JPH01149769A - Production of 4-methylimidazole - Google Patents
Production of 4-methylimidazoleInfo
- Publication number
- JPH01149769A JPH01149769A JP30748787A JP30748787A JPH01149769A JP H01149769 A JPH01149769 A JP H01149769A JP 30748787 A JP30748787 A JP 30748787A JP 30748787 A JP30748787 A JP 30748787A JP H01149769 A JPH01149769 A JP H01149769A
- Authority
- JP
- Japan
- Prior art keywords
- ammonia
- exchange reaction
- salt exchange
- sulfate
- 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.)
- Granted
Links
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 45
- 150000003839 salts Chemical group 0.000 claims abstract description 23
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 20
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims abstract description 16
- 235000011130 ammonium sulphate Nutrition 0.000 claims abstract description 16
- AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 claims abstract description 10
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims abstract description 7
- 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 22
- 238000000034 method Methods 0.000 abstract description 12
- 239000006227 byproduct Substances 0.000 abstract description 10
- 150000001875 compounds Chemical class 0.000 abstract 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000004811 liquid chromatography Methods 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 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
- CHJJGSNFBQVOTG-UHFFFAOYSA-N methylguanidine Chemical compound CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture 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
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-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
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- SBMBNVSFFOSNAD-UHFFFAOYSA-N 5-methyl-1h-imidazole;sulfuric acid Chemical compound OS([O-])(=O)=O.CC1=C[NH2+]C=N1 SBMBNVSFFOSNAD-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 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
- 239000012736 aqueous medium Substances 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
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- -1 diacetyl compound Chemical class 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003814 drug Substances 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
- 150000002460 imidazoles Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 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
- 239000003799 water insoluble solvent 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−メチルイミダゾール（以下、４−旧
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 relates to a method for producing high purity 4-methylimidazole (hereinafter abbreviated as 4-old).
４−Ｍｌは医薬品を製造するための価値ある中間体であ
る。4-Ml is a valuable intermediate for manufacturing pharmaceuticals.
４−旧の製造方性としては米国特許第３，７１５，３６
５号に記載がある。該発明は電離定数が１×１０−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。 ＭＧＸか
ら４−ＭＩ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、ＰＨ４，７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−？ｌＩを
得ることを開示している。4-The old manufacturing method is U.S. Patent No. 3,715,36
It is stated in No. 5. The invention uses an ammonium salt of an acid with an ionization constant greater than 1 x 10-, and produces glyoxal or methylglyoxal (hereinafter referred to as
It is abbreviated as MGX. ) is reacted with formaldehyde to produce imidazoles, and specifically mentions ammonium sulfate and oxalic acid as the nucleic acids. As a specific example of producing 4-MI from MGX, MGx, ammonium sulfate and formaldehyde are mixed, aqueous ammonia is added dropwise to the mixture, the mixture is reacted from pH 4.7 to 4.4, and then calcium hydroxide is added. Then, ammonia is scattered, sulfate radicals are precipitated as calcium sulfate, and the precipitate is filtered, dehydrated and distilled to produce 4-? It is disclosed that obtaining lI.
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
、そのため収率が低下し、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、４−１’ｌｌを得ることを開示し、Ｐｌ＋
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
必要なくなり、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 U.S. patent by reacting ammonia, aldehyde, and MGX under conditions where the pH is 7 or higher and by giving characteristics to the feed order of the raw materials. Disclose getting 'll, Pl+
7 or more, and the use of ammonia eliminates the problem of reactor corrosion and the need for extra operations with large amounts of inorganic salt solutions, which is advantageous over U.S. Pat. No. 3,715,365. .
しかし、実施例に示される如＜ 、Ｐｌ＋ ９．２〜９
．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−ＤＩ’ｌｌ と略記する。）の副生が多
くなる。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。However, as shown in the examples, Pl+ 9.2-9
．． When the reaction occurs in region 4, MGX decomposes, acetaldehyde is produced, and 2,4-dimethylimidazole (
Hereinafter, it will be abbreviated as 2.4-DI'll. ) becomes more of a by-product. 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−ＭＴ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
In No. 5664, as an improved method of U.S. Patent No. 3,715,365, high purity 4-MT is obtained 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−Ｄ旧の副生及び４−旧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とホルマリンと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 have succeeded in suppressing the by-product of 2.4-D former and the by-product of methylene bisimidazoles generated from 2 moles of 4-form and 1 mole of formaldehyde, and also because the reaction concentration is high and complicated filtration etc. As a result of our study to develop a process that does not involve any steps, is simplified, can be easily implemented industrially, and can obtain 4-Ml with high purity and high yield, we found that while adjusting the pH to 2 to 4, we can combine MGX and 4-Ml. Good results were obtained by reacting formalin and ammonia in an aqueous medium in the presence of ammonium sulfate, and an application was filed earlier.
しかし、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と硫酸アンモニウムとする際、４．５−ジメチ
ルイミダゾール（以下、４．５−ＤＭｒと略記する。）
の副生が増大するという大きな欠点を有し、４−Ｍｌと
４．５−ＤＭＩが簡単に分離することが困難であるため
純度低下の原因となることが判明した。However, when MGX, formaldehyde, 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-Ml and ammonium sulfate, 4.5 -Dimethylimidazole (hereinafter abbreviated as 4.5-DMr)
It has been found that 4-Ml and 4.5-DMI have a major drawback of increasing by-products, and that it is difficult to easily separate 4-Ml and 4.5-DMI, which causes a decrease in 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、塩交換反応を行う際、４．５−Ｄ旧の副生を抑制す
べく鋭意検討した結果、４．５−Ｄ旧の副生は原料ＭＧ
Ｘ中に不純物として存在するジアセチル体が原因である
のか、また、副生ずる中間体の転移反応で生成するのか
不明であるが、塩交換反応を５０℃以下で実施すれば抑
制できることを見出し、本発明を完成させるに至った。[Means and effects for solving the problem] The present inventors have conducted extensive studies to suppress the by-product of 4.5-D old when performing a salt exchange reaction. By-product is raw material MG
Although it is unclear whether the cause is the diacetyl compound present as an impurity in The invention was completed.
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
で反応させて４−メチルイミダゾールの硫酸塩を得た後
、アンモニアを用いて塩交換反応を行い、遊離の４−メ
チルイミダゾールと硫酸アンモニウムとする際、塩交換
反応を５０°Ｃ以下で実施することを特徴とする４−メ
チルイミダゾールの製造方法である。That is, in the present invention, 4-methylimidazole sulfate is obtained by reacting methylglyoxal, formaldehyde, and ammonia in the presence of ammonium sulfate, and then a salt exchange reaction is performed using ammonia to obtain free 4-methyl This is a method for producing 4-methylimidazole, characterized in that a salt exchange reaction is carried out at 50°C or lower when forming imidazole and ammonium sulfate.
塩交換反応温度が５０″Ｃを越えると、４．５−ＤＭＩ
の副生が多くなり、４−Ｍｌと４．５−ＤＭＩが簡単に
分離することが困難なため純度が低下する。When the salt exchange reaction temperature exceeds 50"C, 4.5-DMI
The amount of by-products increases, and it is difficult to easily separate 4-Ml and 4.5-DMI, resulting in a decrease in purity.
本発明の製造方法によれば、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で反応させて
４−？ＩＩ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と硫酸アンモニウムとする
が、塩交換反応で用いるアンモニアの量は反応液中の酸
分を中和するに足りる量を用いれば十分である。又該硫
酸塩は、ＭＧＸとホルムアルデヒドとを、反応温度５０
〜１００″Ｃ１反応時間２〜５時間、ＰＨ２〜４もしく
は初期ＰＨ価値−酸アンモニウム水溶液のＰＨ値とし反
応中ＰＨ２〜４に調節するという条件下で、硫酸アンモ
ニウムの存在下、アンモニアを反応させて得られる。According to the production method of the present invention, MGX, formaldehyde and ammonia are reacted in the presence of ammonium sulfate to produce 4-? After obtaining the sulfate of II, a salt exchange reaction is performed using ammonia to produce free 4-Ml and ammonium sulfate, but the amount of ammonia used in the salt exchange reaction is sufficient to neutralize the acid content in the reaction solution. It is sufficient to use quantities. In addition, the sulfate can be used to react MGX and formaldehyde at a reaction temperature of 50°C.
~100''C1 Reaction time 2-5 hours, pH 2-4 or initial PH value - pH value of acid ammonium aqueous solution, obtained by reacting ammonia in the presence of ammonium sulfate under the conditions that the pH value of the acid ammonium aqueous solution is adjusted to 2-4 during the reaction. It will be done.
塩交換反応に用いるアンモニアは、アンモニア水溶液或
いはアンモニアガスを用いる。The ammonia used in the salt exchange reaction is an aqueous ammonia solution or ammonia gas.
塩交換反応時間は、特に規定する必要がなく、反応温度
が５０°Ｃ以下となるように時間を調節する。The salt exchange reaction time does not need to be particularly specified, and is adjusted so that the reaction temperature is 50°C or less.
塩交換反応方法としては、反応進行中の温度を５０°Ｃ
以下に維持しながら、反応液にアンモニア水溶液或いは
アンモニアガスを加えて塩交換反応を実施する。For the salt exchange reaction method, the temperature during the reaction is set at 50°C.
A salt exchange reaction is carried out by adding an ammonia aqueous solution or ammonia gas to the reaction solution while maintaining the following conditions.
前記の方法で塩交換反応が終了した液に、水に不溶な有
１媒、例えば、イソブタノール等を加えて４−旧を抽出
し、抽出液を減圧蒸留して４−旧を分取する。A water-insoluble solvent, such as isobutanol, is added to the solution in which the salt exchange reaction has been completed in the above method to extract 4-old, and the extract is distilled under reduced pressure to separate 4-old. .
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３！ガラス製セパラブル
フラスコに蒸留水１３３１ｇ 、硫酸アンモニウム６０
８ｇを仕込み、溶解後８０°Ｃまで昇温し、９５重世％
硫酸５３ｇを仕込んでＰＨを２とした。その後４０重量
％ＭＧＸ水溶液７５０ｇと３７重量％ホルマリン３３８
ｇ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２３９ｇを追加し
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。１（ＰＬＣ分析結果、４
−ＭＩ収率（対？ＩＧＸ 、以下同じ）は８７．５％、
４゜５−ＤＭＩの４−）’ＩＩに対する液体クロマトグ
ラフ分析（以下、液クロ分析と略記する。）による面積
％は０．０８％であった。Example 1 3! with stirrer and reflux condenser! Distilled water 1331g, ammonium sulfate 60g in a glass separable flask
Pour 8g, heat up to 80°C after melting, and reduce to 95%
53 g of sulfuric acid was charged to adjust the pH to 2. After that, 750g of 40wt% MGX aqueous solution and 338g of 37wt% formalin
A mixture of g was added dropwise over 2 hours. During this time, 239 g of a 28% by weight aqueous ammonia solution was added to maintain the 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. 1 (PLC analysis results, 4
-MI yield (vs. IGX, same hereinafter) is 87.5%,
The area percentage of 4-)'II of 4°5-DMI by liquid chromatography analysis (hereinafter abbreviated as liquid chromatography analysis) was 0.08%.
この反応液２００ｇを用い、２８重量％アンモニア水溶
液３１．８ｇを温度２０°Ｃを保つように加え、塩交換
反応を行った。その結果４．５−ＤＭＩの４−Ｍｌに対
する液クロ分析による面積％は０．２０％であった。Using 200 g of this reaction solution, 31.8 g of a 28% by weight ammonia aqueous solution was added while maintaining the temperature at 20° C. to carry out a salt exchange reaction. As a result, the area % of 4.5-DMI relative to 4-Ml was 0.20% by liquid chromatography analysis.
実施例２
実施例１で得られた反応液２００ｇを用い、２８重量％
アンモニア水溶液３１．８ｇを温度４０℃を保つように
加え、塩交換反応を行った。その結果４．５−ＤＭＩの
４−旧に対する液クロ分析による面積％は０．２０％で
あった。Example 2 Using 200 g of the reaction solution obtained in Example 1, 28% by weight
31.8 g of ammonia aqueous solution was added while maintaining the temperature at 40° C., and a salt exchange reaction was carried out. As a result, the area % of 4.5-DMI relative to 4-old was 0.20% by liquid chromatography analysis.
実施例３
実施例１で得られた反応液２００ｇを用い、２８重世％
アンモニア水溶液３１．８ｇを温度５０°Ｃを保つよう
に加え、塩交換反応を行った。その結果４．５−ＤＭｒ
の４−Ｍｌに対する液クロ分析による面積％は０．２４
％であった。Example 3 Using 200 g of the reaction solution obtained in Example 1, 28%
31.8 g of ammonia aqueous solution was added while maintaining the temperature at 50°C, and a salt exchange reaction was carried out. The result is 4.5-DMr
The area% by liquid chromatography for 4-Ml is 0.24
%Met.
比較例１
実施例１で得られた反応液２００ｇを用い、２８重量％
アンモニア水溶液３１．８ｇを温度６０°Ｃを保つよう
に加え、塩交換反応を行った。その結果４．５−Ｄ旧の
４−Ｍｌに対する液クロ分析による面積％は０．６５％
であった。Comparative Example 1 Using 200 g of the reaction solution obtained in Example 1, 28% by weight
31.8 g of ammonia aqueous solution was added while maintaining the temperature at 60°C, and a salt exchange reaction was carried out. As a result, the area% of 4.5-D old 4-Ml by liquid chromatography was 0.65%.
Met.
比較例２
実施例１で得られた反応液２００ｇを用い、２８重量％
アンモニア水溶液３１．８ｇを温度８０°Ｃを保つよう
に加え、塩交換反応を行った。その結果４．５−ＤＭＩ
の４−旧に対する液クロ分析による面積％は１．１５％
であった。Comparative Example 2 Using 200 g of the reaction solution obtained in Example 1, 28% by weight
31.8 g of ammonia aqueous solution was added while maintaining the temperature at 80°C, and a salt exchange reaction was carried out. The result is 4.5-DMI
4-The area% by liquid chromatography for the old is 1.15%
Met.
本発明の方法は、２．４−Ｄ門１．４．５−Ｄ旧及び二
量体の副生を抑制し、高純度、高収率の４−ＭＩが得ら
れる、簡略化されたプロセスである。The method of the present invention is a simplified process that suppresses the by-products of 2.4-D group 1.4.5-D and dimer, and obtains 4-MI of high purity and high yield. It is.
本発明の方法によって得られた４−ＭＩは、特別の精製
をしなくでも純度９７％以上で、４．５−ＤＭＩの４−
旧に対する液クロ分析による面積％は０．５％以下であ
る。4-MI obtained by the method of the present invention has a purity of 97% or more without special purification, and the 4-MI of 4.5-DMI
The area percentage by liquid chromatography analysis with respect to the old one is 0.5% or less.
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で反応させ
て４−メチルイミダゾールの硫酸塩を得た後、アンモニ
アを用いて塩交換反応を行い、遊離の４−メチルイミダ
ゾールと硫酸アンモニウムとする際、塩交換反応を５０
℃以下で実施することを特徴とする４−メチルイミダゾ
ールの製造方法。(1) After reacting methylglyoxal, formaldehyde, and ammonia in the presence of ammonium sulfate to obtain the sulfate of 4-methylimidazole, a salt exchange reaction is performed using ammonia to form free 4-methylimidazole and ammonium sulfate. When the salt exchange reaction is
1. A method for producing 4-methylimidazole, which is carried out at a temperature of 0.degree. C. or lower.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62307487A JPH07100699B2 (en) | 1987-12-07 | 1987-12-07 | Process for producing 4-methylimidazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62307487A JPH07100699B2 (en) | 1987-12-07 | 1987-12-07 | Process for producing 4-methylimidazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01149769A true JPH01149769A (en) | 1989-06-12 |
| JPH07100699B2 JPH07100699B2 (en) | 1995-11-01 |
Family
ID=17969681
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62307487A Expired - Lifetime JPH07100699B2 (en) | 1987-12-07 | 1987-12-07 | Process for producing 4-methylimidazole |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07100699B2 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3715365A (en) * | 1971-02-08 | 1973-02-06 | Jefferson Chem Co Inc | Imidazole synthesis |
-
1987
- 1987-12-07 JP JP62307487A patent/JPH07100699B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3715365A (en) * | 1971-02-08 | 1973-02-06 | Jefferson Chem Co Inc | Imidazole synthesis |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07100699B2 (en) | 1995-11-01 |
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