JPH03200751A - Production of 2-amino-1-(4-hydroxyphenyl)-ethanone mineral acid salt - Google Patents
Production of 2-amino-1-(4-hydroxyphenyl)-ethanone mineral acid saltInfo
- Publication number
- JPH03200751A JPH03200751A JP1344742A JP34474289A JPH03200751A JP H03200751 A JPH03200751 A JP H03200751A JP 1344742 A JP1344742 A JP 1344742A JP 34474289 A JP34474289 A JP 34474289A JP H03200751 A JPH03200751 A JP H03200751A
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- solvent
- ethylene dichloride
- layer
- mineral acid
- 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
- 229910052500 inorganic mineral Inorganic materials 0.000 title claims abstract description 32
- 239000011707 mineral Substances 0.000 title claims abstract description 32
- 150000003839 salts Chemical class 0.000 title claims abstract description 31
- 239000002253 acid Substances 0.000 title claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- MLKZSLFDXAYSHO-UHFFFAOYSA-N 2-amino-1-(4-hydroxyphenyl)ethanone Chemical compound NCC(=O)C1=CC=C(O)C=C1 MLKZSLFDXAYSHO-UHFFFAOYSA-N 0.000 title claims description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 16
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims abstract description 15
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 14
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- DFNYGALUNNFWKJ-UHFFFAOYSA-N aminoacetonitrile Chemical compound NCC#N DFNYGALUNNFWKJ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 10
- 150000002466 imines Chemical class 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 239000007789 gas Substances 0.000 claims abstract description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 5
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract 2
- XFKYKTBPRBZDFG-UHFFFAOYSA-N 2-aminoacetonitrile;hydrochloride Chemical compound Cl.NCC#N XFKYKTBPRBZDFG-UHFFFAOYSA-N 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 2
- WOXTWTXRXKAZPT-UHFFFAOYSA-N 2-amino-1-(4-hydroxyphenyl)ethanone;hydrochloride Chemical compound Cl.NCC(=O)C1=CC=C(O)C=C1 WOXTWTXRXKAZPT-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 239000013078 crystal Substances 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract 3
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 235000010755 mineral Nutrition 0.000 description 23
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 15
- 150000003840 hydrochlorides Chemical class 0.000 description 6
- -1 adrenaline analog compounds Chemical class 0.000 description 5
- 238000000034 method Methods 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- AYTGUZPQPXGYFS-UHFFFAOYSA-N urea nitrate Chemical compound NC(N)=O.O[N+]([O-])=O AYTGUZPQPXGYFS-UHFFFAOYSA-N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VYWQTJWGWLKBQA-UHFFFAOYSA-N [amino(hydroxy)methylidene]azanium;chloride Chemical compound Cl.NC(N)=O VYWQTJWGWLKBQA-UHFFFAOYSA-N 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000004434 industrial solvent Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- NUKLDTSTOVGVDB-UHFFFAOYSA-N 1,1-dichloroethane;1,2-dichloroethane Chemical compound CC(Cl)Cl.ClCCCl NUKLDTSTOVGVDB-UHFFFAOYSA-N 0.000 description 1
- PUMZXCBVHLCWQG-UHFFFAOYSA-N 1-(4-Hydroxyphenyl)-2-aminoethanol hydrochloride Chemical compound [Cl-].[NH3+]CC(O)C1=CC=C(O)C=C1 PUMZXCBVHLCWQG-UHFFFAOYSA-N 0.000 description 1
- MCRINSAETDOKDE-UHFFFAOYSA-N 2-chloro-1-(4-methoxyphenyl)ethanone Chemical compound COC1=CC=C(C(=O)CCl)C=C1 MCRINSAETDOKDE-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- SSBRSHIQIANGKS-UHFFFAOYSA-N [amino(hydroxy)methylidene]azanium;hydrogen sulfate Chemical compound NC(N)=O.OS(O)(=O)=O SSBRSHIQIANGKS-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229940046937 octopamine hydrochloride Drugs 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000004065 wastewater treatment Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- Y—GENERAL 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、２−アミノ−１−（４−ヒドロキシフェニル
）−エタノン（以下アミノケトンという）鉱酸塩就中塩
酸塩の改良された製造方法に関するものである。更に詳
しくは、塩酸オクトパミン等のアドレナリン類縁化合物
の医薬中間体として有用であるアミノケトン鉱酸塩就中
塩酸塩を収率よく、且つ工業的に有利に製造する方法に
関するものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention provides an improved method for producing 2-amino-1-(4-hydroxyphenyl)-ethanone (hereinafter referred to as aminoketone) mineral acid salts, especially hydrochloride salts. It is related to. More specifically, the present invention relates to a method for producing aminoketone mineral salts, especially hydrochloride salts, which are useful as pharmaceutical intermediates for adrenaline analog compounds such as octopamine hydrochloride, in a high yield and industrially advantageously.
アニソールと塩化クロルアセチルからフリーデルタラッ
ク反応により２−クロロ−１−（４−メトキシフェニル
）−エタノンを合威し、脱メチル化後、無水酢酸を用い
てアセチル化し、その後、フタルイミドカリウムと縮合
させて得られる２−フタルイミド−１−（４−アセトキ
シフェニル）−エタノンを封管中、氷酢酸及び濃塩酸と
共に加熱することによってアミノケトンが合成されてい
る（Ｊ、Ｃｈｅｍ、Ｓｏｃ、Ｌｏｎｄｏｎ、 ９５，２
１１７−９） 、 しかし彊ら、この方法は工程が複
雑であるため工業的には適さない。2-chloro-1-(4-methoxyphenyl)-ethanone is synthesized from anisole and chloroacetyl chloride by Friedel-Track reaction, demethylated, acetylated using acetic anhydride, and then condensed with potassium phthalimide. Aminoketones have been synthesized by heating 2-phthalimido-1-(4-acetoxyphenyl)-ethanone obtained in a sealed tube with glacial acetic acid and concentrated hydrochloric acid (J, Chem, Soc, London, 95, 2).
117-9), However, this method is not suitable for industrial use due to the complicated process.
またニトロベンゼンまたはクロロベンゼン中、フェノー
ルとアミノアセトニトリル塩酸塩を、無水塩化アルミニ
ウム及び乾燥塩化水素ガス存在下で反応させて、収率５
１％でアミノケトン塩酸塩を合成している〔米国特許２
，５８５，９８８ ； Ｒｅｃ、ｔｒａｖ。Alternatively, phenol and aminoacetonitrile hydrochloride are reacted in nitrobenzene or chlorobenzene in the presence of anhydrous aluminum chloride and dry hydrogen chloride gas, yielding 5.
Aminoketone hydrochloride is synthesized at 1% [US Patent 2]
, 585, 988; Rec, trav.
ｃｈｉｍ、、 ６８．９６０−８（１９４９） ）。chim, 68.960-8 (1949)).
しかし乍ら、これらのような反応溶媒は、毒性を有する
ため排水処理など問題がある上に、沸点が高く分離回収
が容易でないなどの欠点を有する。However, these reaction solvents are toxic and pose problems in wastewater treatment, and also have drawbacks such as a high boiling point and difficulty in separation and recovery.
しかもこれら従来方法に於いては、反応溶媒の難点ばか
りでなく、収率も高くて５０％程度であり、この点でも
工業的に決して優れているものではない。Moreover, these conventional methods not only have problems with the reaction solvent, but also have high yields of about 50%, which are also not industrially superior.
［発明が解決しようとする問題点］
本発明は、無水塩化アルよニウム触媒を用い、フェノー
ルとアミノアセトニトリル鉱酸塩からアミノケトン鉱酸
塩就中塩酸塩を製造するに際し、工業的溶媒として毒性
の低い、しかも反応生成物から分離回収が容易な溶媒を
用い、アミノケトン鉱酸塩就中塩酸塩を収率よく製造す
る方法を提供すること目的としてなされたものである。[Problems to be Solved by the Invention] The present invention uses an anhydrous aluminum chloride catalyst to produce aminoketone mineral salts, particularly hydrochlorides, from phenol and aminoacetonitrile mineral salts, using toxic as an industrial solvent. The purpose of this invention is to provide a method for producing aminoketone mineral salts, especially hydrochlorides, in high yield using a low-volume solvent that can be easily separated and recovered from the reaction product.
上記目的を達成するために鋭意研究を重ねた結果、二塩
化エチレン（ジクロロエタン）を反応溶媒とした場合に
反応が進行するにしたがって形成されたアミノケトンの
中間体であるイミンの鉱酸塩が二塩化エチレンと分層す
ることを見出しこの知見に基づいて本発明を完成するに
至った。As a result of intensive research to achieve the above objective, we found that when ethylene dichloride (dichloroethane) is used as a reaction solvent, the mineral acid salt of imine, which is an intermediate of aminoketone formed as the reaction progresses, becomes dichloride. It was discovered that it forms a layer with ethylene, and based on this knowledge, the present invention was completed.
即ち、本発明は溶媒中に於いて無水塩化アルミニウム触
媒の存在下、乾燥塩化水素ガスを導入し、フェノールと
アミノアセトニトリル鉱酸塩を用いてアミノケトン鉱酸
塩就中塩酸塩を製造するにあたり、溶媒として二塩化エ
チレンを用いて反応させ、反応終了後、分離した上層の
二塩化エチレン層はそのまま次の反応溶媒として用い、
下層のイミン層のみを加水分解すること特徴とするアミ
ノケトン鉱酸塩就中塩酸塩の製造方法を提供するもので
ある。That is, the present invention introduces dry hydrogen chloride gas into a solvent in the presence of an anhydrous aluminum chloride catalyst, and uses phenol and aminoacetonitrile mineral salts to produce aminoketone mineral salts, especially hydrochloride. After the reaction is completed, the separated upper ethylene dichloride layer is used as it is as the next reaction solvent,
The present invention provides a method for producing aminoketone mineral salts, particularly hydrochlorides, which is characterized in that only the lower imine layer is hydrolyzed.
以下、本発明の詳細な説明する。 The present invention will be explained in detail below.
本発明方法に於いては、溶媒として二塩化エチレンが用
いられその使用量については、反応に支障のない範囲で
あればよく特に制限はないが、通常、フェノール、アミ
ノアセトニトリル鉱酸塩及び無水塩化アルミニウムの合
計重量に対して２〜３倍重量用いられる。二塩化エチレ
ン以外の塩化アルカンを反応溶媒として用いた場合には
、アミノケトン鉱酸塩就中塩酸塩の収率は極めて低いも
のとなる。In the method of the present invention, ethylene dichloride is used as a solvent, and the amount used is not particularly limited as long as it does not interfere with the reaction, but usually phenol, aminoacetonitrile mineral salts and anhydrous chloride The weight used is 2 to 3 times the total weight of aluminum. When a chlorinated alkane other than ethylene dichloride is used as a reaction solvent, the yield of the aminoketone mineral salt, particularly the hydrochloride, becomes extremely low.
また、アミノセトニトリル鉱酸塩は、フェノール１モル
に対して０．６〜１．０モルの範囲で用いられ、無水塩
アルミニウムは、フェノールとアミノアセトニトリル鉱
酸塩それぞれの使用モル数の合計と同量乃至それ以上で
用いられる。反応温度は、３０〜６０℃好ましくは３５
〜４５°Ｃの範囲で選ばれる。アミノアセトニトリル鉱
酸塩の鉱酸塩としては、塩酸塩をはじめ、その他硫酸塩
等が使用される。In addition, the aminocetonitrile mineral salt is used in a range of 0.6 to 1.0 mol per 1 mol of phenol, and the anhydrous aluminum salt is the sum of the moles of phenol and aminoacetonitrile mineral salt used. It is used in the same amount or more. The reaction temperature is 30 to 60°C, preferably 35°C.
-45°C. As mineral acid salts of aminoacetonitrile mineral salts, hydrochloride and other sulfates are used.
反応終了後、下層のイミン層のみを抜き出し加水分解し
てアミノケトン鉱酸塩の粗結晶を得る。After the reaction is completed, only the lower imine layer is extracted and hydrolyzed to obtain crude crystals of aminoketone mineral salt.
また、上層の二塩化エチレン層は次、回の反応溶媒とし
てそのまま使用しても、何等支障をきたさないばかりで
なく、かえって未反応試料の再利用によりアごノヶトン
の収率向上をもたらすものである。そのアミノケトン鉱
酸塩の粗結晶を精製し、例えば塩酸塩化すると、アミノ
ケトン塩酸塩が６０％以上の収率で得られ、また所望す
る鉱酸塩にする場合には所望する鉱酸塩化すればよい。Furthermore, even if the upper ethylene dichloride layer is used as it is as a reaction solvent in the next reaction, it not only does not cause any problems, but also improves the yield of Agonokaton by reusing the unreacted sample. be. When the crude crystals of the aminoketone mineral salt are purified and, for example, converted into hydrochloride, aminoketone hydrochloride can be obtained in a yield of 60% or more, and in order to obtain the desired mineral salt, the desired mineral acid salt can be converted into the desired mineral acid salt. .
本発明方法は、無水塩化アルミニウム触媒を用い、フェ
ノールとアミノアセトニトリル鉱酸塩からアミノケトン
鉱酸塩就中塩酸塩を製造する際に、工業的溶媒として、
毒性や回収の面で問題のあるニトロベンゼン等を用いず
に、毒性が低く、そして生成物と分層しそのまま再利用
可能な二塩化エチレンを用い、アミノケトン鉱酸塩就中
塩酸塩を収率よく製造する方法であって工業的に実施す
るのに極めて有利な方法である。The method of the present invention uses an anhydrous aluminum chloride catalyst to produce aminoketone mineral salts, particularly hydrochloride, from phenol and aminoacetonitrile mineral salts, as an industrial solvent.
Aminoketone mineral salts, especially hydrochlorides, can be produced in high yields by using ethylene dichloride, which has low toxicity and can be separated from the product and reused as is, without using nitrobenzene, which has problems in terms of toxicity and recovery. This is a manufacturing method that is extremely advantageous for industrial implementation.
次に実施例により本発明を更に詳しく説明するが、本発
明はこれらの例によって何等限定されるものではない。EXAMPLES Next, the present invention will be explained in more detail with reference to examples, but the present invention is not limited to these examples in any way.
実施例！
二塩化エチレン１５０ｇ中に無水塩化アルミニウム４０
ｇ （０，３０モル）を加え、窒素置換した後、撹拌
しながら、フェノール１４ ｇ （０，１５モル）とア
ミノアセトニトリル塩酸塩１３．９ｇ （０，１５モル
）を加えた。次にこの反応液を撹拌下に、反応温度を４
０″Ｃに維持しながら乾燥塩化水素ガスを導入した。反
応の終点は、原料であるフェノールの減少を高速液体ク
ロマトグラフィーを用いて分析することにより決定した
。反応終了後、反応液下層のイミン層を抜き出し、氷水
中で加水分解した後、濾過、洗浄し、アミノケトン硝酸
塩の粗結晶を得た。その粗結晶を高速液体クロマトグラ
フィーを用いて分析した結果、生成されたアミノケトン
硝酸塩は２１．１ｇ’（収率７５％）であった。Example! Anhydrous aluminum chloride 40g in 150g ethylene dichloride
After the mixture was purged with nitrogen, 14 g (0.15 mol) of phenol and 13.9 g (0.15 mol) of aminoacetonitrile hydrochloride were added with stirring. Next, this reaction solution was stirred and the reaction temperature was increased to 4.
Dry hydrogen chloride gas was introduced while maintaining the temperature at 0"C. The end point of the reaction was determined by analyzing the reduction of the raw material phenol using high performance liquid chromatography. After the reaction was completed, the imine in the lower layer of the reaction solution was The layer was extracted, hydrolyzed in ice water, filtered and washed to obtain crude crystals of aminoketone nitrate.The crude crystals were analyzed using high performance liquid chromatography, and the amount of aminoketone nitrate produced was 21.1g. ' (yield 75%).
実施例２
アミノアセトニトリル塩酸塩１５．７５ ｇ （０，０
７５モル）を用いた以外は、実施例１と同様にして反応
を行った結果、生成されたアミノケトン硫酸塩は１２．
６ｇ （収率４２％）であった。Example 2 Aminoacetonitrile hydrochloride 15.75 g (0,0
The reaction was carried out in the same manner as in Example 1, except that 12.75 mol) of aminoketone sulfate was used.
6g (yield 42%).
実施例３〜６
実施例１と全く同様にして反応を行った。反応終了後の
二塩化エチレン層を次回の反応溶媒として使用し、３回
再利用した。結果を第１表に示す。Examples 3 to 6 Reactions were carried out in exactly the same manner as in Example 1. The ethylene dichloride layer after the completion of the reaction was used as the next reaction solvent and reused three times. The results are shown in Table 1.
第１表
ＥＤＣ：試薬二塩化エチレン
実施例７
実施例１で得られた粗結晶を水３００ｍに溶解後活性炭
脱色し乳酸ナトリウム水溶液を加えた。Table 1 EDC: Reagent Ethylene dichloride Example 7 The crude crystals obtained in Example 1 were dissolved in 300 ml of water, decolorized with activated carbon, and an aqueous sodium lactate solution was added.
それから、アンモニア水を用いてわずかにアルカリ性に
すると直ちにアごノヶトンが析出した。収量は、１７．
６ｇ （含有アミノケトン１６．４ｇ）。Then, when the mixture was made slightly alkaline using aqueous ammonia, Agonokaton precipitated immediately. The yield is 17.
6g (contains aminoketone 16.4g).
そのアミノケトンを希塩酸に溶解後２−プロパツールを
加え、減圧濃縮して、アミノケトン硝酸塩１８．３ｇ
（収率６５．０％）を得た。After dissolving the aminoketone in dilute hydrochloric acid, 2-propanol was added and concentrated under reduced pressure to obtain 18.3 g of aminoketone nitrate.
(yield: 65.0%).
実施例８
希塩酸の代わりに希硝酸を用いた以外は、実施例７と同
様にして処理した結果、アミノケトン硝酸塩１８．４ｇ
（収率５７．８％）を得た。Example 8 As a result of treatment in the same manner as in Example 7 except that dilute nitric acid was used instead of dilute hydrochloric acid, 18.4 g of aminoketone nitrate was obtained.
(yield 57.8%).
比較例１〜５
反応溶媒として第２表に示す所定の塩化アルカンを用い
た以外は、実施例１と同様にして反応を行った。結果を
第２表に示す。Comparative Examples 1 to 5 Reactions were carried out in the same manner as in Example 1, except that the specified chlorinated alkane shown in Table 2 was used as the reaction solvent. The results are shown in Table 2.
第２表Table 2
Claims (3)
下、乾燥塩化水素ガスを導入し、フェノールとアミノア
セトニトリル鉱酸塩を用いて次式、▲数式、化学式、表
等があります▼ （式中、ＨＡは鉱酸を示す） で表される２−アミノ−１−（４−ヒドロキシフェニル
）−エタノン鉱酸塩を製造するにあたり、溶媒として二
塩化エチレンを用いて反応させ、反応終了後、分離した
下層の中間体であるイミン層を加水分解すること特徴と
する２−アミノ−１−（４−ヒドロキシフェニル）−エ
タノン鉱酸塩の製造方法。(1) Dry hydrogen chloride gas is introduced into a solvent in the presence of an anhydrous aluminum chloride catalyst, and using phenol and aminoacetonitrile mineral salt, the following formula, ▲mathematical formula, chemical formula, table, etc. , HA indicates mineral acid) To produce 2-amino-1-(4-hydroxyphenyl)-ethanone mineral acid salt, the reaction was carried out using ethylene dichloride as a solvent, and after the reaction was completed, separation was performed. A method for producing 2-amino-1-(4-hydroxyphenyl)-ethanone mineral salt, which comprises hydrolyzing an imine layer which is an intermediate in the lower layer.
酸塩としてアミノアセトニトリル塩酸塩を用いる２−ア
ミノ−１−（４−ヒドロキシフェニル）−エタノン塩酸
塩の製造法。(2) The method for producing 2-amino-1-(4-hydroxyphenyl)-ethanone hydrochloride according to claim (1), using aminoacetonitrile hydrochloride as the aminoacetonitrile mineral salt.
の二塩化エチレン層をそのまま次の反応溶媒として使用
する２−アミノ−１−（４−ヒドロキシフェニル）−エ
タノン絋酸塩乃至塩酸塩の製造法。(3) In claims (1) to (3), 2-amino-1-(4-hydroxyphenyl)-ethanone salt, wherein the separated upper ethylene dichloride layer is used as it is as the next reaction solvent. A method for producing hydrochloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1344742A JPH03200751A (en) | 1989-12-27 | 1989-12-27 | Production of 2-amino-1-(4-hydroxyphenyl)-ethanone mineral acid salt |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1344742A JPH03200751A (en) | 1989-12-27 | 1989-12-27 | Production of 2-amino-1-(4-hydroxyphenyl)-ethanone mineral acid salt |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03200751A true JPH03200751A (en) | 1991-09-02 |
Family
ID=18371628
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1344742A Pending JPH03200751A (en) | 1989-12-27 | 1989-12-27 | Production of 2-amino-1-(4-hydroxyphenyl)-ethanone mineral acid salt |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03200751A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7994315B2 (en) | 2005-07-22 | 2011-08-09 | Mitsubishi Tanabe Pharma Corporation | Intermediate compound for synthesizing pharmaceutical agent and production method thereof |
| CN105712892A (en) * | 2016-02-29 | 2016-06-29 | 苏州艾缇克药物化学有限公司 | Synthetic method of tyramine |
-
1989
- 1989-12-27 JP JP1344742A patent/JPH03200751A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7994315B2 (en) | 2005-07-22 | 2011-08-09 | Mitsubishi Tanabe Pharma Corporation | Intermediate compound for synthesizing pharmaceutical agent and production method thereof |
| CN105712892A (en) * | 2016-02-29 | 2016-06-29 | 苏州艾缇克药物化学有限公司 | Synthetic method of tyramine |
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