JP2000026369A - Production of 3-acetoxy-2-methylbenzoyl chloride - Google Patents
Production of 3-acetoxy-2-methylbenzoyl chlorideInfo
- Publication number
- JP2000026369A JP2000026369A JP10211939A JP21193998A JP2000026369A JP 2000026369 A JP2000026369 A JP 2000026369A JP 10211939 A JP10211939 A JP 10211939A JP 21193998 A JP21193998 A JP 21193998A JP 2000026369 A JP2000026369 A JP 2000026369A
- Authority
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- Japan
- Prior art keywords
- ambc
- mol
- acetoxy
- amba
- crystals
- Prior art date
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Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【0001】[0001]
【発明の属する技術分野】本発明は、3−アセトキシ−
2−メチル安息香酸クロライドの製造方法に関する。詳
しくは、3−アセトキシ−2−メチル安息香酸を原料と
し、3−アセトキシ−2−メチル安息香酸クロライドを
結晶として高収率で製造する方法に関する。The present invention relates to 3-acetoxy-
The present invention relates to a method for producing 2-methylbenzoic acid chloride. More specifically, the present invention relates to a method for producing 3-acetoxy-2-methylbenzoic acid chloride as crystals using 3-acetoxy-2-methylbenzoic acid as a raw material in high yield.
【0002】[0002]
【従来の技術】3−アセトキシ−2−メチル安息香酸ク
ロライド(以下AMBCという)は、米国特許第548
4926号の明細書に記載されているように、例えばヒ
ト免疫不全症ウイルスプロテアーゼ阻害剤等の医薬品の
中間体として有用な化合物である。2. Description of the Related Art 3-Acetoxy-2-methylbenzoic acid chloride (hereinafter referred to as AMBC) is disclosed in U.S. Pat.
As described in the specification of US Pat. No. 4,926, the compound is useful as an intermediate of a pharmaceutical such as a human immunodeficiency virus protease inhibitor.
【0003】AMBCの製造方法としては、3−アセト
キシ−2−メチル安息香酸(以下AMBAという)を原
料とし、メチル−t−ブチルエーテル(以下MTBEと
いう)溶媒中で、ジメチルホルムアミド(以下DMFと
いう)を触媒とし、塩化チオニル(SOCl2)でクロ
ル化する方法(WO98/09951)が知られてい
る。As a method for producing AMBC, 3-acetoxy-2-methylbenzoic acid (hereinafter referred to as AMBA) is used as a starting material, and dimethylformamide (hereinafter referred to as DMF) is used in a methyl-t-butyl ether (hereinafter referred to as MTBE) solvent. A method of chlorinating with thionyl chloride (SOCl 2 ) as a catalyst (WO 98/09951) is known.
【0004】[0004]
【発明が解決しようとする課題】上記WO98/099
51に開示の方法は、溶媒であるMTBEが高価であ
り、経済的に有利な方法とはいえない。また、当該特許
では、AMBCを結晶として取得するために、MTBE
を濃縮してトルエンで置換したのち、さらにトルエンを
濃縮して最終的にヘプタンで再結晶をしており、AMB
Cの収率も82.3%と低いばかりでなく、使用溶媒の
種類が多く、操作が煩雑であるという欠点を有してい
る。The above-mentioned WO 98/099
The method disclosed in No. 51 is not economically advantageous because MTBE as a solvent is expensive. In this patent, in order to obtain AMBC as a crystal, MTBE is used.
Is concentrated and replaced with toluene, and then toluene is further concentrated and finally recrystallized with heptane.
Not only is the yield of C as low as 82.3%, but there are drawbacks in that many types of solvents are used and the operation is complicated.
【0005】カルボン酸をクロル化する場合は、一般的
に無溶媒か、またはカルボン酸と反応しないベンゼン、
トルエン等の芳香族炭化水素、塩化メチレン、クロロホ
ルム等のハロゲン化炭化水素などの不活性溶媒を用いる
ことが多い。しかし、芳香族炭化水素やハロゲン化炭化
水素などの溶媒では、生成するAMBCの溶解度が大き
いため、AMBCを結晶として高収率で取得することは
困難である。When chlorinating a carboxylic acid, benzene is generally used without solvent or without reacting with the carboxylic acid.
Inert solvents such as aromatic hydrocarbons such as toluene and halogenated hydrocarbons such as methylene chloride and chloroform are often used. However, in the case of a solvent such as an aromatic hydrocarbon or a halogenated hydrocarbon, it is difficult to obtain AMBC as a crystal in a high yield because the generated AMBC has high solubility.
【0006】一方、ヘキサン、ヘプタン等の脂肪族炭化
水素は、AMBCの溶解度が小さいため、AMBCを結
晶として高収率で取得することは容易であるが、クロル
化反応に使用する原料であるAMBAの溶解度が小さす
ぎるために、クロル化反応は進行しないと考えられてい
た。On the other hand, since aliphatic hydrocarbons such as hexane and heptane have low solubility of AMBC, it is easy to obtain AMBC as crystals in high yield, but AMBA which is a raw material used for chlorination reaction is used. It was thought that the chlorination reaction did not proceed because the solubility of was too low.
【0007】本発明の目的は、上記従来技術の欠点を解
消し、AMBAを原料として用い、AMBCを高純度結
晶として高収率で製造できる3−アセトキシ−2−メチ
ル安息香酸クロライドの製造方法を提供することにあ
る。An object of the present invention is to provide a method for producing 3-acetoxy-2-methylbenzoic acid chloride which can solve the above-mentioned disadvantages of the prior art and can produce AMBC as a high-purity crystal in high yield using AMBA as a raw material. To provide.
【0008】[0008]
【課題を解決するための手段】本発明者らは、上記欠点
を解決するために鋭意試験研究を行った結果、ヘキサ
ン、ヘプタン等の脂肪族炭化水素を溶媒として用いて
も、ピリジン類またはDMF触媒存在下であれば、カル
ボン酸のクロル化反応が進行することを究明し、本発明
を完成させるに至った。Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned drawbacks. As a result, even when an aliphatic hydrocarbon such as hexane or heptane is used as a solvent, pyridines or DMF can be used. It was determined that the carboxylic acid chlorination reaction proceeds in the presence of a catalyst, and the present invention has been completed.
【0009】本発明のAMBCの製造方法は、AMBA
を塩化チオニルでクロル化するに際し、脂肪族炭化水素
溶媒中で、ピリジン類またはDMF存在下にクロル化反
応させることを特徴とする。このように、AMBAを塩
化チオニルでクロル化するに際し、脂肪族炭化水素溶媒
中で、ピリジン類またはDMF存在下にクロル化反応さ
せることによって、脂肪族炭化水素溶媒に対し、生成す
るAMBCの溶解度が小さいため、AMBCを高純度結
晶として高収率で製造することができる。The method for producing AMBC according to the present invention comprises the steps of:
Is characterized by a chlorination reaction in an aliphatic hydrocarbon solvent in the presence of pyridines or DMF. Thus, when chlorinating AMBA with thionyl chloride, the chlorination reaction in the presence of pyridines or DMF in an aliphatic hydrocarbon solvent allows the solubility of AMBC to be produced in the aliphatic hydrocarbon solvent to be increased. Because of its small size, AMBC can be produced as high-purity crystals in high yield.
【0010】[0010]
【発明の実施の形態】本発明において出発原料として使
用するAMBAは、例えば、3−ニトロ−O−トルイル
酸を還元して3−アミノ−2−メチル安息香酸となし、
これをジアゾ化・加水分解して得た3−ヒドロキシ−2
−メチル安息香酸をアセチル化することによって製造で
きる。ただし、本発明で用いるAMBAは、前記の製造
法で得られたものに限定されるものではなく、いずれの
製造法によって得られたものであっても使用することが
できる。BEST MODE FOR CARRYING OUT THE INVENTION AMBA used as a starting material in the present invention is, for example, reduction of 3-nitro-O-toluic acid to give 3-amino-2-methylbenzoic acid,
3-hydroxy-2 obtained by diazotization and hydrolysis of this
-Can be prepared by acetylating methylbenzoic acid. However, the AMBA used in the present invention is not limited to the one obtained by the above-mentioned production method, and any one obtained by any of the production methods can be used.
【0011】本発明において使用する溶媒は、ヘキサ
ン、ヘプタン等の脂肪族炭化水素である。脂肪族炭化水
素溶媒の使用量は、AMBAと溶媒を仕込んだ際に、ハ
ンドリングできればよく、特に制限はないが、通常原料
であるAMBAに対して重量で0.5〜10倍である。The solvent used in the present invention is an aliphatic hydrocarbon such as hexane and heptane. The amount of the aliphatic hydrocarbon solvent used is not particularly limited as long as it can be handled when AMBA and the solvent are charged, and is not particularly limited, but is usually 0.5 to 10 times the weight of AMBA as a raw material.
【0012】本発明において使用する触媒は、ピリジ
ン、ピコリン、ルチジン等のピリジン類またはDMFで
あり、好ましくはピリジン、DMFである。触媒の使用
量は、原料であるAMBA1モルに対して、0.000
001〜0.1モル、好ましくは0.00001〜0.
01モルの範囲である。0.1モルを超えて添加して
も、クロル化反応に影響しないが、必要量以上の使用は
経済的でない。また、0.000001モル未満では、
クロル化反応に長時間を必要とし、好ましくない。The catalyst used in the present invention is a pyridine such as pyridine, picoline, lutidine or the like, or DMF, preferably pyridine or DMF. The amount of the catalyst used is 0.000 to 1 mol of AMBA as a raw material.
001 to 0.1 mol, preferably 0.00001 to 0.1 mol.
The range is 01 mole. Addition of more than 0.1 mol does not affect the chlorination reaction, but using more than the required amount is not economical. Also, if it is less than 0.000001 mol,
The chlorination reaction requires a long time, which is not preferable.
【0013】本発明においてクロル化剤として使用する
塩化チオニルの使用量は、原料であるAMBA1モルに
対して1.0〜2.0モル、好ましくは1.0〜1.5
モルである。AMBA1モルに対して1.0モル未満で
は、AMBAの転化率が低下し、得られるAMBCの品
質が悪化する。また、2.0モルを超えて添加しても、
クロル化反応に影響しないが、必要以上の使用は経済的
でないばかりでなく、後工程で過剰分を除去する場合や
濾過などの作業に支障をきたすこととなる。The amount of thionyl chloride used as a chlorinating agent in the present invention is 1.0 to 2.0 mol, preferably 1.0 to 1.5 mol, per mol of AMBA as a raw material.
Is a mole. If the amount is less than 1.0 mol per 1 mol of AMBA, the conversion rate of AMBA decreases, and the quality of the obtained AMBC deteriorates. Also, even if it is added in excess of 2.0 mol,
Although it does not affect the chlorination reaction, use beyond necessity is not only economical, but also hinders operations such as removal of excess in a later step and filtration.
【0014】本発明においてクロル化の反応温度は、2
5〜70℃、好ましくは30〜60℃の範囲である。反
応温度が70℃を超えると、塩化チオニルの蒸発によっ
て塩化チオニル量が不足するばかりでなく、得られるA
MBCの品質が悪化する。また、25℃未満では、クロ
ル化反応に長時間を必要とし、好ましくない。In the present invention, the chlorination reaction temperature is 2
It is in the range of 5 to 70C, preferably 30 to 60C. When the reaction temperature exceeds 70 ° C., not only the amount of thionyl chloride becomes insufficient due to the evaporation of thionyl chloride, but also the resulting A
MBC quality is degraded. If the temperature is lower than 25 ° C., the chlorination reaction requires a long time, which is not preferable.
【0015】本発明におけるクロル化反応は、通常AM
BAと溶媒および触媒を仕込んだ液中に、塩化チオニル
を滴下して実施する。塩化チオニルの滴下時間は、仕込
み容量、反応温度、反応により生成した塩化水素および
二酸化硫黄の除害能力等に合わせて決定するが、通常
0.5〜24時間程度である。また、塩化チオニルの滴
下終了後は、同じ温度に保持して0.5〜10時間撹拌
すれば、クロル化反応が完結する。[0015] The chlorination reaction in the present invention is usually carried out by AM
The reaction is carried out by dropping thionyl chloride in a solution containing BA, a solvent and a catalyst. The dropping time of thionyl chloride is determined according to the charged capacity, the reaction temperature, the ability to remove hydrogen chloride and sulfur dioxide generated by the reaction, and the like, and is usually about 0.5 to 24 hours. After completion of the dropwise addition of thionyl chloride, the mixture is stirred at the same temperature for 0.5 to 10 hours to complete the chlorination reaction.
【0016】クロル化反応が終了すれば、反応系を減圧
にし、過剰の塩化チオニル、生成した塩化水素および二
酸化硫黄を留出させて除去するのが好ましい。その際、
溶媒が留出した場合は、必要量の溶媒は補充する。When the chlorination reaction is completed, it is preferable to reduce the pressure of the reaction system and distill and remove excess thionyl chloride, generated hydrogen chloride and sulfur dioxide. that time,
If the solvent distills off, replenish the required amount of solvent.
【0017】クロル化反応終了後または過剰の塩化チオ
ニル、反応により生成した塩化水素および二酸化硫黄を
留出させて除去したのち、反応液を10℃以下に冷却す
ると、脂肪族炭化水素に対するAMBCの溶解度が小さ
いため、AMBCが結晶として析出する。析出したAM
BC結晶は、遠心分離、減圧濾過等の手段を用いて分離
する。分離したAMBCは、減圧乾燥すればAMBCを
高純度結晶として回収することができる。After the completion of the chlorination reaction or after distilling off excess thionyl chloride, hydrogen chloride formed by the reaction and sulfur dioxide, the reaction mixture is cooled to 10 ° C. or lower, and the solubility of AMBC in aliphatic hydrocarbons is reduced. Is small, AMBC precipitates as crystals. AM deposited
BC crystals are separated by means such as centrifugation and filtration under reduced pressure. The separated AMBC can be recovered as high-purity crystals by drying under reduced pressure.
【0018】回収したAMBCの色相は、原料であるA
MBAの色相に影響され、白色のAMBAを用いると白
色のAMBCが得られるが、着色したAMBAを用いる
と同様に着色したAMBCが得られる。したがって、着
色したAMBAを原料として使用し、白色のAMBCが
必要な場合には、クロル化反応終了後または過剰の塩化
チオニル、生成した塩化水素および二酸化硫黄を留出さ
せて除去したのち、反応液に活性炭を添加して脱色処理
するか、分離回収したAMBCを再度ヘキサン、ヘプタ
ン等に溶解して活性炭により脱色処理すればよい。The hue of the recovered AMBC is A
Depending on the hue of the MBA, white AMBC can be obtained using white AMBA, but similarly colored AMBC can be obtained using colored AMBA. Therefore, when colored AMBA is used as a raw material and white AMBC is required, after completion of the chlorination reaction or after distilling off excess thionyl chloride, generated hydrogen chloride and sulfur dioxide, the reaction solution Activated carbon may be added to decolorize, or AMBC separated and recovered may be dissolved again in hexane, heptane or the like and decolorized with activated carbon.
【0019】[0019]
【実施例】実施例1 撹拌機、還流冷却器および温度計を備えた容量100m
lのガラス製フラスコに、純度99.2%、淡褐色のA
MBA19.4g(0.1モル)とヘプタン19.4g
およびピリジン0.008g(0.0001モル)を仕
込み、撹拌しながら50℃まで加熱した。次に滴下漏斗
を用いて塩化チオニル13.1g(0.11モル)を反
応温度50℃に保ちながら1時間かけて滴下し、さらに
3時間同温度に保持して撹拌しつつクロル化反応させ
た。クロル化反応終了後、反応液を5℃まで冷却して析
出した結晶を吸引濾過により濾別分離し、減圧乾燥して
淡褐色のAMBC結晶19.7gを得た。このAMBC
結晶を高速液体クロマトグラフを用いて面積百分率法に
より分析した結果、AMBC98.9%、AMBA0.
7%であり、AMBC収率は、91.7%モルであっ
た。その結果を表1に示す。EXAMPLES Example 1 100 m capacity equipped with a stirrer, reflux condenser and thermometer
In a 1 l glass flask, 99.2% pure, light brown A
MBA 19.4 g (0.1 mol) and heptane 19.4 g
And 0.008 g (0.0001 mol) of pyridine were heated to 50 ° C. while stirring. Then, using a dropping funnel, 13.1 g (0.11 mol) of thionyl chloride was added dropwise over 1 hour while maintaining the reaction temperature at 50 ° C., and a chlorination reaction was performed with stirring at the same temperature for 3 hours. . After the completion of the chlorination reaction, the reaction solution was cooled to 5 ° C., and the precipitated crystals were separated by filtration by suction filtration and dried under reduced pressure to obtain 19.7 g of light brown AMBC crystals. This AMBC
As a result of analyzing the crystals by an area percentage method using a high performance liquid chromatograph, 98.9% of AMBC and 0.2% of AMBA were analyzed.
7%, and the AMBC yield was 91.7% mol. Table 1 shows the results.
【0020】実施例2 ピリジン添加量を0.005g(0.00006モル)
とした以外は、実施例1と同一条件でクロル化反応さ
せ、反応液を5℃まで冷却して析出した結晶を吸引濾過
により濾別分離し、減圧乾燥して淡褐色のAMBC結晶
19.7gを得た。このAMBC結晶を高速液体クロマ
トグラフを用いて面積百分率法により分析した結果、A
MBC97.4%、AMBA1.6%であり、AMBC
収率は、90.4モル%であった。その結果を表1に示
す。Example 2 0.005 g (0.00006 mol) of pyridine was added.
The reaction solution was cooled to 5 ° C., and the precipitated crystals were separated by filtration by suction filtration, dried under reduced pressure, and dried under reduced pressure to obtain 19.7 g of light brown AMBC crystals. I got The AMBC crystal was analyzed by area percentage method using a high performance liquid chromatograph.
MBC 97.4%, AMBA 1.6%, AMBC
The yield was 90.4 mol%. Table 1 shows the results.
【0021】実施例3 ピリジン添加量を0.04g(0.0005モル)、塩
化チオニル滴下量を14.3g(0.12モル)とした
以外は、実施例1と同一条件でクロル化反応させ、反応
液を5℃まで冷却して析出した結晶を吸引濾過により濾
別分離し、減圧乾燥して淡褐色のAMBC結晶18.5
gを得た。このAMBC結晶を高速液体クロマトグラフ
を用いて面積百分率法により分析した結果、AMBC9
8.1%、AMBA1.6%であり、AMBC収率は、
85.4モル%であった。その結果を表1に示す。Example 3 A chlorination reaction was carried out under the same conditions as in Example 1 except that the amount of pyridine added was 0.04 g (0.0005 mol) and the amount of thionyl chloride added was 14.3 g (0.12 mol). The reaction solution was cooled to 5 ° C., and the precipitated crystals were separated by filtration by suction filtration and dried under reduced pressure to obtain 18.5 of light brown AMBC crystals.
g was obtained. As a result of analyzing the AMBC crystal by an area percentage method using a high performance liquid chromatograph, it was found that AMBC 9
8.1%, AMBA 1.6%, AMBC yield is
85.4 mol%. Table 1 shows the results.
【0022】実施例4 ピリジン添加量を0.4g(0.005モル)、塩化チ
オニル滴下量を14.3g(0.12モル)とした以外
は、実施例1と同一条件でクロル化反応させ、反応液を
5℃まで冷却して析出した結晶を吸引濾過により濾別分
離し、減圧乾燥して淡褐色のAMBC結晶19.3gを
得た。このAMBC結晶を高速液体クロマトグラフを用
いて面積百分率法により分析した結果、AMBC97.
0%、AMBA2.1%であり、AMBC収率は、8
8.1モル%であった。その結果を表1に示す。Example 4 A chlorination reaction was carried out under the same conditions as in Example 1 except that the amount of pyridine added was 0.4 g (0.005 mol) and the amount of thionyl chloride added was 14.3 g (0.12 mol). The reaction solution was cooled to 5 ° C., and the precipitated crystals were separated by filtration by suction filtration and dried under reduced pressure to obtain 19.3 g of light brown AMBC crystals. The AMBC crystal was analyzed by an area percentage method using a high performance liquid chromatograph.
0% and AMBA 2.1%, and the AMBC yield was 8%.
It was 8.1 mol%. Table 1 shows the results.
【0023】実施例5 ピリジン添加量を0.005g(0.00006モ
ル)、反応温度を40℃とした以外は、実施例1と同一
条件でクロル化反応させ、反応液を5℃まで冷却して析
出した結晶を吸引濾過により濾別分離し、減圧乾燥して
淡褐色のAMBC結晶18.0gを得た。このAMBC
結晶を高速液体クロマトグラフを用いて面積百分率法に
より分析した結果、AMBC99.6%、AMBA0%
であり、AMBC収率は、84.4モル%であった。そ
の結果を表1に示す。Example 5 A chlorination reaction was carried out under the same conditions as in Example 1 except that the amount of pyridine added was 0.005 g (0.00006 mol) and the reaction temperature was 40 ° C., and the reaction solution was cooled to 5 ° C. The precipitated crystals were separated by filtration by suction filtration and dried under reduced pressure to obtain 18.0 g of light brown AMBC crystals. This AMBC
The crystals were analyzed by an area percentage method using a high performance liquid chromatograph. As a result, 99.6% of AMBC and 0% of AMBA were analyzed.
And the AMBC yield was 84.4 mol%. Table 1 shows the results.
【0024】実施例6 ピリジン添加量を0.04g(0.0005モル)、塩
化チオニル滴下量を14.3g(0.12モル)、触媒
をDMF0.073g(0.001モル)とした以外
は、実施例1と同一条件でクロル化反応させ、反応液を
5℃まで冷却して析出した結晶を吸引濾過により濾別分
離し、減圧乾燥して淡褐色のAMBC結晶18.8gを
得た。このAMBC結晶を高速液体クロマトグラフを用
いて面積百分率法により分析した結果、AMBC96.
3%、AMBA3.3%であり、AMBC収率は、8
5.2モル%であった。その結果を表1に示す。Example 6 Except that the amount of pyridine added was 0.04 g (0.0005 mol), the amount of thionyl chloride added was 14.3 g (0.12 mol), and the catalyst was DMF 0.073 g (0.001 mol). A chlorination reaction was carried out under the same conditions as in Example 1. The reaction solution was cooled to 5 ° C., and the precipitated crystals were separated by filtration by suction filtration and dried under reduced pressure to obtain 18.8 g of light brown AMBC crystals. The AMBC crystals were analyzed by area percentage method using a high performance liquid chromatograph.
3%, AMBA 3.3%, AMBC yield 8
It was 5.2 mol%. Table 1 shows the results.
【0025】実施例7 溶媒としてヘプタンに代えてヘキサン19.4gを用い
た以外は、実施例1と同一条件でクロル化反応させ、反
応液を5℃まで冷却して析出した結晶を吸引濾過により
濾別分離し、減圧乾燥して淡褐色のAMBC結晶20.
3gを得た。このAMBC結晶を高速液体クロマトグラ
フを用いて面積百分率法により分析した結果、AMBC
99.1%、AMBA0.3%であり、AMBC収率
は、94.8モル%であった。その結果を表1に示す。Example 7 The chlorination reaction was carried out under the same conditions as in Example 1 except that 19.4 g of hexane was used instead of heptane as a solvent. The reaction solution was cooled to 5 ° C. Separated by filtration and dried under reduced pressure to give light brown AMBC crystals.
3 g were obtained. As a result of analyzing the AMBC crystal by an area percentage method using a high performance liquid chromatograph, the AMBC crystal was analyzed.
99.1%, AMBA 0.3%, and the AMBC yield was 94.8 mol%. Table 1 shows the results.
【0026】[0026]
【表1】 [Table 1]
【0027】表1に示すように、実施例1〜7のいずれ
においても、純度96%以上のAMBC結晶を、84モ
ル%以上の高収率で得ることができた。As shown in Table 1, in each of Examples 1 to 7, AMBC crystals having a purity of 96% or more could be obtained in a high yield of 84 mol% or more.
【0028】実施例8 撹拌機、還流冷却器および温度計を備えた容量100m
lのガラス製フラスコに、純度99.2%、淡褐色のA
MBA19.4g(0.1モル)とヘキサン19.4g
およびピリジン0.008g(0.0001モル)を仕
込み、撹拌しながら50℃まで加熱した。次に滴下漏斗
を用いて塩化チオニル14.3g(0.12モル)を反
応温度50℃に保ちながら1時間かけて滴下し、さらに
同温度に保持して3時間撹拌しつつクロル化反応させ
た。クロル化反応終了後、反応系を減圧にし、過剰の塩
化チオニル、塩化水素および二酸化硫黄をヘキサンとと
もに留出させて除去した。次にヘキサン19.4gと活
性炭(武田薬品工業株式会社製の商品名:カルボラフィ
ンー20)0.78gを添加し、50℃で0.5時間撹
拌したのち、活性炭を濾別した。濾液を5℃まで冷却し
て析出した結晶を吸引濾過により濾別分離し、減圧乾燥
して白色のAMBC結晶19.7gを得た。このAMB
C結晶を高速液体クロマトグラフを用いて面積百分率法
により分析した結果、AMBC97.7%、AMBA
1.6%であり、AMBC収率は、90.6モル%であ
った。Example 8 A capacity of 100 m equipped with a stirrer, a reflux condenser and a thermometer
In a 1 l glass flask, 99.2% pure, light brown A
19.4 g (0.1 mol) of MBA and 19.4 g of hexane
And 0.008 g (0.0001 mol) of pyridine were heated to 50 ° C. while stirring. Next, 14.3 g (0.12 mol) of thionyl chloride was added dropwise using a dropping funnel over 1 hour while maintaining the reaction temperature at 50 ° C., and the chlorination reaction was performed while maintaining the same temperature and stirring for 3 hours. . After the completion of the chlorination reaction, the pressure of the reaction system was reduced, and excess thionyl chloride, hydrogen chloride and sulfur dioxide were distilled off together with hexane and removed. Next, 19.4 g of hexane and 0.78 g of activated carbon (trade name: Carbofin-20 manufactured by Takeda Pharmaceutical Co., Ltd.) were added, and the mixture was stirred at 50 ° C. for 0.5 hour, and then the activated carbon was filtered off. The filtrate was cooled to 5 ° C., and the precipitated crystals were separated by filtration by suction filtration and dried under reduced pressure to obtain 19.7 g of white AMBC crystals. This AMB
As a result of analyzing the C crystal by an area percentage method using a high performance liquid chromatograph, 97.7% of AMBC, AMBA
It was 1.6% and the AMBC yield was 90.6 mol%.
【0029】比較例1 撹拌機、還流冷却器および温度計を備えた容量100m
lのガラス製フラスコに、純度99.2%、淡褐色のA
MBA19.4g(0.1モル)と塩化メチレン19.
4gおよびピリジン0.008g(0.0001モル)
を仕込み、撹拌しながら40℃まで加熱した。次に滴下
漏斗を用いて塩化チオニル13.1g(0.11モル)
を反応温度40℃に保ちながら1時間かけて滴下し、さ
らに同温度に保持して3時間撹拌しつつクロル化反応さ
せた。クロル化反応終了後、反応液を2℃まで冷却して
析出した結晶を吸引濾過により濾別分離し、減圧乾燥し
て淡褐色のAMBC結晶8.3gを得た。このAMBC
結晶を高速液体クロマトグラフを用いて面積百分率法に
より分析した結果、AMBC99.6%、AMBA0.
3%であり、AMBC収率は、38.9モル%であっ
た。その結果を表2に示す。Comparative Example 1 A capacity of 100 m equipped with a stirrer, a reflux condenser and a thermometer
In a 1 l glass flask, 99.2% pure, light brown A
19.4 g (0.1 mol) of MBA and methylene chloride 19.
4 g and pyridine 0.008 g (0.0001 mol)
And heated to 40 ° C. with stirring. Then, using a dropping funnel, 13.1 g (0.11 mol) of thionyl chloride was used.
Was added dropwise over 1 hour while maintaining the reaction temperature at 40 ° C., and the chlorination reaction was carried out while maintaining the same temperature and stirring for 3 hours. After completion of the chlorination reaction, the reaction solution was cooled to 2 ° C., and the precipitated crystals were separated by filtration by suction filtration and dried under reduced pressure to obtain 8.3 g of light brown AMBC crystals. This AMBC
The crystals were analyzed by an area percentage method using a high performance liquid chromatograph. As a result, 99.6% of AMBC and 0.2% of AMBA were analyzed.
3%, and the AMBC yield was 38.9 mol%. Table 2 shows the results.
【0030】比較例2 溶媒を塩化メチレンに代えてトルエンを用い、反応温度
を50℃とした以外は、比較例1と同一条件でクロル化
反応させ、反応液を2℃まで冷却して析出した結晶を吸
引濾過により濾別分離し、減圧乾燥して淡褐色のAMB
C結晶12.3gを得た。このAMBC結晶を高速液体
クロマトグラフを用いて面積百分率法により分析した結
果、AMBC99.2%、AMBA0.4%であり、A
MBC収率は、57.4モル%であった。その結果を表
2に示す。Comparative Example 2 A chlorination reaction was performed under the same conditions as in Comparative Example 1 except that toluene was used instead of methylene chloride and the reaction temperature was changed to 50 ° C., and the reaction solution was cooled to 2 ° C. to precipitate. The crystals are separated by suction filtration and dried under reduced pressure to give a light brown AMB.
12.3 g of C crystal was obtained. As a result of analyzing the AMBC crystal by an area percentage method using a high performance liquid chromatograph, it was found that AMBC was 99.2% and AMBA was 0.4%.
The MBC yield was 57.4 mol%. Table 2 shows the results.
【0031】[0031]
【表2】 [Table 2]
【0032】表2に示すように、比較例1、2において
は、AMBC結晶純度が99%以上と高純度であるが、
AMBC収率は60モル%を下回っており、実施例のA
MBC収率84モル%以上に比較して大幅に低収率であ
る。As shown in Table 2, in Comparative Examples 1 and 2, the AMBC crystal purity was as high as 99% or more.
The AMBC yield was less than 60 mol%,
The yield is significantly lower than the MBC yield of 84 mol% or more.
【0033】[0033]
【発明の効果】本発明のAMBCの製造方法は、AMB
Aを塩化チオニルでクロル化するに際し、脂肪族炭化水
素溶媒中で、ピリジン類またはDMF触媒存在下にクロ
ル化反応させることによって、脂肪族炭化水素溶媒に対
する生成するAMBCの溶解度が小さいため、AMBC
を高純度で、しかも高収率で得ることができる。According to the method for producing AMBC of the present invention, AMB
When chlorinating A with thionyl chloride, the chlorination reaction is carried out in an aliphatic hydrocarbon solvent in the presence of a pyridine or DMF catalyst, so that the solubility of AMBC formed in the aliphatic hydrocarbon solvent is low, so that AMBC
Can be obtained with high purity and high yield.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 楠 善勝 茨城県鹿嶋市光3番地 住金ケミカル株式 会社開発研究所内 Fターム(参考) 4H006 AA02 AC47 BA51 BB11 BE51 BJ50 BS10 BS30 BS90 4H039 CA52 CD30 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Yoshikatsu Kusunoki, Inventor 3 Hikari, Kashima-shi, Ibaraki Pref.
Claims (1)
塩化チオニルでクロル化するに際し、脂肪族炭化水素溶
媒中で、ピリジン類またはジメチルホルムアミドの存在
下にクロル化反応させることを特徴とする3−アセトキ
シ−2−メチル安息香酸クロライドの製造方法。1. A process for chlorinating 3-acetoxy-2-methylbenzoic acid with thionyl chloride, wherein the chlorination reaction is carried out in an aliphatic hydrocarbon solvent in the presence of pyridines or dimethylformamide. A method for producing acetoxy-2-methylbenzoic acid chloride.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP10211939A JP2000026369A (en) | 1998-07-10 | 1998-07-10 | Production of 3-acetoxy-2-methylbenzoyl chloride |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP10211939A JP2000026369A (en) | 1998-07-10 | 1998-07-10 | Production of 3-acetoxy-2-methylbenzoyl chloride |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2000026369A true JP2000026369A (en) | 2000-01-25 |
Family
ID=16614199
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP10211939A Pending JP2000026369A (en) | 1998-07-10 | 1998-07-10 | Production of 3-acetoxy-2-methylbenzoyl chloride |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP2000026369A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010525006A (en) * | 2007-04-25 | 2010-07-22 | エフ.ホフマン−ラ ロシュ アーゲー | New synthesis method of acid chloride |
-
1998
- 1998-07-10 JP JP10211939A patent/JP2000026369A/en active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010525006A (en) * | 2007-04-25 | 2010-07-22 | エフ.ホフマン−ラ ロシュ アーゲー | New synthesis method of acid chloride |
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