JPH06256313A - Production of 5-formylimidazoles - Google Patents
Production of 5-formylimidazolesInfo
- Publication number
- JPH06256313A JPH06256313A JP5051516A JP5151693A JPH06256313A JP H06256313 A JPH06256313 A JP H06256313A JP 5051516 A JP5051516 A JP 5051516A JP 5151693 A JP5151693 A JP 5151693A JP H06256313 A JPH06256313 A JP H06256313A
- Authority
- JP
- Japan
- Prior art keywords
- catalyst
- hydroxymethylimidazole
- reaction
- formylimidazole
- yield
- 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
- ZQEXIXXJFSQPNA-UHFFFAOYSA-N 1h-imidazole-5-carbaldehyde Chemical class O=CC1=CNC=N1 ZQEXIXXJFSQPNA-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 26
- QDYTUZCWBJRHKK-UHFFFAOYSA-N imidazole-4-methanol Chemical compound OCC1=CNC=N1 QDYTUZCWBJRHKK-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910000510 noble metal Inorganic materials 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 239000003513 alkali Substances 0.000 abstract description 3
- 239000007864 aqueous solution Substances 0.000 abstract 1
- 238000000034 method Methods 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 13
- 238000007254 oxidation reaction Methods 0.000 description 12
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 12
- 230000003197 catalytic effect Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 238000012937 correction Methods 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 5
- 229910052697 platinum Inorganic materials 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 229910052797 bismuth Inorganic materials 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 229940030600 antihypertensive agent Drugs 0.000 description 3
- 239000002220 antihypertensive agent Substances 0.000 description 3
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 3
- 239000002934 diuretic Substances 0.000 description 3
- 229940030606 diuretics Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229910001385 heavy metal Inorganic materials 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- UZKBZGAMRJRWLR-UHFFFAOYSA-N (2-butyl-1H-imidazol-4-yl)methanol Chemical compound CCCCC1=NC=C(CO)N1 UZKBZGAMRJRWLR-UHFFFAOYSA-N 0.000 description 2
- DXSZKDOOHOBZMT-UHFFFAOYSA-N (2-butyl-4-chloro-1h-imidazol-5-yl)methanol Chemical compound CCCCC1=NC(Cl)=C(CO)N1 DXSZKDOOHOBZMT-UHFFFAOYSA-N 0.000 description 2
- MQRMTENGXFRETM-UHFFFAOYSA-N (2-methyl-1h-imidazol-5-yl)methanol Chemical compound CC1=NC=C(CO)N1 MQRMTENGXFRETM-UHFFFAOYSA-N 0.000 description 2
- ZOMATQMEHRJKLO-UHFFFAOYSA-N 1h-imidazol-2-ylmethanol Chemical compound OCC1=NC=CN1 ZOMATQMEHRJKLO-UHFFFAOYSA-N 0.000 description 2
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- TUCQOIQFSKJKPH-UHFFFAOYSA-N (2-propyl-1h-imidazol-5-yl)methanol Chemical compound CCCC1=NC(CO)=CN1 TUCQOIQFSKJKPH-UHFFFAOYSA-N 0.000 description 1
- AXJZCJSXNZZMDU-UHFFFAOYSA-N (5-methyl-1h-imidazol-4-yl)methanol Chemical compound CC=1N=CNC=1CO AXJZCJSXNZZMDU-UHFFFAOYSA-N 0.000 description 1
- PTHGVOCFAZSNNA-UHFFFAOYSA-N 2-butyl-1h-imidazole-5-carbaldehyde Chemical compound CCCCC1=NC=C(C=O)N1 PTHGVOCFAZSNNA-UHFFFAOYSA-N 0.000 description 1
- KMWCSNCNHSEXIF-UHFFFAOYSA-N 5-methyl-1h-imidazole-4-carbaldehyde Chemical compound CC=1N=CNC=1C=O KMWCSNCNHSEXIF-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- ZOKDWBDDYVCACM-UHFFFAOYSA-N bismuth platinum Chemical compound [Pt].[Bi] ZOKDWBDDYVCACM-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical compound [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
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
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、利尿剤、降圧剤等医薬
品の原料として有用な２−アルキル−５−ホルミルイミ
ダゾール等の５−ホルミルイミダゾール類の製造法に関
する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a process for producing 5-formylimidazoles such as 2-alkyl-5-formylimidazole, which are useful as raw materials for pharmaceuticals such as diuretics and antihypertensive agents.
【０００２】[0002]
【従来の技術】アルキルホルミルイミダゾールは上記の
如く有用な用途を有し、近年注目されている化学品であ
るがその製造法に関する公知文献はあまりなく例えば、
出発原料として２−アルキル−５−ヒドロキシメチルイ
ミダゾールを用い、重金属類による試薬酸化法、硝酸に
よる酸化法が研究されている。2. Description of the Related Art Alkylformyl imidazole has useful applications as described above and is a chemical product which has been attracting attention in recent years, but there are not many known documents regarding its production method.
Using 2-alkyl-5-hydroxymethylimidazole as a starting material, a reagent oxidation method using heavy metals and an oxidation method using nitric acid have been studied.
【０００３】[0003]
【本発明が解決しようとする課題】しかしながらかかる
技術では、前者の場合は重金属類の取り扱いや廃触媒の
処理に多大の労力を必要とすること、後者の場合は目的
物の収率面や窒素酸化物の発生の点等において、工業的
規模での実施に非常に不利となり満足し得る方法とは言
い難い。故に、かかる問題点を避け工業的に安全な方法
でかつ高収率で目的物が製造できる、２−アルキル−５
−ホルミルイミダゾールの新たな製造方法の開発が当業
者間で強く望まれており、本出願人はかかる目的を達成
すべく鋭意研究を重ねた結果、先に２−アルキル−５−
ヒドロキシメチルイミダゾールを貴金属触媒の存在下
で、接触酸化させる場合に、その目的が達成出来ること
を出し、特許出願を行ったが、更なる収率の向上を目的
として研究を続けた。However, in such a technique, in the former case, a great deal of labor is required for handling heavy metals and in treating the waste catalyst, and in the latter case, the yield of the target product and the nitrogen content. In terms of generation of oxides, etc., it is very disadvantageous for implementation on an industrial scale and cannot be said to be a satisfactory method. Therefore, 2-alkyl-5, which can avoid the above problems and can produce the target product in a high yield in an industrially safe method.
-Development of a new method for producing formylimidazole is strongly desired among those skilled in the art, and as a result of earnest studies by the present applicant to achieve such an object, 2-alkyl-5-
When the catalytic oxidation of hydroxymethylimidazole was carried out in the presence of a noble metal catalyst, the purpose was achieved, and a patent application was filed, but the research was continued for the purpose of further improving the yield.
【０００４】[0004]
【課題を解決するための手段】しかるに本発明者は、ア
ルカリ水溶媒中で、５−ヒドロキシメチルイミダゾール
類を貴金属触媒の存在下に接触酸化させる場合に、その
目的が達成出来ることを出し、本発明を完成するに至っ
た。本発明の反応は化１で示される。However, the present inventor has shown that the objective can be achieved when catalytically oxidizing 5-hydroxymethylimidazoles in the presence of a noble metal catalyst in an alkaline water solvent. The invention was completed. The reaction of the present invention is shown in Chemical formula 1.
【０００５】[0005]
【化１】 [Chemical 1]
【０００６】ここでＲは水素、炭素数１〜５のアルキル
基であり、好ましくはｎ−ブチル基が有用である。４位
の炭素に結合する水素はクロル、ブロム等のハロゲンあ
るいは炭素数１〜１２のアルキル基あるいは置換アルキ
ル基で置換されていても差し支えない。具体的に原料を
例示すれば、５−ヒドロキシメチルイミダゾール、４−
メチル−５−ヒドロキシメチルイミダゾール、２−メチ
ル−５−ヒドロキシメチルイミダゾール、２−プロピル
−５−ヒドロキシメチルイミダゾール、２−ブチル−５
−ヒドロキシメチルイミダゾール、２−ブチル−４−ク
ロル−５−ヒドロキシメチルイミダゾール等が挙げられ
る。Here, R is hydrogen or an alkyl group having 1 to 5 carbon atoms, and preferably an n-butyl group is useful. The hydrogen bonded to the 4-position carbon may be substituted with halogen such as chlorine and bromine, or an alkyl group having 1 to 12 carbon atoms or a substituted alkyl group. Specific examples of the raw materials include 5-hydroxymethylimidazole and 4-hydroxymethylimidazole.
Methyl-5-hydroxymethylimidazole, 2-methyl-5-hydroxymethylimidazole, 2-propyl-5-hydroxymethylimidazole, 2-butyl-5
-Hydroxymethylimidazole, 2-butyl-4-chloro-5-hydroxymethylimidazole and the like can be mentioned.
【０００７】本発明では接触酸化反応に当たって、アル
カリ水溶媒を使用することが必須条件であり、かかる溶
媒の使用により目的物の収率が向上する。アルカリ水に
おけるアルカリとしては水酸化ナトリウム、水酸化カリ
ウム、炭酸ナトリウム、炭酸カリウム、酢酸ナトリウム
等が挙げられる。アルカリの使用量は原料の５−ヒドロ
キシメチルイミダゾール１モルに対して０．９モル以
上、好ましくは１．０〜１．５モルが必要である。０．
９モル以下では生成する５−ホルミルイミダゾール類が
系に溶解しない。In the present invention, the use of an alkaline water solvent is an essential condition for the catalytic oxidation reaction, and the use of such a solvent improves the yield of the desired product. Examples of the alkali in the alkaline water include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium acetate and the like. The amount of alkali used is 0.9 mol or more, preferably 1.0 to 1.5 mol, per 1 mol of 5-hydroxymethylimidazole as a raw material. 0.
When the amount is less than 9 mol, the 5-formylimidazoles formed are not dissolved in the system.
【０００８】本発明で使用する貴金属触媒は白金、パラ
ジウム、金等であり、白金及びパラジウムが実用的であ
る。又かかる貴金属触媒には第二成分としてビスマス、
セリウム、鉛、インジウム等を添加することも可能であ
る。かかる触媒は金属状態ばかりでなく塩、酸化物等の
状態であっても良い。本発明で用いる貴金属触媒はその
まま、あるいは必要に応じて活性炭、シリカ、アルミナ
等の担体に担持されて用いられる。接触酸化反応を実施
するに当たっては、反応器に反応溶媒を仕込み、これに
上記の触媒、原料の５−ヒドロキシメチルイミダゾール
類を供給する。The noble metal catalyst used in the present invention is platinum, palladium, gold or the like, and platinum and palladium are practical. Also, for such a precious metal catalyst, bismuth as the second component,
It is also possible to add cerium, lead, indium and the like. Such a catalyst may be not only in a metallic state but also in a state of salt, oxide or the like. The noble metal catalyst used in the present invention is used as it is, or if necessary, supported on a carrier such as activated carbon, silica or alumina. In carrying out the catalytic oxidation reaction, a reaction solvent is charged in the reactor, and the above catalyst and 5-hydroxymethylimidazole as a raw material are supplied thereto.
【０００９】本発明で使用されるすべての薬剤の仕込み
手段は任意であり、一括仕込み、分割仕込み、連続仕込
み、滴下仕込み等いずれも実施可能であるが、特に一括
仕込みが有利である。本発明の趣旨を逸脱しない範囲で
あれば、各種の有機溶媒を併用することもできる。触媒
の使用量は原料の５−ヒドロキシメチルイミダゾール類
１モルに対して０．０１〜５０モル％、好ましくは０．
１〜２０モル％が適当である。溶媒は原料の３〜５０重
量倍で使用する。反応温度は０℃〜還流温度のいずれで
も良いが、通常は室温以上、好ましくは２０〜８０℃が
適当であり、又反応時間は１〜２４時間、好ましくは２
〜１５時間が有利である。The means for charging all the chemicals used in the present invention is arbitrary, and batch charging, divided charging, continuous charging, dropping charging and the like can all be carried out, but batch charging is particularly advantageous. Various organic solvents may be used in combination without departing from the spirit of the present invention. The amount of the catalyst used is 0.01 to 50 mol%, preferably 0.1% to 1 mol of the starting 5-hydroxymethylimidazoles.
1 to 20 mol% is suitable. The solvent is used in an amount of 3 to 50 times the weight of the raw material. The reaction temperature may be any of 0 ° C to reflux temperature, but it is usually room temperature or higher, preferably 20 to 80 ° C, and the reaction time is 1 to 24 hours, preferably 2
~ 15 hours is advantageous.
【００１０】接触酸化に際しては、上記の系内に酸素あ
るいは空気を導入する。系は常圧でも加圧でもよく、酸
素あるいは空気の導入速度は反応溶液１リットルに対し
て０．１〜１０リットル／分程度である。反応は懸濁系
で進行し酸素の吸収が停止した時点で反応を終了させ、
反応終了液から触媒を濾別する。濾液には５−ホルミル
イミダゾール類が塩の形で溶解しているので、硫酸、塩
酸等の鉱酸で中和して目的物である５−ホルミルイミダ
ゾール類の結晶を得る。必要であれば更に精製が行われ
る。目的物の収率は、原料５−ヒドロキシメチルイミダ
ゾール類に対して９０％以上である。At the time of catalytic oxidation, oxygen or air is introduced into the above system. The system may be atmospheric pressure or pressurized, and the introduction rate of oxygen or air is about 0.1 to 10 liters / minute per 1 liter of the reaction solution. When the reaction proceeds in a suspension system and the absorption of oxygen is stopped, the reaction is terminated,
The catalyst is filtered off from the reaction completed liquid. Since 5-formylimidazoles are dissolved in the filtrate in the form of a salt, they are neutralized with a mineral acid such as sulfuric acid and hydrochloric acid to obtain the desired crystals of 5-formylimidazoles. Further purification is performed if necessary. The yield of the desired product is 90% or more based on the starting 5-hydroxymethylimidazoles.
【００１１】[0011]
【作 用】本発明は利尿剤や降圧剤等医薬品の原料と
して有用な２−アルキル−５−ホルミルイミダゾール等
の５−ホルミルイミダゾール類の製造法として、特定の
溶媒を使用しかつ工業的に取り扱い容易な触媒を用いる
ことによって、高収率で目的物が得られるので経済面、
製造面において非常に有利である。[Working] The present invention is a method for producing 5-formylimidazoles such as 2-alkyl-5-formylimidazole, which is useful as a raw material for drugs such as diuretics and antihypertensive agents, and uses a specific solvent and is industrially handled. By using an easy catalyst, the target product can be obtained in high yield, which is economical.
It is very advantageous in terms of manufacturing.
【００１２】[0012]
【実施例】以下、本発明において実例を挙げて詳述す
る。 実施例１ ２−ｎ−ブチル−４−クロロ−５−ヒドロキシメチルイ
ミダゾール２０ｇ（１０５ミリモル）を、水酸化ナトリ
ウム５．１ｇ（１２８ミリモル）を溶解させたアルカリ
水２００ｍｌに懸濁させ、更に、白金−ビスマス系触媒
（活性炭に白金５％及びビスマス２％を担持、含水率５
０％）５．４ｇを加えた後、室温（２１〜２６℃）で撹
拌下に酸素を８０ｍｌ／分の割合で２．５時間吹き込
み、接触酸化反応を行った。反応終了後、反応液から触
媒を濾別し濾液を２０％硫酸水で中和して収率９５％で
淡黄色結晶を得た。赤外線分析、ＮＭＲ分析の結果、２
−ｎ−ブチル−４−クロロ−５−ホルミルイミダゾール
と確認できた。The present invention will be described in detail below with reference to actual examples. Example 1 20 g (105 mmol) of 2-n-butyl-4-chloro-5-hydroxymethylimidazole was suspended in 200 ml of alkaline water in which 5.1 g (128 mmol) of sodium hydroxide was dissolved, and platinum was further added. -Bismuth-based catalyst (activated carbon supporting 5% platinum and 2% bismuth, water content 5
After the addition of 5.4 g of 0%), oxygen was blown thereinto at a rate of 80 ml / min for 2.5 hours with stirring at room temperature (21 to 26 ° C.) to carry out a catalytic oxidation reaction. After completion of the reaction, the catalyst was filtered off from the reaction solution and the filtrate was neutralized with 20% sulfuric acid water to obtain pale yellow crystals with a yield of 95%. Results of infrared analysis and NMR analysis, 2
It could be confirmed to be -n-butyl-4-chloro-5-formylimidazole.
【００１３】実施例２ 実施例１に水酸化ナトリウムを水酸化カリウムに変更し
た以外は同例に従って実験をした。収率９４％で２−ｎ
−ブチル−４−クロロ−５−ホルミルイミダゾールを得
た。 実施例３ 実施例１において水酸化ナトリウムを炭酸カリウムに変
更した以外は同例に従って実験をした。収率８３％で２
−ｎ−ブチル−４−クロロ−５−ホルミルイミダゾール
を得た。Example 2 An experiment was carried out in the same manner as in Example 1 except that sodium hydroxide was changed to potassium hydroxide. 2-n with 94% yield
-Butyl-4-chloro-5-formylimidazole was obtained. Example 3 An experiment was conducted according to the same example as in Example 1 except that sodium hydroxide was changed to potassium carbonate. 2 with 83% yield
-N-Butyl-4-chloro-5-formylimidazole was obtained.
【００１４】実施例４ ２−ｎ−ブチル−５−ヒドロキシメチルイミダゾール
７．５ｇ（４８ミリモル）を、水酸化ナトリウム２．０
ｇを溶解させたアルカリ水２００ｍｌに懸濁させた。更
に、白金−ビスマス系触媒（活性炭に白金５％及びビス
マス２％を担持、含水率５０％）２．０ｇを加えた後、
室温で６時間、６５℃で２時間撹拌下に酸素を８０ｍｌ
／分の割合で吹き込み、接触酸化反応を行った。反応終
了後、反応液から触媒を濾別し濾液を２０％硫酸水で中
和して収率９１％で淡黄色結晶を得た。赤外線分析、Ｎ
ＭＲ分析の結果、２−ｎ−ブチル−５−ホルミルイミダ
ゾールと確認できた。Example 4 7.5 g (48 mmol) of 2-n-butyl-5-hydroxymethylimidazole was added to 2.0 g of sodium hydroxide.
It was suspended in 200 ml of alkaline water in which g was dissolved. Furthermore, after adding 2.0 g of a platinum-bismuth-based catalyst (activated carbon carrying 5% platinum and 2% bismuth, water content 50%),
80 ml of oxygen with stirring at room temperature for 6 hours and at 65 ° C for 2 hours
The mixture was blown at a rate of / min to carry out a catalytic oxidation reaction. After completion of the reaction, the catalyst was filtered off from the reaction solution and the filtrate was neutralized with 20% sulfuric acid water to obtain pale yellow crystals with a yield of 91%. Infrared analysis, N
As a result of MR analysis, it was confirmed to be 2-n-butyl-5-formylimidazole.
【００１５】実施例５ 実施例６において触媒を白金黒１．０ｇに変えて、接触
酸化反応を行った。赤外線分析、ＮＭＲ分析の結果、２
−ｎ−ブチル−５−ホルミルイミダゾールと確認でき
た。収率は９２％であった。Example 5 In Example 6, the catalyst was changed to 1.0 g of platinum black to carry out the catalytic oxidation reaction. Results of infrared analysis and NMR analysis, 2
It was confirmed to be -n-butyl-5-formylimidazole. The yield was 92%.
【００１６】実施例６ 実施例１において、４−メチル−５−ヒドロキシメチル
イミダゾールの接触酸化反応を行った。赤外線分析、Ｎ
ＭＲ分析の結果、４−メチル−５−ホルミルイミダゾー
ルと確認できた。収率は８３％であった。Example 6 In Example 1, a catalytic oxidation reaction of 4-methyl-5-hydroxymethylimidazole was carried out. Infrared analysis, N
As a result of MR analysis, it was confirmed to be 4-methyl-5-formylimidazole. The yield was 83%.
【００１７】[0017]
【発明の効果】本発明は、利尿剤や降圧剤等医薬品の原
料として有用な２−アルキル−５−ホルミルイミダゾー
ルを初めとする５−ホルミルイミダゾール類を、特定の
溶媒を使用しかつ工業的に取り扱い容易な貴金属触媒を
用いることによって、高収率で得られるので経済面、製
造面において非常に有利に製造できる。INDUSTRIAL APPLICABILITY The present invention uses 5-formylimidazoles such as 2-alkyl-5-formylimidazole, which are useful as raw materials for drugs such as diuretics and antihypertensive agents, in a specific solvent and industrially. By using a noble metal catalyst which is easy to handle, it can be obtained in a high yield, so that it can be produced very advantageously in terms of economy and production.
─────────────────────────────────────────────────────
─────────────────────────────────────────────────── ───
【手続補正書】[Procedure amendment]
【提出日】平成６年２月１８日[Submission date] February 18, 1994
【手続補正１】[Procedure Amendment 1]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】０００３[Name of item to be corrected] 0003
【補正方法】変更[Correction method] Change
【補正内容】[Correction content]
【０００３】[0003]
【本発明が解決しようとする課題】しかしながらかかる
技術では、前者の場合は重金属類の取り扱いや廃触媒の
処理に多大の労力を必要とすること、後者の場合は目的
物の収率面や窒素酸化物の発生の点等において、工業的
規模での実施に非常に不利となり満足し得る方法とは言
い難い。故に、かかる問題点を避け工業的に安全な方法
でかつ高収率で目的物が製造できる、２−アルキル−５
−ホルミルイミダゾールの新たな製造方法の開発が当業
者間で強く望まれており、本出願人はかかる目的を達成
すべく鋭意研究を重ねた結果、先に２−アルキル−５−
ヒドロキシメチルイミダゾールを貴金属触媒の存在下
で、接触酸化させる場合に、その目的が達成出来ること
を見出し、特許出願を行ったが、更なる収率の向上を目
的として研究を続けた。However, in such a technique, in the former case, a great deal of labor is required for handling heavy metals and in treating the waste catalyst, and in the latter case, the yield of the target product and the nitrogen content. In terms of generation of oxides, etc., it is very disadvantageous for implementation on an industrial scale and cannot be said to be a satisfactory method. Therefore, 2-alkyl-5, which can avoid the above problems and can produce the target product in a high yield in an industrially safe method.
-Development of a new method for producing formylimidazole is strongly desired among those skilled in the art, and as a result of earnest studies by the present applicant to achieve such an object, 2-alkyl-5-
The inventors have found that the object can be achieved when catalytically oxidizing hydroxymethylimidazole in the presence of a noble metal catalyst, and have filed a patent application, but continued the research for the purpose of further improving the yield.
【手続補正２】[Procedure Amendment 2]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】００１０[Correction target item name] 0010
【補正方法】変更[Correction method] Change
【補正内容】[Correction content]
【００１０】接触酸化に際しては、上記の系内に酸素あ
るいは空気を導入する。系は常圧でも加圧でもよく、酸
素あるいは空気の導入速度は反応溶液１リットルに対し
て０．００１〜１．０リットル／分程度である。反応は
懸濁系で進行し酸素の吸収が停止した時点で反応を終了
させ、反応終了液から触媒を濾別する。濾液には５−ホ
ルミルイミダゾール類が塩の形で溶解しているので、硫
酸、塩酸等の鉱酸で中和して目的物である５−ホルミル
イミダゾール類の結晶を得る。必要であれば更に精製が
行われる。目的物の収率は、原料５−ヒドロキシメチル
イミダゾール類に対して９０％以上である。At the time of catalytic oxidation, oxygen or air is introduced into the above system. The system may be atmospheric pressure or pressurized, and the introduction rate of oxygen or air is about 0.001 to 1.0 liter / minute per 1 liter of the reaction solution. The reaction proceeds in a suspension system, the reaction is terminated when the absorption of oxygen is stopped, and the catalyst is filtered off from the reaction-terminated liquid. Since 5-formylimidazoles are dissolved in the filtrate in the form of a salt, they are neutralized with a mineral acid such as sulfuric acid and hydrochloric acid to obtain the desired crystals of 5-formylimidazoles. Further purification is performed if necessary. The yield of the desired product is 90% or more based on the starting 5-hydroxymethylimidazoles.
【手続補正３】[Procedure 3]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】００１５[Name of item to be corrected] 0015
【補正方法】変更[Correction method] Change
【補正内容】[Correction content]
【００１５】実施例５実施例４ において触媒を白金黒１．０ｇに変えて、接触
酸化反応を行った。赤外線分析、ＮＭＲ分析の結果、２
−ｎ−ブチル−５−ホルミルイミダゾールと確認でき
た。収率は９２％であった。Example 5 In Example 4 , the catalyst was changed to 1.0 g of platinum black to carry out the catalytic oxidation reaction. Results of infrared analysis and NMR analysis, 2
It was confirmed to be -n-butyl-5-formylimidazole. The yield was 92%.
Claims (2)
チルイミダゾール類を貴金属触媒の存在下に、接触酸化
させることを特徴とする５−ホルミルイミダゾール類の
製造方法1. A method for producing 5-formylimidazole, which comprises catalytically oxidizing 5-hydroxymethylimidazole in an alkaline water solvent in the presence of a noble metal catalyst.
系触媒を使用することを特徴とする請求項１記載の製造
方法2. The production method according to claim 1, wherein a platinum- or palladium-based catalyst is used as the noble metal catalyst.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP05151693A JP3391837B2 (en) | 1993-02-16 | 1993-02-16 | Method for producing 5-formylimidazoles |
| US08/125,220 US5336779A (en) | 1992-10-08 | 1993-09-23 | Method of producing formylimidazoles |
| GB9319890A GB2271353B (en) | 1992-10-08 | 1993-09-27 | Method of producing formylimidazoles |
| CH2916/93A CH685496A5 (en) | 1992-10-08 | 1993-09-28 | A process for the preparation of formylimidazoles. |
| FR9311742A FR2696742B1 (en) | 1992-10-08 | 1993-10-01 | PROCESS FOR THE MANUFACTURE OF FORMYLIMIDAZOLES FROM 4- OR 5-HYDROXYMETHYLIMIDAZOLES. |
| ITMI932097A IT1270841B (en) | 1992-10-08 | 1993-10-01 | METHOD FOR PRODUCING FORMILIMIDAZOLI |
| DE4333642A DE4333642C2 (en) | 1992-10-08 | 1993-10-02 | Process for the preparation of 2-alkyl-5-formylimidazoles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP05151693A JP3391837B2 (en) | 1993-02-16 | 1993-02-16 | Method for producing 5-formylimidazoles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH06256313A true JPH06256313A (en) | 1994-09-13 |
| JP3391837B2 JP3391837B2 (en) | 2003-03-31 |
Family
ID=12889179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP05151693A Expired - Fee Related JP3391837B2 (en) | 1992-10-08 | 1993-02-16 | Method for producing 5-formylimidazoles |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3391837B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6040457A (en) * | 1997-11-14 | 2000-03-21 | Lonza Ag | Process for the preparation of formylimidazoles |
| JP2002518376A (en) * | 1998-06-15 | 2002-06-25 | ロンツァ・アクチェンゲゼルシャフト | Method for producing formyl imidazole |
-
1993
- 1993-02-16 JP JP05151693A patent/JP3391837B2/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6040457A (en) * | 1997-11-14 | 2000-03-21 | Lonza Ag | Process for the preparation of formylimidazoles |
| JP2002518376A (en) * | 1998-06-15 | 2002-06-25 | ロンツァ・アクチェンゲゼルシャフト | Method for producing formyl imidazole |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3391837B2 (en) | 2003-03-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5073133B2 (en) | Catalyst and method for direct synthesis of hydrogen peroxide | |
| CA2407605A1 (en) | Precious metal recovery from organics-precious metal compositions with supercritical water reactant | |
| US5336779A (en) | Method of producing formylimidazoles | |
| JP3391837B2 (en) | Method for producing 5-formylimidazoles | |
| JP3391836B2 (en) | Method for producing 5-formylimidazoles | |
| WO2009149590A1 (en) | Atmospherically catalyzing and oxidizing method of refractory gold concentrate with high arsenic and high sulfur | |
| EP0747359B1 (en) | Method of obtaining nicotinic acid | |
| JPS62198641A (en) | Production of carboxylic acid salt | |
| JP3168079B2 (en) | Method for producing 2-alkylformylimidazole | |
| JP4442952B2 (en) | Process for producing 5-formylimidazoles | |
| JP4442951B2 (en) | Process for producing 5-formylimidazoles | |
| JP4796776B2 (en) | Method for producing 4,4'-dicarboxy-2,2'-bipyridine | |
| US3799961A (en) | Process for producing palladium(o)and platinum(o)complex compounds with triphenylphosphine | |
| US4659683A (en) | Regeneration of inactive and poisoned platinum catalysts | |
| CN108440451B (en) | Preparation method of 4- (1-tert-butyloxycarbonylpiperazin-4-yl) aniline | |
| JPH07116097B2 (en) | Method for producing pyromellitic acid | |
| JPS5945666B2 (en) | Method for producing aminocarboxylic acids | |
| JP2001002651A (en) | Production of 5-formylimidazoles | |
| JPS60193939A (en) | Production of 2-chloro-4-fluorophenol | |
| JPS6078948A (en) | Production of iminodiacetate | |
| JP2001002652A (en) | Production of 5-formylimidazoles | |
| JPH03271275A (en) | Production of quinolinic acid | |
| JP3282357B2 (en) | Piperonal manufacturing method | |
| JPH03157371A (en) | Production of quinolinic acid | |
| JPH10158227A (en) | Production of n,n-dimethylformamide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20080124 Year of fee payment: 5 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090124 Year of fee payment: 6 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090124 Year of fee payment: 6 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090124 Year of fee payment: 6 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100124 Year of fee payment: 7 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100124 Year of fee payment: 7 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100124 Year of fee payment: 7 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110124 Year of fee payment: 8 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110124 Year of fee payment: 8 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120124 Year of fee payment: 9 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120124 Year of fee payment: 9 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120124 Year of fee payment: 9 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130124 Year of fee payment: 10 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130124 Year of fee payment: 10 |
|
| LAPS | Cancellation because of no payment of annual fees |