JP3547497B2 - Method for producing benzothiazolone compound - Google Patents
Method for producing benzothiazolone compound Download PDFInfo
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- JP3547497B2 JP3547497B2 JP25471394A JP25471394A JP3547497B2 JP 3547497 B2 JP3547497 B2 JP 3547497B2 JP 25471394 A JP25471394 A JP 25471394A JP 25471394 A JP25471394 A JP 25471394A JP 3547497 B2 JP3547497 B2 JP 3547497B2
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- Prior art keywords
- reaction
- benzothiazolone
- aminothiophenol
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- urea
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Description
【０００１】
【産業上の利用分野】
本発明はベンゾチアゾロン化合物の製造方法に関する。ベンゾチアゾロン類は、医薬、農薬をはじめとして工業用の重要な中間体原料として利用される。
【０００２】
【従来の技術】
ベンゾチアゾロン化合物の合成法としてアミノチオフェノール類と尿素を反応させる方法は、特開昭５５−３５３８８号と特公平２−３５７５５号において開示されている。特開昭５５−３５３８８号はアミノチオフェノール化合物と尿素を水溶媒中、酸の存在下で反応させる方法であり、アミノチオフェノール類を酸との塩にして反応させている。このために、高濃度の酸を必要とするなど反応容器の材質の選択において不利な点がある。
【０００３】
また特公平２−３５７５５号に示される沸点が１２０℃以上の有機溶媒中でのアミノチオフェノールと尿素の反応においては、反応温度の維持や目的物の分離のためクロルベンゼンや混合キシレン、エチルベンゼン、テトラクロルエタン等の溶媒が好ましく用いられているが、これらの溶媒には尿素が溶解せず、不純物として未反応の尿素が混存するため精製を必要としたり、アミノチオフェノールの劣下を防ぐため、窒素置換をすることが必須であること、さらに高温反応であるので目的物の劣化による収率の低下など不利益な点が多い。
【０００４】
【発明が解決しようとする課題】
アミノチオフェノール類と尿素を溶媒中で反応しベンゾチアゾロン化合物を製造する際、従来反応溶媒として強酸や、沸点が１２０℃以上の溶媒が用いられている。これら従来の反応はその温度が高く、アミノチオフェノールの酸化を防ぐ必要があり、また反応容器の材質も限定されるなど不利な点が多く、より簡便で工業化可能な合成方法の確立が求められている。
【０００５】
【課題を解決するための手段】
本発明は、ベンゾチアゾロン化合物を高収率及び高純度でしかも精製工程を必要としない製造方法を求め、鋭意検討を重ねた結果、ベンゾチアゾロン類を効率よく、しかも高純度で製造する方法を確立することができた。すなわち本発明は化３に示されるアミノチオフェノール類と尿素をアルコール溶媒中、８０℃以上１２０℃未満の温度で反応することを特徴とした、化４で示されるベンゾチアゾロン化合物の製造方法である。
（Ｒは化３、化４に共通して水素原子、ハロゲン、ニトロ、メチル基のいずれかを意味する。）
【０００６】
【化３】
【化４】
本発明で用いられるアルコール系溶媒としてはＣ1〜Ｃ6のアルコールがあげられる。これらのアルコール類は特異的にアミノチオフェノール及び尿素の相方とも溶解せしめるため、８０℃以上１２０℃未満の比較的穏和な条件下で反応が行うことができるものである。かつまた、合成されたベンゾチアゾロンは溶媒としてのアルコール類に室温下では、ほとんど不溶であるため、未反応物は、室温下に冷却したあと、ろ過だけで除くことのできる利点があり、さらには、反応温度が低いため、アミノチオフェノール類の酸化が最小限に抑えられる。また、通常このような反応においては、窒素置換などの酸化防止方法を講じているが、本反応においては、アミノチオフェノール類が酸化反応を受けることのないようなおだやかな条件下であるため、窒素置換を必ずしも必要とせず、副生物の生成も少ないなどの利点がある。
【０００９】
【作用】
本発明で用いられるアルコール系溶媒としては、メタノール、イソプロピルアルコール、ブタノールが例示される。これらのアルコールは、加温下、アミノチオフェノール類、尿素を溶解せしめるため、反応性が良く、８０℃以上１２０℃未満での温度でのベンゾチアゾロン化合物の製造が可能である。この反応温度が８０℃未満では、反応速度が遅く時間的に不利である。
【００１０】
１２０℃以上ではアミノチオフェノールの劣化が見られるほか、これ以上の加熱による、反応速度の向上も実質上認め難く、工業化において経済的にも不利である。尿素の添加量はアミノチオフェノール類に対して、１．０〜１．４モルの添加がよい。これ以上の添加は収率の向上には無関係であり、さらに未反応の尿素が反応生成物中に残存するなど不利な点があるので好ましくない。
【００１１】
【実施例】
以下に実施例を示し本発明を具体的に説明するが、これらにより本発明の範囲が限定されるものではない。
実施例 １
Ｏ−アミノチオフェノール６２ｇ、尿素４２ｇ、１−ブタノール３００ｍｌを還流冷却器付の反応容器中で、攪拌下加熱溶解し、さらに、１１０℃で５時間反応する。反応後室温まで冷却し、２モルの硫酸で弱酸性とし、得られた結晶をろ過し、次いで少量の１−ブタノールで洗浄した。２−ベンゾチアゾロン６６．５ｇを得た。（アミノチオフェノールに対して収率８９％）ＨＰＬＣによる純度は、９９．４％，融点は１３７〜１３９．５℃であった。
【００１２】
実施例 ２〜５
実施例１のＯ−アミノチオフェノールの代わりに、同方法で製造された他の化合物の実施例を示す。
実施例 ６
実施例１の１−ブタノールに代えて１−ペンタノールを用い、同方法で反応し、２−ベンゾチアゾロン６４．８ｇを得た。（アミノチオフェノールに対して収率８７％）ＨＰＬＣによる純度は９９．１％であった。
【００１４】
実施例 ７
Ｏ−アミノチオフェノール３１ｇと尿素２１ｇ、メタノール５０ｍｌを加え、オートクレーブ中で１００℃、１２時間反応した。反応後冷却、さらに２モルの硫酸で弱酸性とし、得られた結晶物をろ過し、少量のメタノールで洗浄した。２−ベンゾチアゾロン３２．９ｇを得た。（アミノチオフェノールに対して８８％）ＨＰＬＣによる純度は９９．３％，融点は１３７〜１３９℃であった。
【００１５】
実施例 ８
実施例７のメタノールの代わりにイソプロピルアルコールを用いて同方法で反応し、２−ベンゾチアゾロン３３．１ｇを得た。（アミノチオフェノールに対して、収率８９％）ＨＰＬＣによる純度は９９．２％であった。
【００１６】
比較例 １
実施例１の反応組成において、反応温度を７５℃で２０時間反応したところ得られた２−ベンゾチアゾロンは６．２ｇであった。（アミノチオフェノールに対して収率８％）
【００１７】
比較例 ２
実施例１の１−ブタノールに代えてキシレンを用い同方法で反応した。２−ベンゾチアゾロンは９．１ｇであった。（アミノチオフェノールに対して収率１２％）
【００１８】
比較例 ３
実施例１の１−ブタノールに代えてにトルエンを用い１１０℃で１０時間反応した。得られた２−ベンゾチアゾロンは６．７ｇであった。（アミノチオフェノールに対して収率９％）
【００１９】
【発明の効果】
アミノチオフェノール類と尿素を反応させ、ベンゾチアゾロン類を得る反応において、アルコール系溶媒を用い、８０℃以上１２０℃未満という反応温度で高収率、高純度品が得られることが判明した。この反応においては、アミノチオフェノールの酸化を防ぐための窒素置換が必ずしも必要でないことや、反応の容易性、さらには強い酸や塩基を必要としないため反応容器の材質を選択する必要がないことなど数多くの利点があり、工業化においても経済的であり、その効果は大きい。[0001]
[Industrial applications]
The present invention relates to a method for producing a benzothiazolone compound. Benzothiazolones are used as important intermediate raw materials for industry, including pharmaceuticals and agricultural chemicals.
[0002]
[Prior art]
Methods for synthesizing benzothiazolone compounds with aminothiophenols and urea are disclosed in JP-A-55-35388 and JP-B-2-35755. JP-A-55-35388 discloses a method in which an aminothiophenol compound and urea are reacted in an aqueous solvent in the presence of an acid, and the aminothiophenol is reacted with an acid as a salt. For this reason, there are disadvantages in selecting the material of the reaction vessel, such as the need for a high concentration of acid.
[0003]
In addition, in the reaction of aminothiophenol and urea in an organic solvent having a boiling point of 120 ° C. or higher as shown in JP-B-2-35755, chlorobenzene, mixed xylene, ethylbenzene, Solvents such as tetrachloroethane are preferably used, but urea does not dissolve in these solvents, and unreacted urea is present as an impurity, so that purification is required, and in order to prevent degradation of aminothiophenol. In addition, there are many disadvantages such as the necessity of replacing with nitrogen, and the reduction of the yield due to the deterioration of the target product due to the high temperature reaction.
[0004]
[Problems to be solved by the invention]
When an aminothiophenol is reacted with urea in a solvent to produce a benzothiazolone compound, a strong acid or a solvent having a boiling point of 120 ° C. or higher has conventionally been used as a reaction solvent. These conventional reactions have high temperatures, need to prevent oxidation of aminothiophenol, and have many disadvantages such as limited material of the reaction vessel.Therefore, it is required to establish a more convenient and industrializable synthesis method. ing.
[0005]
[Means for Solving the Problems]
The present invention seeks a method for producing a benzothiazolone compound with a high yield and a high purity and does not require a purification step, and as a result of intensive studies, establishes a method for producing a benzothiazolone compound efficiently and with a high purity. Was completed. That is, the present invention is a method for producing a benzothiazolone compound represented by Chemical Formula 4, characterized by reacting an aminothiophenol represented by Chemical Formula 3 with urea in an alcohol solvent at a temperature of 80 ° C. or more and less than 120 ° C.
(R represents a hydrogen atom, a halogen, a nitro, or a methyl group in common with Chemical formulas 3 and 4.)
[0006]
Embedded image
Embedded image
Examples of the alcohol solvent used in the present invention the alcohol of C 1 -C 6 and the like. Since these alcohols specifically dissolve both aminothiophenol and urea, the reaction can be carried out under relatively mild conditions of 80 ° C. or more and less than 120 ° C. In addition, since the synthesized benzothiazolone is almost insoluble in alcohols as solvents at room temperature, unreacted substances have the advantage that they can be removed only by filtration after cooling to room temperature, and furthermore, The low reaction temperature minimizes the oxidation of aminothiophenols. Usually, in such a reaction, an antioxidant method such as nitrogen substitution is taken, but in this reaction, since aminothiophenols are under mild conditions such that they do not undergo an oxidation reaction, There are advantages such that nitrogen substitution is not necessarily required and the generation of by-products is small.
[0009]
[Action]
Examples of the alcohol solvent used in the present invention include methanol, isopropyl alcohol, and butanol. Since these alcohols dissolve aminothiophenols and urea under heating, they have good reactivity and can produce benzothiazolone compounds at a temperature of 80 ° C. or more and less than 120 ° C. If the reaction temperature is lower than 80 ° C., the reaction rate is low, which is disadvantageous in terms of time.
[0010]
At a temperature of 120 ° C. or higher, degradation of aminothiophenol is observed, and an increase in the reaction rate due to further heating is practically difficult to recognize, which is economically disadvantageous in industrialization. The addition amount of urea is preferably 1.0 to 1.4 mol based on aminothiophenols. Addition beyond this is irrelevant to the improvement of the yield, and it is not preferable because there are disadvantages such as unreacted urea remaining in the reaction product.
[0011]
【Example】
Hereinafter, the present invention will be described specifically with reference to Examples, but the scope of the present invention is not limited by these Examples.
Example 1
62 g of O-aminothiophenol, 42 g of urea and 300 ml of 1-butanol are heated and dissolved in a reaction vessel equipped with a reflux condenser with stirring, and further reacted at 110 ° C. for 5 hours. After the reaction, the mixture was cooled to room temperature, made weakly acidic with 2 mol of sulfuric acid, and the obtained crystals were filtered and then washed with a small amount of 1-butanol. 66.5 g of 2-benzothiazolone were obtained. (Yield: 89% based on aminothiophenol) The purity by HPLC was 99.4%, and the melting point was 137 to 139.5 ° C.
[0012]
Examples 2 to 5
Examples of other compounds produced by the same method in place of O-aminothiophenol of Example 1 are shown.
Example 6
Using 1-pentanol in place of 1-butanol of Example 1, the reaction was carried out in the same manner to obtain 64.8 g of 2-benzothiazolone. (87% yield based on aminothiophenol) Purity by HPLC was 99.1%.
[0014]
Example 7
31 g of O-aminothiophenol, 21 g of urea and 50 ml of methanol were added, and reacted in an autoclave at 100 ° C. for 12 hours. After the reaction, the reaction mixture was cooled and further made weakly acidic with 2 mol of sulfuric acid, and the obtained crystal was filtered and washed with a small amount of methanol. 32.9 g of 2-benzothiazolone were obtained. (88% based on aminothiophenol) The purity by HPLC was 99.3%, and the melting point was 137 to 139 ° C.
[0015]
Example 8
The reaction was carried out in the same manner as in Example 7 except that isopropyl alcohol was used instead of methanol, to obtain 33.1 g of 2-benzothiazolone. (89% yield based on aminothiophenol) The purity by HPLC was 99.2%.
[0016]
Comparative Example 1
In the reaction composition of Example 1, the reaction temperature was 75 ° C. for 20 hours, and the amount of 2-benzothiazolone obtained was 6.2 g. (8% yield based on aminothiophenol)
[0017]
Comparative Example 2
The reaction was carried out in the same manner as in Example 1, except that xylene was used instead of 1-butanol. The amount of 2-benzothiazolone was 9.1 g. (12% yield based on aminothiophenol)
[0018]
Comparative Example 3
The reaction was carried out at 110 ° C. for 10 hours using toluene instead of 1-butanol in Example 1. The obtained 2-benzothiazolone was 6.7 g. (9% yield based on aminothiophenol)
[0019]
【The invention's effect】
It has been found that in a reaction of reacting an aminothiophenol with urea to obtain a benzothiazolone, a high-yield, high-purity product can be obtained at a reaction temperature of 80 ° C. or more and less than 120 ° C. using an alcohol-based solvent. In this reaction, nitrogen substitution to prevent oxidation of aminothiophenol is not always necessary, and the reaction is easy.In addition, there is no need to select a material for the reaction vessel because a strong acid or base is not required. It has many advantages, such as being economical in industrialization, and its effect is great.
Claims (4)
（Ｒは化１、化２に共通して水素原子、ハロゲン、ニトロ、メチル基のいずれかを意味する。）
(R represents a hydrogen atom, a halogen, a nitro, or a methyl group in common with Chemical formulas 1 and 2.)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25471394A JP3547497B2 (en) | 1994-09-22 | 1994-09-22 | Method for producing benzothiazolone compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25471394A JP3547497B2 (en) | 1994-09-22 | 1994-09-22 | Method for producing benzothiazolone compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0892229A JPH0892229A (en) | 1996-04-09 |
| JP3547497B2 true JP3547497B2 (en) | 2004-07-28 |
Family
ID=17268819
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP25471394A Expired - Fee Related JP3547497B2 (en) | 1994-09-22 | 1994-09-22 | Method for producing benzothiazolone compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3547497B2 (en) |
-
1994
- 1994-09-22 JP JP25471394A patent/JP3547497B2/en not_active Expired - Fee Related
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| Publication number | Publication date |
|---|---|
| JPH0892229A (en) | 1996-04-09 |
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