KR0185280B1 - Process for preparation of 2,2-dibromo-3-nitrilopropionamide - Google Patents
Process for preparation of 2,2-dibromo-3-nitrilopropionamide Download PDFInfo
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- KR0185280B1 KR0185280B1 KR1019960015746A KR19960015746A KR0185280B1 KR 0185280 B1 KR0185280 B1 KR 0185280B1 KR 1019960015746 A KR1019960015746 A KR 1019960015746A KR 19960015746 A KR19960015746 A KR 19960015746A KR 0185280 B1 KR0185280 B1 KR 0185280B1
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- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
- C07C255/29—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton containing cyano groups and acylated amino groups bound to the carbon skeleton
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Abstract
본 발명은 하기 구조식(Ⅰ)로 표시되는 2,2-디브로모-3-니트릴로프로피온아미드의 제조방법에 관한 것으로, 좀 더 상세하게는 원료의 효율적 사용, 공정의 단순화 및 유독한 브롬화수소의 외부로의 노출을 방지할 수 있는 고순도의 2,2-디브로모-3-니트릴로프로피온아미드의 제조방법에 관한 것이다.The present invention relates to a method for producing 2,2-dibromo-3-nitrilopropionamide represented by the following structural formula (I), and more particularly, efficient use of raw materials, simplification of the process and toxic hydrogen bromide. The present invention relates to a method for producing high purity 2,2-dibromo-3-nitrilopropionamide that can prevent exposure to the outside.
Description
본 발명은 하기 구조식(Ⅰ)로 표시되는 2,2-디브로모-3-니트릴로프로피온아미드의 제조방법에 관한 것으로, 좀 더 상세하게는 원료의 효율적 사용, 공정의 단순화 및 유독한 브롬화수소의 외부로의 노출을 방지할 수 있는 고순도의 2,2-디브로모-3-니트릴로프로피온아미드의 제조방법에 관한 것이다.The present invention relates to a method for producing 2,2-dibromo-3-nitrilopropionamide represented by the following structural formula (I), and more particularly, efficient use of raw materials, simplification of the process and toxic hydrogen bromide. The present invention relates to a method for producing high purity 2,2-dibromo-3-nitrilopropionamide that can prevent exposure to the outside.
일반적으로 상기 구조식(Ⅰ)로 표시되는 2,2-디브로모-3-니트릴로프로피온아미드 화합물은 제지용 슬라임처리제로 널리 사용되는 중요한 화합물로서 제조방법은 미합중국 특허 제 3,751,444호, 유럽특허 제 308,184호, 영국특허 제 1,103,391호 등에 제안되어 있다.Generally, the 2,2-dibromo-3-nitrilopropionamide compound represented by the above structural formula (I) is an important compound widely used as a slime treatment agent for papermaking. The manufacturing method is US Patent No. 3,751,444 and European Patent No. 308,184. And British Patent No. 1,103,391.
미합중국 특허 제 3,751,444호에서는 하기 구조식(Ⅱ)로 표시되는 시아노아세트아미드와 브롬을 브롬화수소가 포함된 물에서 반응시킨 다음, 이때 부생되는 브롬화수소를 브롬산나트륨(NaBrO3)을 사용하여 브롬으로 치환시키고, 상기 브롬을 이용하여 하기 구조식(Ⅱ)로 표시되는 미반응 시아노아세트아미드와 반응시킴으로써 상기구조식(Ⅰ)로 표시되는 목적화합물을 제조하는 반응시킴으로써 상기 구조식(Ⅰ)로 표시되는 목적화합물을 제조하는 방법을 게시하고 있으나, 브롬화수소가 포함된 여액을 반응수로 사용하기 때문에 전 공정이 유리나 테프론 등으로 코팅된 고가의 장치가 필요할뿐만 아니라 부생되는 브롬화수소를 산화시키기 위해서 고체인 브롬산나트륨을 사용함으로써 금속염이 축적되는 것을 피할 수 없기에 이를 조절하기 위해 여액을 항상 일정량씩 제거해 주어야 하는 공정상의 불편함이 있다.In U.S. Patent No. 3,751,444, cyanoacetamide represented by Structural Formula (II) and bromine are reacted in water containing hydrogen bromide, and the by-product hydrogen bromide is converted to bromine using sodium bromide (NaBrO 3 ). Substituting and reacting with unreacted cyanoacetamide represented by the following structural formula (II) using bromine to produce the target compound represented by the above structural formula (I). It is published a method of preparing a solution, but because the filtrate containing hydrogen bromide is used as the reaction water, not only an expensive device coated with glass or Teflon is required, but also bromic acid as a solid to oxidize by-product hydrogen bromide. Accumulation of the filtrate in order to control There is an inconvenience in the process that must always be removed by a certain amount.
유럽특허 제 308,184호에서는 물을 용매로 이용하여 상기 구조식(Ⅱ)로 표시되는 시아노아세트아미드, 브롬, 브롬산나트륨 및 과산화수소(H2O2)를 투입한 후, 80∼100℃에서 연속 반응장치를 사용하여 2,2-디브로모-3-니트릴로프로피온아미드 화합물을 제조하는 방법을 게시하고 있으나, 80℃이상의 고온에서 연속적으로 반응시켜 원하는 목적화합물을 제조하므로 고체인 목적화합물 분리가 어려운 단점이 있다. 즉, 반응여액에 포함된 브롬화수소가 완전 제거됨 없이 목적화합물과 분리하게 되므로 전 공정에서 부식성이 심한 브롬화수소를 견딜 수 있는고가의 장비가 필요하게 된다. 또한 반응온도가 80℃이상의 고온이므로 부생되는 브롬화수소의 증발이 용이해 이의 조절이 어렵고 유독한 가스가 반응기 밖으로 분산될 위험성이 크다는 문제점이 있다.In European Patent No. 308,184, using cyanoacetamide, bromine, sodium bromide and hydrogen peroxide (H 2 O 2 ) represented by the above formula (II) using water as a solvent, the reaction is continuously carried out at 80 ~ 100 ℃ Although a method for producing 2,2-dibromo-3-nitrilopropionamide compound is disclosed using a device, it is difficult to separate the target compound as a solid because the target compound is prepared by continuously reacting at a high temperature of 80 ° C. or higher. There are disadvantages. That is, since the hydrogen bromide contained in the reaction filtrate is completely removed from the target compound, expensive equipment capable of withstanding highly corrosive hydrogen bromide is required in the entire process. In addition, since the reaction temperature is a high temperature of more than 80 ℃ easy to evaporate the by-product hydrogen bromide, there is a problem that it is difficult to control the toxic gases are dispersed out of the reactor.
영국특허 제 1,103,391호에서는 상기 구조식(Ⅱ)로 표시되는 시아노아세트아미드와 브롬을 반응시킨 후, 부생되는 브롬화수소를 초산 나트륨(CH3COONa)으로 처리하여 브롬화나트륨(NaBr)으로 치환시켜서 2,2-디브로모-3-니트릴로프로피온아미드 화합물을 제조하는 방법을 게시하고 있다.In British Patent No. 1,103,391, the cyanoacetamide represented by Structural Formula (II) is reacted with bromine, and the by-product hydrogen bromide is treated with sodium acetate (CH 3 COONa) to replace sodium bromide (NaBr). A method for preparing a 2-dibromo-3-nitrilopropionamide compound is disclosed.
상기 제조방법 또한 부생되는 브롬화수소 제거를 위해 초산나트륨을 사용함으로써 다량의 초산이 생성되게 된다. 이에 따라 목적화합물의 여과시 초산의 독특한 냄새가 발생하고, 이의 세척을 위해 과량의 물로 사용하게 됨에 따라 다량의 폐수가 발생하는 단점이 있다.The production method also produces a large amount of acetic acid by using sodium acetate to remove by-product hydrogen bromide. Accordingly, a unique odor of acetic acid is generated when the target compound is filtered, and a large amount of wastewater is generated as it is used as excess water for washing thereof.
상기 특허들에서 제안된 제조방법은 모두 그 출발물질이 고체인 시아노아세트아미드를 사용함에 따라 별도의 저장 등의 시설이 필요할 뿐 아니라 취급상에 많은 문제점을 안고 있다. 또한 에틸시아노아세테이트로부터 제조되는 시아노아세트아미드 가격이 에틸시아노아세테이트보다 고가이므로 원가가 상승하는 단점이 있다.All of the manufacturing methods proposed in the above patents require many facilities such as separate storage as well as use of cyanoacetamide as a starting material, and have many problems in handling. In addition, since the cyanoacetamide produced from ethyl cyanoacetate is more expensive than ethyl cyanoacetate, there is a disadvantage in that the cost increases.
한편, 상기 구조식(Ⅱ)로 표시되는 시아노아세트아미드의 제법이 명시된 Organic Synthesis Collective Volume, 179쪽∼181쪽에 따르면, 하기 구조식(A)로 표시되는 에틸시아노아세테이트와 암모니아수를 반응시킨후 냉각, 여과, 세척하여 조(組)생성된 시아노아세트아미드를 얻은 다음, 상기 공정중 남은 여액 및 세척액을 증류하여 남은 잔사를 뜨거운 알코올에 녹인후, 여과, 냉각함으로써 나머지 조(組)생성물을 얻고, 상기 두 조생성물을 재결정시킴으로써 원하는 목적화합물인 상기 구조식(Ⅰ)로 표시되는 시아노아세트아미드를 제조할 수 있다.On the other hand, according to the Organic Synthesis Collective Volume, page 179 to 181, where the preparation method of cyanoacetamide represented by the above formula (II) is specified, after cooling the reaction with ethyl cyanoacetate represented by the following formula (A) and ammonia water, Filtration and washing yield crude crude cyanoacetamide, and then the remaining filtrate and wash liquid are distilled off to dissolve the remaining residue in hot alcohol, followed by filtration and cooling to obtain the remaining crude product. By recrystallizing the two crude products can be prepared cyanoacetamide represented by the above formula (I) as a desired target compound.
한편, 시아노아세트아미드의 제조방법은 앞서 언급한 것처럼 상기 구조식(A)로 표시되는 에틸시아노아세테이트를 출발물질로 제조한 후, 여과, 증류, 고온여과 재결정 및 건조 등의 복잡한 처리과정을 거쳐 고체의 시아노아세트아미드를 제조함으로써 공정상 복잡해지고 다량의 폐수가 발생하는 문제점을 안고 있다.On the other hand, the manufacturing method of cyanoacetamide, as mentioned above, after preparing the ethyl cyanoacetate represented by the above formula (A) as a starting material, through a complex process such as filtration, distillation, hot filtration recrystallization and drying The production of solid cyanoacetamide has the problem of complicated process and generation of large amounts of waste water.
따라서, 본 발명의 목적은 보다 간편하게 목적화합물을 제조할 뿐만 아니라, 목적화합물 제조시 반응액중에서 정제를 수행함으로서 유독한 브롬화수소의 외부로 노출없이 고순도로 제품을 제조할 수 있는 제조방법을 제공하는데 있다.Accordingly, an object of the present invention is to provide a method for preparing a product with high purity without exposure to toxic hydrogen bromide by performing purification in the reaction solution when preparing the target compound more simply. have.
상기 목적을 달성하기 위한 본 발명의 방법은 하기 구조식(Ⅰ)로 표시되는 2,2-디브로모-3-니트릴로프로피온아미드의 제조방법에 있어서, 하기 구조식(Ⅲ)으로 표시되는 알킬시아노아세테이트를 물에 용해시킨 다음, 암모니아수를 적가하여 하기 식(Ⅱ)로 표시되는 시아노아세트아미드를 제조한후, 무기산으로 중화시키고, 브롬과 과산화수소를 순차적으로 적가하여 반응시킨 다음, 약산성의 무기염으로 처리하여 여과시키는 것으로 이루어진다.The method of the present invention for achieving the above object is an alkylcyano represented by the following structural formula (III) in the method for producing 2,2-dibromo-3-nitrilopropionamide represented by the following structural formula (I) Acetate was dissolved in water, and ammonia water was added dropwise to prepare cyanoacetamide represented by the following formula (II), neutralized with an inorganic acid, reacted with dropwise addition of bromine and hydrogen peroxide, and then a weakly acidic inorganic salt. Treatment and filtering.
여기서, R은 CH3또는 C2H5이다.Wherein R is CH 3 or C 2 H 5 .
이하 본 발명의 방법을 좀 더 구체적으로 살펴보면 다음과 같다.Hereinafter, the method of the present invention will be described in more detail.
본 발명에 따르면, 목적화합물의 중간체인 상기 구조식(Ⅱ)로 표시되는 시아노아세트아미드의 제조시, 상기 구조식(Ⅲ)으로 표시되는 알킬시아노아세테이트에 암모니아수를 적가하여 아민화 반응시켜 상기 식(Ⅱ)로 표시되는 시아노아세트아미드를 제조한 다음, 무기산으로 상기 반응액의 pH를 7이하로 조절하여 미반응 암모니아가 브롬화공정의 생성물과 부반응을 일으키는 것을 방지한 후에, 후속 공정인 브롬화공정에 사용한다. 이때 시아노아세트아미드를 반응액으로 부터 분리해내지 않고, 동일한 반응기에서 연이어 브롬화반응을 수행할 수 있게 되었으므로 이를 통하여 복잡한 후처리 공정의 생략이 가능해졌으며, 폐수의 발생도 없앨 수 있다. 본 발명에 바람직한 상기 무기산으로는 황산, 염산, 질산, 인산 또는 탄산 등이 있다.According to the present invention, in the preparation of cyanoacetamide represented by the above formula (II), which is an intermediate of the target compound, ammonia water is added dropwise to the alkylcyanoacetate represented by the above formula (III) to amination reaction After preparing the cyanoacetamide represented by II), the pH of the reaction solution is adjusted to 7 or less with an inorganic acid to prevent unreacted ammonia from causing side reaction with the product of the bromination step, and then to the bromination step. use. The cyanoacetamide can be subsequently brominated in the same reactor without separating cyanoacetamide from the reaction solution, thereby making it possible to omit complicated post-treatment processes and to eliminate wastewater. Preferred inorganic acids of the present invention include sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid or carbonic acid.
본 발명에 따르면, 상기 목적화합물 제조시 출발물질을 액체이고 값이 싼 알킬시아노아세테이트를 사용하여 중간체인 시아노아세트아미드를 생성시키고 무기산으로 pH를 조절한 후 생성된 시아노아세트아미드를 용액과 분리함 없이 바로 브롬화 반응에 투입하는 고정을 택하였다. 이를 통하여 시아노아세트아미드를 고체로 얻기위해 필요한 후처리 공정의 생략은 물론, 시아노아세트아미드가 물에 대한 용해성이 좋은 관계로 발생하는 필연적인 손실을 방지할 수 있었다. 또한, 동일 반응기에서 바로 브롬화 공정이 가능함으로서 이송 등에 따른 시간상의 손실 등도 방지할 수 있어 생산성을 크게 향상시킬 수 있었을 뿐만 아니라, 시아노아세트아미드 제조시의 용액을 그대로 브롬화 반응에 사용함에 따라 폐수의 발생이 전혀 발생하지 않는다는 장점을 갖는다.According to the present invention, in the preparation of the target compound, a cyanoacetamide, which is an intermediate, is prepared using a liquid and inexpensive alkylcyanoacetate, and the pH is adjusted with an inorganic acid. The fixation was chosen to put directly into the bromination reaction without separation. Through this, it was possible to omit the post-treatment process necessary to obtain cyanoacetamide as a solid, and to prevent the inevitable loss caused by the good solubility of cyanoacetamide in water. In addition, since the bromination process can be performed directly in the same reactor, it is possible to prevent the loss of time due to the transfer and the like, thereby greatly improving the productivity, and also by using the solution for producing cyanoacetamide as it is for the bromination reaction, It has the advantage that no occurrence occurs at all.
본 발명의 브롬화공정은 상세히 설명하면, 상기 구조식(Ⅱ)로 표시되는 시아노아세트아미드를 제조한 다음, 반응온도를 20∼40℃로 유지시키면서 브롬을 적가하고 브롬이 모두 탈색된 것을 확인한 다음, 과산화수소를 적가하여 반응시킨다. 그후, 상기 반응물을 약산성의 무기염으로 처리하여 pH를 조절한 다음, 여과, 건조시켜 본 발명의 목적화합물을 제조하였다. 이때 브롬과 과산화수소의 사용량은 알킬시아노아세테이트에 대하여 1.0∼1.20몰이 바람직하다.When the bromination process of the present invention will be described in detail, after preparing the cyanoacetamide represented by the above formula (II), while maintaining the reaction temperature at 20 ~ 40 ℃ dropwise dropping brom and confirming that all the bromine is decolorized, The reaction is carried out by dropwise addition of hydrogen peroxide. Thereafter, the reaction product was treated with a weakly acidic inorganic salt to adjust pH, and then filtered and dried to prepare the target compound of the present invention. In this case, the amount of bromine and hydrogen peroxide is preferably 1.0 to 1.20 mol based on alkylcyanoacetate.
한편, 과산화수소는 브롬화 반응시 부생되는 브롬화수소를 20∼40℃에서 산화시켜 브롬으로 재생시킴으로써 브롬량 절감 및 부식성이 심한 브롬화수소를 제거할 수 있는 효과가 있으며, 브롬화 반응후 인산나트륨, 구연산소다, 인산칼륨, 구연산나트륨, 또는 구연산칼륨과 같은 약산성 무기염으로 소량 잔존하는 브롬화수소를 제거함으로서 제품의 안정성을 유지하고 냄새를 제거하였다.Hydrogen peroxide, on the other hand, oxidizes hydrogen bromide by-produced in the bromination reaction at 20 to 40 ° C. and regenerates it into bromine, thereby reducing the amount of bromine and removing highly corrosive hydrogen bromide. By removing the small amount of hydrogen bromide remaining with a weakly acidic inorganic salt such as potassium phosphate, sodium citrate, or potassium citrate, the stability of the product was maintained and the odor was removed.
다시말하면, 브롬화 반응시 부생되어 잔존하는 브롬화수소를 구연산소다나 인산나트륨 등과 같은 무기염으로 처리하여 브롬화수소에 의한 부식을 방지하고 생성물의 분리를 용이하게 하였다. 한편, 무기염의 사용으로 물에 용해된 무기염이 목적화합물이 포함된 반응액에 투입되어도 목적화합물의 순도저하가 없을 뿐만 아니라 여과된 목적화합물에서도 냄새가 발생하지 않는 효과가 있다. 본 발명의 실험결과 15% 염산 용액에서는 목적화합물이 2∼3시간 경과후 순도가 5%정도 저하되며, 염기성 용액인 15% 가성소다 용액이나 10% 아황산나트륨 용액, 10% 중아황산나트륨 용액 등에서는 목적화합물의 분해가 심하게 진행되어 수율이 크게 저하되었다.In other words, the hydrogen bromide remaining by-produced during the bromination reaction was treated with an inorganic salt such as sodium citrate or sodium phosphate to prevent corrosion by hydrogen bromide and facilitate separation of the product. On the other hand, even when the inorganic salt dissolved in water is added to the reaction solution containing the target compound by the use of the inorganic salt, there is no effect on the purity of the target compound, and the odor is not generated even in the filtered target compound. In the 15% hydrochloric acid solution, the purity of the target compound decreased by about 5% after 2 to 3 hours, and in the basic solution, 15% caustic soda solution, 10% sodium sulfite solution, 10% sodium bisulfite solution, etc. Degradation of the compound proceeded severely and the yield greatly decreased.
이하 실시예를 통하여 본 발명의 제조방법 및 그 효과에 대해 구체적으로 설명하지만 이것이 본 발명의 범주를 한정하는 것은 아니다.Hereinafter, the manufacturing method and effects of the present invention will be described in detail with reference to the following examples, but this does not limit the scope of the present invention.
[실시예 1]Example 1
3ℓ플라스크에 메틸시아노아세테이트 400g과 물 300g을 넣고 교반하면서 5∼10℃의 온도에서 28% 암모니아수 235g을 적가하였다. 반응온도를 그대로 유지시키면서 2시간 더 교반시켜 시아노아세트아미드 합성을 완료하였다. 35% 황산용액을 적가시켜 반응물의 pH를 9.5에서 4.0으로 조정한 후, 상기 시아노아세트아미드가 녹아있는 물층의 온도를 30∼35℃로 유지시키면서 브롬 565g을 적가하였고 브롬이 모두 탈색된 것을 확인한 후에 과산화수소(30% 용액) 400g을 적가하여 반응시켰다. 1시간 동안 숙성하여 브롬화 반응을 종결시켰다. 10%의 구연산소다 용액으로 pH를 4.5까지 조정한 후 여과, 건조시켜 목적화합물 645g을 얻었다. 이를 액체 크로마토그라피로 분석한 결과 순도는 98.4%였다.400 g of methyl cyano acetate and 300 g of water were added to a 3 L flask, and 235 g of 28% ammonia water was added dropwise at a temperature of 5 to 10 ° C. while stirring. The cyanoacetamide synthesis was completed by stirring for 2 hours while maintaining the reaction temperature. After adding 35% sulfuric acid solution dropwise to adjust the pH of the reaction from 9.5 to 4.0, bromine 565g was added dropwise while maintaining the temperature of the water layer in which the cyanoacetamide was dissolved at 30-35 ° C. Thereafter, 400 g of hydrogen peroxide (30% solution) was added dropwise to react. The bromination reaction was terminated by aging for 1 hour. The pH was adjusted to 4.5 with 10% sodium citrate solution, filtered and dried to obtain 645 g of the target compound. This was analyzed by liquid chromatography and the purity was 98.4%.
[실시예 2]Example 2
3ℓ플라스크에 메틸시아노아세테이트 350g과 물 300g을 넣고 교반하면서 5∼10℃의 온도에서 28% 암모니아수 225g을 적가하였다. 반응온도를 그대로 유지시키면서 2시간 더 교반시켜 시아노아세트아미드 합성을 완료하였다. 35% 염산용액을 적가시켜 반응물의 pH를 9.5에서 4.0으로 조정한 후, 상기 시아노아세트아미드가 녹아있는 물층의 온도를 30∼35℃로 유지시키면서 브롬 565g을 적가하였고 브롬이 모두 탈색된 것을 확인한 후에 과산화수소(30% 용액) 400g을 적가하여 반응시켰다. 1시간 동안 숙성하여 브롬화 반응을 종결시켰다. 10% 구연산소다 용액으로 pH를 4.5까지 조정한 후 여과, 건조시켜 목적화합물 638g을 얻었다. 이를 액체 크로마토그라피로 분석한 결과 순도는 98.8%였다.350 g of methylcyanoacetate and 300 g of water were added to a 3 L flask, and 225 g of 28% ammonia water was added dropwise at a temperature of 5 to 10 ° C. while stirring. The cyanoacetamide synthesis was completed by stirring for 2 hours while maintaining the reaction temperature. After adding 35% hydrochloric acid solution to adjust the pH of the reaction product from 9.5 to 4.0, bromine 565g was added dropwise while maintaining the temperature of the water layer in which the cyanoacetamide was dissolved at 30-35 ° C. Thereafter, 400 g of hydrogen peroxide (30% solution) was added dropwise to react. The bromination reaction was terminated by aging for 1 hour. The pH was adjusted to 4.5 with 10% sodium citrate solution, filtered and dried to obtain 638 g of the target compound. This was analyzed by liquid chromatography and the purity was 98.8%.
[실시예 3]Example 3
3ℓ플라스크에 메틸시아노아세테이트 350g과 물 300g을 넣고 교반하면서 5∼10℃의 온도에서 28% 암모니아수 235g을 적가하였다. 반응온도를 그대로 유지시키면서 2시간 더 교반시켜 시아노아세트아미드 합성을 완료하였다. 35% 염산용액을 적가시켜 반응물의 pH를 9.5에서 4.0으로 조정한 후, 상기 시아노아세트아미드가 녹아있는 물층의 온도를 30∼35℃로 유지시키면서 브롬 565g을 적가하였고 브롬이 모두 탈색된 것을 확인한 후에 과산화수소(30% 용액) 400g을 적가하여 반응시켰다. 1시간 동안 숙성하여 브롬화 반응을 종결시켰다. 10%의 인산나트륨 용액으로 pH를 4.5까지 조정한 후 여과, 건조시켜 목적화합물 643g을 얻었다. 이를 액체 크로마토그라피로 분석한 결과 순도는 98.2%였다.350 g of methylcyano acetate and 300 g of water were added to a 3 L flask, and 235 g of 28% ammonia water was added dropwise at a temperature of 5 to 10 ° C. while stirring. The cyanoacetamide synthesis was completed by stirring for 2 hours while maintaining the reaction temperature. After adding 35% hydrochloric acid solution to adjust the pH of the reaction product from 9.5 to 4.0, bromine 565g was added dropwise while maintaining the temperature of the water layer in which the cyanoacetamide was dissolved at 30-35 ° C. Thereafter, 400 g of hydrogen peroxide (30% solution) was added dropwise to react. The bromination reaction was terminated by aging for 1 hour. The pH was adjusted to 4.5 with 10% sodium phosphate solution, filtered and dried to give 643 g of the target compound. This was analyzed by liquid chromatography and the purity was 98.2%.
[실시예 4]Example 4
3ℓ플라스크에 메틸시아노아세테이트 350g과 물 300g을 넣고 교반하면서 5∼10℃의 온도에서 28% 암모니아수 225g을 적가하였다. 반응온도를 그대로 유지시키면서 2시간 더 교반시켜 시아노아세트아미드 합성을 완료하였다. 35% 염산용액을 적가시켜 반응물의 pH를 9.5에서 4.0으로 조정한 후, 상기 시아노아세트아미드가 녹아있는 물층의 온도를 30∼35℃로 유지시키면서 브롬 565g을 적가하였고 브롬이 모두 탈색된 것을 확인한 후에 과산화수소(30% 용액) 400g을 적가하여 반응시켰다. 1시간 동안 숙성하여 브롬화 반응을 종결시켰다. 10% 인산카륨 용액으로 pH를 4.5까지 조정한 후 여과, 건조시켜 목적화합물 632g을 얻었다. 이를 액체 크로마토그라피로 분석한 결과 순도는 98.3%였다.350 g of methylcyanoacetate and 300 g of water were added to a 3 L flask, and 225 g of 28% ammonia water was added dropwise at a temperature of 5 to 10 ° C. while stirring. The cyanoacetamide synthesis was completed by stirring for 2 hours while maintaining the reaction temperature. After adding 35% hydrochloric acid solution to adjust the pH of the reaction product from 9.5 to 4.0, bromine 565g was added dropwise while maintaining the temperature of the water layer in which the cyanoacetamide was dissolved at 30-35 ° C. Thereafter, 400 g of hydrogen peroxide (30% solution) was added dropwise to react. The bromination reaction was terminated by aging for 1 hour. The pH was adjusted to 4.5 with 10% sodium phosphate solution, filtered and dried to obtain 632 g of the target compound. This was analyzed by liquid chromatography and the purity was 98.3%.
[실시예 5]Example 5
3ℓ플라스크에 메틸시아노아세테이트 350g과 물 300g을 넣고 교반하면서 5∼10℃의 온도에서 28% 암모니아수 235g을 적가하였다. 반응온도를 그대로 유지시키면서 2시간 더 교반시켜 시아노아세트아미드 합성을 완료하였다. 35% 염산용액을 적가시켜 반응물의 pH를 9.5에서 4.0으로 조정한 후, 상기 시아노아세트아미드가 녹아있는 물층의 온도를 30∼35℃로 유지시키면서 브롬 615g을 적가하였고, 브롬이 모두 탈색된 것을 확인한 후에 과산화수소(30% 용액) 400g을 적가하여 반응시켰다. 1시간 동안 숙성하여 브롬화 반응을 종결시켰다. 10% 인산나트륨 용액으로 pH를 4.5까지 조정한 후 여과, 건조시켜 목적화합물 680g을 얻었다. 이를 액체 크로마토그라피로 분석한 결과 순도는 99.0%였다.350 g of methylcyano acetate and 300 g of water were added to a 3 L flask, and 235 g of 28% ammonia water was added dropwise at a temperature of 5 to 10 ° C. while stirring. The cyanoacetamide synthesis was completed by stirring for 2 hours while maintaining the reaction temperature. After dropping 35% hydrochloric acid solution to adjust the pH of the reaction from 9.5 to 4.0, bromine 615g was added dropwise while maintaining the temperature of the water layer in which the cyanoacetamide was dissolved at 30-35 ° C, and all of the bromine was decolored. After confirmation, 400 g of hydrogen peroxide (30% solution) was added dropwise to react. The bromination reaction was terminated by aging for 1 hour. The pH was adjusted to 4.5 with 10% sodium phosphate solution, filtered and dried to obtain 680 g of the target compound. This was analyzed by liquid chromatography and the purity was 99.0%.
[실시예 6]Example 6
3ℓ플라스크에 메틸시아노아세테이트 350g과 물 300g을 넣고 교반하면서 5∼10℃의 온도에서 28% 암모니아수 235g을 적가하였다. 반응온도를 그대로 유지시키면서 2시간 더 교반시켜 시아노아세트아미드 합성을 완료하였다. 35% 염산용액을 적가시켜 반응물의 pH를 9.5에서 4.0으로 조정한 후, 상기 시아노아세트아미드가 녹아있는 물층의 온도를 30∼35℃로 유지시키면서 브롬 660g을 적가하였고 브롬이 모두 탈색된 것을 확인한 후에 과산화수소(30% 용액) 400g을 적가하여 반응시켰다. 1시간 동안 숙성하여 브롬화 반응을 종결시켰다. 10% 구연산소다 용액으로 pH를 4.5까지 조정한 후 여과, 건조시켜 목적화합물 648g을 얻었다. 이를 액체 크로마토그라피로 분석한 결과 순도는 98.2%였다.350 g of methylcyano acetate and 300 g of water were added to a 3 L flask, and 235 g of 28% ammonia water was added dropwise at a temperature of 5 to 10 ° C. while stirring. The cyanoacetamide synthesis was completed by stirring for 2 hours while maintaining the reaction temperature. After dropping 35% hydrochloric acid solution to adjust the pH of the reaction from 9.5 to 4.0, 660 g of bromine was added dropwise while maintaining the temperature of the water layer in which the cyanoacetamide was dissolved at 30-35 ° C. Thereafter, 400 g of hydrogen peroxide (30% solution) was added dropwise to react. The bromination reaction was terminated by aging for 1 hour. The pH was adjusted to 4.5 with 10% sodium citrate solution, filtered and dried to obtain 648 g of the target compound. This was analyzed by liquid chromatography and the purity was 98.2%.
[실시예 7]Example 7
3ℓ플라스크에 메틸시아노아세테이트 350g과 물 300g을 넣고 교반하면서 5∼10℃의 온도에서 28% 암모니아수 235g을 적가하였다. 반응온도를 그대로 유지시키면서 2시간 더 교반시켜 시아노아세트아미드 합성을 완료하였다. 35% 염산용액을 적가시켜 반응물의 pH를 9.5에서 4.0으로 조정한 후, 상기 시아노아세트아미드가 녹아있는 물층의 온도를 30∼35℃로 유지시키면서 브롬 640g을 적가하였고 브롬이 모두 탈색된 것을 확인한 후에 과산화수소(30% 용액) 420g을 적가하여 반응시켰다. 1시간 동안 숙성하여 브롬화 반응을 종결시켰다. 10%의 인산나트륨 용액으로 pH를 4.5까지 조정한 후 여과, 건조시켜 목적화합물 671g을 얻었다. 이를 액체 크로마토그라피로 분석한 결과 순도는 98.6%였다.350 g of methylcyano acetate and 300 g of water were added to a 3 L flask, and 235 g of 28% ammonia water was added dropwise at a temperature of 5 to 10 ° C. while stirring. The cyanoacetamide synthesis was completed by stirring for 2 hours while maintaining the reaction temperature. After adding 35% hydrochloric acid solution to adjust the pH of the reaction product from 9.5 to 4.0, bromine 640g was added dropwise while maintaining the temperature of the water layer in which the cyanoacetamide was dissolved at 30-35 ° C. Thereafter, 420 g of hydrogen peroxide (30% solution) was added dropwise to react. The bromination reaction was terminated by aging for 1 hour. The pH was adjusted to 4.5 with 10% sodium phosphate solution, filtered and dried to obtain 671 g of the target compound. This was analyzed by liquid chromatography and the purity was 98.6%.
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| KR1019960015746A KR0185280B1 (en) | 1996-05-08 | 1996-05-08 | Process for preparation of 2,2-dibromo-3-nitrilopropionamide |
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| KR1019960015746A KR0185280B1 (en) | 1996-05-08 | 1996-05-08 | Process for preparation of 2,2-dibromo-3-nitrilopropionamide |
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