Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-12-12
2003-01-07
Morris, Patricia L. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C546S257000
Reexamination Certificate
active
06504032
ABSTRACT:
TECHNICAL FIELD
This invention provides a process for producing a 2-pyridylpyridine derivative, which is an important intermediate for producing medicines, agricultural chemicals, catalyst ligands, and organic photosensitive materials or dyes for use in electrophotography or electroluminescence elements, in a high yield and with a high purity at a low production cost.
BACKGROUND ART
Various processes for producing 2-pyridylpyridines have been reported. For example, there has been reported a process of condensing a pyridine compound with an N-oxide of a pyridine compound in the presence of Pt— added Pd—C under heating (Yakugaku Zasshi, 99 (12) 1176, 1181 (1979)), but this process provides anendproduct ina low yield. Cross-coupling reaction utilizing Grignard reaction has also been reported (Japanese Patent Laid-Open No. 3169/1989), but this process involves such problems as that a pyridyl iodide compound necessary for obtaining a Grignard reagent for a pyridine is difficult to obtain or synthesize and that special equipment is required. Further, there have been proposed Ullmann condensation reaction between halogenated pyridines (Khim. Geol. Nauk., 114 (1970)) and a process of cross-coupling a halogenated pyridine compound with various metal derivatives in the presence of a Pd catalyst. For example, there have been reported a process of cross-coupling a borane derivative (Chem. Pharm. Bull., 33 (11) 4755 (1985)), (Heterocycles, 23 (9) 2375 (1985)), a process of cross-coupling an alkyltin derivative (Tetrahedron Lett., 33, 2199 (1992)), and a process of cross-coupling a halogenated pyridine compound in the presence of a Ni catalyst (WO9852922).
These processes, however, involve many problems for producing the end product on a large scale. For example, they require extremely expensive catalysts or reagents and require a special treatment for metal-containing waste liquor to be generated. In addition, these reactions produce by-products in a large amount which are extremely difficult to separate, thus products with a purity high enough to be used as intermediates for medicines or electronic materials not having been obtained.
On the other hand, as a process for synthesizing a 1,2,4-triazine using glyoxal, there have been reported a process of acting formamidrazone hydrochloride (Chem. Ber., 101, 3952 (1968)), a process of acting methylthioamidrazone (J. Heterocyclic Chem., 7, 767 (1970)), and an improved process of a process of acting ethyloxalamidrazonate (Synthesis, 5, 351 (1974)), since a process was reported which comprises reacting glyoxal with ethyloxalamidrazonate, then conducting decarboxylation (J. Org. Chem., 31, 1720 (1966)).
In every case, however, glyoxal having a high reactivity yields by-products in large amounts, leading to a low yield. In addition, it requires a special apparatus such as equipment for low temperature and requires a number of steps, thus processes using glyoxal not having been satisfactory as industrial processes.
In addition, it has recently been reported to synthesize a 1,2,4-triazine using a ketone which is less reactive than glyoxal (Tetrahedron Lett., 39, 8817, 8821, 8825 (1998)). However, since this synthesis needs excess hydrazine, a step of removing hydrazine is required, and the substrate is limited to ketones. Thus, the synthesisis applicable only to synthesis of pyridines having a substituent. Accordingly, a process of synthesizing a 2-pyridylpyridine derivative (e.g., 2,4′-dipyridyl, 2,3′-dipyridyl or 2,2′-dipyridyl) via a 1,2,4-triazine using highly reactive glyoxal is so difficult that there have been no reports on the process.
The invention provides a process for producing a 2-pyridylpyridine derivative usable as an intermediate for medicines and agricultural chemicals, which does not require to use expensive metal catalysts, which does not cause environmental problems, and which can be conducted on an industrial scale and, more particularly, it provides a process for producing a 2-pyridylpyridine derivative with an extremely high purity and a high selectivity in a high yield, which can be conducted in a sequential manner at a low production cost.
DISCLOSURE OF THE INVENTION
The objects of the invention can be attained by the following processes.
(1) A process for producing a 2-pyridylpyridine derivative, which comprises:
(A) a step of producing an amidrazone compound from a cyano group-containing heterocyclic compound in a water solvent;
(B) a step of producing a 1,2,4-triazine compound from the amidrazone compound in a water solvent; and
(C) a step of producing a 2-pyridylpyridine derivative from the 1,2,4-triazine compound.
(2) The process for producing a 2-pyridylpyridine derivative as described in (1), wherein the step (A) of producing an amidrazone compound from a cyano group-containing heterocyclic compound comprises reacting the cyano group-containing heterocyclic compound with a hydrazine compound in a water solvent.
(3) The process for producing a 2-pyridylpyridine derivative as described in (1), wherein the step (B) of producing a 1,2,4-triazine compound from the amidrazone compound comprises reacting the amidrazone compound with glyoxal in a water solvent.
(4) The process for producing a 2-pyridylpyridine derivative as described in (1), wherein the step (C) of producing a 2-pyridylpyridine derivative from the 1,2,4-triazine compound comprises reacting the 1,2,4-triazine compound with a 2,5-norbornadiene in a reaction solvent.
(5) The process for producing a 2-pyridylpyridine derivative as described in (1), wherein the amount of water to be used as a solvent in the step (A) of producing an amidrazone compound from a cyano group-containing heterocyclic compound is 0.1 to 10 times by weight the amount of the cyano group-containing heterocyclic compound.
(6) The process for producing a 2-pyridylpyridine derivative as described in (1), wherein the reaction temperature in the step (A) of producing an amidrazone compound from a cyano group-containing heterocyclic compound ranges from 0 to 120° C.
(7) The process for producing a 2-pyridylpyridine derivative as described in (1), wherein the amount of water to be used as a solvent in the step (B) of producing a 1,2,4-triazine compound from the amidrazone compound is 1 to 100 times by weight the amount of the cyano group-containing heterocyclic compound.
(8) The process for producing a 2-pyridylpyridine derivative as described in (1), wherein the reaction temperature in the step (B) of producing a 1,2,4-triazine derivative from the amidrazone compound ranges from 0 to 100° C.
(9) The process for producing a 2-pyridylpyridine derivative as described in (4), wherein the reaction solvent to be used in the step (C) of producing a 2-pyridylpyridine derivative from the 1,2,4-triazine compound is an aromatic hydrocarbon.
The invention is described in more detail below.
In order to describe the invention in more detail, one embodiment of the process of the invention is shown below which, however, does not limit the invention in any way.
The invention is a process for producing a 2-pyridylpyridine derivative in a sequential manner from a cyano group-containing heterocyclic compound via an amidrazone compound and a 1,2,4-triazine compound.
Water is used as a solvent in the step of preparing an amidrazone compound from a cyano group-containing heterocyclic compound and the step of preparing a triazine compound from the amidrazone compound in accordance with the invention. In conducting the reaction in the step of preparing an amidrazone compound from a cyano group-containing heterocyclic compound in a water solvent, production of a tetrazine by dimerization of the amidrazone compound is depressed in comparison with the case of using a conventionally proposed solvent and, in addition, a hydrazine need not be used in a large excess amount based on the cyano group-containing heterocyclic compound.
That is, in case where the reaction is carried out using other solvent than water as in the conventional processes, the reaction does not stop at the stage where the amidrazone compo
Ikeuchi Fumiaki
Shintou Taichi
Suda Hirokazu
Morris Patricia L.
Sankio Chemical Co., Ltd.
Sughrue & Mion, PLLC
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