JPH0262845A - Production of carboxylic acid phenyl esters - Google Patents
Production of carboxylic acid phenyl estersInfo
- Publication number
- JPH0262845A JPH0262845A JP63213725A JP21372588A JPH0262845A JP H0262845 A JPH0262845 A JP H0262845A JP 63213725 A JP63213725 A JP 63213725A JP 21372588 A JP21372588 A JP 21372588A JP H0262845 A JPH0262845 A JP H0262845A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- cobalt
- anhydride
- carboxylic acid
- 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.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- -1 cobalt halide Chemical class 0.000 claims abstract description 14
- 239000010941 cobalt Substances 0.000 claims abstract description 9
- 229910017052 cobalt Inorganic materials 0.000 claims abstract description 9
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 claims abstract description 4
- 125000000524 functional group Chemical group 0.000 claims abstract description 3
- 239000011541 reaction mixture Substances 0.000 claims abstract 2
- 239000000126 substance Substances 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 150000002989 phenols Chemical class 0.000 claims description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 abstract description 16
- 238000006243 chemical reaction Methods 0.000 abstract description 14
- 150000001875 compounds Chemical class 0.000 abstract description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract description 7
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 abstract description 5
- 150000002430 hydrocarbons Chemical group 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 3
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 abstract description 2
- 239000004215 Carbon black (E152) Substances 0.000 abstract description 2
- 229910021583 Cobalt(III) fluoride Inorganic materials 0.000 abstract description 2
- AVWLPUQJODERGA-UHFFFAOYSA-L cobalt(2+);diiodide Chemical compound [Co+2].[I-].[I-] AVWLPUQJODERGA-UHFFFAOYSA-L 0.000 abstract description 2
- YCYBZKSMUPTWEE-UHFFFAOYSA-L cobalt(ii) fluoride Chemical compound F[Co]F YCYBZKSMUPTWEE-UHFFFAOYSA-L 0.000 abstract description 2
- 229930195733 hydrocarbon Natural products 0.000 abstract description 2
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 abstract description 2
- VRYMTAVOXVTQEF-UHFFFAOYSA-N acetic acid [4-[2-(dimethylamino)ethoxy]-2-methyl-5-propan-2-ylphenyl] ester Chemical compound CC(C)C1=CC(OC(C)=O)=C(C)C=C1OCCN(C)C VRYMTAVOXVTQEF-UHFFFAOYSA-N 0.000 abstract 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 abstract 1
- 229960003509 moxisylyte Drugs 0.000 abstract 1
- 210000000056 organ Anatomy 0.000 abstract 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 238000000034 method Methods 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
- 150000008065 acid anhydrides Chemical class 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000000862 absorption spectrum Methods 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000005844 Thymol Substances 0.000 description 3
- HHTWOMMSBMNRKP-UHFFFAOYSA-N carvacrol Natural products CC(=C)C1=CC=C(C)C(O)=C1 HHTWOMMSBMNRKP-UHFFFAOYSA-N 0.000 description 3
- RECUKUPTGUEGMW-UHFFFAOYSA-N carvacrol Chemical compound CC(C)C1=CC=C(C)C(O)=C1 RECUKUPTGUEGMW-UHFFFAOYSA-N 0.000 description 3
- 235000007746 carvacrol Nutrition 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- WYXXLXHHWYNKJF-UHFFFAOYSA-N isocarvacrol Natural products CC(C)C1=CC=C(O)C(C)=C1 WYXXLXHHWYNKJF-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 229960000790 thymol Drugs 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- UQRONKZLYKUEMO-UHFFFAOYSA-N 4-methyl-1-(2,4,6-trimethylphenyl)pent-4-en-2-one Chemical group CC(=C)CC(=O)Cc1c(C)cc(C)cc1C UQRONKZLYKUEMO-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000002592 cumenyl group Chemical group C1(=C(C=CC=C1)*)C(C)C 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000005244 neohexyl group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000810 peripheral vasodilating agent Substances 0.000 description 1
- 229960002116 peripheral vasodilator Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000005023 xylyl group Chemical group 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
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【発明の詳細な説明】
〔発明の目的〕
（産業上の利用分野）
本発明は、カルボン酸フェニルエステル須の製侍方法に
関するものである。DETAILED DESCRIPTION OF THE INVENTION [Object of the Invention] (Industrial Application Field) The present invention relates to a method for producing carboxylic acid phenyl ester.
（従来の技術及びその問題点）
次式（八）
で示される置換アミノエトキシカルハクロール誘導体は
、末梢血管拡張剤、血圧降下剤、脳循環代謝政庁剤、抗
喘息剤として有用であり、例えば、Ｒ−、＝Ｒａ ＝Ｉ
ｌ 、Ｒ７−アラルキル基の構造を有する４（Ｎ−モノ
アラルキルアミノエトキシ）カルバクロールが特開昭５
６−１００７４５号公報に開示されている。また、Ｒ，
−アセチル基、Ｒ６＝ Ｒ，−メチル基の構造を有する
モキシシリトの塩酸塩は、ｉ原器系用医薬品として有用
な化合物として知られている。(Prior art and its problems) The substituted aminoethoxycarhachlor derivative represented by the following formula (8) is useful as a peripheral vasodilator, an antihypertensive agent, a cerebral circulation metabolic agent, and an anti-asthmatic agent. ,R-,=Ra=I
4(N-monoaralkylaminoethoxy)carvacrol having a structure of R7-aralkyl group was disclosed in JP-A No. 5
It is disclosed in Japanese Patent No. 6-100745. Also, R,
-acetyl group, R6=R, -methyl group, moxysilito hydrochloride is known as a compound useful as a prototype drug.
これらの医薬品の製法においては、構造式（）：
で示されるフェノール類を（Ｒ１、［？２、Ｒ３は後述
の置換基である。）の水Ｍ基の部分をエステル化する工
程が重要となる場合がある。特に、上記モキシシリトの
塩酸塩を製造する工程では、原料チモール（ＪＲａ 式
（■） Ｒ１−イソプロピル、Ｒ２＝ 水素、Ｒ３＝メ
チル）をアシル化する工程、５−（２−ジメチルアミノ
エトキシ）−力ルハクロール（構造式％式％
シ、Ｒ３−イソプロピル］をアシル化してモキシシリト
を製造する工程等があり、エステル化を高収率、高純度
かつ工業的に有利な方法で行う必要がある。In the manufacturing method of these pharmaceuticals, the step of esterifying the water M group of the phenol represented by the structural formula (R1, [?2, R3 are substituents described later) is important. It may happen. In particular, in the process of producing the hydrochloride of moxysilito, a process of acylating the raw material thymol (JRa formula (■) R1-isopropyl, R2 = hydrogen, R3 = methyl), 5-(2-dimethylaminoethoxy)-power There are steps such as acylating ruhachlor (structural formula: %, R3-isopropyl) to produce moxysilito, and the esterification needs to be carried out in a high yield, high purity, and in an industrially advantageous method.
現在までに、このようなエステル化の様々な方法が捉示
されているが大別すると一２種の方法に分けられる。１
つの方法は、酸ハロゲン化物を用いる方法で塩化アセチ
ルを用いるアセチル化が特開昭５８−１２１２５１号公
報に開示されている。しかしながら、酸ハロゲン化物は
反応の進行に従って腐食性の塩素ガスを系外に発生する
ために、耐腐食性の反応容器を用いる必要がある。さら
に、酸ハロゲン化物自体も水と激しく反応して塩酸ガス
を発生ずるため工業的取扱の難しい物質であり、工業的
には不利な方法である。To date, various methods for such esterification have been proposed, but they can be broadly classified into 12 types. 1
One method is a method using an acid halide, and acetylation using acetyl chloride is disclosed in JP-A-58-121251. However, since acid halides generate corrosive chlorine gas outside the system as the reaction progresses, it is necessary to use a corrosion-resistant reaction vessel. Furthermore, the acid halide itself is a substance that is difficult to handle industrially because it reacts violently with water and generates hydrochloric acid gas, and this is an industrially disadvantageous method.
もう１つの方法は、酸無水物を用いる方法で、無水酢酸
を用いるアセチル化が特開昭６０−１１５５５５号公報
に開示されている。この方法では腐食性塩酸ガスの発生
も無く、酸無水物も取扱易い上に安価であり、工業的に
有利な方法である。しかし居から、酸ハロゲン化物に比
べやや反応性が悪く、特にフェノール性水酸基をエステ
ル化する際には、加熱するか、もしくは添加物を加え、
反応を加速する必要がある。このような添加物として、
無機酸、酢酸塩、有機塩基等が挙げられる。無機酸とし
て用いられるものは、硫酸、塩酸、リン酸、無水リン酸
などが挙げられるが、例えば３級アミノ基をもつ５−（
２−ジメチルアミノエトキシ）、カルバクロールでは３
級アミノ基と無ａ酸とで塩を生成する反応が併発し、生
成物の単一性が１石なわれるため工業的に不利となる。Another method is a method using an acid anhydride, and acetylation using acetic anhydride is disclosed in JP-A-60-115555. This method does not generate corrosive hydrochloric acid gas, and the acid anhydride is easy to handle and inexpensive, making it an industrially advantageous method. However, due to its nature, it is slightly less reactive than acid halides, and when esterifying phenolic hydroxyl groups in particular, heating or adding additives is required.
It is necessary to accelerate the reaction. As such additives,
Examples include inorganic acids, acetates, and organic bases. Examples of inorganic acids used include sulfuric acid, hydrochloric acid, phosphoric acid, and phosphoric anhydride. For example, 5-(
2-dimethylaminoethoxy), 3 for carvacrol
This is industrially disadvantageous because the reaction of forming a salt between the amino group and the acetic acid occurs simultaneously, and the unity of the product is lost.
有機塩基として用いられるものは、ピリジン、１−リエ
チルアミン、４−ジメチルアミノピリジンなどが挙げら
れるが、反応の進行に従って生成する酸を有機塩基との
塩の形で除去するために、はぼ原料と同等量を加える必
要がある。さらに、このようにして副生ずる塩を除去す
るための操作が必要となり、やはり、工業的に不利なも
のとなる。Examples of organic bases used include pyridine, 1-ethylamine, and 4-dimethylaminopyridine. It is necessary to add an equivalent amount. Furthermore, an operation is required to remove the salt by-produced in this way, which is still industrially disadvantageous.
酢酸塩として用いられるものは、酢酸す１リウム、酢酸
アンモニウム等があるが、これらの塩シよ反応の加速効
果が弱く、原料の３０〜４０モル％程度加えなければ成
らずケーキ状に固まり易い。このため、反応層の攪拌が
困難となる上、後処理工程でも酢酸塩を除くための余計
な操作が必要となり、やはり工業的に不利な方法である
。本発明者らは、前記の種々の問題点を解決するべく鋭
意研究を重ねた結果、次式（ＩＩ）：
（式中Ｒ１、Ｒ２、Ｒ３は後述のとおりである。）で示
されるフェノール類とカルボン酸無水物が、触媒量のコ
バルトハロゲン化物の存在下、均−系でエステル化反応
を行い、その反応速度、収率、操作性ともに良好である
ことを見出し、本発明を完成するに至った。Examples of acetate salts used include monolithium acetate and ammonium acetate, but these salts have a weak effect of accelerating the reaction, and must be added in an amount of about 30 to 40 mol% of the raw materials, and tend to harden into a cake. . For this reason, it becomes difficult to stir the reaction layer, and an extra operation for removing the acetate is required in the post-treatment process, which is still an industrially disadvantageous method. As a result of extensive research to solve the various problems mentioned above, the present inventors found that phenols represented by the following formula (II): (wherein R1, R2, and R3 are as described below) and a carboxylic acid anhydride in the presence of a catalytic amount of cobalt halide, and discovered that the reaction rate, yield, and operability were good, and in order to complete the present invention. It's arrived.
［発明の構成〕
（問題点を解決するだめの手段）
すなわち、本発明は、 次式（ＩＩ）：〔式中Ｒ１、Ｒ
３は水素原子又は炭化水素基を表し、Ｒ２ば水素原子又
は弐（ＩＩＩ）ニー、０Ｃ１（□ＣＨ２Ｘ（■）（式中
Ｘは反応混合物に対して不活性な官能基を表す。）で表
される２−置換エトキシ基を表す。〕で示されるフェノ
ール類をハロゲン化コバルトの存在下にカルボン酸無水
物と反応させるごとを特徴とする
次式（Ｉ）；
（式中、Ｒ，、Ｒ２、Ｒ：Ｊは、前記と同義である。ま
た、Ｒ４は水素原子または炭化水素基を表す。）で示さ
れるカルボン酸フェニルエステル類の製造方法を提供す
るものである。[Structure of the invention] (Means for solving the problem) That is, the present invention provides the following formula (II): [In the formula, R1, R
3 represents a hydrogen atom or a hydrocarbon group, R2 is a hydrogen atom or 2(III), 0C1 (□CH2X(■) (in the formula, represents a 2-substituted ethoxy group represented by the following formula (I), which is characterized by reacting a phenol represented by , R:J has the same meaning as defined above; R4 represents a hydrogen atom or a hydrocarbon group).
前記式（１）及び（ＩＩ）において、Ｒｏ、Ｒ１及びＲ
４における炭化水素基としては、アルキル基もしくはア
リール基が挙げられる。このアルキル基としては、通常
、炭素数１〜１０、好ましくは炭素数１〜６のアルキル
基であり、例えばメチル基、エチル基、プロピル基、イ
ソプロピル基、ブチル基、イソブチル基、５ｅｃ−ブチ
ル基、ｔｉ＝ｒｔ−ブチル基、ペンチル基、イソペンチ
ル基、ネオペンチル基、ヘキシル基、イソヘキシル基、
ネオヘキシル基等が挙げられる。In the formulas (1) and (II), Ro, R1 and R
Examples of the hydrocarbon group in 4 include an alkyl group and an aryl group. The alkyl group is usually an alkyl group having 1 to 10 carbon atoms, preferably 1 to 6 carbon atoms, such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, 5ec-butyl group. , ti=rt-butyl group, pentyl group, isopentyl group, neopentyl group, hexyl group, isohexyl group,
Examples include neohexyl group.
同様に、了り−ル基としては、例えばフェニル基、トリ
ル基、クメニル基、キシリル基、メシチル基、ヘンシル
基等が挙げられる。Similarly, examples of the oryl group include phenyl, tolyl, cumenyl, xylyl, mesityl, hensyl, and the like.
前記アルキル基及びアリール基は、適当な置換基で置換
されていてもよい。ここで、適当な置換基とは本発明の
製造方法における反応条件下において安定な置換基を言
い、例えばハロゲン原子、アルコキシ基、アルキル基、
ニトロ基等が挙げられる。The alkyl group and aryl group may be substituted with a suitable substituent. Here, an appropriate substituent refers to a substituent that is stable under the reaction conditions in the production method of the present invention, such as a halogen atom, an alkoxy group, an alkyl group,
Examples include nitro group.
前記式（１■）において、Ｘで表される官能基としては
、塩素、臭素、ヨウ素等のハロゲン原子及び３級アミノ
基が挙げられる。In the formula (1), examples of the functional group represented by X include halogen atoms such as chlorine, bromine, and iodine, and tertiary amino groups.
前記式（１）で示されるカルボン酸フェニルエステル類
は、前記式（ＩＩ）で示されるフェノール類をハロゲン
化コバルト存在下、酸無水物で処理することより製造す
ることができる。The carboxylic acid phenyl esters represented by the formula (1) can be produced by treating the phenol represented by the formula (II) with an acid anhydride in the presence of cobalt halide.
ここで用いられる酸無水物としは、例えば、無水酢酸、
無水プロピオン酸、無水ｎ−醋酸、無水安息香酸等が挙
げられ、混合酸無水物であっても構わない。これらの酸
無水物の使用量は、弐（ＩＩ ）で示されるフェノール
類に対し、通常１〜２倍当量、好ましくは１．２〜１．
８倍当計である。Examples of the acid anhydride used here include acetic anhydride,
Examples include propionic anhydride, n-acetic anhydride, benzoic anhydride, and mixed acid anhydrides may be used. The amount of these acid anhydrides to be used is usually 1 to 2 times the equivalent of the phenol represented by II (II), preferably 1.2 to 1.
It is 8 times the allowance.
エステル化反応の溶媒としては、アセトニトリル、・＼
ンゼン、トルエン、ニトロヘンゼン、ジグ００エタン、
塩化メチレン、トリクロ１コエチレン、’／ｌ：Ｊｃｌ
ホルム、四塩化炭素、モノクロロヘンセン、ジクロロヘ
ンゼン、二硫化炭素等、反応に関与しないものであれば
いかなるものでもよい。As a solvent for the esterification reaction, acetonitrile, \
Nitrohenzene, toluene, nitrohenzene, Zig00 ethane,
Methylene chloride, trichloromonoethylene, '/l: Jcl
Any substance may be used as long as it does not participate in the reaction, such as form, carbon tetrachloride, monochlorohensen, dichlorohensene, and carbon disulfide.
触媒として添加するハロゲン化コバルトとしてはフン化
コバルト、塩化コバルト、ヨウ化コバルト等が挙げられ
る。Examples of the cobalt halide added as a catalyst include cobalt fluoride, cobalt chloride, and cobalt iodide.
触媒の使用量は、式（ｎ）で示されるフェノール類に対
し、通常０．０１〜２０モル％、好ましくは０．１〜１
５モル％、より好ましくは１〜１０モル％である。The amount of the catalyst used is usually 0.01 to 20 mol%, preferably 0.1 to 1 mol%, based on the phenol represented by formula (n).
It is 5 mol%, more preferably 1 to 10 mol%.
反応温度は、通常０〜１８０’Ｃ１好ましくは０〜１０
０°Ｃである。The reaction temperature is usually 0 to 180'C1, preferably 0 to 10
It is 0°C.
反応の進行は、反応溶液の一部をガスクロマトグラフィ
ーにより分析することにより、追跡することができる。The progress of the reaction can be monitored by analyzing a portion of the reaction solution by gas chromatography.
原料フェノール類が消費された時点で反応を止め溶媒を
留去すると粗カルボン酸フェニルエステル類カ得られる
。ハロゲン化コバルト、未反応物等は、水洗、目的生成
物の結晶化等により簡単に除去、分離できる。必要に応
じてカラムクロマトグラフィー、再結晶、藤留の方法を
用いて精製して、式（１）で示されるカルボン酸フェニ
ルエステル類を得ることができる。When the raw material phenols are consumed, the reaction is stopped and the solvent is distilled off to obtain crude carboxylic acid phenyl esters. Cobalt halides, unreacted substances, etc. can be easily removed and separated by washing with water, crystallizing the desired product, etc. If necessary, the carboxylic acid phenyl esters represented by formula (1) can be obtained by purification using column chromatography, recrystallization, and Fujitome's method.
（発明の実施例）
以下、実施例により本発明を更に詳糸田に説明するが、
以下の実施例は本発明の範囲を何ら制限するものではな
い。(Examples of the Invention) The present invention will be explained in more detail with reference to Examples below.
The following examples are not intended to limit the scope of the invention in any way.
実施例１゜
原料の５−（２−ジメチルアミノエトキシ）カルバクロ
ール塩酸塩〔弐（ＩＩ）：Ｒ１＝メチル、Ｒ２−２−ジ
メチルアミノエトキシ塩酸塩、Ｒ３−イソプロピル〕５
．４７ｇ（２０ミリモル）をアセトニトリル２０ｍ１に
懸濁させ、無水酢酸３．０６ｇ（３０ミリモル）及び塩
化コバルト０．１３ｇ（１ミリモル）を加え８０°Ｃで
１時間加熱攪拌する。溶媒を留去（溶媒中に溶けている
ハロゲン化コハル甲（除かれる）してほぼ定量的に目的
物固体を単離し、６．４５ｇアセトニトリルで再結晶を
行い、上記反応物の結晶５．９６ｇ（収率９４．３％）
を得た。Example 1゜Raw material 5-(2-dimethylaminoethoxy)carvacrol hydrochloride [2(II): R1=methyl, R2-2-dimethylaminoethoxyhydrochloride, R3-isopropyl]5
．． 47 g (20 mmol) was suspended in 20 ml of acetonitrile, 3.06 g (30 mmol) of acetic anhydride and 0.13 g (1 mmol) of cobalt chloride were added, and the mixture was heated and stirred at 80°C for 1 hour. The target solid was almost quantitatively isolated by distilling off the solvent (the halogenated cohalide dissolved in the solvent was removed), and recrystallized with 6.45 g of acetonitrile to obtain 5.96 g of crystals of the above reaction product. (Yield 94.3%)
I got it.
このようにして得られた反応物は、標準試料との赤外吸
収スペクトルの比較によって化学構造を確認し、式（Ｉ
）（Ｒ，＝メチル、Ｒ２−２−ジメチルエトキシ塩酸塩
、Ｒ３−イソプロピル、Ｒ４＝メチルである。）で示さ
れる化合物であることを確認した。The chemical structure of the reactant thus obtained was confirmed by comparing the infrared absorption spectrum with a standard sample, and the formula (I
) (R,=methyl, R2-2-dimethylethoxy hydrochloride, R3-isopropyl, R4=methyl).
赤外吸収スペクトル（ｃ＋＋ｒ’）
３４００、２９５０．２５５０．２４３０．１７５０
（カルボニル基）１２０５、（〜０−） 、 １１７０
（−０−） 、 ９２０実施例２゜
原料のチモール（式（Ｉｔ）；ｉ？＋−イソプロピル、
Ｒ２−水素、Ｒ３−メチル） ４．５ｇ（３０ミリモル
）をアセｌ−二ｌ−リル２０ｍ１に溶かし、無水酢酸３
．９８ｇ（：３９ミリモル）及び無水塩化コバルト０．
１９ｇ（１，５ミリモル）を加え８０°Ｃで２時間加熱
攪拌する。溶媒を留去しトルエン２０ｍ１に溶かし、水
２０戚で２回洗浄しくハロゲン化コバルト等を水洗除去
出来る。）、無水硫酸マグネシウムで乾燥後、４４ｍす
ると釜残として液体が５．４７ｇが得られる。この中に
目的とするエステル５．２５ｇ（収率９１．０％）が含
まれていた。Infrared absorption spectrum (c++r') 3400, 2950.2550.2430.1750
(Carbonyl group) 1205, (~0-), 1170
(-0-), 920 Example 2゜ Raw material thymol (formula (It); i?+-isopropyl,
R2-hydrogen, R3-methyl) 4.5 g (30 mmol) was dissolved in 20 ml of acetyl-dyl-lyl, and acetic anhydride 3
．． 98 g (:39 mmol) and 0.98 g (:39 mmol) of anhydrous cobalt chloride.
Add 19 g (1.5 mmol) and heat and stir at 80°C for 2 hours. The solvent is distilled off, the solution is dissolved in 20ml of toluene, and the solution is washed twice with 20ml of water to remove cobalt halides and the like. ), and after drying with anhydrous magnesium sulfate, 5.47 g of liquid was obtained as a residue after 44 m. This contained 5.25 g (yield: 91.0%) of the desired ester.
このようにして得られた反応物は、標準試料との赤外吸
収スペクトルとの比較によって化学構造を確認し、式（
１）（Ｌ−イソプロピル、Ｉ？、−水素、Ｒ３−メチル
、Ｒ４−メチルである。）で示される化合物であること
を確認した。The chemical structure of the reactant thus obtained was confirmed by comparing its infrared absorption spectrum with that of a standard sample, and the chemical structure was determined by the formula (
1) It was confirmed that it was a compound represented by (L-isopropyl, I?, -hydrogen, R3-methyl, R4-methyl).
赤外吸収スペクトル（ｃｍ−’）
２９５０、１７５０ （カルボニル基） 、 １３６０
、１２００ （−０−）１０８０、１０１０，８９０
，８１０
実施例３゜
原ｒｌのチモール（式（１１）；１７１−イソプロピル
、Ｒ２−水素、Ｒ３−メチル） ４．５ｇ（３０ミリモ
ル）をアセトニトリル２０ｍ１に溶かし、無水酢酸３．
９８ｇ（３９ミリモル）及び無水塩化コバルト０．３３
ｇ（２，５ミリモル）を加え８０°Ｃで２時間加熱・攪
拌する。）８媒を留去しトルエン２０ｍ１に）容かし、
水２０ｍ１で２回；先浄しくハロゲン化コバルト等を水
洗除去出来る。）、無水硫酸マグネシウムで乾燥後、濃
（宿すると釜残として液体が５．１６ｇが得られる。こ
の中に目的とするエステル５．０１ｇ（収率８７％）が
含まれていた。Infrared absorption spectrum (cm-') 2950, 1750 (carbonyl group), 1360
, 1200 (-0-) 1080, 1010,890
, 810 Example 3 4.5 g (30 mmol) of original rl thymol (formula (11); 171-isopropyl, R2-hydrogen, R3-methyl) was dissolved in 20 ml of acetonitrile, and 3.5 g (30 mmol) of the original rl was dissolved in 20 ml of acetonitrile.
98 g (39 mmol) and 0.33 anhydrous cobalt chloride
g (2.5 mmol) and heated and stirred at 80°C for 2 hours. ) 8 medium was distilled off to 20 ml of toluene),
Cobalt halide etc. can be removed by washing with water twice with 20 ml of water. ), dried over anhydrous magnesium sulfate, and concentrated (5.16 g of liquid was obtained as a residue. This contained 5.01 g of the desired ester (yield: 87%).
実施例２と同様にして、標準試料との赤外吸収スペクト
ルの比較によって化学構造を化学構造を６′Ｃ認し、弐
（１）（Ｒ，−イソプロピル、Ｒ２＝水素、ρよ一メチ
ル、Ｒ４−メチルである。）で示される化合物であるこ
とを確認した。In the same manner as in Example 2, the chemical structure was identified by 6'C by comparison of the infrared absorption spectrum with the standard sample, and 2(1) (R, -isopropyl, R2 = hydrogen, ρ = 1 methyl, It was confirmed that the compound was R4-methyl.
本発明によれば、カルボン酸フェニルエステルを短時間
で簡便かつ、高純度、高収率でｉ）するごとができ、医
薬として有用な塩酸モキシジリトを効率よく提供するこ
とができる。According to the present invention, carboxylic acid phenyl ester can be prepared in a short time, easily, with high purity, and in high yield (i), and moxidyrite hydrochloride useful as a pharmaceutical can be efficiently provided.
特許出願人 宇部興産株式会社Patent applicant: Ube Industries Co., Ltd.
Claims (1)
、Ｒ＿２は水素原子又は式（III）：−ＯＣＨ＿２ＣＨ
＿２Ｘ（III）（式中Ｘは、反応混合物に対して不活性
な官能基を表す。）で表される２−置換エトキシ基を表
す。〕で示されるフェノール類をハロゲン化コバルトの
存在下にカルボン酸無水物と反応させることを特徴とす
る 次式（ I ）： ▲数式、化学式、表等があります▼（ I ） （式中、Ｒ＿１、Ｒ＿２、Ｒ＿３は、前記と同義である
。また、Ｒ＿４は水素原子または炭化水素基を表す。）
で示されるカルボン酸フェニルエステル類の製造方法。(1) The following formula (II): ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) [In the formula, R_1 and R_3 represent a hydrogen atom or a hydrocarbon group, and R_2 is a hydrogen atom or a formula (III): -OCH_2CH
Represents a 2-substituted ethoxy group represented by _2X(III) (in the formula, X represents a functional group inert to the reaction mixture). ] The following formula (I) is characterized by reacting the phenols represented by the above with carboxylic acid anhydride in the presence of cobalt halide: ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R_1 , R_2, and R_3 have the same meanings as above. Also, R_4 represents a hydrogen atom or a hydrocarbon group.)
A method for producing carboxylic acid phenyl esters represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63213725A JPH0262845A (en) | 1988-08-30 | 1988-08-30 | Production of carboxylic acid phenyl esters |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63213725A JPH0262845A (en) | 1988-08-30 | 1988-08-30 | Production of carboxylic acid phenyl esters |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0262845A true JPH0262845A (en) | 1990-03-02 |
Family
ID=16643962
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63213725A Pending JPH0262845A (en) | 1988-08-30 | 1988-08-30 | Production of carboxylic acid phenyl esters |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0262845A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100725582B1 (en) * | 2004-06-29 | 2007-06-08 | 주식회사 동부하이텍 | Alkylphenol derivatives having phytopathogenic fungi activities |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5163144A (en) * | 1974-10-04 | 1976-06-01 | Dynamit Nobel Ag | Fuenoorurui mataha chiofuenooruruinokurorumechiruuansokukosanesuterunoseiho |
-
1988
- 1988-08-30 JP JP63213725A patent/JPH0262845A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5163144A (en) * | 1974-10-04 | 1976-06-01 | Dynamit Nobel Ag | Fuenoorurui mataha chiofuenooruruinokurorumechiruuansokukosanesuterunoseiho |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100725582B1 (en) * | 2004-06-29 | 2007-06-08 | 주식회사 동부하이텍 | Alkylphenol derivatives having phytopathogenic fungi activities |
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