JP2001081087A - New 2-(2-pyridyl)pyrimidine derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide the new subject compound which is useful, or used as an intermediate, in the fields of medicament, agricultural chemical, ligand, liquid crystal, surfactant, electrophotography and organic electroluminescence. SOLUTION: A compound of 2-(2-pyridyl)pyrimidine derivative expressed by formula I (R1 and R2 are each H, an alkyl or an aryl, or may mutually combine to form a ring, provided that R1 is an alkyl or an aryl when R2 is phenyl), for example, 2-(5,6-dimethyl-2-pyridyl)pyrimidine which is expressed by formula II. The compound of formula I is, for example, obtained by reacting 2-cyanopyrimidine with hydrazine (for example, hydrazine hydrate is used) to form a amidrazone compound, then reacting the formed amidrazone compound with an aldehyde or ketone compound (for example, 2,3-butanedione) to form 1,2,4-triazine compound, and further reacting the formed triazine compound with 2,5-norbornadiene.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to novel 2- (2-pyridyl) compounds which are useful compounds and intermediates in the fields of pharmaceuticals, pesticides, ligands, liquid crystals, surfactants, electrophotography and organic electroluminescence. ) Pyrimidine derivatives.

[0002]

2. Description of the Related Art In recent years, pyridine derivatives and pyrimidine derivatives have received attention in a wide range of fields. In the field of pharmaceuticals and agricultural chemicals, for example, pyrimidine derivatives have high affinity for endothelin receptors as endothelin antagonists (JP-A-5-222003, JP-A-9-162449, JP-A-10-194974). ,
Japanese Patent Application Laid-Open No. H11-92458) is disclosed. However, the affinity of the receptor is insufficient, and creation of an endothelin antagonist having a stronger receptor affinity has been desired.

In the field of ligands, for example, dendrimer-type polynuclear metal complexes contained in dendrimer-type compounds have a new property as a polynuclear metal complex when the interaction between subunits is strong. Research is being actively conducted. One of them is a light or redox active ruthenium (II) polypyridine complex as a subunit,
Polynuclear complexes using pyrazines having electron interaction between skeletons as bridging ligands (Chemistry and Industry, 52 (7), 89)
0 (1999); Am. Chem. Soc. , 12
0, 5480 (1998)) have been synthesized and reported its electrochemical properties. Such a dendrimer-type polynuclear metal complex is likely to be used in an artificial conversion process of solar energy, and has been regarded as very promising. It is also expected to be useful as a ligand for various reaction catalysts.
For example, GB2328686, Journal of the Society of Synthetic Organic Chemistry,
56 (9), 78 (1998).
By using it as a ligand of a metal copper catalyst in a mann-like reaction, it is expected to work as a reactivity promoter.

[0004] In the field of liquid crystals, studies have been actively conducted since various properties of liquid crystals can be obtained by including a pyridine derivative and a pyrimidine derivative in the molecular structure of the liquid crystal compound. For example, JP-A-8
-295584, JP-A-9-25567, JP-A-9
-110856, JP-A-10-7596, JP-A-1
No. 237002 is disclosed.

[0005] Organic electroluminescence (EL) has attracted attention as a next-generation display material.
In the field of (1), the lack of effective electron-transporting materials has become a problem (the introduction of a π-electron system with high electron-accepting properties is an essential condition for electron-transporting materials). Silole derivatives having low (LUMO) and high electron acceptability (silole (silacyclopentadiene)
Is a silicon homolog of cyclopentadiene), and among them, 2,5-dipyridylsilole having a 2-pyridyl group as an aryl group has an extremely high electron transporting property. It has been reported to be superior to tris (8-hydroxyquinoline) aluminum Alq, which is regarded as one of the best electron transporting materials (Journal of Synthetic Organic Chemistry, 56 (6), 50 (199).
8); Am. Chem. Soc. , 118 , 119
74 (1996)). Thus, in the further molecular design of a silole π-electron system, particularly a 2,5-diarylsilole derivative, how to control its electronic structure and physical properties (for example, control by a substituent on the 2,5-position aryl group) Attention has been paid to

In the field of electrophotography, as described in, for example, JP-A-3-282478 and JP-A-10-265690, it is used as a part of a dye of a recording material. By having a substituent capable of forming a bidentate conformation in a dye, the dye is used for the purpose of improving the stability of an image, particularly the fixability and light resistance, and has been actively studied. In recent years, with a rapid increase in the amount of information, a large-capacity optical storage medium has been spotlighted, and is a field that is very promising.

[0007]

An object of the present invention is to provide a novel 2-(-) as a useful substance or intermediate in the fields of pharmaceuticals, agricultural chemicals, ligands, liquid crystals, surfactants, electrophotography and organic electroluminescence. (2-pyridyl) pyrimidine derivatives.

[0008]

As a result of intensive studies, the present inventors have found that 2- (2-pyridyl) useful in the fields of pharmaceuticals, pesticides, ligands, liquid crystals, surfactants, electrophotography and organic electroluminescence. ) The pyrimidine derivative was successfully obtained, and the present invention was completed. The present invention relates to a 2- (2-pyridyl) pyrimidine derivative represented by the following general formula (I).

[0009]

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In the formula, R1 and R2 may be the same or different and represent a hydrogen atom, an alkyl group or an aryl group. Further, R1 and R2 may combine with each other to form a ring. However, when R2 is a phenyl group, R1 represents an alkyl group or an aryl group.

[0011]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail. The compound of the formula (I) of the present invention will be described in more detail as follows. In the present specification, examples of the alkyl group include a linear or branched alkyl group having 1 to 18 carbon atoms, preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group,
1 to 1 carbon atoms such as sec-butyl group and tert-butyl group
It is four alkyl groups, more preferably an alkyl group having 1 to 4 carbon atoms in which R1 and R2 are the same, and particularly preferably a methyl group derivable to carboxylic acid or aldehyde.

In the present specification, the aryl group includes a phenyl group, a p-tolyl group, a naphthyl group and the like. Preferred are a phenyl group and a p-tolyl group, and more preferred is a phenyl group.

Preferred specific examples (I-1) to (I-18) of the compound represented by formula (I) of the present invention are shown below, but the present invention is not limited thereto.

[0014]

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[0015]

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The 2- (2) represented by the general formula (I) of the present invention
The (-pyridyl) pyrimidine derivative can be produced by the following method.

[0017]

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In the formula, R1 and R2 have the same meaning as described above. Next, each step will be described.

Step A: 2-Cyanopyrimidine (II) is reacted with hydrazine,
An amidrazone compound (III) is obtained. The amidrazone compound (III) can be obtained by the method described in Japanese Patent Application No. 11-167308 or a method analogous thereto.

Step B The amidrazone compound (III) is reacted with the aldehyde or ketone compound represented by the general formula (IV) to obtain a 1,2,4-triazine compound represented by the general formula (V). 1,2,4-triazine compound (V)
-167308, TetrahedronLet
t. , 39 , 8817, 8821, 8825 (199
8) and the like, or a method analogous thereto.

Specific examples of the aldehyde or ketone compound represented by the general formula (IV) include the following. (I) Dialdehyde compounds (when R1 and R2 are hydrogen atoms) Concretely, aqueous glyoxal solution, glyoxal di (sodium bisulfite), glyoxal equivalent 1,4-dioxane-2,3-diol, glyoxalte Limeric dihydrate and the like. Preferably aqueous glyoxal solution, 1,4-dioxane-2,3
-Diol, more preferably an aqueous glyoxal solution which is inexpensive and easy to obtain and handle.

(Ii) Symmetric diketone compounds (R1 and R2
Is the same alkyl group or aryl group) A compound represented by the general formula (IV), wherein R1 and R2 are the same alkyl group or aryl group. Further, R1 and R2 may combine with each other to form a ring. Preferably, the alkyl group has 1 to 4 carbon atoms,
Examples of the aryl group include a phenyl group and a 4-methylphenyl group. Specifically, 1,2-cyclohexanedione, 2,3-butanedione, 3,4-hexanedione,
4,5-octanedione, 5,6-decandione, 2,
5-dimethyl-3,4-hexanedione, 2,7-dimethyl-4,5-octanedione, 3,6-dimethyl-
4,5-octanedione, 2,2,5,5-tetramethyl-3,4-hexanedione, benzyl (Benzil), 4,
4'-dimethylbenzyl, di-α-naphthylethanedione, di-β-naphthylethanedione and the like. Particularly preferably, 1,2-cyclohexanedione, 2,3-
Butanedione, 3,4-hexanedione and benzyl.

(Iii) Asymmetric diketone compound (when R1 and R2 are different alkyl groups or aryl groups) R1 and R2 are each different alkyl groups or aryl groups represented by the compound represented by formula (IV) . Preferably, the alkyl group includes an alkyl group having 1 to 4 carbon atoms, and the aryl group includes a phenyl group and a 4-methylphenyl group. Specifically, 2,3-pentanedione, 2,3-hexanedione, 2,3-heptanedione, 4-methyl-2,3-pentanedione, 4-methyl-2,3-hexanedione, 5-methyl -2,3-hexanedione, 3,4-heptanedione, 3,4-octanedione, 2-methyl-3,4-hexanedione, 4,4
-Dimethyl-2,3-pentanedione, 5-methyl-
3,4-heptanedione, 6-methyl-3,4-heptanedione, 2,2-dimethyl-3,4-hexanedione, 4,5-nonanedione, 3-methyl-4,5-octanedione, 2- Methyl-4,5-octanedione,
2,2-dimethyl-3,4-heptanedione, 2-methyl-3,4-heptanedione, 2-methyl-3,4-octanedione, 2,5-dimethyl-3,4-heptanedione, 2, 6-dimethyl-3,4-heptanedione,
2,2,5-trimethyl-3,4-hexanedione, 2
-Methyl-3,4-octanedione, 3-methyl-4,
5-nonanedione, 2-methyl-4,5-nonanedione, 2,2-dimethyl-3,4-octanedione, 2,
5-dimethyl-3,4-heptanedione, 2,6-dimethyl-4,5-octanedione, 2,2,5-trimethyl-heptanedione, 2,5-dimethyl-3,4-hexanedione, 2, 6-dimethyl-4,5-octanedione, 2,2,6-trimethyl-3,4-heptanedione, 2,2,6-trimethyl-3,4-hexanedione, 2,2,5-trimethyl-3 , 4-Heptanedione, 2,2,6-trimethyl-3,4-heptanedione, 1-phenyl-1,2-propanedione, 1-phenyl-1,2-butanedione, 1-phenyl-1,2-
Heptanedione, 3-methyl-1-phenyl-1,2-
Butanedione, 1-phenyl-1,2-hexanedione, 3-methyl-1-phenyl-1,2-heptanedione, 4-methyl-1-phenyl-1,2-heptanedione, 3,3-dimethyl-1 -Phenyl-1,2-butanedione and the like. Particularly preferably, 2,3-pentanedione, 2,3-hexanedione, 2,3-heptanedione, 1-phenyl-1,2-propanedione, 1-
Phenyl-1,2-butanedione.

(Iv) Ketoaldehyde compound (when one of R1 and R2 is a hydrogen atom and the other is an alkyl group) One of R1 and R2 is a hydrogen atom and the other is an alkyl or aryl group represented by the general formula (IV ) Is shown. Preferably, the alkyl group is an alkyl group having 1 to 4 carbon atoms, and the aryl group is a phenyl group. Specifically, methylglyoxal (pyruvic aldehyde), ethylglyoxal, propylglyoxal, isopropylglyoxal, butylglyoxal, t-butyl Glyoxal, isobutylglyoxal, sec-
Butylglyoxal, phenylglyoxal and the like. Particularly preferred are methylglyoxal and phenylglyoxal.

Step C: A 1,2,4-triazine compound represented by the general formula (V) is reacted with 2,5-norbornadiene to obtain a compound of the general formula (I)
To obtain a 2- (2-pyridyl) pyrimidine derivative represented by the formula: 2- (2-pyridyl) pyrimidine derivatives represented by the general formula (I) are described in Tetrahedron Lett. , 3
9 , 8817, 8821, 8825 (1998) and the like, or a method analogous thereto.

[0026]

EXAMPLES Next, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples. The purity was evaluated by high performance liquid chromatography (HPL).
C).

Example 1 Synthesis of 2- (5,6-dimethyl-2-pyridyl) pyrimidine (A-2) In a 50 ml eggplant flask, 1.0 ml of water and 1.0 g (9.5 mmol) of 2-cyanopyrimidine were added. Then, 5.5 g (0.095 mol) of hydrazine monohydrate was charged and reacted at 30 ° C. for 3 hours with stirring. After confirming the disappearance of the raw materials by HPLC analysis, 10 ml of toluene was added, and water and excess hydrazine were distilled off under reduced pressure. After repeating this operation a total of three times, 5.5 ml of water was added to the residue, and then 2,3-
0.82 g (9.5 mmol) of butanedione was added and reacted at an external temperature of 100 ° C. for 2 hours. Toluene 10
ml was added and the solvent was distilled off under reduced pressure. 8.8 g (95 mmol) of 2,5-norbonadiene in 10 ml of xylene
Was added to the residue and reacted under reflux for 24 hours. After completion of the reaction, xylene and excess 2,5-
Norbornadiene was distilled off, and 10 ml of toluene was further added to completely distill off 2,5-norbornadiene. The residue was purified by silica gel column chromatography and recrystallized from hexane to obtain 0.77 g (yield: 43.8%) of the desired product as pale yellow crystals. Purity 99.3
%Met. 84-86 ° C.

Examples 2 to 8 In the same manner as in Example 1, compounds A-1 and A-3 to A-8 were synthesized. The structures and properties of the novel 2- (2-pyridyl) pyrimidine derivatives represented by the general formula (I) synthesized by the method of the present invention are shown in Tables 1 and 2 below.

[0029]

[Table 1]

[0030]

[Table 2]

Examples 9 to 15 In the same manner as in Example 1, A-9 to A-
Fifteen compounds could be synthesized and identified in the same manner as above.

[0032]

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Next, a novel compound according to the present invention, 2
An application example using a-(2-pyridyl) pyrimidine derivative will be described. However, the content of the present invention is by no means limited to this. This application example is used as a promoter (ligand) of a metal copper catalyst in the Ullmann reaction, as described in GB2328686. The following substrates were used.

[0034]

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Application Example 1 Synthesis of N, N'-diphenyl-N, N'-di (3-methylphenyl) -1,4-phenylenediamine (VI) N, N'-diphenyl-N, N'-p -Phenylenediamine 31.2 g (0.12 mol), m-iodotoluene 54.5 g (0.25 mol), potassium carbonate 65 g
(0.47 mol), 0.54 g of copper sulfate pentahydrate (2.
0 mmol), 0.37 g of 2- (5,6-dimethyl-2-pyridyl) pyrimidine (A-2) (2.0 mmol)
l), a mixture of 32 ml of terpinolene was added to
The reaction was performed at 00 to 210 ° C for 5 hours. After the reaction, 66 ml of toluene and 66 ml of water were added. After liquid separation, the toluene was concentrated under reduced pressure. 39 ml of ethyl acetate and 253 of isopropanol
of the desired product 4 as pale yellow crude crystals.
9.8 g (94.3% yield) was obtained. Melting point 170-17
1 ° C., HPLC content (column YMC-A-002, detection UV 310 nm, flow rate 1.1 ml / min eluent) is 9
It was 9.4%.

Application Examples 2 to 4 The same procedures as in Application Example 1 were carried out except that cocatalysts shown in Table 3 below were used instead of 2- (5,6-dimethyl-2-pyridyl) pyrimidine (A-2). Operate in the same way as 1 and N,
N′-diphenyl-N, N′-di (3-methylphenyl) -1,4-phenylenediamine was synthesized, and the yield and purity were evaluated by HPLC.

Comparative Examples 1 to 3 The procedure of Example 1 was repeated, except that 2- (5,6-dimethyl-2-pyridyl) pyrimidine (A-2) was not added. '-Diphenyl-N, N'
-Di (3-methylphenyl) -1,4-phenylenediamine was synthesized, and the effect of promoting the reaction time, yield and HP
Purity was evaluated by LC. Table 3 shows the above results.

[0038]

[Table 3]

As can be seen from Table 3, the reaction is carried out by adding a co-catalyst (ligand) such as a 2- (2-pyridyl) pyrimidine derivative, rather than conducting the reaction only with a copper catalyst as in the prior art. Is remarkably promoted, and a high-yield and high-purity target compound can be obtained. Further, when the reaction is stopped in a state where the raw materials remain as in Comparative Examples 1 and 2, the purity is extremely reduced because purification is difficult.

[0040]

According to the present invention, a novel compound, 2
Providing-(2-pyridyl) pyrimidine derivatives expands the route of acquiring novel pharmaceuticals, agricultural chemicals, ligands, liquid crystals, surfactants, electrophotography and organic electroluminescence, especially containing pyridine and pyrimidine nuclei. It is very important in research and development of these research fields, and also in industrial and practical applications.

Claims (1)

[Claims] 1. A 2- (2-pyridyl) pyrimidine derivative represented by the following general formula (I). Embedded image In the formula, R1 and R2 may be the same or different and represent a hydrogen atom, an alkyl group, or an aryl group. Also,
R1 and R2 may combine with each other to form a ring. However, when R2 is a phenyl group, R1 represents an alkyl group or an aryl group.