CN115160196A - 对称硫醚类化合物的制备方法 - Google Patents
对称硫醚类化合物的制备方法 Download PDFInfo
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- CN115160196A CN115160196A CN202210765539.0A CN202210765539A CN115160196A CN 115160196 A CN115160196 A CN 115160196A CN 202210765539 A CN202210765539 A CN 202210765539A CN 115160196 A CN115160196 A CN 115160196A
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- Prior art keywords
- symmetrical
- reaction
- preparing
- molecular sieve
- thioether
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Links
- 150000003568 thioethers Chemical class 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 239000002808 molecular sieve Substances 0.000 claims abstract description 51
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims abstract description 51
- 239000003054 catalyst Substances 0.000 claims abstract description 46
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 45
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 45
- 238000006243 chemical reaction Methods 0.000 claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 42
- 239000002904 solvent Substances 0.000 claims abstract description 22
- 239000012074 organic phase Substances 0.000 claims abstract description 19
- 238000001035 drying Methods 0.000 claims abstract description 16
- 150000004820 halides Chemical class 0.000 claims abstract description 16
- 239000010949 copper Substances 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052802 copper Inorganic materials 0.000 claims abstract description 11
- 238000002156 mixing Methods 0.000 claims abstract description 11
- 150000001879 copper Chemical class 0.000 claims abstract description 10
- 238000005470 impregnation Methods 0.000 claims abstract description 10
- 238000003756 stirring Methods 0.000 claims abstract description 10
- 239000002253 acid Substances 0.000 claims abstract description 8
- 239000011230 binding agent Substances 0.000 claims abstract description 8
- 238000005406 washing Methods 0.000 claims abstract description 8
- 150000001412 amines Chemical class 0.000 claims abstract description 7
- 238000010791 quenching Methods 0.000 claims abstract description 5
- 230000035484 reaction time Effects 0.000 claims abstract description 4
- 238000000605 extraction Methods 0.000 claims abstract description 3
- 230000000171 quenching effect Effects 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 72
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Natural products CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- 229920001223 polyethylene glycol Polymers 0.000 claims description 19
- 239000002202 Polyethylene glycol Substances 0.000 claims description 11
- -1 bis-dimethylamino ethyl Chemical group 0.000 claims description 11
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 claims description 7
- YSAANLSYLSUVHB-UHFFFAOYSA-N 2-[2-(dimethylamino)ethoxy]ethanol Chemical compound CN(C)CCOCCO YSAANLSYLSUVHB-UHFFFAOYSA-N 0.000 claims description 6
- 239000012752 auxiliary agent Substances 0.000 claims description 5
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 claims description 4
- MNNZINNZIQVULG-UHFFFAOYSA-N 2-chloroethylbenzene Chemical compound ClCCC1=CC=CC=C1 MNNZINNZIQVULG-UHFFFAOYSA-N 0.000 claims description 4
- BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 claims description 4
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 claims description 4
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims description 4
- 229940073608 benzyl chloride Drugs 0.000 claims description 4
- 239000006185 dispersion Substances 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 4
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 229910018072 Al 2 O 3 Inorganic materials 0.000 claims description 3
- 229910004298 SiO 2 Inorganic materials 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- HJLHTTJLVALHOP-UHFFFAOYSA-N hexane;hydron;chloride Chemical compound Cl.CCCCCC HJLHTTJLVALHOP-UHFFFAOYSA-N 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- IZUOFDKRBUHNPE-UHFFFAOYSA-N 2-methylpropane hydrochloride Chemical compound CC(C)C.Cl IZUOFDKRBUHNPE-UHFFFAOYSA-N 0.000 claims description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 abstract description 5
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 17
- 238000002390 rotary evaporation Methods 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 238000005859 coupling reaction Methods 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- 230000002194 synthesizing effect Effects 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- 239000011593 sulfur Substances 0.000 description 9
- 229910052717 sulfur Inorganic materials 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 8
- 230000006872 improvement Effects 0.000 description 7
- 150000001350 alkyl halides Chemical class 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000010189 synthetic method Methods 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- LUFPJJNWMYZRQE-UHFFFAOYSA-N benzylsulfanylmethylbenzene Chemical compound C=1C=CC=CC=1CSCC1=CC=CC=C1 LUFPJJNWMYZRQE-UHFFFAOYSA-N 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 150000001502 aryl halides Chemical class 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- NHPPIJMARIVBGU-UHFFFAOYSA-N 1-iodonaphthalene Chemical compound C1=CC=C2C(I)=CC=CC2=C1 NHPPIJMARIVBGU-UHFFFAOYSA-N 0.000 description 2
- AQZABFSNDJQNDC-UHFFFAOYSA-N 2-[2,2-bis(dimethylamino)ethoxy]-1-n,1-n,1-n',1-n'-tetramethylethane-1,1-diamine Chemical compound CN(C)C(N(C)C)COCC(N(C)C)N(C)C AQZABFSNDJQNDC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 150000001499 aryl bromides Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- LTYMSROWYAPPGB-UHFFFAOYSA-N diphenyl sulfide Chemical compound C=1C=CC=CC=1SC1=CC=CC=C1 LTYMSROWYAPPGB-UHFFFAOYSA-N 0.000 description 2
- QTBFPMKWQKYFLR-UHFFFAOYSA-N isobutyl chloride Chemical compound CC(C)CCl QTBFPMKWQKYFLR-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 125000001741 organic sulfur group Chemical group 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 150000003463 sulfur Chemical class 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- MLRVZFYXUZQSRU-UHFFFAOYSA-N 1-chlorohexane Chemical compound CCCCCCCl MLRVZFYXUZQSRU-UHFFFAOYSA-N 0.000 description 1
- LHNRHYOMDUJLLM-UHFFFAOYSA-N 1-hexylsulfanylhexane Chemical compound CCCCCCSCCCCCC LHNRHYOMDUJLLM-UHFFFAOYSA-N 0.000 description 1
- QLAWAFBTLLCIIM-UHFFFAOYSA-N 1-naphthalen-1-ylsulfanylnaphthalene Chemical compound C1=CC=C2C(SC=3C4=CC=CC=C4C=CC=3)=CC=CC2=C1 QLAWAFBTLLCIIM-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- WJBDTRSHWOPBAZ-UHFFFAOYSA-N 2-(2-phenylethylsulfanyl)ethylbenzene Chemical compound C=1C=CC=CC=1CCSCCC1=CC=CC=C1 WJBDTRSHWOPBAZ-UHFFFAOYSA-N 0.000 description 1
- CMWSRWTXVQLHNX-UHFFFAOYSA-N 2-methyl-1-(2-methylpropylsulfanyl)propane Chemical compound CC(C)CSCC(C)C CMWSRWTXVQLHNX-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- XGJOFCCBFCHEHK-UHFFFAOYSA-N 4-pyridin-4-ylsulfanylpyridine Chemical compound C=1C=NC=CC=1SC1=CC=NC=C1 XGJOFCCBFCHEHK-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- HTIRHQRTDBPHNZ-UHFFFAOYSA-N Dibutyl sulfide Chemical compound CCCCSCCCC HTIRHQRTDBPHNZ-UHFFFAOYSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- XURCIPRUUASYLR-UHFFFAOYSA-N Omeprazole sulfide Chemical compound N=1C2=CC(OC)=CC=C2NC=1SCC1=NC=C(C)C(OC)=C1C XURCIPRUUASYLR-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 239000004734 Polyphenylene sulfide Substances 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 150000001500 aryl chlorides Chemical class 0.000 description 1
- 150000001503 aryl iodides Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- DHSUYTOATWAVLW-WFVMDLQDSA-N cilastatin Chemical compound CC1(C)C[C@@H]1C(=O)N\C(=C/CCCCSC[C@H](N)C(O)=O)C(O)=O DHSUYTOATWAVLW-WFVMDLQDSA-N 0.000 description 1
- 229960004912 cilastatin Drugs 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 238000006772 olefination reaction Methods 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 150000002898 organic sulfur compounds Chemical class 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229940113115 polyethylene glycol 200 Drugs 0.000 description 1
- 229920000069 polyphenylene sulfide Polymers 0.000 description 1
- 229920006295 polythiol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229950004147 ufiprazole Drugs 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J29/00—Catalysts comprising molecular sieves
- B01J29/04—Catalysts comprising molecular sieves having base-exchange properties, e.g. crystalline zeolites
- B01J29/06—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof
- B01J29/064—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof containing iron group metals, noble metals or copper
- B01J29/072—Iron group metals or copper
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J29/00—Catalysts comprising molecular sieves
- B01J29/04—Catalysts comprising molecular sieves having base-exchange properties, e.g. crystalline zeolites
- B01J29/06—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof
- B01J29/08—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof of the faujasite type, e.g. type X or Y
- B01J29/10—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof of the faujasite type, e.g. type X or Y containing iron group metals, noble metals or copper
- B01J29/14—Iron group metals or copper
- B01J29/143—X-type faujasite
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J29/00—Catalysts comprising molecular sieves
- B01J29/04—Catalysts comprising molecular sieves having base-exchange properties, e.g. crystalline zeolites
- B01J29/06—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof
- B01J29/08—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof of the faujasite type, e.g. type X or Y
- B01J29/10—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof of the faujasite type, e.g. type X or Y containing iron group metals, noble metals or copper
- B01J29/14—Iron group metals or copper
- B01J29/146—Y-type faujasite
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J29/00—Catalysts comprising molecular sieves
- B01J29/04—Catalysts comprising molecular sieves having base-exchange properties, e.g. crystalline zeolites
- B01J29/06—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof
- B01J29/40—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof of the pentasil type, e.g. types ZSM-5, ZSM-8 or ZSM-11, as exemplified by patent documents US3702886, GB1334243 and US3709979, respectively
- B01J29/42—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof of the pentasil type, e.g. types ZSM-5, ZSM-8 or ZSM-11, as exemplified by patent documents US3702886, GB1334243 and US3709979, respectively containing iron group metals, noble metals or copper
- B01J29/46—Iron group metals or copper
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/26—Separation; Purification; Stabilisation; Use of additives
- C07C319/28—Separation; Purification
-
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- C07—ORGANIC CHEMISTRY
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Abstract
本发明公开了一种对称硫醚类化合物的制备方法,包括以下步骤:利用可溶性铜盐、胺助剂、分子筛,采用浸渍法制备铜基负载型催化剂;将铜基负载型催化剂、卤化物、单质硫、缚酸剂与溶剂混合后,于40~120℃下搅拌反应8~12h;反应时间到达后淬灭反应,用乙酸乙酯萃取,萃取所得有机相洗涤后干燥除水,再除去溶剂,最后分离纯化,得到对称硫醚类化合物。采用本发明方法制备对称硫醚类化合物具有工艺简单、环境友好、收率高、选择性好等特点。
Description
技术领域
本发明属于化学领域,具体涉及一种对称硫醚类化合物的合成方法。
背景技术
硫醚类化合物是指具有-S-键结构的有机硫化合物,其在医药、功能材料以及有机合成等领域有着重要的应用价值。首先,硫醚类化合物是合成药物的重要中间体,许多硫醚骨架都广泛存在于药物和生物分子中,如具有抗菌活性的Cilastatin、治疗抗消化性溃疡的Ufiprazole、常用抗生素Penicillin、人体必需氨基酸之一Methionine等。其次,一些聚硫醚类化合物在材料领域也有很高的应用价值,如聚苯硫醚已广泛应用于新能源汽车、电子电器、航空航天等领域。最后,硫醚类化合物在有机合成领域也有着广泛的应用,如硫醚结构可以作为导向基团诱导醋酸钯催化的不对称烯烃C-H键烯基化反应。因此,硫醚类化合物的合成研究一直以来是有机合成中的热点之一,其中较为重要的方法是以C-S偶联反应构建硫醚类化合物。另一方面,卤化物作为一类重要的物质,具有较高的反应活性,通常用来高效地构建其他官能团化合物。因此以卤化物为底物的C-S偶联反应构建硫醚类化合物的方法一直受到有机硫工作者的关注。其中,最为经典的方法是卤化物与硫醇在强碱存在下通过C-S偶联进行取代反应。然而,该方法存在以下不足之处:如产量低、底物范围窄以及直接使用有毒且恶臭的硫醇等。因此,采用绿色安全的硫源,开发新颖、实用、高效的合成方法是迫切需要的。例如,蔡春(Green Chem.Lett.Rev.,2012,5(3):481-485):采用硫脲作为硫源,与有机卤化物在碱性条件下进行了C-S偶联反应制备对称硫醚类化合物,但是该策略仅适用于烷基卤化物。
近些年,单质硫逐渐被用作为一种高效的硫源参与到多种有机反应中。例如,AminRostami等人(Tetrahedron Letters,2016,57(2):192-195.),报道了一种醋酸铜催化的以单质硫为硫源在110℃下与芳基卤化物合成对称芳基硫醚的新方法,不过该方法仅适用于芳基卤化物。相比于有机硫源和其他无机硫源,单质硫具有储量丰富、价格便宜,原子经济性高,绿色、安全、不存在特殊气味等优势。
尽管如此,从单质硫与烷基卤化物出发合成对称二烷基硫醚的策略还未见报道。主要原因是环状的单质硫在碱性环境中会被活化而分裂成具有不同硫原子个数的硫团簇,这些硫团簇与烷基卤化物反应会生成具有不同硫原子个数的烷基硫醚(R-Sn-R),这导致烷基卤化物与单质硫的反应选择性很差。另外,由于这些具有不同硫原子个数的烷基硫醚的性质非常接近,难以分离纯化。因此如果不能做到高选择性合成对称烷基硫醚,那么烷基卤化物与单质硫的反应就没有任何意义。
对于对称二芳基硫醚类化合物的合成,虽然存在一些芳基卤化物与单质硫偶联反应的报道,但是这些已报道的方法主要集中在以活性较高的芳基碘化物为起始底物,采用活性较低的芳基卤化物或芳基溴化物则较难实现对称二芳基硫醚类化合物的构建(主要原因如上所述)。
综上所述,要实现对称硫醚类化合物的高选择性、高收率地绿色化生产,不仅涉及硫源的选择,还涉及到高效催化体系的开发。
发明内容
本发明要解决的技术问题是提供一种温和、高效、清洁的对称硫醚类化合物的合成方法。为解决上述技术问题,本发明提供一种对称硫醚类化合物的制备方法,包括以下步骤:
1)、浸渍法制备铜基负载型催化剂:
将可溶性铜盐与胺助剂溶解于甲醇中,得混合溶液;将分子筛分散于甲醇中,得分散液;
将混合溶液与分散液充分混合后静置,静置所得沉淀先干燥,再于400~600℃下焙烧6±0.5h,得铜基负载型催化剂;
铜盐与胺助剂的摩尔比为1:1~2;铜盐与分子筛的质量比为1:20~50;
2)、将铜基负载型催化剂、卤化物、单质硫、缚酸剂与溶剂混合后,于40~120℃下搅拌反应8~12h;所述卤化物:单质硫:缚酸剂=1:0.6:2的摩尔比,所述铜基负载型催化剂为卤化物质量的5~10%;
反应结束后,经后处理,得到对称硫醚类化合物(纯度≥97%)。
说明:反应可在干燥洁净的Schlenk管中进行,采用GC或HPLC监测反应进程。
作为本发明的对称硫醚类化合物的制备方法的改进:所述步骤1)中:
可溶性铜盐为:Cu(OAc)2、CuSO4、Cu(NO3)2、CuCl2、CuBr2;
胺助剂为:三乙烯二胺(TEDA)、双二甲氨基乙基醚(BDMAEE)、二甲氨基乙氧基乙醇(DMAEE)。
作为本发明的对称硫醚类化合物的制备方法的进一步改进:所述步骤1)中的分子筛为:X型、Y型、ZSM-5型或纯Al2O3、纯SiO2、纯ZrO2。
分子筛作为载体,一般4~7g分子筛配用1.0mmol可溶性铜盐,且4.0~7g的分子筛充分分散于50mL甲醇中。
作为本发明的对称硫醚类化合物的制备方法的进一步改进,所述步骤1)中:
混合时间为5±1h,静置时间为2±0.5h。
作为本发明的对称硫醚类化合物的制备方法的进一步改进,所述步骤2)中:
卤化物为:氯代正丁烷、氯代异丁烷、氯代正己烷、氯化苄、1-氯-2-苯乙烷、碘苯、4-溴吡啶;
缚酸剂为:K2CO3、Na2CO3、Cs2CO3、NaOH、KOH。
作为本发明的对称硫醚类化合物的制备方法的进一步改进,步骤2)中的溶剂为:聚乙二醇PEG200、聚乙二醇PEG400、DMF(N,N-二甲基甲酰胺)、DMSO(二甲基亚砜)。
作为本发明的对称硫醚类化合物的制备方法的进一步改进,所述步骤2)中,每30mmol的卤化物配用30±10mL的溶剂。
作为本发明的对称硫醚类化合物的制备方法的进一步改进,所述步骤2)中的后处理为:
反应时间到达后淬灭反应(反应时间到达后,将反应所得物冷却至室温,加水淬灭反应),用乙酸乙酯萃取,萃取所得有机相洗涤(用饱和食盐水洗涤)后干燥除水(无水硫酸钠干燥),再除溶(除去包含乙酸乙酯等的溶剂),最后分离纯化,得到对称硫醚类化合物(纯度≥97%)。
作为本发明的对称硫醚类化合物的制备方法的进一步改进,步骤2)中,分离纯化方法为减压蒸馏或柱层析法分离纯化。
本发明的对称硫醚类化合物合成方法的反应方程式如下:
其中所述-R为正丁基、异丁基、正己基、苄基、2-苯基乙基、苯基、吡啶基、萘基中的任一。
其中所述-X为氯、溴、碘中的任一。
本发明经比较不同硫源的反应特点,综合考虑合成策略的难易,确立了在新型分子筛负载的铜基催化剂催化下,以卤化物为原料、单质硫为硫源经C-S偶联反应高效合成对称硫醚类化合物的技术开发路线。其关键的技术难点在于高效催化剂的开发。本发明首次实现了单质硫与烷基卤代物C-S偶联反应高选择、高收率合成对称二烷基硫醚,实现了活性较低的芳基溴化物和芳基氯化物与单质硫的偶联反应制备对称二芳基硫醚。
本发明的对称硫醚类化合物合成方法,采用自制的铜基负载型催化剂,实现了卤化物与单质硫的偶联反应高选择性合成对称硫醚类化合物,有效地避免了极性相近副产物的生成,为后处理过程扫除了障碍。此外,该过程使用廉价易得、无味无臭的单质硫作为硫源,原子利用率高,无其他废弃物产生,保证生产过程环境友好。采用本发明方法制备对称硫醚类化合物具有工艺简单、环境友好、收率高、选择性好等特点。
综上,本发明提供一种对称硫醚类化合物的合成方法,开发新型铜基催化剂,催化卤化物和单质硫的C-S偶联反应直接生成对称硫醚类化合物;对称硫醚类化合物的收率高。
具体实施方式
下面结合具体实施例对本发明进行进一步描述,但本发明的保护范围并不仅限于此:
实施例1、一种对称硫醚类化合物合成方法,以氯代正丁烷与单质硫为原料,依次进行以下步骤:
1)、浸渍法制备Cu-TEDA/Y型分子筛催化剂:
将醋酸铜(0.20g,1.0mmol)与三乙烯二胺(0.11g,1.0mmol)充分溶解于5mL的甲醇中;同时将4.0g的Y型分子筛充分分散于50mL甲醇中;将两者充分混合5h,静置2h,干燥(60℃烘箱干燥4h,目的是为了除去残存的甲醇溶剂)后于400℃下焙烧6h,即可获得Cu-TEDA/Y型分子筛催化剂(约3.5g)。
2)、向干燥洁净的Schlenk管中加入氯代正丁烷(2.8g,30mmol)、单质硫(0.6g,18mmol)、步骤1)所得的Cu-TEDA/Y型分子筛催化剂(0.28g,10wt%)、碳酸铯(19.5g,60mmol)和聚乙二醇PEG200(30mL);随后,于40℃下搅拌反应10h;并采用GC监测反应进程,此时反应已完成。
将反应所得的混合物冷却至室温;加入30mL水淬灭反应,并用乙酸乙酯萃取三次(20mL×3)。合并有机相(位于上层)后,用饱和食盐水洗涤三次(20mL×3),无水硫酸钠(约5.0g)干燥,砂芯漏斗过滤,旋转蒸发除去溶剂(乙酸乙酯),采用减压蒸馏法(温度为40℃,压力为0.01MPa)分离纯化,收集蒸气温度为36℃的馏分,得到二丁基硫醚1.9g(收率为85%,纯度为98%),为无色液体,1H NMR(400MHz,CDCl3)δ2.50–2.39(m,4H),1.51(dt,J=14.8,7.2Hz,4H),1.35(dq,J=14.2,7.2Hz,4H),0.86(t,J=7.4Hz,6H);13C NMR(101MHz,CDCl3)δ31.87,22.08,13.71;GC-MS(EI)m/z:calcd.for C8H18S[M]:146.11,found:146.12。
实施例2、一种对称硫醚类化合物合成方法,以氯代异丁烷与单质硫为原料,依次进行以下步骤:
1)、浸渍法制备Cu-BDMAEE/Y型分子筛催化剂:
将硫酸铜(0.16g,1.0mmol)与双二甲氨基乙基醚(0.24g,1.5mmol)充分溶解于5mL的甲醇中,同时将6.4g的Y型分子筛充分分散于50mL甲醇中,将两者充分混合5h,静置2h,干燥后于500℃下焙烧6h,即可获得Cu-BDMAEE/Y型分子筛催化剂(约5.6g)。
2)、向干燥洁净的Schlenk管中加入氯代异丁烷(2.8g,30mmol)、单质硫(0.6g,18mmol)、步骤1)所得的Cu-BDMAEE/Y型分子筛催化剂(0.28g,10wt%)、碳酸钾(8.3g,60mmol)和聚乙二醇PEG400(30mL);随后,于80℃下搅拌反应9h;并采用GC监测反应进程。此时反应已完成。
将反应所得的混合物冷却至室温;加入30mL水淬灭反应,并用乙酸乙酯萃取三次。合并有机相后,用饱和食盐水洗涤三次,无水硫酸钠干燥,砂芯漏斗过滤,旋转蒸发除去溶剂,采用减压蒸馏法(温度为35℃,压力为0.01MPa)分离纯化,收集蒸气温度为35℃的馏分,得到二异丁基硫醚1.8g(收率为82%,纯度为97%),为无色液体,1H NMR(400MHz,CDCl3)δ2.34(d,J=6.8Hz,4H),1.80–1.70(m,2H),0.95(d,J=6.8Hz,12H);13C NMR(101MHz,CDCl3)δ42.21,28.74,22.11;GC-MS(EI)m/z:calcd.for C8H18S[M]:146.11,found:146.12。
实施例3、一种对称硫醚类化合物合成方法,以氯代正己烷与单质硫为原料,依次进行以下步骤:
1)、浸渍法制备Cu-DMAEE/X型分子筛催化剂:
将氯化铜(0.13g,1.0mmol)与二甲氨基乙氧基乙醇(0.27g,2.0mmol)充分溶解于5mL的甲醇中,同时将6.5g的X型分子筛充分分散于50mL甲醇中,将两者充分混合5h,静置2h,干燥后于600℃下焙烧6h,即可获得Cu-DMAEE/X型分子筛催化剂(约4.7g)。
2)、向干燥洁净的Schlenk管中加入氯代正己烷(3.6g,30mmol)、单质硫(0.6g,18mmol)、步骤1)所得的Cu-DMAEE/X型分子筛催化剂(0.29g,8wt%)、碳酸钠(6.4g,60mmol)和聚乙二醇PEG200(30mL);随后,于60℃下搅拌反应8h;并采用GC监测反应进程。此时反应已完成。
将反应所得的混合物冷却至室温;加入30mL水淬灭反应,并用乙酸乙酯萃取三次。合并有机相后,用饱和食盐水洗涤三次,无水硫酸钠干燥,砂芯漏斗过滤,旋转蒸发除去溶剂,采用减压蒸馏法(温度为52℃,压力为0.01MPa)分离纯化,收集蒸气温度为38℃的馏分,得到二己基硫醚2.4g(收率为80%,纯度为98%),为无色液体,1H NMR(400MHz,CDCl3)δ2.51–2.42(m,4H),1.54(p,J=7.2Hz,4H),1.39–1.20(m,12H),0.85(t,J=7.0Hz,6H);13CNMR(101MHz,CDCl3)δ32.25,31.54,29.76,28.70,22.62,14.07;GC-MS(EI)m/z:calcd.forC12H26S[M]:202.18,found:202.19。
实施例4、一种对称硫醚类化合物合成方法,以氯化苄与单质硫为原料,依次进行以下步骤:
1)、浸渍法制备Cu-TEDA/ZSM-5型分子筛催化剂:
将溴化铜(0.22g,1.0mmol)与三乙烯二胺(0.11g,1.0mmol)充分溶解于5mL的甲醇中,同时将6.6g的ZSM-5型分子筛充分分散于50mL甲醇中,将两者充分混合5h,静置2h,干燥后于500℃下焙烧6h,即可获得Cu-TEDA/ZSM-5型分子筛催化剂(约5.2g)。
2)、向干燥洁净的Schlenk管中加入氯化苄(3.8g,30mmol)、单质硫(0.6g,18mmol)、步骤1)所得的Cu-TEDA/ZSM-5型分子筛催化剂(0.27g,7wt%)、碳酸铯(19.5g,60mmol)和聚乙二醇PEG200(30mL);随后,于40℃下搅拌反应8h;并采用HPLC监测反应进程;此时反应已完成。
将反应所得的混合物冷却至室温;加入30mL水淬灭反应,并用乙酸乙酯萃取三次。合并有机相后,用饱和食盐水洗涤三次,无水硫酸钠干燥,砂芯漏斗过滤,旋转蒸发除去溶剂,采用柱层析法(层析柱为硅胶色谱柱,洗脱剂:纯石油醚,洗脱流速为30mL/min)分离纯化,收集Rf=0.9(TLC检测,展开剂为纯石油醚)的洗脱液;旋转蒸发除去洗脱剂,得到二苄基硫醚3.1g(收率为95%,纯度为97%),为白色固体(熔程:48.9–50.0℃),1H NMR(400MHz,CDCl3)δ7.35–7.20(m,10H),3.59(s,4H);13C NMR(101MHz,CDCl3)δ138.18,129.06,128.53,127.02,35.61;GC-MS(EI)m/z:calcd.for C14H14S[M]:214.08,found:214.09。
实施例5、一种对称硫醚类化合物合成方法,以1-氯-2-苯乙烷与单质硫为原料,依次进行以下步骤:
1)、浸渍法制备Cu-DMAEE/Al2O3型分子筛催化剂:
将硝酸铜(0.19g,1.0mmol)与二甲氨基乙氧基乙醇(0.27g,2.0mmol)充分溶解于5mL的甲醇中,同时将5.7g的Al2O3型分子筛充分分散于50mL甲醇中,将两者充分混合5h,静置2h,干燥后于400℃下焙烧6h,即可获得Cu-DMAEE/Al2O3型分子筛催化剂(约4.4g)。
2)、向干燥洁净的Schlenk管中加入1-氯-2-苯乙烷(4.2g,30mmol)、单质硫(0.6g,18mmol)、步骤1)所得的Cu-DMAEE/Al2O3型分子筛催化剂(0.21g,5wt%)、碳酸铯(19.5g,60mmol)和聚乙二醇200(30mL);随后,于40℃下搅拌反应10h;并采用HPLC监测反应进程,此时反应已完成。
将反应所得的混合物冷却至室温;加入30mL水淬灭反应,并用乙酸乙酯萃取三次。合并有机相后,用饱和食盐水洗涤三次,无水硫酸钠干燥,砂芯漏斗过滤,旋转蒸发除去溶剂,采用柱层析法(层析柱为硅胶色谱柱,洗脱剂:纯石油醚,洗脱流速为30mL/min)分离纯化,收集Rf=0.8(TLC检测,展开剂为纯石油醚)的洗脱液;旋转蒸发除去洗脱剂,得到双(2-苯乙基)硫醚3.2g(收率为87%,纯度为98%),为无色油状液体,1H NMR(400MHz,CDCl3)δ7.32(t,J=7.2Hz,4H),7.26–7.21(m,6H),2.93–2.89(m,4H),2.83–2.79(m,4H);13C NMR(101MHz,CDCl3)δ140.69,128.61,128.60,126.48,36.46,33.92;GC-MS(EI)m/z:calcd.forC16H18S[M]:242.11,found:242.09。
实施例6、一种对称硫醚类化合物合成方法,以碘苯与单质硫为原料,依次进行以下步骤:
1)、浸渍法制备Cu-BDMAEE/SiO2型分子筛催化剂:
将醋酸铜(0.20g,1.0mmol)与双二甲氨基乙基醚(0.24g,1.5mmol)充分溶解于5mL的甲醇中,同时将6.0g的SiO2型分子筛充分分散于50mL甲醇中,将两者充分混合5h,静置2h,干燥后于600℃下焙烧6h,即可获得Cu-BDMAEE/SiO2型分子筛催化剂(约5.3g)。
2)、向干燥洁净的Schlenk管中加入碘苯(6.1g,30mmol)、单质硫(0.6g,18mmol)、步骤1)所得的Cu-BDMAEE/SiO2型分子筛催化剂(0.55g,9wt%)、氢氧化钾(3.4g,60mmol)和N,N-二甲基甲酰胺(30mL);随后,于120℃下搅拌反应12h;并采用HPLC监测反应进程,此时反应已完成。
将反应所得的混合物冷却至室温;加入30mL水淬灭反应,并用乙酸乙酯萃取三次。合并有机相后,用饱和食盐水洗涤三次,无水硫酸钠干燥,砂芯漏斗过滤,旋转蒸发除去溶剂,采用柱层析法(层析柱为硅胶色谱柱,洗脱剂:纯石油醚,洗脱流速为30mL/min)分离纯化,收集Rf=0.8(TLC检测,展开剂为纯石油醚)的洗脱液;旋转蒸发除去洗脱剂,得到二苯硫醚2.2g(收率为81%,纯度为97%),为淡黄色油状液体,1H NMR(400MHz,CDCl3)δ7.47–7.42(m,4H),7.42–7.36(m,4H),7.36–7.30(m,2H);13C NMR(101MHz,CDCl3)δ135.82,131.08,129.24,127.09;GC-MS(EI)m/z calcd.for:C12H10S[M]:186.05,found:186.03。
实施例7、一种对称硫醚类化合物合成方法,以4-溴吡啶与单质硫为原料,依次进行以下步骤:
1)、浸渍法制备Cu-TEDA/ZrO2型分子筛催化剂:
将溴化铜(0.22g,1.0mmol)与三乙烯二胺(0.11g,1.0mmol)溶解于5mL的甲醇中,充分分散溶解;同时将4.4g的ZrO2型分子筛充分分散于50mL甲醇中,将两者充分混合5h,静置2h,干燥后于400℃下焙烧6h,即可获得Cu-TEDA/ZrO2型分子筛催化剂(约3.9g)。
2)、向干燥洁净的Schlenk管中加入4-溴吡啶(4.7g,30mmol)、单质硫(0.6g,18mmol)、步骤1)所得的Cu-TEDA/ZrO2型分子筛催化剂(0.47g,10wt%)、氢氧化钠(2.4g,60mmol)和二甲基亚砜(30mL);随后,于100℃下搅拌反应12h;并采用HPLC监测反应进程,此时反应已完成。
将反应所得的混合物冷却至室温;加入30mL水淬灭反应,并用乙酸乙酯萃取三次。合并有机相后,用饱和食盐水洗涤三次,无水硫酸钠干燥,砂芯漏斗过滤,旋转蒸发除去溶剂,采用柱层析法(层析柱为硅胶色谱柱,洗脱剂:乙酸乙酯:石油醚=1:10,v/v,洗脱流速为30mL/min)分离纯化,收集Rf=0.5(TLC检测,展开剂为乙酸乙酯:石油醚=1:10,v/v)的洗脱液;旋转蒸发除去洗脱剂,得到二(4-吡啶基)硫醚2.3g(收率为80%,纯度为99%),为白色固体(熔程:71.3–72.4℃),1H NMR(400MHz,CDCl3)δ8.51(d,J=6.6Hz,4H),7.21(d,J=6.4Hz,4H);13C NMR(101MHz,CDCl3)δ150.37,143.95,124.79;GC-MS(EI)m/z calcd.for:C10H8N2S[M]:188.04,found:188.02。
实施例8、一种对称硫醚类化合物合成方法,以1-碘萘与单质硫为原料,依次进行以下步骤:
1)、浸渍法制备Cu-DMAEE/ZSM-5型分子筛催化剂:
将氯化铜(0.13g,1.0mmol)与二甲氨基乙氧基乙醇(0.27g,2.0mmol)溶解于5mL的甲醇中,充分分散溶解;同时将5.2g的ZSM-5型分子筛充分分散于50mL甲醇中,将两者充分混合5h,静置2h,干燥后于500℃下焙烧6h,即可获得Cu-DMAEE/ZSM-5型分子筛催化剂(约4.0g)。
2)、向干燥洁净的Schlenk管中加入1-碘萘(7.6g,30mmol)、单质硫(0.6g,18mmol)、步骤1)所得的Cu-DMAEE/ZSM-5型分子筛催化剂(0.38g,5wt%)、氢氧化钾(3.4g,60mmol)和二甲基亚砜(30mL);随后,于120℃下搅拌反应12h;并采用HPLC监测反应进程;此时反应已完成。
将反应所得的混合物冷却至室温;加入30mL水淬灭反应,并用乙酸乙酯萃取三次。合并有机相后,用饱和食盐水洗涤三次,无水硫酸钠干燥,砂芯漏斗过滤,旋转蒸发除去溶剂,采用柱层析法(层析柱为硅胶色谱柱,洗脱剂:纯石油醚,洗脱流速为30mL/min)分离纯化,收集Rf=0.7(TLC检测,展开剂为纯石油醚)的洗脱液;旋转蒸发除去洗脱剂,得到二(1-萘基)硫醚3.3g(收率为76%,纯度为97%),为白色固体(熔程:111.0–111.9℃),1H NMR(400MHz,CDCl3)δ8.52–8.52(m,2H),7.97–7.89(m,2H),7.81(d,J=7.8Hz,2H),7.61–7.54(m,4H),7.42–7.30(m,4H);13C NMR(101MHz,CDCl3)δ134.27,132.77,132.58,130.07,128.75,128.14,126.91,126.57,126.03,125.24;GC-MS(EI)m/z calcd.for:C20H14S[M]:286.08,found:286.05。
对比例1-1、将实施例4步骤2)中的单质硫改成硫脲,摩尔用量保持不变(即,为18mmol),其余等同于实施例4。
所得结果为:目标产物二苄基硫醚的收率下降,仅仅为68%。
对比例1-2、相对于实施例4,作如下更改:
1)、取消三乙烯二胺的使用,催化剂的制备方法具体如下:
将溴化铜(0.22g,1.0mmol)溶解于5mL的甲醇中,同时将6.6g的ZSM-5型分子筛充分分散于50mL甲醇中,将两者充分混合5h,静置2h,干燥后于500℃下焙烧6h,即可获得Cu/ZSM-5型分子筛催化剂。
2)、将Cu-TEDA/ZSM-5型分子筛催化剂0.27g改成Cu/ZSM-5型分子筛催化剂0.27g;其余等同于实施例4的步骤2)。
所得结果为:目标产物二苄基硫醚的收率下降,仅仅为53%。
对比例1-3、相对于实施例4,作如下更改:
1)、三乙烯二胺(1.0mmol)改成相同摩尔用量的三乙胺(TEA),即,TEA为1.0mmol,其余等同于实施例4的步骤1),得分子筛催化剂Ⅰ。
2)、以上述步骤1)所得的分子筛催化剂Ⅰ替代Cu-TEDA/ZSM-5型分子筛催化剂,用量保持不变,仍然为0.27g;其余同实施例4的步骤2)。
所得结果为:目标产物二苄基硫醚的收率下降,仅仅为59%。
对比例2、取消实施例6步骤1)催化剂的制备过程,改成直接采用醋酸铜作为催化剂(醋酸铜的重量为0.55g),其余等同于实施例6。
所得结果为:目标产物二苯硫醚的收率下降明显,为39%。
对比例3、取消实施例4中的缚酸剂---碳酸铯的使用,其余同实施例4的步骤2)。
所得结果为:无目标产物二苄基硫醚生成。
最后,还需要注意的是,以上列举的仅是本发明的若干个具体实施例。显然,本发明不限于以上实施例,还可以有许多变形。本领域的普通技术人员能从本发明公开的内容直接导出或联想到的所有变形,均应认为是本发明的保护范围。
Claims (9)
1.对称硫醚类化合物的制备方法,其特征在于包括以下步骤:
1)、浸渍法制备铜基负载型催化剂:
将可溶性铜盐与胺助剂溶解于甲醇中,得混合溶液;将分子筛分散于甲醇中,得分散液;
将混合溶液与分散液混合后静置,静置所得沉淀先干燥,再于400~600℃下焙烧6±0.5h,得铜基负载型催化剂;
铜盐与胺助剂的摩尔比为1:1~2;铜盐与分子筛的质量比为1:20~50;
2)、将铜基负载型催化剂、卤化物、单质硫、缚酸剂与溶剂混合后,于40~120℃下搅拌反应8~12h;所述卤化物:单质硫:缚酸剂=1:0.6:2的摩尔比,所述铜基负载型催化剂为卤化物质量的5~10%;
反应结束后,经后处理,得到对称硫醚类化合物。
2.根据权利要求1所述的对称硫醚类化合物的制备方法,其特征在于所述步骤1)中:
可溶性铜盐为:Cu(OAc)2、CuSO4、Cu(NO3)2、CuCl2、CuBr2;
胺助剂为:三乙烯二胺、双二甲氨基乙基醚、二甲氨基乙氧基乙醇。
3.根据权利要求2所述的对称硫醚类化合物的制备方法,其特征在于:所述步骤1)中的分子筛为:X型、Y型、ZSM-5型或纯Al2O3、纯SiO2、纯ZrO2。
4.根据权利要求3所述的对称硫醚类化合物的制备方法,其特征在于所述步骤1)中:
混合时间为5±1h,静置时间为2±0.5h。
5.根据权利要求1~4任一项所述的对称硫醚类化合物的制备方法,其特征在于所述步骤2)中:
卤化物为:氯代正丁烷、氯代异丁烷、氯代正己烷、氯化苄、1-氯-2-苯乙烷、碘苯、4-溴吡啶;
缚酸剂为:K2CO3、Na2CO3、Cs2CO3、NaOH、KOH。
6.根据权利要求5所述的对称硫醚类化合物的制备方法,其特征在于所述步骤2)中的溶剂为:PEG200、PEG400、DMF、DMSO。
7.根据权利要求6所述的对称硫醚类化合物的制备方法,其特征在于所述步骤2)中,每30mmol的卤化物配用30±10mL的溶剂。
8.根据权利要求1~7任一所述的对称硫醚类化合物的制备方法,其特征在于所述步骤2)中的后处理为:
反应时间到达后淬灭反应,用乙酸乙酯萃取,萃取所得有机相洗涤后干燥除水,再除溶,最后分离纯化,得到对称硫醚类化合物。
9.根据权利要求8所述的对称硫醚类化合物的制备方法,其特征在于所述步骤2)中,分离纯化方法为减压蒸馏或柱层析法分离纯化。
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