JP2005336103A - Method for producing phenylhydrazine compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a phenylhydrazine compound capable of essentially removing unnecessary metal salts after the reaction by reducing a diazonium salt with a metal salt reducing agent. <P>SOLUTION: A phenylhydrazine compound expressed by general formula (2) is produced by reducing a diazonium salt expressed by general formula (1) with a metal salt reducing agent and, after the reaction, essentially removing the unnecessary metal salt with a chelating agent. In formulas (1) and (2), R<SB>1</SB>is a substituent and n is an integer of 0-5. When n is ≥2, the R<SB>1</SB>groups may be the same or different and may be connected with each other to form a ring. In general formula (1), X<SP>-</SP>is an anion. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a method for producing phenylhydrazines.

The hydrazine compound is a useful compound for organic synthesis, which is used as an intermediate for pharmaceuticals and photographic couplers. For example, pyrazole compounds produced using hydrazines as raw materials are used in pharmaceuticals, agricultural chemicals, dyes, photographic couplers, and the like. Hydrazines can be generally produced by reducing a corresponding diazonium salt with sodium sulfite, tin chloride or the like (see, for example, Non-Patent Documents 1 and 2 and Patent Documents 1 to 3 below).
However, there are some problems in the production of hydrazines by these methods. That is, in order to perform reduction with a water-soluble inorganic reducing agent typified by sodium sulfite, the problem is that the reaction does not proceed unless the raw diazonium salt has some water solubility. In addition, when using a metal salt reducing agent typified by tin (II) chloride, even a diazonium salt with low water solubility will react, but the by-product derived from the metal salt may gel during filtration after the reaction. When the solid is deposited as a poor solid, the handling property of the reaction solution is deteriorated, and the production suitability such as workability is remarkably lowered.
New Experimental Chemistry Course, 1978, published by Maruzen Co., Ltd. Laboratory Chemistry 1992 Maruzen Co., Ltd., Volume 20, 338 pages JP-A-57-4957 Japanese Laid-Open Patent Publication No. 57-4949 JP 2001-233841 A

  An object of the present invention is to provide a method for producing phenylhydrazines capable of substantially removing unnecessary metal salts after the reaction in a method for producing phenylhydrazines by reducing a diazonium salt using a metal salt reducing agent. There is.

The above problems are solved by providing a method for producing phenylhydrazines.
(1) In the method for producing the phenylhydrazines represented by the general formula (2) by reducing the diazonium salt represented by the general formula (1) using a metal salt reducing agent, it is unnecessary after completion of the reaction. A method for producing a phenylhydrazine represented by the general formula (2), wherein the metal salt is substantially removed with a chelating agent.

Formula (1) and general formula (2), R ₁ represents a substituent, n is an integer of 0-5. When n is 2 or more, R ₁ may be the same or different, and may be connected to each other to form a ring. In the general formula (1), X ⁻ represents an anion.
(2) The method for producing phenylhydrazines according to (1) above, wherein tin (II) chloride is used as the metal salt reducing agent (3) The chelating agent has two or more carboxyl groups in the molecule The method for producing phenylhydrazines according to (1) or (2) above, wherein
(4) The phenylhydrazine according to any one of (1) to (3), wherein the chelating agent is selected from the group consisting of tartaric acid, a salt of tartaric acid, ethylenediaminetetraacetic acid, and a salt of ethylenediaminetetraacetic acid. Manufacturing method.

  When synthesizing phenylhydrazines by reducing a diazonium salt with a metal salt reducing agent, the unnecessary metal salt is substantially removed with a chelating agent after the reaction. The production of the solid can be suppressed and the target product can be produced efficiently.

  The present invention provides a method for producing phenylhydrazines represented by the general formula (2) from a diazonium salt represented by the following general formula (1), wherein an unnecessary metal salt is substantially added with a chelating agent after completion of the reaction. It is characterized by removing. Here, “substantially remove” means post-treatment after the reaction, specifically, for example, when purifying the target product after stopping the reaction by adding water or an aqueous base solution and an organic solvent. It means that the metal salt is removed at least to such an extent that gelation occurs or a solid having poor filterability is deposited and the handling of the reaction solution becomes impossible.

  The chelating agent added to remove unnecessary metal salts after the reaction is a compound added to avoid various troubles caused by metal ions by generally strongly coordinating with metal ions. Detailed explanations regarding such chelating agents are reported in various literatures and reports including specific compounds (for example, “Introduction Chelate Chemistry” published by Nanedo in 1944, “ Metal chelates [see [I], [II] ”).

  As the chelating agent used in the production method of the present invention, the above-mentioned ones are used without particular limitation. Specifically, ethylenediamine, diethylenediamine, triethylenetetramine, toaminotriethylamine, triethanolamine, N, N '-Dimethylethylenediamine, 1,3-diaminopropane, 1,2-diaminopropane, pyridine, bipyridine, glycine, aspartic acid, N-dihydroxyethylglycine, iminodiacetic acid, ethylenediaminetetraacetic acid, N-hydroxyethylethylenediaminetriacetic acid, Examples include diethylenetriaminepentaacetic acid, ethylenediaminetetrapropionic acid, citric acid, tartaric acid, ascorbic acid, triglycolic acid, thiourea, 8-hydroxyquinoline, acetylacetone, and salts of these compounds. That.

  Among them, as a chelating agent used in the present invention, N, N′-dimethylethylenediamine, aspartic acid, N-dihydroxyethylglycine, iminodiacetic acid, ethylenediaminetetraacetic acid, N-hydroxyethylethylenediaminetriacetic acid, ethylenediaminetetrapropionic acid, Citric acid, tartaric acid, ascorbic acid, triglycolic acid, and salts thereof (Na salt, K salt, Li salt, Cs salt, ammonium salt, etc.) are preferred, and tartaric acid, ethylenediaminetetraacetic acid and their salts (Na salt, K salts, Li salts, ammonium salts, etc.) are most preferred.

  These chelating agents may be added by any method, and may be added directly to the reaction solution after the reaction or may be added as an aqueous solution of the chelating agent. Moreover, 2-100 equivalent is preferable with respect to the metal reducing agent used by reaction, and, as for the addition amount of a chelating agent, 4-10 equivalent is more preferable. If the amount of chelating agent is less than this, metal ions cannot be captured sufficiently, resulting in problems such as deterioration of filterability during post-treatment and the inclusion of unnecessary metal salts in the target product, and excessive amounts of chelating agent. If added, an unnecessarily large amount of reagents will be used.

  Next, the diazonium salt used for production of the phenylhydrazines of the present invention will be described. The diazonium salt compound is represented by the following structural formula.

In the general formula (1), R ₁ represents a substituent, and n represents an integer of 0 to 5. When n is 2 or more, R ₁ may be the same or different, and may be connected to each other to form a ring. X ⁻ represents an anion.

Examples of the substituent represented by R ₁ in the general formula (1) and the general formula (2) include an alkyl group having 1 to 20 carbon atoms, an aryl group having 6 to 30 carbon atoms, and an alkoxy group having 1 to 20 carbon atoms. An aryloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 20 carbon atoms, an aryloxycarbonyl group having 7 to 30 carbon atoms, an acyloxy group having 2 to 20 carbon atoms, an acyl group having 2 to 20 carbon atoms, An amide group having 2 to 20 carbon atoms, a carbamoyl group having 1 to 20 carbon atoms, a sulfamoyl group having 1 to 30 carbon atoms, a sulfonamido group having 1 to 20 carbon atoms, a halogen atom, an alkylthio group having 1 to 20 carbon atoms, carbon An arylthio group having 6 to 30 carbon atoms, an alkylsulfonyl group having 1 to 20 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an amino group having 1 to 20 carbon atoms, Amino group, a hydrazino group, a hydroxyamino group, a urea group having 1 to 20 carbon atoms, thiourea group having 1 to 20 carbon atoms, a nitro group.

  Among them, hydrogen atom, halogen atom, alkyl group, aryl group, alkoxy group, aryloxy group, alkylthio group, arylthio group, alkylsulfonyl group, arylsulfonyl group, alkoxycarbonyl group, aryloxycarbonyl group, acyloxy group, acyl group, carbamoyl Group, amide group, sulfamoyl group, sulfonamido group, amino group, cyano group, hydrazino group, urea group, thiourea group are preferable, hydrogen atom, halogen atom, alkyl group, aryl group, alkoxy group, aryloxy group, alkylthio group An arylthio group and a nitro group are particularly preferable.

In General Formula (1) and General Formula (2), R ₁ may further have a substituent, and examples of the substituent include the following.

  A linear or cyclic alkyl group having 1 to 20 carbon atoms (for example, methyl, ethyl, isopropyl, cyclohexyl), an aryl group having 6 to 18 carbon atoms (for example, phenyl, chlorophenyl, 2,4-di-t-amylphenyl) 1-naphthyl), an aralkyl group having 7 to 18 carbon atoms (for example, benzyl, anisyl), an alkenyl group having 2 to 20 carbon atoms (for example, vinyl, 2-methylvinyl), and an alkynyl group having 2 to 20 carbon atoms. (For example, ethynyl, 2-methylethynyl, 2-phenylethynyl), halogen atom (for example, F, Cl, Br, I), cyano group, hydroxyl group, carboxyl group, C2-C20 acyl group (for example, Acetyl, benzoyl, salicyloyl, pivaloyl), an alkoxy group having 1 to 20 carbon atoms (for example, methoxy, butoxy) Cyclohexyloxy), aryloxy groups having 6 to 20 carbon atoms (for example, phenoxy, 1-naphthoxy, toluoyl), alkylthio groups having 1 to 20 carbon atoms (for example, methylthio, butylthio, benzylthio, 3-methoxypropylthio), carbon An arylthio group having 6 to 20 carbon atoms (for example, phenylthio, 4-chlorophenylthio), an alkylsulfonyl group having 1 to 20 carbon atoms (for example, methanesulfonyl, butanesulfonyl), an arylsulfonyl group having 6 to 20 carbon atoms (for example, benzene) Sulfonyl, paratoluenesulfonyl), a carbamoyl group having 1 to 17 carbon atoms (for example, unsubstituted carbamoyl, methylcarbamoyl, ethylcarbamoyl, n-butylcarbamoyl, dimethylcarbamoyl), an amide group having 1 to 16 carbon atoms (for example, acetoamido) Benzamide), an acyloxy group having 2 to 10 carbon atoms (for example, acetoxy, benzoyloxy), an alkoxycarbonyl group having 2 to 10 carbon atoms (for example, methoxycarbonyl, ethoxycarbonyl), a 5- or 6-membered heterocyclic group (for example, , Pyridyl, thienyl, furyl, thiazolyl, imidazolyl, pyrazolyl and other aromatic heterocycles, pyrrolidine ring, piperidine ring, morpholine ring, pyran ring, thiopyran ring, dioxane ring, dithiolane ring, etc.), amino group, acylamino group Is mentioned.

Further, X ⁻ in the general formula (1) represents an anion which is a counter ion for diazonium, and examples of the inorganic anion include hexafluorophosphate ion, borofluoride ion, chloride ion, sulfate ion, Examples of the organic anion include polyfluoroalkylcarboxylate ions, polyfluoroalkylsulfonate ions, tetraphenylborate ions, aromatic carboxylate ions, and aromatic sulfonate ions.

  Specific examples of phenylhydrazines represented by the general formula (2) produced by the production method of the present invention are shown below, but the present invention is not limited thereto. (Specific examples of the diazonium salt compound used in the production method of the present invention are diazonium salts corresponding to the specific examples of phenylhydrazines shown below.)

  The reaction from the diazonium salt represented by the general formula (1) to the phenylhydrazine represented by the general formula (2) using a metal salt reducing agent is a known reaction and can be produced by various methods ( For example, see Non-Patent Document 1 and Non-Patent Document 2 listed in the Background Art section) The diazonium salt can be produced from the corresponding aniline by a conventional method.

In addition, the metal salt reducing agent used in this reaction is generally a compound containing a low-valent metal or a compound comprising a metal ion and a hydride source (for example, “Organic Synthesis Experiment Method Handbook” 1990, Synthetic Organic Chemistry Association of Japan). Edited by Maruzen Co., Ltd. (see page 810). Examples include NaAlH ₄ , NaAlH _n (OR) _m , LiAlH 4, iBu ₂ AlH, LiBH ₄ , NaBH ₄ , SnCl ₂ , CrCl ₂ , TiCl _3, etc., but LiAlH ₄ , NaBH ₄ , SnCl ₂ are preferred, SnCl ₂ Is most preferred.

The phenylhydrazines produced by the production method of the present invention can be produced, for example, by the methods described in JP-A Nos. 61-236768 and 4-275277 and the like to produce an aminopyrazole compound. The compound is useful as a coupler for photography and the like.
EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto. In the following description, “part” means “part by mass” unless otherwise specified.
Example 1
(Synthesis of Compound Example 2-7)
1.85 g (0.015 mol) of 2-methoxyaniline was dissolved in 15 mL of methanol. To this was added 5 mL of 35 mass% concentrated hydrochloric acid, and the mixture was cooled to −5 ° with an acetone / ice bath. To this was added dropwise 10 mL of an aqueous solution containing 1.24 g of sodium nitrite. Progress of the reaction was confirmed by TLC. Separately, 10.2 g of tin (II) chloride dihydrate and 2.5 mL of concentrated hydrochloric acid were dissolved in 100 mL of water, and then the reaction solution was added dropwise to an aqueous solution cooled to 0 °. After confirming that the reaction had progressed by TLC, 200 mL of 15 mass% Rochelle salt (sodium potassium tartrate tetrahydrate: manufactured by Wako Pure Chemical Industries, Ltd.) aqueous solution and 100 mL of ethyl acetate were added to the reaction solution and stirred. The precipitated white solid was separated by filtration, the target product was further extracted with ethyl acetate, the organic phase was concentrated under reduced pressure, and purified by column chromatography to obtain 1.36 g of phenylhydrazine of Compound Example 2-7. The yield was 66%.
In the post-treatment step after the reaction, gelation did not occur and filtration could be performed easily.
¹ H-NMR (300 MHz, DMSO-d6) 3.8 (s, 3H), 4.0 (ds, 3H), 7.0 (m, 4H)

Example 2
(Synthesis of Compound Example 2-16)
3.28 g of phenylhydrazine of Compound Example 2-16 was obtained in the same manner as in Example 1 except that 5.24 g of 2,5-dihexyloxyaniline was used instead of 1.85 g of 2-methoxyaniline. The yield was 60%.
In the post-treatment step after the reaction, gelation did not occur and filtration could be performed easily.
¹ H-NMR (300 MHz, DMSO-d6) 1.20-1.55 (m, 20H), 1.94 (m, 2H), 3.90 (s, 2H),
3.92 (s, 2H), 6.58 (d, 1H), 6.68 (s, 1H), 7.00 (d, 1H)

Example 3
(Synthesis of Compound Example 2-15)
3.12 g of Compound Example 2-15 was obtained in the same manner as in Example 1 except that 4.58 g of 2,5-dibenzyloxyaniline was used instead of 1.85 g of 2-methoxyaniline. The yield was 60%.
¹ H-NMR (300 MHz, DMSO-d6) 5.00 (s, 2H), 5.10 (s, 2H), 6.56 (d, 1H),
6.70 (s, 1H), 7.00 (d, 1H), 7.10-7.60 (m, 10H)

Example 4
(Synthesis of Compound Example 2-43)
In the same manner as in Example 1 except that 3.24 g of 2-methoxy-4-dodecylthioaniline was used instead of 1.85 g of 2-methoxyaniline, 2.5 g of Compound Example 2-43 was obtained. The yield was 74%.
¹ H-NMR (300MHz, DMSO-d6) 0.80 (t, 3H), 1.20-1.40 (m, 18H), 2.95 (t, 2H),
3.80 (s, 3H), 6.95 (m, 2H), 7.12 (d, 1H)

Example 5
(Synthesis of Compound Example 2-7)
In Example 1, 1.25 g of Compound Example 2-7 was obtained in the same manner as in Example 1 except that 200 ml of a 15% by mass aqueous solution of EDTA diammonium salt (manufactured by Dojin Chemical Laboratory) was used as a chelating agent. . The yield was 61%.

Comparative Example 1
In Example 2, phenylhydrazines were synthesized in the same manner as in Example 1 except that 200 ml of ion-exchanged water was added instead of the Rochelle salt aqueous solution after the reaction. Both the filterability and the filterability were remarkably deteriorated, making it difficult to purify the target product.

Claims (4)

In the method for producing the phenylhydrazines represented by the general formula (2) by reducing the diazonium salt represented by the general formula (1) using a metal salt reducing agent, an unnecessary metal salt is removed after the reaction is completed. A method for producing a phenylhydrazine represented by the general formula (2), wherein the phenylhydrazine is substantially removed with a chelating agent.

Formula (1) and general formula (2), R ₁ represents a substituent, n is an integer of 0-5. When n is 2 or more, R ₁ may be the same or different, and may be connected to each other to form a ring. In the general formula (1), X ⁻ represents an anion.   The method for producing phenylhydrazines according to claim 1, wherein tin (II) chloride is used as the metal salt reducing agent.   The method for producing a phenylhydrazine according to claim 1 or 2, wherein the chelating agent has two or more carboxyl groups in the molecule.   The method for producing phenylhydrazines according to any one of claims 1 to 3, wherein the chelating agent is selected from the group consisting of tartaric acid, a salt of tartaric acid, ethylenediaminetetraacetic acid, and a salt of ethylenediaminetetraacetic acid. .