JPS6254296B2 - - Google Patents
Info
- Publication number
- JPS6254296B2 JPS6254296B2 JP5847580A JP5847580A JPS6254296B2 JP S6254296 B2 JPS6254296 B2 JP S6254296B2 JP 5847580 A JP5847580 A JP 5847580A JP 5847580 A JP5847580 A JP 5847580A JP S6254296 B2 JPS6254296 B2 JP S6254296B2
- Authority
- JP
- Japan
- Prior art keywords
- general formula
- group
- formula
- compound represented
- methyl
- 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
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- 150000001875 compounds Chemical class 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 8
- 239000003125 aqueous solvent Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 150000001868 cobalt Chemical class 0.000 claims description 3
- 159000000003 magnesium salts Chemical class 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- -1 4-pentenyl group Chemical group 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- KZYVOZABVXLALY-UHFFFAOYSA-N 4-hydroxy-3-methyl-2-prop-2-enylcyclopent-2-en-1-one Chemical compound CC1=C(CC=C)C(=O)CC1O KZYVOZABVXLALY-UHFFFAOYSA-N 0.000 description 2
- HNNRFEWGWVQYNP-UHFFFAOYSA-N 4-hydroxy-4-methyl-5-prop-2-enylcyclopent-2-en-1-one Chemical compound CC1(O)C=CC(=O)C1CC=C HNNRFEWGWVQYNP-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- YIXJRHPUWRPCBB-UHFFFAOYSA-N magnesium nitrate Chemical compound [Mg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O YIXJRHPUWRPCBB-UHFFFAOYSA-N 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- ZCVAOQKBXKSDMS-AQYZNVCMSA-N (+)-trans-allethrin Chemical compound CC1(C)[C@H](C=C(C)C)[C@H]1C(=O)OC1C(C)=C(CC=C)C(=O)C1 ZCVAOQKBXKSDMS-AQYZNVCMSA-N 0.000 description 1
- FMTFEIJHMMQUJI-NJAFHUGGSA-N 102130-98-3 Natural products CC=CCC1=C(C)[C@H](CC1=O)OC(=O)[C@@H]1[C@@H](C=C(C)C)C1(C)C FMTFEIJHMMQUJI-NJAFHUGGSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- ISFGTDAAYLSOFY-UHFFFAOYSA-N 4-hydroxy-3-methyl-2-prop-2-ynylcyclopent-2-en-1-one Chemical compound CC1=C(CC#C)C(=O)CC1O ISFGTDAAYLSOFY-UHFFFAOYSA-N 0.000 description 1
- BLXRCUAXNAVKIQ-UHFFFAOYSA-N 4-hydroxy-4-methyl-5-prop-2-ynylcyclopent-2-en-1-one Chemical compound CC1(O)C=CC(=O)C1CC#C BLXRCUAXNAVKIQ-UHFFFAOYSA-N 0.000 description 1
- OUDFNZMQXZILJD-UHFFFAOYSA-N 5-methyl-2-furaldehyde Chemical compound CC1=CC=C(C=O)O1 OUDFNZMQXZILJD-UHFFFAOYSA-N 0.000 description 1
- OMIHGPLIXGGMJB-UHFFFAOYSA-N 7-oxabicyclo[4.1.0]hepta-1,3,5-triene Chemical compound C1=CC=C2OC2=C1 OMIHGPLIXGGMJB-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 238000005882 aldol condensation reaction Methods 0.000 description 1
- 229940024113 allethrin Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 229940011182 cobalt acetate Drugs 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- QAHREYKOYSIQPH-UHFFFAOYSA-L cobalt(II) acetate Chemical compound [Co+2].CC([O-])=O.CC([O-])=O QAHREYKOYSIQPH-UHFFFAOYSA-L 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 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
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 150000002696 manganese Chemical class 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- 229940099607 manganese chloride Drugs 0.000 description 1
- 239000011356 non-aqueous organic solvent Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明はシクロペンテノロン類の新規な製造方
法に関し、更に詳しくは一般式（）
〔式中、R1は炭素数６までのアルキル基、ア
ルケニル基、アルキニル基または一般式
The present invention relates to a new method for producing cyclopentenolones, more specifically, the general formula () [In the formula, R 1 is an alkyl group, alkenyl group, alkynyl group having up to 6 carbon atoms, or a general formula
【式】で示される基を表わし、こ
こにR2は水素原子、メチル基またはハロゲン原
子を表わす。〕
で示される化合物を水溶媒中、マグネシウム塩、
マンガン塩、亜鉛塩、銅塩またはコバルト塩の存
在下に処理することを特徴とする一般式（）
〔式中、R1は前述と同じ意味を表わす。〕
で示されるシクロペンテノロン類の工業的に極め
て有利な製造方法に関する。
上記一般式（）で示される化合物は、例えば
有用な農薬として知られるアレスリンのアルコー
ル成分（R1＝アリル基）など農薬、医薬の重要
な中間体であり、その一部は既に工業的に製造さ
れているものもある。
従来、一般式（）で示されるシクロペンテノ
ロン類を一般式（）で示される化合物から製造
する方法としては、
一般式（）で示される化合物に塩基性アル
ミナをベンゼン―エーテル混合溶媒中で作用さ
せる方法（G.Piancatelliら、Tetrahedron，
Vol34，2775（1978））。
一般式（）で示される化合物に５％炭酸水
素ナトリウム水を作用させる方法（特開昭53−
21146号公報）。
が知られている。
しかしながら塩基性アルミナを使用する方法で
は高価なアルミナを多量必要とし、また炭酸水素
ナトリウム水溶液を用いる方法では、一般式
（）で示される化合物が炭素水素ナトリウム水
溶液に難溶であるために、均一に分散溶解させる
には強力な撹拌を必要とし、さらに副生成物およ
び収率などの面でも問題点を有し、これらの方法
は何れも工業的には必ずしも満足のいく方法では
ない。
また、本発明方法に関連の転移反応として式
で示されるプロスタグランジン中間体に水―ジオ
キサンの混合溶媒中で1N―H2SO4を作用させる
ことにより式
で示されるプロスタグランジンを得る方法（M.
B.フロイド，ジヤーナルオブオルガニツクケミス
トリー（M.B.Floyd，J.Org.chem.）43，（No.９）
1641（1978））が知られている。しかしながら、
本発明に係わる一般式（）で示される化合物を
該反応条件で反応させた場合、副生物が多く、ま
た収率も極めて低く、一般式（）で示されるシ
クロペンテノン類の製造法には到底適用し得な
い。
このような状況の下に本発明者らは前記一般式
（）で示される化合物から、一般式（）で示
されるシクロペンテノロン類を工業的に有利に製
造する方法につき鋭意検討した結果、意外にも一
般式（）で示される化合物を水性溶媒中、金属
塩の存在下中性付近のPHで反応させることにより
容易に且つ収率よく短時間で一般式（）で示さ
れるシクロペンテノロン類が得られることを見出
し、これに種々の検討を加え本発明を完成するに
至つた。
本発明の反応機構については必ずしも明らかで
はないものの、酸触媒の場合とまつたく同一と考
えられているが、本発明は酸触媒の反応とは異な
り、中性付近で反応が行えるため、生成したシク
ロペンテノロンのアルドール縮合によると考えら
れる副成物を極度に抑制でき、しかも反応時間が
短時間ですむことを見い出したもので、このよう
な事実は極めて驚くべき事実である。以下、本発
明を具体的に説明する。
一般式（）で示される化合物においてR1の
具体例としては、メチル基、プロピル基、ヘキシ
ル基、シクロヘキシル基、アリル基、４―ペンテ
ニル基、プロパルギル基、ベンジル基、ｐ―メチ
ル―ベンジル基、ｐ―クロル―ベンジル基などが
あげられる。また、本発明で用いる金属塩は、マ
グネシウム塩、マンガン塩、亜鉛塩、銅塩または
コバルト塩であつて、例えば塩化マグネシウム、
臭化マグネシウム、硝酸マグネシウム、硫酸マグ
ネシウム、塩化マンガン、塩化亜鉛、塩化銅、硫
酸銅、酢酸コバルト、塩化コバルト等が例示され
る。
かかる金属塩の使用量は、一般式（）で示さ
れる化合物に対して0.001〜10倍モル、さらに好
ましくは0.01〜１倍モルである。
本発明におけるPHは４〜８であり、好ましくは
4.5〜7.5である。
酸性およびアルカリ性が強すぎると共にアルド
ール型の縮合物と思われる副成物が増加する。
本発明においては金属塩を水に溶解した時のPH
で反応を行うことも可能であるが、少量の塩基を
加えて各金属塩の最適PHにし、反応速度をあげる
ことも可能である。
たとえば塩化マグネシウムを使用する場合は、
塩化マグネシウムを溶解したままのPH約6.1で反
応を行つても良いが、少量の塩基を加え、PH7.3
にすると約３倍の速度で反応は進行する。
本発明に使用する水溶媒とは、実質的には水単
独または少量の非水有機溶媒（トルエン、キシレ
ン、ジイソプロピルエーテル、ベンゼンなど）ま
たは水性有機溶媒（アセトン、THF、ジオキサ
ンなど）を含んだ水性溶媒を意味する。
かかる水溶媒の使用量は、一般式（）で示さ
れる化合物に対して0.5倍〜100倍、好ましくは５
倍〜40倍重量使用するのがよい。
反応温度は通常20℃〜200℃であり、好ましく
は80℃〜150℃である。
本発明の出発原料である一般式（）で示され
る化合物は、一般式（）
R1X ……（）
〔式中、R1は前述と同じ意味を表わし、Ｘは
塩素、臭素またはヨウ素原子を表わす。〕
で示される化合物にMg、Zn、Al金属を作用さ
せ、一般式（）
R1MX ……（）
〔式中、R1、Ｘは前述の意味を表わし、Ｍは
Mg、ZnまたはAl2/3原子を表わす。〕
で示される化合物を合成した後、これを５―メチ
ルフルフラールと反応させることにより、一般式
（）
〔式中、R1は前述と同じ意味を表わす。〕
で示される化合物を得、該化合物を水および金属
塩の存在下に加温処理することにより容易に得る
ことができる。また、下記に示す特開昭53−
21146号公報に記載の方法。
さらにはG.Piancatelliらの方法
（Tetrahedron，Vol34、2775（1978））
によつても得ることができる。
以下、実施例で具体的に説明する。
実施例 １
４―ハイドロオキシ―４―メチル―５―アリル
―２―シクロペンテノン３ｇとMgCl2・6H2O4.0
ｇを水120mlに溶解した液を仕込み、100℃に昇温
した後、0.1N NaOH液でPH7.3にする。PH7.0〜
7.3を保持しながら100℃で４時間撹拌した。冷却
後NaCl40ｇを加えた後、エーテル120mlで４回抽
出した。抽出液を無水硫酸マグネシウムで乾燥
後、40℃で減圧下にエーテルを留去し、2.7ｇの
油状物を得た。次にシリカゲル30ｇを使用して酢
酸エチル―ヘキサン（１容対２容）で展開して、
２―アリル―３―メチル―４―ハイドロオキシ―
２―シクロペンテノン2.6ｇを得た。収率87％
N.M.Rデータ（CDCl3、内部標準TMS、δ
ppm、90MHz）
5.71（complex ｍ，1H，―CH2―ＣＨ＝
CHaHb）
5.06（ｍ、1H、―CH2―CH＝CHaHb）
4.93（ｍ、1H、―CH2―CH＝CHaHｂ）
4.74（broad ｄ、1H、４―Ｈ）
3.94（broad Ｓ、1H、４―ＯＨ）
2.96（ｄ、2H、―CH ２―CH＝CHaHb）
2.85（ｄ of ｄ、1H、５―Ｈ）
2.27（ｄ of ｄ、1H、５―Ｈ）
2.11（ｓ、3H、３―CH3）
実施例 ２
４―ハイドロオキシ―４―メチル―５―プロパ
ルギル―２―シクロペンテノン３ｇとMgCl2・
6H2O4.0ｇを水120mlに溶解した液を仕込み、100
℃に昇温した後、0.1N NaOH液でPH6.8にする。
PH6.8〜7.0を保持しながら100℃で４時間撹拌し
た。冷却後NaCl40ｇを加えた後、エーテル120ml
で４回抽出した。抽出液を無水硫酸マグネシウム
で乾燥後、40℃で減圧下にエーテルを留去した所
2.5ｇの油状物を得た。
次にシリカゲル30ｇを使用して酢酸エチル―ヘ
キサン（１容対２容）で展開して、２―プロパル
ギル―３―メチル―４―ハイドロキシ―２―シク
ロペンテノン2.3ｇを得た。
収率77％
N.M.Rデータ（CDCl3、内部標準TMS、δ
ppm、90MHz）
4.60（broad ｄ、1H、４―Ｈ）
3.95（broad ｓ、1H、４―ＯＨ）
3.04（ｄ、2H、―ＣＨ ２―Ｃ≡CH）
2.65（dofd、1H、５―Ｈ）
2.38（dofd、1H、５―Ｈ）
2.20（ｓ、3H、３―ＣＨ ３）
1.98（ｓ、1H、Ｃ≡ＣＨ）
実施例 ３〜10
下記３―オキソシクロペンテン化合物３ｇを使
用して下記の条件下で実施例１と同様の操作を行
い、夫々のシクロペンテノロン化合物を得た。It represents a group represented by the formula: where R 2 represents a hydrogen atom, a methyl group or a halogen atom. ] In an aqueous solvent, the compound represented by magnesium salt,
General formula () characterized by treatment in the presence of manganese, zinc, copper or cobalt salts [In the formula, R 1 represents the same meaning as above. ] This invention relates to an industrially extremely advantageous manufacturing method for cyclopentenolones shown in the following. The compound represented by the above general formula () is an important intermediate for agricultural chemicals and medicines, such as the alcohol component (R 1 = allyl group) of allethrin, which is known as a useful agricultural chemical, and some of them have already been manufactured industrially. Some have been. Conventionally, the method for producing cyclopentenolones represented by the general formula () from the compound represented by the general formula () is to treat the compound represented by the general formula () with basic alumina in a benzene-ether mixed solvent. (G. Piancatelli et al., Tetrahedron,
Vol34, 2775 (1978)). A method of reacting 5% sodium bicarbonate water on the compound represented by the general formula () (JP-A-53-
Publication No. 21146). It has been known. However, the method using basic alumina requires a large amount of expensive alumina, and the method using sodium bicarbonate aqueous solution requires that the compound represented by the general formula () is sparingly soluble in the sodium bicarbonate aqueous solution, so Dispersion and dissolution require strong stirring, and furthermore, there are problems in terms of by-products and yield, and none of these methods is necessarily industrially satisfactory. In addition, as a transfer reaction related to the method of the present invention, the formula By reacting 1N-H 2 SO 4 in a mixed solvent of water and dioxane with the prostaglandin intermediate represented by the formula How to obtain prostaglandin shown in (M.
B. Floyd, Journal of Organ Chemistry (MBFloyd, J.Org.chem.) 43 , (No.9)
1641 (1978)) is known. however,
When the compound represented by the general formula () according to the present invention is reacted under the above reaction conditions, there are many by-products and the yield is extremely low. It cannot be applied at all. Under these circumstances, the present inventors conducted intensive studies on an industrially advantageous method for producing cyclopentenolones represented by the general formula () from the compound represented by the general formula (), and as a result, unexpectedly Cyclopentenolones represented by the general formula (2) can be easily produced in a short time with good yield by reacting the compound represented by the general formula (2) in an aqueous solvent in the presence of a metal salt at a pH around neutrality. The present inventors have found that the following can be obtained, and have completed the present invention by making various studies. Although the reaction mechanism of the present invention is not necessarily clear, it is thought to be exactly the same as that of acid catalysts. It was discovered that by-products thought to be caused by aldol condensation of cyclopentenolone can be extremely suppressed, and the reaction time is short, which is an extremely surprising fact. The present invention will be specifically explained below. Specific examples of R 1 in the compound represented by the general formula () include methyl group, propyl group, hexyl group, cyclohexyl group, allyl group, 4-pentenyl group, propargyl group, benzyl group, p-methyl-benzyl group, Examples include p-chlorobenzyl group. Further, the metal salt used in the present invention is a magnesium salt, a manganese salt, a zinc salt, a copper salt or a cobalt salt, such as magnesium chloride,
Examples include magnesium bromide, magnesium nitrate, magnesium sulfate, manganese chloride, zinc chloride, copper chloride, copper sulfate, cobalt acetate, and cobalt chloride. The amount of the metal salt to be used is 0.001 to 10 times, more preferably 0.01 to 1 times, the amount of the compound represented by the general formula (). The PH in the present invention is 4 to 8, preferably
It is 4.5 to 7.5. If the acidity and alkalinity are too strong, the amount of by-products that are considered to be aldol-type condensates increases. In the present invention, the pH when the metal salt is dissolved in water is
Although it is possible to carry out the reaction with a small amount of base, it is also possible to increase the reaction rate by adding a small amount of base to the optimum pH for each metal salt. For example, when using magnesium chloride,
The reaction may be carried out at a pH of approximately 6.1 with magnesium chloride dissolved, but by adding a small amount of base, the pH may be reduced to 7.3.
The reaction proceeds about three times faster. The aqueous solvent used in the present invention is essentially water alone or an aqueous solvent containing a small amount of a non-aqueous organic solvent (toluene, xylene, diisopropyl ether, benzene, etc.) or an aqueous organic solvent (acetone, THF, dioxane, etc.). means solvent. The amount of the water solvent used is 0.5 to 100 times, preferably 5 times, the amount of the compound represented by the general formula ().
It is best to use between twice and 40 times the weight. The reaction temperature is usually 20°C to 200°C, preferably 80°C to 150°C. The compound represented by the general formula (), which is the starting material of the present invention, has the general formula () R 1 represents. [In the formula, R 1 and
Represents Mg, Zn or Al2/3 atoms. ] After synthesizing the compound represented by the formula (), by reacting it with 5-methylfurfural, the compound represented by the general formula () is synthesized. [In the formula, R 1 represents the same meaning as above. ] It can be easily obtained by heating the compound in the presence of water and a metal salt. In addition, the following JP-A-53-
The method described in Publication No. 21146. Furthermore, the method of G. Piancatelli et al. (Tetrahedron, Vol34, 2775 (1978)) It can also be obtained by Hereinafter, this will be specifically explained in Examples. Example 1 3 g of 4-hydroxy-4-methyl-5-allyl-2-cyclopentenone and MgCl 2.6H 2 O4.0
Pour a solution prepared by dissolving 1.0 g of 100 g in 120 ml of water, raise the temperature to 100°C, and then adjust the pH to 7.3 with 0.1N NaOH solution. PH7.0～
The mixture was stirred at 100°C for 4 hours while maintaining the temperature of 7.3. After cooling, 40 g of NaCl was added, followed by extraction four times with 120 ml of ether. After drying the extract over anhydrous magnesium sulfate, the ether was distilled off under reduced pressure at 40°C to obtain 2.7 g of oil. Next, using 30 g of silica gel, develop with ethyl acetate-hexane (1 volume to 2 volumes),
2-allyl-3-methyl-4-hydroxy-
2.6 g of 2-cyclopentenone was obtained. Yield 87% NMR data (CDCl 3 , internal standard TMS, δ
ppm, 90MHz) 5.71 (complex m, 1H, -CH 2 -CH =
CH a H b ) 5.06 (m, 1H, -CH 2 -CH=CH a H b ) 4.93 (m, 1H, -CH 2 -CH=CH a H b ) 4.74 (broad d, 1H, 4-H) 3.94 (broad S, 1H, 4- OH ) 2.96 (d, 2H, - CH 2 - CH=CH a H b ) 2.85 (d of d, 1H, 5-H) 2.27 (d of d, 1H, 5 -H) 2.11 (s, 3H, 3-CH 3 ) Example 2 3 g of 4-hydroxy-4-methyl-5-propargyl-2-cyclopentenone and MgCl 2 .
Prepare a solution of 4.0 g of 6H 2 O dissolved in 120 ml of water, and
After raising the temperature to ℃, adjust the pH to 6.8 with 0.1N NaOH solution.
The mixture was stirred at 100° C. for 4 hours while maintaining pH 6.8 to 7.0. After cooling, add 40g of NaCl, then add 120ml of ether.
Extracted 4 times. After drying the extract over anhydrous magnesium sulfate, the ether was distilled off under reduced pressure at 40°C.
2.5 g of oil was obtained. Next, 30 g of silica gel was developed with ethyl acetate-hexane (1 volume to 2 volumes) to obtain 2.3 g of 2-propargyl-3-methyl-4-hydroxy-2-cyclopentenone. Yield 77% NMR data ( CDCl3 , internal standard TMS, δ
ppm, 90MHz) 4.60 (broad d, 1H, 4-H) 3.95 (broad s, 1H, 4- OH ) 3.04 (d, 2H, -CH 2 -C≡CH) 2.65 (dofd, 1H, 5- H) 2.38 (dofd, 1H, 5-H) 2.20 (s, 3H, 3-C H 3 ) 1.98 (s, 1H, C≡C H ) Examples 3 to 10 Using 3 g of the following 3-oxocyclopentene compound The same operation as in Example 1 was carried out under the following conditions to obtain each cyclopentenolone compound.
【表】
実施例 11
４―ハイドロオキシ―４―メチル―５―アリル
―２―シクロペンテノン３ｇとZnCl25ｇを水120
mlに溶解した液を仕込み、100℃に昇温した後、
15時間還流下撹拌した。冷却後NaCl40ｇを加え
た後、トルエン120mlで４回抽出した。この抽出
液より50℃減圧下にトルエンを留去し、2.5ｇの
油状物を得た。次にシリカゲル30ｇを使用して酢
酸エチル―ヘキサン（１容対２容）で展開して、
実施例１で得たものと同質の２―アリル―３―メ
チル―４―ハイドロオキシ―２―シクロペンテノ
ン2.4ｇを得た。収率80％
実施例 12〜15
４―ハイドロオキシ―４―メチル―５―アリル
―２―シクロペンテノ３ｇを使用して下記の金属
塩について、下記の条件下で実施例11と同様の操
作を行い、２―アリル―３―メチル―４―ハイド
ロオキシ―２―シクロペンテノンを得た。[Table] Example 11 Add 3 g of 4-hydroxy-4-methyl-5-allyl-2-cyclopentenone and 5 g of ZnCl 2 to 120 g of water.
After preparing the solution dissolved in ml and raising the temperature to 100℃,
The mixture was stirred under reflux for 15 hours. After cooling, 40 g of NaCl was added, followed by extraction four times with 120 ml of toluene. Toluene was distilled off from this extract under reduced pressure at 50°C to obtain 2.5 g of oil. Next, using 30 g of silica gel, develop with ethyl acetate-hexane (1 volume to 2 volumes),
2.4 g of 2-allyl-3-methyl-4-hydroxy-2-cyclopentenone of the same quality as that obtained in Example 1 was obtained. Yield 80% Examples 12 to 15 Using 3 g of 4-hydroxy-4-methyl-5-allyl-2-cyclopenteno, the following metal salts were subjected to the same operation as in Example 11 under the following conditions. , 2-allyl-3-methyl-4-hydroxy-2-cyclopentenone was obtained.
Claims (1)
ルケニル基、アルキニル基または一般式
【式】で示される基を表わし、こ こにR2は水素原子、メチル基またはハロゲン原
子を表わす。〕 で示される化合物を水溶媒中、マグネシウム塩、
マンガン塩、亜鉛塩、銅塩またはコバルト塩の存
在下に処理することを特徴とする一般式 〔式中、R1は前述と同じ意味を表わす。〕 で示されるシクロペンテノロン類の製造方法。 ２ 処理を20〜200℃で行う特許請求の範囲第１
項に記載の方法。[Claims] 1. General formula [In the formula, R 1 represents an alkyl group, alkenyl group, alkynyl group having up to 6 carbon atoms, or a group represented by the general formula [Formula], and R 2 represents a hydrogen atom, a methyl group, or a halogen atom. ] In an aqueous solvent, the compound represented by magnesium salt,
General formula characterized by treatment in the presence of manganese, zinc, copper or cobalt salts [In the formula, R 1 represents the same meaning as above. ] A method for producing a cyclopentenolone. 2 Claim 1 where the treatment is carried out at 20 to 200°C
The method described in section.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5847580A JPS56154430A (en) | 1980-04-30 | 1980-04-30 | Preparation of cyclopentenolone |
| US06/256,570 US4347386A (en) | 1980-04-30 | 1981-04-22 | Process for preparing cyclopentenolones |
| HU111681A HU188043B (en) | 1980-04-30 | 1981-04-29 | Process for producing cyclopentenolene derivatives |
| DK190981A DK151796C (en) | 1980-04-30 | 1981-04-29 | PROCEDURE FOR THE PREPARATION OF CYCLOPENTENOLONS |
| DE8181103288T DE3161108D1 (en) | 1980-04-30 | 1981-04-30 | Process for preparing cyclopentenolones |
| EP19810103288 EP0039089B1 (en) | 1980-04-30 | 1981-04-30 | Process for preparing cyclopentenolones |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5847580A JPS56154430A (en) | 1980-04-30 | 1980-04-30 | Preparation of cyclopentenolone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS56154430A JPS56154430A (en) | 1981-11-30 |
| JPS6254296B2 true JPS6254296B2 (en) | 1987-11-13 |
Family
ID=13085452
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5847580A Granted JPS56154430A (en) | 1980-04-30 | 1980-04-30 | Preparation of cyclopentenolone |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS56154430A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0615486B2 (en) * | 1983-02-03 | 1994-03-02 | 住友化学工業株式会社 | Process for producing optically active 4-hydroxy-2-cyclopentenones |
| JP2518499B2 (en) * | 1992-11-30 | 1996-07-24 | 住友化学工業株式会社 | Process for producing optically active 4-hydroxy-2-cyclopentenones |
-
1980
- 1980-04-30 JP JP5847580A patent/JPS56154430A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS56154430A (en) | 1981-11-30 |
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