JP2000080058A - Production of iodophthalic acid compounds - Google Patents

Production of iodophthalic acid compounds

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Publication number
JP2000080058A
JP2000080058A JP11152024A JP15202499A JP2000080058A JP 2000080058 A JP2000080058 A JP 2000080058A JP 11152024 A JP11152024 A JP 11152024A JP 15202499 A JP15202499 A JP 15202499A JP 2000080058 A JP2000080058 A JP 2000080058A
Authority
JP
Japan
Prior art keywords
acid
formula
compound
general formula
iodophthalic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
JP11152024A
Other languages
Japanese (ja)
Inventor
Kozo Machitani
幸三 町谷
Akira Seo
明 瀬尾
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nihon Nohyaku Co Ltd
Original Assignee
Nihon Nohyaku Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nihon Nohyaku Co Ltd filed Critical Nihon Nohyaku Co Ltd
Priority to JP11152024A priority Critical patent/JP2000080058A/en
Publication of JP2000080058A publication Critical patent/JP2000080058A/en
Pending legal-status Critical Current

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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

Abstract

PROBLEM TO BE SOLVED: To obtain an iodophthalic acid compound useful as a raw material compound for obtaining various kinds of medicines, agrochemicals and chemicals at a low cost in a high yield by treating a specific nitrophthalic acid compound with a base in water solvent, hydrogenating the obtained compound in the presence of a palladium-based catalyst in water solvent under pressurization. SOLUTION: This method for producing an iodophthalic acid compound of formula IV comprises treating 1 mole of a nitrophthalic acid compound of formula I with preferably 2-2.1 moles of a base in water solvent, hydrogenating the obtained dialkali metal nitrophthalate of formula II (M is an alkali metal) in the presence of a palladium-based catalyst in water solvent under pressurization (preferably 2-6 atm) preferably at room temperature to 40 deg.C, isolating or not isolating the obtained aminophthalic acid dialkali metal salt of formula III, reacting the compound of formula III with a nitrite (for example, sodium nitrite) in an acid aqueous solution, and subsequently reacting the obtained diazonium salt with an alkali metal iodate.

Description

【発明の詳細な説明】DETAILED DESCRIPTION OF THE INVENTION

【０００１】[0001]

【発明の属する技術分野】本発明は、種々の医薬、農薬
又は化学品を製造するための原料化合物であるヨードフ
タル酸類の新規な製造方法に関するものである。The present invention relates to a novel method for producing iodophthalic acids, which are starting compounds for producing various medicines, agricultural chemicals or chemicals.

【０００２】[0002]

【従来の技術】ニトロフタル酸類の製造方法として
は、例えばニトロフタル酸のジナトリウム塩をｐＨ８〜
９に調整した水−酢酸溶媒中で、加圧下にラネーニッケ
ル又は酸化白金を触媒として水素添加し、アミノフタル
酸を製造する方法が報告されている（Ｊ．Ｏｒｇ．Ｃｈ
ｅｍ．，２５，１８８２（１９６０）。又、アミノフ
タル酸からサンドマイヤー(Sandmeyer) 反応によりヨー
ドフタル酸を製造する方法が報告されている（Ｊ．Ｍｅ
ｄ．Ｃｈｅｍ．，９，１６５（１９６６）。2. Description of the Related Art As a method for producing nitrophthalic acids, for example, a disodium salt of nitrophthalic acid is prepared at pH 8 to
9, a method for producing aminophthalic acid by hydrogenating under pressure and using Raney nickel or platinum oxide as a catalyst in a water-acetic acid solvent (J. Org. Ch.).
em. , 25 , 1882 (1960). A method for producing iodophthalic acid from aminophthalic acid by a Sandmeyer reaction has been reported (J. Me.).
d. Chem. , 9 , 165 (1966).

【０００３】[0003]

【発明が解決しようとする課題】しかし、の方法では
製造工程で微妙なｐＨ調整を必要とし、反応後の廃液処
理で問題のあるラネーニッケルあるいは高価な酸化白金
を使用し、工業化の面で不利となり、の方法では収率
が低く、高価なヨウ化カリウムを大過剰使用し、更に製
造工程で危険なジアゾニウム塩の溶液を滴下する工程が
あり、これらの面でも工業化には不利となる。However, this method requires a delicate pH adjustment in the production process, and uses Raney nickel or expensive platinum oxide, which is problematic in the treatment of waste liquid after the reaction, which is disadvantageous in terms of industrialization. In the methods (1) and (2), the yield is low, a large excess of expensive potassium iodide is used, and there is a step of dropping a dangerous diazonium salt solution in the production process, which is disadvantageous for industrialization.

【０００４】[0004]

【課題を解決するための手段】本発明者等は上記課題を
解決するために鋭意研究を重ねた結果、本発明を見出し
たものであり、本発明はヨードフタル酸類を、より簡便
に、安価且つ高収率で、しかも工業的に安全で新規な製
造方法を提供するものである。更に詳しくは、本発明は
一般式(IV)Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have found the present invention. The present invention provides iodophthalic acids in a simpler, more inexpensive and less expensive manner. An object of the present invention is to provide a novel production method which has a high yield and is industrially safe. More specifically, the present invention provides a compound of the general formula (IV)

【化５】 で表されるニトロフタル酸類を水溶媒中で塩基を処理
し、一般式(III)Embedded image A nitrophthalic acid represented by the formula (III)

【化６】 （式中、Ｍはアルカリ金属原子を示す。）で表されるニ
トロフタル酸ジアルカリ金属塩類とし、該ニトロフタル
酸ジアルカリ金属塩類を、加圧下に水溶媒中で、パラジ
ウム系触媒の存在下に接触水素添加反応し、一般式(II)Embedded image (Wherein, M represents an alkali metal atom). The dialkali metal nitrophthalate is catalytically hydrogenated in an aqueous solvent under pressure in the presence of a palladium-based catalyst. Reacts with the general formula (II)

【０００５】[0005]

【化７】 （式中、Ｍは前記に同じ。）で表されるアミノフタル酸
ジアルカリ金属塩類とし、該金属塩類を単離し又は単離
せずして、酸水溶液中で亜硝酸塩と反応させてジアゾニ
ウム塩とし、次いでヨード酸のアルカリ金属塩を反応さ
せることを特徴とする一般式(I)Embedded image (Wherein M is the same as described above) represented by a dialkali metal salt of aminophthalic acid, isolated or not isolated, reacted with nitrite in an aqueous acid solution to form a diazonium salt, General formula (I) characterized by reacting an alkali metal salt of iodo acid

【化８】 で表されるヨードフタル酸類の製造方法に関するもので
ある。Embedded image And a method for producing iodophthalic acids represented by the formula:

【０００６】本発明の製造方法の第一工程は、The first step of the production method of the present invention comprises:

【化９】 （式中、Ｍは前記に同じ。） 即ち、一般式(IV)で表されるニトロフタル酸類に水溶媒
中で塩基を処理し、一般式(III) で表されるニトロフタ
ル酸ジアルカリ金属塩類とし、該ニトロフタル酸ジアル
カリ金属塩類を、加圧下に水溶媒中で、パラジウム系触
媒の存在下に接触水素添加反応することにより一般式(I
I)表されるアミノフタル酸ジアルカリ金属塩類を製造す
ることができる。本反応でアルカリ金属原子としては、
例えばリチウム、ナトリウム、カリウム等のアルカリ金
属原子を示す。本反応で使用する塩基としては、例えば
水酸化ナトリウム、水酸化カリウム、水酸化リチウム等
のアルカリ金属の水酸化物を使用することができ、その
使用量は一般式(IV)で表されるニトロフタル酸類１モル
に対して２〜２．５モル、好ましくは２〜２．１モルの
範囲から適宜選択して使用することができ、アルカリ金
属の水酸化物は固体又は水溶液の形で使用することがで
きる。Embedded image (In the formula, M is the same as described above.) That is, a nitrophthalic acid represented by the general formula (IV) is treated with a base in an aqueous solvent to give a dialkali metal nitrophthalate represented by the general formula (III): The dialkali metal nitrophthalate is subjected to a catalytic hydrogenation reaction in an aqueous solvent under pressure in the presence of a palladium-based catalyst to obtain a compound of the general formula (I
I) The dialkali metal aminophthalates represented can be produced. In this reaction, as the alkali metal atom,
For example, it represents an alkali metal atom such as lithium, sodium and potassium. As the base used in this reaction, for example, hydroxides of alkali metals such as sodium hydroxide, potassium hydroxide, and lithium hydroxide can be used, and the amount of nitrophthalate represented by the general formula (IV) can be used. It can be appropriately selected from the range of 2 to 2.5 mol, preferably 2 to 2.1 mol per mol of the acid, and the alkali metal hydroxide is used in the form of a solid or an aqueous solution. Can be.

【０００７】溶媒として使用する水の量はアルカリ金属
の水酸化物を溶解した水を加えて、一般式(IV)で表され
るニトロフタル酸類１モル当たり０．４〜２Ｌ（リット
ル）、好ましくは０．５〜１Ｌの範囲である。パラジウ
ム系触媒としては、例えば５％パラジウム−カーボンが
好ましく、その使用量は一般式(IV)で表されるニトロフ
タル酸類の重量に対して０．１〜１０％、好ましくは１
〜５％の量で使用すれば良く、本パラジウム系触媒は容
易に回収、再利用することができる。本反応は加圧下に
行われ、１以上１０気圧の範囲で行われ、好ましくは２
〜６気圧の範囲である。反応温度は１０〜６０℃、好ま
しくは室温〜４０℃の範囲である。反応終了後、目的物
を常法により単離することもでき、単離せずに次の反応
に供することもでき、好ましくは反応系から触媒を濾過
により除き、得られたジアルカリ金属塩の水溶液をその
まま供するのが良い。The amount of water used as a solvent is 0.4 to 2 L (liter) per mole of nitrophthalic acid represented by the general formula (IV), preferably water in which an alkali metal hydroxide is dissolved. It is in the range of 0.5 to 1 L. As the palladium-based catalyst, for example, 5% palladium-carbon is preferable, and its use amount is 0.1 to 10%, preferably 1 to 10% by weight of the nitrophthalic acids represented by the general formula (IV).
The palladium-based catalyst can be easily recovered and reused. This reaction is carried out under pressure, in the range of 1 to 10 atm, preferably 2 to 10 atm.
６6 atm. The reaction temperature ranges from 10 to 60 ° C, preferably from room temperature to 40 ° C. After completion of the reaction, the desired product can be isolated by a conventional method, or can be subjected to the next reaction without isolation.Preferably, the catalyst is removed from the reaction system by filtration, and the obtained aqueous solution of the dialkali metal salt is removed. It is good to serve as it is.

【０００８】次いで本発明の製造方法の第二工程は、Next, the second step of the production method of the present invention comprises:

【化１０】 （式中、Ｍは前記に同じ。） 一般式(II)で表されるアミノフタル酸ジアルカリ金属塩
類を酸水溶液中で冷却下に亜硝酸塩と反応させてジアゾ
ニウム塩とし、次いでヨード酸のアルカリ金属塩を反応
させることにより一般式(I) で表されるヨードフタル酸
類を製造することができる。ジアゾ化反応で使用する酸
としては、例えば塩酸又は硫酸等の鉱酸類が良く、その
使用濃度は１Ｎ〜１２Ｎの範囲であり、好ましくは３Ｎ
〜８Ｎ濃度の塩酸酸性懸濁液として反応させるのが良
い。Embedded image (Wherein M is the same as above.) The dialkali metal aminophthalate represented by the general formula (II) is reacted with a nitrite under cooling in an aqueous acid solution to form a diazonium salt, and then an alkali metal salt of iodo acid The iodophthalic acids represented by the general formula (I) can be produced by reacting As the acid used in the diazotization reaction, for example, a mineral acid such as hydrochloric acid or sulfuric acid may be used, and its concentration is in the range of 1N to 12N, preferably 3N.
The reaction is preferably performed as a hydrochloric acid suspension having a concentration of ８8N.

【０００９】亜硝酸塩としては、例えば亜硝酸ナトリウ
ムが好ましく、その使用量は一般式(II)で表されるアミ
ノフタル酸ジアルカリ金属塩類１モルに対して１〜１．
５モルを水溶液の形で使用すれば良い。添加時の反応温
度は０〜１５℃の範囲で、添加後は１０〜２０℃の範囲
で行うのが好ましい。As the nitrite, for example, sodium nitrite is preferable, and the amount of the nitrite is from 1 to 1. based on 1 mol of the dialkali metal aminophthalate represented by the general formula (II).
5 mol may be used in the form of an aqueous solution. The reaction temperature during the addition is preferably in the range of 0 to 15 ° C, and after the addition, the reaction is preferably performed in the range of 10 to 20 ° C.

【００１０】本発明の一般式(I) で表されるヨードフタ
ル酸類は、公知の製造方法〔J.Am.Chem.Soc.,1865 (192
9)〕により下記に示す化合物を製造することができ、該
化合物は、医薬、農薬、化学品等の中間体として有用な
化合物である。The iodophthalic acids of the present invention represented by the general formula (I) can be prepared by a known production method [J. Am. Chem. Soc., 1865 (192)
9)], the following compounds can be produced, and these compounds are useful as intermediates for pharmaceuticals, agricultural chemicals, chemicals and the like.

【化１１】 以下に本発明の代表的な実施例を例示するが、本発明は
これらに限定されるものではない。Embedded image Hereinafter, typical examples of the present invention will be illustrated, but the present invention is not limited thereto.

【００１１】[0011]

【実施例】実施例１．３−ニトロフタル酸１００ｇ
（０．４７４モル）を３Ｎ水酸化ナトリウム水溶液３１
７ｍｌに溶解し、水８３ｍｌを加える。該溶液に５％パ
ラジウム炭素５ｇを加えて６ｋｇ／ｃｍ2 の水素圧下で
反応を行った。規定量の水素消費を確認した後、反応液
を濾過し、触媒を水２００ｍｌで洗浄して、合わせた濾
液に氷冷下に濃塩酸８００ｍｌを加える。次いで亜硝酸
ナトリウム３５．４ｇ（９７％、０．４９７モル）の水
（１００ｍｌ）溶液を氷冷下に滴下した。滴下後３時間
攪拌し反応後、ヨウ化カリウム１１８ｇ（０．７１０モ
ル）及び尿素５ｇの水（１２５ｍｌ）溶液を滴下し、滴
下後室温下で４時間攪拌後、一夜放置する。反応終了
後、反応液から目的物を酢酸エチルで抽出し、有機層を
チオ硫酸ナトリウム、次いで飽和食塩水で洗浄し、無水
硫酸ナトリウムで乾燥後、溶媒を留去することにより目
的物である３−ヨードフタル酸１１２．３ｇを得た。 物性 ｍ．ｐ．１８１−１８３℃ 収率 ８１％1 Ｈ−ＮＭＲ〔d-DMSO/TMS、δ値(ppm) 〕 7.72(t.1H), 7.92(d.1H), 8.10(d.1H), 13.4(br.2H).EXAMPLES Example 1.3 100 g of 3-nitrophthalic acid
(0.474 mol) in 3N aqueous sodium hydroxide solution 31
Dissolve in 7 ml and add 83 ml of water. 5 g of 5% palladium carbon was added to the solution, and the reaction was performed under a hydrogen pressure of 6 kg / cm 2 . After confirming the consumption of a specified amount of hydrogen, the reaction solution is filtered, the catalyst is washed with 200 ml of water, and 800 ml of concentrated hydrochloric acid is added to the combined filtrate under ice-cooling. Then, a solution of 35.4 g (97%, 0.497 mol) of sodium nitrite in water (100 ml) was added dropwise under ice cooling. After the dropwise addition, the mixture is stirred for 3 hours, and after the reaction, a solution of 118 g (0.710 mol) of potassium iodide and 5 g of urea in water (125 ml) is added dropwise. After the addition, the mixture is stirred at room temperature for 4 hours and left overnight. After completion of the reaction, the desired product is extracted from the reaction solution with ethyl acetate, the organic layer is washed with sodium thiosulfate and then with a saturated saline solution, dried over anhydrous sodium sulfate, and the solvent is distilled off. -112.3 g of iodophthalic acid were obtained. Physical properties m. p. 181-183 ° C. Yield 81% 1 H-NMR [d-DMSO / TMS, δ value (ppm)] 7.72 (t.1H), 7.92 (d.1H), 8.10 (d.1H), 13.4 (br. 2H).

【００１２】参考例１．実施例１と同様にして得られた
３−ヨードフタル酸１６９．５ｇ（０．５８１モル）を
無水酢酸に懸濁させた後、３０分間加熱還流して反応を
行った。反応終了後、無水酢酸を留去し、得られた結晶
をイソプロピルエーテルで洗浄後、乾燥することにより
３−ヨードフタル酸無水物１３３．１ｇを得た。 物性 ｍ．ｐ．１６１−１６４℃ 収率 ８４％1 Ｈ−ＮＭＲ〔CDCl3/TMS 、δ値(ppm) 〕 7.57(t.1H), 8.01(d.1H), 8.30(d.1H).Reference Example 1 After suspending 169.5 g (0.581 mol) of 3-iodophthalic acid obtained in the same manner as in Example 1 in acetic anhydride, the reaction was carried out by heating and refluxing for 30 minutes. After completion of the reaction, acetic anhydride was distilled off, and the obtained crystals were washed with isopropyl ether and dried to obtain 133.1 g of 3-iodophthalic anhydride. Physical properties m. p. 161-164 ° C Yield 84% 1 H-NMR [CDCl 3 / TMS, δ value (ppm)] 7.57 (t.1H), 8.01 (d.1H), 8.30 (d.1H).

【００１３】[0013]

【発明の効果】本発明の製造方法は、ニトロフタル酸よ
りヨードフタル酸類を高収率で製造することができ、更
には穏やかな反応条件と工業的製造面での安全性の高い
製造方法である。According to the production method of the present invention, iodophthalic acids can be produced at a high yield from nitrophthalic acid, and furthermore, it is a production method with mild reaction conditions and high safety in industrial production.

Claims (1)

【特許請求の範囲】[Claims] 【請求項１】 一般式(IV) 【化１】 で表されるニトロフタル酸類を水溶媒中で塩基を処理
し、一般式(III) 【化２】 （式中、Ｍはアルカリ金属原子を示す。）で表されるニ
トロフタル酸ジアルカリ金属塩類とし、該ニトロフタル
酸ジアルカリ金属塩類を、加圧下に水溶媒中で、パラジ
ウム系触媒の存在下に接触水素添加反応し、一般式(II) 【化３】 （式中、Ｍは前記に同じ。）で表されるアミノフタル酸
ジアルカリ金属塩類とし、該金属塩類を単離し又は単離
せずして、酸水溶液中で亜硝酸塩と反応させてジアゾニ
ウム塩とし、次いでヨード酸のアルカリ金属塩を反応さ
せることを特徴とする一般式(I) 【化４】 で表されるヨードフタル酸類の製造方法。1. A compound of the general formula (IV) A nitrophthalic acid represented by the formula is treated with a base in an aqueous solvent to obtain a compound represented by the general formula (III): (Wherein, M represents an alkali metal atom). The dialkali metal nitrophthalate is catalytically hydrogenated in an aqueous solvent under pressure in the presence of a palladium-based catalyst. Reacts with the general formula (II) (Wherein M is the same as described above) represented by a dialkali metal salt of aminophthalic acid, isolated or not isolated, reacted with nitrite in an aqueous acid solution to form a diazonium salt, General formula (I) characterized by reacting an alkali metal salt of iodo acid. A method for producing an iodophthalic acid represented by the formula:
JP11152024A 1998-06-22 1999-05-31 Production of iodophthalic acid compounds Pending JP2000080058A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP11152024A JP2000080058A (en) 1998-06-22 1999-05-31 Production of iodophthalic acid compounds

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP10-174413 1998-06-22
JP17441398 1998-06-22
JP11152024A JP2000080058A (en) 1998-06-22 1999-05-31 Production of iodophthalic acid compounds

Publications (1)

Publication Number Publication Date
JP2000080058A true JP2000080058A (en) 2000-03-21

Family

ID=26481069

Family Applications (1)

Application Number Title Priority Date Filing Date
JP11152024A Pending JP2000080058A (en) 1998-06-22 1999-05-31 Production of iodophthalic acid compounds

Country Status (1)

Country Link
JP (1) JP2000080058A (en)

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