JPH0436141B2 - - Google Patents
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- Publication number
- JPH0436141B2 JPH0436141B2 JP59034350A JP3435084A JPH0436141B2 JP H0436141 B2 JPH0436141 B2 JP H0436141B2 JP 59034350 A JP59034350 A JP 59034350A JP 3435084 A JP3435084 A JP 3435084A JP H0436141 B2 JPH0436141 B2 JP H0436141B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- group
- examples
- reaction
- 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.)
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- -1 enamine compound Chemical class 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 239000002841 Lewis acid Substances 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 150000007517 lewis acids Chemical class 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 6
- 150000001728 carbonyl compounds Chemical class 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- YQBZNNFVXOBDSJ-UHFFFAOYSA-N 2-[hydroxy(phenyl)methyl]cyclohexan-1-one Chemical compound C=1C=CC=CC=1C(O)C1CCCCC1=O YQBZNNFVXOBDSJ-UHFFFAOYSA-N 0.000 description 3
- 229910015900 BF3 Inorganic materials 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 2
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 2
- 125000006017 1-propenyl group Chemical group 0.000 description 2
- PWGCXMRFKHCNES-UHFFFAOYSA-N 2-(1-hydroxy-2-methylpropyl)hexanal Chemical compound CCCCC(C=O)C(O)C(C)C PWGCXMRFKHCNES-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical group O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 125000006023 1-pentenyl group Chemical group 0.000 description 1
- FHZKOZKYUQDWBE-UHFFFAOYSA-N 2-(1-hydroxy-2-methylpropyl)cyclohexan-1-one Chemical compound CC(C)C(O)C1CCCCC1=O FHZKOZKYUQDWBE-UHFFFAOYSA-N 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical class [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- LVZGQWKTUCVPBQ-UHFFFAOYSA-N acetic acid;trifluoroborane Chemical compound CC(O)=O.FB(F)F LVZGQWKTUCVPBQ-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000005882 aldol condensation reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- ZXIJMRYMVAMXQP-UHFFFAOYSA-N cycloheptene Chemical compound C1CCC=CCC1 ZXIJMRYMVAMXQP-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 150000002466 imines Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 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
Description
本発明は、公知化合物β−ヒドロキシカルボニ
ル化合物類とくに下記式(1)
但し式中、R1及びR2は、夫々、水素原子、ア
ルキル基、アルケニル基もしくはアリール基を示
すか、或はR1及びR2は一緒になつて（−CH2）−o
〔ここで、ｎは３〜５の整数を示す〕を示し、そ
して、R5は水素原子、アルキル基、アルケニル
基もしくはアリール基を示す、
で表わされる香料、農薬、医薬などの分野におけ
る合成中間体として重要なβ−ヒドロキシカルボ
ニル化合物類の製法に関し、従来法における副生
物の生成のトラブルを回避でき、且つ従来法に比
して簡単な操作及び安価且つ入手容易な原料を用
いて、好収率をもつ工業的に有利に、上記式(1)β
−ヒドロキシカルボニル化合物を新しい合成径路
で製造できる製法に関する。
更に詳しくは、本発明は下記式(2)
但し式中、R1およびR2は、夫々、水素原子、
アルキル基、アルケニル基もしくはアリール基を
示すか、或はR1及びR2は一緒になつて（−CH2）−o
〔ここで、ｎは３〜５の整数を示す〕を示し、そ
して、R3およびR4は、夫々、アルキル基もしく
はフエニル基を示すか、或はR3及びR4は一緒に
なつて（−CH2）−n〔ここで、ｍは４又は５を示す〕
もしくは（−CH2）−2Ｏ
（−CH2）−2を示す、
で表わされるエナミン化合物と、下記式(3)
R5CHO (3)
但し式中、R5は水素原子、アルキル基、アル
ケニル基もしくはアリール基を示す、
で表わされるアルデヒド類とを、ルイス酸の存在
下に接触せしめることを特徴とする下記式(1)
但し式中、R1、R2及びR5は前記したと同義、
で表わされるβ−ヒドロキシカルボニル化合物類
の製法に関する。
従来、式(1)β−ヒドロキシカルボニル化合物類
の合成法として、種々の合成法が提案されてい
る。例えば塩基性条件下にカルボニル化合物どう
しによるアルドール縮合反応を利用する方法、イ
ミンとカルボニル化合物との反応を利用する方
法、又、酸性条件下の反応としては、例えばシリ
ールエノールエーテル、エノールエステルあるい
はエノールエーテルとカルボニル化合物との反応
を利用する合成法が知られている。
しかしながら、上記従来提案に於いては、副生
成物の生成が回避し難く、又、反応に用いる原料
が高価であり且その合成が煩雑であつて工業的製
法には適さない欠点がある。
本発明者等は、上述のような従来提案の不利益
乃至欠陥を克服して工業的に有利に式(1)のβ−ヒ
ドロキシカルボニル化合物類を製造できる新しい
合成経路を開発すべく研究を行つてきた。
その結果、工業的に容易に合成でき且つ安価な
前記式(2)エナミン化合物と前記式(3)アルデヒド類
とを、ルイス酸の存在下に接触せしめるという新
しい合成経路によつて、安易な操作で且つ好収率
をもつて式(1)化合物を工業的に有利に製造できる
ことを発見した。
従つて、本発明の目的は、新しい合成経路によ
つて式(1)化合物を工業的に有利に製造できる式(1)
化合物の製造を提供するにある。
本発明の上記目的及び更に多くの他の目的なら
びに利点は以下の記載から一層明らかとなるであ
ろう。
本発明によれば、前記式(2)エナミン化合物と前
記式(3)アルデヒド類とをルイス酸の存在下に接触
させることにより、一挙に式(1)目的化合物を形成
することができる。該式(2)エナミン化合物は、た
とえば、対応するカルボニル化合物とアミンとを
触媒の存在下に常法に従つて反応させることによ
り容易に合成することができる。
上記式(2)エナミン化合物形成工程を含めて、本
発明方法を図式的に示すと、以下のように示すこ
とができる。
上記に於て、R1、R2、R3、R4、R5は前記した
と同義である。上記例に於て、式(4)カルボニル化
合物と式(5)アミンの反応は、それ自体公知のエナ
ミン化合物合成法に従つて〔（文献例：G.Stork
etal.，J.Am.Chem.Soc.，85、207（1963）〕、たと
えば炭酸カリウム、ｐ−トルエンスルホン酸など
の如き触媒の存在下に、式(4)化合物と式(5)化合物
とを接触せしめることにより容易に行うことがで
きる。
例えば、シクロヘキサノン（1.5モル）、モルホ
リン（1.8モル）およびｐ−トルエンスルホン酸
（1.5ｇ）のトルエン（300ml）の溶液を加熱還流
し、共沸する水を除去することにより、１−（Ｎ
−モルホリノ）−１−シクロヘキセンを約80％の
収率で得ることができる。
例えば、上述のようにして得ることのできる式
(2)エナミン化合物に於いて、R1及びR2のアルキ
ル基の例としては、メチル、エチル、プロピル、
イソプロピル、ブチル、イソブチルなどの如き
C1〜C4の直鎖もしくは分枝のアルキル基を例示
することができる。又、アルケニル基の例として
は、ビニル、１−プロペニル、イソプロペニル、
２−メチル−１−プロペニル、１−ブテニル、６
−メチル−５−ヘプテン−２−イルなどの如き
C2〜C8の直鎖もしくは分枝のアルケニル基を例
示することができる。更に、アリール基としては
フエニル基などの如きアリール基を例示すること
ができる。更に、R1及びR2は一緒になつて、−
（CH2）3−〔シクロペンテン〕、−（CH2）4−〔シクロ
ヘキセン〕又は−（CH2）5−〔シクロヘプテン〕を
示すことができる。
このような式(2)化合物の例としては、たとえ
ば、１−（Ｎ−モルホリノ）−１−シクロヘキセ
ン、１−（Ｎ−ピロリジノ）−１−シクロヘキセ
ン、１−（Ｎ−ピペリジノ）−１−シクロヘキセ
ン、５−メチル−２−（Ｎ−モルホリノ）−２，４
−ヘキサジエン、３−メチル−１−（Ｎ−モルホ
リノ）−１−ブテン、α−（Ｎ−モルホリノ）スチ
レン、３，７−ジメチル−１−（Ｎ−モルホリノ）
−１，６−オクタジエン、１−（Ｎ−モルホリノ）
−１−シクロペンテン、１−（Ｎ−モルホリノ）−
１−ヘキセン、１−（Ｎ−ピペリジノ）−１−ヘキ
セン、１−（Ｎ−モルホリノ）−１−プロペンなど
を例示することができる。
本発明方法によれば、上記の如き式(2)エナミン
化合物と、式(3)化合物とを、ルイス酸の存在下に
接触せしめて式(1)目的化合物を得ることができ
る。
上記反応は、好ましくはハロゲン系有機溶媒中
で、ルイス酸の存在下に式(2)化合物と式(3)化合物
とを接触せしめることにより行うことができる。
反応温度は適当に選択できるが、例えば約−20℃
〜約50℃、より好ましくは約０℃〜約30℃の如き
反応温度が例示できる。又、反応時間は適宜に選
択でき、たとえば約0.1時間〜約10時間、より好
ましくは約0.5時間〜約１時間程度の反応時間を
例示することができる。反応に際して、式(2)化合
物に対する式(3)化合物の使用量も適宜に選択で
き、例えば、式(2)化合物１モルに対して式(3)化合
物約１〜約1.5モル程度の使用量を例示すること
ができる。更に、ルイス酸の使用量も適宜に選択
でき、例えば式(2)化合物１モルに対して約1.1〜
1.5モル程度、より好ましくは約1.3モル前後の使
用量を例示することができる。
さらに、上記ハロゲン系有機溶媒の例として
は、例えば、ジクロロメタン、クロロホルム、
１，１−ジクロロエタン、１，２−ジクロロエタ
ン、トリクロロエチレン、あるいはこれらの適当
な混合物例を例示できる。これらの有機溶媒の使
用量には特別の制約はなく適宜に選択でき、式(2)
化合物に対し例えば、約５〜約20重量倍程度の範
囲が例示できる。又、ルイス酸の例としては、四
塩化チタン、四塩化スズ、塩化アルミニウム、塩
化亜鉛、三フツ化ホウ素エーテル錯体、臭化亜
鉛、三フツ化ホウ素酢酸錯体、などを挙げること
ができる。
上記(2)エナミン化合物との反応に用いる式(3)化
合物に於て、R5のアルキル基の例としては例え
ば、メチル、エチル、プロピル、イソプロピル、
ブチル、イソブチル、ペンチル、ヘキシル、ヘプ
チル、オクチルなどの如きC1〜C8のアルキル基
を例示することができる。又アルケニル基の例と
しては、例えば、１−プロペニル、イソプロペニ
ル、１−ブテニル、１−ペンテニル、２，６−ジ
メチル−５−ヘプテニルなどの如きC2〜C8のア
ルケニル基を挙げることができる。更に又、アリ
ール基の具体例としては、例えばフエニル、ベン
ジルフエネチル、３，４−メチレンジオキシフエ
ニルなどが例示できる。反応生成物は、溶媒を留
去したのち、所望によりシリカゲルカラムクロマ
トグラフイーや減圧蒸留等の手段で精製すること
ができる。
本発明方法によれば上記式(1)β−ヒドロキシカ
ルボニル化合物が、容易な操作で、安価且つ入手
容易な原料を用いて好収率で工業的に有利に得ら
れる。
上述のようにして得られた式(1)化合物の例とし
ては、たとえば以下の如き化合物、その他後記実
施例に示すような化合物を例示することができ
る。２−（α−ヒドロキシベンジル）シクロヘキ
サノン、２−（１−ヒドロキシ−２−ブテニル）−
シクロヘキサノン、２−（１−ヒドロキシ−２−
メチルプロピル）シクロヘキサノン、４−ヒドロ
キシ−３−（２−メチル−１−プロペニル）−４−
フエニル−２−ブタノン、４−ヒドロキシ−３−
（２−メチル−１−プロペニル）−２−ノナノン、
４−ホルミル−２−メチル−３−オクタノール、
４−ホルミル−１−フエニル−３−オクタノー
ル、４−ホルミル−５，９−ジメチル−８−デセ
ン−３−オール、６−ホルミル−７，11−ジメチ
ル−10−ドデセン−５−オール、２−ホルミル−
１−（３，４−メチレンジオキシフエニル）−１−
プロパノール。
次に、実施例により、本発明方法実施の数態様
を説明する。
実施例 １
２−（α−ヒドロキシベンジル）シクロヘキサノ
ンの合成
ベンズアルデヒド（1.27ｇ、12mmol）の塩化
メチレン（20ml）溶液を−40℃に冷却し、三フツ
化ホウ素エーテル錯体（1.85ｇ、13mmol）を加
え、引き続き１−（Ｎ−モルホリノ）−１−シクロ
ヘキセン（1.67ｇ、10mmol）を加え、更に室温
に戻して30分間かくはんする。反応後、水を加
え、室温下で１時間かくはんする。有機層を分離
して洗浄し、更に重ソウ水で洗浄後、乾燥、濃縮
する。残渣をシリカゲルカラムクロマトグラフイ
ーで分離精製することにより、２−（α−ヒドロ
キシベンジル）シクロヘキサノンのスレオ体1.46
ｇ（72％）、エリスロ体0.42ｇ（20％）を得た。
合計収率92％
実施例 ２
４−ホルミル−２−メチル−３−オクタノールの
合成
イソブチルアルデヒド（0.432ｇ、6mmol）の
塩化メチレン（10ml）溶液を−40℃に冷却し、三
フツ化ホウ素エーテル錯体（0.923ｇ、6.5mmol）
を加え、更に１−（Ｎ−モルホリノ）−１−ヘキセ
ン（0.845ｇ、5mmol）を加えたのち室温で１時
間かくはんする。反応後、水を加え室温下１時間
かくはんしたのち、有機層を分離洗浄し、更に重
ソウ水で洗浄する。乾燥、濃縮ししたのち残渣を
シリカゲルカラムクロマトグラフイーで分離精製
することにより４−ホルミル−２−メチル−３−
オクタノールのスレオ体、エリスロ体の混合物を
0.622ｇ（72％）を得た。
実施例 ３〜16
前記実施例１〜２と同様にして、後掲表−１に
示した式(2)エナミン化合物、式(3)化合物およびル
イス酸を用いて各種のβ−ヒドロキシカルボニル
化合物類を合成した。その結果を表−１に示す。
The present invention relates to known compounds β-hydroxycarbonyl compounds, particularly those represented by the following formula (1). However, in the formula, R 1 and R 2 each represent a hydrogen atom, an alkyl group, an alkenyl group, or an aryl group, or R 1 and R 2 together represent (-CH 2 ) -o
[Here, n represents an integer of 3 to 5], and R 5 represents a hydrogen atom, an alkyl group, an alkenyl group, or an aryl group. Regarding the production of β-hydroxycarbonyl compounds, which are important for human body, it avoids the trouble of producing by-products in conventional methods, and has a high yield by using simpler operations and cheaper and easily available raw materials than conventional methods. Industrially advantageously, the above formula (1) β
- A method for producing hydroxycarbonyl compounds using a new synthetic route. More specifically, the present invention is based on the following formula (2) However, in the formula, R 1 and R 2 are each a hydrogen atom,
represents an alkyl, alkenyl or aryl group, or R 1 and R 2 taken together (-CH 2 ) -o
[Here, n represents an integer of 3 to 5], and R 3 and R 4 each represent an alkyl group or a phenyl group, or R 3 and R 4 taken together ( -CH 2 ) - n [Here, m indicates 4 or 5]
or (-CH 2 )- 2 O (-CH 2 )- 2 and an enamine compound represented by the following formula (3) R 5 CHO (3) where R 5 is a hydrogen atom, an alkyl group, The following formula (1) is characterized by contacting an aldehyde represented by an alkenyl group or an aryl group in the presence of a Lewis acid. However, in the formula, R 1 , R 2 and R 5 have the same meanings as described above, and relate to a method for producing β-hydroxycarbonyl compounds represented by the following. Conventionally, various synthetic methods have been proposed as methods for synthesizing β-hydroxycarbonyl compounds of formula (1). For example, a method using an aldol condensation reaction between carbonyl compounds under basic conditions, a method using a reaction between an imine and a carbonyl compound, and a method using a reaction under acidic conditions such as silyl enol ether, enol ester, or enol A synthetic method using a reaction between an ether and a carbonyl compound is known. However, in the above-mentioned conventional proposals, it is difficult to avoid the production of by-products, and the raw materials used for the reaction are expensive and the synthesis thereof is complicated, making them unsuitable for industrial production methods. The present inventors have conducted research to overcome the disadvantages and defects of the conventional proposals as described above and to develop a new synthetic route that can industrially advantageously produce β-hydroxycarbonyl compounds of formula (1). It came. As a result, a new synthetic route in which the enamine compound of the formula (2), which can be easily synthesized industrially and is inexpensive, and the aldehyde of the formula (3) are brought into contact in the presence of a Lewis acid, enables easy operation. It has been discovered that the compound of formula (1) can be industrially advantageously produced with a good yield. Therefore, an object of the present invention is to obtain a compound of formula (1) that can be industrially advantageously produced by a new synthetic route.
Provides for the production of compounds. The above objects and many other objects and advantages of the present invention will become more apparent from the following description. According to the present invention, the target compound of formula (1) can be formed all at once by bringing the enamine compound of formula (2) and the aldehyde of formula (3) into contact in the presence of a Lewis acid. The enamine compound of formula (2) can be easily synthesized, for example, by reacting a corresponding carbonyl compound and an amine in the presence of a catalyst according to a conventional method. The method of the present invention, including the step of forming the enamine compound of formula (2) above, can be schematically illustrated as follows. In the above, R 1 , R 2 , R 3 , R 4 and R 5 have the same meanings as described above. In the above example, the reaction between the carbonyl compound of formula (4) and the amine of formula (5) was carried out in accordance with the enamine compound synthesis method known per se [(Literature example: G. Stork
etal., J.Am.Chem.Soc., 85 , 207 (1963)], a compound of formula (4) and a compound of formula (5) in the presence of a catalyst such as potassium carbonate, p-toluenesulfonic acid, etc. This can be easily done by bringing them into contact with each other. For example, 1-(N
-morpholino)-1-cyclohexene can be obtained in a yield of about 80%. For example, the formula that can be obtained as above
(2) Examples of alkyl groups for R 1 and R 2 in enamine compounds include methyl, ethyl, propyl,
Such as isopropyl, butyl, isobutyl, etc.
Examples include C 1 -C 4 straight chain or branched alkyl groups. Examples of alkenyl groups include vinyl, 1-propenyl, isopropenyl,
2-methyl-1-propenyl, 1-butenyl, 6
-such as methyl-5-hepten-2-yl, etc.
Examples include C2 - C8 straight-chain or branched alkenyl groups. Furthermore, examples of the aryl group include aryl groups such as phenyl group. Furthermore, R 1 and R 2 together are −
It can represent ( CH2 ) 3- [cyclopentene], -( CH2 ) 4- [cyclohexene] or -( CH2 ) 5- [cycloheptene]. Examples of such compounds of formula (2) include 1-(N-morpholino)-1-cyclohexene, 1-(N-pyrrolidino)-1-cyclohexene, and 1-(N-piperidino)-1-cyclohexene. , 5-methyl-2-(N-morpholino)-2,4
-Hexadiene, 3-methyl-1-(N-morpholino)-1-butene, α-(N-morpholino)styrene, 3,7-dimethyl-1-(N-morpholino)
-1,6-octadiene, 1-(N-morpholino)
-1-cyclopentene, 1-(N-morpholino)-
Examples include 1-hexene, 1-(N-piperidino)-1-hexene, and 1-(N-morpholino)-1-propene. According to the method of the present invention, the target compound of formula (1) can be obtained by bringing the enamine compound of formula (2) as described above into contact with the compound of formula (3) in the presence of a Lewis acid. The above reaction can be carried out by bringing the compound of formula (2) and the compound of formula (3) into contact in the presence of a Lewis acid, preferably in a halogenated organic solvent.
The reaction temperature can be selected appropriately, for example about -20℃
For example, the reaction temperature may be from about 50°C to about 50°C, more preferably from about 0°C to about 30°C. Further, the reaction time can be selected as appropriate, for example, about 0.1 hour to about 10 hours, more preferably about 0.5 hour to about 1 hour. During the reaction, the amount of the compound of formula (3) to be used relative to the compound of formula (2) can be selected as appropriate; for example, the amount of the compound of formula (3) to be used is about 1 to about 1.5 mol per 1 mol of the compound of formula (2). can be exemplified. Furthermore, the amount of Lewis acid to be used can be selected as appropriate, for example from about 1.1 to 1 mole of the compound of formula (2).
An example of an amount used is about 1.5 mol, more preferably about 1.3 mol. Furthermore, examples of the halogenated organic solvents include dichloromethane, chloroform,
Examples include 1,1-dichloroethane, 1,2-dichloroethane, trichloroethylene, or a suitable mixture thereof. There is no particular restriction on the amount of these organic solvents to be used, and they can be selected as appropriate, and formula (2)
For example, the amount may be about 5 to about 20 times the weight of the compound. Examples of Lewis acids include titanium tetrachloride, tin tetrachloride, aluminum chloride, zinc chloride, boron trifluoride ether complex, zinc bromide, and boron trifluoride acetic acid complex. In the compound of formula (3) used in the reaction with the enamine compound (2) above, examples of the alkyl group for R 5 include methyl, ethyl, propyl, isopropyl,
Examples include C1 - C8 alkyl groups such as butyl, isobutyl, pentyl, hexyl, heptyl, octyl and the like. Examples of alkenyl groups include C2 to C8 alkenyl groups such as 1-propenyl, isopropenyl, 1-butenyl, 1-pentenyl, 2,6-dimethyl-5-heptenyl, and the like. . Furthermore, specific examples of the aryl group include phenyl, benzylphenethyl, 3,4-methylenedioxyphenyl, and the like. After distilling off the solvent, the reaction product can be purified, if desired, by means such as silica gel column chromatography or vacuum distillation. According to the method of the present invention, the β-hydroxycarbonyl compound of the formula (1) can be industrially advantageously obtained in good yield with easy operation and using inexpensive and easily available raw materials. Examples of the compound of formula (1) obtained as described above include the following compounds and other compounds shown in Examples below. 2-(α-hydroxybenzyl)cyclohexanone, 2-(1-hydroxy-2-butenyl)-
Cyclohexanone, 2-(1-hydroxy-2-
methylpropyl)cyclohexanone, 4-hydroxy-3-(2-methyl-1-propenyl)-4-
Phenyl-2-butanone, 4-hydroxy-3-
(2-methyl-1-propenyl)-2-nonanone,
4-formyl-2-methyl-3-octanol,
4-formyl-1-phenyl-3-octanol, 4-formyl-5,9-dimethyl-8-decen-3-ol, 6-formyl-7,11-dimethyl-10-dodecen-5-ol, 2- Formyl-
1-(3,4-methylenedioxyphenyl)-1-
Propanol. Examples now illustrate several aspects of carrying out the method of the invention. Example 1 Synthesis of 2-(α-hydroxybenzyl)cyclohexanone A solution of benzaldehyde (1.27 g, 12 mmol) in methylene chloride (20 ml) was cooled to -40°C, and boron trifluoride ether complex (1.85 g, 13 mmol) was added. Then, 1-(N-morpholino)-1-cyclohexene (1.67 g, 10 mmol) was added, and the mixture was returned to room temperature and stirred for 30 minutes. After the reaction, water is added and stirred at room temperature for 1 hour. The organic layer is separated and washed, further washed with hydrogenated sodium hydroxide solution, dried and concentrated. By separating and purifying the residue using silica gel column chromatography, the threo isomer 1.46 of 2-(α-hydroxybenzyl)cyclohexanone was obtained.
g (72%) and 0.42 g (20%) of erythro form were obtained.
Total yield 92% Example 2 Synthesis of 4-formyl-2-methyl-3-octanol A solution of isobutyraldehyde (0.432 g, 6 mmol) in methylene chloride (10 ml) was cooled to -40°C, and a boron trifluoride ether complex was prepared. (0.923g, 6.5mmol)
After adding 1-(N-morpholino)-1-hexene (0.845 g, 5 mmol), the mixture was stirred at room temperature for 1 hour. After the reaction, water was added and the mixture was stirred at room temperature for 1 hour, and then the organic layer was separated and washed, and further washed with hydrogenated sodium chloride water. After drying and concentrating, the residue was separated and purified using silica gel column chromatography to obtain 4-formyl-2-methyl-3-
A mixture of threo and erythro octanol
0.622g (72%) was obtained. Examples 3 to 16 In the same manner as in Examples 1 to 2, various β-hydroxycarbonyl compounds were prepared using the enamine compound of formula (2), the compound of formula (3), and Lewis acid shown in Table 1 below. Synthesized. The results are shown in Table-1.
【表】【table】
【表】【table】
Claims (1)
アルキル基、アルケニル基もしくはアリール基を
示すか、或はR1及びR2は一緒になつて（−CH2）−o
〔ここで、ｎは３〜５の整数を示す〕を示し、そ
して、R3およびR4は、夫々、アルキル基もしく
はフエニル基を示すか、或はR3及びR4は一緒に
なつて（−CH2）−n〔ここで、ｍは４又は５を示す〕
もしくは（−CH2）−2Ｏ （−CH2）−2を示す、 で表わされるエナミン化合物と、下記式(3) R5CHO (3) 但し式中、R５は水素原子、アルキル基、アル
ケニル基もしくはアリール基を示す、 で表わされるアルデヒド類とを、ルイス酸の存在
下に接触せしめることを特徴とする下記式(1) 但し式中、R1、R2及びR５は前記したと同義、 で表わされるβ−ヒドロキシカルボニル化合物類
の製法。[Claims] 1. The following formula (2) However, in the formula, R 1 and R 2 are each a hydrogen atom,
represents an alkyl, alkenyl or aryl group, or R 1 and R 2 taken together (-CH 2 ) -o
[Here, n represents an integer of 3 to 5], and R 3 and R 4 each represent an alkyl group or a phenyl group, or R 3 and R 4 taken together ( -CH 2 ) - n [Here, m indicates 4 or 5]
or (-CH 2 )- 2 O (-CH 2 )- 2 and an enamine compound represented by the following formula (3) R 5 CHO (3) where R5 is a hydrogen atom, an alkyl group, or an alkenyl group. The following formula (1) is characterized by contacting an aldehyde represented by a group or an aryl group in the presence of a Lewis acid. However, in the formula, R 1 , R 2 and R5 have the same meanings as described above.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59034350A JPS60178838A (en) | 1984-02-27 | 1984-02-27 | Production of beta-hydroxycarbonyl compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59034350A JPS60178838A (en) | 1984-02-27 | 1984-02-27 | Production of beta-hydroxycarbonyl compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60178838A JPS60178838A (en) | 1985-09-12 |
| JPH0436141B2 true JPH0436141B2 (en) | 1992-06-15 |
Family
ID=12411698
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59034350A Granted JPS60178838A (en) | 1984-02-27 | 1984-02-27 | Production of beta-hydroxycarbonyl compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60178838A (en) |
-
1984
- 1984-02-27 JP JP59034350A patent/JPS60178838A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60178838A (en) | 1985-09-12 |
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