JPH01172377A - Production of substituted monocyanopyrazine - Google Patents

Abstract

PURPOSE:To readily obtain the title compound useful as a raw material for agricultural chemicals, medicines, polymers, etc., having various kinds of substitu ent groups, by reacting a compound, e.g., 2-cyano-5-methyl-3-methylsulfonyl pyrazine, with a Grignard reagent. CONSTITUTION:A compound expressed by formula I (R is alkyl, aralkyl or aryl; R<2> and R<3> alone are H, alkyl, aryl or heterocyclic ring) (e.g., 2-cyano-5- methyl-3-ethylsulfonylpyrazine) is reacted with a compound expressed by formula II (X is halogen; R<1> is alkyl, alkenyl, alkynyl, aryl, aralkyl or heterocyclic ring) in a solvent, such as diethyl ether, at 0 deg.C-120 deg.C, preferably 0 deg.C - ambient temperature to afford the aimed compound expressed by formula III. Furthermore, according to the kind of the substituent group, this aimed compound provides a raw material for perfumes in case the substituent group is an alkyl group or raw material for polymers in case the substituent group is an unsaturated group.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing substituted monocyanopyrazines. More specifically, the present invention relates to a novel method for producing substituted monocyanopyrazine, which is useful as a raw material for agricultural medicines, fragrances, polymers, and the like.

[Conventional technology]

For the production method of substituted monocyanopyrazines, see J6^,
C,S, 782141 (1956).

That is, halopyrazine and Cu (CM) z are γ-
Obtained by heating in picoline or pyridine. However, this method was limited to lower alkyl and phenyl groups as substituents for pyrazine, and it was not possible to introduce functional groups or heterocycles. Furthermore, when the halopyrodine used as a raw material is chlorpyrazine, the reaction does not proceed smoothly, and the reaction is limited to the more expensive brompyrazine.

Furthermore, since Cu (CN) t and γ-picoline and pyridine are used as reaction solvents, there are problems such as troublesome post-treatments.

In addition, in Proceedings of the 52nd Spring Annual Meeting of the Chemical Society of Japan ■, p. 1225 (1986), Dodo Furukawa et al. conducted a reaction between 2-phenylsulfonylpyridine and phenyl Grignard reagent, and
Although there is a report that -phenylpyridine was obtained, there is no report regarding the production of the substituted monocyanopyrazine of the present invention.

[Problem that the invention seeks to solve]

Pyrazine derivatives are widely used chemicals that are used in agricultural medicines, fragrances, etc. In particular, cyanopyrazines are an extremely valuable group of compounds since the cyano group can be converted into other functional groups. An object of the present invention is to provide a method for easily producing pyrazine with good practical yield.

[Means for solving problems]

The present inventors have arrived at the present invention as a result of various studies.

That is, the present invention relates to the general formula (1) (wherein R is alkyl, aralkyl, aryl,
and R3 each independently represent hydrogen, alkyl, aryl, or heterocycle) and compounds represented by the general formula %) (wherein, X is halogen, R1 is alkyl, alkenyl,
It is characterized by reacting a compound represented by alkynyl, aryl which may have a substituent, aralkyl, or heterocycle (wherein R1, H1, and R3 have the same meanings as above).
) is a method for producing a compound represented by

The present invention is carried out in a solvent at a reaction temperature of 0°C to 120°C, preferably 0°C to room temperature, for 1 to 6 hours.

Solvents used in the present invention include diethyl ether,
Ethers such as dimethoxyethane and TI(F) or mixed solvents of ethers and aliphatic or aromatic hydrocarbons such as hexane, benzene, and toluene are preferred.

After the reaction is completed, the desired product can be obtained by carrying out usual post-treatments. The structure of the compound is IR.

Identified by NMR and M^SS.

〔Example〕

Next, the present invention will be explained with reference to Examples.

Example 1 2-cyano-3,5-dimethylpyrazine (compound no. 2
) 1.97 g (0.01 mol) of 2-cyano-5-methyl-3-methylsulfonylpyrazine was dissolved in 30 m of anhydrous tetrahydrofuran and heated to 0 °C under a nitrogen stream without stirring to prepare commercially available methylmagnesium zolomide 7. .6 m (0,
015 mol) (1,96 mol THF solution) was gradually added dropwise, the reaction temperature was raised to room temperature, and stirring was continued for 1 hour. The reaction mixture was poured into 200 d of ice water and acidified with dilute hydrochloric acid. The extract was extracted twice with 50 d of ethyl acetate and dried over magnesium sulfate. Ethyl acetate was distilled off under reduced pressure and the remaining oil was purified by column chromatography to obtain 1.2 g (yield 90x) of a yellow liquid. n:'
1.5270 Example 2 Synthesis of 2-cyano-5-methyl-3-phenylpyrazine (Compound No. 4) 1.5g, commercially available phenylmagnesium bromide 5.7d
(2 molar THF solution) in the same manner as in Example 1. 0.56 g (yield 40%) of a yellow liquid was obtained.

Synthesis of hardware number 8) Obtained by reacting 0.55 g of virol and 8.2 d of commercially available ethylmagnesium bromide (0.99 mol of tetrahydrofuran solution) in ether at 0°C. 2-
The virol magnesium bromide solution was gradually added to the 501d ether solution of Ig's 2-cyano-3-phenylsulfonylpyrazine at 0°C. After the dropwise addition was completed, the reaction temperature was raised to room temperature and stirring was continued for 6 hours. reaction mixture to 10
0 I11 After pouring into ice water and making acidic with dilute hydrochloric acid, 100
The ether from step d was added to separate the aqueous and ether layers, and the ether layer was dried over magnesium sulfate. Column chromatography 96-'48 g (yield 70%) of the target product was obtained.

Melting point 145.0-146.0°C Synthesis of Compound No. 6) Ether '1111-teg was gradually added to an ether 50d solution of 2-cyano-3-phenylsulfonylpyrazine. Produced in the same manner as in Example 3, 0.61 g (yield 80%)
Obtained the desired object. Melting point 94. O~95.0°C Compounds prepared according to the present invention, including the compounds of the above examples, are shown in Table 1.

Table 1 [Effects of the Invention] According to the present invention, the desired product can be produced by a simple method without using raw materials that require troublesome post-treatment. Furthermore, in particular, a functional group or a heterocycle can be introduced into the cyanopyrazine ring.

Substituted monocyanopyrazines synthesized by the final method have a wide variety of substituent groups, and are useful as intermediates in the synthesis of various organic compounds. That is, depending on the type of substituent, the pyrazines synthesized according to the present invention not only serve as a raw material for perfumes when the substituent is an alkyl group, but also serve as a raw material for a polymer having cyanopyrazine when the pyrazines are an unsaturated group.

Furthermore, the cyano group is converted to other functional groups (e.g. amide,
ester, amino group), it can be introduced into other skeletons, making it extremely useful as a raw material for the synthesis of medicines and agrochemicals.

Applicant: Nippon Soda Co., Ltd.

Claims (1)

[Claims] (1) General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼[I] (In the formula, R is alkyl, aralkyl, aryl, R^2
and R^3 each independently represent hydrogen, alkyl, aryl, or heterocycle. ) and the general formula (II) R^1MgX(II) (wherein, There are ▲ mathematical formulas, chemical formulas, tables, etc. that are characterized by reacting compounds represented by (in the formula, R^1, R^2, R^3 have the same meanings as above). Methods of making the compounds represented.