JP5407332B2 - Method for producing quarterpyridine derivative and its intermediate - Google Patents

Description

  The present invention relates to a method for producing a quarterpyridine derivative and an intermediate thereof, and more specifically, relates to a method for producing a quarterpyridine derivative and an intermediate thereof capable of easily producing a quarterpyridine derivative.

  A dye-sensitized solar cell composed of a dye, a semiconductor electrode, an electrolytic solution, and a metal electrode is called a Gretzel cell, and is advantageous in terms of cost compared to a conventional silicon solar cell. In addition to that, it is also excellent in terms of flexibility and design, and is expected to be applied in a wide range of fields. However, the photoelectric conversion efficiency is still not sufficient, and there is a demand for the development of high-performance dyes for practical use. Various dyes and organic dyes (containing no metal) have been studied as dyes. However, ruthenium complexes are considered promising in terms of performance, and many ruthenium complexes have already been studied and developed. Broadly speaking, bipyridine complexes (for example, see Non-Patent Documents 1, 2, and 3), terpyridine complexes (for example, see Non-Patent Document 4), quarterpyridine complexes (for example, Non-Patent Document 5). , 6 and Patent Document 1). In bipyridine complex and terpyridine complex, two NCS ligands are generally in cis form, but in quarter pyridine complex, it is specific in that it is in trans form. It becomes broad and the absorption on the long wavelength side becomes strong.

  As the quarterpyridine-based ruthenium complex, a ruthenium complex of a quarterpyridine derivative represented by the following formula (1B) is disclosed (for example, see Patent Document 1).

The “COOEt” group of the quarterpyridine derivative is converted to a Ru complex (dye) and then converted into a “COOH” group by hydrolysis. The “COOH” group is a substituent necessary for adsorbing the dye to the TiO ₂ electrode of the dye-sensitized solar cell. Further, the alkyl group of R is important for the weather resistance of the dye-sensitized solar cell. The quarterpyridine derivative is obtained by synthesizing a bipyridine derivative (organic metal) represented by the following formula (2A) from a bipyridine derivative represented by the following formula (1A), and then a bipyridine derivative represented by the following formula (3A): And synthesized by reacting with a bipyridine derivative represented by the following formula (2A).

However, the above-described method for producing quarterpyridine derivatives cannot always produce the desired quarterpyridine derivative easily.
J. et al. Phys. Chem. B, 2003, 107, 8981-8987 Langmuir, 2002, 18, 952-954 Langmuir, 2001, 17, 5999-5999. J. et al. Am. Chem. Soc. 2001, 123, 1613-1624. Inorg. Chem. 2002, 41, 367-378 Inorg. Chem. 2006, 45, 4642-4653 JP-A-2005-190875

  In the production method of the quarterpyridine derivative, 1A and 3A to be produced as intermediates were extremely difficult to synthesize. For this reason, the above-described production method cannot easily produce a quarterpyridine derivative. Further, when industrial use is assumed, it is considered that the production is further difficult.

  This invention is made | formed in view of the above-mentioned problem, and provides the manufacturing method of a quarterpyridine derivative and its intermediate body which can manufacture a quarterpyridine derivative easily.

  The production method of the quarterpyridine derivative of the present invention and the intermediate thereof for solving the above-mentioned problems are as follows.

[1] A bipyridine derivative represented by the following formula (1) and an organometallic intermediate represented by the following formula (2) are reacted using a transition metal catalyst and represented by the following formula (3). A method for producing a quarterpyridine derivative that produces a quarterpyridine derivative.

(In Formula (1), Z is an alkyl group, an aryl group , Y is a perfluoroalkylsulfonyl group, R ³ and R ⁴ are each independently an alkyl group or an aryl group , or are bonded to each other to form a cyclic structure. May be formed.)

(In Formula (2), M is a metal, R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group, L is a ligand, and n is 1 to 3) Is an integer.)

(In Formula (3), Z is an alkyl group or an aryl group , R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group, and R ³ and R ⁴ are each independently And an alkyl group, an aryl group , or a group that may be bonded to each other to form a cyclic structure.)

[2] The acetal and ester of the quarterpyridine derivative represented by the following formula (3) are hydrolyzed to formyl group and carboxyl group, respectively, and the obtained formyl group is oxidized to form a carboxyl group by the following formula (4). A method for producing a quarterpyridine derivative, wherein the quarterpyridine derivative is produced.

(In Formula (3), Z is an alkyl group or an aryl group , R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group, and R ³ and R ⁴ are each independently And an alkyl group, an aryl group , or a group that may be bonded to each other to form a cyclic structure.)

(In Formula (4), R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group.)

[3] A bipyridine derivative represented by the following formula (1).

(In Formula (1), Z is an alkyl group, an aryl group , Y is a perfluoroalkylsulfonyl group, R ³ and R ⁴ are each independently an alkyl group or an aryl group , or are bonded to each other to form a cyclic structure. May be formed.)

[ 4 ] A quarterpyridine derivative represented by the following formula (3).

(In Formula (3), Z is an alkyl group or an aryl group , R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group, and R ³ and R ⁴ are each independently And an alkyl group, an aryl group , or a group that may be bonded to each other to form a cyclic structure.)

  In the production method of the quarterpyridine derivative of the present invention, a predetermined intermediate is easily produced in the production process, and finally the quarterpyridine derivative is produced using them, so that the quarterpyridine derivative is easily produced as a whole. Therefore, it is possible to produce industrially and stably.

  In addition, since the intermediate of the quarterpyridine derivative of the present invention can be easily synthesized, the quarterpyridine derivative can be easily produced as a whole by using these for the production of the quarterpyridine derivative. It is possible to produce industrially and stably.

  Next, the best mode for carrying out the present invention will be described in detail. However, the present invention is not limited to the following embodiments, and is within the scope of the gist of the present invention. It should be understood that design changes, improvements, and the like can be made as appropriate based on the knowledge.

(Method for producing quarterpyridine derivative A)
The production method of the quarterpyridine derivative (quarterpyridine derivative A) of the present invention comprises the bipyridine derivative (bipyridine derivative A) of the present invention represented by the above formula (1) and the present invention represented by the above formula (2). An organic metal intermediate (organic metal intermediate 1) is reacted with a transition metal catalyst to produce a quarterpyridine derivative (quarterpyridine derivative A) of the present invention represented by the above formula (3). . The reaction is preferably performed by adding the organometallic intermediate 1, the bipyridine derivative A, and the transition metal catalyst to an organic solvent under an inert gas atmosphere. The reaction temperature is preferably 20 to 180 ° C., and the reaction time is preferably 1 to 72 hours. Examples of transition metal catalysts include organic palladium catalysts and organic nickel catalysts. Among these, an organic palladium catalyst having phosphine, dibenzylideneacetone, acetyl group or halogen group as a ligand is preferable. Specific examples include Pd (PPh ₃ ) ₄ , Pd ₂ (dba) ₃ , Pd (OAc) ₂ , Pd (PPh ₃ ) ₂ Cl ₂ (Ph is a phenyl group, dba is dibenzylideneacetone, and Ac is Represents an acetyl group). The amount of the transition metal catalyst used is preferably 1 to 20 mol%, more preferably 2 to 5 mol%, relative to the bipyridine derivative A represented by the above formula (1). It is preferable to add a salt such as LiCl, CsF, CuI, AsPh ₃ during the reaction because the yield of the reaction may increase. The addition amount of a salt such as LiCl is preferably 1 to 5 mol, and more preferably 1 to 3 mol, per 1 mol of bipyridine derivative A. As the organic solvent, a hydrocarbon solvent or an amide solvent is preferable, and examples thereof include toluene, xylene, DMF and the like. The addition amount of the organic solvent is preferably 0.1 to 5 L, and more preferably 1 to 3 L with respect to 1 mol of the bipyridine derivative A.

In the above formula (2), examples of the alkyl group include methyl group, ethyl group, propyl group, i-propyl group, butyl group, i-butyl group, s-butyl group, t-butyl group and the like. Examples of the aryl group include a phenyl group and a naphthyl group. Examples of the substituted alkyl group include a benzyl group and a methoxymethyl group. Among these, as R ¹ and R ² , hydrogen, a methyl group, a pentyl group, a nonyl group, and a heptadecyl group are preferable. As the metal (M), tin, zinc, boron and the like are preferable. Examples of the ligand L include an alkyl group, an aryl group, an alkoxyl group, chlorine, bromine and iodine.

(Quarterpyridine derivative A)
One embodiment of the quarterpyridine derivative of the present invention obtained by the production method of the quarterpyridine derivative A of the present invention is a quarterpyridine derivative (quarterpyridine derivative A) represented by the above formula (3).

In the above formula (3), Z is a monovalent organic group, R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group, and R ³ and R ⁴ are each independently Are monovalent organic groups which may be bonded to each other to form a cyclic structure. Examples of the alkyl group for R ¹ and R ² include a methyl group, an ethyl group, a propyl group, an i-propyl group, a butyl group, an i-butyl group, an s-butyl group, and a t-butyl group. Examples of the aryl group include a phenyl group and a naphthyl group. Examples of the substituted alkyl group include a benzyl group and a methoxymethyl group. Among these, as R ¹ and R ² , hydrogen, a methyl group, a pentyl group, a nonyl group, and a heptadecyl group are preferable. Examples of Z that is a monovalent organic group include an alkyl group and an aryl group. Examples of the alkyl group include an ethyl group, a propyl group, an i-propyl group, a butyl group, an i-butyl group, and a cyclohexyl group. Z is preferably an i-propyl group. Examples of R ³ and R ⁴ include an alkyl group and an aryl group. As an alkyl group, a C1-C4 thing is preferable. Further, when R ³ and R ⁴ are bonded to each other to form a cyclic structure, “—CH ₂ C (CH ₃ ) ₂ CH ₂ —” or the like is preferable.

  The quarterpyridine derivative A of the present invention is an intermediate of the quarterpyridine derivative B represented by the above formula (4). Since the quarterpyridine derivative A can be synthesized from the organometallic intermediate 1 of the present invention synthesized from the following bipyridine derivative B and the bipyridine derivative A of the present invention, it can be easily synthesized in a high yield. Therefore, the quarterpyridine derivative B can be easily produced at a high yield, and thus can be produced stably industrially.

(Method for producing quarterpyridine derivative B)
In the production method of the quarterpyridine derivative (quarterpyridine derivative B) represented by the above formula (4), first, the acetal and ester of the quarterpyridine derivative A represented by the above formula (3) are hydrolyzed to formyl group and The quarterpyridine derivative B is generated by converting the formyl group obtained by converting to a carboxyl group and then oxidizing the formyl group to a carboxyl group. Hydrolysis is acid hydrolysis and can be performed by stirring in an aqueous solution in the presence of an acid. The oxidation can be performed by using a general oxidizing agent. Examples of the acid that can be used for the acid hydrolysis include acetic acid, sulfuric acid, hydrochloric acid, p-toluenesulfonic acid, TFA, and the like. The amount of the acid used is preferably 100 to 500 mL with respect to 1 mol of quarterpyridine derivative A. The amount of water is preferably 100 to 500 mL with respect to 1 mol of the quarterpyridine derivative A. It is preferable to add an aldehyde compound such as pyridinecarboxaldehyde during the reaction because the yield of the reaction increases. The addition amount of the aldehyde compound is preferably 1 to 10 mol with respect to 1 mol of the quarterpyridine derivative A. The reaction temperature is preferably 0 to 100 ° C. The reaction time is preferably 0.5 to 24 hours. Examples of the oxidizing agent that can be used for the oxidation of aldehydes include chromates, permanganates, silver oxide, and chlorites. The amount of the oxidizing agent used is preferably 0.5 to 5 mol with respect to 1 mol of quarterpyridine derivative A. The reaction temperature is preferably 0 to 50 ° C. The reaction time is preferably 1 to 12 hours. By this reaction, the target compound can be obtained in a yield of 50 to 80 mol%.

In the above formula (4), the alkyl group preferably has 1 to 20 carbon atoms and may be linear or branched. Specific examples include a methyl group, an ethyl group, a propyl group, an i-propyl group, a butyl group, an i-butyl group, an s-butyl group, and a t-butyl group. As an aryl group, C1-C20 is preferable and a phenyl group, a naphthyl group, etc. are mentioned specifically ,. The substituted alkyl group preferably has 1 to 20 carbon atoms and may be linear or branched. Specific examples include a benzyl group and a methoxymethyl group. Among these, as R ¹ and R ² , hydrogen, a methyl group, a pentyl group, a nonyl group, and a heptadecyl group are preferable.

  As shown below, the bipyridine derivative A represented by the above formula (1) and the organometallic intermediate 1 represented by the above formula (2) can be easily synthesized. The quarterpyridine derivative A represented by the above formula (3) can be easily synthesized from the derivative A and the organometallic intermediate 1, and the quarterpyridine derivative B represented by the above formula (4) can be easily synthesized from the quarterpyridine derivative A. Can be synthesized. Therefore, according to the present invention, the quarterpyridine derivative A represented by the above formula (3) and the quarterpyridine derivative B represented by the above formula (4) can be easily produced in high yield. And by using these manufacturing methods, it is possible to produce industrially stably.

(Bipyridine derivative A)
The bipyridine derivative of the present invention, which is an intermediate in the production method of the quarterpyridine derivative of the present invention, is a bipyridine derivative (bipyridine derivative A) represented by the above formula (1).

In the formula (1), examples of the monovalent organic group (Z) include an alkyl group and an aryl group. Examples of the alkyl group include an ethyl group and a propyl group, and examples of the perfluoroalkylsulfonyl group include “CF ₃ SO ₂ —” and “C ₄ F ₉ SO ₂ —”. Examples of R ³ and R ⁴ include an alkyl group. As an alkyl group, a C1-C4 thing is preferable. Further, when R ³ and R ⁴ are bonded to each other to form a cyclic structure, “—CH ₂ C (CH ₃ ) ₂ CH ₂ —” or the like is preferable.

The bipyridine derivative A of the present invention is a synthetic equivalent of the bipyridine derivative 3A described above, and is an intermediate of the quarterpyridine derivative of the present invention. In the present invention, bipyridine derivative A, which is an intermediate in the production of quarterpyridine derivatives, can be easily synthesized in high yield by a simple operation using only a low-toxic reactant. In general, when synthesizing a quarterpyridine derivative, there are many examples using a pyridine compound having a chlorine group or a bromine group, but when introducing a chlorine group or a bromine group, a highly toxic reactant such as POCl ₃ or POBr ₃ is used. At the same time, the reaction operation becomes complicated. On the other hand, when a perfluoroalkyl sulfonate group is introduced instead of a chlorine group or a bromine group, it can be synthesized in a high yield by a simple reaction operation using a general-purpose reagent. For this reason, it becomes possible to produce a quarterpyridine derivative easily, efficiently and in high yield.

(Production method of bipyridine derivative A)
In the production method of the bipyridine derivative A of the present invention, first, a pyridine derivative 2 represented by the following formula (6) in which a formyl group is protected is produced by reacting a pyridine derivative represented by the following formula (5) with an alcohol. . The reaction is carried out in an organic solvent in the presence of an acid while stirring an alcohol and a pyridine derivative represented by the following formula (5). As the alcohol, a diol is preferable, and 2,2-dimethyl-1,3-propanediol is particularly preferable. The reaction temperature is preferably 0 to 120 ° C., and the reaction time is preferably 1 to 72 hours. As the organic solvent, dichloromethane, toluene and the like are preferable. Examples of the acid include p-toluenesulfonic acid, sulfuric acid, phosphoric acid and the like. The amount of 2,2-dimethylpropanediol added is preferably 1 to 5 moles and more preferably 1 to 2 moles relative to 1 mole of the pyridine derivative represented by the following formula (5). 0.1-3 mol is preferable with respect to 1 mol of pyridine derivatives represented by following formula (5), and, as for the addition amount of an acid, 1-2 mol is more preferable. By this reaction, the target pyridine derivative 2 can be obtained in a yield of 80 to 95 mol%.

In formulas (6) and (7), M is a metal, L is a ligand, n is an integer of 1 to ^3, and R ³ and R ⁴ are each independently a monovalent organic group. And a group that may be bonded to each other to form a cyclic structure. Examples of R ³ and R ⁴ include an alkyl group and an aryl group. As an alkyl group, a C1-C4 thing is preferable. Further, when R ³ and R ⁴ are bonded to each other to form a cyclic structure, “—CH ₂ C (CH ₃ ) ₂ CH ₂ —” or the like is preferable. Examples of the ligand L include an alkyl group, an aryl group, an alkoxyl group, chlorine, bromine and iodine. As the metal (M), tin, zinc, boron and the like are preferable.

Next, the pyridine derivative 2 and the metal compound are reacted to generate the organometallic intermediate 2 represented by the above formula (7). The reaction is carried out by adding and stirring the pyridine derivative 2, strong base and activator in an organic solvent under an inert gas atmosphere, and then adding and stirring the metal compound. Nitrogen or argon is preferable as the inert gas. As the organic solvent, those which are stable to strong bases are preferable, and hydrocarbon solvents or ether solvents are particularly preferable. As the hydrocarbon solvent, hexane and toluene are particularly preferable. As the ether solvent, diethyl ether, THF, and t-butyl methyl ether are particularly preferable. 1-5L is preferable with respect to 1 mol of pyridine derivatives represented by the said Formula (6), and, as for the quantity of an organic solvent, 2-4L is still more preferable. As the strong base, n-butyllithium, s-butyllithium, t-butyllithium, lithium tetramethylpiperidine and the like are preferable. 0.1-5 mol is preferable with respect to 1 mol of pyridine derivatives represented by the said Formula (6), and, as for the addition amount of a strong base, 1-3 mol is still more preferable. As the activator, lithium dimethylamino ethoxide (Me ₂ N (CH ₂ ) ₂ OLi, Me represents a methyl group) and boron trifluoride are preferable. 0.1-5 mol is preferable with respect to 1 mol of pyridine derivatives represented by the said Formula (6), and, as for the addition amount of an activator, 1-3 mol is still more preferable. Stirring before the addition of the metal compound is preferably performed at a temperature of −100 to 30 ° C., more preferably −80 to −40 ° C. The stirring time is preferably from 0.1 to 10 hours, and more preferably from 1 to 3 hours. As a metal compound, an organic tin compound, an organic boron compound, and a zinc compound are preferable. As the organic tin compound, trialkyltin halide is preferable, and tributyltin chloride is particularly preferable. As the organoboron compound, trialkoxyborane is preferable, and triisopropoxyborane is particularly preferable. As the zinc compound, zinc halide is preferable, and zinc chloride is particularly preferable. 0.1-10 mol is preferable with respect to 1 mol of pyridine derivatives represented by the said Formula (6), and, as for the addition amount of an organometallic compound, 1-4 mol is still more preferable. Stirring after the addition of the metal compound is preferably performed at a temperature of −100 to 100 ° C., more preferably −80 to 30 ° C. The stirring time is preferably 0.1 to 24 hours, and more preferably 2 to 4 hours. If the temperature is too high, side reactions may occur, and if the temperature is too low, the reaction may be slow. By this reaction, the organometallic intermediate 2 can be obtained in a yield of 40 to 90 mol%.

Next, the organometallic intermediate 2 and the pyridine derivative A represented by the following formula (8) are reacted using a transition metal catalyst to produce the bipyridine derivative (bipyridine derivative A) of the present invention represented by the above formula (1). ) Is generated. Examples of transition metal catalysts include organic palladium catalysts and organic nickel catalysts. Among these, an organic palladium catalyst having phosphine, dibenzylideneacetone, acetyl group or halogen group as a ligand is preferable. Specific examples include Pd (PPh ₃ ) ₄ , Pd ₂ (dba) ₃ , Pd (OAc) ₂ , Pd (PPh ₃ ) ₂ Cl ₂ (Ph is a phenyl group, dba is dibenzylideneacetone, and Ac is Represents an acetyl group). The amount of the transition metal catalyst used is preferably 0.01 to 0.20 moles with respect to 1 mole of the organometallic intermediate 2 represented by the above formula (7). More preferably, it is a mole. The reaction is preferably performed between the organometallic intermediate 2 and the pyridine derivative A in the presence of the transition metal catalyst in an organic solvent under an inert gas atmosphere. As the organic solvent, a hydrocarbon solvent, an ether solvent or an amide solvent is preferable, and for example, toluene, xylene, THF, DMF, DMAc and the like are preferably used. The amount of the organic solvent used is preferably 0.1 to 5 L, more preferably 1 to 3 L with respect to 1 mol of the organometallic intermediate 2 represented by the above formula (7). The reaction temperature is preferably 15 to 200 ° C, more preferably 50 to 180 ° C. If the temperature is too high, side reactions may occur, and if the temperature is too low, the reaction may be slow. The reaction time is preferably 1 to 72 hours. In addition, it is preferable to add a salt such as LiCl, CsF, CuI, AsPh ₃ during the reaction because the reaction yield may increase. The addition amount of a salt such as LiCl is preferably 1 to 5 mol, more preferably 1 to 3 mol with respect to 1 mol of the organometallic intermediate 2 represented by the above formula (7). . By this reaction, the bipyridine derivative A of the present invention can be obtained in a yield of 5 to 30 mol%.

(Pyridine derivative A)
The pyridine derivative which is an intermediate in the method for producing the bipyridine derivative A and is an intermediate in the method for producing the quarterpyridine derivative of the present invention is a pyridine derivative (pyridine derivative A) represented by the following formula (8).

In the above formula (8), Z is a monovalent organic group, and Y is a perfluoroalkylsulfonyl group. As monovalent organic group (Z), a C1-C10 alkyl group and an aryl group are preferable. Specific examples include an ethyl group, a propyl group, an i-propyl group, a butyl group, an i-butyl group, a cyclohexyl group, and a phenyl group. As the perfluoroalkylsulfonyl group, “CF ₃ SO ₂ —” , “C ₄ F ₉ SO ₂ —” and the like.

(Method for producing pyridine derivative A)
The method for producing the pyridine derivative A includes esterifying the carboxyl group of the pyridine derivative represented by the following formula (9), substituting each hydrogen of two hydroxyl groups with a perfluoroalkylsulfonyl group, and then formula (8) The pyridine derivative (pyridine derivative A) represented by these is produced | generated.

  The esterification of the carboxyl group of the pyridine derivative represented by the above formula (9) is preferably performed by reacting the carboxyl group with an alcohol while refluxing at 70 to 150 ° C. in the presence of an acid. Examples of the acid used include sulfuric acid and p-toluenesulfonic acid. 0.1-2 mol is preferable with respect to 1 mol of pyridine derivatives represented by the said Formula (9), and, as for the addition amount of an acid, 0.5-1 mol is still more preferable. Examples of the alcohol include ethanol, 2-propanol, and cyclohexanol. 0.1-2 mol is preferable with respect to 1 mol of pyridine derivatives represented by the said Formula (9), and, as for the addition amount of alcohol, 0.5-1 mol is still more preferable. In this reaction, alcohol is also a reaction solvent. By this reaction, the target ester can be obtained in a yield of 40 to 90 mol%.

As a method of substituting each hydrogen of the two hydroxyl groups of the pyridine derivative represented by the above formula (9) with a perfluoroalkylsulfonyl group, (CF ₃ SO ₂ ) ₂ O, ( A method of stirring at 40 to 30 ° C. for 1 to 12 hours in an organic solvent to which a perfluoroalkylsulfonic acid anhydride such as C ₄ F ₉ SO ₂ ) ₂ O and a base are added is preferable. Examples of the organic solvent include dichloromethane, chloroform, pyridine and the like. The amount of the perfluoroalkylsulfonic anhydride added is preferably 1 to 4 mol, and more preferably 2 to 3 mol, per 1 mol of the pyridine derivative represented by the above formula (9). Examples of the base include triethylamine and pyridine. The amount of the base added is preferably 1 to 4 mol, more preferably 2 to 3 mol, per 1 mol of the pyridine derivative represented by the above formula (9). 0.1-10L is preferable with respect to 1 mol of pyridine derivatives represented by the said Formula (9), and, as for the usage-amount of an organic solvent, 0.5-2L is still more preferable. By this reaction, a pyridine derivative substituted with the target perfluoroalkylsulfonyl group can be obtained in a yield of 80 to 95 mol%. This reaction is preferably performed after the esterification of the carboxyl group.

(Organic metal intermediate 1)
In the organometallic intermediate 1 represented by the above formula (2) used in the production method of the quarterpyridine derivative A of the present invention, R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group or a substituted group. It is an alkyl group, and the alkyl group preferably has 1 to 20 carbon atoms, and may be linear or branched. Specific examples include methyl, ethyl, propyl, i-propyl, butyl, i-butyl, s-butyl, t-butyl and the like. The aryl group preferably has 1 to 20 carbon atoms, and specific examples thereof include phenyl and naphthyl. The substituted alkyl group preferably has 1 to 20 carbon atoms and may be linear or branched. Specific examples include benzyl and methoxymethyl. Among these, as R ¹ or R ² , hydrogen, a methyl group, a pentyl group, a nonyl group, and a heptadecyl group are particularly preferable. M is a metal, and examples of the metal include tin, zinc, and boron. L is a ligand, and examples of the ligand include an alkyl group, an alkoxyl group, chlorine, bromine and the like.

(Method for producing organometallic intermediate 1)
The organometallic intermediate 1 represented by the above formula (2) is produced by reacting the bipyridine derivative B represented by the following formula (10) with a metal compound. The organometallic intermediate 1 can be obtained by reacting a bipyridine derivative B represented by the following formula (10), metallic magnesium and a metallic compound in an organic solvent under an inert gas atmosphere. At this time, the timing for adding the metal compound is not limited. That is, it can be obtained by first synthesizing a Grignard reagent of the bipyridine derivative B and then adding a metal compound and conducting a metal exchange reaction. It can also be obtained by a so-called Barbier type method in which the reaction is carried out by adding to the derivative B and magnesium. The method for producing the Grignard reagent is not particularly limited, and a known method described in “J. Org. Chem., 2004, 69, 1401-1404” or the like can be used. The metal exchange reaction is not particularly limited, and a known method described in “J. Org. Chem., 2004, 69, 1401-1404” or the like can be used. As the organic solvent used for the reaction, ether solvents such as THF and diethyl ether are preferable. The amount of the organic solvent used is preferably 0.1 to 1 L, more preferably 0.3 to 0.5 L mol per mol of bipyridine derivative B represented by the following formula (10). preferable. The magnesium metal used in the reaction is preferably 0.5 to 5 moles, more preferably 1 to 3 moles per mole of bipyridine derivative B represented by the following formula (10). The reaction temperature is preferably 0 to 40 ° C, more preferably 15 to 30 ° C. Moreover, as a metal compound used for a metal exchange reaction, an organic tin compound, an organic boron compound, and a zinc compound are preferable. As the organic tin compound, trialkyltin halide is preferable, and tributyltin chloride is particularly preferable. As the organoboron compound, trialkoxyborane is preferable, and triisopropoxyborane is particularly preferable. As the zinc compound, zinc halide is preferable, and zinc chloride is particularly preferable. The addition amount of the metal compound is preferably 0.5 to 5 mol, and more preferably 1 to 3 mol with respect to 1 mol of the bipyridine derivative B represented by the following formula (10). The solvent used for the metal exchange reaction is preferably THF, diethyl ether, DMF or the like. The amount of the solvent used is preferably 0.1 to 1 L, more preferably 0.4 to 0.6 L with respect to 1 mol of the bipyridine derivative B represented by the following formula (10). The reaction temperature is preferably 0 to 140 ° C.

(Bipyridine derivative B)
The bipyridine derivative, which is an intermediate in the method for producing the organometallic intermediate 1 and is an intermediate in the method for producing the quarterpyridine derivative of the present invention, is a bipyridine derivative (bipyridine derivative B) represented by the following formula (10). It is.

In formula (10), R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group. The alkyl group preferably has 1 to 20 carbon atoms and may be linear or branched. Specific examples include methyl, ethyl, propyl, i-propyl, butyl, i-butyl, s-butyl, t-butyl and the like. The aryl group preferably has 1 to 20 carbon atoms, and specific examples thereof include phenyl and naphthyl. The substituted alkyl group preferably has 1 to 20 carbon atoms and may be linear or branched. Specific examples include benzyl and methoxymethyl. Among these, as R ¹ or R ² , hydrogen, a methyl group, a pentyl group, a nonyl group, and a heptadecyl group are particularly preferable.

  In the production method of the quarterpyridine derivative of the present invention, the bipyridine derivative B, which is an intermediate in the production of the quarterpyridine derivative, can be easily synthesized, so that the quarterpyridine derivative can be easily produced. Therefore, it is possible to produce stably.

(Production method of bipyridine derivative B)
In the production method of the bipyridine derivative B, first, a pyridine derivative represented by the following formula (11) is reacted with a metal compound to produce an organometallic intermediate 3 represented by the following formula (12). The reaction is carried out by adding and stirring a pyridine derivative represented by the following formula (11), a strong base and an activator in an organic solvent under an inert gas atmosphere, and then adding and stirring a metal compound. Nitrogen or argon is preferable as the inert gas. As the organic solvent, those which are stable to strong bases are preferable, and hydrocarbon solvents or ether solvents are particularly preferable. As the hydrocarbon solvent, hexane and toluene are particularly preferable. As the ether solvent, diethyl ether, THF, and t-butyl methyl ether are particularly preferable. The amount of the organic solvent is preferably 1 to 5 L (liter) and more preferably 2 to 4 L (liter) with respect to 1 mol of the pyridine derivative represented by the following formula (11). As the strong base, n-butyllithium, s-butyllithium, t-butyllithium, lithium tetramethylpiperidine and the like are preferable. 0.1-5 mol is preferable with respect to 1 mol of pyridine derivatives represented by following formula (11), and, as for the addition amount of a strong base, 1-3 mol is still more preferable. As the activator, lithium dimethylamino ethoxide (Me ₂ N (CH ₂ ) ₂ OLi, Me represents a methyl group) and boron trifluoride are preferable. 0.1-5 mol is preferable with respect to 1 mol of pyridine derivatives represented by following formula (11), and, as for the addition amount of an activator, 1-3 mol is still more preferable. Stirring before the addition of the metal compound is preferably performed at a temperature of −100 to 30 ° C., more preferably −80 to −40 ° C. The stirring time is preferably from 0.1 to 10 hours, and more preferably from 1 to 3 hours. As a metal compound, an organic tin compound, an organic boron compound, and a zinc compound are preferable. As the organic tin compound, trialkyltin halide is preferable, and tributyltin chloride is particularly preferable. As the organoboron compound, trialkoxyborane is preferable, and triisopropoxyborane is particularly preferable. As the zinc compound, zinc halide is preferable, and zinc chloride is particularly preferable. 0.1-10 mol is preferable with respect to 1 mol of pyridine derivatives represented by following formula (11), and, as for the addition amount of an organometallic compound, 1-4 mol is still more preferable. Stirring after the addition of the metal compound is preferably performed at a temperature of −100 to 100 ° C., more preferably −80 to 30 ° C. The stirring time is preferably 0.1 to 24 hours, and more preferably 2 to 4 hours. If the temperature is too high, side reactions may occur, and if the temperature is too low, the reaction may be slow. By this reaction, the organometallic intermediate 3 represented by the following formula (12) can be obtained in a yield of 60 to 90 mol%.

  In the method for producing the bipyridine derivative B, the chlorine group of the bipyridine derivative B represented by the above formula (10) as a product is derived from the chlorine group of the pyridine derivative represented by the above formula (11). Therefore, it is necessary that the chlorine group of the pyridine derivative represented by the above formula (11) does not change during the reaction process, and the production method of the bipyridine derivative B has one feature that the chlorine group does not change. is there. The bipyridine derivative B needs to have a halogen group for the subsequent reaction. If the halogen group is a bromine group or an iodine group, it is as strong as the present invention during the reaction process. When a base is used, this halogen group such as bromine reacts and the bipyridine derivative B cannot be easily produced. On the other hand, if it is a chlorine group, it does not react even if a strong base is used, and the bipyridine derivative B can be easily synthesized by the reaction step shown in the production method of the bipyridine derivative B. In addition, a pyridine derivative having a chlorine group is inexpensive and easily available as compared with a pyridine derivative having a bromine group or an iodine group.

Next, the organometallic intermediate 3 represented by the above formula (12) and the pyridine derivative 1 represented by the above formula (13) are reacted with each other using a transition metal catalyst, which is represented by the above formula (14). A bipyridine derivative (bipyridine derivative B) is produced. Examples of transition metal catalysts include organic palladium catalysts and organic nickel catalysts. Among these, an organic palladium catalyst having phosphine, dibenzylideneacetone, acetyl group or halogen group as a ligand is preferable. Specific examples include Pd (PPh ₃ ) ₄ , Pd ₂ (dba) ₃ , Pd (OAc) ₂ , Pd (PPh ₃ ) ₂ Cl ₂ (Ph is a phenyl group, dba is dibenzylideneacetone, and Ac is Represents an acetyl group). 0.1-20 mol% is preferable with respect to the pyridine derivative 1 represented by the said Formula (13), and, as for the usage-amount of a catalyst, 2-5 mol% is still more preferable. In addition, the organometallic intermediate 3 is preferably 0.5 to 2 moles, more preferably 0.8 to 1.2 moles per mole of the pyridine derivative 1. The reaction is preferably performed between the organometallic intermediate 3 and the pyridine derivative 1 under reflux conditions in the presence of the transition metal catalyst in an organic solvent under an inert gas atmosphere. As the inert gas, nitrogen or argon is preferable. As the organic solvent, a hydrocarbon solvent, an ether solvent or an amide solvent is preferable, and for example, toluene, xylene, THF, DMF, DMAc and the like are preferably used. The amount of the organic solvent is preferably 0.1 to 5 L (liter) and more preferably 1 to 3 L (liter) with respect to 1 mole of the pyridine derivative 1. The reaction temperature is preferably 15 to 200 ° C, more preferably 50 to 180 ° C. If the temperature is too high, side reactions may occur, and if the temperature is too low, the reaction may be slow. The reaction time is preferably 1 to 72 hours. In addition, it is preferable to add a salt such as LiCl, CsF, CuI, AsPh ₃ during the reaction because the reaction yield may increase. The amount of salt such as LiCl added is preferably 1 to 5 moles, more preferably 1 to 3 moles per mole of pyridine derivative 1. By this reaction, a bipyridine derivative (bipyridine derivative B) can be obtained in a yield of 50 to 80 mol%.

Apart from the above method, a bipyridine derivative B represented by the above formula (10) can be produced by reacting a bipyridine derivative in which R ¹ and R ² are CH ₃ with an alkyl halide. This reaction is preferably performed by the method described in “Langmuir, 2002, 18, 952-954”. In the reaction, a bipyridine derivative and lithium diisopropylamide (LDA) are added to an organic solvent under an inert gas atmosphere, and the mixture is stirred at a temperature of −80 to −40 ° C. for 1 to 3 hours. It is preferably carried out by adding and stirring at −40 to 0 ° C. for 2 to 6 hours. By this reaction, the hydrogen atom of the methyl group of the bipyridine derivative is substituted with the alkyl group contained in the alkyl halide, whereby the bipyridine derivative B of the above formula (10) can be obtained. The amount of LDA added is preferably 1 to 3 moles, more preferably 2.0 to 2.5 moles, assuming that the bipyridine derivative is 1 mole. As the organic solvent, tetrahydrofuran (THF), diethyl ether or the like is preferably used. The amount of the organic solvent is preferably 1 to 5 L and more preferably 2 to 4 L with respect to 1 mol of the pyridine derivative. As alkyl halide, C1-C20 is preferable. Specific examples include butane bromide, octane bromide, hexadecane bromide and the like. The addition amount of the alkyl halide is preferably 1 to 5 mol, more preferably 2 to 3 mol, when the bipyridine derivative is 1 mol.

In the above formulas (11) to (14), R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group, M is a metal, L is a ligand, n is an integer of 1 to 3, and X ¹ is bromine, iodine or trifluoromethanesulfonate (“—OSO ₂ CF ₃ ”). n varies depending on the metal M. For example, when M is Sn, n = 3, when M is B, n = 2, and when M is Zn, n = 1. The alkyl group preferably has 1 to 20 carbon atoms and may be linear or branched. Specific examples include a methyl group, an ethyl group, a propyl group, an i-propyl group, a butyl group, an i-butyl group, an s-butyl group, and a t-butyl group. As an aryl group, C1-C20 is preferable and a phenyl group, a naphthyl group, etc. are mentioned specifically ,. The substituted alkyl group preferably has 1 to 20 carbon atoms and may be linear or branched. Specific examples include benzyl and methoxymethyl. Among these, as R ¹ or R ² , hydrogen, a methyl group, a pentyl group, a nonyl group, and a heptadecyl group are particularly preferable. As the metal (M), tin, zinc, boron and the like are preferable. Examples of the ligand L include an alkyl group, an alkoxyl group, chlorine, bromine and the like.

(Method for producing quarterpyridine derivative C)
In another method for producing a quarterpyridine derivative C represented by the following formula (16), the bipyridine derivative B represented by the above formula (10) is reacted with an organic metal to produce the above formula (2). ), An organometallic intermediate 1 represented by the following formula (15) is reacted with a bipyridine derivative represented by the following formula (15) using a transition metal catalyst. The quarter pyridine derivative C is produced. Since the production method of the quarterpyridine derivative C is thus produced using the bipyridine derivative represented by the above formula (10), it is necessary to use a bipyridine derivative which is difficult to produce as represented by the above formula (1A). Therefore, the quarterpyridine derivative C can be easily produced. The quarterpyridine derivative C is produced using a bipyridine derivative B represented by the above formula (10) and a bipyridine derivative represented by the following formula (15) which is a bipyridine derivative having a more general structure. However, when the quarterpyridine derivative is produced using the bipyridine derivative A represented by the above formula (1) as the bipyridine derivative represented by the following formula (15), it is represented by the above formula (3). This is a method for producing quarterpyridine derivative A.

In the above formulas (15) and (16), R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group or a substituted alkyl group, R is each independently a monovalent organic group, j is Is an integer of 1 to 3, k is an integer of 1 to 4, and X ¹ is bromine, iodine, or “—OSO ₂ CF ₃ ”. Examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an i-propyl group, a butyl group, an i-butyl group, an s-butyl group, and a t-butyl group. Examples of the aryl group include a phenyl group and a naphthyl group. Examples of the substituted alkyl group include a benzyl group and a methoxymethyl group. Among these, as R ¹ and R ² , hydrogen, a methyl group, a pentyl group, a nonyl group, and a heptadecyl group are preferable. As the metal (M), tin, zinc, boron and the like are preferable. Examples of the ligand L include an alkyl group, an aryl group, an alkoxyl group, chlorine, bromine and iodine. Examples of the monovalent organic group (R) include alkyl groups, carboxyl groups and derivatives thereof, formyl groups and derivatives thereof.

  In the production method of the quarterpyridine derivative C, a method of reacting the bipyridine derivative B represented by the above formula (10) with an organic metal to produce the organometallic intermediate 1 represented by the above formula (2), It is preferable to be the same as in the case of the “method for producing quarterpyridine derivative A”.

  The bipyridine derivative represented by the above formula (15) can be obtained, for example, by the method described in “J. Org. Chem., 2002, 67, 8269-8272”. In particular, when the bipyridine derivative A represented by the above formula (1) is used as the bipyridine derivative represented by the above formula (15), it can be obtained by the above-described method for producing the bipyridine derivative A. Specific examples of the bipyridine derivative represented by the formula (15) include 6-bromo-4,4'-dimethyl-2,2'-bipyridine.

  As a method of reacting the organometallic intermediate 1 represented by the above formula (2) with the bipyridine derivative represented by the above formula (15) using a transition metal catalyst, the production of the quarter pyridine derivative A described above is possible. In the method, a method of producing a quarterpyridine derivative A represented by the above formula (3) by reacting the organometallic intermediate 1 with the bipyridine derivative A represented by the above formula (1) using a transition metal catalyst. It is preferable to use the same method.

(Method for producing quarterpyridine derivative D)
In the method for producing quarterpyridine derivative D of the present invention, a bipyridine derivative represented by the following formula (17) is reacted with an organic metal to produce an organometallic intermediate 4 represented by the following formula (18), A bipyridine derivative represented by the formula (1) and the organometallic intermediate 4 are reacted using a transition metal catalyst to produce a quarterpyridine derivative D represented by the following formula (19).

In the above formulas (17) to (19), R is each independently a monovalent organic group, j is an integer of 1 to 3, k is an integer of 1 to 4, and X ² is a halogen atom. Yes, M is a metal, L is a ligand, n is an integer of 1 to 3, Z is a monovalent organic group, and R ³ and R ⁴ are each independently a monovalent organic group. It is a group that may be bonded to each other to form a cyclic structure. As the metal (M), tin, zinc, boron and the like are preferable. Examples of the ligand L include an alkyl group, an aryl group, an alkoxyl group, chlorine, bromine and iodine. Examples of the monovalent organic group (R) include alkyl groups, carboxyl groups and derivatives thereof, formyl groups and derivatives thereof. Examples of the monovalent organic group (Z) include an alkyl group and an aryl group. Examples of R ³ and R ⁴ include an alkyl group and an aryl group. As an alkyl group, a C1-C4 thing is preferable. Further, when R ³ and R ⁴ are bonded to each other to form a cyclic structure, “—CH ₂ C (CH ₃ ) ₂ CH ₂ —” or the like is preferable.

  The bipyridine derivative represented by the above formula (17) can be obtained, for example, by the method described in “J. Org. Chem., 2002, 67, 8269-8272”. In particular, when the bipyridine derivative B represented by the above formula (10) is used as the bipyridine derivative represented by the above formula (17), it can be obtained by the above-described “production method of the bipyridine derivative B”. Specific examples of the bipyridine derivative represented by the formula (17) include 6-bromo-4,4'-dimethyl-2,2'-bipyridine.

  In the method for producing quarterpyridine derivative D of the present invention, a method of producing an organometallic intermediate 4 represented by the above formula (18) by reacting a bipyridine derivative represented by the above formula (17) with an organometallic. Is preferably the same as in the above-mentioned “method for producing quarterpyridine derivative A”.

  As a method of reacting the organometallic intermediate 4 represented by the above formula (18) and the bipyridine derivative A represented by the above formula (1) using a transition metal catalyst, the above-described quarterpyridine derivative A can be used. In the production method, the organopyridine intermediate 1 and the bipyridine derivative A represented by the above formula (1) are reacted using a transition metal catalyst to produce the quarterpyridine derivative A represented by the above formula (3). It is preferable to use a method similar to the method.

(Method for producing terpyridine derivative A)
In the production method (1) of the terpyridine derivative represented by the following formula (21), a bipyridine derivative B represented by the above formula (10) is reacted with an organic metal to produce an organometallic represented by the above formula (2). Intermediate 1 is produced, and organometallic intermediate 1 is reacted with a pyridine derivative represented by the following formula (20) using a transition metal catalyst to produce terpyridine derivative A represented by the following formula (21). Is.

In the formulas (20) and (21), R is each independently a monovalent organic group, j is an integer of 1 to 4, X ¹ is bromine, iodine or “—OSO ₂ CF ₃ ”, R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group. Examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an i-propyl group, a butyl group, an i-butyl group, an s-butyl group, and a t-butyl group. Examples of the aryl group include a phenyl group and a naphthyl group. Examples of the substituted alkyl group include a benzyl group and a methoxymethyl group. Among these, as R ¹ and R ² , hydrogen, a methyl group, a pentyl group, a nonyl group, and a heptadecyl group are preferable. Examples of the monovalent organic group (R) include alkyl groups, carboxyl groups and derivatives thereof, formyl groups and derivatives thereof.

  In the method for producing terpyridine derivative A of the present invention, a method of producing an organometallic intermediate 1 represented by the above formula (2) by reacting a bipyridine derivative B represented by the above formula (10) with an organometallic. Is preferably the same as in the above-mentioned “method for producing quarterpyridine derivative A”.

  The pyridine derivative represented by the above formula (20) can be obtained, for example, by the method described in “Eur. J. Org. Chem., 2003, 19, 3855-3860”. Specific examples of the pyridine derivative represented by the formula (20) include 2-bromo-4-methylpyridine.

  As a method of reacting the organometallic intermediate 1 represented by the above formula (2) with the pyridine derivative represented by the above formula (20) using a transition metal catalyst, the production of the quarter pyridine derivative A described above is possible. In the method, a method of producing a quarterpyridine derivative A represented by the above formula (3) by reacting the organometallic intermediate 1 with the bipyridine derivative A represented by the above formula (1) using a transition metal catalyst. It is preferable to use the same method.

(Method for producing terpyridine derivative B)
In the production method of terpyridine derivative B represented by the following formula (24), a pyridine derivative represented by the following formula (22) and an organic metal are reacted to produce an organometallic intermediate 5 represented by the following formula (23). The bipyridine derivative represented by the above formula (1) and the organometallic intermediate 5 are reacted using a transition metal catalyst to produce a terpyridine derivative B represented by the following formula (24). is there.

In the formulas (22) to (24), R is each independently a monovalent organic group, j is an integer of 1 to 4, X ² is a halogen atom, L is a ligand, n Is an integer of 1 to 3, Z is a monovalent organic group, R ³ and R ⁴ are each independently a monovalent organic group, and may be bonded to each other to form a cyclic structure. It is. As the metal (M), tin, zinc, boron and the like are preferable. Examples of the ligand L include an alkyl group, an aryl group, an alkoxyl group, chlorine, bromine and iodine. Examples of the monovalent organic group (R) include alkyl groups, carboxyl groups and derivatives thereof, formyl groups and derivatives thereof. Examples of the monovalent organic group (Z) include an alkyl group and an aryl group. Examples of R ³ and R ⁴ include an alkyl group and an aryl group. As an alkyl group, a C1-C4 thing is preferable. Further, when R ³ and R ⁴ are bonded to each other to form a cyclic structure, “—CH ₂ C (CH ₃ ) ₂ CH ₂ —” or the like is preferable.

  The pyridine derivative represented by the above formula (20) can be obtained, for example, by the method described in “Eur. J. Org. Chem., 2003, 19, 3855-3860”. Specific examples of the pyridine derivative represented by the formula (20) include 2-bromo-4-methylpyridine.

  In the method for producing terpyridine derivative B of the present invention, a method of reacting a pyridine derivative represented by the above formula (22) with an organic metal to produce an organometallic intermediate 5 represented by the above formula (23) is as follows. In the above-mentioned “Production Method of Bipyridine Derivative B”, the same method as the method of producing the organometallic intermediate 3 represented by the formula (12) by reacting the pyridine derivative represented by the formula (11) with the organometallic. It is preferable to use this method.

  As a method of reacting the organometallic intermediate 5 represented by the above formula (23) with the bipyridine derivative A represented by the above formula (1) using a transition metal catalyst, the above-described quarterpyridine derivative A In the production method, the organopyridine intermediate 1 and the bipyridine derivative A represented by the above formula (1) are reacted using a transition metal catalyst to produce the quarterpyridine derivative A represented by the above formula (3). It is preferable to use a method similar to the method.

(Synthesis Example 1)
In a 1 L flask equipped with a magnetic stirrer and a three-way cock, 2-bromo-4-methylpyridine (10.0 g, 58 mmol) and anhydrous THF (400 mL) were taken and stirred under a nitrogen stream using a dry ice bath. And cooled to -78 ° C. To the solution, a 2 mol / L lithium diisopropylamide in THF / heptane / ethylbenzene solution (44 mL, 88 mmol) was added dropwise over about 5 minutes using a syringe and stirred at −78 ° C. for 1.5 hours. To this solution, a THF solution (100 mL) of 1-bromohexadecane (19.5 g, 64 mol) was added at once using a syringe. After the addition, the temperature was raised to −20 ° C. over about 15 minutes, and the mixture was stirred at −20 ° C. for 2 hours. The mixture was further warmed to room temperature over about 15 minutes and stirred for 2 hours. Water (about 50 mL) was added, and the mixture was extracted 3 times with ethyl acetate. The combined organic phase of the three extracts was dried over magnesium sulfate and then concentrated using a rotary evaporator. The obtained crude product was purified using a silica gel column to obtain a yellow oil of 2-bromo-4-heptadecylpyridine represented by the following formula (25) (16.7 g, 42 mmol, yield). 73%).

The analysis values are as follows.
¹ H-NMR (270 MHz, CDCl ₃ ) δ: 8.23 ppm (d, J = 5.0 Hz, 1H), 7.31 (s, 1H), 7.05 (d, 5.2 Hz, 1H), 2 .57 (t, 7.7 Hz, 2H), 1.61 (m, 2H), 1.29 (m, 28H), 0.88 (t, 6.6 Hz, 3H)
LC / MS (API-ES) m / z: 396.2 (100%, [M + H] ⁺ ), 398.2 (100%), 397.2 (25%), 399.2 (25%)

(Synthesis Example 2)
In a 300 mL flask equipped with a magnetic stirrer and a three-way cock, 2- (N, N-dimethylamino) ethanol (10 mL, 100 mmol) and hexane (50 mL) were taken and stirred in a nitrogen stream using an ice bath. Cooled down. To this solution, a 1.6 mol / L n-butyllithium hexane solution (125 mL, 200 mmol) was added dropwise over about 10 minutes using a syringe. After stirring at 0 ° C. for 15 minutes, the mixture was cooled to −78 ° C. using a dry ice bath. To this solution, a hexane solution (50 mL) of 2-chloropyridine (5.67 g, 50 mmol) was added dropwise over about 5 minutes using a syringe. After stirring at −78 ° C. for 2 hours, tributyltin chloride (29 mL, 100 mmol) was added to the solution all at once using a syringe. After heating up to room temperature over about 1 hour, it stirred at room temperature for 2 hours. After adding water (about 100 mL) to this solution, it extracted 3 times using ethyl acetate. The combined organic phase of the three extracts was dried over magnesium sulfate and then concentrated using a rotary evaporator. The resulting crude product was purified using a silica gel column to obtain a yellow oil of 2-tributylstannyl-6-chloropyridine.

The analysis values are as follows.
LC / MS (API-ES) m / z: 404.1 (100%, [M + H] ⁺ ), 402.1 (75%), 403.1 (40%), 406.1 (40%), 400 .1 (35%), 401.1 (30%), 405.1 (25%), 408.1 (20%), 407.1 (10%)

  2-Bromo-4-methylpyridine (7.74 g, 45 mmol) and p-xylene (25 mL) were added to 2-tributylstannyl-6-chloropyridine synthesized above, and then three times using a vacuum apparatus. I was degassed. Tetrakis (triphenylphosphine) palladium (1.45 g, 1.3 mmol) is taken in a 500 mL flask equipped with a magnetic stirrer, oil bath, three-way cock and Dimroth condenser, and after nitrogen substitution, the above-mentioned degassed mixed solution is added. It was added using a syringe. The mixed solution was refluxed at 150 ° C. for about 10 hours under a nitrogen stream. After cooling to room temperature, the solution was acidified with 1N hydrochloric acid, and this solution was extracted three times with 1N hydrochloric acid. The aqueous phase combined with the three extracts was made basic with sodium carbonate, and the aqueous phase was extracted 5 times with ethyl acetate. The ethyl acetate phase combined with the extract of 5 times was dried over magnesium sulfate and then concentrated using a rotary evaporator. The obtained crude product was purified using a silica gel column to obtain white crystals of 6-chloro-4′-methyl-2,2′-bipyridine represented by the following formula (26) (7.32 g). 35 mmol, 71% yield).

The analysis values are as follows.
¹ H-NMR (270 MHz, CDCl ₃ ) δ: 8.52 ppm (d, J = 4.9 Hz, 1H), 8.34 (d, 8.1 Hz, 1H), 8.24 (s, 1H), 7 .76 (dd, 7.8 Hz, 7.6 Hz, 1 H), 7.33 (d, 7.8 Hz, 1 H), 7.15 (d, 5.1 Hz, 1 H), 2.44 (s, 3 H)
LC / MS (API-ES) m / z: 205.1 (100%, [M + H] ⁺ ), 207.1 (30%), 206.1 (15%)

(Synthesis Example 3)
In a 50 mL flask equipped with a magnetic stirrer and a three-way cock, 6-chloro-4′-methyl-2,2′-bipyridine (2.05 g, 10 mmol) and anhydrous THF (20 mL) were taken and stirred under a nitrogen stream. Then, it was cooled to −78 ° C. using a dry ice bath. To this solution, 2.0 mol / L of lithium diisopropylamide in THF / heptane / ethylbenzene (6 mL, 12 mmol) was added dropwise using a syringe over about 5 minutes, and the mixture was stirred at -78 ° C for 2 hours. To this solution was added 1-bromohexadecane (3.05 g, 10 mmol) in THF (20 mL) all at once using a syringe. After the addition, the temperature was raised to −20 ° C. over about 1 hour, and the mixture was stirred at −20 ° C. for 4 hours. After adding water, the mixture was warmed to room temperature and extracted three times with ethyl acetate. The combined organic phase of the three extracts was dried over magnesium sulfate and then concentrated using a rotary evaporator. The obtained crude product was purified using a silica gel column to obtain a yellowish white powder of 6.chloro-4′-heptadecyl-2,2′-bipyridine represented by the following formula (27) (2.96 g). 6.9 mmol, 69% yield).

The analysis values are as follows.
¹ H-NMR (270 MHz, CDCl ₃ ) δ: 8.54 ppm (d, J = 5.1 Hz, 1H), 8.34 (d, 7.6 Hz, 1H), 8.23 (s, 1H), 7 .76 (dd, 7.8 Hz, 7.6 Hz, 1H), 7.33 (d, 7.6 Hz, 1H), 7.15 (d, 5.1 Hz, 1H), 2.69 (t, 7.H). 8Hz, 2H), 1.68 (m, 2H), 1.40-1.25 (m, 28H), 0.88 (t, 7.0Hz, 3H)
LC / MS (API-ES) m / z: 429.3 (100%, [M + H] ⁺ ), 431.3 (45%), 430.3 (40%), 432.3 (10%)

(Synthesis Example 4)
2- (N, N-dimethylamino) ethanol (4 mL, 40 mmol) and hexane (10 mL) are placed in a 100 mL flask equipped with a magnetic stirrer and a three-way cock and cooled using an ice bath while stirring under a nitrogen stream. did. To this solution, a 1.6 mol / L n-butyllithium hexane solution (50 mL, 80 mmol) was added dropwise over about 10 minutes using a syringe. After stirring at 0 ° C. for 15 minutes, the mixture was cooled to −78 ° C. using a dry ice bath. To this solution, a hexane solution (10 mL) of 2-chloropyridine (2.27 g, 20 mmol) was dropped over about 5 minutes using a syringe. After stirring at −78 ° C. for 2 hours, tributyltin chloride (5.5 mL, 20 mmol) was added to the solution all at once using a syringe. After heating up to room temperature over about 1 hour, it stirred at room temperature for 2 hours. Water was added to this solution and then extracted three times with ethyl acetate. The combined organic phase of the three extracts was dried over magnesium sulfate and then concentrated using a rotary evaporator. The resulting crude product was purified using a silica gel column to obtain a yellow oil of 2-tributylstannyl-6-chloropyridine.

  2-Bromo-4-heptadecylpyridine (6.90 g, 17 mmol) and p-xylene (40 mL) were added to 2-tributylstannyl-6-chloropyridine synthesized above, and then 3 using a vacuum apparatus. I degassed once. Tetrakis (triphenylphosphine) palladium (0.69 g, 0.6 mmol) is taken into a 50 mL flask equipped with a magnetic stirrer, oil bath, three-way cock and Dimroth condenser, and after nitrogen substitution, the above-mentioned degassed mixed solution is added. Was added using a syringe. The mixed solution was refluxed at 140 ° C. for about 8 hours under a nitrogen stream. After allowing to cool to room temperature, water (about 40 mL) was added, and the mixture was extracted 3 times with ethyl acetate. The combined organic phase of the three extracts was dried over magnesium sulfate and then concentrated using a rotary evaporator. By purifying the obtained crude product using a silica gel column, white crystals of 6-chloro-4′-heptadecyl-2,2′-bipyridine represented by the above formula (27) were obtained (2.83 g, 6.6 mmol, yield 33%).

(Synthesis Example 5)
In a 50 mL flask equipped with a magnetic stirrer and a three-way cock, 6-chloro-4′-methyl-2,2′-bipyridine (2.05 g, 10 mmol) and anhydrous THF (20 mL) were taken and stirred under a nitrogen stream. Then, it was cooled to −78 ° C. using a dry ice bath. To the solution, a 2.0 mol / L lithium diisopropylamide in THF / heptane / ethylbenzene solution (6 mL, 12 mmol) was added dropwise over about 5 minutes using a syringe, and the mixture was stirred at −78 ° C. for 2 hours. . To this solution, a THF solution (20 mL) of 1-bromooctane (2.06 g, 10 mmol) was added dropwise using a syringe. After dripping, it heated up to -20 degreeC over about 1 hour, and stirred at -20 degreeC for 4 hours. After adding water, the mixture was warmed to room temperature and extracted three times with ethyl acetate. The combined organic phase of the three extracts was dried over magnesium sulfate and then concentrated using a rotary evaporator. The obtained crude product was purified using a silica gel column to obtain a yellow oil of 6-chloro-4′-nonyl-2,2′-bipyridine represented by the following formula (28) (2.05 g, 6.5 mmol, yield 65%).

The analysis values are as follows.
¹ H-NMR (270 MHz, CDCl ₃ ) δ: 8.54 ppm (d, J = 4.9 Hz, 1 H), 8.34 (dd, 7.8 Hz, 1.1 Hz, 1 H), 8.23 (d, J = 1.1 Hz, 1H), 7.76 (dd, 7.8 Hz, 7.6 Hz, 1H), 7.33 (dd, 7.6 Hz, 1.1 Hz, 1H), 7.15 (dd, 4 .9 Hz, 1.9 Hz, 1 H), 2.69 (t, 8.0 Hz, 2 H), 1.68 (m, 2 H), 1.33 to 1.23 (m, 12 H), 0.88 (t , 6.8Hz, 3H)
LC / MS (API-ES) m / z: 317.2 (100%, [M + H] ⁺ ), 319.2 (40%), 318.2 (25%), 320.2 (10%)

(Synthesis Example 6)
2-L (N, N-dimethylamino) ethanol (20 mL, 200 mmol) and hexane (100 mL) were placed in a 1 L flask equipped with a magnetic stirrer and a three-way cock, and cooled using an ice bath while stirring under a nitrogen stream. did. To this solution, a 1.6 mol / L n-butyllithium hexane solution (250 mL, 400 mmol) was added dropwise over about 5 minutes using a syringe. After stirring at 0 ° C. for 15 minutes, the mixture was cooled to −78 ° C. using a dry ice bath. To this solution, a mixture of 2-chloro-4-methylpyridine (12.8 g, 100 mmol) and hexane (100 mL) was added dropwise over about 5 minutes using a syringe. After stirring at −78 ° C. for 2 hours, tributyltin chloride (57 mL, 210 mmol) was added to the solution all at once using a syringe. After heating up to room temperature over about 1 hour, it stirred at room temperature for 2 hours. Water (about 200 mL) was added to this solution and then extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and then concentrated using a rotary evaporator. The resulting crude product was purified using a silica gel column to obtain 2-tributylstannyl-6-chloro-4-methylpyridine.

The analysis values are as follows.
¹ H-NMR (270 MHz, CDCl ₃ ) δ: 7.11 ppm (s, 1H), 6.97 (s, 1H), 2.28 (s, 3H), 1.54 (m, 6H), 1. 31 (m, 6H), 1.12 (t, J = 8.1 Hz, 6H), 0.88 (t, 7.3 Hz, 9H)
LC / MS (API-ES) m / z: 418.1 (100%, [M + H] ⁺ ), 416.1 (80%), 417.1 (40%), 420.1 (40%), 414 .1 (35%), 415.1 (25%), 419.1 (25%), 422.1 (20%), 421.1 (10%)

  2-Bromo-4-methylpyridine (14.2 g, 80 mmol) and p-xylene (150 mL) were added to 2-tributylstannyl-6-chloro-4-methylpyridine synthesized above, and then vacuum was used. And degassed three times. Tetrakis (triphenylphosphine) palladium (2.14 g, 1.9 mmol) is placed in a 1 L flask equipped with a magnetic stirrer, oil bath, three-way cock, and Dimroth condenser, and after purging with nitrogen, the above-mentioned degassed mixed solution is added. added. The solution was refluxed at 150 ° C. for about 10 hours under a nitrogen stream. After cooling to room temperature, the solution was acidified with 1N hydrochloric acid, and this solution was extracted three times with 1N hydrochloric acid. The combined aqueous phase was basified with sodium carbonate and the aqueous phase was extracted 5 times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and then concentrated using a rotary evaporator. The obtained crude product was purified using a silica gel column to obtain white crystals of 6-chloro-4,4′-dimethyl-2,2′-bipyridine represented by the following formula (29) (13. 3 g, 60 mmol, 60% yield).

The analysis values are as follows.
¹ H-NMR (270 MHz, CDCl ₃ ) δ: 8.49 ppm (d, J = 4.9 Hz, 1H), 8.20 (s, 1H), 8.14 (s, 1H), 7.13 (s 1H), 7.11 (d, 4.9 Hz, 1H), 2.41 (s, 3H), 2.39 (s, 3H)
LC / MS (API-ES) m / z: 219.1 (100%, [M + H] ⁺ ), 221.1 (40%), 220.1 (20%)

(Synthesis Example 7)
A 50 mL flask equipped with a magnetic stirrer and a three-way cock was charged with 6-chloro-4,4′-dimethyl-2,2′-bipyridine (0.66 g, 3.0 mmol) and anhydrous THF (9 mL), and a nitrogen stream Cooling to −78 ° C. using a dry ice bath while stirring under. To the solution, a 2 mol / L lithium diisopropylamide in THF / heptane / ethylbenzene solution (6 mL, 12 mmol) was added dropwise over about 5 minutes using a syringe and stirred at −78 ° C. for 2 hours. To this solution, a THF solution (3 mL) of 1-bromobutane (0.90 g, 6.6 mmol) was added dropwise using a syringe. After the dropwise addition, the mixture was brought to 0 ° C. using an ice bath and stirred for 3 hours. After adding water at 0 ° C., the mixture was warmed to room temperature and extracted three times with ethyl acetate. The combined organic phase of the three extracts was dried over magnesium sulfate and then concentrated using a rotary evaporator. The obtained crude product was purified using a silica gel column to obtain a yellow oil of 6-chloro-4,4′-dipentyl-2,2′-bipyridine represented by the following formula (30) (0. 38 g, 1.1 mmol, 38% yield).

The analysis values are as follows.
¹ H-NMR (270 MHz, CDCl ₃ ) δ: 8.53 ppm (d, 4.9 Hz, 1 H), 8.22 (s, 1 H), 8.17 (s, 1 H), 7.16 (s, 1 H ), 7.14 (dd, 5.1 Hz, 1.6 Hz, 1H), 2.69 (t, 7.8 Hz, 2H), 2.67 (t, 7.8 Hz, 2H), 1.69 (m) 4H), 1.35 (m, 8H), 0.90 (t, 6.5 Hz, 6H)
LC / MS (API-ES) m / z: 331.2 (100%, [M + H] ⁺ ), 333.2 (40%), 332.2 (30%), 334.2 (10%)

(Synthesis Example 8)
Citrazic acid (71 g, 460 mmol) and 2-propanol (about 1 L) were taken in a 2 L flask equipped with a magnetic stirrer, oil bath and Dimroth condenser. Concentrated sulfuric acid (about 50 mL) was added to this suspension and then refluxed for about 60 hours. Water (about 1 L) was taken in a 2 L beaker equipped with a magnetic stirrer, and a solid was obtained by dropping the previous solution (solution after refluxing for 60 hours) into this water. This solid was collected by filtration using a Kiriyama funnel, and the obtained solid was washed with ethanol. This solid was heat-dried under vacuum (<10 torr, about 50 ° C.) to obtain a white solid of isopropyl citrate represented by the following formula (31) (74 g, 380 mmol, yield 82%).

The analysis values are as follows.
¹ H-NMR (270 MHz, DMSO-d6) δ: 6.29 ppm (s, 2H), 5.09 (qq, J = 6.3 Hz, 1H), 1.30 (d, 6.3 Hz, 6H)
LC / MS (API-ES) m / z: 198.1 (100%, [M + H] ⁺ ), 156.1 (40%), 199.1 (10%)

(Synthesis Example 9)
Isopropyl citrate (50 g, 250 mmol) and dichloromethane (about 1.2 L) were placed in a 2 L flask equipped with a magnetic stirrer and a three-way cock and stirred under a nitrogen stream. Triethylamine (104 mL, 750 mmol) was added thereto, and then cooled to −78 ° C. using a dry ice bath. Trifluoromethanesulfonic anhydride (126 mL, 750 mmol) was added dropwise to the solution using a syringe over about 5 minutes, and the mixture was stirred at −78 ° C. for about 0.5 hours. After raising the temperature to room temperature over about 0.5 hours, the mixture was further stirred at room temperature for 2 hours. The reaction solution was washed twice with a saturated aqueous sodium hydrogen carbonate solution, dried over magnesium sulfate, and concentrated using a rotary evaporator. By purifying the obtained crude product using a silica gel column, yellow crystals of 2,6-bis (trifluoromethanesulfonoxy) -4-isopropoxycarbonylpyridine represented by the following formula (32) were obtained ( 97.3 g, 211 mmol, 84% yield).

The analysis values are as follows.
¹ H-NMR (90 MHz, CDCl ₃ ) δ: 7.81 ppm (s, 2H), 5.33 (qq, J = 6.2 Hz, 1H), 1.43 (d, 6.5 Hz, 6H)

(Synthesis Example 10)
To a 2 L flask equipped with a magnetic stirrer, 4-pyridinecarboxaldehyde (40.7 g, 375 mmol), 2,2-dimethyl-1,3-propanediol (77.7 g, 750 mmol), p-toluenesulfonic acid mono Hydrate (40.7 g, 750 mmol) and dichloromethane (about 1 L) were taken. Stir in air for about 24 hours at room temperature. The reaction solution was washed with a saturated aqueous solution of sodium hydrogen carbonate four times, dried over magnesium sulfate, and concentrated using a rotary evaporator to give 4- (4,4-dimethyl-2, White crystals of 6-dioxanyl) pyridine were obtained (63.5 g, 329 mmol, 88% yield).

The analysis values are as follows.
¹ H-NMR (90 MHz, CDCl ₃ ) δ: 8.63 ppm (d, J = 6.2 Hz, 2H), 7.42 (d, 6.2 Hz, 2H), 5.38 (s, 1H), 3 .75 (d, 10.7 Hz, 2H), 3.70 (d, 10.7 Hz, 2H), 1.27 (s, 3H), 0.81 (s, 3H)
LC / MS (API-ES) m / z: 194.1 (100%, [M + H] ⁺ ), 195.1 (15%)

Example 1
2- (N, N-dimethylamino) ethanol (5 mL, 50 mmol) and t-butyl methyl ether (30 mL) were placed in a 300 mL flask equipped with a magnetic stirrer and a three-way cock, and stirred while stirring under a nitrogen stream. Cooled using a bath. To this solution, a 1.6 mol / L n-butyllithium hexane solution (63 mL, 100 mmol) was added dropwise over about 5 minutes using a syringe. After stirring at 0 ° C. for 15 minutes, the mixture was cooled to −78 ° C. using a dry ice bath. To this solution was added 4- (4,4-dimethyl-2,6-dioxanyl) pyridine (4.83 g, 25 mmol) in t-butyl methyl ether (30 mL) using a syringe over about 5 minutes. And dripped. After stirring at −78 ° C. for 2 hours, tributyltin chloride (14 mL, 50 mmol) was added to the solution all at once using a syringe. After heating up to room temperature over about 1 hour, it stirred at room temperature for 2 hours. After adding water (about 100 mL) to this solution, it extracted 3 times using ethyl acetate. The combined organic phase of the three extracts was dried over magnesium sulfate and then concentrated using a rotary evaporator. The 2-tributylstannyl-4- (4,4-dimethyl-2,6-dioxanyl) pyridine thus obtained was used in the next coupling reaction without further purification.

The analysis values are as follows.
LC / MS (API-ES) m / z: 484.2 (100%, [M + H] ⁺ ), 482.2 (80%), 480.2 (40%), 483.2 (40%), 481 .2 (35%), 485.2 (25%), 486.2 (20%), 488.2 (20%)

  To 2-tributylstannyl-4- (4,4-dimethyl-2,6-dioxanyl) pyridine synthesized above, 2,6-bis (trifluoromethanesulfonyloxy) -4-isopropoxycarbonylpyridine (11.7 g) 25 mmol) and toluene (75 mL), followed by degassing three times using a vacuum apparatus. Tetrakis (triphenylphosphine) palladium (0.87 g, 0.75 mmol) and lithium chloride (3.18 g, 75 mmol) are taken into a 300 mL flask equipped with a magnetic stirrer, oil bath, three-way cock and Dimroth condenser, and nitrogen is added. After the replacement, the aforementioned degassed mixed solution was added. The mixture was refluxed at 110 ° C. for 8 hours under a nitrogen stream. After cooling to room temperature, the mixture was concentrated using a rotary evaporator. By purifying the obtained crude product using a silica gel column, 4-isopropoxycarbonyl-4 ′-(4,4-dimethyl-2,6-dioxanyl) -6- (shown by the following formula (34): A yellow solid of trifluoromethanesulfonoxy) -2,2′-bipyridine was obtained (3.40 g, yield 26%).

The analysis values are as follows.
¹ H-NMR (270 MHz, CDCl ₃ ) δ: 9.02 ppm (s, 1H), 8.74 (d, J = 4.9 Hz, 1H), 8.45 (s, 1H), 7.72 (s) 1H), 7.55 (dd, 4.9 Hz, 1.6 Hz, 1H), 5.48 (s, 1H), 5.33 (qq, 6.2 Hz, 1H), 3.83 (d, 11 .3 Hz, 2 H), 3.70 (d, 10.8 Hz, 2 H), 1.43 (d, 6.3 Hz, 6 H), 1.30 (s, 3 H), 0.84 (s, 3 H)
LC / MS (API-ES) m / z: 505.1 (100%, [M + H] ⁺ ), 506.1 (30%), 507.1 (10%)

(Example 2)
Into a 100 mL flask equipped with a magnetic stirrer, condenser and three-way cock, magnesium metal (30 mg, 1.2 mmol) was taken and dried by heating under reduced pressure, followed by anhydrous THF (0.5 mL) and nitrogen under a nitrogen stream. I ₂ (small piece) was added and stirred at room temperature for about 10 minutes. Thereto, an anhydrous THF solution (5 mL) of 6-bromo-2,2′-bipyridine (200 mg, 0.8 mmol) was dropped over about 10 minutes using a syringe. After dropping, the mixture was stirred at room temperature for about 4 hours. To this solution, anhydrous THF (10 mL) and 0.5 mol / L zinc chloride in THF (1.6 mL, 0.8 mmol) were added at once using a syringe and stirred at room temperature for about 3 hours. . Of 4-isopropoxycarbonyl-4 ′-(4,4-dimethyl-2,6-dioxanyl) -6- (trifluoromethanesulfonyloxy) -2,2′-bipyridine (390 mg, 0.8 mmol) A THF solution (10 mL) was added and degassed three times using a vacuum apparatus. Tetrakis (triphenylphosphine) palladium (92 mg, 0.08 mmol) was placed in a 100 mL flask equipped with a magnetic stirrer, oil bath, three-way cock, and Dimroth condenser, and after purging with nitrogen, the aforementioned degassed mixed solution was added. . The mixture was refluxed at 70 ° C. for about 6 hours under a nitrogen stream. After allowing to cool to room temperature, water was added, the mixture was filtered through celite, and extracted three times with ethyl acetate. The combined organic phase of the three extracts was dried over magnesium sulfate and then concentrated using a rotary evaporator. By purifying the obtained crude product using a silica gel column, 4′-isopropoxycarbonyl-4- (4,4-dimethyl-2,6-dioxanyl) -2,2 represented by the following formula (35) is obtained. A yellow solid of ': 6', 2 ″: 6 ″, 2 ′ ″-quarterpyridine was obtained (12 mg, 3% yield).

The analysis values are as follows.
¹ H-NMR (270 MHz, CDCl ₃ ) δ: 9.18 ppm (d, J = 1.4 Hz, 1 H), 8.96 (d, 1.6 Hz, 1 H), 8.78 (d, 5.1 Hz, 1H), 8.72 (m, 3H), 8.70 (s, 1H), 8.52 (dd, 8.1 Hz, 0.9 Hz, 1H), 8.03 (dd, 8.1, 8. 1 Hz, 1 H), 7.90 (dd, 7.6 Hz, 7.6 Hz, 1 H), 7.56 (d, 4.9 Hz, 1 H), 7.35 (dd, 7.3 Hz, 4.9 Hz, 1 H) ), 5.54 (s, 1H), 5.38 (qq, 6.2 Hz, 1H), 3.86 (d, 11.3 Hz, 2H), 3.73 (d, 10.5 Hz, 2H), 1.47 (d, 6.1 Hz, 6H), 1.33 (s, 3H), 0.85 (s, 3H)

(Example 3)
Into a 100 mL flask equipped with a magnetic stirrer, condenser and three-way cock, magnesium metal (96 mg, 4 mmol) was taken, dried by heating under reduced pressure, and then anhydrous THF (0.5 mL) and I ₂ under a nitrogen stream. (Small) was added and stirred at room temperature for about 10 minutes. An anhydrous THF solution (4 mL) of a mixture of 6-chloro-4′-heptadecyl-2,2′-bipyridine (5.86 g, 2 mmol) and tributyltin chloride (1 mL, 4 mmol) was used with a syringe. Added at once. After the addition, the mixture was stirred at room temperature for 3 hours. Water was added to this solution, followed by filtration using celite and extraction three times using ethyl acetate. The combined organic phase of the three extracts was dried over magnesium sulfate and then concentrated using a rotary evaporator. The 2-tributylstannyl-4′-heptadecyl-2,2′bipyridine thus obtained was used in the next coupling reaction without further purification.

The analysis values are as follows.
LC / MS (API-ES) m / z: 685.4 (100%, [M + H] ⁺ ), 683.4 (80%), 684.4 (55%), 681.4 (40%), 682 .4 (40%), 686.4 (40%), 687.4 (20%), 689.4 (15%), 688.4 (5%), 690.4 (5%)

  To 2-tributylstannyl-4′-heptadecyl-2,2′bipyridine synthesized above, 4-isopropoxycarbonyl-4 ′-(4,4-dimethyl-2,6-dioxanyl) -6- (trifluoromethanesulfo Nyloxy) -2,2′-bipyridine (0.50 g, 1 mmol) and p-xylene (3 mL) were added, followed by degassing three times using a vacuum apparatus. Tetrakis (triphenylphosphine) palladium (58 mg, 0.05 mmol) and lithium chloride (0.13 g, 3 mmol) were placed in a 100 mL flask equipped with a magnetic stirrer, oil bath, three-way cock and Dimroth condenser, and purged with nitrogen. The aforementioned degassed mixed solution was added. The mixture was refluxed at 140 ° C. for about 5 hours under a nitrogen stream. After allowing to cool to room temperature, water was added, the mixture was filtered through celite, and extracted three times with ethyl acetate. The combined organic phase of the three extracts was dried over magnesium sulfate and then concentrated using a rotary evaporator. By purifying the obtained crude product using a silica gel column, 4′-isopropoxycarbonyl-4- (4,4-dimethyl-2,6-dioxanyl) -4 ″ represented by the following formula (36): A yellow solid of '-heptadecyl-2,2': 6 ', 2' ': 6' ', 2' ''-quarterpyridine was obtained (368 mg, 24% yield).

The analysis values are as follows.
¹ H-NMR (270 MHz, CDCl ₃ ) δ: 9.19 ppm (d, J = 1.6 Hz, 1H), 8.98 (d, 1.4 Hz, 1H), 8.78 (d, 5.4 Hz, 1H), 8.71 (s, 1H), 8.68 (d, 7.6 Hz, 1H), 8.63 (d, 5.1 Hz, 1H), 8.52 (d, 7.8 Hz, 1H) 8.51 (s, 1 H), 8.02 (dd, 7.8, 7.8 Hz, 1 H), 7.55 (d, 4.9 Hz, 1 H), 7.18 (d, 4.9 Hz, 1H), 5.54 (s, 1H), 5.36 (qq, 6.3 Hz, 1H), 3.86 (d, 11.9 Hz, 2H), 3.77 (d, 12.7 Hz, 2H) , 2.77 (t, 7.8 Hz, 2H), 1.75 (m, 2H), 1.47 (d, 6.2 Hz, 6H), 1.33 (s, 3H), 1.3- .2 (m), 0.87 (t, 6.5Hz, 3H), 0.85 (s, 3H)
LC / MS (API-ES) m / z: 749.4 (60%, [M + H] ⁺ ), 375.3 (100%, [M + 2H] ²⁺ ), 750.4 (30%), 751.4 ( 10%)

(Synthesis Example 11)
In a 50 mL flask equipped with a magnetic stirrer, 4′-isopropoxycarbonyl-4- (4,4-dimethyl-2,6-dioxanyl) -4 ′ ″-heptadecyl-2,2 ′: 6 ′, 2 ″: Take 6 ″, 2 ′ ″-quarterpyridine (0.76 g, 1 mmol), 4-pyridinecarboxaldehyde (1.4 mL, 15 mmol) and concentrated hydrochloric acid (1.5 mL) at 60 ° C. for about 6 hours. Stir. After allowing to cool to room temperature, saturated brine was added, and the mixture was extracted 5 times with THF. The combined organic phase of the five extracts was concentrated using a rotary evaporator. The resulting crude 4-formyl-4′-carboxy-4 ′ ″-heptadecyl-2,2 ′: 6 ′, 2 ″: 6 ″, 2 ′ ″-quatpyridine is not further purified. Used for the next reaction.

The analysis values are as follows.
LC / MS (API-ES) m / z: 621.3 (100%, [M + H] ⁺ ), 622.3 (45%), 623.3 (10%), 311.3 (5%, [M + 2H] ²⁺ )

  4-formyl-4′-carboxy-4 ′ ″-heptadecyl-2,2 ′: 6 ′, 2 ″: 6 ″, 2 ′ ″-quatpyridine and ethanol (20 mL) obtained above are magnetically mixed. The sample was taken in a 50 mL flask equipped with a stirrer and stirred in air. Silver oxide is formed by adding an aqueous solution (10 mL) of sodium hydroxide (0.40 g, 10 mmol) to an aqueous solution (2 mL) of silver nitrate (0.34 g, 2 mmol). Added to the suspension. The mixture thus obtained was stirred in air at room temperature for about 2 hours. Hydrochloric acid was added to acidify the solution, and the mixture was extracted 3 times with an 8: 2 mixture of THF and concentrated hydrochloric acid. The organic phase combined with the three extracts was filtered through a membrane filter (0.10 μm, PTFE), and then concentrated using a rotary evaporator. The obtained solid was washed with water and ethyl acetate and dried under vacuum, whereby 4,4′-dicarboxy-4 ′ ″-heptadecyl-2,2 ′: 6 ′, represented by the following formula (37), 2 ″: 6 ″, 2 ′ ″-quarterpyridine was obtained (0.46 g, yield 70%).

The analysis values are as follows.
¹ H-NMR (270 MHz, DMSO-d6) δ: 9.14 ppm (s, 1H), 9.02 (s, 1H), 8.97 (d, J = 5.4 Hz, 1H), 8.96 ( s, 1H), 8.73 (m, 1H), 8.70 (d, 8.6 Hz, 1H), 8.55 (d, 7.0 Hz, 1H), 8.54 (s, 1H), 8 .32 (dd, 8.2, 7.0 Hz, 1H), 7.97 (d, 4.6 Hz, 1H), 7.59 (m, 1H), 2.85 (t, 7.0 Hz, 2H) 1.74 (m, 2H), 1.23-1.05 (m, 28H), 0.82 (t, 6.6 Hz, 3H)
LC / MS (API-ES) m / z: 637.3 (100%, [M + H] ⁺ ), 638.3 (45%), 319.3 (25%, [M + 2H] ²⁺ ), 639.3 ( 10%)

  The production method of a quarterpyridine derivative of the present invention and its intermediate can be used for the production of a quarterpyridine derivative which is a dye raw material used in a dye-sensitized solar cell, and the production method of a quarterpyridine derivative of the present invention And quarter pyridine derivatives can be easily produced by the intermediates thereof.

Claims (4)

A quarterpyridine derivative represented by the following formula (3) by reacting a bipyridine derivative represented by the following formula (1) with an organometallic intermediate represented by the following formula (2) using a transition metal catalyst. A method for producing a quarterpyridine derivative that produces
(In Formula (1), Z is an alkyl group, an aryl group, Y is a perfluoroalkylsulfonyl group, R ³ and R ⁴ are each independently an alkyl group or an aryl group, or are bonded to each other to form a cyclic structure. May be formed.)
(In Formula (2), M is a metal, R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group, L is a ligand, and n is 1 to 3) Is an integer.)
(In Formula (3), Z is an alkyl group or an aryl group, R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group, and R ³ and R ⁴ are each independently And an alkyl group, an aryl group, or a group that may be bonded to each other to form a cyclic structure.) The acetal and ester of the quarterpyridine derivative represented by the following formula (3) are hydrolyzed to formyl group and carboxyl group, respectively, and the obtained formyl group is oxidized to represent a carboxyl group represented by the following formula (4). A method for producing a quarterpyridine derivative that produces a quarterpyridine derivative.
(In Formula (3), Z is an alkyl group or an aryl group, R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group, and R ³ and R ⁴ are each independently And an alkyl group, an aryl group, or a group that may be bonded to each other to form a cyclic structure.)
(In Formula (4), R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group.) A bipyridine derivative represented by the following formula (1).
(In Formula (1), Z is an alkyl group, an aryl group, Y is a perfluoroalkylsulfonyl group, R ³ and R ⁴ are each independently an alkyl group or an aryl group, or are bonded to each other to form a cyclic structure. May be formed.) A quarterpyridine derivative represented by the following formula (3).
(In Formula (3), Z is an alkyl group or an aryl group, R ¹ and R ² are each independently hydrogen, an alkyl group, an aryl group, or a substituted alkyl group, and R ³ and R ⁴ are each independently And an alkyl group, an aryl group, or a group that may be bonded to each other to form a cyclic structure.)