JPH03178973A - Production of isocumarins - Google Patents
Production of isocumarinsInfo
- Publication number
- JPH03178973A JPH03178973A JP31848989A JP31848989A JPH03178973A JP H03178973 A JPH03178973 A JP H03178973A JP 31848989 A JP31848989 A JP 31848989A JP 31848989 A JP31848989 A JP 31848989A JP H03178973 A JPH03178973 A JP H03178973A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- expressed
- reaction
- methoxycarbonylstyrenes
- isocoumarins
- 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.)
- Granted
Links
- IQZZFVDIZRWADY-UHFFFAOYSA-N isocoumarin Chemical class C1=CC=C2C(=O)OC=CC2=C1 IQZZFVDIZRWADY-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims abstract description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000001301 oxygen Substances 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 239000007789 gas Substances 0.000 claims abstract description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims abstract description 4
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 claims abstract description 4
- 150000002512 isocoumarins Chemical class 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 claims description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 3
- 229940045803 cuprous chloride Drugs 0.000 claims description 3
- 229920000166 polytrimethylene carbonate Polymers 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 3
- 229940035437 1,3-propanediol Drugs 0.000 claims 1
- -1 cyclic acetal compound Chemical class 0.000 abstract description 15
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 abstract description 7
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 abstract description 4
- MPHUYCIKFIKENX-UHFFFAOYSA-N methyl 2-ethenylbenzoate Chemical class COC(=O)C1=CC=CC=C1C=C MPHUYCIKFIKENX-UHFFFAOYSA-N 0.000 abstract description 4
- 239000002904 solvent Substances 0.000 abstract description 4
- 229910052801 chlorine Inorganic materials 0.000 abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 abstract description 3
- 150000002334 glycols Chemical class 0.000 abstract description 3
- 238000010438 heat treatment Methods 0.000 abstract description 3
- 238000007363 ring formation reaction Methods 0.000 abstract description 3
- 239000003905 agrochemical Substances 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 abstract 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 abstract 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 abstract 1
- 239000007795 chemical reaction product Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000000034 method Methods 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- IKSBUASJFRTIPW-UHFFFAOYSA-N methyl 2-ethenylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=CC=C1C=C IKSBUASJFRTIPW-UHFFFAOYSA-N 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- KDNBBIYFOJMAEN-UHFFFAOYSA-N 3-methylisochromen-1-one Chemical compound C1=CC=C2C(=O)OC(C)=CC2=C1 KDNBBIYFOJMAEN-UHFFFAOYSA-N 0.000 description 1
- VQGVFYNTGCMHGH-UHFFFAOYSA-N 5-methylisochromen-1-one Chemical compound C1=COC(=O)C2=C1C(C)=CC=C2 VQGVFYNTGCMHGH-UHFFFAOYSA-N 0.000 description 1
- CDGCXOLDNLDURP-UHFFFAOYSA-N 7-nitroisochromen-1-one Chemical compound C1=COC(=O)C2=CC([N+](=O)[O-])=CC=C21 CDGCXOLDNLDURP-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical class O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- FCSKBCLKWKBLRS-UHFFFAOYSA-N ClC1=C2C=COC(=O)C2=CC=C1 Chemical compound ClC1=C2C=COC(=O)C2=CC=C1 FCSKBCLKWKBLRS-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910052785 arsenic Inorganic materials 0.000 description 1
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003426 co-catalyst Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 125000004122 cyclic group Chemical class 0.000 description 1
- PPSZHCXTGRHULJ-UHFFFAOYSA-N dioxazine Chemical compound O1ON=CC=C1 PPSZHCXTGRHULJ-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 125000003151 isocoumarinyl group Chemical group C1(=O)OC(=CC2=CC=CC=C12)* 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- CCRCUPLGCSFEDV-UHFFFAOYSA-N methyl cinnamate Chemical compound COC(=O)C=CC1=CC=CC=C1 CCRCUPLGCSFEDV-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pyrane Compounds (AREA)
Abstract
Description
本発明は、２−メトキシ力ルホニルスチレ〉・類を出発
原料とする。イソクマリン類の製造方法に関するもので
゛ある。
イソクマリン類は、香料、医薬、農薬などの分野におい
て広範囲に使用されている化合物であり、特にイソクマ
リン類の合成原料として有用性が高いものである。The present invention uses 2-methoxysulfonylstyrene as a starting material. It concerns a method for producing isocoumarins. Isocoumarins are compounds that are widely used in the fields of fragrances, medicines, agricultural chemicals, etc., and are particularly useful as raw materials for the synthesis of isocoumarins.
イソクマリン類の合成法としては、古くから数多くの方
法か研究されてきた。例えは、２−ヒ１〜ロキシー１−
インダノンの過沃素酸による酸化によりイックマリ〉・
か得られ、ホモフタール酸エチルを金属す１〜リウムの
存在下ギ酸ニスデルと反応させた後、敢て閉環すると４
−工Ｉ−キシ力ルホニルイソクマリンを得る方法がある
が、一般に適用されるような良好な合成方法はまだ開拓
されていない。Many methods have been studied since ancient times to synthesize isocoumarins. For example, 2-Hi1~Roxy1-
Due to the oxidation of indanone with periodic acid,
is obtained, and when ethyl homophthalate is reacted with Nisdel formate in the presence of metals 1 to 3 and then ring-closed, 4 is obtained.
Although there is a method for obtaining sulfonyl isocoumarin, a generally applicable synthetic method has not yet been developed.
本発明の目的は、特にイソクマリン環の、５〜８位の位
置に少なくとも１つの置換基を有するイソクマリン類を
、高純度かつ好収率に製造する方法を提供するものであ
る。An object of the present invention is to provide a method for producing isocoumarins having at least one substituent at positions 5 to 8 of the isocoumarin ring with high purity and good yield.
すなわち、本発明は、一般式（１）
〔式中、Ｒ＋ 、Ｒ２、Ｒ３、Ｒ４は、それぞれ水素原
子、フッ素原子、塩素原子、炭素数１〜３のアルキル基
、炭素数１〜３のアルコキシ基、二Ｉ・０基などから選
ばれる１種の基を表す〕て示される２−メトキシカルボ
ニルスチレン類に塩化パラジウムと塩化第一銅および酸
素含有ガスの存在下、１．３−プロパンジオールまたは
エチレングリコールを反応させて一般式（ＩＩ）〔式中
、Ｒ＋ 、Ｒ２、Ｒ３、Ｒ４は前記定義に同し、ｎは２
または３の整数を表す〕
で示される環状アセタール化合物とした後、酸性条件下
に一般式（１１）の環状アセタールを環化することを特
徴とする一般式（Ｉｌｌ）
〔式中、Ｒ＋ 、Ｒ２、Ｒ３、Ｒ４は前記定義に同じ〕
で示されるインクマリン類の製造方法に関するものであ
る。
本発明により製造できるインクマリン類は、未置換のイ
ンクマリンおよび５〜８位の位置に少なくとも１つの置
換基を有するイソクマリンである。置換基は、フッ素原
子、塩素原子、炭素数１〜３のアルキル基、炭素数１〜
３のアルキル基、ニトロ基である。
本発明のイソクマリン類を具体的に示せは、イソクマリ
ン、７−フロロイソクマリン、５−クロロイソクマリン
、６−クロロイソクマリン、５メチルイソクマリン、６
−メチルイソクマリン、７−メチルインクマリン、８−
メチルイソクマリン、６−メドキシイソクマリン、７−
メチルイソクマリン、７−ニトキシイソクマリンおよび
７ニトロイソクマリンなどが挙けられる。
本発明の出発原料となる一般式（Ｉ）で示される２−メ
トキシカルボニルスチレン類は、２−ブロム安息香酸メ
チルエステル類にｉ！ｉｉ：酸パラジウム触媒の存在下
、エチレンガスを反応させることにより容易に製造てき
る（Ｒ，Ｆ、Ｈｅｃｋ、 ＯＢ、 Ｒｅａｃｔ、。
２７、３４．５． （１９ｇ２） ）。
本発明の第１工程は、２−メ１ヘキシカルボニルスチレ
＞類に塩ｆヒバラジウムと塩ｆヒ第−銅および酸素含有
カスの存在下にグリコール類を反応させて、一般式（Ｉ
Ｉ）で示される環状アセタールを製造することである４
、オレフィ〉ｆヒ合物をバラシム鎖体触媒を用いて酸化
Ｌカルボニルｆヒき物を得る反応は、一般にワラカー反
応と１〜で知られているが、スチレ〉・誘導体のワラカ
ー反応ではアセｌ−フェノン誘導体か得られるのか通例
である。本発明者らは、へ′ノシウムＳ１１体触媒によ
るスチレン話導体の酸化反応の研究を鋭意進めた結果、
塩化第銅を助触媒としてエチレンクリコールまたは１．
３−−−プロパンジオールのようなりリコール類の存在
下、酸素雰囲気中で２−メトキシカルボニルスチレン類
かパラジウム触媒によって環状アセタール化合物に効率
的に変換できることを見いたし本発明を完成させたもの
である。
本発明の第一の工程条件について詳しく述へれば、塩化
パラジムは２−メトキシ力ルホニルスチレ〉′類に対し
て１〜］００モル％、塩化第一銅は１〜２倍モル使用す
るのかよい。クリコール類は、２−メトキシカルボニル
スチレン類の１〜１５倍モル使用するのか好ましく、溶
媒としてはジオキザシ、テ１〜ラヒドロフラン、１，２
−シメトーＸ−シエタンが好適である。反応は、はぼ常
圧の酸素含有ガスの存在下、４０〜８０℃に加熱攪拌す
ることにより容易に進行する。反応後は、蒸留またはカ
ラムクロマトグラフィーといった一般的な精製手段て゛
、環状アセタール化合物を単離することかてきる。
本発明の第２工程は、酸性条件下に環状アセタール類を
環化する反応である。本工程はアセタールの加水分解と
環化という工程を一段階で行うものであるが、環化の方
法としては、希塩酸アルコール系、希硫酸−アルコール
系なとの鉱酸アルコール系て加熱することにより容易に
行うことができる。反応終了後、再結晶などの簡単な精
製を行うたけて高純度のイソクマリン類を得ることがで
きる。
本発明の特徴は、反応の全工程か極めて温和な反応条件
で進行するため、反応途中における置換基の転移や副生
成物の生成か少なく、出発原料として使用する２−メｌ
−キシ力ルホニルスチレ〉′類の置換基の位置かそのま
ま保持され相当するイソクマリン類を高純度かつ好収率
て得ることがてきる。
以下、実施例により本発明をより詳細に説明する。That is, the present invention is directed to the general formula (1) [wherein R+, R2, R3, and R4 are each a hydrogen atom, a fluorine atom, a chlorine atom, an alkyl group having 1 to 3 carbon atoms, or an alkoxy group having 1 to 3 carbon atoms] 1,3-propanediol or Ethylene glycol was reacted to form the general formula (II) [wherein R+, R2, R3, and R4 are as defined above, and n is 2].
or an integer of 3] [In the formula, R+, R2 , R3, and R4 are the same as defined above. Inkmarins that can be produced according to the present invention are unsubstituted inkmarins and isocoumarins having at least one substituent at the 5-8 positions. Substituents include fluorine atom, chlorine atom, alkyl group having 1 to 3 carbon atoms, and 1 to 3 carbon atoms.
3 is an alkyl group and a nitro group. Specific examples of the isocoumarins of the present invention include isocoumarin, 7-fluoroisocoumarin, 5-chloroisocoumarin, 6-chloroisocoumarin, 5-methylisocoumarin, 6-chloroisocoumarin, and 6-chloroisocoumarin.
-Methyl isocoumarin, 7-methyl inkmarin, 8-
Methylisocoumarin, 6-Medoxyisocoumarin, 7-
Examples include methylisocoumarin, 7-nitoxyisocoumarin, and 7-nitroisocoumarin. The 2-methoxycarbonylstyrenes represented by the general formula (I), which are the starting materials of the present invention, are converted into i! ii: It can be easily produced by reacting ethylene gas in the presence of an acid palladium catalyst (R, F, Heck, OB, React, 27, 34.5. (19g2)). In the first step of the present invention, 2-m-hexycarbonylstyrene is reacted with glycols in the presence of salts f hybaradium, salts f cupric arsenic, and oxygen-containing scum, and the general formula (I
I) is to produce a cyclic acetal represented by 4
The reaction to obtain L carbonyl oxide compounds using a barasym chain catalyst is generally known as the Waraker reaction and 1~, but in the Waraker reaction of the Stille derivative, the - It is customary to obtain phenone derivatives. As a result of intensive research into the oxidation reaction of styrene conductors using henosium S11 catalysts, the present inventors found that
Ethylene glycol or 1. using cupric chloride as a co-catalyst.
We have found that 2-methoxycarbonylstyrenes can be efficiently converted into cyclic acetal compounds using a palladium catalyst in the presence of a recall such as 3--propanediol in an oxygen atmosphere, and have completed the present invention. . To explain in detail the first process conditions of the present invention, palladium chloride is used in an amount of 1 to 00 mol % based on 2-methoxysulfonyl styrene, and cuprous chloride is used in an amount of 1 to 2 times the mole amount. . It is preferable to use glycols in an amount of 1 to 15 times the mole of 2-methoxycarbonylstyrenes, and examples of solvents include dioxazine, tetrahydrofuran, 1,2
-SimethoX-siethane is preferred. The reaction proceeds easily by heating and stirring at 40 to 80° C. in the presence of an oxygen-containing gas at approximately normal pressure. After the reaction, the cyclic acetal compound can be isolated by common purification means such as distillation or column chromatography. The second step of the present invention is a reaction in which cyclic acetals are cyclized under acidic conditions. This process involves the hydrolysis and cyclization of acetal in one step, but the cyclization method involves heating with a mineral acid alcohol system such as dilute hydrochloric acid-alcohol system or dilute sulfuric acid-alcohol system. It can be done easily. After the reaction is completed, highly pure isocoumarins can be obtained by simple purification such as recrystallization. The feature of the present invention is that all the steps of the reaction proceed under extremely mild reaction conditions, so there is little transfer of substituents or the formation of by-products during the reaction, and the 2-mer used as the starting material is
The position of the substituent group of -xysulfonylstyrene is maintained as is, and corresponding isocoumarins can be obtained with high purity and good yield. Hereinafter, the present invention will be explained in more detail with reference to Examples.
マクネチックスクーラーと酸素カスを入れたゴム風船を
装着した５０ｍ１三つロフラスコに、塩化パラジウム０
．２４８ ｇ （１，４ｍｍｏｌ）と塩化第一銅１、．
３８６ ｇ（Ｉ Ａ ｍｍｏｌ）を入れた。ついて、２
７メトキシカルホニルスチレン２．２６８ｇ（１４ｍｍ
ｏ１）と１，３−プロパンジオール１ｍ１（１，４ｍｍ
ｏｌ＞を溶解した１、２−ジメトキシエタン溶液２５ｍ
１をこれに加え、酸素雰囲気下５０〜６０℃で２４時間
攪拌した。反応液を冷却後、酢酸エチル１００ｍ１を加
え不溶物は濾過により除去した。
濾液はシリカゲルカラムクロマトグラフィーにかけｌ−
［（２−メトキシカルボニルフェニル）メチル］−１，
３−ジオキサン２．７０９（収率８２％）を得た。
この環状アセタール化合物１．１８０ｇ（５ｍｍｏｌ）
を１００ｍ１のエタノールに溶解し、５％塩酸５０ｍ１
を加え２時間攪拌した。反応終了後、減圧で溶媒を追い
出し、残渣をエーテルで抽出した。抽出物はベンゼン−
ヘキサンを溶媒とするシリカゲルカラムクロマトグラフ
ィーで精製し、イソクマリン５．９８６ｇ（収率８２％
）が得られた。融点を測定すると４６−４７℃（文献値
：４７°Ｃ）であり、高純度のものであることがわかっ
た。
実施例２〜８
実施例１と同様にして、各種のイソクマリン類を合成し
た。その結果を第１表に示す。
−１０−Palladium chloride 0
．． 248 g (1.4 mmol) and cuprous chloride 1,.
386 g (IA mmol) was added. Followed by 2
7 methoxycarbonylstyrene 2.268g (14mm
o1) and 1 ml of 1,3-propanediol (1,4 mm
25ml of 1,2-dimethoxyethane solution containing ol>
1 was added to this, and the mixture was stirred at 50 to 60°C for 24 hours under an oxygen atmosphere. After cooling the reaction solution, 100 ml of ethyl acetate was added and insoluble matter was removed by filtration. The filtrate was subjected to silica gel column chromatography.
[(2-methoxycarbonylphenyl)methyl]-1,
2.709 g of 3-dioxane (yield: 82%) was obtained. This cyclic acetal compound 1.180g (5mmol)
Dissolve in 100ml of ethanol and add 50ml of 5% hydrochloric acid.
was added and stirred for 2 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the residue was extracted with ether. The extract is benzene-
Purified by silica gel column chromatography using hexane as a solvent, 5.986 g of isocoumarin (yield 82%)
)was gotten. When the melting point was measured, it was 46-47°C (literature value: 47°C), indicating that it was of high purity. Examples 2 to 8 Various isocoumarins were synthesized in the same manner as in Example 1. The results are shown in Table 1. -10-
本発明により、 従来合成が困難であったイソク マリン類を高純度かつ好収率で得ることができる。 特許用願人 研ファインケミカル株式会社 ↓ According to the present invention, Isox, which was previously difficult to synthesize Marine products can be obtained with high purity and good yield. patent applicant Ken Fine Chemical Co., Ltd. ↓
Claims (1)
水素原子、フッ素原子、塩素原子、炭素数１〜３のアル
キル基、炭素数１〜３のアルコキシ基、ニトロ基などか
ら選ばれる１種の基を表す〕 で示される２−メトキシカルボニルスチレン類に塩化パ
ラジウムと塩化第一銅および酸素含有ガスの存在下、１
，３−プロパンジオールまたはエチレングリコールを反
応させて一般式（II） ▲数式、化学式、表等があります▼（II） 〔式中、Ｒ＿１、Ｒ＿２、Ｒ＿３、Ｒ＿４は前記定義に
同じ、ｎは２または３の整数を表す〕 で示される環状アセタール化合物とした後、酸性条件下
に一般式（II）の環状アセタールを環化することを特徴
とする一般式（III） 〔式中、Ｒ＿１、Ｒ＿２、Ｒ＿３、Ｒ＿４は前記定義に
同じ〕 ▲数式、化学式、表等があります▼（III） で示されるイソクマリン類の製造方法。(1) General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) represents one type of group selected from an alkyl group, an alkoxy group having 1 to 3 carbon atoms, a nitro group, etc.] In the presence of palladium chloride, cuprous chloride, and an oxygen-containing gas, 1
, 3-propanediol or ethylene glycol to form the general formula (II) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) [In the formula, R_1, R_2, R_3, R_4 are the same as the above definitions, n is 2 or represents an integer of 3] [In the formula, R_1, R_2 , R_3, and R_4 are the same as the above definitions] ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) A method for producing isocoumarins shown in (III).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1318489A JP3010264B2 (en) | 1989-12-07 | 1989-12-07 | Method for producing isocoumarins |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1318489A JP3010264B2 (en) | 1989-12-07 | 1989-12-07 | Method for producing isocoumarins |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH03178973A true JPH03178973A (en) | 1991-08-02 |
| JP3010264B2 JP3010264B2 (en) | 2000-02-21 |
Family
ID=18099688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1318489A Expired - Lifetime JP3010264B2 (en) | 1989-12-07 | 1989-12-07 | Method for producing isocoumarins |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3010264B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013516392A (en) * | 2009-12-30 | 2013-05-13 | ザンナン・サイテック・カンパニー・リミテッド | Highly efficient metathesis catalyst for ROMP and RCM reaction |
| CN103224482A (en) * | 2013-04-10 | 2013-07-31 | 上海交通大学 | Isocoumarin compound, derivatives and synthesis method thereof |
| JP2018012804A (en) * | 2016-07-22 | 2018-01-25 | Jnc株式会社 | Liquid crystalline compound having benzopyran skeleton, liquid crystal composition, and liquid crystal display element |
-
1989
- 1989-12-07 JP JP1318489A patent/JP3010264B2/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013516392A (en) * | 2009-12-30 | 2013-05-13 | ザンナン・サイテック・カンパニー・リミテッド | Highly efficient metathesis catalyst for ROMP and RCM reaction |
| CN103224482A (en) * | 2013-04-10 | 2013-07-31 | 上海交通大学 | Isocoumarin compound, derivatives and synthesis method thereof |
| JP2018012804A (en) * | 2016-07-22 | 2018-01-25 | Jnc株式会社 | Liquid crystalline compound having benzopyran skeleton, liquid crystal composition, and liquid crystal display element |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3010264B2 (en) | 2000-02-21 |
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