CN116102605A - Dehalogenation method of 9-halogenated steroid compound - Google Patents
Dehalogenation method of 9-halogenated steroid compound Download PDFInfo
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- CN116102605A CN116102605A CN202310060498.XA CN202310060498A CN116102605A CN 116102605 A CN116102605 A CN 116102605A CN 202310060498 A CN202310060498 A CN 202310060498A CN 116102605 A CN116102605 A CN 116102605A
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- -1 steroid compound Chemical class 0.000 title claims abstract description 112
- 238000000034 method Methods 0.000 title claims abstract description 67
- 238000005695 dehalogenation reaction Methods 0.000 title claims abstract description 45
- 150000001875 compounds Chemical class 0.000 claims abstract description 173
- 239000003054 catalyst Substances 0.000 claims abstract description 169
- 238000006243 chemical reaction Methods 0.000 claims abstract description 82
- 239000012752 auxiliary agent Substances 0.000 claims abstract description 55
- 238000013032 photocatalytic reaction Methods 0.000 claims abstract description 37
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 claims description 68
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 60
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 50
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 46
- 229910010413 TiO 2 Inorganic materials 0.000 claims description 44
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 38
- 239000000463 material Substances 0.000 claims description 36
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 34
- 229910052799 carbon Inorganic materials 0.000 claims description 33
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 32
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 32
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 claims description 30
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 28
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims description 28
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- 230000008569 process Effects 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 235000011054 acetic acid Nutrition 0.000 claims description 24
- RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 claims description 23
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical group COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 235000019253 formic acid Nutrition 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 22
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 21
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 15
- NJRXVEJTAYWCQJ-UHFFFAOYSA-N thiomalic acid Chemical compound OC(=O)CC(S)C(O)=O NJRXVEJTAYWCQJ-UHFFFAOYSA-N 0.000 claims description 15
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 14
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 claims description 14
- HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 claims description 14
- KWSLGOVYXMQPPX-UHFFFAOYSA-N 5-[3-(trifluoromethyl)phenyl]-2h-tetrazole Chemical group FC(F)(F)C1=CC=CC(C2=NNN=N2)=C1 KWSLGOVYXMQPPX-UHFFFAOYSA-N 0.000 claims description 14
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 14
- APTGPWJUOYMUCE-UHFFFAOYSA-N S-Ethyl thioacetate Chemical compound CCSC(C)=O APTGPWJUOYMUCE-UHFFFAOYSA-N 0.000 claims description 14
- UIJGNTRUPZPVNG-UHFFFAOYSA-N benzenecarbothioic s-acid Chemical compound SC(=O)C1=CC=CC=C1 UIJGNTRUPZPVNG-UHFFFAOYSA-N 0.000 claims description 14
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 14
- 229940102253 isopropanolamine Drugs 0.000 claims description 14
- 229910001380 potassium hypophosphite Inorganic materials 0.000 claims description 14
- CRGPNLUFHHUKCM-UHFFFAOYSA-M potassium phosphinate Chemical compound [K+].[O-]P=O CRGPNLUFHHUKCM-UHFFFAOYSA-M 0.000 claims description 14
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 claims description 14
- 229910001379 sodium hypophosphite Inorganic materials 0.000 claims description 14
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 claims description 14
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 12
- 239000004408 titanium dioxide Substances 0.000 claims description 12
- RMVRSNDYEFQCLF-UHFFFAOYSA-N phenyl mercaptan Natural products SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims description 11
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 claims description 11
- WVDYBOADDMMFIY-UHFFFAOYSA-N Cyclopentanethiol Chemical compound SC1CCCC1 WVDYBOADDMMFIY-UHFFFAOYSA-N 0.000 claims description 10
- 229910000416 bismuth oxide Inorganic materials 0.000 claims description 10
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical class C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 claims description 10
- TYIXMATWDRGMPF-UHFFFAOYSA-N dibismuth;oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Bi+3].[Bi+3] TYIXMATWDRGMPF-UHFFFAOYSA-N 0.000 claims description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 229910052797 bismuth Inorganic materials 0.000 claims description 9
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims description 9
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 9
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 claims description 9
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 8
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical group [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 8
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 8
- 239000002671 adjuvant Substances 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 8
- ZREIPSZUJIFJNP-UHFFFAOYSA-K bismuth subsalicylate Chemical compound C1=CC=C2O[Bi](O)OC(=O)C2=C1 ZREIPSZUJIFJNP-UHFFFAOYSA-K 0.000 claims description 8
- 229960000782 bismuth subsalicylate Drugs 0.000 claims description 8
- NNLOHLDVJGPUFR-UHFFFAOYSA-L calcium;3,4,5,6-tetrahydroxy-2-oxohexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(=O)C([O-])=O.OCC(O)C(O)C(O)C(=O)C([O-])=O NNLOHLDVJGPUFR-UHFFFAOYSA-L 0.000 claims description 8
- 239000000975 dye Substances 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- NBOMNTLFRHMDEZ-UHFFFAOYSA-N thiosalicylic acid Chemical compound OC(=O)C1=CC=CC=C1S NBOMNTLFRHMDEZ-UHFFFAOYSA-N 0.000 claims description 8
- 229940103494 thiosalicylic acid Drugs 0.000 claims description 8
- 239000010936 titanium Substances 0.000 claims description 8
- 229910052719 titanium Inorganic materials 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 239000011701 zinc Substances 0.000 claims description 8
- 229910052725 zinc Inorganic materials 0.000 claims description 8
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical compound NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 239000000460 chlorine Chemical group 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- 150000001242 acetic acid derivatives Chemical class 0.000 claims description 6
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 claims description 6
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 6
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 6
- UJOBWOGCFQCDNV-UHFFFAOYSA-N Carbazole Natural products C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 5
- 229910004298 SiO 2 Inorganic materials 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- IAJNLJPHAMEYLW-UHFFFAOYSA-N benzenethiol 1,3-xylene Chemical compound C1(=CC=CC=C1)S.CC1=CC=CC(=C1)C IAJNLJPHAMEYLW-UHFFFAOYSA-N 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 150000002429 hydrazines Chemical class 0.000 claims description 5
- 229910052741 iridium Inorganic materials 0.000 claims description 5
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 claims description 5
- 229910052707 ruthenium Inorganic materials 0.000 claims description 5
- 150000003573 thiols Chemical class 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- 229910015902 Bi 2 O 3 Inorganic materials 0.000 claims description 4
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 4
- 150000001716 carbazoles Chemical class 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 239000011630 iodine Chemical group 0.000 claims description 4
- 229910052740 iodine Chemical group 0.000 claims description 4
- 150000002988 phenazines Chemical class 0.000 claims description 4
- 150000002990 phenothiazines Chemical class 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 150000003222 pyridines Chemical class 0.000 claims description 4
- 150000003303 ruthenium Chemical class 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 125000005259 triarylamine group Chemical group 0.000 claims description 4
- 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 claims description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 3
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 claims description 3
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical group C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 claims description 3
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 claims description 3
- 239000002028 Biomass Substances 0.000 claims description 3
- 229920000049 Carbon (fiber) Polymers 0.000 claims description 3
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 3
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 claims description 3
- 229910006404 SnO 2 Inorganic materials 0.000 claims description 3
- 239000004280 Sodium formate Substances 0.000 claims description 3
- KZKQFFFEMJUSJN-UHFFFAOYSA-N [N].CN1CCOCC1 Chemical compound [N].CN1CCOCC1 KZKQFFFEMJUSJN-UHFFFAOYSA-N 0.000 claims description 3
- GJYJYFHBOBUTBY-UHFFFAOYSA-N alpha-camphorene Chemical compound CC(C)=CCCC(=C)C1CCC(CCC=C(C)C)=CC1 GJYJYFHBOBUTBY-UHFFFAOYSA-N 0.000 claims description 3
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 3
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 claims description 3
- 239000012965 benzophenone Substances 0.000 claims description 3
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 3
- 239000004917 carbon fiber Substances 0.000 claims description 3
- 239000003610 charcoal Substances 0.000 claims description 3
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 3
- 229940043279 diisopropylamine Drugs 0.000 claims description 3
- 239000012971 dimethylpiperazine Substances 0.000 claims description 3
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical group C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 claims description 3
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 claims description 3
- 150000004675 formic acid derivatives Chemical class 0.000 claims description 3
- 239000000543 intermediate Substances 0.000 claims description 3
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 claims description 3
- 229910001383 lithium hypophosphite Inorganic materials 0.000 claims description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 3
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 claims description 3
- 229960000907 methylthioninium chloride Drugs 0.000 claims description 3
- KJOLVZJFMDVPGB-UHFFFAOYSA-N perylenediimide Chemical compound C=12C3=CC=C(C(NC4=O)=O)C2=C4C=CC=1C1=CC=C2C(=O)NC(=O)C4=CC=C3C1=C42 KJOLVZJFMDVPGB-UHFFFAOYSA-N 0.000 claims description 3
- 229950000688 phenothiazine Drugs 0.000 claims description 3
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 claims description 3
- 229910052697 platinum Inorganic materials 0.000 claims description 3
- 150000004032 porphyrins Chemical class 0.000 claims description 3
- WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 claims description 3
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical group [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 claims description 3
- 235000019254 sodium formate Nutrition 0.000 claims description 3
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 claims description 3
- 229910052721 tungsten Inorganic materials 0.000 claims description 3
- 239000010937 tungsten Substances 0.000 claims description 3
- ZCYMRZHNYXPSKC-UHFFFAOYSA-N 1,5-dimethyl-7-thiabicyclo[4.1.0]hepta-2,4-diene Chemical group CC1=CC=CC2(C)SC12 ZCYMRZHNYXPSKC-UHFFFAOYSA-N 0.000 claims description 2
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- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-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
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
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- 239000003246 corticosteroid Substances 0.000 claims description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
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- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
- C07J5/0061—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16
- C07J5/0069—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group
- C07J5/0076—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group by an alkyl group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
- C07J5/0053—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa not substituted in position 16
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
- C07J5/0061—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16
- C07J5/0092—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by an OH group free esterified or etherified
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a dehalogenation method of 9-halogenated steroid compounds, which comprises the following steps: the compound I is subjected to photocatalytic reaction by utilizing visible light in the presence of an auxiliary agent and a catalyst, and is reduced to obtain a compound II, wherein the reaction formula is as follows. The dehalogenation method has the advantages of low cost, less environmental pollution, high yield and less byproducts.
Description
Technical Field
The invention belongs to the field of organic chemical synthesis, and in particular relates to a dehalogenation method of a 9-halogenated steroid compound.
Background
The corticoids have a plurality of pharmacological actions such as anti-inflammatory, antiallergic, antitoxin, antishock, immunosuppression and the like, and have very wide application. The dehalogenation of 9-halosteroids is typically involved in the preparation of key intermediates for such drugs, and prior art processes have generally employed the processes disclosed in U.S. Pat. No. 3,182 or improved processes based thereon. However, the methods disclosed in the prior art basically use chromium, bivalent chromium salt, trivalent chromium salt and other reagents, and some related documents use tributyltin hydride and other reagents. The common characteristics of the prior art are that heavy metals or heavy metal-containing materials are used as catalysts, so that the problems of high toxicity, serious environmental pollution, high environmental protection treatment cost, excessive heavy metal residues and the like of products are solved, and the use safety of the products is seriously influenced.
Photogenerated Semi-Enone Radical Anions: A New Perspective on the Reaction of 10- (hydroymethyl) -2-octalone Tosylate, richard S.Givens and Beauford W.Atwater, journal of the American Chemical Society,1986, vol.108.No.16, P5028-5030 reported the following reactions:
when the reaction uses excessive tertiary amine (TEA or DABCO as electron donor) under the illumination condition of 345-368nm, the amount of the generated compound 5 is more than 95%.
In 2008, macMillan task group (Merging Photoredox Catalysis with Organocatalysis: the Direct Asymmetric Alkylation of Aldehydes, david A. Nicewicz, et al, science, vol322, page 77-80) reported the use of a photo-reduction catalyst Ru (bpy) 3 Cl 2 And an imidazolidone organic catalyst, under the catalysis of visible light, aldehyde and racemic alpha-bromocarbonyl compound are used as raw materials, and a series of enantiomer alpha-alkylated aldehydes are synthesized in a green and efficient way. The reaction formula is as follows:
the visible light catalytic reaction has the advantages of low cost, easy obtainment, no environmental pollution, few byproducts and the like, and is widely applied to the organic chemical synthesis reaction. The mechanism of the reaction is that active carbon halogen bond is easy to form carbon free radical under the catalysis of visible light, and a hydrogen atom is obtained to generate hydrogenation dehalogenation product. However, the catalysts disclosed in this reference contain the rare metal ruthenium, resulting in high costs for the reaction route.
In recent years, dehalogenation reaction under the condition of visible light catalysis has been reported in related literature, dehalogenation reaction of applying visible light catalysis to 9-halogenated steroid compounds has not been reported in related literature and patent, and the invention provides a new reaction of visible light catalysis for the first time in the field.
Disclosure of Invention
The invention aims to provide a dehalogenation method of a 9-halogenated steroid compound, which comprises the following steps:
(1) In the presence of an auxiliary agent and a catalyst, the compound I is subjected to photocatalytic reaction by utilizing visible light to generate a compound II, wherein the reaction formula is as follows:
wherein, in the structural formulas of the compound I and the compound II,
represents a single bond or a double bond,
R 1 h, C of a shape of H, C 1～6 Alkyl or fluoro;
R 2 is O, OH, C 1～6 Alkyl, phenyl, benzyl, O-C 1～6 Alkyl, O-Ph or OCOR 6 The R is 6 Selected from H, CF 3 、C 1～6 Alkyl, phenyl or benzyl;
R 3 is H, OH, C 1～6 Alkyl, O-C 1～6 Alkyl, O-Ph or OCOR 7 Wherein R is 7 H, C of a shape of H, C 1～6 Alkyl, phenyl or benzyl;
when C 16 ，C 17 When connected by single bond, R 4 H, OH, or
R 3 ，R 4 And C 16 、C 17 Together form a three-membered ring containing 1 oxygen atom, or a five-membered heterocyclic ring containing 2 oxygen atoms, wherein the five-membered ring has the structure
Wherein R is 8 、R 9 Each independently is H or C 1～6 Alkyl, phenyl or benzyl;
When C 16 ，C 17 When connected by double bonds, R 4 Absence of;
R 5 is COR 10 Wherein R is 10 H, C of a shape of H, C 1～6 Alkyl or CH 2 R 11 Wherein R is 11 Is OH, halogen or OCOR 12 Wherein R is 12 Is C 1～6 Alkyl, phenyl or benzyl;
x is selected from fluorine, chlorine, bromine and iodine;
wherein the wavelength of the visible light is 370-550nm;
the auxiliary agent is selected from formic acid and formate, hypophosphorous acid and hypophosphite, acetic acid and substituted acetic acid, hydrazine compounds, cyclohexene, hanes, organic amines containing 1-6 carbon atoms, nitrogen-containing heterocyclic compounds, organic alcohol amines containing 1-4 carbon atoms, mercaptan containing 1-6 carbon atoms, thio organic acid or a combination thereof,
the catalyst is selected from titanium-containing materials, zinc-containing materials, bismuth-containing materials, g-C-containing materials 3 N 4 The material of (C) is selected from the group consisting of aromatic thiophenol compounds, diaryl disulfide compounds, phenazine compounds, phenothiazine compounds, carbazole compounds, triarylamine compounds, dyes, photoinitiators, iridium or ruthenium complexes with pyridine compounds, or combinations thereof.
In some preferred embodiments of the present invention, R in the structural formulae of Compound I and Compound II 1 Is H, methyl or fluorine.
In some preferred embodiments of the invention, R 2 For O, OH or OCOR 6 The R is 6 Selected from H, CF 3 Or C 1～6 An alkyl group; in some preferred embodiments of the invention, R 6 H, CF of a shape of H, CF 3 Or methyl.
In some preferred embodiments of the invention, R 3 H, OH is a,CH 3 。
In some preferred embodiments of the invention, C 16 ，C 17 R is connected by single bond 4 H, OH.
In some preferred embodiments of the invention, C 16 ，C 17 R is connected by single bond 3 ，R 4 And C 16 、C 17 Together forming a three-membered ring containing 1 oxygen atom.
In some preferred embodiments of the invention, R 5 Is COR 10 Wherein R is 10 Is CH 2 R 11 Wherein R is 11 Is OH or OCOR 12 Wherein R is 12 Is C 1～6 An alkyl group; in some more preferred embodiments of the invention, R 12 Is methyl.
In some preferred embodiments of the present invention, the formate is selected from sodium formate, potassium formate, ammonium formate, or a combination thereof.
In some preferred embodiments of the present invention, the hypophosphite is selected from sodium hypophosphite, potassium hypophosphite, ammonium hypophosphite, lithium hypophosphite, or combinations thereof.
In some preferred embodiments of the invention, the substituted acetic acid is selected from thioglycolic acid.
In some preferred embodiments of the invention, the hydrazine compound is selected from hydrazine and/or hydrazine hydrate.
In some preferred embodiments of the present invention, the organic amine containing 1 to 6 carbon atoms is selected from the group consisting of methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, propylamine, dipropylamine, tri-n-propylamine, diisopropylamine, diisopropylethylamine, butylamine, tetramethylethylenediamine, cyclohexylamine.
In some preferred embodiments of the present invention, the nitrogen-containing heterocyclic compound is selected from dimethylaniline, azomethylmorpholine, imidazole, piperazine, methylpiperazine, dimethylpiperazine, pyrrolidine, N-methylpyrrolidine, piperidine, N-methylpiperidine, pyridine, 4-Dimethylaminopyridine (DMAP), tetramethylguanidine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, or a combination thereof.
In some preferred embodiments of the present invention, the organic alcohol amine containing 1 to 4 carbons is selected from the group consisting of ethanolamine, diethanolamine, triethanolamine, isopropanolamine, or combinations thereof.
In some preferred embodiments of the present invention, the thiol containing 1 to 6 carbons is selected from the group consisting of ethanethiol, propanethiol, cyclopentathiol, benzylthiol, or combinations thereof.
In some preferred embodiments of the present invention, the thioorganic acid is selected from thioacetic acid, thiomalic acid, thiobenzoic acid, ethyl thioacetate, or combinations thereof.
In some preferred embodiments of the present invention, the titanium-containing material is selected from titanium dioxide, nitrogen-doped TiO 2 、Bi 2 O 3 /TiO 2 Strontium-doped titanium dioxide, cu-doped TiO 2 、Fe/TiO 2 、Fe 3 O 4 /SiO 2 /TiO 2 Mesoporous titanium dioxide/porous carbon, V 2 O 5 /BiVO 4 /TiO 2 Titanium dioxide with surface modified by organic matters, g-C 3 N 4 /TiO 2 、TiO 2 /Cds、WO 3 /TiO 2 Ag doped TiO 2 Iron-doped TiO 2 Or a combination thereof.
In some preferred embodiments of the present invention, the zinc-containing material is selected from ZnO, bi 2 O 3 -ZnO, co/ZnO, carbon fiber/ZnO, biomass charcoal/ZnO, ag-ZnO, zn 2 SnO4-ZnO、CuS/ZnO、Ce/ZnO、Fe 3 O 4 -ZnO, pt-ZnO/C, znSe/ZnO, or combinations thereof.
In some preferred embodiments of the present invention, the bismuth-containing material is selected from the group consisting of bismuth oxide, biOCl, biOBr, agBr/BiOBr, negative Pt, au and Ru BiOBr, I-ion doped BiOBr, la doped BiOBr, tungsten doped BiOBr, bi 2 S 3 /BiOBr、g-C 3 N 4 /BiOBr、BiOBr/NaBiO、Ag 3 PO 4 /BiOBr、Pd/BiOBr、BiOBr/NaBiO 3 Ni/BiOBr, bi-containing complexes, or combinations thereof.
In some preferred embodiments of the present invention, the said g-C containing 3 N 4 Is selected from g-C 3 N 4 /MoO 3 、WO 3 /g-C 3 N 4 、CeO 2 /g-C 3 N 4 、g-C 3 N 4 /SnO 2 、g-C 3 N 4 /MoS 2 、g-C 3 N 4 /Ag 3 PO 4 、g-C 3 N 4 /Bi 2 WO 6 、g-C 3 N 4 /MnO 2 、g-C 3 N 4 /CoS 2 Or a combination thereof.
In some preferred embodiments of the present invention, the aromatic thiophenol compound is selected from the group consisting of compounds having the structure
Wherein A is carbon or nitrogen, R is hydrogen, alkyl, hydroxy, methoxy, aryl, carboxyl, amino or halogen, and m is 1-5.
In some preferred embodiments of the present invention, the diaryl disulfide compound is selected from the group consisting of compounds having the structure 
Wherein R is hydrogen, alkyl, hydroxy, methoxy, aryl, carboxyl, amino or halogen, and n is 1-5.
In some preferred embodiments of the present invention, the phenazine compound is selected from the group consisting of having the structure
Wherein R is a compound of formula (I) 1 And R is 2 Each independently is hydrogen, alkyl, aryl, R 1 And R is 2 May be the same or different.
In some preferred embodiments of the present invention, the phenothiazine-type compound is selected from the group consisting of the structures
Wherein R is a compound of formula (I) 1 Is hydrogen, alkyl or aryl.
In some advantages of the inventionIn alternative embodiments, the carbazole compound is selected from the group consisting of
Wherein Cz is a carbazole group, CN is cyano, FG is alkyl, aryl, methoxy, mercapto, carboxyl or hydroxyl, 2.ltoreq.m.ltoreq.5, n is 1 or 2, m+n+x.ltoreq.6.
In some preferred embodiments of the present invention, the triphenylamine compound is selected from the group consisting of compounds having the structure
Wherein DPA is a diphenylamine group, CN is cyano, FG is alkyl, aryl, methoxy, mercapto, carboxyl or hydroxy, 2.ltoreq.m.ltoreq.5, n is 1 or 2, m+n+x.ltoreq.6.
In some preferred embodiments of the present invention, the dye is selected from coumarin, acridine, fluorescein, phthalocyanine, porphyrin, perylene diimide, methylene blue, xanthene, benzophenone, or combinations thereof.
In some more preferred embodiments of the present invention, the adjuvant is selected from thioglycolic acid, tetramethyl ethylenediamine, triethylamine, hanes, tri-N-propylamine, formic acid, triethanolamine, thioglycolic acid, diethylamine, hypophosphorous acid, butylamine, cyclohexylamine, thiobenzoic acid, hypophosphorous acid, diisopropylethylamine, potassium hypophosphite, hydrazine hydrate, thioacetic acid, DMAP, thiomalic acid, 1, 4-dimethylpiperazine, benzylmercaptan, azamethylpyrrolidine, ethyl thioacetate, azamethylmorpholine, cyclopentanethiol, N-methylpiperidine, acetic acid, 1, 8-diazabicyclo [5.4.0] undec-7-ene, sodium hypophosphite, tetramethylguanidine, phosphorous acid, dimethylaniline, glycolic acid, isopropanolamine, thioglycolic acid, or combinations thereof.
In some more preferred embodiments of the present invention, the adjuvant is selected from the group consisting of a combination of thioglycolic acid and tetramethyl ethylenediamine, a combination of triethylamine and hans ester, a combination of tri-N-propylamine and formic acid, a combination of triethanolamine and thioglycolic acid, a combination of diethylamine and hypophosphorous acid, a combination of butylamine and formic acid, a combination of cyclohexylamine and thiobenzoic acid, a combination of triethanolamine and hypophosphorous acid, a combination of diisopropylethylamine and potassium hypophosphite, a combination of hydrazine hydrate and thioacetic acid, a combination of DMAP and thiomalic acid, a combination of 1, 4-dimethylpiperazine and benzyl mercaptan, a combination of azamethylpyrrolidine and ethyl thioacetate, a combination of azamethylmorpholine and cyclopentanethiol, a combination of N-methylpiperidine and acetic acid, a combination of 1, 8-diazabicyclo [5.4.0] undec-7-ene and sodium hypophosphite, a combination of tetramethylguanidine and phosphorous acid, a combination of dimethylaniline and glycolic acid, and isopropanolamine and a combination of thioglycolic acid.
In some more preferred embodiments of the present invention, the catalyst is selected from the group consisting of catalyst 10, pt (0.3 wt.%)/TiO 2 、g-C 3 N 4 /MoO 3 Bismuth oxide, 2, 6-dimethylbenzene thiophenol, bismuth subsalicylate, bismuth sulfide, ortho-amino thiophenol, thiosalicylic acid, titanium oxide, catalyst 11, catalyst 12, catalyst 13, catalyst 14, catalyst 15, catalyst 16, catalyst 17, catalyst 18, catalyst 19, catalyst 20, or combinations thereof, wherein the catalysts 10-20 have the structural formula:
in some more preferred embodiments of the present invention, the visible light has a wavelength of 370-480nm.
In some preferred embodiments of the invention, the molar ratio of compound I, auxiliary and catalyst is 1 (1-20): 0.01-2. In some more preferred embodiments of the invention, the molar ratio of compound I, auxiliary and catalyst is 1 (3-10): 0.1-0.5.
In some preferred embodiments of the present invention, the temperature of the photocatalytic reaction is between 0 and 70 ℃. In some more preferred embodiments of the present invention, the temperature of the photocatalytic reaction is 4 to 40 ℃, and more preferably 15 to 35 ℃.
In some preferred embodiments of the present invention, the solvent for the photocatalytic reaction is selected from alcohols containing 1 to 4 carbons, tetrahydrofuran, 2-methyltetrahydrofuran, N-dimethylformamide, N-dimethylacetamide, azomethylpyrrolidone, acetone, butanone, methyl isobutyl ketone, methylene chloride, ethyl acetate, or a mixture thereof with water.
In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is the compound I-1, the auxiliary agent is thioglycollic acid and tetramethyl ethylenediamine, the catalyst is the catalyst 10, and the wavelength of the visible light is 440nm. In a specific embodiment of the present invention, in the dehalogenation method of a 9-halogeno steroid compound, the compound I is compound I-2, the auxiliary agent is triethylamine and hans ester, and the catalyst is Pt (0.3 wt.%)/TiO 2 The wavelength of the visible light is 370nm. In one embodiment of the invention, in the dehalogenation method of 9-halogeno steroid compounds, the compound I is compound I-3, the auxiliary agent is tri-n-propylamine and formic acid, and the catalyst is g-C 3 N 4 /MoO 3 The wavelength of the visible light is 370nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-4, the auxiliary agent is triethanolamine and thioglycollic acid, the catalyst is bismuth oxide, and the wavelength of visible light is 440nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-5, the auxiliary agent is diethylamine and hypophosphorous acid, the catalyst is 2, 6-dimethylbenzene thiophenol, and the wavelength of visible light is 390nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-6, the auxiliary agent is butylamine and formic acid, the catalyst is bismuth subsalicylate, and the wavelength of the visible light is 370nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-7, the auxiliary agent is cyclohexylamine and thiobenzoic acid, the catalyst is bismuth sulfide, and the wavelength of visible light is 440nm. In one embodiment of the present invention, the compound I is a compound in a dehalogenation process of a 9-halosteroid compound And the auxiliary agent is triethanolamine and hypophosphorous acid, the catalyst is o-amino thiophenol, and the wavelength of visible light is 370nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is the compound I-9, the auxiliary agent is diisopropylethylamine and potassium hypophosphite, the catalyst is thiosalicylic acid, and the wavelength of visible light is 456nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-10, the auxiliary agent is diisopropylethylamine, the catalyst is titanium oxide, and the wavelength of visible light is 420nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-11, the auxiliary agent is hydrazine hydrate and thioacetic acid, the catalyst is a catalyst 11, and the wavelength of visible light is 450nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-12, the auxiliary agent is DMAP and thiomalic acid, the catalyst is a catalyst 12, and the wavelength of visible light is 390nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-13, the auxiliary agent is DMAP and thiomalic acid, the catalyst is a catalyst 13, and the wavelength of visible light is 400nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-14, the auxiliary agent is nitrogen methyl pyrrolidine and ethyl thioacetate, the catalyst is a catalyst 14, and the wavelength of visible light is 440nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-15, the auxiliary agent is nitrogen methylmorpholine and cyclopentanethiol, the catalyst is a catalyst 15, and the wavelength of visible light is 400nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-16, the auxiliary agent is N-methylpiperidine and acetic acid, the catalyst is a catalyst 16, and the wavelength of visible light is 370nm. In one embodiment of the invention, the 9-halosteroid compound In the dehalogenation method of (2), the compound I is a compound I-17, and the auxiliary agent is 1, 8-diazabicyclo [5.4.0 ]]Undec-7-ene and sodium hypophosphite, wherein the catalyst is catalyst 17, and the wavelength of visible light is 370nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-18, the auxiliary agent is tetramethyl guanidine and phosphorous acid, the catalyst is a catalyst 18, and the wavelength of visible light is 370nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-19, the auxiliary agent is dimethylaniline and glycollic acid, the catalyst is a catalyst 19, and the wavelength of the visible light is 370nm. In a specific embodiment of the invention, in the dehalogenation method of the 9-halogenated steroid compound, the compound I is a compound I-20, the auxiliary agent is isopropanolamine and thioglycollic acid, the catalyst is a catalyst 20, and the wavelength of visible light is 500nm.
The structures, auxiliaries and catalysts of compounds I-1 to I-20 are shown in Table 1 below:
TABLE 1
The invention also provides a corticosteroid drug and an intermediate thereof prepared by the dehalogenation method of the 9-halogenated steroid compound.
The invention also provides the use of a combination of an auxiliary agent selected from the group consisting of formic acid and formate salts, hypophosphorous acid and hypophosphite salts, acetic acid and substituted acetic acid, hydrazines, cyclohexene, hanes, organic amines containing 1 to 6 carbons, nitrogen containing heterocyclic compounds, organic alcohols amines containing 1 to 4 carbons, thiols containing 1 to 6 carbons, thioorganic acids, or combinations thereof, and a catalyst selected from the group consisting of titanium-containing materials, zinc-containing materials, bismuth-containing materials, g-C-containing materials, for removing halogen from the compound 3 N 4 The material of (C) is selected from the group consisting of aromatic thiophenol compounds, diaryl disulfide compounds, phenazine compounds, phenothiazine compounds, carbazole compounds, triarylamine compounds, dyes, photoinitiators, iridium or ruthenium complexes with pyridine compounds, or combinations thereof.
In some preferred embodiments of the invention, the use is performed in the presence of visible light.
In some preferred embodiments of the present invention, the visible light has a wavelength of 370-550nm, more preferably 370-480nm.
In some preferred embodiments of the invention, the halogen is attached to a primary, secondary, tertiary, or ethylenic carbon of the compound.
In some more preferred embodiments of the present invention, the compound is selected from the group consisting of compounds I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-13, I-14, I-15, I-16, I-17, I-18, I-19, I-20.
In some preferred embodiments of the present invention, the formate is selected from sodium formate, potassium formate, ammonium formate, or a combination thereof. In some preferred embodiments of the present invention, the hypophosphite is selected from sodium hypophosphite, potassium hypophosphite, ammonium hypophosphite, lithium hypophosphite, or combinations thereof. In some preferred embodiments of the invention, the substituted acetic acid is selected from thioglycolic acid. In some preferred embodiments of the invention, the hydrazine compound is selected from hydrazine and/or hydrazine hydrate. In some preferred embodiments of the present invention, the organic amine containing 1 to 6 carbon atoms is selected from the group consisting of methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, propylamine, dipropylamine, tri-n-propylamine, diisopropylamine, diisopropylethylamine, butylamine, tetramethylethylenediamine, cyclohexylamine. In some preferred embodiments of the present invention, the nitrogen-containing heterocyclic compound is selected from dimethylaniline, azomethylmorpholine, imidazole, piperazine, methylpiperazine, dimethylpiperazine, pyrrolidine, N-methylpyrrolidine, piperidine, N-methylpiperidine, pyridine, 4-dimethylaminopyridine, tetramethylguanidine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, or a combination thereof. In some preferred embodiments of the present invention, the organic alcohol amine containing 1 to 4 carbons is selected from the group consisting of ethanolamine, diethanolamine, triethanolamine, isopropanolamine, or combinations thereof. In some preferred embodiments of the present invention, the thiol containing 1 to 6 carbons is selected from the group consisting of ethanethiol, propanethiol, cyclopentathiol, benzylthiol, or combinations thereof. In some preferred embodiments of the present invention, the thioorganic acid is selected from thioacetic acid, thiomalic acid, thiobenzoic acid, ethyl thioacetate, or combinations thereof.
In some preferred embodiments of the present invention, the titanium-containing material is selected from titanium dioxide, nitrogen-doped TiO 2 、Bi 2 O 3 /TiO 2 Strontium-doped titanium dioxide, cu-doped TiO 2 、Fe/TiO 2 、Fe 3 O 4 /SiO 2 /TiO 2 Mesoporous titanium dioxide/porous carbon, V 2 O 5 /BiVO 4 /TiO 2 Titanium dioxide with surface modified by organic matters, g-C 3 N 4 /TiO 2 、TiO 2 /Cds、WO 3 /TiO 2 Ag doped TiO 2 Iron-doped TiO 2 Or a combination thereof. In some preferred embodiments of the present invention, the zinc-containing material is selected from ZnO, bi 2 O 3 -ZnO, co/ZnO, carbon fiber/ZnO, biomass charcoal/ZnO, ag-ZnO, zn 2 SnO4-ZnO、CuS/ZnO、Ce/ZnO、Fe 3 O 4 -ZnO, pt-ZnO/C, znSe/ZnO, or combinations thereof. In some preferred embodiments of the inventionIn an embodiment, the bismuth-containing material is selected from bismuth oxide, biOCl, biOBr, agBr/BiOBr, negative Pt, au and Ru BiOBr, I-ion doped BiOBr, la doped BiOBr, tungsten doped BiOBr, bi 2 S 3 /BiOBr、g-C 3 N 4 /BiOBr、BiOBr/NaBiO、Ag 3 PO 4 /BiOBr、Pd/BiOBr、BiOBr/NaBiO 3 Ni/BiOBr, bi-containing complexes, or combinations thereof. In some preferred embodiments of the present invention, the said g-C containing 3 N 4 Is selected from g-C 3 N 4 /MoO 3 、WO 3 /g-C 3 N 4 、CeO 2 /g-C 3 N 4 、g-C 3 N 4 /SnO 2 、g-C 3 N 4 /MoS 2 、g-C 3 N 4 /Ag 3 PO 4 、g-C 3 N 4 /Bi 2 WO 6 、g-C 3 N 4 /MnO 2 、g-C 3 N 4 /CoS 2 Or a combination thereof. In some preferred embodiments of the present invention, the aromatic thiophenol compound is selected from the group consisting of compounds having the structure
Wherein A is carbon or nitrogen, R is hydrogen, alkyl, hydroxy, methoxy, aryl, carboxyl, amino or halogen, and m is 1-5. In some preferred embodiments of the present invention, the diaryl disulfide compound is selected from the group consisting of compounds having the structure +. >
Wherein R is hydrogen, alkyl, hydroxy, methoxy, aryl, carboxyl, amino or halogen, and n is 1-5. In some preferred embodiments of the present invention, the phenazine compound is selected from the group consisting of having the structure +.>
Wherein R is a compound of formula (I) 1 And R is 2 Each independently is hydrogen, alkyl, aryl, R 1 And R is 2 May be the same or different. In some preferred embodiments of the inventionThe phenothiazine compound is selected from the structure +.>
Wherein R is a compound of formula (I) 1 Is hydrogen, alkyl or aryl. In some preferred embodiments of the present invention, the carbazole-based compound is selected from the group consisting of compounds having the structure +.>
Wherein Cz is a carbazole group, CN is cyano, FG is alkyl, aryl, methoxy, mercapto, carboxyl or hydroxyl, 2.ltoreq.m.ltoreq.5, n is 1 or 2, m+n+x.ltoreq.6. In some preferred embodiments of the present invention, the triphenylamine compound is selected from the group consisting of the structures +.>
Wherein DPA is a diphenylamine group, CN is cyano, FG is alkyl, aryl, methoxy, mercapto, carboxyl or hydroxy, 2.ltoreq.m.ltoreq.5, n is 1 or 2, m+n+x.ltoreq.6. In some preferred embodiments of the present invention, the dye is selected from coumarin, acridine, fluorescein, phthalocyanine, porphyrin, perylene diimide, methylene blue, xanthene, benzophenone, or combinations thereof.
In some more preferred embodiments of the present invention, the adjuvant is selected from thioglycolic acid, tetramethyl ethylenediamine, triethylamine, hanes, tri-N-propylamine, formic acid, triethanolamine, thioglycolic acid, diethylamine, hypophosphorous acid, butylamine, cyclohexylamine, thiobenzoic acid, hypophosphorous acid, diisopropylethylamine, potassium hypophosphite, hydrazine hydrate, thioacetic acid, DMAP, thiomalic acid, 1, 4-dimethylpiperazine, benzylmercaptan, azamethylpyrrolidine, ethyl thioacetate, azamethylmorpholine, cyclopentanethiol, N-methylpiperidine, acetic acid, 1, 8-diazabicyclo [5.4.0 ]]Undec-7-ene, sodium hypophosphite, tetramethylguanidine, phosphorous acid, dimethylaniline, glycolic acid, isopropanolamine, thioglycolic acid, or a combination thereof, and the catalyst is selected from the group consisting of catalyst 10, pt (0.3 wt.%)/TiO 2 、g-C 3 N 4 /MoO 3 Bismuth oxide2, 6-dimethylbenzene thiophenol, bismuth subsalicylate, bismuth sulfide, ortho-aminothiophenol, thiosalicylic acid, titanium oxide, catalyst 11, catalyst 12, catalyst 13, catalyst 14, catalyst 15, catalyst 16, catalyst 17, catalyst 18, catalyst 19, catalyst 20, or a combination thereof, wherein the catalysts 10-20 have the following structural formulas:
In some more preferred embodiments of the present invention, the adjuvant is selected from the group consisting of a combination of thioglycolic acid and tetramethyl ethylenediamine, a combination of triethylamine and hanes, a combination of tri-N-propylamine and formic acid, a combination of triethanolamine and thioglycolic acid, a combination of diethylamine and hypophosphorous acid, a combination of butylamine and formic acid, a combination of cyclohexylamine and thiobenzoic acid, a combination of triethanolamine and hypophosphorous acid, a combination of diisopropylethylamine and potassium hypophosphite, a combination of hydrazine hydrate and thioacetic acid, a combination of DMAP and thiomalic acid, a combination of 1, 4-dimethylpiperazine and benzylmercaptan, a combination of azamethylpyrrolidine and ethyl thioacetate, a combination of azamethylmorpholine and cyclopentanethiol, a combination of N-methylpiperidine and acetic acid, and 1, 8-diazabicyclo [5.4.0]The composition of undec-7-ene and sodium hypophosphite, the composition of tetramethylguanidine and phosphorous acid, the composition of dimethylaniline and glycolic acid, the composition of isopropanolamine and thioglycolic acid, and the catalyst is selected from the group consisting of catalyst 10, pt (0.3 wt.%)/TiO 2 、g-C 3 N 4 /MoO 3 Bismuth oxide, 2, 6-dimethylbenzene thiophenol, bismuth subsalicylate, bismuth sulfide, ortho-amino thiophenol, thiosalicylic acid, titanium oxide, catalyst 11, catalyst 12, catalyst 13, catalyst 14, catalyst 15, catalyst 16, catalyst 17, catalyst 18, catalyst 19, catalyst 20, or a combination thereof.
In some more preferred embodiments of the present invention, combinations of promoters and catalysts for the above uses are shown in Table 2 below:
TABLE 2
The dehalogenation method of the 9-halogenated steroid compound has the following advantages:
1. the method of the invention avoids the heavy metal used in the dehalogenation method of 9-halogenated steroid compounds in the prior art, has little environmental pollution and no heavy metal residue problem of products.
2. The dehalogenation method of the invention has high product yield and good purity.
3. The dehalogenation method of the invention uses the auxiliary agent which is the traditional bulk chemicals, has low cost and is easy to obtain, and the catalyst can be reused after being recovered.
Drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of Compound I-1;
FIG. 2 is a nuclear magnetic hydrogen spectrum of Compound II-1;
FIG. 3 is a nuclear magnetic carbon spectrum of Compound II-1
FIG. 4 is a mass spectrum of compound II-1;
FIG. 5 is a liquid phase diagram of compound II-1.
Detailed Description
The inventor of the present invention has conducted extensive and intensive studies and has found that 9-halogeno steroid compounds can obtain dehalogenated products with high purity in high yield under the catalysis of visible light by using the auxiliary agent and the catalyst of the present invention. On this basis, the present invention has been completed.
Terminology
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
The term "halogen" as used herein includes fluorine, chlorine, bromine, iodine, unless otherwise indicated.
Unless otherwise indicated, the term "alkyl" as such or as part of another substituent herein refers to a straight or branched hydrocarbon radical having the indicated number of carbon atoms.
In the description of the present specification, unless otherwise indicated, C 1～6 Alkyl means an alkyl group having 1 to 6 carbon atoms. Examples of such alkyl groups include, but are not limited to: methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl and the like.
In the description of this specification, unless otherwise stated, the term "aryl" means a polyunsaturated (usually aromatic) hydrocarbon group, which may be a single ring or multiple rings (up to three rings) fused together or covalently linked. Non-limiting examples of aryl groups include phenyl, naphthyl, and biphenyl.
In the description of the present specification, the "alkyl", "phenyl", "aryl", "benzyl" and the like groups may be unsubstituted or substituted, may be substituted with one substituent or may be substituted with plural substituents, and when substituted with plural substituents, the substituents may be the same or different.
In the description of this specification, unless otherwise indicated, "substituted" means that one or more hydrogens in the groups are replaced with a corresponding number of substituents, independently of each other. Unless otherwise indicated, "substituted" or "substituted" both mean that a group may be substituted with one or more groups selected from the group consisting of: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, alkenyl, hydroxy, nitro, cyano, cycloalkyl, heterocyclyl, aryl, benzyl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, amino, haloalkyl, hydroxyalkyl, carboxyl, carboxylate and like substituents.
In the description of the invention "/" means "and", for example "Fe 3 O 4 /SiO 2 /TiO 2 "means Fe 3 O 4 And SiO 2 And TiO 2 The composition of (C), "V 2 O 5 /BiVO 4 /TiO 2 "means V 2 O 5 And BiVO 4 And TiO 2 Is a composition of (a).
In the description of the present specification, unless otherwise indicated, the term "room temperature" or "normal temperature" means a temperature of 4 to 40 ℃, preferably 25±5 ℃.
Dehalogenation method of 9-halogenated steroid compound
The dehalogenation method of the present invention comprises the steps of:
in the presence of an auxiliary agent and a catalyst, the compound I is subjected to photocatalytic reaction by utilizing visible light to generate a compound II, wherein the reaction formula is as follows:
Wherein, in the structural formulas of the compound I and the compound II,
represents a single bond or a double bond,
R 1 h, C of a shape of H, C 1～6 Alkyl or fluoro;
R 2 is O, OH, C 1～6 Alkyl, phenyl, benzyl, O-C 1～6 Alkyl, O-Ph or OCOR 6 The R is 6 Selected from H, CF 3 、C 1～6 Alkyl, phenyl or benzyl;
R 3 is H, OH, C 1～6 Alkyl, O-C 1～6 Alkyl, O-Ph or OCOR 7 Wherein R is 7 H, C of a shape of H, C 1～6 Alkyl, phenyl or benzyl;
when C 16 ，C 17 When connected by single bond, R 4 Is H or OH, or R 3 ，R 4 And C 16 、C 17 Together form a three-membered ring containing 1 oxygen atom, or a five-membered heterocyclic ring containing 2 oxygen atoms, wherein the five-membered ring has the structure
Wherein R is 8 、R 9 Each independently H, C 1～6 Alkyl, phenyl or benzyl;
when C 16 ，C 17 When connected by double bonds, R 4 Absence of;
R 5 is COR 10 Wherein R is 10 H, C of a shape of H, C 1～6 Alkyl or CH 2 R 11 Wherein R is 11 Is OH, halogen or OCOR 12 Wherein R is 12 Is C 1～6 Alkyl, phenyl or benzyl;
x is selected from fluorine, chlorine, bromine and iodine;
wherein the wavelength of the visible light is 370-550nm;
adjuvants useful in the present invention include, but are not limited to, formic acid and formates, hypophosphorous acid and hypophosphites, acetic acid and substituted acetic acids, hydrazines, cyclohexene, hanes, organic amines containing 1 to 6 carbons, organic alcohols amines containing 1 to 4 carbons, thiols containing 1 to 6 carbons, thio organic acids.
Catalysts useful in the present invention include, but are not limited to, titanium-containing materials, zinc-containing materials, bismuth-containing materials, g-C-containing materials 3 N 4 The material comprises an aromatic thiophenol compound, a diaryl disulfide compound, a phenazine compound, a phenothiazine compound, a carbazole compound, a triarylamine compound, a dye, a photoinitiator, iridium or a complex of ruthenium and a pyridine compound.
The basic principle of the dehalogenation method of the present invention is: under the irradiation of light, the catalyst absorbs light energy to transition to an excited state, and the high-activity excited state catalyst obtains an electron from the auxiliary agent to form a free radical anion species which has strong reducibility and generates electron transfer with a substrate to remove halogen ions in the substrate and generate substrate free radicals, and the free radicals obtain a hydrogen atom from the auxiliary agent to generate dehalogenated products. The catalyst returns to the initial state, and the reduced and removed halogen anions form salts with the auxiliary agent.
The invention provides the use of a combination of an adjunct and a catalyst for removing halogen from a compound, the halogen being selected from fluorine, chlorine, bromine or iodine. Preferably, the auxiliary and catalyst remove halogen from the compound under visible light conditions, the halogen may be attached to any carbon, such as primary, secondary, tertiary or olefinic carbon, that is, any halogen attached to the primary, secondary, tertiary or olefinic carbon may be removed. Such compounds include, but are not limited to, the compounds of the present invention I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-13, I-14, I-15, I-16, I-17, I-18, I-19, I-20.
The invention is further illustrated below in connection with examples, but the invention is not limited to these examples. The experimental methods used in the following examples are conventional methods unless otherwise specified. Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
The structures of the catalysts 10 to 20 mentioned in the following example 1 are as follows:
example 1.
To a reaction vessel were successively added 20L of acetone, 500g of thioglycollic acid, 500g of tetramethyl ethylenediamine, 500g of Compound I-1 and 6.5g of catalyst 10 at room temperature. Under the protection of nitrogen, the photocatalytic reaction is carried out for 5 hours at room temperature under the light effect of 440 nanometers wavelength, stirring is carried out during the photocatalytic reaction, the reaction is detected by HPLC until the reaction of I-1 is complete, solid is separated out after post treatment (the specific process is that the reaction liquid is decompressed and concentrated to remove the solvent, the residue is obtained, water is added into the residue, the solid is separated out), 378.6g of the crude product of the compound II-1 is obtained after filtering and drying, the yield is 90%, and the purity of HPLC is 98.7%.
And recrystallizing the solid crude product of the compound II-1 by using a mixed solvent of methanol and dichloromethane to obtain the pure compound II-1. Heavy weightThe catalyst in the mother liquor after crystallization can be recycled, the nuclear magnetic hydrogen spectrum of the compound II-1 is shown in figure 2, the nuclear magnetic carbon spectrum of the compound II-1 is shown in figure 3, the mass spectrum of the compound II-1 is shown in figure 4, and the mass spectrum information is as follows: m/z=419.2 (m+h) + The liquid-phase spectrum of the compound II-1 is shown in FIG. 5.
Example 2.
300ml of LDMF, 8.2g of triethylamine and 20.5g of Hans ester, 20g of Compound I-2 and 1.8g of Pt (0.3 wt.%)/TiO were successively added to a reaction flask at room temperature 2 . Under the protection of nitrogen, the photocatalysis reaction is carried out for 2 hours under the light effect of 370 nanometers wavelength at room temperature, stirring is carried out during the photocatalysis reaction, the reaction is detected by HPLC until the I-2 reaction is complete, solid is separated out after post treatment (specifically, the reaction liquid is filtered, insoluble matters are removed, the filtrate is decompressed and concentrated to remove the solvent, the residue is obtained, water is added into the residue, the solid is separated out), the filtration and drying are carried out, and 13.5g of crude compound II-2 solid is obtained, the yield is 80%, and the HPLC purity is 97%.
Mass spectrometry information: m/z=417.2 (m+h) +
Example 3.
500mL of acetonitrile, 13.1g of tri-n-propylamine, 4.2g of formic acid, 20g of Compound I-3 and 1.3g g-C were sequentially added to a reaction flask at room temperature 3 N 4 /MoO 3 . Under the protection of nitrogen, the photocatalysis reaction is carried out for 3 hours under the light effect of 370 nanometers wavelength at room temperature, stirring is carried out during the photocatalysis reaction, the reaction of the I-3 is detected by HPLC, solid is separated out after the post treatment (the specific process of the post treatment is the same as that of the example 2), the filtration and the drying are carried out, 13.1g of crude solid of the compound II-3 is obtained, the yield is 80%, and the purity of the HPLC is 96.5%.
Mass spectrometry information: m/z= 381.1 (m+na) +
Example 4.
600mL of acetone, 10.6g of triethanolamine, 8.4g of thioglycolic acid, 20g of Compound I-4, and 2.1g of bismuth oxide were sequentially added to the reaction flask at room temperature. Under the protection of nitrogen, the photocatalytic reaction is carried out for 1.5 hours under the light effect of 440 nanometers wavelength at room temperature, stirring is carried out during the photocatalytic reaction, the reaction of the I-4 is detected by HPLC until the reaction is complete, solid is separated out after the post-treatment (the specific post-treatment process is the same as that of example 2), 14g of crude compound II-4 solid is obtained after filtering and drying, the yield is 85%, and the purity of the HPLC is 97.5%.
Mass spectrometry information: m/z=361.2 (m+h) +
Example 5.
150mL of methanol, 150mL of methylene chloride, 6.1g of diethylamine and 5.5g of hypophosphorous acid, 20g of Compound I-5 and 1.1g of 2, 6-dimethylbenzenesulfide were sequentially added to the reaction flask at room temperature. Under the protection of nitrogen, the photocatalytic reaction is carried out for 1 hour under the light effect of 390 nanometers wavelength at room temperature, stirring is carried out during the photocatalytic reaction, the reaction of the I-5 is detected by HPLC until the reaction is complete, solid is separated out after the post-treatment (the specific post-treatment process is the same as that of example 1), 16.2g of crude compound II-5 solid is obtained after filtering and drying, the yield is 94%, and the purity of the HPLC is 98.5%.
Mass spectrometry information: m/z=403.2 (m+h) +
Example 6.
300mL of butanone, 6.1g of butylamine, 3.8g of formic acid, 20g of Compound I-6 and 1.5g of bismuth subsalicylate were successively added to the reaction flask at room temperature. Under the protection of nitrogen, the photocatalysis reaction is carried out for 0.5 hour under the light effect of 370 nanometers wavelength at room temperature, stirring is carried out during the photocatalysis reaction, the reaction of the I-6 is detected by HPLC, solid is separated out after the post treatment (the specific post treatment process is the same as that of example 2), 15g of crude compound II-6 solid is obtained after the filtration and the drying, the yield is 93 percent, and the purity of the HPLC is 98.2 percent.
Mass spectrometry information: m/z= 401.2 (m+h) +
Example 7.
300mL of tetrahydrofuran, 8.2g of cyclohexylamine, 11.5g of thiobenzoic acid, 20g of Compound I-7 and 4.3g of bismuth sulfide were successively charged into a reaction flask at room temperature. Under the protection of nitrogen, the photocatalytic reaction is carried out for 3 hours under the light effect of 440 nanometers wavelength at room temperature, stirring is carried out during the photocatalytic reaction, the reaction of the I-7 is detected by HPLC until the reaction is complete, solid is separated out after the post-treatment (the specific post-treatment process is the same as that of example 2), the filtering and drying are carried out, 15.1g of crude solid product of the compound II-7 is obtained, the yield is 90%, and the purity of the HPLC is 96.5%.
Mass spectrometry information: m/z=403.2 (m+h) +
Example 8.
200mL of acetone, 13.5g of triethanolamine, 6g of hypophosphorous acid, 20g of compound I-8 and 1.1g of o-aminophenylthiophenol were sequentially added to the reaction flask at room temperature. Under the protection of nitrogen, the photocatalysis reaction is carried out for 1 hour under the light effect of 370 nanometers wavelength at room temperature, stirring is carried out in the photocatalysis reaction process, the reaction of the I-8 is detected by HPLC until the reaction is complete, solid is separated out after the post-treatment (the specific post-treatment process is the same as that of example 1), the solid is filtered, and 13.1g of crude solid of the compound II-8 is obtained after the drying, the yield is 80%, and the purity of the HPLC is 97%.
Mass spectrometry information: m/z= 363.2 (m+h) +
Example 9.
400mL of butanone, 10.7g of diisopropylethylamine, 8.6g of potassium hypophosphite, 20g of Compound I-9 and 1.3g of thiosalicylic acid were sequentially added to the reaction flask at room temperature. Under the protection of nitrogen, the photocatalytic reaction is carried out for 2 hours at room temperature under the light action of 456 nanometers wavelength, stirring is carried out during the photocatalytic reaction, the reaction of the I-9 is detected by HPLC, solid is separated out after the post-treatment (the specific post-treatment process is the same as that of example 2), 15.7g of crude compound II-9 solid is obtained after the filtering and drying, the yield is 91%, and the purity of the HPLC is 98.1%.
Mass spectrometry information: m/z= 444.3 (m+k) +
Example 10.
500mL of acetonitrile, 11.4g of diisopropylethylamine, 20g of Compound I-10 and 1.8g of titanium oxide were sequentially added to a reaction flask at room temperature. Under the protection of nitrogen, the photocatalytic reaction is carried out for 1 hour under the light effect of 420 nanometers wavelength at room temperature, stirring is carried out during the photocatalytic reaction, the reaction of the I-10 is detected by HPLC, solid is separated out after the post-treatment (the specific post-treatment process is the same as that of example 2), 15.3g of crude compound II-10 solid is obtained after the filtering and drying, the yield is 90%, and the purity of the HPLC is 96.6%.
Mass spectrometry information: m/z=405.2 (m+h) +
Example 11.
400mL of tetrahydrofuran, 3.9g of hydrazine hydrate, 6g of thioacetic acid, 20g of Compound I-11, and 1.6g of catalyst 11 were sequentially added to the reaction flask at room temperature. Under the protection of nitrogen, the photocatalytic reaction is carried out for 2 hours at room temperature under the light effect of 450 nanometers wavelength, stirring is carried out during the photocatalytic reaction, the reaction of the I-11 is detected by HPLC until the reaction is complete, solid is separated out after the post-treatment (the specific post-treatment process is the same as that of example 1), 14.5g of crude solid of the compound II-11 is obtained after filtering and drying, the yield is 86%, and the purity of the HPLC is 97.3%.
Mass spectrometry information: m/z= 433.2 (m+h) +
Example 12.
200mL of acetone, 10mL of water, 8.4g of DMAP and 10.4g of thiomalic acid, 20g of Compound I-12 and 1.5g of catalyst 12 were successively introduced into a reaction flask at room temperature. Under the protection of nitrogen, the photocatalytic reaction is carried out for 1 hour under the light effect of 390 nanometers wavelength at room temperature, stirring is carried out during the photocatalytic reaction, the reaction of the I-12 is detected by HPLC, solid is separated out after the post-treatment (the specific post-treatment process is the same as that of example 1), 13.8g of crude compound II-12 solid is obtained after the filtering and drying, the yield is 80%, and the HPLC purity is 96.3%.
Mass spectrometry information: m/z=501.2 (m+h) +
Example 13.
200mL of acetone, 10mL of water, 9.8g of 1, 4-dimethylpiperazine and 10.6g of benzyl mercaptan, 20g of Compound I-13 and 1.7g of catalyst 13 were successively added to the reaction flask at room temperature. Under the protection of nitrogen, the photocatalytic reaction is carried out for 2 hours at room temperature under the light action of 400 nanometers wavelength, stirring is carried out during the photocatalytic reaction, the reaction of the I-13 is detected by HPLC, solid is separated out after the post-treatment (the specific post-treatment process is the same as that of example 1), 13.5g of crude compound II-13 solid is obtained after the filtering and drying, the yield is 81%, and the HPLC purity is 96.8%.
Mass spectrometry information: m/z= 433.2 (m+h) +
Example 14.
Into a reaction flask were successively charged 100mL of azamethylpyrrolidone, 10mL of water, 6.7g of azamethylpyrrolidine and 8.2g of ethyl thioacetate, 20g of Compound I-14 and 1.6g of catalyst 14 at room temperature. Under the protection of nitrogen, the photocatalytic reaction is carried out for 2 hours under the light effect of 440 nanometers wavelength at room temperature, stirring is carried out during the photocatalytic reaction, the reaction of the I-14 is detected by HPLC until the reaction is complete, solid is separated out after the post-treatment (the specific post-treatment process is the same as that of example 1), the filtering and drying are carried out, and 15.2g of crude solid of the compound II-14 is obtained, the yield is 90%, and the purity of the HPLC is 98%.
Mass spectrometry information: m/z= 431.2 (m+h) +
Example 15.
Into a reaction flask were successively charged 100mL of azamethylpyrrolidone, 10mL of water, 8.1g of azamethylmorpholine and 8.2g of cyclopentanethiol, 20g of Compound I-15 and 1.8g of catalyst 15 at room temperature. Under the protection of nitrogen, the photocatalytic reaction is carried out for 1.5 hours under the light effect of 400 nanometers wavelength at room temperature, stirring is carried out during the photocatalytic reaction, the reaction of the I-15 is detected by HPLC, solid is separated out after the post-treatment (the specific post-treatment process is the same as that of example 1), the filtration and the drying are carried out, and 15.0g of crude compound II-15 solid is obtained, the yield is 90.5%, and the HPLC purity is 98.5%.
Mass spectrometry information: m/z= 375.2 (m+h) +
Example 16.
150mL of methanol, 150mL of methylene chloride, 7.5g of N-methylpiperidine and 4.6g of acetic acid, 20g of Compound I-16 and 1.6g of catalyst 16 were successively added to the reaction flask at room temperature. Under the protection of nitrogen, the photocatalysis reaction is carried out for 2 hours under the light effect of 370 nanometers wavelength at room temperature, stirring is carried out during the photocatalysis reaction, the reaction of the I-16 is detected by HPLC, solid is separated out after the post treatment (the specific post treatment process is the same as that of example 1), 15.9g of crude solid of the compound II-16 is obtained after the filtration and drying, the yield is 94%, and the purity of the HPLC is 98.1%.
Mass spectrometry information: m/z= 447.2 (m+h) +
Example 17.
150mL of methanol, 150mL of methylene chloride, 13.4g of 1, 8-diazabicyclo [5.4.0] undec-7-ene, 7.8g of sodium hypophosphite, 20g of compound I-17 and 2.86g of catalyst 17 were sequentially added to the reaction flask at room temperature. Under the protection of nitrogen, the photocatalysis reaction is carried out for 2 hours under the light effect of 370 nanometers wavelength at room temperature, stirring is carried out during the photocatalysis reaction, the reaction of the I-17 is detected by HPLC, solid is separated out after the post treatment (the specific post treatment process is the same as that of example 1), 13.2g of crude solid of the compound II-17 is obtained after the filtration and drying, the yield is 80%, and the purity of the HPLC is 96.3%.
Mass spectrometry information: m/z=377.1 (m+na) +
Example 18.
150mL of methanol, 150mL of methylene chloride, 10.9g of tetramethylguanidine, 7.7g of phosphorous acid, 20g of Compound I-18, and 1.26g of catalyst 18 were sequentially added to the reaction flask at room temperature. Under the protection of nitrogen, the photocatalysis reaction is carried out for 1 hour under the light effect of 370 nanometers wavelength at room temperature, stirring is carried out during the photocatalysis reaction, the reaction of the I-18 is detected by HPLC, solid is separated out after the post treatment (the specific post treatment process is the same as that of example 1), 15.1g of crude solid of the compound II-18 is obtained after the filtration and drying, the yield is 93 percent, and the purity of the HPLC is 97.1 percent.
Mass spectrometry information: m/z= 345.2 (m+h) +
Example 19.
150mL of methanol, 150mL of methylene chloride, 10.1g of dimethylaniline and 6.3g of glycolic acid, 20g of Compound I-19 and 2.72g of catalyst 19 were sequentially added to the reaction flask at room temperature. Under the protection of nitrogen, the photocatalysis reaction is carried out for 2 hours under the light effect of 370 nanometers wavelength at room temperature, stirring is carried out during the photocatalysis reaction, the reaction of the I-21 is detected by HPLC, solid is separated out after the post treatment (the specific post treatment process is the same as that of example 1), 14.5g of crude solid of the compound II-19 is obtained after the filtration and drying, the yield is 87%, and the purity of the HPLC is 96.2%.
Mass spectrometry information: m/z=429.2 (m+h) +
Example 20.
150mL of methanol, 150mL of methylene chloride, 5.9g of isopropanolamine and 9.4g of thioglycolic acid, 20g of compound I-20 and 1.9g of catalyst 20 were sequentially added to the reaction flask at room temperature. Under the protection of nitrogen, the photocatalytic reaction is carried out for 1.5 hours under the light effect of 500 nanometers wavelength at room temperature, stirring is carried out during the photocatalytic reaction, the reaction of the I-22 is detected by HPLC until the reaction is complete, solid 1 is separated out after post treatment, the filtration and the drying are carried out, and 15.5g of compound II-20 solid crude product is obtained, the yield is 91.5%, and the purity of the HPLC is 97.6%.
Mass spectrometry information: m/z= 435.2 (m+h) +
Comparative example 1.
100mL of acetone, 2.5g of thioglycollic acid, 2.5g of tetramethyl ethylenediamine and 2.5g of compound I-1 (the structure of which is shown in example 1) are sequentially added into a reaction kettle at room temperature, the reaction kettle is subjected to photocatalytic reaction for 1 hour under the action of 440 nm wavelength light at room temperature under the protection of nitrogen, stirring is carried out during the photocatalytic reaction, and the TLC detection shows that the compound I-1 is basically absent. A catalyst is essential for the reaction.
Comparative example 2.
100mL of acetone, 2.5g of thioglycollic acid, 2.5g of tetramethyl ethylenediamine, 2.5g of compound I-1 and 32.5mg of catalyst 10 are sequentially added into a reaction kettle at room temperature, the photocatalytic reaction is carried out for 1 hour under the protection of nitrogen at the room temperature under the light effect of 350 nanometers wavelength, stirring is carried out during the photocatalytic reaction, HPLC detection reaction is carried out, and the raw materials are found to be remained and simultaneously more impurities are produced. The reason may be that light in the ultraviolet range causes the steroid of the present invention having a complicated structure to produce impurities.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the corresponding technical solutions from the technical scope of the embodiments of the present invention.
Claims (11)
1. A process for dehalogenating a 9-halogenated steroid compound, said dehalogenation process comprising the steps of: (1) In the presence of an auxiliary agent and a catalyst, the compound I is subjected to photocatalytic reaction by utilizing visible light to generate a compound II, wherein the reaction formula is as follows:
wherein, in the structural formulas of the compound I and the compound II,
represents a single bond or a double bond,
R 1 h, C of a shape of H, C 1～6 Alkyl or fluoro;
R 2 is O, OH, C 1～6 Alkyl, phenyl, benzyl, O-C 1～6 Alkyl, O-Ph or OCOR 6 The R is 6 Selected from H, CF 3 、C 1～6 Alkyl, phenyl or benzyl;
R 3 is H, OH, C 1～6 Alkyl, O-C 1～6 Alkyl, O-Ph or OCOR 7 Wherein R is 7 Is H,C 1～6 Alkyl, phenyl or benzyl;
when C 16 ，C 17 When connected by single bond, R 4 Is H or OH, or R 3 ，R 4 And C 16 、C 17 Together form a three-membered ring containing 1 oxygen atom, or a five-membered heterocyclic ring containing 2 oxygen atoms, wherein the five-membered ring has the structure
Wherein R is 8 、R 9 Each independently H, C 1～6 Alkyl, phenyl or benzyl;
when C 16 ，C 17 When connected by double bonds, R 4 Absence of;
R 5 is COR 10 Wherein R is 10 H, C of a shape of H, C 1～6 Alkyl or CH 2 R 11 Wherein R is 11 Is OH, halogen or OCOR 12 Wherein R is 12 Is C 1～6 Alkyl, phenyl or benzyl;
x is selected from fluorine, chlorine, bromine and iodine;
the wavelength of the visible light is 370-550nm;
the auxiliary agent is selected from formic acid and formate, hypophosphorous acid and hypophosphite, acetic acid and substituted acetic acid, hydrazine compounds, cyclohexene, hanes, organic amines containing 1-6 carbon atoms, nitrogen-containing heterocyclic compounds, organic alcohol amines containing 1-4 carbon atoms, mercaptan containing 1-6 carbon atoms, thio organic acid or a combination thereof,
the catalyst is selected from titanium-containing materials, zinc-containing materials, bismuth-containing materials, g-C-containing materials 3 N 4 The material of (C) is selected from the group consisting of aromatic thiophenol compounds, diaryl disulfide compounds, phenazine compounds, phenothiazine compounds, carbazole compounds, triarylamine compounds, dyes, photoinitiators, iridium or ruthenium complexes with pyridine compounds, or combinations thereof.
2. The method for dehalogenating a 9-halogeno steroid compound according to claim 1,
in the structural formulas of the compound I and the compound II,
R 1 is H, methyl or fluorine; and/or
R 2 For O, OH or OCOR 6 The R is 6 Selected from H, CF 3 Or C 1～6 An alkyl group; and/or
R 3 H, OH or CH 3 The method comprises the steps of carrying out a first treatment on the surface of the And/or
C 16 ，C 17 R is connected by single bond 4 Is H or OH, and/or
C 16 ，C 17 R is connected by single bond 3 ，R 4 And C 16 、C 17 Together forming a three-membered ring containing 1 oxygen atom,
R 5 is COR 10 Wherein R is 10 Is H or CH 2 R 11 Wherein R is 11 Is OH or OCOR 12 Wherein R is 12 Is C 1～6 An alkyl group.
3. The dehalogenation process of a 9-halosteroid compound according to claim 1, wherein said formate is selected from sodium formate, potassium formate, ammonium formate, or a combination thereof; and/or the number of the groups of groups,
the hypophosphite is selected from sodium hypophosphite, potassium hypophosphite, ammonium hypophosphite, lithium hypophosphite, or a combination thereof; and/or the number of the groups of groups,
the substituted acetic acid is selected from thioglycolic acid,
the hydrazine compound is selected from hydrazine and/or hydrazine hydrate, and/or,
the organic amine containing 1-6 carbon atoms is selected from methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, propylamine, dipropylamine, tri-n-propylamine, diisopropylamine, diisopropylethylamine, butylamine, tetramethyl ethylenediamine, cyclohexylamine, and/or,
The nitrogen-containing heterocyclic compound is selected from dimethylaniline, nitrogen methylmorpholine, imidazole, piperazine, methylpiperazine, dimethylpiperazine, pyrrolidine, N-methylpyrrolidine, piperidine, N-methylpiperidine, pyridine, 4-dimethylaminopyridine, tetramethylguanidine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, or a combination thereof, and/or,
the organic alcohol amine containing 1-4 carbon atoms is selected from ethanolamine, diethanolamine, triethanolamine, isopropanolamine, or a combination thereof, and/or,
the mercaptan containing 1-6 carbon atoms is selected from ethanethiol, propanethiol, cyclopentathiol, benzylmercaptan, or combinations thereof, and/or,
the thioorganic acid is selected from thioacetic acid, thiomalic acid, thiobenzoic acid, ethyl thioacetate, or a combination thereof, and/or,
the titanium-containing material is selected from titanium dioxide and nitrogen-doped TiO 2 、Bi 2 O 3 /TiO 2 Strontium-doped titanium dioxide, cu-doped TiO 2 、Fe/TiO 2 、Fe 3 O 4 /SiO 2 /TiO 2 Mesoporous titanium dioxide/porous carbon, V 2 O 5 /BiVO 4 /TiO 2 Titanium dioxide with surface modified by organic matters, g-C 3 N 4 /TiO 2 、TiO 2 /Cds、WO 3 /TiO 2 Ag doped TiO 2 Iron-doped TiO 2 Or a combination thereof, and/or
The zinc-containing material is selected from ZnO and Bi 2 O 3 -ZnO, co/ZnO, carbon fiber/ZnO, biomass charcoal/ZnO, ag-ZnO, zn 2 SnO4-ZnO、CuS/ZnO、Ce/ZnO、Fe 3 O 4 -ZnO, pt-ZnO/C, znSe/ZnO, or combinations thereof, and/or
The bismuth-containing material is selected from bismuth oxide, biOCl, biOBr, agBr/BiOBr, negative Pt, au and Ru BiOBr, I-ion doped BiOBr, la doped BiOBr, tungsten doped BiOBr, bi 2 S 3 /BiOBr、g-C 3 N 4 /BiOBr、BiOBr/NaBiO、Ag 3 PO 4 /BiOBr、Pd/BiOBr、BiOBr/NaBiO 3 Ni/BiOBr, bi-containing complexes or combinations thereof, and/or
The composition contains g-C 3 N 4 Is selected from g-C 3 N 4 /MoO 3 、WO 3 /g-C 3 N 4 、CeO 2 /g-C 3 N 4 、g-C 3 N 4 /SnO 2 、g-C 3 N 4 /MoS 2 、g-C 3 N 4 /Ag 3 PO 4 、g-C 3 N 4 /Bi 2 WO 6 、g-C 3 N 4 /MnO 2 、g-C 3 N 4 /CoS 2 Or a combination thereof, and/or
The aromatic thiophenol compound is selected from the group consisting of the structures
Wherein A is carbon or nitrogen, R is hydrogen, alkyl, hydroxy, methoxy, aryl, carboxyl, amino or halogen, 1.ltoreq.m.ltoreq.5, and/or
The diaryl disulfide compound is selected from the group consisting of structures of
Wherein R is hydrogen, alkyl, hydroxy, methoxy, aryl, carboxyl, amino or halogen, 1.ltoreq.n.ltoreq.5, and/or
The phenazine compound is selected from the structure of
Wherein R is a compound of formula (I) 1 And R is 2 Each independently is hydrogen, alkyl, aryl, R 1 And R is 2 May be the same or different; and/or +.>
The phenothiazine compound is selected from the group consisting of the following structures
Wherein R is a compound of formula (I) 1 Is hydrogen, alkyl or aryl; and/or
The carbazole compound is selected from the structure of
Wherein Cz is a carbazole group, CN is cyano, FG is alkyl, aryl, methoxy, mercapto, carboxyl or hydroxy, 2.ltoreq.m.ltoreq.5, n is 1 or 2, m+n+x.ltoreq.6, and/or
The triphenylamine compound is selected from the structure of
Wherein DPA is a diphenylamine group, CN is cyano, FG is alkyl, aryl, methoxy, mercapto, carboxyl or hydroxy, 2.ltoreq.m.ltoreq.5, n is 1 or 2, m+n+x.ltoreq.6,
the dye is selected from coumarin, acridine, fluorescein, phthalocyanine, porphyrin, perylene diimide, methylene blue, xanthene, benzophenone, or their combination.
4. The dehalogenation method of a 9-halogenostatic compound according to claim 1, wherein said auxiliary is selected from the group consisting of thioglycolic acid, tetramethyl ethylenediamine, triethylamine, hanes, tri-N-propylamine, formic acid, triethanolamine, thioglycolic acid, diethylamine, hypophosphorous acid, butylamine, cyclohexylamine, thiobenzoic acid, hypophosphorous acid, diisopropylethylamine, potassium hypophosphite, hydrazine hydrate, thioacetic acid, 4-dimethylaminopyridine, thiomalic acid, 1, 4-dimethylpiperazine, benzyl mercaptan, azamethylpyrrolidine, ethyl thioacetate, azamethylmorpholine, cyclopentathiol, N-methylpiperidine, acetic acid, 1, 8-diazabicyclo [5.4.0] undec-7-ene, sodium hypophosphite, tetramethylguanidine, phosphorous acid, dimethylaniline, glycolic acid, isopropanolamine, thioglycolic acid, or combinations thereof,
More preferably, the adjuvant is selected from the group consisting of a combination of thioglycolic acid and tetramethyl ethylenediamine, a combination of triethylamine and hans ester, a combination of tri-N-propylamine and formic acid, a combination of triethanolamine and thioglycolic acid, a combination of diethylamine and hypophosphorous acid, a combination of butylamine and formic acid, a combination of cyclohexylamine and thiobenzoic acid, a combination of triethanolamine and hypophosphorous acid, a combination of diisopropylethylamine and potassium hypophosphite, a combination of hydrazine hydrate and thioacetic acid, a combination of 4-dimethylaminopyridine and thiomalic acid, a combination of 1, 4-dimethylpiperazine and benzylmercaptan, a combination of azamethylpyrrolidine and ethyl thioacetate, a combination of azamethylmorpholine and cyclopentanethiol, a combination of N-methylpiperidine and acetic acid, a combination of 1, 8-diazabicyclo [5.4.0] undec-7-ene and sodium hypophosphite, a combination of tetramethylguanidine and phosphorous acid, a combination of dimethylaniline and glycolic acid, a combination of isopropanolamine and thioglycolic acid.
5. The dehalogenation process of a 9-halogeno steroid according to claim 1, wherein said catalyst is selected from the group consisting of catalyst 10, pt (0.3 wt.%)/TiO 2 、g-C 3 N 4 /MoO 3 Bismuth oxide, 2, 6-dimethylbenzene thiophenol, bismuth subsalicylate, bismuth sulfide, ortho-amino thiophenol, thiosalicylic acid, titanium oxide, catalyst 11, catalyst 12, catalyst 13, catalyst 14, catalyst 15, catalyst 16, catalyst 17, catalyst 18, catalyst 19, catalyst 20, or combinations thereof, wherein the catalysts 10-20 have the structural formula:
6. The method for dehalogenation of a 9-halogeno steroid compound according to claim 1, wherein the wavelength of visible light is 370-480nm, and/or
The molar ratio of the compound I, the auxiliary agent and the catalyst is 1 (1-20): 0.01-2, and/or
The temperature of the photocatalytic reaction is 0 to 70 ℃, more preferably 4 to 40 ℃, and/or
The solvent for the photocatalytic reaction is selected from alcohols containing 1 to 4 carbons, tetrahydrofuran, 2-methyltetrahydrofuran, N-dimethylformamide, N-dimethylacetamide, azomethylpyrrolidone, acetone, butanone, methyl isobutyl ketone, methylene chloride, ethyl acetate, or a mixture thereof with water.
7. The dehalogenation method of a 9-halogeno steroid compound according to claim 1, wherein said compound I is compound I-1, said auxiliary agents are thioglycolic acid and tetramethyl ethylenediamine, said catalyst is catalyst 10, and the wavelength of said visible light is 440nm; or (b)
The compound I is a compound I-2, the auxiliary agent is triethylamine and hans ester, and the catalyst is Pt/TiO 2 Wherein the weight of Pt containsThe amount is 0.3%, and the wavelength of the visible light is 370nm; or (b)
The compound I is a compound I-3, the auxiliary agent is tri-n-propylamine and formic acid, and the catalyst is g-C 3 N 4 /MoO 3 The wavelength of the visible light is 370nm; or (b)
The compound I is a compound I-4, the auxiliary agent is triethanolamine and thioglycollic acid, the catalyst is bismuth oxide, and the wavelength of visible light is 440nm; or (b)
The compound I is a compound I-5, the auxiliary agent is diethylamine and hypophosphorous acid, the catalyst is 2, 6-dimethylbenzenesulfide, and the wavelength of visible light is 390nm; or (b)
The compound I is a compound I-6, the auxiliary agent is butylamine and formic acid, the catalyst is bismuth subsalicylate, and the wavelength of visible light is 370nm; or (b)
The compound I is a compound I-7, the auxiliary agent is cyclohexylamine and thiobenzoic acid, the catalyst is bismuth sulfide, and the wavelength of visible light is 440nm; or (b)
The compound I is a compound I-8, the auxiliary agent is triethanolamine and hypophosphorous acid, the catalyst is o-amino thiophenol, and the wavelength of visible light is 370nm; or (b)
The compound I is a compound I-9, the auxiliary agent is diisopropylethylamine and potassium hypophosphite, the catalyst is thiosalicylic acid, and the wavelength of visible light is 456nm; or (b)
The compound I is a compound I-10, the auxiliary agent is diisopropylethylamine, the catalyst is titanium oxide, and the wavelength of visible light is 420nm; or (b)
The compound I is a compound I-11, the auxiliary agent is hydrazine hydrate and thioacetic acid, the catalyst is a catalyst 11, and the wavelength of visible light is 450nm; or (b)
The compound I is a compound I-12, the auxiliary agent is 4-dimethylaminopyridine and thiomalic acid, the catalyst is a catalyst 12, and the wavelength of visible light is 390nm; or (b)
The compound I is a compound I-13, the auxiliary agent is 1, 4-dimethylpiperazine and benzyl mercaptan, the catalyst is a catalyst 13, and the wavelength of visible light is 400nm; or (b)
The compound I is a compound I-14, the auxiliary agent is nitrogen methyl pyrrolidine and ethyl thioacetate, the catalyst is a catalyst 14, and the wavelength of visible light is 440nm; or (b)
The compound I is a compound I-15, the auxiliary agent is nitrogen methylmorpholine and cyclopentanethiol, the catalyst is a catalyst 15, and the wavelength of visible light is 400nm; or (b)
The compound I is a compound I-16, the auxiliary agent is N-methylpiperidine and acetic acid, the catalyst is a catalyst 16, and the wavelength of visible light is 370nm; or (b)
The compound I is a compound I-17, the auxiliary agent is 1, 8-diazabicyclo [5.4.0] undec-7-ene and sodium hypophosphite, the catalyst is a catalyst 17, and the wavelength of visible light is 370nm; or (b)
The compound I is a compound I-18, the auxiliary agent is tetramethyl guanidine and phosphorous acid, the catalyst is a catalyst 18, and the wavelength of visible light is 370nm; or (b)
The compound I is a compound I-19, the auxiliary agent is dimethylaniline and glycollic acid, the catalyst is a catalyst 19, and the wavelength of visible light is 370nm; or (b)
The compound I is a compound I-20, the auxiliary agent is isopropanolamine and thioglycollic acid, the catalyst is a catalyst 20, the wavelength of visible light is 500nm,
wherein the structures, auxiliaries and catalysts of compounds I-1 to I-20 are shown in Table 1 below:
TABLE 1
8. A corticosteroid drug prepared by the dehalogenation process of any one of claims 1 to 7 and intermediates thereof.
9. Use of a combination of an auxiliary agent and a catalyst for removing halogen from a compound, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine and iodine, and the auxiliary agent is selected from the group consisting of formic acid and formate salts, hypophosphorous acid and hypophosphite salts, acetic acid and substituted acetic acids, hydrazines, cyclohexene, hanes, organic amines containing 1 to 6 carbons, nitrogen containing heterocyclic compounds, organic alcohols amines containing 1 to 4 carbons, thiols containing 1 to 6 carbons, thioorganic acids, or combinations thereof, and
The catalyst is selected from titanium-containing materials, zinc-containing materials, bismuth-containing materials, g-C-containing materials 3 N 4 The material of (C) is selected from the group consisting of aromatic thiophenol compounds, diaryl disulfide compounds, phenazine compounds, phenothiazine compounds, carbazole compounds, triarylamine compounds, dyes, photoinitiators, iridium or ruthenium complexes with pyridine compounds, or combinations thereof.
10. The use according to claim 9, wherein the adjuvant is selected from thioglycolic acid, tetramethyl ethylenediamine, triethylamine, hanes, tri-N-propylamine, formic acid, triethanolamine, thioglycolic acid, diethylamine, hypophosphorous acid, butylamine, cyclohexylamine, thiobenzoic acid, hypophosphorous acid, diisopropylethylamine, potassium hypophosphite, hydrazine hydrate, thioacetic acid, 4-dimethylaminopyridine, thiomalic acid, 1, 4-dimethylpiperazine, benzylmercaptan, azamethylpyrrolidine, ethyl thioacetate, azamethylmorpholine, cyclopentanethiol, N-methylpiperidine, acetic acid, 1, 8-diazabicyclo [5.4.0] undec-7-ene, sodium hypophosphite, tetramethylguanidine, phosphorous acid, dimethylaniline, glycolic acid, isopropanolamine, thioglycolic acid, or combinations thereof,
more preferably, the adjuvant is selected from the group consisting of a combination of thioglycolic acid and tetramethyl ethylenediamine, a combination of triethylamine and hanes, a combination of tri-N-propylamine and formic acid, a combination of triethanolamine and thioglycolic acid, a combination of diethylamine and hypophosphorous acid, a combination of butylamine and formic acid, a combination of cyclohexylamine and thiobenzoic acid, a combination of triethanolamine and hypophosphorous acid, a combination of diisopropylethylamine and potassium hypophosphite, a combination of hydrazine hydrate and thioacetic acid, a combination of 4-dimethylaminopyridine and thiomalic acid, a combination of 1, 4-dimethylpiperazine and benzylmercaptan, a combination of azamethylpyrrolidine and ethyl thioacetate, a combination of azamethylmorpholine and cyclopentanethiol, a combination of N-methylpiperidine and acetic acid, a combination of 1, 8-diazabicyclo [5.4.0] undec-7-ene and sodium hypophosphite, a combination of tetramethylguanidine and phosphorous acid, a combination of dimethylaniline and glycolic acid, a combination of isopropanolamine and thioglycolic acid, and
The catalyst is selected from catalyst 10, pt (0.3 wt.%)/TiO 2 、g-C 3 N 4 /MoO 3 Bismuth oxide, 2, 6-dimethylbenzene thiophenol, bismuth subsalicylate, bismuth sulfide, ortho-amino thiophenol, thiosalicylic acid, titanium oxide, catalyst 11, catalyst 12, catalyst 13, catalyst 14, catalyst 15, catalyst 16, catalyst 17, catalyst 18, catalyst 19, catalyst 20, or combinations thereof, wherein the catalysts 10-20 have the structural formula:
11. use according to claim 9 or 10, characterized in that the combination of promoter and catalyst is shown in table 2 below:
TABLE 2
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| CN105566426A (en) * | 2016-01-27 | 2016-05-11 | 山东赛托生物科技股份有限公司 | Synthesis method for 16alpha-hydroxyprednisolone |
| CN108002991A (en) * | 2017-12-20 | 2018-05-08 | 陕西师范大学 | A kind of visible light catalytic halogenated aryl hydrocarbon dehalogenation method without photoredox catalyst |
| CN111018932A (en) * | 2019-11-28 | 2020-04-17 | 奥锐特药业股份有限公司 | 9-position dehalogenation method for steroid compound |
| CN111333690A (en) * | 2018-12-18 | 2020-06-26 | 奥锐特药业股份有限公司 | Preparation method of 9-site dehalogenation of 9-halogenated steroid hormone compound |
| CN111499677A (en) * | 2019-01-31 | 2020-08-07 | 奥锐特药业股份有限公司 | Preparation method of steroid hormone compound 9-position dehalogenation |
| CN112142543A (en) * | 2019-06-26 | 2020-12-29 | 北京工商大学 | Dehalogenation method of covalent organic framework material photocatalytic halogenated aromatic compound |
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| CN105566426A (en) * | 2016-01-27 | 2016-05-11 | 山东赛托生物科技股份有限公司 | Synthesis method for 16alpha-hydroxyprednisolone |
| CN108002991A (en) * | 2017-12-20 | 2018-05-08 | 陕西师范大学 | A kind of visible light catalytic halogenated aryl hydrocarbon dehalogenation method without photoredox catalyst |
| CN111333690A (en) * | 2018-12-18 | 2020-06-26 | 奥锐特药业股份有限公司 | Preparation method of 9-site dehalogenation of 9-halogenated steroid hormone compound |
| CN111499677A (en) * | 2019-01-31 | 2020-08-07 | 奥锐特药业股份有限公司 | Preparation method of steroid hormone compound 9-position dehalogenation |
| CN112142543A (en) * | 2019-06-26 | 2020-12-29 | 北京工商大学 | Dehalogenation method of covalent organic framework material photocatalytic halogenated aromatic compound |
| CN111018932A (en) * | 2019-11-28 | 2020-04-17 | 奥锐特药业股份有限公司 | 9-position dehalogenation method for steroid compound |
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