JP4207270B2 - Method for producing alkyl cyanobenzoate - Google Patents
Method for producing alkyl cyanobenzoate Download PDFInfo
- Publication number
- JP4207270B2 JP4207270B2 JP30296198A JP30296198A JP4207270B2 JP 4207270 B2 JP4207270 B2 JP 4207270B2 JP 30296198 A JP30296198 A JP 30296198A JP 30296198 A JP30296198 A JP 30296198A JP 4207270 B2 JP4207270 B2 JP 4207270B2
- Authority
- JP
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- Prior art keywords
- alkyl ester
- substituent
- benzene ring
- phthalonitrile
- group
- 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.)
- Expired - Fee Related
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- -1 alkyl cyanobenzoate Chemical compound 0.000 title claims description 20
- 238000004519 manufacturing process Methods 0.000 title claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 39
- 229920006391 phthalonitrile polymer Polymers 0.000 claims description 33
- XQZYPMVTSDWCCE-UHFFFAOYSA-N phthalonitrile Chemical compound N#CC1=CC=CC=C1C#N XQZYPMVTSDWCCE-UHFFFAOYSA-N 0.000 claims description 30
- 125000001424 substituent group Chemical group 0.000 claims description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 16
- BHXFKXOIODIUJO-UHFFFAOYSA-N benzene-1,4-dicarbonitrile Chemical compound N#CC1=CC=C(C#N)C=C1 BHXFKXOIODIUJO-UHFFFAOYSA-N 0.000 claims description 12
- 125000002560 nitrile group Chemical group 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 10
- 125000005907 alkyl ester group Chemical group 0.000 claims description 9
- 239000002994 raw material Substances 0.000 claims description 7
- LAQPNDIUHRHNCV-UHFFFAOYSA-N isophthalonitrile Chemical compound N#CC1=CC=CC(C#N)=C1 LAQPNDIUHRHNCV-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- GYLKKXHEIIFTJH-UHFFFAOYSA-N 3-cyanobenzoic acid Chemical compound OC(=O)C1=CC=CC(C#N)=C1 GYLKKXHEIIFTJH-UHFFFAOYSA-N 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 229910052731 fluorine Chemical group 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 239000000243 solution Substances 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- JLSSWDFCYXSLQX-UHFFFAOYSA-N ethyl 4-cyanobenzoate Chemical compound CCOC(=O)C1=CC=C(C#N)C=C1 JLSSWDFCYXSLQX-UHFFFAOYSA-N 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000004817 gas chromatography Methods 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 239000007789 gas Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- TXRVDQMSXQKAPG-UHFFFAOYSA-N 2,3,5,6-tetrachlorobenzene-1,4-dicarbonitrile Chemical compound ClC1=C(Cl)C(C#N)=C(Cl)C(Cl)=C1C#N TXRVDQMSXQKAPG-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-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
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- DTNSDCJFTHMDAK-UHFFFAOYSA-N 2-cyanobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C#N DTNSDCJFTHMDAK-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 125000005277 alkyl imino group Chemical group 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- CRQQGFGUEAVUIL-UHFFFAOYSA-N chlorothalonil Chemical compound ClC1=C(Cl)C(C#N)=C(Cl)C(C#N)=C1Cl CRQQGFGUEAVUIL-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000001033 ether group Chemical group 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- KPSSIOMAKSHJJG-UHFFFAOYSA-N neopentyl alcohol Chemical compound CC(C)(C)CO KPSSIOMAKSHJJG-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- CPRMKOQKXYSDML-UHFFFAOYSA-M rubidium hydroxide Chemical compound [OH-].[Rb+] CPRMKOQKXYSDML-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- QPRQEDXDYOZYLA-YFKPBYRVSA-N (S)-2-methylbutan-1-ol Chemical compound CC[C@H](C)CO QPRQEDXDYOZYLA-YFKPBYRVSA-N 0.000 description 1
- PCRSJGWFEMHHEW-UHFFFAOYSA-N 2,3,5,6-tetrafluorobenzene-1,4-dicarbonitrile Chemical compound FC1=C(F)C(C#N)=C(F)C(F)=C1C#N PCRSJGWFEMHHEW-UHFFFAOYSA-N 0.000 description 1
- WVHMPQKZPHOCRD-UHFFFAOYSA-N 2,4,5,6-tetrafluorobenzene-1,3-dicarbonitrile Chemical compound FC1=C(F)C(C#N)=C(F)C(C#N)=C1F WVHMPQKZPHOCRD-UHFFFAOYSA-N 0.000 description 1
- NHWQMJMIYICNBP-UHFFFAOYSA-N 2-chlorobenzonitrile Chemical compound ClC1=CC=CC=C1C#N NHWQMJMIYICNBP-UHFFFAOYSA-N 0.000 description 1
- QPRQEDXDYOZYLA-UHFFFAOYSA-N 2-methyl-1-butanol Substances CCC(C)CO QPRQEDXDYOZYLA-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
- ADCUEPOHPCPMCE-UHFFFAOYSA-N 4-cyanobenzoic acid Chemical compound OC(=O)C1=CC=C(C#N)C=C1 ADCUEPOHPCPMCE-UHFFFAOYSA-N 0.000 description 1
- 0 CC(c(cc1)ccc1C#N)=* Chemical compound CC(c(cc1)ccc1C#N)=* 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 238000000297 Sandmeyer reaction Methods 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- JFDZBHWFFUWGJE-KWCOIAHCSA-N benzonitrile Chemical group N#[11C]C1=CC=CC=C1 JFDZBHWFFUWGJE-KWCOIAHCSA-N 0.000 description 1
- WPJWIROQQFWMMK-UHFFFAOYSA-L beryllium dihydroxide Chemical compound [Be+2].[OH-].[OH-] WPJWIROQQFWMMK-UHFFFAOYSA-L 0.000 description 1
- 229910001865 beryllium hydroxide Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 238000007323 disproportionation reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- WCFVQUSRBOTUDF-UHFFFAOYSA-N methyl 2,3,5,6-tetrachloro-4-cyanobenzoate Chemical compound COC(=O)C1=C(Cl)C(Cl)=C(C#N)C(Cl)=C1Cl WCFVQUSRBOTUDF-UHFFFAOYSA-N 0.000 description 1
- XPBHWSMZTSSEJE-UHFFFAOYSA-N methyl 3-cyanobenzoate Chemical compound COC(=O)C1=CC=CC(C#N)=C1 XPBHWSMZTSSEJE-UHFFFAOYSA-N 0.000 description 1
- KKZMIDYKRKGJHG-UHFFFAOYSA-N methyl 4-cyanobenzoate Chemical compound COC(=O)C1=CC=C(C#N)C=C1 KKZMIDYKRKGJHG-UHFFFAOYSA-N 0.000 description 1
- BBEJNBLSSWFDSN-UHFFFAOYSA-N methylamino benzoate Chemical compound CNOC(=O)C1=CC=CC=C1 BBEJNBLSSWFDSN-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical group O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 1
- 235000019801 trisodium phosphate Nutrition 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【０００１】
【発明の属する技術分野】
本発明は置換または無置換シアノ安息香酸アルキルエステル、特に一般式（３）で示されるシアノ安息香酸アルキルエステルの製造方法に関する。シアノ安息香酸アルキルエステルは医薬・農薬その他有機化学品などの合成原料または中間体として有用である。
【０００２】
【従来の技術】
シアノ安息香酸アルキルエステルの製造方法としては、（１）特開昭５８−１１３１４５号公報のクロロベンゾニトリルのようにハロゲンが置換されたベンゾニトリルを触媒を用いて一酸化炭素及びアルコールと反応させる方法、（２）Bull.Chem.Soc.Jpn.,61,6,1985,(1988) とJ.Org.Chem.,51,24,4714,(1986) に報告されているアミノ安息香酸メチルのようにアミノ化された安息香酸アルキルエステルをサンドマイヤー反応によりジアゾニウム塩を経由して製造する方法、（３）特公昭４１−１８８１８号公報のニトリルとエステルの不均化反応による方法等の報告があるが、（１）、（２）は原料の入手が困難で工業的に有利ではない、（３）は過酷な条件が必要であること等いずれもシアノ安息香酸アルキルエステルを工業的に有利に製造する方法とはならない。このようにシアノ安息香酸アルキルエステルを製造する工業的に有利な方法はこれまで知られておらず、更なる改善が望まれている。
【０００３】
【発明が解決しようとする課題】
本発明の目的は、工業的に有利に入手可能な原料であるフタロニトリルから一般式（３）で示されるシアノ安息香酸アルキルエステルを工業的に有利な方法により高選択的かつ高収率で製造することにあり、特に医薬の合成中間体として有用なｍ−シアノ安息香酸アルキルエステルまたはｐ−シアノ安息香酸アルキルエステルを高選択的かつ高収率で製造することにある。
【０００４】
【課題を解決するための手段】
本発明者らは、前記の従来の問題点を解決すべく鋭意検討した結果、置換または無置換フタロニトリルと脂肪族アルコールを酸の存在下反応させて１個のニトリル基のみを選択的にアルキルイミノエーテル基に変換し、次いで水と反応させてアルキルイミノエーテル基のみをアルキルエステル基に変換することにより高選択的かつ高収率でシアノ安息香酸アルキルエステルを製造する方法を見出し、本発明を完成するに至った。本発明は以下の（１）〜（５）に示される製造方法に関する。
【０００５】
［１］ベンゼン環上に置換基を有してもよいフタロニトリルからベンゼン環上に置換基を有してもよいシアノ安息香酸アルキルエステル（３−シアノ−２，４−ジハロゲノ−５−フルオロ安息香酸を除く。）を製造する方法において、（ａ）ベンゼン環上に置換基を有してもよいフタロニトリルと脂肪族アルコールを酸の存在下反応させて１個のニトリル基のみをアルキルイミノエーテル基に変換する第１反応工程と、（ｂ）該アルキルイミノエーテル基のみを水と反応させてアルキルエステル基に変換する第２反応工程からなることを特徴とするベンゼン環上に置換基を有してもよいシアノ安息香酸アルキルエステル（３−シアノ−２，４−ジハロゲノ−５−フルオロ安息香酸を除く。）の製造方法。
［２］ベンゼン環上に置換基を有してもよいフタロニトリルが下記一般式（１）
【化３】
ＲＯＨ （２）
（式中、Ｒは炭素数が１〜５のアルキル基を表わす。）で示される脂肪族アルコールであり、ベンゼン環上に置換基を有してもよいシアノ安息香酸アルキルエステルが下記一般式（３）
【化４】
【０００６】
［３］一般式（１）で示されるフタロニトリルがイソフタロニトリルまたはテレフタロニトリルであり、一般式（３）で示されるシアノ安息香酸アルキルエステルがｍ−またはｐ−シアノ安息香酸アルキルエステルである上記［２］に記載のベンゼン環上に置換基を有してもよいシアノ安息香酸アルキルエステル（３−シアノ−２，４−ジハロゲノ−５−フルオロ安息香酸を除く。）の製造方法。
［４］一般式（２）で示される脂肪族アルコールがメタノールまたはエタノールである上記［２］乃至［３］のいずれかに記載のベンゼン環上に置換基を有してもよいシアノ安息香酸アルキルエステル（３−シアノ−２，４−ジハロゲノ−５−フルオロ安息香酸を除く。）の製造方法。
［５］未反応のベンゼン環上に置換基を有してもよいフタロニトリルを回収し、再び原料として再使用することを特徴とする上記［１］乃至［４］のいずれかに記載のベンゼン環上に置換基を有してもよいシアノ安息香酸アルキルエステル（３−シアノ−２，４−ジハロゲノ−５−フルオロ安息香酸を除く。）の製造方法。
【０００７】
すなわち本発明は、置換または無置換フタロニトリルと脂肪族アルコールを混合し、冷却または加熱下に攪拌し、１個のニトリル基のみを選択的にアルキルイミノエーテル基に変換するのに好ましい量の酸を加えて反応させ、次いで反応液に、あるいはアルキルイミノエーテルを分離した後に水を加える２段階反応により置換または無置換シアノ安息香酸アルキルエステルを高選択的かつ高収率で得る方法である。
【０００８】
【発明の実施の形態】
以下本発明について説明する。
本発明は置換または無置換フタロニトリル、好適には一般式（１）で示されるフタロニトリルと一般式（２）で示される脂肪族アルコールを１個のニトリル基のみをアルキルイミノエーテル基に変換するのに好ましい量の酸を加えて反応させることにより得られる下記一般式（４）
【化５】
【０００９】
本発明を更に詳細に説明する。
先ず、本発明で用いられるフタロニトリルは、置換または無置換フタロニトリルを使用することができる。無置換フタロニトリルとしては好適にイソフタロニトリルあるいはテレフタロニトリルが例示される。次に置換フタロニトリルとしては、本発明の反応においては不活性な置換基を有するフタロニトリルが使用できるが、例えばハロゲン原子、アルキル基、アリール基、アラルキル基、アルコキシ基、アリールオキシ基、アラルキルオキシ基などが１乃至４置換したフタロニトリルが挙げられる。２以上置換した場合は同一又は相異なる置換基であってもよい。
【００１０】
ハロゲン原子で置換されたフタロニトリルについて説明する。テトラクロロイソフタロニトリル、テトラクロロテレフタロニトリルなどの塩素化フタロニトリル化合物はイソフタロニトリルおよびテレフタロニトリルの塩素化反応により製造できる。テトラフルオロイソフタロニトリル、テトラフルオロテレフタロニトリルなどのフッ素化フタロニトリル化合物はテトラクロロイソフタロニトリルなどの塩素化イソフタロニトリル化合物およびテトラクロロテレフタロニトリルなどの塩素化テレフタロニトリル化合物のフッ素化反応で得られる。
【００１１】
反応溶媒には該アルキルエステルのアルキル基を有する炭素数が１〜５の脂肪族アルコールが使用される。炭素数が１〜５のアルキル基を有する脂肪族アルコールとしては、例えばメタノール、エタノール、ｎ−プロパノール、ｎ−ブタノール、ｎ−ペンタノール、イソプロパノール、イソブタノール、ｓｅｃ−ブタノール、ｔｅｒｔ−ブタノール、イソアミルアルコール、活性アミルアルコール、ネオペンチルアルコール等が挙げられ、メタノールまたはエタノールが特に好ましい。
【００１２】
第１反応工程は、常圧または場合によっては加圧下で行うことができる。
第１反応工程の反応温度は特に制限はないが、０℃〜２００℃の範囲内であることが好ましい。反応温度が低い場合は反応が遅く、また脂肪族アルコールへのフタロニトリルの溶解度が低いので反応時間がかなり長くなり好ましくなく、また反応温度が高い場合は生成したアルキルイミノエーテルが分解して収率が低くなり好ましくなく、加圧下での反応は高温・高圧となるため特殊な反応容器を必要とする。
【００１３】
第１反応工程の反応時間は１０分〜４８時間、好ましくは１〜２４時間の範囲内とするのがよい。ただし使用する脂肪族アルコールによって反応時間は適時調整される。反応時間が短い場合はフタロニトリルの転化率が低く、また長い場合は収率の低下、または生産性の面で問題がある。
【００１４】
第１反応工程であるニトリル基をアルキルイミノエーテル基に変換する反応に使用される酸としては、塩酸、硫酸、硝酸、リン酸等の鉱酸、ギ酸、酢酸、などの有機酸、塩化第一鉄、塩化第二鉄、塩化第一スズ、塩化アルミ等のルイス酸が挙げられる。好ましくは塩化水素、濃硫酸が用いられる。これらの酸は単独でも２種以上を任意の割合で組み合わせて使用してもよい。
加える酸の量はフタロニトリル１モルに対して０．１モル〜５．０モル、好ましくは０．８モル〜３モルの範囲内とするのがよい。酸の量を少なくすると反応性が悪くなり収率が低下し、また多すぎるとフタロニトリルの２個のニトリル基が共にアルキルイミノエーテル基に変換してしまい、収率が低下し、好ましくない。
【００１５】
第２反応工程では第１反応工程で生成したアルキルイミノエーテルまたはその塩の脂肪族アルコール溶液に水を加えるだけでシアノ安息香酸アルキルエステルが合成される。また、第１反応工程で生成したアルキルイミノエーテルまたはその塩を取り出した後で水と反応させてシアノ安息香酸アルキルエステルを合成することもできる。いずれの場合も加える水はアルキルイミノエーテルまたはその塩に対して０．８モル〜２０モルの量を混合する。水の添加量が少ない場合はアルキルエステル基に変換される量が少なくなり収率が低くなり、多い場合はシアノ安息香酸アルキルエステルも析出し、未反応のフタロニトリル化合物との分離が困難となる。また、水は反応液に添加しても、水に反応液を投入してもよい。
【００１６】
未反応のフタロニトリル化合物は、第１反応工程で生成したアルキルイミノエーテルまたはその塩と比較して脂肪族アルコールに対して溶解度がかなり低いことを利用してろ別回収され、反応に再使用可能である。またシアノ安息香酸アルキルエステルもフタロニトリル化合物と比較して、脂肪族アルコールに対し溶解度が高いので、第１反応工程で生成したアルキルイミノエーテルまたはその塩に水を加え、シアノ安息香酸アルキルエステルとした後フタロニトリル化合物をろ別してもよい。
【００１７】
第２反応工程終了後、未反応のフタロニトリル化合物をろ別し、ろ液を冷却あるいは濃縮をして粗シアノ安息香酸アルキルエステルを得ることができる。得られたろ液はアルカリで中和してもよく、中和に使用されるアルカリは水酸化リチウム、水酸化ナトリウム、水酸化カリウム、水酸化ルビジウム等のアルカリ金属水酸化物；炭酸ナトリウム、炭酸カリウム等のアルカリ金属の炭酸塩；リン酸三ナトリウム、ピロリン酸ナトリウム、リン酸三カリウム等のアルカリ金属のリン酸塩；水酸化ベリリウム、水酸化カルシウム、水酸化マグネシウム等のアルカリ土類金属の水酸化物、アンモニア、トリエチルアミン等のアミン類等のいずれでもよく、これらは単独でも２種以上を任意の割合で組み合わせて使用してもよい。
【００１８】
さらに第２反応工程終了後、未反応のフタロニトリル化合物をろ別し、ろ液を有機溶媒を使用して抽出し、濃縮を行ってシアノ安息香酸アルキルエステルの結晶を分離することもできる。抽出に使用する有機溶媒としては、例えばトルエン、キシレン等の炭化水素系、ジクロロメタン、クロロホルム等のハロゲン系、ジエチルエーテル等のエーテル系、酢酸エチル等のエステル系等の有機溶媒を使用することができる。また、必要ならば例えば同じ脂肪族アルコール水溶液を用いた再結晶等や減圧蒸留により精製を行う。微量の未反応フタロニトリルは活性炭吸着によっても除去可能である。
【００１９】
【実施例】
以下に実施例を用いてさらに詳しく本発明を説明するが、本発明はこれら実施例に限定されるものではない。
（実施例１）
テレフタロニトリル１２．8 ｇ、９５％硫酸１０．３ｇ、エタノール７２．５ｇをガラス製オートクレーブに入れ、１３０℃で６時間反応させた。冷却後、反応液に水９ｇを加え、ガスクロマトグラフで分析することにより、ｐ−シアノ安息香酸エチルが収率３３％、選択率８３％で得られることを確認した。
【００２０】
（実施例２）
テレフタロニトリル１２．８ｇ、塩化水素ガス２．２４Ｌ、エタノール７２．５ｇをガラス製オートクレーブに入れ、１３０℃で６時間反応させた。冷却後、反応液に水９ｇを加え、ガスクロマトグラフで分析することにより、ｐ−シアノ安息香酸エチルが収率３０％、選択率９６％で得られることを確認した。
【００２１】
（実施例３）
テレフタロニトリル１２．８ｇ、塩化水素ガス２．２４Ｌ、メタノール７２．５ｇをガラス製オートクレーブに入れ、１３０℃で７時間反応させた。冷却後、反応液に水９ｇを加え、ガスクロマトグラフで分析することにより、ｐ−シアノ安息香酸メチルが収率４０％、選択率９１％で得られることを確認した。
【００２２】
（実験例４）
イソフタロニトリル１２．８ｇ、塩化水素ガス２．２４Ｌ、メタノール７２．５ｇをガラス製オートクレーブに入れ、１３０℃で７時間反応させた。冷却後、反応液に水９ｇを加え、ガスクロマトグラフで分析することにより、ｍ−シアノ安息香酸メチルが収率３８％、選択率８３％で得られることを確認した。
【００２３】
（実施例５）
実施例１の方法と同様に反応させ、水を加える前に析出したテレフタロニトリルをろ別回収してまた反応に使用し、一方ろ液には水を加えてｐ−シアノ安息香酸エチルを取り出すという操作を２回繰り返した。その結果、原料テレフタロニトリルに対し収率７６％でｐ−シアノ安息香酸エチルを得た（純度９６％）。
【００２４】
（実施例６）
実施例３の方法と同様に反応させ、冷却後、反応液に水１．８ｇを加えた後、不溶なテレフタロニトリルはろ過・回収してまた反応に使用するという操作を２回繰り返した、各ろ液をまとめてｐ−シアノ安息香酸エチルを回収したところ、純度９４％のｐ−シアノ安息香酸エチル１２．９ｇを得た（収率７５％−原料テレフタロニトリル基準）。
【００２５】
（実施例７）
テトラクロロテレフタロニトリル２６．６ｇ、塩化水素ガス２．２４Ｌ、メタノール１４５ｇをガラス製オートクレーブに入れ、１４０℃で６時間反応させた。冷却後、反応液に水１８ｇを加え、ガスクロマトグラフで分析することにより、２，３，５，６−テトラクロロ−４−シアノ安息香酸メチルが収率２８％、選択率７５％で得られることを確認した。
【００２６】
【発明の効果】
本発明により、入手が容易で比較的安価なフタロニトリル化合物を原料として温和な条件で選択率良くシアノ安息香酸アルキルエステルを合成できる。シアノ安息香酸アルキルエステルは医薬・農薬その他有機化学品などの合成原料または中間体として広く利用することができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing a substituted or unsubstituted cyanobenzoic acid alkyl ester, particularly a cyanobenzoic acid alkyl ester represented by the general formula (3). Cyanobenzoic acid alkyl esters are useful as synthetic raw materials or intermediates for pharmaceuticals, agricultural chemicals and other organic chemicals.
[0002]
[Prior art]
As a method for producing cyanobenzoic acid alkyl ester, (1) a method in which a benzonitrile substituted with a halogen such as chlorobenzonitrile in JP-A No. 58-113145 is reacted with carbon monoxide and an alcohol using a catalyst. (2) Like methyl aminobenzoate reported in Bull. Chem. Soc. Jpn., 61, 6, 1985, (1988) and J. Org. Chem., 51, 24, 4714, (1986). There are reports on a method for producing an alkylated benzoic acid ester by a Sandmeyer reaction via a diazonium salt, and a method by a disproportionation reaction between a nitrile and an ester described in Japanese Patent Publication No. 41-18818. However, (1) and (2) are not industrially advantageous because it is difficult to obtain raw materials, and (3) is an industrially advantageous production of cyanobenzoic acid alkyl esters, such as harsh conditions required. What is the way to . Thus, an industrially advantageous method for producing an alkyl ester of cyanobenzoic acid has not been known so far, and further improvement is desired.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to produce a cyanobenzoic acid alkyl ester represented by the general formula (3) from phthalonitrile, which is an industrially advantageously available raw material, in a highly selective and high yield by an industrially advantageous method. In particular, it is to produce an alkyl ester of m-cyanobenzoic acid or an alkyl ester of p-cyanobenzoic acid that is particularly useful as a pharmaceutical intermediate in a highly selective and high yield.
[0004]
[Means for Solving the Problems]
As a result of diligent investigations to solve the above-mentioned conventional problems, the present inventors have reacted a substituted or unsubstituted phthalonitrile and an aliphatic alcohol in the presence of an acid to selectively alkylate only one nitrile group. A method for producing a cyanobenzoic acid alkyl ester in a highly selective and high yield by converting it to an imino ether group and then reacting with water to convert only the alkyl imino ether group to an alkyl ester group was found. It came to be completed. The present invention relates to the production methods shown in the following (1) to (5).
[0005]
[1] From phthalonitrile which may have a substituent on the benzene ring to cyanobenzoic acid alkyl ester which may have a substituent on the benzene ring (3-cyano-2,4-dihalogeno-5-fluorobenzoic acid In the method for producing ( excluding an acid) , (a) a phthalonitrile which may have a substituent on a benzene ring and an aliphatic alcohol are reacted in the presence of an acid, so that only one nitrile group is an alkylimino ether. And a second reaction step in which only the alkyliminoether group is reacted with water to convert it to an alkyl ester group, and a substituent is present on the benzene ring. A method for producing an alkyl ester of cyanobenzoic acid (excluding 3-cyano-2,4-dihalogeno-5-fluorobenzoic acid) .
[2] A phthalonitrile which may have a substituent on the benzene ring is represented by the following general formula (1)
[Chemical 3]
ROH (2)
(Wherein R represents an alkyl group having 1 to 5 carbon atoms), and a cyanobenzoic acid alkyl ester which may have a substituent on the benzene ring is represented by the following general formula ( 3)
[Formula 4]
[0006]
[3] The phthalonitrile represented by the general formula (1) is isophthalonitrile or terephthalonitrile, and the cyanobenzoic acid alkyl ester represented by the general formula (3) is m- or p-cyanobenzoic acid alkyl ester. The manufacturing method of the cyanobenzoic acid alkylester (except 3-cyano-2,4-dihalogeno-5-fluorobenzoic acid) which may have a substituent on the benzene ring as described in said [2] .
[4] The alkyl cyanobenzoate which may have a substituent on the benzene ring according to any one of the above [2] to [3] , wherein the aliphatic alcohol represented by the general formula (2) is methanol or ethanol A method for producing an ester (excluding 3-cyano-2,4-dihalogeno-5-fluorobenzoic acid) .
[5] The benzene according to any one of the above [1] to [4] , wherein phthalonitrile which may have a substituent on the unreacted benzene ring is recovered and reused as a raw material again A method for producing a cyanobenzoic acid alkyl ester (excluding 3-cyano-2,4-dihalogeno-5-fluorobenzoic acid) which may have a substituent on the ring.
[0007]
That is, the present invention mixes a substituted or unsubstituted phthalonitrile and an aliphatic alcohol, stirs under cooling or heating, and converts a single nitrile group selectively into an alkyliminoether group in a preferable amount. In the reaction solution, or after separation of the alkyliminoether, a two-step reaction in which water is added followed by obtaining a substituted or unsubstituted cyanobenzoic acid alkyl ester with high selectivity and high yield.
[0008]
DETAILED DESCRIPTION OF THE INVENTION
The present invention will be described below.
The present invention converts a substituted or unsubstituted phthalonitrile, preferably a phthalonitrile represented by the general formula (1) and an aliphatic alcohol represented by the general formula (2) into only one nitrile group to an alkylimino ether group. The following general formula (4) obtained by adding a preferred amount of acid and reacting
[Chemical formula 5]
[0009]
The present invention will be described in further detail.
First, as the phthalonitrile used in the present invention, substituted or unsubstituted phthalonitrile can be used. The unsubstituted phthalonitrile is preferably exemplified by isophthalonitrile or terephthalonitrile. As the substituted phthalonitrile, phthalonitrile having an inert substituent can be used in the reaction of the present invention. For example, a halogen atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group, an aryloxy group, an aralkyloxy group can be used. Examples thereof include phthalonitrile substituted with 1 to 4 groups. When two or more are substituted, the same or different substituents may be used.
[0010]
The phthalonitrile substituted with a halogen atom will be described. Chlorinated phthalonitrile compounds such as tetrachloroisophthalonitrile and tetrachloroterephthalonitrile can be produced by chlorination reaction of isophthalonitrile and terephthalonitrile. Fluorinated phthalonitrile compounds such as tetrafluoroisophthalonitrile and tetrafluoroterephthalonitrile are fluorinated reactions of chlorinated isophthalonitrile compounds such as tetrachloroisophthalonitrile and chlorinated terephthalonitrile compounds such as tetrachloroterephthalonitrile. It is obtained by.
[0011]
As the reaction solvent, an aliphatic alcohol having 1 to 5 carbon atoms and having an alkyl group of the alkyl ester is used. Examples of the aliphatic alcohol having an alkyl group having 1 to 5 carbon atoms include methanol, ethanol, n-propanol, n-butanol, n-pentanol, isopropanol, isobutanol, sec-butanol, tert-butanol, and isoamyl alcohol. Active amyl alcohol, neopentyl alcohol and the like, and methanol or ethanol is particularly preferable.
[0012]
The first reaction step can be carried out at normal pressure or optionally under pressure.
The reaction temperature in the first reaction step is not particularly limited, but is preferably in the range of 0 ° C to 200 ° C. When the reaction temperature is low, the reaction is slow, and since the solubility of phthalonitrile in aliphatic alcohol is low, the reaction time is considerably long, which is not preferable. When the reaction temperature is high, the produced alkylimino ether decomposes and yields. The reaction under pressure becomes high temperature and pressure and requires a special reaction vessel.
[0013]
The reaction time of the first reaction step is 10 minutes to 48 hours, preferably 1 to 24 hours. However, the reaction time is adjusted in a timely manner depending on the aliphatic alcohol used. When the reaction time is short, the conversion rate of phthalonitrile is low, and when the reaction time is long, there is a problem in terms of yield reduction or productivity.
[0014]
Examples of the acid used in the reaction for converting the nitrile group to the alkyliminoether group in the first reaction step include mineral acids such as hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid, organic acids such as formic acid and acetic acid, and first chloride. Examples include Lewis acids such as iron, ferric chloride, stannous chloride, and aluminum chloride. Preferably, hydrogen chloride and concentrated sulfuric acid are used. These acids may be used alone or in combination of two or more at any ratio.
The amount of acid to be added is 0.1 to 5.0 mol, preferably 0.8 to 3 mol per mol of phthalonitrile. If the amount of the acid is decreased, the reactivity is deteriorated and the yield is lowered. On the other hand, if the amount is too large, two nitrile groups of phthalonitrile are both converted into alkyliminoether groups, and the yield is lowered.
[0015]
In the second reaction step, a cyanobenzoic acid alkyl ester is synthesized simply by adding water to the aliphatic alcohol solution of the alkylimino ether or salt thereof produced in the first reaction step. Alternatively, the alkyliminoether produced in the first reaction step or a salt thereof can be taken out and reacted with water to synthesize cyanobenzoic acid alkyl ester. In any case, the added water is mixed in an amount of 0.8 mol to 20 mol with respect to the alkylimino ether or a salt thereof. When the amount of water added is small, the amount converted to an alkyl ester group is small and the yield is low, and when it is large, cyanobenzoic acid alkyl ester is also precipitated, making it difficult to separate from the unreacted phthalonitrile compound. . Further, water may be added to the reaction solution or the reaction solution may be added to water.
[0016]
Unreacted phthalonitrile compounds can be recovered by filtration and reused in the reaction, taking advantage of their considerably lower solubility in aliphatic alcohols than the alkylimino ethers or salts thereof produced in the first reaction step. is there. In addition, since cyanobenzoic acid alkyl ester is also more soluble in aliphatic alcohol than phthalonitrile compound, water is added to the alkylimino ether or salt thereof produced in the first reaction step to obtain cyanobenzoic acid alkyl ester. The post phthalonitrile compound may be filtered off.
[0017]
After completion of the second reaction step, the unreacted phthalonitrile compound is filtered off, and the filtrate is cooled or concentrated to obtain a crude cyanobenzoic acid alkyl ester. The obtained filtrate may be neutralized with an alkali, and the alkali used for neutralization is an alkali metal hydroxide such as lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide; sodium carbonate, potassium carbonate Alkali metal carbonates such as trisodium phosphate, sodium pyrophosphate, tripotassium phosphate, etc .; alkaline earth metal hydroxides such as beryllium hydroxide, calcium hydroxide and magnesium hydroxide Products, ammonia, amines such as triethylamine, etc., and these may be used alone or in combination of two or more in any proportion.
[0018]
Further, after completion of the second reaction step, the unreacted phthalonitrile compound is filtered off, the filtrate is extracted using an organic solvent, and concentrated to separate crystals of alkyl cyanobenzoate. As the organic solvent used for extraction, for example, hydrocarbon solvents such as toluene and xylene, halogen solvents such as dichloromethane and chloroform, ether solvents such as diethyl ether, and ester solvents such as ethyl acetate can be used. . If necessary, purification is performed by, for example, recrystallization using the same aliphatic alcohol aqueous solution or vacuum distillation. Trace amounts of unreacted phthalonitrile can also be removed by adsorption with activated carbon.
[0019]
【Example】
Hereinafter, the present invention will be described in more detail using examples, but the present invention is not limited to these examples.
Example 1
12.8 g of terephthalonitrile, 10.3 g of 95% sulfuric acid, and 72.5 g of ethanol were placed in a glass autoclave and reacted at 130 ° C. for 6 hours. After cooling, 9 g of water was added to the reaction solution and analyzed by gas chromatography to confirm that ethyl p-cyanobenzoate was obtained with a yield of 33% and a selectivity of 83%.
[0020]
(Example 2)
12.8 g of terephthalonitrile, 2.24 L of hydrogen chloride gas, and 72.5 g of ethanol were placed in a glass autoclave and reacted at 130 ° C. for 6 hours. After cooling, 9 g of water was added to the reaction solution, and analysis by gas chromatography confirmed that ethyl p-cyanobenzoate was obtained with a yield of 30% and a selectivity of 96%.
[0021]
(Example 3)
12.8 g of terephthalonitrile, 2.24 L of hydrogen chloride gas, and 72.5 g of methanol were placed in a glass autoclave and reacted at 130 ° C. for 7 hours. After cooling, 9 g of water was added to the reaction solution, and analysis by gas chromatography confirmed that methyl p-cyanobenzoate was obtained with a yield of 40% and a selectivity of 91%.
[0022]
(Experimental example 4)
12.8 g of isophthalonitrile, 2.24 L of hydrogen chloride gas, and 72.5 g of methanol were placed in a glass autoclave and reacted at 130 ° C. for 7 hours. After cooling, 9 g of water was added to the reaction solution, and analysis by gas chromatography confirmed that methyl m-cyanobenzoate was obtained with a yield of 38% and a selectivity of 83%.
[0023]
(Example 5)
The reaction was carried out in the same manner as in Example 1, and the terephthalonitrile precipitated before the addition of water was collected by filtration and used for the reaction. On the other hand, water was added to the filtrate to extract ethyl p-cyanobenzoate. This operation was repeated twice. As a result, ethyl p-cyanobenzoate was obtained with a yield of 76% based on the raw material terephthalonitrile (purity 96%).
[0024]
(Example 6)
The reaction was carried out in the same manner as in Example 3, and after cooling, 1.8 g of water was added to the reaction solution, and then the insoluble terephthalonitrile was filtered and recovered and used again for the reaction twice. When each filtrate was collected and ethyl p-cyanobenzoate was recovered, 12.9 g of ethyl p-cyanobenzoate having a purity of 94% was obtained (yield 75%-based on raw terephthalonitrile).
[0025]
(Example 7)
26.6 g of tetrachloroterephthalonitrile, 2.24 L of hydrogen chloride gas, and 145 g of methanol were placed in a glass autoclave and reacted at 140 ° C. for 6 hours. After cooling, 18 g of water is added to the reaction solution and analyzed by gas chromatography to obtain methyl 2,3,5,6-tetrachloro-4-cyanobenzoate at a yield of 28% and a selectivity of 75%. It was confirmed.
[0026]
【The invention's effect】
According to the present invention, a cyanobenzoic acid alkyl ester can be synthesized with good selectivity under mild conditions using a phthalonitrile compound that is easily available and relatively inexpensive. Cyanobenzoic acid alkyl esters can be widely used as synthetic raw materials or intermediates for pharmaceuticals, agricultural chemicals and other organic chemicals.
Claims (5)
ＲＯＨ （２）
（式中、Ｒは炭素数が１〜５のアルキル基を表わす。）で示される脂肪族アルコールであり、ベンゼン環上に置換基を有してもよいシアノ安息香酸アルキルエステルが下記一般式（３）
ROH (2)
(Wherein R represents an alkyl group having 1 to 5 carbon atoms), and a cyanobenzoic acid alkyl ester which may have a substituent on the benzene ring is represented by the following general formula ( 3)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30296198A JP4207270B2 (en) | 1998-10-23 | 1998-10-23 | Method for producing alkyl cyanobenzoate |
| DE69934034T DE69934034T2 (en) | 1998-09-24 | 1999-09-23 | Process for the preparation of derivatives of cyanobenzoic acid |
| EP04022598A EP1508567B1 (en) | 1998-09-24 | 1999-09-23 | Process for producing cyanobenzoic acid derivatives |
| AT04022599T ATE345325T1 (en) | 1998-09-24 | 1999-09-23 | METHOD FOR PRODUCING CYANOBENZOIC ACID DERIVATIVES |
| EP04022599A EP1514866B1 (en) | 1998-09-24 | 1999-09-23 | Process for producing cyanobenzoic acid derivatives |
| EP99118800A EP0989115A3 (en) | 1998-09-24 | 1999-09-23 | Process for producing cyanobenzoic acid derivatives |
| DE69934033T DE69934033T2 (en) | 1998-09-24 | 1999-09-23 | Process for the preparation of derivatives of cyanobenzoic acid |
| AT04022598T ATE345324T1 (en) | 1998-09-24 | 1999-09-23 | METHOD FOR PRODUCING CYANOBENZOIC ACID DERIVATIVES |
| US09/404,362 US6433211B1 (en) | 1998-09-24 | 1999-09-24 | Process for producing cyanobenzoic acid derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30296198A JP4207270B2 (en) | 1998-10-23 | 1998-10-23 | Method for producing alkyl cyanobenzoate |
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| Publication Number | Publication Date |
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| JP2000128845A JP2000128845A (en) | 2000-05-09 |
| JP4207270B2 true JP4207270B2 (en) | 2009-01-14 |
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| JP30296198A Expired - Fee Related JP4207270B2 (en) | 1998-09-24 | 1998-10-23 | Method for producing alkyl cyanobenzoate |
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