JPS6156148A - Preparation of macrocyclic ketone - Google Patents

Abstract

PURPOSE:To improve the yield with ease in one process in preparing the titled substance useful as perfumes, etc. from a diester of a straight chain alkanedioic acid having a specific carbon number with a lower alcohol as a raw material, through condensation and reduction, by using a common solvent in both reactions of condensation and reduction. CONSTITUTION:A diester os 12-18C straight chain alkanedioic acid with a lower alcohol as a raw material is dissolved in an organic solvent, having 60 deg.C boiling point, forming an azetropic mixture with water, but substantially incompatible therewith at room temperature (example, benzen, toluene, raphthalene, etc.). The amount to be dissolves is preferably in 1-60wt% range. Then 4-6 molar equivalents, based on the diester, alkali matel such as metalic sodium is dispersed in the solution of the raw material dissolved therein, the refluxed under heating at 60-140 deg.C to obtain an acyloin condensation product. Then the condensate is subjected to reductive reaction without isolation to obtain the aimed compound. The reduction is carried out by contact with a mineral acid in the presence of zinc, etc.

Description

【発明の詳細な説明】 産業上の利用分野 本発明は炭素数１２〜１８の直鎖アルカン二酸のジエス
テルをアシロイン縮合反応及び還元反応によ如、シクロ
テトラデカノン、シクロペンタデカノン、シクロヘキサ
デカノン等の炭素数１２〜１８の大環状ケトンを製造す
る方法に関する。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to the production of cyclotetradecanone, cyclopentadecanone, and cyclohexyl diester by acyloin condensation reaction and reduction reaction of linear alkanedioic acids having 12 to 18 carbon atoms. The present invention relates to a method for producing a macrocyclic ketone having 12 to 18 carbon atoms such as sadecanone.

尚、炭素数１２〜１８の大環状ケトンはムスク様の匂い
を呈し、香料またはその調合基材として用いられる。Macrocyclic ketones having 12 to 18 carbon atoms exhibit a musk-like odor and are used as perfumes or base materials for their preparation.

従来の技術 大環状ケトンの製造方法として、下記式に示すように、
直鎖アルカ／ジカルボン酸のジエステルをアシロイン縮
合反応により分子内環化し。Conventional technology As a method for producing macrocyclic ketones, as shown in the following formula,
A diester of a linear alkali/dicarboxylic acid is intramolecularly cyclized by an acyloin condensation reaction.

還元する方法が提案されている（　Ｈｅ１ｖ、　（！ｈ
ｉｍ、　Ａｃｔａ　、。A method of reducing the amount has been proposed ( He1v, (!h
im, Acta,.

旦Ｐ１７４１（１９４７））。Dan P1741 (1947)).

上記方法においては、アシロイン縮合反応後メタノール
を加えて未反応のナトリウムを付加物とし２次いで、希
硫酸を加えて中和し、酸水層を分離し、キシレン溶液を
炭酸ナトリウム水溶液及び水で洗浄し硫酸す）　ＩＪウ
ムで乾燥して。In the above method, after the acyloin condensation reaction, methanol is added to convert unreacted sodium into an adduct.Next, dilute sulfuric acid is added to neutralize, the acid aqueous layer is separated, and the xylene solution is washed with an aqueous sodium carbonate solution and water. (sulfuric acid) and dry with IJum.

減圧蒸留によりアシロイン縮合生成物を分取して単離し
、この単離精製されたアシロイン縮合生成物を氷酢酸に
溶解して還元反応に供していた。The asiloin condensation product was fractionated and isolated by vacuum distillation, and the isolated and purified asiloin condensation product was dissolved in glacial acetic acid and subjected to a reduction reaction.

上述した方法においては、アシロイン縮合反応と還元反
応との溶媒が異なるため、アシロイン縮合生成物を一度
蒸留等により単離しなければならず、操作が煩維となり
、また、蒸留時の加熱によるアシロイン縮合生成物の変
性によるロスが生じ、最終目的物である大環状ケトンの
生産効率が悪い等の問題があった。In the above-mentioned method, since the solvents used in the acyloin condensation reaction and the reduction reaction are different, the acyloin condensation product must be isolated once by distillation, etc., which makes the operation complicated. There were problems such as loss of product due to denaturation and poor production efficiency of the final target product, a macrocyclic ketone.

本発明者は、かかる問題を解決すべく鋭意検討した結果
、アシロイン縮合反応及び還元反応において共通の溶媒
を用いることができることさらには、アシロイン縮合生
成物を単離しなく１　　　　ても還元反応を行うことが
できることを見い出した。As a result of intensive studies to solve this problem, the inventors of the present invention found that a common solvent can be used in the asiloin condensation reaction and the reduction reaction, and that the reduction reaction can be carried out without isolating the asiloin condensation product. I discovered that it can be done.

本発明は、かかる知見に基いてなされたものであり１本
発明の目的はアシロイン縮合生成物の分離操作及び熱変
性によるロスがほとんどなく１反応操作が簡便で生産効
率の高い大環状ケトンの製造方法を提供することＫある
。The present invention has been made based on this knowledge, and the object of the present invention is to produce a macrocyclic ketone with a simple reaction operation and high production efficiency, with almost no loss due to separation operations and thermal denaturation of the acyloin condensation product. K is to provide a method.

問題点を解決するための手段 本発明は、炭素数１２〜１８の直鎖アルカン二酸の低級
アルコールとのジエステル化物をアシロイン縮合反応に
より分子内環化し、得られたアシロイン縮合反応生成物
を還元して大環状ケトンを製造する方法において、前記
アシロイン縮合反応を沸点が６０℃以上で、かつ水と共
沸し室温において実質的に水と相溶しない有機溶媒の存
在下に行い１次いで得られたアシロイン縮合反応生成物
を当該有機溶媒から単離することなく還元することを特
徴とする大環状ケトンを製造する方法である、 作用 本発明に用いられる炭素数１２〜１８の直鎖アルカン二
酸の低級アルコールとのジエステル化物は、炭素数１２
〜１８の直鎖アルカン二酸をメ・ボラ− タノール又はエタノール等の低級アルコールと酸触媒の
存在下に加熱還流してエステル化することにより容易に
得られる。尚、前記炭素数１２〜１８の直鎖アルカン二
酸は９石油留分等からモレキュラーシープ法又は尿素法
により分離し、精製した炭素数１２〜１６の直鎖アルカ
ンを微生物を利用して酸化させる（例えば、特公昭５７
−２９９９４号公報参照）方法により安価に得ることが
できる。Means for Solving the Problems The present invention involves intramolecularly cyclizing a diester of a linear alkanedioic acid having 12 to 18 carbon atoms with a lower alcohol through an acyloin condensation reaction, and reducing the resulting acyloin condensation reaction product. In the method for producing a macrocyclic ketone, the acyloin condensation reaction is carried out in the presence of an organic solvent having a boiling point of 60° C. or higher, which is azeotropic with water and is substantially incompatible with water at room temperature. A method for producing a macrocyclic ketone, characterized in that the acyloin condensation reaction product is reduced without isolating it from the organic solvent. The diesterified product with lower alcohol has 12 carbon atoms.
It can be easily obtained by heating and refluxing a linear alkanedioic acid of 1 to 18 in the presence of a lower alcohol such as mevolathanol or ethanol and an acid catalyst to esterify it. The linear alkanedioic acid having 12 to 18 carbon atoms is separated from 9 petroleum fractions by the molecular sheep method or the urea method, and the purified linear alkane having 12 to 16 carbon atoms is oxidized using microorganisms. (For example, Tokuko Sho 57
29994)) can be obtained at low cost.

アシロイン縮合反応の溶剤として用いる沸点が６０℃以
上で、かつ水と共沸し室温において実質的に水と相溶し
ない有機溶媒としては、ベンゼン、トルエン、キシレン
、シクロヘキサン。Examples of organic solvents used as a solvent for the acyloin condensation reaction that have a boiling point of 60° C. or higher, are azeotropic with water, and are substantially incompatible with water at room temperature are benzene, toluene, xylene, and cyclohexane.

ヘキサン、ナフタレン、イソプロピルエーテル等を例示
し得る。尚、これらの溶媒は、もちろん二種以上の混合
溶媒として用いることもできる。ところで、アシロイン
縮合反応及び後続の還元反応は６０℃以下の反応温度で
は１反応速度が極めて遅いため、有機溶媒は沸点が６０
℃以上のものを用いる必要がある。また、還元度４一 応において還元反応の進み過ぎを防止するためＫは、当
該反応系から生成水等を除く必要があり、この水の除去
を容易にするために、水と共沸する有機溶媒を用いる必
要がある。また、この有機溶媒はアシロイン縮合反応終
了後の未反応物、副生物を水で洗浄除去する場合、アシ
ロイン反応生成物のロスを少なくするためには。Examples include hexane, naphthalene, and isopropyl ether. Incidentally, these solvents can of course also be used as a mixed solvent of two or more kinds. By the way, the reaction rate of the acyloin condensation reaction and the subsequent reduction reaction is extremely slow at a reaction temperature of 60°C or lower, so the organic solvent has a boiling point of 60°C.
It is necessary to use a temperature higher than ℃. In addition, in order to prevent the reduction reaction from proceeding too much at reduction degree 4, it is necessary to remove produced water etc. from the reaction system, and in order to facilitate the removal of this water, an organic solvent that is azeotropic with water must be used. It is necessary to use In addition, this organic solvent is used in order to reduce the loss of asiloin reaction products when unreacted substances and by-products are washed away with water after the completion of the asiloin condensation reaction.

室温において実質的に水と相溶しない好捷しくは水への
溶解度が室温で１係以下のものを用いる。It is preferable to use a material that is substantially incompatible with water at room temperature, and preferably has a solubility in water of 1 part or less at room temperature.

本発明においては、先ず、前述したジエステル化物を前
記の有機溶媒に溶解させる。溶解量としては１〜６０重
量憾が好ましい。１重量係以下となると反応効率が悪く
、また６０重量係以上となると重合及応等、環化物以外
の副反応生成物が多く生じ好ましくない。次に、ジエス
テル化物を溶解した溶液に金属す）　ＩＪウム等のアル
カリ金属をジエステルに対し４〜６モル当量懸濁して、
好ましくけ６０〜１４０℃の温度に０．５〜４８時間加
熱還流することＫよりアシロイン縮合反応を行わしめる
。この場合、窒素雰囲気下に反応させることにより生酸
物の酸化を防止でき、また無水の条件下で反応させるこ
とによυ反応が円滑に進む。反応終了後は当該反応液を
冷却し、メタノール等のアルコールを加えて過剰のアル
カリ金属を反応させ、氷酢酸又は塩酸の水溶液等酸を用
いて中和し、当該水溶液層を分離し水で数回洗浄する。In the present invention, first, the above-mentioned diester compound is dissolved in the above-mentioned organic solvent. The amount to be dissolved is preferably 1 to 60 weight. If it is less than 1 weight ratio, the reaction efficiency is poor, and if it is more than 60 weight ratio, many side reaction products other than cyclized products, such as polymerization reactions, will occur, which is not preferable. Next, 4 to 6 molar equivalents of an alkali metal such as IJium are suspended in a solution containing the diester,
The acyloin condensation reaction is preferably carried out by heating under reflux at a temperature of 60 to 140°C for 0.5 to 48 hours. In this case, oxidation of the bioacid can be prevented by carrying out the reaction under a nitrogen atmosphere, and the υ reaction proceeds smoothly by carrying out the reaction under anhydrous conditions. After the reaction is completed, the reaction solution is cooled, alcohol such as methanol is added to react the excess alkali metal, neutralized using an acid such as glacial acetic acid or an aqueous solution of hydrochloric acid, and the aqueous solution layer is separated and diluted with water. Wash twice.

以上のようにして得られたアシロイン縮合生成物を含有
した溶液から当該アシロイン縮合生成物を単離すること
なく還元反応に供する。すなわち、前記アシロイン縮合
生成物を含有した溶液、又は有機溶媒を一部除いた濃縮
溶液に、還元剤金属例えば亜鉛、スズ、アルミニウム等
の金属又はこれらの合金粉末を加え、６０〜１４０℃の
温度に保持しながら塩酸又は硫酸等を滴下し還元反応を
行う。還元剤金属の添加量は、溶液中のアシロイン縮合
生成物に対し１．５〜５倍モル当量とすることが好まし
い。１．５倍モル当量以下では還元反応が十分に進行せ
ず、また５倍モル当量以上とすると反応に関与しない金
属量が増大し不経済なためである。鉱酸は１反応期間を
通じ全体として前記還元剤金属の１〜３倍モル当量添加
すればよい。The solution containing the asiloin condensation product obtained as described above is subjected to a reduction reaction without isolating the asylloin condensation product. That is, a reducing agent metal such as zinc, tin, aluminum, or an alloy powder thereof is added to a solution containing the above-mentioned acyloin condensation product or a concentrated solution from which the organic solvent has been partially removed, and the mixture is heated at a temperature of 60 to 140°C. While maintaining the temperature, hydrochloric acid or sulfuric acid is added dropwise to perform a reduction reaction. The amount of the reducing agent metal added is preferably 1.5 to 5 times the molar equivalent of the acyloin condensation product in the solution. This is because if the amount is less than 1.5 times the molar equivalent, the reduction reaction will not proceed sufficiently, and if it is more than 5 times the molar equivalent, the amount of metal that does not participate in the reaction will increase, which is uneconomical. The mineral acid may be added in a total amount of 1 to 3 times the molar equivalent of the reducing agent metal throughout one reaction period.

また、還元の他の方法としてアシロイン縮合反応生成物
を含有する溶液に亜鉛等の触媒金属を添加し、水素を吹
き込んで還元する方法も可能であ。Further, as another method of reduction, a method of adding a catalytic metal such as zinc to a solution containing the acyloin condensation reaction product and blowing hydrogen into the solution is also possible.

以上のようなアシロイン縮合反応及び渦→→還元反応は
１図に例示したような反応装置を用いると好適である。The above-mentioned acyloin condensation reaction and vortex→→reduction reaction are preferably carried out using a reaction apparatus as illustrated in FIG.

以下に、この図に基き反応操作の一例を説明する。An example of reaction operation will be explained below based on this figure.

捷ず、アルカンジカルボン酸のジエステルを沸点が６０
℃以上で、水と共沸する有機溶媒に溶解し９反応容器１
内に収容する。次に、この溶液に金属す）　ＩＪウムを
分散状態で入れ、ガス供給管２から窒素ガスを連続的に
供給しながら加熱器（図示せず）により６０〜１４０℃
の温　　　　”度に加熱し反応させる。反応中はモータ
３の回転により攪拌翼４を回転させて溶液を攪拌する。Diester of alkanedicarboxylic acid with a boiling point of 60
℃ or above, dissolved in an organic solvent that is azeotropic with water.9 Reaction vessel 1
to be contained within. Next, metal (IJ) is added to this solution in a dispersed state, and heated to 60 to 140°C using a heater (not shown) while continuously supplying nitrogen gas from the gas supply pipe 2.
The solution is heated to a temperature of 100° and reacted.During the reaction, the stirring blade 4 is rotated by the rotation of the motor 3 to stir the solution.

加熱により蒸気となった有機溶媒は冷却器５により冷却
され、一旦受器６に保留され連通管７をオーバーフロー
して反応容器１内に戻る。温度計８で温度を監視しなが
ら０．５〜４８時間の加熱、還流して反応を終了させる
。反応終了後。The organic solvent turned into vapor by heating is cooled by the cooler 5, temporarily retained in the receiver 6, overflows the communication pipe 7, and returns to the reaction vessel 1. The reaction is completed by heating and refluxing for 0.5 to 48 hours while monitoring the temperature with a thermometer 8. After the reaction is complete.

反応容器１内の溶液を冷却した後給液ロート９からメタ
ノールを供給し、未反応の金属ナトリウムを反応させ窒
素の供給を停止する。次いで給液ロート９から氷酢酸水
溶液を供給する。静置した後水溶液層を下部ノズル１０
の弁を開いて除去する。さらに給液ロート９から水を入
れ。After cooling the solution in the reaction vessel 1, methanol is supplied from the feed funnel 9 to react unreacted metallic sodium, and the supply of nitrogen is stopped. Next, a glacial acetic acid aqueous solution is supplied from the liquid supply funnel 9. After standing still, the aqueous solution layer is transferred to the lower nozzle 10.
Remove by opening the valve. Add water from the liquid supply funnel 9.

洗浄した後に同様に水層を下部ノズル１０から除く。同
様の操作を数回繰υ返す。After washing, the water layer is similarly removed from the lower nozzle 10. Repeat the same operation several times.

次いで１反応容器１内の溶液に滴下ロート９を介して亜
鉛等の還元剤金属を加える。次に当該溶液を６０℃以上
に加熱し、・、有機溶媒を還流させる。供給ロート９に
は塩酸又は硫酸等の鉱酸が収容され１反応期間中少量ず
つ反応容器１内に滴下供給される。反応により生成した
水及び鉱酸中に含まれている水は、有機溶媒との共沸に
より蒸気となり冷却器５で冷却され、有機溶媒とともに
受器６に保留される。受器６内で有機溶媒と水は分離し
、水は受器６の下部から弁１１を介して抜き出され、ま
た有機溶媒は連通管７からオーバーフローして反応容器
１内に戻る。Next, a reducing agent metal such as zinc is added to the solution in one reaction vessel 1 via the dropping funnel 9. Next, the solution is heated to 60° C. or higher, and the organic solvent is refluxed. A mineral acid such as hydrochloric acid or sulfuric acid is stored in the supply funnel 9 and is supplied dropwise into the reaction vessel 1 little by little during one reaction period. The water produced by the reaction and the water contained in the mineral acid are turned into steam by azeotropy with the organic solvent, cooled by the cooler 5, and retained in the receiver 6 together with the organic solvent. The organic solvent and water are separated in the receiver 6, the water is withdrawn from the lower part of the receiver 6 through the valve 11, and the organic solvent overflows from the communication pipe 7 and returns into the reaction vessel 1.

抜き出す。反応後の溶液は無機物を濾過しだ後水洗し蒸
留により有機溶媒を除去し減圧蒸留操作で公地すること
により大環状ケトンを得ることができる。Pull it out. After the reaction, the solution is filtered to remove inorganic substances, washed with water, distilled to remove the organic solvent, and distilled under reduced pressure to obtain a macrocyclic ketone.

実施例 実施例１ 図に示すような反応装置を用い、１０ｔの反応容器に脱
水したキシレン４ｔを入れ、これに金属す）　ＩＪウム
３９．８　Ｆを加えた。窒素通気下にキシレ／の温度を
１０５℃に保ち。Examples Example 1 Using a reaction apparatus as shown in the figure, 4 tons of dehydrated xylene was placed in a 10 ton reaction vessel, and 39.8 F of metal (IJ) was added thereto. The temperature of the xylem was maintained at 105°C under nitrogen aeration.

該キシレン液中にあらかじめ脱水キシレン２５０−にｎ
−ペンタデカン二酸のジメチルエステル１１０ｆを溶解
した溶液を１５時間かけて滴下してアシロイン縮合反応
を行わしめた。滴下終了後、１時間１０５℃の温度に保
ち２次いで冷却してメタノール２００ｓ／を徐々に滴下
した。次に氷酢酸１５０−を加えて中和、静置した後水
層を分離し、１ｔの飽和食塩水で２回洗浄した。In the xylene solution, 250-n of dehydrated xylene was added in advance.
-Asiloin condensation reaction was carried out by dropping a solution of dimethyl ester of pentadecanedioic acid 110f over 15 hours. After the dropwise addition was completed, the temperature was maintained at 105° C. for 1 hour, and then cooled, and 200 s of methanol was gradually added dropwise. Next, 150 g of glacial acetic acid was added to neutralize the mixture, and after standing still, the aqueous layer was separated and washed twice with 1 t of saturated brine.

次に、このアシロイン縮合反応生成物を含むキシレン溶
液を４００−までキシレンを留去して濃縮し、この溶液
に亜鉛粉末８０ｔを添加し還流条件下に濃塩酸６００ｔ
Ｒｔを１．５時間かけて滴下し還元反応を行わしめた。Next, the xylene solution containing the acyloin condensation reaction product was concentrated by distilling off the xylene to a concentration of 400 ml, 80 t of zinc powder was added to this solution, and 60 t of concentrated hydrochloric acid was added to the solution under reflux conditions.
Rt was added dropwise over 1.5 hours to carry out the reduction reaction.

反応終了後、亜鉛粉末等を戸別し、１０憾炭酸す）　Ｉ
Ｊウム水溶液及び蒸留水で洗浄した後無水硫酸す）　Ｉ
Ｊウム約１０ｆを添加乾燥し。After the reaction is completed, the zinc powder, etc. is taken from house to house and carbonated for 10 minutes)
After washing with Jum aqueous solution and distilled water, wash with anhydrous sulfuric acid)
Add about 10 f of Jum and dry.

蒸発器でキシレンの大部分を留去した後減圧蒸留（２Ｔ
ｏｒｒ以下）によりシクロベンタデカッｒ　　　　　ン
５１．　Ｏｆを得た。これはペンタデカン二酸ジメチル
エステルに対する理論収量の６２．１係であった。After removing most of the xylene using an evaporator, vacuum distillation (2T
orr below) by cyclobentadecane 51. I got Of. This was 62.1 times the theoretical yield for pentadecanedioic acid dimethyl ester.

実施例２ ｎ−ヘキサデカン二酸ジエチルエステル１００ｔを出発
原料とし、有機溶媒としてトルエンを用い、他は実施例
１に記載しだのと同じ方法でシクロヘキサデカノンを合
成した。Example 2 Cyclohexadecanone was synthesized using 100 t of n-hexadecanedioic acid diethyl ester as a starting material and using toluene as an organic solvent, but in the same manner as described in Example 1, except for using toluene as an organic solvent.

この結果、シクロヘキサデカン４２３２を得。As a result, cyclohexadecane 4232 was obtained.

△ ｎ−ヘキサデカン二酸ジエチルエステルに対する理論収
量の５４．６４であった。Δ The theoretical yield for n-hexadecanedioic acid diethyl ester was 54.64.

実施例３ ｎ−）リデカン二酸ジメチルエステル１００ｔを出発原
料とし、有機溶媒としてトルエンを用い、他は実施例１
に記載したのと同じ方法でシクロトリデカノン３９２ｆ
を合成した。Example 3 n-) 100 t of dimethyl didecanedioic acid ester was used as the starting material, toluene was used as the organic solvent, and the rest was as in Example 1.
Cyclotridecanone 392f in the same manner as described in
was synthesized.

これは、ｎ−トリデカン二酸ジメチルエステルに対する
理論収量の５２．５４であった。This was a theoretical yield of 52.54 for n-tridecanedioic acid dimethyl ester.

比較例 １ｒｌｔ（７）４つロヘルツフラスコに脱水したキシレ
ン４ｔを入れ、これに金属ナトリウム賃８Ｖを添加し、
窒素通気下に１０５℃の温度に保持した。次に当該液に
ｎ−ペンタデカン二酸のジメチルエステル１１０ｆをキ
シレン２５〇−に溶解した溶液を１５時間かけて滴下し
た。滴下終了後１時間そのまま１０５℃の温度に保ち。Comparative Example 1rlt (7) 4 tons of dehydrated xylene was placed in a Rohrtz flask, 8V of metallic sodium was added to it,
The temperature was maintained at 105°C under nitrogen bubbling. Next, a solution of 110f dimethyl ester of n-pentadecanedioic acid dissolved in 250-xylene was added dropwise to the solution over 15 hours. After the completion of dropping, keep the temperature at 105°C for 1 hour.

次いで、８０℃以下の温度に冷却してメタノール２００
−を徐々に滴下した。Next, it is cooled to a temperature of 80°C or less and methanol 200°C is added.
- was gradually added dropwise.

次に、当該液を氷冷し９反応混合物に氷酢酸１５０−を
加え中和した。水層を分離した後。Next, the liquid was cooled with ice, and 150-g of glacial acetic acid was added to the reaction mixture to neutralize it. After separating the aqueous layer.

減圧蒸留を行い１５２〜１６６℃（０，３！Ｓ〜０，９
５ｍＨｇ　）の温度での留分を分取するととＫよジアジ
ロイン縮合反応生成物＋ｓ　５．　Ｏｒ　（２−ヒドロ
キシシクロペンタデカノンの純度はｓｑ、ｓｉ景憾）を
得た。Perform vacuum distillation at 152~166℃ (0,3!S~0,9
5. When the fraction at a temperature of 5 mHg is collected, the diaziloin condensation reaction product +s is obtained. Or (purity of 2-hydroxycyclopentadecanone is sq, si Jing) was obtained.

次に、酢酸１００＋ｄＫ亜鉛粉末４５．５Ｆを分散させ
ておき、これに上述した方法で得られたアシロイン縮合
反応生成物を６ｓ、　ｏ　ｔ　９ｈ溶解し７５〜８０℃
の温度に加熱保持して濃塩酸５〇−を５〜１０分かけて
滴下し、２０〜２５分間攪拌する。この滴下及び攪拌操
作を３回縁シ返した後反応を終了し、亜鉛粉末を戸別し
た後。Next, acetic acid 100 + dK zinc powder 45.5F was dispersed, and the acyloin condensation reaction product obtained by the above method was dissolved therein for 6 seconds and 9 hours at 75 to 80°C.
While heating and maintaining the temperature, 50% of concentrated hydrochloric acid is added dropwise over 5 to 10 minutes, and the mixture is stirred for 20 to 25 minutes. After repeating this dropping and stirring operation three times, the reaction was completed and the zinc powder was removed from house to house.

飽和食塩水５００−を加えエーテル２００−で２回抽出
した。次に、当該抽出物を１０弧炭酸ソーダ水溶液２０
０−で洗浄し、さらに飽和食塩水２００−で洗浄した。Added 500% of saturated brine and extracted twice with 200% of ether. Next, the extract was added to a 10% aqueous solution of 20% sodium carbonate.
It was washed with 200-ml of saturated saline solution.

次いで、無水硫酸マグネシウム約１Ｏｆを添加して乾燥
した後炉別し、蒸発器でエーテルの大部分を留去した後
。Next, about 1Of of anhydrous magnesium sulfate was added and dried, then separated in a furnace, and most of the ether was distilled off in an evaporator.

減圧蒸留によりシクロペンタデカノン３７．４　ｔを得
た。これはペンタデカン二酸ジメチルエステルに対する
理論収量の４５．５４であった。37.4 t of cyclopentadecanone was obtained by distillation under reduced pressure. This was a theoretical yield of 45.54 for pentadecanedioic acid dimethyl ester.

効果 一１％１のロスが少なく、また反応操作が簡便で。effect The loss of 1% is small, and the reaction operation is simple.

生産効率を著るしく高めることができる格別の効果を奏
するものである。This has a special effect of significantly increasing production efficiency.

【図面の簡単な説明】[Brief explanation of drawings]

図は１本発明の方法に用いる好適ガ反応装置の一例を示
すものである。図中１は反応容器。 ４け攪拌機、５は冷却器、９は供給ロートを示す。The figure shows an example of a suitable reaction apparatus for use in the method of the present invention. In the figure, 1 is a reaction vessel. 4 stirrers, 5 a cooler, and 9 a feeding funnel.

Claims (1)

【特許請求の範囲】[Claims] 炭素数１２〜１８の直鎖アルカン二酸の低級アルコール
とのジエステル化物をアシロイン縮合反応により分子内
環化し、得られたアシロイン縮合反応生成物を還元して
大環状ケトンを製造する方法において、前記アシロイン
縮合反応を沸点が６０℃以上でかつ水と共沸し室温にお
いて実質的に水と相溶しない有機溶媒の存在下に行い、
次いで、得られたアシロイン縮合反応生成物を当該有機
溶媒から単離することなく還元することを特徴とする大
環状ケトンを製造する方法。In the method of producing a macrocyclic ketone by intramolecularly cyclizing a diester product of a linear alkanedioic acid having 12 to 18 carbon atoms with a lower alcohol by an acyloin condensation reaction and reducing the obtained acyloin condensation reaction product, The acyloin condensation reaction is carried out in the presence of an organic solvent having a boiling point of 60° C. or higher, azeotropic with water, and substantially incompatible with water at room temperature,
A method for producing a macrocyclic ketone, which comprises then reducing the obtained acyloin condensation reaction product without isolating it from the organic solvent.