JPH01207271A - Production of 4-hydroxyoligopyridines - Google Patents

Abstract

PURPOSE:To produce the title compounds useful as a synthetic intermediate, by reacting readily available oligopyridines having the substituted 4-position as a raw material with a hydroxide, such as NaOH, in a solvent having a specific dielectric constant. CONSTITUTION:Oligopyridines expressed by formula I (m and n are 0-2; R<1>-R<3> are substituent group; R<4> is halogen, alkylsulfonyl or arylsulfonyl: a is 0-3; b and c are 0-4) (e.g., 4'-methanesulfonyl-2,2':6',2''-terpyridine) are reacted with a hydroxide expressed by formula II (M is metallic ion; x is the valence of the metallic ion) in a solvent having >=10 dielectric constant (value at 25 deg.C) (e.g., dimethyl sulfoxide, water or methanol) to afford the aimed 4- hydroxyoligopyridines (e.g., 4'-hydroxy-2,2':6,2''-terppidine) expressed by formula III.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for producing 4-hydroxyoligopyridines, and more particularly, the present invention relates to a method for producing 4-hydroxyoligopyridines, and more specifically, a method for producing 4-hydroxyoligopyridines using a starting material as a starting material and producing 4-hydroxyoligopyridines in a single step with good yield. The present invention relates to a method for producing 4-hydroxyoligopyridines.

(Prior art) Oligopyridines have long been known to be effective ligands for various metals, and since many of their complexes exhibit color, they have been used not only in coordination chemistry but also in the field of analytical chemistry. It has been widely studied.

In recent years, it has become clear that oligopyridines and their hybrid complexes act as various functional molecules.

It is attracting new attention. Its functions include the following: 1) Use as a photocatalyst to convert solar energy; 2) Use as medicines such as antihypertensive agents and tuberculosis inhibitors; 3) Use as organic pigments. While new functions have been discovered in this way, the synthesis of oligopyridines having functional groups has not yet been fully developed.

In particular, no research has been conducted on hydroxy derivatives of oligopyridine. (For example, John Wiley & Song, Pyridine &It's Derivatives, P.
yridine and its derivative
es), Volume 3 (I974), Synthesis
hesis), p. 1 (I976), etc.).

The present invention provides an effective method for synthesizing 4-hydroxyoligopyridines. Furthermore, 4-
Hydroxyoligopyridines can be bonded to other molecules via oxygen, nitrogen, or carbon atoms within their molecules, making them useful synthetic intermediates.

(Problems to be Solved by the Invention) An object of the present invention is to provide a method for producing 4-hydroxyoligopyridine with simple steps using raw materials that can be easily synthesized.

A second object of the present invention is to provide a simple method for producing 4-hydroxyoligopyridine, which is a useful synthetic intermediate that can be derived into various compounds via its nitrogen, oxygen or carbon atoms.

(Means for Solving the Problems) The above-mentioned object of the present invention is to obtain a 4-
4- represented by the following general formula (I), which is characterized by reacting a substituted oligopyridine with a hydroxide represented by the following general formula (III) in a solvent having a dielectric constant of 10 or more at 25°C. This was achieved by a method for producing hydroxyoligopyridine. Further, the compound represented by the following general formula (I) is usually in an equilibrium relationship with the compound represented by the following general formula (rV), and the two are treated as having the same meaning here.

General formula (I) General formula (If) General formula (III) M(OH)x General formula (mV) (wherein m and n represent integers of O to 2, t+i, R
゜R3 represents a substituent, and R4 represents a halogen, alkylsulfonyl or arylsulfonyl group.

M represents a metal ion, and X represents the same number as the valence of the metal ion. a, lt, represents an integer from o to 3, b, c
represents an integer from O to 4. ) The present invention will be specifically explained below.

General formula (II) used as a starting material in the present invention
) are listed in, for example, the Journal of Organic Chemistry (J, Org.

Chem-e), Volume 47, Page 3028 (I982) or Journal of the American Chemical Society (J, Am, Chew, Soc, ),
It can be synthesized by the method shown in Vol. 109, p. 3961 (I987). That is, the ketene dithioacetal obtained by reacting a 2-acetylpyridine derivative with sodium hydride, carbon disulfide, or an alkyl halide in a solvent such as dimethyl sulfoxide or tetrahydrofuran is further reacted with a carbonyl compound and ammonium acetate. Obtained by oxidation.

Further, some of the compounds represented by the general formula (II) are described, for example, in the Journal of the American Chemical Society (J, Am, Chem-Soc, ), Vol. 100.

5567 pages (I978), Tetrahedron Letter, Volume 25,
2549 pages (I984), Chemical Review (Ch.
Em, Rev.), vol. 64, p. 613 (I964), or Journal of Organometallic Chemistry (J.
,).

It can be synthesized by the method shown in Vol. 56, p. 53 (I973). That is, it can be synthesized by a coupling reaction using a 2-halopyridine derivative or the like as a raw material and using an organometallic reagent, a base, or the like.

R1, R2, and R3 in general formula (II) preferably represent an alkyl group, an aryl group, an alkenyl group, an alkynyl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, an arylthio group, an amino group, or the like. More specifically, R1, R2, and R3 are alkyl groups (e.g. methyl,
ethyl, 1-butyl, 2-phenylethyl, 2-propyl), aryl groups (e.g. phenyl), alkenyl groups (
(e.g. vinyl, styryl), alkynyl groups (e.g. phenylethynyl), heterocyclic groups (e.g. 4-pyridyl),
Alkoxy groups (e.g. methoxy, ethoxy), aryloxy groups (e.g. phenoxy), alkylthio groups (e.g. methylthio, butylthio), arylthio groups (e.g. phenylthio), amino groups (e.g. N,N-dimethylamino, N-methyl-N- phenylamino), etc.

More specifically, 84 in the general formula (II) is an alkylsulfonyl group (e.g. methanesulfonyl, ethanesulfonyl, robanesulfonyl, benzylsulfonyl), an arylsulfonyl group (e.g. ρ-nitrobenzenesulfonyl)
, halogen atoms (fluorine atom, chlorine atom, bromine atom, iodine atom). In the present specification, alkyl groups, aryl groups, heterocyclic groups, and amino groups are used to include substituted forms thereof. The substituents include aryl group, alkenyl group, alkynyl group, heterocyclic group, alkoxy,
Examples include aryloxy groups, alkylthio groups, amino groups, etc., and specific examples thereof are the same as those mentioned in the explanation of R1, nZ, and R3. a, b, and c are preferably O or 1.

Typical specific examples of the compound represented by the general formula (■) are shown in Table 1, but the present invention is not limited thereto.

The hydroxide represented by the general formula (III) is preferably a hydroxide of a metal belonging to the alkali metal or alkaline earth metal of the periodic table.

Typical specific examples of the compound represented by the general formula (I[I) are shown in Table 2, but the present invention is not limited thereto.

Table 2 M(○H)x The reaction of the present invention is represented by the reaction scheme (I) shown below.

Reaction scheme (I) (II) (III) in the formula P
S represents a solvent having a dielectric constant of 10 or more at 25°C. ) A compound represented by the above general formula (II) and a compound represented by the general formula (II)
The reaction with the compound represented by I) is carried out by dissolving or dispersing it in an appropriate solvent having a dielectric constant of 10 or more at 25°C. Examples of solvents that can be used in the reaction of the present invention and their dielectric constants are shown in parentheses. Specific examples include dimethyl sulfoxide (46,68), N,N-dimethylformamide (36,7), N,N-dimethylacetamide (37,8), hexamethylphosphoric triamide (
30), aprotic polar solvents such as acetonitrile (37,5), propionitrile (27,2) or water (
78,3), methanol (32,7), ethanol (2
Protic solvents such as 4 and 6) are preferred. These solvents may be used alone or in combination of two or more. When using a mixture of two or more types, even if the individual dielectric constants of these solvents are 10 or less, it is sufficient that the dielectric constant of the mixed solvent is 10 or more.

(For the definition of relative permittivity, see, for example, "Physical and Chemistry Dictionary," 4th edition, edited by Hitoshi et al., Iwanami Publishing, 1987, and for its value, for example, in "Electrochemistry Handbook," 4th edition, edited by Electrochemistry Handbook.)
It is shown in the edition, round neck, 1985, etc. ) The solvent is 0.5 to 1 part by weight of the compound represented by general formula (II).
It is used in a proportion of 1000 parts by weight, preferably 1 to 100 parts by weight.

The compound represented by the general formula (II) and the compound represented by the general formula (I) are used in a molar ratio of I:]/x~]:1000, preferably 1:1/x"l:
used in a molar ratio of 100 to 100. Here, X is the general formula (I
This is the same as explained in ll).

The reaction temperature is preferably from 20°C to 180°C.

The reaction time varies depending on the type of compound of the general formula (III) used, the type and amount of the solvent, the scale of the reaction, the substituents, etc., but if the reaction temperature is not higher than 40°C, it is usually 0. The reaction is completed in 1 to 20 hours.

On the other hand, if the reaction temperature is 40° C. or lower, several days may be required.

Post-treatment of the reaction can be carried out by the following method. The first method is to carry out the reaction of the present invention, then add a suitable organic solvent or water to the reaction solution cooled to room temperature or lower, and filter the precipitated crystals or precipitates. In the second method, after carrying out the reaction of the present invention,
The reaction solution cooled to room temperature or below is extracted with an alkaline aqueous solution,
This method involves neutralizing the aqueous layer with an acid and then extracting it with an organic solvent such as chloroform or ethyl acetate.

The third method is to perform the reaction of the present invention and then neutralize the reaction solution cooled to room temperature or below with an acid, followed by extraction with an organic solvent such as chloroform or ethyl acetate. Fourth
In the method of the present invention, after carrying out the reaction of the present invention, the reaction solution cooled to below room temperature is neutralized with an acid, and if necessary, after drying, the target product is extracted from one reaction solution by distillation. be. The 4-hydroxyoligopyridine thus obtained can be further purified by column chromatography, recrystallization, distillation, etc. using alumina or the like as a carrier.

According to the method of the present invention, 4 represented by the following general formula (I)
-Hydroxyoligopyridines are obtained.

General formula (I) R1, R2, R3, a, b, c, m and n are R1, R2, R3, a described above in the explanation of general formula (II)
, b, c, m and n.

Next, typical examples of the 4-hydroxyoligopyridines represented by the general formula (I) are shown below, but the present invention is not limited thereto.

The 4-hydroxyoligopyridines represented by the general formula (I) obtained by the method of the present invention are crystals or oils.

(Effects of the Invention) By using the present reaction method, industrially useful 4-hydroxyoligopyridines can be obtained from easily available raw materials through simple reaction operations.

(Examples) Specific examples of the present invention are shown below, but the present invention is not limited thereto.

(Example 1) 4'-hydroxy-2,2': 6',
Synthesis of 2'-thylpyridine 4'-methanesulfonyl-2,2': 6', 2'-
Chilpyridine (I55g) and sodium hydroxide (2,
0g), dimethyl sulfoxide (relative dielectric constant 46.68.
A mixture consisting of 20m0) was reacted at 120°C for 4 hours. After the solvent was distilled off under reduced pressure, the residue was suspended in ether, and the resulting solution was extracted with a 2N aqueous sodium hydroxide solution. After neutralizing the aqueous layer with hydrochloric acid and extracting with chloroform,
By concentrating the extract, the title compound (I, 15
g) was obtained. m, 9.128°C. Yield 93%.

(Example 2) Synthesis of 4-hydroxy-2,2'-bipyridine (synthesis in N,N-dimethylacetamide) 4-chloro-2,2'-bipyridine (I, 0 g) and potassium hydroxide (2 , 8g) in N,N-dimethylacetamide (20mQ) at 60°C for 3 hours. The title compound (0.85 g) was obtained by performing the same treatment as in Example 1 and recrystallizing from acetone. m, p, 14
5℃. Yield 94%.

(Example 3) 4.6-dimethyl-47-hydroxy-2°2': Synthesis of 6',2'-thylpyridine 4.
6-dimethyl-4'-chloro-2,2': 6', 2
'-Tylpyridine (0,90 g) and potassium hydroxide (0
, 17g) in dimethyl sulfoxide (I9mΩ) and water (
The reaction was carried out at 80° C. for 6 hours in a mixed solvent of ImΩ (relative permittivity: 48). After cooling to room temperature, the reaction mixture was poured into an aqueous sodium chloride solution (I00mQ). The precipitated crystals were collected by suction filtration, washed with water and hexane, and dried to obtain 0.82 g of the title compound. m, p, 93°C. Yield 97%
.

(Example 4) Synthesis of 4-hydroxy-2,2'-bipyridine (synthesis in ethanol solvent) 4-bromo-2,2'-bipyridine (I, 0 g) and potassium hydroxide (2,8 g) Ethanol (dielectric constant 24.6
．． 20 mΩ) under reflux for 4 hours. The same treatment as in Example 1 was followed by recrystallization from acetone to obtain the compound (0.82 g). m, p, 145℃
. Yield 91%.

(Comparative Example 1) The solvent for the reaction shown in Example 1 was dimethyl sulfoxide (
dielectric constant 46.68) to toluene (dielectric constant Ti, rate 2.
4), and the same reaction was carried out at 110°C.

4'-methanesulfonyl-2,2': 6', 2'-
Chilpyridine (I, 55g) and sodium hydroxide (2
,0g) and toluene (20m12).
The reaction was carried out at 10°C for 4 hours. 50 ml of drained water cooled to room temperature
Added mQ. After separating the organic layer, the aqueous layer was extracted with chloroform.

The raw material 4'-methanesulfonyl-2,2': 6', 2'- is obtained by combining the extracts (toluene layer and chloroform layer), drying with sodium sulfate, and concentrating.
Chilpyridine (I, 54 g) was recovered. Recovery rate 99
%.

” 1 Continued N City t L Maq 1985 3J118th! h11 Director's own degree 1,! Indication with ii Special revised application No. 28895 of 1988 2, Title of the invention 4-Method for producing human (]-1 thioligoviridins) 3,
Relationship with correction Runi+Jifl: Patent applicant name: (520) Hatakesha Photom 11 Film Co., Ltd.? 1
4. Agent 5: Increased number of inventions due to amendment: 0 Claims: Oligopyridines represented by the following formula (II) and hydroxides represented by the following formula (Ilff) with relative permittivity (value at 25°C) is 10 or more in a solvent represented by the following - ritual (I) 4-
A method for producing hydroxyoligopyridines.

-Rituals (I) General formula ([I) General formula (III) M(OR), (In the formula, m and n represent integers of 0 to 2, and R1 and Rz.

R3 represents a substituent, and R4 represents a halogen, alkylsulfonyl or arylsulfonyl group. M represents a metal ion, and X represents the same number as the valence of the metal ion. b represents an integer of 0 to 3, and a and c represent integers of 0 to 4. However, when a plurality of R1, R2 or R4 are present in one molecule, they may be the same or different. )

Claims (1)

[Scope of Claims] Oligopyridines represented by the following general formula (II) and hydroxides represented by the following general formula (III) have a dielectric constant (25
A method for producing 4-hydroxyoligopyridines represented by the following general formula (I), characterized in that the reaction is carried out in a solvent with a value at °C of 10 or more. General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ General formula (III) M(OH)_x (In the formula, m and n are 0 to Represents an integer of 2, R^1, R^
2, R^3 represents a substituent, and R^4 represents a halogen, alkylsulfonyl or arylsulfonyl group. M represents a metal ion, and x represents the same number as the valence of the metal ion. a represents an integer of 0 to 3, and b and c represent integers of 0 to 4. However, R^1, R^2 or R^ in one molecule
When a plurality of 4's exist, they may be the same or different. )