PBDBXAQKXCXZCJ-UHFFFAOYSA-L palladium(2+);2,2,2-trifluoroacetate Chemical compound [Pd+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F PBDBXAQKXCXZCJ-UHFFFAOYSA-L 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940074386 skatole Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000006177 thiolation reaction Methods 0.000 description 1
- 238000004073 vulcanization Methods 0.000 description 1
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention provides a catalytic synthetic method for an aryl sulfide compound shown in a formula (IV). The method comprises: in an organic solvent, in the presence of a catalyst, an accelerant and alkali, carrying out a reaction on a compound shown in a formula (I), a compound shown in a formula (II) and a compound shown in a formula (III) so as to obtain the compound shown in the formula (IV). The formula (IV) is shown in the description, wherein R is H, C1-C6 alkyl, C1-C6 alkoxyl or halogen; n is an integer of 1-4. The method comprehensively selects and coordinates the catalyst, the accelerant, the alkali, the organic solvent and the like so as to obtain a target product with a high yield, thereby providing a brand new method for synthesis of the compounds and developing a novel synthetic channel for the field of chemical industry and medicines. The method has wide market value and potential productivity.
Description
Technical field
The present invention relates to a kind of synthetic method of sulphur compound, relate more specifically to a kind of process for catalytic synthesis of aryl thioether compound, belong to technical field of organic synthesis especially medicine intermediate synthesis field.
Background technology
Sulfide based structural is the important construction unit in natural product, medical compounds, functional materials, and it gives these molecules diversified functional and modifiability.What the reaction kinetic along with c h bond was studied gos deep into, about the studying team also growing growth that C-S key is constructed.Novel, the effective C-S key forming strategies of development all has very significant meaning to fields such as synthesis, materials.
The method of existing report often adopts polytype thiolating reagent to realize the Thiolation reaction of c h bond, such as, adopt disulphide, sulfonyl hydrazide, SULPHURYL CHLORIDE,-sulfinate etc.
Also the method using aryl sulfonyl chloride to prepare aryl thioether compound is there is in prior art, illustratively as follows:
WuQian etc. (" Synthesisofdi (hetero) arylsulfidesbydirectlyusingarylsulfonylchloridesasasulfu rsource ", Chem.Commun., 2011,47,9188-9190) report a kind of diaryl sulphur preparing process, under the effect of triphenylphosphine, achieve reaction, its reaction formula is as follows:
ChenMin etc. (" Visiblelight-induced3-sulfenylationofN-methylindoleswith arylsulfonylchlorides ", Chem.Commun., 2012,48,11686-11688) report a kind of N-skatole of visible light-inducing and the vulcanization reaction method of aryl sulfonyl chloride, its reaction formula is as follows:
As mentioned above, in prior art, disclose the multiple synthetic method of aryl thioether compound, but these methods of prior art still also exist the problem that not high enough, consuming time longer, the substrate spectrum of reaction yield needs to be expanded.
In view of this, the present inventor is by reading a large amount of scientific documents and carrying out systematic experimental study, and aim to provide a kind of process for catalytic synthesis of aryl thioether compound, it adopts multiple complex reaction reagent to work in coordination with carrying out smoothly of auxiliary catalysis reaction, and reach the object of high yield, less energy-consumption, show market outlook widely.
Summary of the invention
In order to overcome above-mentioned pointed many defects and the new synthetic method seeking aryl thioether compound, present inventor has performed deep research and exploration, after having paid enough creative works, thus completing the present invention.
Specifically, technical scheme of the present invention and content relate to the process for catalytic synthesis of aryl thioether compound shown in a kind of following formula (IV), described method comprises: in organic solvent, under catalyzer, promotor and alkali exist, following formula (I) compound, following formula (II) compound and following formula (III) compound react, thus obtain described formula (IV) compound
Wherein, R is H, C
1-C
6alkyl, C
1-C
6alkoxy or halogen;
N is the integer of 1-4.
In described process for catalytic synthesis of the present invention, described C
1-C
6the implication of alkyl refers to the straight or branched alkyl with 1-6 carbon atom, such as can be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, the tertiary butyl, n-pentyl, isopentyl or n-hexyl etc. in non-limiting manner.
In described process for catalytic synthesis of the present invention, described C
1-C
6alkoxyl group refers to " C defined above
1-C
6alkyl " be connected with O atom after group.
In described process for catalytic synthesis of the present invention, the implication of described halogen refers to haloid element, non-exclusively such as can be F, Cl, Br or I.
In described process for catalytic synthesis of the present invention, n is the integer of 1-4, such as, can be 1,2,3 or 4.
In described process for catalytic synthesis of the present invention, described catalyzer is organic palladium compound and Rh (cod)
2bF
4mixture, wherein organic palladium compound and Rh (cod)
2bF
4mol ratio be 1:1.5-2.
Wherein, described organic palladium compound is Pd (OAc)
2(acid chloride), Pd (TFA)
2(palladium trifluoroacetate), Pd (NH
3) Cl
2(dichloro diamino palladium), Pd (acac)
2(palladium acetylacetonate), Pd (PhCN)
2cl
2(two (cyano group benzene) palladium chloride), PdCl
2(cod) any one in ((1,5-cyclooctadiene) palladium chloride), Palladous chloride, Palladous nitrate, most preferably is Pd (TFA)
2.
In described process for catalytic synthesis of the present invention, described promotor is zinc iodide (ZnI
2) with the mixture of copper trifluoromethanesulfcomposite, wherein, the mol ratio of zinc iodide and copper trifluoromethanesulfcomposite is 1:2.
In described process for catalytic synthesis of the present invention, described alkali is any one or mixture multiple arbitrarily in triethylamine, tri-isopropanolamine, NaOH, sodium carbonate, pyridine, sodium ethylate, sodium bicarbonate, potassium tert.-butoxide, Dimethylamino pyridine (DMPA), Tetramethyl Ethylene Diamine, N-methylmorpholine, hexahydroaniline, vulkacit H, most preferably is N-methylmorpholine.
In described process for catalytic synthesis of the present invention, described organic solvent is acetonitrile, Macrogol 200 (PEG-200), benzyl cyanide, N-Methyl pyrrolidone (NMP), 1,4-dioxane, dimethyl sulfoxide (DMSO) (DMSO), N, any one in dinethylformamide (DMF), toluene, benzene, ethanol etc., most preferably is benzyl cyanide.
Wherein, there is no particular limitation for the consumption of described organic solvent, can according to reaction need carry out suitable selection, this is the conventional capability that has of those skilled in the art and technical knowledge.
In described process for catalytic synthesis of the present invention, described formula (I) compound and formula (II) compound mole be 1:1.5-2, in non-limiting manner such as can 1:1.5,1:1.7,1:1.9 or 1:2.
In described process for catalytic synthesis of the present invention, the mol ratio of described formula (I) compound and formula (III) compound is 1:2-3, such as, can be 1:2,1:2.5 or 1:3.
In described process for catalytic synthesis of the present invention, the mol ratio of described formula (I) compound and catalyzer is 1:0.05-0.1, i.e. the mole dosage of described formula (I) compound and the organic palladium compound of the described catalyzer of composition and Rh (cod)
2bF
4the ratio of total mole dosage be 1:0.05-0.1, such as can be 1:0.05,1:0.07,1:0.09 or 1:0.1.
In described process for catalytic synthesis of the present invention, the mol ratio of described formula (I) compound and promotor is 1:0.2-0.3, such as, can be 1:0.2,1:0.25 or 1:0.3.
In described process for catalytic synthesis of the present invention, the mol ratio of described formula (I) compound and alkali is 1:0.5-0.8, such as, can be 1:0.5,1:0.6,1:0.7 or 1:0.8.
In described process for catalytic synthesis of the present invention, temperature of reaction is 60-80 DEG C, such as, can be 60 DEG C, 70 DEG C or 80 DEG C.
In described process for catalytic synthesis of the present invention, the reaction times is 5-8 hour, such as, can be 5 hours, 6 hours, 7 hours or 8 hours.
In described process for catalytic synthesis of the present invention, aftertreatment after reaction terminates is specific as follows: after reaction terminates, and reaction system is filtered, in filtrate, adds saturated aqueous common salt, abundant vibration, then add extraction into ethyl acetate 2-3 time, merge organic phase, anhydrous sodium sulfate drying, concentrating under reduced pressure, gained residue is crossed 300-400 order silica gel column chromatography to be separated, using isopyknic acetoneand ethyl acetate mixed solution as eluent, thus obtain described formula (IV) compound.
In sum, the invention provides a kind of process for catalytic synthesis of aryl thioether compound, described method passes through the comprehensive selection of catalyzer, promotor, alkali and organic solvent etc. with collaborative, thus high yield can obtain object product, for the synthesis of this compounds provides completely new approach, for opening new synthesized channel for chemical industry, field of medicaments, there are marketable value and production potential widely.
Embodiment
Below by specific embodiment, the present invention is described in detail; but the purposes of these exemplary embodiments and object are only used for exemplifying the present invention; not any type of any restriction is formed to real protection scope of the present invention, more non-protection scope of the present invention is confined to this.
Embodiment 1
Under room temperature, to in appropriate organic solvent benzyl cyanide, add 100mmol above formula (I) compound, 150mmol above formula (II) compound and 200mmol above formula (III) compound, then to add 5mmol catalyzer (be 2mmolPd (TFA)
2with 3mmolRh (cod)
2bF
4mixture), 21mmol promotor (mixture for 7mmol zinc iodide and 14mmol copper trifluoromethanesulfcomposite) and 50mmol alkali N-methylmorpholine, be then warming up to 60 DEG C, and stirring reaction 8 hours at such a temperature.
After reaction terminates, reaction system is filtered, in filtrate, adds saturated aqueous common salt, fully vibrate, then extraction into ethyl acetate is added 2-3 time, merge organic phase, anhydrous sodium sulfate drying, concentrating under reduced pressure, gained residue is crossed 300-400 order silica gel column chromatography to be separated, using isopyknic acetoneand ethyl acetate mixed solution as eluent, thus obtain above formula (IV) compound, productive rate is 98.5%.
1HNMR(CDCl
3,400MHz):δ7.39-7.35(m,1H),7.21-7.09(m,3H),3.14-3.06(m,1H),2.42(s,3H),2.03(d,J＝11.3Hz,2H),1.78(d,J＝5.0Hz,2H),1.64-1.60(m,1H),1.44-1.26(m,5H)。
Embodiment 2
Under room temperature, to in appropriate organic solvent benzyl cyanide, add 100mmol above formula (I) compound, 170mmol above formula (II) compound and 250mmol above formula (III) compound, then to add 7mmol catalyzer (be 2.55mmolPd (TFA)
2with 4.45mmolRh (cod)
2bF
4mixture), 27mmol promotor (mixture for 9mmol zinc iodide and 18mmol copper trifluoromethanesulfcomposite) and 65mmol alkali N-methylmorpholine, be then warming up to 70 DEG C, and stirring reaction 6 hours at such a temperature.
After reaction terminates, reaction system is filtered, in filtrate, adds saturated aqueous common salt, fully vibrate, then extraction into ethyl acetate is added 2-3 time, merge organic phase, anhydrous sodium sulfate drying, concentrating under reduced pressure, gained residue is crossed 300-400 order silica gel column chromatography to be separated, using isopyknic acetoneand ethyl acetate mixed solution as eluent, thus obtain above formula (IV) compound, productive rate is 98.2%.
1HNMR(CDCl
3,400MHz):δ7.36(d,J＝8.7Hz,2H),6.83(d,J＝8.7Hz,2H),3.77(s,3H),3.29-3.16(m,1H),1.66-1.60(m,2H),1.58-1.47(m,12H)。
Embodiment 3
Under room temperature, to in appropriate organic solvent benzyl cyanide, add 100mmol above formula (I) compound, 200mmol above formula (II) compound and 300mmol above formula (III) compound, then to add 10mmol catalyzer (be 3.34mmolPd (TFA)
2with 6.66mmolRh (cod)
2bF
4mixture), 30mmol promotor (mixture for 10mmol zinc iodide and 20mmol copper trifluoromethanesulfcomposite) and 80mmol alkali N-methylmorpholine, be then warming up to 80 DEG C, and stirring reaction 5 hours at such a temperature.
After reaction terminates, reaction system is filtered, in filtrate, adds saturated aqueous common salt, fully vibrate, then extraction into ethyl acetate is added 2-3 time, merge organic phase, anhydrous sodium sulfate drying, concentrating under reduced pressure, gained residue is crossed 300-400 order silica gel column chromatography to be separated, using isopyknic acetoneand ethyl acetate mixed solution as eluent, thus obtain above formula (IV) compound, productive rate is 98.1%.
1HNMR(CDCl
3,400MHz):δ7.38-7.35(m,2H),7.29(dd,J＝7.2,1.8Hz,2H),7.21-7.15(m,1H),3.64-3.57(m,1H),2.09-2.03(m,2H),1.81-1.75(m,2H),1.66-1.58(m,4H)。
Embodiment 4
Under room temperature, to in appropriate organic solvent benzyl cyanide, add 100mmol above formula (I) compound, 160mmol above formula (II) compound and 270mmol above formula (III) compound, then to add 8mmol catalyzer (be 2.86mmolPd (TFA)
2with 5.14mmolRh (cod)
2bF
4mixture), 27mmol promotor (mixture for 9mmol zinc iodide and 18mmol copper trifluoromethanesulfcomposite) and 70mmol alkali N-methylmorpholine, be then warming up to 75 DEG C, and stirring reaction 6 hours at such a temperature.
After reaction terminates, reaction system is filtered, in filtrate, adds saturated aqueous common salt, fully vibrate, then extraction into ethyl acetate is added 2-3 time, merge organic phase, anhydrous sodium sulfate drying, concentrating under reduced pressure, gained residue is crossed 300-400 order silica gel column chromatography to be separated, using isopyknic acetoneand ethyl acetate mixed solution as eluent, thus obtain above formula (IV) compound, productive rate is 97.8%.
1HNMR(CDCl
3,400MHz):δ7.53(dd,J＝7.8,1.1Hz,1H),7.33-7.22(m,2H),7.04-6.96(m,1H),3.71-3.64(m,1H),2.16-2.11(m,2H),1.84-1.79(m,2H),1.72-1.63(m,4H)。
Embodiment 5-40
Embodiment 5-8: remove the Pd (TFA) in catalyzer
2replace with Pd (OAc)
2outward, other operation is all constant, thus is repeated embodiment 1-4, obtains embodiment 5-8.
Embodiment 9-12: remove the Pd (TFA) in catalyzer
2replace with Pd (NH
3) Cl
2outward, other operation is all constant, thus is repeated embodiment 1-4, obtains embodiment 9-12.
Embodiment 13-16: remove the Pd (TFA) in catalyzer
2replace with Pd (acac)
2outward, other operation is all constant, thus is repeated embodiment 1-4, obtains embodiment 13-16.
Embodiment 17-20: remove the Pd (TFA) in catalyzer
2replace with Pd (PhCN)
2cl
2outward, other operation is all constant, thus is repeated embodiment 1-4, obtains embodiment 17-20.
Embodiment 21-24: remove the Pd (TFA) in catalyzer
2replace with PdCl
2(cod) outward, other operation is all constant, thus is repeated embodiment 1-4, obtains embodiment 21-24.
Embodiment 25-28: remove the Pd (TFA) in catalyzer
2replace with outside Palladous chloride, other operation is all constant, thus is repeated embodiment 1-4, obtains embodiment 25-28.
Embodiment 29-32: remove the Pd (TFA) in catalyzer
2replace with outside Palladous nitrate, other operation is all constant, thus is repeated embodiment 1-4, obtains embodiment 29-32.
Embodiment 33-36: except catalyzer is replaced with the one-component Pd (TFA) that consumption is the total consumption sum of original two kinds of components
2outward, other operation is all constant, thus is repeated embodiment 1-4, obtains embodiment 33-36.
Embodiment 37-40: except catalyzer is replaced with the one-component Rh (cod) that consumption is the total consumption sum of original two kinds of components
2bF
4outward, other operation is all constant, thus is repeated embodiment 1-4, obtains embodiment 37-40.
The results are shown in following table 1.
Table 1
"--" represents not exist.
As can be seen here, Pd (TFA)
2be the organic palladium compound with best catalytic effect, the catalytic performance of other palladium compound all has remarkable reduction (even if acid chloride very similar with it); In addition it can also be seen that, when being used alone Pd (TFA)
2or Rh (cod)
2bF
4time, productive rate bacterium has remarkable reduction.This demonstrate that to only have and use Pd (TFA) simultaneously
2with Rh (cod)
2bF
4the catalyzer of composition, the synergy of competence exertion uniqueness between the two, thus achieve excellent productive rate of the present invention.
Embodiment 41-52
Embodiment 41-44: except replacing with except the one-component zinc iodide that consumption is the total consumption sum of original two kinds of components by wherein promotor, other operation is all constant, thus is repeated embodiment 1-4, obtains embodiment 41-44.
Embodiment 45-48: except replacing with except the one-component copper trifluoromethanesulfcomposite that consumption is the total consumption sum of original two kinds of components by wherein promotor, other operation is all constant, thus is repeated embodiment 1-4, obtains embodiment 45-48.
Embodiment 49-52: except promotor wherein being omitted, other operation is all constant, thus is repeated embodiment 1-4, obtains embodiment 49-52.
The results are shown in following table 2.
Table 2
"--" represents not exist.
As can be seen here, when being used alone zinc iodide or copper trifluoromethanesulfcomposite as promotor, its products collection efficiency all will be starkly lower than the effect during composition of both uses, and when not using any promotor, then productive rate reduces more obvious.This proves that the mixture of zinc iodide and copper trifluoromethanesulfcomposite can play optimum promoter action.
Embodiment 53-64
Except using following alkali, other operation is all constant, thus implements embodiment 1-4, use alkali, corresponding embodiment and products collection efficiency to see the following form 3.
Table 3
As can be seen here, in all alkali, N-methylmorpholine has best effect, and other alkali all causes productive rate to decrease.
Embodiment 65-73
Except using following organic solvent, other operation is all constant, thus implements embodiment 1-4, use alkali, corresponding embodiment and products collection efficiency to see the following form 4.
Table 4
As can be seen here, the kind of organic solvent equally also affects the height of productive rate, and wherein, benzyl cyanide has best solvent effect, and the productive rate of other organic solvent all decreases.
Comprehensively above-mentioned, present inventors have proposed a kind of process for catalytic synthesis of aryl thioethers, described method passes through the comprehensive selection of catalyzer, promotor, alkali and organic solvent etc. with collaborative, thus high yield can obtain object product, for the synthesis of this compounds provides completely new approach, for opening new synthesized channel for chemical industry, field of medicaments, there are marketable value and production potential widely.
Should be appreciated that the purposes of these embodiments is only not intended to for illustration of the present invention limit the scope of the invention.In addition; also should understand; after having read technology contents of the present invention, those skilled in the art can make various change, amendment and/or modification to the present invention, and these all equivalent form of values fall within the protection domain that the application's appended claims limits equally.
Claims (10)
1. the process for catalytic synthesis of aryl thioether compound shown in a following formula (IV), described method comprises: in organic solvent, under catalyzer, promotor and alkali exist, following formula (I) compound, following formula (II) compound and following formula (III) compound react, thus obtain described formula (IV) compound
Wherein, R is H, C
1-C
6alkyl, C
1-C
6alkoxy or halogen;
N is the integer of 1-4.
2. process for catalytic synthesis as claimed in claim 1, is characterized in that: described catalyzer is organic palladium compound and Rh (cod)
2bF
4mixture, wherein organic palladium compound and Rh (cod)
2bF
4mol ratio be 1:1.5-2.
3. process for catalytic synthesis as claimed in claim 1 or 2, it is characterized in that: described promotor is the mixture of zinc iodide and copper trifluoromethanesulfcomposite, wherein, the mol ratio of zinc iodide and copper trifluoromethanesulfcomposite is 1:2.
4. the process for catalytic synthesis as described in any one of claim 1-3, it is characterized in that: described alkali is any one or mixture multiple arbitrarily in triethylamine, tri-isopropanolamine, NaOH, sodium carbonate, pyridine, sodium ethylate, sodium bicarbonate, potassium tert.-butoxide, Dimethylamino pyridine (DMPA), Tetramethyl Ethylene Diamine, N-methylmorpholine, hexahydroaniline, vulkacit H, most preferably is N-methylmorpholine.
5. the process for catalytic synthesis as described in any one of claim 1-4, it is characterized in that: described solvent is acetonitrile, Macrogol 200 (PEG-200), benzyl cyanide, N-Methyl pyrrolidone (NMP), 1,4-dioxane, dimethyl sulfoxide (DMSO) (DMSO), N, any one in dinethylformamide (DMF), toluene, benzene, ethanol etc., most preferably is benzyl cyanide.
6. the process for catalytic synthesis as described in any one of claim 1-5, is characterized in that: described formula (I) compound and formula (II) compound mole be 1:1.5-2.
7. the process for catalytic synthesis as described in any one of claim 1-6, is characterized in that: the mol ratio of described formula (I) compound and formula (III) compound is 1:2-3.
8. the process for catalytic synthesis as described in any one of claim 1-7, is characterized in that: the mol ratio of described formula (I) compound and catalyzer is 1:0.05-0.1.
9. the process for catalytic synthesis as described in any one of claim 1-8, is characterized in that: the mol ratio of described formula (I) compound and promotor is 1:0.2-0.3.
10. the process for catalytic synthesis as described in any one of claim 1-9, is characterized in that: the mol ratio of described formula (I) compound and alkali is 1:0.5-0.8.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6124462A (en) * | 1999-11-30 | 2000-09-26 | E. I. Du Pont De Nemours And Company | Catalysis using phosphine oxide compounds |
| CN104045589A (en) * | 2014-05-07 | 2014-09-17 | 华东师范大学 | Aryl alkyl thioether compound and synthetic method thereof |
-
2015
- 2015-08-18 CN CN201510507295.6A patent/CN105111116B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6124462A (en) * | 1999-11-30 | 2000-09-26 | E. I. Du Pont De Nemours And Company | Catalysis using phosphine oxide compounds |
| CN104045589A (en) * | 2014-05-07 | 2014-09-17 | 华东师范大学 | Aryl alkyl thioether compound and synthetic method thereof |
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| MIYAURA, N.: "Product subclass 7: hydroxyboranes", 《SCIENCE OF SYNTHESIS》 * |
| RIMA DAS 等: "Silver catalyzed C–C and C–S coupling of aryl halides and thiols with boronic acids", 《TETRAHEDRON LETTERS》 * |
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