WO2014069674A1 - 6-bromo-2-naphthoic acid production method - Google Patents
6-bromo-2-naphthoic acid production method Download PDFInfo
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- WO2014069674A1 WO2014069674A1 PCT/JP2013/080361 JP2013080361W WO2014069674A1 WO 2014069674 A1 WO2014069674 A1 WO 2014069674A1 JP 2013080361 W JP2013080361 W JP 2013080361W WO 2014069674 A1 WO2014069674 A1 WO 2014069674A1
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- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/363—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
Definitions
- the present invention relates to a method for producing 6-bromo-2-naphthoic acid (6-bromo-2-naphthalenecarboxylic acid).
- the target compound of the present invention 6-bromo-2-naphthoic acid (CAS number: 5773-80-8), is a known substance, and is a useful compound as a synthetic intermediate in the production of pharmaceuticals, agricultural chemicals and the like. Therefore, establishment of an inexpensive and industrial production method is strongly desired.
- 6-hydroxy-2-methylnaphthalene is brominated with a triphenylphosphine-bromine complex to give 6-bromo-2-methylnaphthalene in an organic solvent, and the compound is converted to acetic acid or the like.
- Patent Document 1 In the method described in Patent Document 1, it is necessary to use relatively expensive raw materials and reaction reagents. Moreover, since an organic solvent is used, there is a problem that the cost including the recovery cost increases. Furthermore, the total yield is about 60%, and there is a problem that a heavy metal catalyst is used. Therefore, the method described in Patent Document 1 is not appropriate as a method for producing 6-bromo-2-naphthoic acid easily and inexpensively. Further, in the method described in Patent Document 2, 2-bromonaphthalene is acetylated by Friedel-Crafts reaction, the impurities increase, and it is difficult to obtain high-purity 6-bromo-2-acetylnaphthalene in high yield. .
- Patent Document 2 the yield of 6-bromo-2-acetylnaphthalene after recrystallization is 21%, and it is difficult to obtain 6-bromo-2-naphthoic acid, which is the final target product, in high yield.
- a large amount of fuming anhydrous aluminum chloride is used, there are problems in the working environment and wastewater treatment.
- Patent Document 2 since an organic solvent is used in Patent Document 2, there is also a problem of an increase in cost.
- the conventional method for producing 6-bromo-2-naphthoic acid has various problems, and an industrially established method for producing 6-bromo-2-naphthoic acid is not known.
- the present inventors examined an industrial production method of 6-bromo-2-naphthoic acid.
- a hydroxyl group of 6-hydroxy-2-naphthoic acid was converted to an amino group by a Bucherer reaction.
- 6-amino-2-naphthoic acid is converted to a group, and the obtained 6-amino-2-naphthoic acid is subjected to a diazotization reaction to form a diazotized product, which is then reacted with copper bromide to give 6
- -bromo-2-naphthoic acid was obtained in high yield.
- This invention is based on the knowledge which concerns, and this invention provides the industrial manufacturing method of 6-bromo- 2-naphthoic acid.
- the raw materials and the reaction reagent are inexpensive, and the production cost can be reduced.
- any reaction proceeds using water as a solvent, an increase in cost due to the use of an organic solvent can be avoided.
- the reaction position is specified, there are few side reactions and the target product can be obtained with high purity. Therefore, according to the production method of the present invention, there is an effect that 6-bromo-2-naphthoic acid can be produced industrially and inexpensively.
- the present invention comprises the above-described configuration.
- 6-hydroxy-2-naphthoic acid is obtained by reacting 6-hydroxy-2-naphthoic acid with ammonia in the presence of sulfite or bisulfite. Is converted to an amino group to obtain 6-amino-2-naphthoic acid, and this reaction is known as a Bucherer reaction. In this reaction, sulfite or bisulfite is used as a catalyst, and both may be used in combination.
- sulfite used examples include alkali metal salts of sulfite (for example, sodium salt, potassium salt, etc.), ammonium salts, and the like, and bisulfite salts are also exemplified by similar salts.
- bisulfite is preferably used, and ammonium bisulfite is particularly preferably used from the viewpoint of yield.
- the amount of sulfite or bisulfite used is in the range of 0.1 to 1.5 molar ratio, preferably 0.2 to 1.0 molar ratio, relative to 6-hydroxy-2-naphthoic acid.
- the molar ratio is less than 0.1, it is difficult to proceed with the reaction, and if it exceeds 1.5, there is no particular problem, but it is sufficient if it is less than 1.5.
- ammonia ammonia gas, ammonia water (for example, 28% ammonia water) or the like is used.
- the amount of ammonia used is in the range of 2 to 12 molar ratio, preferably 3 to 7 molar ratio with respect to 6-hydroxy-2-naphthoic acid. If the molar ratio is less than 2, the progress of the reaction is difficult, and if it exceeds 12, the yield may decrease.
- This reaction is usually carried out in a solvent, and any solvent can be used as long as the solvent does not adversely influence the reaction, but an aqueous solvent is usually used.
- the reaction temperature is 80 to 150 ° C, preferably 110 to 130 ° C. As a preferred embodiment, it is carried out under pressure and heating conditions using a pressure vessel such as an autoclave.
- the pressure is 0.2 to 1.0 MPa, preferably 0.3 to 0.7 MPa, and the reaction temperature is 110 to 150 ° C.
- the reaction time is 5 to 15 hours, usually 8 to 12 hours.
- 6-amino-2-naphthoic acid is produced from 6-hydroxy-2-naphthoic acid.
- 6-amino-2-naphthoic acid obtained above is subjected to a diazotization reaction to give a diazotized product, and then reacted with copper bromide to give 6-bromo-2-naphthoic acid. It is the process of obtaining.
- the diazotization reaction is a reaction well known to those skilled in the art, and a normal method can be used for the synthesis of the diazotized product.
- the diazotization reaction can be carried out by subjecting 6-amino-2-naphthoic acid to diazotization with a nitroso source under acidic conditions in an aqueous solvent according to a conventional method.
- nitroso source used in the diazotization reaction examples include nitrous acid, nitrite (for example, sodium nitrite), isoamyl nitrite and the like.
- the amount of the nitroso source used is in the range of 1 to 10 molar ratio, preferably 1 to 5 molar ratio with respect to 6-amino-2-naphthoic acid. If the molar ratio is less than 1, the reaction does not proceed sufficiently. On the other hand, if it exceeds 10, there is no problem, but the amount up to that point is sufficient.
- inorganic acid such as hydrochloric acid, sulfuric acid, hydrogen halide solution (for example, hydrobromic acid solution, hydroiodic acid solution, etc.) and organic acid such as acetic acid are used.
- the reaction is carried out for cooling (about 0 to 5 ° C.), and the reaction is completed within 30 minutes to 3 hours, usually about 1 to 2 hours, and a diazotized product is formed.
- the diazotide obtained above can be used in the next step as it is, and 6-bromo-2-naphthoic acid is produced by reacting with copper (I) bromide. This reaction is well known as the Sandmeyer reaction.
- This reaction is usually performed in an aqueous solvent in the presence of an acid, and examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid, and a hydrogen halide solution. Among them, a hydrogen halide solution is preferable, and particularly hydrobromic acid.
- a liquid is preferably used.
- the amount of copper (I) bromide to be used is in the range of 0.5 to 5 molar ratio, preferably 1 to 4 molar ratio with respect to the diazotized product. When the molar ratio is less than 0.5, the reaction does not proceed sufficiently. On the other hand, when the molar ratio exceeds 5, there is no problem, but the reaction proceeds sufficiently with the previous amount.
- the reaction temperature is 5 to 80 ° C, preferably room temperature to 70 ° C.
- the reaction time is 1 to 20 hours, usually 10 to 16 hours.
- 6-bromo-2-naphthoic acid is precipitated from the reaction system by this process, and can be obtained by filtering the precipitate. If necessary, purification is performed by a conventional method such as recrystallization.
- Example 1 To an autoclave of 6- amino-2-naphthoic acid 2 L, 188.2 g (1.0 mol) of 6-hydroxy-2-naphthoic acid, 500 mL of water, 99.3 g (0.74 mol) of ammonium sulfite, 219% aqueous ammonia 219 .2 g (3.61 mol) was charged, and the autoclave was sealed. The temperature was raised to 130 ° C. with stirring. After the temperature increase, the reaction was conducted at 0.6 MPa for 11 hours at the same temperature. After cooling to 5 ° C.
- Example 2 In Example 1, it reacted similarly except using ammonium hydrogensulfite instead of ammonium sulfite, and 6-amino- 2-naphthoic acid was obtained (purity: 98%, yield: 93%).
- Example 3 In Example 1, instead of ammonium sulfite, ammonium bisulfite (1.0 molar ratio with respect to 6-hydroxy-2-naphthoic acid) was used in the same manner except that ammonium bisulfite was used.
- Example 4 In Example 1, instead of ammonium sulfite, the reaction was carried out in the same manner except that ammonium hydrogen sulfite (0.2 molar ratio with respect to 6-hydroxy-2-naphthoic acid) was used. The acid was obtained (yield 92%).
- Example 5 In Example 1, 6-amino-2-naphthoic acid was obtained in the same manner as in Example 1 except that sodium hydrogen sulfite was used instead of ammonium sulfite and the pressure was 0.4 MPa (yield 92%).
- Example 6 In a 3 L flask of 6- bromo -2-naphthoic acid, 71.8 g (0.376 mol) of 6-amino-2-naphthoic acid, 972.6 g of water, 262.3 g of 47% hydrobromic acid (4.05 mol ratio) ), And cooled to 5 ° C. or lower. 146.2% sodium nitrite aqueous solution 206.2g (1.1 molar ratio) was dripped at 5 degrees C or less, and it stirred for 2 hours, and obtained the diazotization liquid.
- Example 7 In the Sandmeyer reaction step of Example 6, the reaction was carried out in the same manner except that the amount of copper (I) bromide used was 2.66 molar ratio to obtain 6-bromo-2-naphthoic acid (yield 78%). ).
- 6-bromo-2-naphthoic acid which is useful as a raw material for pharmaceuticals, agricultural chemicals and the like, can be produced industrially and inexpensively.
Abstract
Provided is method of producing 6-bromo-2-naphthoic acid useful as a raw material in pharmaceuticals, agricultural chemicals, etc. This 6-bromo-2-naphthoic acid production method involves reacting 6-hydroxy-2-naphthoic acid with ammonia in the presence of sulfite or bisulfite to obtain 6-amino-2-naphthoic acid, subjecting the obtained 6-amino-2-naphthoic acid to a diazotization reaction to obtain a diazotized compound, and subsequently reacting the diazotized compound with copper bromide in the presence of an acid. By means of the present invention, it is possible to produce 6-bromo-2-naphthoic acid with high yield and high purity at low cost.
Description
本発明は６−ブロモ−２−ナフトエ酸（６−ブロモ−２−ナフタレンカルボン酸）の製造方法に関する。
The present invention relates to a method for producing 6-bromo-2-naphthoic acid (6-bromo-2-naphthalenecarboxylic acid).
本発明の目的化合物である６−ブロモ−２−ナフトエ酸（ＣＡＳ番号：５７７３−８０−８）は公知物質であり、医薬、農薬などを製造する際の合成中間体として有用な化合物であって、その安価かつ工業的な製造方法の確立が強く望まれている。
当該化合物の公知の製造法としては、有機溶媒中、６−ヒドロキシ−２−メチルナフタレンをトリフェニルフォスフィン−臭素錯体で臭素化して６−ブロモ−２−メチルナフタレンとし、当該化合物を酢酸などの低級脂肪酸の溶媒中、酢酸コバルトのような重金属触媒と臭素化合物からなる酸化触媒の存在下、分子状酸素により酸化して６−ブロモ−２−ナフトエ酸を得る方法が知られている（特許文献１参照）。
また、他の製造方法としては、ニトロベンゼン溶媒中、２−ブロモナフタレンに無水塩化アルミニウム触媒の存在下、アセチルクロリドを反応させるフリーデルクラフツ反応により６−ブロモ−２−アセチルナフタレンとし、当該化合物を次亜塩素酸ナトリウムと反応（ハロホルム反応）させて６−ブロモ−２−ナフトエ酸を得る方法が知られている（特許文献２参照）。 The target compound of the present invention, 6-bromo-2-naphthoic acid (CAS number: 5773-80-8), is a known substance, and is a useful compound as a synthetic intermediate in the production of pharmaceuticals, agricultural chemicals and the like. Therefore, establishment of an inexpensive and industrial production method is strongly desired.
As a known method for producing the compound, 6-hydroxy-2-methylnaphthalene is brominated with a triphenylphosphine-bromine complex to give 6-bromo-2-methylnaphthalene in an organic solvent, and the compound is converted to acetic acid or the like. There is known a method of obtaining 6-bromo-2-naphthoic acid by oxidation with molecular oxygen in the presence of an oxidation catalyst comprising a heavy metal catalyst such as cobalt acetate and a bromine compound in a lower fatty acid solvent (Patent Literature). 1).
As another production method, 6-bromo-2-acetylnaphthalene is obtained by a Friedel-Crafts reaction in which acetyl chloride is reacted with 2-bromonaphthalene in the presence of an anhydrous aluminum chloride catalyst in a nitrobenzene solvent. A method of obtaining 6-bromo-2-naphthoic acid by reacting with sodium chlorite (haloform reaction) is known (see Patent Document 2).
当該化合物の公知の製造法としては、有機溶媒中、６−ヒドロキシ−２−メチルナフタレンをトリフェニルフォスフィン−臭素錯体で臭素化して６−ブロモ−２−メチルナフタレンとし、当該化合物を酢酸などの低級脂肪酸の溶媒中、酢酸コバルトのような重金属触媒と臭素化合物からなる酸化触媒の存在下、分子状酸素により酸化して６−ブロモ−２−ナフトエ酸を得る方法が知られている（特許文献１参照）。
また、他の製造方法としては、ニトロベンゼン溶媒中、２−ブロモナフタレンに無水塩化アルミニウム触媒の存在下、アセチルクロリドを反応させるフリーデルクラフツ反応により６−ブロモ−２−アセチルナフタレンとし、当該化合物を次亜塩素酸ナトリウムと反応（ハロホルム反応）させて６−ブロモ−２−ナフトエ酸を得る方法が知られている（特許文献２参照）。 The target compound of the present invention, 6-bromo-2-naphthoic acid (CAS number: 5773-80-8), is a known substance, and is a useful compound as a synthetic intermediate in the production of pharmaceuticals, agricultural chemicals and the like. Therefore, establishment of an inexpensive and industrial production method is strongly desired.
As a known method for producing the compound, 6-hydroxy-2-methylnaphthalene is brominated with a triphenylphosphine-bromine complex to give 6-bromo-2-methylnaphthalene in an organic solvent, and the compound is converted to acetic acid or the like. There is known a method of obtaining 6-bromo-2-naphthoic acid by oxidation with molecular oxygen in the presence of an oxidation catalyst comprising a heavy metal catalyst such as cobalt acetate and a bromine compound in a lower fatty acid solvent (Patent Literature). 1).
As another production method, 6-bromo-2-acetylnaphthalene is obtained by a Friedel-Crafts reaction in which acetyl chloride is reacted with 2-bromonaphthalene in the presence of an anhydrous aluminum chloride catalyst in a nitrobenzene solvent. A method of obtaining 6-bromo-2-naphthoic acid by reacting with sodium chlorite (haloform reaction) is known (see Patent Document 2).
上記特許文献１に記載の方法では比較的高価な原料及び反応試薬を使用する必要がある。また、有機溶媒を使用するので、その回収費用を含めてコストが上昇するという問題がある。更に、トータル収率が約６０％であり、また重金属触媒を使用するという問題もある。従って、特許文献１に記載の方法は、安価且つ簡便に６−ブロモ−２−ナフトエ酸を製造する方法として適切とはいいがたい。
また、特許文献２に記載の方法は、２−ブロモナフタレンをフリーデルクラフツ反応によってアセチル化しており不純物が多くなり、高純度の６−ブロモ−２−アセチルナフタレンを高収率で得るのが難しい。特許文献２では再結晶後の６−ブロモ−２−アセチルナフタレンの収率が２１％であり、最終目的物である６−ブロモ−２−ナフトエ酸を高収率で得ることは困難である。また、発煙性を有する無水塩化アルミニウムを多量に使用するので、作業環境の問題及び排水処理の問題がある。更に、特許文献２でも有機溶媒を使用するので、それによるコストの上昇の問題もある。
このように、従来の６−ブロモ−２−ナフトエ酸の製造方法には種々の問題があり、６−ブロモ−２−ナフトエ酸の工業的に確立された製造方法は知られていない。 In the method described in Patent Document 1, it is necessary to use relatively expensive raw materials and reaction reagents. Moreover, since an organic solvent is used, there is a problem that the cost including the recovery cost increases. Furthermore, the total yield is about 60%, and there is a problem that a heavy metal catalyst is used. Therefore, the method described in Patent Document 1 is not appropriate as a method for producing 6-bromo-2-naphthoic acid easily and inexpensively.
Further, in the method described in Patent Document 2, 2-bromonaphthalene is acetylated by Friedel-Crafts reaction, the impurities increase, and it is difficult to obtain high-purity 6-bromo-2-acetylnaphthalene in high yield. . In Patent Document 2, the yield of 6-bromo-2-acetylnaphthalene after recrystallization is 21%, and it is difficult to obtain 6-bromo-2-naphthoic acid, which is the final target product, in high yield. In addition, since a large amount of fuming anhydrous aluminum chloride is used, there are problems in the working environment and wastewater treatment. Furthermore, since an organic solvent is used in Patent Document 2, there is also a problem of an increase in cost.
As described above, the conventional method for producing 6-bromo-2-naphthoic acid has various problems, and an industrially established method for producing 6-bromo-2-naphthoic acid is not known.
また、特許文献２に記載の方法は、２−ブロモナフタレンをフリーデルクラフツ反応によってアセチル化しており不純物が多くなり、高純度の６−ブロモ−２−アセチルナフタレンを高収率で得るのが難しい。特許文献２では再結晶後の６−ブロモ−２−アセチルナフタレンの収率が２１％であり、最終目的物である６−ブロモ−２−ナフトエ酸を高収率で得ることは困難である。また、発煙性を有する無水塩化アルミニウムを多量に使用するので、作業環境の問題及び排水処理の問題がある。更に、特許文献２でも有機溶媒を使用するので、それによるコストの上昇の問題もある。
このように、従来の６−ブロモ−２−ナフトエ酸の製造方法には種々の問題があり、６−ブロモ−２−ナフトエ酸の工業的に確立された製造方法は知られていない。 In the method described in Patent Document 1, it is necessary to use relatively expensive raw materials and reaction reagents. Moreover, since an organic solvent is used, there is a problem that the cost including the recovery cost increases. Furthermore, the total yield is about 60%, and there is a problem that a heavy metal catalyst is used. Therefore, the method described in Patent Document 1 is not appropriate as a method for producing 6-bromo-2-naphthoic acid easily and inexpensively.
Further, in the method described in Patent Document 2, 2-bromonaphthalene is acetylated by Friedel-Crafts reaction, the impurities increase, and it is difficult to obtain high-purity 6-bromo-2-acetylnaphthalene in high yield. . In Patent Document 2, the yield of 6-bromo-2-acetylnaphthalene after recrystallization is 21%, and it is difficult to obtain 6-bromo-2-naphthoic acid, which is the final target product, in high yield. In addition, since a large amount of fuming anhydrous aluminum chloride is used, there are problems in the working environment and wastewater treatment. Furthermore, since an organic solvent is used in Patent Document 2, there is also a problem of an increase in cost.
As described above, the conventional method for producing 6-bromo-2-naphthoic acid has various problems, and an industrially established method for producing 6-bromo-2-naphthoic acid is not known.
上記の問題点に鑑み、本発明者らは６−ブロモ−２−ナフトエ酸の工業的製造方法を検討したところ、ブッヘラー反応（Ｂｕｃｈｅｒｅｒ ｒｅａｃｔｉｏｎ）により、６−ヒドロキシ−２−ナフトエ酸の水酸基をアミノ基に変換して６−アミノ−２−ナフトエ酸とし、得られた６−アミノ−２−ナフトエ酸をジアゾ化反応に付してジアゾ化物とし、次いで臭化銅と反応させるザンドマイヤー反応により６−ブロモ−２−ナフトエ酸が高収率で得られることを見出した。
本発明は係る知見に基づくもので、本発明は６−ブロモ−２−ナフトエ酸の工業的製造方法を提供するものである。 In view of the above problems, the present inventors examined an industrial production method of 6-bromo-2-naphthoic acid. As a result, a hydroxyl group of 6-hydroxy-2-naphthoic acid was converted to an amino group by a Bucherer reaction. 6-amino-2-naphthoic acid is converted to a group, and the obtained 6-amino-2-naphthoic acid is subjected to a diazotization reaction to form a diazotized product, which is then reacted with copper bromide to give 6 It was found that -bromo-2-naphthoic acid was obtained in high yield.
This invention is based on the knowledge which concerns, and this invention provides the industrial manufacturing method of 6-bromo- 2-naphthoic acid.
本発明は係る知見に基づくもので、本発明は６−ブロモ−２−ナフトエ酸の工業的製造方法を提供するものである。 In view of the above problems, the present inventors examined an industrial production method of 6-bromo-2-naphthoic acid. As a result, a hydroxyl group of 6-hydroxy-2-naphthoic acid was converted to an amino group by a Bucherer reaction. 6-amino-2-naphthoic acid is converted to a group, and the obtained 6-amino-2-naphthoic acid is subjected to a diazotization reaction to form a diazotized product, which is then reacted with copper bromide to give 6 It was found that -bromo-2-naphthoic acid was obtained in high yield.
This invention is based on the knowledge which concerns, and this invention provides the industrial manufacturing method of 6-bromo- 2-naphthoic acid.
本発明の６−ブロモ−２−ナフトエ酸の製造方法では、原料及び反応試薬が安価であり、製造コストの低減を図ることができる。また、何れの反応も水を溶媒として反応が進行するので、有機溶媒を使用することによるコスト上昇を回避することができる。更に、反応位置が特定されているので、副反応が少なく、目的物を高純度で得ることができる。
従って、本発明の製造方法によれば、６−ブロモ−２−ナフトエ酸を工業的且つ安価に製造し得るという効果を奏する。 In the method for producing 6-bromo-2-naphthoic acid of the present invention, the raw materials and the reaction reagent are inexpensive, and the production cost can be reduced. In addition, since any reaction proceeds using water as a solvent, an increase in cost due to the use of an organic solvent can be avoided. Furthermore, since the reaction position is specified, there are few side reactions and the target product can be obtained with high purity.
Therefore, according to the production method of the present invention, there is an effect that 6-bromo-2-naphthoic acid can be produced industrially and inexpensively.
従って、本発明の製造方法によれば、６−ブロモ−２−ナフトエ酸を工業的且つ安価に製造し得るという効果を奏する。 In the method for producing 6-bromo-2-naphthoic acid of the present invention, the raw materials and the reaction reagent are inexpensive, and the production cost can be reduced. In addition, since any reaction proceeds using water as a solvent, an increase in cost due to the use of an organic solvent can be avoided. Furthermore, since the reaction position is specified, there are few side reactions and the target product can be obtained with high purity.
Therefore, according to the production method of the present invention, there is an effect that 6-bromo-2-naphthoic acid can be produced industrially and inexpensively.
本発明は前記の構成からなり、本発明の第１工程は、６−ヒドロキシ−２−ナフトエ酸を亜硫酸塩又は亜硫酸水素塩の存在下にアンモニアと反応させて、６−ヒドロキシ−２−ナフトエ酸の水酸基をアミノ基に変換して６−アミノ−２−ナフトエ酸を得るものであり、この反応はブッヘラー反応として知られている。
この反応では触媒として亜硫酸塩、亜硫酸水素塩が使用され、両者は併用してもよい。使用される亜硫酸塩としては、亜硫酸のアルカリ金属塩（例えば、ナトリウム塩、カリウム塩など）、アンモニウム塩などが例示され、亜硫酸水素塩も同様な塩類が例示される。この反応において、好ましくは亜硫酸水素塩が使用され、特に収率の点から亜硫酸水素アンモニウムを使用するのが好適である。
亜硫酸塩又は亜硫酸水素塩の使用量は、６−ヒドロキシ−２−ナフトエ酸に対して０．１~１．５モル比、好ましくは０．２~１．０モル比の範囲である。当該モル比が０．１未満では反応の進行が難しく、また１．５を超えても特に問題はないがそれ以下で充分である。
アンモニアとしてはアンモニアガス、アンモニア水（例えば２８％アンモニア水）などが使用される。アンモニア分の使用量は、６−ヒドロキシ−２−ナフトエ酸に対して２~１２モル比、好ましくは３~７モル比の範囲である。当該モル比が２未満では反応の進行が難しく、また１２を超えると収率が低下するおそれがある。
この反応は通常、溶媒中で行われ、溶媒としては反応に悪影響を及ぼさない溶媒中であれば何れの溶媒も使用し得るが、通常は水溶媒が使用される。反応温度としては８０~１５０℃、好ましくは１１０~１３０℃の条件下に行われる。好ましい態様としては、オートクレーブのような耐圧容器を使用して加圧・加熱条件下に行われる。圧力としては０．２~１．０ＭＰａ、好ましくは０．３~０．７ＭＰａ、反応温度としては１１０~１５０℃の条件下に行われる。
反応時間としては５~１５時間、通常は８~１２時間程度で終了する。
かくして、６−ヒドロキシ−２−ナフトエ酸から６−アミノ−２−ナフトエ酸が生成する。
本発明の第２工程は、上記で得られた６−アミノ−２−ナフトエ酸をジアゾ化反応に付してジアゾ化物とし、次いで臭化銅と反応させることにより６−ブロモ−２−ナフトエ酸を得る工程である。
上記の工程において、ジアゾ化反応は当業者によく知られた反応であり、ジアゾ化物の合成は通常の方法を用いることができる。
ジアゾ化反応は、常法に準じ、６−アミノ−２−ナフトエ酸を、水溶媒中、酸性下においてニトロソ源によりジアゾ化することにより行うことができる。
ジアゾ化反応に使用されるニトロソ源としては、亜硝酸、亜硝酸塩（例えば亜硝酸ナトリウムなど）、亜硝酸イソアミルなどが例示される。ニトロソ源の使用量としては、６−アミノ−２−ナフトエ酸に対して１~１０モル比、好ましくは１~５モル比の範囲である。当該モル比が１未満では反応が充分に進行し難く、一方１０を超えても問題はないがそれまでの量で充分である。
酸としては、塩酸、硫酸、ハロゲン化水素溶液（例えば臭化水素酸溶液、ヨウ化水素酸溶液等）などの無機酸、酢酸等の有機酸が使用される。
反応は冷却化（０~５℃程度）に行われ、反応は３０分~３時間、通常は１~２時間程度で終了し、ジアゾ化物が生成する。
上記で得られたジアゾ化物はそのまま次の工程に使用することができ、臭化銅（Ｉ）と反応させることにより６−ブロモ−２−ナフトエ酸が生成する。この反応はザンドマイヤー反応としてよく知られている。
この反応は通常、水溶媒中で酸の存在下に行われ、酸としては塩酸、硫酸、ハロゲン化水素溶液等の無機酸などが例示され、そのうちハロゲン化水素溶液が好ましく、特に臭化水素酸液が好適に使用される。
臭化銅（Ｉ）の使用量は、ジアゾ化物に対して０．５~５モル比、好ましくは１~４モル比の範囲である。当該モル比が０．５未満では充分に反応が進行せず、一方５を超えても問題はないがそれまでの量で充分に反応は進行する。
反応温度は５~８０℃、好ましくは室温~７０℃の範囲で行われる。反応時間としては１~２０時間、通常は１０~１６時間で終了する。
係る工程により、通常、６−ブロモ−２−ナフトエ酸は反応系から析出するので、析出物を濾取することにより得ることができ、必要に応じて再結晶などの常法により精製を行う。 The present invention comprises the above-described configuration. In the first step of the present invention, 6-hydroxy-2-naphthoic acid is obtained by reacting 6-hydroxy-2-naphthoic acid with ammonia in the presence of sulfite or bisulfite. Is converted to an amino group to obtain 6-amino-2-naphthoic acid, and this reaction is known as a Bucherer reaction.
In this reaction, sulfite or bisulfite is used as a catalyst, and both may be used in combination. Examples of the sulfite used include alkali metal salts of sulfite (for example, sodium salt, potassium salt, etc.), ammonium salts, and the like, and bisulfite salts are also exemplified by similar salts. In this reaction, bisulfite is preferably used, and ammonium bisulfite is particularly preferably used from the viewpoint of yield.
The amount of sulfite or bisulfite used is in the range of 0.1 to 1.5 molar ratio, preferably 0.2 to 1.0 molar ratio, relative to 6-hydroxy-2-naphthoic acid. If the molar ratio is less than 0.1, it is difficult to proceed with the reaction, and if it exceeds 1.5, there is no particular problem, but it is sufficient if it is less than 1.5.
As the ammonia, ammonia gas, ammonia water (for example, 28% ammonia water) or the like is used. The amount of ammonia used is in the range of 2 to 12 molar ratio, preferably 3 to 7 molar ratio with respect to 6-hydroxy-2-naphthoic acid. If the molar ratio is less than 2, the progress of the reaction is difficult, and if it exceeds 12, the yield may decrease.
This reaction is usually carried out in a solvent, and any solvent can be used as long as the solvent does not adversely influence the reaction, but an aqueous solvent is usually used. The reaction temperature is 80 to 150 ° C, preferably 110 to 130 ° C. As a preferred embodiment, it is carried out under pressure and heating conditions using a pressure vessel such as an autoclave. The pressure is 0.2 to 1.0 MPa, preferably 0.3 to 0.7 MPa, and the reaction temperature is 110 to 150 ° C.
The reaction time is 5 to 15 hours, usually 8 to 12 hours.
Thus, 6-amino-2-naphthoic acid is produced from 6-hydroxy-2-naphthoic acid.
In the second step of the present invention, 6-amino-2-naphthoic acid obtained above is subjected to a diazotization reaction to give a diazotized product, and then reacted with copper bromide to give 6-bromo-2-naphthoic acid. It is the process of obtaining.
In the above steps, the diazotization reaction is a reaction well known to those skilled in the art, and a normal method can be used for the synthesis of the diazotized product.
The diazotization reaction can be carried out by subjecting 6-amino-2-naphthoic acid to diazotization with a nitroso source under acidic conditions in an aqueous solvent according to a conventional method.
Examples of the nitroso source used in the diazotization reaction include nitrous acid, nitrite (for example, sodium nitrite), isoamyl nitrite and the like. The amount of the nitroso source used is in the range of 1 to 10 molar ratio, preferably 1 to 5 molar ratio with respect to 6-amino-2-naphthoic acid. If the molar ratio is less than 1, the reaction does not proceed sufficiently. On the other hand, if it exceeds 10, there is no problem, but the amount up to that point is sufficient.
As the acid, inorganic acid such as hydrochloric acid, sulfuric acid, hydrogen halide solution (for example, hydrobromic acid solution, hydroiodic acid solution, etc.) and organic acid such as acetic acid are used.
The reaction is carried out for cooling (about 0 to 5 ° C.), and the reaction is completed within 30 minutes to 3 hours, usually about 1 to 2 hours, and a diazotized product is formed.
The diazotide obtained above can be used in the next step as it is, and 6-bromo-2-naphthoic acid is produced by reacting with copper (I) bromide. This reaction is well known as the Sandmeyer reaction.
This reaction is usually performed in an aqueous solvent in the presence of an acid, and examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid, and a hydrogen halide solution. Among them, a hydrogen halide solution is preferable, and particularly hydrobromic acid. A liquid is preferably used.
The amount of copper (I) bromide to be used is in the range of 0.5 to 5 molar ratio, preferably 1 to 4 molar ratio with respect to the diazotized product. When the molar ratio is less than 0.5, the reaction does not proceed sufficiently. On the other hand, when the molar ratio exceeds 5, there is no problem, but the reaction proceeds sufficiently with the previous amount.
The reaction temperature is 5 to 80 ° C, preferably room temperature to 70 ° C. The reaction time is 1 to 20 hours, usually 10 to 16 hours.
In general, 6-bromo-2-naphthoic acid is precipitated from the reaction system by this process, and can be obtained by filtering the precipitate. If necessary, purification is performed by a conventional method such as recrystallization.
この反応では触媒として亜硫酸塩、亜硫酸水素塩が使用され、両者は併用してもよい。使用される亜硫酸塩としては、亜硫酸のアルカリ金属塩（例えば、ナトリウム塩、カリウム塩など）、アンモニウム塩などが例示され、亜硫酸水素塩も同様な塩類が例示される。この反応において、好ましくは亜硫酸水素塩が使用され、特に収率の点から亜硫酸水素アンモニウムを使用するのが好適である。
亜硫酸塩又は亜硫酸水素塩の使用量は、６−ヒドロキシ−２−ナフトエ酸に対して０．１~１．５モル比、好ましくは０．２~１．０モル比の範囲である。当該モル比が０．１未満では反応の進行が難しく、また１．５を超えても特に問題はないがそれ以下で充分である。
アンモニアとしてはアンモニアガス、アンモニア水（例えば２８％アンモニア水）などが使用される。アンモニア分の使用量は、６−ヒドロキシ−２−ナフトエ酸に対して２~１２モル比、好ましくは３~７モル比の範囲である。当該モル比が２未満では反応の進行が難しく、また１２を超えると収率が低下するおそれがある。
この反応は通常、溶媒中で行われ、溶媒としては反応に悪影響を及ぼさない溶媒中であれば何れの溶媒も使用し得るが、通常は水溶媒が使用される。反応温度としては８０~１５０℃、好ましくは１１０~１３０℃の条件下に行われる。好ましい態様としては、オートクレーブのような耐圧容器を使用して加圧・加熱条件下に行われる。圧力としては０．２~１．０ＭＰａ、好ましくは０．３~０．７ＭＰａ、反応温度としては１１０~１５０℃の条件下に行われる。
反応時間としては５~１５時間、通常は８~１２時間程度で終了する。
かくして、６−ヒドロキシ−２−ナフトエ酸から６−アミノ−２−ナフトエ酸が生成する。
本発明の第２工程は、上記で得られた６−アミノ−２−ナフトエ酸をジアゾ化反応に付してジアゾ化物とし、次いで臭化銅と反応させることにより６−ブロモ−２−ナフトエ酸を得る工程である。
上記の工程において、ジアゾ化反応は当業者によく知られた反応であり、ジアゾ化物の合成は通常の方法を用いることができる。
ジアゾ化反応は、常法に準じ、６−アミノ−２−ナフトエ酸を、水溶媒中、酸性下においてニトロソ源によりジアゾ化することにより行うことができる。
ジアゾ化反応に使用されるニトロソ源としては、亜硝酸、亜硝酸塩（例えば亜硝酸ナトリウムなど）、亜硝酸イソアミルなどが例示される。ニトロソ源の使用量としては、６−アミノ−２−ナフトエ酸に対して１~１０モル比、好ましくは１~５モル比の範囲である。当該モル比が１未満では反応が充分に進行し難く、一方１０を超えても問題はないがそれまでの量で充分である。
酸としては、塩酸、硫酸、ハロゲン化水素溶液（例えば臭化水素酸溶液、ヨウ化水素酸溶液等）などの無機酸、酢酸等の有機酸が使用される。
反応は冷却化（０~５℃程度）に行われ、反応は３０分~３時間、通常は１~２時間程度で終了し、ジアゾ化物が生成する。
上記で得られたジアゾ化物はそのまま次の工程に使用することができ、臭化銅（Ｉ）と反応させることにより６−ブロモ−２−ナフトエ酸が生成する。この反応はザンドマイヤー反応としてよく知られている。
この反応は通常、水溶媒中で酸の存在下に行われ、酸としては塩酸、硫酸、ハロゲン化水素溶液等の無機酸などが例示され、そのうちハロゲン化水素溶液が好ましく、特に臭化水素酸液が好適に使用される。
臭化銅（Ｉ）の使用量は、ジアゾ化物に対して０．５~５モル比、好ましくは１~４モル比の範囲である。当該モル比が０．５未満では充分に反応が進行せず、一方５を超えても問題はないがそれまでの量で充分に反応は進行する。
反応温度は５~８０℃、好ましくは室温~７０℃の範囲で行われる。反応時間としては１~２０時間、通常は１０~１６時間で終了する。
係る工程により、通常、６−ブロモ−２−ナフトエ酸は反応系から析出するので、析出物を濾取することにより得ることができ、必要に応じて再結晶などの常法により精製を行う。 The present invention comprises the above-described configuration. In the first step of the present invention, 6-hydroxy-2-naphthoic acid is obtained by reacting 6-hydroxy-2-naphthoic acid with ammonia in the presence of sulfite or bisulfite. Is converted to an amino group to obtain 6-amino-2-naphthoic acid, and this reaction is known as a Bucherer reaction.
In this reaction, sulfite or bisulfite is used as a catalyst, and both may be used in combination. Examples of the sulfite used include alkali metal salts of sulfite (for example, sodium salt, potassium salt, etc.), ammonium salts, and the like, and bisulfite salts are also exemplified by similar salts. In this reaction, bisulfite is preferably used, and ammonium bisulfite is particularly preferably used from the viewpoint of yield.
The amount of sulfite or bisulfite used is in the range of 0.1 to 1.5 molar ratio, preferably 0.2 to 1.0 molar ratio, relative to 6-hydroxy-2-naphthoic acid. If the molar ratio is less than 0.1, it is difficult to proceed with the reaction, and if it exceeds 1.5, there is no particular problem, but it is sufficient if it is less than 1.5.
As the ammonia, ammonia gas, ammonia water (for example, 28% ammonia water) or the like is used. The amount of ammonia used is in the range of 2 to 12 molar ratio, preferably 3 to 7 molar ratio with respect to 6-hydroxy-2-naphthoic acid. If the molar ratio is less than 2, the progress of the reaction is difficult, and if it exceeds 12, the yield may decrease.
This reaction is usually carried out in a solvent, and any solvent can be used as long as the solvent does not adversely influence the reaction, but an aqueous solvent is usually used. The reaction temperature is 80 to 150 ° C, preferably 110 to 130 ° C. As a preferred embodiment, it is carried out under pressure and heating conditions using a pressure vessel such as an autoclave. The pressure is 0.2 to 1.0 MPa, preferably 0.3 to 0.7 MPa, and the reaction temperature is 110 to 150 ° C.
The reaction time is 5 to 15 hours, usually 8 to 12 hours.
Thus, 6-amino-2-naphthoic acid is produced from 6-hydroxy-2-naphthoic acid.
In the second step of the present invention, 6-amino-2-naphthoic acid obtained above is subjected to a diazotization reaction to give a diazotized product, and then reacted with copper bromide to give 6-bromo-2-naphthoic acid. It is the process of obtaining.
In the above steps, the diazotization reaction is a reaction well known to those skilled in the art, and a normal method can be used for the synthesis of the diazotized product.
The diazotization reaction can be carried out by subjecting 6-amino-2-naphthoic acid to diazotization with a nitroso source under acidic conditions in an aqueous solvent according to a conventional method.
Examples of the nitroso source used in the diazotization reaction include nitrous acid, nitrite (for example, sodium nitrite), isoamyl nitrite and the like. The amount of the nitroso source used is in the range of 1 to 10 molar ratio, preferably 1 to 5 molar ratio with respect to 6-amino-2-naphthoic acid. If the molar ratio is less than 1, the reaction does not proceed sufficiently. On the other hand, if it exceeds 10, there is no problem, but the amount up to that point is sufficient.
As the acid, inorganic acid such as hydrochloric acid, sulfuric acid, hydrogen halide solution (for example, hydrobromic acid solution, hydroiodic acid solution, etc.) and organic acid such as acetic acid are used.
The reaction is carried out for cooling (about 0 to 5 ° C.), and the reaction is completed within 30 minutes to 3 hours, usually about 1 to 2 hours, and a diazotized product is formed.
The diazotide obtained above can be used in the next step as it is, and 6-bromo-2-naphthoic acid is produced by reacting with copper (I) bromide. This reaction is well known as the Sandmeyer reaction.
This reaction is usually performed in an aqueous solvent in the presence of an acid, and examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid, and a hydrogen halide solution. Among them, a hydrogen halide solution is preferable, and particularly hydrobromic acid. A liquid is preferably used.
The amount of copper (I) bromide to be used is in the range of 0.5 to 5 molar ratio, preferably 1 to 4 molar ratio with respect to the diazotized product. When the molar ratio is less than 0.5, the reaction does not proceed sufficiently. On the other hand, when the molar ratio exceeds 5, there is no problem, but the reaction proceeds sufficiently with the previous amount.
The reaction temperature is 5 to 80 ° C, preferably room temperature to 70 ° C. The reaction time is 1 to 20 hours, usually 10 to 16 hours.
In general, 6-bromo-2-naphthoic acid is precipitated from the reaction system by this process, and can be obtained by filtering the precipitate. If necessary, purification is performed by a conventional method such as recrystallization.
以下、本発明の詳細について実施例によって具体的に説明するが、本発明の範囲はこれらの実施例に限定されるものではない。
実施例１
６−アミノ−２−ナフトエ酸
２Ｌのオートクレーブに６−ヒドロキシ−２−ナフトエ酸１８８．２ｇ（１．０モル）、水５００ｍＬ、亜硫酸アンモニウム９９．３ｇ（０．７４モル）、２８％アンモニア水２１９．２ｇ（３．６１モル）をそれぞれ仕込み、オートクレーブを密封した。撹拌下、１３０℃まで昇温した。昇温後、０．６ＭＰａで１１時間同温度にて反応させた。５℃以下まで冷却した後、オートクレーブを開封し、同温度で結晶をろ過後、乾燥することによって１６０．４ｇの６−アミノ−２−ナフトエ酸を微黄白色結晶で得た（純度：９８％、収率：８４％）。
実施例２
実施例１において、亜硫酸アンモニウムの代わりに、亜硫酸水素アンモニウムを使用する以外は同様に反応させて、６−アミノ−２−ナフトエ酸を得た（純度：９８％、収率：９３％）。
実施例３
実施例１において、亜硫酸アンモニウムの代わりに、亜硫酸水素アンモニウム（６−ヒドロキシ−２−ナフトエ酸に対して１．０モル比）を使用する以外は同様に反応させて、６−アミノ−２−ナフトエ酸を得た（収率９３％）。
実施例４
実施例１において、亜硫酸アンモニウムの代わりに、亜硫酸水素アンモニウム（６−ヒドロキシ−２−ナフトエ酸に対して０．２モル比）を使用する以外は同様に反応させて、６−アミノ−２−ナフトエ酸を得た（収率９２％）。
実施例５
実施例１において、亜硫酸アンモニウムの代わりに、亜硫酸水素ナトリウムを使用し、圧力を０．４ＭＰａする以外は同様に反応させて、６−アミノ−２−ナフトエ酸を得た（収率９２％）。
実施例６
６−ブロモ−２−ナフトエ酸
３Ｌのフラスコに６−アミノ−２−ナフトエ酸７１．８ｇ（０．３７６モル）、水９７２．６ｇ、４７％臭化水素酸２６２．３ｇ（４．０５モル比）をそれぞれ仕込み、５℃以下まで冷却した。１４％亜硝酸ナトリウム水溶液２０６．２ｇ（１．１モル比）を５℃以下で滴下し、２時間撹拌し、ジアゾ化液を得た。
別途５Ｌのフラスコに４７％臭化水素酸２９１．３ｇ（４．５モル比）と臭化銅（Ｉ）７５．６ｇ（１．３３モル比）を仕込み、６０℃まで昇温後、先のジアゾ化液を発泡に注意しながら断続的に加えた。６０℃にて１６時間反応した後、同温度でろ過後、５３９．３ｇの水で洗浄し、乾燥することによって７３．０ｇの６−ブロモ−２−ナフトエ酸を淡黄白色結晶で得た（純度：９９％、収率：７６．５％）。
実施例７
実施例６のザンドマイヤー反応工程において、臭化銅（Ｉ）の使用量を２．６６モル比とする以外は同様に反応させ、６−ブロモ−２−ナフトエ酸を得た（収率７８％）。 Hereinafter, the details of the present invention will be specifically described by way of examples. However, the scope of the present invention is not limited to these examples.
Example 1
To an autoclave of 6- amino-2-naphthoic acid 2 L, 188.2 g (1.0 mol) of 6-hydroxy-2-naphthoic acid, 500 mL of water, 99.3 g (0.74 mol) of ammonium sulfite, 219% aqueous ammonia 219 .2 g (3.61 mol) was charged, and the autoclave was sealed. The temperature was raised to 130 ° C. with stirring. After the temperature increase, the reaction was conducted at 0.6 MPa for 11 hours at the same temperature. After cooling to 5 ° C. or lower, the autoclave was opened, the crystals were filtered at the same temperature, and dried to obtain 160.4 g of 6-amino-2-naphthoic acid as slightly yellowish white crystals (purity: 98% Yield: 84%).
Example 2
In Example 1, it reacted similarly except using ammonium hydrogensulfite instead of ammonium sulfite, and 6-amino- 2-naphthoic acid was obtained (purity: 98%, yield: 93%).
Example 3
In Example 1, instead of ammonium sulfite, ammonium bisulfite (1.0 molar ratio with respect to 6-hydroxy-2-naphthoic acid) was used in the same manner except that ammonium bisulfite was used. The acid was obtained (93% yield).
Example 4
In Example 1, instead of ammonium sulfite, the reaction was carried out in the same manner except that ammonium hydrogen sulfite (0.2 molar ratio with respect to 6-hydroxy-2-naphthoic acid) was used. The acid was obtained (yield 92%).
Example 5
In Example 1, 6-amino-2-naphthoic acid was obtained in the same manner as in Example 1 except that sodium hydrogen sulfite was used instead of ammonium sulfite and the pressure was 0.4 MPa (yield 92%).
Example 6
In a 3 L flask of 6- bromo -2-naphthoic acid, 71.8 g (0.376 mol) of 6-amino-2-naphthoic acid, 972.6 g of water, 262.3 g of 47% hydrobromic acid (4.05 mol ratio) ), And cooled to 5 ° C. or lower. 146.2% sodium nitrite aqueous solution 206.2g (1.1 molar ratio) was dripped at 5 degrees C or less, and it stirred for 2 hours, and obtained the diazotization liquid.
Separately, 291.3 g (4.5 molar ratio) of 47% hydrobromic acid and 75.6 g (1.33 molar ratio) of copper bromide (I) were charged into a 5 L flask, and the temperature was raised to 60 ° C. The diazotization liquid was added intermittently taking care of foaming. After reacting at 60 ° C. for 16 hours, filtering at the same temperature, washing with 539.3 g of water and drying, 73.0 g of 6-bromo-2-naphthoic acid was obtained as pale yellowish white crystals ( (Purity: 99%, yield: 76.5%).
Example 7
In the Sandmeyer reaction step of Example 6, the reaction was carried out in the same manner except that the amount of copper (I) bromide used was 2.66 molar ratio to obtain 6-bromo-2-naphthoic acid (yield 78%). ).
実施例１
６−アミノ−２−ナフトエ酸
２Ｌのオートクレーブに６−ヒドロキシ−２−ナフトエ酸１８８．２ｇ（１．０モル）、水５００ｍＬ、亜硫酸アンモニウム９９．３ｇ（０．７４モル）、２８％アンモニア水２１９．２ｇ（３．６１モル）をそれぞれ仕込み、オートクレーブを密封した。撹拌下、１３０℃まで昇温した。昇温後、０．６ＭＰａで１１時間同温度にて反応させた。５℃以下まで冷却した後、オートクレーブを開封し、同温度で結晶をろ過後、乾燥することによって１６０．４ｇの６−アミノ−２−ナフトエ酸を微黄白色結晶で得た（純度：９８％、収率：８４％）。
実施例２
実施例１において、亜硫酸アンモニウムの代わりに、亜硫酸水素アンモニウムを使用する以外は同様に反応させて、６−アミノ−２−ナフトエ酸を得た（純度：９８％、収率：９３％）。
実施例３
実施例１において、亜硫酸アンモニウムの代わりに、亜硫酸水素アンモニウム（６−ヒドロキシ−２−ナフトエ酸に対して１．０モル比）を使用する以外は同様に反応させて、６−アミノ−２−ナフトエ酸を得た（収率９３％）。
実施例４
実施例１において、亜硫酸アンモニウムの代わりに、亜硫酸水素アンモニウム（６−ヒドロキシ−２−ナフトエ酸に対して０．２モル比）を使用する以外は同様に反応させて、６−アミノ−２−ナフトエ酸を得た（収率９２％）。
実施例５
実施例１において、亜硫酸アンモニウムの代わりに、亜硫酸水素ナトリウムを使用し、圧力を０．４ＭＰａする以外は同様に反応させて、６−アミノ−２−ナフトエ酸を得た（収率９２％）。
実施例６
６−ブロモ−２−ナフトエ酸
３Ｌのフラスコに６−アミノ−２−ナフトエ酸７１．８ｇ（０．３７６モル）、水９７２．６ｇ、４７％臭化水素酸２６２．３ｇ（４．０５モル比）をそれぞれ仕込み、５℃以下まで冷却した。１４％亜硝酸ナトリウム水溶液２０６．２ｇ（１．１モル比）を５℃以下で滴下し、２時間撹拌し、ジアゾ化液を得た。
別途５Ｌのフラスコに４７％臭化水素酸２９１．３ｇ（４．５モル比）と臭化銅（Ｉ）７５．６ｇ（１．３３モル比）を仕込み、６０℃まで昇温後、先のジアゾ化液を発泡に注意しながら断続的に加えた。６０℃にて１６時間反応した後、同温度でろ過後、５３９．３ｇの水で洗浄し、乾燥することによって７３．０ｇの６−ブロモ−２−ナフトエ酸を淡黄白色結晶で得た（純度：９９％、収率：７６．５％）。
実施例７
実施例６のザンドマイヤー反応工程において、臭化銅（Ｉ）の使用量を２．６６モル比とする以外は同様に反応させ、６−ブロモ−２−ナフトエ酸を得た（収率７８％）。 Hereinafter, the details of the present invention will be specifically described by way of examples. However, the scope of the present invention is not limited to these examples.
Example 1
To an autoclave of 6- amino-2-naphthoic acid 2 L, 188.2 g (1.0 mol) of 6-hydroxy-2-naphthoic acid, 500 mL of water, 99.3 g (0.74 mol) of ammonium sulfite, 219% aqueous ammonia 219 .2 g (3.61 mol) was charged, and the autoclave was sealed. The temperature was raised to 130 ° C. with stirring. After the temperature increase, the reaction was conducted at 0.6 MPa for 11 hours at the same temperature. After cooling to 5 ° C. or lower, the autoclave was opened, the crystals were filtered at the same temperature, and dried to obtain 160.4 g of 6-amino-2-naphthoic acid as slightly yellowish white crystals (purity: 98% Yield: 84%).
Example 2
In Example 1, it reacted similarly except using ammonium hydrogensulfite instead of ammonium sulfite, and 6-amino- 2-naphthoic acid was obtained (purity: 98%, yield: 93%).
Example 3
In Example 1, instead of ammonium sulfite, ammonium bisulfite (1.0 molar ratio with respect to 6-hydroxy-2-naphthoic acid) was used in the same manner except that ammonium bisulfite was used. The acid was obtained (93% yield).
Example 4
In Example 1, instead of ammonium sulfite, the reaction was carried out in the same manner except that ammonium hydrogen sulfite (0.2 molar ratio with respect to 6-hydroxy-2-naphthoic acid) was used. The acid was obtained (yield 92%).
Example 5
In Example 1, 6-amino-2-naphthoic acid was obtained in the same manner as in Example 1 except that sodium hydrogen sulfite was used instead of ammonium sulfite and the pressure was 0.4 MPa (yield 92%).
Example 6
In a 3 L flask of 6- bromo -2-naphthoic acid, 71.8 g (0.376 mol) of 6-amino-2-naphthoic acid, 972.6 g of water, 262.3 g of 47% hydrobromic acid (4.05 mol ratio) ), And cooled to 5 ° C. or lower. 146.2% sodium nitrite aqueous solution 206.2g (1.1 molar ratio) was dripped at 5 degrees C or less, and it stirred for 2 hours, and obtained the diazotization liquid.
Separately, 291.3 g (4.5 molar ratio) of 47% hydrobromic acid and 75.6 g (1.33 molar ratio) of copper bromide (I) were charged into a 5 L flask, and the temperature was raised to 60 ° C. The diazotization liquid was added intermittently taking care of foaming. After reacting at 60 ° C. for 16 hours, filtering at the same temperature, washing with 539.3 g of water and drying, 73.0 g of 6-bromo-2-naphthoic acid was obtained as pale yellowish white crystals ( (Purity: 99%, yield: 76.5%).
Example 7
In the Sandmeyer reaction step of Example 6, the reaction was carried out in the same manner except that the amount of copper (I) bromide used was 2.66 molar ratio to obtain 6-bromo-2-naphthoic acid (yield 78%). ).
本発明によれば、医薬、農薬等の原料として有用である６−ブロモ−２−ナフトエ酸を工業的且つ安価に製造することができる。
According to the present invention, 6-bromo-2-naphthoic acid, which is useful as a raw material for pharmaceuticals, agricultural chemicals and the like, can be produced industrially and inexpensively.
Claims (4)
- ６−ヒドロキシ−２−ナフトエ酸を亜硫酸塩又は亜硫酸水素塩の存在下にアンモニアと反応させて６−アミノ−２−ナフトエ酸とし、得られた６−アミノ−２−ナフトエ酸をジアゾ化反応に付してジアゾ化物とし、次いでジアゾ化物を酸の存在下、臭化銅と反応させることにより６−ブロモ−２−ナフトエ酸を得ることを特徴とする６−ブロモ−２−ナフトエ酸の製造方法。 6-Hydroxy-2-naphthoic acid is reacted with ammonia in the presence of sulfite or bisulfite to give 6-amino-2-naphthoic acid, and the resulting 6-amino-2-naphthoic acid is used for diazotization reaction. To 6-bromo-2-naphthoic acid, which is obtained by reacting the diazotized product with copper bromide in the presence of an acid. .
- 亜硫酸水素塩として、亜硫酸水素アンモニウムを使用する請求項１記載の製造方法。 The production method according to claim 1, wherein ammonium bisulfite is used as the bisulfite.
- ６−ヒドロキシ−２−ナフトエ酸を亜硫酸塩又は亜硫酸水素塩の存在下にアンモニアと反応させる工程を、耐圧容器中で加圧・加熱条件下に行う請求項１記載の製造方法。 The process according to claim 1, wherein the step of reacting 6-hydroxy-2-naphthoic acid with ammonia in the presence of sulfite or bisulfite is carried out under pressure and heating conditions in a pressure-resistant vessel.
- ジアゾ化物を酸の存在下、臭化銅と反応させる工程において、酸として臭化水素酸を使用する請求項１に記載の製造方法。 The production method according to claim 1, wherein hydrobromic acid is used as the acid in the step of reacting the diazotide with copper bromide in the presence of an acid.
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Cited By (2)
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| CN110590541A (en) * | 2019-10-16 | 2019-12-20 | 吕东 | Preparation method of 5-bromo-2-chlorobenzoic acid |
| CN112778116A (en) * | 2020-12-30 | 2021-05-11 | 湖北鸿鑫化工有限公司 | Preparation method of 1,4-naphthalenedicarboxylic acid |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110590541A (en) * | 2019-10-16 | 2019-12-20 | 吕东 | Preparation method of 5-bromo-2-chlorobenzoic acid |
| CN112778116A (en) * | 2020-12-30 | 2021-05-11 | 湖北鸿鑫化工有限公司 | Preparation method of 1,4-naphthalenedicarboxylic acid |
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