JP2843499B2 - Method for producing imidazole compound - Google Patents
Method for producing imidazole compoundInfo
- Publication number
- JP2843499B2 JP2843499B2 JP6083892A JP8389294A JP2843499B2 JP 2843499 B2 JP2843499 B2 JP 2843499B2 JP 6083892 A JP6083892 A JP 6083892A JP 8389294 A JP8389294 A JP 8389294A JP 2843499 B2 JP2843499 B2 JP 2843499B2
- Authority
- JP
- Japan
- Prior art keywords
- glyoxal
- compound
- ammonia
- monoacetal
- compound represented
- 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.)
- Expired - Lifetime
Links
- -1 imidazole compound Chemical class 0.000 title claims description 26
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title claims description 15
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 claims description 64
- 229940015043 glyoxal Drugs 0.000 claims description 39
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 35
- 150000001875 compounds Chemical class 0.000 claims description 28
- 229910021529 ammonia Inorganic materials 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 6
- 239000011707 mineral Substances 0.000 claims description 6
- BGAXCPSNMHVHJC-UHFFFAOYSA-N phenacyl acetate Chemical compound CC(=O)OCC(=O)C1=CC=CC=C1 BGAXCPSNMHVHJC-UHFFFAOYSA-N 0.000 claims description 6
- 239000007795 chemical reaction product Substances 0.000 claims description 4
- 150000004699 copper complex Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000000243 solution Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 235000010755 mineral Nutrition 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical class O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 2
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 229910052979 sodium sulfide Inorganic materials 0.000 description 2
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KKKDZZRICRFGSD-UHFFFAOYSA-N 1-benzylimidazole Chemical compound C1=CN=CN1CC1=CC=CC=C1 KKKDZZRICRFGSD-UHFFFAOYSA-N 0.000 description 1
- IFYTUUDFOJDWBQ-UHFFFAOYSA-N 2,2-diethoxyacetaldehyde Chemical compound CCOC(C=O)OCC IFYTUUDFOJDWBQ-UHFFFAOYSA-N 0.000 description 1
- DSSLAGQNEMWAEH-UHFFFAOYSA-N 2-(dimethoxymethyl)-1h-imidazole Chemical compound COC(OC)C1=NC=CN1 DSSLAGQNEMWAEH-UHFFFAOYSA-N 0.000 description 1
- CWYBYUXFTJTOJW-UHFFFAOYSA-N 2-(dimethoxymethyl)-4,5-dimethyl-1H-imidazole Chemical compound COC(OC)c1nc(C)c(C)[nH]1 CWYBYUXFTJTOJW-UHFFFAOYSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- QOBANTAIDKARPU-UHFFFAOYSA-N N1C(C(OC)OC)=NC=C1C1=CC=CC=C1 Chemical compound N1C(C(OC)OC)=NC=C1C1=CC=CC=C1 QOBANTAIDKARPU-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- OMZSGWSJDCOLKM-UHFFFAOYSA-N copper(II) sulfide Chemical compound [S-2].[Cu+2] OMZSGWSJDCOLKM-UHFFFAOYSA-N 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、医農薬中間体として有
用な２位にジアルコキシメチル基あるいはホルミル基を
有するイミダゾール系化合物の製造方法に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a process for producing an imidazole compound having a dialkoxymethyl group or a formyl group at the 2-position, which is useful as an intermediate for medical and agricultural chemicals.
【０００２】[0002]
【従来の技術】２−ホルミルイミダゾール系化合物の製
法として、１−ベンジルイミダゾール化合物とブチルリ
チウムを反応させ、さらにジメチルホルムアミドを反応
させたのち、酸触媒の存在下でエタノールと反応させて
１−ベンジル−２−ジエトキシメチルイミダゾール化合
物とし、前記反応生成物に液体アンモニア及び金属ナト
リウムを反応させて、２−ジエトキシメチルイミダゾー
ル化合物を合成し、これに希塩酸を反応させて目的物を
製造する方法が知られている。（例えば、アクタ・ケミ
カ・スカンジナビカ、1966年、20巻、2649〜2657頁）2. Description of the Related Art As a method for producing a 2-formylimidazole compound, a 1-benzylimidazole compound is reacted with butyllithium, further reacted with dimethylformamide, and then reacted with ethanol in the presence of an acid catalyst to form 1-benzylimidazole. A method for producing a 2-diethoxymethylimidazole compound, reacting the reaction product with liquid ammonia and metallic sodium to synthesize a 2-diethoxymethylimidazole compound, and reacting the compound with dilute hydrochloric acid to produce a target product. Are known. (For example, Acta Chemika Scandinabinica, 1966, Volume 20, 2649-2657)
【０００３】しかしながら、この方法は２−ジアルコキ
シメチルイミダゾール化合物を合成する過程において、
高価な原料を使用しなければならず、反応工程が多くし
かも極低温の処理を伴うので、工業的な製法として実用
に供し難いものであった。[0003] However, this method involves a process of synthesizing a 2-dialkoxymethylimidazole compound.
Since expensive raw materials must be used, the number of reaction steps is large, and the process involves cryogenic treatment, it has been difficult to use the method as an industrial production method.
【０００４】また、２−ホルミルイミダゾール化合物を
製造する方法としては、例えば前記のアクタ・ケミカ・
スカンジナビカ、1966年、20巻、2649〜2657頁、特開平
1-131163号公報などに記載されているように、ブチルリ
チウムとイミダゾール化合物を反応させ、これにジメチ
ルホルムアルデヒドを反応させる方法、２−メチルイミ
ダゾール化合物をセレン酸化物を用いて酸化させる方
法、あるいは１−ベンジルイミダゾール化合物をホルマ
リンと反応させたのち、ベンジル基の脱保護によって得
られる２−ヒドロキシメチルイミダゾール化合物を、二
酸化マンガンを用いて酸化する方法などが知られてい
る。As a method for producing a 2-formylimidazole compound, for example, the above-mentioned acta-chemica-
Scandinavian, 1966, Volume 20, 2649-2657, JP
As described in JP-A-1-131163, a method of reacting butyllithium with an imidazole compound and reacting it with dimethylformaldehyde, a method of oxidizing a 2-methylimidazole compound using selenium oxide, or A method is known in which, after a benzylimidazole compound is reacted with formalin, a 2-hydroxymethylimidazole compound obtained by deprotection of a benzyl group is oxidized using manganese dioxide.
【０００５】しかしながら、これらはいずれも高価な反
応試薬を用いかつ反応工程が多く、極低温の処理を伴う
ため、工業的に実施しうる製法が希求されていた。[0005] However, all of these methods use expensive reaction reagents, have many reaction steps, and require cryogenic treatment. Therefore, there has been a demand for a production method which can be carried out industrially.
【０００６】[0006]
【発明が解決しようとする課題】この発明の目的は、前
述の２−ジアルコキシメチルイミダゾール化合物を経由
して２−ホルミルイミダゾール化合物を製造するに当
り、２−ジアルコキシメチルイミダゾール化合物の製造
工程を簡素化し、工業的に２−ホルミルイミダゾール化
合物を合成する方法を提供することにある。An object of the present invention is to provide a method for producing a 2-formylimidazole compound via the aforementioned 2-dialkoxymethylimidazole compound. An object of the present invention is to provide a method for simplifying and industrially synthesizing a 2-formylimidazole compound.
【０００７】[0007]
【課題を解決するための手段】本発明者等は、このよう
な問題を解決するため数多くの試験を繰り返した結果、
グリオキザールモノアセタール化合物とアンモニア及び
グリオキザール化合物を反応させるか、あるいはグリオ
キザールモノアセタール化合物、アンモニア、酢酸銅及
びベンゾイルカルビノールアセテートを反応させること
によって、反応工程を簡素化し安価に２−ジアルコキシ
メチルイミダゾール化合物を製造する方法を見い出し、
さらにはグリオキザールモノアセタール化合物、アンモ
ニア及びグリオキザール化合物を反応させ、その反応生
成物を単離精製することなく鉱酸と反応させれば、容易
に２−ホルミルイミダゾール化合物が合成できることを
知見して、これらの量産に適する製法を確立するに至っ
た。The present inventors have repeated a number of tests to solve such a problem.
By reacting a glyoxal monoacetal compound with ammonia and a glyoxal compound, or by reacting a glyoxal monoacetal compound, ammonia, copper acetate and benzoylcarbinol acetate, the reaction process is simplified and the 2-dialkoxymethylimidazole compound is inexpensively prepared. Find a way to make it,
Furthermore, it was found that if a glyoxal monoacetal compound, ammonia and a glyoxal compound were reacted and reacted with a mineral acid without isolating and purifying the reaction product, a 2-formylimidazole compound could be easily synthesized. Has established a manufacturing method suitable for mass production.
【０００８】本発明の２−ジアルコキシメチルイミダゾ
ール化合物を製造する一つの方法は、 一般式 ＨＣＯ
ＣＨ（ＯＲ）2 （式中、Ｒはアルキル基を表す）で
示されるグリオキザールモノアセタール化合物とアンモ
ニア及び 一般式 Ｒ4 ＣＯＣＲ5 Ｏ （式中、Ｒ4 とＲ5 は水素原子またはアルキル基を表
す）で示されるグリオキザール化合物を反応させること
により、化４で示されるイミダゾール系化合物を製造す
る方法である。One method for preparing the 2-dialkoxymethylimidazole compounds of the present invention is represented by the general formula HCO
A glyoxal monoacetal compound represented by CH (OR) 2 (wherein R represents an alkyl group), ammonia and a general formula R 4 COCR 5 O (where R 4 and R 5 represent a hydrogen atom or an alkyl group) This is a method for producing an imidazole compound represented by Chemical Formula 4 by reacting a glyoxal compound represented by the formula (1).
【０００９】[0009]
【化４】 Embedded image
【００１０】本発明のグリオキザールモノアセタール化
合物とアンモニア及びグリオキザール化合物を反応させ
る方法は、グリオキザールモノアセタール化合物１モル
に対してグリオキザール化合物を０．８〜１．５モル、
好ましくは１．０〜１．２モル、またアンモニアを１．
５〜３．５モル、好ましくは２．０〜２．５モルになる
ように混合し、４０〜９０℃の温度で１〜１０時間、好
ましくは５０〜７５℃の温度範囲で２〜５時間加熱して
反応させる。これを反応式で示すと化５のとおりであ
る。The method of reacting a glyoxal monoacetal compound with ammonia and a glyoxal compound according to the present invention comprises the step of reacting the glyoxal compound with 0.8 to 1.5 mol of the glyoxal monoacetal compound per mol of the glyoxal monoacetal compound.
Preferably 1.0 to 1.2 moles, and ammonia in 1.
5 to 3.5 moles, preferably 2.0 to 2.5 moles, mixed at a temperature of 40 to 90 ° C. for 1 to 10 hours, preferably 50 to 75 ° C. for 2 to 5 hours. Heat to react. This is shown by the reaction formula in Chemical formula 5.
【００１１】[0011]
【化５】 Embedded image
【００１２】前記の方法において使用されるグリオキザ
ールモノアセタール化合物の代表的なものとしては、グ
リオキザールジメチルモノアセタール、グリオキザール
ジエチルモノアセタール、グリオキザールジプロピルモ
ノアセタール、グリオキザールジブチルモノアセター
ル、グリオキザールジペンチルモノアセタール及びグリ
オキザールジヘキシルモノアセタールなどであり、アン
モニアとしてはアンモニア水、酢酸アンモニウムあるい
は炭酸アンモニウムなどであり、またグリオキザール化
合物の代表的なものとしては、グリオキザール、メチル
グリオキザール及びジアセチルなどが挙げられる。Representative examples of the glyoxal monoacetal compound used in the above method include glyoxal dimethyl monoacetal, glyoxal diethyl monoacetal, glyoxal dipropyl monoacetal, glyoxal dibutyl monoacetal, glyoxal dipentyl monoacetal and glyoxal dihexyl. Monoacetal and the like, ammonia include ammonia water, ammonium acetate and ammonium carbonate, and typical examples of glyoxal compounds include glyoxal, methylglyoxal and diacetyl.
【００１３】また、本発明における２−ジアルコキシメ
チルイミダゾール化合物を製造する他の方法は、グリオ
キザールモノアセタール化合物、アンモニア、酢酸銅及
びベンゾイルカルビノールアセテートを反応させ、生成
する銅錯体に硫化水素を反応させることにより、化６で
示すイミダゾール系化合物を合成する。Another method for producing a 2-dialkoxymethylimidazole compound according to the present invention is to react a glyoxal monoacetal compound, ammonia, copper acetate and benzoylcarbinol acetate, and react hydrogen sulfide with a copper complex formed. By doing so, an imidazole-based compound represented by Chemical Formula 6 is synthesized.
【００１４】[0014]
【化６】 Embedded image
【００１５】グリオキザールモノアセタール化合物、ア
ンモニア、酢酸銅及びベンゾイルカルビノールアセテー
トを反応させる方法は、グリオキザールモノアセタール
化合物１モルに対してベンゾイルカルビノールアセテー
トを０．８〜１．５モル、好ましくは１．０〜１．３モ
ル、アンモニアを１．５〜５．０モル、好ましくは２．
０〜３．０モル、また酢酸銅を０．８〜２．０モル、好
ましくは１．０〜１．３モルになるように混合し、４０
〜９０℃の温度で１〜１０時間、好ましくは５０〜７５
℃の温度範囲で２〜５時間加熱して反応させたのち、得
られた銅錯体に硫化水素を反応させてこれを分解するこ
とにより、２−ジアルコキシメチルイミダゾール化合物
が得られる。これを反応式によって示すと化７に示すと
おりである。The method of reacting the glyoxal monoacetal compound, ammonia, copper acetate and benzoylcarbinol acetate is such that benzoylcarbinol acetate is used in an amount of 0.8 to 1.5 mol, preferably 1. mol, per mol of the glyoxal monoacetal compound. 0 to 1.3 mol, 1.5 to 5.0 mol of ammonia, preferably 2.
0 to 3.0 moles, and 0.8 to 2.0 moles of copper acetate, preferably 1.0 to 1.3 moles, and 40
1 to 10 hours at a temperature of ~ 90C, preferably 50-75
After heating and reacting in a temperature range of 2 ° C. for 2 to 5 hours, hydrogen sulfide is reacted with the obtained copper complex to decompose it, thereby obtaining a 2-dialkoxymethylimidazole compound. This is shown in Chemical formula 7 by a reaction formula.
【００１６】[0016]
【化７】 Embedded image
【００１７】この方法の実施において用いられるグリオ
キザールモノアセタール化合物及びアンモニアは、前記
の方法で用いられるものと同じであり、硫化水素として
は、硫化水素ガスのほか、水硫化ナトリウムあるいは硫
化ナトリウムなどの硫化水素発生試剤が挙げられる。The glyoxal monoacetal compound and ammonia used in the practice of this method are the same as those used in the above-mentioned method. Examples of the hydrogen sulfide include hydrogen sulfide gas and sodium sulfide such as sodium hydrosulfide or sodium sulfide. Hydrogen generating agents.
【００１８】本発明方法の実施に当たって、必要に応じ
て溶媒を併用することが可能であり、溶媒としてはメタ
ノール、エタノール、イソプロパノール等のアルコール
類、ジエチルケトン、モノグライム、ジグライム、テト
ラヒドロフラン、ジオキサン、ジエチレングリコール等
のエーテル類、ジメチルスルホキシドあるいは水などを
単独あるいは混合して使用することができる。In carrying out the method of the present invention, a solvent can be used in combination if necessary. Examples of the solvent include alcohols such as methanol, ethanol and isopropanol, diethyl ketone, monoglyme, diglyme, tetrahydrofuran, dioxane and diethylene glycol. Ethers, dimethyl sulfoxide, water, or the like can be used alone or as a mixture.
【００１９】さらに本発明においてはグリオキザールモ
ノアセタール化合物、アンモニア及びグリオキザール化
合物を反応させ、生成した２−ジアルコキシメチルイミ
ダゾール化合物を単離精製せず、その反応混合物に鉱酸
を加えて反応させることにより、化８で示される２−ホ
ルミルイミダゾール系化合物が得られる。Further, in the present invention, a glyoxal monoacetal compound, ammonia and a glyoxal compound are reacted, and the resulting 2-dialkoxymethylimidazole compound is not isolated and purified, but is reacted by adding a mineral acid to the reaction mixture. A 2-formylimidazole compound represented by the following formula (8) is obtained.
【００２０】[0020]
【化８】 Embedded image
【００２１】本発明の実施において用いられる鉱酸の代
表的なものとしては、塩酸、硝酸、硫酸、酢酸、シュウ
酸などがあり、出発原料であるグリオキザールモノアセ
タール化合物１モルに対して、これらの鉱酸を１．１〜
１０．０モル、好ましくは３．０〜６．０モル加えたの
ち、室温〜１００℃の温度で２〜５時間攪拌すれば良
い。Representative examples of mineral acids used in the practice of the present invention include hydrochloric acid, nitric acid, sulfuric acid, acetic acid, and oxalic acid. These are based on 1 mol of a glyoxal monoacetal compound as a starting material. 1.1 to mineral acid
After adding 10.0 mol, preferably 3.0 to 6.0 mol, the mixture may be stirred at room temperature to 100 ° C. for 2 to 5 hours.
【００２２】また反応終了後に前記の鉱酸を中和するた
めには、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、炭酸カルシウム、重炭酸ナトリ
ウム、重炭酸カリウムあるいはこれら化合物の水溶液な
どが用いられる。この２−ホルミルイミダゾール系化合
物を合成する一連の反応は、化９に示す式のとおりであ
る。In order to neutralize the mineral acid after the completion of the reaction, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, calcium carbonate, sodium bicarbonate, potassium bicarbonate or an aqueous solution of these compounds is used. Used. A series of reactions for synthesizing this 2-formylimidazole-based compound is as shown in the chemical formula (9).
【００２３】[0023]
【化９】 Embedded image
【００２４】[0024]
【実施例】以下、実施例によって本発明方法を具体的に
説明する。 〔実施例１〕温度計、冷却器、攪拌機及び滴下ロートを
備えた四つ口フラスコに５８％グリオキザールジメチル
モノアセタール水溶液３２．４ｇ(0.181モル) 、水６０
ｍｌ及び２５％アンモニア水３０．０ｇ(0.441モル) を
仕込み、攪拌下に６５℃の温度で４０％グリオキザール
水溶液２７．４ｇ(0.189モル) を約１時間かけて滴下し
た。滴下終了後、７０℃の温度でさらに約３時間攪拌し
ながら反応させた。反応終了後、得られた反応混合物を
減圧下で濃縮し、析出した結晶をろ取し、この結晶を水
で再結晶し乾燥したところ、融点 120.0〜120.5 ℃の２
−ジメトキシメチルイミダゾール１６．９ｇが得られ、
その収率は66％であった。EXAMPLES The method of the present invention will be specifically described below with reference to examples. Example 1 A four-necked flask equipped with a thermometer, a cooler, a stirrer and a dropping funnel was charged with 32.4 g (0.181 mol) of a 58% aqueous glyoxal dimethyl monoacetal solution and water 60.
Then, 27.4 g (0.189 mol) of a 40% aqueous glyoxal solution was added dropwise with stirring at a temperature of 65 ° C. over about 1 hour. After completion of the dropwise addition, the mixture was reacted at 70 ° C. for about 3 hours while stirring. After the completion of the reaction, the obtained reaction mixture was concentrated under reduced pressure, and the precipitated crystals were collected by filtration. The crystals were recrystallized from water and dried to obtain a solution having a melting point of 120.0 to 120.5 ° C.
16.9 g of dimethoxymethylimidazole are obtained,
The yield was 66%.
【００２５】〔実施例２〕実施例１と同じ四つ口フラス
コに５８％グリオキザールジメチルモノアセタール水溶
液３２．４ｇ(0.181モル) 水６０ｍｌ及び２５％アンモ
ニア水２６．０ｍｌ(0.38 モル) を仕込み、攪拌下に６
８℃の温度で４０．９％グリオキザール水溶液３３．３
ｇ(0.189モル) を約１時間かけて滴下した。滴下終了
後、７０℃の温度で約３時間攪拌しながら反応させた。
反応終了後、得られた反応混合物を減圧下に蒸留して、
沸点が 120〜127 ℃(9mm/Hg の２−ジメトキシメチル−
４−メチルイミダゾール１７．２８ｇが得られ、その収
率は62％であった。Example 2 The same four-necked flask as in Example 1 was charged with 32.4 g (0.181 mol) of an aqueous 58% glyoxal dimethyl monoacetal solution, 60 ml of water, and 26.0 ml (0.38 mol) of 25% aqueous ammonia and stirred. 6 below
43.3% aqueous glyoxal solution at a temperature of 8 ° C. 33.3
g (0.189 mol) was added dropwise over about 1 hour. After the completion of the dropwise addition, the reaction was carried out at 70 ° C. for about 3 hours while stirring.
After completion of the reaction, the obtained reaction mixture was distilled under reduced pressure,
Boiling point of 120-127 ° C (2-dimethoxymethyl-9mm / Hg
17.28 g of 4-methylimidazole was obtained, and the yield was 62%.
【００２６】〔実施例３〕実施例１と同じ四つ口フラス
コに５８％グリオキザールジメチルモノアセタール水溶
液１６．２ｇ(0.09 モル) 水３０ｍｌ及び２５％アンモ
ニア水１３．０ｍｌ(0.19 モル) を仕込み、攪拌下に６
８℃の温度でジアセチル７．８ｇ(0.09 モル) を約１時
間かけて滴下した。滴下終了後、７０℃の温度で約３時
間攪拌しながら反応させた。反応終了後、得られた反応
混合物を減圧下で蒸留して、沸点が 124〜130 ℃(9mm/H
g の２−ジメトキシメチル−４，５−ジメチルイミダゾ
ール１０．３６ｇが得られ、その収率は68％であった。Example 3 The same four-necked flask as in Example 1 was charged with 16.2 g (0.09 mol) of a 58% aqueous glyoxal dimethyl monoacetal solution, 30 ml of water and 13.0 ml (0.19 mol) of 25% aqueous ammonia, and stirred. 6 below
At a temperature of 8 ° C., 7.8 g (0.09 mol) of diacetyl were added dropwise over about 1 hour. After the completion of the dropwise addition, the reaction was carried out at 70 ° C. for about 3 hours while stirring. After completion of the reaction, the obtained reaction mixture was distilled under reduced pressure to have a boiling point of 124 to 130 ° C (9 mm / H
10.36 g of 2-dimethoxymethyl-4,5-dimethylimidazole were obtained with a yield of 68%.
【００２７】〔実施例４〕温度計、冷却器及び攪拌機を
備えた三つ口フラスコに、ベンゾイルカルビノールアセ
テート５３ｇ(0.3モル) 、５８％グリオキザールモノメ
チルアセテート水溶液５４ｇ(0.3モル) 、２５％アンモ
ニア水５００ｍｌ、及び酢酸銅８０ｇ(0.4モル) を仕込
み、６５℃の温度で約２時間攪拌下に反応させた。反応
終了後、析出した沈澱物をろ取し、この沈澱物に水５０
０ｍｌ及び水硫化ナトリウム１００ｇを加えて３時間攪
拌し、次いで５Ｎ塩酸５００ｍｌを加えてさらに室温で
１時間攪拌をした。析出した硫化銅を濾別し、５Ｎ水酸
化ナトリウム水溶液を用いて中和したのち、析出する結
晶を濾別し、乾燥して２−ジメトキシメチル−４−フエ
ニルイミダゾール４２ｇ（収率64％）を得た。本品の融
点は 152〜154 ℃であった。Example 4 A three-necked flask equipped with a thermometer, a condenser and a stirrer was charged with 53 g (0.3 mol) of benzoylcarbinol acetate, 54 g (0.3 mol) of a 58% aqueous solution of glyoxal monomethyl acetate, and 25% aqueous ammonia. 500 ml and 80 g (0.4 mol) of copper acetate were charged and reacted under stirring at a temperature of 65 ° C. for about 2 hours. After the completion of the reaction, the deposited precipitate was collected by filtration, and the precipitate was added with 50 parts of water.
0 ml and 100 g of sodium hydrosulfide were added, and the mixture was stirred for 3 hours. Then, 500 ml of 5N hydrochloric acid was added, and the mixture was further stirred at room temperature for 1 hour. The precipitated copper sulfide was separated by filtration and neutralized with a 5N aqueous solution of sodium hydroxide. The precipitated crystals were separated by filtration, dried and 42 g of 2-dimethoxymethyl-4-phenylimidazole (yield 64%). I got The melting point of this product was 152-154 ° C.
【００２８】〔実施例５〕実施例１と同じ四つ口フラス
コに５８％グリオキザールジメチルモノアセタール水溶
液３２．４ｇ(0.181モル) 、水６０ｍｌ及び２５％アン
モニア水３０．０ｇ(0.441モル) を仕込み、攪拌下に６
５℃の温度で４０％グリオキザール水溶液２７．４ｇ
(0.189モル) を約１時間かけて滴下した。滴下終了後、
７０℃の温度で約３時間攪拌下に反応させ、次いで濃硫
酸１０ｍｌを加え、攪拌下に約３時間加熱還流した。そ
の後反応混合物を冷却し、これに炭酸カリウム水溶液を
加えて中和し、減圧下で濃縮し析出する結晶を濾別し、
水を用いて再結晶したところ、２−ホルミルイミダゾー
ル１１．９ｇ（収率69％）が得られた。本品の融点は２
０９℃であった。Example 5 The same four-necked flask as in Example 1 was charged with 32.4 g (0.181 mol) of a 58% aqueous glyoxal dimethyl monoacetal solution, 60 ml of water and 30.0 g (0.441 mol) of 25% aqueous ammonia. 6 with stirring
27.4 g of 40% aqueous glyoxal solution at a temperature of 5 ° C.
(0.189 mol) was added dropwise over about 1 hour. After dropping,
The reaction was carried out with stirring at a temperature of 70 ° C. for about 3 hours, then 10 ml of concentrated sulfuric acid was added, and the mixture was heated under reflux with stirring for about 3 hours. Thereafter, the reaction mixture was cooled, neutralized by adding an aqueous solution of potassium carbonate thereto, concentrated under reduced pressure, and the precipitated crystals were separated by filtration.
Recrystallization using water gave 11.9 g (69% yield) of 2-formylimidazole. The melting point of this product is 2
09 ° C.
Claims (3)
ールモノアセタール化合物とアンモニア及び 一般式 Ｒ4 ＣＯＣＲ5 Ｏ （式中、Ｒ4 とＲ5 は水素原子またはアルキル基を表
す）で示されるグリオキザール化合物を反応させること
を特徴とする化１で示されるイミダゾール系化合物の製
造方法。 【化１】 1. A glyoxal monoacetal compound represented by the general formula HCOCH (OR) 2 (wherein R represents an alkyl group), ammonia and a general formula R 4 COCR 5 O (where R 4 and R 5 are A glyoxal compound represented by a hydrogen atom or an alkyl group). Embedded image
ールモノアセタール化合物、アンモニア、酢酸銅及びベ
ンゾイルカルビノールアセテートを反応させ、生成する
銅錯体に硫化水素を反応させることを特徴とする化２で
示されるイミダゾール系化合物の製造方法。 【化２】 2. A copper complex formed by reacting a glyoxal monoacetal compound represented by the general formula HCOCH (OR) 2 (where R represents an alkyl group), ammonia, copper acetate and benzoylcarbinol acetate, A method for producing an imidazole compound represented by Chemical Formula 2, characterized by reacting hydrogen. Embedded image
ールモノアセタール化合物とアンモニア及び 一般式 Ｒ4 ＣＯＣＲ5 Ｏ （式中、Ｒ4 とＲ5 は水素原子またはアルキル基を表
す）で示されるグリオキザール化合物を反応させ、その
反応生成物を単離精製することなく鉱酸と反応させるこ
とを特徴とする化３で示されるイミダゾール系化合物の
製造方法。 【化３】 3. A glyoxal monoacetal compound represented by the general formula HCOCH (OR) 2 (wherein R represents an alkyl group), ammonia and a general formula R 4 COCR 5 O (where R 4 and R 5 are A glyoxal compound represented by a hydrogen atom or an alkyl group), and reacting the reaction product with a mineral acid without isolating and purifying the reaction product, thereby producing an imidazole compound represented by Chemical Formula 3. Embedded image
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6083892A JP2843499B2 (en) | 1994-03-29 | 1994-03-29 | Method for producing imidazole compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6083892A JP2843499B2 (en) | 1994-03-29 | 1994-03-29 | Method for producing imidazole compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH07267933A JPH07267933A (en) | 1995-10-17 |
| JP2843499B2 true JP2843499B2 (en) | 1999-01-06 |
Family
ID=13815300
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6083892A Expired - Lifetime JP2843499B2 (en) | 1994-03-29 | 1994-03-29 | Method for producing imidazole compound |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4841053B2 (en) * | 2001-04-06 | 2011-12-21 | 日本合成化学工業株式会社 | Method for producing formylimidazoles |
| JP2010070479A (en) * | 2008-09-17 | 2010-04-02 | Shikoku Chem Corp | 4-aryl-2-(1-naphthylmethyl)imidazole compound |
| JP2010070535A (en) * | 2008-09-22 | 2010-04-02 | Shikoku Chem Corp | 2-benzyl-4,5-diphenylimidazole compound |
| JP2010077071A (en) * | 2008-09-26 | 2010-04-08 | Shikoku Chem Corp | 2-alkyl-4-(3,4-dichlorophenyl)-5-methylimidazole compound |
| JP2015209502A (en) * | 2014-04-25 | 2015-11-24 | 株式会社Adeka | Curing agent, and curable resin composition prepared using the same |
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1994
- 1994-03-29 JP JP6083892A patent/JP2843499B2/en not_active Expired - Lifetime
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|---|---|
| JPH07267933A (en) | 1995-10-17 |
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