JPH01139569A - Production of 4-methylimidazole - Google Patents
Production of 4-methylimidazoleInfo
- Publication number
- JPH01139569A JPH01139569A JP29610587A JP29610587A JPH01139569A JP H01139569 A JPH01139569 A JP H01139569A JP 29610587 A JP29610587 A JP 29610587A JP 29610587 A JP29610587 A JP 29610587A JP H01139569 A JPH01139569 A JP H01139569A
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- formaldehyde
- ammonium sulfate
- ammonia
- mgx
- 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
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 8
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 title claims description 16
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 42
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 37
- 238000006243 chemical reaction Methods 0.000 claims abstract description 27
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims abstract description 22
- 235000011130 ammonium sulphate Nutrition 0.000 claims abstract description 22
- AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 18
- 239000000203 mixture Substances 0.000 claims abstract description 4
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 13
- 239000007864 aqueous solution Substances 0.000 abstract description 9
- 239000006227 byproduct Substances 0.000 abstract description 5
- LLPKQRMDOFYSGZ-UHFFFAOYSA-N 2,5-dimethyl-1h-imidazole Chemical compound CC1=CN=C(C)N1 LLPKQRMDOFYSGZ-UHFFFAOYSA-N 0.000 abstract description 4
- 239000000539 dimer Substances 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000002994 raw material Substances 0.000 description 6
- 238000004064 recycling Methods 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000032683 aging Effects 0.000 description 3
- 239000012736 aqueous medium Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-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
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000012153 distilled water Substances 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
- 239000000047 product Substances 0.000 description 2
- 150000003839 salts Chemical group 0.000 description 2
- 238000001577 simple distillation Methods 0.000 description 2
- 239000002351 wastewater 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
- 239000002253 acid Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- -1 ammonium ions 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
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000605 extraction 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
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N methylguanidine Chemical compound CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 239000011259 mixed solution Substances 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
- 239000005416 organic matter Substances 0.000 description 1
- 239000003960 organic solvent Substances 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
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 230000035484 reaction time Effects 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
- 238000007086 side reaction Methods 0.000 description 1
- 239000002699 waste material 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−Ｍ
ｌ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-methylimidazole (hereinafter referred to as 4-M
It is abbreviated as l. ).
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−ＭＩ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ｌＸｌ０−３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。The method for producing 4-MI is described in U.S. Patent No. 3,715.3.
It is stated in No. 65. This invention produces imidazoles by reacting glyoxal or methylglyoxal (hereinafter abbreviated as MGX) with formaldehyde in an aqueous medium with a pH of 7 or less using an ammonium salt of an acid with an ionization constant greater than 1X10-3. , which specifically mentions ammonium sulfate and oxalic acid as nucleic acids.
ＭＧＸから４−ＭＩを製造する具体例としては、？ＩＧ
Ｘ、硫酸アンモニウム及びホルマリンを混合し、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Ｒ物を濾別した後、脱水、蒸留して４−ＭＩ
を得ると開示している。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％である。それは医薬中間体として用いるに
は、更に精製操作が必要であり、そのため収率も低下し
、その方法４ま満足な方法ではない。What is a specific example of producing 4-MI from MGX? I.G.
X, ammonium sulfate and formalin are mixed, aqueous ammonia is added dropwise to this, the pH is changed from 4.7 to 4.4, and then calcium hydroxide is added to scatter the ammonia and the sulfate group is converted into calcium sulfate. After precipitating and filtering the precipitate, it is dehydrated and distilled to obtain 4-MI.
It is disclosed that it will be obtained. However, the product purity was 77.2% in terms of area purity as determined by gas chromatography analysis.
Yield is 59%. In order to use it as a pharmaceutical intermediate, further purification operations are required, resulting in lower yields, and Method 4 is not a satisfactory method.
また、特開昭５７−９７６６は前記米国特許を改良する
方法として、ＰＩ（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４−旧を得ることを開示し、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くなり
、米国特許第３，７１５，３６５号より存利であること
も開示している。In addition, JP-A-57-9766 discloses a method for improving the above-mentioned US patent by reacting ammonia, aldehyde, and MGX under conditions where PI (is 7 or more) and giving characteristics to the order in which the raw materials are supplied to obtain 4-old. Disclose that, and the pH is 7 or higher,
It is also disclosed that 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 more advantageous than U.S. Pat. No. 3,715,365.
しかし、実施例に示される如く、ＰＨ９，２〜Ｐ）！９
．４の領域で反応すると？ＩＧＸ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、Ｉ）Ｍｌ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, PH9,2~P)! 9
．． What if it reacts in area 4? Decomposition of IGX occurs and acetaldehyde is produced, abbreviated as 2,4-dimethylimidazole (hereinafter referred to as I)Ml. ) 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−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−ＭＩ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. In order to use ammonium oxalate as an ammonia source, there are many steps such as filtration of 4-MI oxalate and filtration of ammonium oxalate after decomposing the open group with ammonia, making the process complicated and uneconomical.
（発明が解決しようとする問題点）
本発明者らは、副生するＤＭＩ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−門Ｉが得られるプロセス
を開発すべく検討した結果、ＰＨ２〜Ｐ）１４に調節し
ながら、ＭＧＸとホルムアルデヒド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。(Problems to be Solved by the Invention) The present inventors have developed a method that suppresses the methylene bisimidazoles produced from 2 moles of DMI and 4-Ml as by-products and 1 mole of formaldehyde, and has a high reaction concentration, so that filtration, etc. As a result of our study to develop a process that does not involve complicated steps, is simplified, can be easily carried out industrially, and can obtain 4-group I with high purity and high yield, we found that the pH was adjusted to 2 to 14. However, good results were obtained by reacting MGX with formaldehyde and ammonia in an aqueous medium in the presence of ammonium sulfate, and the application was filed earlier.
しかし、先の出願では、生成４−旧を抽出、回収し、抽
残水を元の反応系にリサイクルするときに大きな欠点を
有することが判明した。However, the previous application was found to have major drawbacks when extracting and recovering the product 4-old and recycling the raffinate water back to the original reaction system.
即ち、硫酸アンモニウム存在下、水媒体中で生成した４
−旧は、４−旧の硫酸塩として存在し、これを抽出、回
収するためには、アンモニアを用いてＰＩ（８〜ＰＦＩ
９とし硫酸アンモニウムと遊離の４−［とじて抽出し、
抽残水中の硫酸アンモニウムは元の反応系にリサイクル
される。このリサイクル系で反応と抽残水のＰＨが異な
り、Ｐ Ｈ調節用に硫酸を追加しなければならない、そ
のためリサイクル系の硫酸バランスが取れず、原料原単
位の悪化及び廃水負荷の増加をもたらし好ましくない。That is, 4 produced in an aqueous medium in the presence of ammonium sulfate
-Old exists as a sulfate of 4-Old, and in order to extract and recover it, ammonia is used to extract PI (8-PFI).
9 and extracted with ammonium sulfate and free 4-[
Ammonium sulfate in the raffinate water is recycled to the original reaction system. In this recycling system, the PH of the reaction and raffinate water is different, and sulfuric acid has to be added to adjust the PH.As a result, the sulfuric acid balance in the recycling system cannot be achieved, resulting in deterioration of the raw material consumption rate and increase in wastewater load, which is not desirable. do not have.
Ｃ問題点を解決するための手段および作用〕本発明者ら
は、このリサイクル系の完全クローズ化を目的として鋭
意検討した結果、原料の供給方法及び反応液中のＰＨを
調節するタイミングを工夫することにより、高収率で高
純度の４−？ＩＩが得られるのは勿論のこと、リサイク
ル系が完全クローズ化可能であることを見出し、本発明
を完成させるに至ったものである。Means and action for solving problem C] As a result of intensive study with the aim of completely closing this recycling system, the present inventors devised a raw material supply method and the timing of adjusting the PH in the reaction solution. By this, high yield and high purity of 4-? They discovered that not only can they obtain II, but also that the recycling system can be completely closed, leading to the completion of the present invention.
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、
反応させて４−メチルイミダゾールを製造する際、硫酸
アンモニウム水溶液にメチルグリオキザールとホルムア
ルデヒドの混合液を滴下、若しくはメチルグリオキザー
ルとホルムアルデヒドを各々同時に滴下し、反応液中の
ＰＨが２〜４の領域内になった後、同領域内を保つよう
にアンモニアを追加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, the present invention provides methylglyoxal, formaldehyde, and ammonia in the presence of ammonium sulfate.
When reacting to produce 4-methylimidazole, a mixture of methylglyoxal and formaldehyde is added dropwise to an aqueous ammonium sulfate solution, or methylglyoxal and formaldehyde are each added dropwise at the same time, so that the pH of the reaction solution falls within the range of 2 to 4. This is a method for producing 4-methylimidazole, which is characterized by adding ammonia so as to maintain the same range.
本発明方法によれば、反応初期における硫酸アンモニウ
ム水溶液のＰＨは調節する必要がなく、反応によって硫
酸アンモニウムのアンモニアが消費され、ＰＨが徐々に
低下してＰＨ２〜ＰＨ４になった後、アンモニアを追加
して同領域を保ちながら反応を進行させるために、硫酸
を追加する必要がなくリサイクル系が可能となったもの
である。According to the method of the present invention, there is no need to adjust the pH of the ammonium sulfate aqueous solution at the initial stage of the reaction, and after the ammonia in ammonium sulfate is consumed by the reaction and the pH gradually decreases to PH2 to PH4, ammonia is added. In order to allow the reaction to proceed while maintaining the same range, there is no need to add sulfuric acid, making a recycling system possible.
本発明による製造方法は、硫酸アンモニウム存在下、？
ＩＧＸとホルムアルデヒド及びアンモニアとを反応させ
るのが主であり、ＰＨが４を越えると硫酸アンモ；、ラ
ムのアンモニウムイオンが反応に大きく関与してくると
推定される。The production method according to the present invention is performed in the presence of ammonium sulfate.
IGX is mainly reacted with formaldehyde and ammonia, and when the pH exceeds 4, ammonium ions of ammonium sulfate and rum are presumed to be significantly involved in the reaction.
硫酸アンモニウムの使用量はＭＧＸに対して１以上であ
れば良く、アンモニアは反応に使用されると共に反応Ｐ
Ｈを２〜４に維持するために使用されるのでモル比は２
以上となる。The amount of ammonium sulfate used should be 1 or more based on MGX, and ammonia is used in the reaction and also in the reaction P.
It is used to maintain H between 2 and 4, so the molar ratio is 2.
That's all.
ホルムアルデヒドの過剰は、ＭＧＸに対して１．１倍程
度は可能であるが、それを越えると副反応を促進し不都
合である。It is possible to use formaldehyde in excess of about 1.1 times that of MGX, but if it exceeds this, side reactions will be promoted, which is disadvantageous.
反応温度は５０〜１００℃、好ましくは７０〜８０°Ｃ
が良い。Reaction temperature is 50-100°C, preferably 70-80°C
is good.
反応時間は温度に依存するが２〜５時間で良い。The reaction time depends on the temperature, but may be 2 to 5 hours.
以上の条件で反応して得られた４−Ｍｌは、硫酸塩とし
て存在しているので、アンモニアを用いてＰＩ（を８〜
９にすると４−Ｍｌは遊離となり、硫酸は硫酸アンモニ
ウムとなる。この塩交換液から水に不溶な有機溶媒、例
えばイソブタノール等を用いて４−旧を抽出し、抽出後
の抽残水は原料系より増加する分の水を単蒸留で除去後
、反応系に戻される。反応系に戻される抽残水のＰＨは
５〜６であり、硫酸の追加はな（、そのまま反応に用い
られてリサイクルされる。Since 4-Ml obtained by the reaction under the above conditions exists as a sulfate, PI (from 8 to
9, 4-Ml becomes free and sulfuric acid becomes ammonium sulfate. 4-O is extracted from this salt exchange solution using a water-insoluble organic solvent such as isobutanol, and the raffinate water after the extraction is used to remove the water that increases from the raw material system by simple distillation. will be returned to. The pH of the raffinate water returned to the reaction system is 5 to 6, and sulfuric acid is not added (it is used as is for the reaction and recycled.
原料系より入る水は単蒸留で除去可能であり、無機塩及
び有機物含有廃液は系外に出ることな（、クローズ化さ
れてリサイクルされ、原料原単位の向上は勿論のこと廃
水の低減化をもたらす。The water that enters the raw material system can be removed by simple distillation, and the waste liquid containing inorganic salts and organic matter does not leave the system (it is closed and recycled, which not only improves the raw material consumption rate but also reduces waste water). bring.
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１２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、８０°Ｃまで昇温した。昇温後、Ｐ
Ｈは５．０であった。 ＰＨを確認後、４０重量％ＭＧ
Ｘ水溶液１７７．６ｇと３７重景％ホルマリン８０．８
ｇの混合液を２時間で滴下した。その間ＰＨが低下し、
ＰＨが２になった後、ＰＨ２を維持するために２８重量
％アンモニア水溶液４０．５ｇを追加しながら行った０
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。 ＨＰＬＣ分析結果、４−Ｍ１収率は（
対ＭＧＸ 、以下同じ）８８．６６％、ＤＭＩ収率は（
対ＭＧＸ 。Example 1 316.9 g of distilled water and 14 ammonium sulfate were placed in a 12 glass separable flask equipped with a stirrer and a reflux condenser.
5.4g was charged and the temperature was raised to 80°C. After heating up, P
H was 5.0. After checking the pH, 40% by weight MG
177.6g of X aqueous solution and 80.8g of 37% formalin
A mixture of g was added dropwise over 2 hours. During that time, the pH decreases,
After the pH reached 2, 40.5 g of 28% by weight ammonia aqueous solution was added to maintain the pH.
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 HPLC analysis, the yield of 4-M1 is (
MGX (hereinafter the same)) 88.66%, DMI yield (
Against MGX.
以下同じ）０．２１％であった。(same below) was 0.21%.
実施例２
実施例１と同じ反応器に蒸留水３１６．９ｇ、硫酸アン
モニウム１４５．４ｇを仕込み、８０°Ｃに昇温して溶
解させた。 ＰＨを確認後、４０重景％？ＩＧＸ水溶液
１７７．６ｇと３７重景％ホルマリン８０．８ｇの混合
液を２時間で滴下した。その間ＰＲが低下し、ＰＨが４
になった後ＰＨ４を維持するために２８重量％アンモニ
ア水溶液６２．７ｇを追加しながら行った０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。Example 2 316.9 g of distilled water and 145.4 g of ammonium sulfate were charged into the same reactor as in Example 1, and the temperature was raised to 80°C to dissolve them. After checking the pH, 40%? A mixed solution of 177.6 g of IGX aqueous solution and 80.8 g of 37% formalin was added dropwise over 2 hours. During that time, PR decreases and PH increases to 4.
After the addition of 62.7 g of a 28 wt % ammonia aqueous solution was completed to maintain the pH at 4, an aging reaction was carried out for 2 hours at the same pH value to complete the reaction.
）ＩＰＬｃ分析結果、４−Ｍ！収率は８５゜７％、［１
ＭＩ収率は０．４４％であった。) IPLc analysis results, 4-M! Yield: 85.7%, [1
MI yield was 0.44%.
比較例１
実施例１において、９５重量％硫酸を添加せず、硫酸ア
ンモニウムのみとし、そのままのＰＨ５，１を２８重量
％アンモニア水溶液を追加して維持しながら、実施例１
と同じように反応を行った。その結果、４−Ｍ１収率は
８０％、聞Ｉ収率は０．６２％であった。Comparative Example 1 In Example 1, 95% by weight sulfuric acid was not added, only ammonium sulfate was used, and while maintaining the same pH of 5.1 by adding 28% by weight ammonia aqueous solution, Example 1
I reacted in the same way. As a result, the yield of 4-M1 was 80%, and the yield of 4-M1 was 0.62%.
比較例２
比較例１において、２８重量％アンモニア水溶液の追加
はなく、反応に従ってｐＨが低下するままに反応を行っ
た。熟成反応２時間後のＰＩ（は１．２であり、その結
果、４−Ｍ１収率は７９．４％、ＤＭＩ収率は０．７７
％であった。Comparative Example 2 In Comparative Example 1, the 28% by weight ammonia aqueous solution was not added, and the reaction was carried out with the pH decreasing as the reaction progressed. PI after 2 hours of aging reaction was 1.2, and as a result, the 4-M1 yield was 79.4% and the DMI yield was 0.77.
%Met.
本発明の方法によれば、簡略化されたプロセスで副生す
る［１ＭＩや二量体の生成を抑制し、高純度、高収率の
４−Ｍｌが得られる。According to the method of the present invention, 4-Ml of high purity and high yield can be obtained by suppressing the production of by-product [1Ml and dimer] through a simplified process.
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、反応させ
て４−メチルイミダゾールを製造する際、硫酸アンモニ
ウム水溶液にメチルグリオキザールとホルムアルデヒド
の混合液を滴下、若しくはメチルグリオキザールとホル
ムアルデヒドを各々同時に滴下し、反応液中のＰＨが２
〜４の領域内になった後、同領域内を保つようにアンモ
ニアを追加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) When producing 4-methylimidazole by reacting methylglyoxal, formaldehyde, and ammonia in the presence of ammonium sulfate, a mixture of methylglyoxal and formaldehyde is added dropwise to an aqueous ammonium sulfate solution, or methylglyoxal and formaldehyde are each added simultaneously. dropwise until the pH in the reaction solution is 2.
A method for producing 4-methylimidazole, which comprises adding ammonia to maintain the temperature within the range of 4 to 4 after reaching the range of 4.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29610587A JPH01139569A (en) | 1987-11-26 | 1987-11-26 | Production of 4-methylimidazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29610587A JPH01139569A (en) | 1987-11-26 | 1987-11-26 | Production of 4-methylimidazole |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01139569A true JPH01139569A (en) | 1989-06-01 |
Family
ID=17829199
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP29610587A Pending JPH01139569A (en) | 1987-11-26 | 1987-11-26 | Production of 4-methylimidazole |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01139569A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6177575B1 (en) * | 1998-06-12 | 2001-01-23 | E. I. Du Pont De Nemours And Company | Process for manufacture of imidazoles |
-
1987
- 1987-11-26 JP JP29610587A patent/JPH01139569A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6177575B1 (en) * | 1998-06-12 | 2001-01-23 | E. I. Du Pont De Nemours And Company | Process for manufacture of imidazoles |
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