JP2001026591A - Azoniaadamantane compound, production of azaadamantane compound from the same and production of the azoniaadamantane compound - Google Patents
Azoniaadamantane compound, production of azaadamantane compound from the same and production of the azoniaadamantane compoundInfo
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- JP2001026591A JP2001026591A JP11196101A JP19610199A JP2001026591A JP 2001026591 A JP2001026591 A JP 2001026591A JP 11196101 A JP11196101 A JP 11196101A JP 19610199 A JP19610199 A JP 19610199A JP 2001026591 A JP2001026591 A JP 2001026591A
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- compound
- formula
- azoniaadamantane
- azaadamantane
- production
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Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、新規反応中間体で
あるアゾニアアダマンタン化合物およびこのものからア
ザアダマンタン化合物を製造する方法並びに該アゾニア
アダマンタン化合物の製造方法に関する。The present invention relates to a novel reaction intermediate, an azonia adamantane compound, a method for producing an aza adamantane compound therefrom, and a method for producing the azonia adamantane compound.
【０００２】[0002]
【従来の技術】アダマンタン骨格内に窒素原子を１個有
するアザアダマンタン化合物およびその第４級アンモニ
ウム塩は既知物質である（N. Risch 他, Chem. Ber., V
ol. 125, 459 (1992)）。しかしながら、従来このもの
は、下記の反応工程に示されるように少なくとも４段階
の製造過程を経なければならず、また内分泌かく乱物質
の可能性を指摘されているトリブチルスズの使用を必要
とするといった、問題があり、その簡便な合成法が望ま
れていた。2. Description of the Related Art Azaadamantane compounds having one nitrogen atom in the adamantane skeleton and quaternary ammonium salts thereof are known substances (N. Risch et al., Chem. Ber., V.
ol. 125, 459 (1992)). However, in the past, this had to go through at least a four-step production process as shown in the following reaction steps, and required the use of tributyltin, which has been pointed out as a potential endocrine disruptor. There is a problem, and a simple synthesis method has been desired.
【化５】 （式中、Meはメチル基、Buはブチル基、Phはフェニル
基）Embedded image (In the formula, Me is a methyl group, Bu is a butyl group, and Ph is a phenyl group.)
【０００３】[0003]
【発明が解決しようとする課題】本発明は、上記事情に
鑑みなされたものであって、より製造段階が少なく、安
全で工業的に有利なアザアダマンタン化合物の製造方法
及びそのための中間体並びに該中間体の簡便な製造方法
を提供することを目的とする。DISCLOSURE OF THE INVENTION The present invention has been made in view of the above circumstances, and has been made in view of the above circumstances. It is a method of producing a safe and industrially advantageous azaadamantane compound having fewer production steps, an intermediate therefor, and an intermediate therefor. An object of the present invention is to provide a simple method for producing an intermediate.
【０００４】[0004]
【課題を解決するための手段】本発明者らは上記課題を
解決すべく、鋭意研究を重ねた結果、トリフルオロメタ
ンスルホン酸エステルと第一級アミンとの反応により得
られる新規物質である、アゾニアアダマンタン化合物を
出発原料とすれば、アザアダマンタン化合物が一段階で
しかも高収率で得られることを見い出し、本発明を完成
するに至った。即ち、本発明によれば、第一に、下記一
般式（Ｉ）で示されるアゾニアアダマンタン化合物が提
供される。Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have obtained a novel substance, azo, which is obtained by reacting trifluoromethanesulfonic acid ester with a primary amine. Using a near-adamantane compound as a starting material, the inventors have found that an aza-adamantane compound can be obtained in one step and in high yield, and have completed the present invention. That is, according to the present invention, first, an azonia adamantane compound represented by the following general formula (I) is provided.
【化６】 （式中、Ｒ１はアルキル基を示す。） 第二に、前記一般式（Ｉ）で示されるアゾニアアダマン
タン化合物を酸あるいは塩基で処理することを特徴とす
る下記一般式（ＩＩ）で示されるアザアダマンタン化合
物の製造方法が提供される。Embedded image (In the formula, R 1 represents an alkyl group.) Second, the azonia adamantane compound represented by the general formula (I) is treated with an acid or a base, and is represented by the following general formula (II). A method for producing an azaadamantane compound is provided.
【化７】 （式中、Ｒ１はアルキル基を示す。） 第三に、下記一般式（ＩＩＩ）で示されるトリフルオロ
メタンスルホン酸エステルと下記式（ＩＶ）で示される
第一級アミン化合物とを反応させることを特徴とする前
記一般式（Ｉ）で示されるアゾニアアダマンタン化合物
の製造方法が提供される。Embedded image (Wherein, R 1 represents an alkyl group.) Third, reacting a trifluoromethanesulfonic acid ester represented by the following general formula (III) with a primary amine compound represented by the following formula (IV). A method for producing an azonia adamantane compound represented by the general formula (I), characterized by comprising the following:
【化８】 （式中、OTfは、トリフルオロメタンスルホン酸基、Ｒ
１はアルキル基を示す。）Embedded image (Where OTf is a trifluoromethanesulfonic acid group, R
1 represents an alkyl group. )
【化９】 Embedded image
【０００５】[0005]
【発明の実施の形態】本発明の新規中間体である、前記
一般式（Ｉ）で表されるアゾニアアダマンタン化合物
は、アダマンタン環に窒素原子を１個有する基本骨格を
もち、N＋とピリジン環の間にβ-メチレン基を有するこ
とを特徴とする第４級アンモニウム塩である。BEST MODE FOR CARRYING OUT THE INVENTION The azonia adamantane compound represented by the above general formula (I), which is a novel intermediate of the present invention, has a basic skeleton having one nitrogen atom in an adamantane ring, and contains N + and pyridine. A quaternary ammonium salt having a β-methylene group between rings.
【０００６】本発明者の検討によれば、このアゾニアア
ダマンタン化合物（Ｉ）のN＋とピリジン環の間にある
β-メチレン基は、極めて活性が高く、酸や塩基に接触
するとプロトン引き抜き反応を起こし、アザアダマンタ
ンとビニルピリジン（アルケン）を生成することを知見
した。According to the study of the present inventor, the β-methylene group between N + and the pyridine ring of the azonia adamantane compound (I) has extremely high activity, and upon contact with an acid or a base, a proton abstraction reaction occurs. And produced azaadamantane and vinylpyridine (alkene).
【０００７】従って、本発明によれば、このアゾニアア
ダマンタン化合物（Ｉ）とアルケン脱離剤としての酸あ
るいは塩基を作用させると、下記の反応式に従い、一段
階でアザアダマンタン化合物（ＩＩ）を得ることができ
る。Therefore, according to the present invention, when the azonia adamantane compound (I) is allowed to act on an acid or a base as an alkene releasing agent, the aza adamantane compound (II) is converted in one step according to the following reaction formula. Obtainable.
【化１０】 この場合の酸としては、プロトン供与性の塩化水素をは
じめとするブレンステッド酸を用いることができる。酸
の添加量は触媒量でよい。また、塩基としては、リチウ
ムメトキシド、ナトリウムエトキシドなどの金属アルコ
キシドが用いられる。塩基の添加量はアゾニアアダマン
タン化合物（Ｉ）に対して等モル量程度とすることが好
ましい。Embedded image As the acid in this case, a Bronsted acid such as proton-donating hydrogen chloride can be used. The amount of acid added may be a catalytic amount. As the base, a metal alkoxide such as lithium methoxide and sodium ethoxide is used. The amount of the base added is preferably about equimolar to the azonia adamantane compound (I).
【０００８】反応溶媒としては、酸を用いる場合、クロ
ロホルムなどの極性溶媒を、また塩基を用いる場合、メ
タノールなどのアルコール系極性溶媒を用いればよい。
反応温度は、特に制限はないが、０〜７０ ℃程度の範
囲で行うことが望ましい。When an acid is used, a polar solvent such as chloroform may be used as a reaction solvent. When a base is used, an alcoholic polar solvent such as methanol may be used.
The reaction temperature is not particularly limited, but is desirably performed in the range of about 0 to 70 ° C.
【０００９】そして、本発明の目的とするアザアダマン
タン化合物は、上記反応式に従い反応を行い、反応終了
後に抽出処理し、粗生成物を得、ついでこれを再結晶あ
るいは昇華などの精製手段を講じることにより高収率で
得ることができる。The azaadamantane compound which is the object of the present invention is reacted according to the above reaction formula, and after the completion of the reaction, is subjected to an extraction treatment to obtain a crude product, which is then subjected to purification means such as recrystallization or sublimation. Thereby, a high yield can be obtained.
【００１０】本発明の新規中間体である、前記一般式
（Ｉ）で表されるアゾニアアダマンタン化合物は、例え
ば既知の方法で製造される前記一般式（ＩＩＩ）で示さ
れるトリフルオロメタンスルホン酸エステル（H. A. Ma
yer 他, Chem. Ber., Vol. 126, 1341 (1993)）と前記
一般式（ＩＶ）で示される第一級アミンを反応させるこ
とにより簡単に得ることができる。The azonia adamantane compound represented by the general formula (I), which is a novel intermediate of the present invention, is prepared, for example, by a trifluoromethanesulfonic acid ester represented by the general formula (III), which is produced by a known method. (HA Ma
Yer et al., Chem. Ber., Vol. 126, 1341 (1993)) and the primary amine represented by the general formula (IV) can be easily obtained.
【００１１】この反応式を以下に示す。The reaction formula is shown below.
【化１１】 Embedded image
【００１２】この場合、第一級アミンはトリフルオロメ
タンスルホン酸エステルに対して３当量以上加える必要
がある。反応溶媒としては塩化メチレンなどの極性溶媒
が用いられる。 反応温度は、特に制限はないが、０〜
７０ ℃程度で行うことが望ましい。In this case, the primary amine needs to be added in an amount of 3 equivalents or more based on trifluoromethanesulfonic acid ester. A polar solvent such as methylene chloride is used as a reaction solvent. The reaction temperature is not particularly limited.
It is desirable to carry out at about 70 ° C.
【００１３】そして、本願発明の目的とする中間体であ
る、アゾニアアダマンタン化合物は上記反応式に従い反
応を行い、反応終了後に反応液をアルカリ処理および抽
出処理し、粗生成物を得、ついでこれを再結晶などの精
製手段を講じることにより高収率で得ることができる。The azonia adamantane compound, which is an intermediate aimed at by the present invention, undergoes a reaction according to the above reaction formula, and after completion of the reaction, the reaction solution is subjected to an alkali treatment and an extraction treatment to obtain a crude product. Can be obtained in high yield by taking purification means such as recrystallization.
【００１４】[0014]
【実施例】次に本発明を実施例により、さらに詳細に説
明する。Next, the present invention will be described in more detail by way of examples.
【００１５】実施例１ トリフルオロメタンスルホン酸エステル（ＩＩＩ）2.05
g、2(2-アミノエチル)ピリジン1.85 gの混合物を塩化
メチレン中室温で１日撹拌した。反応後水酸化ナトリウ
ム水溶液でアルカリ処理し、常法に従い抽出処理して得
られた粗生成物を、塩化メチレン/ジエチルエーテルか
ら再結晶し、無色板状結晶として338 mg（23 %）のアゾ
ニアアダマンタン化合物（I）（R１；メチル基）を得
た。このもののNMR及びIRを以下に示す。１ H NMR(CDCl３):δ 0.99(s, 9H, メチルH)、1.33(d, 3
H, メチレンH)、1.50(d,3H, メチレンH)、3.24(s, 6H,
メチレンH)、3.55(m, 2H, メチレンH)、3.92(m,2H, メ
チレンH)、7.42(m, 1H, ピリジンH)、7.86(m, 1H, ピリ
ジンH)、7.95(m,1H, ピリジンH)、8.49(m, 1H, ピリジ
ンH) IR(KBr): 1259、1167、1026、637 cm−１ Example 1 Trifluoromethanesulfonic acid ester (III) 2.05
g and 2.85 g of 2 (2-aminoethyl) pyridine were stirred in methylene chloride at room temperature for 1 day. After the reaction, the crude product obtained by alkali treatment with an aqueous sodium hydroxide solution and extraction treatment according to a conventional method was recrystallized from methylene chloride / diethyl ether to obtain 338 mg (23%) of azonia as colorless plate-like crystals. An adamantane compound (I) (R 1 ; methyl group) was obtained. Its NMR and IR are shown below. 1 H NMR (CDCl 3 ): δ 0.99 (s, 9H, methyl H), 1.33 (d, 3
H, methylene H), 1.50 (d, 3H, methylene H), 3.24 (s, 6H,
Methylene H), 3.55 (m, 2H, methylene H), 3.92 (m, 2H, methylene H), 7.42 (m, 1H, pyridine H), 7.86 (m, 1H, pyridine H), 7.95 (m, 1H, Pyridine H), 8.49 (m, 1H, pyridine H) IR (KBr): 1259, 1167, 1026, 637 cm -1
【００１６】実施例２ 実施例１で得たアゾニアアダマンタン化合物76 mgのメ
タノール溶液にリチウムメトキシド12 %メタノール溶液
2 mlを加え、室温で１０時間撹拌した。反応後、水 1
mlを加え、常法に従い抽出処理して得られた粗生成物を
昇華精製し、25 mg（79 %）のアダマンタン化合物（Ｉ
Ｉ）（R１；メチル基）を得た。EXAMPLE 2 A 12% methanol solution of lithium methoxide was added to a methanol solution of 76 mg of the azonia adamantane compound obtained in Example 1.
2 ml was added, and the mixture was stirred at room temperature for 10 hours. After the reaction, water 1
of the adamantane compound (I) (25 mg, 79%).
I) (R 1 ; methyl group) was obtained.
【００１７】[0017]
【発明の効果】本発明方法によれば、 既存の製造法に
比べ、より少ない製造過程で安全かつ高収率で、アザア
ダマンタン化合物を得ることが出来る。そしてこのもの
は、抗不整脈、心臓血管疾患等の薬剤、固体電解質、セ
ンサーなどの用途が期待されている有用なものである。
また、本発明に係る新規中間体であるアゾニアアダマン
タンは、既知物質から容易に製造することができ、上記
アザアダマンタンの製造原料として使用されるほか、構
造の類似性から抗不整脈、心臓血管疾患等の薬剤、固体
電解質、センサーおよび分子認識剤などの新規ホスト化
合物の開発への応用が期待される。According to the method of the present invention, an azaadamantane compound can be obtained safely and in a high yield in a smaller number of production steps as compared with an existing production method. These are useful ones that are expected to be used for drugs such as antiarrhythmias and cardiovascular diseases, solid electrolytes, and sensors.
In addition, azonia adamantane, a novel intermediate according to the present invention, can be easily produced from a known substance, is used as a raw material for producing the aza adamantane, and has antiarrhythmic and cardiovascular diseases due to structural similarity. It is expected to be applied to the development of new host compounds such as drugs, solid electrolytes, sensors and molecular recognition agents.
Claims (3)
マンタン化合物。 【化１】 （式中、Ｒ１はアルキル基を示す。）1. An azonia adamantane compound represented by the following general formula (I). Embedded image (In the formula, R 1 represents an alkyl group.)
マンタン化合物を酸あるいは塩基で処理することを特徴
とする下記一般式（ＩＩ）で示されるアザアダマンタン
化合物の製造方法。 【化２】 （式中、Ｒ１はアルキル基を示す。）2. A method for producing an azaadamantane compound represented by the following general formula (II), comprising treating the azonia adamantane compound represented by the general formula (I) with an acid or a base. Embedded image (In the formula, R 1 represents an alkyl group.)
オロメタンスルホン酸エステルと下記式（ＩＶ）で示さ
れる第一級アミン化合物とを反応させることを特徴とす
る前記一般式（Ｉ）で示されるアゾニアアダマンタン化
合物の製造方法。 【化３】 （式中、OTfは、トリフルオロメタンスルホン酸基、Ｒ
１はアルキル基を示す。） 【化４】 3. A compound represented by the above general formula (I), wherein a trifluoromethanesulfonic acid ester represented by the following general formula (III) is reacted with a primary amine compound represented by the following formula (IV): Of producing an azonia adamantane compound. Embedded image (Where OTf is a trifluoromethanesulfonic acid group, R
1 represents an alkyl group. )
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19610199A JP3303050B2 (en) | 1999-07-09 | 1999-07-09 | Azonia adamantane compound, method for producing azaadamantane compound therefrom and method for producing said azoniaadamantane compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19610199A JP3303050B2 (en) | 1999-07-09 | 1999-07-09 | Azonia adamantane compound, method for producing azaadamantane compound therefrom and method for producing said azoniaadamantane compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001026591A true JP2001026591A (en) | 2001-01-30 |
| JP3303050B2 JP3303050B2 (en) | 2002-07-15 |
Family
ID=16352253
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP19610199A Expired - Lifetime JP3303050B2 (en) | 1999-07-09 | 1999-07-09 | Azonia adamantane compound, method for producing azaadamantane compound therefrom and method for producing said azoniaadamantane compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3303050B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004010512A2 (en) * | 2002-07-18 | 2004-01-29 | Chevron U.S.A. Inc. | Heteroatom-containing diamondoid transistors |
| CN109516986A (en) * | 2017-09-19 | 2019-03-26 | 南京理工大学 | Five nitros of 2,4,4,8,8- -2-aza-adamantane and its synthetic method |
| CN114195787A (en) * | 2021-12-28 | 2022-03-18 | 南京理工大学 | 2-nitro-2-azaadamantane-4, 6, 8-triol trinitrate and preparation method thereof |
-
1999
- 1999-07-09 JP JP19610199A patent/JP3303050B2/en not_active Expired - Lifetime
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004010512A2 (en) * | 2002-07-18 | 2004-01-29 | Chevron U.S.A. Inc. | Heteroatom-containing diamondoid transistors |
| WO2004010512A3 (en) * | 2002-07-18 | 2004-10-28 | Chevron Usa Inc | Heteroatom-containing diamondoid transistors |
| US7402835B2 (en) | 2002-07-18 | 2008-07-22 | Chevron U.S.A. Inc. | Heteroatom-containing diamondoid transistors |
| CN109516986A (en) * | 2017-09-19 | 2019-03-26 | 南京理工大学 | Five nitros of 2,4,4,8,8- -2-aza-adamantane and its synthetic method |
| CN109516986B (en) * | 2017-09-19 | 2021-02-12 | 南京理工大学 | 2,4,4,8, 8-pentanitro-2-azaadamantane and synthetic method thereof |
| CN114195787A (en) * | 2021-12-28 | 2022-03-18 | 南京理工大学 | 2-nitro-2-azaadamantane-4, 6, 8-triol trinitrate and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3303050B2 (en) | 2002-07-15 |
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