JP2012193123A - Method for producing nitrogen-containing condensed heterocyclic compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a nitrogen-containing condensed heterocyclic compound in a high yield and selectivity.SOLUTION: For example, an objective compound 3-1 is obtained (yield: 79.8%) by adding a compound 1-1, a compound 2-1, ethylene glycol dimethyl ether, triphenylphosphine and a ruthenium catalyst, reacting at 85-90°C for 3 hr, adding THF and NaCl aqueous solution, filtering under reduced pressure, separating an organic layer, distilling out the solvent under reduced pressure, purifying the distilled fraction with a column and recrystallizing the product.

Description

  The present invention relates to a method for producing a nitrogen-containing fused heterocyclic compound useful as a synthetic intermediate for organic compounds and a material for organic electroluminescence.

  The nitrogen-containing fused heterocyclic compound is useful as a synthetic intermediate for organic compounds and a material for organic electroluminescence.

  As a production method for obtaining a nitrogen-containing fused heterocyclic compound by forming a C—C bond from an aryl halide and a nitrogen-containing fused heterocyclic compound, a method carried out in the presence of a Ni catalyst or a Pd catalyst is widely known (non-patent document). 1, 2, 3). In addition, a method using an inexpensive catalyst such as Fe is known (see Patent Document 1).

  On the other hand, a method is known in which phenylpyridine and aryl halide are reacted in the presence of a Ru catalyst to form a C—C bond (Non-patent Documents 4 and 2). These methods produce products with relatively high yields, but higher yields are desired, and when unsubstituted phenylpyridine is used, there are two reaction centers, resulting in high production of by-products. Therefore, a production method with high selectivity has been desired.

JP 2000-229243 A JP 2008-222687 A

K. Tamao et al. , J .; Am. Chem. Soc. 94, 4374 (1972) E. Negishi et al. , J .; Org. Chem. , 42, 1821 (1977) N. Miyaura et al. Tetrahedron Lett. , 20 pages, 3437 pages (1979) S. Oi et al. Org. Lett. Vol.3, 2579 pages (2001)

  This invention is made | formed in view of the said subject, The objective is to provide the manufacturing method of a nitrogen-containing condensed heterocyclic compound with a high yield and high selectivity.

  The above object of the present invention is achieved by the following configurations.

  1. By reacting a compound represented by the following general formula (1a) or general formula (1b) with a compound represented by the following general formula (2) in the presence of a ruthenium catalyst and glycol ethers, the following general formula ( A method for producing a nitrogen-containing condensed heterocyclic compound, comprising obtaining a nitrogen-containing condensed heterocyclic compound represented by 3a) or general formula (3b).

(In the formula, Z ₁ and Z ₂ represent a nonmetallic atom group necessary for forming an aromatic hydrocarbon ring or an aromatic heterocyclic ring. Z ₃ represents a simple bond or a divalent linking group. X Represents a halogen atom, R ₁ and R ₂ represent a hydrogen atom or a substituent, R ₃ and R ₄ represent a substituent, and n1 and n2 represent an integer of 0 to 4.)
2. By reacting the compound represented by the following general formula (4a) or the general formula (4b) with the compound represented by the following general formula (2), it is represented by the following general formula (5a) or the general formula (5b). 2. The method for producing a nitrogen-containing fused heterocyclic compound as described in 1 above, wherein the nitrogen-containing fused heterocyclic compound is obtained.

(In the formula, Z ₁ and Z ₂ represent a nonmetallic atom group necessary for forming an aromatic hydrocarbon ring or an aromatic heterocyclic ring. X represents a halogen atom. R ₁ and R ₂ represent a hydrogen atom or R ₃ and R ₄ each represent a substituent, and n1 and n2 each represent an integer of 0 to 4.
3. The glycol ethers are ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, ethylene glycol methyl ethyl ether or ethylene glycol monomethyl. 3. The method for producing a nitrogen-containing fused heterocyclic compound as described in 1 or 2 above, which is an ether acetate.

  According to the present invention, a method for producing a nitrogen-containing fused heterocyclic compound with high yield and high selectivity could be provided. This nitrogen-containing fused heterocyclic compound is a compound useful as a synthetic intermediate for organic compounds and a material for organic electroluminescence.

  As a result of intensive studies in view of the above problems, the present inventor has obtained a compound represented by the general formula (1a) or the general formula (1b) and a phenylpyridine compound represented by the general formula (2), By reacting in the presence of a ruthenium catalyst and glycol ethers, the nitrogen-containing condensed heterocyclic compound represented by the general formula (3a) or the general formula (3b) can be obtained with high yield and high selectivity. As a result, they have reached the present invention.

  Hereinafter, the constituent elements of the present invention and modes for carrying out the present invention will be described in detail.

[Compounds represented by the general formulas (1a), (1b), (3a), (3b), (4a), (4b), (5a), (5b), (2)]
In the above general formulas, Z ₁ and Z ₂ represent a nonmetallic atom group necessary for forming an aromatic hydrocarbon ring or an aromatic heterocyclic ring.

  Examples of the aromatic hydrocarbon ring include benzene ring, biphenyl ring, naphthalene ring, azulene ring, anthracene ring, phenanthrene ring, pyrene ring, chrysene ring, naphthacene ring, triphenylene ring, o-terphenyl ring, and m-terphenyl ring. Ring, p-terphenyl ring, acenaphthene ring, coronene ring, fluorene ring, fluoranthrene ring, naphthacene ring, pentacene ring, perylene ring, pentaphen ring, picene ring, pyranthrene ring, anthraanthrene ring, dibenzofuran ring, dibenzodio Examples include a phen ring and a carbazole ring. Of these, a benzene ring is preferred.

  Examples of the aromatic heterocycle include a furan ring, a thiophene ring, a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a triazine ring, a benzimidazole ring, an oxadiazole ring, a triazole ring, an imidazole ring, a pyrazole ring, and a thiazole ring. , Indole ring, benzimidazole ring, benzothiazole ring, benzoxazole ring, quinoxaline ring, quinazoline ring, phthalazine ring, and oxazole ring. Of these, preferred is a pyridine ring.

Z ₃ represents a simple bond or a divalent linking group.

A mere bond is a mere bond that directly bonds the connecting substituents together. Examples of the divalent linking group represented by Z ₃ may include hydrocarbon groups such as alkylene, alkenylene, alkynylene, and arylene, and those containing a hetero atom, and also include a thiophene-2,5-diyl group, It may be a divalent linking group derived from a compound having an aromatic heterocycle such as a pyrazine-2,3-diyl group (also referred to as a heteroaromatic compound), and may be a chalcogen atom such as oxygen or sulfur. Also good. Further, it may be a group linked via a hetero atom such as an alkylimino group, a dialkylsilanediyl group or a diarylgermandiyl group. Of these, preferred is a mere bond.

  X represents a halogen atom. A preferable halogen atom is a chlorine atom, a bromine atom or an iodine atom, more preferably a bromine atom.

  n1 and n2 represent an integer of 0 to 4. n1 is preferably 0. n2 is preferably 0.

R ₁ and R ₂ represent a hydrogen atom or a substituent. R ₃ and R ₄ represent a substituent.

Examples of the substituent represented by R _{1 to} R ₄ include an alkyl group, a cycloalkyl group, an alkenyl group, an aryl group, an acylamino group, a sulfonamide group, an alkylthio group, an arylthio group, a halogen atom, a heterocyclic group, a sulfonyl group, and a sulfinyl group. Group, phosphonyl group, acyl group, carbamoyl group, sulfamoyl group, cyano group, alkoxy group, aryloxy group, heterocyclic oxy group, siloxy group, acyloxy group, carbamoyloxy group, amino group, alkylamino group, imide group, ureido Groups, sulfamoylamino group, alkoxycarbonylamino group, alkoxycarbonylamino group, aryloxycarbonylamino group, alkoxycarbonyl group, aryloxycarbonyl group, carboxyl, 2- (2-pyridyl) phenyl group and the like. Et That. A preferable thing in R < ₁ >, R < ₂ > is a hydrogen atom.

  The above group may be further substituted with a substituent, and examples of the substituent include the same groups as the above groups.

  The typical examples of the compounds represented by the general formula (1a), general formula (1b), general formula (4a) and general formula (4b) used in the present invention are shown below. It is not limited.

  Below, the typical example of a compound represented by General formula (2) used for this invention is shown, However, This invention is not limited to these.

  Hereinafter, typical specific examples of the compounds represented by the general formula (3a), the general formula (3b), the general formula (5a), and the general formula (5b) obtained by the production method of the present invention are shown. Is not limited to these.

  The compound represented by the general formula (2) is in a range of 1 to 10 mol with respect to 1 mol of the compound represented by the general formula (1a), the general formula (1b), the general formula (4a), or the general formula (4b). Although it is preferable to use, it is especially preferable to use in the range of 3 to 5 mol.

[Glycol ethers]
In the present invention, glycol ethers refer to ethers having an ethylene glycol skeleton, preferably ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, ethylene glycol monomethyl. Ether, diethylene glycol monomethyl ether, ethylene glycol methyl ethyl ether, ethylene glycol monomethyl ether acetate. Of these, ethylene glycol dimethyl ether and ethylene glycol diethyl ether are more preferable, and ethylene glycol diethyl ether is more preferable.

  The amount of the glycol ethers used is preferably 1 to 20 times by mass with respect to the compound represented by the general formula (1a), general formula (1b), general formula (4a) or general formula (4b). Especially preferably, it is 3 to 10 times.

[Ruthenium catalyst]
The ruthenium catalyst used in the present invention is not particularly limited. For example, benzene ruthenium (II) chloride (dimer), dichloro (p-cymene) ruthenium (II) (dimer), dichloro (1,5-cyclooctadiene) Ruthenium (II) polymer, [2,2′-bis (diphenylphosphino) -1,1′-binaphthyl] ruthenium (II) dichloride, tris (2,2′-bipyridyl) ruthenium (II) chloride hexahydrate Etc. Of these, benzene ruthenium (II) chloride (dimer) is preferred.

  The ruthenium catalyst is preferably used in the range of 0.01 to 0.3 mol with respect to 1 mol of the compound represented by the general formula (1a), general formula (1b), general formula (4a) or general formula (4b). However, it is particularly preferable to use in the range of 0.01 to 0.1 mol.

[Organic phosphorus compounds]
In the production of the present invention, it is preferable to use an organic phosphorus compound in combination. Although it does not specifically limit as an organic phosphorus compound, For example, a triphenylphosphine, a tri (t-butyl) phosphine, a tricyclohexyl phosphine, a tri (o-tolyl) phosphine, a trifuryl phosphine, 1, 1-bis (diphenylphosphino) ferrocene Etc. Of these, triphenylphosphine is preferred.

  The organophosphorus compound is preferably used in the range of 0.01 to 1 mol with respect to 1 mol of the compound represented by the general formula (1a), general formula (1b), general formula (4a) or general formula (4b). , 0.05 to 0.2 mol is particularly preferable.

  Moreover, it is preferable to use a base together. Examples of the base include alkali metal salts (sodium carbonate, potassium carbonate, sodium hydrogen carbonate, cesium carbonate, cesium fluoride, potassium phosphate, sodium hydroxide, potassium hydroxide, sodium t-butoxide, etc.), amine derivatives (triethylamine, tetra Methyl guanidine, etc.). Of these, potassium carbonate is preferred.

  The reaction temperature is usually preferably from 70 to 200 ° C, particularly preferably from 80 to 130 ° C.

  EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited thereto.

Comparative Example 1
(Synthesis of Exemplary Compound 3-1)
Exemplified Compound 3-1 was synthesized according to the following scheme.

Under a nitrogen stream, Exemplified Compound 1-1 10 g (0.0405 mol), Exemplified Compound 2-1 18.8 g (3 times mol of Exemplified Compound 1-1), K ₂ CO ₃ 11.2 g (Exemplified Compound 1-1 2 times mol) and 50 ml of 1-methylpyrrolidin-2-one (NMP) were stirred for 20 minutes. 1.1 g of triphenylphosphine (PPh ₃ ) (0.1 times mol of Exemplified Compound 1-1), 0.61 g of ruthenium catalyst [RuCl ₂ (C ₆ H ₆ )] ₂ (0.03 of Exemplified Compound 1-1) Times mol), and the mixture was stirred at 85 to 90 ° C. for 3 hours. As a result of measuring the reaction solution by HPLC, the reaction rate was 84% and the dimer by-product was 14%. To the reaction solution, 250 ml of THF and 250 ml of NaCl aqueous solution were added, unnecessary portions were removed by filtration under reduced pressure, the organic layer was separated, and the solvent was distilled off under reduced pressure. The obtained fraction was purified by column and recrystallized from acetonitrile to obtain 9.19 g (yield 70.7%) of Exemplary Compound 3-1.

  Identification of Exemplified Compound 3-1 and dimer by-product was performed by MASS and NMR spectra.

Example 1 (present invention)
Exemplified Compound 3-1 was synthesized according to the following scheme.

Under a nitrogen stream, Exemplified Compound 1-1 10 g (0.0405 mol), Exemplified Compound 2-1 18.8 g (3 times mol of Exemplified Compound 1-1), K ₂ CO ₃ 11.2 g (Exemplified Compound 1-1 2 times mol) and 50 ml of ethylene glycol dimethyl ether were stirred for 20 minutes. 1.1 g of triphenylphosphine (PPh ₃ ) (0.1 times mol of Exemplified Compound 1-1), 0.61 g of ruthenium catalyst [RuCl ₂ (C ₆ H ₆ )] ₂ (0.03 of Exemplified Compound 1-1) Times mol), and the mixture was stirred at 85 to 90 ° C. for 3 hours. As a result of measuring the reaction solution by HPLC, the reaction rate was 90% and the dimer by-product was 8.0%. To the reaction solution, 250 ml of THF and 250 ml of NaCl aqueous solution were added, unnecessary portions were removed by filtration under reduced pressure, the organic layer was separated, and the solvent was distilled off under reduced pressure. The obtained fraction was purified by column and recrystallized from acetonitrile to obtain 10.3 g (yield: 79.8%) of Exemplary Compound 3-1.

  Identification of Exemplified Compound 3-1 and dimer by-product was performed by MASS and NMR spectra.

NMR spectrum of Exemplified Compound 3-1:
¹ H NMR (400 MHz, CDCl ₃ ): δ = 8.64 (dd, 1H), 8.57 (dd, 1H), 8.39 (d, 1H), 8.24 (s, 1H), 7. 77-7.69 (m, 2H), 7.59-7.55 (m, 1H), 7.50-7.47 (m, 2H), 7.33 (dd, 1H), 7.28 ( dd, 1H), 7.20 (dd, 1H), 7.10 (dd, 1H), 7.16 (td, 1H), 6.91 (d, 1H)
Example 2 (Invention)
Exemplified Compound 3-1 was synthesized according to the following scheme.

Under a nitrogen stream, Exemplified Compound 1-1 10 g (0.0405 mol), Exemplified Compound 2-1 18.8 g (3 times mol of Exemplified Compound 1-1), K ₂ CO ₃ 11.2 g (Exemplified Compound 1-1 2 times mol) and 50 ml of ethylene glycol diethyl ether were stirred for 20 minutes. 1.1 g of triphenylphosphine (PPh ₃ ) (0.1 times mol of Exemplified Compound 1-1), 0.61 g of ruthenium catalyst [RuCl ₂ (C ₆ H ₆ )] ₂ (0.03 of Exemplified Compound 1-1) Times mol), and the mixture was stirred at 115 to 120 ° C. for 3 hours. As a result of measuring the reaction solution by HPLC, the reaction rate was 91% and the dimer by-product was 7.0%. To the reaction solution, 250 ml of THF and 250 ml of NaCl aqueous solution were added, unnecessary portions were removed by filtration under reduced pressure, the organic layer was separated, and the solvent was distilled off under reduced pressure. The obtained fraction was purified by column and recrystallized from acetonitrile to obtain 10.5 g (yield 81.0%) of Exemplary Compound 3-1.

  Identification of Exemplified Compound 3-1 and dimer by-product was performed by MASS and NMR spectra.

Example 3 (Invention)
Exemplified Compound 3-1 was synthesized according to the following scheme.

  << Synthesis of Exemplary Compound 3-1 >>

Under a nitrogen stream, Exemplified Compound 1-1 10 g (0.0405 mol), Exemplified Compound 2-1 18.8 g (3 times mol of Exemplified Compound 1-1), K ₂ CO ₃ 11.2 g (Exemplified Compound 1-1 2 mol) and 50 ml of diethylene glycol dimethyl ether were stirred for 20 minutes. 1.1 g of triphenylphosphine (PPh ₃ ) (0.1 times mol of Exemplified Compound 1-1), 0.61 g of ruthenium catalyst [RuCl ₂ (C ₆ H ₆ )] ₂ (0.03 of Exemplified Compound 1-1) Times mol), and the mixture was stirred at 115 to 120 ° C. for 3 hours. As a result of measuring the reaction solution by HPLC, the reaction rate was 88% and the dimer by-product was 10%. To the reaction solution, 250 ml of THF and 250 ml of NaCl aqueous solution were added, unnecessary portions were removed by filtration under reduced pressure, the organic layer was separated, and the solvent was distilled off under reduced pressure. The obtained fraction was purified by column and recrystallized from acetonitrile to obtain 9.9 g of Exemplified Compound 3-1 (yield: 76.0%).

  Identification of Exemplified Compound 3-1 and dimer by-product was performed by MASS and NMR spectra.

Example 4 (Invention)
Exemplified compound 3-11 was synthesized according to the following scheme.

Under a nitrogen stream, Exemplified Compound 1-13 10 g (0.0405 mol), Exemplified Compound 2-7 20.6 g (3 times mol of Exemplified Compound 1-13), K ₂ CO ₃ 11.2 g (Exemplified Compound 1-13 2 times mol) and 50 ml of ethylene glycol diethyl ether were stirred for 20 minutes. 1.1 g of triphenylphosphine (PPh ₃ ) (0.1 times mol of Exemplified Compound 1-13), 0.61 g of ruthenium catalyst [RuCl ₂ (C ₆ H ₆ )] ₂ (0.03 of Exemplified Compound 1-13) Times mol), and the mixture was stirred at 115 to 120 ° C. for 3 hours. As a result of measuring the reaction solution by HPLC, the reaction rate was 91% and the dimer by-product was 7.1%. To the reaction solution, 250 ml of THF and 250 ml of NaCl aqueous solution were added, unnecessary portions were removed by filtration under reduced pressure, the organic layer was separated, and the solvent was distilled off under reduced pressure. The obtained fraction was purified by column and recrystallized from acetonitrile to obtain 11.0 g (yield: 81.0%) of Exemplary Compound 3-11.

  Identification of Exemplified Compound 3-11 and dimer by-product was performed by MASS and NMR spectra.

Example 5 (Invention)
Exemplified compound 3-14 was synthesized according to the following scheme.

Under a nitrogen stream, Exemplified Compound 1-17 6.1 g (0.0405 mol), Exemplified Compound 2-6 20.6 g (3 times mol of Exemplified Compound 1-17), K ₂ CO ₃ 11.2 g (Exemplified Compound 1- 1 17 times 2) and 50 ml of ethylene glycol diethyl ether were stirred for 20 minutes. 1.1 g of triphenylphosphine (PPh ₃ ) (0.1 times mol of Exemplified Compound 1-17), 0.61 g of ruthenium catalyst [RuCl ₂ (C ₆ H ₆ )] ₂ (0.03 of Exemplified Compound 1-17) Times mol), and the mixture was stirred at 120 to 130 ° C. for 3 hours. As a result of measuring the reaction solution by HPLC, the reaction rate was 89% and the dimer by-product was 8.5%. To the reaction solution, 250 ml of THF and 250 ml of NaCl aqueous solution were added, unnecessary portions were removed by filtration under reduced pressure, the organic layer was separated, and the solvent was distilled off under reduced pressure. The obtained fraction was purified by column and recrystallized from acetonitrile to obtain 9.1 g (yield: 79.0%) of Exemplary Compound 3-14.

  Identification of Exemplified Compound 3-14 and dimer by-product was performed by MASS and NMR spectra.

  Other exemplary compounds can also be synthesized according to the above method.

Claims (3)

By reacting a compound represented by the following general formula (1a) or general formula (1b) with a compound represented by the following general formula (2) in the presence of a ruthenium catalyst and glycol ethers, the following general formula ( A method for producing a nitrogen-containing condensed heterocyclic compound, comprising obtaining a nitrogen-containing condensed heterocyclic compound represented by 3a) or general formula (3b).

(In the formula, Z ₁ and Z ₂ represent a nonmetallic atom group necessary for forming an aromatic hydrocarbon ring or an aromatic heterocyclic ring. Z ₃ represents a simple bond or a divalent linking group. X Represents a halogen atom, R ₁ and R ₂ represent a hydrogen atom or a substituent, R ₃ and R ₄ represent a substituent, and n1 and n2 represent an integer of 0 to 4.) By reacting the compound represented by the following general formula (4a) or the general formula (4b) with the compound represented by the following general formula (2), it is represented by the following general formula (5a) or the general formula (5b). The method for producing a nitrogen-containing condensed heterocyclic compound according to claim 1, wherein the nitrogen-containing condensed heterocyclic compound is obtained.

(In the formula, Z ₁ and Z ₂ represent a nonmetallic atom group necessary for forming an aromatic hydrocarbon ring or an aromatic heterocyclic ring. X represents a halogen atom. R ₁ and R ₂ represent a hydrogen atom or R ₃ and R ₄ each represent a substituent, and n1 and n2 each represent an integer of 0 to 4.   The glycol ethers are ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, ethylene glycol methyl ethyl ether or ethylene glycol monomethyl. It is ether acetate, The manufacturing method of the nitrogen-containing condensed heterocyclic compound of Claim 1 or 2 characterized by the above-mentioned.