JPS61126076A - Production of 3-(1-piperidinylmethyl)phenol - Google Patents

Production of 3-(1-piperidinylmethyl)phenol

Info

Publication number
JPS61126076A
JPS61126076A JP59247805A JP24780584A JPS61126076A JP S61126076 A JPS61126076 A JP S61126076A JP 59247805 A JP59247805 A JP 59247805A JP 24780584 A JP24780584 A JP 24780584A JP S61126076 A JPS61126076 A JP S61126076A
Authority
JP
Japan
Prior art keywords
solvent
piperidine
raney
reaction
phenol
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
Application number
JP59247805A
Other languages
Japanese (ja)
Inventor
Toshiaki Kataoka
敏明 片岡
Takeshi Sagara
相良 武士
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Koei Chemical Co Ltd
Original Assignee
Koei Chemical Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Koei Chemical Co Ltd filed Critical Koei Chemical Co Ltd
Priority to JP59247805A priority Critical patent/JPS61126076A/en
Publication of JPS61126076A publication Critical patent/JPS61126076A/en
Pending legal-status Critical Current

Links

Classifications

    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/52Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts

Landscapes

  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

PURPOSE:To obtain the titled substance useful as an intermediate for drugs in high purity in high yield, by reacting 3-hydroxybenzaldehyde with piperidine in a solvent such as an alcohol, etc., and subjecting the reaction product to catalytic hydrogenation in the presence of Raney nickel or Raney Co. CONSTITUTION:A compound shown by the formula I is dissolved in a solvent (preferably methanol), the solution is dropped on piperidine at 40-80 deg.C, the reaction solution is transferred to an autoclave, Raney nickel or Raney cobalt catalyst is added to it, and catalytic hydrogenation is carried out to give a compound shown by the formula II. An amount of the catalyst used is 5-30wt% based on the compound shown by the formula I, the reaction temperature is preferably 50-100 deg.C, and hydrogen pressure is preferably 10-100kg/cm<2>.

Description

【発明の詳細な説明】 産業上の利用分野 本発明は、3−(1−ピペリジニルメチル)フェノール
の製造方法に関するものである。さらに詳シくは、3−
ヒドロキシベンズアμデヒドとピペリジンとの還元アミ
l化反応において、触媒としてラネーニッケル、または
ラネーコバルトを使用することからなる3−(l−ピペ
リジニμメチ/L/)フェノ−〃の製造方法に関するも
のである。
DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a method for producing 3-(1-piperidinylmethyl)phenol. For more details, see 3-
This invention relates to a method for producing 3-(l-piperidini μmeth/L/)pheno-, which comprises using Raney nickel or Raney cobalt as a catalyst in the reductive amylation reaction between hydroxybenza μdehyde and piperidine. be.

この化合物は、医薬品、例えばヒスタミンH2拮抗作用
を有する下記式(A)で示される化合物(抗潰瘍剤)の
合成中間体として有用である(特開昭56−7760号
および同56−115750号参照)。本発明方法、お
よび本発明方法で得られる化合物(1)と医薬として有
用な化合物(A)との(A)N−(3−(3−(1−ピ
ペリジニルノチlし)フエ/キシ〕10ピw〕アセトキ
シアセトアミド従来技術並びに本発明が解決しようとす
る問題、車重 従来、3−(1−ピペリジニルメチルラフエノールの製
造方法として、3−ヒドロキシベンズアルデヒドとピペ
リジンとの還元アミノ化反応を利用する方法が知られて
いる。例えば、3−ヒドロキシベンズアルデヒドとピペ
リジンとを溶媒中で混合した後、パラジウム/炭素触媒
上で水素添加する方法が開示されている(特開昭54−
160391号)。また、その池の製造例として、3−
ヒドロキシベンズアルデヒド、ピペリジン、および水素
化ホウ素すI−IJウムを溶媒中で混合し、−夜装置し
た後、抽出、濃縮、再結晶等の工程を経て製造する方法
が開示されている(特開昭56−115750号〕。し
かしながら、前者は、高価な金属水素化触媒を使用して
いるにもかかわらず収率が37%と低く、後者もまた、
高価な水素化剤である水素化ホウ素ナトリウムを化学量
論以上使用し、かつ長時間反応させているにもかかわら
ず、収率は74.5%であって、必ずしも満足すべき結
果が得られていない。従って、これらの従来方法は、前
記中間体を工業的に大l生産し、もって(A)で示され
名医薬品の製造原料を供給する、という目的fこは適し
ていない。
This compound is useful as a synthetic intermediate for pharmaceuticals, such as the compound represented by the following formula (A) (antiulcer agent) having histamine H2 antagonistic action (see JP-A-56-7760 and JP-A-56-115750). ). (A)N-(3-(3-(1-piperidinylnotyl))fe/xy)10-pyrolytic w] Acetoxyacetamide Prior art and the problem to be solved by the present invention, vehicle weight Previously, as a method for producing 3-(1-piperidinylmethylraphenol), a reductive amination reaction between 3-hydroxybenzaldehyde and piperidine was used. For example, a method is disclosed in which 3-hydroxybenzaldehyde and piperidine are mixed in a solvent and then hydrogenated over a palladium/carbon catalyst (Japanese Unexamined Patent Application Publication No. 1983-1999).
No. 160391). In addition, as an example of manufacturing the pond, 3-
A method is disclosed in which hydroxybenzaldehyde, piperidine, and borohydride are mixed in a solvent, heated overnight, and then subjected to steps such as extraction, concentration, and recrystallization (Japanese Patent Application Laid-Open No. No. 56-115750]. However, the former has a low yield of 37% despite using an expensive metal hydrogenation catalyst, and the latter also has a low yield of 37%.
Despite using more than the stoichiometric amount of sodium borohydride, an expensive hydrogenating agent, and reacting for a long time, the yield was 74.5%, which does not necessarily indicate a satisfactory result. Not yet. Therefore, these conventional methods are not suitable for the purpose of industrially producing a large amount of the intermediate and thereby supplying a raw material for producing the famous drug shown in (A).

このような実情に鑑み、本発明者らは、工業化に適した
3−(1−ピペリジニルメチルラフエノールの製造方法
、即ち、低コストであって、しかも短時間内に高収率で
該化合物を製造する方法を、確立すべく種々研究を行な
った結果、意外なことに、従来この種の還元アミノ化反
応には用いられていなかったラネー金属を使用するだけ
でその目的を達し得ることを刈り、本発明を完成した。
In view of these circumstances, the present inventors have developed a method for producing 3-(1-piperidinylmethylraphenol that is suitable for industrialization, that is, a method for producing 3-(1-piperidinylmethylraphenol) at low cost and in high yield within a short period of time. As a result of conducting various studies to establish a method for producing the compound, it was surprisingly discovered that the purpose could be achieved simply by using Raney metal, which had not been previously used in this type of reductive amination reaction. and completed the present invention.

即ち、本発明方法によれば、ラネーニッケルまたはラネ
ーコバルトを触媒として用い、適当な溶媒中で3−ヒド
ロキシベンズアルデヒドとピペリジンとを反応させるこ
とにより、高純度の3−(1−ピペリジニルメチル)フ
ェノールを短時間の゛  内に高収率で得ることができ
る。加えて、本発明方法により、製造工程を簡略化する
こともできる。
That is, according to the method of the present invention, highly purified 3-(1-piperidinylmethyl)phenol is produced by reacting 3-hydroxybenzaldehyde and piperidine in an appropriate solvent using Raney nickel or Raney cobalt as a catalyst. can be obtained in high yield within a short period of time. In addition, the method of the present invention also allows the manufacturing process to be simplified.

本発明を実施するに際しては、まず3−ヒドロキシベン
ズアルデヒドを溶媒に溶解させ、この溶液をピペリジン
にO″Cから還流温度の間、望ましくは40〜80”C
で滴下する。
In carrying out the present invention, 3-hydroxybenzaldehyde is first dissolved in a solvent, and this solution is added to piperidine at a temperature between 0''C and reflux temperature, preferably 40 to 80''C.
Drip with.

ここで使用しつる溶媒は反応に不活性であれば、いかな
るものであってもよく、例えばメタノールおよびエタノ
ール等のアルコール類、ベンゼン、トルエンおよびキシ
レン等の芳香族炭化水素類、並びにテトラハイドロフラ
ンSよびジオキサン等の環状エーテル類をあげることが
できる。それらの内、後処理の容易さ及び経済性を考慮
するとメタノールが望ましい。
The solvent used here may be any solvent as long as it is inert to the reaction, such as alcohols such as methanol and ethanol, aromatic hydrocarbons such as benzene, toluene and xylene, and tetrahydrofuran S. and cyclic ethers such as dioxane. Among them, methanol is preferred in view of ease of post-treatment and economic efficiency.

ピペリジンの使用機は3−ヒドロキシベンズアルデヒド
の1〜10倍モルであり、1.5〜3.0倍モルである
ことが好ましい。
The amount of piperidine used is 1 to 10 times the molar amount of 3-hydroxybenzaldehyde, preferably 1.5 to 3.0 times the molar amount.

次に、3−ヒドロキシベンズアルデヒドとピペリジンの
反応液をオートクレーブlこ移し、ラネーニッケルある
いはラネーコバルト触媒を添加し、進行するが、反応時
間等を考慮して5〜30重量%使用するのが好ましい。
Next, the reaction solution of 3-hydroxybenzaldehyde and piperidine is transferred to an autoclave, and Raney nickel or Raney cobalt catalyst is added and the reaction proceeds, but it is preferable to use 5 to 30% by weight in consideration of reaction time and the like.

また、反応温度は、常温から150°Cの間、好ましく
は50〜100″C9水素圧は10〜100&g/c1
1が適当である。この条件下では、通常0.5〜1.0
時間で理論量の水素を吸収する。その後、通常の後処理
を行なうことにより目的物が得られる。例えば、触媒を
p別後、p液を減圧蒸留して目的物を得ることができる
。また、溶媒にメタノール等を使用した場合はr液に水
を添加することにより、高純度の3−(1−ピペリジニ
ルメチル)フェノールの白色結晶が析出するので、この
結晶を沖取するだけで容易に目的物を分離することがで
きる。
In addition, the reaction temperature is between room temperature and 150°C, preferably 50~100''C9 hydrogen pressure is 10~100&g/c1
1 is appropriate. Under this condition, typically 0.5 to 1.0
Absorbs the theoretical amount of hydrogen in hours. Thereafter, the desired product can be obtained by performing normal post-processing. For example, after separating the catalyst from p, the target product can be obtained by distilling the p liquid under reduced pressure. In addition, if methanol or the like is used as a solvent, adding water to the r-liquid will precipitate white crystals of high-purity 3-(1-piperidinylmethyl)phenol, so simply remove these crystals. The object can be easily separated.

発明の効果 本発明方法によれば、工業的規模での使用に適したラネ
ーニッケルまたはラネーコバルトを用いて、高純度の3
−(1−<ペリジニルメチル)フェノールを高収率で得
ることができる(実施例1、参照、84.6%)。この
収率は従来方法、即ちパラジウム/炭素による方法(3
7%)並びに水素化ホウ素ナトリウムを用いる方法(y
4.s%、−夜装置)に比べて明らかに上昇している。
Effects of the Invention According to the method of the present invention, high-purity
-(1-<peridinylmethyl)phenol can be obtained in high yield (see Example 1, 84.6%). This yield was higher than the conventional method, namely the palladium/carbon method (3
7%) and the method using sodium borohydride (y
4. s%, - night device).

また、所要時間も短縮され、生産性及び経済性の著しい
向上が認められる。
In addition, the required time is shortened, and a significant improvement in productivity and economic efficiency is recognized.

さらに本発明方法では、定量的に反応が進行するため、
生成物である3−(1−ピペリジニルメチル)フェノー
ルを溶解しない溶媒であってかつ、使用した反応溶媒と
は混和し得る溶媒を反応系に加えることにより、この生
成物を高純度で結晶化させることができる。例えば、反
応溶媒がメタノールである場合には、水を反応系に加え
るだけで高純度の結晶を得ることができる。この様に、
本発明方法では、生成物を更に精製する必要がなく、従
って製造工程の簡略化を達成することができる。
Furthermore, in the method of the present invention, since the reaction proceeds quantitatively,
By adding to the reaction system a solvent that does not dissolve the product 3-(1-piperidinylmethyl)phenol but is miscible with the reaction solvent used, the product can be crystallized with high purity. can be made into For example, when the reaction solvent is methanol, highly pure crystals can be obtained simply by adding water to the reaction system. Like this,
In the method of the invention, there is no need for further purification of the product, and therefore a simplification of the manufacturing process can be achieved.

以上述べた理白で、本発明方法は工業的に極めて価値あ
るものであることが理解されよう。
Based on the above-mentioned reasoning, it will be understood that the method of the present invention is extremely valuable industrially.

以下に実施例を示し、本発明の内容を詳しく説明する。EXAMPLES The contents of the present invention will be explained in detail with reference to Examples below.

実施例1 冷却器、温度計、滴下ロート、および攪拌機をそなえた
1e四ツロ反応器にピペリジン170.3f(2,0モ
ル)を加え、60’Cに保ち、別途調製した、3−ヒド
ロキシベンズアルデヒド122.1!(1,0モル)を
含むメタノール溶液500 rxlを滴下ロートより滴
下して加えた。次いで反応器内容物を14オートクレー
ブ中に移し、ラネーニッケル1oyを加えたのち、水素
圧40 kg / cli、温度70°Cで接触水素添
加を行なった。約30分で水素1,0モルを吸収した。
Example 1 Piperidine 170.3f (2.0 mol) was added to a 1e Yotsuro reactor equipped with a condenser, thermometer, dropping funnel, and stirrer and maintained at 60'C to prepare separately prepared 3-hydroxybenzaldehyde. 122.1! 500 rxl of a methanol solution containing (1.0 mol) was added dropwise from the dropping funnel. The contents of the reactor were then transferred into a 14 autoclave and 1 oy of Raney nickel was added, followed by catalytic hydrogenation at a hydrogen pressure of 40 kg/cli and a temperature of 70°C. 1.0 mol of hydrogen was absorbed in about 30 minutes.

次に内容物を取り出し、ラネーニッケル触媒を沖去した
。漏液に水1gを加えると白色結晶が析出した。これを
O〜5 ”C4こ冷却して十分に結晶を析出させた後、
結晶を戸数し、乾燥して3−(1−ピペリジニルメチル
)フェノールの白色結晶x62.5Fを得た。ガスクロ
マトグラフによジ純度99゜6%であることが示された
。3−ヒドロキシベンズアルデヒド−こ対する収率は8
4.6%であった。融点は135〜6′Gで     
  1あった。
The contents were then removed and the Raney nickel catalyst was removed. When 1 g of water was added to the leaked liquid, white crystals were precipitated. After cooling this to 0~5"C4 to sufficiently precipitate crystals,
The crystals were separated and dried to obtain white crystals of 3-(1-piperidinylmethyl)phenol x62.5F. Gas chromatography showed a dipurity of 99.6%. The yield for 3-hydroxybenzaldehyde is 8
It was 4.6%. Melting point is 135-6'G
There was 1.

実施例2 ラネーニッケルの代わりにラネーコバルトを使用し、実
施例1と同様に操作して、3−(1−ピペリジニルメチ
ル)フェノールを収率83.2%で得た。
Example 2 3-(1-piperidinylmethyl)phenol was obtained in a yield of 83.2% by operating in the same manner as in Example 1, using Raney cobalt instead of Raney nickel.

Claims (2)

【特許請求の範囲】[Claims] (1)3−ヒドロキシベンズアルデヒドとピペリジンと
を溶媒中で反応させた後、ラネーニッケル、またはラネ
ーコバルトの存在下で接触水素添加することを特徴とす
る3−(1−ピペリジニルメチル)フエノールの製造方
法。
(1) Production of 3-(1-piperidinylmethyl)phenol by reacting 3-hydroxybenzaldehyde and piperidine in a solvent, followed by catalytic hydrogenation in the presence of Raney nickel or Raney cobalt. Method.
(2)溶媒がアルコール類、芳香族炭化水素類または環
状エーテル類の中から選ばれるものである第1項に記載
の方法。
(2) The method according to item 1, wherein the solvent is selected from alcohols, aromatic hydrocarbons, and cyclic ethers.
JP59247805A 1984-11-22 1984-11-22 Production of 3-(1-piperidinylmethyl)phenol Pending JPS61126076A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP59247805A JPS61126076A (en) 1984-11-22 1984-11-22 Production of 3-(1-piperidinylmethyl)phenol

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP59247805A JPS61126076A (en) 1984-11-22 1984-11-22 Production of 3-(1-piperidinylmethyl)phenol

Publications (1)

Publication Number Publication Date
JPS61126076A true JPS61126076A (en) 1986-06-13

Family

ID=17168917

Family Applications (1)

Application Number Title Priority Date Filing Date
JP59247805A Pending JPS61126076A (en) 1984-11-22 1984-11-22 Production of 3-(1-piperidinylmethyl)phenol

Country Status (1)

Country Link
JP (1) JPS61126076A (en)

Similar Documents

Publication Publication Date Title
BRPI0613818A2 (en) method for reductively aminating an aldehyde or ketone starting compound, method, method for reductively aminating an alicyclic dialdehyde or alicyclic diketone compound, and continuous or semi-continuous method for reductively aminating an aldehyde or ketone starting compound
EP0002308B1 (en) Catalytic hydrogenation process for the manufacture of aromatic amines
KR100704590B1 (en) Novel process for preparing +-cis-sertraline
US20040106818A1 (en) Process for the preparation of cyclohexanol derivatives
JP2702262B2 (en) Method for producing bis (3-aminophenoxy) compound
JPS61126076A (en) Production of 3-(1-piperidinylmethyl)phenol
JPH053861B2 (en)
JPH02279657A (en) Production of aniline
JPH0669991B2 (en) Process for producing 3-aminomethyl-3,5,5-trimethylcyclohexylamine
JPS63297363A (en) Production of 3-methylindoles
JP4112651B2 (en) Process for producing cis-hexahydroisoindoline
JPH02180854A (en) Production of n,n-diisopropylethylamine
JP4709352B2 (en) Method for purifying 3-aminopropanol
JP3443583B2 (en) Method for producing cis-2,6-dimethylpiperazine
JP2006526622A5 (en)
JPS607619B2 (en) Method for producing indoles
JP4809985B2 (en) Method for producing 3-arylpropylamine
JP2762106B2 (en) Method for producing 3-hydroxypyrrolidine
CA1216862A (en) Process for producing aminobenzylamine
JP2002053535A (en) Method for purifying 3-aminopropanol
JP3950423B2 (en) Process for producing cis-2,6-dimethylpiperazine
CN117209546A (en) Preparation method of 1-amino-1-deoxy-D-glucose
CN113321609A (en) Method for synthesizing 4-hydroxyindole
JPS60120844A (en) Manufacture of 9-carbamoylfluorene derivative
JPS61251659A (en) Production of 2-or 3-aminomethylpiperidine