JP2010031165A - Alkyl-etherified carboxyalkylcellulose - Google Patents
Alkyl-etherified carboxyalkylcellulose Download PDFInfo
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- JP2010031165A JP2010031165A JP2008196098A JP2008196098A JP2010031165A JP 2010031165 A JP2010031165 A JP 2010031165A JP 2008196098 A JP2008196098 A JP 2008196098A JP 2008196098 A JP2008196098 A JP 2008196098A JP 2010031165 A JP2010031165 A JP 2010031165A
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- JP
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- Prior art keywords
- carboxyalkyl cellulose
- alkyl
- alkyl etherified
- cellulose
- etherified
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 238000006467 substitution reaction Methods 0.000 claims abstract description 29
- 238000006266 etherification reaction Methods 0.000 claims abstract description 18
- 239000003513 alkali Substances 0.000 claims abstract description 9
- 229940100198 alkylating agent Drugs 0.000 claims abstract description 8
- 239000002168 alkylating agent Substances 0.000 claims abstract description 8
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 48
- 239000001913 cellulose Substances 0.000 claims description 48
- 229920002678 cellulose Polymers 0.000 claims description 48
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 239000003960 organic solvent Substances 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 11
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 4
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 239000002904 solvent Substances 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 150000005215 alkyl ethers Chemical group 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 5
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 4
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 4
- -1 flakes Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 229960003750 ethyl chloride Drugs 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 229940071870 hydroiodic acid Drugs 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 239000003444 phase transfer catalyst Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- ZUHZGEOKBKGPSW-UHFFFAOYSA-N tetraglyme Chemical compound COCCOCCOCCOCCOC ZUHZGEOKBKGPSW-UHFFFAOYSA-N 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- XLLIQLLCWZCATF-UHFFFAOYSA-N 2-methoxyethyl acetate Chemical compound COCCOC(C)=O XLLIQLLCWZCATF-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 235000019596 Masking bitterness Nutrition 0.000 description 2
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001348 alkyl chlorides Chemical class 0.000 description 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000004210 ether based solvent Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- QFWPJPIVLCBXFJ-UHFFFAOYSA-N glymidine Chemical compound N1=CC(OCCOC)=CN=C1NS(=O)(=O)C1=CC=CC=C1 QFWPJPIVLCBXFJ-UHFFFAOYSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 229940102396 methyl bromide Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- GKQHIYSTBXDYNQ-UHFFFAOYSA-M 1-dodecylpyridin-1-ium;chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+]1=CC=CC=C1 GKQHIYSTBXDYNQ-UHFFFAOYSA-M 0.000 description 1
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 1
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- SVONRAPFKPVNKG-UHFFFAOYSA-N 2-ethoxyethyl acetate Chemical compound CCOCCOC(C)=O SVONRAPFKPVNKG-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- HWBLTYHIEYOAOL-UHFFFAOYSA-N Diisopropyl sulfate Chemical compound CC(C)OS(=O)(=O)OC(C)C HWBLTYHIEYOAOL-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- RJFAYQIBOAGBLC-BYPYZUCNSA-N Selenium-L-methionine Chemical compound C[Se]CC[C@H](N)C(O)=O RJFAYQIBOAGBLC-BYPYZUCNSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- IPTNXMGXEGQYSY-UHFFFAOYSA-N acetic acid;1-methoxybutan-1-ol Chemical compound CC(O)=O.CCCC(O)OC IPTNXMGXEGQYSY-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- 229920013820 alkyl cellulose Polymers 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- VUEDNLCYHKSELL-UHFFFAOYSA-N arsonium Chemical group [AsH4+] VUEDNLCYHKSELL-UHFFFAOYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- VJGNLOIQCWLBJR-UHFFFAOYSA-M benzyl(tributyl)azanium;chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 VJGNLOIQCWLBJR-UHFFFAOYSA-M 0.000 description 1
- KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 229920003064 carboxyethyl cellulose Polymers 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- LMEDOLJKVASKTP-UHFFFAOYSA-N dibutyl sulfate Chemical compound CCCCOS(=O)(=O)OCCCC LMEDOLJKVASKTP-UHFFFAOYSA-N 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000020169 heat generation Effects 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- ULYZAYCEDJDHCC-UHFFFAOYSA-N isopropyl chloride Chemical compound CC(C)Cl ULYZAYCEDJDHCC-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- IUSOXUFUXZORBF-UHFFFAOYSA-N n,n-dioctyloctan-1-amine;hydrochloride Chemical compound [Cl-].CCCCCCCC[NH+](CCCCCCCC)CCCCCCCC IUSOXUFUXZORBF-UHFFFAOYSA-N 0.000 description 1
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- WSGCRAOTEDLMFQ-UHFFFAOYSA-N nonan-5-one Chemical compound CCCCC(=O)CCCC WSGCRAOTEDLMFQ-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 150000004714 phosphonium salts Chemical group 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
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- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
Description
本発明は、アルキルエーテル化カルボキシアルキルセルロースに関する。さらに詳しくは、アルキルエーテル化置換度が高いアルキルエーテル化カルボキシアルキルセルロースとその製造方法に関する。 The present invention relates to an alkyl etherified carboxyalkyl cellulose. More specifically, the present invention relates to an alkyl etherified carboxyalkyl cellulose having a high degree of alkyl ether substitution and a method for producing the same.
従来より、アルキルエーテル化置換度の高いアルキルエーテル化カルボキシアルキルセルロースは、医薬品等の薬剤の添加剤として使用されている。
アルキルエーテル化カルボキシアルキルセルロースの製造方法としては、苛性ソーダなどの強アルカリの存在下、カルボキシアルキルセルロースにアルキルハロゲン化物を反応させる方法が知られている（例えば、特許文献１）。
Hitherto, alkyl etherified carboxyalkyl cellulose having a high degree of alkyl ether substitution has been used as an additive for drugs such as pharmaceuticals.
As a method for producing alkyl etherified carboxyalkyl cellulose, a method is known in which alkyl halide is reacted with carboxyalkyl cellulose in the presence of strong alkali such as caustic soda (for example, Patent Document 1).
しかしながら、カルボキシアルキルセルロースとアルカリとの反応により、まずアルコラートと水が生成し、次に、生成したアルコラートとアルキル化剤との反応により、疎水性が高いアルキルエーテル化カルボキシアルキルセルロースと塩が生成するため、反応の進行に伴い反応系の不均一化が増し、アルキルエーテル化カルボキシアルキルセルロースの凝集が進むため、アルキルエーテル化置換度の高いものが得られにくいという問題があった。
本発明は、アルキルエーテル化置換度の高いアルキルエーテル化カルボキシアルキルセルロース、およびその製造方法を提供することを目的とする。 An object of the present invention is to provide an alkyl etherified carboxyalkyl cellulose having a high degree of alkyl ether substitution and a method for producing the same.
本発明者は鋭意研究した結果、本発明を完成させるに至った。
すなわち本発明は
カルボキシアルキルセルロース（Ａ）中の水酸基がアルキルエーテル化されたアルキルエーテル化カルボキシアルキルセルロースであって、アルキルエーテル化置換度が７０ 〜１００％であることを特徴とするアルキルエーテル化カルボキシアルキルセルロース（Ｂ）；およびカルボキシアルキルセルロース（Ａ）とアルキル化剤（Ｄ）を、アルカリ（Ｅ）と下記一般式（１）で表される有機溶媒（Ｃ）の存在下で反応させて製造され、アルキルエーテル化置換度が７０〜１００％であることを特徴とするアルキルエーテル化カルボキシアルキルセルロース（Ｂ）の製造方法である。
Ｒ１―Ｏ−（Ｃ２Ｈ４Ｏ）ｍ−Ｒ２ （１）
［式中、Ｒ1とＲ２はそれぞれ独立に、メチル基、エチル基を表す。ｍは、１〜５の整数を表す。］
As a result of intensive studies, the present inventors have completed the present invention.
That is, the present invention relates to an alkyl etherified carboxyalkyl cellulose in which a hydroxyl group in the carboxyalkyl cellulose (A) is alkyl etherified, and the degree of substitution with an alkyl ether is 70 to 100%. Produced by reacting an alkyl cellulose (B); and a carboxyalkyl cellulose (A) and an alkylating agent (D) in the presence of an alkali (E) and an organic solvent (C) represented by the following general formula (1) The alkyl etherification substitution degree is 70 to 100%, and this is a method for producing an alkyl etherified carboxyalkyl cellulose (B).
R 1 —O— (C 2 H 4 O) m —R 2 (1)
[Wherein, R 1 and R 2 each independently represent a methyl group or an ethyl group. m represents an integer of 1 to 5. ]
本発明によれば、特定の溶媒を選択することにより アルキルエーテル化反応に伴い進行する凝集による反応性の低下が抑制されるため、アルキルエーテル化置換度の高いアルキルエーテル化カルボキシアルキルセルロースが得られる。 According to the present invention, by selecting a specific solvent, a decrease in reactivity due to aggregation that proceeds with the alkyl etherification reaction is suppressed, so that an alkyl etherified carboxyalkyl cellulose having a high degree of alkyl ether substitution is obtained. .
本発明は、アルキルエーテル化置換度が高いアルキルエーテル化カルボキシアルキルセルロース（Ｂ）；および特定の有機溶媒中で反応させることを特徴とするこのアルキルエーテル化カルボキシアルキルセルロース（Ｂ）である。 The present invention is an alkyl etherified carboxyalkyl cellulose (B) having a high degree of alkyl ether substitution, and this alkyl etherified carboxyalkyl cellulose (B) characterized by reacting in a specific organic solvent.
本発明の目的の化合物であるアルキルエーテル化カルボキシアルキルセルロース（Ｂ）は、カルボキシアルキルセルロース（Ａ）とアルキル化剤（Ｄ）を、アルカリ（Ｅ）と有機溶媒（Ｃ）の存在下で反応させることにより、（Ｂ）のアルキルエーテル化置換度を、７０〜１００％と高くすることができる。好ましくは８０％〜１００％、さらに好ましくは９５％〜１００％である。 The alkyl etherified carboxyalkyl cellulose (B), which is an object compound of the present invention, reacts a carboxyalkyl cellulose (A) with an alkylating agent (D) in the presence of an alkali (E) and an organic solvent (C). Thereby, the alkyl etherification substitution degree of (B) can be as high as 70 to 100%. Preferably they are 80%-100%, More preferably, they are 95%-100%.
ここで、本発明におけるアルキルエーテル化カルボキシアルキルセルロース（Ｂ）のアルキルエーテル化置換度とは、カルボキシアルキルセルロース（Ａ）のグルコース環単位当りの水酸基のうち、アルキルエーテル化された官能基数の割合の平均値を百分率で表わした値として定義する。
例えば、グルコース環単位当り０．５個が置換されたカルボキシアルキルセルロース（Ａ）を原料とし、残りの２．５個のうち２．１個がさらにアルキルエーテル化された場合のアルキルエーテル化置換度は、８４％である。
具体的には、（Ｂ）のアルキルエーテル結合およびカルボキシアルキルエーテル結合をヨウ化水素酸で開裂し、生じたヨウ素酸からヨウ素を遊離させ、これをチオ硫酸ナトリウムで測定することで求められる。詳細は後述する。
Here, the alkyl etherification substitution degree of the alkyl etherified carboxyalkyl cellulose (B) in the present invention is the ratio of the number of functional groups alkylated among the hydroxyl groups per glucose ring unit of the carboxyalkyl cellulose (A). The average value is defined as a percentage value.
For example, alkyl etherification substitution degree when carboxyalkyl cellulose (A) having 0.5 substituted per glucose ring unit is used as a raw material and 2.1 of the remaining 2.5 is further alkyl etherized Is 84%.
Specifically, the alkyl ether bond and carboxyalkyl ether bond of (B) are cleaved with hydroiodic acid, iodine is liberated from the resulting iodic acid, and this is determined by measuring with sodium thiosulfate. Details will be described later.
本発明において、カルボキシアルキルセルロース（Ａ）のグルコース環単位当りのカルボキシアルキル基の置換基数は、０．２〜１．０、さらに０．３〜０．６が好ましい。
（Ａ）としては例えば、カルボキシメチルセルロース、カルボキシエチルセルロース、カルボキシプロピルセルロースなどが挙げられる。これらのうち、好ましくは、カルボキシメチルセルロースである。
In the present invention, the number of substituents of the carboxyalkyl group per glucose ring unit of the carboxyalkyl cellulose (A) is preferably 0.2 to 1.0, more preferably 0.3 to 0.6.
Examples of (A) include carboxymethylcellulose, carboxyethylcellulose, carboxypropylcellulose, and the like. Of these, carboxymethyl cellulose is preferable.
カルボキシアルキル化置換度は、５〜３５％、さらに１０〜２０％が好ましい。 The degree of carboxyalkylation substitution is preferably 5 to 35%, more preferably 10 to 20%.
ここで、カルボキシアルキル化置換度とは、セルロースのグルコース環単位当りの水酸基のうち、カルボキシアルキル化された官能基数の割合の平均値を百分率で表わした値として定義する。
カルボキシアルキル化置換度は、上記のアルキルエーテル化置換度の測定方法と同じく、（Ａ）のカルボキシアルキルエーテル結合をヨウ化水素酸で開裂し、生じたヨウ素酸からヨウ素を遊離させ、これをチオ硫酸ナトリウムで滴定することで求められる。
Here, the degree of carboxyalkylation substitution is defined as a value representing the average value of the ratio of the number of carboxyalkylated functional groups among the hydroxyl groups per glucose ring unit of cellulose as a percentage.
The degree of carboxyalkylation substitution is the same as the method for measuring the degree of alkyletherification substitution described above. The carboxyalkyl ether bond in (A) is cleaved with hydroiodic acid, and iodine is liberated from the resulting iodic acid. It is determined by titration with sodium sulfate.
本発明において、カルボキシアルキルセルロース（Ａ）のアルキルエーテル化のために使用するアルキル化剤（Ｄ）としては、メチルクロライド、エチルクロライド、プロピルクロライド、ブチルクロライド、イソプロピルクロライドなどのアルキルクロライド；メチルブロマイド、エチルブロマイド、プロピルブロマイド、ブチルブロマイド、イソプロピルブロマイドなどのアルキルブロマイド；ジメチル硫酸、ジエチル硫酸、ジプロピル硫酸、ジブチル硫酸、ジイソプロピル硫酸などのジアルキル硫酸などが挙げられる。
好ましくは、アルキルクロライドであり、特に好ましくは、エチルクロライド、メチルクロライドである。
In the present invention, the alkylating agent (D) used for alkyl etherification of the carboxyalkyl cellulose (A) includes alkyl chlorides such as methyl chloride, ethyl chloride, propyl chloride, butyl chloride, and isopropyl chloride; methyl bromide, Examples include alkyl bromides such as ethyl bromide, propyl bromide, butyl bromide, and isopropyl bromide; and dialkyl sulfuric acids such as dimethyl sulfate, diethyl sulfate, dipropyl sulfate, dibutyl sulfate, and diisopropyl sulfate.
Alkyl chloride is preferable, and ethyl chloride and methyl chloride are particularly preferable.
アルカリ（Ｅ）としては、水酸化ナトリウム、水酸化カリウム、水酸化リチウムの固形物が挙げられ、好ましくは水酸化ナトリウム、水酸化カリウムであり、より好ましくは水酸化ナトリウムである。これらの固形アルカリ金属水酸化物は単独でも、２種類以上の混合物であっても良い。
これらの固形アルカリ金属水酸化物の形状は、粒状、フレーク状、粉状の何れでも良い。大きさは、粒状物は好ましくは直径１〜５ｍｍ、フレーク状物は好ましくは０．５〜３ｃｍ角、粉状物は好ましくは３０〜１００μｍであるが、本発明はこれに限定されない。作業従事者の取り扱い上、粒状が好ましい。
カルボキシアルキルセルロース（Ａ）とアルカリ（Ｅ）の重量比（Ａ）／（Ｅ）は、通常１／０．１〜１／２．０であり、１／０．３〜１／１．５が好ましい。
Examples of the alkali (E) include solids of sodium hydroxide, potassium hydroxide and lithium hydroxide, preferably sodium hydroxide and potassium hydroxide, more preferably sodium hydroxide. These solid alkali metal hydroxides may be used alone or as a mixture of two or more.
These solid alkali metal hydroxides may be in the form of granules, flakes, or powders. The size is preferably 1 to 5 mm in diameter for granular materials, 0.5 to 3 cm square for flakes, and preferably 30 to 100 μm for powders, but the present invention is not limited thereto. Granularity is preferable for the handling of workers.
The weight ratio (A) / (E) of the carboxyalkyl cellulose (A) to the alkali (E) is usually 1 / 0.1 to 1 / 2.0, and 1 / 0.3 to 1 / 1.5 is preferable.
本発明の高いアルキルエーテル化置換度を得るための製造方法で用いることができる有機溶媒（Ｃ）は、下記一般式（１）で表されるものに限られる。
Ｒ１―Ｏ−（Ｃ２Ｈ４Ｏ）ｍ−Ｒ２ （１）
[式（１）中、Ｒ1とＲ２はそれぞれ独立に、メチル基、エチル基を表す。ｍは、１〜５の整数を表す。]
The organic solvent (C) that can be used in the production method for obtaining a high degree of alkyl ether substitution of the present invention is limited to those represented by the following general formula (1).
R 1 —O— (C 2 H 4 O) m —R 2 (1)
[In Formula (1), R < 1 > and R < 2 > represents a methyl group and an ethyl group each independently. m represents an integer of 1 to 5. ]
上記化学式で表される有機溶媒（Ｃ）の両末端はメチル基またはエチル基であり、ｍは通常１〜５、好ましくは１〜３である。 Both ends of the organic solvent (C) represented by the above chemical formula are methyl groups or ethyl groups, and m is usually 1 to 5, preferably 1 to 3.
有機溶媒（Ｃ）の具体例としては、エチレングリコールジメチルエーテル（グライム）、ジエチレングリコールジメチルエーテル（ジグライム）、トリエチレングリコールジメチルエーテル（トリグライム）、テトラエチレングリコールジメチルエーテル（テトラグライム）などが挙げられる。
カルボキシアルキルセルロース（Ａ）およびアルキルエーテル化カルボキシアルキルセルロース（Ｂ）との親和性、反応後の除去性の観点から、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルが好ましい。
アルキルエーテル化反応開始時の有機溶媒（Ｃ）とカルボキシアルキルセルロース（Ａ）との重量比（Ｃ）／（Ａ）は通常、０．３／１〜１０／１、好ましくは１／１〜４／である。
Specific examples of the organic solvent (C) include ethylene glycol dimethyl ether (glyme), diethylene glycol dimethyl ether (diglyme), triethylene glycol dimethyl ether (triglyme), and tetraethylene glycol dimethyl ether (tetraglyme).
From the viewpoints of affinity with carboxyalkyl cellulose (A) and alkyl etherified carboxyalkyl cellulose (B) and removability after reaction, ethylene glycol dimethyl ether and diethylene glycol dimethyl ether are preferred.
The weight ratio (C) / (A) of the organic solvent (C) to the carboxyalkyl cellulose (A) at the start of the alkyl etherification reaction is usually 0.3 / 1 to 10/1, preferably 1/1 to 4. /.
また、アルキルエーテル化反応の反応温度は通常４０℃〜１８０℃であり、好ましくは６０〜１６０℃であり、より好ましくは８０〜１４０℃である。４０℃未満であると反応の進行が非常に遅く効率的でない。１６０℃を超えると、容器の材質が耐久性の良いＳＵＳ３１６Ｌであっても腐食を起こす可能性がある。 Moreover, the reaction temperature of alkyl etherification reaction is 40 to 180 degreeC normally, Preferably it is 60 to 160 degreeC, More preferably, it is 80 to 140 degreeC. If it is less than 40 ° C., the reaction proceeds very slowly and is not efficient. If the temperature exceeds 160 ° C., corrosion may occur even if the material of the container is SUS316L having good durability.
反応は、好ましくは窒素等の不活性ガス雰囲気下（酸素濃度が好ましくは１００ｐｐｍ以下）で行うことが好ましい。
カルボキシアルキルセルロース（Ａ）、有機溶媒（Ｃ）、アルキル化剤（Ｄ）、アルカリ（Ｅ）の投入の順序は、急激な反応が生じなければ特に限定されないが、（Ａ）と（Ｃ）を混合し、（Ｅ）を分散させ、室温で減圧と窒素等による不活性ガスでの置換を繰り返した後、減圧にして（Ｄ）を滴下する方法が好ましい。
（Ａ）、（Ｃ）、（Ｄ）を混合し、最後に（Ｅ）を投入する方法では、（Ｅ）の溶解熱で（Ｄ）が突沸したり、急激な発熱により生成物が着色し易くなる。
The reaction is preferably performed in an inert gas atmosphere such as nitrogen (oxygen concentration is preferably 100 ppm or less).
The order of adding the carboxyalkyl cellulose (A), the organic solvent (C), the alkylating agent (D), and the alkali (E) is not particularly limited as long as a rapid reaction does not occur, but (A) and (C) are not limited. It is preferable to mix, disperse (E), repeat decompression at room temperature and substitution with an inert gas such as nitrogen, and then drop (D) dropwise under reduced pressure.
In the method of mixing (A), (C) and (D) and finally adding (E), (D) suddenly boils with the heat of dissolution of (E) or the product is colored due to sudden heat generation. It becomes easy.
本発明において、カルボキシアルキルセルロース（Ａ）を膨潤させて反応を促進する目的で、水を用いることができる。
アルキルエーテル化反応開始時の水とカルボキシアルキルセルロース（Ａ）の重量比［水／（Ａ）］は通常、０／１〜０．３／１、好ましくは０．０１／１〜０．１５／１である。この範囲より多くの水の量になると、不均一性が増してスラリー状反応系を保持できなくなり、凝集を生じるだけではなく、アルキル化剤の主反応への効率が低下する。
In the present invention, water can be used for the purpose of promoting the reaction by swelling the carboxyalkyl cellulose (A).
The weight ratio [water / (A)] of water and carboxyalkyl cellulose (A) at the start of the alkyl etherification reaction is usually 0/1 to 0.3 / 1, preferably 0.01 / 1 to 0.15 /. 1. If the amount of water exceeds this range, the heterogeneity increases and the slurry-like reaction system cannot be maintained, not only causing aggregation, but also reducing the efficiency of the alkylating agent in the main reaction.
本発明において、アルキルエーテル化反応時、必要により、相関移動触媒を用いることができる。
相関移動触媒としては、例えば、第４級アンモニウム塩、第４級ホスホニウム塩、第４級アルソニウム塩等が挙げられ、好ましくは第４級アンモニウム塩である。第４級アンモニウム塩には、例えばテトラメチルアンモニウムクロライド、ベンジルトリメチルアンモニウムクロライド、ベンジルトリエチルアンモニウムクロライド、ベンジルトリブチルアンモニウムクロライド、テトラブチルアンモニウムブロマイド、テトラブチルアンモニウムハイドロサルフェート、トリオクチルアンモニウムクロライド、ｎ−ラウリルピリジニウムクロライド等が挙げられる。これら相間移動触媒を本発明の反応系に添加する場合の添加量は、カルボキシアルキルセルロース（Ａ）に対して、好ましくは８重量％以下であり、より好ましくは５重量％以下である。
In the present invention, a phase transfer catalyst can be used as necessary during the alkyl etherification reaction.
Examples of the phase transfer catalyst include a quaternary ammonium salt, a quaternary phosphonium salt, a quaternary arsonium salt, and the like, and preferably a quaternary ammonium salt. Examples of the quaternary ammonium salt include tetramethylammonium chloride, benzyltrimethylammonium chloride, benzyltriethylammonium chloride, benzyltributylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium hydrosulfate, trioctylammonium chloride, n-laurylpyridinium chloride. Etc. When the phase transfer catalyst is added to the reaction system of the present invention, the addition amount is preferably 8% by weight or less, more preferably 5% by weight or less based on the carboxyalkyl cellulose (A).
本発明において、アルキルエーテル化反応時に、必要により、特定の有機溶媒（Ｃ）以外に、悪影響しない範囲で他の溶媒を共存させて用いることができる。
共存させる溶媒としては、例えば、トルエン、キシレン、エチルベンゼン、テトラリンなどの芳香族炭化水素系溶剤；ｎ−ヘキサン、ｎ−ヘプタン、ミネラルスピリット、シクロヘキサンなどの脂肪族または脂環式炭化水素系溶剤；塩化メチル、臭化メチル、ヨウ化メチル、メチレンジクロライド、四塩化炭素、トリクロロエチレン、パークロロエチレンなどのハロゲン系溶剤；酢酸エチル、酢酸ブチル、メトキシブチルアセテート、メチルセロソルブアセテート、エチルセロソルブアセテートなどのエステル系またはエステルエーテル系溶剤；ジエチルエーテル、テトラヒドロフラン、ジオキサンなどのエーテル系溶剤；アセトン、メチルエチルケトン、メチルイソブチルケトン、ジ−ｎ−ブチルケトン、シクロヘキサノンなどのケトン系溶剤；ｔ−ブタノールなどのアルコール系溶剤；ジメチルホルムアミド、ジメチルアセトアミドなどのアミド系溶剤；ジメチルスルホキシドなどのスルホキシド系溶剤、Ｎ−メチルピロリドンなどの複素環式化合物系溶剤、ならびにこれらの２種以上の混合溶剤が挙げられる。
In the present invention, other than the specific organic solvent (C), other solvents can be used in the coexisting range as long as they do not adversely affect the alkyl etherification reaction.
Examples of the coexisting solvent include aromatic hydrocarbon solvents such as toluene, xylene, ethylbenzene, and tetralin; aliphatic or alicyclic hydrocarbon solvents such as n-hexane, n-heptane, mineral spirit, and cyclohexane; Halogen solvents such as methyl, methyl bromide, methyl iodide, methylene dichloride, carbon tetrachloride, trichloroethylene, perchloroethylene; esters such as ethyl acetate, butyl acetate, methoxybutyl acetate, methyl cellosolve acetate, ethyl cellosolve acetate or Ester ether solvents; Ether solvents such as diethyl ether, tetrahydrofuran and dioxane; Ketone systems such as acetone, methyl ethyl ketone, methyl isobutyl ketone, di-n-butyl ketone and cyclohexanone Agents; alcohol solvents such as t-butanol; amide solvents such as dimethylformamide and dimethylacetamide; sulfoxide solvents such as dimethylsulfoxide; heterocyclic compound solvents such as N-methylpyrrolidone; and two or more of these solvents A mixed solvent is mentioned.
また、本発明において、アルキルエーテル化後、反応物に水と硫酸、塩酸、燐酸などの酸を加え、析出物をろ過水洗し、乾燥することによって、アルキルエーテル化カルボキシアルキルセルロース（Ｂ）を精製することができる。 Further, in the present invention, after alkyl etherification, water and an acid such as sulfuric acid, hydrochloric acid and phosphoric acid are added to the reaction product, and the precipitate is washed with filtered water and dried to purify the alkyl etherified carboxyalkyl cellulose (B). can do.
本発明によって得られるアルキルエーテル化セルロース誘導体の用途は特に限定しないが、本品のｐＨ変化による水への溶解性が変化する性質や、フィルム形成能が用いられる用途に使用される。
通常、医薬品等の薬剤の添加剤、特に腸溶性のコーティング剤、苦みマスキング剤、あるいは頭髪用セット剤として使用することができる。
The use of the alkyl etherified cellulose derivative obtained by the present invention is not particularly limited. However, it is used for applications in which the solubility of the product in water due to pH change or film forming ability is used.
Usually, it can be used as an additive for drugs such as pharmaceuticals, particularly enteric coating agents, bitterness masking agents, or hair hair setting agents.
以下、実施例および比較例により本発明を説明するが、本発明はこれに限定されるものではない。以下、特に記載のないかぎり、「部」は「重量部」、％は重量％を意味する。 Hereinafter, although an example and a comparative example explain the present invention, the present invention is not limited to this. Hereinafter, unless otherwise specified, “part” means “part by weight” and% means wt%.
アルキルエーテル化置換度および収率の測定法は以下の通りである。 The methods for measuring the degree of alkyl etherification substitution and the yield are as follows.
＜アルキルエーテル化置換度＞
（１）試料１５ｍｇとヨウ化水素酸６ｍＬを分解フラスコに入れた後、窒素を通じて、１５０℃で１時間加熱する。生成するヨウ化メチルを気相に追い出し，この後１重量％の赤リン懸濁液で洗浄し、吸収管に送る。吸収管には、酢酸カリウム１５ｇを酢酸／無水酢酸混液（９／１）１５０ｍＬに溶解し、その溶液１４５ｍＬを量り、臭素５ｍＬを加えておく。
（２）酢酸ナトリウム三水和物溶液が入った共栓三角フラスコに、吸収管の内容物を加える。吸着管の内壁に付着した内容物は、水を加えることで流し出す。次に、振り混ぜながら臭素の赤色が消えるまで、ギ酸を加える。
（３）共栓三角フラスコにヨウ化カリウム３ｇと希硫酸１５ｍＬを加え、栓をして軽く振り混ぜ、５分間放置する。遊離したヨウ素を０．１ mol/Lチオ硫酸ナトリウム液で滴定する。
（４）下記式からまずメトキシ基含量（Ｃｍ）を算出し、これを用いて本発明のアルキルエーテル化置換度（ＣＲ）を算出する。
メトキシ基含量（Ｃｍ）（％）＝滴定量（ｍＬ）×５１．７２／試料量（ｍｇ）
アルキルエーテル化置換度（ＣＲ）＝（Ｃｍ×１６２）／（３１００−Ｃｍ×１４）−ＣＡ
但しＣＡ：カルボキシアルキルセルロース（Ａ）のカルボキシアルキル化置換度
<Alkyl etherification substitution degree>
(1) After putting 15 mg of a sample and 6 mL of hydroiodic acid in a decomposition flask, heat at 150 ° C. for 1 hour through nitrogen. The produced methyl iodide is driven out into the gas phase, and then washed with a 1% by weight red phosphorus suspension and sent to an absorption tube. In the absorption tube, 15 g of potassium acetate is dissolved in 150 mL of a mixture of acetic acid / acetic anhydride (9/1), 145 mL of the solution is weighed, and 5 mL of bromine is added.
(2) Add the contents of the absorption tube to the stoppered Erlenmeyer flask containing the sodium acetate trihydrate solution. The contents adhering to the inner wall of the adsorption tube are washed out by adding water. Next, formic acid is added with shaking until the red color of bromine disappears.
(3) Add 3 g of potassium iodide and 15 mL of dilute sulfuric acid to the stoppered Erlenmeyer flask, stopper, shake lightly and leave for 5 minutes. The liberated iodine is titrated with 0.1 mol / L sodium thiosulfate solution.
(4) First, the methoxy group content (C m ) is calculated from the following formula, and this is used to calculate the alkyl etherification substitution degree (C R ) of the present invention.
Methoxy group content (C m ) (%) = Titration volume (mL) × 51.72 / sample amount (mg)
Alkyl etherification substitution degree (C R ) = (C m × 162) / (3100-C m × 14) -C A
However, C A : Carboxyalkylation substitution degree of carboxyalkyl cellulose (A)
＜実施例１＞
オートクレーブ反応容器にジエチレングリコールジメチルエーテル（Ｃ−１）８０．５部、水３．５部、カルボキシメチルセルロース（カルボキシメチル化置換度１８．３％、グルコース環単位当りのカルボキシアルキル基の置換基数０．５５、１％水溶液粘度が１０ｍＰａ・ｓ）（Ａ−１）４５．７部、水酸化ナトリウム（Ｅ−１）２０．８部、テトラメチルアンモニウムクロライド１．８部を投じ、窒素置換後、１２０℃で圧力を見ながらエチルクロライド（Ｄ−１）３３．５部を徐々に加え、１２時間反応した。反応終了後、反応物をグラス容器に移し、水２１５．９部と硫酸１３．３部を加え、析出した粒子を遠心分離機で水洗および脱水し、９０℃で減圧乾燥して、カルボキシメチルエチルセルロースを得た。結果を表１に示した。
<Example 1>
In an autoclave reaction vessel, 80.5 parts of diethylene glycol dimethyl ether (C-1), 3.5 parts of water, carboxymethyl cellulose (carboxymethyl substitution degree 18.3%, number of substituents of carboxyalkyl group per glucose ring unit 0.55, 1% aqueous solution viscosity is 10 mPa · s) (A-1) 45.7 parts, sodium hydroxide (E-1) 20.8 parts, tetramethylammonium chloride 1.8 parts, after nitrogen substitution, at 120 ° C While watching the pressure, 33.5 parts of ethyl chloride (D-1) was gradually added and reacted for 12 hours. After completion of the reaction, the reaction product is transferred to a glass container, 215.9 parts of water and 13.3 parts of sulfuric acid are added, and the precipitated particles are washed with water and dehydrated with a centrifuge, dried at 90 ° C. under reduced pressure, and carboxymethyl ethyl cellulose. Got. The results are shown in Table 1.
＜実施例２＞
実施例１において、有機溶媒をジエチレングリコールジメチルエーテル（Ｃ−１）８０．５部の代わりにエチレングリコールジメチルエーテル（Ｃ−２）８０．５部とした以外は実施例１と同様に操作した。
<Example 2>
In Example 1, the same operation as in Example 1 was carried out except that the organic solvent was changed to 80.5 parts of ethylene glycol dimethyl ether (C-2) instead of 80.5 parts of diethylene glycol dimethyl ether (C-1).
＜比較例１＞
実施例１において、有機溶媒をジエチレングリコールジメチルエーテル（Ｃ−１）８０．５部の代わりにトルエン（Ｃ’−１）８０．５部とした以外は実施例１と同様に操作した。
<Comparative Example 1>
In Example 1, the same operation as in Example 1 was conducted except that 80.5 parts of toluene (C′-1) was used instead of 80.5 parts of diethylene glycol dimethyl ether (C-1).
＜比較例２＞
実施例１において、有機溶媒をジエチレングリコールジメチルエーテル（Ｃ−１）８０．５部の代わりにテトラヒドロフラン （Ｃ’−２）８０．５部とした以外は実施例１と同様に操作した。
<Comparative example 2>
In Example 1, operation was carried out in the same manner as in Example 1 except that 80.5 parts of tetrahydrofuran (C′-2) was used instead of 80.5 parts of diethylene glycol dimethyl ether (C-1).
＜比較例３＞
実施例１において、有機溶媒をジエチレングリコールジメチルエーテル（Ｃ−１）８０．５部の代わりにジエチレングリコールモノメチルエーテル（Ｃ’−３）８０．５部とした以外は実施例１と同様に操作した。
<Comparative Example 3>
In Example 1, the same operation as in Example 1 was conducted except that 80.5 parts of diethylene glycol monomethyl ether (C′-3) was used instead of 80.5 parts of diethylene glycol dimethyl ether (C-1).
＜比較例４＞
実施例１において、有機溶媒をジエチレングリコールジメチルエーテル（Ｃ−１）８０．５部の代わりにエチレングリコールモノメチルエーテル（Ｃ’−４）８０．５部とした以外は実施例１と同様に操作した。
<Comparative example 4>
In Example 1, operation was carried out in the same manner as in Example 1 except that 80.5 parts of ethylene glycol monomethyl ether (C′-4) was used instead of 80.5 parts of diethylene glycol dimethyl ether (C-1).
以上の結果から明らかな通り、特定の化学構造の有機溶媒を用いた本発明の製造方法は、アルキルエーテル化置換度が高いアルキルエーテル化カルボキシアルキルセルロースが得られる。 As is clear from the above results, the production method of the present invention using an organic solvent having a specific chemical structure provides alkyl etherified carboxyalkyl cellulose having a high degree of alkyl ether substitution.
本発明によって得られるアルキルエーテル化置換度が高いアルキルエーテル化カルボキシアルキルセルロースは、ｐＨ変化による水への溶解性が変化する性質や、フィルム形成能が用いられる用途に使用される。通常、医薬品等の薬剤の添加剤、特に腸溶性のコーティング剤、苦みマスキング剤、あるいは頭髪用セット剤として使用することができる。
The alkyl etherified carboxyalkyl cellulose having a high degree of alkyl ether substitution obtained by the present invention is used for applications in which the solubility in water due to pH change and film forming ability are used. Usually, it can be used as an additive for drugs such as pharmaceuticals, particularly enteric coating agents, bitterness masking agents, or hair hair setting agents.
Claims (6)
Ｒ１―Ｏ−（Ｃ２Ｈ４Ｏ）ｍ−Ｒ２ （１）
［式中、Ｒ1とＲ２はそれぞれ独立に、メチル基、エチル基を表す。ｍは、１〜５の整数を表す。］ A carboxyalkyl cellulose (A) and an alkylating agent (D) are produced by reacting an alkali (E) with an organic solvent (C) represented by the following general formula (1). Is 70-100%, The manufacturing method of the alkyl etherified carboxyalkyl cellulose (B) characterized by the above-mentioned.
R 1 —O— (C 2 H 4 O) m —R 2 (1)
[Wherein, R 1 and R 2 each independently represent a methyl group or an ethyl group. m represents an integer of 1 to 5. ]
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|---|---|---|---|---|
| JPS5534279A (en) * | 1978-12-28 | 1980-03-10 | Kohjin Co Ltd | Preparation of carboxymethyl ethyl cellulose |
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| JPS55118902A (en) * | 1979-03-06 | 1980-09-12 | Daicel Chem Ind Ltd | Preparation of ethylcarboxymethylcellulose |
| JPS55118901A (en) * | 1979-03-06 | 1980-09-12 | Daicel Chem Ind Ltd | Preparation of ethylcarboxymethylcellulose |
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| JPS58147402A (en) * | 1982-02-26 | 1983-09-02 | Kohjin Co Ltd | Preparation of carboxymethylethyl cellulose |
| JPS59159801A (en) * | 1983-02-25 | 1984-09-10 | ヘキスト・アクチエンゲゼルシヤフト | Manufacture of cellulose ether from cellulose and etherifier |
| JPH04130101A (en) * | 1990-09-20 | 1992-05-01 | Sanyo Chem Ind Ltd | Production of carboxymethylalkylcellulose |
| JP2000007702A (en) * | 1998-06-23 | 2000-01-11 | Sumitomo Seika Chem Co Ltd | Preparation of hydroxypropyl cellulose |
| JP2000186101A (en) * | 1998-12-22 | 2000-07-04 | Sumitomo Seika Chem Co Ltd | Production of hydroxypropyl cellulose |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5534279A (en) * | 1978-12-28 | 1980-03-10 | Kohjin Co Ltd | Preparation of carboxymethyl ethyl cellulose |
| JPS5590501A (en) * | 1978-12-28 | 1980-07-09 | Wako Pure Chem Ind Ltd | Preparation of ethylcarboxymethylcellulose |
| JPS55118902A (en) * | 1979-03-06 | 1980-09-12 | Daicel Chem Ind Ltd | Preparation of ethylcarboxymethylcellulose |
| JPS55118901A (en) * | 1979-03-06 | 1980-09-12 | Daicel Chem Ind Ltd | Preparation of ethylcarboxymethylcellulose |
| JPS58103501A (en) * | 1981-11-30 | 1983-06-20 | ヘキスト・アクチエンゲゼルシヤフト | Manufacture of cellulose ether |
| JPS58147402A (en) * | 1982-02-26 | 1983-09-02 | Kohjin Co Ltd | Preparation of carboxymethylethyl cellulose |
| JPS59159801A (en) * | 1983-02-25 | 1984-09-10 | ヘキスト・アクチエンゲゼルシヤフト | Manufacture of cellulose ether from cellulose and etherifier |
| JPH04130101A (en) * | 1990-09-20 | 1992-05-01 | Sanyo Chem Ind Ltd | Production of carboxymethylalkylcellulose |
| JP2000007702A (en) * | 1998-06-23 | 2000-01-11 | Sumitomo Seika Chem Co Ltd | Preparation of hydroxypropyl cellulose |
| JP2000186101A (en) * | 1998-12-22 | 2000-07-04 | Sumitomo Seika Chem Co Ltd | Production of hydroxypropyl cellulose |
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