JPS60181047A - Production of fumaric acid monoester - Google Patents
Production of fumaric acid monoesterInfo
- Publication number
- JPS60181047A JPS60181047A JP59036331A JP3633184A JPS60181047A JP S60181047 A JPS60181047 A JP S60181047A JP 59036331 A JP59036331 A JP 59036331A JP 3633184 A JP3633184 A JP 3633184A JP S60181047 A JPS60181047 A JP S60181047A
- Authority
- JP
- Japan
- Prior art keywords
- acid monoester
- reaction
- maleic acid
- fumaric acid
- catalyst
- 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.)
- Granted
Links
Classifications
-
- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05K—PRINTED CIRCUITS; CASINGS OR CONSTRUCTIONAL DETAILS OF ELECTRIC APPARATUS; MANUFACTURE OF ASSEMBLAGES OF ELECTRICAL COMPONENTS
- H05K1/00—Printed circuits
- H05K1/02—Details
- H05K1/03—Use of materials for the substrate
- H05K1/0393—Flexible materials
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
本発明はマレイン酸モノエステルを異性化してフマル酸
モノエステルを製造する方法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing fumaric acid monoester by isomerizing maleic acid monoester.
更に詳しくは、異性化触媒として４級アンモニウムプロ
ミドおよび有機過酸化物を用いて、マレイン酸モノエス
テルカラフマル酸モジエステルヲ製造する方ｋＫ関する
ものである。More specifically, the present invention relates to a method for producing a maleic acid monoester carafumarate modiester using quaternary ammonium bromide and an organic peroxide as an isomerization catalyst.
フマル酸モノエステルは分子内に１個の二重結合、エス
テル結合、および遊離のカルボキシル基を有し、反応性
に富むため、有機合成原料として重要な物質である。Fumaric acid monoester has one double bond, an ester bond, and a free carboxyl group in its molecule and is highly reactive, so it is an important substance as a raw material for organic synthesis.
従来マレイン酸の異性化反応については、種々上記の触
媒を用いてマレイン酸モノエステルをる。水溶液中での
異性化反応においては、酸性水溶液による装置の腐食の
問題があシ、マレイン酸モノエステルの転化率が低い上
にフマル酸モノエステルが水に溶解するため収率の低下
をひきおこし、さらに反応生成物よシ触媒を除去するの
に温水洗浄、塩析等の煩雑な操作が必要となシ、しかも
排水中には 反応混合物を含有するため、ＴＯＣ（全有
機体炭素）負荷上昇に応じて排水対策を閉じなければな
らない等多くの欠点があった。Conventionally, in the isomerization reaction of maleic acid, various of the above-mentioned catalysts are used to produce maleic acid monoester. In the isomerization reaction in an aqueous solution, there is a problem of corrosion of the equipment due to the acidic aqueous solution, the conversion rate of maleic acid monoester is low, and the fumaric acid monoester dissolves in water, causing a decrease in yield. Furthermore, removing reaction products and catalysts requires complicated operations such as hot water washing and salting out, and furthermore, since the wastewater contains reaction mixtures, the TOC (total organic carbon) load increases. There were many drawbacks, such as having to close drainage measures accordingly.
吊下で異性化反応を行なえる特殊な触媒を見い出して高
収率でフマル酸モノエステルを製造する方法を発明した
。We discovered a special catalyst that can carry out the isomerization reaction under suspension, and invented a method for producing fumaric acid monoester in high yield.
本発明は、マレイン酸モノエステルから対応するフマル
酸エステルを製造する際に、４級アンモニウムプロミド
および有機過酸化物の存在下で反応させる仁とを特徴と
するフマル酸モノエステルの製造法を提供するものであ
る。The present invention provides a method for producing a fumaric acid monoester, which comprises reacting a corresponding fumaric acid ester from a maleic acid monoester in the presence of a quaternary ammonium bromide and an organic peroxide. This is what we provide.
本例明鏡おいて原料のマレイン酸モノエステルる。マレ
イン酸モノエステルの例としては、ルイン酸モノメチル
、マレイン酸モノエチル、マレイ／ｌ！ｉ！モノインプ
ロピル、マレイン酸モツプチル等のアルキルエステルが
ある。In this example, the raw material used in Meikyo is maleic acid monoester. Examples of maleic acid monoesters include monomethyl ruinate, monoethyl maleate, malei/l! i! There are alkyl esters such as monoinpropyl and motuptil maleate.
トラグロビルアンモニウムブロミド、テトラブチルアン
モニウムプロミド、テトラペンチルアンモニウムプロミ
ド等があり、その使用権はマレイン酸モノエステル１０
０重量部に対してｏ、ｏｉ〜１０重量部が好ましく、特
に好ましくは０．１〜５重量部である。There are traglobylammonium bromide, tetrabutylammonium bromide, tetrapentylammonium bromide, etc., and the right to use them is maleic acid monoester 10.
It is preferably o, oi to 10 parts by weight, particularly preferably 0.1 to 5 parts by weight, relative to 0 parts by weight.
一オキサイド、２ウロイルバーオキサイド、ステアロイ
ルパーオキサイド、ｔ−ブチルパーオキシイソブチレー
ト、ジクミルパーオキサイド等があシ、ソの使用量はマ
レイン酸モノエステル１００重量部に対して、０．０１
〜ｉｏ重量部が好ましく、特に好ましくは、０．３〜５
重量部である。Monooxide, diuroyl peroxide, stearoyl peroxide, t-butylperoxyisobutyrate, dicumyl peroxide, etc. The amount used is 0.01 parts by weight per 100 parts by weight of maleic acid monoester.
-io parts by weight are preferred, particularly preferably 0.3-5
Parts by weight.
上記の触媒の使用量がそれぞれ０．０１重量部未満では
、フマル酸モノエステルの収率が著しく低くな９、また
１０重量部を越えても収率はそれ＃１と向上せず経済的
理由で好ましくない。If the amount of each of the above catalysts used is less than 0.01 parts by weight, the yield of fumaric acid monoester will be extremely low9, and even if it exceeds 10 parts by weight, the yield will not improve to #1 for economic reasons. So it's not desirable.
本発明において異性化反応は、無溶媒または有機溶媒中
で行なうことが好ましい。ここで使用できる有機溶媒と
しては、反応条件下においてマレイン酸モノエステル、
フマル酸モジエステルオヨび触媒に不活性であり、且つ
熱安定性を有していればよく、例えば、ｎ−ヘキサン、
ｎ−へブタンのごとき飽和脂肪族炭化水素、ベンゼン、
トルエン等の芳香族炭化水素などがある。In the present invention, the isomerization reaction is preferably carried out without a solvent or in an organic solvent. Organic solvents that can be used here include maleic acid monoester,
It is sufficient that the fumaric acid moddiester is inert to the catalyst and has thermal stability, for example, n-hexane,
Saturated aliphatic hydrocarbons such as n-hebutane, benzene,
Examples include aromatic hydrocarbons such as toluene.
本発明の製造法において反応温度は触媒の種類、濃度等
によって変化するが、通常５０〜１２０℃が適当であシ
特に好ましくは、６０℃〜１１０℃である。反応温度が
５０℃未満ではフマル酸モノエステルの収率が低下する
。又反応温度を高くすると、マレイン酸モノエステルか
ら無水マレイン酸への分解反応が生じ好ましくない。In the production method of the present invention, the reaction temperature varies depending on the type of catalyst, concentration, etc., but it is usually suitably 50 to 120°C, and particularly preferably 60 to 110°C. If the reaction temperature is less than 50°C, the yield of fumaric acid monoester will decrease. Moreover, if the reaction temperature is raised, a decomposition reaction of maleic acid monoester to maleic anhydride occurs, which is not preferable.
本発明の製造法において、反応時間は触媒の量、反応温
度等圧よって変化するが、通常１〜８時間が適当である
。又、この異性化反応は、酸素の影響が大巻＜、酸素が
存在するとフマル酸モノエステルの収率が悪化するので
、空気を窒素で充分置換し、窒素雰囲気中で、反応させ
る＃１うが好ましい。In the production method of the present invention, the reaction time varies depending on the amount of catalyst and the reaction temperature and pressure, but is usually suitable for 1 to 8 hours. In addition, this isomerization reaction is greatly influenced by oxygen, and the presence of oxygen will deteriorate the yield of fumaric acid monoester, so the air is sufficiently replaced with nitrogen and the reaction is carried out in a nitrogen atmosphere. is preferred.
本発明の製造法によれば、非水系で異性化反応が可能な
ので、従来の水溶液中での異性化反応と異なシ、フマル
酸モノエステルの加水分解はなく、高収率でフマル酸モ
ノエステルに異性化することができる。又、触媒等の除
去には、反応混合物をろ過又は蒸留することで達せられ
、水洗、塩析等の操作は不要である。さらに水を使用し
ないことで排水処理の工程も不要となシ設備面でも有理
である。According to the production method of the present invention, since the isomerization reaction is possible in a non-aqueous system, unlike the conventional isomerization reaction in an aqueous solution, there is no hydrolysis of fumaric acid monoester, and fumaric acid monoester can be produced in high yield. It can be isomerized into Further, removal of the catalyst and the like can be achieved by filtering or distilling the reaction mixture, and operations such as washing with water and salting out are not necessary. Furthermore, since no water is used, there is no need for a wastewater treatment process, which is advantageous in terms of equipment.
次に本発明の方法を実施例によって具体的に説明するが
本発明はこれＫより限定されるものではない。Next, the method of the present invention will be specifically explained with reference to Examples, but the present invention is not limited thereto.
実権例 １
５００−フラスコにマレイン酸モノエチル２００１とテ
トラメチルアンモニウムプロミド２ｆを加え、窒素を吹
自込みながらかきまぜ８５℃に昇温し、ベンゾイルパー
オキサイド２ｔを加え、同温度で３時間かきまぜた後、
反応物を減圧蒸留によ実施例 ２
５００ｒｘ１７ラスコにマレイン酸モノイソプロピル２
００１とテトラエチルアンモニウムプロミド２ｆを加え
、窒素を吹き込みながら、かきまぜ８０℃に昇温し、ベ
ンゾイルパーオキサイド２２を加え、同温度で４時間か
きまぜた後、反応混合実施例 ３
５００ｒｎｌフラスコにマレイン酸モノブチル２００１
、トルエン１００ｆ、テトラペンチルアンモニウムプロ
ミド４ｆを加え、窒素を吹き込みながらかきまぜ、８５
℃に昇温し、ラウロイルパーオキサイド３２を加え同温
度で４時間かきまぜた陵、実施例 ４
２ｔフラスコにマレイン酸モノメチルｌ０ＩＩＩＩＦ、
ベンゼン９ Ｇ Ｏｆ、テトラメチルアンモニウムプロ
ミド１ｔを加え、窒素を吹き込み門から７５℃に昇温し
、ステアロイルパーオキサイド１ｆを加え同温度で５時
間かきまぜると反応の進行に伴ない、無色の結晶フマル
酸モノメチルが析出した。Actual example 1 Add monoethyl maleate 2001 and 2f of tetramethylammonium bromide to a 500-flask, stir while blowing in nitrogen and raise the temperature to 85°C, add 2t of benzoyl peroxide, and stir at the same temperature for 3 hours. ,
Example 2 Monoisopropyl maleate 2 was added to a 500rx17 flask by distilling the reaction product under reduced pressure.
001 and tetraethylammonium bromide 2f were added, stirred and heated to 80°C while blowing nitrogen, and benzoyl peroxide 22 was added and stirred at the same temperature for 4 hours. 2001
, add 100 f of toluene and 4 f of tetrapentylammonium bromide, stir while blowing nitrogen, 85
℃, added lauroyl peroxide 32 and stirred at the same temperature for 4 hours.Example 4 Monomethyl maleate 10IIIF in a 2t flask,
9 G Of benzene and 1 t of tetramethylammonium bromide were added, nitrogen was blown in and the temperature was raised to 75°C through the gate, stearoyl peroxide 1f was added and the mixture was stirred at the same temperature for 5 hours. Acid monomethyl precipitated.
ヒれを冷却後、吸引ろ過し、エチルアルコールで実施例
５
窒素の吹き込みなしで実施例２と同様に操作し５００ｄ
フラスコにマレイン酸モノイソプロピル２００ ｔ、水
１００ ｆ、チオ尿素８ｇ″を加え、窒素を吹き込みな
がら８５℃に昇温し、同温度で４時間かｔ！まぜた。反
応後、混合物を洗浄、塩析し、油層を回収、減圧にて水
を留去し、黒色に着色した反応物１０４ｔを得た。After cooling the fins, the fins were suction filtered and treated with ethyl alcohol.
200 t of monoisopropyl maleate, 100 f of water, and 8 g of thiourea were added to a flask, and heated to 85°C while blowing nitrogen, and mixed at the same temperature for 4 hours. After the reaction, the mixture was washed and salted. The oil layer was collected, and water was distilled off under reduced pressure to obtain 104 tons of a black colored reaction product.
比較例 ２
５００ｄフラスコにマレイン酸モノイソプロピル２００
Ｆ、水１００２、臭化７ｙモニ＋７ム２１Ｆを加え、窒
素を吹き込みながら８５℃に昇温ｌ−過硫酸アンモニウ
ム２１を加え、同温度で４時間かきまぜた。反応後、混
合物を塩析し、油層を減圧脱水して着色した反応物１１
０１を得た。Comparative Example 2 200% monoisopropyl maleate in a 500d flask
F, water 1002, and 7ymonium bromide + 7mmonium 21F were added, and the temperature was raised to 85°C while nitrogen was being blown into the mixture.21 l-ammonium persulfate was added, and the mixture was stirred at the same temperature for 4 hours. After the reaction, the mixture was salted out and the oil layer was dehydrated under reduced pressure to obtain colored reaction product 11.
I got 01.
特許出願人 日本油脂株式会社Patent applicant: NOF Corporation
Claims (1)
エステルを製造する際に、４級アンモニウムプロミドお
よび有機過酸化物の存在下で反応させることを特徴とす
るフマル酸モノエステルの製造法。 非 ２、 反応を一水系でしかも窒素雰囲気下で行なうこと
を特徴とする特許請求の範囲第１項記載のＩＩ潰法。[Claims] 1. A fumaric acid monoester characterized in that the reaction is carried out in the presence of quaternary ammonium bromide and an organic peroxide when producing the corresponding fumaric acid monoester from a maleic acid monoester. manufacturing method. 2. The method II according to claim 1, characterized in that the reaction is carried out in a monoaqueous system and under a nitrogen atmosphere.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59036331A JPS60181047A (en) | 1984-02-29 | 1984-02-29 | Production of fumaric acid monoester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59036331A JPS60181047A (en) | 1984-02-29 | 1984-02-29 | Production of fumaric acid monoester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60181047A true JPS60181047A (en) | 1985-09-14 |
| JPH0359894B2 JPH0359894B2 (en) | 1991-09-12 |
Family
ID=12466846
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59036331A Granted JPS60181047A (en) | 1984-02-29 | 1984-02-29 | Production of fumaric acid monoester |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60181047A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8101701B2 (en) | 2006-12-01 | 2012-01-24 | Menicon Nect Co., Ltd. | Fumaric acid derivatives and ophthalmic lenses using the same |
| WO2014197860A1 (en) | 2013-06-07 | 2014-12-11 | Xenoport, Inc. | Method of making monomethyl fumarate |
| US9682057B2 (en) | 2013-09-06 | 2017-06-20 | Xenoport, Inc. | Crystalline forms of (N,N-Diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate, methods of synthesis and use |
| JP2017109913A (en) * | 2015-12-18 | 2017-06-22 | 株式会社 エースネット | Method for producing radical and method for producing oxidation reaction product |
| JP2017109196A (en) * | 2015-12-18 | 2017-06-22 | 株式会社 エースネット | Radical generation catalyst, method for producing radical and method for producing oxidation reaction product |
| US9999672B2 (en) | 2014-03-24 | 2018-06-19 | Xenoport, Inc. | Pharmaceutical compositions of fumaric acid esters |
| US10179118B2 (en) | 2013-03-24 | 2019-01-15 | Arbor Pharmaceuticals, Llc | Pharmaceutical compositions of dimethyl fumarate |
| US10716760B2 (en) | 2012-08-22 | 2020-07-21 | Arbor Pharmaceuticals, Llc | Oral dosage forms of methyl hydrogen fumarate and prodrugs thereof |
| US10870102B2 (en) | 2015-12-18 | 2020-12-22 | Acenet Inc. | Radical generating catalyst, method for producing radical, method for producing oxidation reaction product, drug, and drug for agriculture and livestock |
| US10945984B2 (en) | 2012-08-22 | 2021-03-16 | Arbor Pharmaceuticals, Llc | Methods of administering monomethyl fumarate and prodrugs thereof having reduced side effects |
-
1984
- 1984-02-29 JP JP59036331A patent/JPS60181047A/en active Granted
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8101701B2 (en) | 2006-12-01 | 2012-01-24 | Menicon Nect Co., Ltd. | Fumaric acid derivatives and ophthalmic lenses using the same |
| US10940117B2 (en) | 2012-08-22 | 2021-03-09 | Arbor Pharmaceuticals, Llc | Oral dosage forms of methyl hydrogen fumarate and prodrugs thereof |
| US10945984B2 (en) | 2012-08-22 | 2021-03-16 | Arbor Pharmaceuticals, Llc | Methods of administering monomethyl fumarate and prodrugs thereof having reduced side effects |
| US10716760B2 (en) | 2012-08-22 | 2020-07-21 | Arbor Pharmaceuticals, Llc | Oral dosage forms of methyl hydrogen fumarate and prodrugs thereof |
| US11938111B2 (en) | 2013-03-24 | 2024-03-26 | Arbor Pharmaceuticals, Llc | Pharmaceutical compositions of dimethyl fumarate |
| US10179118B2 (en) | 2013-03-24 | 2019-01-15 | Arbor Pharmaceuticals, Llc | Pharmaceutical compositions of dimethyl fumarate |
| WO2014197860A1 (en) | 2013-06-07 | 2014-12-11 | Xenoport, Inc. | Method of making monomethyl fumarate |
| US9302977B2 (en) | 2013-06-07 | 2016-04-05 | Xenoport, Inc. | Method of making monomethyl fumarate |
| US9682057B2 (en) | 2013-09-06 | 2017-06-20 | Xenoport, Inc. | Crystalline forms of (N,N-Diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate, methods of synthesis and use |
| US9999672B2 (en) | 2014-03-24 | 2018-06-19 | Xenoport, Inc. | Pharmaceutical compositions of fumaric acid esters |
| US11135296B2 (en) | 2014-03-24 | 2021-10-05 | Arbor Pharmaceuticals, Llc | Pharmaceutical compositions of fumaric acid esters |
| US10870102B2 (en) | 2015-12-18 | 2020-12-22 | Acenet Inc. | Radical generating catalyst, method for producing radical, method for producing oxidation reaction product, drug, and drug for agriculture and livestock |
| JP2017109196A (en) * | 2015-12-18 | 2017-06-22 | 株式会社 エースネット | Radical generation catalyst, method for producing radical and method for producing oxidation reaction product |
| US11673129B2 (en) | 2015-12-18 | 2023-06-13 | Acenet Inc. | Radical generating catalyst, method for producing radical, method for producing oxidation reaction product, drug, and drug for agriculture and livestock |
| JP2017109913A (en) * | 2015-12-18 | 2017-06-22 | 株式会社 エースネット | Method for producing radical and method for producing oxidation reaction product |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0359894B2 (en) | 1991-09-12 |
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