KR980009216A - Method for producing 4-methylacetophenone as radioisotope labeled compound - Google Patents
Method for producing 4-methylacetophenone as radioisotope labeled compound Download PDFInfo
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- KR980009216A KR980009216A KR1019960026830A KR19960026830A KR980009216A KR 980009216 A KR980009216 A KR 980009216A KR 1019960026830 A KR1019960026830 A KR 1019960026830A KR 19960026830 A KR19960026830 A KR 19960026830A KR 980009216 A KR980009216 A KR 980009216A
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Abstract
본 발명은 방사성동위원소 표지화합물로서의 4-메틸아세토페논의 제조방법에 관한 것으로서, 더욱 상세하게는 톨루엔의 방사성동위원소로 치환된 소디움 아세테이트(CH3COONA-14C)를 반응시켜 방사성동위원소 표지화합물로서 약리, 대사 연구에 유용한 다음 구조식(I)로 표시되는 4-메틸아세토페논을 제조하는 방법에 관한 것이다.The present invention relates to a method for producing 4-methylacetophenone as a radioisotope labeled compound, and more particularly, to a method for producing 4-methylacetophenone by reacting sodium acetate (CH 3 COONA- 14 C) substituted with a radioactive isotope of toluene, Methylacetophenone represented by the following structural formula (I) useful for pharmacological and metabolic studies as a compound.
상기 식에서,*C는14C를 나타낸다.In the above formula, * C represents 14C .
Description
본 발명은 방사성동위원소 표지화합물로서의 4-메틸아세토페논의 제조방법에 관한 것으로서, 더욱 상세하게는 톨루엔의 방사성동위원소로 치환된 소디움 아세테이트(CH3COONA-14C)를 반응시켜 방사성동위원소 표지화합물로서 약리, 대사 연구에 유용한 다음 구조식(I)로 표시되는 4-메틸아세토페논을 제조하는 방법에 관한 것이다.The present invention relates to a method for producing 4-methylacetophenone as a radioisotope labeled compound, and more particularly, to a method for producing 4-methylacetophenone by reacting sodium acetate (CH 3 COONA- 14 C) substituted with a radioactive isotope of toluene, Methylacetophenone represented by the following structural formula (I) useful for pharmacological and metabolic studies as a compound.
상기 식에서,*C는14C를 나타낸다.In the above formula, * C represents 14C .
방사성동위원소 표지화합물은 화합물의 일부가 방사성동위원소로 치환된 화합물로서 약물의 약리, 또한 사연구에 있어서 없어서는 안될 필수적인 화합물로 그 가격 역시 매우 고가(高價)이다.A radioisotope labeled compound is a compound in which a part of a compound is substituted with a radioactive isotope, which is an indispensable compound in the pharmacology of the drug and also in the study of the phage, and its price is also very expensive.
방사성동위원소로 치환된 4-메틸아세토페논의 일반적인 제조방법은 다음과 같다.A general method for preparing 4-methylacetophenone substituted with a radioactive isotope is as follows.
상기 식에서,*C는14C를 나타낸다.In the above formula, * C represents 14C .
상기 종래의 4-메틸아세토페논의 제조방법에서는 소디움 아세테이트와 염산을 사용한 가수분해반응에 의해 아세트산을 제조한 다음, 프탈로일 클로라이드와 반응시켜 아세틸 클로라이드를 제조하였다. 그리고 나서 아세틸 클로라이드에 알루미늄 클로라이드와 톨루엔을 반응시켜 4-메틸아세토페논을 제조하였다.In the conventional method for producing 4-methylacetophenone, acetic acid was prepared by hydrolysis reaction using sodium acetate and hydrochloric acid, and then reacted with phthaloyl chloride to prepare acetyl chloride. Then, 4-methylacetophenone was prepared by reacting acetyl chloride with aluminum chloride and toluene.
그러나, 상기와 같은 제조방법은 3단계의 다단계 반응으로 이루어져 있고 제조수율이 20% 이하로 매우 낮으며, 특히 최종 단계에서 부산물로 생성되는 2-메틸아세톤페논의 양이 많아 이를 분리하는데는 많은 어려움이 있었다.However, the above-mentioned production method is composed of three stages of multistage reaction, and the yield is as low as 20% or less. Especially, since the amount of 2-methylacetonephenon produced as a by-product in the final stage is large, .
본 발명에서는 종래의 제조방법과는 달리 방사성동위원소로 치환되어 있는 소디움 아세테이트(CH3COONA-14C)에 알루미늄 클로라이드와 톨루엔을 직접 반응시키되 이들의 사용량과 반응온도를 특정범위로 한정하므로써 높은 제조수율과 제조과정의 단축으로 경제성을 크게 향상시킨 방사성동위원소 표지화합물로서의 4-메틸아세토페논을 제조하는 방법을 제공하고자 한다.In the present invention, aluminum chloride and toluene are directly reacted with sodium acetate (CH 3 COONA- 14 C), which is substituted with a radioactive isotope, unlike the conventional production method. However, by limiting the amount of the aluminum chloride and the reaction temperature to a specific range, Methyl acetophenone as a radioactive isotope labeled compound which is greatly improved in economic efficiency by shortening the yield and the production process.
본 발명은 방사성동위원소 표지화합물로서의 4-메틸아세토페논을 제조하는 방법에 있어서, 톨루엔 1몰에 방사성동위원소로 치환되어 있는 소디움 아세테이트(CH3COONA-14C) 0.05~0.3몰과 알루미늄 클로라이드 0.2~0.3몰을 첨가하고 150~200℃에서 반응시켜 상기 구조식(I)로 표시되는 4-메틸아세토페논을 제조하는 방법을 그 특징으로 한다.The present invention relates to a method for producing 4-methylacetophenone as a radioactive isotope labeled compound, which comprises 0.05 to 0.3 mol of sodium acetate (CH 3 COONA- 14 C) substituted with radioactive isotopes in 1 mol of toluene, To about 0.3 mol of the compound represented by the formula (I) and reacting the compound at 150 to 200 ° C to produce 4-methylacetophenone represented by the formula (I).
이와같은 본 발명을 더욱 상세히 설명하면 다음과 같다.Hereinafter, the present invention will be described in detail.
본 발명은 약리작용 또는 대사연구에 유용한 방사성동위원소 표지화합물로서의 4-메틸아세토페논의 제조방법에 관한 것으로서, 본 발명에 따른 제조과정을 간략히 나타내면 다음 반응식과 같다.The present invention relates to a process for preparing 4-methylacetophenone as a radioactive isotope labeled compound useful for pharmacological or metabolic studies, and the production process according to the present invention is briefly described as follows.
상기 식에서,*C는14C를 나타낸다.In the above formula, * C represents 14C .
상기 반응식에서 나타낸 바와같이 본 발명의 제조방법은 1단계 제조공정으로 이루어져 있다. 상기 반응에 있어서, 구조식(II)로 표시되는 톨루엔 1몰에 대하여 방사성동위원소로 치환되어 있는 소디움 아세테이트(CH3COONA-14C) 0.05~0.3몰 사용하는 바, 만약 그 사용량이 0.05몰 미만이면 수율이 저하되고, 0.3몰을 초과하여 사용하는 것은 경제성이 결여된다. 그리고 알루미늄 클로라이드는 0.2~0.3몰 사용하는 바, 만약 그 사용량이 0.2몰 미만이면 수율이 저하되고, 0.3몰을 초과하면 과량의 알루미늄 클로라이드를 제거해야 하는 별도의 공정이 추가되어야만 한다. 또한 그 반응온도가 150℃미만이면 수율이 저하되고, 200℃를 초과하면 부생성물이 생성되는 문제가 있다.As shown in the above reaction formula, the production method of the present invention comprises a one-step production process. In this reaction, 0.05 to 0.3 mol of sodium acetate (CH 3 COONA- 14 C) substituted with a radioactive isotope is used relative to 1 mol of the toluene represented by the structural formula (II). If the amount is less than 0.05 mol The yield is lowered, and use of more than 0.3 mol is economically disadvantageous. If the amount of aluminum chloride is less than 0.2 mol, the yield decreases. If the amount of aluminum chloride is more than 0.3 mol, a separate step of removing excess aluminum chloride must be added. If the reaction temperature is lower than 150 ° C, the yield is lowered, and if it exceeds 200 ° C, by-products are formed.
상기와 같은 본 발명의 제조방법에 의한 경우 목적 화합물인 상기 구조식(I)로 표시되는 4-메틸아세토페논은 80% 이상의 고수율로 얻을 수 있다.According to the production process of the present invention as described above, 4-methylacetophenone represented by the structural formula (I) which is a target compound can be obtained at a yield of 80% or more.
방사성동위원소가 함유된 화합물의 제조에 있어서 반응 단계가 길어질수록 작업자가 피폭될 우려가 있으므로 가능하면 반응단계를 단축시키는 것이 바람직하다. 이러한 관점에서 볼 때 상기와 같은 본 발명의 제조방법은 종래의 제조방법에 비교하여 그 제조과정이 단축되므로써 고가의 방사성동위원소 표지화합물로서의 4-메틸아세토페논을 싼 가격으로 그리고 높은 수율로 제조할 수 있다.In the production of a compound containing a radioactive isotope, it is preferable to shorten the reaction step as much as possible because the longer the reaction step becomes, the more likely the worker is to be exposed. From this point of view, the production method of the present invention as described above is shorter in production process than the conventional production method, so that 4-methylacetophenone as an expensive radioactive isotope labeled compound can be produced at a low price and in a high yield .
본 발명의 제조과정에서 생성된 생성물은 끓는점(b.p), 적외선 스펙트럼(IR) 및 핵자기 공명스펙트럼(NMR)로 확인하였으며, 또한 방사능의 양 및 화합물의 순도는 액체 신틸레이션 계수기 또는 TLC 측정기로 확인하였다.The product produced in the production process of the present invention was confirmed by boiling point (bp), infrared spectrum (IR) and nuclear magnetic resonance spectrum (NMR), and the amount of radioactivity and the purity of the compound were confirmed by liquid scintillation counter or TLC meter .
이하 본 발명을 실시예에 의거하여 상세히 설명하면 다음과 같은 바, 본 발명이 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples, but it should be understood that the present invention is not limited to the following Examples.
실시예Example
4-메틸아세토페논의 제조Preparation of 4-methylacetophenone
방사성동위원소로 치환된 소디움 아세테이트(CH3COONA-14C; 3mmol, 150mCi)에 알루미늄 클로라이드(1.6g, 12mmol)와 톨루엔(5㎖)을 투입하고 170℃에서 6시간동안 교반시킨 다음, 상온까지 냉각시켰다. 반응물을 물(10㎖)에 조금씩 넣고, 에테르로 추출하였다. 에테르층은 무수 황산마그네슘으로 건조하고 감압농축한 후, 실리카겔 크로마토그래피하므로써 목적화합물인 4-메틸아세토페논 322㎎(2.4mmol, 120mCi, 수율 80%)을 얻었다.Aluminum chloride (1.6 g, 12 mmol) and toluene (5 ml) were added to sodium acetate substituted with a radioactive isotope (CH 3 COONA- 14 C; 3 mmol, 150 mCi), stirred at 170 ° C for 6 hours, Lt; / RTI > The reaction was poured into water (10 ml) little by little and extracted with ether. The ether layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and then subjected to silica gel chromatography to obtain 322 mg (2.4 mmol, 120 mCi, yield 80%) of 4-methylacetophenone as a target compound.
본 발명은 약리, 대사 연구에 유용한 상기 구조식(I)로 표시되는 4-메틸아세토페논을 높은 제조수율로 제조하고, 또한 제조과정의 단축으로 경제성을 크게 향상시키는 효과를 가진다.The present invention has the effect of producing 4-methylacetophenone represented by the above structural formula (I) useful for pharmacological and metabolic studies at a high production yield and greatly improving the economical efficiency by shortening the manufacturing process.
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| KR1019960026830A KR980009216A (en) | 1996-07-03 | 1996-07-03 | Method for producing 4-methylacetophenone as radioisotope labeled compound |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5545667A (en) * | 1978-09-28 | 1980-03-31 | Sumitomo Chem Co Ltd | Production of p-methylacetophenone |
| JPH10182544A (en) * | 1996-10-30 | 1998-07-07 | Eisai Kagaku Kk | Production of p-acylalkylbenzene derivative |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5545667A (en) * | 1978-09-28 | 1980-03-31 | Sumitomo Chem Co Ltd | Production of p-methylacetophenone |
| JPH10182544A (en) * | 1996-10-30 | 1998-07-07 | Eisai Kagaku Kk | Production of p-acylalkylbenzene derivative |
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