JPH04112845A - Production of hydroxystilbenes - Google Patents
Production of hydroxystilbenesInfo
- Publication number
- JPH04112845A JPH04112845A JP2233997A JP23399790A JPH04112845A JP H04112845 A JPH04112845 A JP H04112845A JP 2233997 A JP2233997 A JP 2233997A JP 23399790 A JP23399790 A JP 23399790A JP H04112845 A JPH04112845 A JP H04112845A
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- acid ester
- formula
- base
- hydroxybenzylphosphonic acid
- 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
- AYPZAZPOYROADP-UHFFFAOYSA-N 2-(2-phenylethenyl)phenol Chemical class OC1=CC=CC=C1C=CC1=CC=CC=C1 AYPZAZPOYROADP-UHFFFAOYSA-N 0.000 title claims description 14
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- -1 hydroxybenzylphosphonic acid ester Chemical class 0.000 claims abstract description 16
- 150000003935 benzaldehydes Chemical class 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 abstract description 12
- 150000001875 compounds Chemical class 0.000 abstract description 12
- 239000002994 raw material Substances 0.000 abstract description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 abstract description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 abstract description 6
- 125000000217 alkyl group Chemical group 0.000 abstract description 5
- 239000011541 reaction mixture Substances 0.000 abstract description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 abstract description 4
- 238000007086 side reaction Methods 0.000 abstract description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 abstract description 2
- 125000003545 alkoxy group Chemical group 0.000 abstract description 2
- 229920000642 polymer Polymers 0.000 abstract description 2
- 229910000104 sodium hydride Inorganic materials 0.000 abstract description 2
- 239000012312 sodium hydride Substances 0.000 abstract description 2
- 229910052736 halogen Inorganic materials 0.000 abstract 2
- 150000002367 halogens Chemical class 0.000 abstract 2
- 229940079593 drug Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 238000011084 recovery Methods 0.000 abstract 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 26
- 239000002585 base Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 9
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 239000003513 alkali Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical class OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- JZSAHUBCZHLLJF-UHFFFAOYSA-N (3-methoxyphenyl)methylphosphonic acid Chemical compound COC1=CC=CC(CP(O)(O)=O)=C1 JZSAHUBCZHLLJF-UHFFFAOYSA-N 0.000 description 1
- ZHBRSHSRMYZHLS-UHFFFAOYSA-N (4-hydroxyphenyl)methylphosphonic acid Chemical compound OC1=CC=C(CP(O)(O)=O)C=C1 ZHBRSHSRMYZHLS-UHFFFAOYSA-N 0.000 description 1
- CKADNPRLDAEDMO-MDZDMXLPSA-N 2-[(e)-2-(3-methoxyphenyl)ethenyl]phenol Chemical compound COC1=CC=CC(\C=C\C=2C(=CC=CC=2)O)=C1 CKADNPRLDAEDMO-MDZDMXLPSA-N 0.000 description 1
- YINYVRLKOAKPLN-UHFFFAOYSA-N 2-[2-(2-hydroxyphenyl)ethenyl]phenol Chemical group OC1=CC=CC=C1C=CC1=CC=CC=C1O YINYVRLKOAKPLN-UHFFFAOYSA-N 0.000 description 1
- DYXAWSYYBVJGRQ-UHFFFAOYSA-N 2-methoxy-6-(2-phenylethenyl)phenol Chemical compound COC1=CC=CC(C=CC=2C=CC=CC=2)=C1O DYXAWSYYBVJGRQ-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- OKRCXSCDWKJWSW-UHFFFAOYSA-N [4-(chloromethyl)phenyl] acetate Chemical compound CC(=O)OC1=CC=C(CCl)C=C1 OKRCXSCDWKJWSW-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000003916 acid precipitation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- HUMNYLRZRPPJDN-KWCOIAHCSA-N benzaldehyde Chemical group O=[11CH]C1=CC=CC=C1 HUMNYLRZRPPJDN-KWCOIAHCSA-N 0.000 description 1
- 238000007193 benzoin condensation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- HEZQRPHEDDAJTF-UHFFFAOYSA-N chloro(phenyl)methanol Chemical compound OC(Cl)C1=CC=CC=C1 HEZQRPHEDDAJTF-UHFFFAOYSA-N 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- TUHQILXYEWBBDR-UHFFFAOYSA-N ethoxy-[(4-hydroxyphenyl)methyl]phosphinic acid Chemical compound CCOP(O)(=O)CC1=CC=C(O)C=C1 TUHQILXYEWBBDR-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940114123 ferulate Drugs 0.000 description 1
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000006289 hydroxybenzyl group Chemical group 0.000 description 1
- NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical compound COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 1
- 150000003008 phosphonic acid esters Chemical class 0.000 description 1
- ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 239000012485 toluene extract Substances 0.000 description 1
- QVLMUEOXQBUPAH-VOTSOKGWSA-N trans-stilben-4-ol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC=CC=C1 QVLMUEOXQBUPAH-VOTSOKGWSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-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
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明はヒドロキシスチルベン類の製法に関するもので
あり、詳しくは、新規反応による副生物の少ない工業的
に有利なヒドロキシスチルベン類の製法に関するもので
ある。[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a method for producing hydroxystilbenes, and more particularly, it relates to an industrially advantageous method for producing hydroxystilbenes with few by-products due to a novel reaction. be.
［従来の技術とその問題点１
ヒドロキシスチルベン類は、例えば、医薬中間体、感光
性ポリマー用原料として有用な上、それ自体、抗菌剤、
農薬安定剤及び蛍光増感剤などにも利用されている。従
来、ヒドロキシスチルベン類の製造法としては、例えば
、次の合成ルートが知られている。[Prior art and its problems 1 Hydroxystilbenes are useful, for example, as pharmaceutical intermediates and raw materials for photosensitive polymers, and they are also useful as antibacterial agents,
It is also used as a pesticide stabilizer and fluorescent sensitizer. Conventionally, as a method for producing hydroxystilbenes, for example, the following synthetic route is known.
しかしながら、上記■及び■の反応の場合、原料となる
ベンズアルデヒド誘導体のヒドロキシ基をアルキルエー
テルとして保護した後、反応を行ない、次いで、反応後
にこれを加水分解しヒドロキシ基を生成させる必要があ
るので、全体の反応工程が長くなる上、前記加水分解時
における副反応が著しく、高収率で目的化合物を得るこ
とができない。また、上記■の反応の場合、ヒドロキシ
ベンズアルデヒド同志又はベンズアルデヒド同志のベン
ゾイン縮合も併発するが、この副生物と目的化合物との
分離操作は極めて難しく、容易に高純度品を回収するこ
とはできない。更に、上記■の反応の場合には、ヒドロ
キシ基の保護が不要で、しかも、目的化合物の選択性も
良好であるが、原料として高価なトリフェニルホスフィ
ンを用いる必要があり、また、反応により副生ずるトリ
フェニルホスフィンオキサイドと目的化合物との分離に
当たっては、多段抽出法などの複雑な工程を要する。However, in the case of the reactions (1) and (2) above, it is necessary to carry out the reaction after protecting the hydroxy group of the benzaldehyde derivative used as a raw material as an alkyl ether, and then, after the reaction, it is necessary to hydrolyze this to generate a hydroxy group. Not only does the entire reaction process take a long time, but also the side reactions during the hydrolysis are significant, making it impossible to obtain the target compound in high yield. Furthermore, in the case of the above reaction (2), benzoin condensation of hydroxybenzaldehydes or benzaldehydes occurs simultaneously, but separation of this by-product from the target compound is extremely difficult, and a highly purified product cannot be easily recovered. Furthermore, in the case of reaction (2) above, protection of the hydroxyl group is not required and the selectivity of the target compound is also good, but it is necessary to use expensive triphenylphosphine as a raw material, and the reaction causes side effects. Separation of the resulting triphenylphosphine oxide from the target compound requires complex steps such as multistage extraction.
［発明の課題と解決手段］
本発明者は上記実状に鑑み、副生物の生成が少なく、し
かも、目的生成物の回収が容易なヒドロキシスチルベン
類の合成法について種々検討を行った結果、ヒドロキシ
ベンジルホスホン酸エステルとベンズアルデヒドとを原
料としてヒドロキシスチルベン類を合成する場合、高収
率で目的化合物が得られる上、反応混合物からの目的化
合物の回収も簡単にできることを見い出した。[Problems to be solved by the invention and means for solving the problem] In view of the above-mentioned circumstances, the present inventor conducted various studies on a method for synthesizing hydroxystilbenes that produces less by-products and can easily recover the desired product, and found that hydroxybenzyl It has been found that when hydroxystilbenes are synthesized using phosphonic acid ester and benzaldehyde as raw materials, the target compound can be obtained in high yield, and the target compound can also be easily recovered from the reaction mixture.
すなわち、本発明の要旨は、ヒドロキシベンジルホスホ
ン酸エステルとベンズアルデヒド誘導体とを、塩基の存
在下、非プロトン性有機溶媒中で反応させることを特徴
とするヒドロキシスチルベン類の製法に存する。That is, the gist of the present invention resides in a method for producing hydroxystilbenes, which is characterized by reacting a hydroxybenzylphosphonic acid ester and a benzaldehyde derivative in an aprotic organic solvent in the presence of a base.
以下、本発明の詳細な説明する。The present invention will be explained in detail below.
本発明の原料となる、ヒドロキシベンジルホスホン酸エ
ステルとしては、通常、
下記−数式［１］
（式中、Ｒ１は低級アルキル基を表わし、Ｒ２及びＲ３
は水素原子、低級アルキル基、低級アルキル基又はハロ
ゲン原子を表わす）で示される化合物であり、具体的に
は例えば、０−もしくはｐ−ヒドロキシベンジルホスホ
ン酸エステル、３−ヒドロキシ−４−メトキシベンジル
ホスホン酸エステル、３−メトキシ−４−ヒドロキシベ
ンジルホスホン酸エステル、２−ヒドロキシ−３−メチ
ル−５−クロロベンジルホスホン酸エステルなどが挙げ
られる。The hydroxybenzylphosphonic acid ester, which is a raw material of the present invention, usually has the following formula [1] (wherein, R1 represents a lower alkyl group, R2 and R3
represents a hydrogen atom, a lower alkyl group, a lower alkyl group, or a halogen atom), specifically, for example, 0- or p-hydroxybenzylphosphonic acid ester, 3-hydroxy-4-methoxybenzylphosphonate Examples include acid ester, 3-methoxy-4-hydroxybenzylphosphonic acid ester, and 2-hydroxy-3-methyl-5-chlorobenzylphosphonic acid ester.
このヒドロキシベンジルホスホン酸エステルは、通常、
そのヒドロキシル基をアセチル基またはアルコキシカル
ボニル基で保護したヒドロキシベンジルクロリド類と亜
リン酸エステルとを反応させ、その後保護基を脱離させ
る方法（ツーカーケミカル、米国特許３，９８３，１７
８号公報）または、０−ヒドロキシ−ベンジルアルコー
ル類と亜リン酸エステルとを直接反応させる方法（Ｊ
、Ａ 、Ｍｉｌｅｓ ｅｔ ａｌＪ、Ｏ，Ｃ，、４７，
１６７７（１９８２） ）等により、容易に得ることが
できる。This hydroxybenzylphosphonic acid ester is usually
A method in which a hydroxybenzyl chloride whose hydroxyl group is protected with an acetyl group or an alkoxycarbonyl group is reacted with a phosphite, and then the protecting group is removed (Zuker Chemical, U.S. Pat. No. 3,983,17
8) or a method of directly reacting 0-hydroxy-benzyl alcohols and phosphites (J
,A.,Miles et al.,O.C.,,47,
1677 (1982)).
一方、ベンズアルデヒド誘導体としては、通常、下記−
数式（ＩＩ ）
（式中、Ｒ４及びＲ６は水素原子、ヒドロキシル基、低
級アルコキシ基又はハロゲン原子を表わす）で示される
化合物であり、例えば、ベンズアルデヒド、〇−もしく
はｐ−ヒドロキシベンズアルデヒド、ｍ−メトキシベン
ズアルデヒド、０−ブロモベンズアルデヒド、３−メト
キシ−４−ヒドロキシベンズアルデヒドなどが挙げられ
る。On the other hand, as benzaldehyde derivatives, the following -
A compound represented by formula (II) (wherein R4 and R6 represent a hydrogen atom, a hydroxyl group, a lower alkoxy group, or a halogen atom), such as benzaldehyde, 〇- or p-hydroxybenzaldehyde, m-methoxybenzaldehyde , 0-bromobenzaldehyde, 3-methoxy-4-hydroxybenzaldehyde, and the like.
なお、前示一般式（ＩＩのヒドロキシベンジルホスホン
酸エステルと前示一般式（ＩＩ）のベンズアルデヒド誘
導体から合成されるヒドロキシスチルベン類は下記−数
式［■旧
（式中、Ｒ２−Ｒ５は前記と同じ意味を表わす）で示さ
れる化合物となる。The hydroxystilbenes synthesized from the hydroxybenzylphosphonic acid ester of the general formula (II) and the benzaldehyde derivative of the general formula (II) are represented by the following formula [■ old (where R2-R5 are the same as above) It becomes a compound shown by (representing the meaning).
ベンズアルデヒド誘導体に対するヒドロキシベンジルホ
スホン酸エステルの使用量は、通常、０．７〜１．５モ
ル倍、好ましくは０．９〜１．１モル倍である。The amount of hydroxybenzylphosphonic acid ester to be used is usually 0.7 to 1.5 times by mole, preferably 0.9 to 1.1 times by mole relative to the benzaldehyde derivative.
本発明の反応は塩基の存在下で実施されるが、塩基とし
ては、通常、水素化ナトリウムなどの水素化アルカリ又
はカリウムも一ブトキサイド、ナトリウムメトキサイド
、ナトリウムメトキサイドなどのアルカリアルコラード
などが挙げられるが、収率から考えると、塩基強度の高
いカリウムｔ−ブトキサイドが最も好ましい。この塩基
の使用量は、通常、ヒドロキシベンジルホスホン酸エス
テルに対して、１．５〜４．５モル倍、好ましくは２．
５〜３．５モル倍である。本発明の反応では、この塩基
の作用により、まず、水酸基がフェルレート化され、つ
いでベンジル位の活性化が行われるので、塩基の使用量
があまり少ないとベンジル位の活性化が不十分となり収
率が低下し、また、あまり多すぎても効果に変わりはな
いので経済的ではない。The reaction of the present invention is carried out in the presence of a base, and the base usually includes an alkali hydride such as sodium hydride or an alkali alcoholade such as potassium monobutoxide, sodium methoxide, and sodium methoxide. However, from the viewpoint of yield, potassium t-butoxide, which has a high base strength, is most preferable. The amount of this base to be used is usually 1.5 to 4.5 moles, preferably 2.
It is 5 to 3.5 times the mole. In the reaction of the present invention, the action of the base first converts the hydroxyl group into ferulate, and then activates the benzyl position. Therefore, if the amount of base used is too small, the activation of the benzyl position will be insufficient, resulting in insufficient yield. It is not economical because the effect decreases and the effect remains the same even if the amount is too large.
本発明で使用する非プロトン性有機溶媒とじては活性水
素を持たず塩基に対して不活性な溶媒であれば特に限定
されないが、通常、トルエン、テトラリンなどの炭化水
素、テトラヒドロフラン、ジフェニルエーテルなどのエ
ーテル類、ジメチルホルムアミドなどのアルキルアミド
類等が望ましい。有機溶媒の使用量は通常、全反応原料
に対して、０．５〜５０重量倍、好ましくは１〜３０重
量倍程度である。The aprotic organic solvent used in the present invention is not particularly limited as long as it does not have active hydrogen and is inert to bases, but it is usually a hydrocarbon such as toluene or tetralin, or an ether such as tetrahydrofuran or diphenyl ether. and alkylamides such as dimethylformamide are preferable. The amount of the organic solvent used is usually about 0.5 to 50 times by weight, preferably about 1 to 30 times by weight based on the total reaction raw materials.
本発明における反応温度は、通常、−３０〜１００°Ｃ
１好ましくは一１０〜５０°Ｃ１特に好ましくは一１０
〜３０°Ｃである。反応温度があまり低いと反応速度が
遅く目的化合物を良好に得ることが出来ず、逆にあまり
高いと副反応が起こり副生物量が増加するので好ましく
ない。なお、反応時間は反応条件及び反応方式により異
なるが、例えば、０．５〜５時間程度である。The reaction temperature in the present invention is usually -30 to 100°C
1 Preferably -10 to 50°C 1 Particularly preferably -10
~30°C. If the reaction temperature is too low, the reaction rate is slow and the target compound cannot be obtained satisfactorily, whereas if the reaction temperature is too high, side reactions occur and the amount of byproducts increases, which is not preferable. Note that the reaction time varies depending on the reaction conditions and reaction method, but is, for example, about 0.5 to 5 hours.
本発明の反応を実施するには、通常、塩基を含有する有
機溶媒を敷液とし、これを所、定温度に維持しながら、
撹拌下、ヒドロキシベンジルホスホン酸エステルとベン
ズアルデヒド誘導体とを供給する方法が最も高収率で目
的とするヒドロキシスチルベン類を得ることができるの
で望ましい。この場合、ヒドロキシベンジルホスホン酸
エステルとベンズアルデヒド誘導体は各々別々に、又は
、混合して一緒に供給してもよく、また、場合により有
機溶媒で希釈して供給することもできる。To carry out the reaction of the present invention, an organic solvent containing a base is usually used as a bedding solution, and while maintaining this at a constant temperature,
A method of supplying the hydroxybenzylphosphonic acid ester and the benzaldehyde derivative under stirring is preferable because the desired hydroxystilbenes can be obtained in the highest yield. In this case, the hydroxybenzylphosphonic acid ester and the benzaldehyde derivative may be supplied separately or together as a mixture, and optionally diluted with an organic solvent.
これら原料の供給速度は反応に伴う発熱を除熱し得れば
速やかに添加しても差支えない。また、反応時間は、通
常、０．３〜１０時間望ましくは０．５〜５時間である
。These raw materials may be added as quickly as possible as long as the heat generated by the reaction can be removed. Further, the reaction time is usually 0.3 to 10 hours, preferably 0.5 to 5 hours.
反応後の混合物は、まず、炭酸アルカリ水溶液で処理し
て酸性成分を抽出除去した後、有機相をカセイアルカリ
で処理して生成したヒドロキシスチルベン類を水相に抽
出し、次いで、この水相を酸析して目的物を得る。After the reaction, the mixture is first treated with an aqueous alkali carbonate solution to extract and remove acidic components, then the organic phase is treated with a caustic alkali to extract the generated hydroxystilbenes into the aqueous phase, and then this aqueous phase is extracted. The target product is obtained by acid precipitation.
［実施例］
次に、本発明を実施例により更に詳細に説明するが、本
発明はその要旨を越えない限り以下の実施例に限定され
るものではい。[Examples] Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to the following Examples unless the gist thereof is exceeded.
実施例１
（ヒドロキシベンジルホスホン酸エステルの調製）撹拌
機及び温度調節機を備えたガラス製１００ｍ１反応器に
、０−ヒドロキシベンジルアルコール１２．２ｇ及び溶
媒としてキシレン２５ｍ１を仕込み、これを８０°Ｃの
温度に調節しながら、撹拌下、亜リン酸トノエチル１９
．９４ｇを供給速度０．３ｇ ／ ｍｉｎで連続的に滴
下し、次いで、同温度で１２０分間、引き続き反応を行
った。Example 1 (Preparation of hydroxybenzylphosphonic acid ester) 12.2 g of 0-hydroxybenzyl alcohol and 25 ml of xylene as a solvent were charged into a 100 ml glass reactor equipped with a stirrer and a temperature controller, and the mixture was heated at 80°C. tonoethyl phosphite 19 under stirring while adjusting the temperature.
．． 94 g was continuously added dropwise at a feed rate of 0.3 g/min, and then the reaction was continued at the same temperature for 120 minutes.
次いで、反応後の混合物に対し、減圧で８０°Ｃ１２０
Ｃ１２０Ｏにて上記反応中生成したエタノールを留出さ
せ、その後さらに同温度、５０ｍｍＨｇにて溶媒のキシ
レン、２０ｍｍＨｇにて過剰の亜リン酸トリエチルを留
去して、２１．９ｇ （９８％）の０−ヒドロキシベン
ジルホスホン酸エチルエステルを得た。Then, the reaction mixture was heated at 80°C120 under reduced pressure.
The ethanol produced during the above reaction was distilled off at C120O, and then the solvent xylene was distilled off at the same temperature and 50 mmHg, and the excess triethyl phosphite was distilled off at 20 mmHg, resulting in 21.9 g (98%) of 0. -Hydroxybenzylphosphonic acid ethyl ester was obtained.
（ヒドロキシスチルベン類の合成）
撹拌機及び温度調節機を備えたガラス製１００ｍ１反応
器に、カリウムｔ−ブトキサイド１４．７ｇ及び溶媒と
してテトラヒドロフラン４０ｍ１を仕込み、これを３０
°Ｃの温度に調節しながら、撹拌下、上記調製例で得た
０−ヒドロキシベンジルホスホン酸エステル９．７６
ｇとｍ−メトキシベンズアルデヒド５．４４ｇの混合物
を供給速度０．２５ ｇ ／ ｍｉｎで連続的に滴下し
、次いで、同温度で１２０分間、引き続き反応を行なっ
た。(Synthesis of hydroxystilbenes) In a 100 ml glass reactor equipped with a stirrer and a temperature controller, 14.7 g of potassium t-butoxide and 40 ml of tetrahydrofuran as a solvent were charged.
9.76 0-Hydroxybenzylphosphonic acid ester obtained in the above preparation example under stirring while controlling the temperature at °C.
A mixture of g.
反応混合物に水１００ｍ１、トルエン１００ｍ１を加え
る。さらに２Ｎ塩酸６２ｍ１を加え水層を酸性化し、生
成したヒドロキシスチルベン誘導体をトルエン層に抽出
した。このトルエン抽出層を炭酸アルカリ水溶液で洗浄
し、強酸成分を除去し、水１００ｍ１で２回洗浄した後
、溶媒を減圧留去し、６．４８ ｇ （収率ニア１％）
の２−ヒドロキシ−３−メトキシスチルベンを得た。Add 100 ml of water and 100 ml of toluene to the reaction mixture. Further, 62 ml of 2N hydrochloric acid was added to acidify the aqueous layer, and the generated hydroxystilbene derivative was extracted into the toluene layer. This toluene extract layer was washed with an aqueous alkali carbonate solution to remove strong acid components, and washed twice with 100 ml of water, and then the solvent was distilled off under reduced pressure to obtain 6.48 g (yield near 1%).
2-hydroxy-3-methoxystilbene was obtained.
（生成物の同定確認）
上記で得られた２−ヒドロキシ−３′−メトキシスチル
ベンは、５ｙｎｔｈｅｓｉｓ、 ９，７１２−７１４
（１９７９）に記載の方法に従って、サリチルアルデヒ
ドメトキシメチルエーテル及びｍ−メトキシベンジルホ
スホン酸から合成した標品と、融点及び分析値（ＬＣ，
ＮＭＲ，ＵＶ及びＭＳ）が一致した。(Confirmation of product identity) The 2-hydroxy-3'-methoxystilbene obtained above is 5ynthesis, 9,712-714
(1979), a sample synthesized from salicylaldehyde methoxymethyl ether and m-methoxybenzylphosphonic acid, and melting point and analytical values (LC,
NMR, UV and MS) were consistent.
実施例２
実施例１の方法において、ｍ−メトキシベンズアルデヒ
ドの代りに、ベンズアルデヒド４．２４ ｇを用い、同
様の操作で反応及び後処理を行なった。生成物として２
−ヒドロキシスチルベン５．８６ｇ（収率ニア４．６％
、ｍ、 ｐ、 １４４．５−１４５°Ｃ）を得た。これ
は、Ａｎｎ 。Example 2 In the method of Example 1, 4.24 g of benzaldehyde was used instead of m-methoxybenzaldehyde, and the reaction and post-treatment were carried out in the same manner. 2 as a product
-Hydroxystilbene 5.86g (yield near 4.6%)
, m, p, 144.5-145°C). This is Ann.
４３３ 、２４１ （１９２３）に記載の方法で合成し
た標品と融点及び分析値が一致した。433, 241 (1923), the melting point and analytical values were identical.
実施例３
実施例１の方法において、ｍ−メトキシベンズアルデヒ
ドの代りに、サリチルアルデヒド４．８８ ｇを用い、
同様に反応及び後処理を行なった。生成物は２，２′−
ジヒドロキシスチルベン３．２２ ｇ （収率：３８％
、ｍ、 ｐ、 ９４−９５°Ｃ）であった。Example 3 The method of Example 1, using 4.88 g of salicylaldehyde instead of m-methoxybenzaldehyde,
Reactions and post-treatments were carried out in the same manner. The product is 2,2'-
Dihydroxystilbene 3.22 g (Yield: 38%
, m, p, 94-95°C).
これは、Ｂｅｒ 、 ５５ 、２，６６４ （１９２２
）に記載の方法で合成した標品と、融点及び分析値が良
く一致した。This is described in Ber, 55, 2,664 (1922
The melting point and analytical values were in good agreement with the standard product synthesized by the method described in ).
実施例４
ｐ−アセトキシベンジルクロライドと亜リン酸トノエチ
ルエステルを反応させて、 ヒドロキシベンジルホス
ホン酸エチルエステルを合成した。Example 4 Hydroxybenzylphosphonic acid ethyl ester was synthesized by reacting p-acetoxybenzyl chloride and phosphorous acid tonoethyl ester.
実施例１と同じ方法でｐ−ヒドロキシベンジルホスホン
酸エチル９．７６ ｇとベンズアルデヒド４．２４ ｇ
を用いて反応及び後処理を行なった。9.76 g of ethyl p-hydroxybenzylphosphonate and 4.24 g of benzaldehyde were prepared in the same manner as in Example 1.
The reaction and post-treatment were carried out using
生成物は４−ヒドロキシスチルベン５．４５ｇ（収率ニ
ア０％、ｍ、 ｐ、 １８８−１８９°Ｃ）で得た。The product was obtained in 5.45 g of 4-hydroxystilbene (yield near 0%, m, p, 188-189°C).
これは、Ｊ、 Ｃｈｅｍ、 Ｓｏｃ、 １０１ 、６０
５ （１９１２）に記載の方法で合成した標品と融点及
び分析値が一致した。This is J, Chem, Soc, 101, 60
5 (1912), the melting point and analytical values were identical to those of the specimen synthesized by the method described in 1912.
実施例５〜７
実施例１において、使用する塩基又は溶媒の種類を変え
、他は同様にして反応を行ない、第１表の結混合物から
の目的化合物の回収も容易に行うことができる。Examples 5 to 7 The reaction was carried out in the same manner as in Example 1 except that the type of base or solvent used was changed, and the target compound can be easily recovered from the resulting mixture shown in Table 1.
Claims (1)
アルデヒド誘導体とを、塩基の存在下、非プロトン性有
機溶媒中で反応させることを特徴とするヒドロキシスチ
ルベン類の製法。(1) A method for producing hydroxystilbenes, which comprises reacting a hydroxybenzylphosphonic acid ester and a benzaldehyde derivative in an aprotic organic solvent in the presence of a base.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2233997A JPH04112845A (en) | 1990-09-04 | 1990-09-04 | Production of hydroxystilbenes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2233997A JPH04112845A (en) | 1990-09-04 | 1990-09-04 | Production of hydroxystilbenes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04112845A true JPH04112845A (en) | 1992-04-14 |
Family
ID=16963936
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2233997A Pending JPH04112845A (en) | 1990-09-04 | 1990-09-04 | Production of hydroxystilbenes |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04112845A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2711481A1 (en) * | 1993-10-25 | 1995-05-05 | Kioritz Corp | Chlorinated hydroxystilbenes used in nematicides, their preparation process and new dichlorohydroxystilbenes. |
| EP0739877A3 (en) * | 1995-04-27 | 1997-03-12 | Sumitomo Chemical Co | Epoxy resin, resin composition, and resin-encapsulated semiconductor device |
| JP2014516973A (en) * | 2011-05-25 | 2014-07-17 | ダウ グローバル テクノロジーズ エルエルシー | Phosphorus-containing compounds useful for the production of halogen-free ignition resistant polymers |
| US20150126690A1 (en) * | 2004-05-28 | 2015-05-07 | Dow Global Technologies Llc | Phosphorus-containing compounds useful for making halogen-free, ignition-resistant polymers |
-
1990
- 1990-09-04 JP JP2233997A patent/JPH04112845A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2711481A1 (en) * | 1993-10-25 | 1995-05-05 | Kioritz Corp | Chlorinated hydroxystilbenes used in nematicides, their preparation process and new dichlorohydroxystilbenes. |
| EP0739877A3 (en) * | 1995-04-27 | 1997-03-12 | Sumitomo Chemical Co | Epoxy resin, resin composition, and resin-encapsulated semiconductor device |
| US20150126690A1 (en) * | 2004-05-28 | 2015-05-07 | Dow Global Technologies Llc | Phosphorus-containing compounds useful for making halogen-free, ignition-resistant polymers |
| JP2014516973A (en) * | 2011-05-25 | 2014-07-17 | ダウ グローバル テクノロジーズ エルエルシー | Phosphorus-containing compounds useful for the production of halogen-free ignition resistant polymers |
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