JPH01149772A - Production of 4-methylimidazole - Google Patents
Production of 4-methylimidazoleInfo
- Publication number
- JPH01149772A JPH01149772A JP30749087A JP30749087A JPH01149772A JP H01149772 A JPH01149772 A JP H01149772A JP 30749087 A JP30749087 A JP 30749087A JP 30749087 A JP30749087 A JP 30749087A JP H01149772 A JPH01149772 A JP H01149772A
- Authority
- JP
- Japan
- Prior art keywords
- ammonia
- water
- reaction solution
- reaction
- methylimidazole
- 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.)
- Pending
Links
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 57
- 239000003957 anion exchange resin Substances 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 15
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims abstract description 14
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims abstract description 12
- 235000011130 ammonium sulphate Nutrition 0.000 claims abstract description 12
- 150000003839 salts Chemical group 0.000 claims abstract description 12
- AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 10
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 abstract description 15
- 238000000034 method Methods 0.000 abstract description 11
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 abstract description 10
- 238000000605 extraction Methods 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract 2
- 230000002378 acidificating effect Effects 0.000 abstract 1
- 239000002253 acid Substances 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- CHJJGSNFBQVOTG-UHFFFAOYSA-N methylguanidine Chemical compound CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- LLPKQRMDOFYSGZ-UHFFFAOYSA-N 2,5-dimethyl-1h-imidazole Chemical compound CC1=CN=C(C)N1 LLPKQRMDOFYSGZ-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- VBIXEXWLHSRNKB-UHFFFAOYSA-N ammonium oxalate Chemical compound [NH4+].[NH4+].[O-]C(=O)C([O-])=O VBIXEXWLHSRNKB-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- DKWVMFVZPTZPJE-UHFFFAOYSA-N 2-(1h-imidazol-2-ylmethyl)-1h-imidazole Chemical class N=1C=CNC=1CC1=NC=CN1 DKWVMFVZPTZPJE-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- SWNDNOHEVRPIDI-UHFFFAOYSA-N 6-methoxy-1h-pyrimidine-2,4-dione Chemical compound COC1=CC(O)=NC(O)=N1 SWNDNOHEVRPIDI-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は高純度４−′／チルイミダゾール（以下、４−
Ｍ［と略記する。）の製造方法に関する。[Detailed Description of the Invention] [Industrial Application Field] The present invention provides high purity 4-'/tylimidazole (hereinafter referred to as 4-'
Abbreviated as M[. ).
４−旧は医薬品を製造するための価値ある中間体である
。4-Old is a valuable intermediate for manufacturing pharmaceutical products.
４−Ｍｌの製造方法としては米国特許第３，７１５，３
６５号に記載がある。該発明は電離定数がｌＸｌ０−’
より大きい酸のアンモニウム塩を用い、ＰＨ７以下の水
媒体中でグリオキザール又はメチルグリオキザール（以
下、ＭＧＸと略記する。）をホルムアルデヒドと反応さ
せて、イミダゾール類を製造するものであり、核酸とし
て特に硫酸アンモニウム及び蓚酸を挙げている。 ＭＧ
Ｘから４−旧を製造する具体例としては、ＭＧＸ 、硫
酸アンモニウム及びホルムアルデヒドを混合し、これに
アンモニア水を滴下して、Ｆｉ＋ ４゜７からＰＨ４，
４で反応せしめ、その後、水酸化カルシウムを添加して
、アンモニアを飛散させ、硫酸根を硫酸カルシウムとし
て沈澱させ、沈澱物を濾別した後、脱水、蒸留して４−
ＭＩを得ることを開示している。The method for producing 4-Ml is described in U.S. Patent No. 3,715,3.
It is stated in No. 65. The invention has an ionization constant of lXl0-'
Imidazole is produced by reacting glyoxal or methylglyoxal (hereinafter abbreviated as MGX) with formaldehyde in an aqueous medium with a pH of 7 or lower using an ammonium salt of a larger acid. It mentions oxalic acid. MG
As a specific example of producing 4-old from
After that, calcium hydroxide is added to scatter ammonia, the sulfate radical is precipitated as calcium sulfate, the precipitate is filtered, and then dehydrated and distilled to obtain 4-
Discloses obtaining MI.
しかしながら、その製品純度はガスクロマトグラフ分析
による面積純度で７７．２％、収率は５９％であり、医
薬品中間体として用いるには更に精製操作が必要となり
、そのため収率も低下し、その方法は満足なものではな
い。However, the product purity was 77.2% in terms of area purity and yield was 59% as determined by gas chromatography analysis, and further purification was required to use it as a pharmaceutical intermediate, resulting in a lower yield, and the method was It's not satisfying.
また、特開昭５７−９７６６号は前記米国特許を改良す
る方法として、ＰＨが７以上の条件下、原料の供給順序
に特徴をもたせて、アンモニアとアルデヒドとＭＧＸを
反応させて、４−Ｍｌを得ることを開示し、また、ＰＨ
が７以上で、且つアンモニアを用いることにより反応器
の腐食の問題及び大量の無機塩溶液による余分の操作が
必要な（なり、米国特許第３．７１５，３６５号より有
利であることも開示している。Furthermore, JP-A No. 57-9766 discloses a method for improving the above-mentioned US patent, in which ammonia, aldehyde, and MGX are reacted under conditions where the pH is 7 or higher, and the order of supply of raw materials is unique. Discloses obtaining PH and also discloses that PH
7 or more, and the use of ammonia leads to problems of reactor corrosion and the need for extra operations with large amounts of inorganic salt solution, which is advantageous over U.S. Pat. No. 3,715,365. ing.
しかし、実施例に示される如＜ 、ＰＨ９，２〜９．４
の領域で反応するとＭＧＸの分解が起こり、アセトアル
デヒドが生成し、２．４−ジメチルイミダゾール（以下
、２．４−ＤＭＩ と略記する。）の副生が多くなる。However, as shown in the examples, PH9.2-9.4
When the reaction occurs in this region, MGX decomposes, acetaldehyde is produced, and a large amount of 2,4-dimethylimidazole (hereinafter abbreviated as 2.4-DMI) is produced as a by-product.
該特許では、この副生を抑制するために希薄溶液で実施
しているが完全ではない。In this patent, a dilute solution is used to suppress this by-product, but it is not perfect.
更に特開昭６０−１０４０７２号及び特開昭６０−１０
５６６４号では、米国特許第３，７１５，３６５号の改
良法として、ＭＧＸに対して総水量を規制することによ
り、高純度の４−旧を高収率で得ているが、米国特許と
同じようにアンモニア源として蓚酸アンモニウムを用い
るために、４−Ｍｌの蓚酸塩の濾過及びアンモニアで開
基を分解した後の蓚酸アンモニウムの濾過と濾過工程が
多く、プロセスが複雑となり、経済的でない。Furthermore, JP-A-60-104072 and JP-A-60-10
No. 5664, as an improved method of U.S. Patent No. 3,715,365, obtains high-purity 4-old at a high yield by regulating the total amount of water for MGX, but it is the same as the U.S. patent. Since ammonium oxalate is used as an ammonia source, there are many steps such as filtration of 4-Ml oxalate and filtration of ammonium oxalate after decomposing open groups with ammonia, making the process complicated and uneconomical.
本発明者らは、２．４−ＤＭＩの副生及び４−Ｍｌ ２
モルとホルムアルデヒド１モルより生成するメチレンビ
スイミダゾール類の副生を抑制し、且つ反応濃度が濃く
、濾過等の複雑な工程を含まない、簡略化された工業的
に容易に実施可能な、高純度、高収率の４−Ｍｌが得ら
れるプロセスを開発すべく検討した結果、ＰＨ２〜４に
調節しながら、ＭＧＸとホルマリン及びアンモニアを硫
酸アンモニウム存在下、水媒体中で反応させて好結果を
得、先に出願した。The present inventors discovered that the by-product of 2.4-DMI and 4-Ml 2
It suppresses the by-product of methylene bisimidazoles produced from 1 mole of formaldehyde, has a high reaction concentration, does not involve complicated steps such as filtration, and has a high purity that can be easily implemented industrially. As a result of studying to develop a process to obtain 4-Ml in high yield, good results were obtained by reacting MGX with formalin and ammonia in an aqueous medium in the presence of ammonium sulfate while adjusting the pH to 2 to 4. I applied first.
しかし、？ＩＧＸ 、ホルマリンとアンモニアを硫酸ア
ンモニウム存在下で反応させて４−Ｍｌの硫酸塩を得た
後、アンモニアを用いて塩交換反応を行い、遊離の４−
Ｍｌとし、その後、水に不溶解な有機溶媒で抽出を行い
、蒸留により４−Ｍｌを単離する際、原料ＭＧＸ中に含
まれる酢酸或いは反応中に副生ずる酸分が４−ＭＩ中に
混入し、製品純度を低下させる原因となりうるという大
きな欠点があることが判明した。but,? IGX, formalin and ammonia are reacted in the presence of ammonium sulfate to obtain 4-Ml sulfate, and then a salt exchange reaction is performed using ammonia to form free 4-
When extracting with an organic solvent insoluble in water and isolating 4-Ml by distillation, acetic acid contained in the raw material MGX or an acid content by-produced during the reaction mixes into 4-Ml. However, it has been found that there is a major drawback in that it can cause a decrease in product purity.
更に、抽残水をもとの反応系にリサイクルする際、酸分
のかなりの部分もリサイクルされ、抽出液中への酸分の
蓄積が激しく、蒸留により４−旧を単離する際、原料Ｍ
ＧＸ中に含まれる酢酸あるいは反応中に副生ずる酸分が
４−Ｍｌ中に混入し、製品純度を低下させる原因となり
うるという大きな欠点があることも判明した。Furthermore, when the raffinate water is recycled back to the original reaction system, a considerable portion of the acid content is also recycled, resulting in a large accumulation of acid content in the extract. M
It has also been found that there is a major drawback in that acetic acid contained in GX or acid content by-produced during the reaction mixes into 4-Ml and can cause a decrease in product purity.
〔問題点を解決するための手段および作用〕本発明者ら
は、ＭＧＸ中に存在する酢酸及び反応中に副生ずる酸分
が蒸留時４−Ｍ１中に混入し、４−？ｌＩ純度を低下さ
せないよう、また、抽残水を反応系ヘリサイクルする際
、硫酸アンモニウム以外の酸分かリサイクルされるのを
極力抑えるべく鋭意検討した結果、ＭＧＸ 、ホルムア
ルデヒドとアンモニアを硫酸アンモニウム存在下、ＰＨ
が２〜４の領域で反応させて４−ＭＩを得、該４−Ｍ１
反応液をアンモニア水もしくはアンモニアガス又は液体
アンモニアを用いてＰＨを５〜６とした後、弱塩基性陰
イオン交換樹脂処理をし、更にアンモニア水もしくはア
ンモニアガス又は液体アンモニアを用いてＰ）Ｉを８〜
９として塩交換し、その後、水に不溶解な有機溶媒で４
−ＭＩを抽出した後、蒸留することにより、４−Ｍｌ中
に酸分の混入することなく、純度の高い４−Ｍｌが得ら
れること及び抽残水中の硫酸アンモニウム以外の酸分ち
微小でありリサイクルによる抽出液への蓄積もないこと
を見出し、本発明を完成させるに至った。[Means and actions for solving the problem] The present inventors discovered that acetic acid present in MGX and acid content by-produced during the reaction mix into 4-M1 during distillation, resulting in 4-? As a result of intensive studies to avoid reducing lI purity and to suppress as much as possible the recycling of acids other than ammonium sulfate when raffinate water is recycled to the reaction system, we found that MGX, formaldehyde and ammonia were mixed in the presence of ammonium sulfate, and PH
is reacted in the region of 2 to 4 to obtain 4-MI, and the 4-M1
After adjusting the pH of the reaction solution to 5 to 6 using ammonia water, ammonia gas, or liquid ammonia, it is treated with a weakly basic anion exchange resin, and then P)I is added using ammonia water, ammonia gas, or liquid ammonia. 8~
Salt exchange was performed as 9, followed by 4 with an organic solvent insoluble in water.
- By distilling after extracting MI, highly pure 4-Ml can be obtained without any acid components being mixed into 4-Ml, and the acid components other than ammonium sulfate in the raffinate water are minute and can be recycled. The present invention was completed based on the discovery that there was no accumulation in the extract due to the above.
即ち、本発明は、メチルグリオキザールと、ホルムアル
デヒドとおよびアンモニアとを硫酸アンモニウム存在下
、ＰＨが２〜４の領域で反応させて４−メチルイミダゾ
ール反応液を得、該４−メチルイミダゾール反応液をア
ンモニア水、アンモニアガス又は液体アンモニアを用い
てＰＨを５〜６とした後、弱塩基性陰イオン交換樹脂で
処理をし、更にアンモニア水、アンモニアガス又は液体
アンモニアを用いてＰＨを８〜９として塩交換し、その
後、水に不溶解な有機溶媒で４−メチルイミダゾールを
抽出し、抽残水を反応系にリサイクルすることによる４
−メチルイミダゾールの製造方法である。That is, in the present invention, methylglyoxal, formaldehyde, and ammonia are reacted in the presence of ammonium sulfate in a pH range of 2 to 4 to obtain a 4-methylimidazole reaction solution, and the 4-methylimidazole reaction solution is mixed with aqueous ammonia. After adjusting the pH to 5 to 6 using ammonia gas or liquid ammonia, treatment with a weakly basic anion exchange resin, and then salt exchange to adjust the pH to 8 to 9 using ammonia water, ammonia gas or liquid ammonia. Then, 4-methylimidazole was extracted with a water-insoluble organic solvent, and the raffinate water was recycled to the reaction system.
- A method for producing methylimidazole.
４−？ｌＩ反応液は、ＭＧＸと、ホルムアルデヒドとお
よびアンモニアとを硫酸アンモニウム存在下、ＰＨが２
〜４の領域もしくは反応初期においては硫酸アンモニウ
ムが示すＰＨで、その後はＰＨ２〜４の領域で、反応温
度５０〜１００″Ｃ１反応時間２〜５時間という反応条
件下で反応させて得られる。塩交換反応は、該４−Ｍｒ
反応液を５０°Ｃ以下の温度でアンモニア水、アンモニ
アガス又は液体アンモニアを用いて行う。4-? The lI reaction solution was prepared by combining MGX, formaldehyde, and ammonia in the presence of ammonium sulfate at a pH of 2.
It is obtained by reacting at the pH indicated by ammonium sulfate in the range of ~4 or at the initial stage of the reaction, and then in the pH range of 2 to 4 under the reaction conditions of a reaction temperature of 50 to 100 cm and a reaction time of 2 to 5 hours.Salt exchange The reaction is carried out using the 4-Mr
The reaction solution is carried out at a temperature of 50° C. or less using aqueous ammonia, ammonia gas or liquid ammonia.
前記の４−Ｍ１反応液は、アンモニア水、アンモニアガ
ス又は液体アンモニアを用いてＰＨを５〜６とした後、
弱塩基性陰イオン交換樹脂で処理を行い、その後、更に
アンモニア水、アンモニアガスまたは液体アンモニアを
用いてｐＨを８〜９として塩交換を行うのが望ましい。After adjusting the pH of the 4-M1 reaction solution to 5 to 6 using ammonia water, ammonia gas, or liquid ammonia,
It is desirable to perform treatment with a weakly basic anion exchange resin, and then further perform salt exchange by adjusting the pH to 8 to 9 using aqueous ammonia, ammonia gas, or liquid ammonia.
勿論４−Ｍ１反応液のまま、あるいは塩交換を行った後
に弱塩基性陰イオン交換樹脂で処理を行っても差し支え
ないが、弱塩基性陰イオン交換樹脂のイオン交換能力の
点で不利となる。Of course, it is possible to treat the 4-M1 reaction solution as is or after salt exchange with a weakly basic anion exchange resin, but this will be disadvantageous in terms of the ion exchange ability of the weakly basic anion exchange resin. .
弱塩基性陰イオン交換樹脂としては、特殊なものを使用
する必要がなく一般的なもので十分である。強塩基性陰
イオン交換樹脂は、処理液中の硫酸アンモニウムもイオ
ン交換してしまうため、４−Ｍ［を抽出した後の抽残水
を反応系にリサイクルする際、原単位上不利となる。As the weakly basic anion exchange resin, it is not necessary to use a special one, and a common one is sufficient. Since the strongly basic anion exchange resin also ion-exchanges ammonium sulfate in the treatment liquid, it is disadvantageous in terms of basic unit when the raffinate water after extracting 4-M[ is recycled to the reaction system.
弱塩基性陰イオン交換樹脂の使用量、操作条件としては
、−船釣な使用条件で十分である。Regarding the amount of the weakly basic anion exchange resin used and the operating conditions, - boat fishing conditions are sufficient.
水に不溶解な有機溶媒には、イソブタノール等が含まれ
る。Organic solvents that are insoluble in water include isobutanol and the like.
弱塩基性陰イオン交換樹脂処理した液から４−Ｍｌを抽
出した後の抽残水中には酸分が微量であり、この抽残水
を次の反応系にリサイクルしても酸分の蓄積はみられな
い。There is a trace amount of acid content in the raffinate water after extracting 4-Ml from a solution treated with a weakly basic anion exchange resin, and even if this raffinate water is recycled to the next reaction system, acid content will not accumulate. I can't see it.
前記の方法により弱塩基性陰イオン交換樹脂で処理した
４−１抽出液を減圧蒸留して４−ＭＩを分取する。The 4-1 extract treated with a weakly basic anion exchange resin by the method described above is distilled under reduced pressure to separate 4-MI.
以下に実施例を挙げ本発明を具体的に説明する。 The present invention will be specifically explained below with reference to Examples.
実施例１
攪拌機、還流コンデンサー付の１！ガラス製セパラブル
フラスコに蒸留水３１６．９ｇ、硫酸アンモニウム１４
５．４ｇを仕込み、溶解後８０°Ｃまで昇温し、９５重
世％硫酸１７．１８ｇを仕込んでＰＨを２とした。その
後４０重量％ＭＧＸ水溶液１７７．５ｇと３７重量％ホ
ルマリン８０．９ｇの混合液を２時間で滴下した。その
間ＰＨ２を維持するために２８重量％アンモニア水溶液
５３．６ｇを追加させながら行った。滴下終了後、同じ
ＰＨ値で２時間熟成反応を行い、反応を完結させた。）
ＩＰＬＣ分析結果、４−Ｍ１収率（対ＭＧＸ 、以下同
じ）は８８．３％であった。Example 1 1 with stirrer and reflux condenser! 316.9 g of distilled water and 14 ammonium sulfate in a separable glass flask
After dissolving 5.4 g of the solution, the temperature was raised to 80°C, and 17.18 g of 95% sulfuric acid was added to adjust the pH to 2. Thereafter, a mixed solution of 177.5 g of a 40% by weight MGX aqueous solution and 80.9 g of 37% by weight formalin was added dropwise over 2 hours. During this time, 53.6 g of a 28% by weight ammonia aqueous solution was added to maintain pH2. After completion of the dropwise addition, an aging reaction was carried out for 2 hours at the same pH value to complete the reaction. )
As a result of IPLC analysis, the yield of 4-M1 (relative to MGX, hereinafter the same) was 88.3%.
この反応液に、２８重量％アンモニア水溶液１７３．９
ｇ−ｔ−温度４０°Ｃを保つようにして加え、塩交換反
応を行った。To this reaction solution, 173.9% of a 28% by weight ammonia aqueous solution was added.
The g-t-temperature was maintained at 40°C and a salt exchange reaction was carried out.
この塩交換の途中、ＰＨが５．５となったところで一旦
アンモニア水の添加を中断し、この液を弱塩基性陰イオ
ン交換樹脂（レバチッ） （Ｌｅｗａｔｉｔ ）ＭＰ
６２）１００ 成を用い、ＳＶ３にて通液した。弱塩基
性陰イオン交換樹脂に通液する前後の酸根を測定したと
ころ、通液前の酸根は０．０２５当量であり、通液後の
酸根は０．００１当量以下であった。During this salt exchange, when the pH reached 5.5, the addition of ammonia water was temporarily stopped, and this solution was mixed with a weakly basic anion exchange resin (Lewatit) MP.
62) Using 100% liquid, the solution was passed at SV3. When the acid radicals before and after passing through the weakly basic anion exchange resin were measured, the acid radicals before passing the solution were 0.025 equivalent, and the acid radicals after passing the solution were 0.001 equivalent or less.
更に塩交換液にイソブタノール２２０ｇを加えて４−Ｍ
ｌの抽出を行った。イソブタノール層と水層を分離し、
水層に関して同様の抽出操作を合計３回行った。３回分
のイソブタノール層を混合し、その混合液を減圧蒸留し
たところ、純度９９．４％の４−旧を得た。Furthermore, add 220 g of isobutanol to the salt exchange solution to make 4-M
l was extracted. Separate the isobutanol and aqueous layers,
Similar extraction operations were performed for the aqueous layer three times in total. Three isobutanol layers were mixed and the mixture was distilled under reduced pressure to obtain 4-old with a purity of 99.4%.
実施例２
実施例１で得られた抽残水を用い、実施例１と同様の操
作を行った。弱塩基性陰イオン交換樹脂に通液する前の
酸根を測定したところ、酸根は０．０２６当量であり、
酸根の蓄積はみられず、純度９９．６％の４−旧が得ら
れた。Example 2 The same operation as in Example 1 was performed using the raffinate water obtained in Example 1. When the acid radicals were measured before passing through the weakly basic anion exchange resin, the acid radicals were 0.026 equivalent,
No acid radical accumulation was observed, and 4-old with a purity of 99.6% was obtained.
比較例１
塩基性陰イオン交換樹脂処理を行わなかった他は実施例
１と同様の操作を行った。その結果、４−旧の純度は９
２．８％であった。Comparative Example 1 The same operation as in Example 1 was performed except that the basic anion exchange resin treatment was not performed. As a result, 4-old purity is 9
It was 2.8%.
本発明の方法によって得られた４−ＭＩは、特別の精製
をしなくても純度９７％以上であり、酸分の混入は認め
られない。本発明の方法に基づくプロセスは高純度の４
−Ｍｌが高収率で得られる簡略化されたプロセスである
。4-MI obtained by the method of the present invention has a purity of 97% or more even without special purification, and no acid content is observed. The process based on the method of the invention produces high purity 4
- It is a simplified process that provides high yields of Ml.
特許出願人 三井東圧化学株式会社Patent applicant: Mitsui Toatsu Chemical Co., Ltd.
Claims (1)
よびアンモニアとを硫酸アンモニウム存在下、ＰＨが２
〜４の領域で反応させて４−メチルイミダゾール反応液
を得、該４−メチルイミダゾール反応液をアンモニア水
、アンモニアガス又は液体アンモニアを用いてＰＨを５
〜６とした後、弱塩基性陰イオン交換樹脂で処理をし、
更にアンモニア水、アンモニアガス又は液体アンモニア
を用いてＰＨを８〜９として塩交換し、その後、水に不
溶解な有機溶媒で４−メチルイミダゾールを抽出し、抽
残水を反応系にリサイクルすることによる４−メチルイ
ミダゾールの製造方法。(1) Methylglyoxal, formaldehyde, and ammonia are mixed in the presence of ammonium sulfate until the pH is 2.
4-4 to obtain a 4-methylimidazole reaction solution, and the pH of the 4-methylimidazole reaction solution was adjusted to 5 using ammonia water, ammonia gas, or liquid ammonia.
~6, then treated with a weakly basic anion exchange resin,
Furthermore, salt exchange is performed using ammonia water, ammonia gas, or liquid ammonia to adjust the pH to 8 to 9, and then, 4-methylimidazole is extracted with an organic solvent that is insoluble in water, and the raffinate water is recycled to the reaction system. A method for producing 4-methylimidazole.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30749087A JPH01149772A (en) | 1987-12-07 | 1987-12-07 | Production of 4-methylimidazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30749087A JPH01149772A (en) | 1987-12-07 | 1987-12-07 | Production of 4-methylimidazole |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01149772A true JPH01149772A (en) | 1989-06-12 |
Family
ID=17969716
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP30749087A Pending JPH01149772A (en) | 1987-12-07 | 1987-12-07 | Production of 4-methylimidazole |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01149772A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014201573A (en) * | 2013-04-09 | 2014-10-27 | 広栄化学工業株式会社 | Method for extracting alkyl imidazole compound |
-
1987
- 1987-12-07 JP JP30749087A patent/JPH01149772A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014201573A (en) * | 2013-04-09 | 2014-10-27 | 広栄化学工業株式会社 | Method for extracting alkyl imidazole compound |
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