JPH0770078A - Production of indazole - Google Patents

Abstract

PURPOSE:To readily obtain the subject compound useful as a raw material for coloring agents, a UV light absorber, etc., by treating an azo compound having a specific structure with an acid. CONSTITUTION:The objective compound of formula II is obtained by treating an azo compound of formula I (R1 is H, an alkyl or an aryl; R2 is H, an alkyl, an acyl, etc.; R3 and R4 are H, an acyl, a halogen, etc.; Ar is an aromatic ring) [e.g. hydroxymethyl-4-(2-ethoxyphenyl-azo)phenol] with an acid (preferably hydrochloric acid). Furthermore, the compound of formula I is preferably obtained by reacting a phenol having CR1HOR2 at 3 position, e.g. 3- hydroxymethylphenol with an aromatic diazonium salt derived from an aromatic amine such as O-ethoxyaniline at a low temperature under a basic atmosphere. The acid is preferably used in 0.6-1.2mol equivalent weight based on 1mol equivalent weight of the compound of formula I.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention has a substituent of a specific skeleton which is useful for various purposes such as a color former raw material, a UV absorber raw material, and pharmaceuticals, agricultural chemicals, dyes, heterocyclic raw materials having a hydroxyl group, and coupler raw materials. The present invention relates to a method for producing an azo compound and a method for producing 2-aryl-5-hydroxyindazole using the same.

[0002]

2. Description of the Related Art Most of azo compounds having a specific partial skeleton having a hydroxy group at the 4-position and an α-hydroxyalkyl or aryl group at the 2-position proposed by the present invention (shown by the general formula later) are almost It has never been considered. or,
There has never been any study regarding the ease with which a 5-hydroxyindazole compound (shown by the general formula later) can be easily produced. For example, conventional reactions of azo compounds or diazonium salts are well summarized in the following textbooks. However, the azo compounds having a partial skeleton and 5-
Little is mentioned about hydroxyindazole compounds. (a) Patai, S. The Chemistry of Diazonium Salt and Dia
zo Groups; John-Wiley & Sons, New York, 1978. (b) Saunde
rs, KHAromatic Diazocompounds.3rd ed.Edward Arnol
d.London, 1985. In particular, the compound of the present invention is used as an azo dye, as an amino compound raw material, and as an important new heterocyclic raw material for a color former and a UV absorber, a 5-hydroxyindazole derivative. Is particularly useful as

[0003]

The present inventors have found that these compounds can be used as color formers, UV absorbers, reducing agents, radical quenchers, pharmaceuticals, agricultural chemicals, dyes, coupler raw materials, alkaloid precursors and recording materials. Focusing on the fact that it is an important intermediate useful for a wide variety of applications such as material applications, the inventors have made earnest studies and have developed the production method of the present invention.

[0004]

[Means for Solving the Problems] The above problem is characterized by treating an azo compound represented by the following general formula (1) with an acid, and a 2-aryl-5-hydroxy group represented by the following general formula (2). Method for producing indazole General formula (1)

[Chemical 3]Where R₁Is a hydrogen atom, optionally substituted alkyl
Group, aryl group, R ₂Is a hydrogen atom, replaced
Represents an alkyl group, an aryl group or an acyl group. R
₃, R_FourIs a hydrogen atom, an alkyl group, an aryl group, an acyl group
Group, halogen atom, cyano group, nitro group, substituted amino
Group, sulfo group, carboxyl group, alkoxy group, aryl
Ar is a group selected from the group consisting of ruoxy group and hydroxy group.
Represents an incense ring. General formula (2)

[Chemical 4]Where R₁Is a hydrogen atom, optionally substituted alkyl
Group, aryl group, R ₂Is a hydrogen atom, replaced
Represents an alkyl group, an aryl group or an acyl group. R
₃, R_FourIs a hydrogen atom, an alkyl group, an aryl group, an acyl group
Group, halogen atom, cyano group, nitro group, substituted amino
Group, sulfo group, carboxyl group, alkoxy group, aryl
Ar is a group selected from the group consisting of ruoxy group and hydroxy group.
Represents an incense ring. R_FiveRepresents a hydrogen atom or a halogen atom.
You It was achieved by developing. This compound returns
Original reaction, nitration, acylation, halogenation, etherification
Or by performing a unit operation such as esterification
It can be easily induced to various derivatives. In particular, 5-hydroxy
Cindazoles are useful by dehydration condensation with keto acids
It is an important intermediate that gives a color former. Also, Ar is 2-position
Indazoles with alkoxy groups are UV absorber raw materials
It is extremely useful as a material and can be easily dealkylated
Can be induced by UV absorbers.

The aromatic ring of the aromatic diazonium salt has an alkyl group, an alkoxy group, a hydroxy group, a halogen atom, an aryl group, an acyl group, an optionally substituted amino group,
For example, various substituents such as amino group, dialkylamino group, acylamino group, ureido group, alkylamino group, arylamino group, carboxyl group, sulfo group, oxo group, cyano group, aryloxy group, alkoxycarbonyl group, etc. It may contain about 4 or 4 pieces.
The aromatic ring includes a benzene ring, a naphthalene ring and the like, as well as a hetero ring such as a pyridine ring, a thiophene ring and a furan ring. These may be bis type.

The azo compound of the present invention has CR ₁ HO at the 3-position of
It can be synthesized by reacting a phenol derivative having an R ₂ group with an aromatic diazonium salt. This phenol derivative is
It is preferable that the 4-position is unsubstituted. , May be substituted with a group capable of leaving in the diazo coupling reaction. 2-
The 5-position, 5-position or 6-position is an alkyl group, an alkoxy group, a halogen atom, an aryl group, an acyl group, a hydroxy group, an optionally substituted amino group, for example, a dialkylamino group, an acylamino group, a ureido group, an alkylamino. Base,
It can have various substituents such as an arylamino group, such as a carboxyl group, a sulfo group, a cyano group, an aryloxy group and an alkoxycarbonyl group, which do not interfere with the diazo coupling reaction. These are connected by adjacent comrades and have 5 to 6 members.
May form a ring which may have a heteroatom consisting of members. As the 5- or 6-position substituent, an alkyl group, an alkoxy group, a halogen atom or an aryl group is particularly preferable.

R ₁ is preferably a hydrogen atom or an alkyl group, an alkenyl group or an aryl group having 12 or less carbon atoms. It does not matter that it is branched or has a double bond. R ₂ is preferably a hydrogen atom or an alkyl group having 12 or less carbon atoms, an alkenyl group, an aryl group or an acyl group. Here, the acyl group includes carbonic acid ester, carbamic acid ester and the like. That is,
These substituents are other aliphatic or aromatic groups having a total number of carbon atoms of about 18 or less, such as an acyl group, a hydroxy group, an alkoxy group, a halogen atom, an aryl group, an aryloxy group, a glycidyl group, a carbonyl group, and a carboxyl group. It may have one or more groups, optionally substituted amino groups, alkenyl groups, and the like.

Methyl group, ethyl group, butyl group, benzyl group, phenyl group, phenoxyethyl group, isoamyl group,
Pentadecyl group, cyclohexyl group, cyclododecyl group, vinylbenzyl group, glycidyl group, dimethylaminoethyl group, methoxyethyl group, chlorophenyl group, chlorotolyl group, acetylphenyl group, ethoxycarbonylbutyl group, toluenesulfonylphenyl group, methanesulfonylphenyl group , Mesityl group, diethylaminoethoxycarbonylmethyl group, phenoxyacetyloxyethyl group, allyl group, vinyl group, butadienyl group, bromoethyl group, phenethyl group, styryl group, substituted styryl group,
A hydroxyethyl group is an example of a preferred substituent of the present invention. Specific examples of the phenol having a CR ₁ HOR ₂ group at the 3-position which is conveniently used in the present invention are shown below.

M-hydroxymethylphenol, 3-hydroxymethyl-6-methoxyphenol, m- (α-hydroxybutyl) phenol, 3-hydroxymethyl-6-butylphenol, m- (α-hydroxynonyl) phenol,
3-hydroxymethyl-6-amylphenol, 3-hydroxymethyl-5-propyl-6-methoxyphenol, m- (α-
Hydroxyphenethyl) phenol, 3-hydroxymethyl-5-chloro-6-methylphenol, m- (α-hydroxyethyl) phenol, 3-hydroxymethyl-6-acetylphenol,

3-hydroxymethyl-6-ethoxyphenol, m- (α-hydroxycetyl) phenol, 3-hydroxymethyl-5,6-dibutylphenol, m- (α-hydroxy-γ-phenyl) phenol, 3- Hydroxymethyl
-6-Bromo-5-ethoxyphenol, 3-hydroxymethyl-5-propyl-6-phenoxyphenol, m- (α-hydroxybenzyl) phenol, 3-hydroxymethyl-5
-Chloro-6-methoxypropylphenol, m- (α-hydroxyoctyl) phenol, 3-hydroxymethyl-6
-Propionylphenol, 3- (α-hydroxymethyl
) -6-Carboxyphenol, 3-hydroxymethyl-6-
Methoxycarbonylphenol, and the like.

Examples of aromatic amines include aniline and 2
-Ethoxyaniline, 2-ethoxy-4-butylaniline, 2-benzyloxy-4,6-dioctylaniline,
Aniline sulfonic acid, perjuteroaniline, methoxychloroaniline, pentafluoroaniline, chloroaniline, toluidine, xylidine, naphthylamine sulfonic acid, H acid, J acid, chromotropic acid, nitroaniline, nitrotoluidine, dichlorofluoroaniline, anthranilic acid , Anisidine, 2-benzyloxy-4,6
-Dibutylaniline, variamin blue B, dibutylaniline, 2,5-dibutoxy-4-morpholinoaniline, aminothiophene, 2-benzyloxy-4,6-dimethylaniline, aminoaniline, 2-methoxymethoxy-4,6 -Dibutylaniline, 2-butoxy-4,6-didodecylaniline, 2-butoxy-4-dodecylaniline, 2-butoxy-4-dodecyl-6-methylaniline, 2
-Butoxy-4-dodecyl-6-methoxyaniline, etc. From the viewpoint of cost and handling, aromatic amines having a carboxyl group or a sulfo group are preferable. or,
Various diazonium salts are already on the market, and it is possible to use them.

The azo compound used in the present invention can be synthesized by various methods. For example, a diazonium salt derived from an aromatic amine on a phenol derivative having a substituent at a specific position can be conveniently produced by acting at low temperature, preferably under a basic atmosphere. It is also possible to induce this substituent after the azo coupling. In the azo coupling reaction, the amount of the diazonium salt is about 0.5 to 2.5 mol, preferably about 0.9 to 1.1 mol, based on the phenol used.
It is also possible to use a diazonium salt precursor to substantially produce the diazonium salt in the system.

In preparing the diazonium salt and synthesizing the starting materials, various reaction conditions and reagents conventionally known as unit operations can be used. Regarding these, for example, in addition to the above literature, A. Katritzky, CWRees.Comprehe
nsive Heterocyclic Chemistry vol.4 (1984) Pergamon
Detailed in Press. And Maruzen's experimental chemistry course (including positive, continuous, and new). Various reaction conditions such as addition method, processing conditions or processing temperature can be referred to.

For example, in the azo coupling reaction, a halide type, alcohol type, ether type, ketone type, amide type or alcohol derivative may be used in combination with water or used in place of water. It is a preferred embodiment to use this in combination with an organic base or to use only an organic base. Ether-based, ketone-based, amide-based or alcohol derivatives are particularly preferable. It is also preferable to carry out the neutralization reaction in an inert gas atmosphere, and to use a disperser such as a homomixer or a sand mill, an emulsifier or a crusher. 3- (α-hydroxyalkyl or aryl) -4- (arylazo) phenol, as described in detail in Examples, is completely unexpected, but it is extremely easy to treat the molecule with an inorganic acid so that It was first found to give 5-hydroxyindazoles by condensation cyclization with.

As the inorganic acid, mineral acid, sulfuric acid, phosphoric acid, methanesulfonic acid, polystyrenesulfonic acid, trichloroacetic acid, toluenesulfonic acid, formic acid, polyphosphoric acid, antimony chloride, aluminum chloride or nitric acid can be used. From the viewpoint of handling, hydrochloric acid, hydrobromic acid, hydrofluoric acid, hydrogen chloride, hydrogen bromide and the like are particularly preferable. In the reaction, various solvents such as halides, alcohols, ethers, ketones, carbonates, amides, carboxylic acids or alcohol derivatives can be used, and water can be used in combination. The amount of solvent depends on the reagent
If it is used in an amount of about 50 to 200 ml with respect to 0.1 mol, the reaction system becomes uniform and handling becomes very easy. Particularly, from the viewpoint of post-treatment, it is preferable to use formic acid, acetic acid, propionic acid and the like. These acids are used in an amount of 0.1 to 50 equivalents, preferably 0.6 to 1 molar equivalent of the azo compound.
~ 1.2 equivalents are used. During the reaction, an inert gas may be used or the temperature may be raised to 30 ° C to 150 ° C. At the time of reaction, various techniques described in the above-mentioned books,
For example, it is preferable to appropriately employ stirring and the like. Hereinafter, the present invention will be described in detail with reference to Examples.

[0016]

【Example】

Example 1 An example of indazole derived from a phenol having a hydroxymethyl group at the 3-position and an aromatic diazonium salt substituted with an alkoxy group is shown. Method for producing 3-hydroxymethyl-4- (2-ethoxyphenylazo) phenol A diazonium salt was prepared from 0.010 mol of o-ethoxyaniline according to a conventional method. An equal amount of 3-hydroxymethylphenol was dissolved in 30 ml of acetone and 6 ml of triethylamine, and a stirrer was attached, and the mixture was gradually added to a reaction vessel cooled to 5 ° C or lower. After the dropping, the mixture was stirred for 20 minutes. Then, the solution was gradually added dropwise to 300 ml of ice water containing 3 ml of hydrochloric acid to obtain crude crystals. It was purified by using ethyl acetate-hexane as a recrystallization solvent. Melting point 136.5-138.4 ° C. 1 g of the azo compound thus obtained was thoroughly mixed with 10 ml of hydrochloric acid and 20 ml of acetic acid at 50 ° C. for 15 minutes. Then, it was poured into water and the precipitated crystal was separated by filtration.
Recrystallization from benzene was performed to give 2- (2-ethoxyphenyl) -5-hydroxyindazole having a melting point of 131.3 to 132.3.
Isolated as crystals at 0 ° C.

Example 2 An example of indazole derived from a phenol having an α-hydroxyamyl group at the 3-position and a benzenediazonium salt is shown. Instead of 3-hydroxymethylphenol of Example 1, 3- (α-hydroxyamyl) phenol was also used.
3- (α-Hydroxyamyl) -4- (phenylazo) phenol was obtained in the same manner except that aniline was used instead of o-ethoxyaniline. This azo compound was treated in the same manner as in Example 1 to obtain crystals. 2- (Phenyl) -3-butyl-5-hydroxyindazole; melting point 137.2-137.6
° C.

Example 3 An example of indazole derived from a phenol having an α-hydroxyethyl group at the 3-position and a methoxy group at the 6-position and an o-ethoxybenzenediazonium salt is shown.
Instead of 3-hydroxymethylphenol of Example 1,
3- (α-Hydroxyethyl) -6-methoxy-4- (o-ethoxyphenylazo) phenol was obtained in the same manner except that 3- (α-hydroxyethyl) -6-methoxyphenol was used. Example 1 using this azo compound
A crystal was obtained by the same treatment as described above. 2- (o-Ethoxyphenyl) -3-methyl-6-methoxy-5-hydroxyindazole; mp 176.2-177.5 ° C.

Example 4 An example of indazole derived from a phenol having an α-hydroxymethyl group at the 3-position and a methoxy group at the 6-position and an o-ethoxybenzenediazonium salt is shown. Instead of 3-hydroxymethylphenol of Example 1, 3- (
3- (Hydroxymethyl) -6-methoxy-4- (o-ethoxyphenylazo) phenol was obtained in the same manner except that hydroxymethyl) -6-methoxyphenol was used. This azo compound was treated in the same manner as in Example 1 to obtain crystals. 2- (o-Ethoxyphenyl) -6-methoxy-5-hydroxyindazole; melting point 132.5-133 ° C.
As described above, the azo bond activated by the p-hydroxyl group is easily subjected to the action of an acid catalyst in the molecule to give 2-aryl-indazol-5-ol in a substantially quantitative manner.

Claims (1)

[Claims] 1. A method for producing a 2-aryl-5-hydroxyindazole represented by the following general formula (2), which comprises treating an azo compound represented by the following general formula (1) with an acid. General formula (1) In the formula, R ₁ represents a hydrogen atom, an optionally substituted alkyl group or an aryl group, and R ₂ represents a hydrogen atom, an optionally substituted alkyl group, an aryl group or an acyl group. R
₃ , R ₄ are selected from a hydrogen atom, an alkyl group, an aryl group, an acyl group, a halogen atom, a cyano group, a nitro group, a substituted amino group, a sulfo group, a carboxyl group, an alkoxy group, an aryloxy group and a hydroxy group. And Ar represents an aromatic ring. General formula (2) In the formula, R ₁ represents a hydrogen atom, an optionally substituted alkyl group or an aryl group, and R ₂ represents a hydrogen atom, an optionally substituted alkyl group, an aryl group or an acyl group. R
₃ , R ₄ are selected from a hydrogen atom, an alkyl group, an aryl group, an acyl group, a halogen atom, a cyano group, a nitro group, a substituted amino group, a sulfo group, a carboxyl group, an alkoxy group, an aryloxy group and a hydroxy group. And Ar represents an aromatic ring. R ₅ represents a hydrogen atom or a halogen atom.