JP2832319B2 - Production method of pivalic acid chloromethyl ester - Google Patents
Production method of pivalic acid chloromethyl esterInfo
- Publication number
- JP2832319B2 JP2832319B2 JP3315476A JP31547691A JP2832319B2 JP 2832319 B2 JP2832319 B2 JP 2832319B2 JP 3315476 A JP3315476 A JP 3315476A JP 31547691 A JP31547691 A JP 31547691A JP 2832319 B2 JP2832319 B2 JP 2832319B2
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- catalyst
- pfa
- pivalic acid
- pom
- 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.)
- Expired - Fee Related
Links
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
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明はアルキルハロゲン化アシ
ルとパラホルムアルデヒド（以後ＰＦＡと略称する）と
の反応によつて、医薬、農薬、その他多くの有機合成化
合物の原料又は中間体として有用なピバリン酸クロロメ
チルエステル（以下ＰＯＭと略称する）を工業的に、高
収率で製造する方法に関するものである。The present invention relates to pivalin which is useful as a raw material or intermediate of pharmaceuticals, agricultural chemicals and many other organic synthetic compounds by reacting an alkyl halide with paraformaldehyde (hereinafter abbreviated as PFA). The present invention relates to a method for industrially producing acid chloromethyl ester (hereinafter abbreviated as POM) in high yield.
【０００２】[0002]
【従来の技術】従来アルキルハロゲン化アシル（Ｃ
Ｈ３）３ＣＣＯＣｌとＰＦＡとを原料としてＺｎＣｌ２
等のルイス酸を触媒としてＰＯＭを製造する方法は既に
公知である。〔特開昭４８−１４６４６号、又はＪ，
Ａ，Ｃ，Ｓ，８９，５４３９（１９６７）〕上記従来の
製造法を反応式で示すと下記の通りである。 2. Description of the Related Art Conventional alkyl halide acyl (C)
H 3 ) 3 CCOCl and PFA as raw materials and ZnCl 2
A method for producing POM using a Lewis acid as a catalyst is already known. [JP-A-48-14646, or J.
A, C, S, 89, 5439 (1967)] The above conventional production method is represented by the following reaction formula.
【０００３】[0003]
【発明が解決しようとする課題】前記従来のＰＯＭ製造
法はＣＨ2 Ｃｌ2 又はＣＨＣｌ3 等のハロゲン化炭化水
素の溶媒中、還流状態で反応する方法であるが、収率が
低く僅かに55重量％程度である。また蒸留によつて製品
が得られるがＰＯＭと反応溶媒との分離が困難であり、
また未反応のＰＦＡが昇華する問題があるため工業的に
有利な方法ではない。SUMMARY OF THE INVENTION An object of the conventional POM preparation in a solvent of halogenated hydrocarbons such as CH 2 Cl 2 or CHCl 3, is a method of reacting at reflux, slightly 55 low yield % By weight. The product can be obtained by distillation, but it is difficult to separate POM from the reaction solvent,
Further, there is a problem that unreacted PFA sublimes, so that it is not an industrially advantageous method.
【０００４】本発明者等は鋭意研究した結果、ピバロイ
ルクロライドとＰＦＡとの反応によるＰＯＭの製造にお
いて、ＺｎＣｌ2 などのルイス酸を触媒として、塩化チ
オニルを助触媒として使用した場合、反応溶媒を使用す
ることなしに優れた触媒効果を発揮することを見出し
た。本発明は上記の知見に基づいて、反応溶媒を使用せ
ずに高収率で工業的に有利なＰＯＭの製造法を提供する
ことを目的とするものである。The present inventors have conducted intensive studies and have found that in the production of POM by the reaction of pivaloyl chloride with PFA, when a Lewis acid such as ZnCl 2 is used as a catalyst and thionyl chloride is used as a co-catalyst, the reaction solvent is reduced. It has been found that an excellent catalytic effect can be exerted without the use of. An object of the present invention is to provide an industrially advantageous method for producing POM at a high yield without using a reaction solvent, based on the above findings.
【０００５】[0005]
【課題を解決するための手段】本発明は（ＣＨ3)3 ＣＣ
ＯＣｌで示されアルキルハロゲン化アシルとＰＦＡとの
反応において、反応溶媒を使用することなく触媒として
ルイス酸を使用し、助触媒として塩化チオニルを使用す
ることによつてＰＯＭを製造する方法に関するものであ
る。The present invention provides (CH 3 ) 3 CC
The present invention relates to a method for producing POM by using a Lewis acid as a catalyst and using thionyl chloride as a cocatalyst without using a reaction solvent in a reaction between an alkyl halide represented by OCI and PFA. is there.
【０００６】上記のＰＯＭの製造方法において、ＰＦＡ
中の水分によつてピバロイルクロライドが加水分解され
て塩化水素と（ＣＨ3)3 ＣＣＯ2 Ｈで示されるピバリン
酸を副生する。In the above POM manufacturing method, PFA
The pivaloyl chloride is hydrolyzed by the moisture therein to produce hydrogen chloride and pivalic acid represented by (CH 3 ) 3 CCO 2 H as a by-product.
【０００７】本発明者等の研究結果、助触媒として塩化
チオニルを使用することにより、ＰＦＡ中の水分によつ
て塩化チオニルが分解され、生成する塩化水素が反応を
促進することが判明した。また塩化チオニルが系内の水
分を消費するためピバリン酸の副生を抑制する効果があ
る。また少量のピバリン酸が副生するが以下に記載する
反応式によつて出発原料であるピバロイルクロライドが
生成する。As a result of the study by the present inventors, it has been found that by using thionyl chloride as a cocatalyst, thionyl chloride is decomposed by water in PFA, and the generated hydrogen chloride accelerates the reaction. In addition, thionyl chloride consumes water in the system, and has an effect of suppressing the by-product of pivalic acid. Although a small amount of pivalic acid is by-produced, pivaloyl chloride, which is a starting material, is produced by the following reaction formula.
【０００８】 前記のように本発明に塩化チオニルを助触媒として使用
することによつて、反応溶媒を必要とせずにＰＯＭを常
圧下で安全にかつほぼ定量的に高品質で得られることが
確認された。即ち本発明は溶媒を使用することなしにピ
バロイルクロライドと触媒としてＺｎＣｌ2 と、また助
触媒として塩化チオニルを使用して混合し、常圧下でＰ
ＦＡを添加して反応を行う方法である。反応終了後水洗
によつてＺｎＣｌ2 を除去し、乾燥剤で脱水して減圧蒸
留によつてＰＯＭが得られる。この場合使用する触媒と
してはＺｎＣｌ2 のような弱いルイス酸が好ましくＡｌ
Ｃｌ3,ＦｅＣｌ3,ＳｎＣｌ3 のような強力なものでは副
反応が生じやすい。触媒量はピバロイルクロライドに対
して2.0 〜4.0 重量％の範囲がよい。助触媒としては上
記副生成物を抑制するという点から塩化チオニルが最も
有利である。助触媒の使用量はピバロイルクロライドに
対し、20〜40モル％の範囲で使用するのが好適である。[0008] As described above, it was confirmed that by using thionyl chloride as a cocatalyst in the present invention, POM can be obtained safely and almost quantitatively at high quality under normal pressure without the need for a reaction solvent. That is, in the present invention, pivaloyl chloride is mixed with ZnCl 2 as a catalyst and thionyl chloride as a cocatalyst without using a solvent,
In this method, FA is added to carry out the reaction. After completion of the reaction, ZnCl 2 is removed by washing with water, dehydrated with a drying agent, and POM is obtained by distillation under reduced pressure. The catalyst used in this case is preferably a weak Lewis acid such as ZnCl 2.
With strong substances such as Cl 3 , FeCl 3 , and SnCl 3 , side reactions tend to occur. The amount of the catalyst is preferably in the range of 2.0 to 4.0% by weight based on pivaloyl chloride. Thionyl chloride is most advantageous as a co-catalyst in terms of suppressing the by-products. The use amount of the cocatalyst is preferably in the range of 20 to 40 mol% based on pivaloyl chloride.
【０００９】[0009]
【作用】反応方法としては上記のピバロイルクロライ
ド、ＺｎＣｌ２触媒及び塩化チオニル助触媒を混合し、
ついで常圧下ＰＦＡを添加する方法及びピバロイルクロ
ライドと塩化チオニルの混合溶液を滴下する方法とがあ
るが、何れの方法でもＰＯＭを合成することができる。
しかしながら上記の反応では系内のＰＦＡの量が過剰に
なると副反応により構造式〔（ＣＨ３）３ＣＣＯ２〕２
ＣＨ２で示されるメチレンジピパレートを多く副生す
る。そのため上記のＰＦＡを添加する方法では添加時間
を延長するのが好ましく、またピバロイルクロライドと
塩化チオニルとの混合溶液を滴下する方法ではできるだ
け短時間に滴下するのが好ましい。しかしながら後者の
方法では反応が発熱反応であるため、温度制御が困難で
あり、工業的には不適当である。またＰＦＡの使用量は
ピバロイルクロライドに対して、１１５〜１２０モル％
が好適で、これ以上の量では未反応のＰＦＡが析出して
くるため後処理工程が困難となる。反応温度は０〜１０
０℃の範囲で行い得るが、操作性、反応速度及び副反応
の点より１０〜６０℃の範囲が好適である。また反応時
間は３〜１０時間の範囲で行われるが、反応時間を延長
すると反応液が着色するため３〜５時間の範囲が好適で
ある。反応終了後水洗による触媒の除去が必要であり、
蒸留時に触媒が存在する場合にはＰＯＭの熱分解が促進
される。The reaction method is to mix the above pivaloyl chloride, ZnCl 2 catalyst and thionyl chloride co-catalyst,
Next, there are a method of adding PFA under normal pressure and a method of dropping a mixed solution of pivaloyl chloride and thionyl chloride, and any of these methods can synthesize POM.
However, in the above reaction, when the amount of PFA in the system becomes excessive, a side reaction causes a structural formula [(CH 3 ) 3 CCO 2 ] 2
Methylene dipipalate represented by CH 2 is produced as a by-product. Therefore, in the above-mentioned method of adding PFA, it is preferable to extend the addition time, and in the method of dropping a mixed solution of pivaloyl chloride and thionyl chloride, it is preferable to drop the solution as short as possible. However, in the latter method, since the reaction is exothermic, it is difficult to control the temperature, which is not industrially appropriate. The amount of PFA used is 115 to 120 mol% based on pivaloyl chloride.
If the amount is more than that, unreacted PFA is precipitated, so that the post-treatment process becomes difficult. Reaction temperature is 0-10
The reaction can be carried out in the range of 0 ° C, but the range of 10 to 60 ° C is preferred from the viewpoint of operability, reaction rate and side reactions. The reaction time is in the range of 3 to 10 hours. However, if the reaction time is extended, the reaction solution is colored, so that the reaction time is preferably in the range of 3 to 5 hours. After the completion of the reaction, it is necessary to remove the catalyst by washing with water,
Thermal decomposition of POM is promoted when the distillation during the catalyst is present.
【００１０】[0010]
【実施例１】 純度９８％のピバロイルクロライド２４
６．０ｇと塩化チオニル４７．６ｇ及び塩化亜鉛４．０
ｇを反応器に取り６０℃まで昇温後撹拌しながら純度９
５％のＰＦＡ７５．９ｇを５時間かけて添加した後、６
０℃で５時間反応した。反応後室温まで冷却し、水１６
０．０ｇを添加し、洗浄を行った後、下層の水層を抜き
出す。ＣａＣｌ２ を３０．０ｇを添加して脱水し、濾過
にてＣａＣｌ２を除去後蒸留して、無色透明の液体ＰＯ
Ｍ２８１．７ｇ（収率９３．５％、純度９９．７％）を
得た。Example 1 Pivaloyl chloride 24 having a purity of 98%
6.0 g, 47.6 g of thionyl chloride and 4.0 of zinc chloride
g in a reactor, heated to 60 ° C., and stirred to a purity of 9%.
After adding 75.9 g of 5% PFA over 5 hours, 6%
The reaction was performed at 0 ° C. for 5 hours. After the reaction, cool to room temperature and add water 16
After adding 0.0 g and washing, the lower aqueous layer is extracted. 30.0 g of CaCl 2 was added for dehydration, and after removing CaCl 2 by filtration, distillation was carried out.
281.7 g of M (93.5% yield, 99.7% purity) were obtained.
【００１１】[0011]
【実施例２】 純度95％のＰＦＡ9.09g と塩化亜鉛0.5g
とを反応器に仕込み、10℃まで冷却後撹拌しながら、純
度98％のピバロイルクロライド30.6g と塩化チオニル4.
46g の混合溶液を30分間で滴下した後、10℃で２時間反
応した。反応後水20.0g を添加し、洗浄した後分液して
粗ＰＯＭ35.6g （収率94.5％、純度95.6％）を得た。[Example 2] 9.09 g of 95% pure PFA and 0.5 g of zinc chloride
And 30.6 g of 98% pure pivaloyl chloride and thionyl chloride 4.
After dropping 46 g of the mixed solution over 30 minutes, the mixture was reacted at 10 ° C. for 2 hours. After the reaction, 20.0 g of water was added, washed and separated to obtain 35.6 g of crude POM (yield 94.5%, purity 95.6%).
【００１２】[0012]
【発明の効果】本発明の効果を纏めると下記の通りであ
る。アルキルハロゲン化アシルとパラホルムアルデヒド
との反応によるピバリン酸クロルメチルエステルの製造
法において、ＺｎＣｌ2 などのルイス酸を触媒として使
用し、助触媒として塩化チオニルを使用し、溶媒を使用
することなく製造されたピバリン酸クロロメチルエステ
ルはその色相、沸点等が充分満足するものが得られた。
しかも得られたピバリン酸クロロメチルエステルは高純
度、高収率であり、本発明によつて始めて工業的生産が
確立された。更に本発明は反応溶媒を使用しないため工
業的生産における反応缶容積当りの収量が著しく大きい
利点がある。The effects of the present invention are summarized as follows. In a process for producing chloromethyl pivalate by the reaction of an alkyl halide acyl with paraformaldehyde, the process is carried out using a Lewis acid such as ZnCl 2 as a catalyst, using thionyl chloride as a cocatalyst, and using no solvent. Further, pivalic acid chloromethyl ester whose hue, boiling point and the like were sufficiently satisfied was obtained.
Moreover, the obtained chloromethyl pivalate has high purity and high yield, and industrial production has been established for the first time according to the present invention. Further, the present invention has an advantage that the yield per reactor volume in industrial production is extremely large because no reaction solvent is used.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 ＦＩ // Ｃ０７Ｂ 61/00 ３００ Ｃ０７Ｂ 61/00 ３００ (56)参考文献 特開 昭48−14646（ＪＰ，Ａ) 特開 平４−5259（ＪＰ，Ａ) 特開 平５−78280（ＪＰ，Ａ) 仏国特許出願公開2269508（ＲＦ，Ａ １) ソ連国特許発明1313850（ＳＵ，Ａ)──────────────────────────────────────────────────続 き Continuation of the front page (51) Int.Cl. 6 Identification symbol FI // C07B 61/00 300 C07B 61/00 300 (56) References JP-A-48-14646 (JP, A) JP-A-4 -5259 (JP, A) Japanese Patent Application Laid-Open No. 5-78280 (JP, A) French Patent Application Publication 2269508 (RF, A1) USSR Patent Invention 1313850 (SU, A)
Claims (1)
アルキルハロゲン化アシルとパラホルムアルデヒドとの
反応に、反応溶媒を使用することなしに、触媒としてル
イス酸を使用し、助触媒として塩化チオニルを使用する
ことを特徴とする構造式（ＣＨ3)3 ＣＣＯ2 ＣＨ2 Ｃｌ
で示されるピバリン酸クロロメチルエステルの製造法。1. A reaction between an alkyl acyl halide represented by the structural formula (CH 3 ) 3 CCOCl and paraformaldehyde using a Lewis acid as a catalyst and a thionyl chloride as a cocatalyst without using a reaction solvent. Structural formula (CH 3 ) 3 CCO 2 CH 2 Cl characterized by using
A process for producing pivalic acid chloromethyl ester represented by the formula:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3315476A JP2832319B2 (en) | 1991-11-01 | 1991-11-01 | Production method of pivalic acid chloromethyl ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3315476A JP2832319B2 (en) | 1991-11-01 | 1991-11-01 | Production method of pivalic acid chloromethyl ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05125017A JPH05125017A (en) | 1993-05-21 |
| JP2832319B2 true JP2832319B2 (en) | 1998-12-09 |
Family
ID=18065818
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3315476A Expired - Fee Related JP2832319B2 (en) | 1991-11-01 | 1991-11-01 | Production method of pivalic acid chloromethyl ester |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2832319B2 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5206993B2 (en) | 2007-03-07 | 2013-06-12 | 日産化学工業株式会社 | Isoxazoline-substituted benzamide compounds and pest control agents |
| US8053452B2 (en) | 2007-06-29 | 2011-11-08 | Nissan Chemical Industries, Ltd. | Substituted isoxazoline or enone oxime compound, and pest control agent |
| EP2873658B1 (en) | 2012-07-12 | 2018-09-05 | Nissan Chemical Industries, Ltd. | Oxime-substituted amide compound and pest control agent |
| CN104016954B (en) * | 2014-06-06 | 2016-01-27 | 常州市第四制药厂有限公司 | The preparation of Nebivolol Intermediates and purification process |
-
1991
- 1991-11-01 JP JP3315476A patent/JP2832319B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH05125017A (en) | 1993-05-21 |
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