JP4366704B2 - Method for recovering 4-dimethylaminopyridine - Google Patents

Description

（式中、Ｒ₁及びＲ₂はそれぞれ水素原子又は低級アルキル基を、Ｘ₁〜Ｘ₆はそれぞれ水素原子、置換基を有してもよいアルキル基又はその環内に硫黄原子又は酸素原子を含有する複素環基を示す。）で表される化合物を水難溶性有機溶媒中、水の存在下に分解することを特徴とするＤＭＡＰの回収方法である。
【０００４】
【発明の実施の形態】
本発明に適用できる化合物としては、特に制限はないが、Ｒ₁、Ｒ₂のうち一方が水素原子で他方がメチル、エチル、プロピル等の低級アルキル基である化合物、Ｘ₁、Ｘ₂、Ｘ₄、Ｘ₅、Ｘ₆が水素原子でＸ₃がエチルチオプロピル等の低級アルキルチオ低級アルキル、３−テトラヒドロチオピラニル、４−テトラヒドロピラニル等の複素環基を有する化合物が例示できる。
【０００５】
分解に使用できる水難溶性有機溶媒としては、トルエン、キシレン、クロロベンゼン等が使用できるが、分解温度等の関係からトルエンが好ましい。分解は、ＤＭＡＰを使用したＯ−アシル化合物からＣ−アシル化合物への転位反応に使用した、実際の反応液を使用して行なう場合、この反応液を塩酸等の鉱酸水溶液でＤＭＡＰ及び式［1］で表される化合物を抽出し、必要により水難溶性有機溶媒を加え、更に苛性ソーダ等の塩基で中和し、過剰の水を分解した後、９０〜１３０℃、好ましくは、１００〜１１０℃の範囲で行なわれる。分解終了後は、水洗等の処理を行なうことにより、ＤＭＡＰの有機溶媒として回収することができる。もちろん、必要によりＤＭＡＰを単離することは可能であるが、通常は、溶液のまま、次回の転位反応にくり返し使用される。
【０００６】
また、分解時、ジメチルアミン等のアミン、あるいは、ｔ−ブチルメルカプタン、エチルメルカプタン等のある種のメルカプタン類を存在させることにより、より分解がスムースに進行する。
尚、式［1］で表される化合物は、Ｘ₁〜Ｘ₆の置換基の種類によっては互変異性体が存在するが、本発明はそれら全ての化合物が含まれる。
【０００７】
［実施例］
以下に実施例及び比較例を示し、本発明を具体的に説明するが、以下の実施例に限定されるものではない。
［実施例１］
２５．６６ｇのＤＭＡＰを使用して行った転位反応液から希塩酸を用いて抽出したＤＭＡＰ（１８．４３ｇ；７１．８％）及び式［２］
【化３】

で表されるＤＭＡＰと５−（２−エチルチオプロピル）−２−ブタノイルシクロヘキセン−２−オン−１との反応物（ＡＰＡと略称：７．４４ｇ；９．１％相当）を含有する水溶液（ジメチルアミン、０．４２ｇを含む）にトルエン４３５ｇ及び２８％苛性ソーダ水溶液１３５ｇを添加し、充分攪拌後静置した。
溶液はトルエン層、水層及びＡＰＡを含む中間層に分離した。
水層を除いた後、トルエン層と中間層を加熱し内温が１００℃になるまで共沸蒸留により水分を留去した。
１００〜１０５℃で２時間加熱してＡＰＡを分解させた後、冷却し少量の水（６ｇ）を加え分液、水層は初めの水層と合わせトルエン４３５ｇで抽出した。
トルエン層を合わせてＨＰＬＣで分析した結果ＤＭＡＰ、２０．０５ｇを含み回収率は水層中の量に対して１０８．８％、反応に使用した量に対して７８．１％であった。
【０００８】
［実施例２］
式［３］
【化４】

で表される化合物３．８７ｇ（１０ｍｍｏｌ）をトルエン７５ｇ中に入れ、水４ｇと５０％ジメチルアミン水溶液０．１８ｇ（２ｍｍｏｌ）を加えた。
内温が１０５℃になるまで水分を共沸脱水で除いた後、その温度で２時間加熱した。
ＨＰＬＣで分析した結果、ＤＭＡＰ１．２０ｇ（９．８２ｍｍｏｌ：収率９８．２％）が生成し、式［３］で表される化合物の残存量は０．０１ｇ以下であった。
【０００９】
［実施例３］
７．４５ｇのＤＭＡＰを使用して行った転位反応液から希塩酸を用いて抽出したＤＭＡＰ（５．７９ｇ；７７．７％）及び式［４］
【化５】

で表される化合物（Ｏ−ＡＰＡと略称：２．８５ｇ；１３．１％相当）を含有する水溶液にトルエン１５０ｇ及び２８％苛性ソーダ水溶液７０ｇを添加し、充分攪拌後静置した。
溶液はトルエン層、水層及びＯ−ＡＰＡを含む中間層に分離した。
水層を除いた後、トルエン層と中間層にジメチルアミン塩酸塩２．１９ｇを加え内温が９５℃になるまで共沸蒸留により水分を留去した。
９５〜１００℃で４時間加熱してＯ−ＡＰＡを分解させた後、冷却し少量の水（４ｇ）を加え分液、水層は初めの水層と合わせトルエン１５０ｇで抽出した。
トルエン層を合わせてＨＰＬＣで分析した結果ＤＭＡＰ、６．３６ｇを含み回収率は水層中の量に対して１０９．８％、反応に使用した量に対して８５．４％であった。
【００１０】
［参考例１］
２５．６６ｇのＤＭＡＰを使用して行った転位反応液から希塩酸を用いて抽出したＤＭＡＰ（１８．４３ｇ；７１．８％）及び式［２］で表されるＡＰＡ（７．４４ｇ；９．１％相当）を含有する水溶液（実施例１と同じもの）にトルエン４３５ｇ及び２８％苛性ソーダ水溶液１３５ｇを添加し、充分攪拌後静置した。
溶液はトルエン層、水層及びＡＰＡを含む中間層に分離した。トルエン層を分離後水層、中間層は更にトルエン４３５ｇで抽出した。
トルエン層を合わせてＨＰＬＣで分析した結果ＤＭＡＰ、１７．９１ｇを含み回収率は水層中の量に対して９７．２％、反応に使用した量に対して６９．８％であった。
【００１１】
［比較例１］
１６．６ｇのＤＭＡＰを使用した転位反応液から得られた５．６４ｇのＯ−ＡＰＡを含む中間層２４．０ｇに水、トルエンをそれぞれ１０ｍｌ加えた後塩酸でｐＨを８〜９に調整した。
この溶液を加熱し溶媒と水を留去した後、更に１４０℃で７時間加熱した。反応液をＨＰＬＣで分析した結果、１．２７ｇのＤＭＡＰ（Ｏ−ＡＰＡからの理論値に対して６６％）が生成していたが、副生物が多く単純な手段ではこれらからＤＭＡＰを分離できず、次ロットの反応に使用することはできなかった。
【００１２】
【発明の効果】
本発明の回収方法は、加水分解によりＤＭＡＰを回収するので、反応温度は、９０〜１１０℃と比較的低温で反応が進行するので工業的回収方法として有用である。
更に、転位反応に使用した有機溶媒溶液として回収できるので、そのまま、次回の転位反応に使用できる、反応物からＤＭＡＰを分解させて得られる式［５］
【化６】

で表されるシクロヘキサン系化合物が回収できる等優れた回収方法である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for recovering 4-dimethylaminopyridine (hereinafter referred to as DMAP).
[0002]
[Prior art]
DMAP is used as a catalyst for various reactions, and particularly as a catalyst for rearrangement of a cyclohexanedione-based compound from an O-acyl to a C-acyl. As a side reaction, a reaction product of DMAP and a cyclohexanedione compound is generated. Conventionally, this reaction product was thermally decomposed at 130 to 140 ° C. for 6 to 7 hours to recover DMAP. However, the recovery rate was poor, the cyclohexanedione compound could not be recovered, and the decomposition temperature was high. There were problems such as not being able to be said to be an effective recovery method.
[0003]
[Means for Solving the Problems]
As a result of diligent research on an industrially advantageous recovery method for DMAP, the present inventors have found that the above problems can be solved by hydrolyzing the reaction product, and have solved the present invention. That is, the present invention provides the formula [1]
[Chemical formula 2]

(In the formula, R ₁ and R ₂ are each a hydrogen atom or a lower alkyl group, X _{1 to} X ₆ are each a hydrogen atom, an alkyl group which may have a substituent, or a sulfur atom or an oxygen atom in the ring thereof. And a DMAP recovery method characterized by decomposing the compound represented by (1) in a water-insoluble organic solvent in the presence of water.
[0004]
DETAILED DESCRIPTION OF THE INVENTION
The compound applicable to the present invention is not particularly limited, but a compound in which _one of R ₁ and R ₂ is a hydrogen atom and the other is a lower alkyl group such as methyl, ethyl or propyl, X ₁ , X ₂ , X ₄ , X ₅ , and X ₆ are hydrogen atoms and X ₃ is a compound having a heterocyclic group such as lower alkylthio-lower alkyl such as ethylthiopropyl, 3-tetrahydrothiopyranyl, 4-tetrahydropyranyl.
[0005]
As the poorly water-soluble organic solvent that can be used for decomposition, toluene, xylene, chlorobenzene, and the like can be used, but toluene is preferable in view of the decomposition temperature and the like. When the decomposition is carried out using the actual reaction solution used for the rearrangement reaction from the O-acyl compound to the C-acyl compound using DMAP, the reaction solution is treated with DMAP and the formula [ 1] is extracted, and if necessary, a poorly water-soluble organic solvent is added, and further neutralized with a base such as caustic soda to decompose excess water, and then 90 to 130 ° C., preferably 100 to 110 ° C. It is performed in the range. After completion of the decomposition, it can be recovered as an organic solvent of DMAP by performing a treatment such as washing with water. Of course, it is possible to isolate DMAP if necessary, but it is usually used repeatedly in the next rearrangement reaction in the form of a solution.
[0006]
Further, at the time of decomposition, the decomposition proceeds more smoothly by the presence of an amine such as dimethylamine or certain mercaptans such as t-butyl mercaptan and ethyl mercaptan.
The compound represented by formula [1], depending on the type of the substituents X ₁ to X ₆ but tautomers, the present invention includes all compounds thereof.
[0007]
[Example]
EXAMPLES The present invention will be specifically described below with reference to examples and comparative examples, but is not limited to the following examples.
[Example 1]
DMAP (18.43 g; 71.8%) extracted with dilute hydrochloric acid from the rearrangement reaction liquid carried out using 25.66 g of DMAP and the formula [2]
[Chemical 3]

An aqueous solution containing a reaction product of DMAP and 5- (2-ethylthiopropyl) -2-butanoylcyclohexen-2-one-1 (abbreviated as APA: 7.44 g; equivalent to 9.1%) 435 g of toluene and 135 g of a 28% aqueous sodium hydroxide solution were added to (containing dimethylamine and 0.42 g), and the mixture was allowed to stand after sufficient stirring.
The solution was separated into an intermediate layer containing a toluene layer, an aqueous layer and an APA.
After removing the aqueous layer, the toluene layer and the intermediate layer were heated, and water was distilled off by azeotropic distillation until the internal temperature reached 100 ° C.
After heating at 100-105 ° C. for 2 hours to decompose APA, the mixture was cooled, a small amount of water (6 g) was added, and the liquid separation and the aqueous layer were combined with the first aqueous layer and extracted with 435 g of toluene.
The toluene layers were combined and analyzed by HPLC. As a result, the recovery rate was 108.8% with respect to the amount in the aqueous layer and 78.1% with respect to the amount used in the reaction.
[0008]
[Example 2]
Formula [3]
[Formula 4]

3.87 g (10 mmol) of the compound represented by formula (1) was placed in 75 g of toluene, and 4 g of water and 0.18 g (2 mmol) of a 50% aqueous dimethylamine solution were added.
Water was removed by azeotropic dehydration until the internal temperature reached 105 ° C., and the mixture was heated at that temperature for 2 hours.
As a result of analysis by HPLC, 1.20 g (9.82 mmol: yield 98.2%) of DMAP was produced, and the residual amount of the compound represented by the formula [3] was 0.01 g or less.
[0009]
[Example 3]
DMAP (5.79 g; 77.7%) extracted with dilute hydrochloric acid from a rearrangement reaction performed using 7.45 g of DMAP and the formula [4]
[Chemical formula 5]

150 g of toluene and 70 g of 28% aqueous sodium hydroxide solution were added to an aqueous solution containing a compound represented by the formula (abbreviated as O-APA: 2.85 g; equivalent to 13.1%), and the mixture was allowed to stand after sufficient stirring.
The solution was separated into an intermediate layer containing a toluene layer, an aqueous layer and O-APA.
After removing the aqueous layer, 2.19 g of dimethylamine hydrochloride was added to the toluene layer and the intermediate layer, and water was distilled off by azeotropic distillation until the internal temperature reached 95 ° C.
After heating at 95 to 100 ° C. for 4 hours to decompose O-APA, the mixture was cooled and a small amount of water (4 g) was added to separate the solution, and the aqueous layer was combined with the first aqueous layer and extracted with 150 g of toluene.
The toluene layers were combined and analyzed by HPLC. As a result, 6.36 g of DMAP was contained, and the recovery rate was 109.8% with respect to the amount in the aqueous layer and 85.4% with respect to the amount used in the reaction.
[0010]
[Reference Example 1]
DMAP (18.43 g; 71.8%) extracted with dilute hydrochloric acid from the rearrangement reaction performed using 25.66 g of DMAP and APA (7.44 g; 9.1) expressed by the formula [2] 435 g of toluene and 135 g of 28% caustic soda aqueous solution were added to an aqueous solution containing the same (as in Example 1).
The solution was separated into an intermediate layer containing a toluene layer, an aqueous layer and an APA. After separating the toluene layer, the aqueous layer and the intermediate layer were further extracted with 435 g of toluene.
The toluene layers were combined and analyzed by HPLC. As a result, 17.91 g of DMAP was contained, and the recovery rate was 97.2% with respect to the amount in the aqueous layer and 69.8% with respect to the amount used in the reaction.
[0011]
[Comparative Example 1]
10 ml of water and toluene were added to 24.0 g of the intermediate layer containing 5.64 g of O-APA obtained from the rearrangement reaction solution using 16.6 g of DMAP, and then the pH was adjusted to 8-9 with hydrochloric acid.
This solution was heated to distill off the solvent and water, and further heated at 140 ° C. for 7 hours. As a result of analyzing the reaction solution by HPLC, 1.27 g of DMAP (66% based on the theoretical value from O-APA) was produced. However, DMAP was not separated from these by simple means because of many by-products. Could not be used for the next lot reaction.
[0012]
【The invention's effect】
Since the recovery method of the present invention recovers DMAP by hydrolysis, the reaction proceeds at a relatively low temperature of 90 to 110 ° C., which is useful as an industrial recovery method.
Furthermore, since it can be recovered as an organic solvent solution used for the rearrangement reaction, it can be used as it is for the next rearrangement reaction, and is obtained by decomposing DMAP from the reaction product [5]
[Chemical 6]

It is an excellent recovery method such as being able to recover a cyclohexane compound represented by

Claims (4)

Formula [1]

(Wherein R ₁ and R ₂ are each independently a hydrogen atom or a lower alkyl group, X _{1 to} X ₆ are each a hydrogen atom, an alkyl group which may have a substituent, or a sulfur atom in the ring) Or a heterocyclic group containing an oxygen atom.) In the presence of water in a poorly water-soluble organic solvent. The recovery method according to claim 1, wherein X ₃ is a lower alkylthio-lower alkyl group, a 3-tetrahydrothiopyranyl group or a 4-tetrahydropyranyl group. The recovery method according to claim 1 or 2, wherein the organic solvent is toluene. The recovery method according to claim 1, wherein the decomposition is performed in the presence of a secondary amine.