JPS61112056A - Imidazole derivative and production thereof - Google Patents
Imidazole derivative and production thereofInfo
- Publication number
- JPS61112056A JPS61112056A JP59233075A JP23307584A JPS61112056A JP S61112056 A JPS61112056 A JP S61112056A JP 59233075 A JP59233075 A JP 59233075A JP 23307584 A JP23307584 A JP 23307584A JP S61112056 A JPS61112056 A JP S61112056A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- reaction
- represented
- following formula
- 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 description 9
- 150000002460 imidazoles Chemical class 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 150000008050 dialkyl sulfates Chemical class 0.000 claims abstract description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical class C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 abstract description 46
- 238000006243 chemical reaction Methods 0.000 abstract description 10
- 239000003795 chemical substances by application Substances 0.000 abstract description 10
- 238000005886 esterification reaction Methods 0.000 abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 10
- 239000002904 solvent Substances 0.000 abstract description 4
- 150000008051 alkyl sulfates Chemical class 0.000 abstract description 3
- 150000003839 salts Chemical class 0.000 abstract description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 2
- 239000012298 atmosphere Substances 0.000 abstract description 2
- 239000001257 hydrogen Substances 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 2
- 239000011261 inert gas Substances 0.000 abstract description 2
- 238000009833 condensation Methods 0.000 abstract 1
- 230000005494 condensation Effects 0.000 abstract 1
- 230000032050 esterification Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 150000002894 organic compounds Chemical class 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000007810 chemical reaction solvent Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- -1 alcohols or phenols Chemical class 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 150000002989 phenols Chemical class 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000004020 conductor Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- YFQBFBATCINSHI-BGERDNNASA-N (2s)-2,6-diamino-1-(2-diphenoxyphosphorylpyrrolidin-1-yl)hexan-1-one Chemical compound NCCCC[C@H](N)C(=O)N1CCCC1P(=O)(OC=1C=CC=CC=1)OC1=CC=CC=C1 YFQBFBATCINSHI-BGERDNNASA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940127573 compound 38 Drugs 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-N methyl sulfate Chemical class COS(O)(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は、例えば、アルコール類もしくはフェノール類
の如きエステル形成性水酸基含有有機化合物もしくはそ
の官能性誘導体と、例えば、カルボン酸類の如きエステ
ル形成性カルボキシル基含有有機化合物もしくはその官
能性誘導体とから対応するエステル類を形成するエステ
ル化反応、その他一般的にエステル化反応に際して縮合
剤として利用するのに有用な従来公知文献未記載のカル
ボニルジイミダゾール誘導体及びその製法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the combination of an ester-forming hydroxyl group-containing organic compound such as alcohols or phenols or a functional derivative thereof, and an ester-forming carboxyl group-containing organic compound such as carboxylic acids or its functional derivative. The present invention relates to carbonyldiimidazole derivatives which have not been previously described in known literature and which are useful as condensing agents in esterification reactions to form corresponding esters from functional derivatives and other general esterification reactions, and methods for producing the same.
更に詳しくは、本発明は下記式（＋）
但し式中、Ｒは低級アルキル基を示す、で表わされるカ
ルボニルシイミグゾール誘導体（３、３′−ジアルキル
−１、ｌ Ｌカルボニルジイミダゾリウム・二（アルキ
ル硫酸）塩〕に関する。More specifically, the present invention is directed to carbonylsiimiguzole derivatives (3,3'-dialkyl-1, 1 L carbonyl diimidazolium 2 (alkyl sulfate) salt].
本発明はまた、下記式（璽）
で表わされる１、１′−力ルボニルジイミダゾールと下
記式（璽）
Ｒ，５０４・・・ （蓋）
但し式中、Ｒは低級アルキル基を示す、で表わされるジ
アルキル硫醪とを接触させることを特徴とする前記式（
１）で表わされるカルボニルジイミダゾール誘導体の製
法にも関する。The present invention also relates to 1,1'-carbonyldiimidazole represented by the following formula (Seal) and the following formula (Seal) R,504... (Lid) However, in the formula, R represents a lower alkyl group. The above formula (
The present invention also relates to a method for producing the carbonyldiimidazole derivative represented by 1).
従来、たとえばアルコール類もしくはフェノール類の如
きエステル形成性水酸基含有有機化合物もしくはその官
能性誘導体とたとえばカルボン酸類の如きエステル形成
性カルボキシル基含有有機化合物もしくはその官能性誘
導体から対応するエステル類を生成させるエステル化反
応に際して、該エステル化反応を適当々縮合剤の存在下
に行なうことは知られている。Conventionally, esters are produced by forming corresponding esters from ester-forming hydroxyl group-containing organic compounds such as alcohols or phenols, or their functional derivatives, and ester-forming carboxyl group-containing organic compounds such as carboxylic acids, or their functional derivatives. It is known that the esterification reaction is carried out in the presence of an appropriate condensing agent.
本発明者等は、このような縮合剤として優れた作用効果
を示す化合物を開発すべく研究を行ってきた。The present inventors have conducted research to develop a compound that exhibits excellent effects as such a condensing agent.
その結果、前記式（冨）で表わされる従来公知文献未記
載の３．３Ｌジアルキル−１，１′−カルボニルジイミ
ダゾリニウムー＝（アルキル硫酸）塩の合成に成功し且
つ線式（ｆ）化合物が広いエステル化反応一般における
縮合剤として、極めて有用な化合物であることを発見し
た。As a result, we successfully synthesized a 3.3L dialkyl-1,1'-carbonyldiimidazolinium (alkyl sulfate) salt represented by the above formula (f), which has not been described in any prior art literature, and also synthesized the compound of the linear formula (f). We have discovered that this compound is extremely useful as a condensing agent in a wide range of esterification reactions in general.
従って、本発明の目的はエステル化反応一般における縮
合剤として有用な式（ｆ）新規化合物及びその製法を提
供するＫある。Accordingly, it is an object of the present invention to provide a novel compound of formula (f) useful as a condensing agent in general esterification reactions and a method for producing the same.
本発明の上記目的及び更に多くめ他の目的ならびに利点
は、以下の記載から一層明らかとなるでちろう。The above objects and many other objects and advantages of the present invention will become more apparent from the following description.
本発明の式（１）カルボニルジイミダゾール誘導体は下
記式（１）で表わすことのできる、通常、室温でアメ状
物としで得られる化合物である。The carbonyldiimidazole derivative of formula (1) of the present invention is a compound that can be represented by the following formula (1) and is usually obtained as a candy-like substance at room temperature.
上記式（璽）におけるＲは低級アルキル基を示し、その
具体例としてはメチル基、エチル基の如き低級アルキル
基を例示することができる。R in the above formula (seal) represents a lower alkyl group, and specific examples thereof include lower alkyl groups such as methyl and ethyl groups.
該弐〇）カルボニルシイミグゾール誘導体は、例えば、
下記式（１）
で表わされる公知化合物ｌ、１′−カルボニルジイミダ
ゾールと下記式（ＩＩ）
Ｒ，ＳＯ，・・・ （厘）
但し式中、Ｒは式（電）について上記したと同じ、
で表わされる公知ジアルキル硫酸とを接触させることに
より、容易に且り高収率で形成することができる。Said 2〇) carbonylciimiguzole derivative is, for example,
The known compound l,1'-carbonyldiimidazole represented by the following formula (1) and the following formula (II) R,SO,... (厘) However, in the formula, R is the same as described above for the formula (den), It can be easily formed in a high yield by contacting it with a known dialkyl sulfate represented by:
反応に用いる式（Ｉ）化合物及び式１厘）化合物は公知
化合物であり、その製法も知られているが、市場で入手
可能であり、本発明式（１）化合物の製造に利用できる
。式（ｍ）ｔ、ｘ′−カルボニルジイミダゾールは、例
えば、Ｃｈｅｍ、ｌｈｒ、。The compounds of formula (I) and compounds of formula (1) used in the reaction are known compounds, and their production methods are also known, but they are commercially available and can be used to produce the compound of formula (1) of the present invention. Formula (m) t,x'-carbonyldiimidazole is, for example, Chem, lhr.
９３．２９１Ｇ（１９６０）に記載の方法に従って製造
することができる。93.291G (1960).
式（１）化合物と式（１）化合物とを接触させることに
より反応を行なうに際して、反応溶媒を使用することが
でき、好ましい。利用する反応溶媒の例としては、アセ
トニトリル、クロロホルム、Ｎ、Ｎ−ジメチルホルムア
ミド、これらの任意の混合物などを例示することができ
る。溶媒の使用量にとくぺつな制約はなく、適宜に選択
変更できるが、式（璽）化合物に対して例えば約５〜約
１０倍量の如き使用量を例示することができる。When carrying out a reaction by bringing a compound of formula (1) into contact with a compound of formula (1), a reaction solvent can be used and is preferred. Examples of the reaction solvent to be used include acetonitrile, chloroform, N,N-dimethylformamide, and any mixture thereof. There is no particular restriction on the amount of the solvent to be used, and it can be selected as appropriate, but for example, the amount used may be about 5 to about 10 times the amount of the compound of formula (1).
又、式（璽）化合物と式（璽）化合物との使用割合も適
当に選択変更できるが、好ましくは、式（冨）化合物１
モル当シ、式（１）化合物約１〜約２モルの如き使用割
合を例示することができる。In addition, the ratio of the compound of the formula (P) and the compound of the formula (P) can be appropriately selected and changed, but preferably, the compound of the formula (P) 1 is used.
Examples of the usage ratio include about 1 to about 2 moles of the compound of formula (1).
反応温度及び時間は適宜に選択できるが、例えば、約−
２０＠〜約８０℃の如き反応温度及び約１〜約９６時間
の如き反応時間を例示することができる。The reaction temperature and time can be selected as appropriate, but for example, about -
Reaction temperatures such as from 20° C. to about 80° C. and reaction times such as from about 1 to about 96 hours may be exemplified.
反応は窒素、アルゴンなどの如き不活性ガス雰囲気下で
行なうことができ、好ましい。また、反応は水その他の
活性水素含有化合物が実質的な量で存在しない系で行な
うのが好ましい。反応生成物は、たとえばクロロホルム
で洗浄し、たとえば真空乾燥して式（夏）化合物を得る
ことができる。The reaction can be preferably carried out under an inert gas atmosphere such as nitrogen, argon, etc. Further, the reaction is preferably carried out in a system in which water and other active hydrogen-containing compounds are not present in substantial amounts. The reaction product can be washed, for example with chloroform, and dried, for example in vacuum, to obtain a compound of formula (summer).
たとえば、以上に例示した態様で製造することができる
本発明式（１）カルボニルジイミダゾール誹導体は、例
えばアルコール類もしくはフェノール類などの如きエス
テル形成性水酸基含有有機化合物もしくはその官能性誘
導体と例えばカルボン酸類の如きエステル形成性カルボ
キシル基含有有機化合物もしくはその官能性誘導体とか
ら対応するエステル類を生成させるエステル化反応の如
き広いエステル化反応一般において縮合剤として極めて
有用な新規化合物であって、たとえば、収率の向上、反
応性の改善、純度の向上、その他において、優れたエス
テル化反応用縮合剤としての改善性能を発揮できる。For example, the carbonyldiimidazole derivative of the formula (1) of the present invention, which can be produced in the manner exemplified above, can be prepared by combining an ester-forming hydroxyl group-containing organic compound such as an alcohol or a phenol, or a functional derivative thereof, with a carbonyl diimidazole conductor, such as a carbonyl diimidazole conductor of the present invention. A novel compound that is extremely useful as a condensing agent in a wide range of esterification reactions in general, such as esterification reactions that produce corresponding esters from ester-forming carboxyl group-containing organic compounds such as acids or functional derivatives thereof, and for example, It can exhibit excellent improved performance as a condensing agent for esterification reactions in terms of improved yield, improved reactivity, improved purity, and others.
以下に式（り化合物のエステル化反応における縮合剤と
しての利用の一態様として、エチル−４−（６−ゲアニ
ジノヘキサノイルオキシ）ベンゾエート−パラトルエン
スルホン酸塩の製法を例に説明する。Below, as an example of the use of a compound of formula (2) as a condensing agent in an esterification reaction, a method for producing ethyl-4-(6-geanidinohexanoyloxy)benzoate-paratoluenesulfonate will be explained.
上記利用態様は下記式で表わすことができる。The above usage mode can be expressed by the following formula.
（Ｍ）
・Ｒ５へ〕□
式（■）で表わされるエチル４−（６−ゲアニジノヘキ
サノイルオキシ）ベンゾエートＰ−トルエンスルホン酸
塩を得るには、式（Ｐ／）で表わされる６−ゲアニジノ
カブロン酸の？−）ルエ／スルホ／酸塩と弐〇）本発明
化合物とを反応溶媒中で反応させて式（Ｖ）で表わされ
る中間体を生成せしめ、次いで式（ｌで表わされるノシ
ラヒドロキシ安息香酸エチルを加えて反応せしめて式（
■）化合物を製造することができる（後記参考列２を内
照）。(M) ・To R5]□ To obtain ethyl 4-(6-geanidinohexanoyloxy)benzoate P-toluenesulfonate represented by formula (■), 6-toluenesulfonate represented by formula (P/) Of geanidinocabronic acid? -) Rue/sulfo/acid acid and 2〇) the compound of the present invention are reacted in a reaction solvent to produce an intermediate represented by formula (V), and then ethyl nosilahydroxybenzoate represented by formula (l) Adding and reacting, the formula (
(2) Compounds can be produced (see Reference Column 2 below).
上記例で利用する反応溶媒の例としては、アセトニリル
、クロロホルム、塩化メチン／、Ｎ、Ｎ−ジメチルホル
ムアミド、Ｎ、Ｎ−ジメチルアセトアミド或いはこれら
の溶媒の任意の混合物等を例示することができる。その
使用量には特別な制約はなく、適当に選択変更できるが
、式（Ｆ／）化合物に対して例えば約３〜約１０倍容量
の如き使用量を例示できる。Examples of the reaction solvent used in the above examples include acetonylyl, chloroform, methine chloride/N,N-dimethylformamide, N,N-dimethylacetamide, or any mixture of these solvents. There is no particular restriction on the amount used, and the amount can be changed as appropriate, but the amount used may be, for example, about 3 to about 10 times the amount of the compound of formula (F/).
縮合剤式（冒）本発明化合物の使用量も適宜に選択変更
できるが、式（ｌ化合物に対して例えば約ｌ〜約２モル
量程度を使用するのが好ましい。The amount of the condensing agent compound of the present invention (formula 2) can be selected and changed as appropriate, but it is preferable to use, for example, about 1 to about 2 moles based on the compound of formula (1).
式（ｌのフェノール性化合物の使用量としては、式（Ｆ
／）化合物に対して例えば約１〜約２モル量の如き使用
量を例示することができる。反応温度及び時間は適当に
選択変更でき、例えば約−４０＠〜約８０℃の如き反応
温度及び約１〜約２４時間の如き反応時間を例示するこ
とができる。The amount of the phenolic compound of the formula (l) to be used is the formula (F
/) The amount used can be exemplified, for example, in an amount of about 1 to about 2 mol based on the compound. The reaction temperature and time can be changed as appropriate; for example, the reaction temperature can be from about -40° C. to about 80° C. and the reaction time can be from about 1 to about 24 hours.
さらに、このようＫして得られた式（■）化合物は急性
膵炎の治療薬として有用な下記式（ｌで表わされる公知
化合物エチル４−（６−ゲアニジノヘキサノイルオキシ
）ベンゾエートのメシル塩の製造中間体として有用であ
る。この式（■）化合物から式（ｌ化合物の製造態様は
下記式で表わすことができる。Furthermore, the compound of formula (■) obtained in this manner is a mesyl salt of ethyl 4-(6-geanidinohexanoyloxy)benzoate, a known compound represented by the following formula (l), which is useful as a therapeutic agent for acute pancreatitis. It is useful as an intermediate for the production of the compound of the formula (■).The method of producing the compound of the formula (I) from the compound of the formula (■) can be represented by the following formula.
ＮａＨＣＯ。NaHCO.
式（■）化合物
（■）
上記製造態様において、式（■）化合物を得るには、式
（■）化合物を例えばアセトンの如き有機溶媒中で塩酸
の如き鉱酸で処理した後、次いで重炭酸ソーダの如き重
炭酸塩を作用させることにより製造することができる（
参考例３を参照）。Compound (■) of formula (■) In the above manufacturing method, the compound of formula (■) is obtained by treating the compound of formula (■) with a mineral acid such as hydrochloric acid in an organic solvent such as acetone, and then treating the compound with a mineral acid such as hydrochloric acid in an organic solvent such as acetone. It can be produced by reacting bicarbonate such as (
(See Reference Example 3).
更に、式（ｌ化合物を得るには、上述のようにして得る
ことのできる式（１）化合物に、例えばアセトンの如き
有機溶媒中でメタンスルホン酸を作用させ、次いで結晶
化させることにより容易に製造することができる（参考
例４．を参照）。Furthermore, the compound of formula (l) can be easily obtained by reacting the compound of formula (1), which can be obtained as described above, with methanesulfonic acid in an organic solvent such as acetone, and then crystallizing the compound. (See Reference Example 4).
以下参考例と共に実施例をあげて本発明の数態様につい
て更に詳しく例示する。Hereinafter, several embodiments of the present invention will be illustrated in more detail by referring to reference examples and examples.
実ｔＩｆ４同１
３．３乙ジメチル−ｔ 、 ｔ ’−カルボニルジイミ
ダゾリウム・二（メチル硫酸）塩 式（１）化合物！、
１′−カルボニルジイミダゾール８００ｊｌＦにクロロ
ホルム５ＩＩＩｅを加え、アルゴン雰囲気下、２０℃で
懸濁攪拌条件下にジメチル硫酸０．９４ Ｍｅを滴下し
、同温度にて１６時間攪拌した。１６時間後にはアメ状
物が沈殿した。上澄液を捨てて、さらにクロロホルム５
ｍｌで２回、アメ状物を洗浄し、５０℃で真空乾燥し
て表題化合物をアメ状物として２．０２．９得た。収率
９９．Ｏチ。Actual tIf4 same 1 3.3 O dimethyl-t, t'-carbonyldiimidazolium di(methyl sulfate) salt Formula (1) compound! ,
Chloroform 5IIIe was added to 800 jIF of 1'-carbonyldiimidazole, and 0.94 Me dimethyl sulfate was added dropwise under suspension stirring conditions at 20° C. under an argon atmosphere, followed by stirring at the same temperature for 16 hours. A syrupy substance precipitated after 16 hours. Discard the supernatant and add chloroform
The candy was washed twice with 2.0 ml and dried in vacuo at 50°C to obtain the title compound as a candy 2.02.9. Yield: 99. Ochi.
１４００．１３２０．１２２０．１０５Ｇ。1400.1320.1220.105G.
１０００．８４０，７２０゜
ＮＭＲ（Ｄ）ＷＳＯ−ｄ’、 、ＴＭＳ） δ；λ
ｓ（８，６Ｈ）
４０（ｇ、６Ｂ）
７．９（ｂｓ、４１１）
９．４（６ｇ、２Ｈ）
参考例Ｌ
６−ゲアニジ７カプロ７ｈ２Ｐ−トルエンスルホン酸
式（ｌ化合物
６−ゲアニジノカブロン酸２０．１５Ｆ、水４０９ｔの
混合物を５０°Ｃに加温し、Ｐ−トルエンスルホ／酸・
ｌ水和物２２．１３１を加えて攪拌し溶解させた。若干
の不溶物を戸別したＰ液の水を留去して得た粘稠な油状
物にアセトン１００１１／を加え結晶化させた。これを
７取して乾燥し、表題化合物３８、７８．９を得た。収
率９６．５％。1000.840,720°NMR(D)WSO-d', ,TMS) δ;λ
s(8,6H) 40(g, 6B) 7.9(bs, 411) 9.4(6g, 2H) Reference Example L 6-geanid7capro7h2P-toluenesulfonic acid
Formula (l) A mixture of 20.15 F of 6-geanidinocabronic acid and 409 t of water was heated to 50°C, and P-toluenesulfo/acid.
1 hydrate was added and stirred to dissolve. Acetone 10011/ was added to a viscous oily substance obtained by distilling off the water of the P solution after removing some insoluble matter, and crystallized it. Seven portions of this were taken and dried to obtain the title compound 38, 78.9. Yield 96.5%.
ｍｐ、１１ Ｒ−１２０℃。mp, 11 R-120°C.
参考例２
エチル４−（６−ゲアニジノヘキサノイルオキシ）ベン
ゾエート７’−）ルエンスルホン酸塩’実施例１の表題
化合物４．５０ 、Ｆにクロロホルム２０＋／、６−ゲ
アニジノカプロン酸／’−）ルエンスルホン酸塩３．０
９８Ｊ’を加えて２２℃で攪拌下にジメチルホルムアミ
ドＢｍｔを滴下した。さらに同温度で３時間攪拌した後
、ついでＰ−ヒドロキシ安息香酸エチル１．４９１ Ｎ
を加えて同温度で１時間攪拌後、更に３時間加熱還流し
た。終了後溶媒を留去して得た残分に酢酸エチル３Ｑ哨
／、水３０ゴを加えて水冷下に攪拌した。析出した結晶
を７取し、水１３ ｍｌ ％酢酸エチル１３ｎｒにて洗
浄し、乾燥して表題化合物３．１７０１１を得た。Reference Example 2 Ethyl 4-(6-geanidinohexanoyloxy)benzoate 7'-)luenesulfonate' Title compound of Example 1 4.50%, chloroform 20+/, 6-geanidinocaproic acid/ '-) luenesulfonate 3.0
98J' was added, and dimethylformamide Bmt was added dropwise at 22° C. while stirring. After further stirring at the same temperature for 3 hours, 1.491 N of ethyl P-hydroxybenzoate was added.
After stirring at the same temperature for 1 hour, the mixture was further heated under reflux for 3 hours. After the completion of the reaction, the solvent was distilled off, and to the resulting residue were added 3Q of ethyl acetate and 30Q of water, and the mixture was stirred under water cooling. Seven precipitated crystals were collected, washed with 13 ml of water and 13 nr of ethyl acetate, and dried to obtain the title compound 3.17011.
収率７６．０チ。慣ｐ、１３０−１３１℃。Yield: 76.0 cm. Temperature p, 130-131°C.
参考例λ
エチル４−（６−ゲアニジノヘキサノイルオキシ）ぺ／
シェード炭酸塩 式（■）化合物
エチル４− （６−ゲアニジノヘキサノイルオキシ）ベ
ンゾニー）Ｐ−）ルエンスルホン酸［１８，３４１１ア
セトン１８３１１／、濃塩酸９．９ ｍｌを攪拌し溶解
させた。この溶液に重炭酸ソーダ２０１１水２５０ ｄ
の溶液を水冷下に加えた。析出した結晶をＦ取し、さら
に水、アセトンの順で洗浄し、乾燥した。表題化合物１
λ２５．ｆを得た。収率９２９ｓ、ｍｐｍ ９０〜９３
℃（分解）。Reference example λ Ethyl 4-(6-geanidinohexanoyloxy)pe/
Shade carbonate Formula (■) Compound ethyl 4- (6-geanidinohexanoyloxy)benzony)P-)luenesulfonic acid [18,3411 acetone 18311/, concentrated hydrochloric acid 9.9 ml were stirred and dissolved. Add 2011 d of bicarbonate of soda and 250 d of water to this solution.
A solution of was added under water cooling. The precipitated crystals were collected by F, washed with water and acetone in that order, and dried. Title compound 1
λ25. I got f. Yield 929s, mpm 90-93
°C (decomposition).
参考何本
エチル４− （６−ゲアニジノヘキサノイルオキシ）ベ
ンゾエートメタンスルホン酸塩 式（■）化合物
エチル４−（６−ゲアニジノヘキサノイルオキシ）ベン
ゾエート炭酸塩１２Ｆ、アセトン１２０ｍ／、メタンス
ルホン酸ｚｏｓ＊ｇを攪拌し溶解させた。次いでアセト
ンを留去して得た粘性残分に再びアセト７２６Ｍｔを加
えて溶解し、冷却結晶化させた。析出した結晶を７取し
、アセトンにて洗浄し、乾燥した。表題化合物１０．６
０ Ｉｉを得た。収率８１．１ ％。ｍｐ、９１〜９２
−５℃。Reference number Ethyl 4-(6-geanidinohexanoyloxy)benzoate methanesulfonate Formula (■) Compound ethyl 4-(6-geanidinohexanoyloxy)benzoate carbonate 12F, acetone 120m/, methanesulfone Acid zos*g was stirred and dissolved. Next, acetone 726Mt was added again to the viscous residue obtained by distilling off the acetone to dissolve it, and the mixture was cooled and crystallized. Seven precipitated crystals were collected, washed with acetone, and dried. Title compound 10.6
0 Ii was obtained. Yield 81.1%. mp, 91-92
-5℃.
乎続補正書
昭和６０年５月２８日
特許庁長官 志 賀 学 殿
１、事件の表示
昭和５９年特許Ｈ第２３３０７５号
２、発明の名称
イミグゾール誘導体及Ｖその製法
３、補正をする者
事件との関係 特許出願人
名 称 日本医薬品工業株式会社
電 話 ５８５−２２５６
５、補正命令の日付 なしく自発）６、Ｍ正の対
象
（１）明細書第１０頁１行目の式（Ｖ）中、左端部分に
、
とあるを、
と訂正する。Continuing amendment May 28, 1985 Manabu Shiga, Commissioner of the Patent Office1, Indication of the case, 1982 Patent H No. H2330752, Name of the invention: Imigusol derivative and its manufacturing process3, Person making the amendment Case and Relationship between patent applicant name: Japan Pharmaceutical Industry Co., Ltd. Telephone number: 585-2256 5. Date of amendment order: spontaneously issued) 6. Target of M (1) In formula (V) on page 10, line 1 of the specification, In the leftmost part, correct the text as .
（２）明細書第１Ｏ頁３行目の式（Ｘｌ）中、左端部分
に、
とあるを、
と訂・Ｅする。(2) In formula (Xl) on page 1, line 3 of the specification, the text at the left end is revised to read.
Claims (1)
（III） Ｒ＿２ＳＯ＿４…（III） 但し式中、Ｒは低級アルキル基を示す、 で表わされるジアルキル硫酸とを接触させることを特徴
とする下記式（ I ） ▲数式、化学式、表等があります▼…（ I ） で表わされるカルボニルジイミダゾール誘導体の製法。[Claims] 1. A carbonyldiimidazole derivative represented by the following formula (1) ▲ Numerical formulas, chemical formulas, tables, etc.▼...(I) In the formula, R represents a lower alkyl group. 2. 1,1'-carbonyldiimidazo represented by the following formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(II) and the following formula (III) R_2SO_4...(III) However, in the formula, R is lower A method for producing a carbonyldiimidazole derivative represented by the following formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(I), which is characterized by contacting with a dialkyl sulfate represented by an alkyl group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59233075A JPS61112056A (en) | 1984-11-07 | 1984-11-07 | Imidazole derivative and production thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59233075A JPS61112056A (en) | 1984-11-07 | 1984-11-07 | Imidazole derivative and production thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS61112056A true JPS61112056A (en) | 1986-05-30 |
Family
ID=16949407
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59233075A Pending JPS61112056A (en) | 1984-11-07 | 1984-11-07 | Imidazole derivative and production thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61112056A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5475138A (en) * | 1994-07-07 | 1995-12-12 | Pharm-Eco Laboratories Incorporated | Method preparing amino acid-derived diaminopropanols |
| US6410744B1 (en) * | 1997-06-12 | 2002-06-25 | Basf Aktiengesellschaft | Carbonyldiimidazoles, their ester derivatives and method for their production |
| JP2014185390A (en) * | 2013-03-25 | 2014-10-02 | Ishihara Chemical Co Ltd | Electrolytic copper plating bath, electrolytic copper plating method and electronic part having copper film formed by using the plating bath |
-
1984
- 1984-11-07 JP JP59233075A patent/JPS61112056A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5475138A (en) * | 1994-07-07 | 1995-12-12 | Pharm-Eco Laboratories Incorporated | Method preparing amino acid-derived diaminopropanols |
| US6410744B1 (en) * | 1997-06-12 | 2002-06-25 | Basf Aktiengesellschaft | Carbonyldiimidazoles, their ester derivatives and method for their production |
| JP2014185390A (en) * | 2013-03-25 | 2014-10-02 | Ishihara Chemical Co Ltd | Electrolytic copper plating bath, electrolytic copper plating method and electronic part having copper film formed by using the plating bath |
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