WO2013170535A1 - Method for synthesizing homopolymer n-vinyl butyrolactam with low residual monomer and low molecular weight - Google Patents
Method for synthesizing homopolymer n-vinyl butyrolactam with low residual monomer and low molecular weight Download PDFInfo
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- WO2013170535A1 WO2013170535A1 PCT/CN2012/079062 CN2012079062W WO2013170535A1 WO 2013170535 A1 WO2013170535 A1 WO 2013170535A1 CN 2012079062 W CN2012079062 W CN 2012079062W WO 2013170535 A1 WO2013170535 A1 WO 2013170535A1
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- WIPO (PCT)
- Prior art keywords
- molecular weight
- vinyl butyrolactam
- weight
- initiator
- composite multi
- Prior art date
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- 239000000178 monomer Substances 0.000 title claims abstract description 49
- 238000000034 method Methods 0.000 title claims abstract description 45
- 229920001519 homopolymer Polymers 0.000 title claims abstract description 41
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 10
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 117
- 239000003999 initiator Substances 0.000 claims abstract description 69
- 239000002131 composite material Substances 0.000 claims abstract description 49
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 150000002978 peroxides Chemical class 0.000 claims abstract description 21
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- 239000012986 chain transfer agent Substances 0.000 claims abstract description 18
- 239000007864 aqueous solution Substances 0.000 claims abstract description 16
- 239000012190 activator Substances 0.000 claims abstract description 15
- 239000002253 acid Substances 0.000 claims abstract description 14
- 238000001035 drying Methods 0.000 claims abstract description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 68
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 8
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 8
- 150000001451 organic peroxides Chemical class 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 238000001308 synthesis method Methods 0.000 claims description 8
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 6
- 229920002554 vinyl polymer Polymers 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 5
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 4
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 claims description 4
- XRXANEMIFVRKLN-UHFFFAOYSA-N 2-hydroperoxy-2-methylbutane Chemical compound CCC(C)(C)OO XRXANEMIFVRKLN-UHFFFAOYSA-N 0.000 claims description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical class ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- -1 alkyl mercaptans Chemical class 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 229960002089 ferrous chloride Drugs 0.000 claims description 3
- 239000011790 ferrous sulphate Substances 0.000 claims description 3
- 235000003891 ferrous sulphate Nutrition 0.000 claims description 3
- 239000011261 inert gas Substances 0.000 claims description 3
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 claims description 3
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 3
- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims description 3
- 238000005502 peroxidation Methods 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 125000005385 peroxodisulfate group Chemical group 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- WJEIYVAPNMUNIU-UHFFFAOYSA-N [Na].OC(O)=O Chemical compound [Na].OC(O)=O WJEIYVAPNMUNIU-UHFFFAOYSA-N 0.000 claims 1
- 239000001273 butane Substances 0.000 claims 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical group CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000013461 design Methods 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 28
- 230000008569 process Effects 0.000 description 21
- 239000000047 product Substances 0.000 description 14
- 230000000694 effects Effects 0.000 description 12
- 230000000977 initiatory effect Effects 0.000 description 12
- 239000000126 substance Substances 0.000 description 11
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical group [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
- 235000011114 ammonium hydroxide Nutrition 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 9
- 229920000642 polymer Polymers 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 4
- WNAHIZMDSQCWRP-UHFFFAOYSA-N dodecane-1-thiol Chemical compound CCCCCCCCCCCCS WNAHIZMDSQCWRP-UHFFFAOYSA-N 0.000 description 4
- 238000010528 free radical solution polymerization reaction Methods 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- AKUNSTOMHUXJOZ-UHFFFAOYSA-N 1-hydroperoxybutane Chemical compound CCCCOO AKUNSTOMHUXJOZ-UHFFFAOYSA-N 0.000 description 3
- 239000004342 Benzoyl peroxide Substances 0.000 description 3
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 3
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 239000012086 standard solution Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- DVPHDWQFZRBFND-DMHDVGBCSA-N 1-o-[2-[(3ar,5r,6s,6ar)-2,2-dimethyl-6-prop-2-enoyloxy-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-2-[4-[(2s,3r)-1-butan-2-ylsulfanyl-2-(2-chlorophenyl)-4-oxoazetidin-3-yl]oxy-4-oxobutanoyl]oxyethyl] 4-o-[(2s,3r)-1-butan-2-ylsulfanyl-2-(2-chloropheny Chemical group C1([C@H]2[C@H](C(N2SC(C)CC)=O)OC(=O)CCC(=O)OC(COC(=O)CCC(=O)O[C@@H]2[C@@H](N(C2=O)SC(C)CC)C=2C(=CC=CC=2)Cl)[C@@H]2[C@@H]([C@H]3OC(C)(C)O[C@H]3O2)OC(=O)C=C)=CC=CC=C1Cl DVPHDWQFZRBFND-DMHDVGBCSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- VUIWFPMVUDPADO-UHFFFAOYSA-N C(=C)C1C(=O)NCC1.C1=CC=CC=2C3=CC=CC=C3CC12 Chemical compound C(=C)C1C(=O)NCC1.C1=CC=CC=2C3=CC=CC=C3CC12 VUIWFPMVUDPADO-UHFFFAOYSA-N 0.000 description 1
- 239000004970 Chain extender Substances 0.000 description 1
- 101000748141 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 32 Proteins 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 102100040050 Ubiquitin carboxyl-terminal hydrolase 32 Human genes 0.000 description 1
- 206010049040 Weight fluctuation Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000012644 addition polymerization Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- SWXQKHHHCFXQJF-UHFFFAOYSA-N azane;hydrogen peroxide Chemical compound [NH4+].[O-]O SWXQKHHHCFXQJF-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012496 blank sample Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- ZZBBCSFCMKWYQR-UHFFFAOYSA-N copper;dioxido(oxo)silane Chemical compound [Cu+2].[O-][Si]([O-])=O ZZBBCSFCMKWYQR-UHFFFAOYSA-N 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229940063781 nitrogen 99 % Drugs 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000000864 peroxy group Chemical group O(O*)* 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-N peroxydisulfuric acid Chemical compound OS(=O)(=O)OOS(O)(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000019394 potassium persulphate Nutrition 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000013215 result calculation Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 229940126589 solid medicine Drugs 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F4/00—Polymerisation catalysts
- C08F4/28—Oxygen or compounds releasing free oxygen
- C08F4/30—Inorganic compounds
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F126/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
- C08F126/06—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a heterocyclic ring containing nitrogen
- C08F126/10—N-Vinyl-pyrrolidone
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F4/00—Polymerisation catalysts
- C08F4/28—Oxygen or compounds releasing free oxygen
- C08F4/32—Organic compounds
- C08F4/34—Per-compounds with one peroxy-radical
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2/00—Processes of polymerisation
- C08F2/04—Polymerisation in solution
- C08F2/10—Aqueous solvent
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2/00—Processes of polymerisation
- C08F2/38—Polymerisation using regulators, e.g. chain terminating agents, e.g. telomerisation
Definitions
- the invention relates to the technical field of compound synthesis, in particular to the technical field of homopolymerization of N-vinyl butyrolactam, in particular to a method for synthesizing a low residual single low molecular weight homopolymerized N-vinyl butyrolactam.
- the low molecular weight homopolymer N-vinyl butyrolactam refers to a N-vinyl butyrolactam homopolymer having a molecular weight of from 30,000 to 50,000.
- the molecular weight range of homopolymerized N-vinyl butyrolactam is the most widely used series of homopolymers of N-vinyl butyrolactam, which is widely used as a binder for drugs such as tablets and granules.
- Homopolymerized N-vinyl butyrolactam is widely used due to its unique properties. It not only has excellent solubility, chemical stability, film formation, physiological inertness, bonding ability and protective rubber action, but also Combined with many inorganic and organic compounds, homopolymeric N-vinyl butyrolactam has been widely used in medicine, cosmetics, food, brewing, coatings, adhesives, printing and dyeing auxiliaries, separation membranes, and sensitization since its introduction. Materials and other fields (Yan Ruizhen. Water-soluble polymer 2nd edition [M]. Beijing: Chemical Industry Press, 2010, 215-220). Especially as a pharmaceutical excipient, homopolymeric N-vinyl butyrolactam has many applications in solid medicines. Low molecular weight homopolymeric N-vinyl butyrolactam is also important in injections and eye drops. effect.
- the method for synthesizing homopolymerized N-vinyl butyrolactam is generally carried out by solution polymerization, and the solvents used for solution polymerization thereof are mainly water, ethanol, isopropanol, methanol and the like.
- the solvents used for solution polymerization thereof are mainly water, ethanol, isopropanol, methanol and the like.
- different solvents have different effects on the molecular weight of the homopolymerized N-vinyl butyrolactam in solution polymerization, and it is easier to polymerize high molecular weight homopolymerized N-ethylene in general solvents.
- the butyrolactam product while the lower molecular weight homopoly N-vinyl butyrolactam product, such as homopolymeric N-vinyl butyrolactam having a molecular weight of between 2,000 and 50,000, is more difficult to prepare. This is mainly because the polymerization of N-vinyl butyrolactam is a chain reaction, the reaction is difficult to terminate once it starts, and the molecular weight is difficult to control; at the same time, even a lower molecular weight homopolymeric N-vinyl butyrolactam is made.
- the product has a high residual monomer content in the slurry, which is difficult to meet its application requirements in the fields of medicine and daily makeup.
- the content of N-vinyl butyrolamide in the pharmaceutical or food grade homo- N-vinyl butyrolactam residual monomer is less than 10 ppm.
- Polyurethane polymer post-treatment processes such as activated carbon adsorption, solvent extraction or ultrafiltration, radiation, etc. (Nuber, Dr. Adolf, Sanner, Dr. Axel, Urban, Dr. Dieter. Use of an adsorbent for the removal of vinylpyrrolidon from Vinylpyrrolidon polymer solutions [P].
- the object of the present invention is to overcome the above-mentioned shortcomings of the prior art and to provide a method for synthesizing a low residue single low molecular weight homopolymerized N-vinyl butyrolactam, the low residual single low molecular weight homopolymer N-vinylbutylene
- the synthesis method of amide is ingeniously designed, and the preparation of the low residual single low molecular weight homopolymer N-vinyl butyrolactam has a residual amount of less than 10 ppm and a K value of 24-31, which is suitable for large-scale popularization and application.
- the method for synthesizing the low residue single low molecular weight homopolymerized N-vinyl butyrolactam of the present invention is characterized in that
- the compound-based composite multi-initiator accounts for 35% by weight, and the azo-based composite multi-initiator accounts for 30% by weight; in the presence of inert gas, firstly 45% of the total weight of water, N-vinyl butyl 30% of the total weight of the lactam monomer, 70% of the total weight of the catalyst and 70% of the total weight of the chain transfer agent, and the pH of the reaction system is adjusted to 7.0 by the activator.
- the reaction is carried out at a polymerization temperature of 60-85 ° C, and the remaining water, the remaining N-vinyl butyrolactam monomer, and the organic peroxide-based composite multi-initiator are added in batches within 4-9 hours from the start of the reaction.
- the pH of the system should be 7.0-8.0, then 80-100 ° C for 30 minutes, then add the azo-based composite multi-initiator, continue to keep 1-3 'J, then add N-vinyl butyrolactam 0.01% ⁇ 1% of the total weight of the peroxide is further incubated for 2 hours, then the acid is adjusted to acidity at a temperature of 90-120 ° C, and the reaction is refluxed for 1-3 hours to obtain a colorless transparent low molecular weight homopolymerized N-ethylene.
- the aqueous solution of succinimide is dried to obtain a powdery low residual single low molecular weight homopolymeric N-vinyl butyrolactam having a K value of 24-31, a molecular weight of 30,000 to 50,000, and a residual amount of less than 10 ppm.
- the composite multi-initiator may be composed of any suitable material. More preferably, the composite multi-initiator is selected from the group consisting of hydrogen peroxide, t-butyl hydroperoxide, t-amyl hydroperoxide, peroxodisulfuric acid, and Two or more of potassium sulfate, potassium persulfate, azobisisobutyronitrile, and azobisisoheptanenitrile.
- the inorganic peroxide-based composite multi-initiator, the organic peroxide-based composite multi-initiator, and the azo-based composite multi-initiator may be any suitable
- the composite initiator preferably, the inorganic peroxide-based composite multicomponent initiator is a mixture of hydrogen peroxide and t-butyl hydroperoxide mainly composed of hydrogen peroxide;
- the peroxide-based composite multi-component bow hair agent is a mixture of t-butyl hydroperoxide and hydrogen peroxide mainly composed of t-butyl hydroperoxide;
- the azo-based composite multi-initiator It is a mixture of azobisisoheptanenitrile and t-butyl hydroperoxide mainly composed of azobisisoheptanenitrile.
- the catalyst may be any suitable catalyst.
- the catalyst is selected from one or more of an aqueous solution of ferrous sulfate, an aqueous solution of ferrous chloride and an aqueous solution of copper silicate.
- the chain transfer agent may be any suitable chain transfer agent.
- the chain transfer agent is selected from one or more of the group consisting of ethanol, n-propanol, isopropanol, dodecyl alcohol and acid salt. kind.
- the activator may be any suitable activator.
- the activator is aqueous ammonia, sodium hydroxide, triethanolamine, hydroxylammonium salt or sodium carbonate.
- the peroxide may be any suitable peroxide, preferably the peroxide is hydrogen peroxide or t-butyl hydroperoxide.
- the acid can be any suitable acid, preferably the acid is acetic acid or citric acid.
- the beneficial effects of the present invention are specifically as follows:
- the compound multi-initiator comprises 35% by weight of an inorganic peroxide-based composite multi-initiator, and the organic peroxide-based composite multi-initiator accounts for 35% by weight, and the azo-based composite
- the multi-component initiator accounts for 30% by weight; in the presence of an inert gas, firstly, 45% of the total weight of water, 30% of the total weight of the N-vinyl butyrolactam monomer, and the composite multi-component
- the reaction is refluxed for 1-3 hours to obtain a colorless transparent low molecular weight homopolymerized N-vinylbutyrolactam solution, which is dried to obtain a powdery low residual single low molecular weight homopolymeric N-vinyl butyrolactam having a K value of 24-31.
- the molecular weight is between 30,000 and 50,000, and the residual single is below 10 ppm.
- the design is ingenious, and the single sheet is prepared.
- the residual residue of the low residual single low molecular weight homopolymer N-vinyl butyrolactam is prepared at 10 ppm.
- K value 24-31 suitable for large-scale promotion and application.
- N-vinyl butyrolactam monomer to water ratio of 4:16 ⁇ 8:12 composite multi-initiator 0.5% ⁇ 5.0% (based on N-vinylbutyrolactam), catalyst 0.1% ⁇ 5.0% (based on N-vinyl butyrolactam), a small amount of activator to adjust the pH of the reaction system, chain transfer agent 0.1% to 10% (based on N-vinyl butyrolactam); It may be hydrogen peroxide, t-butyl hydroperoxide, tert-amyl hydroperoxide, peroxodisulfate, potassium peroxydisulfate, potassium persulfate, azobisisobutyronitrile, azobisisoheptanenitrile.
- the activator may be ammonia water, sodium hydroxide, triethanolamine, hydroxylammonium salt, sodium carbonate, etc.; the catalyst may be one of ferrous sulfate, ferrous chloride, copper sulfate, or the like, or a low concentration of several metal sulfates;
- the aqueous solution; the chain transfer agent may be one or more of ethanol, n-propanol, isopropanol, dodecyl mercaptan, sulfite, and the like.
- the pH is 7.0-8.0
- the temperature is raised to 60-85 °C by heating in an oil bath, and all the remaining monomers and the composite multi-initiator B are mixed in the range of 4-9 hours from the start of the reaction, that is, the composite multi-initiator based on organic peroxide. (accounting for 35% of the total amount of initiator), all remaining catalyst, chain transfer agent and residual water.
- the pH of the solution is adjusted to 7.0-8.0 with ammonia water, and then the composite multi-initiator is added after 80-100 ° C for 30 min.
- C is an azo-based composite multi-initiator (accounting for 30% of the total amount of initiator), and after adding 1-3 hours, add 0.01% to 1% (based on N-vinyl butyrolactam).
- the oxide is kept for another 2 hours, after which the temperature is raised to 90-120 ° C and a small amount of acid is added to adjust the pH to acidity.
- the reaction can be carried out for 1-3 hours to obtain a colorless transparent low molecular weight homopolymeric N-vinylbutyrolactam solution with a K value of 24-31 and a molecular weight of 30,000-50,000. Drying gives a powdery low molecular weight homopolymer N-vinyl group. Butyrolactam.
- the weight average molecular weight was determined by Waters 515 gel chromatograph, Waters 2410 differential refractive index detector; column: Waters Ultrahydrogel 500he Ultrahydrogel 120 two columns in series (7.8 x 300mm); mobile phase: 0.1M sodium nitrate aqueous solution; flow rate: 0.8ml/min Injection volume: 5 (3 ⁇ 4 liter; column temperature: 40 °C;
- K value of the Fikentscher formula is a parameter that is only related to molecular weight and does not change with the concentration of homopolymeric N-vinyl butyrolactam.
- a commonly used method for determining the K value is a viscosity method.
- the Ubbel viscometer measures the relative viscosity r) r of the solution against water at a water bath temperature of 25 ⁇ 0.2 °C.
- K is the Fikentscher constant
- c is the number of grams of homopolymerized N-vinyl butyrolactam dissolved in 0.1 L solution
- Relative viscosity (the ratio of solution effluent time to pure solvent effluent time T/T 0 )
- the determination of the residual monomer content in the homopolymerized fluorene-vinyl butyrolactam is based on the method specified in the 21st edition of the United States Pharmacopoeia. Take 10g of homopolyindole-vinyl butyrolactam (accurate to 0.002g, based on anhydrous matter), dissolve in 80ml of distilled water, add lg sodium acetate, titrate with 0.1 mol/L iodine solution until the solution no longer fades, then Add 3 ml of 0.1 mol/L iodine solution for 10 minutes, then titrate excess iodine with 0.1 mol/L sodium thiosulfate. Add 3 ml of starch indicator when approaching the end point, continue titration until the solution color disappears. At the same time, compared with the blank experiment.
- Vj the volume of iodine standard solution (mL) consumed by titrating the blank sample
- V 2 the volume of iodine standard solution (mL) consumed by titrating the sample
- N-vinyl butyrolactam (g)
- the initiator When the initiator initiates the reaction polymerization, the initiator can initiate the reaction polymerization only when the thermal energy reaches the decomposition activation energy of the initiator. Therefore, it is necessary to place the reaction system at a certain temperature when the reaction is initiated. With hydrogen peroxide as the initiator, the influence of the quality of the reaction product at different temperatures was analyzed. The results are shown in Table 2 below:
- Solution polymerization of homopolymeric N-vinyl butyrolactam can be carried out using three different types of initiators (Haaf F, Sanner A, Straub F. Polymer of N-vinyl pyrrolidone: Synthesis, characterization and uses [J], Polym J, 1985, 17(1): 143- 152; Wolfgang L, Friedrich G M.
- polyvinyl pyrrolidone versatile specialty polymer [J], Polym News, 1987, 12(8): 232-237), known as peroxidation System, such as: hydrogen peroxide (H 2 O 2 ), t-butyl hydroperoxide, benzoyl peroxide; redox system, such as: ammonium persulfate-sodium bisulfite; azo, such as: azo Isobutyronitrile, azobisisoheptanenitrile.
- peroxidation System such as: hydrogen peroxide (H 2 O 2 ), t-butyl hydroperoxide, benzoyl peroxide; redox system, such as: ammonium persulfate-sodium bisulfite; azo, such as: azo Isobutyronitrile, azobisisoheptanenitrile.
- the homo- N-vinyl butyrolactam residue prepared by using an inorganic peroxy initiator such as hydrogen peroxide is higher than other initiator systems, mainly because of the use of a peroxygen initiator.
- the cleavage of the pyrrolidone ring occurs in the planting reaction of the chain in the polymerization mechanism, resulting in the second terminal group of the homopolymerized N-vinyl butyrolactam being a base, and a part of the pyrrolidone remains in the product, resulting in a higher residue in the product;
- the redox-I or azo initiator is used to prepare homo- N-vinyl butyrolactam, the azo initiator is easy to initiate polymerization, which causes the system to decompose more free radicals during the entire polymerization process.
- the reaction rate is faster and the polymerization is difficult to control.
- the persulfate initiator introduces sulfate impurities during the polymerization process, which is likely to cause excessive ash.
- the K value of homopolymerized N-vinyl butyrolactam was stable at 24-31, and the weight average molecular weight was between 30,000 and 50,000. Requirements for applications such as medicine.
- N-vinyl butyrolactam is easily hydrolyzed in the presence of acid or certain salts to form pyrrolidone and acetaldehyde (Cui Yingde, Yi Guobin, Liao Liwen. Synthesis and application of polyvinylpyrrolidone [M]. Science Press, 2001, 2:8).
- J. Ferguson et al. J. Ferguson and V. Sunder ajan, Polymer Journal., (15), 627 (1979) conducted a comprehensive study on the hydrolysis of N-vinyl butyrolactam. Therefore, in order to ensure the smooth progress of the polymerization reaction, it is necessary to adjust the pH of the reaction system to neutral or alkaline.
- the known initiation processes are generally as follows: one-time addition polymerization initiation, multi-stage initiation polymerization, and late reaction initiation polymerization.
- segmentation multiple initiation polymerization and the reaction late addition initiation polymerization are compared with the one-time direct addition initiation polymerization, the homopolymer N-vinyl butyrolactam has a lower residue and a certain molecular weight selectivity, but These two processes still have certain defects: First, the steps are complicated and it is difficult to achieve real industrial production; Second, the conditions are demanding, and it is necessary to strictly control the temperature, the rotational speed, the amount of addition, etc. for each feeding, and there are some errors.
- the initiator is added in three time periods: from the first 30-50 minutes from the start of the raw material to the first time period, at which time the inorganic peroxide-based composite multi-initiator is selectively added;
- the second addition of N-vinyl butyrolactam monomer to all the monomers is completed for the second period of time, in this process, the organic peroxide-based composite multi-initiator is selected to be added in portions; from N-vinyl butyl
- a 30-50 min period from the start of the lactam monomer addition is a third period of time during which a small amount of an azo-based complex multi-initiator is added.
- the unique composite multi-component initiation process has a lower homo- N-vinyl butyrolactam residue, a lower molecular weight fluctuation and a higher reproducibility than the conventional process.
- N-vinyl butyrolactam has a high content of residual N-vinyl butyrolactam at the end of the reaction due to the large number of free radical collisions and other various reasons.
- a better chain extender can be selected; on the other hand, the residual N-vinyl butyrolactam monomer can be eliminated by adding acid, and the prior art has been patented (the first industry is only a company.
- Vinyl A method for producing a pyrrolidone polymer: China, 200710105080.7. [ ⁇ ] 2007-11-28.) This has been described. However, the experiment found that the above two methods did not achieve very good results.
- this experiment found a unique disintegration treatment process: Add a small amount of peroxide in the later stage of the reaction, then keep the reaction for a period of time, then raise the temperature to 90-12CTC plus a small amount. The acid is adjusted to pH for a period of l-3 h.
- Example 1 The same procedure as in Example 1 was carried out except that "0.5 parts of hydrogen peroxide" in the latter stage of the reaction was replaced with "0.5 parts of t-butyl hydroperoxide” to obtain a colorless transparent aqueous solution of homopolymerized N-vinylbutyrolactam. Spray dried to a powdery product, As a result, the K value of the homopolymeric N-vinyl butyrolactam was 24.8, the weight average molecular weight was 31,860, and the residual amount was 3 ppm. Comparative example 1:
- Example 2 The same procedure as in Example 2 was carried out except that "0.5 parts of hydrogen peroxide" added at the end of the reaction was removed, and a yellowish transparent aqueous solution of homopolymerized N-vinylbutyrolactam was obtained, which was spray-dried to obtain a powdery product.
- the homopolymeric N-vinyl butyrolactam was detected to have a K value of 31.2, a molecular weight of 51,100, and a residual residue of 113 ppm.
- the present invention develops a low molecular weight low residue by studying the influence of the initiation system, the amount of the initiator, the time, and the polymerization process on the final product during the synthesis of the homopolymerized N-vinyl butyrolactam.
- a method of homopolymerizing N-vinyl butyrolactam (molecular weight between 30,000 and 50,000), the quality of the product produced by this method can fully meet the latest international pharmacopoeia standards.
- the method for synthesizing the low residue single low molecular weight homopolymerized N-vinyl butyrolactam of the present invention is ingeniously designed to prepare a single residue, and the residue of the low residual single low molecular weight homopolymeric N-vinyl butyrolactam prepared is prepared.
- K value 24-31 suitable for large-scale promotion and application.
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Abstract
Disclosed in the present invention is a method for synthesizing a homopolymer N-vinyl butyrolactam with low residual monomer and a low molecular weight, using an N-vinyl butyrolactam monomer and water at a weight ratio of 4:16—8:12 and then using 0.5%-5.0% weight of a composite polybasic initiator, 0.1%-0.5% weight of a catalyst, and 0.1%-10% weight of a chain transfer agent, on the basis of the N-vinyl butyrolactam monomer, in the presence of an insert gas, adding in batches the above raw materials, using an activator to adjust the reaction system to be at pH 7.0—8.0, the reaction being carried out at a polymerization temperature of 60°C—85°C; finally, adding a peroxide and maintaining the temperature for 2 hours and then using an acid to adjust the pH to acidity and maintaining this for l—3 h, so as to obtain a colourless and transparent aqueous solution of the homopolymer N-vinyl butyrolactam; after drying, a powdery homopolymer N-vinyl butyrolactam with a K value of 24-31, a low molecular weight and residual monomer below 10 ppm is obtained. The present invention is ingenious in design and simple in preparation. The prepared homopolymer N-vinyl butyrolactam with low residual monomer and low molecular weight has residual monomer below 10 ppm, a K value of 24-31, and is suitable for a large scale of popularization and application.
Description
低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法 技术领域 Method for synthesizing low residue single low molecular weight homopolymerized N-vinyl butyrolactam
本发明涉及化合物合成技术领域， 特别涉及均聚 N-乙烯基丁内酰胺合成技术领域， 具体 是指一种低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法。 背景技术 The invention relates to the technical field of compound synthesis, in particular to the technical field of homopolymerization of N-vinyl butyrolactam, in particular to a method for synthesizing a low residual single low molecular weight homopolymerized N-vinyl butyrolactam. Background technique
低分子量均聚 N-乙烯基丁内酰胺是指分子量在 30000-50000之间的 N-乙烯基丁内酰胺均 聚物。该分子量范围的均聚 N-乙烯基丁内酰胺是 N-乙烯基丁内酰胺一系列均聚物中应用最广 泛的， 其广泛用作片剂、 颗粒剂等药物的粘合剂。 The low molecular weight homopolymer N-vinyl butyrolactam refers to a N-vinyl butyrolactam homopolymer having a molecular weight of from 30,000 to 50,000. The molecular weight range of homopolymerized N-vinyl butyrolactam is the most widely used series of homopolymers of N-vinyl butyrolactam, which is widely used as a binder for drugs such as tablets and granules.
均聚 N-乙烯基丁内酰胺由于其独特的性能而得到日益广泛的应用， 它不仅具有优异的溶 解性、 化学稳定性、 成膜性、 生理惰性、 粘接能力和保护胶作用， 还可与许多无机、 有机化 合物结合， 因此， 均聚 N-乙烯基丁内酰胺自面世至今， 已被广泛用于医药、 化妆品、 食品、 酿造、涂料、粘接剂、 印染助剂、分离膜、感光材料等领域（严瑞瑄. 水溶性高分子第 2版 [M]. 北京： 化学工业出版社， 2010, 215-220 )。 特别是作为医药辅料的应用， 均聚 N-乙烯基丁内酰 胺除了在固体药物中有诸多应用外， 低分子量的均聚 N-乙烯基丁内酰胺还在注射液及眼药中 也有重要的作用。 Homopolymerized N-vinyl butyrolactam is widely used due to its unique properties. It not only has excellent solubility, chemical stability, film formation, physiological inertness, bonding ability and protective rubber action, but also Combined with many inorganic and organic compounds, homopolymeric N-vinyl butyrolactam has been widely used in medicine, cosmetics, food, brewing, coatings, adhesives, printing and dyeing auxiliaries, separation membranes, and sensitization since its introduction. Materials and other fields (Yan Ruizhen. Water-soluble polymer 2nd edition [M]. Beijing: Chemical Industry Press, 2010, 215-220). Especially as a pharmaceutical excipient, homopolymeric N-vinyl butyrolactam has many applications in solid medicines. Low molecular weight homopolymeric N-vinyl butyrolactam is also important in injections and eye drops. effect.
目前工业上合成均聚 N-乙烯基丁内酰胺的方法一般釆用溶液聚合法， 而用于其溶液聚合 的溶剂主要有水、 乙醇、 异丙醇、 甲醇等。 通过张光华等人的研究成果发现： 在溶液聚合法 中不同溶剂对聚合产物均聚 N-乙烯基丁内酰胺分子量的影响不同， 而且在一般溶剂中较容易 聚合出高分子量的均聚 N-乙烯基丁内酰胺产品，而较低分子量的均聚 N-乙烯基丁内酰胺产品 如分子量在 2000-50000之间的均聚 N-乙烯基丁内酰胺则较难制备出。 这主要是因为 N-乙烯 基丁内酰胺的聚合属于链式反应， 反应一旦开始就难以终止， 分子量难以控制； 与此同时， 即便是做出较低分子量的均聚 N-乙烯基丁内酰胺产品， 其浆料中的残余单体含量也很高， 难 以满足其在医药以及日用化妆等领域的应用要求。 At present, the method for synthesizing homopolymerized N-vinyl butyrolactam is generally carried out by solution polymerization, and the solvents used for solution polymerization thereof are mainly water, ethanol, isopropanol, methanol and the like. According to the research results of Zhang Guanghua et al., different solvents have different effects on the molecular weight of the homopolymerized N-vinyl butyrolactam in solution polymerization, and it is easier to polymerize high molecular weight homopolymerized N-ethylene in general solvents. The butyrolactam product, while the lower molecular weight homopoly N-vinyl butyrolactam product, such as homopolymeric N-vinyl butyrolactam having a molecular weight of between 2,000 and 50,000, is more difficult to prepare. This is mainly because the polymerization of N-vinyl butyrolactam is a chain reaction, the reaction is difficult to terminate once it starts, and the molecular weight is difficult to control; at the same time, even a lower molecular weight homopolymeric N-vinyl butyrolactam is made. The product has a high residual monomer content in the slurry, which is difficult to meet its application requirements in the fields of medicine and daily makeup.
根据美国药典 USP32的规定， 医药或者食品级的均聚 N-乙烯基丁内酰胺残留单体 N-乙 烯基丁内酰胺含量要求低于 lOppm, 目前， 均聚 N-乙烯基丁内酰胺工业化生产多釆用聚合物 料后处理工艺如活性炭吸附、 溶剂萃取或者超滤、 辐射等方式（Nuber, Dr. Adolf , Sanner, Dr. Axel ,Urban, Dr. Dieter. Use of an adsorbent for the removal of vinylpyrrolidon from vinylpyrrolidon polymer solutions[P]. EP 0258854, 1991-3-13； Juergen Detering, Limburgerhof, Hartwig Voss, Frankenthal. Preparation of ultrapure N-vinylpyrrolidone polymers [P]. US 5354945,
1994-10-11; 黎新明. 一种消除聚合物中残留单体 N-乙烯基吡咯烷酮的方法 [P]. CN 1712432, 2005-12-28 )。 这些消残方式都大大增加了原料和设备投入成本， According to the USP32, the content of N-vinyl butyrolamide in the pharmaceutical or food grade homo- N-vinyl butyrolactam residual monomer is less than 10 ppm. Currently, the production of homopolymerized N-vinyl butyrolactam is industrialized. Polyurethane polymer post-treatment processes such as activated carbon adsorption, solvent extraction or ultrafiltration, radiation, etc. (Nuber, Dr. Adolf, Sanner, Dr. Axel, Urban, Dr. Dieter. Use of an adsorbent for the removal of vinylpyrrolidon from Vinylpyrrolidon polymer solutions [P]. EP 0258854, 1991-3-13; Juergen Detering, Limburgerhof, Hartwig Voss, Frankenthal. Preparation of ultrapure N-vinylpyrrolidone polymers [P]. US 5354945, 1994-10-11; Li Xinming. A method for eliminating residual monomer N-vinylpyrrolidone in polymers [P]. CN 1712432, 2005-12-28 ). These disintegration methods have greatly increased the input cost of raw materials and equipment.
因此， 如果能够通过对均聚 N-乙烯基丁内酰胺合成过程中的引发体系、 引发剂用量、 时 间以及聚合工艺等对最终产品的影响研究， 研发出一种可以制备出低分子量低残单均聚 N-乙 烯基丁内酰胺（分子量在 30000-50000 )的方法， 该方法做出的产品质量完全可以满足国际上 最新药典标准， 则具有非常重要的意义。 发明内容 Therefore, if the influence of the initiator system, the amount of initiator, the time, and the polymerization process on the final product during the synthesis of homopolymerized N-vinyl butyrolactam can be studied, a low molecular weight low residue can be prepared. The method of homopolymerizing N-vinyl butyrolactam (molecular weight between 30,000 and 50,000), the quality of the product produced by this method can fully meet the latest international pharmacopoeia standards, and is of great significance. Summary of the invention
本发明的目的是克服了上述现有技术中的缺点， 提供一种低残单低分子量均聚 N-乙烯基 丁内酰胺的合成方法， 该低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法设计巧妙， 制备 筒单， 制备出的低残单低分子量均聚 N-乙烯基丁内酰胺的残单在 lOppm以下、 K值 24-31 , 适于大规模推广应用。 SUMMARY OF THE INVENTION The object of the present invention is to overcome the above-mentioned shortcomings of the prior art and to provide a method for synthesizing a low residue single low molecular weight homopolymerized N-vinyl butyrolactam, the low residual single low molecular weight homopolymer N-vinylbutylene The synthesis method of amide is ingeniously designed, and the preparation of the low residual single low molecular weight homopolymer N-vinyl butyrolactam has a residual amount of less than 10 ppm and a K value of 24-31, which is suitable for large-scale popularization and application.
为了实现上述目的， 本发明的低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法， 其特 点是， In order to achieve the above object, the method for synthesizing the low residue single low molecular weight homopolymerized N-vinyl butyrolactam of the present invention is characterized in that
釆用质量比为 4:16~8:12的 N-乙烯基丁内酰胺单体与水， 再以 N-乙烯基丁内酰胺单体为基 准， 釆用 0.5%~5.0%重量的复合多元引发剂、 0.1%~5.0%重量的催化剂和 0.1%~10%重量的链 转移剂， 其中复合多元引发剂中以无机过氧化物为主的复合多元引发剂占 35%重量， 以有机 过氧化物为主的复合多元引发剂占 35%重量， 以偶氮类为主的复合多元引发剂占 30%重量； 在惰性气体存在条件下， 首先加入水总重量的 45%、 N-乙烯基丁内酰胺单体总重量的 30%、 以无机过氧化物为主的复合多元引发剂、 催化剂总重量的 70%和链转移剂总重量的至 少 70%, 用活化剂调节反应体系 pH至 7.0-8.0, 在聚合温度 60-85 °C进行反应， 反应开始 4-9小时 内分批次加入剩余水、剩余 N-乙烯基丁内酰胺单体、 以有机过氧化物为主的复合多元引发剂、 剩余催化剂和剩余链转移剂， 期间用活化剂调节反应体系 pH至 7.0-8.0, 然后 80-100°C保温 30 分钟后加入以偶氮类为主的复合多元引发剂，继续保温 1 -3 'J、时后加入 N-乙烯基丁内酰胺单体 总重量的 0.01%~1%的过氧化物再保温 2小时， 然后在温度 90-120°C加酸调节 pH至酸性， 回流 反应 1-3小时得到无色透明低分子量均聚 N-乙烯基丁内酰胺水溶液，干燥即得粉末状低残单低 分子量均聚 N-乙烯基丁内酰胺， K值在 24-31 , 分子量在 30000-50000, 残单在 lOppm以下。 NUse N-vinyl butyrolactam monomer with a mass ratio of 4:16~8:12 and water, and then use 0.5%~5.0% by weight of composite multiplex based on N-vinyl butyrolactam monomer. Initiator, 0.1%~5.0% by weight of catalyst and 0.1%~10% by weight of chain transfer agent, wherein the composite multi-initiator comprises 35% by weight of inorganic peroxide-based composite multi-initiator, with organic peroxidation The compound-based composite multi-initiator accounts for 35% by weight, and the azo-based composite multi-initiator accounts for 30% by weight; in the presence of inert gas, firstly 45% of the total weight of water, N-vinyl butyl 30% of the total weight of the lactam monomer, 70% of the total weight of the catalyst and 70% of the total weight of the chain transfer agent, and the pH of the reaction system is adjusted to 7.0 by the activator. 8.0, the reaction is carried out at a polymerization temperature of 60-85 ° C, and the remaining water, the remaining N-vinyl butyrolactam monomer, and the organic peroxide-based composite multi-initiator are added in batches within 4-9 hours from the start of the reaction. , residual catalyst and residual chain transfer agent, during conditioning with activator The pH of the system should be 7.0-8.0, then 80-100 ° C for 30 minutes, then add the azo-based composite multi-initiator, continue to keep 1-3 'J, then add N-vinyl butyrolactam 0.01%~1% of the total weight of the peroxide is further incubated for 2 hours, then the acid is adjusted to acidity at a temperature of 90-120 ° C, and the reaction is refluxed for 1-3 hours to obtain a colorless transparent low molecular weight homopolymerized N-ethylene. The aqueous solution of succinimide is dried to obtain a powdery low residual single low molecular weight homopolymeric N-vinyl butyrolactam having a K value of 24-31, a molecular weight of 30,000 to 50,000, and a residual amount of less than 10 ppm.
所述复合多元引发剂可以由任何合适的物质组成， 更佳地， 所述复合多元引发剂选自过 氧化氢、 叔丁基过氧化氢、 叔戊基过氧化氢、 过二硫酸、 过二硫酸钾、 过硫酸钾、 偶氮二异 丁腈和偶氮二异庚腈中的两种以上。
所述的以无机过氧化物为主的复合多元引发剂、 所述的以有机过氧化物为主的复合多元 引发剂、 所述的以偶氮类为主的复合多元引发剂可以是任何合适的复合引发剂， 较佳地， 所 述的以无机过氧化物为主的复合多元引发剂是以过氧化氢为主的过氧化氢与叔丁基过氧化氢 混合液； 所述的以有机过氧化物为主的复合多元弓 I发剂是以叔丁基过氧化氢为主的叔丁基过 氧化氢与过氧化氢混合液； 所述的以偶氮类为主的复合多元引发剂是以偶氮二异庚腈为主的 偶氮二异庚腈与叔丁基过氧化氢混合液。 The composite multi-initiator may be composed of any suitable material. More preferably, the composite multi-initiator is selected from the group consisting of hydrogen peroxide, t-butyl hydroperoxide, t-amyl hydroperoxide, peroxodisulfuric acid, and Two or more of potassium sulfate, potassium persulfate, azobisisobutyronitrile, and azobisisoheptanenitrile. The inorganic peroxide-based composite multi-initiator, the organic peroxide-based composite multi-initiator, and the azo-based composite multi-initiator may be any suitable The composite initiator, preferably, the inorganic peroxide-based composite multicomponent initiator is a mixture of hydrogen peroxide and t-butyl hydroperoxide mainly composed of hydrogen peroxide; The peroxide-based composite multi-component bow hair agent is a mixture of t-butyl hydroperoxide and hydrogen peroxide mainly composed of t-butyl hydroperoxide; the azo-based composite multi-initiator It is a mixture of azobisisoheptanenitrile and t-butyl hydroperoxide mainly composed of azobisisoheptanenitrile.
所述催化剂可以是任何合适的催化剂， 较佳地， 所述催化剂选自硫酸亚铁水溶液、 氯化 亚铁水溶液和石克酸铜水溶液中的一种或几种。 The catalyst may be any suitable catalyst. Preferably, the catalyst is selected from one or more of an aqueous solution of ferrous sulfate, an aqueous solution of ferrous chloride and an aqueous solution of copper silicate.
所述链转移剂可以是任何合适的链转移剂， 较佳地， 所述链转移剂选自乙醇、 正丙醇、 异丙醇、 十二烷基^ 醇和亚 酸盐中的一种或几种。 The chain transfer agent may be any suitable chain transfer agent. Preferably, the chain transfer agent is selected from one or more of the group consisting of ethanol, n-propanol, isopropanol, dodecyl alcohol and acid salt. Kind.
所述活化剂可以是任何合适的活化剂， 较佳地， 所述活化剂是氨水、 氢氧化钠、 三乙醇 胺、 羟铵盐或碳酸钠。 The activator may be any suitable activator. Preferably, the activator is aqueous ammonia, sodium hydroxide, triethanolamine, hydroxylammonium salt or sodium carbonate.
所述过氧化物可以是任何合适的过氧化物， 较佳地， 所述过氧化物是过氧化氢或叔丁基 过氧化氢。 The peroxide may be any suitable peroxide, preferably the peroxide is hydrogen peroxide or t-butyl hydroperoxide.
所述酸可以是任何合适的酸， 较佳地， 所述酸是醋酸或柠檬酸。 The acid can be any suitable acid, preferably the acid is acetic acid or citric acid.
本发明的有益效果具体在于： 本发明的低残单低分子量均聚 N-乙烯基丁内酰胺的合成方 法， 釆用质量比为 4:16~8:12的 N-乙烯基丁内酰胺单体与水， 再以 N-乙烯基丁内酰胺单体为 基准， 釆用 0.5%~5.0%重量的复合多元引发剂、 0.1%~5.0%重量的催化剂和 0.1%~10%重量的 链转移剂， 其中复合多元引发剂中以无机过氧化物为主的复合多元引发剂占 35%重量， 以有 机过氧化物为主的复合多元引发剂占 35%重量，以偶氮类为主的复合多元引发剂占 30%重量； 在惰性气体存在条件下， 首先加入水总重量的 45%、 N-乙烯基丁内酰胺单体总重量的 30%、 以无机过氧化物为主的复合多元引发剂、催化剂总重量的 70%和链转移剂总重量的至少 70%, 用活化剂调节反应体系 pH至 7.0-8.0, 在聚合温度 60-85 °C进行反应， 反应开始 4-9小时内分 批次加入剩余水、 剩余 N-乙烯基丁内酰胺单体、 以有机过氧化物为主的复合多元引发剂、 剩 余催化剂和剩余链转移剂， 期间用活化剂调节反应体系 pH至 7.0-8.0, 然后 80-100°C保温 30 分钟后加入以偶氮类为主的复合多元引发剂， 继续保温 1-3小时后加入 N-乙烯基丁内酰胺单 体总重量的 0.01%~1%的过氧化物再保温 2小时， 然后在温度 90-120°C加酸调节 pH至酸性， 回流反应 1-3小时得到无色透明低分子量均聚 N-乙烯基丁内酰胺水溶液， 干燥即得粉末状低 残单低分子量均聚 N-乙烯基丁内酰胺， K值在 24-31 , 分子量在 30000-50000, 残单在 lOppm 以下，设计巧妙，制备筒单，制备出的低残单低分子量均聚 N-乙烯基丁内酰胺的残单在 lOppm
以下、 K值 24-31 , 适于大规模推广应用。 The beneficial effects of the present invention are specifically as follows: The method for synthesizing the low residual single low molecular weight homopolymerized N-vinyl butyrolactam of the present invention, using N-vinyl butyrolactam with a mass ratio of 4:16 to 8:12 Body and water, based on N-vinyl butyrolactam monomer, using 0.5% to 5.0% by weight of composite multi-initiator, 0.1% to 5.0% by weight of catalyst and 0.1% to 10% by weight of chain transfer The compound multi-initiator comprises 35% by weight of an inorganic peroxide-based composite multi-initiator, and the organic peroxide-based composite multi-initiator accounts for 35% by weight, and the azo-based composite The multi-component initiator accounts for 30% by weight; in the presence of an inert gas, firstly, 45% of the total weight of water, 30% of the total weight of the N-vinyl butyrolactam monomer, and the composite multi-component initiated by inorganic peroxide 70% of the total weight of the agent, the catalyst and at least 70% of the total weight of the chain transfer agent, the pH of the reaction system is adjusted to 7.0-8.0 with an activator, and the reaction is carried out at a polymerization temperature of 60-85 ° C, and the reaction starts within 4-9 hours. Batch addition of residual water, residual N-vinyl butyrolactam monomer, organic peroxide The main composite multi-initiator, the remaining catalyst and the remaining chain transfer agent, during which the pH of the reaction system is adjusted to 7.0-8.0 with an activator, and then the temperature is maintained at 80-100 ° C for 30 minutes, and then the azo-based composite multi-initiator is added. After continuing to hold for 1-3 hours, add 0.01%~1% of the total weight of the N-vinyl butyrolactam monomer to the peroxide for another 2 hours, then add the acid at a temperature of 90-120 ° C to adjust the pH to acidity. The reaction is refluxed for 1-3 hours to obtain a colorless transparent low molecular weight homopolymerized N-vinylbutyrolactam solution, which is dried to obtain a powdery low residual single low molecular weight homopolymeric N-vinyl butyrolactam having a K value of 24-31. The molecular weight is between 30,000 and 50,000, and the residual single is below 10 ppm. The design is ingenious, and the single sheet is prepared. The residual residue of the low residual single low molecular weight homopolymer N-vinyl butyrolactam is prepared at 10 ppm. The following, K value 24-31, suitable for large-scale promotion and application.
为了能够更清楚地理解本发明的技术内容， 特举以下实施例详细说明。 In order to more clearly understand the technical content of the present invention, the following embodiments are specifically described.
1.1 实验原料 1.1 Experimental materials
表 1 主要原料 Table 1 Main raw materials
名称 规格 生产厂家 Name Specifications Manufacturer
Ν-乙烯基丁内酰胺 工业级（减压蒸馏） 上海宇昂化工科技发展有限公司 偶氮二异丁腈 (ΑΙΒΝ) 化学纯 上海试四赫维化工有限公司 偶氮二异庚腈（ABVN ) 化学纯 上海试四赫维化工有限公司 过氧化苯甲酰（ΒΡΟ ) 化学纯 国药集团化学试剂有限公司 亚石克酸钠 分析纯 国药集团化学试剂有限公司 双氧水 ( 30% )化学纯 国药集团化学试剂有限公司 氨水 ( 25% )化学纯 国药集团化学试剂有限公司 叔丁基过氧化氢 化学纯 国药集团化学试剂有限公司 蒸馏水 自制 Ν-vinyl butyrolactam industrial grade (decompression distillation) Shanghai Yuang Chemical Technology Development Co., Ltd. azobisisobutyronitrile (ΑΙΒΝ) Chemically pure Shanghai test Sihewei Chemical Co., Ltd. azobisisoheptanenitrile (ABVN) Chemically pure Shanghai test Sihewei Chemical Co., Ltd. benzoyl peroxide (ΒΡΟ) Chemical pure Chinese medicine group chemical reagents Co., Ltd. Sodium gram sodium analysis pure Sinopharm Chemical Reagent Co., Ltd. hydrogen peroxide (30%) chemical pure Chinese medicine group chemical reagents Ammonia Water ( 25% ) Chemical Pure Sinopharm Chemical Reagent Co., Ltd. T-butyl hydroperoxide chemical pure Sinopharm Chemical Reagent Co., Ltd. distilled water homemade
异丙醇 化学纯 国药集团化学试剂有限公司 十二烷基^ 醇 化学纯 梯希爱化成工业发展有限公司 三乙醇胺 化学纯 国药集团化学试剂有限公司 过硫酸铵 分析纯 国药集团化学试剂有限公司 亚石克酸氢钠 化学纯 国药集团化学试剂有限公司 氮气 99% 上海沪康气体 Isopropanol Chemical Pure Sinopharm Chemical Reagent Co., Ltd. Dodecyl^ Alcohol Chemical Pure Tingxi Aihuacheng Industrial Development Co., Ltd. Triethanolamine Chemical Pure Sinopharm Chemical Reagent Co., Ltd. Ammonium Persulfate Analysis Pure Sinopharm Chemical Reagent Co., Ltd. Sodium Hydrogen Sulfate Chemically Pure Sinopharm Chemical Reagent Co., Ltd. Nitrogen 99% Shanghai Hukang Gas
1.2 实验仪器 1.2 Experimental instruments
2XZ-2型旋片式真空泵、 RE52CS旋转蒸发器、 250ml三口烧瓶、 HH-WO恒温油浴锅、 乌式粘度计 （O=0.5mm )、 100°C温度计、 S312电动搅拌器、 注射器、 FA2004分析天平、 滴 液漏斗、 冷凝管、 锥形瓶、 10 mL移液管、 碱式滴定管。 2XZ-2 rotary vane vacuum pump, RE52CS rotary evaporator, 250ml three-necked flask, HH-WO thermostatic oil bath, U-type viscometer (O=0.5mm), 100°C thermometer, S312 electric mixer, syringe, FA2004 Analytical balance, dropping funnel, condenser, Erlenmeyer flask, 10 mL pipette, Alkaline burette.
1.3 聚合 1.3 Aggregation
注： 在下面的内容中， 除非特殊说明， 将 "重量份，， 仅表示为 "份"， "重量％" 仅表示
为 "％，，。 Note: In the following content, unless otherwise stated, "% by weight, only "parts", "% by weight" means only For "%,,.
物料准备： N-乙烯基丁内酰胺单体与水之比为 4:16~8:12、 复合多元引发剂 0.5%~5.0% (以 N-乙烯基丁内酰胺为基准）、催化剂 0.1%~5.0% (以 N-乙烯基丁内酰胺为基准）、 少量活 化剂用以调节反应体系 pH、 链转移剂 0.1%~10% (以 N-乙烯基丁内酰胺为基准）； 其中引发 剂可以是过氧化氢、 叔丁基过氧化氢、 叔戊基过氧化氢、 过二硫酸、 过二硫酸钾、 过硫酸钾、 偶氮二异丁腈、 偶氮二异庚腈中的几种； 活化剂可以是氨水、 氢氧化钠、 三乙醇胺、 羟铵盐、 碳酸钠等； 催化剂可以是硫酸亚铁、 氯化亚铁、 硫酸铜等中的一种或几种金属硫酸盐的低浓 度水溶液； 链转移剂可以是乙醇、 正丙醇、 异丙醇、 十二烷基硫醇、 亚硫酸盐等中的一种或 几种。 Material preparation: N-vinyl butyrolactam monomer to water ratio of 4:16~8:12, composite multi-initiator 0.5%~5.0% (based on N-vinylbutyrolactam), catalyst 0.1% ~5.0% (based on N-vinyl butyrolactam), a small amount of activator to adjust the pH of the reaction system, chain transfer agent 0.1% to 10% (based on N-vinyl butyrolactam); It may be hydrogen peroxide, t-butyl hydroperoxide, tert-amyl hydroperoxide, peroxodisulfate, potassium peroxydisulfate, potassium persulfate, azobisisobutyronitrile, azobisisoheptanenitrile. The activator may be ammonia water, sodium hydroxide, triethanolamine, hydroxylammonium salt, sodium carbonate, etc.; the catalyst may be one of ferrous sulfate, ferrous chloride, copper sulfate, or the like, or a low concentration of several metal sulfates; The aqueous solution; the chain transfer agent may be one or more of ethanol, n-propanol, isopropanol, dodecyl mercaptan, sulfite, and the like.
操作步骤： 在带有回流冷凝管和搅拌器的三口烧瓶中先加入水的总量的 45%, 通 N2搅 拌下加入 N-乙烯基丁内酰胺单体总量的 30%、复合多元引发剂 A即以无机过氧化物为主的复 合多元引发（占引发剂总量的 35% )、 催化剂总量的 70%以及至少加入链转移剂总量的 70%, 再用适量活化剂调节溶液 pH至 7.0-8.0, 油浴加热升温至 60-85 °C , 反应开始 4-9小时内分数 次加入剩余全部单体、 复合多元引发剂 B即以有机过氧化物为主的复合多元引发剂 （占引发 剂总量的 35% )、 剩余所有催化剂、 链转移剂以及剩余水， 在此过程中用氨水调节溶液 pH为 7.0-8.0, 之后 80-100°C保温 30min后加入复合多元引发剂 C即以偶氮类为主的复合多元引发 剂 （占引发剂总量的 30% ), 继续保温 1-3小时后加入 0.01%~1% (以 N-乙烯基丁内酰胺为基 准）过氧化物再保温 2小时， 之后温度升至 90-120°C加少量酸调节 pH至酸性， 回流反应 1-3 小时既可以得到无色透明低分子量均聚 N-乙烯基丁内酰胺水溶液， K值在 24-31 , 分子量在 30000-50000, 干燥即得粉末状低分子量均聚 N-乙烯基丁内酰胺。 Operation steps: 45% of the total amount of water is added to the three-necked flask with reflux condenser and stirrer, and 30% of the total amount of N-vinyl butyrolactam monomer is added under stirring with N 2 Agent A is an inorganic peroxide-based composite multi-component initiation (accounting for 35% of the total amount of the initiator), 70% of the total amount of the catalyst, and at least 70% of the total amount of the chain transfer agent, and then adjusting the solution with an appropriate amount of activator. The pH is 7.0-8.0, the temperature is raised to 60-85 °C by heating in an oil bath, and all the remaining monomers and the composite multi-initiator B are mixed in the range of 4-9 hours from the start of the reaction, that is, the composite multi-initiator based on organic peroxide. (accounting for 35% of the total amount of initiator), all remaining catalyst, chain transfer agent and residual water. In this process, the pH of the solution is adjusted to 7.0-8.0 with ammonia water, and then the composite multi-initiator is added after 80-100 ° C for 30 min. C is an azo-based composite multi-initiator (accounting for 30% of the total amount of initiator), and after adding 1-3 hours, add 0.01% to 1% (based on N-vinyl butyrolactam). The oxide is kept for another 2 hours, after which the temperature is raised to 90-120 ° C and a small amount of acid is added to adjust the pH to acidity. The reaction can be carried out for 1-3 hours to obtain a colorless transparent low molecular weight homopolymeric N-vinylbutyrolactam solution with a K value of 24-31 and a molecular weight of 30,000-50,000. Drying gives a powdery low molecular weight homopolymer N-vinyl group. Butyrolactam.
1.4 分子量与残单测定 1.4 Determination of molecular weight and residual
1.4.1 分子量的测定 1.4.1 Determination of molecular weight
重均分子量测定选用 Waters 515型凝胶色谱仪， Waters2410示差折光检测器；柱子： Waters Ultrahydrogel 500he Ultrahydrogel 120两柱串联（ 7.8 x 300mm ); 流动相： 0.1M硝酸钠水溶液； 流速： 0.8ml/min; 进样量： 5( ¾升； 柱温： 40 °C ; The weight average molecular weight was determined by Waters 515 gel chromatograph, Waters 2410 differential refractive index detector; column: Waters Ultrahydrogel 500he Ultrahydrogel 120 two columns in series (7.8 x 300mm); mobile phase: 0.1M sodium nitrate aqueous solution; flow rate: 0.8ml/min Injection volume: 5 (3⁄4 liter; column temperature: 40 °C;
通常我们用 Fikentscher公式的 K值来表征均聚 N-乙烯基丁内酰胺的分子量， K值是只 与分子量有关， 不随均聚 N-乙烯基丁内酰胺的浓度而改变的参数。 测定 K值常用的方法是粘 度法， 乌式粘度计在水浴温度 25±0.2°C下， 测定该溶液对水的相对粘度 r)r。 Usually we use the K value of the Fikentscher formula to characterize the molecular weight of homopolymeric N-vinyl butyrolactam, which is a parameter that is only related to molecular weight and does not change with the concentration of homopolymeric N-vinyl butyrolactam. A commonly used method for determining the K value is a viscosity method. The Ubbel viscometer measures the relative viscosity r) r of the solution against water at a water bath temperature of 25 ± 0.2 °C.
才艮据 Fikentscher公式计算 1 _值:¾口下( H. Fikentscher, Die Messung der Viskositat solvatisierter
Sole. Morden Plastics[J], 1945,23(3): 157 ): Calculated according to the Fikentscher formula 1 _ value: 3⁄4 mouth (H. Fikentscher, Die Messung der Viskositat solvatisierter Sole. Morden Plastics [J], 1945, 23(3): 157 ):
K ^300c lg^r + (c + \ .5c lg77r )2 + 1.5c lg^r - c K ^300c lg^ r + (c + \ .5c lg77 r ) 2 + 1.5c lg^ r - c
0.15c + 0.003c2 0.15c + 0.003c 2
式中： K为 Fikentscher常数； Where: K is the Fikentscher constant;
c 为 0.1 L溶液中溶解均聚 N-乙烯基丁内酰胺的克数 c is the number of grams of homopolymerized N-vinyl butyrolactam dissolved in 0.1 L solution
为相对黏度 (；溶液流出时间与纯溶剂流出时间的比值 T/T0) Relative viscosity (the ratio of solution effluent time to pure solvent effluent time T/T 0 )
1.4.2 残留单体的含量 1.4.2 Residual monomer content
1 )碘量法 1) Iodometric method
均聚 Ν-乙烯基丁内酰胺中残留单体含量的测定是参照美国药典第 21版规定的方法。 取 10g 均聚 Ν-乙烯基丁内酰胺 (准确至 0.002g, 以无水物计）， 溶于 80ml蒸馏水中， 加入 lg醋 酸钠， 用 0.1 mol/L碘溶液滴定至溶液不再褪色， 再另加入 3 ml 0.1 mol/L的碘溶液， 放置 10 分钟， 然后用 0.1 mol/L的硫代硫酸钠滴定过量的碘， 当接近终点时加 3 ml的淀粉指示剂， 继 续滴定至溶液颜色消失， 同时与空白实验对照。 The determination of the residual monomer content in the homopolymerized fluorene-vinyl butyrolactam is based on the method specified in the 21st edition of the United States Pharmacopoeia. Take 10g of homopolyindole-vinyl butyrolactam (accurate to 0.002g, based on anhydrous matter), dissolve in 80ml of distilled water, add lg sodium acetate, titrate with 0.1 mol/L iodine solution until the solution no longer fades, then Add 3 ml of 0.1 mol/L iodine solution for 10 minutes, then titrate excess iodine with 0.1 mol/L sodium thiosulfate. Add 3 ml of starch indicator when approaching the end point, continue titration until the solution color disappears. At the same time, compared with the blank experiment.
结果计算： Result calculation:
NVP (^二 ν「ν Χ 0.106 χ 100 NVP (^ 2ν " ν Χ 0 . 106 χ 100
m m
式中： Vj ——滴定空白样品所消耗的碘标准溶液体积 (mL); Where: Vj - the volume of iodine standard solution (mL) consumed by titrating the blank sample;
V2 ——滴定样品所消耗的碘标准溶液体积 (mL); V 2 - the volume of iodine standard solution (mL) consumed by titrating the sample;
c ——碘标准液的浓度 (mol/L); c —— concentration of iodine standard solution (mol/L);
0.106 —— 1 mmol/L N-乙烯基丁内酰胺 (NVP)的质量 (g); 0.106 —— the mass of 1 mmol/L N-vinyl butyrolactam (NVP) (g);
m __样品的质量 (g) 。 m __sample quality (g).
2 ) 气相色谱法（廖列文， 康正， 崔英德.气相色谱法测定 PVP中残余单体的研究， 现代化工 , 1997 (增刊 ) :97 ) (略） 2) Gas Chromatography (Liao Liwen, Kang Zheng, Cui Yingde. Determination of Residual Monomers in PVP by Gas Chromatography, Modern Chemicals, 1997 (Supplement) : 97 ) (Omitted)
2.1温度的影响 2.1 The effect of temperature
引发剂在引发反应聚合时， 只有当热能达到引发剂的分解活化能， 引发剂才能引发反应 聚合。 因此， 在引发反应时需要将反应体系放置于一定温度下。 以过氧化氢为引发剂， 通过 不同温度下对反应产品质量影响分析， 结果如下表 2: When the initiator initiates the reaction polymerization, the initiator can initiate the reaction polymerization only when the thermal energy reaches the decomposition activation energy of the initiator. Therefore, it is necessary to place the reaction system at a certain temperature when the reaction is initiated. With hydrogen peroxide as the initiator, the influence of the quality of the reaction product at different temperatures was analyzed. The results are shown in Table 2 below:
表 2: 温度的影响 Table 2: Effect of temperature
温度 rc 残单 /% K Temperature rc residuals /% K
"^5 L57 222
60 0.86 24.7 "^5 L57 222 60 0.86 24.7
65 0.43 27.1 65 0.43 27.1
70 0.21 28.3 70 0.21 28.3
75 0.09 31.7 75 0.09 31.7
80 0.08 31.5 80 0.08 31.5
95 0.15 34.5 由表 2可看出， 随着温度的升高， K值逐渐增大， 残单逐渐降低。 这是因为温度升高时， 引发剂分解速率加快， 自由基浓度迅速升高； 链的增长速率的反应速率常数升高， 链的传递 速率高于链的终止速率， 反应速度大大升高， 充分反应程度也提高。 但是实验亦发现， 温度 的大幅提高， 导致做出的均聚 N-乙烯基丁内酰胺外观发黄。 所以温度的选择应该以引发剂的 活化能和平緩的聚合速率为依据， 本实验优先选择 65-80 °C。 95 0.15 34.5 It can be seen from Table 2 that as the temperature increases, the K value gradually increases and the residual order gradually decreases. This is because when the temperature rises, the rate of decomposition of the initiator increases, and the concentration of the radical increases rapidly. The rate constant of the growth rate of the chain increases, the rate of chain transfer is higher than the rate of termination of the chain, and the reaction rate is greatly increased. Also improved. However, experiments have also found that a significant increase in temperature results in a yellowish appearance of the homopolymerized N-vinyl butyrolactam. Therefore, the temperature should be selected based on the activation energy of the initiator and the slow polymerization rate. This experiment is preferred to 65-80 °C.
同时， 在聚合反应过程中会放出大量的反应热 （崔英德， 易国斌， 廖列文.聚乙烯吡咯烷 酮的合成与应用 [M].科学出版社， 2001 , 2:130 ), 需要及时释放反应产生的热量保持聚合温度 恒定， 否则温度过高副反应增加， 均聚 N-乙烯基丁内酰胺的分子量不能控制， 并可能会导致 均聚 N-乙烯基丁内酰胺变色。 At the same time, a large amount of reaction heat will be released during the polymerization process (Cui Yingde, Yi Guobin, Liao Lewen. Synthesis and application of polyvinylpyrrolidone [M]. Science Press, 2001, 2:130), need to release the reaction in time The heat keeps the polymerization temperature constant, otherwise the temperature is too high and the side reaction increases. The molecular weight of the homopolymerized N-vinyl butyrolactam is uncontrollable and may cause discoloration of the homopolymerized N-vinyl butyrolactam.
2.2 不同引发剂的影响 2.2 Effects of different initiators
均聚 N-乙烯基丁内酰胺的溶液聚合可以釆用三种不同类型的引发剂进行聚合 （Haaf F,Sanner A,Straub F.Polymer of N-vinyl pyrrolidone:Synthesis,characterization and uses[J],Polym J, 1985, 17(1): 143- 152； Wolfgang L,Friedrich G M. Polyvinyl pyrrolidone versatile specialty polymer[J],Polym News,1987,12(8):232-237 ), 公知的有过氧化物体系， 如： 双氧水（ H202 ), 叔丁基过氧化氢， 过氧化苯甲酰； 氧化还原体系， 如： 过硫酸铵一亚硫酸氢钠； 偶氮类， 如： 偶氮二异丁腈， 偶氮二异庚腈。 本实验分别测试这些体系对做出产品的影响。 如表 3: Solution polymerization of homopolymeric N-vinyl butyrolactam can be carried out using three different types of initiators (Haaf F, Sanner A, Straub F. Polymer of N-vinyl pyrrolidone: Synthesis, characterization and uses [J], Polym J, 1985, 17(1): 143- 152; Wolfgang L, Friedrich G M. Polyvinyl pyrrolidone versatile specialty polymer [J], Polym News, 1987, 12(8): 232-237), known as peroxidation System, such as: hydrogen peroxide (H 2 O 2 ), t-butyl hydroperoxide, benzoyl peroxide; redox system, such as: ammonium persulfate-sodium bisulfite; azo, such as: azo Isobutyronitrile, azobisisoheptanenitrile. This experiment tests the impact of these systems on the product being made. As shown in Table 3:
表 3: 不同引发剂的影响 Table 3: Effects of different initiators
编号 引发剂种类 残单 K值 No. Initiator type Residual value K value
1 过氧化氢 -氨水 0.12% 33.1 1 Hydrogen peroxide - Ammonia 0.12% 33.1
2 叔丁基过氧化氢 0.05% 21.5 2 tert-butyl hydroperoxide 0.05% 21.5
3 过氧化氢 +叔丁基过氧化氢 0.01% 26.3 3 hydrogen peroxide + t-butyl hydroperoxide 0.01% 26.3
4 过硫酸铵 +亚硫酸氢钠 0.07% 39.2 4 ammonium persulfate + sodium hydrogen sulfite 0.07% 39.2
5 过氧化苯甲酰 0.09% 28.7
6 偶氮二异丁腈 0.03% 35.5 5 benzoyl peroxide 0.09% 28.7 6 azobisisobutyronitrile 0.03% 35.5
7 偶氮二异庚腈 0.07% 34.7 7 azobisisoheptanenitrile 0.07% 34.7
8 偶氮二异丁腈 +过氧化氢 0.05% 29.1 8 azobisisobutyronitrile + hydrogen peroxide 0.05% 29.1
由表 3可知： 用过氧化氢等无机过氧类引发剂制备出的均聚 N-乙烯基丁内酰胺残单与其 他引发体系相比较高， 这主要是因为釆用过氧类引发剂时， 聚合机理中链的种植反应中发生 吡咯烷酮环的裂解， 导致均聚 N-乙烯基丁内酰胺的第二个端基是 基， 产物中会残留一部分 吡咯烷酮， 致使产品中残单较高； 用氧化还原弓 I发体系或偶氮类引发剂制备出均聚 N-乙烯基 丁内酰胺时， 由于偶氮类引发剂很容易引发聚合， 引发体系在整个聚合过程中分解出较多的 自由基， 导致反应速度较快聚合难以控制； 同时， 过硫酸盐引发剂在聚合过程中引入了硫酸 盐杂质， 这很有可能导致灰分超标。 我们发现只有当过氧化氢和叔丁基过氧化氢结合使用时， 做出的均聚 N-乙烯基丁内酰胺 K值稳定在 24-31 , 重均分子量在 30000-50000, 残单低满足 医药等应用领域要求。 It can be seen from Table 3 that the homo- N-vinyl butyrolactam residue prepared by using an inorganic peroxy initiator such as hydrogen peroxide is higher than other initiator systems, mainly because of the use of a peroxygen initiator. The cleavage of the pyrrolidone ring occurs in the planting reaction of the chain in the polymerization mechanism, resulting in the second terminal group of the homopolymerized N-vinyl butyrolactam being a base, and a part of the pyrrolidone remains in the product, resulting in a higher residue in the product; When the redox-I or azo initiator is used to prepare homo- N-vinyl butyrolactam, the azo initiator is easy to initiate polymerization, which causes the system to decompose more free radicals during the entire polymerization process. The reaction rate is faster and the polymerization is difficult to control. At the same time, the persulfate initiator introduces sulfate impurities during the polymerization process, which is likely to cause excessive ash. We found that only when hydrogen peroxide and t-butyl hydroperoxide were used in combination, the K value of homopolymerized N-vinyl butyrolactam was stable at 24-31, and the weight average molecular weight was between 30,000 and 50,000. Requirements for applications such as medicine.
2.3体系 pH的影响 2.3 System pH effect
N-乙烯基丁内酰胺,在酸性或某些盐类存在的条件下很容易发生水解反应， 生成吡咯烷酮 和乙醛（崔英德， 易国斌，廖列文.聚乙烯吡咯烷酮的合成与应用 [M].科学出版社， 2001 , 2:8 )。 其中 , J.Ferguson等人 ( J.Ferguson and V. Sunder ajan,Polymer Journal.,(15),627(1979) )对 N- 乙烯基丁内酰胺的水解进行了比较全面的研究。 因此， 为了确保聚合反应的顺利进行， 必须 调节反应体系的 pH至中性或偏碱性。 同时，公知的是溶液的 pH对反应的诱导期和反应速度 也有一定的影响反而不会影响到产品的分子量和残单。本实验通过用 5%氨水调节体系的 pH, 考察 pH的影响， 如表 4: N-vinyl butyrolactam is easily hydrolyzed in the presence of acid or certain salts to form pyrrolidone and acetaldehyde (Cui Yingde, Yi Guobin, Liao Liwen. Synthesis and application of polyvinylpyrrolidone [M]. Science Press, 2001, 2:8). Among them, J. Ferguson et al. (J. Ferguson and V. Sunder ajan, Polymer Journal., (15), 627 (1979)) conducted a comprehensive study on the hydrolysis of N-vinyl butyrolactam. Therefore, in order to ensure the smooth progress of the polymerization reaction, it is necessary to adjust the pH of the reaction system to neutral or alkaline. At the same time, it is well known that the pH of the solution also has a certain influence on the induction period and the reaction rate of the reaction, but does not affect the molecular weight and residue of the product. In this experiment, the pH of the system was adjusted by adjusting the pH of the system with 5% ammonia, as shown in Table 4:
表 4: 体系 pH的影响 Table 4: Effect of system pH
体系 pH值 诱导期（min ) 残单 K值 System pH induction period (min) residual order K value
5 3h未引发 ― ― 5 3h did not trigger ― ―
6 75 0.04% 29.3 6 75 0.04% 29.3
7 10 0.03% 27.1 7 10 0.03% 27.1
8 0 0.05% 25.9 8 0 0.05% 25.9
9 0 0.02% 30.5 9 0 0.02% 30.5
10 0 0.03% 28.1 10 0 0.03% 28.1
13 3h未引发 ― ―
由表 4数据可知， 当体系 pH偏酸时， 较长时间内引发剂都未能引发聚合； 当 pH在 6-10 时， 引发剂才顺利引发， 为了降低工业化大生产成本， 可缩短诱导期优选 pH在 7-9之间。 因 为当体系 pH偏酸性时， 某些引发剂和 N-乙烯基丁内酰胺单体都会发生分解 , NVP分解机理 下： 13 3h did not raise -- ― It can be seen from the data in Table 4 that when the pH of the system is too acidic, the initiator fails to initiate polymerization for a long time; when the pH is 6-10, the initiator is successfully initiated, and the induction period can be shortened in order to reduce the industrialized production cost. Preferably the pH is between 7-9. Because when the pH of the system is acidic, some initiators and N-vinyl butyrolactam monomers will decompose, under the NVP decomposition mechanism:
当 pH过高时， 实验发现诱导期非常长， 同时聚合速率很低。 When the pH is too high, the experiment found that the induction period is very long and the polymerization rate is very low.
2.4独特的复合多元引发工艺与传统引发工艺对比 2.4 Unique composite multi-initiation process and traditional initiation process comparison
公知的引发工艺大致有： 一次性加入引发聚合、 分段多次引发聚合、 反应后期增补引发 聚合等。 虽然分段多次引发聚合和反应后期增补引发聚合与一次性直接加入引发聚合相比， 做出的均聚 N-乙烯基丁内酰胺的残单较低、 分子量亦有一定的选择性， 但是这两种工艺仍存 在一定的缺陷： 一是步骤复杂难以实现真正的工业化生产； 二是条件要求苛刻， 需要严格控 制每次加料时的温度、 转速、 加入量等诸多因素， 稍有差错就有可能造成均聚 N-乙烯基丁内
酰胺的分子量过高或是残单超标。 在此条件下， 结合多次实验验证找到一套独特的复合多元 引发工艺。 该引发工艺与以上传统工艺相比比较稳定， 可以很筒单的做出符合当前最新药典 要求的均聚 N-乙烯基丁内酰胺 K25。 该工艺筒单叙述如下： The known initiation processes are generally as follows: one-time addition polymerization initiation, multi-stage initiation polymerization, and late reaction initiation polymerization. Although the segmentation multiple initiation polymerization and the reaction late addition initiation polymerization are compared with the one-time direct addition initiation polymerization, the homopolymer N-vinyl butyrolactam has a lower residue and a certain molecular weight selectivity, but These two processes still have certain defects: First, the steps are complicated and it is difficult to achieve real industrial production; Second, the conditions are demanding, and it is necessary to strictly control the temperature, the rotational speed, the amount of addition, etc. for each feeding, and there are some errors. May cause homopolymerization of N-vinylbutene The molecular weight of the amide is too high or the residue is excessive. Under this condition, combined with multiple experiments, a unique composite multi-initiation process was found. The initiation process is relatively stable compared to the above conventional processes, and the homopolymeric N-vinyl butyrolactam K25 which meets the requirements of the latest pharmacopoeia can be made in a very simple manner. The process cartridge is described as follows:
在整个聚合过程中， 引发剂分三个时间段加入： 从加入原料开始的前 30-50min为第一时 间段， 在该时间选择加入以无机过氧化物为主的复合多元引发剂； 从第二次加入 N-乙烯基丁 内酰胺单体到所有单体投料完毕为第二时间段， 这个过程中选择以有机过氧化物为主的复合 多元引发剂分次加入； 从 N-乙烯基丁内酰胺单体加完开始的 30min-50min为第三时间段， 在 这一时间段加入少量的以偶氮类为主的复合多元引发剂。 以 K25为例， 实验结果对比如下表 表 5: 两种工艺效果对比 During the whole polymerization process, the initiator is added in three time periods: from the first 30-50 minutes from the start of the raw material to the first time period, at which time the inorganic peroxide-based composite multi-initiator is selectively added; The second addition of N-vinyl butyrolactam monomer to all the monomers is completed for the second period of time, in this process, the organic peroxide-based composite multi-initiator is selected to be added in portions; from N-vinyl butyl A 30-50 min period from the start of the lactam monomer addition is a third period of time during which a small amount of an azo-based complex multi-initiator is added. Taking K25 as an example, the experimental results are compared as shown in the following table. Table 5: Comparison of the two process effects
编号 残单 K值 Number residual K value
1 55ppm 27 1 55ppm 27
传统工艺 2 79ppm 24 Traditional Process 2 79ppm 24
3 67ppm 28 3 67ppm 28
1 7ppm 25 1 7ppm 25
独特工艺 2 3ppm 26 Unique Process 2 3ppm 26
3 4ppm 25 由此可看出， 独特的复合多元引发工艺与传统工艺相比， 做出的均聚 N-乙烯基丁内酰胺 残单低， 分子量波动小， 重现性高。 3 4ppm 25 It can be seen that the unique composite multi-component initiation process has a lower homo- N-vinyl butyrolactam residue, a lower molecular weight fluctuation and a higher reproducibility than the conventional process.
2.5独特的消残处理工艺的效果考察 2.5 The effect of the unique dismantling treatment process
N-乙烯基丁内酰胺在聚合过程中， 由于大量自由基碰撞几率不同以及其他多方面原因， 导致反应终止时体系残留 N-乙烯基丁内酰胺含量较高。 为了降低残留单体含量， 一方面可以 选用更好的引链剂； 另一方面可以通过加酸消除残余 N-乙烯基丁内酰胺单体， 已有专利 （第 一工 业 只 要株式会社 . 乙 烯基吡咯烷酮 聚合物 的 制 造方 法 ： 中 国 ， 200710105080.7.[Ρ]2007-11-28. )对此进行过描述。 但是， 实验发现以上两种方法得到的效果 都不是很好。 为了有效的降低产品中残留单体含量， 本实验找到一种独特的消残处理工艺： 在反应后期先加少量的过氧化物， 然后保温反应一段时间后， 升高温度到 90-12CTC加少量酸 调节 pH至酸性保持 l-3h。 During the polymerization process, N-vinyl butyrolactam has a high content of residual N-vinyl butyrolactam at the end of the reaction due to the large number of free radical collisions and other various reasons. In order to reduce the residual monomer content, on the one hand, a better chain extender can be selected; on the other hand, the residual N-vinyl butyrolactam monomer can be eliminated by adding acid, and the prior art has been patented (the first industry is only a company. Vinyl) A method for producing a pyrrolidone polymer: China, 200710105080.7. [Ρ] 2007-11-28.) This has been described. However, the experiment found that the above two methods did not achieve very good results. In order to effectively reduce the residual monomer content in the product, this experiment found a unique disintegration treatment process: Add a small amount of peroxide in the later stage of the reaction, then keep the reaction for a period of time, then raise the temperature to 90-12CTC plus a small amount. The acid is adjusted to pH for a period of l-3 h.
表 6: 两种消残工艺效果对比
残余单体含量 Table 6: Comparison of the effects of two disintegration processes Residual monomer content
未消残处理 独特消残工艺 筒单加酸消残 No disintegration treatment, unique disintegration process
1 112ppm 9ppm 83ppm 1 112ppm 9ppm 83ppm
2 56ppm 2ppm 50ppm 2 56ppm 2ppm 50ppm
3 74ppm 4ppm 67ppm 3 74ppm 4ppm 67ppm
4 97ppm 5ppm 78ppm 4 97ppm 5ppm 78ppm
5 126ppm 2ppm 83ppm 由表 6可看出， 该消残工艺效果相对比较明显。 而且， 实验发现通过该消残工艺处理之 后的均聚 N-乙烯基丁内酰胺 K25的稳定性与未处理之前相比大幅提高。 5 126ppm 2ppm 83ppm As can be seen from Table 6, the effect of the disintegration process is relatively obvious. Moreover, it was found that the stability of the homopolymerized N-vinyl butyrolactam K25 after the treatment by the elimination process was greatly improved as compared with that before the treatment.
3结 论 3 Conclusion
水为溶剂， 加入 20%~40%的 N-乙烯基丁内酰胺单体， 再以 N-乙烯基丁内酰胺为基准， 加入 0.5%~5.0%复合多元引发剂、 0.1%~5.0%催化剂、 0.1%~10%链转移剂并用适量活化剂调 节反应体系 pH至 7.0-8.0, 在一定温度下反应 6-12h, 其中在不同时间段选用不同复合多元引 发剂； 最后再加入少量过氧化物一段时间后用酸调节体系 pH至酸性保持 l-3h, 得到无色透 明的均聚 N-乙烯基丁内酰胺水溶液， 经喷雾干燥即得 K值在 24-31 , 残单低于 lOppm的粉末 状低分子量均聚 N-乙烯基丁内酰胺。 下面列举几个实施例更具体地说明本发明， 但本发明不受这些实施例的限制。 在下面的 内容中， 除非特殊说明， 将 "重量份" 仅表示为 "份"， 将 "重量％" 仅表示为 "％"。 Water as solvent, adding 20%~40% N-vinyl butyrolactam monomer, and adding 0.5%~5.0% composite multi-initiator, 0.1%~5.0% catalyst based on N-vinyl butyrolactam , 0.1%~10% chain transfer agent and adjust the pH of the reaction system to 7.0-8.0 with an appropriate amount of activator, react at a certain temperature for 6-12h, in which different composite multi-initiators are selected at different time periods; finally, a small amount of peroxide is added. After a period of time, the pH of the system is adjusted to acidity with acid to maintain l-3h, and a colorless and transparent aqueous solution of homopolymerized N-vinylbutyrolactam is obtained. After spray drying, a powder having a K value of 24-31 and a residual amount of less than 10 ppm is obtained. Low molecular weight homopolymeric N-vinyl butyrolactam. The invention will be more specifically illustrated by the following examples, but the invention is not limited by these examples. In the following, unless otherwise stated, "parts by weight" is only expressed as "parts", and "% by weight" is only expressed as "%".
实施例 1 Example 1
在带有回流冷凝管和搅拌器的三口烧瓶中加入 135份水， 通 N2搅拌下加入 36份 N-乙烯 基丁内酰胺单体、 2.1份重量比为 6:4的过氧化氢与叔丁基过氧化氢混合液、 1.7份 0.001%的 硫酸铜溶液和 0.1份十二烷基硫醇， 稀氨水调节溶液 pH为 7.0-8.0, 放置于 60°C油浴中， 反 应开始 4小时内分 4次加入 84份 N-乙烯基丁内酰胺单体、 2.1份重量比为 8:2的叔丁基过氧 化氢与过氧化氢混合液、 0.7份 0.001%的硫酸铜溶液、 0.02份十二烷基硫醇和 165份水， 在 此段时间中用稀氨水调节溶液 pH为 7.0-8.00,之后温度升至 90°C保温 30min加入 1.8份重量 比为 7:3的偶氮二异庚腈与叔丁基过氧化氢混合液，继续保温 1小时后加入 1.2份过氧化氢再 保温 2小时， 之后温度升至 11CTC加少量醋酸调节 pH至酸性， 回流反应 3小时冷却得到无色 透明的低分子量均聚 N-乙烯基丁内酰胺溶液，经喷雾干燥得白色粉末状均聚 N-乙烯基丁内酰
胺。 结果检测该均聚 N-乙烯基丁内酰胺的 K值为 25.5 , 重均分子量为 33000, 残单为 7ppm。 实施例 2 In a three-necked flask equipped with a reflux condenser and a stirrer, 135 parts of water was added, and 36 parts of N-vinyl butyrolactam monomer and 2.1 parts by weight of hydrogen peroxide and unbranched were added under stirring with N 2 . a mixture of butyl hydroperoxide, 1.7 parts of 0.001% copper sulfate solution and 0.1 part of dodecyl mercaptan, dilute ammonia water to adjust the pH of the solution to 7.0-8.0, placed in a 60 ° C oil bath, within 4 hours of the start of the reaction 84 parts of N-vinyl butyrolactam monomer, 2.1 parts by weight of 8:2 mixture of t-butyl hydroperoxide and hydrogen peroxide, 0.7 parts of 0.001% copper sulfate solution, 0.02 parts of ten Dialkyl mercaptan and 165 parts water, adjust the pH of the solution to 7.0-8.00 with dilute ammonia water during this period, then increase the temperature to 90 ° C for 30 min and add 1.8 parts of azobisisoheptonitrile with a weight ratio of 7:3. After mixing with t-butyl hydroperoxide for 1 hour, add 1.2 parts of hydrogen peroxide for 2 hours, then increase the temperature to 11 CTC and add a small amount of acetic acid to adjust the pH to acidity, and reflux for 3 hours to obtain a colorless and transparent low. Molecular weight homopolymerized N-vinyl butyrolactam solution, spray dried to obtain a white powdery homogeneous N-vinyl butyl Acyl Amine. As a result, the K value of the homo- N-vinyl butyrolactam was 25.5, the weight average molecular weight was 33,000, and the residue was 7 ppm. Example 2
在带有回流冷凝管和搅拌器的三口烧瓶中加入 144份水， 通 N2搅拌下加入 24份 N-乙烯 基丁内酰胺单体、 0.14份重量比为 8:2的过氧化氢与叔丁基过氧化氢混合液、 0.06份 0.001% 的硫酸铜溶液和 6份十二烷基硫醇， 稀氨水调节溶液 pH为 7.0-8.0, 放置于 75 °C油浴中， 反 应开始 9小时内分 4次加入 56份 N-乙烯基丁内酰胺单体、0.14份重量比为 7:3的叔丁基过氧 化氢与过氧化氢混合液、 0.02份 0.001%的硫酸铜溶液、 2份十二烷基硫醇和 176份水， 在此 段时间中用稀氨水调节溶液 pH为 7.0-8.00, 之后温度升至 80°C保温 30min加入 0.12份重量 比为 7:3的偶氮二异庚腈与叔丁基过氧化氢混合液， 继续保温 1.5小时后加入 0.4份过氧化氢 再保温 2小时， 之后温度升至 90°C加少量柠檬酸调节 pH至酸性， 回流反应 1.5小时冷却得 到无色透明的低分子量均聚 N-乙烯基丁内酰胺溶液，经喷雾干燥得白色粉末状均聚 N-乙烯基 丁内酰胺。 结果检测该均聚 N-乙烯基丁内酰胺的 K值为 30.6, 重均分子量为 50000, 残单为 5ppm。 实施例 3 In a three-necked flask equipped with a reflux condenser and a stirrer, 144 parts of water was added, and 24 parts of N-vinyl butyrolactam monomer, 0.14 parts by weight of hydrogen peroxide and untwisted by 8:2 were added with stirring of N 2 . a mixture of butyl hydroperoxide, 0.06 parts of 0.001% copper sulfate solution and 6 parts of dodecyl mercaptan, dilute ammonia water to adjust the pH of the solution to 7.0-8.0, placed in an oil bath at 75 ° C, within 9 hours of the start of the reaction Adding 56 parts of N-vinyl butyrolactam monomer, 0.14 parts by weight of 7:3 mixture of t-butyl hydroperoxide and hydrogen peroxide, 0.02 parts of 0.001% copper sulfate solution, 2 parts of ten Dialkyl mercaptan and 176 parts water, adjust the pH of the solution to 7.0-8.00 with dilute ammonia water during this period, then increase the temperature to 80 ° C for 30 min to add 0.12 parts by weight of 7:3 azobisisoheptonitrile After mixing with t-butyl hydroperoxide for 1.5 hours, add 0.4 parts of hydrogen peroxide for 2 hours, then increase the temperature to 90 ° C, add a small amount of citric acid to adjust the pH to acidity, and reflux for 1.5 hours to obtain colorless. Transparent low molecular weight homopolymerized N-vinyl butyrolactam solution, spray dried to obtain white powdered homogeneous N-B Butyric lactam. As a result, it was examined that the homopolymeric N-vinyl butyrolactam had a K value of 30.6, a weight average molecular weight of 50,000, and a residual amount of 5 ppm. Example 3
在带有回流冷凝管和搅拌器的三口烧瓶中加入 108份水， 通 N2搅拌下加入 48份 N-乙烯 基丁内酰胺单体、 1.12份重量比为 8:2的过氧化氢与叔丁基过氧化氢混合液、 5.6份 0.001% 的硫酸铜溶液和 5.6份十二烷基硫醇， 稀氨水调节溶液 pH为 7.0-8.0, 放置于 85 °C油浴中， 反应开始 6小时内分 4次加入 112份 N-乙烯基丁内酰胺单体、 1.12份重量比为 7:3的叔丁基 过氧化氢与过氧化氢混合液、 2.4份 0.001%的硫酸铜溶液、 2.4份十二烷基硫醇和 132份水， 在此段时间中用稀氨水调节溶液 pH为 7.0-8.00,之后温度升至 120°C保温 30min加入 0.96份 重量比为 7:3的偶氮二异庚腈与叔丁基过氧化氢混合液，继续保温 3小时后加入 0.016份过氧 化氢再保温 2小时， 之后温度升至 120°C加少量柠檬酸调节 pH至酸性， 回流反应 1小时冷却 得到无色透明的低分子量均聚 N-乙烯基丁内酰胺溶液，经喷雾干燥得白色粉末状均聚 N-乙烯 基丁内酰胺。 结果检测该均聚 N-乙烯基丁内酰胺的 K值为 30.6, 重均分子量为 50000, 残单 为 5ppm。 实施例 4 In a three-necked flask equipped with a reflux condenser and a stirrer, 108 parts of water was added, and 48 parts of N-vinyl butyrolactam monomer was added under stirring with N 2 , and 1.12 parts by weight of hydrogen peroxide and uncle of 8:2 were added. a mixture of butyl hydroperoxide, 5.6 parts of 0.001% copper sulfate solution and 5.6 parts of dodecyl mercaptan, dilute ammonia water to adjust the pH of the solution to 7.0-8.0, placed in an oil bath at 85 ° C, within 6 hours of the start of the reaction Add 112 parts of N-vinyl butyrolactam monomer, 1.12 parts by weight of 7:3 mixture of t-butyl hydroperoxide and hydrogen peroxide, 2.4 parts of 0.001% copper sulfate solution, 2.4 parts of ten Dialkyl mercaptan and 132 parts water, adjust the pH of the solution to 7.0-8.00 with dilute ammonia water during this period, then increase the temperature to 120 ° C for 30 min to add 0.96 parts by weight of 7:3 azobisisoheptonitrile After mixing with t-butyl hydroperoxide for 3 hours, add 0.016 parts of hydrogen peroxide for 2 hours, then increase the temperature to 120 ° C, add a small amount of citric acid to adjust the pH to acidity, and reflux for 1 hour to obtain colorless. Transparent low molecular weight homopolymerized N-vinyl butyrolactam solution, spray dried to obtain white powdered homogeneous N-B Alkenyl butyrolactam. As a result, it was examined that the homopolymeric N-vinyl butyrolactam had a K value of 30.6, a weight average molecular weight of 50,000, and a residual amount of 5 ppm. Example 4
除了将反应后期的 "0.5份过氧化氢" 替换为 "0.5份叔丁基过氧化氢" 以外， 进行和实 施例 1同样的操作，得到无色透明的均聚 N-乙烯基丁内酰胺水溶液，喷雾干燥得粉末状产品，
结果检测该均聚 N-乙烯基丁内酰胺 K值为 24.8, 重均分子量为 31860, 残单为 3ppm。 对比例 1 : The same procedure as in Example 1 was carried out except that "0.5 parts of hydrogen peroxide" in the latter stage of the reaction was replaced with "0.5 parts of t-butyl hydroperoxide" to obtain a colorless transparent aqueous solution of homopolymerized N-vinylbutyrolactam. Spray dried to a powdery product, As a result, the K value of the homopolymeric N-vinyl butyrolactam was 24.8, the weight average molecular weight was 31,860, and the residual amount was 3 ppm. Comparative example 1:
除了将整个反应过程中的 "重量比为 6:4 的过氧化氢与叔丁基过氧化氢混合液" 替换为 过氧化氢、 "重量比为 8:2的叔丁基过氧化氢与过氧化氢混合液"替换为叔丁基过氧化氢、 "重 量比为 7:3 的偶氮二异庚腈与叔丁基过氧化氢混合液" 替换为叔丁基过氧化氢以外， 进行和 实施例 1同样的操作， 得到微黄色透明的均聚 N-乙烯基丁内酰胺水溶液， 喷雾干燥得粉末状 产品， 结果检测该均聚 N-乙烯基丁内酰胺的 K值为 29.2, 分子量 49850, 残单为 147ppm。 对比例 2 In addition to replacing the "6:4 by weight mixture of hydrogen peroxide and t-butyl hydroperoxide" with hydrogen peroxide, "8:2 by weight of t-butyl hydroperoxide" The hydrogen peroxide mixture is replaced with t-butyl hydroperoxide, a mixture of azobisisoheptanenitrile and t-butyl hydroperoxide in a weight ratio of 7:3, replaced with t-butyl hydroperoxide, and In the same manner as in Example 1, a yellowish transparent aqueous solution of homopolymerized N-vinylbutyrolactam was obtained, which was spray-dried to obtain a powdery product. As a result, the K value of the homopolymerized N-vinylbutyrolactam was 29.2, and the molecular weight was 49,850. The residual order is 147ppm. Comparative example 2
除了将整个反应过程中的 "重量比为 8:2 的过氧化氢与叔丁基过氧化氢混合液" 替换为 过氧化氢、 "重量比为 7:3的叔丁基过氧化氢与过氧化氢混合液"替换为叔丁基过氧化氢、 "重 量比为 7:3 的偶氮二异庚腈与叔丁基过氧化氢混合液" 替换为叔丁基过氧化氢以外， 进行和 实施例 2同样的操作， 得到微黄色透明的均聚 N-乙烯基丁内酰胺水溶液， 喷雾干燥得粉末状 产品， 结果检测该均聚 N-乙烯基丁内酰胺的 K值为 35.2, 分子量为 70500, 残单为 78ppm。 对比例 3: In addition to replacing the "8:2 by weight mixture of hydrogen peroxide and t-butyl hydroperoxide" with hydrogen peroxide, "a ratio of 7:3 by weight of t-butyl hydroperoxide" The hydrogen peroxide mixture is replaced with t-butyl hydroperoxide, a mixture of azobisisoheptanenitrile and t-butyl hydroperoxide in a weight ratio of 7:3, replaced with t-butyl hydroperoxide, and In the same manner as in Example 2, a yellowish transparent aqueous solution of homopolymerized N-vinylbutyrolactam was obtained, which was spray-dried to obtain a powdery product. As a result, the K value of the homopolymerized N-vinylbutyrolactam was 35.2, and the molecular weight was 70500, the residual order is 78ppm. Comparative example 3:
除了将反应最后加入的 "0.5份过氧化氢"取消之外， 进行和实施例 2同样的操作， 得到 微黄色透明的均聚 N-乙烯基丁内酰胺水溶液， 喷雾干燥得粉末状产品， 结果检测该均聚 N- 乙烯基丁内酰胺的 K值为 31.2, 分子量为 51100, 残单为 113ppm。 因此， 本发明通过对均聚 N-乙烯基丁内酰胺合成过程中的引发体系、 引发剂用量、 时间 以及聚合工艺等对最终产品的影响研究， 研发出一种可以制备出低分子量低残单均聚 N-乙烯 基丁内酰胺（分子量在 30000-50000 )的方法， 该方法做出的产品质量完全可以满足国际上最 新药典标准。 The same procedure as in Example 2 was carried out except that "0.5 parts of hydrogen peroxide" added at the end of the reaction was removed, and a yellowish transparent aqueous solution of homopolymerized N-vinylbutyrolactam was obtained, which was spray-dried to obtain a powdery product. The homopolymeric N-vinyl butyrolactam was detected to have a K value of 31.2, a molecular weight of 51,100, and a residual residue of 113 ppm. Therefore, the present invention develops a low molecular weight low residue by studying the influence of the initiation system, the amount of the initiator, the time, and the polymerization process on the final product during the synthesis of the homopolymerized N-vinyl butyrolactam. A method of homopolymerizing N-vinyl butyrolactam (molecular weight between 30,000 and 50,000), the quality of the product produced by this method can fully meet the latest international pharmacopoeia standards.
综上，本发明的低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法设计巧妙，制备筒单， 制备出的低残单低分子量均聚 N-乙烯基丁内酰胺的残单在 lOppm以下、 K值 24-31 , 适于大 规模推广应用。 In summary, the method for synthesizing the low residue single low molecular weight homopolymerized N-vinyl butyrolactam of the present invention is ingeniously designed to prepare a single residue, and the residue of the low residual single low molecular weight homopolymeric N-vinyl butyrolactam prepared is prepared. Below lOppm, K value 24-31, suitable for large-scale promotion and application.
在此说明书中， 本发明已参照其特定的实施例作了描述。 但是， 很显然仍可以作出各种 修改和变换而不背离本发明的精神和范围。 因此，说明书应被认为是说明性的而非限制性的。
In this specification, the invention has been described with reference to specific embodiments thereof. However, it will be apparent that various modifications and changes can be made without departing from the spirit and scope of the invention. Accordingly, the description is to be considered as illustrative and not restrictive.
Claims
1、 一种低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法， 其特征在于， 1. A method for synthesizing low-residue low-molecular-weight homopolymer N-vinylbutyrolactam, which is characterized by:
釆用质量比为 4:16~8:12的 N-乙烯基丁内酰胺单体与水， 再以 N-乙烯基丁内酰胺单体为基 准， 釆用 0.5%~5.0%重量的复合多元引发剂、 0.1%~5.0%重量的催化剂和 0.1%~10%重量的链 转移剂， 其中复合多元引发剂中以无机过氧化物为主的复合多元引发剂占 35%重量， 以有机 过氧化物为主的复合多元引发剂占 35%重量， 以偶氮类为主的复合多元引发剂占 30%重量； 惰性气体存在条件下， 首先加入水总重量的 45%、 N-乙烯基丁内酰胺单体总重量的 30%、 以 无机过氧化物为主的复合多元引发剂、 催化剂总重量的 70%和链转移剂总重量的至少 70%, 用活化剂调节反应体系 pH至 7.0-8.0, 在聚合温度 60-85 °C进行反应， 反应开始 4-9小时内分批 次加入剩余水、 剩余 N-乙烯基丁内酰胺单体、 以有机过氧化物为主的复合多元引发剂、 剩余 催化剂和剩余链转移剂， 期间用活化剂调节反应体系 pH至 7.0-8.0, 然后 80-100°C保温 30分钟 后加入以偶氮类为主的复合多元弓 I发剂，继续保温 1 -3小时后加入 N-乙烯基丁内酰胺单体总重 量的 0.01%~1%的过氧化物再保温 2小时， 然后在温度 90-120°C加酸调节 pH至酸性， 回流反应 1-3小时得到无色透明低分子量均聚 N-乙烯基丁内酰胺水溶液，干燥即得粉末状低残单低分子 量均聚 N-乙烯基丁内酰胺， K值在 24-31 , 分子量在 30000-50000, 残单在 lOppm以下。 Use N-vinyl butyrolactam monomer and water with a mass ratio of 4:16~8:12, and then use N-vinyl butyrolactam monomer as the basis, use 0.5%~5.0% by weight of composite multi-component Initiator, 0.1% to 5.0% by weight of catalyst and 0.1% to 10% by weight of chain transfer agent. Among the composite multi-component initiators, inorganic peroxide-based composite multi-component initiators account for 35% by weight, with organic peroxidation as the main component. The composite multi-component initiator based on azo compounds accounts for 35% by weight, and the composite multi-component initiator based on azo compounds accounts for 30% by weight; in the presence of inert gas, first add 45% of the total weight of water and N-vinyl butane. 30% of the total weight of the amide monomer, a composite multi-initiator based on inorganic peroxide, 70% of the total weight of the catalyst and at least 70% of the total weight of the chain transfer agent, use an activator to adjust the pH of the reaction system to 7.0-8.0 , carry out the reaction at a polymerization temperature of 60-85 °C, and add remaining water, remaining N-vinyl butyrolactam monomer, and a composite multi-initiator mainly composed of organic peroxides in batches within 4-9 hours after the reaction starts. The remaining catalyst and remaining chain transfer agent, during this period, use an activator to adjust the pH of the reaction system to 7.0-8.0, and then keep it at 80-100°C for 30 minutes, then add a composite multi-component hair agent mainly based on azo, and continue to keep it warm for 1 - After 3 hours, add 0.01%~1% peroxide based on the total weight of N-vinyl butyrolactam monomer and keep the temperature for another 2 hours. Then add acid at a temperature of 90-120°C to adjust the pH to acidic, and perform reflux reaction 1-3 A colorless and transparent low molecular weight homopolymer N-vinyl butyrolactam aqueous solution is obtained in 24 hours. After drying, a powdery low-residue low molecular weight homopolymer N-vinyl butyrolactam is obtained. The K value is 24-31 and the molecular weight is 30000-50000. , the residual order is below lOppm.
2、 根据权利要求 1所述的低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法， 其特征在 于， 所述复合多元引发剂选自过氧化氢、 叔丁基过氧化氢、 叔戊基过氧化氢、 过二硫酸、 过 二硫酸钾、 过硫酸钾、 偶氮二异丁腈和偶氮二异庚腈中的两种以上。 2. The synthesis method of low residual monomer and low molecular weight homopolymer N-vinylbutyrolactam according to claim 1, characterized in that the composite multi-initiator is selected from the group consisting of hydrogen peroxide, tert-butyl hydroperoxide, Two or more of tert-amyl hydroperoxide, peroxodisulfate, potassium peroxodisulfate, potassium persulfate, azobisisobutyronitrile and azobisisoheptanitrile.
3、 根据权利要求 2所述的低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法， 其特征在 于， 所述的以无机过氧化物为主的复合多元弓 I发剂是以过氧化氢为主的过氧化氢与叔丁基过 氧化氢混合液； 所述的以有机过氧化物为主的复合多元引发剂是以叔丁基过氧化氢为主的叔 丁基过氧化氢与过氧化氢混合液； 所述的以偶氮类为主的复合多元引发剂是以偶氮二异庚腈 为主的偶氮二异庚腈与叔丁基过氧化氢混合液。 3. The synthesis method of low residual monomer and low molecular weight homopolymer N-vinyl butyrolactam according to claim 2, characterized in that the composite multi-component hair agent mainly composed of inorganic peroxides is based on A mixture of hydrogen peroxide and tert-butyl hydroperoxide based on hydrogen peroxide; the composite multi-component initiator based on organic peroxide is tert-butyl peroxide based on tert-butyl hydroperoxide. Mixed liquid of hydrogen and hydrogen peroxide; The azo-based composite multi-component initiator is a mixed liquid of azobisisoheptanitrile and tert-butyl hydroperoxide, which is mainly azobisisoheptanitrile.
4、 根据权利要求 1所述的低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法， 其特征在 于， 所述催化剂选自硫酸亚铁水溶液、 氯化亚铁水溶液和硫酸铜水溶液中的一种或几种。 4. The synthesis method of low residual monomer and low molecular weight homopolymer N-vinyl butyrolactam according to claim 1, characterized in that the catalyst is selected from the group consisting of ferrous sulfate aqueous solution, ferrous chloride aqueous solution and copper sulfate aqueous solution. one or more of them.
5、 根据权利要求 1所述的低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法， 其特征在 于， 所述链转移剂选自乙醇、 正丙醇、 异丙醇、 十二烷基硫醇和亚硫酸盐中的一种或几种。 5. The synthesis method of low residual monomer and low molecular weight homopolymer N-vinyl butyrolactam according to claim 1, characterized in that the chain transfer agent is selected from the group consisting of ethanol, n-propanol, isopropyl alcohol, and dodecyl alcohol. One or more of alkyl mercaptans and sulfites.
6、 根据权利要求 1所述的低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法， 其特征在 于， 所述活化剂是氨水、 氢氧化钠、 三乙醇胺、 羟铵盐或碳酸钠。
6. The synthesis method of low residual monomer and low molecular weight homopolymer N-vinyl butyrolactam according to claim 1, characterized in that the activator is ammonia, sodium hydroxide, triethanolamine, hydroxylammonium salt or carbonic acid sodium.
7、 根据权利要求 1所述的低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法， 其特征在 于， 所述过氧化物是过氧化氢或叔丁基过氧化氢。 7. The synthesis method of low residual monomer and low molecular weight homopolymer N-vinylbutyrolactam according to claim 1, characterized in that the peroxide is hydrogen peroxide or tert-butyl hydroperoxide.
8、 根据权利要求 1所述的低残单低分子量均聚 N-乙烯基丁内酰胺的合成方法， 其特征在 于， 所述酸是醋酸或柠檬酸。
8. The synthesis method of low residual monomer and low molecular weight homopolymer N-vinylbutyrolactam according to claim 1, characterized in that the acid is acetic acid or citric acid.
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| CN1213670A (en) * | 1997-06-27 | 1999-04-14 | Basf公司 | Preparation of low molecular mass homopolymers of N-vinylpyrrolidone |
| CN1448415A (en) * | 2002-04-04 | 2003-10-15 | 株式会社日本触媒 | Vinylpyrrolidone polymer |
| US20090131549A1 (en) * | 2007-11-16 | 2009-05-21 | Basf Se | Process for preparing polyvinylpyrrolidones by spray polymerization |
| CN101585893A (en) * | 2009-06-26 | 2009-11-25 | 博爱新开源制药股份有限公司 | Method for preparing ultra-low molecular weight polyvinylpyrrolidone |
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| CN1213670A (en) * | 1997-06-27 | 1999-04-14 | Basf公司 | Preparation of low molecular mass homopolymers of N-vinylpyrrolidone |
| CN1448415A (en) * | 2002-04-04 | 2003-10-15 | 株式会社日本触媒 | Vinylpyrrolidone polymer |
| US20090131549A1 (en) * | 2007-11-16 | 2009-05-21 | Basf Se | Process for preparing polyvinylpyrrolidones by spray polymerization |
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