JPH051023A - Production of alkanesulfonanilide derivative - Google Patents
Production of alkanesulfonanilide derivativeInfo
- Publication number
- JPH051023A JPH051023A JP12218791A JP12218791A JPH051023A JP H051023 A JPH051023 A JP H051023A JP 12218791 A JP12218791 A JP 12218791A JP 12218791 A JP12218791 A JP 12218791A JP H051023 A JPH051023 A JP H051023A
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- salt
- derivative
- general formula
- formula
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Abstract
Description
【発明の詳細な説明】Detailed Description of the Invention
【０００１】[0001]
【産業上の利用分野】この発明は、アルカンスルホンア
ニリド誘導体またはその塩の新規な製法に関し、詳細に
は、抗炎症作用や鎮痛作用を有するアルカンスルホンア
ニリド誘導体またはその塩を、少ない工程数で収率良く
製造することのできる方法に関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel method for producing an alkanesulfoneanilide derivative or a salt thereof, and more specifically, to obtain an alkanesulfoneanilide derivative or a salt thereof having an anti-inflammatory action or an analgesic action in a small number of steps. The present invention relates to a method that can be efficiently manufactured.
【０００２】[0002]
【従来の技術】下記一般式PRIOR ART The following general formula
【０００３】[0003]
【化３】 [Chemical 3]
【０００４】で表わされるアルカンスルホンアニリド誘
導体またはその塩は公知であり（特開昭63-190869 号及
び同63-313765号公報）、またこのアルカンスルホンア
ニリド誘導体またはその塩が医薬として抗炎症作用、鎮
痛作用等を有していることも上記公開公報によって知ら
れている。The alkane sulfone anilide derivative represented by or its salt is known (Japanese Patent Laid-Open Nos. 63-190869 and 63-313765), and the alkane sulfone anilide derivative or its salt has an anti-inflammatory effect as a medicine. It is also known from the above publication that it has an analgesic effect and the like.
【０００５】ところでこのアルカンスルホンアニリド誘
導体またはその塩は、たとえば以下に示す如く多数の工
程を経て製造されている。By the way, the alkanesulfoneanilide derivative or a salt thereof is manufactured through a number of steps, for example, as shown below.
【０００６】[0006]
【化４】 [Chemical 4]
【０００７】しかして上記の反応工程において、たとえ
ばアニリン誘導体［Ｂ］のアミノ基をニトロ基に変換す
る酸化工程を省略し、これをフェノール誘導体[II']
と直接反応させてジフェニルエーテル誘導体［Ｅ］を製
造しようとしても、アニリン誘導体［Ｂ］中のアミノ基
の反応性が高いため目的化合物を得ることができず、ま
たこのアミノ基を保護基で保護しておいた場合でも、フ
ェノール誘導体[II']との反応（一般にウルマン反応
として知られている）がかなり激しい条件下に行なわれ
ることになるため保護基の離脱が避けられず、対応する
ジフェニルエーテル化合物を得ることができないからで
ある。However, in the above reaction step, the oxidation step of converting the amino group of the aniline derivative [B] into a nitro group is omitted, and the phenol derivative [II '] is used.
Even if the diphenyl ether derivative [E] is directly reacted with the aniline derivative [B], the target compound cannot be obtained because the reactivity of the amino group in the aniline derivative [B] is high, and the amino group is protected by a protecting group. Even if it is stored, the reaction with the phenol derivative [II '] (generally known as the Ullmann reaction) will be carried out under considerably violent conditions, and therefore the elimination of the protecting group is unavoidable. Because you can't get.
【０００８】その結果、アニリン誘導体［Ｂ］のアミノ
基を予めニトロ基に変えるための酸化工程が不可欠と
なるばかりでなく、上記ウルマン反応の後はニトロ基
をアミノ基に戻すための還元工程が必須となり、工程
数が増えるばかりでなく目的化合物の収率も低くなると
いう問題があった。As a result, not only an oxidation step for previously converting the amino group of the aniline derivative [B] into a nitro group is indispensable, but also a reduction step for returning the nitro group to an amino group is required after the above Ullmann reaction. This is essential, and there is a problem that not only the number of steps increases but also the yield of the target compound decreases.
【０００９】[0009]
【発明の目的】この発明は上記の様な事情に着目してな
されたものであって、その構成は、冒頭で示した様なア
ルカンスルホンアニリド誘導体を、少ない工程数で収率
良く製造することのできる方法を提供しようとするもの
である。SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and its constitution is to produce an alkanesulfonanilide derivative as shown at the beginning with a small number of steps and a high yield. It is intended to provide a possible method.
【００１０】[0010]
【発明の構成】この発明は、下記一般式[I] で示される
化合物またはその塩に、下記一般式[II]で示されるフェ
ノール誘導体またはその塩を反応させて、下記一般式[I
II] で示されるアルカンスルホンアニリド誘導体または
その塩を製造するところに要旨を有するものである。BEST MODE FOR CARRYING OUT THE INVENTION The present invention comprises reacting a compound represented by the following general formula [I] or a salt thereof with a phenol derivative represented by the following general formula [II] or a salt thereof,
[II]] and has a gist in producing an alkanesulfonanilide derivative or a salt thereof.
【００１１】尚、化合物[I] またはその塩はそれ自身新
規な化合物であり、下記一般式[IV]で示されるアニリン
誘導体またはアミノ基におけるその反応性誘導体もしく
はその塩に、下記一般式[V] で示されるアルカンスルホ
ン酸またはスルホン酸基におけるその反応性誘導体もし
くはその塩を反応させて下記一般式[VI]で示される化合
物またはその塩とし、該化合物[VI]またはその塩をハロ
ゲン化することによって得ることができる。The compound [I] or a salt thereof is a novel compound itself, and the aniline derivative represented by the following general formula [IV] or its reactive derivative at the amino group or its salt can be added to the following general formula [V ] By reacting an alkanesulfonic acid represented by the formula [1] or a reactive derivative thereof in the sulfonic acid group or a salt thereof to a compound represented by the following general formula [VI] or a salt thereof, and halogenating the compound [VI] or a salt thereof. Can be obtained by
【００１２】[0012]
【化５】 [Chemical 5]
【００１３】以下、この発明の範囲に包含される種々の
定義および好ましい具体例等について詳細に説明する。Hereinafter, various definitions and preferable specific examples included in the scope of the present invention will be described in detail.
【００１４】上記一般式[I] ，[II]，[III] ，[VI]で示
される各化合物の塩とは、医薬として許容される無毒性
塩であり、具体例としては、リチウム塩、ナトリウム
塩、カリウム塩などのアルカリ金属塩；カルシウム塩、
マグネシウム塩等のアルカリ土類金属塩；アンモニウム
塩の如き無機塩基との塩、トリエチルアミン塩、エタノ
ールアミン塩、トリエタノールアミン塩、ジシクロヘキ
シルアミン塩、Ｎ，Ｎ’−ジベンジルエチレンジアミン
塩の如き有機アミン塩等の様な塩基との塩が挙げられ
る。The salt of each compound represented by the above general formulas [I], [II], [III] and [VI] is a pharmaceutically acceptable non-toxic salt. Specific examples thereof include lithium salt, Alkali metal salts such as sodium salts and potassium salts; calcium salts,
Alkaline earth metal salts such as magnesium salts; salts with inorganic bases such as ammonium salts, triethylamine salts, ethanolamine salts, triethanolamine salts, dicyclohexylamine salts, organic amine salts such as N, N′-dibenzylethylenediamine salts Salts with bases such as
【００１５】一般式[IV]で示される化合物のアミノ基に
おける反応性誘導体としては、慣用の誘導体、その例と
して、化合物[IV]とビス（トリメチルシリル）アセトア
ミド、トリメチルシリルアセトアミド等のようなシリル
化合物との反応によって生成するシリル誘導体；イソシ
アン酸塩；イソチオシアン酸塩；アミノ基と例えばアセ
トアルデヒド、イソペンテナール、ベンズアルデヒド、
サリチルアルデヒド、フェニルアセトアルデヒド、ｐ−
ニトロベンズアルデヒド、ｍ−クロロベンズアルデヒ
ド、ｐ−クロロベンズアルデヒド、ヒドロキシナフトア
ルデヒド、フルフラール、チオフェンカルボアルデヒド
等のアルデヒド化合物または例えばアセトン、メチルエ
チルケトン、メチルイソブチルケトン、アセチルアセト
ン、アセト酢酸エチル等のようなケトン化合物のような
カルボニル化合物との反応によって生成するシッフの塩
基またはそのエナミン型互変異性体等が挙げられる。The reactive derivative at the amino group of the compound represented by the general formula [IV] is a conventional derivative, for example, the compound [IV] and a silyl compound such as bis (trimethylsilyl) acetamide or trimethylsilylacetamide. A silyl derivative produced by the reaction of; an isocyanate; an isothiocyanate; an amino group and, for example, acetaldehyde, isopentenal, benzaldehyde,
Salicylaldehyde, phenylacetaldehyde, p-
Aldehyde compounds such as nitrobenzaldehyde, m-chlorobenzaldehyde, p-chlorobenzaldehyde, hydroxynaphthaldehyde, furfural, thiophenecarbaldehyde or ketone compounds such as acetone, methyl ethyl ketone, methyl isobutyl ketone, acetylacetone, ethyl acetoacetate, etc. Examples thereof include Schiff's base formed by reaction with a carbonyl compound or an enamine-type tautomer thereof.
【００１６】一般式[IV]で示されるアニリン誘導体の好
適な塩としては、たとえば塩酸塩、臭素酸塩、硫酸塩等
の無機酸塩；蟻酸塩、酢酸塩、2,2,2-トリフルオロ酢酸
塩、ｐ−トルエンスルホン酸塩等の有機酸塩等が挙げら
れる。Suitable salts of the aniline derivative represented by the general formula [IV] include, for example, inorganic acid salts such as hydrochloride, bromate and sulfate; formate, acetate, 2,2,2-trifluoro. Examples thereof include organic acid salts such as acetate and p-toluenesulfonate.
【００１７】一般式[V] で示されるアルカンスルホン酸
のスルホン酸基における好適な反応性誘導体としては、
酸ハロゲン化物や酸無水物等が挙げられる。その様な反
応性誘導体の好ましい具体例としては、酸塩化物や酸臭
化物の様な酸ハロゲン化物、ジアルキル燐酸やジアルキ
ル硫酸等の様な置換された燐酸や硫酸との混合酸無水物
あるいはメタンスルホン酸やエタンスルホン酸等のアル
カンスルホン酸の様な置換されたスルホン酸との対応酸
無水物等が挙げられ、これらの種類は、Ｒ1として導入
すべき基の種類に応じて適宜選択して決定すればよい。Suitable reactive derivative of the sulfonic acid group of the alkanesulfonic acid represented by the general formula [V] is
Examples thereof include acid halides and acid anhydrides. Preferred specific examples of such a reactive derivative include acid halides such as acid chlorides and acid bromides, substituted acid anhydrides such as dialkylphosphoric acid and dialkylsulfuric acid, and mixed acid anhydrides with sulfuric acid, and methanesulfone. Acids and corresponding acid anhydrides with a substituted sulfonic acid such as alkane sulfonic acid such as ethane sulfonic acid can be mentioned. These types are appropriately selected according to the type of the group to be introduced as R 1. Just decide.
【００１８】上記一般式において、「低級」とは、特に
ことわりのない限り炭素数１〜６個を意味する。従って
「低級アルキル基」としては、メチル、エチル、プロピ
ル、イソピロピル、ブチル、イソブチル、第３級ブチ
ル、ペンチル、ネオペンチル、ヘキシルの様な炭素数１
〜６の直鎖状または分岐状のアルキル基が挙げられ、こ
れらの中でも特に好ましいのは炭素数１〜４個のもので
ある。中でも特に好ましいのはメチルである。In the above general formula, "lower" means 1 to 6 carbon atoms unless otherwise specified. Therefore, the "lower alkyl group" has 1 carbon atoms such as methyl, ethyl, propyl, isopyropyr, butyl, isobutyl, tertiary butyl, pentyl, neopentyl and hexyl.
The straight-chain or branched-chain alkyl groups of 6 to 6 are mentioned, and among these, those having 1 to 4 carbon atoms are particularly preferable. Especially preferred is methyl.
【００１９】「低級アルカノイル基」の好ましい例とし
ては、ホルミル、アセチル、プロピオニル、ブチリル、
イソブチリル、バレリル、イソバレリル、ピバロイル、
ヘキサノイルの様な直鎖状または分岐鎖状のアルカノイ
ル基が挙げられ、それらの中で更に好ましいものとして
炭素数１〜４のアルカノイル基、最も好ましいものとし
てはアセチルが挙げられる。Preferred examples of "lower alkanoyl group" include formyl, acetyl, propionyl, butyryl,
Isobutyryl, valeryl, isovaleryl, pivaloyl,
A straight-chain or branched-chain alkanoyl group such as hexanoyl can be mentioned. Among them, an alkanoyl group having 1 to 4 carbon atoms is more preferable, and acetyl is most preferable.
【００２０】「ハロゲン」としては、ふっ素、塩素、臭
素、ヨウ素が挙げられる。Examples of "halogen" include fluorine, chlorine, bromine and iodine.
【００２１】本発明の目的化合物[III] またはその塩
は、下記反応式で示される通り化合物[I] またはその塩
に、フェノール誘導体[II]またはその塩を反応させるこ
とによって製造することができる。The object compound [III] of the present invention or a salt thereof can be produced by reacting a compound [I] or a salt thereof with a phenol derivative [II] or a salt thereof as shown in the following reaction formula. .
【００２２】[0022]
【化６】 [Chemical 6]
【００２３】この反応は、反応に悪影響を及ぼさない溶
媒を用いて、反応触媒の存在下に進められる。ここで使
用される好ましい溶媒としては、ピリジン、キノリン、
ピコリン、オキシルチジン、ヒドロキシキノリン、モノ
−，ジ−またはトリ−（ポリオキシアルキル）アミン等
の芳香族アミンが例示され、これらの中でも特に好まし
いのはピリジンである。また触媒としては銅粉、塩化
銅、ラネー銅、ヨウ化銅、酸化銅、酢酸銅、還元銅、ウ
ルマン銅等の銅触媒が好ましいものとして例示される。
これらの中でも特に好ましいのは塩化第１銅である。This reaction is carried out in the presence of a reaction catalyst using a solvent that does not adversely influence the reaction. Preferred solvents used here include pyridine, quinoline,
Aromatic amines such as picoline, oxylutidine, hydroxyquinoline, mono-, di- or tri- (polyoxyalkyl) amine are exemplified, and among these, pyridine is particularly preferable. Examples of preferable catalysts include copper powder, copper chloride, Raney copper, copper iodide, copper oxide, copper acetate, reduced copper, and Ullmann copper.
Of these, cuprous chloride is particularly preferable.
【００２４】この反応は通常塩基の存在下で行なうのが
よく、好適な塩基としては、たとえば水酸化ナトリウ
ム、水酸化カリウム、水酸化カルシウム等のアルカリ金
属水酸化物またはアルカリ土類金属水酸化物；たとえば
炭酸水素ナトリウム、炭酸水素カリウム等のアルカリ金
属炭酸水素塩；たとえば炭酸ナトリウム、炭酸カリウム
等のアルカリ金属炭酸塩またはアルカリ土類金属炭酸
塩；たとえば燐酸２水素ナトリウム、燐酸２水素カリウ
ム、燐酸水素２ナトリウム、燐酸水素２カリウム等のア
ルカリ金属燐酸塩の様な無機塩基、または例えばナトリ
ウムメトキシド、カリウムエトキシド等のアルカリ金属
アルコキシド、たとえばトリエチルアミン、ピリジン、
ルチジン等のような有機塩基が挙げられる。これらの中
でも特に好ましい塩基は、アルカリ金属もしくはアルカ
リ土類金属の炭酸塩、特に炭酸カリウムである。This reaction is usually carried out in the presence of a base. Suitable bases include alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide or alkaline earth metal hydroxides. Alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; alkali metal carbonates or alkaline earth metal carbonates such as sodium carbonate and potassium carbonate; sodium dihydrogen phosphate, potassium dihydrogen phosphate, hydrogen phosphate; Inorganic bases such as alkali metal phosphates such as disodium and dipotassium hydrogen phosphate, or alkali metal alkoxides such as sodium methoxide and potassium ethoxide, such as triethylamine and pyridine.
Examples include organic bases such as lutidine and the like. Among these, particularly preferred bases are alkali metal or alkaline earth metal carbonates, particularly potassium carbonate.
【００２５】反応温度および反応時間は特に制限されな
いが、通常は１１０〜１２０℃で３〜７時間程度で反応
は十分に進行する。The reaction temperature and reaction time are not particularly limited, but usually the reaction proceeds sufficiently at 110 to 120 ° C. for about 3 to 7 hours.
【００２６】かくして得られる本発明の目的化合物[II
I] は、フリーの形で得ることができる他、必要により
医薬として許容される塩として得ることができる。医薬
として許容される塩は、フリーの目的化合物[III] を、
水酸化ナトリウムや水酸化カリウム等のアルカリ金属化
合物；水酸化カルシウムや水酸化マグネシウム等のアル
カリ土類金属化合物；アンモニア等の無機塩基；トリエ
チルアミン、ジシクロヘキシルアミン等の有機塩基で処
理すると、対応する塩を得ることができる。The object compound of the present invention thus obtained [II
[I] can be obtained in a free form or, if necessary, as a pharmaceutically acceptable salt. The pharmaceutically acceptable salt is a free target compound [III],
Alkali metal compounds such as sodium hydroxide and potassium hydroxide; alkaline earth metal compounds such as calcium hydroxide and magnesium hydroxide; inorganic bases such as ammonia; treatment with organic bases such as triethylamine and dicyclohexylamine yields the corresponding salts. Obtainable.
【００２７】この塩は、常法に従ってフリーの目的化合
物[III] に変えることができる。また該目的化合物[II
I] およびその塩は、常法に従って精製することができ
る。This salt can be converted into a free target compound [III] by a conventional method. The target compound [II
I] and its salt can be purified by a conventional method.
【００２８】上記反応の出発原料となる化合物[I] はど
の様な方法で製造したものでもかまわないが、アニリン
誘導体[IV]またはその塩を出発原料として下記の反応に
よって得るのが最も有利である。The compound [I] as a starting material for the above reaction may be produced by any method, but it is most advantageous to obtain it by the following reaction using the aniline derivative [IV] or a salt thereof as a starting material. is there.
【００２９】[0029]
【化７】 [Chemical 7]
【００３０】この反応は、通常、塩化メチレン、クロロ
ホルム、ベンゼン、トルエン、ピリジン、ジエチルエー
テル、ジオキサン、テトラヒドロフラン、アセトン、ア
セトニトリル、酢酸エチル、Ｎ，Ｎ−ジメチルホルムア
ミドの様な常用の溶媒中で行なわれるが、反応に悪影響
を及ぼさない溶媒であればその他いかなる有機溶媒中で
も反応を行なうことができる。アルカンスルホン酸を遊
離の形または塩の形でスルホニル化剤として使用する場
合には、Ｎ，Ｎ’−ジシクロヘキシルカルボジイミド等
の様な常用の縮合剤の存在下に反応を行なうのが好まし
い。This reaction is usually carried out in a conventional solvent such as methylene chloride, chloroform, benzene, toluene, pyridine, diethyl ether, dioxane, tetrahydrofuran, acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide. However, the reaction can be carried out in any other organic solvent as long as it does not adversely affect the reaction. When the alkanesulfonic acid is used as the sulfonylating agent in the free form or salt form, it is preferable to carry out the reaction in the presence of a conventional condensing agent such as N, N′-dicyclohexylcarbodiimide.
【００３１】反応温度は特に限定されず、冷却下、常
温、加温下又は加熱下に反応を行なうことができる。The reaction temperature is not particularly limited, and the reaction can be carried out under cooling, at room temperature, under heating or under heating.
【００３２】この反応は、無機塩基、たとえば水酸化ナ
トリウムまたは水酸化カリウムの様なアルカリ金属水酸
化物、炭酸ナトリウム、炭酸カリウム、炭酸水素ナトリ
ウムまたは炭酸水素カリウムの様なアルカリ金属炭酸塩
または炭酸水素塩の存在下、もしくは有機塩基、たとえ
ばトリエチルアミン、ピリジン、ジメチルアニリン、Ｎ
−メチルモルホリン等の存在下で反応を行なうのが好ま
しい。This reaction is carried out by using an inorganic base, for example, an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide, an alkali metal carbonate such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate or potassium hydrogen carbonate or hydrogen carbonate. In the presence of salts or organic bases such as triethylamine, pyridine, dimethylaniline, N
It is preferable to carry out the reaction in the presence of methylmorpholine and the like.
【００３３】化合物[VI]を化合物[I] に変換するための
ハロゲン化反応は、通常酢酸、トルエン、キシレン、ア
ニソール、塩化メチレン、ジクロロエタン等の様な常用
の溶媒中で行なわれるが、反応に悪影響を及ぼさないそ
の他のいかなる有機溶媒中でも反応を行なうことができ
る。The halogenation reaction for converting the compound [VI] into the compound [I] is usually carried out in a commonly used solvent such as acetic acid, toluene, xylene, anisole, methylene chloride, dichloroethane, etc. The reaction can be carried out in any other organic solvent that does not adversely affect.
【００３４】この反応に使用するハロゲン化剤として
は、たとえば臭素、塩素、ヨード、塩化スルフリル、塩
化チオニル、Ｎ−クロロスクシンイミド、Ｎ−ブロムス
クシンイミド等を使用することができる。As the halogenating agent used in this reaction, for example, bromine, chlorine, iodo, sulfuryl chloride, thionyl chloride, N-chlorosuccinimide, N-bromosuccinimide and the like can be used.
【００３５】反応温度は特に限定されず、冷却下、常
温、加温下または加熱下に反応を行なうことができる。
次に本発明の実施例を示す。The reaction temperature is not particularly limited, and the reaction can be carried out under cooling, at room temperature, under heating or under heating.
Next, examples of the present invention will be described.
【００３６】[0036]
実施例１
(1-1) ４’−アセチルメタンスルホンアニリドの合成
４’−アミノアセトフェノン135.2g（1.00モル）とＮ−
メチルモルホリン126.4g（ 1.25 モル）の塩化メチレン
1350mlとの混合物中に、撹拌下、メタンスルホン酸クロ
ライド 143.2g （1.25モル）を、２０〜２５℃で約３０
分かけて滴下し、滴下終了後同温度で更に１時間撹拌す
る。Example 1 (1-1) Synthesis of 4'-acetylmethanesulfonanilide 13'g (1.00 mol) of 4'-aminoacetophenone and N-
Methylmorpholine 126.4 g (1.25 mol) methylene chloride
In a mixture with 1350 ml, with stirring, 143.2 g (1.25 mol) of methanesulfonic acid chloride was stirred at 20 to 25 ° C for about 30 minutes.
The mixture is added dropwise over a period of time, and after completion of the addition, the mixture is stirred at the same temperature for 1 hour.
【００３７】一方、水酸化ナトリウム108.0g（ 2.70 モ
ル）を水 1350ml に溶かした水溶液を調製しておき、こ
れに上記で得た反応液を撹拌下２５〜３０℃で滴下す
る。滴下終了後同温度で更に１５分間撹拌した後水層を
分取し、有機層には水 270mlを加えて再抽出する。水層
および再抽出水を合し、これに酢酸エチル 3380ml を加
え、更に撹拌下３５％塩酸 270mlを１８〜２５℃で滴下
する。有機層を分取し、この有機層を水 270mlで洗浄し
た後、この有機層を減圧下で 406mlまで濃縮すると、
４’−アセチルメタンスルホンアニリドの白色結晶 19
5.2g （収率90.3％）が得られる。
NMR(DMSO-d6：δ）：2.55(3H,s), 3.15(3H,s), 7.22〜
7.98(4H,m)
マススペクル(m/e) ：213(M+), 198, 119On the other hand, an aqueous solution was prepared by dissolving 108.0 g (2.70 mol) of sodium hydroxide in 1350 ml of water, and the reaction solution obtained above was added dropwise thereto at 25-30 ° C. with stirring. After completion of dropping, the mixture is stirred for 15 minutes at the same temperature, the aqueous layer is separated, and 270 ml of water is added to the organic layer for re-extraction. The aqueous layer and re-extracted water were combined, ethyl acetate (3380 ml) was added thereto, and 270 ml of 35% hydrochloric acid was added dropwise at 18 to 25 ° C. with stirring. The organic layer was separated, washed with 270 ml of water, and the organic layer was concentrated under reduced pressure to 406 ml.
White crystals of 4'-acetylmethanesulfonanilide 19
5.2 g (90.3% yield) are obtained. NMR (DMSO-d 6 : δ): 2.55 (3H, s), 3.15 (3H, s), 7.22 ~
7.98 (4H, m) Mass spectrum (m / e): 213 (M + ), 198, 119
【００３８】(1-2) ４’−アセチル−２’−ブロモメタ
ンスルホンアニリドの合成
上記(1-1) で得た４’−アセチルメタンスルホンアニリ
ド42.7g （0.20モル）と氷酢酸 853mlの水 284mlとの混
合液に、撹拌下１３〜１５℃で臭素 63.9gを１時間かけ
て滴下し、滴下終了後同温度で更に６時間撹拌する。(1-2) 4'-acetyl-2'-bromometa
Synthesis of N-sulfoneanilide 63.9 g of bromine at 13 to 15 ° C under stirring in a mixed solution of 42.7 g (0.20 mol) of 4'-acetylmethanesulfonanilide obtained in (1-1) above and 853 ml of glacial acetic acid in water (284 ml). Is added dropwise over 1 hour, and after completion of the addition, the mixture is stirred at the same temperature for 6 hours.
【００３９】一方、亜硫酸水素ナトリウム 25.0gを水 1
25mlに溶かした水溶液を調製しておき、これに上記で得
た反応液を１５℃以下の温度で滴下する。この反応液を
128mlまで減圧濃縮した後水 1280ml を滴下し、析出す
る結晶を濾取して減圧乾燥すると、４’−アセチル−
２’−ブロモメタンスルホンアニリドの白色結晶 57.5g
（収率98.3％）が得られる。
NMR(DMSO-d6：δ）：2.53(3H,s), 3.18(3H,s), 7.58〜
8.19(3H,m)On the other hand, 25.0 g of sodium hydrogen sulfite was added to 1 part of water.
An aqueous solution dissolved in 25 ml is prepared in advance, and the reaction solution obtained above is added dropwise thereto at a temperature of 15 ° C or lower. This reaction solution
After concentrating to 128 ml under reduced pressure, 1280 ml of water was added dropwise, and the precipitated crystals were collected by filtration and dried under reduced pressure to give 4'-acetyl-.
57.5g of white crystals of 2'-bromomethanesulfonanilide
(Yield 98.3%) is obtained. NMR (DMSO-d 6 : δ): 2.53 (3H, s), 3.18 (3H, s), 7.58 ~
8.19 (3H, m)
【００４０】(1-3) ４’−アセチル−２’−（２，４−
ジフルオロフェノキシ）メタンスルホンアニリドの合成
上記(1-2) で得た４’−アセチル−２’−ブロモメタン
スルホンアニリド５０g （0.171 モル）、２，４−ジフ
ルオロフェノール26.71g （ 0.205モル）、塩化第１銅
12.71g （0.128 モル）、粉砕炭酸カリウム 56.67g （
0.411モル）のピリジン 250mlとの混合液を、還流下(11
8℃）で７時間撹拌する。(1-3) 4'-acetyl-2 '-(2,4-
Synthesis of difluorophenoxy) methanesulfonanilide 50 g (0.171 mol) of 4'-acetyl-2'-bromomethanesulfonanilide obtained in the above (1-2), 26.71 g (0.205 mol) of 2,4-difluorophenol, chloride chloride 1 copper
12.71g (0.128 mol), ground potassium carbonate 56.67g (
A mixture of 0.411 mol of pyridine and 250 ml of pyridine under reflux (11
Stir for 7 hours at 8 ° C).
【００４１】一方、塩化メチレン１リットルと17.5％塩
酸１リットルの混合液を予め調製しておき、この混合液
に上記で得た反応液を３５℃以下で滴下する。有機層を
分取し、γ−アルミナ100gの充填されたカラムに通して
から溶出液を下記の方法で精製しエタノールで再結晶す
ると、４’−アセチル−２’−（２，４−ジフルオロフ
ェノキシ）メタンスルホンアニリドの白色結晶24.24g
(41.5 ％）が得られる。
融点： 117〜118 ℃
NMR(DMSO-d6：δ）：2.50(3H,s),3.18(3H,s),7.16〜7.8
3(4H,m),9.94(1H,s)
マススペクル(m/e) ：341(M+),326,262On the other hand, a mixed solution of 1 liter of methylene chloride and 1 liter of 17.5% hydrochloric acid is prepared in advance, and the reaction solution obtained above is added dropwise to this mixed solution at 35 ° C. or lower. The organic layer was separated, passed through a column packed with 100 g of γ-alumina, and the eluate was purified by the following method and recrystallized from ethanol to give 4′-acetyl-2 ′-(2,4-difluorophenoxy). ) Methanesulfonanilide white crystals 24.24g
(41.5%) is obtained. Melting point: 117 to 118 ° C NMR (DMSO-d 6 : δ): 2.50 (3H, s), 3.18 (3H, s), 7.16 to 7.8
3 (4H, m), 9.94 (1H, s) Mass spectrum (m / e): 341 (M + ), 326,262
【００４２】（精製法）カラム通液後、塩化メチレン20
0ml で２回（合計400ml ）溶出する。溶出液を250ml ま
で減圧濃縮し、この濃縮液を、水酸化ナトリウム13.7g
の水 500ml溶液に２５〜３０℃で滴下する。滴下終了後
更に１時間撹拌した後、２４％水酸化ナトリウム水溶液
100ml を滴下し、５℃に保って一夜（約１５時間）撹拌
する。(Purification method) After passing through the column, methylene chloride 20
Elute twice with 0 ml (total 400 ml). Concentrate the eluate under reduced pressure to 250 ml, and add 13.7 g of sodium hydroxide to the concentrate.
Was added dropwise to a 500 ml solution of water at 25-30 ° C. After the addition was completed, the mixture was stirred for 1 hour, and then a 24% aqueous sodium hydroxide solution was added.
Add 100 ml dropwise, keep at 5 ° C and stir overnight (about 15 hours).
【００４３】析出する結晶を濾取し、これを予め準備し
ておいた塩化メチレン300ml と水 300mlの混合液に注入
して懸濁させ、この懸濁液に３５％塩酸１２mlを２０〜
２５℃で滴下する。有機層を分取してから飽和炭酸水素
ナトリウム水溶液150ml で洗浄し、有機層を、５％の水
酸化カリウム水溶液300 ml中へ約１０分間かけて滴下す
る。次いで水層を分取し、有機層は水５０mlで再抽出す
る。水層と再抽出水を合して活性炭粉末1.5gを加えてか
ら２０〜２５℃で１時間撹拌する。活性炭粉末を濾去し
てからエタノール 200mlを加え、３５％塩酸１５mlを２
５〜３０℃で滴下して１時間撹拌後、更に３５％塩酸１
５mlを滴下する。析出する結晶を濾取し減圧乾燥する
と、白色結晶 26.61g （収率45.6 ％）が得られる。The precipitated crystals were collected by filtration and poured into a previously prepared mixed solution of 300 ml of methylene chloride and 300 ml of water to suspend the mixture, and 12 ml of 35% hydrochloric acid was added to this suspension in an amount of 20 to 20 ml.
Add dropwise at 25 ° C. The organic layer is separated and washed with 150 ml of a saturated aqueous sodium hydrogen carbonate solution, and the organic layer is dropped into 300 ml of a 5% aqueous potassium hydroxide solution over about 10 minutes. The aqueous layer is then separated and the organic layer is reextracted with 50 ml of water. The aqueous layer and re-extracted water were combined, 1.5 g of activated carbon powder was added, and the mixture was stirred at 20 to 25 ° C for 1 hour. After removing the activated carbon powder by filtration, add 200 ml of ethanol and add 2 ml of 15 ml of 35% hydrochloric acid.
After dropping at 5 to 30 ° C and stirring for 1 hour, 35% hydrochloric acid 1
Add 5 ml dropwise. The precipitated crystals are collected by filtration and dried under reduced pressure to give white crystals (26.61 g, yield 45.6%).
【００４４】この白色結晶１５g と活性炭粉末0.75g を
エタノール７５mlに加えた混液を、７８℃で３０分撹拌
した後、活性炭を濾去して濾液を３〜８℃で２時間撹拌
した後、析出する結晶を乾燥すると、白色結晶状の目的
物 13.67g （収率 91.1 ％）が得られる。上記実施例１
と同様の方法で下記の化合物を製造した。A mixture of 15 g of the white crystals and 0.75 g of activated carbon powder added to 75 ml of ethanol was stirred at 78 ° C. for 30 minutes, the activated carbon was filtered off, and the filtrate was stirred at 3-8 ° C. for 2 hours, followed by precipitation. The crystals are dried to give 13.67 g (yield 91.1%) of the desired product as white crystals. Example 1 above
The following compounds were produced by a method similar to.
【００４５】実施例２４’−シアノ−２’−（２，４−ジフルオロフェノキ
シ）メタンスルホンアニリド
融点： 185〜187 ℃
NMR(CDCl3+CD3OD,：δ）：3.14(3H,s),6.9〜7.8(3H,s)
IR(ヌジョール) ：3330,2250,1610,1585,1510cm-1 Example 2 4'-cyano-2 '-(2,4-difluorophenoxy
Si) Methanesulfonanilide Melting point: 185 to 187 ° C NMR (CDCl 3 + CD 3 OD ,: δ): 3.14 (3H, s), 6.9 to 7.8 (3H, s) IR (nujol): 3330,2250,1610, 1585,1510 cm -1
【００４６】実施例３３−（２，４−ジフルオロフェニルチオ）−４−（メタ
ンスルホンアミド）ベンズアミド
融点： 176〜178 ℃
NMR(DMSO-d6：δ）：3.13(3H,s),7.1〜8.1(8H,m),9.50
(1H,s)
IR(ヌジョール) ：3420,3250,3200,1660,1615cm-1
マススペクトル(m/e) ：358(M+)Example 3 3- (2,4-difluorophenylthio) -4- (meta
(Sulfonamide) benzamide Melting point: 176 to 178 ° C NMR (DMSO-d 6 : δ): 3.13 (3H, s), 7.1 to 8.1 (8H, m), 9.50
(1H, s) IR (nujol): 3420,3250,3200,1660,1615cm -1 mass spectrum (m / e): 358 (M + )
【００４７】実施例４３−（２，４−ジフルオロフェノキシ）−４−（メタン
スルホンアミド）ベンズアミド
融点： 147〜150 ℃
NMR(CDCl3：δ）：3.10(3H,s),5.94(2H,ブロードs),6.8
〜7.9(7H,m)
IR(ヌジョール) ：3460,3280,3170,1680,1615,1585,150
5cm-1
マススペクトル(m/e) ：342(M+, ベースピーク)Example 4 3- (2,4-difluorophenoxy) -4- (methane
Sulfonamide) benzamide Melting point: 147 to 150 ° C NMR (CDCl 3 : δ): 3.10 (3H, s), 5.94 (2H, broad s), 6.8
~ 7.9 (7H, m) IR (Nujol): 3460,3280,3170,1680,1615,1585,150
5 cm -1 mass spectrum (m / e): 342 (M + , base peak)
【００４８】実施例５４’−アセチル−２’−（２，４−ジフルオロフェニル
チオ）メタンスルホンアニリド
融点： 114〜117 ℃
NMR(CDCl3：δ）：2.55(3H,s),3.02(3H,s),6.7 〜8.3(7
H,m)
IR(ヌジョール) ：3250,1680,1595,1490cm-1
マススペクトル(m/e) ：357(M+),278,43(ベースピーク)Example 5 4'-acetyl-2 '-(2,4-difluorophenyl
Thio) methanesulfonanilide Melting point: 114-117 ° C NMR (CDCl 3 : δ): 2.55 (3H, s), 3.02 (3H, s), 6.7-8.3 (7
H, m) IR (nujor): 3250,1680,1595,1490cm -1 mass spectrum (m / e): 357 (M + ), 278,43 (base peak)
【００４９】実施例６４’−シアノ−２’−（２，４−ジフルオロフェニルチ
オ）メタンスルホンアニリド
融点： 134〜135 ℃
NMR(CDCl3：δ）：3.05(3H,s),6.7〜8.0(7H,m)
IR(ヌジョール) ：3240,2240,1595,1485cm-1
マススペクトル(m/e) ：340(M+),261,241Example 6 4'-cyano-2 '-(2,4-difluorophenylthio)
E ) Methanesulfonanilide Melting point: 134-135 ° C NMR (CDCl 3 : δ): 3.05 (3H, s), 6.7-8.0 (7H, m) IR (nujol): 3240,2240,1595,1485cm -1 Mass spectrum (m / e): 340 (M + ), 261,241
【００５０】実施例７４’−シアノ−２’−（２，４−ジフルオロフェノキ
シ）メタンスルホンアニリド・ナトリウム塩の合成
４’−シアノ−２’−（２，４−ジフルオロフェノキ
シ）メタンスルホンアニリド（１５ｇ）を、水酸化ナト
リウム（２ｇ）の水（７０ｍｌ）溶液に溶かし、不溶物
を濾別した後、濾液を濃縮する。濃縮物を酢酸エチル
（１００ｍｌ）に溶かした後濾過し、濾液を室温で攪拌
し、生成する沈殿を濾取して酢酸エチルで洗浄すると、
４’−シアノ−２’−（２，４−ジフルオロフェノキ
シ）メタンスルホンアニリドのナトリウム塩（１４．８
ｇ）が得られる。
融点： 267〜268 ℃
NMR(CD3OD ：δ）：2.89(3H,s),6.8〜7.6(6H,m)
IR(ヌジョール) ：2240,1600,1500,1330,1250,1120cm-1 Example 7 4'-Cyano-2 '-(2,4-difluorophenoxy)
Si) Synthesis of methanesulfonanilide sodium salt 4'-cyano-2 '-(2,4-difluorophenoxy) methanesulfonanilide (15 g) was dissolved in a solution of sodium hydroxide (2 g) in water (70 ml) and insoluble. After filtering off the substances, the filtrate is concentrated. The concentrate was dissolved in ethyl acetate (100 ml) and then filtered, the filtrate was stirred at room temperature, the precipitate formed was filtered off and washed with ethyl acetate.
Sodium salt of 4'-cyano-2 '-(2,4-difluorophenoxy) methanesulfonanilide (14.8
g) is obtained. Melting point: 267 to 268 ° C NMR (CD 3 OD: δ): 2.89 (3H, s), 6.8 to 7.6 (6H, m) IR (nujol): 2240,1600,1500,1330,1250,1120cm -1
【００５１】[0051]
【発明の効果】この発明は以上の様に構成されており、
オルト位のハロゲン化されたアルカンスルホンアニリド
誘導体[I] またはその塩とフェノール誘導体[II]または
その塩を反応させることによって、従来法で行なわれて
いた予備工程、即ちアミノ基をニトロ基に変えてからジ
フェニルエーテル合成を行ない、その後ニトロ基を還元
してアミノ基に戻してアルカンスルホニル化するといっ
た工程を省略して、直接アルカンスルホンアニリド誘導
体[III] を製造することができ、工程を短縮することが
できる。しかもニトロベンゼン誘導体とフェノール誘導
体を反応する従来法では１４０℃程度の高温が必要であ
るが、本発明を実施する際の化合物[I] と化合物[II]の
反応は１２０℃程度以下でも十分に進行するので、原料
物質および目的物質の分解も抑えられ、こうした効果が
相まって全体としての収率を大幅に高めること（従来法
では２５〜３０％程度であったものが、本発明法によれ
ば36.5〜４０％となる）ができる。The present invention is constituted as described above,
By reacting the halogenated alkane sulfone anilide derivative [I] or its salt at the ortho position with the phenol derivative [II] or its salt, a preliminary step which was carried out by the conventional method, that is, the amino group was changed to a nitro group It is possible to directly synthesize the alkanesulfonanilide derivative [III] by omitting the step of performing diphenyl ether synthesis afterwards, then reducing the nitro group to return it to the amino group and converting it to an alkanesulfonyl group. You can Moreover, the conventional method of reacting a nitrobenzene derivative with a phenol derivative requires a high temperature of about 140 ° C., but the reaction between the compound [I] and the compound [II] in carrying out the present invention proceeds sufficiently even at about 120 ° C. or less. Therefore, the decomposition of the raw material and the target substance can be suppressed, and the combined effect can significantly increase the overall yield (from the conventional method of about 25 to 30%, the yield of the present invention is 36.5%). Up to 40%).
Claims (7)
その塩に、下記一般式で[II]示されるフェノール誘導体
またはその塩を反応させることを特徴とする、下記一般
式[III] で示されるアルカンスルホンアニリド誘導体ま
たはその塩の製法。 【化１】 1. A compound represented by the following general formula [I] or a salt thereof is reacted with a phenol derivative represented by the following general formula [II] or a salt thereof. A process for producing the indicated alkanesulfoneanilide derivative or a salt thereof. [Chemical 1]
チル基、Ｒ2がアセチル基、Ｒ3、Ｒ4がいずれもふっ
素、Ａが−Ｏ−である請求項１記載の製法。2. In the general formulas [I] to [III], R 1 is a methyl group, R 2 is an acetyl group, R 3 and R 4 are all fluorine, and A is —O—. Manufacturing method.
チル基、Ｒ2がシアノ基、Ｒ3、Ｒ4がいずれもふっ素、
Ａが−Ｏ−である請求項１記載の製法。3. In the general formulas [I] to [III], R 1 is a methyl group, R 2 is a cyano group, R 3 and R 4 are all fluorine,
The method according to claim 1, wherein A is -O-.
チル基、Ｒ2がカルバモイル基、Ｒ3、Ｒ4がいずれもふ
っ素、Ａが−Ｓ−である請求項１記載の製法。4. The formulas [I] to [III], wherein R 1 is a methyl group, R 2 is a carbamoyl group, R 3 and R 4 are all fluorine, and A is —S—. Manufacturing method.
と塩基の存在下で反応を行なう請求項１〜４のいずれか
に記載の製法。5. The method according to claim 1, wherein the reaction is carried out in the presence of a copper catalyst and a base using an aromatic amine solvent.
銅、塩基が炭酸カリウムである請求項５に記載の製法。6. The solvent is pyridine and the copper-based catalyst is chloride first.
The method according to claim 5, wherein the copper and the base are potassium carbonate.
導体またはそのアミノ基における反応性誘導体もしくは
その塩に、下記一般式[V] で示されるアルカンスルホン
酸またはスルホン酸基におけるその反応性誘導体もしく
はその塩を反応させて下記一般式[VI]で示される化合物
またはその塩とし、該化合物[VI]またはその塩をハロゲ
ン化して一般式[I] で示される化合物またはその塩とし
た後、これに一般式[II]で示されるフェノール誘導体ま
たはその塩を反応させて一般式[III] で示されるアルカ
ンスルフホンアニリド誘導体またはその塩を得る請求項
１〜６のいずれかに記載の製法。 【化２】 7. An aniline derivative represented by the following general formula [IV] or a reactive derivative thereof in an amino group or a salt thereof, and an alkanesulfonic acid represented by the following general formula [V] or a reactive derivative thereof in a sulfonic acid group. Alternatively, by reacting a salt thereof with a compound represented by the following general formula [VI] or a salt thereof, and halogenating the compound [VI] or a salt thereof into a compound represented by the general formula [I] or a salt thereof, The method according to any one of claims 1 to 6, wherein the phenol derivative represented by the general formula [II] or a salt thereof is reacted with this to obtain an alkane sulfone anilide derivative represented by the general formula [III] or a salt thereof. . [Chemical 2]
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI911633A FI911633A (en) | 1990-04-27 | 1991-04-05 | FOERFARANDE FOER FRAMSTAELLNING AV ALKANSULFONANILIDDERIVAT. |
| IE119191A IE911191A1 (en) | 1990-04-27 | 1991-04-09 | Method of producing alkanesulfonanilide derivatives |
| GR910100162A GR1000822B (en) | 1990-04-27 | 1991-04-16 | Method of producing alkanesulfonanilide derivatives |
| JP12218791A JPH0625102B2 (en) | 1990-04-27 | 1991-04-23 | Process for producing alkane sulfone anilide derivative |
| AU75321/91A AU7532191A (en) | 1990-04-27 | 1991-04-24 | Method of producing alkanesulfonanilide derivatives |
| NO91911672A NO911672L (en) | 1990-04-27 | 1991-04-26 | PROCEDURE FOR THE PREPARATION OF ALKANSULPHONANILIDE DERIVATIVES. |
| CN91102731.9A CN1056100A (en) | 1990-04-27 | 1991-04-26 | The preparation method of alkane sulfonyl aniline derivatives |
| PT97494A PT97494A (en) | 1990-04-27 | 1991-04-26 | Process for the preparation of alkane-sulphonanilide derivatives |
| HU911429A HU209543B (en) | 1990-04-27 | 1991-04-26 | New method for production of alkanesulfonanilide-derivatives |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11222590 | 1990-04-27 | ||
| JP2-112225 | 1990-04-27 | ||
| JP11565391 | 1991-04-18 | ||
| JP3-115653 | 1991-04-18 | ||
| JP12218791A JPH0625102B2 (en) | 1990-04-27 | 1991-04-23 | Process for producing alkane sulfone anilide derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH051023A true JPH051023A (en) | 1993-01-08 |
| JPH0625102B2 JPH0625102B2 (en) | 1994-04-06 |
Family
ID=27312207
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12218791A Expired - Lifetime JPH0625102B2 (en) | 1990-04-27 | 1991-04-23 | Process for producing alkane sulfone anilide derivative |
Country Status (9)
| Country | Link |
|---|---|
| JP (1) | JPH0625102B2 (en) |
| CN (1) | CN1056100A (en) |
| AU (1) | AU7532191A (en) |
| FI (1) | FI911633A (en) |
| GR (1) | GR1000822B (en) |
| HU (1) | HU209543B (en) |
| IE (1) | IE911191A1 (en) |
| NO (1) | NO911672L (en) |
| PT (1) | PT97494A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5723222A (en) * | 1995-04-11 | 1998-03-03 | National Starch And Chemical Investment Holding Corporation | Hot melt adhesives and disposable products utilizing the same |
| US11498438B2 (en) | 2007-05-09 | 2022-11-15 | Irobot Corporation | Autonomous coverage robot |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102125669B (en) * | 2010-10-27 | 2012-05-30 | 宋爱民 | Chinese medicinal preparation for treating chronic bronchitis of phlegm-dampness accumulation in lung |
| CN109608370A (en) * | 2019-01-22 | 2019-04-12 | 山西康斯亚森生物科技有限公司 | Aulin derivative and Preparation method and use |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3906024A (en) * | 1971-02-24 | 1975-09-16 | Minnesota Mining & Mfg | Perfluoroalkanesulfonamidoaryl compounds |
| US4005141A (en) * | 1972-07-03 | 1977-01-25 | Minnesota Mining And Manufacturing Company | Perfluoroalkylsulfonamidoaryl compounds |
| PT86407B (en) * | 1986-12-31 | 1990-11-20 | Fujisawa Pharmaceutical Co | METHOD FOR PREPARING NEW ALCANO-SULFONANILIDA DERIVATIVES, AND OF PHARMACEUTICAL COMPOSITIONS UNDERSTANDING THE SAME |
| EP0379915A1 (en) * | 1989-01-26 | 1990-08-01 | Bayer Ag | Substituted phenoxybenzonitrile derivatives, processes for their preparation and their use as herbicides and plant growth regulators |
-
1991
- 1991-04-05 FI FI911633A patent/FI911633A/en not_active Application Discontinuation
- 1991-04-09 IE IE119191A patent/IE911191A1/en unknown
- 1991-04-16 GR GR910100162A patent/GR1000822B/en unknown
- 1991-04-23 JP JP12218791A patent/JPH0625102B2/en not_active Expired - Lifetime
- 1991-04-24 AU AU75321/91A patent/AU7532191A/en not_active Abandoned
- 1991-04-26 PT PT97494A patent/PT97494A/en not_active Application Discontinuation
- 1991-04-26 NO NO91911672A patent/NO911672L/en unknown
- 1991-04-26 HU HU911429A patent/HU209543B/en not_active IP Right Cessation
- 1991-04-26 CN CN91102731.9A patent/CN1056100A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5723222A (en) * | 1995-04-11 | 1998-03-03 | National Starch And Chemical Investment Holding Corporation | Hot melt adhesives and disposable products utilizing the same |
| US11498438B2 (en) | 2007-05-09 | 2022-11-15 | Irobot Corporation | Autonomous coverage robot |
Also Published As
| Publication number | Publication date |
|---|---|
| FI911633A (en) | 1991-10-28 |
| CN1056100A (en) | 1991-11-13 |
| NO911672L (en) | 1991-10-28 |
| JPH0625102B2 (en) | 1994-04-06 |
| AU7532191A (en) | 1991-11-07 |
| HU911429D0 (en) | 1991-11-28 |
| HU209543B (en) | 1994-07-28 |
| PT97494A (en) | 1992-01-31 |
| FI911633A0 (en) | 1991-04-05 |
| NO911672D0 (en) | 1991-04-26 |
| IE911191A1 (en) | 1991-12-04 |
| GR1000822B (en) | 1993-01-25 |
| HUT58284A (en) | 1992-02-28 |
| GR910100162A (en) | 1992-07-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 19940927 |