JP4111777B2 - 2- (3-Sulfopropoxy) anilines and process for producing the same - Google Patents

Description

（式中Ｒは（Ｃ１〜Ｃ４）アルキル基、（Ｃ１〜Ｃ４）アルコキシ基又はハロゲンを表す）
（２）ａ）一般式（１−２）で示される２−ヒドロキシアセトアニリド類
【化９】

（式中Ｒ’は水素原子、（Ｃ１〜Ｃ４）アルキル基、（Ｃ１〜Ｃ４）アルコキシ基又はハロゲンを表す）とプロパンスルトンとを溶媒中反応させることによる一般式（２−２）で示される２−（３−スルホプロポキシ）アセトアニリド類
【化１０】

（式中Ｒ’は前記と同じ意味を有し、Ｍはアルカリ金属またはアルカリ土類金属を表す）を得る第一工程、
ｂ）一般式（２−２）を加水分解することによる一般式（３−２）で示される２−（３−スルホプロポキシ）アニリン類の製造方法、
【化１１】

（式中Ｒ’は前記と同じ意味を有す）
（３）ａ）一般式（１−２）で示される２−ヒドロキシアセトアニリド類
【化１２】

（式中Ｒ’は水素原子、（Ｃ１〜Ｃ４）アルキル基、（Ｃ１〜Ｃ４）アルコキシ基又はハロゲンを表す）とプロパンスルトンとを非プロトン性極性溶媒とアルキルベンゼンの混合溶媒中、無機塩基存在下反応させることによる一般式（２−２）で示される２−（３−スルホプロポキシ）アセトアニリド類
【化１３】

（式中Ｒ’は前記と同じ意味を有し、Ｍはアルカリ金属またはアルカリ土類金属を表す）を得る第一工程、
ｂ）一般式（２−２）を鉱酸水溶液中で加水分解することによる一般式（３−２）で示される２−（３−スルホプロポキシ）アニリン類の製造方法、
【化１４】

（式中Ｒ’は前記と同じ意味を有す）
を提供する。
本発明によれば反応中に分解を起こすことなく高純度の２−（３−スルホプロポキシ）アニリン類を安定に単離することができ工業的にも優れている。
【０００５】
【発明の実施の形態】
次に好ましい実施の形態を挙げて本発明を詳しく説明する。本発明の製法における第一工程の反応において使用される２−ヒドロキシアセトアニリド類は２−ヒドロキシアニリンを公知の方法でアセチル化することにより得ることが出来る。２−ヒドロキシアセトアニリド類とプロパンスルトンとの反応は、下式のように表され、
【０００６】
【化１５】

【０００７】
（Ｍはアルカリ金属またはアルカリ土類金属を示し、Ｌｉ、Ｋ、Ｎａ、Ｍｇ、Ｃａが好ましい。）
【０００８】
この工程は、実質的に無水の状態で反応させることが好ましい。即ち反応は例えば、非プロトン性極性溶媒と芳香族炭化水素溶媒中に２−ヒドロキシアセトアニリド類を仕込み加熱下、必要により、あらかじめ共沸脱水によって反応系より水を除いたのち無機塩基(アルカリ金属塩またはアルカリ土類金属塩、好ましくはＬｉ、Ｋ、Ｎａ、Ｍｇ、Ｃａの塩）を仕込み、加熱下にプロパンスルトンを滴下し付加させる方法がとられる。ここで非プロトン性極性溶媒としてはジメチルホルムアミド、ジメチルアセトアミド、１，３−ジメチルイミダゾリジノン、ジメチルスルホキシド、スルホラン等が用いられ、好ましくはジメチルホルムアミド、１，３−ジメチルイミダゾリジノンである。また芳香族炭化水素溶媒としてはトルエン、キシレン、モノクロロベンゼン、ニトロベンゼン等が用いられ、好ましくはトルエン、キシレンである。反応温度は通常１００〜１６０℃、好ましくは１１０〜１４０℃、反応時間は、通常３０分間〜７時間、好ましくは１時間〜４時間行う。プロパンスルトンの使用量は２−ヒドロキシアセトアニリド類１モルに対し通常１．０〜２．０モル、好ましくは１．１〜１．５モル使用する。また無機塩基としては炭酸ナトリウム、炭酸カリウム、炭酸カルシウム、炭酸水素ナトリウム、炭酸水素カリウム、水酸化リチウム、水酸化ナトリウム、水酸化カリウム、水酸化マグネシウム、酸化マグネシウム、酢酸ナトリウム、酢酸カリウムなどが使用できる。無機塩基の使用量はプロパンスルトン１モルに対し０．５〜３．０モル、好ましくは０．７〜２．２モル使用する。反応生成物はそのまま取り出さずに次工程に使用できるが、好ましくは使用した溶媒の約半量を回収し、更に副生する無機塩を分離後次工程に使用する。
第二工程は、前工程で得られた反応液から無機塩と溶媒を除去後、水に溶解し鉱酸にて中和後、更に鉱酸の酸性下にてアセトアニリド類を加水分解する。加水分解条件は通常酸濃度１．０〜１０．０質量％、好ましくは３．０〜７．０質量％で行うのがよい。鉱酸の使用量は２−（３−スルホプロポキシ）アセトアニリド１．０モルに対し通常３．０〜１０．０モル、好ましくは４．０〜８．０モルである。反応温度は通常７０〜１１０℃、好ましくは８０〜１００℃である。反応時間は通常３０分間〜５時間、好ましくは１〜３時間である。鉱酸としては塩酸、硫酸、硝酸等が使用できる。加水分解が進むに従って結晶が析出してくるので、それを濾別する事により高純度の２−（３−スルホプロポキシ）アニリン類が得られる。
【０００９】
本発明によれば、強酸性化で反応することより生成物中のアミノ基がスルホン酸基と分子内塩を形成し安定な状態で、しかも高純度で２−（３−スルホプロポキシ）アニリン類を安定に製造することが可能となる。また、結晶が安定な構造形であるため、濾過性が良好であり、工業的にも有位である。また、得られた水溶性芳香族アミンは、機能性色素、農薬、医薬用の中間体として有用である。
【００１０】
【実施例】
次に実施例及び比較例を挙げて本発明を更に詳細に説明するが、本発明はこれらにより何ら限定されるものではない。尚、％は断りのない限り質量％である。
【００１１】
実施例１
（第一工程 ２−（３−スルホプロポキシ）アセトアニリドの製造）
攪拌機、ディーンスターク・トラップ、還流管、及び温度計を備えた５００ｍｌフラスコに、２−ヒドロキシアセトアニリド６８．０ｇ（０．４５モル）、ジメチルホルムアミド２００ｍｌ、トルエン６０ｍｌを仕込み、８０〜１２０℃で６０分間還流させ、この間トルエンとの共沸により原料中の水分を除去した。次に反応液を８０℃以下に冷却し無水炭酸カリウム６２．１ｇを仕込み後、再び加熱し１２０℃〜１３５℃でプロパンスルトン６０．４ｇを約1時間要して滴下した。滴下終了後同温度で２時間還流し反応を完結させた。次いでディーンスターク・トラップのコックを開けて同温度で加熱を続けて溶媒を１００ｍｌ回収後、冷却した。
（第二工程 ２−（３−スルホプロポキシ）アニリンの製造）
攪拌機、還流管、及び温度計を備えた１０００ｍｌフラスコに水４００ｍｌを仕込み、次いで第一工程で得られた反応液を上記水に溶解した。得られた水溶液を３５％塩酸５０ｇにて中和後、更に３５％塩酸１２５ｇを加えたのち、９５〜１００℃で２時間加熱し、反応させた。反応終了後、冷却し４０℃以下となったら析出した結晶を濾別し、５％塩酸１００ｇで洗浄する事により２−（３−スルホプロポキシ）アニリン１０９．３ｇ（通算収率９２％）を得た。純度：８７．５％（ジアゾ化値）、９８％（ＨＰＬＣ面積比）
【００１２】
実施例２
（第一工程 ５−メチル−２−（３−スルホプロポキシ）アセトアニリドの製造）
攪拌機、ディーンスターク・トラップ、還流管、及び温度計を備えた５００ｍｌフラスコに、２−ヒドロキシ−５−メチルアセトアニリド６２．７ｇ（０．３８モル）、ジメチルホルムアミド１５０ｍｌ、トルエン５０ｍｌを仕込み、８０〜１２０℃で６０分間還流させ、この間トルエンとの共沸により原料中の水分を除去した。次にこの液を、８０℃以下に冷却し、無水炭酸カリウム４２．０ｇを仕込み後、再び加熱し１２０℃〜１３５℃でプロパンスルトン５５．６ｇを約１時間要して滴下した。滴下終了後同温度で２時間還流し反応を完結させた。次いでディーンスターク・トラップのコックを開けて同温度で加熱を続けて溶媒を５０ｍｌ回収後、冷却した。
（第二工程 ５−メチル−２−（３−スルホプロポキシ）アニリンの製造）
攪拌機、還流管、及び温度計を備えた１０００ｍｌフラスコに水３００ｍｌを仕込み、次いで第一工程で得られた反応液をこの水に溶解する。得られた水溶液を３５％塩酸２０ｇにて中和後、更に３５％塩酸７２ｇを加えたのち、９５〜１００℃で４時間反応させ加水分解した。反応後、冷却し４０℃以下となったら析出した結晶を濾別し、５％塩酸１００ｇで洗浄する事により５―メチル―２−（３−スルホプロポキシ）アニリン９９．２ｇ（通算収率９４．８％）を得た。純度：８９％（ジアゾ化値）、９８．５％（ＨＰＬＣ面積比）
【００１３】
実施例３
実施例２において第二工程における塩酸の代わりに硫酸を使用する以外は実施例２と同様に反応を行い５―メチル―２−（３−スルホプロポキシ）アニリン９４．４ｇ（通算収率９０．０％）を得た。純度：８８．８％（ジアゾ化値）、９８．０％（ＨＰＬＣ面積比）
【００１４】
実施例４
（第一工程 ５−メチル−２−（３−スルホプロポキシ）アセトアニリドの製造）
攪拌機、ディーンスターク・トラップ、還流管、及び温度計を備えた５００ｍｌフラスコに、２−ヒドロキシ−５−メチルアセトアニリド６２．７ｇ（０．３８モル）、無水炭酸ナトリウム３２．２ｇ（０．３０モル）、１，３−ジメチルイミダゾリジノン１５０ｍｌ、トルエン５０ｍｌを仕込み、８０〜１２０℃で６０分間還流させ、この間トルエンとの共沸により原料中の水分を除去した。次いで、１２０〜１３５℃でプロパンスルトン５５．６ｇを約１時間要して滴下した。滴下終了後同温度で２時間還流し反応を完結させた。次いでディーンスターク・トラップのコックを開けて同温度で加熱を続けて溶媒を５０ｍｌ回収後、冷却した。
（第二工程 ５−メチル−２−（３−スルホプロポキシ）アニリンの製造）
攪拌機、還流管、及び温度計を備えた１０００ｍｌフラスコに水３００ｍｌ仕込み、次いで第一工程で得られた反応液をこの水に溶解する。得られた水溶液を５０％硫酸４０ｇにて中和後、更に５０％硫酸２５．０ｇを加えたのち、９５〜１００℃で６時間反応させた。反応後、冷却し４０℃以下となったら析出した結晶を濾別し、５％塩酸１００ｇで洗浄する事により５―メチル―２−（３−スルホプロポキシ）アニリン１００．７ｇ（通算収率９２．０％）を得た。純度：８５％（ジアゾ化値）、９８％（ＨＰＬＣ面積比）
【００１５】
参考例１
水９００ｇ中に式（４）の化合物７４．３ｇを塩酸でｐＨ１．０〜３．０に調整しながら溶解した後、５〜１０℃とし、３５％塩酸５３．２ｇ、４０％亜硝酸ナトリウム水溶液２７．０ｇを添加しジアゾ化した。
【００１６】
【化１６】

【００１７】
次いで、得られた式（４）の化合物のジアゾ懸濁液に、実施例２により得られた化合物３６．８ｇを含む溶液を０〜１０℃の温度でゆっくり滴下した。滴下終了後、ｐＨ値を水酸化ナトリウム水溶液の添加により３．０〜４．０とし、その後５〜１０℃で１時間、１５〜２５℃で８時間、いずれの間もｐＨ３．０〜４．０で撹拌しカップリング反応を完結させ、式（５）の化合物を含む反応液を得た。
【００１８】
【化１７】

【００１９】
次に上記で得られた式（５）の化合物を含む溶液を、水酸化ナトリウム水溶液で弱アルカリ性とし、ここに４０％亜硝酸ナトリウム水溶液３３．５ｇを添加した。この溶液を水２００ｇ、３５％塩酸６２．６ｇの溶液中に３０分かけて滴下してジアゾ化し、この懸濁液を７−アミノ−１−ヒドロキシナフタレン−３−スルホン酸３５．９ｇのアルカリ性水溶液に１５〜３０℃で滴下した。滴下中は溶液のｐＨ値を炭酸ナトリウムにて８．５〜９．５に保持した。滴下終了後、更に１５〜３０℃で３時間、ｐＨ８．５〜９．５で攪拌しカップリング反応を完結させ、式（６）の化合物を含む反応液を得た。（式（６）中、Ｔｓはｐ−トルエンスルホン酸残基を示す）
【００２０】
【化１８】

【００２１】
上記で得られた式（６）の化合物を含む反応液を７５℃に加熱した。加熱後、水酸化ナトリウムにてｐＨ１０．７とし、７０〜７５℃、ｐＨ１０．６〜１０．８の条件で約１時間保持した。その後、塩酸によってｐＨを約８．０とし、塩化ナトリウムを加えて塩析を行い、濾過、単離して式（７）の化合物９４．９ｇを得た。
【００２２】
【化１９】

【００２３】
上記反応で得られた式（７）の化合物８．６ｇを水１２０ｇに溶解後、４０％亜硝酸ナトリウム水溶液２．５ｇを添加し、この水溶液を５％塩酸水溶液５０ｇに１５〜３０℃で滴下し、ジアゾ化し、これを８−アミノ−２−ナフタレンスルホン酸２．３ｇの水溶液に１５〜３０℃で滴下した。滴下中はカップリング溶液のｐＨ値を炭酸ナトリウムにて６．０〜７．０に保持した。滴下終了後、１５〜３０℃、ｐＨ６．０〜７．０で１時間攪拌し、その後、ｐＨ値を炭酸ナトリウムにて約８．５とし、１５〜３０℃、ｐＨ７．５〜８．５で５時間攪拌しカップリング反応を完結させた。このあと塩化ナトリウムを加えて塩析を行い、濾過した。得られたケーキ全量を水１５０ｇに溶解し、２−プロパノール８０ｇの添加により晶析させ濾過することにより脱塩し、次いで乾燥して式（８）のトリスアゾ化合物９．６ｇを得た。
【００２４】
【化２０】

【００２５】
上記反応で得られた式（８）の化合物５．８ｇを水１００ｇに溶解後、更に塩化シアヌール１．２ｇを１５〜３０℃で添加した。添加後、１５〜３０℃、ｐＨ値を炭酸ナトリウムにて６．０〜６．７に保持しながら２時間攪拌した。次にモノエタノールアミン２．５ｇを１５〜３０℃、ｐＨ値を５％塩酸にて８．０〜９．０に保持しながら３０分で滴下した。滴下終了後、ｐＨ値を炭酸ナトリウムにて８．０〜９．０に保持しながら１５〜３０℃で３時間、更に８５〜９５℃に昇温後、ｐＨ値を炭酸ナトリウムにて８．５〜９．０に保持しながら４時間攪拌した。２０〜３０℃まで冷却後、３５％塩酸にてｐＨ値を５．５〜６.５とした後、不溶解分を濾過にて除去し、塩化ナトリウムを加えて塩析を行い、濾過した。得られたケーキ全量を水７０ｇに溶解し、メタノール７０ｇの添加により晶析させ濾過することにより脱塩し、次いで乾燥して式（９）の化合物４．８ｇを得た。この化合物の水中での最大吸収波長（λｍａｘ）は６１１ｎｍであった。この化合物は、高純度の機能性色素、とりわけインクジェット用のブラックとして有用である。
【００２６】
【化２１】

【００２７】
【発明の効果】
高純度の２−（３−スルホプロポキシ）アニリン類を安定な構造形で製造することが可能となり、これを中間体として用いて、機能性色素、農薬、医薬などを製造することができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing a water-soluble aromatic amine useful as an intermediate for functional dyes, agricultural chemicals and pharmaceuticals.
[0002]
[Prior art]
As a method for water-solubilizing water-insoluble aromatic amines or phenols, for example, a method of sulfopropylating a hydroxyl group of these compounds using propane sultone is known. However, there is no known method for selective sulfopropoxylation of a hydroxyl group for a compound in which an amino group and a hydroxyl group coexist in an aromatic nucleus. This is because it is difficult to selectively react propane sultone with the hydroxyl group because the amino group is more reactive than the hydroxyl group when sulfopropylation is carried out under normal conditions.
Japanese Patent No. 3271173 discloses a method for obtaining a target product by reducing a nitro group after sulfopropylating a nitrophenol which is an amino group precursor. However, sulfopropoxyanilines obtained by reduction are easily oxidized in the reaction solution, and it is difficult to obtain a high-purity target product.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to provide an industrially advantageous production method for 2- (3-sulfopropoxy) anilines which cannot be satisfied by conventional methods.
[0004]
[Means for Solving the Problems]
As a result of intensive studies to solve the above problems, the present inventors have reached the present invention. That is, the present invention
(1) 2- (3-sulfopropoxy) anilines represented by the general formula (3-1),
[Chemical 8]

(Wherein R represents a (C1-C4) alkyl group, a (C1-C4) alkoxy group or a halogen).
(2) a) 2-Hydroxyacetanilides represented by the general formula (1-2)

(Wherein R ′ represents a hydrogen atom, (C1 to C4) alkyl group, (C1 to C4) alkoxy group or halogen) and propane sultone are reacted in a solvent and represented by the general formula (2-2). 2- (3-Sulfopropoxy) acetanilides

Wherein R ′ has the same meaning as described above, and M represents an alkali metal or an alkaline earth metal,
b) a process for producing 2- (3-sulfopropoxy) anilines represented by general formula (3-2) by hydrolyzing general formula (2-2);
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(Wherein R ′ has the same meaning as above)
(3) a) 2-Hydroxyacetanilides represented by the general formula (1-2)

(Wherein R ′ represents a hydrogen atom, (C1 to C4) alkyl group, (C1 to C4) alkoxy group or halogen) and propane sultone in a mixed solvent of an aprotic polar solvent and an alkylbenzene in the presence of an inorganic base. 2- (3-sulfopropoxy) acetanilides represented by the general formula (2-2) by reaction:

Wherein R ′ has the same meaning as described above, and M represents an alkali metal or an alkaline earth metal,
b) A process for producing 2- (3-sulfopropoxy) anilines represented by general formula (3-2) by hydrolyzing general formula (2-2) in an aqueous mineral acid solution,
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(Wherein R ′ has the same meaning as above)
I will provide a.
According to the present invention, high-purity 2- (3-sulfopropoxy) anilines can be stably isolated without causing decomposition during the reaction, which is industrially excellent.
[0005]
DETAILED DESCRIPTION OF THE INVENTION
Next, the present invention will be described in detail with reference to preferred embodiments. The 2-hydroxyacetanilides used in the reaction in the first step in the production method of the present invention can be obtained by acetylating 2-hydroxyaniline by a known method. The reaction between 2-hydroxyacetanilides and propane sultone is represented by the following formula:
[0006]
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[0007]
(M represents an alkali metal or an alkaline earth metal, and Li, K, Na, Mg, and Ca are preferable.)
[0008]
This step is preferably performed in a substantially anhydrous state. That is, the reaction is carried out, for example, by adding 2-hydroxyacetanilides in an aprotic polar solvent and an aromatic hydrocarbon solvent and, if necessary, removing water from the reaction system by azeotropic dehydration in advance and then removing an inorganic base (alkali metal salt). Alternatively, an alkaline earth metal salt (preferably a salt of Li, K, Na, Mg, Ca) is charged, and propane sultone is added dropwise under heating. Here, as the aprotic polar solvent, dimethylformamide, dimethylacetamide, 1,3-dimethylimidazolidinone, dimethylsulfoxide, sulfolane and the like are used, and dimethylformamide and 1,3-dimethylimidazolidinone are preferable. As the aromatic hydrocarbon solvent, toluene, xylene, monochlorobenzene, nitrobenzene or the like is used, and preferably toluene or xylene. The reaction temperature is usually 100 to 160 ° C., preferably 110 to 140 ° C., and the reaction time is usually 30 minutes to 7 hours, preferably 1 hour to 4 hours. The amount of propane sultone to be used is generally 1.0 to 2.0 mol, preferably 1.1 to 1.5 mol, per 1 mol of 2-hydroxyacetanilide. Examples of inorganic bases that can be used include sodium carbonate, potassium carbonate, calcium carbonate, sodium bicarbonate, potassium bicarbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, magnesium oxide, sodium acetate, and potassium acetate. . The amount of the inorganic base used is 0.5 to 3.0 mol, preferably 0.7 to 2.2 mol, relative to 1 mol of propane sultone. The reaction product can be used in the next step without being taken out as it is, but preferably about half of the solvent used is recovered, and the inorganic salt produced as a by-product is separated and used in the next step.
In the second step, the inorganic salt and the solvent are removed from the reaction solution obtained in the previous step, dissolved in water, neutralized with a mineral acid, and then acetanilides are hydrolyzed under the acidity of the mineral acid. The hydrolysis conditions are usually carried out at an acid concentration of 1.0 to 10.0% by mass, preferably 3.0 to 7.0% by mass. The amount of mineral acid used is usually 3.0 to 10.0 mol, preferably 4.0 to 8.0 mol, per 1.0 mol of 2- (3-sulfopropoxy) acetanilide. The reaction temperature is usually 70 to 110 ° C, preferably 80 to 100 ° C. The reaction time is usually 30 minutes to 5 hours, preferably 1 to 3 hours. As the mineral acid, hydrochloric acid, sulfuric acid, nitric acid and the like can be used. Crystals precipitate as the hydrolysis proceeds, and high purity 2- (3-sulfopropoxy) anilines can be obtained by filtering them.
[0009]
According to the present invention, 2- (3-sulfopropoxy) anilines are highly stable in a stable state in which the amino group in the product forms an inner salt with a sulfonic acid group by reacting with strong acidification. Can be manufactured stably. Moreover, since the crystal is a stable structural form, the filterability is good and it is industrially dominant. The obtained water-soluble aromatic amine is useful as an intermediate for functional dyes, agricultural chemicals and pharmaceuticals.
[0010]
【Example】
EXAMPLES Next, although an Example and a comparative example are given and this invention is demonstrated further in detail, this invention is not limited at all by these. % Is% by mass unless otherwise noted.
[0011]
Example 1
(First step 2- (3-sulfopropoxy) acetanilide production)
A 500 ml flask equipped with a stirrer, Dean-Stark trap, reflux tube, and thermometer was charged with 68.0 g (0.45 mol) of 2-hydroxyacetanilide, 200 ml of dimethylformamide, and 60 ml of toluene at 80 to 120 ° C. for 60 minutes. During this period, water in the raw material was removed by azeotropy with toluene. Next, the reaction liquid was cooled to 80 ° C. or lower, charged with 62.1 g of anhydrous potassium carbonate, heated again, and 60.4 g of propane sultone was added dropwise at 120 to 135 ° C. over about 1 hour. After completion of the dropping, the reaction was completed by refluxing at the same temperature for 2 hours. Next, the Dean Stark trap cock was opened and heating was continued at the same temperature to recover 100 ml of the solvent, followed by cooling.
(Second Step 2-Production of 2- (3-sulfopropoxy) aniline)
400 ml of water was charged into a 1000 ml flask equipped with a stirrer, a reflux tube, and a thermometer, and then the reaction solution obtained in the first step was dissolved in the water. The obtained aqueous solution was neutralized with 50 g of 35% hydrochloric acid, 125 g of 35% hydrochloric acid was further added, and the mixture was heated at 95-100 ° C. for 2 hours to be reacted. After the completion of the reaction, the mixture was cooled to 40 ° C. or lower, and the precipitated crystals were separated by filtration and washed with 100 g of 5% hydrochloric acid to obtain 109.3 g of 2- (3-sulfopropoxy) aniline (92% overall yield). It was. Purity: 87.5% (diazotization value), 98% (HPLC area ratio)
[0012]
Example 2
(First step: production of 5-methyl-2- (3-sulfopropoxy) acetanilide)
A 500 ml flask equipped with a stirrer, a Dean-Stark trap, a reflux tube, and a thermometer was charged with 62.7 g (0.38 mol) of 2-hydroxy-5-methylacetanilide, 150 ml of dimethylformamide, and 50 ml of toluene. The mixture was refluxed at 60 ° C. for 60 minutes, during which time water in the raw material was removed by azeotropy with toluene. Next, this liquid was cooled to 80 ° C. or lower, charged with 42.0 g of anhydrous potassium carbonate, heated again, and 55.6 g of propane sultone was added dropwise at 120 ° C. to 135 ° C. over about 1 hour. After completion of the dropping, the reaction was completed by refluxing at the same temperature for 2 hours. Next, the Dean Stark trap cock was opened and heating was continued at the same temperature to recover 50 ml of the solvent, followed by cooling.
(Second step: production of 5-methyl-2- (3-sulfopropoxy) aniline)
A 1000 ml flask equipped with a stirrer, a reflux tube, and a thermometer is charged with 300 ml of water, and then the reaction solution obtained in the first step is dissolved in this water. The obtained aqueous solution was neutralized with 20 g of 35% hydrochloric acid, and further 72 g of 35% hydrochloric acid was added, followed by hydrolysis at 95-100 ° C. for 4 hours. After the reaction, the reaction mixture was cooled to 40 ° C. or lower, and the precipitated crystals were separated by filtration and washed with 100 g of 5% hydrochloric acid to obtain 99.2 g of 5-methyl-2- (3-sulfopropoxy) aniline (total yield: 94. 8%). Purity: 89% (diazotization value), 98.5% (HPLC area ratio)
[0013]
Example 3
The reaction was carried out in the same manner as in Example 2 except that sulfuric acid was used in place of hydrochloric acid in the second step in Example 2, and 94.4 g of 5-methyl-2- (3-sulfopropoxy) aniline (total yield 90.0) %). Purity: 88.8% (diazotization value), 98.0% (HPLC area ratio)
[0014]
Example 4
(First step: production of 5-methyl-2- (3-sulfopropoxy) acetanilide)
In a 500 ml flask equipped with a stirrer, Dean-Stark trap, reflux tube, and thermometer, 62.7 g (0.38 mol) of 2-hydroxy-5-methylacetanilide and 32.2 g (0.30 mol) of anhydrous sodium carbonate 1,3-dimethylimidazolidinone 150 ml and toluene 50 ml were charged and refluxed at 80 to 120 ° C. for 60 minutes. During this time, water in the raw material was removed by azeotropy with toluene. Subsequently, 55.6 g of propane sultone was added dropwise at 120 to 135 ° C. over about 1 hour. After completion of the dropping, the reaction was completed by refluxing at the same temperature for 2 hours. Next, the Dean Stark trap cock was opened and heating was continued at the same temperature to recover 50 ml of the solvent, followed by cooling.
(Second step: production of 5-methyl-2- (3-sulfopropoxy) aniline)
A 1000 ml flask equipped with a stirrer, a reflux tube, and a thermometer is charged with 300 ml of water, and then the reaction solution obtained in the first step is dissolved in this water. The obtained aqueous solution was neutralized with 40 g of 50% sulfuric acid, 25.0 g of 50% sulfuric acid was further added, and the mixture was reacted at 95-100 ° C. for 6 hours. After the reaction, the reaction mixture was cooled to 40 ° C. or lower, and the precipitated crystals were filtered out and washed with 100 g of 5% hydrochloric acid to give 100.7 g of 5-methyl-2- (3-sulfopropoxy) aniline (total yield: 92. 0%) was obtained. Purity: 85% (diazotization value), 98% (HPLC area ratio)
[0015]
Reference example 1
After dissolving 74.3 g of the compound of the formula (4) in 900 g of water while adjusting the pH to 1.0 to 3.0 with hydrochloric acid, the temperature is adjusted to 5 to 10 ° C., 53.2 g of 35% hydrochloric acid, 40% aqueous sodium nitrite solution 27.0 g was added and diazotized.
[0016]
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[0017]
Next, a solution containing 36.8 g of the compound obtained in Example 2 was slowly added dropwise at a temperature of 0 to 10 ° C. to the obtained diazo suspension of the compound of formula (4). After completion of the dropwise addition, the pH value is adjusted to 3.0 to 4.0 by adding an aqueous sodium hydroxide solution, and then 5 to 10 ° C. for 1 hour and 15 to 25 ° C. for 8 hours. The coupling reaction was completed by stirring at 0 to obtain a reaction solution containing the compound of formula (5).
[0018]
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[0019]
Next, the solution containing the compound of the formula (5) obtained above was made weakly alkaline with an aqueous sodium hydroxide solution, and 33.5 g of a 40% aqueous sodium nitrite solution was added thereto. This solution was dropped into a solution of 200 g of water and 62.6 g of 35% hydrochloric acid over 30 minutes for diazotization, and this suspension was converted into an alkaline aqueous solution of 35.9 g of 7-amino-1-hydroxynaphthalene-3-sulfonic acid. At 15-30 ° C. During the dropwise addition, the pH value of the solution was maintained at 8.5 to 9.5 with sodium carbonate. After completion of dropping, the mixture was further stirred at 15 to 30 ° C. for 3 hours at pH 8.5 to 9.5 to complete the coupling reaction, thereby obtaining a reaction solution containing the compound of formula (6). (In formula (6), Ts represents a p-toluenesulfonic acid residue)
[0020]
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[0021]
The reaction solution containing the compound of the formula (6) obtained above was heated to 75 ° C. After heating, the pH was adjusted to 10.7 with sodium hydroxide, and the mixture was held at 70 to 75 ° C. and pH 10.6 to 10.8 for about 1 hour. Thereafter, the pH was adjusted to about 8.0 with hydrochloric acid, sodium chloride was added for salting out, filtration and isolation to obtain 94.9 g of the compound of formula (7).
[0022]
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[0023]
After dissolving 8.6 g of the compound of formula (7) obtained in the above reaction in 120 g of water, 2.5 g of 40% aqueous sodium nitrite solution is added, and this aqueous solution is added dropwise to 50 g of 5% aqueous hydrochloric acid solution at 15-30 ° C. Then, it was diazotized, and this was dropwise added to an aqueous solution of 2.3 g of 8-amino-2-naphthalenesulfonic acid at 15 to 30 ° C. During the dropping, the pH value of the coupling solution was maintained at 6.0 to 7.0 with sodium carbonate. After completion of the dropwise addition, the mixture is stirred at 15 to 30 ° C. and pH 6.0 to 7.0 for 1 hour, and then the pH value is adjusted to about 8.5 with sodium carbonate at 15 to 30 ° C. and pH 7.5 to 8.5. Stir for 5 hours to complete the coupling reaction. Thereafter, sodium chloride was added for salting out, followed by filtration. The total amount of the cake obtained was dissolved in 150 g of water, crystallized by adding 80 g of 2-propanol, and desalted by filtration, and then dried to obtain 9.6 g of a trisazo compound of the formula (8).
[0024]
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[0025]
After dissolving 5.8 g of the compound of the formula (8) obtained in the above reaction in 100 g of water, 1.2 g of cyanuric chloride was further added at 15 to 30 ° C. After the addition, the mixture was stirred for 2 hours while maintaining the pH value at 6.0 to 6.7 with sodium carbonate at 15 to 30 ° C. Next, 2.5 g of monoethanolamine was added dropwise in 30 minutes while maintaining the pH value at 8.0 to 9.0 with 5% hydrochloric acid at 15 to 30 ° C. After completion of the dropping, while maintaining the pH value at 8.0 to 9.0 with sodium carbonate, the temperature was raised to 15 to 30 ° C. for 3 hours and further to 85 to 95 ° C., and then the pH value was adjusted to 8.5 with sodium carbonate. While maintaining at ˜9.0, the mixture was stirred for 4 hours. After cooling to 20-30 ° C., the pH value was adjusted to 5.5-6.5 with 35% hydrochloric acid, the insoluble matter was removed by filtration, sodium chloride was added for salting out, and filtration was performed. The total amount of the cake obtained was dissolved in 70 g of water, crystallized by adding 70 g of methanol, filtered to desalinate, and then dried to obtain 4.8 g of the compound of formula (9). The maximum absorption wavelength (λmax) of this compound in water was 611 nm. This compound is useful as a high-purity functional dye, particularly black for inkjet.
[0026]
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[0027]
【The invention's effect】
High-purity 2- (3-sulfopropoxy) anilines can be produced in a stable structural form, and functional dyes, agricultural chemicals, pharmaceuticals and the like can be produced using this as an intermediate.

Claims (3)

2- (3-sulfopropoxy) anilines represented by general formula (3-1)

(Wherein R represents a (C1-C4) alkyl group, a (C1-C4) alkoxy group or a halogen). a) 2-hydroxyacetanilides represented by the general formula (1-2)

(Wherein R ′ represents a hydrogen atom, (C1 to C4) alkyl group, (C1 to C4) alkoxy group or halogen) and propane sultone are reacted in a solvent and represented by the general formula (2-2). 2- (3-Sulfopropoxy) acetanilides

Wherein R ′ has the same meaning as described above, and M represents an alkali metal or an alkaline earth metal,
b) Method for producing 2- (3-sulfopropoxy) anilines represented by general formula (3-2) by hydrolyzing general formula (2-2)

(Wherein R ′ has the same meaning as above) a) 2-hydroxyacetanilides represented by the general formula (1-2)

(Wherein R ′ represents a hydrogen atom, (C1 to C4) alkyl group, (C1 to C4) alkoxy group or halogen) and propane sultone in a mixed solvent of an aprotic polar solvent and an alkylbenzene in the presence of an inorganic base. 2- (3-sulfopropoxy) acetanilides represented by general formula (2-2) by reaction

Wherein R ′ has the same meaning as described above, and M represents an alkali metal or an alkaline earth metal,
b) Method for producing 2- (3-sulfopropoxy) anilines represented by general formula (3-2) by hydrolyzing general formula (2) in an aqueous mineral acid solution

(Wherein R ′ has the same meaning as above)