CN110563670A - sulfur-containing piperazine derivative and application thereof - Google Patents
sulfur-containing piperazine derivative and application thereof Download PDFInfo
- Publication number
- CN110563670A CN110563670A CN201910798061.XA CN201910798061A CN110563670A CN 110563670 A CN110563670 A CN 110563670A CN 201910798061 A CN201910798061 A CN 201910798061A CN 110563670 A CN110563670 A CN 110563670A
- Authority
- CN
- China
- Prior art keywords
- formula
- sulfur
- piperazine derivative
- reaction
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 239000011593 sulfur Substances 0.000 title claims abstract description 41
- 229910052717 sulfur Inorganic materials 0.000 title claims abstract description 41
- 150000004885 piperazines Chemical class 0.000 title claims abstract description 37
- 150000001875 compounds Chemical class 0.000 claims abstract description 56
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 56
- 238000006243 chemical reaction Methods 0.000 claims abstract description 49
- 230000003647 oxidation Effects 0.000 claims abstract description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 20
- 239000000758 substrate Substances 0.000 claims abstract description 13
- 150000001299 aldehydes Chemical class 0.000 claims abstract description 12
- 150000002576 ketones Chemical class 0.000 claims abstract description 12
- 239000007800 oxidant agent Substances 0.000 claims abstract description 9
- 239000012074 organic phase Substances 0.000 claims description 22
- 239000000243 solution Substances 0.000 claims description 16
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 8
- 230000003213 activating effect Effects 0.000 claims description 7
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 239000012190 activator Substances 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 150000007530 organic bases Chemical class 0.000 claims description 6
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- YQRQLDYRHQGYBC-UHFFFAOYSA-N 1,3-dibromourea Chemical group BrNC(NBr)=O YQRQLDYRHQGYBC-UHFFFAOYSA-N 0.000 claims description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000001118 alkylidene group Chemical group 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims 1
- 150000008065 acid anhydrides Chemical class 0.000 claims 1
- 238000011084 recovery Methods 0.000 abstract description 12
- 230000001590 oxidative effect Effects 0.000 abstract description 11
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 description 11
- 239000005660 Abamectin Substances 0.000 description 11
- 229950008167 abamectin Drugs 0.000 description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- DOIYNXTZSLKLEH-UHFFFAOYSA-N 1,4-bis(7-methylsulfanylheptyl)piperazine Chemical compound CSCCCCCCCN1CCN(CCCCCCCSC)CC1 DOIYNXTZSLKLEH-UHFFFAOYSA-N 0.000 description 7
- FEUGALVUZSBIDW-UHFFFAOYSA-N 1-methyl-4-(3-methylsulfanylpropyl)piperazine Chemical compound CSCCCN1CCN(C)CC1 FEUGALVUZSBIDW-UHFFFAOYSA-N 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- QULXYLWCVZBLGF-UHFFFAOYSA-N CN1CCN(CCCS(C)=O)CC1 Chemical compound CN1CCN(CCCS(C)=O)CC1 QULXYLWCVZBLGF-UHFFFAOYSA-N 0.000 description 5
- 238000005191 phase separation Methods 0.000 description 5
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 229960003276 erythromycin Drugs 0.000 description 4
- 238000009776 industrial production Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- JHHIWKMSYXNJJA-UHFFFAOYSA-N 1,4-bis(7-methylsulfinylheptyl)piperazine Chemical compound CS(CCCCCCCN1CCN(CCCCCCCS(C)=O)CC1)=O JHHIWKMSYXNJJA-UHFFFAOYSA-N 0.000 description 3
- ONXOFGPJUBUHAR-UHFFFAOYSA-N 1-(2-methoxypropyl)-4-(3-methylsulfanylpropyl)piperazine Chemical compound CC(CN1CCN(CCCSC)CC1)OC ONXOFGPJUBUHAR-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 229930006677 Erythromycin A Natural products 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000007086 side reaction Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000006257 total synthesis reaction Methods 0.000 description 3
- KKEYLVXRRZWHRB-UHFFFAOYSA-N 1-bromo-7-methylsulfanylheptane Chemical compound CSCCCCCCCBr KKEYLVXRRZWHRB-UHFFFAOYSA-N 0.000 description 2
- RAVGOEYQXCTKGT-UHFFFAOYSA-N 1-chloro-3-methylsulfanylpropane Chemical compound CSCCCCl RAVGOEYQXCTKGT-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 238000006859 Swern oxidation reaction Methods 0.000 description 2
- 238000001994 activation Methods 0.000 description 2
- 150000001263 acyl chlorides Chemical class 0.000 description 2
- -1 aldehyde ketone Chemical class 0.000 description 2
- 125000005012 alkyl thioether group Chemical group 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- UPWOEMHINGJHOB-UHFFFAOYSA-N oxo(oxocobaltiooxy)cobalt Chemical compound O=[Co]O[Co]=O UPWOEMHINGJHOB-UHFFFAOYSA-N 0.000 description 2
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- RXZBMPWDPOLZGW-XMRMVWPWSA-N (E)-roxithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=N/OCOCCOC)/[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 RXZBMPWDPOLZGW-XMRMVWPWSA-N 0.000 description 1
- TWVLNKKMSLYUQQ-UHFFFAOYSA-N 1,3,4,6-tetrachloro-3a,6a-dihydroimidazo[4,5-d]imidazole-2,5-dione Chemical compound ClN1C(=O)N(Cl)C2C1N(Cl)C(=O)N2Cl TWVLNKKMSLYUQQ-UHFFFAOYSA-N 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- OFTZZDZZNXTWFO-UHFFFAOYSA-N 1,3-dichloro-5-ethyl-5-methylimidazolidine-2,4-dione Chemical compound CCC1(C)N(Cl)C(=O)N(Cl)C1=O OFTZZDZZNXTWFO-UHFFFAOYSA-N 0.000 description 1
- FEDWUGYKPJNTNR-UHFFFAOYSA-N 1-(2-methoxypropyl)piperazine Chemical compound COC(C)CN1CCNCC1 FEDWUGYKPJNTNR-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- 238000005675 Corey-Kim oxidation reaction Methods 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 229960005224 roxithromycin Drugs 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
the invention relates to the technical field of organic synthesis, and particularly discloses a sulfur-containing piperazine derivative and application thereof. The structural formula of the sulfur-containing piperazine derivative is shown as a formula I or II, and the sulfur-containing piperazine derivative is applied to an oxidation system: the compound shown as the formula I or II is used as an oxidizing agent to oxidize the hydroxyl of a reaction substrate into corresponding aldehyde or ketone. The sulfur-containing piperazine derivative provided by the invention has no generation of foreign matters in the reaction process in a hydroxyl oxidation system, and the sulfur-containing piperazine derivative serving as an oxidant after the reaction is finished can be recycled after being activated, so that the recovery rate is more than 90%.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a sulfur-containing piperazine derivative and application thereof.
background
The synthesis of drugs belongs to a branch of organic synthetic chemistry, and the organic synthesis can be divided into total synthesis and semi-synthesis from the used raw materials. Semi-synthetic (semi synthesis): the process of preparing complex compound with natural product with certain basic structure includes chemical structure modification and physical treatment. Total synthesis (total synthesis): the process of preparing complex compound with chemical product with simple chemical structure as initial material and through a series of chemical reactions and physical treatment. In the drug synthesis, the complex organic compounds are very important compounds, and have outstanding effects in the aspects of antibiosis, antiphlogosis, anticancer and the like, such as erythromycin, roxithromycin, azithromycin, abamectin, various marine products and the like.
In the synthesis of complex compounds, oxidation schemes are often involved, of which the Stevens oxidation and the Critical-MOS reactions are two important reaction types. Stevens oxidation (Swern oxidation): under the action of dimethyl sulfoxide and acyl chloride, alcohol is treated by alkali to obtain corresponding aldehyde ketone, and dimethyl sulfoxide is converted into dimethyl sulfide in the reaction process; cori-gold oxidation (Corey-kim oxidation): the alcohol is treated by alkali under the action of N-chlorosuccinimide and dimethyl sulfide to obtain the corresponding aldehyde ketone. However, dimethyl sulfide, which is involved in the traditional Stevens oxidation and Critical-gold oxidation reactions, has an unpleasant odor and has an olfactive threshold of about 0.37mg/m3Extremely low concentrations can be sniffed. If the traditional Stevens oxidation reaction and the traditional Kerri-gold oxidation reaction are adopted for large-scale production and use, peculiar smell can be generated in the production field and the surrounding environment, and the environment is greatly polluted, so that the dimethyl sulfoxide and the dimethyl sulfide are difficult to be applied to industrial production.
At present, the structure of the morpholine ring-containing sulfur-containing compound is shown as the formula (A) in the literature report, and the morpholine ring-containing sulfur-containing compound is applied to a Stevens oxidation reaction system and a Critical-metal oxidation reaction system. However, in the actual reaction process, the compound is found to have particularly good water solubility, the organic solvent is difficult to extract and recover, the recovery rate is less than 20 percent, and the compound is difficult to be used for industrial production. In addition, it has been reported that a sulfur-containing compound linked to a resin is used in a schwen oxidation reaction, and the structure thereof is represented by the formula (B), and the purpose of recovering the compound can be achieved by filtering the resin after the reaction is completed. However, the resin compound has the problems of easy breakage and aging of resin particles, poor stability, small contact area of solid and liquid phases in the reaction process, low reaction efficiency and the like in industrial production, and is difficult to be applied to industrial production on a large scale. Therefore, it is necessary to develop a compound which is free from offensive odor (sulfide including thioether, thiol, etc.), easily recovered, highly stable, and highly efficient, and which can be applied to the swern oxidation and the coriolis-mos oxidation reaction systems on a large scale.
Disclosure of Invention
The invention provides a sulfur-containing piperazine derivative and application thereof, aiming at the problems of peculiar smell, low recovery rate and the like of an oxidant in the existing Stevens oxidation and Critical-metal oxidation reaction system.
In order to achieve the purpose of the invention, the embodiment of the invention adopts the following technical scheme:
A sulfur-containing piperazine derivative, the structural formula is shown as formula I or II,
Wherein X is S or sulfinyl, R is hydrogen or C1-C4A straight-chain or branched alkane radical of (A), R1And R3Is C1-C10Linear or branched alkyl or alkoxy of, R2And R4is C2-C10Linear or branched alkylidene or alkoxy groups of (a); in formulae I or II, R, R1and R3are identical or different from one another, in formula I, R2And R4the same or different from each other.
Compared with the prior art, the sulfur-containing piperazine derivative provided by the invention has the advantages that the boiling point is higher, the stability is good, the water solubility is good, the sulfur-containing piperazine derivative is used for oxidizing hydroxyl in a complex organic structure, the reaction efficiency is high, no peculiar smell is generated, the reaction is terminated by washing after the reaction is finished, the oxidized product enters an organic phase, the sulfur-containing piperazine derivative enters an aqueous phase, the sulfur-containing piperazine derivative can be recovered by adjusting the pH value, the recovery is convenient, and the recovery rate is high. Therefore, the sulfur-containing piperazine derivative provided by the invention can be recycled while generating no peculiar smell substances, greatly reduces the cost and is beneficial to environmental protection.
Further, said R1And R3The alkoxy contains a methoxy or ethoxy structure. Improves the stability of the compound, simultaneously adopts methoxy or ethoxy end capping, reduces reactable sites, avoids side reactions,Ensuring the efficiency of the oxidation reaction.
Further, the preparation method of the compound shown in the formula I or II comprises the following steps:
When X is S (sulfur), the compound shown in formula I or II is prepared by condensing corresponding halogenated alkyl thioether and piperazine ring (or piperazine ring) containing substituent under alkaline condition to obtain a compound containing thioether bond, wherein the reaction process is shown as the following formula, and Y is Cl, Br or I;
When X is sulfinyl, the compound shown in formula I or II is prepared into a compound containing thioether bond by condensing corresponding halogenated alkyl thioether and piperazine ring containing substituent under alkaline condition, and then is prepared into a compound containing sulfinyl through oxidation reaction, wherein the reaction process is shown as the following formula, and Y is Cl, Br or I. The oxidant used in the oxidation reaction can be selected from hydrogen peroxide, sodium hypochlorite, peroxybenzoic acid or peroxyacetic acid. Adding a catalytic amount of Fe-containing catalyst during the oxidation reaction3+or Co3+Of (e.g. FeCl)3、Co2O3) The conversion selectivity is improved, the generation of byproducts is reduced, and the purity of a target product is improved.
The invention also provides the application of the sulfur-containing piperazine derivative in an oxidation system, wherein the compound shown in the formula I or II is used as an oxidant to oxidize the hydroxyl of a reaction substrate into corresponding aldehyde or ketone.
Furthermore, the dosage of the compound shown in the formula I or II is 90-300% of the mole number of the substrate, and the proper addition amount is selected according to the specific selection of the sulfur-containing piperazine derivative and the number of target hydroxyl groups in the reaction substrate, so that the target hydroxyl groups in the reaction substrate are completely oxidized into corresponding aldehyde or ketone.
Furthermore, the temperature of the oxidation reaction is-78 ℃ to-5 ℃, the stability of the oxidant is ensured, side reactions are reduced, the efficiency of the oxidation reaction is improved, and the yield of the target product is ensured.
further, when X is S, the compound shown in formula I or II is applied to a Critical-metal oxidation system, and is used for oxidizing hydroxyl of a reaction substrate into corresponding aldehyde or ketone under the condition of organic base and the combined action of an activator; when X is sulfinyl, the compound shown in the formula I or II is applied to a Stevens oxidation system, and under the condition of organic base, the compound and an activating agent are combined to act, so that the hydroxyl of a reaction substrate is oxidized into corresponding aldehyde or ketone. The sulfur-containing piperazine derivative and an activating agent form an oxidation activator, and under the action of an organic base, the hydroxyl of a reaction substrate is oxidized into a corresponding aldehyde or ketone structure.
Further, in the Critical-MOS system, the activator includes chlorine gas, N-chlorosuccinimide, N-bromosuccinimide, and a compound having an N, N' -dichloro or dibromourea structure (e.g., 1, 3-dichloro-5, 5-dimethylhydantoin, 1, 3-dichloro-5-ethyl-5-methylimidazoline-2, 4-dione, or tetrachloroglycoluril); in the schwann oxidation system, the activating agent is acyl chloride or anhydride, and concretely comprises phenyl phosphate diacid chloride, solid phosgene, oxalyl chloride and acetic anhydride. The molar ratio of the activating agent to the compound shown in the formula I, II, III or IV is 0.25-3:1, so that the oxidation activating agent is formed, the reaction activity is high, and the side reaction is less.
Further, the organic base includes triethylamine, tetramethylethylenediamine, tributylamine, diisopropylethylamine, and pyridine. The molar ratio of organic base to compound of formula I or II is 0.5-3:1, deprotonating the intermediate formed by the hydroxyl group and the oxidizing active agent to ultimately form the corresponding aldehyde or ketone structure.
Further, the method for recovering the compound shown in the formula I or II after the oxidation reaction is finished comprises the following steps: dissolving the product corresponding to the compound shown in the formula I or II after reaction in an aqueous solution with the pH value less than 5, adjusting the pH value of the solution to be more than 9, extracting by using an organic solvent, collecting an organic phase, concentrating and drying to obtain the compound shown in the formula I or II. After the sulfur-containing piperazine derivative is used for the hydroxyl oxidation reaction, the recovery is convenient, the recovery rate is more than or equal to 90 percent, the cyclic utilization can be realized, and the cost is saved.
the sulfur-containing piperazine derivative provided by the invention is applied to an oxidation system as an oxidant, the hydroxyl of a reaction substrate is oxidized into corresponding aldehyde or ketone, no peculiar smell substance is generated in the reaction process, the yield of a target product is ensured, and the sulfur-containing piperazine derivative can be recycled, so that the cost is saved, and the sulfur-containing piperazine derivative is green and environment-friendly.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example 1
a sulfur-containing piperazine derivative, N-methyl-N' - [3- (methylthio) propyl ] piperazine, has a structural formula shown in formula V.
the preparation method of the N-methyl-N' - [3- (methylthio) propyl ] piperazine comprises the following steps: 2.8g of 3-chloropropyl-methyl sulfide is dissolved in 10ml of N, N-dimethylformamide, then 1.92g of N-methylpiperazine and 2.4g of sodium methoxide are added, the mixture is stirred and heated to 80 ℃, the reaction is finished after 2 hours of stirring at constant temperature, 20ml of dichloromethane is added, water (30ml multiplied by 2 times) is used for washing, phase separation is carried out, and the organic phase is dried by anhydrous magnesium sulfate and then concentrated to obtain 3.5g of colorless oily matter. The yield thereof was found to be 87.5%. The hydrogen spectrum is: 1H NMR (CDCl3) δ ppm 2.44-2.48(m,4H),2.35(m,8H),2.26(s,3H),2.14(s,3H),1.76(t, J ═ 3.0, 2H). LC-MS [ M + H ] +: 189.1347.
the compound is used in a Critical-metal oxidation system to oxidize a 4' -hydroxyl in a structure of 5-allyloxycarbonyl ester abamectin B1 (prepared by taking abamectin B1 as an initial raw material and protecting the 5-hydroxyl), and the method specifically comprises the following steps:
(1) Under the protection of nitrogen, 1.4g of N-chlorosuccinimide (NCS) is suspended and dispersed in 20ml of dichloromethane, after the temperature is reduced to-25 ℃, 1.5g of compound N-methyl-N' - [3- (methylthio) propyl ] piperazine is added, and the mixture is stirred for 30min at low temperature;
(2) 5g of 5-allyloxycarbonyl ester abamectin B1 is dissolved in 5ml of dichloromethane and is dripped into the step (1), after dripping is finished for about 10min, the stirring is continued for 30min under the condition of keeping at-25 ℃;
(3) Adding 1.0g of triethylamine into the step (2), keeping the temperature and stirring for 1 hour, and finishing the reaction;
(4) Heating the reaction system to room temperature, adding 20ml of water, stirring, adjusting the pH value to 4 by using a 5% hydrochloric acid solution, carrying out layering, collecting an organic phase, retaining a water phase, drying the organic phase by using anhydrous magnesium sulfate, and concentrating to obtain 4.5g of an oxidation product, wherein the yield is 90%;
(5) after a 20% sodium hydroxide solution was added to the aqueous phase in step (4) to adjust the pH to 10, 30ml of a dichloromethane solution was added to conduct extraction, and the organic phase was collected, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure at 50 ℃.
example 2
A sulfur-containing piperazine derivative, N- [2- (methoxyl) propyl ] -N' - [3- (methylthio) propyl ] piperazine, has a structural formula shown in formula VI.
N- [2- (methoxy) propyl ] -N' - [3- (methylthio) propyl ] piperazine was prepared by condensing 3-chloropropyl-methyl sulfide with 1- (2-methoxypropyl) piperazine, and the reaction equation is as follows.
The compound is used in a Critical-metal oxidation system to oxidize the 4' -hydroxyl in the structure of 5-allyloxycarbonyl ester abamectin B1, and the method specifically comprises the following steps:
(1) Under the protection of nitrogen, 1.4g of NCS is suspended and dispersed in 20ml of dichloromethane, after the temperature is reduced to-25 ℃, 2.0g of compound N- [2- (methoxy) propyl ] -N' - [3- (methylthio) propyl ] piperazine is added, and the mixture is stirred for 30min under the condition of keeping low temperature;
(2) 5g of 5-allyloxycarbonyl ester abamectin B1 is dissolved in 5ml of dichloromethane and is dripped into the step (1), after dripping is finished for about 10min, the stirring is continued for 30min at the temperature of minus 25 ℃;
(3) adding 1.0g of triethylamine into the step (2), keeping the temperature and stirring for 1 hour, and finishing the reaction;
(4) Heating the reaction system to room temperature, adding 20ml of water, stirring, adjusting the pH value to 3.5 by using a 5% hydrochloric acid solution, layering, collecting an organic phase, retaining an aqueous phase, drying the organic phase by using anhydrous magnesium sulfate, and concentrating to obtain 4.6g of an oxidation product, wherein the yield is 92%;
(5) To the aqueous phase in step (4), 20% sodium hydroxide solution was added to adjust pH to 11, 35ml of dichloromethane was added and extraction was performed with stirring, and the organic phase was collected and dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure at 50 ℃.
Example 3
A sulfur-containing piperazine derivative, N-methyl-N' - [3- (methylsulfinyl) propyl ] piperazine, has a structural formula shown in formula VII.
N-methyl-N' - [3- (methylsulfinyl) propyl]The preparation method of piperazine comprises the following steps: taking N-methyl-N' - [3- (methylthio) propyl group]Adding 1.0g of piperazine into 3ml of water, stirring and cooling to 0-5 ℃, slowly dropping 0.64g of 30% hydrogen peroxide, keeping the temperature at 0-5 ℃, stirring for 1h, completing the reaction, reducing the pressure at 40 ℃, and carrying out rotary evaporation for 1h to evaporate the solvent to dryness, thus obtaining 1.10 of colorless oily matter with the yield of 94%. The hydrogen spectrum is:1H NMR(CDCl3)δppm:2.58(t,J＝4.6,2H),2.50(s,3H),2.46(t,J＝4.8,2H),2.35(m,8H),2.26(s,3H),1.73(t,J＝3.0,2H).LC-MS[M+H]+:205.1296。
the compound is used in a Stevens oxidation system to oxidize the 4' hydroxyl in the structure of 5-allyloxycarbonyl ester abamectin B1, and the method specifically comprises the following steps:
(1) Dissolving 10g of 5-allyloxycarbonyl ester abamectin B1, 1.3g of tetramethylethylenediamine and 4.5g of the compound N-methyl-N' - [3- (methylsulfinyl) propyl ] piperazine in 40ml of dichloromethane at room temperature, stirring and cooling to-5 ℃;
(2) Dissolving 1.8g of solid phosgene in 10ml of dichloromethane, slowly dropwise adding into the system in the step (1), finishing the addition for about 10min, stirring for 30min at the temperature of minus 5 ℃ after the dropwise addition is finished, and finishing the reaction;
(3) Heating the reaction system to room temperature, adding 40ml of water, adjusting the pH value to 4 by using a 5% hydrochloric acid solution, carrying out phase separation, collecting an organic phase, retaining a water phase, drying the organic phase by using anhydrous magnesium sulfate, and concentrating to obtain 9.18g of an oxidation product, wherein the yield is 92%;
(4) After a 20% NaOH solution was added to the aqueous phase in step (3) to adjust pH to 10, 50ml of dichloromethane was added for extraction, and the organic phase was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure at 50 ℃, and the compound N-methyl-N' - [3- (methylthio) propyl ] piperazine was recovered in an amount of 3.93g, with a recovery rate of 94.92%.
example 4
a sulfur-containing piperazine derivative, N-methyl-N '- [3- (methylsulfinyl) propyl ] piperazine, obtained by activating N-methyl-N' - [3- (methylthio) propyl ] piperazine recovered in example 3, the specific activation process comprises:
3.73g of N-methyl-N '- [3- (methylthio) propyl ] piperazine recovered in example 3 was added with 2.5g of 30% hydrogen peroxide and 3ml of water at 0 ℃ and reacted under stirring for 1 hour, followed by concentration under reduced pressure at 20 ℃ to obtain 4.05g of activated N-methyl-N' - [3- (methylsulfinyl) propyl ] piperazine.
The compound is used in a Stevens oxidation system to oxidize a 4' hydroxyl in a structure of 5-allyloxycarbonyl ester group abamectin B2 (prepared by taking abamectin B2 as an initial raw material and protecting the 5-hydroxyl), and the method specifically comprises the following steps:
(1) Dissolving 9g of 5-allyloxycarbonyl ester abamectin B2, 1.13g of tetramethylethylenediamine and activated N-methyl-N' - [3- (methylsulfinyl) propyl ] piperazine in 40ml of dichloromethane at room temperature, and cooling to-75 ℃;
(2) dissolving 1.8g of phenyl phosphate diacyl chloride in 10ml of dichloromethane, slowly dropwise adding into the step (1), wherein the addition is completed within about 10min, and stirring for 30min at-75 ℃ after the dropwise addition is completed to complete the reaction;
(3) Heating the reaction system to room temperature, adding 40ml of water, adjusting the pH value to 3 by using a 5% hydrochloric acid solution, carrying out phase separation, collecting an organic phase, retaining a water phase, drying the organic phase by using anhydrous magnesium sulfate, and concentrating to obtain 8.1g of an oxidation product, wherein the yield is 90.2%;
(4) After a 20% NaOH solution was added to the aqueous phase in step (3) to adjust pH 11, 50ml of dichloromethane was added for extraction, and the organic phase was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure at 50 ℃, and the compound N-methyl-N' - [3- (methylthio) propyl ] piperazine was recovered in an amount of 3.57g, with a recovery rate of 95.96%.
example 5
A sulfur-containing piperazine derivative, N, N' -di [7- (methylsulfinyl) heptyl ] piperazine, has a structural formula shown in formula VIII.
The N, N ' -bis [7- (methylsulfinyl) heptyl ] piperazine is prepared by reacting 7-bromoheptyl methyl sulfide with piperazine to obtain N, N ' -bis [7- (methylthio) heptyl ] piperazine, and oxidizing the N, N ' -bis [7- (methylthio) heptyl ] piperazine, wherein the reaction equation is as follows.
The compound is used in a Stevens oxidation system to oxidize the 3 'and 4' hydroxyl groups in the structure of the erythromycin A, and the method specifically comprises the following steps:
(1) Dissolving 10g of erythromycin A, 1.92g of tetramethylethylenediamine and 7.1g of the compound N, N' -bis [7- (methylsulfinyl) heptyl ] piperazine in 40ml of dichloromethane, stirring and cooling to-40 ℃;
(2) 2.73g of solid phosgene is dissolved in 10ml of dichloromethane and slowly dripped into the step (1), after dripping is finished for about 10min, stirring is carried out for 45min at the temperature of minus 40 ℃, and the reaction is finished;
(3) Heating the reaction system to room temperature, adding 40ml of water, adjusting the pH value to 3.5 by using a 5% hydrochloric acid solution, carrying out phase separation, collecting an organic phase, retaining an aqueous phase, drying the organic phase by using anhydrous magnesium sulfate, and concentrating to obtain 8.45g of an oxidation product, wherein the yield is 85%;
(4) After a 20% NaOH solution was added to the aqueous phase in step (3) to adjust pH to 10, 50ml of dichloromethane was added for extraction, and the organic phase was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure at 50 ℃, the compound N, N' -bis [7- (methylthio) heptyl ] piperazine was recovered in an amount of 5.98g, and the recovery rate was 91.40%.
example 6
A sulfur-containing piperazine derivative, N, N' -bis [7- (methylthio) heptyl ] piperazine, has a structural formula shown as formula IX.
N, N' -bis [7- (methylthio) heptyl ] piperazine was prepared by reacting 7-bromoheptyl methyl sulfide with piperazine, and the reaction equation is as follows.
The compound is used in a Critical-metal oxidation system to oxidize the 3 'and 4' hydroxyl groups in an erythromycin A structure, and the method specifically comprises the following steps:
(1) under the protection of nitrogen, 4.3g of NCS is suspended and dispersed in 40ml of dichloromethane, the temperature is reduced to minus 30 ℃, 4.7g of compound N, N' -bis [7- (methylthio) heptyl ] piperazine is added, and the mixture is kept warm and stirred for 30 min;
(2) dissolving 10g of erythromycin A in 10ml of dichloromethane, dropwise adding into the step (1), keeping the temperature and stirring for 30min after dropwise adding is finished for about 10 min;
(3) adding 3.1g of triethylamine in the step (2), keeping the temperature and stirring for 1 hour, and finishing the reaction;
(4) Heating the reaction system to room temperature, adding 40ml of water, adjusting the pH value to 4 by using a 5% hydrochloric acid solution, carrying out phase separation, collecting an organic phase, retaining a water phase, drying the organic phase by using anhydrous magnesium sulfate, and concentrating to obtain 8.3g of an oxidation product, wherein the yield is 83.5%;
(5) After a 20% NaOH solution was added to the aqueous phase in step (3) to adjust pH to 10, 50ml of dichloromethane was added for extraction, and the organic phase was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure at 50 ℃, and the compound N, N' -bis [7- (methylthio) heptyl ] piperazine was recovered in an amount of 4.33g, and the recovery rate was 92.10%.
From the above data, it can be seen that the sulfur-containing piperazine derivative provided in the embodiment of the present invention can replace dimethyl sulfoxide to perform a schner oxidation reaction or replace dimethyl sulfide to perform a curie-mos oxidation reaction, so as to oxidize hydroxyl groups in complex organic compounds into corresponding aldehydes or ketones, no odor substances are generated during the reaction process, and the sulfur-containing piperazine derivative serving as an oxidant after the reaction is completed can be recovered and recycled after activation, with a recovery rate of > 90%.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents or improvements made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (7)
1. A sulfur-containing piperazine derivative characterized by: the structural formula is shown as a formula I or a formula II,
Wherein X is S or sulfinyl, R is hydrogen or C1-C4A straight-chain or branched alkane radical of (A), R1and R3is C1-C10linear or branched alkyl or alkoxy of, R2And R4Is C2-C10Linear or branched alkylidene or alkoxy groups of (a); in formulae I or II, R, R1And R3Are identical or different from one another, in formula I, R2and R4The same or different from each other.
2. Use of a sulfur-containing piperazine derivative of claim 1 in an oxidation system, wherein: the compound shown in formula I or II is used as an oxidizing agent to oxidize the hydroxyl of a reaction substrate into corresponding aldehyde or ketone.
3. Use of a sulfur-containing piperazine derivative according to claim 2 in an oxidation system, wherein: the dosage of the compound shown in the formula I or II is 90-300% of the mole number of the substrate.
4. Use of a sulfur-containing piperazine derivative according to claim 2 in an oxidation system, wherein: the oxidation reaction temperature is-78 to-5 ℃.
5. use of a sulfur-containing piperazine derivative according to claim 2 in an oxidation system, wherein: when X is S, the compound shown in formula I or II is applied to a Critical-metal oxidation system, and under the condition of organic alkali, the compound and an activator act together to oxidize the hydroxyl of a reaction substrate into corresponding aldehyde or ketone; when X is sulfinyl, the compound shown in the formula I or II is applied to a Stevens oxidation system, and under the condition of organic base, the compound and an activating agent are combined to act, so that the hydroxyl of a reaction substrate is oxidized into corresponding aldehyde or ketone.
6. Use of a sulfur-containing piperazine derivative according to claim 5 in an oxidation system, wherein: in the Coriolis-MOS system, the activator comprises chlorine gas, N-chlorosuccinimide, N-bromosuccinimide, and a compound having an N, N' -dichloro or dibromourea structure; in the schwen oxidation system, the activator is an acid chloride or an acid anhydride.
7. use of a sulfur-containing piperazine derivative according to any one of claims 2 to 6 in an oxidation system, wherein: the method for recovering the compound shown as the formula I or II after the oxidation reaction is finished comprises the following steps: dissolving the product corresponding to the compound shown in the formula I or II after reaction in an aqueous solution with the pH value less than 5, adjusting the pH value of the solution to be more than 9, extracting by using an organic solvent, collecting an organic phase, concentrating and drying to obtain the compound shown in the formula I or II.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910798061.XA CN110563670B (en) | 2019-08-27 | 2019-08-27 | Sulfur-containing piperazine derivative and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910798061.XA CN110563670B (en) | 2019-08-27 | 2019-08-27 | Sulfur-containing piperazine derivative and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110563670A true CN110563670A (en) | 2019-12-13 |
| CN110563670B CN110563670B (en) | 2021-09-28 |
Family
ID=68776346
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910798061.XA Active CN110563670B (en) | 2019-08-27 | 2019-08-27 | Sulfur-containing piperazine derivative and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110563670B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111961012A (en) * | 2020-09-14 | 2020-11-20 | 河北威远生物化工有限公司 | Methionine derivative and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2672268A1 (en) * | 2006-12-15 | 2008-06-26 | Schering Corporation | Bisulfite purification of an alpha-keto amide |
| CN101565344A (en) * | 2008-04-25 | 2009-10-28 | 中国科学院大连化学物理研究所 | Method for preparing aldehyde or alkone by oxygen catalysis and alcohol oxidation under mild condition |
| CN105585540A (en) * | 2015-06-05 | 2016-05-18 | 浙江工业大学 | Preparation and application of novel Swern reagent |
-
2019
- 2019-08-27 CN CN201910798061.XA patent/CN110563670B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2672268A1 (en) * | 2006-12-15 | 2008-06-26 | Schering Corporation | Bisulfite purification of an alpha-keto amide |
| CN101565344A (en) * | 2008-04-25 | 2009-10-28 | 中国科学院大连化学物理研究所 | Method for preparing aldehyde or alkone by oxygen catalysis and alcohol oxidation under mild condition |
| CN105585540A (en) * | 2015-06-05 | 2016-05-18 | 浙江工业大学 | Preparation and application of novel Swern reagent |
Non-Patent Citations (4)
| Title |
|---|
| ACS: "RN：1880875-99-9", 《STN REGISTRY数据库》 * |
| C.B.POLLARD 等: "Alkyl- and Arylthiomethylpiperazines", 《NOTES》 * |
| DAISUKE TSUCHIYA 等: "Efficient Swern oxidation and Corey-Kim oxidation with ion-supported methyl sulfoxides and methyl sulfides", 《TETRAHEDRON》 * |
| 王博 等: "新型含硫哌嗪无异味试剂在甲维盐合成中的应用", 《农药》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111961012A (en) * | 2020-09-14 | 2020-11-20 | 河北威远生物化工有限公司 | Methionine derivative and application thereof |
| CN111961012B (en) * | 2020-09-14 | 2022-05-06 | 河北威远生物化工有限公司 | Methionine derivative and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110563670B (en) | 2021-09-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103880903B (en) | A kind of preparation method of tylosin class macrolide and derivant thereof | |
| EP2042497B1 (en) | Method for producing strontium ranelate and its hydrates | |
| CN110563670B (en) | Sulfur-containing piperazine derivative and application thereof | |
| JP4257574B2 (en) | Synthesis of R (+) α-lipoic acid | |
| FI105402B (en) | Process for Preparation of 2 ', 3' '- Didehydro-2', 3'-Dideoxynucleosides on a Large Scale | |
| CN101323567B (en) | Process for preparing cinnamate and derivates thereof | |
| EP1503983B1 (en) | A process for the preparation of modafinil | |
| EP3728167B1 (en) | A process for the preparation of crisaborole | |
| CN110551123A (en) | Preparation method of 5- (tert-butyloxycarbonyl) -2-methyl-4, 5,6, 7-tetrahydro-2H-pyrazolo [4,3-C ] pyridine-7-carboxylic acid | |
| CN111039838B (en) | Preparation method of 3-acetylmercapto-2-methylpropanoic acid | |
| CN114315575A (en) | Preparation method and application of photoinitiator intermediate | |
| CN110330422B (en) | Preparation method of 2, 6-diethyl-4-methylphenylacetic acid | |
| CN110590621B (en) | Method for synthesizing 1, 2-bis (arylsulfonyl) ethylene derivative by copper-catalyzed terminal alkyne | |
| KR100367986B1 (en) | Optically active cyanobutantriol derivatives and process for preparing same | |
| CN111961012B (en) | Methionine derivative and application thereof | |
| KR20070092309A (en) | Process for preparing carbon-reduced aldose compound | |
| CN113651715B (en) | Method for synthesizing coumaroyl dopamine by one-pot method | |
| CN114213230B (en) | Method for preparing 1, 3-dihydroxyacetone | |
| CN111303006B (en) | A kind of preparation method of amlodipine key intermediate | |
| CN116462622B (en) | Preparation method of N-Boc-L-prolyl | |
| CN117946039A (en) | Chiral synthesis process of englitz intermediate | |
| JP2000198779A (en) | Purification method of 3-alkyl flavanol derivative | |
| CN117447351A (en) | Preparation method of lidocaine | |
| KR100525468B1 (en) | Improved process of preparing fenpyroximate | |
| CN113336753A (en) | Riociguat synthesis method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |