JP4649743B2 - Process for producing macrocyclic ketone compounds - Google Patents
Process for producing macrocyclic ketone compounds Download PDFInfo
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- JP4649743B2 JP4649743B2 JP2001017711A JP2001017711A JP4649743B2 JP 4649743 B2 JP4649743 B2 JP 4649743B2 JP 2001017711 A JP2001017711 A JP 2001017711A JP 2001017711 A JP2001017711 A JP 2001017711A JP 4649743 B2 JP4649743 B2 JP 4649743B2
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- cycloalkenone
- hydroxycyclopentadecanone
- cyclopentadecenone
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Description
【0001】
【発明の属する技術分野】
本発明は、香料等の原体やその中間体として利用される大環状ケトン化合物を高効率で製造する方法に関する。
【0002】
【従来の技術】
大環状ケトン、例えば、次の化学式(1)で示されるシクロペンタデカノンや化学式(2)で示される3-メチルシクロペンタデカノン、いわゆるムスコンは麝香の香気成分として知られ、非常に高価で取引されている。
【化1】
【0003】
このうちのシクロペンタデカノンの工業的な製造方法の一つとして、ペンタデカン二酸ジエステルをアシロイン縮合させて得られた2-ヒドロキシシクロペンタデカノンを原料とし、亜鉛と所定濃度の硫酸などの鉱酸の存在下に有機溶媒中で還元を行いシクロペンタデカノンとする方法が知られている(特許第3087921号公報など)。この方法は2-ヒドロキシシクロペンタデカノンを収率良く還元できる優れた方法であるが、この方法では還元が金属表面でおこるために、鉱酸水溶液と有機溶媒との2相中に亜鉛を高分散させることが必要であり、十分な分散に必要な撹拌を得るためには比較的小容積の反応器を使用する必要があり、生産効率を向上させるためにスケールアップを考えた場合には問題があった。
【0004】
また、2-ヒドロキシシクロペンタデカノンのカルボニル基を保護した後、ヒドロキシル基をトシル基などの脱離基に変換し、塩基の存在下に引き抜くことにより二重結合を生成させ、カルボニル基を脱保護することにより、2-シクロペンタデセノンを合成する方法が公知であり(特公平7-108876号公報)、この2-シクロペンタデセノンを水素化してシクロペンタデカノンが得られるだろうと述べられている(Alvin S. Williams, Synthesis, (1999), 10, 1707-1723)。しかし、この2-シクロペンタデセノン合成方法は多段階の反応工程が必要であり、経済性に問題がある。
【0005】
さらに、2-ヒドロキシシクロペンタデカノンを原料とし、気相反応でアルミナを触媒として脱水し、直接、2-シクロペンタデセノンに導く方法(Stoll, M.; Commarmont, A. Helv. Chim. Acta 1948, 31, 554)が知られ、これを水素化すればシクロペンタデカノンが得られることは予測される。しかし、気相反応の採用は装置及び操作上必ずしも簡単ではない。
【0006】
一方、3-メチルシクロペンタデカノンの合成法として、2-ヒドロキシシクロペンタデカノンのカルボニル基を保護した後、ヒドロキシル基をトシル基などの脱離基に変換し、塩基の存在下に引き抜くことにより二重結合を生成させ、カルボニル基を脱保護することで得た2-シクロペンタデセノンを常法によりメチル化する合成法が知られている(特公平7-108876号公報)。しかし、この方法は2-シクロペンタデセノンを得るまでに長い工程が必要であり、経済的ではない。
【0007】
また、シクロペンタデカノンを原料とし、この2位にハロゲン等の脱離基を導入し、塩基の存在下に引き抜くことにより二重結合を生成させることで得た、2-シクロペンタデセノンを常法によりメチル化する合成法やその変法(Journal of the Korean Chemical Society, 40, 4, 243 (1996)など)も知られている。しかし、この方法も、シクロペンタデカノンが2-ヒドロキシシクロペンタデカノンから合成されていることを考えると、必ずしも経済性に優れているとは言いがたい。
【0008】
【発明が解決しようとする課題】
本発明は上記課題を解決するもので、本発明の目的は液相反応において、効率的にシクロアルケノンを製造する方法、このシクロアルケノンを原料として水素化してシクロアルカノンを製造する方法、及びシクロアルケノンへアルキル基を導入することにより、アルキルシクロアルカノンを製造する方法を提供することにある。
【0009】
【課題を解決するための手段】
本発明者は、スケールアップによる生産効率向上に好ましく、かつ、短い反応工程で良く、さらには、汎用性のある装置での製造が容易な液相反応が可能な、2-ヒドロキシシクロアルカノンを原料とした脱水反応によるシクロアルケノンの合成方法について、鋭意、研究を進めた結果、酸触媒を存在させることにより、驚くべきことに液相反応においても保護基を導入する必要がなく、高収率で脱水反応が進行すること、得られたシクロアルケノンは還元により容易にシクロアルカノンにできること、シクロアルケノン中の2-シクロアルケノンは常法によりアルキル化でき、経済的に3-アルキルシクロアルカノンに導けることを見出し、本発明に想到した。
【0010】
すなわち、本発明の大環状ケトン化合物の製造方法は、
1)炭素数12〜18の2−ヒドロキシシクロアルカノン、特に好ましくは2−ヒドロキシシクロペンタデカノンを液相で酸触媒、特にはリン酸類または固体酸類の存在下に脱水させてシクロアルケノン、特にはシクロペンタデセノンを製造する方法、
2)上記方法で得られたシクロアルケノン、特にはシクロペンタデセノンを還元してシクロアルカノン、特にシクロペンタデカノンを製造する方法、
3)上記方法で得られたシクロアルケノン、特には2−シクロペンタデセノンをアルキル化、特にはメチル化してアルキルシクロアルカノン、特には3−メチルシクロペンタデカンを製造する方法、
を含むものである。
【0011】
【発明の実施の態様】
本発明の原料である炭素数12〜18の2-ヒドロキシシクロアルカノンは、対応する炭素数の直鎖アルカンジカルボン酸ジエステルを有機溶媒中で金属ナトリウムの存在下にアシロイン縮合させることにより、容易に合成できる。
【0012】
これらの2-ヒドロキシシクロアルカノンを原料として、酸触媒の存在下、必要に応じて溶媒を用いて、加熱して脱水反応を行う。この場合、酸触媒としては、リン酸類、例えばオルトリン酸、メタリン酸、ピロリン酸等のポリリン酸、あるいは固体酸類、例えば、シリカアルミナ、ゼオライト、ジルコニアおよび/またはアルミナに硫酸を担持させた硫酸ジルコニアまたは硫酸ジルコニアアルミナ等(特公昭59−6181号公報、特開平11−809727号公報等参照)が好ましい。これらの触媒の使用量は、触媒の種類によって異なるが、例えばリン酸類の場合は、2-ヒドロキシシクロアルカノン1モルに対して0.01〜0.5モル、固体酸類の場合は、2-ヒドロキシシクロアルカノン1重量部当たり0.01〜1重量部の範囲から適宜選定することが好ましい。
【0013】
この反応において溶媒を用いて行う場合、当該溶媒は本反応に不活性なものであれば特に支障なく使用できるが、安定性の面から飽和炭化水素、芳香族炭化水素を用いることが好ましい。この場合の溶媒の使用量は多すぎると反応が遅くなり、一定容積当たりの反応効率が悪くなるなどの不都合を生じるため、2-ヒドロキシシクロアルカノンの濃度が0.1モル/リットル以上になるような範囲から適宜選定すると良い。
【0014】
反応温度は100〜400℃、好ましくは150〜300℃とすると良く、低沸点の溶媒を用いる場合には、オートクレーブ中で加圧反応として実施してもよい。
【0015】
反応時間は選定した反応液の濃度、反応温度などを勘案して決定される。
【0016】
このような脱水反応では異性化等も同時に起こるため、反応生成物であるシクロアルケノンは、主に2-シクロアルケノンと3-シクロアルケノンからなっている。これらの混合物は、触媒を利用した水素化反応等によって、容易にシクロアルカノンとすることができる。この水素化反応に使用できる触媒としては、ニッケル触媒、コバルト触媒、銅触媒、パラジウム触媒、白金触媒、ルテニウム触媒、ロジウム触媒等が例示できる。これらの触媒の使用量は、触媒の種類、活性度によって異なるが、シクロアルケノン1重量部当たり0.001〜0.1重量部の範囲から適宜選定することが好ましい。
【0017】
この反応は溶媒を用いて溶液の形態で行うことが好ましく、当該溶媒は本反応に不活性なものであれば特に支障なく使用できるが、脱水反応において使用しているために利便性の面から飽和炭化水素、芳香族炭化水素を用いることが、特に好ましい。この場合、シクロアルケノンの濃度が0.1モル/リットル以上になるようにすると効率よく反応を行うことができる。
【0018】
反応温度は0〜400℃、好ましくは室温〜100℃とすると良く、常圧の水素ガス封入下で行うのが簡便であるが、水素ガスをバブリングしてもよく、また、オートクレーブを用いて、0〜30kg/cm2の水素加圧下で実施してもよい。さらには、充填した触媒中を反応液と水素ガスを並流させる流通方式で行ってもよい。
【0019】
得られた水素化反応生成物は蒸留等の常法で精製することができる。
【0020】
一方、上述の脱水反応で得られた反応生成物の主として2-シクロアルケノンと3-シクロアルケノンの混合物を直接に、あるいは必要に応じて、2-シクロアルケノンを蒸留やクロマトグラフィー等の常法により分離した後に、例えば、銅試薬、グリニアル試薬の存在下にマイケル反応などの常法によって、3-アルキル化シクロアルカノンとすることができる(Journal of the Korean Chemical Society, 40, 4, 243 (1996)を参照)。
【0021】
以下に、具体例を挙げ、本発明を説明するが、本発明の範囲はこれらに限定されるものではない。
【0022】
【実施例】
(実施例1)
100ml容3つ口フラスコに、温度計、冷却管をセットしたところに、2-ヒドロキシシクロペンタデカノン6.0g、シリカアルミナ触媒(触媒化成社製HA)1.0g、テトラデカン54.0gを加え、マグネチックスターラーで撹拌しながら、マントルヒーターで加熱し、反応液温220℃で7時間反応させた。反応液に内部標準物質としてエイコサンを加え、ガスクロマトグラフィーで定量したところ、2-ヒドロキシシクロペンタデカノンに対して、収率85%でシクロペンタデセノン混合物を得た。
【0023】
(実施例2)
200ml容オートクレーブに、2-ヒドロキシシクロペンタデカノン6.0g、シリカアルミナ触媒(触媒化成社製HA)1.0g、トルエン54.0gを加え、マグネチックスターラーで撹拌しながら、オイルバス温240℃で5時間反応させた。反応液に内部標準物質としてエイコサンを加え、ガスクロマトグラフィーで定量したところ、2-ヒドロキシシクロペンタデカノンに対して、収率90%でシクロペンタデセノン混合物を得た。
【0024】
(実施例3)
100ml容3つ口フラスコに、温度計、冷却管をセットしたところに、2-ヒドロキシシクロペンタデカノン6.0g、シリカアルミナ触媒(触媒化成社製LA)0.5g、テトラデカン12.0gを加え、200℃で1時間反応させた。反応液に内部標準物質としてエイコサンを加え、ガスクロマトグラフィーで定量したところ、2-ヒドロキシシクロペンタデカノンに対して、収率11%でシクロペンタデセノン混合物を得た。
【0025】
(実施例4)
100ml容3つ口フラスコに、温度計、冷却管をセットしたところに、2-ヒドロキシシクロペンタデカノン6.0g、ゼオライト触媒(Zeolyst社製CBV720)1.0g 、テトラデカン12.0gを加え、マグネチックスターラーで撹拌しながら、マントルヒーターで加熱し、200℃で12時間反応させた。反応液に内部標準物質としてエイコサンを加え、ガスクロマトグラフィーで定量したところ、2-ヒドロキシシクロペンタデカノンに対して、収率41%でシクロペンタデセノン混合物を得た。
【0026】
(実施例5)
100ml容3つ口フラスコに、温度計、冷却管をセットしたところに、2-ヒドロキシシクロペンタデカノン6.0g、硫酸ジルコニアアルミナ(特開平11−809727号公報記載の方法で調製したもの)5.0g、テトラデカン54.0gを加え、マグネチックスターラーで撹拌しながら、マントルヒーターで加熱し、200℃で4時間反応させた。反応液に内部標準物質としてエイコサンを加え、ガスクロマトグラフィーで定量したところ、2-ヒドロキシシクロペンタデカノンに対して、収率73%でシクロペンタデセノン混合物を得た。
【0027】
(実施例6)
100ml容3つ口フラスコに、温度計、冷却管をセットしたところに、2-ヒドロキシシクロペンタデカノン6.0g、H3PO4 0.1gを加え、マグネチックスターラーで撹拌しながら、マントルヒーターで加熱し、240℃で20分間反応させた。反応液に内部標準物質としてエイコサンを加え、ガスクロマトグラフィーで定量したところ、2-ヒドロキシシクロペンタデカノンに対して、収率64%でシクロペンタデセノン混合物を得た。
【0028】
(実施例7)
100ml容3つ口フラスコに、温度計、冷却管をセットしたところに、2-ヒドロキシシクロペンタデカノン6.0g、H4P2O7 0.1gを加え、マグネチックスターラーで撹拌しながら、マントルヒーターで加熱し、240℃で20分間反応させた。反応液に内部標準物質としてエイコサンを加え、ガスクロマトグラフィーで定量したところ、2-ヒドロキシシクロペンタデカノンに対して、収率65%でシクロペンタデセノン混合物を得た。
【0029】
(実施例8)
100ml容3つ口フラスコに、温度計、冷却管をセットしたところに、2-ヒドロキシシクロペンタデカノン6.0g、HPO3 0.5g、テトラデカン18.0gを加え、マグネチックスターラーで撹拌しながら、マントルヒーターで加熱し、250℃で6時間反応させた。反応液に内部標準物質としてエイコサンを加え、ガスクロマトグラフィーで定量したところ、2-ヒドロキシシクロペンタデカノンに対して、収率63%でシクロペンタデセノン混合物を得た。
【0030】
(実施例9)
100ml容3つ口フラスコに、温度計、冷却管をセットしたところに、2-ヒドロキシシクロトリデカノン6.0g、シリカアルミナ触媒(触媒化成社製HA)1.0g、テトラデカン54.0gを加え、マグネチックスターラーで撹拌しながら、マントルヒーターで加熱し、反応液温220℃で7時間反応させた。反応液に内部標準物質としてエイコサンを加え、ガスクロマトグラフィーで定量したところ、2-ヒドロキシシクロトリデカノンに対して、収率81%でシクロトリデセノン混合物を得た。
【0031】
(実施例10)
100ml容ナスフラスコに、シクロペンタデセノン混合物2.0g、5%Pd/C 0.1g、トルエン18.0gを加え、水素雰囲気下、室温で3時間反応させた。反応液に内部標準物質としてエイコサンを加え、ガスクロマトグラフィーで定量したところ、水素化収率100%でシクロペンタデカノンを得た。
【0032】
(実施例11)
100ml容3つ口フラスコに、温度計、滴下漏斗をセットし、フラスコに無水CuCl 0.44g、CH3MgIのエーテル溶液(0.84mol/l)1.3ml、乾燥エーテル15mlを加え、氷浴で冷やしながら、滴下漏斗のシクロペンタデセノン混合物(脱水反応生成物をカラム精製して得た。2-シクロペンタデセノン62%を含む。)1.2g、乾燥エーテル5ml溶液を、約1時間かけてゆっくり滴下した。滴下終了後反応液温を10℃にあげ、さらに2時間撹拌を続けた。氷冷しながら、10%塩酸水溶液10mlを滴下し、有機相を分相した。水相をジクロロメタンで抽出したものをこの有機相に混ぜ、飽和炭酸水素ナトリウム水溶液、水で洗った後に、無水MgSO4で乾燥させた。濃縮して、黄色い粗生成物0.98gを得た。シリカゲルカラム精製により、3-メチルシクロペンタデカノン0.72gを得た。2-シクロペンタデセノンに対して、収率68%であった。
【0033】
【発明の効果】
本発明は、短い反応工程で、しかも汎用性のある装置により工業的に効率よくシクロアルケノンを、またこのシクロアルケノンから効率的にシクロアルカノンを、さらには、アルキルシクロアルカノンを製造することができるという格別の効果を奏する。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing a macrocyclic ketone compound used as a raw material such as a fragrance or an intermediate thereof with high efficiency.
[0002]
[Prior art]
Macrocyclic ketones such as cyclopentadecanone represented by the following chemical formula (1) and 3-methylcyclopentadecanone represented by chemical formula (2), so-called muskone, are known as aroma components of musk and are very expensive. It is traded.
[Chemical 1]
[0003]
As one of the industrial production methods of cyclopentadecanone, 2-hydroxycyclopentadecanone obtained by acyloin condensation of pentadecanedioic acid diester is used as a raw material and minerals such as zinc and sulfuric acid with a predetermined concentration are used. A method is known in which reduction is performed in an organic solvent in the presence of an acid to form cyclopentadecanone (Japanese Patent No. 3087921). This method is an excellent method that can reduce 2-hydroxycyclopentadecanone with good yield. However, in this method, since reduction occurs on the metal surface, zinc is highly contained in the two phases of the mineral acid aqueous solution and the organic solvent. It is necessary to disperse, and it is necessary to use a relatively small volume reactor to obtain the agitation necessary for sufficient dispersion, and this is a problem when considering scale-up to improve production efficiency. was there.
[0004]
In addition, after protecting the carbonyl group of 2-hydroxycyclopentadecanone, the hydroxyl group is converted to a leaving group such as a tosyl group, and then extracted in the presence of a base to form a double bond, thereby removing the carbonyl group. A method for synthesizing 2-cyclopentadecenone by protecting is known (Japanese Patent Publication No. 7-108876), and it is said that cyclopentadecanone will be obtained by hydrogenating this 2-cyclopentadecenone. (Alvin S. Williams, Synthesis, (1999), 10, 1707-1723). However, this 2-cyclopentadecenone synthesis method requires a multi-step reaction process, which is economically problematic.
[0005]
Furthermore, a method in which 2-hydroxycyclopentadecanone is used as a raw material, and dehydration is performed using alumina as a catalyst in a gas phase reaction to directly lead to 2-cyclopentadecenone (Stoll, M .; Commarmont, A. Helv. Chim. Acta 1948, 31, 554) is known, and it is predicted that cyclopentadecanone can be obtained by hydrogenating this. However, adoption of a gas phase reaction is not always easy in terms of apparatus and operation.
[0006]
On the other hand, as a method for synthesizing 3-methylcyclopentadecanone, after protecting the carbonyl group of 2-hydroxycyclopentadecanone, the hydroxyl group is converted to a leaving group such as a tosyl group and then extracted in the presence of a base. There is known a synthesis method in which 2-cyclopentadecenone obtained by generating a double bond by deprotection and deprotecting a carbonyl group is methylated by a conventional method (Japanese Patent Publication No. 7-108876). However, this method requires a long process until 2-cyclopentadecenone is obtained, and is not economical.
[0007]
Also, 2-cyclopentadecenone obtained by using cyclopentadecanone as a raw material, introducing a leaving group such as halogen at the 2-position, and generating a double bond by extracting in the presence of a base, Synthetic methods for methylation by conventional methods and variations thereof (Journal of the Korean Chemical Society, 40, 4, 243 (1996), etc.) are also known. However, it is difficult to say that this method is also economically superior considering that cyclopentadecanone is synthesized from 2-hydroxycyclopentadecanone.
[0008]
[Problems to be solved by the invention]
The present invention solves the above-mentioned problems, and an object of the present invention is to efficiently produce a cycloalkenone in a liquid phase reaction, a method for producing a cycloalkanone by hydrogenating this cycloalkenone as a raw material, and a cycloalkane. An object of the present invention is to provide a method for producing an alkylcycloalkanone by introducing an alkyl group into alkenone.
[0009]
[Means for Solving the Problems]
The inventor has preferred 2-hydroxycycloalkanone, which is preferable for improving production efficiency by scale-up, requires a short reaction step, and enables a liquid phase reaction that can be easily produced by a versatile apparatus. As a result of earnestly researching the synthesis method of cycloalkenone by dehydration reaction as a raw material, the presence of an acid catalyst surprisingly eliminates the need to introduce a protecting group even in a liquid phase reaction, resulting in a high yield. The cycloalkenone obtained can be easily converted to a cycloalkanone by reduction, and the 2-cycloalkenone in the cycloalkenone can be alkylated by a conventional method, economically converting to a 3-alkylcycloalkanone. The present invention has been found and the present invention has been conceived.
[0010]
That is, the method for producing the macrocyclic ketone compound of the present invention includes:
1) C2-C18 2-hydroxycycloalkanone, particularly preferably 2-hydroxycyclopentadecanone, is dehydrated in the liquid phase in the presence of an acid catalyst, particularly phosphoric acid or solid acid, and cycloalkenone, especially Is a method for producing cyclopentadecenone,
2) A method for producing cycloalkanone, particularly cyclopentadecanone by reducing cycloalkenone obtained by the above method, particularly cyclopentadecenone,
3) A method for producing an alkylcycloalkanone, particularly 3-methylcyclopentadecane by alkylating, in particular methylating, the cycloalkenone obtained by the above method, particularly 2-cyclopentadecenone,
Is included.
[0011]
BEST MODE FOR CARRYING OUT THE INVENTION
The 2-hydroxycycloalkanone having 12 to 18 carbon atoms, which is a raw material of the present invention, can be easily obtained by performing acyloin condensation of a linear alkanedicarboxylic acid diester having a corresponding carbon number in the presence of sodium metal in an organic solvent. Can be synthesized.
[0012]
Using these 2-hydroxycycloalkanones as raw materials, a dehydration reaction is performed by heating in the presence of an acid catalyst using a solvent as necessary. In this case, as the acid catalyst, phosphoric acids such as polyphosphoric acid such as orthophosphoric acid, metaphosphoric acid and pyrophosphoric acid, or solid acids such as silica alumina, zeolite, zirconia and / or zirconia sulfate with sulfuric acid supported on alumina or Zirconia alumina sulfate and the like (see Japanese Patent Publication No. 59-6181, Japanese Patent Application Laid-Open No. 11-809727, etc.) are preferable. The amount of these catalysts used varies depending on the type of the catalyst. For example, in the case of phosphoric acids, 0.01 to 0.5 mol per 1 mol of 2-hydroxycycloalkanone, and in the case of solid acids, 2-hydroxycycloalkanone It is preferable to select appropriately from the range of 0.01 to 1 part by weight per part by weight.
[0013]
When this reaction is carried out using a solvent, the solvent can be used without any problem as long as it is inert to this reaction, but from the viewpoint of stability, it is preferable to use a saturated hydrocarbon or an aromatic hydrocarbon. In this case, if the amount of the solvent used is too large, the reaction slows down, causing inconveniences such as poor reaction efficiency per fixed volume, so that the concentration of 2-hydroxycycloalkanone is 0.1 mol / liter or more. It is good to select appropriately from the range.
[0014]
The reaction temperature is 100 to 400 ° C., preferably 150 to 300 ° C. When a low boiling point solvent is used, the reaction may be carried out as a pressure reaction in an autoclave.
[0015]
The reaction time is determined in consideration of the concentration of the selected reaction solution, the reaction temperature, and the like.
[0016]
In such a dehydration reaction, isomerization and the like occur simultaneously, so the cycloalkenone that is a reaction product mainly consists of 2-cycloalkenone and 3-cycloalkenone. These mixtures can be easily converted to cycloalkanones by a hydrogenation reaction using a catalyst or the like. Examples of the catalyst that can be used for the hydrogenation reaction include a nickel catalyst, a cobalt catalyst, a copper catalyst, a palladium catalyst, a platinum catalyst, a ruthenium catalyst, and a rhodium catalyst. The amount of these catalysts to be used varies depending on the type and activity of the catalyst, but is preferably selected from the range of 0.001 to 0.1 parts by weight per 1 part by weight of cycloalkenone.
[0017]
This reaction is preferably carried out in the form of a solution using a solvent, and the solvent can be used without any problem as long as it is inert to this reaction, but from the viewpoint of convenience because it is used in a dehydration reaction. It is particularly preferable to use a saturated hydrocarbon or an aromatic hydrocarbon. In this case, the reaction can be carried out efficiently if the concentration of cycloalkenone is 0.1 mol / liter or more.
[0018]
The reaction temperature is 0 to 400 ° C., preferably room temperature to 100 ° C., and it is convenient to carry out under normal pressure hydrogen gas filling, but hydrogen gas may be bubbled, or using an autoclave, You may implement under 0-30 kg / cm < 2 > hydrogen pressurization. Furthermore, it may be carried out by a flow system in which the reaction liquid and hydrogen gas flow in the packed catalyst.
[0019]
The resulting hydrogenation reaction product can be purified by a conventional method such as distillation.
[0020]
On the other hand, a mixture of 2-cycloalkenone and 3-cycloalkenone of the reaction product obtained by the dehydration reaction described above is directly or, if necessary, 2-cycloalkenone obtained by a conventional method such as distillation or chromatography. After separation, for example, a 3-alkylated cycloalkanone can be obtained by a conventional method such as a Michael reaction in the presence of a copper reagent or a grinal reagent (Journal of the Korean Chemical Society, 40, 4, 243 (1996). )).
[0021]
Hereinafter, the present invention will be described with specific examples, but the scope of the present invention is not limited thereto.
[0022]
【Example】
Example 1
A thermometer and a condenser tube are set in a 100 ml three-necked flask, and 6.0 g of 2-hydroxycyclopentadecanone, 1.0 g of silica-alumina catalyst (HA manufactured by Catalyst Kasei Co., Ltd.) and 54.0 g of tetradecane are added, and magnetic. While stirring with a stirrer, the mixture was heated with a mantle heater and reacted at a reaction solution temperature of 220 ° C. for 7 hours. When eicosane was added to the reaction solution as an internal standard substance and quantitatively determined by gas chromatography, a cyclopentadecenone mixture was obtained at a yield of 85% based on 2-hydroxycyclopentadecanone.
[0023]
(Example 2)
Add 200g of 2-hydroxycyclopentadecanone, 1.0g of silica-alumina catalyst (HA made by Catalyst Kasei Co., Ltd.) and 54.0g of toluene to a 200ml autoclave and stir with a magnetic stirrer at an oil bath temperature of 240 ° C for 5 hours. Reacted. When eicosane was added to the reaction solution as an internal standard substance and quantitatively determined by gas chromatography, a cyclopentadecenone mixture was obtained in a yield of 90% based on 2-hydroxycyclopentadecanone.
[0024]
(Example 3)
Place a thermometer and cooling tube in a 100 ml three-necked flask, add 6.0 g of 2-hydroxycyclopentadecanone, 0.5 g of silica-alumina catalyst (LA from Catalytic Chemicals), and 12.0 g of tetradecane at 200 ° C. For 1 hour. When eicosane was added to the reaction solution as an internal standard substance and quantitatively determined by gas chromatography, a cyclopentadecenone mixture was obtained at a yield of 11% based on 2-hydroxycyclopentadecanone.
[0025]
Example 4
Place a thermometer and cooling tube in a 100 ml three-necked flask, add 6.0 g of 2-hydroxycyclopentadecanone, 1.0 g of zeolite catalyst (CBV720 made by Zeolyst) and 12.0 g of tetradecane, and use a magnetic stirrer. While stirring, the mixture was heated with a mantle heater and reacted at 200 ° C. for 12 hours. When eicosan was added as an internal standard substance to the reaction solution and quantitatively determined by gas chromatography, a cyclopentadecenone mixture was obtained in a yield of 41% based on 2-hydroxycyclopentadecanone.
[0026]
(Example 5)
When a thermometer and a condenser tube were set in a 100 ml three-necked flask, 6.0 g of 2-hydroxycyclopentadecanone and zirconia alumina sulfate (prepared by the method described in JP-A-11-809727) 5.0 g Then, 54.0 g of tetradecane was added, and the mixture was heated with a mantle heater while stirring with a magnetic stirrer, and reacted at 200 ° C. for 4 hours. When eicosan was added as an internal standard substance to the reaction solution and quantitatively determined by gas chromatography, a cyclopentadecenone mixture was obtained in a yield of 73% based on 2-hydroxycyclopentadecanone.
[0027]
(Example 6)
To a 100 ml three-necked flask, set a thermometer and a condenser tube, add 6.0 g of 2-hydroxycyclopentadecanone and 0.1 g of H 3 PO 4 , and heat with a mantle heater while stirring with a magnetic stirrer. And reacted at 240 ° C. for 20 minutes. When eicosan was added as an internal standard substance to the reaction solution and quantitatively determined by gas chromatography, a cyclopentadecenone mixture was obtained in a yield of 64% with respect to 2-hydroxycyclopentadecanone.
[0028]
(Example 7)
Place a thermometer and cooling tube in a 100 ml three-necked flask, add 6.0 g of 2-hydroxycyclopentadecanone and 0.1 g of H 4 P 2 O 7 , and stir with a magnetic stirrer. And reacted at 240 ° C. for 20 minutes. When eicosane was added to the reaction solution as an internal standard substance and quantitatively determined by gas chromatography, a cyclopentadecenone mixture was obtained at a yield of 65% with respect to 2-hydroxycyclopentadecanone.
[0029]
(Example 8)
Place a thermometer and cooling tube in a 100 ml three-necked flask, add 6.0 g of 2-hydroxycyclopentadecanone, 0.5 g of HPO 3 and 18.0 g of tetradecane, and stir with a magnetic stirrer. And reacted at 250 ° C. for 6 hours. When eicosan was added to the reaction solution as an internal standard substance and quantitatively determined by gas chromatography, a cyclopentadecenone mixture was obtained in a yield of 63% based on 2-hydroxycyclopentadecanone.
[0030]
(Example 9)
A thermometer and a cooling tube were set in a 100 ml three-necked flask, and 6.0 g of 2-hydroxycyclotridecanone, 1.0 g of silica alumina catalyst (HA manufactured by Catalyst Kasei Co., Ltd.), and 54.0 g of tetradecane were added. The mixture was heated with a mantle heater while being stirred at, and reacted at a reaction solution temperature of 220 ° C. for 7 hours. When eicosan was added as an internal standard substance to the reaction solution and quantitatively determined by gas chromatography, a cyclotridecenone mixture was obtained in a yield of 81% based on 2-hydroxycyclotridecanone.
[0031]
(Example 10)
To a 100 ml eggplant flask, 2.0 g of a cyclopentadecenone mixture, 0.1 g of 5% Pd / C, and 18.0 g of toluene were added and reacted at room temperature for 3 hours in a hydrogen atmosphere. When eicosane was added to the reaction solution as an internal standard substance and quantified by gas chromatography, cyclopentadecanone was obtained with a hydrogenation yield of 100%.
[0032]
(Example 11)
Set a thermometer and dropping funnel in a 100 ml three-necked flask. Add 0.44 g of anhydrous CuCl, 1.3 ml of CH 3 MgI ether solution (0.84 mol / l), and 15 ml of dry ether to the flask, and cool in an ice bath. , 1.2 g of cyclopentadecenone mixture in the dropping funnel (obtained by column purification of the dehydrated reaction product, containing 62% 2-cyclopentadecenone) and 5 ml of dry ether dropwise slowly over about 1 hour did. After completion of the dropping, the temperature of the reaction solution was raised to 10 ° C., and stirring was further continued for 2 hours. While cooling with ice, 10 ml of a 10% aqueous hydrochloric acid solution was added dropwise to separate the organic phase. The aqueous phase extracted with dichloromethane was mixed with this organic phase, washed with a saturated aqueous sodium hydrogen carbonate solution and water, and then dried over anhydrous MgSO 4 . Concentration gave 0.98 g of a crude yellow product. By silica gel column purification, 0.72 g of 3-methylcyclopentadecanone was obtained. The yield was 68% based on 2-cyclopentadecenone.
[0033]
【The invention's effect】
In the present invention, cycloalkenone can be produced industrially and efficiently from a short reaction step and using a versatile apparatus, cycloalkanone can be efficiently produced from this cycloalkenone, and further, alkylcycloalkanone can be produced. There is a special effect that you can.
Claims (6)
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US7479574B2 (en) * | 2004-11-11 | 2009-01-20 | Takasago International Corporation | Method of producing macrocyclic ketone, and intermediate thereof |
JP2008100951A (en) * | 2006-10-19 | 2008-05-01 | Kawaguchi Yakuhin Kk | Method for preparing 2-cyclopentadecenone |
EP2412696A4 (en) * | 2009-03-27 | 2012-08-22 | Masaharu Doya | Process for production of 3-methyl-cyclopentadecenone, process for production of r/s-muscone, and process for production of optically active muscone |
CN101979367B (en) * | 2010-10-22 | 2014-03-05 | 刘畅 | Preparation method of trimethyl macrocyclic ketone |
CN104560359A (en) * | 2014-12-24 | 2015-04-29 | 江南大学 | Method for catalyzing cellulose to be liquefied into biological oil by using magnetic solid acid |
CN106946679B (en) * | 2017-05-08 | 2020-07-31 | 苏州碳壹科技有限公司 | Preparation method of E-2-cyclopentadecanone |
CN114621069B (en) * | 2022-03-16 | 2023-04-07 | 宏济堂制药(商河)有限公司 | Method for preparing macrocyclic ketone by using binary composite solvent system |
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US2656391A (en) * | 1947-10-07 | 1953-10-20 | Firmenich & Co | Processes for the preparation of alpha-beta unsaturated cyclopolymethylenic ketones |
JPS5148635A (en) * | 1974-10-16 | 1976-04-26 | Toray Industries | Daikanjoketonno seizoho |
JPH04139144A (en) * | 1990-09-29 | 1992-05-13 | Nippon Zeon Co Ltd | Production of large ring ketones |
JPH05155802A (en) * | 1991-12-02 | 1993-06-22 | Nikko Kyodo Co Ltd | Production of large cyclic ketone |
JPH11315044A (en) * | 1998-02-12 | 1999-11-16 | Basf Ag | Production of 2-cycloalkenone |
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US2656391A (en) * | 1947-10-07 | 1953-10-20 | Firmenich & Co | Processes for the preparation of alpha-beta unsaturated cyclopolymethylenic ketones |
JPS5148635A (en) * | 1974-10-16 | 1976-04-26 | Toray Industries | Daikanjoketonno seizoho |
JPH04139144A (en) * | 1990-09-29 | 1992-05-13 | Nippon Zeon Co Ltd | Production of large ring ketones |
JPH05155802A (en) * | 1991-12-02 | 1993-06-22 | Nikko Kyodo Co Ltd | Production of large cyclic ketone |
JPH11315044A (en) * | 1998-02-12 | 1999-11-16 | Basf Ag | Production of 2-cycloalkenone |
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