JPH0558985A - Production of cyanoguanidine derivative - Google Patents
Production of cyanoguanidine derivativeInfo
- Publication number
- JPH0558985A JPH0558985A JP3244901A JP24490191A JPH0558985A JP H0558985 A JPH0558985 A JP H0558985A JP 3244901 A JP3244901 A JP 3244901A JP 24490191 A JP24490191 A JP 24490191A JP H0558985 A JPH0558985 A JP H0558985A
- Authority
- JP
- Japan
- Prior art keywords
- derivative
- formula
- isocyanide
- expressed
- nickel chloride
- 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
Links
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
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、医薬品として有用なシ
アノグアニジン誘導体の製造法に関する。さらに詳しく
は、本発明はカリウムチャンネル開口薬として有用な一
般式（４）TECHNICAL FIELD The present invention relates to a method for producing a cyanoguanidine derivative useful as a medicine. More specifically, the present invention provides compounds of general formula (4) useful as potassium channel openers.
【０００２】[0002]
【化３】 （式中、Ｒ1およびＲ2はそれぞれ独立してハロゲン原
子、シアノ基又はニトロ基を表し、Ｒ3は該１位に分枝
鎖を有する炭素数４〜７のアルキル基を表す。）で示さ
れるシアノグアニジン誘導体の製造法に関するものであ
る。[Chemical 3] (In the formula, R 1 and R 2 each independently represent a halogen atom, a cyano group or a nitro group, and R 3 represents an alkyl group having a branched chain at the 1-position and having 4 to 7 carbon atoms.) The present invention relates to a method for producing the cyanoguanidine derivative shown.
【０００３】[0003]
【従来の技術】シアノグアニジン誘導体の製造法として
特開平3-31250号公報および特開平2-290841号公報に
は、チオ尿素誘導体を得、次いでカルボジイミド誘導体
に導き、シアナミドと反応させることによるシアノグア
ニジン誘導体の製造法が開示されている。また、特開平
2-91057号公報にはＮ−シアノチオ尿素誘導体を経由す
るシアノグアニジン誘導体の製造法が開示されている。2. Description of the Related Art As a method for producing a cyanoguanidine derivative, JP-A-3-31250 and JP-A-2-290841 disclose thiourea derivatives, which are then introduced into carbodiimide derivatives and reacted with cyanamide. A method of making the derivative is disclosed. In addition,
2-91057 discloses a method for producing a cyanoguanidine derivative via an N-cyanothiourea derivative.
【０００４】[0004]
【発明が解決しようとする課題】上記特開平2-91057
号、特開平2-290841号および特開平3-31250号に開示さ
れている製造法においては、チオ尿素およびＮ−シアノ
チオ尿素誘導体の原料となるイソチオシアネートを得る
反応に毒性の高いチオホスゲンを使用する必要がある。
また、これらの製造法は工程数が多く操作が繁雑であ
る。DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention
In the production methods disclosed in JP-A Nos. 2-290841 and 3-31250, highly toxic thiophosgene is used in the reaction to obtain isothiocyanate as a raw material for thiourea and N-cyanothiourea derivatives. There is a need.
Further, these manufacturing methods have many steps and are complicated in operation.
【０００５】[0005]
【課題を解決するための手段】本発明者らは、安全で且
つ簡便なシアノグアニジン誘導体の製造法を開発する目
的で合成中間体となるカルボジイミドの製造法を検討し
た。カルボジイミド類の一般的な合成法としては、ザ・
ジャーナル・オブ・オルガニック・ケミストリー(J.Or
g.Chem.),40巻,2981-2982頁(1975年)にアミンとイソシ
アニドとを塩化パラジウムと酸化銀の存在下に反応させ
る方法が報告されている。しかしここに記載された方法
では、高価な酸化銀を酸化剤として化学量論量使用する
必要があるため、改良の余地がある。Means for Solving the Problems The present inventors have studied a method for producing a carbodiimide as a synthetic intermediate for the purpose of developing a safe and convenient method for producing a cyanoguanidine derivative. As a general synthetic method of carbodiimides, the
Journal of Organic Chemistry (J.Or
g. Chem.), 40, 2981-2982 (1975), a method of reacting an amine with an isocyanide in the presence of palladium chloride and silver oxide is reported. However, the method described here has room for improvement because it requires the use of expensive silver oxide in stoichiometric amounts as oxidant.
【０００６】本発明者らは、種々検討した結果工業的に
有利なカルボジイミドの製造法を見い出し、安全で且つ
工程数の少ないシアノグアニジン誘導体の製造法を完成
させた。本発明は、アニリン誘導体（１）とイソシアニ
ド誘導体（２）とを、不活性有機溶媒中、触媒として塩
化ニッケル、塩化ニッケル錯体又はゼロ価パラジウム錯
体を用い、脱水剤存在下、酸素ガスまたは乾燥空気を吹
き込みながら反応させることによりカルボジイミド誘導
体（３）を得、次いで非プロトン性有機溶媒中でシアナ
ミドと反応させることを特徴とするシアノグアニジン誘
導体（４）の製造法である。As a result of various studies, the present inventors have found an industrially advantageous method for producing a carbodiimide, and have completed a method for producing a cyanoguanidine derivative which is safe and has a small number of steps. The present invention uses an aniline derivative (1) and an isocyanide derivative (2) in an inert organic solvent, using nickel chloride, a nickel chloride complex or a zero-valent palladium complex as a catalyst, in the presence of a dehydrating agent, oxygen gas or dry air. Is a method for producing a cyanoguanidine derivative (4), which comprises reacting with a cyanamide in an aprotic organic solvent by reacting while blowing the carbodiimide derivative (3).
【０００７】[0007]
【化４】 [Chemical 4]
【０００８】以下に本発明を詳細に述べる。本発明に用
いるアニリン誘導体（１）としては、例えば３，５−ジ
クロロアニリン、３−アミノ−５−クロロベンゾニトリ
ル、３−クロロ−５−ニトロアニリン等が挙げられる。
又、イソシアニド誘導体（２）としてはｔ−ブチルイソ
シアニド、ｔ−ペンチルイソシアニド等の該１位に分枝
鎖を有する炭素数４〜７のアルキルイソシアニドを挙げ
ることができる。The present invention will be described in detail below. Examples of the aniline derivative (1) used in the present invention include 3,5-dichloroaniline, 3-amino-5-chlorobenzonitrile, 3-chloro-5-nitroaniline and the like.
Examples of the isocyanide derivative (2) include alkyl isocyanide having 4 to 7 carbon atoms, which has a branched chain at the 1-position, such as t-butyl isocyanide and t-pentyl isocyanide.
【０００９】カルボジイミド（３）を合成する反応はベ
ンゼン、トルエン等の不活性有機溶媒中、触媒および脱
水剤の存在下、反応液中に酸素ガスまたは乾燥空気を吹
き込みながら、化合物（１）と化合物（２）とを、７０
〜１５０℃で１〜４時間反応させることにより行う。化
合物（２）の使用量は通常化合物（１）１モルに対して
１．０〜５．０モル、好ましくは２．５〜３．０モルで
あり、２回以上に分割して加えてもよい。The reaction for synthesizing the carbodiimide (3) is carried out in the presence of a catalyst and a dehydrating agent in an inert organic solvent such as benzene or toluene, while blowing oxygen gas or dry air into the reaction solution and the compound (1) and the compound. (2) and 70
It is carried out by reacting at ˜150 ° C. for 1 to 4 hours. The amount of the compound (2) used is usually 1.0 to 5.0 mol, preferably 2.5 to 3.0 mol, per 1 mol of the compound (1), and may be added in two or more portions. Good.
【００１０】触媒としては塩化ニッケル又は塩化ニッケ
ルのホスフィン錯体例えば、塩化ビス（トリフェニルホ
スフィン）ニッケル(II)、塩化ビス（トリ−ｎ−ブチル
ホスフィン）ニッケル(II)、塩化〔１，１′−ビス（ジ
フェニルホスフィノ）フェロセン〕ニッケル(II)を用い
ることができる。塩化ニッケルと上記ホスフィン配位子
を反応系に加えることにより触媒とすることもできる。
また、触媒として、ゼロ価パラジウム錯体、例えばテト
ラキス（トリフェニルホスフィン）パラジウムを用いる
こともできる。これらの触媒は化合物（１）に対して通
常0.01〜0.1当量用いられる。As the catalyst, nickel chloride or a phosphine complex of nickel chloride, for example, bis (triphenylphosphine) nickel (II) chloride, bis (tri-n-butylphosphine) nickel (II) chloride, [1,1'-chloride] Bis (diphenylphosphino) ferrocene] nickel (II) can be used. It can also be used as a catalyst by adding nickel chloride and the above phosphine ligand to the reaction system.
A zero-valent palladium complex such as tetrakis (triphenylphosphine) palladium can also be used as the catalyst. These catalysts are usually used in 0.01 to 0.1 equivalent based on the compound (1).
【００１１】脱水剤としては例えばモレキュラーシーブ
や無水硫酸ナトリウムを用いることができる。生成した
カルボジイミド誘導体（３）は蒸留又はカラムクロマト
グラフィーにより容易に精製できる。As the dehydrating agent, for example, molecular sieve or anhydrous sodium sulfate can be used. The produced carbodiimide derivative (3) can be easily purified by distillation or column chromatography.
【００１２】次いで非プロトン性有機溶媒中、上記カル
ボジイミド（３) とシアナミドを50℃から溶媒の沸点温
度で30分〜72時間反応させることによりシアノグアニジ
ン誘導体（４）を製造することができる。本反応におい
て用いられる非プロトン性有機溶媒としてはテトラヒド
ロフラン、Ｎ、Ｎ−ジメチルホルムアミド（以下、ＤＭ
Ｆと略す。）、ジメチルスルホキシド等が挙げられる。
シアナミドは化合物（３）に対して１〜１０当量使用さ
れる。本反応にはジイソプロピルエチルアミン等の塩基
を触媒として用いることもできる。本発明によって製造
されるシアノグアニジン誘導体は常法によりカラムクロ
マトグラフィー及び／又は再結晶等によって分離精製す
ることができる。Then, the carbodiimide (3) and cyanamide are reacted in an aprotic organic solvent at 50 ° C. to the boiling point of the solvent for 30 minutes to 72 hours to produce a cyanoguanidine derivative (4). As the aprotic organic solvent used in this reaction, tetrahydrofuran, N, N-dimethylformamide (hereinafter, DM
Abbreviated as F. ), Dimethyl sulfoxide and the like.
Cyanamide is used in the amount of 1 to 10 equivalents based on compound (3). In this reaction, a base such as diisopropylethylamine can be used as a catalyst. The cyanoguanidine derivative produced by the present invention can be separated and purified by a conventional method such as column chromatography and / or recrystallization.
【００１３】[0013]
【発明の効果】本発明は、カリウムチャンネル開口薬と
して有用なシアノグアニジン誘導体（４）を安全で且つ
短い工程で製造することができ、工業的製法として優れ
ている。INDUSTRIAL APPLICABILITY According to the present invention, the cyanoguanidine derivative (4) useful as a potassium channel opener can be produced safely and in a short process, and is an excellent industrial production method.
【００１４】[0014]
【実施例】以下、実施例および参考例を挙げて本発明を
さらに具体的に説明する。 実施例１Ｎ−ｔ−ブチル−Ｎ′−シアノ−Ｎ″−（３，５−ジク
ロロフェニル）グアニジンの製造： （１）Ｎ−ｔ−ブチル−Ｎ′−（３，５−ジクロロフェ
ニル）カルボジイミド：ベンゼン4.4gに３，５−ジクロ
ロアニリン648mg、塩化ニッケル52mgおよび無水硫酸ナ
トリウム1.00gを加え、酸素ガスを吹き込み溶媒の沸点
温度で撹拌しながら、t-ブチルイソシアニドのベンゼン
溶液5.7g（ｔ−ブチルイソシアニド998mgを含む。）を
１時間かけて加えた。さらに酸素ガスを吹き込みながら
溶媒の沸点温度で20分間撹拌した。不溶物を濾別し溶媒
を減圧留去した後、残渣をシリカゲルカラムクロマトグ
ラフィー（溶媒；シクロヘキサン）で精製し、Ｎ−ｔ−
ブチル−Ｎ′−（３，５−ジクロロフェニル）カルボジ
イミド414mgを得た。1 Ｈ−ＮＭＲ(CDCl3) δ:1.43(9H,s),6.94(2H,d),7.08(1
H,t).EXAMPLES The present invention will be described in more detail below with reference to examples and reference examples. Example 1 Nt-Butyl-N'-cyano-N "-(3,5-dic
Production of ( lorophenyl) guanidine: (1) Nt-butyl-N '-(3,5-dichlorophenyl) carbodiimide: To 4.4 g of benzene, 648 mg of 3,5-dichloroaniline, 52 mg of nickel chloride and 1.00 g of anhydrous sodium sulfate were added. Then, 5.7 g of a benzene solution of t-butyl isocyanide (containing 998 mg of t-butyl isocyanide) was added over 1 hour while stirring at a boiling temperature of the solvent by blowing oxygen gas. Further, the mixture was stirred for 20 minutes at the boiling point of the solvent while blowing oxygen gas. The insoluble material was filtered off, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (solvent; cyclohexane), Nt-
414 mg of butyl-N '-(3,5-dichlorophenyl) carbodiimide was obtained. 1 H-NMR (CDCl 3 ) δ: 1.43 (9H, s), 6.94 (2H, d), 7.08 (1
H, t).
【００１５】（２）Ｎ−ｔ−ブチル−Ｎ′−シアノ−
Ｎ″−（３，５−ジクロロフェニル）グアニジン：Ｎ−
ｔ−ブチル−Ｎ′−（３，５−ジクロロフェニル）カル
ボジイミド335mg、シアナミド290mgおよびジイソプロピ
ルエチルアミン71mgをＤＭＦ3.0mlに溶解し、90〜95℃
で40分間加熱撹拌した後、酢酸エチルと水を加え分液
し、水層を酢酸エチルで抽出した。無水硫酸マグネシウ
ムで乾燥した後、シリカゲルカラムクロマトグラフィー
（溶媒；ヘキサン／酢酸エチル＝１０／３）で精製し、
Ｎ−ｔ−ブチル−Ｎ′−シアノ−Ｎ″−（３，５−ジク
ロロフェニル）グアニジン215mgを得た。 m.p. 191.0-192.5゜C1 Ｈ−ＮＭＲ(DMSO-d6)δ:1.33(9H,s),7.09(2H,d),7.25
(1H,t),7.39(1H,bs),9.29(1H,bs).(2) Nt-butyl-N'-cyano-
N "-(3,5-dichlorophenyl) guanidine: N-
335 mg of t-butyl-N '-(3,5-dichlorophenyl) carbodiimide, 290 mg of cyanamide and 71 mg of diisopropylethylamine were dissolved in 3.0 ml of DMF and heated at 90-95 ° C.
After stirring with heating for 40 minutes, ethyl acetate and water were added and the layers were separated, and the aqueous layer was extracted with ethyl acetate. After dried over anhydrous magnesium sulfate, purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 10/3),
215 mg of Nt-butyl-N'-cyano-N "-(3,5-dichlorophenyl) guanidine were obtained. Mp 191.0-192.5 ° C 1 H-NMR (DMSO-d 6 ) δ: 1.33 (9H, s. ), 7.09 (2H, d), 7.25
(1H, t), 7.39 (1H, bs), 9.29 (1H, bs).
【００１６】実施例２Ｎ−（３−クロロ−５−シアノフェニル）−Ｎ′−シア
ノ−Ｎ″−ｔ−ペンチルグアニジンの製造： （１）Ｎ−（３−クロロ−５−シアノフェニル）−Ｎ′
−ｔ−ペンチルカルボジイミド：ｔ−ペンチルイソシア
ニドのベンゼン溶液6.76g（ｔ−ペンチルイソシアニド5
83mgを含む。）に、３−アミノ−５−クロロベンゾニト
リル763mg、テトラキス（トリフェニルホスフィン）パ
ラジウム578mgおよびモレキュラシーブ４Ａ 1.50gを加
え、反応溶液に酸素ガスを吹き込みながら溶媒の沸点温
度で15分間撹拌した。さらにｔ−ペンチルイソシアニド
のベンゼン溶液13.5g（ｔ−ペンチルイソシアニド1.17g
を含む。）を加え、酸素ガスを吹き込みながら溶媒の沸
点温度で２時間45分撹拌した。室温まで放冷し、不溶物
を濾別して溶媒を減圧留去した後、残渣をシリカゲルカ
ラムクロマトグラフィー( 溶媒; シクロヘキサン/ 酢酸
エチル＝１０／１）で精製し、Ｎ−（３−クロロ−５−
シアノフェニル）−Ｎ′−ｔ−ペンチルカルボジイミド
675mgを得た。1Ｈ−ＮＭＲ(CDCl3) δ：1.01(3H,t),1.3
9(6H,s),1.65(2H,q),7.15〜7.35(3H,m).Example 2 N- (3-chloro-5-cyanophenyl) -N'-sia
Preparation of no-N ″ -t-pentylguanidine: (1) N- (3-chloro-5-cyanophenyl) -N ′
-T-pentyl carbodiimide: 6.76 g of a benzene solution of t-pentyl isocyanide (t-pentyl isocyanide 5
Contains 83 mg. ), 763 mg of 3-amino-5-chlorobenzonitrile, 578 mg of tetrakis (triphenylphosphine) palladium and 1.50 g of molecular sieve 4A were added thereto, and the mixture was stirred for 15 minutes at the boiling temperature of the solvent while blowing oxygen gas into the reaction solution. Furthermore, 13.5 g of a benzene solution of t-pentyl isocyanide (t-pentyl isocyanide 1.17 g
including. ) Was added, and the mixture was stirred at the boiling point of the solvent for 2 hours and 45 minutes while blowing oxygen gas. The mixture was allowed to cool to room temperature, the insoluble material was filtered off, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (solvent; cyclohexane / ethyl acetate = 10/1) and N- (3-chloro-5-
Cyanophenyl) -N'-t-pentylcarbodiimide
675 mg was obtained. 1 H-NMR (CDCl 3 ) δ: 1.01 (3H, t), 1.3
9 (6H, s), 1.65 (2H, q), 7.15 ~ 7.35 (3H, m).
【００１７】（２）Ｎ−（３−クロロ−５−シアノフェ
ニル）−Ｎ′−シアノ−Ｎ″−ｔ−ペンチルグアニジ
ン：Ｎ−（３−クロロ−５−シアノフェニル）−Ｎ′−
ｔ−ペンチルカルボジイミド7.5g、シアナミド6.5gおよ
びジイソプロピルエチルアミン319mgをＤＭＦ40mlに溶
解し、90〜95℃で２時間加熱撹拌した。室温まで冷却
後、反応溶液を400mlの水にそそぎ、析出した結晶を濾
取し、エタノールから再結晶してＮ−（３−クロロ−５
−シアノフェニル）−Ｎ′−シアノ−Ｎ″−ｔ−ペンチ
ルグアニジン5.7gを得た。 m.p. 181.0-183.0℃1 Ｈ−ＮＭＲ(DMSO-d6) δ:0.83(3H,t),1.29(6H,s),1.70
(2H,q),7.29(1H,bs),7.4〜7.5(2H,m),7.6〜7.7(1H,m),
9.43(1H,bs).(2) N- (3-chloro-5-cyanophenyl) -N'-cyano-N "-t-pentylguanidine: N- (3-chloro-5-cyanophenyl) -N'-
7.5 g of t-pentylcarbodiimide, 6.5 g of cyanamide and 319 mg of diisopropylethylamine were dissolved in 40 ml of DMF, and the mixture was heated with stirring at 90 to 95 ° C for 2 hours. After cooling to room temperature, the reaction solution was poured into 400 ml of water, and the precipitated crystals were collected by filtration and recrystallized from ethanol to give N- (3-chloro-5).
5.7 g of -cyanophenyl) -N'-cyano-N "-t-pentylguanidine was obtained. Mp 181.0-183.0 ° C 1 H-NMR (DMSO-d 6 ) δ: 0.83 (3H, t), 1.29 (6H , s), 1.70
(2H, q), 7.29 (1H, bs), 7.4〜7.5 (2H, m), 7.6〜7.7 (1H, m),
9.43 (1H, bs).
【００１８】参考例 実施例２（１）に記載したＮ−（３−クロロ−５−シア
ノフェニル）−Ｎ′−ｔ−ペンチルカルボジイミドは以
下の方法によっても製造できる。即ち、実施例２（１）
に準じて塩化ニッケル又は塩化ニッケル錯体を触媒に用
い、酸素ガス又は乾燥空気を吹き込むことによりＮ−
（３−クロロ−５−シアノフェニル）−Ｎ′−ｔ−ペン
チルカルボジイミドを製造した。反応条件と収率（ガス
クロマトグラフィーで定量した。）を第１表に示す。Reference Example The N- (3-chloro-5-cyanophenyl) -N'-t-pentylcarbodiimide described in Example 2 (1) can also be produced by the following method. That is, Example 2 (1)
N-chloride by blowing oxygen gas or dry air using nickel chloride or nickel chloride complex as a catalyst according to
(3-Chloro-5-cyanophenyl) -N'-t-pentylcarbodiimide was prepared. The reaction conditions and the yield (quantified by gas chromatography) are shown in Table 1.
【００１９】[0019]
【表１】 [Table 1]
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 // Ｃ０７Ｂ 61/00 ３００ ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification code Office reference number FI technical display location // C07B 61/00 300
Claims (1)
子、シアノ基又はニトロ基を表す。）で示されるアニリ
ン誘導体と、下式（２） ＣＮ−Ｒ3 （２） （式中、Ｒ3は該１位に分枝鎖を有する炭素数４〜７の
アルキル基を表す。）で示されるイソシアニド誘導体と
を、不活性有機溶媒中、触媒として塩化ニッケル、塩化
ニッケル錯体又はゼロ価パラジウム錯体を用い、脱水剤
存在下、酸素ガス又は乾燥空気を吹き込みながら反応さ
せることにより一般式（３） 【化２】 （式中、Ｒ1およびＲ2はそれぞれ独立してハロゲン原
子、シアノ基又はニトロ基を表し、Ｒ3は該１位に分枝
鎖を有する炭素数４〜７のアルキル基を表す。）で示さ
れるカルボジイミド誘導体を得、次いで非プロトン性有
機溶媒中でシアナミドと反応させることを特徴とする一
般式（４） 【化３】 （式中、Ｒ1およびＲ2はそれぞれ独立してハロゲン原
子、シアノ基又はニトロ基を表し、Ｒ3は該１位に分枝
鎖を有する炭素数４〜７のアルキル基を表す。）で示さ
れるシアノグアニジン誘導体の製造法。1. The following formula (1): (In the formula, R 1 and R 2 each independently represent a halogen atom, a cyano group or a nitro group.), And an aniline derivative represented by the following formula (2) CN—R 3 (2) 3 represents an alkyl group having a branched chain at the 1-position and having 4 to 7 carbon atoms), and a nickel chloride, nickel chloride complex or zero-valent palladium complex as a catalyst in an inert organic solvent. By reacting while blowing oxygen gas or dry air in the presence of a dehydrating agent, the compound of the general formula (3) (In the formula, R 1 and R 2 each independently represent a halogen atom, a cyano group or a nitro group, and R 3 represents an alkyl group having a branched chain at the 1-position and having 4 to 7 carbon atoms.) Obtaining the carbodiimide derivative shown, and then reacting with cyanamide in an aprotic organic solvent, a compound of the general formula (4): (In the formula, R 1 and R 2 each independently represent a halogen atom, a cyano group or a nitro group, and R 3 represents an alkyl group having a branched chain at the 1-position and having 4 to 7 carbon atoms.) A method for producing the indicated cyanoguanidine derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3244901A JPH0558985A (en) | 1991-08-29 | 1991-08-29 | Production of cyanoguanidine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3244901A JPH0558985A (en) | 1991-08-29 | 1991-08-29 | Production of cyanoguanidine derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0558985A true JPH0558985A (en) | 1993-03-09 |
Family
ID=17125658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3244901A Pending JPH0558985A (en) | 1991-08-29 | 1991-08-29 | Production of cyanoguanidine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0558985A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999058497A1 (en) * | 1998-05-11 | 1999-11-18 | Novo Nordisk A/S | Substituted guanidines and diaminonitroethenes, their preparation and use |
| CN105294499A (en) * | 2015-04-29 | 2016-02-03 | 中国农业大学 | Preparation method for carbodiimide compounds |
| CN106699608A (en) * | 2016-12-26 | 2017-05-24 | 常州大学 | Benzene guanidine containing strong electron withdrawing group and preparation method of salt thereof |
| CN113698322A (en) * | 2021-08-02 | 2021-11-26 | 大连理工大学 | Continuous production process method of hydroxyguanidine sulfate |
-
1991
- 1991-08-29 JP JP3244901A patent/JPH0558985A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999058497A1 (en) * | 1998-05-11 | 1999-11-18 | Novo Nordisk A/S | Substituted guanidines and diaminonitroethenes, their preparation and use |
| CN105294499A (en) * | 2015-04-29 | 2016-02-03 | 中国农业大学 | Preparation method for carbodiimide compounds |
| CN106699608A (en) * | 2016-12-26 | 2017-05-24 | 常州大学 | Benzene guanidine containing strong electron withdrawing group and preparation method of salt thereof |
| CN113698322A (en) * | 2021-08-02 | 2021-11-26 | 大连理工大学 | Continuous production process method of hydroxyguanidine sulfate |
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