JPS60246349A - 2-substituted-1-dimethylaminomethyl-cyclohexane and its preparation - Google Patents
2-substituted-1-dimethylaminomethyl-cyclohexane and its preparationInfo
- Publication number
- JPS60246349A JPS60246349A JP10304484A JP10304484A JPS60246349A JP S60246349 A JPS60246349 A JP S60246349A JP 10304484 A JP10304484 A JP 10304484A JP 10304484 A JP10304484 A JP 10304484A JP S60246349 A JPS60246349 A JP S60246349A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- cyclohexane
- dimethylaminomethyl
- crystals
- 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
Abstract
Description
【発明の詳細な説明】
本発明は次の一般式（１）
（式中、Ｒ１は水酸基又は低級アシルオキシ基を、Ｒ２
はベンシル基を示すか、Ｒ１とＲ，が−緒になってベン
ザル基を示す）
で表わされる２−置換−１−ジメチルアミノメチル−シ
クロヘキサン及びその酸付加塩、並ひにその製造法に関
する。Detailed Description of the Invention The present invention relates to the following general formula (1) (wherein, R1 is a hydroxyl group or a lower acyloxy group, R2
2-substituted-1-dimethylaminomethyl-cyclohexane (represents a benzyl group, or R1 and R together represent a benzal group), an acid addition salt thereof, and a method for producing the same.
匍して、本発明は鎮痛剤として有用な新規な２−置換−
１−ジメチルアミノメチル−シクロヘキサン（１１及び
その酸付加塩’ｋＷ供するものである。Additionally, the present invention provides novel 2-substituted-
1-dimethylaminomethyl-cyclohexane (11 and its acid addition salts'kW).
史にまた、本発明は、２−置換−１−ジメチルアミノメ
チル−シクロヘキサン（１）及びその酸付加塩（以下、
単に本発明化合物（１１という）のＪｉｒ規な製造法を
提供するものでおる。Historically, the present invention also relates to 2-substituted-1-dimethylaminomethyl-cyclohexane (1) and its acid addition salt (hereinafter referred to as
This merely provides a method for producing the compound of the present invention (referred to as 11).
本発明化合物中は例えば次のいずれかの方法によって製
造される。The compounds of the present invention can be produced, for example, by any of the following methods.
製造法ｌ：
次の反応式ＫＷって、化合物（ｌｌｊ Ｖｌ−グＩＪ
ニヤ試薬（ｌｉ反応せしめて１−ゾメナルアミノメテ＾
−２−ペンシル−２−ハイドロオキシ−シクロヘキサン
（１−）を製造する。Production method 1: The following reaction formula KW is a compound (llj Vl-gIJ
Niya reagent (1-zomenal aminomethe)
-2-Pencyl-2-hydroxy-cyclohexane (1-) is produced.
◇
（式中、Ｘ Ｖｉ、ハロゲン原子を示す）製造法２：
次の反応式に健って、製造法１で侍られた本発明化合物
（１ａ）に酸無水物（ＩＶ）を反応せしめることにより
１−ゾメテルアミノメナルー２−ベンゾルー２−アシル
オキシ−シクロ（ｌｂ）
（式中、Ｒ３は低級アルキル基を７トす）！！！造法令
状
次の反応式に梃って、製造法１で得られた本発明化合物
（１ａ）を無＠酸で処理する仁とによシ１−ゾメチルア
ミノメチルー２−ベンザル−シクロヘキサン（１りをｊ
Ｒ造する。◇ (wherein, 1-zometelaminomenal-2-benzo-2-acyloxy-cyclo(lb) (wherein R3 is a lower alkyl group)! ! ! Preparation Process Using the following reaction formula, the compound (1a) of the present invention obtained in Production Method 1 is treated with no acid to produce 1-zomethylaminomethyl-2-benzal-cyclohexane ( 1st time
Build R.
（１ｃ）
製造法１において使用もれる原料化合物（１）は、例え
は次の反応式に促って、シクロヘキサノン■）にノ♀ラ
ホルムアルデヒド（Ｖｌ）とジメチルアミン（■）を同
時に反応せしめることにより製造される。(1c) The raw material compound (1) that is not used in production method 1 can be obtained by simultaneously reacting cyclohexanone (■) with noraformaldehyde (Vl) and dimethylamine (■), for example, according to the following reaction formula. Manufactured by.
０
本反応は、例えは化合物（ｖ１１モルを例えばエタノー
ル、無水メタノール等の無水の有機溶媒に俗解したもの
に、化合物（Ｖｌ） １モルと化合物（Ｖｌ） ２モル
を加え、更に少量の濃塩酸の存在下、６０〜７０℃に加
温して１〜２時間反応せしめることにより行なわれ′る
。0 This reaction is carried out by adding 1 mole of compound (Vl) and 2 moles of compound (Vl) to an anhydrous organic solvent such as ethanol or anhydrous methanol, and then adding a small amount of concentrated hydrochloric acid. The reaction is carried out by heating to 60 to 70°C and reacting for 1 to 2 hours in the presence of.
製造法１は、上記方法により得られた化合物（ｎ）を、
例えは無水エーテル、テトラヒドロフラン等の有機溶媒
に浴ｍし、この溶液を席法により合成した化合物（１３
のグリニヤ試液中に冷却丁姉刀口し、１．５〜２時間反
応せしめることによシ行なわれる。次いで、反応［Ｋ＄
塩醒苗液を加え、水層を分堆し、これをアルカリ性とし
たのち、水に不溶の有機溶媒で抽出し、有機溶媒層に塩
化水素を飽）口せしめると目的化合ｐ４ＩＪ（１＆）の
結晶が倚られる。Production method 1 is the compound (n) obtained by the above method,
For example, a compound (13
This is done by placing a cooled knife in Grignard reagent and allowing it to react for 1.5 to 2 hours. Then, the reaction [K$
Add salted seedling liquid, separate the aqueous layer, make it alkaline, extract with a water-insoluble organic solvent, and soak the organic solvent layer with hydrogen chloride to obtain the target compound p4IJ(1&). The crystal is swallowed.
製造法２は、製造法１で得られた本発明化合’ＭＩ Ｃ
１＆） Ｋ例えは無水酢飯、無水１０ピオン酸、無水ｆ
ＩＡ酸等の酸無水物（ＩＶ）を過剰に加え、５０〜６０
℃に加温して３〜４時間反応せしめることによシ行なわ
れる。次いで反応液をアルカリ性としたのち、以）製造
法１と１１１」様にすれは目的化合物（ｌｂ）の結晶が
得られる。Production method 2 is the compound of the present invention obtained in production method 1.
1 &) K Examples are anhydrous vinegared rice, anhydrous 10-pionic acid, anhydrous f
Add excess acid anhydride (IV) such as IA acid, and add 50 to 60
This is carried out by heating to 0.degree. C. and reacting for 3 to 4 hours. Then, after making the reaction solution alkaline, crystals of the desired compound (lb) are obtained according to "Production Methods 1 and 111" below.
製造法３は、製造法１で得られた本ｆ６ψ」化金物（１
鼻）を、例えは塩酸、希硫酸尋の無機酸の存在下、６０
〜７０℃に加温して１〜２時間反応せしめることにょシ
行なわれる。次いで反応液をアルカリ性としたのち、以
下製造法１と同様にすれば目的化合物（１ｃ）の結晶が
付られる。Production method 3 is based on the f6ψ” metal compound (1) obtained in production method 1.
nose) in the presence of an inorganic acid, such as hydrochloric acid or dilute sulfuric acid, for 60 min.
The reaction is carried out by heating to ~70°C and reacting for 1 to 2 hours. Next, the reaction solution is made alkaline, and then the same procedure as in Production Method 1 is repeated to obtain crystals of the target compound (1c).
このようにして付られる本発明化合物の鎮楠作用を試験
した結果は次のとおシである。The results of testing the anti-palmogenic effect of the compound of the present invention applied in this manner are as follows.
体重１８〜２５２のｄｄ系雌雄性マウス用い、０．６Ｘ
咋酸１０ｍＪ／’９を腹腔内に投与した際にみしれる％
廟な苦悶反応に対する、薬剤の抑制効果を指標にして検
足した。Using DD male and female mice weighing 18-252, 0.6X
% observed when administering 10 mJ/'9 of holic acid intraperitoneally
The drug's suppressive effect on the severe agony reaction was used as an indicator.
本発明化合物を腹腔内に１００■／に’−ｙ投与し、−
ｇらに３０分ｋＫ０．６％酢酸１０．ｍ／にＦ （を腹
腔内に投与した。１ｃ分依からライチング数を測定した
。対照群には本発明化合物のかわりに生理食塩液を投与
した。その結果を第１表にボす。なお数値は抑制率（２
）でボした。The compound of the present invention was administered intraperitoneally at 100 μ/'-y, and -
30 min kK 0.6% acetic acid 10. F was administered intraperitoneally to the mice. The number of lighting was measured from 1 c infusion. In the control group, physiological saline was administered instead of the compound of the present invention. The results are shown in Table 1. The numerical value is the suppression rate (2
).
第１表
＊本発明化合物は以下に起部の各実施例で得たものを使
用した。Table 1 *The compounds of the present invention used were those obtained in each of Kibe's Examples below.
次に実施ヤリを船けて読切する。Next, I will ship the implementation spear and read it all.
実施？ｌ１１
シクロへキサノン９．８？、ジメチルアミン塩酸塩８．
２り、ノＱラホルムアルデヒド４．５ｆ及び濃塩酸０．
２５−を無水エタノール５０献中に加え、水浴中１時間
加温後、ノＱ２ホルムアルデヒド３ｆを更に加え、つい
で、水浴中１時間加温を絖けたのち、＃に縮すると結晶
が析出してくる。結晶を戸取し、メタノールから再結晶
すると白色の針状結晶が１５．２ ｆ（収車８３兆）侍
られた。implementation? l11 Cyclohexanone 9.8? , dimethylamine hydrochloride8.
2, 4.5f of formaldehyde and 0.5f of concentrated hydrochloric acid.
25- is added to 50 parts of absolute ethanol, heated in a water bath for 1 hour, further added 3F of formaldehyde, heated in a water bath for 1 hour, and then reduced to #, crystals precipitate. . When the crystals were collected and recrystallized from methanol, 15.2 f (83 trillion tons) of white needle-like crystals were obtained.
融点１３６°Ｃ
！
金へマグネシウム２４ｆを無水エーテル５０７ｄに加え
、これに、塩化ベンシル１２．６２をエーテル３０−に
俗事したものを冷却下攪拌しながら滴下する。金＾マグ
ネシウムが俗解したのち、１−ジメチルアミノメチル−
２−シクロヘキサン１４２のエーテル溶液全滴下する。Melting point 136°C! To the gold, 24f of magnesium is added to 507d of anhydrous ether, and to this is added dropwise 12.62 of benzyl chloride in 30% of ether while stirring under cooling. After the common understanding of gold^magnesium, 1-dimethylaminomethyl-
Add the entire ether solution of 2-cyclohexane 142 dropwise.
崗下抜、水浴中３０分間加温した。The mixture was removed from the oven and heated in a water bath for 30 minutes.
冷後、希塩酸３５−を加え、水層を分取する。After cooling, dilute hydrochloric acid (35%) is added and the aqueous layer is separated.
この水浴液に水酸化ナトリウム液を加えて、アルカリ性
としたのち、エーテル２００−で２回抽出する。エーテ
ル増を合せ、乾燥後、塩化水素を飽和すると結晶が析出
してくる。A sodium hydroxide solution is added to the water bath solution to make it alkaline, and then extracted twice with ether 200. After adding ether and drying, crystals begin to precipitate when saturated with hydrogen chloride.
結晶をｐ取し、無水のアセトンから再結晶すると白色の
顆粒状結晶が２２．ＥＭ（収率７８％）得られた。When the crystals were separated and recrystallized from anhydrous acetone, white granular crystals were obtained. EM (yield 78%) was obtained.
融点１６６〜１６７℃
元素分析値（Ｃ１＠Ｈｚ、Ｎｏｃｚとして）計算値（２
） Ｃ，６８，５７；Ｈ，ｅｌ、９２；Ｎ、５．ＯＯ実
験値（至） Ｃ，６８，９１；Ｈ，９，０１；Ｎ、４．
８１実施抄１」２
１−ジメチルアミノメチル−２−ベンゾルー２−ハイド
ロオキシ−シクロヘキサン塩酸塩５，０２を酢酸３０−
に俗解し、磯塩酸１０ｍ１を加えて水浴中２時間加温し
た。次いで、減圧下磯動じ、残留物に水酸化す） ＩＪ
ウム溶液を加えてアルカリ性とし、ベンセン３０蛇で４
回抽出を０なった。抽出液を合せ、さらにベンゼンを留
去し、残留物を少量のベンゼンに俗解したものをアルミ
ナカラムに通し、ベンゼンで流出せしめた部分に塩化水
素ガスを辿じると結晶が析出してくる。結晶をｐ取しゾ
ロ、Ｑノールで再結晶すると白色の板状結晶が２６ｆ（
収率５６５１６）得られた。Melting point 166-167℃ Elemental analysis value (C1@Hz, Nocz) Calculated value (2
) C, 68, 57; H, el, 92; N, 5. OO experimental value (to) C, 68,91; H, 9,01; N, 4.
81 Excerpt 1''2 1-dimethylaminomethyl-2-benzo-2-hydroxy-cyclohexane hydrochloride 5,02 was dissolved in acetic acid 30-
10 ml of isohydrochloric acid was added and heated in a water bath for 2 hours. Then, the residue was oxidized under reduced pressure.) IJ
Add um solution to make it alkaline, and add 30 benzene to make it alkaline.
The number of extractions became 0. The extracts are combined, the benzene is distilled off, and the residue is passed through an alumina column to form a small amount of benzene. If the hydrogen chloride gas is traced to the area where the benzene has flowed out, crystals will precipitate out. When the crystals are taken out and recrystallized with Zoro and Q-nor, white plate-like crystals are obtained as 26f (
A yield of 56,516) was obtained.
融点：】０９〜１１０℃
元素分析値（Ｃ１ｓ Ｈ２ｉ ＮＣＩとして）計算値■
Ｃ，７３，２８；ｎ、８．３９；Ｎ、５．３４実験値
（財） Ｃ，？３．５１；Ｈ，８，１０；Ｎ、５．１１
５実施例３
塩酸塩
１−ジメチルアミノメチに一’１．−ベンゾルー２−ハ
イドロキシ−シクロへキサン５ｔｌ無水ゾロピオン散１
５９と、水浴上に３時間加温し、エステル化反応を行な
う。過剰の無水フ′ロビオン酸を減圧］ｅζ留去し、残
留物をアルカリ性とし、エーテルで抽出し、エーテル層
を分取し炭飯カリウムを加えて乾燥したのち、塩化水素
ガスを通じると結晶が析出してくる。結晶を炉取し、ア
セトン−アルコール混液で再結晶すると白色の葉状結晶
が４．３９（収率６５９６）得られる。Melting point: ]09~110℃ Elemental analysis value (as C1s H2i NCI) Calculated value ■
C, 73, 28; n, 8.39; N, 5.34 Experimental value (goods) C,? 3.51; H, 8, 10; N, 5.11
5 Example 3 Hydrochloride 1-dimethylaminomethyl to 1'1. -Benzol-2-hydroxy-cyclohexane 5tl anhydrous zolopion powder 1
59 and heated on a water bath for 3 hours to carry out the esterification reaction. Excess fluorobionic acid anhydride was distilled off under reduced pressure, the residue was made alkaline, extracted with ether, the ether layer was separated, dried with potassium charcoal, and then passed through hydrogen chloride gas to form crystals. It will precipitate out. The crystals are collected in a furnace and recrystallized from an acetone-alcohol mixture to obtain 4.39 white leaf-shaped crystals (yield: 6596).
融点１４１〜１４３℃
元素分析値（ＣＨＩ３ｏＮｏ、Ｃｔとして）計算１直％
ｃ、６７．１４；ａ、８．９０；Ｎ、４．１２笑験値
％ Ｃ，６７，２０；Ｈ，８，８８；Ｎ、４．１０以上Melting point 141-143℃ Elemental analysis value (as CHI3oNo, Ct) calculation 1%
c, 67.14; a, 8.90; N, 4.12 experimental value% C, 67,20; H, 8,88; N, 4.10 or more
Claims (1)
ｔはベンシル基を示すか、Ｒ１とＲ，が−緒になってベ
ンザル基を示す） で表わされる２−義侠−ｌ−ゾメナルアミノメナルーシ
クロヘキサン及びその酸付加塩。 ２、 次式 で表わされる１−ジメチルアミノメチル−２−シクロヘ
キサノンに、一般式 （式中、Ｘはハロゲン原子を示す） で表わ嘔れるグリニヤ試架を反応せしめることを特徴と
する特許 で表わされる１−ゾメナルブミノメテルー２−ベンゾル
ー２−ハイドロキシ−シクロヘキサンの製造法、[Claims] 1. The following general formula (wherein l represents a hydroxyl group or a lower acyloxy group, R
(t represents a benzyl group, or R1 and R together represent a benzyl group) 2-Yoshiyuki-l-zomenalaminomenal-cyclohexane and its acid addition salt. 2. A patent characterized in that 1-dimethylaminomethyl-2-cyclohexanone represented by the following formula is reacted with a Grignard test rack represented by the general formula (in the formula, X represents a halogen atom) A method for producing 1-zomenalbuminomete-2-benzo-2-hydroxy-cyclohexane,
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10304484A JPS60246349A (en) | 1984-05-22 | 1984-05-22 | 2-substituted-1-dimethylaminomethyl-cyclohexane and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10304484A JPS60246349A (en) | 1984-05-22 | 1984-05-22 | 2-substituted-1-dimethylaminomethyl-cyclohexane and its preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS60246349A true JPS60246349A (en) | 1985-12-06 |
Family
ID=14343664
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10304484A Pending JPS60246349A (en) | 1984-05-22 | 1984-05-22 | 2-substituted-1-dimethylaminomethyl-cyclohexane and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60246349A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5132325A (en) * | 1986-02-28 | 1992-07-21 | Ciba-Geigy Corporation | Benzoylphenylureas the preparation thereof and the use thereof in pest control |
| DE19915601A1 (en) * | 1999-04-07 | 2000-10-19 | Gruenenthal Gmbh | 3-Amino-3-arylpropan-1-ol derivatives, their preparation and use |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5283818A (en) * | 1976-01-01 | 1977-07-13 | Takeda Chem Ind Ltd | Novel cyclohexane derivatives |
-
1984
- 1984-05-22 JP JP10304484A patent/JPS60246349A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5283818A (en) * | 1976-01-01 | 1977-07-13 | Takeda Chem Ind Ltd | Novel cyclohexane derivatives |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5132325A (en) * | 1986-02-28 | 1992-07-21 | Ciba-Geigy Corporation | Benzoylphenylureas the preparation thereof and the use thereof in pest control |
| DE19915601A1 (en) * | 1999-04-07 | 2000-10-19 | Gruenenthal Gmbh | 3-Amino-3-arylpropan-1-ol derivatives, their preparation and use |
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