KR0163467B1 - Process for preparation of 2-arylpropionic acid - Google Patents
Process for preparation of 2-arylpropionic acid Download PDFInfo
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- KR0163467B1 KR0163467B1 KR1019950000518A KR19950000518A KR0163467B1 KR 0163467 B1 KR0163467 B1 KR 0163467B1 KR 1019950000518 A KR1019950000518 A KR 1019950000518A KR 19950000518 A KR19950000518 A KR 19950000518A KR 0163467 B1 KR0163467 B1 KR 0163467B1
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Abstract
본 발명은 2-아릴프로피온산의 제조방법에 관한 것으로서, 더욱 상세하게는 낮은 압력하에서 다음 구조식(II)로 표시되는 1-아릴에틸 알코올, 촉매, 할로겐 화전이금속 조촉매, 트리페닐포스핀, 중합방지제 및 염화수소 등을 사용하여 카르보닐화 반응시켜 높은 수율로 다음 구조식(I)로 표시되는 2-아릴프로피온산을 제조하는 방법에 관한 것이다.The present invention relates to a method for preparing 2-arylpropionic acid, and more particularly, under low pressure, 1-arylethyl alcohol, a catalyst, a halogenated transition metal promoter, triphenylphosphine, and polymerization, represented by the following structural formula (II). The carbonylation reaction using an inhibitor, hydrogen chloride, etc. relates to a method for producing 2-arylpropionic acid represented by the following structural formula (I) in high yield.
상기식에서, Ar은 p-페닐-m-플루오로페닐기, m-벤조일페닐기, m-페녹시페닐기, C1∼C6의 직쇄 또는 측쇄 알킬기로 치환된 p-알킬페닐기, 또는 6-메톡시나프틸기이다.Wherein Ar is p-phenyl-m-fluorophenyl group, m-benzoylphenyl group, m-phenoxyphenyl group, p-alkylphenyl group substituted with C 1 -C 6 linear or branched alkyl group, or 6-methoxynaph Til group.
Description
본 발명은 2-아릴프로피온산의 제조방법에 관한 것으로서, 더욱 상세하게는 낮은 압력하에서 다음 구조식(II)로 표시되는 1-아릴에틸 알코올, 촉매, 할로겐 화전이금속 조촉매, 트리페닐포스핀, 중합방지제 및 염화수소 등을 사용하여 카르보닐화 반응시켜 높은 수율로 다음 구조식(I)로 표시되는 2-아릴프로피온산을 제조하는 방법에 관한 것이다.The present invention relates to a method for preparing 2-arylpropionic acid, and more particularly, under low pressure, 1-arylethyl alcohol, a catalyst, a halogenated transition metal promoter, triphenylphosphine, and polymerization, represented by the following structural formula (II). The carbonylation reaction using an inhibitor, hydrogen chloride, etc. relates to a method for producing 2-arylpropionic acid represented by the following structural formula (I) in high yield.
상기식에서, Ar은 p-페닐-m-플루오로페닐기, m-벤조일페닐기, m-페녹시페닐기, C1∼C6의 직쇄 또는 측쇄 알킬기로 치환된 p-알킬페닐기, 또는 6-메톡시나프틸기이다.Wherein Ar is p-phenyl-m-fluorophenyl group, m-benzoylphenyl group, m-phenoxyphenyl group, p-alkylphenyl group substituted with C 1 -C 6 linear or branched alkyl group, or 6-methoxynaph Til group.
상기 구조식(I)로 표시되는 2-아릴프로피온산 유도체중 일부는 해열 소염진통제 및 신경통 류마티스 관절염 치료제로서 뛰어난 효과를 보유하는 화합물로서 주목받고 있으며, 또한 우수한 약효에 비하여 부작용이 매우 적기 때문에 앞으로 그 응용범위는 확대되리라 기대된다.Some of the 2-arylpropionic acid derivatives represented by the above structural formula (I) have been attracting attention as compounds having excellent effects as antipyretic anti-inflammatory drugs and neuralgia rheumatoid arthritis therapeutics, and also have very low side effects as compared to excellent drug efficacy in the future. Is expected to expand.
이에, 종래에도 상기 구조식(I)로 표시되는 2-아릴프로피온의 제조방법을 좀 더 개선하고자 하는 연구는 활발히 진행되어 왔는 바, 그 예는 다음과 같다.Therefore, studies to improve the manufacturing method of the 2-arylpropion represented by the structural formula (I) in the prior art have been actively conducted, examples are as follows.
최초의 특허(Boots사, 영국)라 할 수 있는 미합중국특허 제3,228,831호(1966년)에 의하면 아릴화합물(AR-H)을 원료로 사용하여 이를 아세틸화 반응, 윌거로트-킨들러 반응(Wilgerodt-Kindler reaction), 말로네이트화 반응, 메틸화 반응 및 가수분해 반응 등에 의하여 2-아릴프로피온산을 얻었다. 그러나 이 제조방법은 다단계 공정을 거치게 되어 수율이 높지 못할 뿐만 아니라 반응 중간체를 정제하는 공정이 매우 복잡하며, 또한 많은 폐수가 발생하는 문제가 있다.According to U.S. Patent No. 3,228,831 (1966), the first patent (Boots, UK), an aryl compound (AR-H) was used as a raw material, and then an acetylation reaction, a Wilgerot-Kindler reaction (Wilgerodt- 2-arylpropionic acid was obtained by Kindler reaction), malonation reaction, methylation reaction and hydrolysis reaction. However, this manufacturing method is not only a high yield due to a multi-step process, but also a very complicated process for purifying the reaction intermediate, there is also a problem that a lot of waste water occurs.
미합중국특허 제3,975,431호와 일본특허공고 소74-55,622호에서는 일명 다젠(Darzen)법이라고도 불리는 제조방법에 의해 2-아릴프로피온산을 제조하였는데, 이 방법은 아릴 화합물(Ar-H)을 아세틸화시켜 생성된 아릴 메틸 케톤(aryl methyl ketone)에 클로로아세토니트릴 등을 부가반응시켜 에폭사이드환을 가지는 중간체를 거쳐 2-아릴프로피온산을 생성시키는 방법이다. 이 방법은 비교적 간단하고 안정된 수율을 보이기 때문에 이와 유사한 많은 제조방법들이 특허 출원되고 있다.In U.S. Patent No. 3,975,431 and Japanese Patent Publication No. 74-55,622, 2-arylpropionic acid was produced by a manufacturing method, also known as the Darzen method, which is produced by acetylating an aryl compound (Ar-H). Chloroacetonitrile and the like are further reacted with aryl methyl ketone to produce 2-arylpropionic acid via an intermediate having an epoxide ring. Since this method is relatively simple and shows a stable yield, many similar manufacturing methods have been patented.
일본특허공고 소80-72,256호 등에서는 2-아릴아크릴산을 중간체로 제조하고, 이를 수소첨가 반응시켜 2-아릴프로피온산을 제조하였으며, 유럽특허 제158,931호에는 촉매 존재하에서 아릴 알파-할로케탈(aryl α-haloketal)을 재배치(rearrangement) 반응시켜 2-아릴프로피온산을 제조하는 방법이 제시되어 있다.In Japanese Patent Publication No. 80-72,256, etc., 2-arylacrylic acid was prepared as an intermediate and hydrogenated to produce 2-arylpropionic acid. European Patent No. 158,931 discloses aryl alpha-haloketal in the presence of a catalyst. A method for preparing 2-arylpropionic acid by rearrangement reaction of -haloketal is provided.
이외에도 전이금속 촉매의 존재하에서 일산화탄소를 이용한 1-아릴에틸알코올의 카로보닐화 반응에 의해 2-아릴프로피온산을 제조하는 방법이 잘 알려져 있는 바, 이 방법은 청정공정(淸淨工程), 높은수율 그리고 비교적 간단한 공정으로 이루어져 있어 각광을 받고 있다. 이와 관련된 종래의 제조방법을 요약하면 다음과 같다.In addition, a method of preparing 2-arylpropionic acid by the carbonylation of 1-arylethyl alcohol using carbon monoxide in the presence of a transition metal catalyst is well known, which is a clean process, high yield and It is made of a relatively simple process and is in the limelight. In summary, the related art manufacturing method is as follows.
1978년 스페인의 페렐 인터내쇼날 소사이티 애너님(Ferrel International Society Annonim)사의 일본특허공개 소56-35,659호가 있는데, 이는 1-아릴에틸 알코올을 원료로 사용하고 비스트리페닐포스핀팔라듐 디클로라이드(bis(triphenylphosphine)palladium dichloride)를 촉매로 이용하여 2-아릴프로피온산 유도체를 얻었다.In 1978, Japanese Patent Publication No. 56-35,659 issued by Ferrel International Society Annonim of Spain, which uses 1-arylethyl alcohol as a raw material and uses bistriphenylphosphinepalladium dichloride (bis). 2-arylpropionic acid derivative was obtained using triphenylphosphine) palladium dichloride) as a catalyst.
미합충국특허 제4,981,995호에서는 요오드화로듐(RHI3)을 촉매로 이용하고, 10kg/㎤ 이하의 낮은 일산화탄소 압력하에서 85℃로 반응시켜 약 60%의 수율로 2-아릴프로피온산을 얻었다. 이 방법은 낮은 압력에서 진행시켜 우수한 수율로 목적물을 제조한다는 장점은 있지만, 값비싼 로듐을 회수하기 위해서는 복잡한 촉매 회수공정이 추가로 필요하다.In U.S. Patent No. 4,981,995, rhodium iodide (RHI3) was used as a catalyst and reacted at 85 DEG C under a low carbon monoxide pressure of 10 kg / cm 3 or less to obtain 2-arylpropionic acid in a yield of about 60%. This method has the advantage of producing the desired product in good yield by running at low pressure, but additional complicated catalyst recovery processes are required to recover expensive rhodium.
미합중국특허 제4,937,362호에서는 아릴 알코올을 5∼500kg/㎤(주로 100kg/㎤)의 일산화탄소 압력에서 요오드화니켈(Nil2) 촉매의 존재하에서 50∼300℃의 온도로 반응시켜 약 80%의 수율로 2-아릴프로피온산을 얻었다.In US Pat. No. 4,937,362, aryl alcohol is reacted at a temperature of 50-300 ° C. in the presence of a nickel iodide (Nil 2) catalyst at a carbon monoxide pressure of 5-500 kg / cm 3 (mainly 100 kg / cm 3), yielding a yield of about 80%. Aryl propionic acid was obtained.
일본특허공개 소59-95,238호에서는 촉매로서 팔라듐 화합물을, 용매로는 벤젠을 사용하여 약 17%의 그다지 높지 않은 수율로 2-아릴프로피온산을 얻었다.In Japanese Patent Laid-Open No. 59-95,238, 2-arylpropionic acid was obtained in a very high yield of about 17% using a palladium compound as a catalyst and benzene as a solvent.
유럽특허 제76,721호, 제76,722호와 독일연방공화국 2,557,011호에서는 코발트 옥타카보닐[(Co)2(Co)8] 촉매를 이용하여 2-아릴프로피온산을 제조하였는데, 이 방법은 수층과 유기층의 두상이 반응용액중에 존재하고 반응을 원활히 진행시키기 위하여 상간 이동 촉매를 사용하는 것이 특징이다.European Patent Nos. 76,721, 76,722 and 2,557,011 have prepared 2-arylpropionic acid using a cobalt octacarbonyl [(Co) 2 (Co) 8 ] catalyst. It is characterized by using a phase transfer catalyst to exist in this reaction solution and to facilitate the reaction.
미합중국특허출원 제91-4,981,995호와 제91-5,166,418호에 의하면 촉매로 팔라듐 클로라이드(Pdcl2)를 사용하고, 트리페닐포스핀, 염화수소 등을 첨가하여 130∼140℃의 반응온도와 1000∼2000psig의 일산화탄소의 압력을 가지는 반응조건하에서 3∼5시간 반응시켜 우수한 수율로 2-아릴프로피온산을 얻었다.According to U.S. Patent Application Nos. 91-4,981,995 and 91-5,166,418, palladium chloride (Pdcl 2 ) is used as a catalyst and triphenylphosphine, hydrogen chloride, etc. are added to the reaction temperature of 130 to 140 ° C and 1000 to 2000 psig. The reaction was carried out for 3 to 5 hours under reaction conditions having a pressure of carbon monoxide to obtain 2-arylpropionic acid with excellent yield.
상기에서는 전이금속 촉매하에서의 카르보닐화 반응에 의한 2-아릴프로피온산의 제조방법의 예를 다수 기재하였다. 그러나 상기 종래방법은 대부분 부식성이 있는 반응원료를 사용하면서도 그 반응온도가 100℃ 이상의 고온, 그리고 1000psig 이상의 고압에서 진행되기 때문에 이를 위한 장치비의 부담이 크며, 또한 값비싼 귀금속 촉매를 사용하는 단점이 있다. 특히 상기 종래 제조방법 중 미합중국특허출원 제91-4,981,995호와 제91-5,166,418호는 반응압력 500psig 이상, 최대 2000psig의 고압에서 실행되기 때문에 그로인한 장치비 문제로 인하여 이를 상업화 하기에는 어려움이 많다. 또한, 10% 이상의 무기산 존재 및 130℃의 반응조건에서 이용될 수 있는 반응용기의 재질은 매우 고가이며, 이러한 재질의 용기를 사용한다 할지라도 높은 압력을 견뎌내기 위해서는 많은 비용이 소요될 뿐아니라 부식문제도 완전히 해결되지 않기 때문에 경제적인 측면에서 상당히 불리하다.In the above, a number of examples of the preparation method of 2-arylpropionic acid by carbonylation reaction under a transition metal catalyst have been described. However, the conventional method has a disadvantage of using a costly precious metal catalyst because the reaction temperature is mostly used in the corrosive reaction material, but the reaction temperature proceeds at a high temperature of 100 ℃ or higher, and a high pressure of 1000 psig or more. . In particular, the United States Patent Application Nos. 91-4,981,995 and 91-5,166,418 of the conventional manufacturing method is difficult to commercialize this due to the apparatus cost problem because it is carried out at a high pressure of 500psig or more, up to 2000psig. In addition, the material of the reaction vessel that can be used in the presence of more than 10% of inorganic acid and reaction conditions of 130 ℃ is very expensive, even if using a container of this material is not only expensive to endure high pressure but also corrosion problems It is also quite disadvantageous from an economic point of view because it is not completely solved.
이에 본 발명의 발명자들은 종래 2-아릴에틸 알코올의 카로보닐화 반응에 따른 제반 문제점을 해결하기 위해 연구 노력한 결과, 할로겐화전이금속 조촉매와 중합방지제를 첨가하여 낮은 반응압력에서 우수한 수율로 2-아릴프로피온산을 제조하므로써 본 발명을 완성하였다.Accordingly, the inventors of the present invention have tried to solve the problems associated with the conventional carbonylation reaction of 2-arylethyl alcohol, and as a result, by adding a halogenated transition metal promoter and an anti-polymerizing agent, 2-aryl with excellent yield at a low reaction pressure The present invention has been completed by preparing propionic acid.
본 발명은 낮은 반응압력하에서 고수율로 2-아릴프로피온산을 제조하는 방법을 제공하는데 그 목적이 있다.It is an object of the present invention to provide a method for preparing 2-arylpropionic acid at high yield under low reaction pressure.
이하, 본 발명을 상세히 설명하면 다음과 같다.Hereinafter, the present invention will be described in detail.
본 발명은 다음 구조식(II)로 표시되는 1-아릴에틸 알코올, 염화팔라듐 촉매, 트리페닐포스핀 및 염화수소 등을 반응시켜 다음 구조식(I)로 표시되는 2-아릴프로피온산을 제조하는 방법에 있어서, 상기 반응에 할로겐화전이금속 조촉매와 중합방지제를 첨가하여 200∼480psig 반응압력으로 실행하는 것을 특징으로 한다.The present invention provides a method for producing 2-arylpropionic acid represented by the following structural formula (I) by reacting 1-arylethyl alcohol, palladium chloride catalyst, triphenylphosphine, hydrogen chloride, and the like represented by the following structural formula (II), The reaction is carried out at 200 to 480 psig reaction pressure by adding a halogenated transition metal promoter and an polymerization inhibitor to the reaction.
상기식에서, Ar은 상기에서 정의한 바와같다.Wherein Ar is as defined above.
이와같은 본 발명을 더욱 상세히 설명하면 다음과 같다.Referring to the present invention in more detail as follows.
본 발명은 조촉매로서 할로겐화전이금속염을 첨가하고, 중합방지제로서 페노치아진 또는 하이드로퀴논 모노메틸 에티르를 첨가하여 반응압력을 500psig 이하로 낮춘 것에 특징이 있다.The present invention is characterized by lowering the reaction pressure to 500 psig or less by adding a halogenated transition metal salt as a cocatalyst and phenoxyazine or hydroquinone monomethyl ethyr as a polymerization inhibitor.
일반적으로 상기 구조식(II)로 표시되는 1-아릴에틸 알코올을 카르보닐화 반응시켜 2-아릴프로피온산을 제조할 경우, 반응 중간체로서 아릴올레핀(aryloleffin)이 생성되는데, 이 중간체는 산성조건(acid condition)하에서 카로보닐화 반응의 경쟁반응(competitive reaction)으로서 중합반응(poltmerization)이 일어나게 된다. 종래에는 1000∼2000psig의 고압하에서 반응을 진행시키므로써 고분자량의 부반응물 생성을 감소시켰는데 반하여, 본 발명에서는 고분자량의 부반응물의 생성을 억제시키기 위해 중합방지제를 첨가하였고, 또한 낮은 압력으로 인한 반응속도 감소를 극복하기 위해 할로겐화전이금속을 조촉매로 사용하였다.In general, when 2-arylpropionic acid is prepared by carbonylating 1-arylethyl alcohol represented by the above formula (II), an aryloleffin is produced as a reaction intermediate, which is an acid condition. Under), the polymerization reaction occurs as a competitive reaction of the carbonylation reaction. Conventionally, the reaction proceeds under a high pressure of 1000 to 2000 psig to reduce the production of high molecular weight side reactions, whereas in the present invention, a polymerization inhibitor is added to suppress the production of high molecular weight side reactions, and due to the low pressure, In order to overcome the decrease in reaction rate, a halogenated transition metal was used as a promoter.
본 발명에 따른 2-아릴프로피온산의 제조공정을 좀 더 구체적으로 설명하면, 상기 구조식(II)로 표시되는 1-아릴에틸 알코올에 염산수용액, 주촉매인 염화팔라듐, 프리페닐포스핀, 중합방지제 및 조촉매인 할로겐화전이금속을 용매에서 혼합한 다음, 여기에 일산화탄소 기체를 주입하여 내부압력을 200∼480psig로 유지시키고 반응온도를 100∼130℃로 유지시키면서 교반 반응시켜 상기 구조식(I)로 표시되는 본 발명의 목적화합물인 2-아릴프로피온산을 제조한다. 상기 일산화탄소 기체의 주입에 의한 반응압력이 200psig 미만이면 반응속도가 너무 느려지는 문제가 있고, 480psig 초과하면 반응기에 대한 투자비가 높아지는 문제가 있다.In more detail, the process for preparing 2-arylpropionic acid according to the present invention, an aqueous solution of hydrochloric acid in the 1-arylethyl alcohol represented by the formula (II), palladium chloride as the main catalyst, prephenylphosphine, polymerization inhibitor and The halide transition metal as a cocatalyst is mixed in a solvent, followed by injecting carbon monoxide gas to maintain the internal pressure at 200 to 480 psig, and stirring and maintaining the reaction temperature at 100 to 130 ° C, which is represented by Structural Formula (I). To prepare 2-arylpropionic acid which is the target compound of the present invention. If the reaction pressure by the injection of the carbon monoxide gas is less than 200 psig, there is a problem that the reaction rate is too slow, if more than 480 psig there is a problem that the investment cost for the reactor increases.
본 발명에서 사용된 반응물에 있어서, 주촉매로 사용된 염화팔라듐은 원료 알코올에 대하여 0.01∼0.1 당량배가 적당하고, 트리페닐포스핀은 염화팔라듐 촉매에 대하여 1∼3 당량배가 적당하고, 용매는 원료 알코올에 대하여 10∼20 당량배가 적당하다. 이때 용매로는 케톤류(ketones)가 사용됨이 바람직한데 예를 들면 메틸 에틸 케톤, 메틸 이소부틸 케톤, 아세토페논 또는 아세톤 등이다.In the reactants used in the present invention, palladium chloride used as the main catalyst is suitably 0.01 to 0.1 equivalent times the raw material alcohol, triphenylphosphine is suitably 1 to 3 equivalent times the palladium chloride catalyst, and the solvent is the raw material. 10-20 equivalent times with respect to alcohol is suitable. At this time, ketones are preferably used as the solvent, for example, methyl ethyl ketone, methyl isobutyl ketone, acetophenone or acetone.
그리고 본 발명의 특징이라 할 수 있는 조촉매로는 VIB, VIIB, VIIIB, IB, IIB족의 할로겐화물이 사용되는데 그중 특히 바람직하기로는 염화물 예를들면, 염화크로뮴, 염화코발트, 염화철, 염화니켈, 염화아연, 염화망간, 염화카드늄, 염화플래티늄, 염화로듐, 염화루테늄, 염화이리듐 등이다. 조촉매의 사용량은 염화팔라듐 주촉매에 대하여 0.01∼10 당량배의 범위가 바람직하며, 더욱 바람직하기로는 0.05∼0.2 당량배이다. 만약 조촉매의 사용량이 주촉매에 대하여 0.01 당량배 미만이면 반응수율이 현저히 감소하는 문제가 있고, 10 당량배 초과하면 촉매량 증가에 따른 수율향상이 더이상 없게된다.The halide of VIB, VIIB, VIIIB, IB, and IIB is used as a cocatalyst which may be a feature of the present invention. Among them, chlorides such as chromium chloride, cobalt chloride, iron chloride, nickel chloride, Zinc chloride, manganese chloride, cadmium chloride, platinum chloride, rhodium chloride, ruthenium chloride, iridium chloride and the like. The amount of the cocatalyst used is preferably in the range of 0.01 to 10 equivalents, more preferably 0.05 to 0.2 equivalents, relative to the palladium chloride main catalyst. If the amount of the promoter is less than 0.01 equivalent times with respect to the main catalyst, there is a problem that the reaction yield is significantly reduced. If the amount exceeds 10 equivalent times, there is no further improvement in yield due to the increase in the amount of catalyst.
또한, 본 발명에서는 중합방지제로서 페노치아진 또는 하이드로퀴논 모노메틸 에테르를 사용하는 바 그 사용량은 원료 알코올에 대하여 0.005∼0.05 당량배가 바람직하며, 더욱 바람직하기로는 0.008∼0.02 당량배이다. 만약 중합방지제의 사용량이 원료 알코올에 대하여 0.005 당량배 미만이면 중합방지 효과가 없고, 0.05 당량배 초과하면 중합방지제 증가에 따른 수율 향상이 더이상 없다.In the present invention, phenoxyazine or hydroquinone monomethyl ether is used as the polymerization inhibitor, and its amount is preferably 0.005 to 0.05 equivalent times, more preferably 0.008 to 0.02 times the amount of the starting alcohol. If the amount of the polymerization inhibitor is less than 0.005 equivalent times with respect to the raw alcohol, there is no polymerization prevention effect, and if the amount of the polymerization inhibitor exceeds 0.05 equivalent times, there is no further improvement in yield due to the increase of the polymerization inhibitor.
상기에서 설명된 바와같이 본 발명에서는 상기 구조식(II)로 표시되는 1-아릴에틸 알코올에 염산수용액, 염화팔라듐 및 트리페닐포스핀 이외에도 중합방지제와 할로겐화전이금속을 부가시키므로써 200∼480psig의 낮은 반응압력에서 고수율의 상기 구조식(I)로 표시되는 2-아릴프로피온산을 제조할 수 있었다.As described above, in the present invention, a low reaction of 200 to 480 psig by adding a polymerization inhibitor and a halogenated transition metal in addition to an aqueous hydrochloric acid solution, palladium chloride and triphenylphosphine to the 1-arylethyl alcohol represented by the formula (II). At high pressure, 2-arylpropionic acid represented by the above structural formula (I) could be prepared.
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 detail with reference to the following Examples, but the present invention is not limited by the Examples.
[실시예 1]Example 1
300ml 용량의 하스텔로이-씨(Hastelloy-C) 재질의 고압반응기에 1-(4-이소부틸페닐)에틸 알코올 17.8g(10 mmol), 10% 염산수용액 36.5g(100 mmol, 염화수소 포함), 염화팔라듐(Pdcl2) 88.7 mg(0.5 mmol), 트리페닐포스핀 419.7 mg(1.6 mmol) 및 용매로서 메틸 에틸 케톤 72.11g(1 mol)를 첨가한 다음 조촉매로서 염화니켈 6수화물(Nicl2·6H2O) 11.9 mg(0.05 mmol)과 중합방지제로서 하이드로퀴논 모노메틸에테르(이하, HOME) 100 mg(0.81 mmol)을 첨가하였다. 반응기에 질소기체를 주입하여 세척한 다음 조촉매로서 염화니켈(Nicl2) 6수화물 0.05 mmol(11.9 mg)를 첨가하였다. 반응기에 질소기체를 주입하여 세척한 다음, 일산화탄소를 350psig로 넣고, 온도를 130℃ 이상 가열하여 반응기 내압을 450psig 정도로 상승시킨다. 이후 일산화탄소의 소모가 차차 줄어들고, 완전히 중단되면 반응생성물을 상온으로 냉각시킨다. 냉각된 반응생성물을 여과하여 환원된 촉매층을 제거한 다음, 여과여액을 증류하여 미반응 원료 및 부반응물 등을 제거하고, 여러번의 재결정을 통하여 순수한 2-(4-이소부틸페닐)프로피온산을 얻었다.17.8 g (10 mmol) of 1- (4-isobutylphenyl) ethyl alcohol, 36.5 g (100 mmol, containing hydrogen chloride), chloride in a 300 ml Hastelloy-C high-pressure reactor 88.7 mg (0.5 mmol) of palladium (Pdcl 2 ), 419.7 mg (1.6 mmol) of triphenylphosphine and 72.11 g (1 mol) of methyl ethyl ketone as solvent were added followed by nickel chloride hexahydrate (Nicl 2 .6H) as a promoter. 2 0) 11.9 mg (0.05 mmol) and 100 mg (0.81 mmol) of hydroquinone monomethyl ether (hereinafter, HOME) were added as an polymerization inhibitor. Nitrogen gas was injected into the reactor and washed, and 0.05 mmol (11.9 mg) of nickel chloride (Nicl 2 ) hexahydrate was added as a promoter. Nitrogen gas is injected into the reactor, followed by washing. Then, carbon monoxide is added to 350 psig, and the temperature is heated to 130 ° C. or higher to increase the internal pressure of the reactor to about 450 psig. After that, the consumption of carbon monoxide gradually decreases, and when completely stopped, the reaction product is cooled to room temperature. The cooled reaction product was filtered to remove the reduced catalyst layer, the filtrate was distilled to remove unreacted raw materials and side reactions, and pure 2- (4-isobutylphenyl) propionic acid was obtained by recrystallization several times.
수율 : 92%Yield: 92%
녹는점 : 75∼77℃Melting Point: 75 ~ 77 ℃
[실시예 2∼13, 비교예 1∼4][Examples 2 to 13 and Comparative Examples 1 to 4]
다음 표의 조건하에서 조촉매의 종류 및 반응조건을 달리하여 상기 실시예 1과 동일한 방법으로 2-(4-이소부틸페닐)프로피온산을 제조하였다.2- (4-isobutylphenyl) propionic acid was prepared in the same manner as in Example 1 by changing the type and reaction conditions of the promoter under the conditions of the following table.
[실시예 14]Example 14
상기 실시예 1과 동일한 방법에 의하되 다만, 원료 알코올로서 1-(6-메톡시나프틸)에틸 알코올을 사용하여 2-(6-메톡시나프틸)프로피온산을 얻었다.According to the same method as in Example 1, except that 2- (6-methoxynaphthyl) propionic acid was obtained using 1- (6-methoxynaphthyl) ethyl alcohol as a starting alcohol.
수율 : 84.4%Yield: 84.4%
녹는점 : 157∼159%Melting Point: 157 ~ 159%
[실시예 15]Example 15
상기 실시예 1과 동일한 방법에 의하되 다만, 원료 알코올로서 1-(m-벤조일페닐)에틸 알코올을 사용하여 2-(m-벤조일페닐)프로피온산을 얻었다.According to the same method as in Example 1, except that 2- (m-benzoylphenyl) propionic acid was obtained using 1- (m-benzoylphenyl) ethyl alcohol as a starting alcohol.
수율 : 80.8%Yield: 80.8%
녹는점 : 93∼94℃Melting Point: 93 ~ 94 ℃
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