KR100543345B1 - A manufacturing process for 6-chlorobenzoxazol-2-one - Google Patents

A manufacturing process for 6-chlorobenzoxazol-2-one Download PDF

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KR100543345B1
KR100543345B1 KR1020030025121A KR20030025121A KR100543345B1 KR 100543345 B1 KR100543345 B1 KR 100543345B1 KR 1020030025121 A KR1020030025121 A KR 1020030025121A KR 20030025121 A KR20030025121 A KR 20030025121A KR 100543345 B1 KR100543345 B1 KR 100543345B1
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chlorobenzoxazol
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김대황
정근회
장해성
고영관
류재욱
우재춘
구동완
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한국화학연구원
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    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles

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Abstract

본 발명은 다음 화학식 1로 표시되는 6-클로로벤족사졸-2-온의 새로운 제조방법에 관한 것으로서, 보다 상세하게는 다음 화학식 2로 표시되는 벤족사졸-2-온과 염소가스(Cl2)를 특정 양성자성 유기용매(protic organic solvent)와 온도조건에서 반응시켜서 높은 순도와 생성 수율로 6-클로로벤족사졸-2-온을 경제적으로 제조하는 방법에 관한 것이다.The present invention relates to a new method for preparing 6-chlorobenzoxazol-2-one represented by the following formula (1), and more particularly to benzoxazol-2-one and chlorine gas (Cl 2 ) represented by the following formula ( 2 ): The present invention relates to a method for economically producing 6-chlorobenzoxazol-2-one with high purity and yield by reacting with a specific protic organic solvent at a temperature condition.

Figure 112003014018191-pat00001
Figure 112003014018191-pat00001

벤족사졸-2-온, 염소가스, 6-클로로벤족사졸-2-온, 양성자성 유기용매(protic organic solvent)Benzoxazole-2-one, chlorine gas, 6-chlorobenzoxazol-2-one, protic organic solvent

Description

6-클로로벤족사졸-2-온의 새로운 제조방법{A manufacturing process for 6-chlorobenzoxazol-2-one}A manufacturing process for 6-chlorobenzoxazol-2-one

본 발명은 다음 화학식 1로 표시되는 6-클로로벤족사졸-2-온의 새로운 제조방법에 관한 것으로서, 보다 상세하게는 다음 화학식 2로 표시되는 벤족사졸-2-온과 염소가스(Cl2)를 특정 양성자성 유기용매(protic organic solvent)와 온도조건에서 반응시켜서 높은 순도와 생성 수율로 6-클로로벤족사졸-2-온을 경제적으로 제조하는 방법에 관한 것이다.The present invention relates to a new method for preparing 6-chlorobenzoxazol-2-one represented by the following formula (1), and more particularly to benzoxazol-2-one and chlorine gas (Cl 2 ) represented by the following formula ( 2 ): The present invention relates to a method for economically producing 6-chlorobenzoxazol-2-one with high purity and yield by reacting with a specific protic organic solvent at a temperature condition.

Figure 112003014018191-pat00002
Figure 112003014018191-pat00002

상기 화학식 1로 표시되는 화합물은 관용적으로 6-클로로벤족사졸론으로 불리어지고 있으며, 이 화합물은 농·의약의 중요한 중간체로서, 특히, 현재 농약으로 사용되고 있는 페녹사프롭 에틸을 합성하는 데 필수적인 화합물이다.  The compound represented by Chemical Formula 1 is commonly referred to as 6-chlorobenzoxazolone, which is an important intermediate for agrochemicals, and is particularly essential for synthesizing phenoxaprop ethyl currently used as agrochemicals. .

6-클로로벤족사졸-2-온의 합성 과정 중에는 그 화학구조상 친핵 치환반응에 의해서 3개의 이성체가 생길 수 있고, 연속반응으로 디클로로 화합물이 생길 수 있다. During the synthesis of 6-chlorobenzoxazol-2-one, due to its chemical structure, three isomers may be generated by nucleophilic substitution reaction, and dichloro compounds may be generated by continuous reaction.

6-클로로벤족사졸-2-온과 이의 유도체들의 합성법에 대해서는 일부 문헌에 공지되어 있다[미국특허 제2,895,877호, Przem. chem. 37, 418(1958년), 미국화학회지 71, 1265(1949년), Dyes Pigm., 15, 275(1991년)]. 그러나, 미국특허 제2,895,877호와 Przem. chem. 37, 418(1958년)에 기재되어 있는 공지방법으로 제조방법을 수행하게 되면 부 반응물로서 디클로로 화합물이 약 20% 생성되므로, 순수한 6-클로로벤족아졸-2-온을 얻기 위하여 재결정과 같은 공업적으로 적용하는 데 한계가 있는 정제과정을 거쳐야 하는 단점이 있다. 미국화학회지 71, 1265(1949년)에 기재되어 있는 공지방법에서는 값비싼 설푸릴 클로라이드(SO2Cl2)를 사용하는 단점이 있고, Dyes Pigm., 15, 275(1991년)의 방법에서는 폭발의 위험성이 있는 과산화수소를 사용하는 문제점이 있다.Methods of synthesizing 6-chlorobenzoxazol-2-one and derivatives thereof are known in some literature [US Pat. No. 2,895,877, Przem. chem . 37 , 418 (1958), American Chemical Society 71 , 1265 (1949), Dyes Pigm. , 15 , 275 (1991). However, US Pat. No. 2,895,877 and Przem. chem . 37 , 418 (1958), when the preparation method is carried out by the known method, about 20% of a dichloro compound is produced as a side reactant. Thus, industrial processes such as recrystallization to obtain pure 6-chlorobenzazol-2-one are obtained. There is a disadvantage in that the purification process has a limitation in applying. The known method described in US chemistry 71 , 1265 (1949) has the disadvantage of using expensive sulfyl chloride (SO 2 Cl 2 ), Dyes Pigm. In, 15275 method (1991), there is a problem in using hydrogen peroxide in the risk of explosion.

본 발명자들은 농·의약의 중요한 중간체로서의 상기 화학식 1로 표시되는 화합물을 높은 순도와 우수한 수율로 제조하는 경제적인 새로운 방법을 개발하고자 노력하였고, 그 결과 벤족사졸-2-온의 염소화 반응에서 디클로로화를 방지하고 C-6 위치에 대한 염소치환 선택성을 높일 수 있는 특정화된 염소화 반응조건을 찾아냄으로써 본 발명을 완성하게 되었다. The present inventors have tried to develop a new economical method for producing a compound represented by Formula 1 as an important intermediate of agro-medicine with high purity and excellent yield, and as a result, dichlorolation in the chlorination of benzoxazol-2-one The present invention has been accomplished by finding specific chlorination reaction conditions that can prevent and increase chlorine substitution selectivity for the C-6 position.                         

따라서, 본 발명은 생성물의 디클로로화를 방지하여 고순도의 6-클로로벤족아졸-2-온을 경제적으로 제조하는 새로운 방법을 제공하는 데 그 목적이 있다.
Accordingly, an object of the present invention is to provide a new method for economically preparing high-purity 6-chlorobenzoxazol-2-one by preventing dichlorolation of a product.

본 발명은 다음에 나타낸 바와 같이 다음 화학식 2로 표시되는 벤족사졸-2-온을 염소화 반응하여 다음 화학식 1로 표시되는 6-클로로벤족사졸-2-온을 합성하는 반응에 있어, 상기 염소화 반응은 염소가스(Cl2)를 사용하여 양성자성 유기용매(protic organic solvent)와 반응온도 -70 ∼ 20 ℃ 조건으로 수행하여 디클로로화의 부반응을 억제하여 고 순도의 6-클로로벤족사졸-2-온을 제조하는 방법을 그 특징으로 한다.In the present invention, in the reaction for synthesizing 6-chlorobenzoxazol-2-one represented by the following Chemical Formula 1 by chlorination of benzoxazol-2-one represented by the following Chemical Formula 2, the chlorination reaction is By using chlorine gas (Cl 2 ) and protic organic solvent (protic organic solvent) at a reaction temperature of -70 ~ 20 ℃ condition to suppress the side reaction of dichlorolation to 6-chlorobenzoxazol-2-one of high purity The manufacturing method is characterized by the above-mentioned.

Figure 112003014018191-pat00003
Figure 112003014018191-pat00003

이와 같은 본 발명을 더욱 상세히 설명하면 다음과 같다.Referring to the present invention in more detail as follows.

본 발명은 벤족사졸-2-온의 염소화하는 반응시약으로서 비교적 가격이 저렴한 염소가스(Cl2)를 선택 사용하면서도 반응용매 및 반응온도를 특정화하여 수행함으로써 C-6위치에 대한 선택적 치환율을 높여 고 수율 및 고 순도로 6-클로로벤족사졸-2-온을 제조하는 방법에 관한 것이다.The present invention improves the selective substitution rate for the C-6 position by performing reaction by specifying the reaction solvent and the reaction temperature while using chlorine gas (Cl 2 ), which is relatively inexpensive, as the reaction reagent for chlorination of benzoxazole-2-one. The present invention relates to a process for preparing 6-chlorobenzoxazol-2-one in yield and high purity.

본 발명이 반응물질로 사용하는 상기 화학식 2로 표시되는 벤족사졸-2-온은 공지의 화합물로서 이미 알려진 방법으로 합성하여 사용하였다. 예컨대, 값싸 게 구입할 수 있는 기초원료인, o-아미노페놀과 우레아를 자일렌 용매에서 반응시켜서 벤족사졸-2-온을 제조하였다.The benzoxazol-2-one represented by Formula 2 used in the present invention as a reactant was synthesized by a known method as a known compound. For example, benzoxazol-2-one was prepared by reacting o-aminophenol and urea, which are basic raw materials, which are cheaply purchased, in a xylene solvent.

또한, 본 발명에서는 염소화하는 시약(chlorination source)으로 가장 값싼 염소가스(Cl2)를 선택 사용한다는 점에서 경제적 유용성이 있다. In addition, the present invention is economically useful in selecting the cheapest chlorine gas (Cl 2 ) as a chlorination source.

한편, 본 발명에 따른 염소치환 반응을 수행함에 있어 반응용매와 반응온도의 조절이 매우 중요한 바, 본 발명에서는 용매의 선택 사용과 저온반응으로 생성물의 디클로로화를 최대한 방지하는 효과를 얻는다. On the other hand, in performing the chlorine substitution reaction according to the present invention, the control of the reaction solvent and the reaction temperature is very important. In the present invention, the effect of preventing the dichlorolation of the product as much as possible by the selective use of the solvent and low temperature reaction.

반응용매로는 알콜, 포름산, 아세트산 등의 양성자성 유기용매(protic organic solvent)를 사용할 수 있으며, 바람직하기는 메탄올 또는 에탄올을 사용하는 것이다. 또한, 메탄올 또는 에탄올의 알콜 수용액을 사용하여도 본 발명이 목적하는 효과를 얻을 수 있다.The reaction solvent may be a protic organic solvent such as alcohol, formic acid, acetic acid, and the like, preferably methanol or ethanol. In addition, even if an aqueous alcohol solution of methanol or ethanol is used, the desired effect of the present invention can be obtained.

반응온도 또한 매우 중요한 요소로서 -70 ∼ 20 ℃가 적당하지만 반응시간, 편리성, 부 반응을 최소화하는 등의 효과를 고려할 때 -20 ∼ -5 ℃가 특히 바람직하다. The reaction temperature is also a very important factor, while -70 to 20 ° C is appropriate, but -20 to -5 ° C is particularly preferable in consideration of effects such as reaction time, convenience, and minimizing side reactions.

상기한 바와 같은 본 발명에 따른 제조방법의 하나의 구현예로서 벤족사졸-2-온을 메탄올 용매에서 -20 ∼ -10 ℃를 유지하면서 염소화 반응을 수행하게 되면 비용이 많이 드는 별도의 정제과정을 거치지 않고도 고 순도의 6-클로로벤족사졸-2-온을 얻을 수 있다. 즉, 상기한 치환반응이 완결되면 용매를 감압 증류하여 분리만 하더라도 본 발명이 목적하는 상기 화학식 1로 표시되는 6-클로로벤족사졸- 2-온을 고 수율 및 고 순도로 쉽게 얻을 수 있다.As an embodiment of the preparation method according to the present invention as described above, if the chlorination reaction is carried out while maintaining benzoxazol-2-one in methanol solvent at -20 to -10 ℃, a separate expensive purification process High purity 6-chlorobenzoxazol-2-one can be obtained without going through. That is, when the above substitution reaction is completed, the solvent may be easily obtained in high yield and high purity even if the solvent is distilled under reduced pressure to separate the 6-chlorobenzoxazol-2-one represented by the general formula (1).

이와 같은 본 발명은 다음의 실시예에 의거하여 더욱 상세히 설명하겠는 바, 본 발명이 이에 한정되는 것은 아니다.Such a present invention will be described in more detail based on the following examples, but the present invention is not limited thereto.

실시예 1Example 1

500 mL 플라스크에서 벤족사졸-2-온 13.5 g(10 mmol)을 메탄올 150 mL에 녹이고 -20 ℃로 냉각한 후 잘 교반하면서 7.2 g의 염소가스(Cl2)를 2시간 동안에 주입하였다. -20 ∼ -10 ℃를 유지하면서 150 mL의 물을 가하고 1시간 동안 더 교반하고 80 ℃에서 메탄올을 상압 증류한 후, 20 ℃로 냉각하고 여과하여 목적 화합물 16.5 g(97% 수득율, 순도 98%)을 얻었다. In a 500 mL flask, 13.5 g (10 mmol) of benzoxazol-2-one was dissolved in 150 mL of methanol, cooled to −20 ° C., and 7.2 g of chlorine gas (Cl 2 ) was added for 2 hours while stirring well. 150 mL of water was added while maintaining the temperature at -20 to -10 ° C, and further stirred for 1 hour, methanol was distilled under atmospheric pressure at 80 ° C, and then cooled to 20 ° C and filtered to give 16.5 g (97% yield, 98% purity) of the target compound. )

mp 192∼194℃(observed); 1H-NMR(CDCl3, 200MHz) δ7.07(m, 1H), 7.17(m, 1H), 7.25(m, 1H); IR(KBr, cm-1) 3209(m), 3083(w), 1729(s), 1479(m), 1391(w), 1293(w), 1264(w), 1241(w); MS(70 eV) m/z 171(M+), 169(M+), 143, 141, 91. mp 192-194 ° C. (observed); 1 H-NMR (CDCl 3 , 200 MHz) δ 7.07 (m, 1H), 7.17 (m, 1H), 7.25 (m, 1H); IR (KBr, cm −1 ) 3209 (m), 3083 (w), 1729 (s), 1479 (m), 1391 (w), 1293 (w), 1264 (w), 1241 (w); MS (70 eV) m / z 171 (M < + >), 169 (M < + >), 143, 141, 91.

상기 실시예 1에 따른 치환 반응을 수행함에 있어 반응조건에 따른 6-클로로벤족사졸-2-온의 수율 및 순도를 비교하기 위하여 다음 표 1에 요약하여 나타내었다.In performing the substitution reaction according to Example 1 in order to compare the yield and purity of 6-chlorobenzoxazol-2-one according to the reaction conditions are summarized in Table 1 below.

Figure 112003014018191-pat00004
Figure 112003014018191-pat00004
반응용매Reaction solvent 반응온도Reaction temperature 시간time 염소화제Chlorinating agent 수율, %(순도1), %)Yield,% (purity 1) ,%) 메탄올Methanol -20∼-10℃-20 ~ -10 ℃ 2시간2 hours Cl2 Cl 2 97∼98(98)97-98 (98) 에탄올ethanol -5∼5℃-5 to 5 ℃ 2시간2 hours Cl2 Cl 2 97(96)97 (96) 이소프로판올Isopropanol 15∼20℃15 ~ 20 ℃ 2시간2 hours Cl2 Cl 2 -* - * 아세트산Acetic acid 15∼17℃15 to 17 ℃ 2시간2 hours Cl2 Cl 2 97(94)97 (94) 포름산Formic acid 5∼7℃5 ~ 7 ℃ 2시간2 hours Cl2 Cl 2 97(95)97 (95) 물water 0∼5℃0 ~ 5 ℃ 2시간2 hours Cl2 Cl 2 -** - ** 1) 순도 : LC로 확인 * 70% 정도 반응이 진행하고 더 이상 진행하지 않음. ** 10% 정도 반응이 진행하고 더 이상 진행하지 않음. 1) Purity: confirmed by LC                                                  * 70% of the reaction proceeds and no more. ** The reaction is about 10% and no longer progress.

실시예 2Example 2

3 L 플라스크에서 2-벤족사졸론 135 g(1.0 mol)을 메탄올 1.5 L에 녹이고 -20 ℃로 냉각한 후 잘 교반하면서 72 g의 염소가스를 3시간 동안에 주입하였다. -20 ∼ -10 ℃를 유지하면서 150 mL의 물을 가하고 1시간 동안 더 교반하고 80 ℃에서 메탄올을 상압 증류한 후, 20 ℃로 냉각하고 여과하여 목적화합물 166 g(98% 수득율, 순도 98%)을 얻었다. In a 3 L flask, 135 g (1.0 mol) of 2-benzoxazolone was dissolved in 1.5 L of methanol, cooled to −20 ° C., and 72 g of chlorine gas was injected for 3 hours while stirring well. 150 mL of water was added thereto while maintaining the temperature at -20 to -10 ° C, and further stirred for 1 hour. The methanol was distilled under atmospheric pressure at 80 ° C. The mixture was cooled to 20 ° C and filtered to obtain 166 g (98% yield, 98% purity) of the target compound. )

비교예Comparative example

공지방법에 따라 6-클로로벤족사졸-2-온의 합성반응을 수행하였고, 생성물의 수율 및 순도를 다음 표 2에 요약하여 나타내었다.Synthesis of 6-chlorobenzoxazol-2-one was carried out according to the known method, and the yield and purity of the product are summarized in Table 2 below.

Figure 112003014018191-pat00005
Figure 112003014018191-pat00005
공지방법Notice 염소화제-반응용매Chlorination Agent-Reaction Solvent 수율, %(순도, %)1) Yield,% (purity,%) 1) 미국특허 2,895,877(1956년) U.S. Patent 2,895,877 (1956) Cl2-클로로포름Cl 2 -chloroform -* - * Przem. chem. 37, 418(1958년) Przem. chem. 37, 418 (1958) Na2ClO3/HCl-물Na 2 ClO 3 / HCl-water -** - ** 미국화학회지 71, 1265(1949년) American Chemical Society 71, 1265 (1949) SO2Cl2-아세트산SO 2 Cl 2 -Acetic acid 95(98)95 (98) Dyes Pigm, 15, 275(1991년) Dyes Pigm, 15, 275 (1991) HCl/H2O2-아세트산HCl / H 2 O 2 -acetic acid 95∼97(95)95-97 (95) 1) 순도 : LC로 확인 *70% 정도 반응이 진행하고 더 이상 진행하지 않음. **순도가 매우 나쁨.1) Purity: Confirmed by LC * Reaction proceeds about 70% and no further. ** Very poor purity.

이상에서 설명한 바와 같은 본 발명에 따른 제조방법에 의하면 6-클로로벤족사졸-2-온을 고 수율과 고 순도로 생산이 가능하므로 고부가가치 창출로 인한 경제적인 효과가 지대하다.According to the production method according to the present invention as described above it is possible to produce 6-chlorobenzoxazol-2-one in high yield and high purity, so the economic effect of the high value-added is great.

Claims (4)

벤족사졸-2-온을 염소가스(Cl2)와의 염소화 반응시켜 6-클로로벤족사졸-2-온을 제조하는 방법에 있어서,In the method for producing 6-chlorobenzoxazol-2-one by chlorination reaction of benzoxazol-2-one with chlorine gas (Cl 2 ), 상기 염소화 반응은 메탄올 또는 에탄올을 용매로 사용하여 -20 ∼ -5 ℃의 온도 조건에서 수행하는 것을 특징으로 하는 고 순도 6-클로로벤족사졸-2-온의 제조방법.The chlorination reaction is a method for producing high purity 6-chlorobenzoxazol-2-one, characterized in that carried out at a temperature of -20 ~ -5 ℃ using methanol or ethanol as a solvent. 삭제delete 삭제delete 제 1 항에서, 상기 반응용매로는 메탄올을 사용하는 것을 특징으로 하는 제조방법.The method according to claim 1, wherein the reaction solvent is methanol.
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