JPH0665212A - Pyrazine derivative and its production - Google Patents

Abstract

PURPOSE:To provide a new bisphenol A compound having a pyrazine ring structure as a center group and useful as various industrial raw materials such as liquid crystal compound for liquid crystal display element monomers for the production of heat-resistant high-molecular compound such as polycarbonate, a synthetic rubber, etc. CONSTITUTION:The pyrazine derivative of formula I (R<1> is 1-20C alkyl, 6-12C aryl or halogen; R<2> is 1-30C alkyl, 1-30C halogenated alkyl, 1-30C alkoxyalkyl, 2-30C alkenyl, 2-30C alkynyl or 6-12C aryl; (a) is integer of 0-4), e.g. 2,5-bis(4- hydroxyphenyl)-3,6-dimethylpyrazine. The compound of formula I can be produced by converting a compound of formula II into an aminoketone, followed by dimerizing the same.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a pyrazine derivative and a method for producing the same, more specifically, a bisphenol compound having a pyrazine ring structure as a central group,
For example, the present invention relates to a pyrazine derivative useful as various industrial raw materials such as a liquid crystal compound for a liquid crystal display device, a heat resistant polymer compound such as polycarbonate, a monomer for producing synthetic rubber and the like, and a method for efficiently and suitably producing the pyrazine derivative.

[0002]

2. Description of the Related Art Many pyrazine derivatives having a substituent on the pyrazine ring are known to exist in vivo or naturally. Further, in recent years, such pyrazine derivatives have been of interest as raw materials for functional materials, and many researchers have been actively conducting research on their application development. Therefore, techniques for obtaining various pyrazine derivatives by synthesis have become important. Conventionally, the following techniques have been used for the synthesis of pyrazine derivatives. For example, as a method for producing 2,5-bisarylpyrazine, a method of self-condensing aminomethylarylketone hydrochloride in the presence of a base,
A method of self-condensing an arylazirine derivative in the presence of a catalyst is known. However, these methods have problems that the steps are very complicated and selective synthesis is difficult.

In addition, H.264. D. Report of Dakin et al. [J.
Biol. Chem. , 78, 91 (1928); ibid. 7
45, ibid. 759] and P. A. Levene et al. [J. Biol. Chem. , 79, 95 (192
8)], 2,5-bisaralkylpyrazine or 2,5-bis (4) having a substituent at the 3,6-position of the pyrazine ring in several steps from amino acids such as phenylalanine and tyrosine.
Methods for making pyrazine derivatives such as -hydroxyphenylmethyl) pyrazines have been shown. However,
It has been found that these conventional methods have a problem that the oxidation is not sufficiently carried out in the last step and a large amount of the precursor dihydropyrazine compound is produced together with the pyrazine derivative.

Among the pyrazine derivatives, 2,5-
Bis (4-hydroxyphenyl) pyrazine, in particular, a bisphenol-type pyrazine derivative having a substituent on it, is
It is considered to be useful as a raw material for manufacturing heat-resistant polymer compounds (eg, polycarbonate) as well as functional materials. Therefore, it is important to actually synthesize the 2,5-bis (4-hydroxyphenyl) pyrazine derivative, and particularly to develop a technique for selectively and efficiently producing them.

Among the 2,5-bis (4-hydroxyphenyl) pyrazine derivatives, examples of the synthesis of 2,5-bis (4-hydroxyphenyl) pyrazine have already been described in H. Report by Schubert et al. [J. Pract.
Chem. , (4) 37, 12 (1968)] and the like. However, there is no synthetic example of 2,5-bis (4-hydroxyphenyl) pyrazine having a substituent (group other than hydrogen atom) at the 3 and 6-positions of the pyrazine ring. Also,
Similarly, it has a substituent at the 3,6 position of the pyrazine ring, and
There is no synthetic example of a 2,5-bis (4-hydroxyphenyl) pyrazine derivative having a substituent on the phenyl group of 4-hydroxyphenyl.

[0006]

Therefore, it is necessary to synthesize a 2,5-bis (4-hydroxyphenyl) pyrazine derivative having a group (ie, a substituent) other than a hydrogen atom at least at the 3 and 6-positions of the pyrazine ring. If so, these are novel compounds, and various applications can be expected as described above.

For the synthesis of these pyrazine derivatives, it is possible to apply the above-mentioned conventional similar methods for synthesizing pyrazine derivatives, but as described above, the conventional methods have the selectivity, the number of steps, etc. Therefore, it is also important to develop a method for selectively producing the desired pyrazine derivative in a high yield efficiently.

The present invention has been made based on the above circumstances.

That is, the first object of the present invention is, more specifically, a novel bisphenol-type pyrazine derivative which is expected to be useful for various purposes such as various functional material compounds and monomers for producing polymer compounds. And a novel pyrazine derivative which is a 2,5-bis (4-hydroxyphenyl) pyrazine having a substituent at least at the 3,6-positions of the pyrazine ring.

Another object of the present invention is to provide a method for producing the pyrazine derivative selectively and efficiently in a high yield.

[0011]

[Means for Solving the Problems] Based on the above circumstances, the present inventors have conducted extensive studies to synthesize a new and useful bisphenol-type pyrazine derivative. As a result, the desired pyrazine derivative, that is, the pyrazine ring 3,
We have succeeded in synthesizing and obtaining various 2,5-bis (4-hydroxyphenyl) pyrazine compounds having a 6-position substituent and various derivatives having a substituent on the phenyl group of these 4-hydroxyphenyl.

It was confirmed that these pyrazine derivatives can be synthesized by various methods. Among them, a predetermined compound in which the α carbon of glycine is substituted with an unsubstituted or substituted p-hydroxyphenyl group A method using a specific synthetic method of using as a raw material, converting this to a ketone type carbonyl group by converting at least the carboxy group of the raw material compound into a ketone type carbonyl group, and dimerizing the obtained aminoketone (hydrochloride, etc.) It has been clarified that the above method is particularly suitable. In this way, we have succeeded in developing an excellent production technique by which various desired pyrazine derivatives can be easily obtained with high selectivity and high yield.

The present inventors have completed the present invention mainly based on these findings.

That is, the present invention provides the following general formula [I]

[0015]

[Chemical 3] (In the formula [I], R ¹ represents an alkyl group having 1 to 20 carbon atoms, an aryl group having 6 to 12 carbon atoms or a halogen atom, and R ² represents an alkyl group having 1 to 30 carbon atoms, or 1 carbon atoms. ~
A halogenated alkyl group having 30 carbon atoms, an alkoxyalkyl group having 1 to 30 carbon atoms, an alkenyl group or alkynyl group having 2 to 30 carbon atoms or an aryl group having 6 to 12 carbon atoms is shown, and a is an integer of 0 to 4. ) The pyrazine derivative represented by

The present invention also provides the following general formula [I] as a preferred method for producing the various pyrazine derivatives of the present invention.
I]

[0017]

[Chemical 4] (However, R ¹ in the formula [II] represents an alkyl group having 1 to 20 carbon atoms, an aryl group having 6 to 12 carbon atoms, or a halogen atom, and a represents an integer of 0 to 4.). The present invention also provides a method characterized in that compound [II] is aminoketonized and then dimerized.

The pyrazine derivative of the present invention is various compounds represented by the above-mentioned general formula [I], and can be used alone or as a mixture for various purposes.

A in the general formula [I] represents an integer of 0 to 4 as the number of the substituents R ¹ which can take independent values for each benzene ring. Regarding the 4-hydroxyphenyl group, the value of a may be the same or different. That is, a pyrazine derivative of the present invention, the 4-R ¹ both in any of hydroxyphenyl groups may be those that are not substituted, R ¹ is substituted only on one of its 4-hydroxyphenyl group Or both of them may have 4-hydroxyphenyl groups substituted with R ¹ .

Among these, those in which the value of a is the same for two 4-hydroxyphenyl groups are usually advantageous in that they can be easily synthesized selectively as a single compound. In addition, when the value of a is 0, 1 or 2, the synthetic raw materials are usually easily available.

In addition, R¹There is no particular restriction on the substitution position of
Not, for example, the phenyl group of 4-hydroxyphenyl
R in only the 3rd place¹ Replaced by R in the 3rd and 5th positions¹Is
It is possible to list various substitution structures such as substituted ones.
Wear.

R ^{1 in the} above formula [I] represents an alkyl group having 1 to 20 carbon atoms, an aryl group having 6 to 12 carbon atoms, or a halogen atom. The alkyl group may be linear, branched, Any of those having a cyclic structure may be used. Specific examples of the alkyl group include, for example, methyl group, ethyl group,
n-propyl group, isopropyl group, n-butyl group, se
c-butyl group, isobutyl group, tert-butyl group, n
-Pentyl group, sec-pentyl group, isopentyl group,
Neopentyl group, tert-pentyl group, cyclopentyl group, and various other hexyl groups, heptyl groups, octyl groups, nonyl groups, decyl groups, undecyl groups, dodecyl groups, tridecyl groups, tetradecyl groups, pentadecyl groups, hexadecyl groups, Examples thereof include a heptadecyl group, an octadecyl group, a nonadecyl group, and an icosyl group. R ¹ is, for example, a cyclohexylmethyl group,
Benzyl group, phenethyl group, methylcyclohexyl group,
It may be a substituted alkyl group having a cyclic structure such as a methylcyclohexylethyl group, a cyclohexylcyclohexyl group, or a phenylcyclohexyl group.

Specific examples of the aryl group as R ¹ include, for example, phenyl group, methylphenyl group,
Unsubstituted or various such as dimethylphenyl group, ethylphenyl group, propylphenyl group, isopropylphenyl group, n-butylphenyl group, isobutylphenyl group, sec-butylphenyl group, tert-butylphenyl group, cyclohexylphenyl group, biphenyl group Examples thereof include a substituted phenyl group, a naphthyl group, a methylnaphthyl group, a dimethylnaphthyl group, and an ethylnaphthyl group.

Examples of the halogen atom as R ¹ include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

The pyrazine derivative of the present invention comprises two or more kinds.
Different types of R above¹ May have
Yes.

The pyrazine derivative of the present invention has R ² which is a substituent other than a hydrogen atom at the 3 and 6-positions of the pyrazine ring, as shown in the above general formula [I]. R ² is an alkyl group having 1 to 30 carbon atoms, a halogenated alkyl group having 1 to 30 carbon atoms, an alkoxyalkyl group having 1 to 30 carbon atoms,
An alkenyl group having 2 to 30 carbon atoms or an aryl group having 6 to 12 carbon atoms is shown. The alkyl group can have various structures similar to R ¹ described above, and specific examples thereof include, for example, Examples thereof include various alkyl groups exemplified as R ¹ and various alkyl groups having 21 or more carbon atoms.

Examples of the halogenated alkyl group as R ² include various halogen atom-substituted alkyl groups in which at least one halogen atom is substituted with the above-mentioned various alkyl groups having 1 to 30 carbon atoms. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Specific examples of the halogenated alkyl group as R ² include, for example, trifluoromethyl group, difluoromethyl group, monofluoromethyl group, trichloromethyl group, dichloromethyl group, monochloromethyl group, tribromomethyl group, dibromomethyl group. A wide variety of groups such as groups, monobromomethyl groups and the like can be mentioned.

Examples of the aryl group as R ² include various aryl groups exemplified as the above R ¹ .

When R ² is the above alkoxyalkyl group,
Examples of the alkoxyalkyl group include a methoxymethyl group, a methoxyethyl group, a methoxybutyl group, an ethoxyethyl group, a phenoxymethyl group, a phenoxyethyl group, and a cyclohexyloxyethyl group.

When R ² is the alkenyl group, examples of the alkenyl group include vinyl group, allyl group, 2-methylvinyl group, 1-methylvinyl group, various butenyl group, pentenyl group, hexenyl group, Heptenyl group, octenyl group, nonenyl group, decenyl group, undecenyl group,
Dodecenyl group, tridecenyl group, tetradecenyl group, pentadecenyl group, hexadecenyl group, heptadecenyl group, cyclohexenyl group, 2-phenylvinyl group, 1-
A phenyl vinyl group etc. can be mentioned.

Further, R ² is the above-mentioned alkyl group, halogenated alkyl group, alkoxyalkyl group, alkenyl group,
The alkynyl group and the aryl group may be each group in which various substituents (for example, a hydroxy group and the like) are substituted.

In the general formula [I], R ^{2 s} bonded to the 3rd and 6th positions of the pyrazine ring may be the same kind of groups or different groups. Among these, those having the same R ^{2 at the} 3 and 6-positions have a synthetic advantage that it is easy to obtain a single compound with high selectivity.

Further, the pyrazine derivative of the present invention may exhibit optical activity.

As described in detail above, the pyrazine derivative of the present invention represented by the above general formula [I] includes
There are various types depending on the presence / absence of R ¹ , the number of substitutions, the substitution position, its type or combination, and the type or combination of R ² . Among these, for example, it has been found that there are useful as a raw material for various functional materials such as those exhibiting liquid crystallinity or a synthetic raw material thereof, and the pyrazine derivative of the present invention is a bisphenol type. Since it is a compound, it is useful as a monomer for synthesizing heat-resistant polymers such as polycarbonate and polyether, and can be suitably used in various fields of application.

The pyrazine derivative of the present invention is not particularly limited in its general production method and can be synthesized by various raw materials and routes by appropriately using various methods such as known synthesis methods. It can be advantageously produced by the method of the invention.

That is, various pyrazine derivatives represented by the above general formula [I] are represented by the following general formula [II]

[0037]

[Chemical 5] (However, R ¹ in the formula [II] represents an alkyl group having 1 to 20 carbon atoms, an aryl group having 6 to 12 carbon atoms, or a halogen atom, and a represents an integer of 0 to 4.). The compound [II] can be suitably produced by the method of the present invention, which is a method characterized by aminoketonization and then dimerization.

Since a and R ¹ in the above formula [II] respectively correspond to a and R ¹ shown in the above general formula [I], they have the same meanings as described above. As explained. That is, depending on the structure of the target pyrazine derivative, the value of a (presence or absence of R ¹ and the number of substitutions), R ¹
In consideration of the kind and the substitution position of the compound, a compound having a predetermined structure is selected from the various compounds [II] represented by the general formula [II], and the compound [II] is used as a starting material for the aminoketonization. Good.

Therefore, the compound [II] used as a raw material for production in the method of the present invention includes various compounds depending on the presence or absence of R ¹ , the number, the substitution position, the type, the combination and the like. From the general structural formula, they can be collectively referred to as 4-hydroxyphenylglycines. Among these various compounds [II], as typical ones, for example, the following compounds

[0040]

[Chemical 6] That is, 4-hydroxyphenylglycine [II
a], 3-methyl-4-hydroxyphenylglycine [IIb], 3,5-dibromo-4-hydroxyphenylglycine [IIc], and the like.
Of course, it is not limited to these.

The 4-hydroxyphenylglycines of the compound [II] are bound to at least four different groups, namely an amino group, a carboxy group, a hydrogen atom and an unsubstituted or substituted 4-hydroxyphenyl group. There are optical isomers based on existing carbon atoms (asymmetric carbon). In the method of the present invention, the compound [II] having any optical purity can be used as a starting compound, and D
Any of isomers, L-isomers, racemic isomers, a mixture of D-isomers and L-isomers at an arbitrary ratio may be used.

In the method of the present invention, the compound [I
Using a predetermined compound of I] as a raw material, it is first aminoketonized. By this aminoketonization,
At least a carboxy group in the compound [II] is converted to a ketone type carbonyl group (—CO—R ² ). Where R
² is a group corresponding to R ² in the general formula [I] and has the same meaning as described above.

This aminoketonization can be carried out by various synthetic methods. In particular, the acid anhydride [(R ²
CO) ₂ O] in the presence of a base, step 1 and acid [acid] in a step 2

[0044]

[Chemical 7] (However, R ² in these formulas has the same meaning as described above.) Can be suitably achieved by sequentially performing. That is, in this case, according to the step 1,
-COOH of the raw material compound (compound [II]) is replaced with -CO-
R ² but with -NH ₂ and unsubstituted or substituted 4
- -OH also anhydrides hydroxyphenyl group [(R ² C
O) ₂ O] and acylated with -NHC, respectively.
Since it is converted to OR ² and —OCOR ² , the acyl ketone body [III] is obtained as the product of this Step 1. At that time, CO ₂ is generated and R ² COOH is desorbed, but this desorption is caused by the action of a coexisting base (catalyst action or action as an acid acceptor, that is, R ² COOH acts as a trapping agent). It will be promoted and the reaction will proceed smoothly.

Then, in order to return -NHCOR ² and -OCOR ² of this acylketone body [III] to -NH ₂ and -OH, respectively, they are reacted with an acid [acid] in step 2 to give hydroxy-aminoketone as a product of step 2. Obtain the body acid salt [IV].

Here, the acid anhydride [(R
^{As 2} CO) ₂ O], it is possible to use those having various groups described above as R ² , and specific examples thereof include
For example, acetic anhydride, propionic anhydride, butyric anhydride, isobutyric anhydride, valeric acid anhydride, isovaleric acid anhydride, pivalic acid anhydride, hexanoic acid anhydride, heptanoic acid anhydride, octanoic acid anhydride, nonanoic acid anhydride, decanoic acid anhydride, anhydrous Undecanoic acid,
Lauric acid anhydride, tridecanoic acid anhydride, myristic acid anhydride, pentadecanoic acid anhydride, heptadecanoic acid anhydride, palmitic acid anhydride, stearic acid anhydride, nonadecanoic acid anhydride, icosanoic acid anhydride, acrylic acid anhydride, propionic acid anhydride, methacrylic acid anhydride, anhydrous Crotonic acid, isocrotonic anhydride, oleic anhydride, hydroatropic anhydride, atropic anhydride, cinnamoyl anhydride, phenoxyacetic anhydride, benzoic anhydride, naphthoic anhydride, phenylacetic anhydride, fluoroacetic anhydride, difluoroacetic anhydride, trifluoroanhydride Examples thereof include acetic acid, chloroacetic anhydride, dichloroacetic anhydride, trichloroacetic anhydride, bromoacetic anhydride, dibromoacetic anhydride, tribromoacetic anhydride, and the like. In addition, although these are usually used alone, if necessary, 2
It is also possible to use two or more species together as a mixture or the like.

Compound [II] used in the reaction in Step 1
The ratio of the acid anhydride and the acid anhydride [(R ² CO) ₂ O] is not particularly limited, but it is usually desirable to select it in consideration of the stoichiometry of the reaction in order to sufficiently aminoketone the compound [II]. . Specifically, it is preferable to use the acid anhydride [(R ² CO) ₂ O] in an amount of usually about 3 to 6 mol, and particularly 3 to 4 mol per 1 mol of the compound [II] used. .

As the base to be coexisted in the reaction system of step 1, various organic bases having no active hydrogen are usually preferably used, and specific examples thereof include pyridine, dimethylaniline, triethylamine and 4-dimethylamino. Pyrazine, tetramethylurea, sodium acetate, potassium acetate and the like are preferably used. These are 2 if necessary.
You may use together 1 or more types as a mixture etc.

The ratio of the base used in step 1 is
There is no particular limitation, but it is usually preferable to use it in a ratio in the range of about catalytic amount to about 5 times the molar amount of the compound [II] used. It can also be used as a reaction solvent.

The reaction in step 1 is usually carried out at 80 to 200 ° C.
Preferably, it can be suitably carried out at a temperature of 100 to 130 ° C. Compound [II] is converted to acylketone body [III]
The reaction time for sufficient conversion varies depending on other conditions such as the reaction temperature, but is usually about 30 minutes to 8 hours.

As described above, the compound [II] can be sufficiently converted into the acylketone body [III],
The acyl ketone body [III] can be produced almost quantitatively.

The acylketone body [III] produced in step 1 may be supplied as it is to the step 2 in the state of the reaction mixture, but it is usually supplied to the step 2 after suitable isolation and purification such as isolation. Is preferred.

On the other hand, the above-mentioned acid [ac
[id] can include, for example, hydrochloric acid, sulfuric acid, nitric acid, hypochlorous acid, chlorous acid, chloric acid, perchloric acid, mineral acids such as borofluoric acid, and organic acids such as acetic acid. . In addition,
These are usually used alone, but if necessary, two or more kinds may be used in combination as a mixture.

The proportion of the acid used in the reaction in this step 2 is not particularly limited, but in general, the reaction is carried out in order to sufficiently convert the acylketone body [III] to be used into the acid salt [IV] of the hydroxy-aminoketone body. It is desirable to select it in consideration of the stoichiometry, etc. Specifically, it is preferable to use the acid in an amount of usually 3 mol or more, preferably about 3 to 4 mol, per 1 mol of the acylketone body [III] to be used.

The reaction of step 2 can usually be suitably carried out at a temperature of 80 to 150 ° C. Acyl ketone body [II
The reaction time for sufficiently converting [I] into the hydroxy-aminoketone acid salt [IV] varies depending on other conditions such as the reaction temperature, but is usually about 1 to 24 hours.

As described above, the acylketone body [II
I] can be sufficiently converted to the hydroxy-aminoketone acid salt [IV], and the hydroxy-aminoketone acid salt [IV] can be produced almost quantitatively.

The reaction in each of the steps 1 and 2 can be suitably carried out without using a solvent, but may be appropriately carried out using a solvent. Examples of this solvent include methylene chloride, chloroform,
Carbon tetrachloride, halogenated hydrocarbons such as chlorobenzene, aromatic hydrocarbons such as benzene, toluene, xylene, ethers such as tetrahydrofuran, dimethyl ether, diethyl ether, alcohols such as methanol and ethanol, esters such as ethyl acetate, acetone , Ketones such as methylethylketone and cyclohexanone, amides such as dimethylformamide (DMF), dimethylacetamide and hexamethylenephosphortriamide, sulfoxides such as dimethylsulfoxide (DMSO), water, and mixed solvents thereof. be able to.

In the method of the present invention, compound [II]
Is aminoketonized as described above, and then dimerized to form a pyrazine derivative [compound of the general formula (I)] as a target. Incidentally, in addition to the desired pyrazine derivative, a hydro form of the pyrazine derivative (-NH-type and / or -CH type compound) is usually obtained by this dimerization reaction. It may be converted to the desired pyrazine derivative [I] by oxidizing the hydro form.

That is, in this dimerization step (step 3)
Is the acid of the hydroxy-aminoketone body obtained in step 2 above.
The salt [IV] was dimerized to give -N in the compound [IV].
H ₂And -CO-R²-CO- of each other is condensed between two molecules.
Form a pyrazine ring or hydropyrazine ring.
It This dimerization reaction is usually suitable in the presence of alkali.
Which can be achieved by the following reaction formula
As in (3), compound [IV] is a pyrazine derivative
[I] and its hydroforms [V], [VI] and [VII]
Can be efficiently converted into a mixture of

[0060]

[Chemical 8] As the acid salt [IV] of the hydroxy-aminoketone used as a raw material for this dimerization reaction, the one produced in the above step 2 may be used as it is in the reaction mixture, but it is usually isolated. It is preferable that the dimerization reaction is carried out after appropriately separating and purifying.

Hydroforms [V] and [V] by-produced as precursors of the desired pyrazine derivative [I] in this dimerization reaction.
I] and [VII] may be converted into the target pyrazine derivative by oxidative dehydrogenation by a usual oxidation method. At that time, the hydro-forms [V], [VI] and [VII] may be subjected to the oxidation reaction after the pyrazine derivative [I] is separated, but usually the state of a mixture containing the pyrazine derivative [I] is used. Therefore, it is preferable to subject it to the oxidation reaction because it is advantageous in the process.

As the alkali used in the dimerization reaction, usually, ammonia (ammonia water, etc.), sodium hydroxide aqueous solution, potassium hydroxide aqueous solution and the like are preferably used, and among them, ammonia water is particularly preferably used. .

The amount of the alkali used is usually 1 mol or more, preferably 2 to 3 mol, per 1 mol of the acid salt [IV] of the hydroxy-aminoketone used.

The dimerization reaction is usually carried out at 0 to 100 ° C.
Preferably, it can be suitably carried out at a temperature of 10 to 30 ° C. The reaction time for sufficiently achieving this dimerization reaction varies depending on other conditions such as the reaction temperature, but is usually
It is about 1 to 8 hours.

On the other hand, as the oxidizing agent used in the above-mentioned oxidation reaction, there are various kinds of oxidizing agents (inorganic oxidizing agents, organic oxidizing agents or their composite type) including the oxidizing agents conventionally used in this kind of oxidizing reaction. Things, etc.) can be used. Some representative examples of the oxidizer are shown below. For example, air, oxygen-containing gas such as oxygen, hydrogen peroxide, HgCl ₂ , KMnO _{4
, Br 2, K 3 Fe (} CN) 6, CuO · Cr 2 O 3, benzoquinone chloranil bromo sulfonyl, 2,3-dichloro -
Examples thereof include 5,6-dicyanobenzoquinone. These can be used in various forms depending on the case. For example, they may be used in the form of a solution such as an aqueous solution, may be used by dispersing a particulate solid, or a gas may be used. It may be used by blowing it into the reaction system, or a combination thereof. Further, this oxidation reaction may be carried out in the presence of a suitable catalyst, if necessary. Among these various oxidants, hydrogen peroxide solution is usually particularly preferably used.

The amount of the oxidizing agent used is the hydro-form [V],
Usually, at least 1 equivalent or more is preferable per 1 mol (1 equivalent) of hydrogen atoms removed when sufficiently converting [VI] and [VII] into the pyrazine derivative [I]. It is preferable to appropriately select the optimum amount to be used according to the type and the like. For example, when hydrogen peroxide solution is used as the oxidant, it is generally preferable to use hydrogen peroxide in an amount of about 1 to 2 equivalents per equivalent of hydrogen atoms to be oxidatively dehydrogenated.

This oxidation reaction can usually be suitably carried out at a temperature of 0 to 120 ° C., but the optimum reaction temperature varies depending on the kind of the oxidizing agent used and the like, so taking these other conditions into consideration. It is better to select appropriately according to the case.
The reaction time cannot be uniformly determined because it depends on the type of oxidant used, reaction temperature, composition of raw materials, etc.
About 1 to 8 hours is sufficient.

The dimerization reaction and the oxidation reaction can be suitably carried out without using a solvent, but may be carried out in a suitable solvent if necessary. Examples of this solvent include the various solvents exemplified above. In addition, it is desirable to appropriately select conditions such as the presence or absence of the use of the solvent, the type of the solvent, the ratio of the solvent used, and the like in consideration of other conditions such as the type of the oxidizing agent.

The desired pyrazine derivative synthesized as described above can be appropriately separated and recovered from the reaction mixture by various methods such as known separation / purification means, and obtained as products with various degrees of purification.

As described above, various pyrazine derivatives of the present invention can be efficiently obtained by aminoketonization of various compounds [II], dimerization, and oxidation of by-produced hydropyrazine. it can. According to this method of the present invention, various desired pyrazine derivatives can be obtained with extremely high selectivity in good yield and easily by a simple operation in a short process.

The method of the present invention, as described above,
Between each step such as step 1, step 2, dimerization reaction step, acid reaction step, etc., without separating an intermediate product on the way,
A continuous process in which all of these series of steps are carried out may be carried out, or if necessary, a major product (intermediate product) of each step is appropriately isolated and used in the next step. It may be a process or a semi-continuous process in which only a part of the process is continuous. The intermediate product isolated in each step (for example, the acylketone product [II
I], a hydroxy-aminoketone acid salt [IV], a pyrazine derivative hydroform [V], [VI] and [VI]
I] etc.) may be obtained as products, respectively, and these may be used for other purposes as required.

[0072]

EXAMPLES The present invention will be described in more detail below with reference to examples of the present invention and comparative examples thereof, but the present invention is not limited to these examples.

Example 1 (1-1) D (-)-p-hydroxyphenylglycine (200 g) was suspended in acetic anhydride (500 ml) and pyridine (100 ml) and heated at 100 ° C. for 2 hours. The solvent was distilled off to obtain 1-acetylamino-1- (4-acetoxyphenyl) -2-propanone (below).

[0074]

[Chemical 9] ¹ H-NMR (CDCl₃) Δ = 1.99 (3H, s),
2.12 (3H, s), 2.29 (3H, s), 5.5
6 (1H, d, J = 6.5Hz), 6.8 (1H, br
 d, NH), 7.10, 7.34 (each 2H,
AA'BB ') ppm (1-2) 1-acetylamino-1- (4-acetoxy)
Cyphenyl) -2-propanone was added to concentrated hydrochloric acid (250 ml)
And heated at 120 ° C. for 12 hours. Evaporate the solvent
Then 1-amino-1- (4-hydroxyphenyl)-
2-Propanone hydrochloride (below) was obtained.

[0075]

[Chemical 10] ¹ H-NMR (CD₃OD) δ = 2.11 (3H, s),
5.22 (1H, s), 6.91, 7.29 (each
 2H, AA′BB ′) ppm (1-3) 1-amino-1- (4-hydroxypheny
) -2-propanone hydrochloride to methanol (200m
l), and add ammonia water (300 ml) to it.
The mixture was stirred at room temperature for 8 hours. Suction filtration of the formed precipitate
And suspend it in methanol (500 ml),
% Hydrogen peroxide solution (200 ml) was added and stirred at room temperature for 8 hours.
I stirred. The produced 2,5-bis (4-hydroxyphenyl)
110 g of (3), 6-dimethylpyrazine (below)
It was

[0076]

[Chemical 11] ¹ H-NMR (CD₃OD + NaOD) δ = 2.59 (6
H, s), 6.76, 7.31 (each 4H, A
A'BB ') ppm

Example 2 (2-1) The acetic anhydride of (1-1) of Example 1 (500
ml) was changed to propionic anhydride (550 ml), the same procedure as in 1-1 of Example 1 was repeated to prepare 1-propionylamino-1- (4-propionyloxyphenyl) -2-.
Butanone (below) was obtained.

[0078]

[Chemical 12] ¹ H-NMR (CDCl₃) Δ = 1.00 (3H, t, J
= 7 Hz), 1.08 (3H, t, J = 7 Hz), 1.
25 (3H, t, J = 7Hz), 2.24 (2H, q,
J = 7 Hz), 2.43 (2H, q, J = 7 Hz),
2.58 (2H, q, J = 7Hz), 5.58 (1H,
d, J = 6.5 Hz), 6.8 (1H, br d, N
H), 7.08, 7.31 (each 2H, AA'B
B ′) ppm (2-2) 1-acetylami of (1-2) of Example 1
No-1- (4-acetoxyphenyl) -2-propanone
1-propionylamino-1- (4-propionyl
Example 1 with the exception that it was changed to (xyphenyl) -2-butanone.
1-amino-1- (4-hydroxy)
Droxyphenyl) -2-butanone hydrochloride (below) was obtained.
It was

[0079]

[Chemical 13] ¹ H-NMR (CD₃OD) δ = 1.00 (3H, t, J
= 7 Hz), 2.43 (2H, qd, J = 7.2H
z), 5.17 (1H, s), 6.89, 7.24 (e
ach 2H, AA′BB ′) ppm (2-3) 1-amino-1 of (1-3) of Example 1
-(4-hydroxyphenyl) -2-propanone hydrochloride
To 1-amino-1- (4-hydroxyphenyl) -2-
Same as 1-3 in Example 1 except that it was changed to butanone hydrochloride.
And 3,6-diethyl-2,5-bis (4-hydro)
115 g of xyphenyl) pyrazine (below) was obtained.

[0080]

[Chemical 14] ¹ H-NMR (CD₃OD + NaOD) δ = 1.21 (6
H, t, J = 7 Hz), 2.91 (4H, q, J = 7H)
z), 6.75, 7.26 (each 4H, AA'B
B ') ppm

Example 3 (3-1) The acetic anhydride (1-1) of Example 1 (500 m
Example 1 except that l) was changed to butyric anhydride (700 ml)
(1-1) of 1-butyrylamino-1-
(4-butyryloxyphenyl) -2-pentanone (below) was obtained.

[0082]

[Chemical 15] ¹ H-NMR (CDCl₃) Δ = 0.81 (3H, t, J
= 7 Hz), 0.90 (3H, t, J = 7 Hz), 1.
04 (3H, t, J = 7Hz), 1.4-2.0 (6
H, m), 2.15 (2H, q, J = 7Hz), 2.3
4 (2H, q, J = 7Hz), 2.50 (2H, q, J
= 7 Hz), 5.56 (1H, d, J = 6.5 Hz),
6.8 (1H, br d, NH), 7.08, 7.32
(Each2H, AA'BB ') ppm (3-2) 1-acetylami of (1-2) of Example 1
No-1- (4-acetoxyphenyl) -2-propanone
1-butyrylamino-1- (4-butyryloxyphene
(1) of Example 1 except that it was changed to (nyl) -2-pentanone
-2), and 1-amino-1- (4-hydroxy)
Cyphenyl) -2-pentanone hydrochloride (below) was obtained.

[0083]

[Chemical 16] ¹ H-NMR (CD₃OD) δ = 0.81 (3H, t, J
= 7 Hz), 1.77 (2H, m), 2.44 (2H,
m), 5.22 (1H, s), 6.91, 7.29.
(Each 2H, AA′BB ′) ppm (3-3) 1-amino-1-of (1-3) of Example 1
(4-hydroxyphenyl) -2-propanone hydrochloride
1-amino-1- (4-hydroxyphenyl) -2-pe
(1-3) of Example 1 except that it was changed to ntanone hydrochloride.
Do the same, 2,5-bis (4-hydroxyphenyl)
-3,6-Dipropylpyrazine (below) was obtained.

[0084]

[Chemical 17] ¹ H-NMR (CD₃OD + NaOD) δ = 1.00 (6
H, t, J = 7 Hz), 1.75 (4H, sext, J
= 7 Hz), 2.95 (4H, q, J = 7 Hz), 6.
76,7.31 (each 4H, AA'BB ') pp
m

Example 4 (4-1) The acetic anhydride of (1-1) of Example 1 (500
ml) stearic anhydride (250 g), D (-)-p
-Hydroxyphenylglycine (200 g) was added to D (-)
-P-Hydroxyphenylglycine (20 g) was replaced by the same procedure as in Example 1-1, except that 1-stearoylamino-1- (4-stearoyloxyphenyl) -2-nonadecanone (below) was used. Obtained.

[0086]

[Chemical 18] ¹ H-NMR (CDCl₃) Δ = 0.8-3.0 (105
H, m), 5.56 (1H, d, J = 6.5 Hz),
6.8 (1H, br d, NH), 7.08, 7.32
(Each 2H, AA'BB ') ppm (4-2) 1-acetylami of (1-2) of Example 1
No-1- (4-acetoxyphenyl) -2-propanone
1-stearoylamino-1- (4-stearoyl
Oxyphenyl) -2-nonadecanone
The same procedure as in (1-2) of Example 1 was repeated to give 1-amino-1-
(4-Hydroxyphenyl) -2-nonadecanone hydrochloride
(Below) was obtained.

[0087]

[Chemical 19] ¹ H-NMR (CD₈OD) δ = 0.8-3.0 (35
H, m), 5.22 (1H, s), 6.91, 7.29.
(Each 2H, AA′BB ′) ppm (4-3) 1-amino-1-of (1-3) of Example 1
(4-hydroxyphenyl) -2-propanone hydrochloride
1-amino-1- (4-hydroxyphenyl) -2-no
Same as 1-3 in Example 1 except that nadecanone hydrochloride was used.
And 3,6-diheptadecyl-2,5-bis (4
15.3 g of -hydroxyphenyl) pyrazine (below)
Obtained.

[0088]

[Chemical 20] ¹ H-NMR (CD₃OD + NaOD) δ = 0.9-3.
0 (70H, m), 6.76, 7.31 (each 4
H, AA'BB ') ppm

Example 5 (5-1) The acetic anhydride of 1-1 of Example 1 (500 m
l) is trifluoroacetic anhydride (50 ml), D (-)-
p-hydroxyphenylglycine (200 g) was added to D
1-Trifluoroacetylamino-1- [4- (trifluoroacetyl) phenyl] -3 was performed in the same manner as in 1-1 of Example 1 except that (-)-p-hydroxyphenylglycine (20 g) was used. , 3,3-trifluoro-2-
Propanone (below) was obtained.

[0090]

[Chemical 21] ¹ H-NMR (CDCl₃) Δ = 5.56 (1H, d, J
= 6.5 Hz), 6.8 (1H, br d, NH),
7.08, 7.32 (each 2H, AA'BB ')
ppm (5-2) 1-acetylami of (1-2) of Example 1
No-1- (4-acetoxyphenyl) -2-propanone
1-trifluoroacetylamino-1- [4- (tri
Fluoroacetyl) phenyl] -3,3,3-triflu
(1- of Example 1) except that Oro-2-propanone was used.
The same procedure as in 2) was performed, and 1-amino-1- (4-hydroxy)
Phenyl) -3,3,3-trifluoro-2-propano
Hydrochloride (below) was obtained.

[0091]

[Chemical formula 22] ¹ H-NMR (CD₃OD) δ = 5.22 (1H, s),
6.91, 7.29 (each 2H, AA'BB ')
 ppm (5-3) 1-amino-1-of (1-3) of Example 1
(4-hydroxyphenyl) -2-propanone hydrochloride
1-amino-1- (4-hydroxyphenyl) -3,
Changed to 3,3-trifluoro-2-propanone hydrochloride
Other than that, the same procedure as 1-3 in Example 1 was repeated to obtain 2,5-bis
(4-hydroxyphenyl) -3,6-bis (triflu
10 g of oromethyl) pyrazine (below) was obtained.

[0092]

[Chemical formula 23] ¹ H-NMR (CD₃OD + NaOD) δ = 6.76,
7.31 (each 4H, AA'BB ') ppm

[0093]

INDUSTRIAL APPLICABILITY According to the present invention, a novel bisphenol-type pyrazine derivative, which is expected to be useful in various applications such as various functional material compounds and monomers for producing polymer compounds, more specifically, at least pyrazine Various 2,5-bis (4-hydroxyphenyl) pyrazines having a substituent at the 3,6-position of the ring can be provided.

Further, according to the present invention, the above-mentioned various pyrazine derivatives of the present invention are selected with high selectivity and at high yield.
It is possible to provide a production method which is particularly advantageous in practical use and can be produced efficiently in a short process.

Claims (2)

[Claims] 1. The following general formula [I]:(However, R in the formula [I]¹Is an alky having 1 to 20 carbon atoms
Group, an aryl group having 6 to 12 carbon atoms or a halogen atom
Show, R² Is an alkyl group having 1 to 30 carbon atoms, and 1 to 1 carbon atoms
30 halogenated alkyl groups, C1-C30 alko
Xyalkyl group, alkenyl group having 2 to 30 carbon atoms
Represents an alkynyl group or an aryl group having 6 to 12 carbon atoms.
, A represents an integer of 0 to 4. ) Pyrazine invitation
conductor. 2. The following general formula [II]: (However, R ¹ in the formula [II] represents an alkyl group having 1 to 20 carbon atoms, an aryl group having 6 to 12 carbon atoms, or a halogen atom, and a represents an integer of 0 to 4). The method for producing a pyrazine derivative according to claim 1, wherein the compound [II] is aminoketonized and then dimerized.