JPH06298731A - Production of heterocyclic compound - Google Patents

Abstract

PURPOSE:To efficiently obtain a compound in which a substituted aryl group is introduced into the heterocyclic nucleus without using a carcinogen by condensing a halogen-substituted benzazole compound with an arylboronic acid compound in the presence of a palladium catalyst. CONSTITUTION:A halogen-substituted benzazole compound expressed by formula I [X is NR1 or CR2R3 (R1 to R3 are H, alkyl or aryl); R is H, alkyl or alkylthio; V1 to V4 are H or substituent group (at least one or more are Br)] reacts with an arylboronic acid compound expressed by formula II (V5 to V9 are H or substituent group) in the presence of a palladium catalyst {e.g. tetrakis[triphenylphosphine]palladium} to afford a compound in which a substituted aryl group expressed by formula III is introduced into the heterocyclic nucleus. For example, a compound expressed by formula IV is cited as the compound expressed by formula I and, e.g. a compound expressed by formula V is cited as the compound expressed by formula II. Furthermore, e.g. a compound expressed by formula VI is cited as the compound expressed by formula III. The compound expressed by formula II is useful as an intermediate and a raw material for functional compounds such as a sensitizing coloring matter for photosensitive materials, dye, laser dyes or medicines.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing a heterocyclic compound.

[0002]

BACKGROUND OF THE INVENTION The heterocyclic compound represented by the general formula (III) is used as a photographic additive itself, and is also an intermediate compound of functional compounds such as sensitizing dyes for dyes, laser dyes and pharmaceuticals. It is useful as a body and raw material. General formula (I
The conventional synthetic method of the heterocyclic compound represented by II) is
The routes shown below are known. 2-methyl-5
Synthesis route of phenylbenzimidazole (see Belgian Patent No. 595,327)

[0003]

[Chemical 4]

[0004]

However, in the conventional synthetic route, in the case of synthesizing 2-methyl-5-phenylbenzimidazole, a carcinogen biphenylamine (designated as class 1 by IARC) is used as a starting material. There is a need. Therefore, it is possible to efficiently introduce a substituted aryl group into a heterocyclic nucleus without using a carcinogen (II
Development of a synthetic method of the heterocyclic compound represented by I) has been desired.

An object of the present invention is to provide a method for synthesizing a heterocyclic compound represented by the general formula (III), which can efficiently introduce a substituted aryl group into a heterocyclic nucleus without using harmful substances. It is in.

[0006]

The inventors of the present invention have conducted various studies to overcome the above-mentioned drawbacks of the conventional method, and as a result,
It was found that the aryl coupling reaction using a palladium catalyst is effective. That is, the above object of the present invention is to provide a compound represented by the following general formula (I) and a compound represented by the general formula (II)
It was achieved by a production method characterized in that a boric acid compound represented by the formula (1) is condensed in the presence of a palladium catalyst to synthesize a heterocyclic compound represented by the general formula (III). General formula (I)

[0007]

[Chemical 5]

In the formula, X represents NR ₁ or CR ₂ R ₃ . R ₁ , R ₂ and R ₃ represent a hydrogen atom, an alkyl group or an aryl group. R represents a hydrogen atom, an alkyl group or an alkylthio group. V ₁ , V ₂ , V ₃ and V ₄ represent a hydrogen atom or a substituent, and at least one or more is a bromine atom. General formula (II)

[0009]

[Chemical 6]

In the formula, V ₅ , V ₆ , V ₇ , V ₈ and V ₉ represent a hydrogen atom or a substituent. General formula (III)

[0011]

[Chemical 7]

In the formula, X, R _{1 to} R ₃ , R and V _{1 to} V ₉ have the same meanings as described above. Next, the above general formula (I)
The compounds represented by (III) to (III) will be described in more detail.

R ₁ , R ₂ and R ₃ are a hydrogen atom, an alkyl group or an aryl group, and a preferred alkyl group is
An unsubstituted alkyl group having 18 or less carbon atoms (for example, methyl, ethyl) and a substituted alkyl group {eg, a halogen atom or an alkoxy group as a substituent}, and a preferable aryl group is an unsubstituted aryl group having 18 or less carbon atoms (for example, phenyl). , 1-naphthyl) and a substituted aryl group (eg, a halogen atom or an alkoxy group as a substituent). R is a hydrogen atom, an alkyl group or an alkylthio group, and preferred alkyl groups are unsubstituted alkyl groups having 18 or less carbon atoms (eg, methyl, ethyl, propyl, butyl, pentyl) and substituted alkyl groups (eg, a halogen atom as a substituent). , Cyano group, sulfo group, alkoxycarbonyl group, alkoxy group, hydroxy group, aryloxy group,
Acyloxy group, aryl group, acyl group and the like}, and preferable alkylthio groups include unsubstituted alkylthio groups having 18 or less carbon atoms (eg methylthio, ethylthio, propylthio, butylthio, pentylthio) and substituted alkylthio groups (as substituents For example, halogen atom, cyano group, sulfo group, alkoxycarbonyl group,
Examples include an alkoxy group, a hydroxy group, an aryloxy group, an acyloxy group, an aryl group, an acyl group, etc.}
Is. R is more preferably an unsubstituted alkyl group (eg methyl, ethyl, propyl) and an unsubstituted alkylthio group (eg methylthio, ethylthio, propylthio).

V ₁ , V ₂ , V ₃ and V ₄ are each a hydrogen atom, a halogen atom (eg, fluorine chlorine, bromine),
Alkyl groups having 18 or less carbon atoms (for example, methyl, ethyl, propyl, butyl, pentyl, substituted alkyl groups (eg, a substituent such as a halogen atom, a cyano group, a sulfo group, an alkoxycarbonyl group, an alkoxy group, a hydroxy group, an aryloxy group, Acyloxy group, aryl group, acyl group, etc.), an acyl group having 8 or less carbon atoms (eg, acetyl, benzoyl), an acyloxy group having 8 or less carbon atoms (eg, acetyloxy), an alkoxycarbonyl group having 8 or less carbon atoms (eg, Methoxycarbonyl, ethoxycarbonyl, benzyloxycarbonyl), carbamoyl group (eg carbamoyl, morpholinocarbamoyl), sulfamoyl group (eg sulfamoyl, N, N-dimethylsulfamoyl), carboxy group, cyano group, hydro Shi group, an amino group, number 10 an alkoxy group having a carbon (e.g., methoxy, ethoxy, benzyloxy), having 10 or less of the alkylthio group having a carbon (e.g., methylthio, ethylthio), carbon atoms 5
The following are alkylsulfonyl groups (for example, methylsulfonyl), sulfonic acid groups, and aryl groups (for example, phenyl and naphthyl), and at least one of V ₁ , V ₂ , V ₃ and V ₄ is a bromine atom. Further, it may form a condensed ring with a benzene ring, and examples thereof include a benzene ring, a naphthalene ring, a pyridine ring and a furan ring. These may be further substituted.

V ₅ , V ₆ , V ₇ , V ₈ and V ₉ each represent a hydrogen atom or a substituent, and the substituents are those described in the explanation of V ₁ , V ₂ , V ₃ and V _4. And so on.

Further, the production method of the present invention is represented by the general formula (I):
The compound represented by (III) is an isotope (for example, ² H,
^It can be applied even if it contains ³ H, ¹³ C). Specific examples of the compounds represented by formulas (I) to (III) are shown below, but the invention is not limited thereto.

[0017]

[Chemical 8]

[0018]

[Chemical 9]

[0019]

[Chemical 10]

[0020]

[Chemical 11]

[0021]

[Chemical 12]

[0022]

[Chemical 13]

[0023]

[Chemical 14]

[0024]

[Chemical 15]

Examples of the palladium catalyst used as a catalyst in the present invention include tetrakis [triphenylphosphine] palladium (Pd (PPh ₃ ) ₄ ) and palladium acetate (Pd (OAc)).
₂ ), palladium chloride (PdCl ₂ ), bis (diphenylphosphinoferrocene) palladium chloride (PdCl ₂ [bis (diphenyl
phosphino) ferrocene]) and so on. The valence of palladium may be 0 or +2. The equivalent number of the palladium catalyst used may be an equivalent amount or a catalytic amount, but is preferably 0.01 mol% to 10.0 mol%, and more preferably 0.10 mol% to 5.0 mol%.

The reaction conditions are preferably carried out in the presence of a base, such as sodium carbonate, triethylamine, sodium hydroxide, sodium methoxide (NaOMe) as the base.
Etc. can be used. For the reaction conditions, the following documents can be referred to. Reference (a) Suzuki et al., Synthetic Communication (S
Synthetic Communication) Vol. 11, pp. 513-519 (19
81 years). Reference (b) V. Snieckus et al., Tetrahedron Letters 28, 5093
~ 5096 pages (1987).

The reaction temperature is preferably 20 ° C. to 150 ° C. When the reaction temperature is lower than 20 ° C., the progress of the reaction may be delayed. Particularly preferably, it is between 60 ° C and 120 ° C.

The reaction system is a water-organic solvent two-phase system,
It may be either a water-containing organic solvent or a homogeneous system of organic solvent. Examples of the organic solvent include hydrocarbon solvents such as toluene, xylene and hexane, amide solvents such as dimethylformamide, ether solvents such as tetrahydrofuran, alcohol solvents such as methanol and ethanol, nitrile solvents such as acetonitrile, and acetone. A ketone-based solvent such as, an ester-based solvent such as ethyl acetate, and the like can be used. Further, two or more kinds of organic solvents may be mixed and used.

[0029]

EXAMPLES The present invention will be described in more detail based on examples. Example 1. Synthesis of compound (III-1)

[0030]

[Chemical 16]

Compound (I-1) 0.23 under nitrogen atmosphere
g was dissolved in 5 ml of toluene, and 34 mg of Pd (PPh ₃ ) ₄ ( ₃ mo
1%), 5 ml of a 2N aqueous sodium carbonate solution and 5 ml of a methanol solution of 0.15 g of the compound (II-1) were added in this order. The reaction solution was heated and stirred at an external temperature of 85 ° C. for 2 hours.
After cooling the reaction solution, the reaction product was extracted with methylene chloride, and then methylene chloride was distilled off. The obtained residue was purified by silica gel column chromatography (eluent: methylene chloride) to obtain 0.22 g of compound (III-1). Yield 98%, melting point 178-182 ° C Example 2. Synthesis of compound (III-3)

[0032]

[Chemical 17]

0.44 g of compound (I-1) and compound (II
-2) 0.40 g to Example 1. By the same operation as
0.40 g of compound (III-3) was obtained. From the result of the yield of 80% or more, the synthetic method of the present invention can be obtained in a high yield with the desired general formula.
It can be seen that it gives the compound represented by (III). Also,
When introducing the Ph group at the 5-position, a carcinogenic substance such as biphenylamine or benzene needs to be used in the conventional method, while the present invention is advantageous in that it can be synthesized using phenylboric acid.

[0034]

INDUSTRIAL APPLICABILITY The synthetic method of the present invention gives a compound represented by the general formula (III) in a high yield, and in the conventional method, a compound requiring the use of a carcinogenic substance can be easily converted from a highly safe compound. It is superior to the conventional method in that it can be synthesized.

Claims (2)

[Claims] 1. A method for producing a heterocyclic compound, which comprises synthesizing an aryl-substituted benzoazole compound by condensing a halogen-substituted benzoazole compound and an aryl boric acid compound in the presence of a palladium catalyst. 2. A heterocyclic compound represented by the general formula (III) is obtained by condensing a compound represented by the following general formula (I) with a boric acid compound represented by the general formula (II) in the presence of a palladium catalyst. A method for producing a heterocyclic compound, which comprises synthesizing. General formula (I) In the formula, X represents NR ₁ or CR ₂ R ₃ . R ₁ and R ₂
And R ₃ represents a hydrogen atom, an alkyl group or an aryl group. R represents a hydrogen atom, an alkyl group or an alkylthio group. V ₁ , V ₂ , V ₃ and V ₄ represent a hydrogen atom or a substituent, and at least one or more is a bromine atom. General formula (II) In the formula, V ₅ , V ₆ , V ₇ , V ₈ and V ₉ represent a hydrogen atom or a substituent. General formula (III): In the formula, X, R _{1 to} R ₃ , R and V _{1 to} V ₉ have the same meanings as described above.