JP2004203844A - Method for production of 2-(alkylidene)cycloalkanone - Google Patents
Method for production of 2-(alkylidene)cycloalkanone Download PDFInfo
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Abstract
Description
【０００１】
【発明の属する技術分野】
本発明は香料素材として有用なジヒドロジャスモン酸メチル、δ−ラクトン等の中間体である２−（アルキリデン）シクロアルカノンの製法、並びにそれを用いた、アルキル（３−オキソ−２−アルキルシクロアルキル）アセテート及び５−アルキル−５−アルカノリドの製法に関する。
【０００２】
【従来の技術】
従来、２−（１−ヒドロキシアルキル）シクロアルカノンから２−（アルキリデン）シクロアルカノンを製造する際には、脱水反応触媒として均一系の酸触媒が一般的に用いられている。
【０００３】
例えば特許文献１では、２−（アルキリデン）シクロアルカノンを得るために、アルドール縮合体にシュウ酸を添加して脱水反応を行っているが、反応後にアルカリによる中和、分層が必要であり、工程が多く、排水も生じる。また、酸により設備が腐食したり、アルカリによる中和時に２−（アルキリデン）シクロアルカノンが重合および分解し収率が低下する場合もある。
【０００４】
さらに、このような重合および分解のため、これを用いて合成されるアルキル（３−オキソ−２−アルキルシクロアルキル）アセテートや５−アルキル−５−アルカノリドの匂いの低下が生じる場合がある。
【０００５】
【特許文献１】
特開昭５６−１４７７４０号公報
【０００６】
【発明が解決しようとする課題】
本発明の課題は、２−（アルキリデン）シクロアルカノンを効率的に高収率で製造する方法、並びにそれを用いた香料素材や生理活性物質として有用なアルキル（３−オキソ−２−アルキルシクロアルキル）アセテート及び５−アルキル−５−アルカノリドの製法を提供することにある。
【０００７】
【課題を解決するための手段】
本発明は、式（１）
【０００８】
【化７】
（式中、ｎは１又は２の整数、Ｒ1及びＲ2はそれぞれ、水素原子又は炭素数１〜８の直鎖もしくは分岐鎖のアルキル基を示すか、あるいはＲ1とＲ2が一緒になって隣接する炭素原子と共にシクロペンタン環もしくはシクロヘキサン環を形成してもよい。）
で表される２−（１−ヒドロキシアルキル）シクロアルカノン（以下化合物（１）という）を、固体酸触媒を用いて脱水反応させる、式（２）
【００１０】
【化８】
（式中、ｎ、Ｒ1及びＲ2は前記の意味を示す。）
で表される２−（アルキリデン）シクロアルカノン（以下化合物（２）という）の製法を提供する。
【００１２】
また、本発明は、上記の製法で得られた化合物（２）を異性化反応させるか、又は化合物（１）を含有する化合物（２）を脱水反応させつつ異性化反応させて、式（３）
【００１３】
【化９】
（式中、ｎ、Ｒ1及びＲ2は前記の意味を示す。）
で表される２−（アルキル）シクロアルケノン（以下化合物（３）という）とし、次いで式（４）
【００１５】
【化１０】
（式中、Ｒ3は炭素数１〜３の直鎖又は分岐鎖のアルキル基を示し、２個のＲ3は同一でも異なっていてもよい。）
で表されるマロン酸ジエステル（以下化合物（４）という）とを反応させ、次いで水を反応させる、式（５）
【００１７】
【化１１】
（式中、ｎ、Ｒ1、Ｒ2及びＲ3は前記の意味を示す。）
で表されるアルキル（３−オキソ−２−アルキルシクロアルキル）アセテート（以下化合物（５）という）の製法、並びに上記製法で得られた化合物（２）を異性化反応させるか、又は化合物（１）を含有する化合物（２）を脱水反応させつつ異性化反応させて、化合物（３）とし、次いで水素還元させた後、バイヤービリガー酸化させる、式（６）で表される５−アルキル−５−アルカノリド（以下化合物（６）という）の製法を提供する。
【００１９】
【化１２】
（式中、ｎ、Ｒ1及びＲ2は前記の意味を示す。）
【００２１】
【発明の実施の形態】
［化合物（２）の製法］
本発明の原料として用いられる、化合物（１）において、１−ヒドロキシアルキル基を構成するアルキル基としては、例えば、メチル基、エチル基、プロピル基、イソプロピル基、ブチル基、イソブチル基、アミル基、イソアミル基、ヘキシル基、ヘプチル基等が挙げられる。
【００２２】
この化合物（１）は、一般的に公知の方法により製造でき、例えば炭素数５又は６のシクロアルカノンと、式（７）
【００２３】
【化１３】
（式中、Ｒ1及びＲ2は前記の意味を示す。）
で表されるアルデヒド又はケトンを反応させることにより得ることができる。本発明では、このような方法で得られる化合物（１）を蒸留せずに用いることもできるが、固体酸触媒の活性が低下する場合は蒸留精製して使用してもよい。
【００２５】
本発明に用いられる固体酸触媒としては、ＡｌＰＯ4、Ａｌ2Ｏ3、活性アルミナ、硫酸ジルコニア、トリポリリン酸二水素アルミニウム、ＴｉＯ2等の無機金属固体触媒や、カチオン交換樹脂、ＳｉＯ2−ＴｉＯ2、ＳｉＯ2−ＣａＯ、ＳｉＯ2−ＭｇＯ、ゼオライト等を用いることができ、ＡｌＰＯ4、ＴｉＯ2、カチオン交換樹脂から選ばれる少なくとも１種が好ましい。
【００２６】
固体酸触媒の形状は、粉末でも成型したものでもよい。さらに、固体酸触媒の使用方法も、懸濁床でも固定床でもよいが、固定床の場合には、触媒と反応終了物との分離工程がいらないことから、大量生産する際には有効である。また、この脱水反応は回分式でも連続式でもよい。
【００２７】
固体酸触媒の使用量は、反応形式により適宜最適化すればよいが、回分式の場合は、反応性、経済性の面から原料である化合物（１）に対して０．５〜２０重量％が好ましく、１〜１０重量％がより好ましい。
【００２８】
また、例えば化合物（３）を得るために脱水反応後に異性化反応を行う場合は、脱水反応転化率が低すぎると、異性化反応中に脱水反応を同時に行わなければならず、異性化反応を効率的に行える温度（８０℃〜２００℃）を維持することが困難となり、また、脱水反応転化率が高すぎると、脱水反応の原料の化合物（１）や生成物の化合物（２）が重合および分解し、収率の低下を招くので、脱水反応転化率は４０〜９０％が好ましく、５０〜８０％がより好ましい。
ここで、脱水反応転化率は、以下の式（Ｉ）で定義される値である。
【００２９】
【数１】
脱水反応の温度は、反応を短時間で終わらせ、化合物（２）の重合および分解を防いで収率の低下を防ぐという観点から、７０〜１５０℃が好ましく、９０〜１２０℃が更に好ましい。また、反応圧力は、常圧でも反応は進行するが、生成する水を効率的に系外へ留去させ、原料および反応生成物を留出させないで効率的に反応させるために、２０〜１０１ｋＰａが好ましく、２０〜８０ｋＰａの減圧下で反応させることが更に好ましい。
【００３１】
本発明の脱水反応においては、生成する水を留去しながら反応を行うことが好ましい。反応後は、固体酸触媒を濾過等により、反応液と容易に分離することができ、リサイクルすることも可能である。
【００３２】
［化合物（５）の製法］
上記製法により得られた化合物（２）、又は化合物（１）を含有する化合物（２）を原料とし、例えば特開昭５６−１４７７４０号公報に記載の方法により香料素材や生理活性剤として有用な化合物（５）を得ることができる。
【００３３】
具体的には、まず化合物（２）を異性化反応させるか、又は化合物（１）を含有する化合物（２）を脱水反応させつつ異性化反応させて、化合物（３）を得る。
【００３４】
この脱水反応及び異性化反応は、既知の方法を用いることができ、例えば特開２００１−３２８９６５号公報に記載されているように、化合物（２）、又は化合物（１）を含有する化合物（２）に、アミンとハロゲン化水素からなる触媒を作用させて行う。
【００３５】
ここで用いるアミンとしては、アニリン、ジフェニルアミン、ピリジン、ピコリン、キノリン、ポリビニルピリジン等の芳香族アミン又は複素芳香環アミンが好ましく、特にピリジン、ピコリン及びキノリンが好ましい。ハロゲン化水素としては、塩化水素、臭化水素又はヨウ化水素等が挙げられ、特に塩化水素又は臭化水素が好ましい。
【００３６】
反応は、アルコール溶媒中又は無溶媒下で行うのが好ましい。アルコール溶媒としては、メタノール、エタノール、１−プロパノール、２−プロパノール、ブタノール、ペンタノール、ヘキサノール、２−エチルヘキサノール、シクロヘキサノール、エチレングリコール、１，８−オクタンジオール、グリセリン、ポリエチレングリコール等が挙げられ、炭素数１〜８の低級アルコール類が特に好ましい。反応温度は８０〜２００℃、特に１００〜１８０℃が好ましい。
【００３７】
次いで、得られる化合物（３）と化合物（４）とを塩基性触媒存在下に反応させて、式（８）で表される化合物（以下化合物（８）という）を得る。
【００３８】
【化１４】
（式中、ｎ、Ｒ1、Ｒ2及びＲ3は前記の意味を示す。）
化合物（３）に対して化合物（４）を、好ましくは１〜５モル倍、更に好ましくは１．２〜２モル倍の割合で反応させる。
【００４０】
塩基性触媒としては、ナトリウム、カリウム等のアルカリ金属、ナトリウムアルコキシド、カリウムアルコキシド等のアルカリ金属アルコキシド等が挙げられる。触媒の使用量は化合物（３）に対して０．０２〜０．２モル倍が好ましい。溶媒としてはアルコール類等の極性溶媒が好ましい。反応温度は−１０〜３０℃の範囲が好ましく、０〜２０℃の範囲が更に好ましい。
【００４１】
次に、得られた化合物（８）と水とを反応させることにより、化合物（５）を製造することができる。水は、化合物（８）に対して１〜３モル倍量を反応系中に滴下しながら反応させることが好ましい。反応温度は１５０〜２２０℃の範囲が好ましい。
【００４２】
このようにして得られた化合物（５）は、脱水反応において均一系の酸触媒を用いた場合に比べ、収率がよく、不純物が少ないので、化合物（５）を高純度で得るための精留負荷が低減でき、香料素材として優れたものである。
【００４３】
［化合物（６）の製法］
上記製法により得られた化合物（２）、又は化合物（１）を含有する化合物（２）を原料とし、既知の一般的な方法により、香料素材や生理活性剤として有用な化合物（６）を得ることができる。
【００４４】
例えば、上記のように化合物（２）を異性化反応させるか、又は化合物（１）を含有する化合物（２）を脱水反応させつつ異性化反応させて、化合物（３）を得る。次いで、Ｐｄ／Ｃ等の触媒存在下で水素還元させ、式（９）で表される化合物（以下化合物（９）という）を得る。
【００４５】
【化１５】
（式中、ｎ、Ｒ1及びＲ2は前記の意味を示す。）
得られた化合物（９）を、例えば特開平９−１０４６８１号公報に記載されているように、過酢酸等を酸化剤として用い、バイヤービリガー（Baeyer-Villiger）酸化させて、化合物（６）を得る。
【００４７】
このようにして得られた化合物（６）は、脱水反応において均一系の酸触媒を用いた場合に比べ、収率がよく、不純物が少ないので、化合物（６）を高純度で得るための精留負荷が低減でき、香料素材として優れたものである。
【００４８】
【実施例】
以下の例において、生成物の定量はガスクロマトグラフィーによる内部標準法（内標は、カルビトール又はウンデカン）によって行った。
【００４９】
製造例１
滴下槽を備えた６ｍ3の反応槽に、シクロペンタノン２２４１ｋｇ（２６．６ｋｍｏｌ）、水１００７ｋｇ、４８％ＮａＯＨ１１ｋｇを仕込み、撹拌しながら１５℃に冷却した後、同温度でバレルアルデヒド９８５ｋｇ（１１．４ｋｍｏｌ）を５時間かけて滴下した。滴下終了後、同温度で１時間撹拌した。反応終了後、中和し、過剰のシクロペンタノンを蒸留回収した後、有機層を分析した結果、反応終了品１８６８ｋｇ中には、２−（１−ヒドロキシペンチル）−シクロペンタノンが１７０６ｋｇ含まれていた。
【００５０】
実施例１
脱水管を備えた３００ｍｌの４つ口フラスコに、製造例１と同様に製造した反応終了品を精留して得られた２−（１−ヒドロキシペンチル）−シクロペンタノン１７０ｇ（０．９９ｍｏｌ）、ＴｉＯ2（球状成型品、直径１．５ｍｍ）８．５ｇを加え、１００℃、５３ｋＰａになるように加熱し混合した。反応６時間後には、留分が１６．７ｇ得られ、反応終了物を分析すると、２−ペンチリデンシクロペンタノンが１４１ｇ含まれていることがわかった。収率は９３％であった。
【００５１】
実施例２
実施例１と同様の装置に、２−（１−ヒドロキシペンチル）−シクロペンタノン１７０ｇ（０．９９ｍｏｌ）、ＡｌＰＯ4（ヌードル状成型品、直径０．８ｍｍ、長さ＜５ｍｍ）８．５ｇを加え、１２０℃、１０１ｋＰａになるように加熱し混合した。反応５時間後には、留分が１６．７ｇ得られ、反応終了物を分析すると、２−ペンチリデンシクロペンタノンが１４１ｇ含まれていることがわかった。収率は９３％であった。
【００５２】
実施例３
固体酸触媒としてＮａｆｉｏｎ ＮＲ−５０（デュポン（株）、ヌードル状成型品）１．７ｇを用いる以外は実施例２と同様にして、反応を行った結果、２−ペンチリデンシクロペンタノンが１２１ｇ得られた。収率は８０％であった。
【００５３】
実施例４
固体酸触媒としてＤＩＡＩＯＮ ＲＣＰ１６０Ｍ（三菱化学（株）、球状成型品、直径約１ｍｍ）８．５ｇを用い、圧力２６．７ｋＰａ、温度１００℃とする以外は実施例２と同様にして、反応を行った結果、２−ペンチリデンシクロペンタノンが９４ｇ得られた。収率は６２％であった。
【００５４】
実施例５
実施例１と同様にして得られた反応終了物中の固体酸触媒を濾過し、１５３ｇの濾過終了物を得た。この中に含まれる２−ペンチリデンシクロペンタノンは１４１ｇ（０．９３ｍｏｌ）であった。この濾過終了物をｎ−ブタノール１５３ｇに溶かし、１３０℃に昇温した後、同温度で３−ピコリン１４．５ｇ（０．１５ｍｏｌ）と３５％塩酸１０．５ｇ（０．１ｍｏｌ）の混合液を３０分で滴下した。滴下終了後、同温度で３．５時間加熱攪拌した。反応終了後、室温まで冷却し、水酸化ナトリウム水溶液で中和した後、有機層を分析した結果、反応終了品中には、２−ペンチル−２−シクロペンテノンが１１８ｇ含まれていることがわかった。この異性化反応の収率は８３％であった。
【００５５】
この反応終了品を精留し、２−ペンチル−２−シクロペンテノンを９５ｇ（０．６ｍｏｌ）得た。さらに、窒素雰囲気下にてマロン酸ジメチル１１８ｇ（０．９ｍｏｌ）を無水メタノール３８ｇに溶解し、０℃に冷却して、ナトリウムメトキシド（３０％メタノール溶液）６．５ｇ（０．０３６ｍｏｌ）を添加したものに、上記で得られた２−ペンチル−２−シクロペンテノン９５ｇ（０．６ｍｏｌ）を０℃で、２時間かけて滴下した。滴下終了後、未反応のマロン酸ジメチルを減圧留去し、１６０ｇのマイケル付加物を得た。
【００５６】
蒸留留出管をつけた反応装置に、上記で得られたマイケル付加物を加え、２１５℃に加熱し、水を３．２ｇ／ｈ（２％／ｈ）の速度で滴下した。発生する二酸化炭素とメタノールを留出させながら、２１５℃で、４時間滴下反応を行った。反応終了後、粗生成物１２６ｇ中に、３−オキソ−２−ペンチルシクロペンチル酢酸メチル１２３ｇを得た。
【００５７】
粗生成物を精留して得られた３−オキソ−２−ペンチルシクロペンチル酢酸メチルは、フルーティでジャスミン様の香気を有しており、香料素材としても優れたものであった。
【００５８】
【発明の効果】
本発明の方法によれば、脱水反応触媒として均一系触媒を用いる場合のように反応後に中和／分層等の工程がなく、設備の腐食の可能性もなく、高収率かつ高生産性で２−（アルキリデン）シクロアルカノンを製造することができる。更に、得られた２−（アルキリデン）シクロアルカノンを用い、香料素材や生理活性物質として有用なアルキル（３−オキソ−２−アルキルシクロアルキル）アセテート及び５−アルキル−５−アルカノリドを高収率、高純度で製造することができる。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method for producing 2- (alkylidene) cycloalkanone which is an intermediate such as methyl dihydrojasmonate and δ-lactone useful as a perfume material, and an alkyl (3-oxo-2-alkylcycloalkyl) using the same. ) Acetate and 5-alkyl-5-alkanolides.
[0002]
[Prior art]
Conventionally, when producing 2- (alkylidene) cycloalkanone from 2- (1-hydroxyalkyl) cycloalkanone, a homogeneous acid catalyst is generally used as a dehydration reaction catalyst.
[0003]
For example, in Patent Document 1, in order to obtain 2- (alkylidene) cycloalkanone, oxalic acid is added to an aldol condensate to perform a dehydration reaction. However, after the reaction, neutralization with an alkali and layer separation are required. There are many processes and wastewater is generated. Further, the equipment may be corroded by an acid, or the 2- (alkylidene) cycloalkanone may be polymerized and decomposed during neutralization with an alkali to lower the yield.
[0004]
Further, due to such polymerization and decomposition, the odor of alkyl (3-oxo-2-alkylcycloalkyl) acetate or 5-alkyl-5-alkanolide synthesized using the same may be reduced.
[0005]
[Patent Document 1]
JP-A-56-147740 [0006]
[Problems to be solved by the invention]
An object of the present invention is to provide a method for efficiently producing 2- (alkylidene) cycloalkanone at a high yield, and an alkyl (3-oxo-2-alkylcyclo) useful as a fragrance material or a physiologically active substance using the same. (Alkyl) acetate and 5-alkyl-5-alkanolides.
[0007]
[Means for Solving the Problems]
The present invention relates to formula (1)
[0008]
Embedded image
(Wherein, n is an integer of 1 or 2, R 1 and R 2 each represent a hydrogen atom or a linear or branched alkyl group having 1 to 8 carbon atoms, or R 1 and R 2 together To form a cyclopentane ring or a cyclohexane ring together with adjacent carbon atoms.)
A 2- (1-hydroxyalkyl) cycloalkanone (hereinafter referred to as compound (1)) represented by the following formula (2):
[0010]
Embedded image
(In the formula, n, R 1 and R 2 have the same meanings as described above.)
A method for producing a 2- (alkylidene) cycloalkanone (hereinafter referred to as compound (2)) represented by the formula:
[0012]
In addition, the present invention provides an isomerization reaction of the compound (2) obtained by the above production method or an isomerization reaction of the compound (2) containing the compound (1) while performing a dehydration reaction on the compound (2) to obtain a compound of the formula (3) )
[0013]
Embedded image
(In the formula, n, R 1 and R 2 have the same meanings as described above.)
2- (alkyl) cycloalkenone (hereinafter referred to as compound (3)) represented by the formula:
[0015]
Embedded image
(In the formula, R 3 represents a linear or branched alkyl group having 1 to 3 carbon atoms, and the two R 3 may be the same or different.)
Reacting with a malonic acid diester represented by the following formula (hereinafter referred to as compound (4)) and then reacting with water:
[0017]
Embedded image
(In the formula, n, R 1 , R 2 and R 3 have the same meanings as described above.)
The compound (2) obtained by the method for producing an alkyl (3-oxo-2-alkylcycloalkyl) acetate (hereinafter referred to as compound (5)) represented by The compound (2) containing the compound (2) is subjected to an isomerization reaction while being subjected to a dehydration reaction to give a compound (3), which is then hydrogen-reduced and then subjected to Bayer-Villiger oxidation, which is a 5-alkyl-5 represented by the formula (6). -A method for producing an alkanolide (hereinafter referred to as compound (6)) is provided.
[0019]
Embedded image
(In the formula, n, R 1 and R 2 have the same meanings as described above.)
[0021]
BEST MODE FOR CARRYING OUT THE INVENTION
[Production method of compound (2)]
In the compound (1) used as a raw material of the present invention, examples of the alkyl group constituting the 1-hydroxyalkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, an amyl group, Examples include an isoamyl group, a hexyl group, and a heptyl group.
[0022]
This compound (1) can be produced by a generally known method. For example, a cycloalkanone having 5 or 6 carbon atoms and a compound represented by the formula (7)
[0023]
Embedded image
(Wherein, R 1 and R 2 have the same meanings as described above.)
By reacting an aldehyde or ketone represented by In the present invention, the compound (1) obtained by such a method can be used without distillation, but if the activity of the solid acid catalyst is reduced, it may be purified by distillation.
[0025]
Examples of the solid acid catalyst used in the present invention include inorganic metal solid catalysts such as AlPO 4 , Al 2 O 3 , activated alumina, zirconia sulfate, aluminum dihydrogen tripolyphosphate, and TiO 2 , cation exchange resins, SiO 2 —TiO 2 , SiO 2 —CaO, SiO 2 —MgO, zeolite and the like can be used, and at least one selected from AlPO 4 , TiO 2 and a cation exchange resin is preferable.
[0026]
The shape of the solid acid catalyst may be powder or molded. Further, the method of using the solid acid catalyst may be either a suspension bed or a fixed bed. However, in the case of a fixed bed, since there is no need for a step of separating the catalyst and the reaction product, it is effective for mass production. . The dehydration reaction may be a batch type or a continuous type.
[0027]
The amount of the solid acid catalyst to be used may be appropriately optimized depending on the reaction mode. In the case of a batch system, from 0.5 to 20% by weight based on the raw material compound (1) from the viewpoint of reactivity and economy , Preferably 1 to 10% by weight.
[0028]
When the isomerization reaction is performed after the dehydration reaction to obtain the compound (3), for example, if the conversion of the dehydration reaction is too low, the dehydration reaction must be performed simultaneously during the isomerization reaction. If it is difficult to maintain a temperature (80 ° C. to 200 ° C.) at which the reaction can be performed efficiently, and if the conversion rate of the dehydration reaction is too high, the compound (1) as a raw material of the dehydration reaction and the compound (2) as a product may be polymerized. In addition, the decomposition rate is reduced and the yield is reduced. Therefore, the conversion rate of the dehydration reaction is preferably 40 to 90%, more preferably 50 to 80%.
Here, the conversion rate of the dehydration reaction is a value defined by the following formula (I).
[0029]
(Equation 1)
The temperature of the dehydration reaction is preferably from 70 to 150 ° C, more preferably from 90 to 120 ° C, from the viewpoint of terminating the reaction in a short time, preventing polymerization and decomposition of the compound (2) and preventing a decrease in yield. Further, the reaction pressure is such that the reaction proceeds even at normal pressure, but in order to efficiently distill off the generated water to the outside of the system and to conduct the reaction efficiently without distilling the raw materials and the reaction products, 20 to 101 kPa The reaction is preferably performed under a reduced pressure of 20 to 80 kPa.
[0031]
In the dehydration reaction of the present invention, it is preferable to carry out the reaction while distilling off generated water. After the reaction, the solid acid catalyst can be easily separated from the reaction solution by filtration or the like, and can be recycled.
[0032]
[Production method of compound (5)]
The compound (2) obtained by the above-mentioned production method or the compound (2) containing the compound (1) is used as a raw material, and is useful as a fragrance material or a physiologically active agent, for example, by the method described in JP-A-56-147740. Compound (5) can be obtained.
[0033]
Specifically, first, the compound (2) is subjected to an isomerization reaction, or the compound (2) containing the compound (1) is subjected to an isomerization reaction while being subjected to a dehydration reaction to obtain a compound (3).
[0034]
For the dehydration reaction and the isomerization reaction, known methods can be used. For example, as described in JP-A-2001-328965, compound (2) or compound (2) containing compound (1) is used. ) Is reacted with a catalyst comprising an amine and hydrogen halide.
[0035]
The amine used here is preferably an aromatic amine such as aniline, diphenylamine, pyridine, picoline, quinoline, or polyvinylpyridine or a heteroaromatic amine, and particularly preferably pyridine, picoline and quinoline. Examples of the hydrogen halide include hydrogen chloride, hydrogen bromide, and hydrogen iodide, and hydrogen chloride or hydrogen bromide is particularly preferable.
[0036]
The reaction is preferably carried out in an alcohol solvent or without solvent. Examples of the alcohol solvent include methanol, ethanol, 1-propanol, 2-propanol, butanol, pentanol, hexanol, 2-ethylhexanol, cyclohexanol, ethylene glycol, 1,8-octanediol, glycerin, polyethylene glycol and the like. And lower alcohols having 1 to 8 carbon atoms are particularly preferred. The reaction temperature is preferably from 80 to 200C, particularly preferably from 100 to 180C.
[0037]
Next, the obtained compound (3) and compound (4) are reacted in the presence of a basic catalyst to obtain a compound represented by the formula (8) (hereinafter, referred to as compound (8)).
[0038]
Embedded image
(In the formula, n, R 1 , R 2 and R 3 have the same meanings as described above.)
The compound (4) is reacted with the compound (3) at a ratio of preferably 1 to 5 moles, more preferably 1.2 to 2 moles.
[0040]
Examples of the basic catalyst include alkali metals such as sodium and potassium, and alkali metal alkoxides such as sodium alkoxide and potassium alkoxide. The amount of the catalyst to be used is preferably 0.02 to 0.2 mol times with respect to the compound (3). As the solvent, a polar solvent such as an alcohol is preferable. The reaction temperature is preferably in the range of -10 to 30C, more preferably in the range of 0 to 20C.
[0041]
Next, the compound (5) can be produced by reacting the obtained compound (8) with water. It is preferable that water is reacted while being dripped in the reaction system in an amount of 1 to 3 times the molar amount of the compound (8). The reaction temperature is preferably in the range of 150 to 220C.
[0042]
The compound (5) thus obtained has a higher yield and fewer impurities as compared with the case where a homogeneous acid catalyst is used in the dehydration reaction. The retention load can be reduced, and it is an excellent fragrance material.
[0043]
[Production method of compound (6)]
Using the compound (2) obtained by the above production method or the compound (2) containing the compound (1) as a raw material, a compound (6) useful as a fragrance material or a bioactive agent is obtained by a known general method. be able to.
[0044]
For example, the compound (2) is subjected to an isomerization reaction as described above, or the compound (2) containing the compound (1) is subjected to an isomerization reaction while being subjected to a dehydration reaction to obtain a compound (3). Next, hydrogen reduction is performed in the presence of a catalyst such as Pd / C to obtain a compound represented by the formula (9) (hereinafter, referred to as compound (9)).
[0045]
Embedded image
(In the formula, n, R 1 and R 2 have the same meanings as described above.)
The obtained compound (9) is oxidized with Baeyer-Villiger using peracetic acid or the like as an oxidizing agent as described in, for example, JP-A-9-104681, to give compound (6). obtain.
[0047]
The compound (6) thus obtained has a higher yield and fewer impurities as compared with the case where a homogeneous acid catalyst is used in the dehydration reaction. The retention load can be reduced, and it is an excellent fragrance material.
[0048]
【Example】
In the following examples, the quantification of the product was performed by an internal standard method using gas chromatography (internal standard was carbitol or undecane).
[0049]
Production Example 1
A reaction vessel of 6 m 3 equipped with a dropping tank was charged with 2241 kg (26.6 kmol) of cyclopentanone, 1007 kg of water and 11 kg of 48% NaOH, cooled to 15 ° C. with stirring, and 985 kg of valeraldehyde (11. 4 kmol) was added dropwise over 5 hours. After completion of the dropwise addition, the mixture was stirred at the same temperature for 1 hour. After completion of the reaction, the mixture was neutralized, and excess cyclopentanone was recovered by distillation, and the organic layer was analyzed. As a result, 1706 kg of 2- (1-hydroxypentyl) -cyclopentanone was contained in 1868 kg of the reaction-completed product. I was
[0050]
Example 1
170 g (0.99 mol) of 2- (1-hydroxypentyl) -cyclopentanone obtained by rectifying a reaction-completed product produced in the same manner as in Production Example 1 in a 300 ml four-necked flask equipped with a dehydration tube. And 8.5 g of TiO 2 (spherical molded product, 1.5 mm in diameter), and heated and mixed at 100 ° C. and 53 kPa. Six hours after the reaction, 16.7 g of a fraction was obtained, and analysis of the reaction completed product revealed that 141 g of 2-pentylidenecyclopentanone was contained. The yield was 93%.
[0051]
Example 2
In a device similar to that of Example 1, 170 g (0.99 mol) of 2- (1-hydroxypentyl) -cyclopentanone and 8.5 g of AlPO 4 (noodle-shaped molded product, diameter 0.8 mm, length <5 mm) were added. In addition, the mixture was heated and mixed at 120 ° C. and 101 kPa. Five hours after the reaction, 16.7 g of a fraction was obtained, and analysis of the reaction completed product revealed that 141 g of 2-pentylidenecyclopentanone was contained. The yield was 93%.
[0052]
Example 3
The reaction was carried out in the same manner as in Example 2 except that 1.7 g of Nafion NR-50 (Dupont, noodle-shaped molded product) was used as the solid acid catalyst. As a result, 121 g of 2-pentylidenecyclopentanone was obtained. Was done. The yield was 80%.
[0053]
Example 4
The reaction was carried out in the same manner as in Example 2 except that 8.5 g of DIAION RCP160M (Mitsubishi Chemical Corporation, spherical molded product, diameter of about 1 mm) was used as the solid acid catalyst, the pressure was 26.7 kPa, and the temperature was 100 ° C. As a result, 94 g of 2-pentylidenecyclopentanone was obtained. The yield was 62%.
[0054]
Example 5
The solid acid catalyst in the reaction product obtained in the same manner as in Example 1 was filtered to obtain 153 g of a filtration product. The amount of 2-pentylidenecyclopentanone contained therein was 141 g (0.93 mol). This filtered product was dissolved in 153 g of n-butanol and heated to 130 ° C., and then a mixture of 14.5 g (0.15 mol) of 3-picoline and 10.5 g (0.1 mol) of 35% hydrochloric acid was heated at the same temperature. It was dropped in 30 minutes. After completion of the dropwise addition, the mixture was heated and stirred at the same temperature for 3.5 hours. After completion of the reaction, the mixture was cooled to room temperature, neutralized with an aqueous sodium hydroxide solution, and analyzed for the organic layer. As a result, it was found that the reaction-completed product contained 118 g of 2-pentyl-2-cyclopentenone. all right. The yield of this isomerization reaction was 83%.
[0055]
The product after the reaction was rectified to obtain 95 g (0.6 mol) of 2-pentyl-2-cyclopentenone. Further, under a nitrogen atmosphere, 118 g (0.9 mol) of dimethyl malonate was dissolved in 38 g of anhydrous methanol, cooled to 0 ° C, and 6.5 g (0.036 mol) of sodium methoxide (30% methanol solution) was added. 95 g (0.6 mol) of 2-pentyl-2-cyclopentenone obtained above was dropped at 0 ° C. over 2 hours. After completion of the dropwise addition, unreacted dimethyl malonate was distilled off under reduced pressure to obtain 160 g of Michael adduct.
[0056]
The Michael adduct obtained above was added to a reactor equipped with a distillation distilling tube, heated to 215 ° C., and water was added dropwise at a rate of 3.2 g / h (2% / h). While distilling off the generated carbon dioxide and methanol, a dropping reaction was performed at 215 ° C. for 4 hours. After completion of the reaction, 123 g of methyl 3-oxo-2-pentylcyclopentylacetate was obtained in 126 g of the crude product.
[0057]
Methyl 3-oxo-2-pentylcyclopentyl acetate obtained by rectifying the crude product had a fruity and jasmine-like odor, and was also excellent as a fragrance material.
[0058]
【The invention's effect】
According to the method of the present invention, there is no neutralization / separation step after the reaction as in the case of using a homogeneous catalyst as the dehydration reaction catalyst, there is no possibility of equipment corrosion, high yield and high productivity. To produce 2- (alkylidene) cycloalkanone. Furthermore, using the obtained 2- (alkylidene) cycloalkanone, alkyl (3-oxo-2-alkylcycloalkyl) acetate and 5-alkyl-5-alkanolide useful as a perfume material or a physiologically active substance are obtained in high yield. , Can be manufactured with high purity.
Claims (5)
で表される２−（１−ヒドロキシアルキル）シクロアルカノン（以下化合物（１）という）を、固体酸触媒を用いて脱水反応させる、式（２）
で表される２−（アルキリデン）シクロアルカノン（以下化合物（２）という）の製法。Equation (1)
A 2- (1-hydroxyalkyl) cycloalkanone (hereinafter referred to as compound (1)) represented by the following formula (2):
A method for producing 2- (alkylidene) cycloalkanone (hereinafter referred to as compound (2)) represented by the formula:
で表される２−（アルキル）シクロアルケノン（以下化合物（３）という）とし、次いで式（４）
で表されるマロン酸ジエステルとを反応させ、次いで水を反応させる、式（５）
で表されるアルキル（３−オキソ−２−アルキルシクロアルキル）アセテートの製法。The compound (2) obtained by the production method according to any one of claims 1 to 3 is isomerized, or the compound (2) containing the compound (1) is subjected to an isomerization reaction while being subjected to a dehydration reaction. And equation (3)
2- (alkyl) cycloalkenone (hereinafter referred to as compound (3)) represented by the formula:
Reacting with malonic diester represented by the formula: and then reacting with water.
A method for producing an alkyl (3-oxo-2-alkylcycloalkyl) acetate represented by the formula:
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