KR100510587B1 - Method for preparing diphenylether derivatives substituted halogen - Google Patents
Method for preparing diphenylether derivatives substituted halogen Download PDFInfo
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- KR100510587B1 KR100510587B1 KR10-2001-0088951A KR20010088951A KR100510587B1 KR 100510587 B1 KR100510587 B1 KR 100510587B1 KR 20010088951 A KR20010088951 A KR 20010088951A KR 100510587 B1 KR100510587 B1 KR 100510587B1
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- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms
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Abstract
본 발명은 할로겐이 치환된 디페닐에테르 유도체의 제조방법에 관한 것으로, 더욱 구체적으로 디페닐에테르 화합물을 출발물질로 하여 산용액하에서 할로겐산나트륨을 혼합하여 할로겐화하는 단계; 프리델-크래프트 아실화 반응을 수행하는 단계; 과산화 수소와 무수말린산을 이용하여 산화시키는 단계; 및 가수분해 단계로 이루어진 할로겐이 치환된 디페닐에테르 유도체의 제조방법에 관한 것으로, 종래 염소화 반응에서 사용되는 염소기체 대신 할로겐산나트륨 및 산용액을 사용하므로, 대규모 생산하는데 있어서 비용 및 제조시간이 절약되며, 정량적인 반응에 의해 부생성물을 줄일 수 있으며, 이로 인해 수율을 더욱 높일 수 있으며, 또한 전 과정에서 단일 용매를 사용할 수 있어 공정상의 조작을 단순히 하여 경제성 있는 제조방법이다.The present invention relates to a method for preparing a halogen-substituted diphenyl ether derivative, and more specifically, using a diphenyl ether compound as a starting material, mixing and halogenating a sodium halide in an acid solution; Performing a Friedel-Craft acylation reaction; Oxidizing with hydrogen peroxide and maleic anhydride; And a method for producing a halogen-substituted diphenyl ether derivative having a hydrolysis step. Instead of using a chlorine gas used in a conventional chlorination reaction, sodium halide and an acid solution are used, thus saving cost and manufacturing time in large scale production. In addition, by-products can be reduced by quantitative reactions, thereby increasing the yield, and also a single solvent can be used in the whole process, thereby simplifying the operation of the process, thereby making it an economical manufacturing method.
Description
본 발명은 할로겐이 치환된 디페닐에테르 유도체의 제조방법에 관한 것으로, 더욱 구체적으로 디페닐에테르 화합물을 출발물질로 하여 산용액하에서 할로겐산나트륨을 혼합하여 할로겐화하는 단계; 프리델-크래프트 아실화 반응을 수행하는 단계; 과산화 수소와 무수말린산을 이용하여 산화시키는 단계; 및 가수분해 단계로 이루어진 할로겐이 치환된 디페닐에테르 유도체의 제조방법에 관한 것이다.The present invention relates to a method for preparing a halogen-substituted diphenyl ether derivative, and more specifically, using a diphenyl ether compound as a starting material, mixing and halogenating a sodium halide in an acid solution; Performing a Friedel-Craft acylation reaction; Oxidizing with hydrogen peroxide and maleic anhydride; And it relates to a method for producing a halogen-substituted diphenyl ether derivative consisting of a hydrolysis step.
하기 화학식 1로 표시되는 할로겐이 치환된 디페닐에테르(diphenylether) 화합물, 특히 2,4,4'-트리클로로-2'-히드록시디페닐에테르(2,4,4'-trichloro-2'-hydroxyphenylether)는 항균 방취제로 많이 사용되고 있는 화합물로서, 그람양성균인 포도상구균, 그람음성균인 살모레라균에 탁월한 항균 효과가 있는 화합물이며, 치약, 비누, 화장품 또는 세제 등 생활건강제품에 많이 사용되고 있다.A halogen substituted diphenylether compound represented by Formula 1, particularly 2,4,4'-trichloro-2'-hydroxydiphenyl ether (2,4,4'-trichloro-2'- Hydroxyphenylether) is a compound widely used as an antibacterial deodorant, and has an excellent antimicrobial effect against Gram-positive bacteria Staphylococcus and Gram-negative bacteria Salmorera, and is widely used in toothpaste, soaps, cosmetics or detergents.
(상기식에서, X는 Cl 또는 Br이다.)Wherein X is Cl or Br.
미합중국특허 제 3,506,720호는 2,4,4'-트리클로로-2'-히드록시디페닐에테르에 대해 보고하였으며, 미합중국특허 제 4,467,117호는 상기 화합물에 대한 개선된 제조방법을 보고하고 있다. 구체적으로, 3,6-디클로로니트로벤젠(3,6-dichloronitrobenzen)과 4,6-디클로로페놀(4,6-dichlorophenol)을 출발물질로 하여 중간체인 2,4,4'-트리클로로-2'-아미노디페닐에테르(2,4,4'-trichloro-2'-aminophenylether)를 합성하고, 이를 디아조늄염(diazonium salt)으로 변형시켜 샌드마이어 반응(sandmayer reaction)으로 히드록시기(hydroxy)를 도입하여 2,4,4'-트리클로로-2'-히드록시디페닐에테르를 제조하였다(반응식 1 참조). 그러나, 상기 제조방법은 부산물로 디벤조퓨란(dibenzofuran)이 다량 생성되어 수득율이 낮으며, 생성물과 부산물의 분리과정을 거쳐야 하는 문제점을 가지고 있다.US 3,506,720 reports on 2,4,4'-trichloro-2'-hydroxydiphenyl ether, and US 4,467,117 reports on improved preparation of these compounds. Specifically, 3,6-dichloronitrobenzen (3,6-dichloronitrobenzen) and 4,6-dichlorophenol (4,6-dichlorophenol) as a starting material intermediate 2,4,4'-trichloro-2 ' -Synthesis of amino diphenyl ether (2,4,4'-trichloro-2'-aminophenylether), it is converted into a diazonium salt (diazonium salt) to introduce a hydroxy group (sand) in the sandmayer reaction (sandmayer reaction) 2,4,4'-trichloro-2'-hydroxydiphenylether was prepared (see Scheme 1). However, the production method has a low yield because a large amount of dibenzofuran (dibenzofuran) is produced as a by-product, and has a problem that the product and the by-product must be separated.
2,4,4'-트리클로로-2'-히드록시디페닐에테르의 제조방법에 있어 핵심은 히드록시기 도입에 있다. 상기 제조방법은 벤젠핵에 전자주기인 히드록시가 있으면 커플링이 어려워 강한 전자끌기(electron withdrawing)인 니트로기(nitro)가 치환된 벤젠핵을 사용하였다. 이를 해결한 것이 바이어-빌리거 산화(Baeyer-Villiger oxidation)(EP 887,333; WO 10310)이다. 이를 이용하여 벤젠핵에 전자 끌기인 아세틸(acetyl)을 도입한 뒤 이를 산화반응시켜 아세톡시(acetoxy)로 변화시킨 뒤 가수분해하여 벤젠핵에 히드록시기가 치환된 목적화합물을 얻을 수 있었다.The key to the preparation of 2,4,4'-trichloro-2'-hydroxydiphenyl ether is the introduction of a hydroxy group. The manufacturing method used a benzene nucleus in which a nitro group, which is a strong electron withdrawing, was substituted because the benzene nucleus had hydroxy as an electron cycle. One solution to this is Bayer-Villiger oxidation (EP 887,333; WO 10310). By using this, acetyl (acetyl), which is an electron draw, was introduced into the benzene nucleus, and then oxidized to change to acetoxy, which was then hydrolyzed to obtain a target compound having a hydroxyl group substituted in the benzene nucleus.
구체적으로, 바이어-빌리거 산화(Baeyer-Villiger oxidation)를 이용한 제조방법은 아세틸이 치환되어 있는 디클로 벤젠핵을 커플링(coupling)하여 이를 바이어-빌리거 산화시켜 원하는 목적화합물을 얻을 수 있는 방법(반응식 2)과 커플링되어 있는 디페닐에테르를 염소화한 후 이를 프리델-크래프트 아실화(Friedel-craft acylation) 한다. 이를 바이어-빌리거 산화하여 아세톡시로 변화시킨 후 가수분해하여 목적화합물을 얻는다(반응식 3).Specifically, the manufacturing method using Bayer-Villiger oxidation is a method of coupling the acetyl-substituted dichloro benzene nucleus (coupling) to the Bayer-Billiger oxidation to obtain the desired target compound Chlorination of the diphenyl ether coupled with Scheme 2 is followed by Friedel-craft acylation. This was subjected to Bayer-Billiger oxidation to acetoxy and hydrolyzed to give the desired compound (Scheme 3).
특히 반응식 3의 제조방법은 첫 번째 단계의 염소화 반응에서 염소기체를 사용하는데 이는 공장에서 대규모 생산하는데 있어서 장치 설비비 및 안전관리 유지비가 많이 드는 단점이 있으며, 기체를 사용함으로서 반응시간이 길고 정량적인 반응이 어려워 부생성물(2,2',4,4'-디페닐에테르, 2,2',4,4'-diphenylether)이 생성되어 수율에 많은 소실을 가져다 주는 단점이 있다.In particular, the manufacturing method of Scheme 3 uses chlorine gas in the first stage chlorination reaction, which is disadvantageous in that the equipment cost and safety maintenance cost are high in large-scale production at the factory, and the reaction time is long and quantitative by using gas. Due to this difficulty, by-products (2,2 ', 4,4'-diphenylether, 2,2', 4,4'-diphenylether) are generated, which causes a lot of loss in yield.
이에, 본 발명자들은 상기 화학식 1로 표시되는 할로겐이 치환된 디페닐에테르 유도체를 제조함에 있어서, 첫 단계에서 염소기체 대신 할로겐산나트륨과 산용액을 이용하여 할로겐화하여 짧은 시간에 적은 비용으로 상기 화합물을 제조할 수 있으며, 정량적인 반응이 가능하며, 적은 부산물로 인한 높은 수율로 얻을 수 있음을 알아내어 본 발명을 완성하였다.Thus, the present inventors in the preparation of the halogen-substituted diphenyl ether derivative represented by the formula (1), in the first step to halogenate using a sodium halide and an acid solution instead of chlorine gas to reduce the compound in a short time at a low cost The present invention was completed by finding that it can be prepared, quantitative reaction is possible, and can be obtained with high yield due to small by-products.
본 발명의 목적은 할로겐이 치환된 디페닐에테르 유도체의 제조방법을 제공하는 것이다. It is an object of the present invention to provide a process for the preparation of halogen-substituted diphenylether derivatives.
상기한 목적을 달성하기 위해서, 본 발명은 할로겐이 치환된 디페닐에테르 유도체의 제조방법을 제공한다.In order to achieve the above object, the present invention provides a method for producing a halogen-substituted diphenyl ether derivative.
이하 본 발명을 더욱 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명은 하기 반응식 4와 같이, 할로겐이 치환된 디페닐에테르 유도체의 제조방법에 있어서,The present invention is a method for producing a halogen-substituted diphenyl ether derivative, as shown in Scheme 4,
디페닐에테르(화학식 2)를 출발물질로 하여 산용액 존재하에서 할로겐산나트륨과 반응시켜 2,4,4'-트리할로겐 디페닐에테르(화학식 3)를 제조하는 단계(단계 1),Preparing 2,4,4'-trihalogen diphenyl ether (Formula 3) by reacting with diphenyl ether (Formula 2) as a starting material with sodium halide in the presence of an acid solution (Step 1),
얻어진 2,4,4'-트리할로겐 디페닐에테르(화학식 3)를 알루미늄 촉매하에 아세틸클로라이드와 반응시켜 2,4,4'-트리할로겐-2'-아세틸-디페닐에테르(화학식 4)를 제조하는 단계(단계 2),The obtained 2,4,4'-trihalogen diphenyl ether (Formula 3) was reacted with acetyl chloride under an aluminum catalyst to prepare 2,4,4'-trihalogen-2'-acetyl-diphenyl ether (Formula 4). Step (step 2),
얻어진 2,4,4'-트리할로겐-2'-아세틸-디페닐에테르(화학식 4)를 과산화수소 존재하에 무수말레인산과 반응시켜 2,4,4'-트리할로겐-2'-아세톡시-디페닐에테르(화학식 5)를 제조하는 단계(단계 3), 및The obtained 2,4,4'-trihalogen-2'-acetyl-diphenyl ether (Formula 4) is reacted with maleic anhydride in the presence of hydrogen peroxide to give 2,4,4'-trihalogen-2'-acetoxy-diphenyl Preparing an ether (Formula 5) (Step 3), and
얻어진 2,4,4'-트리할로겐-2'-아세톡시-디페닐에테르(화학식 5)를 강염기와 반응시켜 2,4,4'-트리할로겐-2'-히드록시-디페닐에테르(화학식 1)를 제조하는 단계로 이루어진 제조방법을 포함한다.The obtained 2,4,4'-trihalogen-2'-acetoxy-diphenyl ether (Formula 5) is reacted with a strong base to give 2,4,4'-trihalogen-2'-hydroxy-diphenyl ether (Formula 5) It includes a manufacturing method consisting of a step of producing 1).
(상기식에서, X는 Cl 또는 Br이다.)Wherein X is Cl or Br.
단계 1은 디페닐에테르(화학식 2)를 출발물질로 하여 산용액 존재하에서 할로겐산나트륨과 반응시켜 염소화 반응하는 것으로, 산용액은 염산, 황산, 또는 초산 용액을 사용할 수 있으며, 바람직하게는 염산(35 %)을 사용한다. 할로겐산나트륨은 염소산나트륨(NaClO3) 또는 브롬산나트륨(NaBrO3)을 사용한다. 또한, 할로겐산나트륨을 5∼45℃에서 천천히 첨가하고, 그 온도를 유지하여 반응시키며, 바람직하게는 15∼30℃에서 첨가 및 반응시킨다.Step 1 is a chlorination reaction by reacting with sodium halide in the presence of an acid solution using diphenyl ether (Formula 2) as a starting material. The acid solution may be hydrochloric acid, sulfuric acid, or acetic acid solution. 35%). Sodium halide uses sodium chlorate (NaClO 3 ) or sodium bromate (NaBrO 3 ). In addition, sodium halide is slowly added at 5 to 45 ° C, the temperature is maintained at the temperature, and reacted, preferably at 15 to 30 ° C.
단계 2는 얻어진 2,4,4'-트리할로겐 디페닐에테르(화학식 3)를 알루미늄 촉매하에 아세틸클로라이드와 혼합하여 프리델-크래프트 아실화(Friedel-Craft acylation) 반응하는 것으로, 알루미늄 촉매에 아세틸클로라이드를 가하면 쉽게 아세틸 치환 화합물을 제조할 수 있다.Step 2 is a Friedel-Craft acylation reaction by mixing the obtained 2,4,4'-trihalogen diphenyl ether (Formula 3) with acetyl chloride under an aluminum catalyst, the acetyl chloride to the aluminum catalyst When added, an acetyl substituted compound can be easily prepared.
단계 3은 얻어진 2,4,4'-트리할로겐-2'-아세틸-디페닐에테르(화학식 4)를 과산화수소 존재하에 무수말레인산과 혼합하여 산화시키는 것으로, 고농도의 과산화수소와 무수말레인산에 의해 제조된 말레인과산(maleic peracid)을 이용하여 상기 단계 2의 화합물을 산화시켜 아세톡시로 치환된 화합물을 제조한다.Step 3 is to oxidize the obtained 2,4,4'-trihalogen-2'-acetyl-diphenyl ether (Formula 4) by mixing with maleic anhydride in the presence of hydrogen peroxide, a male prepared by a high concentration of hydrogen peroxide and maleic anhydride The compound of step 2 is oxidized using maleic peracid to prepare a compound substituted with acetoxy.
단계 4는 얻어진 2,4,4'-트리할로겐-2'-아세톡시-디페닐에테르(화학식 5)를 강염기와 혼합하여 가수분해 반응하는 것으로, 강염기는 통상적으로 사용할 수 있는 강염기를 모두 사용할 수 있으며, 바람직하게는 NaOH를 사용한다.Step 4 is a hydrolysis reaction of the obtained 2,4,4'-trihalogen-2'-acetoxy-diphenyl ether (Formula 5) by mixing with a strong base, the strong base can use all of the commonly available strong base And preferably NaOH.
상기 단계 1∼4에서 사용되는 용매는 1,2-디클로로에탄, 트리클로로에탄 또는 테트라클로로에탄을 사용할 수 있다.As the solvent used in the above steps 1 to 4, 1,2-dichloroethane, trichloroethane or tetrachloroethane may be used.
본 발명의 제조방법의 단계 1은 종래 염소화 반응에서 염소기체를 사용하여 발생되는 문제점을 보완하기 위해 산용액하에 할로겐산나트륨을 사용하며, 이로 인해 대규모 생산에 있어서, 짧은 제조시간, 비용 절감, 정량적인 반응에 의해 부산물을 줄일 수 있으며, 이로 인해 높은 수율의 반응을 할 수 있다. 또한, 본 발명의 단계 1∼4에서 용매를 1,2-디클로로에탄, 트리클로로에탄 또는 테트라클로로에탄의 단일 용매를 사용할 수 있으며, 이로 인해 공정상의 조작을 단순히 하여 경제성 있는 화합물을 제조할 수 있다.Step 1 of the preparation method of the present invention uses sodium halide in an acid solution to compensate for the problems caused by the use of chlorine gas in the conventional chlorination reaction, so that in large-scale production, short production time, cost reduction, quantitative By-products can be reduced by phosphorus reactions, which allows high yield reactions. In addition, a single solvent of 1,2-dichloroethane, trichloroethane or tetrachloroethane may be used as the solvent in steps 1 to 4 of the present invention, and thus, economical compounds may be prepared by simply performing a process operation. .
이하, 하기 실시예에 의해 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail by the following examples.
하기 실시예들은 본 발명을 예시하는 것으로 본 발명의 내용이 실시예에 의해 한정되는 것은 아니다.The following examples are illustrative of the invention and are not intended to limit the scope of the invention.
<실시예 1> 2,4,4'-트리클로로-2'-히드록시-디페닐에테르의 제조Example 1 Preparation of 2,4,4'-Trichloro-2'-hydroxy-diphenyl ether
진한 염산 용액(1000 ㎖, 11.1 ㏖)과 에탄올(300 ㎖)의 혼합 용액에 디페닐에테르(270 g, 1.6 ㏖)를 가한 후 발열반응에 의한 과열을 방지하기 위해 얼음 중탕하에서 염소산나트륨(204 g, 1.90 ㏖)을 첨가하고 1 시간 동안 교반하였다. 교반 후 기체크로마토그래피를 사용하여 출발물질과 다른 화합물의 조성을 확인한 후 1,2-디클로로에탄을 가하고 아래층을 분리하였다(트리클로로 : 76 %, 잔류시간 7.56분, 테트라클로로 : 12 %, 잔류시간 8.85분). 유기층에 알루미늄클로라이드(450 g, 3.37 ㏖)를 첨가하고 20℃에서 10 분간 교반하였다. 교반 후 아세틸클로라이드(265 g, 3.37 ㏖)를 천천히 가하고 40℃에서 3 시간 교반하고, 기체크로마토그래피를 이용하여 반응 정도를 확인한 후 냉수(4000 ㎖)를 가하였다(트리클로로아세틸 : 73 %, 잔류시간 10.28분; 테트라클로로 : 12 %, 잔류시간 8.85분). 10 분 후 아래 유기층을 분리 농축하여 용량을 1/3로 줄여 하기 반응에 사용하였다.Diphenyl ether (270 g, 1.6 mol) was added to a mixed solution of concentrated hydrochloric acid solution (1000 ml, 11.1 mol) and ethanol (300 ml), followed by sodium chlorate (204 g) under ice bath to prevent overheating by exothermic reaction. , 1.90 mol) was added and stirred for 1 hour. After stirring, the composition of the starting material and the other compound was confirmed using gas chromatography, and then 1,2-dichloroethane was added thereto, and the lower layer was separated (trichloro: 76%, retention time 7.56 minutes, tetrachloro: 12%, retention time 8.85). minute). Aluminum chloride (450 g, 3.37 mol) was added to the organic layer, and the mixture was stirred at 20 ° C for 10 minutes. After stirring, acetyl chloride (265 g, 3.37 mol) was slowly added thereto, stirred at 40 ° C. for 3 hours, and after confirming the reaction degree using gas chromatography, cold water (4000 mL) was added (trichloroacetyl: 73%, remaining). Time 10.28 min; tetrachloro 12%, retention time 8.85 min). After 10 minutes, the lower organic layer was separated and concentrated to reduce the volume to 1/3 to be used for the following reaction.
1,2-디클로로에탄(200 ㎖)에 무수 말레인산(800 g, 8.08 ㏖)을 가하고, 25℃에서 60 % 과산화수소(228 g, 4.04 ㏖)를 1 시간에 걸쳐서 가하였다. 상기 반응 용액을 50℃에서 2 시간 동안 교반한 후 상기에서 얻어진 용액을 1 시간 동안 가하고 이를 같은 온도에서 10 시간 동안 교반하여 아세톡시 화합물을 얻었다(트리클로로아세톡시 : 68 %, 잔류시간 9.80분; 테트라클로로 11 %, 잔류시간 8.85분). 상기 용액을 여과한 후 아황산수소나트륨(sodium bisulphite) 용액으로 잔류 과산화수소를 제거하였다. 상기 용액에 30 % NaOH 300 ㎖를 가하고 80℃에서 1 시간 동안 교반하여 가수분해를 완결하였다(화합물이 유기층에서 물층으로 옮겨짐). 물층을 1,2-디클로로에탄으로 2 번 씻어준 후 물층을 60 % 황산으로 중화시켜 크루드(crude) 형태의 목적 화합물을 얻었다. 이를 감압증류(195∼199℃, 4 ㎜Hg)하여 순수한 목적 화합물 310 g을 얻었다. 이를 n-헥산으로 처리하여 백색분말의 2,4,4'-트리클로로-2-히드록시디페닐에테르 290 g을 얻었다.Maleic anhydride (800 g, 8.08 mol) was added to 1,2-dichloroethane (200 mL), and 60% hydrogen peroxide (228 g, 4.04 mol) was added at 25 degreeC over 1 hour. After the reaction solution was stirred at 50 ° C. for 2 hours, the solution obtained above was added for 1 hour and stirred at the same temperature for 10 hours to obtain an acetoxy compound (trichloroacetoxy: 68%, retention time 9.80 minutes; Tetrachloro 11%, retention time 8.85 minutes). The solution was filtered and residual hydrogen peroxide was removed with a sodium bisulphite solution. 300 ml of 30% NaOH was added to the solution and stirred at 80 ° C. for 1 hour to complete the hydrolysis (the compound was transferred from the organic layer to the water layer). The water layer was washed twice with 1,2-dichloroethane, and the water layer was neutralized with 60% sulfuric acid to obtain a target compound in the form of a crude. This was distilled under reduced pressure (195-199 degreeC, 4 mmHg), and 310 g of pure target compounds were obtained. This was treated with n-hexane to give 290 g of 2,4,4'-trichloro-2-hydroxydiphenyl ether of white powder.
수율(디페닐에테르 기준) : 62.5 %Yield (based on diphenyl ether): 62.5%
녹는점 : 57∼58℃Melting Point: 57 ~ 58 ℃
1H NMR(CDCl3) δ(ppm) 5.85(s, 1H, OH), 6.68(d, 2H, J=8.7 ㎐), 6.80(dd, 2H, J=2.4 ㎐, J=2.4 ㎐), 6.94(d, 2H, J=8.8 ㎐), 7.08(d, 2H, J=2.4 ㎐), 7.21(dd, 2H, J=2.5 ㎐, J=2.5 ㎐), 7.49(d, 2H, J=2.5 ㎐) 1 H NMR (CDCl 3 ) δ (ppm) 5.85 (s, 1H, OH), 6.68 (d, 2H, J = 8.7 Hz), 6.80 (dd, 2H, J = 2.4 Hz, J = 2.4 Hz), 6.94 (d, 2H, J = 8.8 Hz), 7.08 (d, 2H, J = 2.4 Hz), 7.21 (dd, 2H, J = 2.5 Hz, J = 2.5 Hz), 7.49 (d, 2H, J = 2.5 Hz) )
상술한 바와 같이, 본 발명의 제조방법은 할로겐이 치환된 디페닐에테르 유도체를 제조함에 있어서, 염소화를 위해 염소기체를 사용하는 종래의 제조방법은 대규모 생산에 있어서 장치 설비비 및 안전관리 유지비가 많이 소요되는 단점이 있으며, 또한 기체를 사용함으로 반응시간이 길고 정량적인 반응이 어려워 부생성물이 생성되어 수율에 많은 손실을 가져다 준다. 이에 본 발명은 할로겐화 반응에 있어서 염소기체 대신 할로겐산나트륨과 산용액을 이용하여 제조시간을 절약, 비용을 절감할 수 있으며, 정량적인 반응이 가능하여 부산물의 감소로 인한 높은 수율을 얻을 수 있다. 또한, 모든 반응 과정의 용매를 단일하게 사용할 수 있어 공정상의 조작을 단순히 하여 경제성 있는 화합물을 제조할 수 있다.As described above, in the production method of the present invention, in the preparation of halogen-substituted diphenyl ether derivatives, the conventional production method using chlorine gas for chlorination requires a lot of equipment installation cost and safety management maintenance cost in large scale production. In addition, the use of gas, the reaction time is long, and the quantitative reaction is difficult to produce a by-product to bring a lot of loss in yield. Accordingly, the present invention can reduce the manufacturing time and cost by using sodium halide and an acid solution instead of chlorine gas in the halogenation reaction, it is possible to obtain a high yield due to the reduction of by-products can be quantitative reaction. In addition, the solvents of all the reaction processes can be used singly, so that simple processes can be used to produce economical compounds.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4467117A (en) * | 1983-02-07 | 1984-08-21 | Ciba-Geigy Corporation | Process for the production and purification of 2,4,4'-trichloro-2'-hydroxydiphenylether |
| KR20000065454A (en) * | 1999-04-03 | 2000-11-15 | 남창우 | Method for preparing 2,4,4'-trichloro-2'-hydroxydiphenyl ether without toxic impurities |
| US6239317B1 (en) * | 1997-06-25 | 2001-05-29 | Ciba Specialty Chemicals Corporation | Process for the production of halogeno-o-hydroxydiphenyl compounds |
| KR20010063960A (en) * | 1999-12-24 | 2001-07-09 | 유승렬 | Method of making 2,4,4'-trichloro-2'-hydroxydiphenylether |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4467117A (en) * | 1983-02-07 | 1984-08-21 | Ciba-Geigy Corporation | Process for the production and purification of 2,4,4'-trichloro-2'-hydroxydiphenylether |
| US6239317B1 (en) * | 1997-06-25 | 2001-05-29 | Ciba Specialty Chemicals Corporation | Process for the production of halogeno-o-hydroxydiphenyl compounds |
| KR20000065454A (en) * | 1999-04-03 | 2000-11-15 | 남창우 | Method for preparing 2,4,4'-trichloro-2'-hydroxydiphenyl ether without toxic impurities |
| KR20010063960A (en) * | 1999-12-24 | 2001-07-09 | 유승렬 | Method of making 2,4,4'-trichloro-2'-hydroxydiphenylether |
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