JP3790290B2 - Method for producing tertiary amine N-oxide - Google Patents
Method for producing tertiary amine N-oxide Download PDFInfo
- Publication number
- JP3790290B2 JP3790290B2 JP02982396A JP2982396A JP3790290B2 JP 3790290 B2 JP3790290 B2 JP 3790290B2 JP 02982396 A JP02982396 A JP 02982396A JP 2982396 A JP2982396 A JP 2982396A JP 3790290 B2 JP3790290 B2 JP 3790290B2
- Authority
- JP
- Japan
- Prior art keywords
- oxide
- tertiary amine
- catalyst
- silicon
- titanium
- 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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- 150000003512 tertiary amines Chemical class 0.000 title claims description 32
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- 239000003054 catalyst Substances 0.000 claims description 31
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 27
- 239000010703 silicon Substances 0.000 claims description 19
- -1 nitrogen-containing heteroaromatic compound Chemical class 0.000 claims description 16
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 15
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 15
- 239000010936 titanium Substances 0.000 claims description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- 229910052814 silicon oxide Inorganic materials 0.000 claims description 14
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 claims description 14
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 11
- 150000002978 peroxides Chemical class 0.000 claims description 11
- 229910052719 titanium Inorganic materials 0.000 claims description 11
- 229910052710 silicon Inorganic materials 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- RUIZBQQGWNBRFH-UHFFFAOYSA-N 1-oxidopyrazin-1-ium Chemical compound [O-][N+]1=CC=NC=C1 RUIZBQQGWNBRFH-UHFFFAOYSA-N 0.000 claims description 8
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 5
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 2
- 150000001204 N-oxides Chemical class 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 24
- 239000000243 solution Substances 0.000 description 14
- 150000003216 pyrazines Chemical class 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 150000003222 pyridines Chemical class 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical class N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- SIOXPEMLGUPBBT-UHFFFAOYSA-N Picolinic acid Natural products OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 3
- OXQOBQJCDNLAPO-UHFFFAOYSA-N 2,3-Dimethylpyrazine Chemical compound CC1=NC=CN=C1C OXQOBQJCDNLAPO-UHFFFAOYSA-N 0.000 description 2
- HPYNZHMRTTWQTB-UHFFFAOYSA-N 2,3-dimethylpyridine Chemical compound CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 2
- BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 2
- JYYNAJVZFGKDEQ-UHFFFAOYSA-N 2,4-Dimethylpyridine Chemical compound CC1=CC=NC(C)=C1 JYYNAJVZFGKDEQ-UHFFFAOYSA-N 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 2
- MUDSDYNRBDKLGK-UHFFFAOYSA-N 4-methylquinoline Chemical compound C1=CC=C2C(C)=CC=NC2=C1 MUDSDYNRBDKLGK-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- PMSVVUSIPKHUMT-UHFFFAOYSA-N cyanopyrazine Chemical compound N#CC1=CN=CC=N1 PMSVVUSIPKHUMT-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000001027 hydrothermal synthesis Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- CAWHJQAVHZEVTJ-UHFFFAOYSA-N methylpyrazine Chemical compound CC1=CN=CC=N1 CAWHJQAVHZEVTJ-UHFFFAOYSA-N 0.000 description 2
- JKQOBWVOAYFWKG-UHFFFAOYSA-N molybdenum trioxide Chemical compound O=[Mo](=O)=O JKQOBWVOAYFWKG-UHFFFAOYSA-N 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- SOQBVABWOPYFQZ-UHFFFAOYSA-N oxygen(2-);titanium(4+) Chemical class [O-2].[O-2].[Ti+4] SOQBVABWOPYFQZ-UHFFFAOYSA-N 0.000 description 2
- DJEHXEMURTVAOE-UHFFFAOYSA-M potassium bisulfite Chemical compound [K+].OS([O-])=O DJEHXEMURTVAOE-UHFFFAOYSA-M 0.000 description 2
- 235000010259 potassium hydrogen sulphite Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical compound C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 2
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 2
- 125000005270 trialkylamine group Chemical group 0.000 description 2
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- XCIZVKSCLVSDHN-UHFFFAOYSA-N 2-ethylquinoline Chemical compound C1=CC=CC2=NC(CC)=CC=C21 XCIZVKSCLVSDHN-UHFFFAOYSA-N 0.000 description 1
- JWZKFUUHTLGIEA-UHFFFAOYSA-N 3-methylpyrazine-2-carbonitrile Chemical compound CC1=NC=CN=C1C#N JWZKFUUHTLGIEA-UHFFFAOYSA-N 0.000 description 1
- DEDJQZNLAXYJBT-UHFFFAOYSA-N 3-methylpyrazine-2-carboxylic acid Chemical compound CC1=NC=CN=C1C(O)=O DEDJQZNLAXYJBT-UHFFFAOYSA-N 0.000 description 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 1
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
- UOYJBGYNFMPCLV-UHFFFAOYSA-N 4-ethylquinoline Chemical compound C1=CC=C2C(CC)=CC=NC2=C1 UOYJBGYNFMPCLV-UHFFFAOYSA-N 0.000 description 1
- SXTKIFFXFIDYJF-UHFFFAOYSA-N 4-oxidopyrazin-1-ium 1-oxide Chemical compound [O-]N1C=C[N+](=O)C=C1 SXTKIFFXFIDYJF-UHFFFAOYSA-N 0.000 description 1
- AYMRPLHDHGMXOF-UHFFFAOYSA-N 5-methylpyrazine-2-carbonitrile Chemical compound CC1=CN=C(C#N)C=N1 AYMRPLHDHGMXOF-UHFFFAOYSA-N 0.000 description 1
- RBYJWCRKFLGNDB-UHFFFAOYSA-N 5-methylpyrazine-2-carboxylic acid Chemical class CC1=CN=C(C(O)=O)C=N1 RBYJWCRKFLGNDB-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- 239000004111 Potassium silicate Substances 0.000 description 1
- 239000004115 Sodium Silicate Substances 0.000 description 1
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000002815 homogeneous catalyst Substances 0.000 description 1
- 238000005470 impregnation Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical class OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- LYYLWJOKAQADDU-UHFFFAOYSA-N n,n-dihexadecylhexadecan-1-amine Chemical compound CCCCCCCCCCCCCCCCN(CCCCCCCCCCCCCCCC)CCCCCCCCCCCCCCCC LYYLWJOKAQADDU-UHFFFAOYSA-N 0.000 description 1
- XTAZYLNFDRKIHJ-UHFFFAOYSA-N n,n-dioctyloctan-1-amine Chemical compound CCCCCCCCN(CCCCCCCC)CCCCCCCC XTAZYLNFDRKIHJ-UHFFFAOYSA-N 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940099427 potassium bisulfite Drugs 0.000 description 1
- NNHHDJVEYQHLHG-UHFFFAOYSA-N potassium silicate Chemical compound [K+].[K+].[O-][Si]([O-])=O NNHHDJVEYQHLHG-UHFFFAOYSA-N 0.000 description 1
- 229910052913 potassium silicate Inorganic materials 0.000 description 1
- 235000019353 potassium silicate Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 description 1
- 229910052911 sodium silicate Inorganic materials 0.000 description 1
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 1
- LFQCEHFDDXELDD-UHFFFAOYSA-N tetramethyl orthosilicate Chemical compound CO[Si](OC)(OC)OC LFQCEHFDDXELDD-UHFFFAOYSA-N 0.000 description 1
- VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- VPYJNCGUESNPMV-UHFFFAOYSA-N triallylamine Chemical compound C=CCN(CC=C)CC=C VPYJNCGUESNPMV-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- ABVVEAHYODGCLZ-UHFFFAOYSA-N tridecan-1-amine Chemical compound CCCCCCCCCCCCCN ABVVEAHYODGCLZ-UHFFFAOYSA-N 0.000 description 1
- SWZDQOUHBYYPJD-UHFFFAOYSA-N tridodecylamine Chemical compound CCCCCCCCCCCCN(CCCCCCCCCCCC)CCCCCCCCCCCC SWZDQOUHBYYPJD-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Quinoline Compounds (AREA)
- Pyridine Compounds (AREA)
- Catalysts (AREA)
- 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】
本発明は第三級アミンＮ−オキシドの製造方法に関する。更に詳しくは、第三級アミンを過酸化物と触媒の存在下で反応させて第三級アミンＮ−オキシドを製造する方法に関する。
本発明方法において、例えば原料の第三級アミンとしてピリジン類又はピラジン類を使用した場合、夫々ピリジンＮ−オキシド類又はピラジンＮ−オキシド類を製造することができる。これらピリジンＮ−オキシド類及びピラジンＮ−オキシド類は、医薬、農薬の中間体として有用な化合物である。
【０００２】
【従来の技術】
従来、第三級アミンＮ−オキシドの製法として、例えば以下の方法が知られている。ピラジンＮ−オキシド類の製法を例にとり、従来法を具体的に説明すると、▲１▼ピラジン類を酢酸中、過酸化水素で処理してピラジンＮ−オキシド類を製造する方法（Ｊ．Ｏｒｇ．Ｃｈｅｍ．，２３，１６０３（１９５８））、▲２▼タングステン酸ナトリウムを触媒に用い、水溶媒中でピラジン類を過酸化水素と反応させる方法（Ｃｈｅｍ．Ｐｈａｒｍ．Ｂｕｌｌ．，２２，２０９７（１９７４））、また▲３▼三酸化モリブデンを触媒として使用し、水溶媒中でピラジン類を過酸化水素と反応させる方法（特開昭６２−１８１２６８号公報）が知られている。
【０００３】
【発明が解決しようとする課題】
しかしながら上記従来法には、以下に示すような問題が存在する。▲１▼の方法は溶媒である酢酸を大量に使用しなければならず、ピラジンＮ−オキシド類及び酢酸の分離、回収に複雑な工程を要する欠点があり、▲２▼の方法では目的物の収率が４７％と低い。一方、▲３▼の方法では目的物が高収率で得られている。しかしながら▲３▼の方法において使用される触媒は、▲２▼の方法において使用される触媒と同様に、反応液に溶解して反応液から容易に分離することができないため、目的物を単離、精製する方法として、反応終了後の反応液から溶媒を留去した後、得られた残渣を再結晶する方法を採用すると、触媒が目的物に混入するという問題点が生じる。
本発明は、上記従来法の問題点を解決することができる第三級アミンＮ−オキシドの製造方法を提供することを目的とする。
【０００４】
【課題を解決するための手段】
本発明者らは、第三級アミンを過酸化物と反応させて第三級アミンＮ−オキシドを製造する方法において、反応終了後、反応液から濾過等の簡単な操作で分離が可能な不均一系触媒を種々検討した。その結果、触媒として珪素及びチタンの酸化物からなる触媒を用いて第三級アミンを過酸化物と反応させると、極めて高収率で第三級アミンＮ−オキシドが製造できることを見出し本発明を完成した。
【０００５】
即ち本発明は、珪素及びチタンの酸化物からなる触媒の存在下、第三級アミンを過酸化物と反応させることを特徴とする第三級アミンＮ−オキシドの製造方法に関する。
【０００６】
本発明によれば、極めて高収率で第三級アミンＮ−オキシドを得ることができる。また本発明の触媒は反応液に実質的に溶けないため、反応終了後の反応液から濾過等により容易に分離でき、第三級アミンＮ−オキシドの製品中に混入することはない。
【０００７】
【発明の実施の形態】
本発明における珪素及びチタンの酸化物からなる触媒は、第三級アミンＮ−オキシドの製造法である従来公知の第三級アミンを過酸化水素等の過酸化物と反応させる触媒として使用できる。
【０００８】
本発明の方法に適用できる第三級アミンとしては、含窒素複素芳香族化合物、非芳香性環状第三級アミン、トリアルキルアミン及びトリアルケニルアミン等が挙げられる。
【０００９】
含窒素複素芳香族化合物としては、例えば、（１）ピリジン、２−メチルピリジン、３−メチルピリジン、４−メチルピリジン、２，３−ジメチルピリジン、２，４−ジメチルピリジン、３，５−ジメチルピリジン、２，４，６−トリメチルピリジン等のピリジン塩基類、２−シアノピリジン、３−シアノピリジン、４−シアノピリジン等のシアノピリジン類、２−ピリジンカルボン酸、３−ピリジンカルボン酸、４−ピリジンカルボン酸等のピリジンカルボン酸類及び上記ピリジン塩基類、シアノピリジン類、ピリジンカルボン酸類のピリジン核の水素原子の１つ以上が塩素原子で置換されたピリジン類等のピリジン類、（２）ピラジン、２−メチルピラジン、２，３−ジメチルピラジン、２，５−ジメチルピラジン等のアルキルピラジン類、２−シアノピラジン、２−シアノ−３−メチルピラジン、２−シアノ−５−メチルピラジン等のシアノピラジン類、２−ピラジンカルボン酸、３−メチル−２−ピラジンカルボン酸、５−メチル−２−ピラジンカルボン酸等のピラジンカルボン酸類及び上記ピラジン、アルキルピラジン類、シアノピラジン類、ピラジンカルボン酸類のピラジン核の水素原子の１つ以上が塩素原子で置換されたピラジン類等のピラジン類、（３）キノリン、２−メチルキノリン、４−メチルキノリン、２−エチルキノリン、４−エチルキノリン等のキノリン類等を挙げることができる。
【００１０】
非芳香性環状第三級アミンとしては、例えば、（１）Ｎ−メチルモルホリン、Ｎ−エチルモルホリン等のＮ−アルキルモルホリン等のＮ−置換モルホリン類、（２）Ｎ−メチルピロリジン、Ｎ−エチルピロリジン等のＮ−アルキルピロリジン等のＮ−置換ピロリジン類などを挙げることができる。
【００１１】
トリアルキルアミンとしては、例えば、トリエチルアミン、トリプロピルアミン、トリブチルアミン、トリオクチルアミン、トリデシルアミン、トリラウリルアミン、トリセチルアミン等を、またトリアルケニルアミンとしては、例えば、トリアリルアミン等を挙げることができる。
【００１２】
第三級アミンとしてピリジン類又はピラジン類を用いたときに得られるピリジンＮ−オキシド類又はピラジンＮ−オキシド類は、医薬、農薬の中間体として有用である。
【００１３】
本発明では、珪素及びチタンの酸化物からなる触媒を使用する。本発明において珪素及びチタンの酸化物からなる触媒とは、化学組成又は化合物として酸化珪素及び酸化チタンを含有する触媒である。
【００１４】
本発明の珪素及びチタンの酸化物からなる触媒の具体例としては、酸化珪素及び酸化チタンの混合物（例えば、二酸化珪素及び二酸化チタンの混合物）が挙げられる。本発明の触媒の他の具体例としては、無定形チタノシリケート（例えば、シリカ−チタニア）、結晶性チタノシリケート等の珪素とチタンの複合酸化物が挙げられる。好ましくは結晶性チタノシリケートであり、更に好ましくは水熱合成法で合成した結晶性チタノシリケートである。当該結晶性チタノシリケートとしては、ＭＦＩ構造のチタノシリケートＴＳ−１、ＭＥＬ構造のチタノシリケートＴＳ−２が挙げられる。これらは市販品として入手することもできる。
【００１５】
本発明の珪素及びチタンの酸化物からなる触媒における珪素とチタンの割合は、通常、Ｓｉ／Ｔｉ＝１０〜２００（原子比）である。
【００１６】
本発明の珪素及びチタンの酸化物からなる触媒は、共沈法、含浸法、浸漬法、イオン交換法、水熱合成法等、種々の従来公知の方法で調製することができる。触媒調製に際して用いられる酸化珪素源としては、例えば、コロイド状のシリカ、珪酸ナトリウム、珪酸カリウム等のアルカリ金属の珪酸塩、テトラメチルオルトシリケート、テトラエチルオルトシリケート等のテトラアルコキシシラン等を挙げることができる。また酸化チタン源としては、例えば、ＴｉＣｌ4、ＴｉＯＣｌ2、テトラエチルチタネート、テトライソプロピルチタネート等のテトラアルコキシチタン等が挙げられる。
【００１７】
本発明において、珪素及びチタンの酸化物からなる触媒は、タブレット、球状、粒状、粉体、柱状、網状、円筒状等種々の形で使用することができ、好ましくは粉体で使用する。
【００１８】
珪素及びチタンの酸化物からなる触媒の使用量は、第三級アミンに対し０．１〜５重量％が好ましい。
【００１９】
過酸化物の代表的な例としては、過酸化水素が挙げられるが、他の過酸化物も本発明において使用し得る。尚、以下、過酸化物について過酸化水素を例として本発明を説明する。過酸化水素は、市販品として入手容易な３０〜３５重量％の水溶液を好適に用いることができる。過酸化水素の使用量は第三級アミン１モルに対してその理論量の１〜２倍モル用いるのが適当である。
【００２０】
但し、原料の第三級アミンに、環の構成原子として窒素原子を２個有する含窒素複素芳香族化合物、例えばピラジン類を使用し、そしてピラジン環の２個の窒素原子のうち一方だけを優先的にＮ−オキシド化するには、過酸化水素の使用量をピラジン類１モルに対して０．４〜１モルとするのが好ましい。
【００２１】
本発明の方法は好ましくは溶媒中で行われる。溶媒としては、原料の第三級アミンの少なくとも一部を溶解し、目的物を溶解して本発明における触媒を溶解せず、かつ反応に関与しないものが使用できる。溶媒の具体例としては、水、水とメタノール又はエタノール等のアルコールとの混合物等が好適に使用されるが、上記性質を有するものであればよい。溶媒の使用量は特に制限はないが、第三級アミン１重量部に対し１〜１０重量部が適当である。
【００２２】
本発明の好ましい実施態様の一例を示すと、反応器に第三級アミン、珪素及びチタンの酸化物からなる触媒及び所望により溶媒を仕込み、得られた混合物中に加熱、撹拌下、過酸化水素水を０．５〜１０時間かけて滴下して反応を行う。過酸化水素水の滴下終了後、同温度で０〜５時間撹拌を続けて反応を完結させれば、目的物である第三級アミンＮ−オキシドが高収率で生成する。当該反応において反応温度は室温〜１００℃、好ましくは５０〜９０℃である。
【００２３】
反応終了後、反応液の処理は、一般に行われている濾過、抽出、蒸留、晶析等の操作を組み合わせて実施することができる。例えば、反応終了後、反応液を室温に冷却して亜硫酸水素カリウムを加えて未反応の過酸化水素を分解処理する。次にこの処理液を濾過して触媒を濾別し、濾液を濃縮して析出する結晶を濾別するか、或は濾液を蒸留すれば、高純度の第三級アミンＮ−オキシドを得ることができる。また分離された触媒は本発明の方法に繰り返し使用が可能である。
【００２４】
【実施例】
次に実施例で更に説明するが、本発明は以下の実施例に限定されるものではない。
尚、以下の実施例における液体クロマトグラフィーによる分析条件は次の通りである。
【００２５】
実施例１
四つ口フラスコにピリジン３０．０ｇ（０．３７９モル）、珪素及びチタンの酸化物からなる触媒としてのエヌ・イー・ケム・キャット（株）製のチタノシリケートＴＳ−１（Ｓｉ／Ｔｉの原子比＝１６）１．０ｇ及び水３０ｇを仕込み、撹拌下、８０℃で１．７時間かけて３５％過酸化水素水４４．４ｇ（０．４５７モル）を滴下した。その後、撹拌下、同温度に２時間保った。反応終了後、反応液を冷却し、この反応液中に少量の亜硫酸水素カリウムを加えて未反応の過酸化水素を分解処理した。この処理液を濾過し、チタノシリケートＴＳ−１を濾別した後、濾液を液体クロマトグラフィーにて分析したところ、ピリジンからピリジンＮ−オキシドが定量的に即ち３６．１ｇ（０．３７９モル）生成していた。
【００２７】
実施例２
四つ口フラスコにピラジン３０．１ｇ（０．３７６モル）、実施例１と同じチタノシリケート１．０ｇ及び水１０．１ｇを仕込み、撹拌下、８０℃で１．２５時間かけて３５％過酸化水素水１８．５ｇ（０．１９０モル）を滴下した。その後、撹拌下、同温度に２時間保った。反応終了後、反応液を冷却し、この反応液を濾過してチタノシリケートＴＳ−１を濾別した。濾液を液体クロマトグラフィーにて分析したところ、ピラジンＮ−オキシド１７．５ｇ（０．１８２モル）、収率は過酸化水素基準で９５．８％であった。またピラジンＮ，Ｎ′−ジオキシドが０．２５ｇ（０．００２２モル）生成していた。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing a tertiary amine N-oxide. More specifically, the present invention relates to a method for producing a tertiary amine N-oxide by reacting a tertiary amine with a peroxide in the presence of a catalyst.
In the method of the present invention, for example, when pyridines or pyrazines are used as the starting tertiary amine, pyridine N-oxides or pyrazine N-oxides can be produced, respectively. These pyridine N-oxides and pyrazine N-oxides are useful compounds as intermediates for pharmaceuticals and agricultural chemicals.
[0002]
[Prior art]
Conventionally, for example, the following methods are known as methods for producing tertiary amine N-oxides. Taking the production method of pyrazine N-oxides as an example, the conventional method will be specifically described. (1) A method of producing pyrazine N-oxides by treating pyrazines with hydrogen peroxide in acetic acid (J. Org. Chem., 23, 1603 (1958)), (2) a method of reacting pyrazines with hydrogen peroxide in an aqueous solvent using sodium tungstate as a catalyst (Chem. Pharm. Bull., 22, 2097 (1974)). 3) A method of reacting pyrazines with hydrogen peroxide in an aqueous solvent using (3) molybdenum trioxide as a catalyst is known (Japanese Patent Laid-Open No. 62-181268).
[0003]
[Problems to be solved by the invention]
However, the conventional method has the following problems. The method (1) requires the use of a large amount of acetic acid as a solvent, and has the disadvantage that complicated steps are required for the separation and recovery of pyrazine N-oxides and acetic acid. The yield is as low as 47%. On the other hand, in the method (3), the target product is obtained in a high yield. However, the catalyst used in the method (3) cannot be easily separated from the reaction solution after being dissolved in the reaction solution in the same manner as the catalyst used in the method (2). As a purification method, if a method of recrystallizing the obtained residue after distilling off the solvent from the reaction solution after completion of the reaction, there arises a problem that the catalyst is mixed into the target product.
An object of this invention is to provide the manufacturing method of the tertiary amine N-oxide which can solve the trouble of the said conventional method.
[0004]
[Means for Solving the Problems]
In the method for producing a tertiary amine N-oxide by reacting a tertiary amine with a peroxide, the present inventors can separate the reaction solution from the reaction solution by a simple operation such as filtration. Various homogeneous catalysts were investigated. As a result, it was found that a tertiary amine N-oxide can be produced in an extremely high yield when a tertiary amine is reacted with a peroxide using a catalyst comprising oxides of silicon and titanium as a catalyst. completed.
[0005]
That is, the present invention relates to a method for producing a tertiary amine N-oxide characterized by reacting a tertiary amine with a peroxide in the presence of a catalyst comprising oxides of silicon and titanium.
[0006]
According to the present invention, tertiary amine N-oxide can be obtained with extremely high yield. Further, since the catalyst of the present invention is substantially insoluble in the reaction solution, it can be easily separated from the reaction solution after completion of the reaction by filtration or the like, and is not mixed into the tertiary amine N-oxide product.
[0007]
DETAILED DESCRIPTION OF THE INVENTION
The catalyst comprising oxides of silicon and titanium in the present invention can be used as a catalyst for reacting a conventionally known tertiary amine, which is a method for producing a tertiary amine N-oxide, with a peroxide such as hydrogen peroxide.
[0008]
Examples of the tertiary amine applicable to the method of the present invention include nitrogen-containing heteroaromatic compounds, non-aromatic cyclic tertiary amines, trialkylamines and trialkenylamines.
[0009]
Examples of the nitrogen-containing heteroaromatic compound include (1) pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 2,3-dimethylpyridine, 2,4-dimethylpyridine, 3,5-dimethyl. Pyridine bases such as pyridine and 2,4,6-trimethylpyridine, cyanopyridines such as 2-cyanopyridine, 3-cyanopyridine and 4-cyanopyridine, 2-pyridinecarboxylic acid, 3-pyridinecarboxylic acid, 4- Pyridine carboxylic acids such as pyridine carboxylic acid, and pyridines such as pyridines in which one or more hydrogen atoms of the pyridine nucleus of the pyridine bases, cyanopyridines, pyridine carboxylic acids are substituted with chlorine atoms, (2) pyrazine, Alkyl pyrazines such as 2-methylpyrazine, 2,3-dimethylpyrazine, 2,5-dimethylpyrazine Cyanopyrazines such as 2-cyanopyrazine, 2-cyano-3-methylpyrazine, 2-cyano-5-methylpyrazine, 2-pyrazinecarboxylic acid, 3-methyl-2-pyrazinecarboxylic acid, 5-methyl-2 -Pyrazine carboxylic acids such as pyrazine carboxylic acid and pyrazines such as pyrazines in which one or more hydrogen atoms of the pyrazine nucleus of the pyrazine, alkylpyrazine, cyanopyrazine, pyrazine carboxylic acid are substituted with a chlorine atom, (3 ) Quinolines such as quinoline, 2-methylquinoline, 4-methylquinoline, 2-ethylquinoline, 4-ethylquinoline, and the like.
[0010]
Examples of the non-aromatic cyclic tertiary amine include (1) N-substituted morpholines such as N-alkylmorpholine such as N-methylmorpholine and N-ethylmorpholine, and (2) N-methylpyrrolidine, N-ethyl. N-substituted pyrrolidines such as N-alkylpyrrolidine such as pyrrolidine can be exemplified.
[0011]
Examples of the trialkylamine include triethylamine, tripropylamine, tributylamine, trioctylamine, tridecylamine, trilaurylamine, tricetylamine and the like, and examples of the trialkenylamine include triallylamine. Can do.
[0012]
Pyridine N-oxides or pyrazine N-oxides obtained when pyridines or pyrazines are used as tertiary amines are useful as intermediates for pharmaceuticals and agricultural chemicals.
[0013]
In the present invention, a catalyst made of silicon and titanium oxide is used. In the present invention, the catalyst composed of oxides of silicon and titanium is a catalyst containing silicon oxide and titanium oxide as chemical compositions or compounds.
[0014]
Specific examples of the catalyst comprising silicon and titanium oxide of the present invention include a mixture of silicon oxide and titanium oxide (for example, a mixture of silicon dioxide and titanium dioxide). Other specific examples of the catalyst of the present invention include composite oxides of silicon and titanium such as amorphous titanosilicate (for example, silica-titania), crystalline titanosilicate and the like. Crystalline titanosilicate is preferred, and crystalline titanosilicate synthesized by hydrothermal synthesis is more preferred. Examples of the crystalline titanosilicate include titanosilicate TS-1 having an MFI structure and titanosilicate TS-2 having an MEL structure. These can also be obtained as commercial products.
[0015]
The ratio of silicon and titanium in the catalyst comprising silicon and titanium oxide of the present invention is usually Si / Ti = 10 to 200 (atomic ratio).
[0016]
The catalyst comprising silicon and titanium oxide of the present invention can be prepared by various conventionally known methods such as coprecipitation method, impregnation method, dipping method, ion exchange method, hydrothermal synthesis method and the like. Examples of the silicon oxide source used for preparing the catalyst include colloidal silica, silicates of alkali metals such as sodium silicate and potassium silicate, and tetraalkoxysilanes such as tetramethylorthosilicate and tetraethylorthosilicate. . Examples of the titanium oxide source include tetraalkoxy titanium such as TiCl 4 , TiOCl 2 , tetraethyl titanate, and tetraisopropyl titanate.
[0017]
In the present invention, the catalyst comprising silicon and titanium oxides can be used in various forms such as tablets, spheres, granules, powders, columns, nets, cylinders, and preferably in powder form.
[0018]
The amount of the catalyst comprising silicon and titanium oxide is preferably 0.1 to 5% by weight based on the tertiary amine.
[0019]
A representative example of a peroxide is hydrogen peroxide, although other peroxides may be used in the present invention. In the following, the present invention will be described using peroxide as an example of peroxide. As the hydrogen peroxide, a 30 to 35% by weight aqueous solution that is easily available as a commercial product can be suitably used. It is appropriate to use hydrogen peroxide in an amount of 1 to 2 times the theoretical amount with respect to 1 mol of the tertiary amine.
[0020]
However, nitrogen-containing heteroaromatic compounds having two nitrogen atoms as ring constituent atoms, such as pyrazines, are used for the tertiary amine of the raw material, and only one of the two nitrogen atoms of the pyrazine ring is given priority For N-oxidation, the amount of hydrogen peroxide used is preferably 0.4 to 1 mole per mole of pyrazines.
[0021]
The process according to the invention is preferably carried out in a solvent. As the solvent, a solvent which dissolves at least a part of the raw material tertiary amine, dissolves the target product and does not dissolve the catalyst in the present invention, and does not participate in the reaction can be used. As a specific example of the solvent, water, a mixture of water and alcohol such as methanol or ethanol, and the like are preferably used. The amount of the solvent used is not particularly limited, but 1 to 10 parts by weight is appropriate for 1 part by weight of the tertiary amine.
[0022]
As an example of a preferred embodiment of the present invention, a reactor is charged with a catalyst comprising tertiary amine, silicon and titanium oxides and optionally a solvent, and the resulting mixture is heated and stirred under hydrogen peroxide. The reaction is carried out by adding water dropwise over 0.5 to 10 hours. If the reaction is completed by continuing stirring at the same temperature for 0 to 5 hours after the dropwise addition of the hydrogen peroxide solution, the target tertiary amine N-oxide is produced in a high yield. In this reaction, the reaction temperature is room temperature to 100 ° C, preferably 50 to 90 ° C.
[0023]
After completion of the reaction, the reaction solution can be treated by combining commonly used operations such as filtration, extraction, distillation, and crystallization. For example, after completion of the reaction, the reaction solution is cooled to room temperature and potassium bisulfite is added to decompose unreacted hydrogen peroxide. Next, the treated liquid is filtered to remove the catalyst, and the filtrate is concentrated to separate the precipitated crystals, or the filtrate is distilled to obtain a high purity tertiary amine N-oxide. Can do. The separated catalyst can be used repeatedly in the process of the present invention.
[0024]
【Example】
Next, the present invention will be further described with reference to examples, but the present invention is not limited to the following examples.
The analysis conditions by liquid chromatography in the following examples are as follows.
[0025]
Example 1
In a four-necked flask, 30.0 g (0.379 mol) of pyridine, titanosilicate TS-1 (Si / Ti) manufactured by N.E. Chem. Atomic ratio = 16) 1.0 g and 30 g of water were charged, and 44.4 g (0.457 mol) of 35% aqueous hydrogen peroxide was added dropwise at 80 ° C. over 1.7 hours with stirring. Thereafter, the mixture was kept at the same temperature for 2 hours under stirring. After completion of the reaction, the reaction solution was cooled, and a small amount of potassium hydrogen sulfite was added to the reaction solution to decompose unreacted hydrogen peroxide. This treated solution was filtered to separate titanosilicate TS-1, and then the filtrate was analyzed by liquid chromatography. As a result, pyridine N-oxide was quantitatively analyzed from pyridine, that is, 36.1 g (0.379 mol). It was generated.
[0027]
Example 2
A four-necked flask was charged with 30.1 g (0.376 mol) of pyrazine, 1.0 g of the same titanosilicate as in Example 1, and 10.1 g of water. 18.5 g (0.190 mol) of hydrogen oxide water was added dropwise. Thereafter, the mixture was kept at the same temperature for 2 hours under stirring. After completion of the reaction, the reaction solution was cooled, and the reaction solution was filtered to separate titanosilicate TS-1. When the filtrate was analyzed by liquid chromatography, 17.5 g (0.182 mol) of pyrazine N-oxide was obtained, and the yield was 95.8% based on hydrogen peroxide. Further, 0.25 g (0.0022 mol) of pyrazine N, N′-dioxide was produced.
Claims (8)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP02982396A JP3790290B2 (en) | 1995-01-23 | 1996-01-23 | Method for producing tertiary amine N-oxide |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7-27488 | 1995-01-23 | ||
| JP2748895 | 1995-01-23 | ||
| JP02982396A JP3790290B2 (en) | 1995-01-23 | 1996-01-23 | Method for producing tertiary amine N-oxide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH08259516A JPH08259516A (en) | 1996-10-08 |
| JP3790290B2 true JP3790290B2 (en) | 2006-06-28 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP02982396A Expired - Fee Related JP3790290B2 (en) | 1995-01-23 | 1996-01-23 | Method for producing tertiary amine N-oxide |
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| Country | Link |
|---|---|
| JP (1) | JP3790290B2 (en) |
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| JPH08259516A (en) | 1996-10-08 |
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