CN117660991A - Three-component electrochemical synthesis method of 5-hydroxypyrazole phosphine sulfur derivative - Google Patents
Three-component electrochemical synthesis method of 5-hydroxypyrazole phosphine sulfur derivative Download PDFInfo
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- CN117660991A CN117660991A CN202311513789.6A CN202311513789A CN117660991A CN 117660991 A CN117660991 A CN 117660991A CN 202311513789 A CN202311513789 A CN 202311513789A CN 117660991 A CN117660991 A CN 117660991A
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- Prior art keywords
- hydroxypyrazole
- synthesis method
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- phosphine
- tetrabutylammonium
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- -1 5-hydroxypyrazole phosphine sulfur derivative Chemical class 0.000 title claims abstract description 42
- 238000001308 synthesis method Methods 0.000 title claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 16
- 229910002804 graphite Inorganic materials 0.000 claims description 13
- 239000010439 graphite Substances 0.000 claims description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 9
- 229910052697 platinum Inorganic materials 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 7
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 6
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 239000003480 eluent Substances 0.000 claims description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- 239000003208 petroleum Substances 0.000 claims description 6
- 239000000654 additive Substances 0.000 claims description 5
- 239000003792 electrolyte Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000006260 foam Substances 0.000 claims description 4
- 229910021397 glassy carbon Inorganic materials 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 claims description 4
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 4
- 229910001220 stainless steel Inorganic materials 0.000 claims description 4
- 239000010935 stainless steel Substances 0.000 claims description 4
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 claims description 4
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 claims description 4
- 230000000996 additive effect Effects 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- LGZDNJBUAAXEMN-UHFFFAOYSA-N 1,2,2,3-tetramethyl-1-oxidopiperidin-1-ium Chemical compound CC1CCC[N+](C)([O-])C1(C)C LGZDNJBUAAXEMN-UHFFFAOYSA-N 0.000 claims description 2
- DKCPKDPYUFEZCP-UHFFFAOYSA-N 2,6-di-tert-butylphenol Chemical compound CC(C)(C)C1=CC=CC(C(C)(C)C)=C1O DKCPKDPYUFEZCP-UHFFFAOYSA-N 0.000 claims description 2
- QKFFSWPNFCXGIQ-UHFFFAOYSA-M 4-methylbenzenesulfonate;tetraethylazanium Chemical compound CC[N+](CC)(CC)CC.CC1=CC=C(S([O-])(=O)=O)C=C1 QKFFSWPNFCXGIQ-UHFFFAOYSA-M 0.000 claims description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 2
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052782 aluminium Inorganic materials 0.000 claims description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
- 239000004202 carbamide Substances 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 239000011133 lead Substances 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 229910052759 nickel Inorganic materials 0.000 claims description 2
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 238000007789 sealing Methods 0.000 claims description 2
- 238000010898 silica gel chromatography Methods 0.000 claims description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 2
- MCZDHTKJGDCTAE-UHFFFAOYSA-M tetrabutylazanium;acetate Chemical compound CC([O-])=O.CCCC[N+](CCCC)(CCCC)CCCC MCZDHTKJGDCTAE-UHFFFAOYSA-M 0.000 claims description 2
- KBLZDCFTQSIIOH-UHFFFAOYSA-M tetrabutylazanium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC KBLZDCFTQSIIOH-UHFFFAOYSA-M 0.000 claims description 2
- WGHUNMFFLAMBJD-UHFFFAOYSA-M tetraethylazanium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CC[N+](CC)(CC)CC WGHUNMFFLAMBJD-UHFFFAOYSA-M 0.000 claims description 2
- MRYQZMHVZZSQRT-UHFFFAOYSA-M tetramethylazanium;acetate Chemical compound CC([O-])=O.C[N+](C)(C)C MRYQZMHVZZSQRT-UHFFFAOYSA-M 0.000 claims description 2
- 229910052719 titanium Inorganic materials 0.000 claims description 2
- 239000010936 titanium Substances 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 abstract description 8
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 abstract description 5
- 238000001212 derivatisation Methods 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 229950009041 edaravone Drugs 0.000 abstract description 3
- 238000010276 construction Methods 0.000 abstract description 2
- 238000005859 coupling reaction Methods 0.000 abstract description 2
- 238000006356 dehydrogenation reaction Methods 0.000 abstract description 2
- 150000002431 hydrogen Chemical class 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 125000000524 functional group Chemical group 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 229910052717 sulfur Inorganic materials 0.000 abstract 1
- 239000011593 sulfur Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 56
- 238000004896 high resolution mass spectrometry Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 238000001228 spectrum Methods 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 238000004679 31P NMR spectroscopy Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- XBYRMPXUBGMOJC-UHFFFAOYSA-N 1,2-dihydropyrazol-3-one Chemical class OC=1C=CNN=1 XBYRMPXUBGMOJC-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- NGPLKXZXQSCKSN-UHFFFAOYSA-N P.[S] Chemical compound P.[S] NGPLKXZXQSCKSN-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 229940051880 analgesics and antipyretics pyrazolones Drugs 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000006880 cross-coupling reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 230000005311 nuclear magnetism Effects 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 description 1
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N Aminoantipyrine Natural products CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 1
- RMMXTBMQSGEXHJ-UHFFFAOYSA-N Aminophenazone Chemical compound O=C1C(N(C)C)=C(C)N(C)N1C1=CC=CC=C1 RMMXTBMQSGEXHJ-UHFFFAOYSA-N 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- YUWBVKYVJWNVLE-UHFFFAOYSA-N [N].[P] Chemical compound [N].[P] YUWBVKYVJWNVLE-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229960000212 aminophenazone Drugs 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- VEQOALNAAJBPNY-UHFFFAOYSA-N antipyrine Chemical compound CN1C(C)=CC(=O)N1C1=CC=CC=C1 VEQOALNAAJBPNY-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000002194 freeze distillation Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- DJGAAPFSPWAYTJ-UHFFFAOYSA-M metamizole sodium Chemical compound [Na+].O=C1C(N(CS([O-])(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 DJGAAPFSPWAYTJ-UHFFFAOYSA-M 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 description 1
- 229960005222 phenazone Drugs 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/07—Oxygen containing compounds
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/05—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/09—Nitrogen containing compounds
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/20—Processes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Materials Engineering (AREA)
- Metallurgy (AREA)
Abstract
The invention relates to the field of chemical synthesis, in particular to a three-component electrochemical synthesis method of a 5-hydroxy pyrazole phosphine sulfur derivative; according to the invention, a three-component electrochemical dehydrogenation coupling reaction system of a phosphinous hydrogen compound, a pyrazolone derivative and a sulfur simple substance is constructed, and the 5-hydroxypyrazole phosphine sulfur derivative is synthesized in one step through construction of a phosphorus-carbon bond and interconversion. The method has the advantages of simple and safe reaction operation, mild reaction conditions, simple and efficient method, easily obtained raw materials, higher tolerance of the functional groups of the compound, convenient post-treatment and generally higher yield, can avoid the use of non-commercialized thiophosphine hydrogen derivatives, has wide substrate applicability, is suitable for mass synthesis, and can realize the derivatization reaction of edaravone as a medicament on the market.
Description
Technical Field
The invention relates to the field of chemical synthesis, in particular to a three-component electrochemical synthesis method of a 5-hydroxy pyrazole phosphine sulfur derivative.
Background
Edaravone (Edaravone, 3-methyl-1-phenyl-2-pyrazolin-5-one) has a pyrazolone skeleton, is a novel free radical scavenger for neuroprotection, was approved by the U.S. food and drug administration in 2017 for the treatment of amyotrophic lateral sclerosis (ALS, "progressive freezing"), and can be used as a raw material for the synthesis of pyrazolone antipyretic analgesics such as analgin, antipyrine, aminopyrine. The pyrazolone can be used as a nucleophilic reagent to participate in various reactions, and products with carbonyl structure maintenance (org.Lett.2018, 20,5840-5844; org.Lett.2019,21,7736-7740; org.Lett.2021,23, 6750-6755), enol-to-hydroxy structure (adv.Synth.Catal.2014, 356,537-556; org.Biomol.chem.2018,16,6470-6478; adv.Synth.Catal.2019,361, 1902-1907) and dehydration elimination of carbonyl and amino groups (J.org.chem.2021, 86, 2658-2666) are currently available. In recent years, the electrochemical Synthesis has been carried out in a rapid development stage, and various reagents have been applied to the cross dehydrogenation coupling reaction of pyrazolones, and a series of pyrazolones (Res. Chem. Intermediate. 2015,42, 2191-2200; catal. Sci. Technical 2015,5,2384-2387; chem. Commun.2021,57,2768-2771;CCS Chem.2022,4,3181-3189; chem. Sci.2022,13, 2783-2788), 5-hydroxypyrazole derivatives (Synthesis 2008,2008,1933-1937;Tetrahedron 2010,66,9880-9887; J. Electric chem. Soc.2014,161, G48-G53) or dehydrated carbonyl-eliminated pyrazole derivatives (Chin. Chem. Lett.2015,26, 973-976) have been obtained. In recent years, 5-hydroxypyrazole derivatives have been found to have potential anti-tubercle bacillus capabilities (ACS effect. Dis.2021,7, 1666-1679), attracting attention of pharmacologists.
Although diaryl phosphine hydrogen has been successfully applied to electrochemical oxidative cross-coupling reactions, only the report that phosphine is directly oxidized with indole (chem. Sci.2022,13, 3002-3008) or phosphorus is oxidized into phosphine oxide and then oxidized with indole and carbazole (chem. Eur. J.2021,27, 14931-14935) to generate a phosphorus-nitrogen product is not seen, and the construction of phosphorus-carbon bonds under electrochemical conditions and the oxidation of elemental sulfur to generate a phosphine-sulfur product are realized. The synthesis of phosphine-sulfur compounds is generally obtained by high temperature reaction with the corresponding phosphines using malodorous Lawson reagents (Angew. Chem. Int. Ed.2022,61, e 20221390). Therefore, an electrochemical synthesis route of three components (pyrazolone, phosphine hydrogen compound and elemental sulfur) with mild reaction conditions and high efficiency is developed to realize the oxidative cross coupling reaction of the in-situ phosphine hydrosulfide compound and pyrazolone, and a unique scheme can be provided for obtaining the 5-hydroxypyrazole phosphine sulfur derivative in one step.
Disclosure of Invention
The main purpose of the invention is to provide an electrochemical three-component synthesis method of 5-hydroxypyrazole phosphine sulfur derivatives, and the method is applied to derivatization of drug molecules.
The technical scheme of the invention is as follows:
a three-component electrochemical synthesis method of 5-hydroxy pyrazole phosphine sulfur derivative, the structural formula of the 5-hydroxy pyrazole phosphine sulfur derivative is shown as I,
wherein: r1 or R2 is one of hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C20 perfluoroalkyl, C6-C12 aryl, benzyl, C2-C8 alkenyl substituent, C2-C8 alkynyl substituent or C2-C10 heterocyclic;
r3 or R4 is any one of C1-C20 alkyl, C6-C12 aryl, benzyl and C2-C10 heterocyclic group;
the synthesis method is characterized by comprising the following steps:
wherein, the preparation steps of the compound I are as follows:
s1, placing a compound II, a compound III, elemental sulfur, an electrolyte and additives in an organic solvent, filling the organic solvent into an anode and a cathode, sealing a reaction vessel, and then introducing constant direct current into the reaction vessel to replace nitrogen for reaction;
s2, after the compound III completely disappears, removing the organic solvent from the reaction mixture under the condition of reduced pressure;
s3, eluting by using a silica gel column chromatography to obtain the compound I.
Further, the molar ratio of the compound II to the compound III to the elemental sulfur is II:III:IV=1.0:1.5-3.0:3.0-5.0.
Further, the anode is an electrode made of graphite sheets, graphite rods, reticular vitreous carbon, graphite felt, foam carbon, platinum sheets, platinum wires or stainless steel.
Further, the cathode is an electrode made of graphite sheets, graphite rods, reticulated vitreous carbon, foam carbon, platinum sheets, nickel, iron, copper, stainless steel, aluminum, zinc, titanium or lead.
Further, the electrolyte includes one or more of tetrabutylammonium tetrafluoroborate, tetrabutylammonium perchlorate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium hydroxide, tetrabutylammonium bromide, tetrabutylammonium iodide, 1, 3-dimethyliodized imidazole, tetraethylammonium p-toluenesulfonate, tetramethylammonium acetate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium hydrogen sulfate, tetraethylammonium tetrafluoroborate, tetraethylammonium hexafluorophosphate, tetrabutylammonium acetate, or tetraethylammonium perchlorate.
Further, the additive comprises one or two of 2, 6-di-tert-butylphenol, tetramethyl piperidine oxide, zinc iodide, trifluoroethanol, hexafluoroisopropanol, methanesulfonic acid, acetic acid, propionic acid, n-butyric acid, isobutyric acid or pivalic acid.
Further, the organic solvent comprises any one or at least two of ethyl acetate, acetonitrile, dichloroethane, dichloromethane, N-methylpyrrolidone, N-dimethylpropenyl urea, dimethylformamide or dimethylacetamide.
Furthermore, the eluent used in the column chromatography is a mixed solution of petroleum ether and ethyl acetate, and the volume ratio of the eluent is V petroleum ether to V ethyl acetate=20:1-1:1.
The beneficial effects of the invention are as follows:
(1) The invention provides an electrochemical synthesis method of a 5-hydroxypyrazole phosphine sulfur derivative, and the compound has potential tubercle bacillus resistance.
(2) The preparation method adopts the current as the traceless oxidant, does not need a catalyst in the reaction, is simple, convenient and safe to operate, has few reaction steps, mild reaction conditions, wide substrate expansion range and high tolerance of compound functional groups, and can achieve the product yield of 82%.
(3) The invention can avoid the use of a commercial P (S) -H compound, and can also prepare 5-hydroxypyrazole phosphine sulfur derivatives in gram grade through derivatization of edaravone analogues.
Drawings
FIG. 1 is a nuclear magnetic resonance spectrum (hydrogen spectrum) of a product I-1 obtained in the example of the present invention;
FIG. 2 is a nuclear magnetic resonance spectrum (carbon spectrum) of the product I-1 obtained in the example of the present invention;
FIG. 3 is a nuclear magnetic resonance spectrum (hydrogen spectrum) of the product I-7 obtained in the example of the present invention;
FIG. 4 is a nuclear magnetic resonance spectrum (carbon spectrum) of the product I-7 obtained in the example of the present invention.
Detailed Description
The technical scheme of the invention is further described below by specific embodiments with reference to the accompanying drawings:
the following are preferred examples of the preparation of the compounds of the invention. In all of the examples below, nuclear magnetic resonance spectroscopy was obtained in CDCl3 by Bruker 400, JEOL 400 instrument. Delta values are internal standard relative values (CHCl 3) scaled delta 7.261H NMR and 77.1613C NMR. High Resolution Mass Spectrometry (HRMS) was obtained by a 4G quadrupole time-of-flight (QTof) mass spectrometer.
Example 1
The reaction scheme of example 1, specifically used compounds II-1, III-1, sulfur powder and product I-1, has the following structure, and experiments show that the preferred anode of the invention is graphite flake, the preferred cathode is platinum flake, the preferred electrolyte is tetrabutylammonium iodide, the preferred additive is Hexafluoroisopropanol (HFIP), the preferred direct current is 6 milliamperes, the preferred organic solvent is acetonitrile (MeCN), the highest yield of the reaction product is 82%, and the best starting molar ratio of compound II to compound III is II: iii=1:2, where compound II is the equivalent value, the optimal concentration of the solution is 0.04M.
The specific experimental steps are as follows: in a 10 mL straight reaction tube, 34.8mg (0.2 mmol,1.0 equivalent) of Compound II-1, 19mg of sulfur powder (0.6 mmol,3.0 equivalent), 74mg of tetrabutylammonium iodide (0.2 mmol,1.0 equivalent) and 0.5mL of hexafluoroisopropanol were dissolved in 4.5mL of acetonitrile, charged with a graphite anode and a platinum sheet cathode, and after replacing the tube with a nitrogen atmosphere, 74mg (0.40 mmol,2.0 equivalent) of Compound III-1 was injected with a microsyringe, and reacted at room temperature under a direct current of 6 mA for 24 hours. After the reaction was completed, the solvent was removed by rotary evaporation of the reaction mixture under reduced pressure by a water pump. The residue is subjected to column chromatography by using 200-300 mesh silica gel, eluent (volume ratio V petroleum ether: V ethyl acetate=20:1-2:1) to obtain a compound shown as I-1, and the product is identified by nuclear magnetism (hydrogen spectrum, carbon spectrum and phosphorus spectrum) and high-resolution mass spectrum.
White solid,64mg,Yield＝82％,Rf＝0.32(PE/EA＝5:1).1H NMR(400MHz,CDCl3)δ7.86–7.82(m,2H),7.82–7.78(m,2H),7.59–7.55(m,2H),7.54–7.50(m,2H),7.46–7.41(m,2H),7.40–7.36(m,2H),7.33–7.28(m,1H),5.67(d,J＝1.1Hz,1H),2.20(s,3H)；13C NMR(100MHz,CDCl3)δ148.80,144.02(d,J＝6.0Hz),138.03,132.84(d,J＝109.8Hz),132.67(d,J＝3.1Hz),131.45(d,J＝11.9Hz),128.95,128.73(d,J＝13.7Hz),127.22,123.91,94.10(d,J＝3.8Hz),14.63；31P NMR(162MHz,CDCl3)δ87.09；HRMS(ESI)m/z:[M+H]+Calcd for C22H20N2OPS 391.1034；Found 391.1031.
Example 2
And synthesizing thiophosphamide by taking phenylhydrazine as a nitrogen source.
The procedure used for the preparation of the examples of other compounds of the invention is the same as in example 1, the reaction conditions being as follows: in a 10 mL straight reaction tube, 20mg (0.2 mmol,1.0 equivalent) of Compound II-7, 19mg of sulfur powder (0.6 mmol,3.0 equivalent), 74mg of tetrabutylammonium iodide (0.2 mmol,1.0 equivalent) and 0.5mL of hexafluoroisopropanol were dissolved in 4.5mL of acetonitrile, charged into a graphite anode and a platinum sheet cathode and replaced with a nitrogen atmosphere in the tube, 74mg (0.40 mmol,2.0 equivalent) of Compound III-1 was injected with a microsyringe, and reacted at room temperature under a direct current of 6 mA for 28 hours. After the reaction was completed, the solvent was removed by rotary evaporation of the reaction mixture under reduced pressure by a water pump. The residue is subjected to column chromatography by using 200-300 mesh silica gel, eluent (volume ratio V petroleum ether: V ethyl acetate=10:1-2:1) to obtain a compound shown as I-1, and the product is identified as follows by nuclear magnetism (hydrogen spectrum, carbon spectrum and phosphorus spectrum) and high-resolution mass spectrum:
White solid,29mg,Yield＝46％,Rf＝0.24(PE/EA＝5:1).1H NMR(400MHz,CDCl3)δ8.03–7.99(m,2H),7.98–7.95(m,2H),7.53–7.48(m,2H),7.47–7.41(m,4H),5.69(s,1H),2.15(s,3H)；13C NMR(100MHz,CDCl3)δ155.30,140.47,134.10(d,J＝110.9Hz),132.24(d,J＝3.0Hz),131.58(d,J＝11.6Hz),128.59(d,J＝13.6Hz),94.96(d,J＝2.7Hz),11.71；31P NMR(162MHz,CDCl3)δ85.34；HRMS(ESI)m/z:[M+H]+Calcd for C16H16N2OPS 315.0721；Found 315.0724.
compound I-1
(5-Hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)diphenylphosphine sulfide was isolated as white solid,64mg,Yield＝82％,Rf＝0.32(PE/EA＝5:1).1H NMR(400MHz,CDCl3)δ7.86–7.82(m,2H),7.82–7.78(m,2H),7.59–7.55(m,2H),7.54–7.50(m,2H),7.46–7.41(m,2H),7.40–7.36(m,2H),7.33–7.28(m,1H),5.67(d,J＝1.1Hz,1H),2.20(s,3H)；13C NMR(100MHz,CDCl3)δ148.80,144.02(d,J＝6.0Hz),138.03,132.84(d,J＝109.8Hz),132.67(d,J＝3.1Hz),131.45(d,J＝11.9Hz),128.95,128.73(d,J＝13.7Hz),127.22,123.91,94.10(d,J＝3.8Hz),14.63；31P NMR(162MHz,CDCl3)δ87.09；HRMS(ESI)m/z:[M+H]+Calcd for C22H20N2OPS 391.1034；Found 391.1031.
Compound I-2
(5-Hydroxy-3-methyl-1-(p-tolyl)-1H-pyrazol-4-yl)diphenylphosphine sulfide was isolated as white solid,64mg,Yield＝79％,Rf＝0.36(PE/EA＝5:1).1H NMR(400MHz,CDCl3)δ7.87–7.76(m,4H),7.56–7.49(m,2H),7.48–7.40(m,4H),7.22–7.14(m,2H),5.65(s,1H),2.38(s,3H),2.19(s,3H)；13C NMR(100MHz,CDCl3)δ149.83,147.06(d,J＝6.0Hz),133.74(d,J＝109.7Hz),132.32(d,J＝3.1Hz),131.47(d,J＝11.9Hz),130.72,128.33(d,J＝14.0Hz),126.96,113.82,20.71,13.66；31P NMR(162MHz,CDCl3)δ86.84；HRMS(ESI)m/z:[M+H]+Calcd for C23H22N2OPS 405.1190；Found 405.1188.
Compound I-3
(5-Hydroxy-1-(4-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl)diphenylphosphine sulfide was isolated as white solid,62mg,Yield＝74％,Rf＝0.22(PE/EA＝5:1).1H NMR(400MHz,CDCl3)δδ7.78–7.70(m,4H),7.51–7.46(m,2H),7.41–7.32(m,4H),7.21(dt,J＝9.0,3.2Hz,2H),,6.60(dt,J＝9.0,3.2Hz,2H),3.74(s,3H),2.26(s,3H)；13C NMR(100MHz,CDCl3)δ159.35,147.27(d,J＝6.0Hz),134.01(d,J＝109.7Hz),132.28(d,J＝3.1Hz),131.47(d,J＝11.9Hz),130.77,128.40(d,J＝14.0Hz),127.23,113.91,55.53,13.42；31P NMR(162MHz,CDCl3)δ87.46；HRMS(ESI)m/z:[M+H]+Calcd for C23H22N2O2PS 421.1140；Found 421.1143.
Compound I-4
(1-(4-Chlorophenyl)-5-hydroxy-3-methyl-1H-pyrazol-4-yl)diphenylphosphine sulfide was isolated as white solid,61mg,Yield＝72％,Rf＝0.36(PE/EA＝5:1).1H NMR(400MHz,CDCl3)δ7.75–7.66(m,4H),7.51–7.44(m,3H),7.40–7.34(m,5H),7.34–7.24(m,2H),5.67(d,J＝1.3Hz,1H),2.21(s,3H)；13C NMR(100MHz,CDCl3)δ149.54,145.12(d,J＝6.3Hz),135.47,132.96(d,J＝133.2Hz),132.54(d,J＝3.1Hz),131.33(d,J＝12.0Hz),130.41(d,J＝24.1Hz),130.00,128.67(d,J＝13.8Hz),127.45,93.38(d,J＝3.7Hz),14.78(d,J＝6.0Hz)；31P NMR(162MHz,CDCl3)δ85.64；HRMS(ESI)m/z:[M+H]+Calcd for C22H19ClN2OPS 425.0664；Found 425.0660.
Compound I-5
(1-(3-Chlorophenyl)-5-hydroxy-3-methyl-1H-pyrazol-4-yl)diphenylphosphine sulfide was isolated as white solid,52mg,Yield＝61％,Rf＝0.36(PE/EA＝5:1).1H NMR(400MHz,CDCl3)δ7.76–7.68(m,4H),7.52–7.46(m,3H),7.42–7.35(m,5H),7.35–7.26(m,2H),5.68(d,J＝1.3Hz,1H),2.23(s,3H)；13C NMR(100MHz,CDCl3)δ149.56,145.14(d,J＝6.4Hz),135.48,132.98(d,J＝114.7Hz),132.54,131.35(d,J＝11.9Hz),130.43(d,J＝25.3Hz),130.02,128.68(d,J＝13.8Hz),127.46,93.39(d,J＝3.1Hz),14.79；(d,J＝6.0Hz)；31P NMR(162MHz,CDCl3)δ87.21；HRMS(ESI)m/z:[M+H]+Calcd for C22H19ClN2OPS 425.0664；Found 425.0667.
Compound I-6
(1-(4-Bromophenyl)-5-hydroxy-3-methyl-1H-pyrazol-4-yl)diphenylphosphine sulfide was isolated as white solid,65mg,Yield＝69％,Rf＝0.41(PE/EA＝5:1).1H NMR(400MHz,CDCl3)δ7.88–7.78(m,4H),7.60–7.53(m,3H),7.50–7.43(m,5H),7.42–7.36(m,2H),5.62(d,J＝1.2Hz,1H),2.19(s,2H)；13C NMR(100MHz,CDCl3)δ149.86,145.12(d,J＝6.3Hz),135.96,132.92(d,J＝133.2Hz),132.56(d,J＝3.1Hz),131.33(d,J＝11.9Hz),130.54(d,J＝23.8Hz),130.04,128.79(d,J＝13.7Hz),127.52,93.42(d,J＝3.6Hz),14.81(d,J＝6.0Hz)；31P NMR(162MHz,CDCl3)δ87.16；HRMS(ESI)m/z:[M+H]+Calcd for C22H19BrN2OPS 469.0139；Found 469.0144.
Compound I-7
(5-Hydroxy-3-methyl-1H-pyrazol-4-yl)diphenylphosphine sulfide was isolated as white solid,29mg,Yield＝46％,Rf＝0.34(PE/EA＝2:1).1H NMR(400MHz,CDCl3)δ8.03–7.99(m,2H),7.98–7.95(m,2H),7.53–7.48(m,2H),7.47–7.41(m,4H),5.69(s,1H),2.15(s,3H)；13C NMR(100MHz,CDCl3)δ155.30,140.47,134.10(d,J＝110.9Hz),132.24(d,J＝3.0Hz),131.58(d,J＝11.6Hz),128.59(d,J＝13.6Hz),94.96(d,J＝2.7Hz),11.71；31P NMR(162MHz,CDCl3)δ85.34；HRMS(ESI)m/z:[M+H]+Calcd for C16H16N2OPS 315.0721；Found 315.0724.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Furthermore, it should be understood that although the present disclosure describes embodiments, not every embodiment is provided with a separate embodiment, and that this description is provided for clarity only, and that the disclosure is not limited to the embodiments described in detail below, and that the embodiments described in the examples may be combined as appropriate to form other embodiments that will be apparent to those skilled in the art.
Claims (8)
1. A three-component electrochemical synthesis method of 5-hydroxy pyrazole phosphine sulfur derivative, the structural formula of the 5-hydroxy pyrazole phosphine sulfur derivative is shown as I,
wherein: r1 or R2 is one of hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C20 perfluoroalkyl, C6-C12 aryl, benzyl, C2-C8 alkenyl substituent, C2-C8 alkynyl substituent or C2-C10 heterocyclic;
r3 or R4 is any one of C1-C20 alkyl, C6-C12 aryl, benzyl and C2-C10 heterocyclic group;
the synthesis method is characterized by comprising the following steps:
wherein, the preparation steps of the compound I are as follows:
s1, placing a compound II, a compound III, elemental sulfur, an electrolyte and additives in an organic solvent, filling the organic solvent into an anode and a cathode, sealing a reaction vessel, and then introducing constant direct current into the reaction vessel to replace nitrogen for reaction;
s2, after the compound III completely disappears, removing the organic solvent from the reaction mixture under the condition of reduced pressure;
s3, eluting by using a silica gel column chromatography to obtain the compound I.
2. The three-component electrochemical synthesis method of the 5-hydroxypyrazole phosphine sulfur derivative according to claim 1, wherein the method comprises the following steps of: the molar ratio of the compound II to the compound III to the elemental sulfur is II:III:IV=1.0:1.5-3.0:3.0-5.0.
3. The three-component electrochemical synthesis method of the 5-hydroxypyrazole phosphine sulfur derivative according to claim 1, wherein the method comprises the following steps of: the anode is an electrode made of graphite sheets, graphite rods, reticular vitreous carbon, graphite felt, foam carbon, platinum sheets, platinum wires or stainless steel.
4. The three-component electrochemical synthesis method of the 5-hydroxypyrazole phosphine sulfur derivative according to claim 1, wherein the method comprises the following steps of: the cathode is an electrode made of graphite sheets, graphite rods, reticular vitreous carbon, foam carbon, platinum sheets, nickel, iron, copper, stainless steel, aluminum, zinc, titanium or lead.
5. The three-component electrochemical synthesis method of the 5-hydroxypyrazole phosphine sulfur derivative according to claim 1, wherein the method comprises the following steps of: the electrolyte includes one or more of tetrabutylammonium tetrafluoroborate, tetrabutylammonium perchlorate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium hydroxide, tetrabutylammonium bromide, tetrabutylammonium iodide, 1, 3-dimethyliodized imidazole, tetraethylammonium p-toluenesulfonate, tetramethylammonium acetate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium hydrogen sulfate, tetraethylammonium tetrafluoroborate, tetraethylammonium hexafluorophosphate, tetrabutylammonium acetate, or tetraethylammonium perchlorate.
6. The three-component electrochemical synthesis method of the 5-hydroxypyrazole phosphine sulfur derivative according to claim 1, wherein the method comprises the following steps of: the additive comprises one or two of 2, 6-di-tert-butylphenol, tetramethyl piperidine oxide, zinc iodide, trifluoroethanol, hexafluoroisopropanol, methanesulfonic acid, acetic acid, propionic acid, n-butyric acid, isobutyric acid or pivalic acid.
7. The three-component electrochemical synthesis method of the 5-hydroxypyrazole phosphine sulfur derivative according to claim 1, wherein the method comprises the following steps of: the organic solvent comprises any one or at least two of ethyl acetate, acetonitrile, dichloroethane, dichloromethane, N-methylpyrrolidone, N-dimethylpropenyl urea, dimethylformamide or dimethylacetamide.
8. The three-component electrochemical synthesis method of the 5-hydroxypyrazole phosphine sulfur derivative according to claim 1, wherein the method comprises the following steps of: the eluent used in the column chromatography is a mixed solution of petroleum ether and ethyl acetate, and the volume ratio of the eluent is V petroleum ether to V ethyl acetate=20:1-1:1.
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