JP2000159752A - Production of 4,5-dichloro-6-(alpha-fluoroalkyl)pyrimidine - Google Patents

Abstract

PROBLEM TO BE SOLVED: To inexpensively, industrially obtain in high yield through a single-step reaction the subject compound useful as an intermediate for synthesizing insecticides by reaction a fluoroalkylpyrimidone with sulfuryl chloride in the presence of a catalyst. SOLUTION: This compound of formula II is obtained by reaction of a 6-(α- fluoroalkyl)-4-pyrimidone of formula I (R1 is an alkyl; R2 is H or an alkyl) with sulfuryl chloride in the presence of a catalyst (e.g. a formamide such as N,N-dimethylformamide, N,N-diethylformamide or N,N-dibutylformamide) pref. at -20 to 150 deg.C, more pref. at -5 to 100 deg.C, normally for 0.5-20 h; wherein the amount of the catalyst to be used is pref. >=0.5 molar time, more pref. >=1 molar time based on the compound of formula I, and the amount of the sulfuryl chloride to be used pref. >=1.8 molar times, more pref. 2.0-10.0 molar times based on the compound of formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to aminopyrimidine derivatives useful as insecticides, acaricides, fungicides, nematocides (JP-A-5-230036, JP-A-6-230036).
JP-A-25187, JP-A-6-116247,
JP-A-6-247939, JP-A-7-25822
No. 3), which is important as a synthetic intermediate of 4,5-dichloro-6- (α-fluoroalkyl) pyrimidine.

[0002]

2. Description of the Related Art The production methods described in JP-A-5-194417, JP-A-6-25187, JP-A-6-116247, JP-A-6-247939 and the like are as follows. 4,5-dichloro-6- (1-
Hydroxyethyl) pyrimidine is reacted with diethylaminosulfur trifluoride to give 4,5-dichloro-
6- (1-Fluoroethyl) pyrimidine is obtained.

[0003]

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[0004] However, this production method is based on 4,5-dichloro-
The synthesis of 6- (1-hydroxyethyl) pyrimidine is complicated, and the fluorinating agent diethylaminosulfur trifluoride is very expensive, so that it is not suitable for industrial production.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide an important synthetic intermediate for insecticides, 4,5-dichloro-1-.
To provide a novel production method for industrially producing (α-fluoroalkyl) pyrimidine from 6- (α-fluoroalkyl) -4-pyrimidone at low cost and with good yield in a one-step reaction. It is.

[0006]

The inventors of the present invention have studied to solve the above-mentioned problems, and as a result, have found that 4,5-dichloro-1- (α-fluoroalkyl) which is important as an intermediate for the synthesis of insecticides. Pyrimidine is converted to 6- (α-fluoroalkyl)
The present invention has been completed by finding that it can be produced industrially at a low cost and in a high yield from -4-pyrimidone in a one-step reaction. That is, the present invention provides the following formula (1):

[0007]

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(Wherein R ¹ represents an alkyl group and R ² represents a hydrogen atom or an alkyl group).
Reacting (fluoroalkyl) -4-pyrimidone with sulfuryl chloride in the presence of a catalyst, characterized by the following formula (2):

[0009]

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(Wherein R ¹ and R ² have the same meanings as described above), and a process for producing 4,5-dichloro-6- (α-fluoroalkyl) pyrimidine represented by the formula:

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. The starting compound, 6- (α-
Fluoroalkyl) -4-pyrimidone [compound (1)]
And 4,5 represented by the above formula (2) which is the target compound
R ¹ and R ² in -dichloro-6- (α-fluoroalkyl) pyrimidine [compound (2)] are as follows. Examples of R ¹ include a linear or branched alkyl group. As the alkyl group for R ¹ ,
It has 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms. Examples of R ² include a hydrogen atom and a linear or branched alkyl group. The alkyl group for R ² has 1 to 10 carbon atoms, preferably 1 to 10 carbon atoms.
It is four, more preferably a methyl group.

The starting compound (1) used in the present invention is
As shown below, from the corresponding 2-fluorocarboxylic acid ester and carboxylic acid ester, 4-fluoro-3-
After obtaining an oxocarboxylic acid ester, it can be obtained by cyclization with formamidine.

[0013]

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(Wherein, R ¹ and R ² have the same meanings as described above; R ³ and R ⁴ each represent an alkyl group.) A method for obtaining a 2-fluorocarboxylic acid ester is as follows.
For example, Tetrahedron Lett. , 199
3 , 293, Tetrahedron and Asymmet
ry, 1994 , 981. As a method for obtaining a 4-fluoro-3-oxocarboxylic acid ester from a 2-fluorocarboxylic acid ester and a carboxylic acid ester, for example, Japanese Patent Application No. 9-342.
342 can be mentioned. 4-
As a method of cyclizing a fluoro-3-oxocarboxylic acid ester with formamidine, for example, Japanese Patent Application No.
The method described in Japanese Patent No. 55174 can be mentioned.
The amount of sulfuryl chloride used in the present invention is the same as that of compound (1)
Is at least 1.8 times the molar amount to the
１10.0 times mol. The catalyst used in the present invention includes formamides such as N, N-dimethylformamide, N, N-diethylformamide, N, N-dibutylformamide.

The amount of the catalyst to be used is 0.5 times or more, preferably 1 time or more, relative to compound (1). In the synthesis of the compound (2) of the present invention, a solvent may or may not be used. When a solvent is used, it is not particularly limited as long as it does not participate in the reaction.
For example, aliphatic halogenated hydrocarbons such as dichloromethane, chloroform and dichloroethane, aromatic halogenated hydrocarbons such as chlorobenzene, aliphatic hydrocarbons such as hexane and heptane, N, N-dimethylformamide,
Amides such as N, N-dimethylacetamide, esters such as ethyl acetate and butyl acetate, tetrahydrofuran,
Ethers such as dimethoxyethane can be exemplified. These solvents can be used alone or as a mixture. The amount of the solvent used is 0 based on the compound (1).
The capacity is preferably up to 50 times, more preferably 2 to 20 times.
Double the amount.

In the synthesis of the compound (2) of the present invention, the reaction temperature used is from -20 to 150 ° C, preferably from -5 to 100 ° C. The reaction time in the synthesis of the compound (2) of the present invention varies depending on the concentration, temperature and amount used, but is usually completed in 0.5 to 20 hours. After completion of the reaction, the target compound (2) produced as described above is subjected to ordinary post-treatments such as washing, extraction and concentration, and if necessary, purified by a known means such as distillation or various chromatography. be able to.

[0017]

The present invention will be specifically described below with reference to examples. Note that these examples do not limit the scope of the present invention.

Example 1 [4,5-dichloro-6- (1-
Synthesis of fluoroethyl) pyrimidine] 6- (1-Fluoroethyl) -4-pyrimidone 1.42
g, in a solution of N, N-
2.92 g of dimethylformamide was added, and while cooling, 3.37 g of sulfuryl chloride was added dropwise at 2 to 4 ° C.
The mixture was reacted at ４4 ° C. for 2 hours, and further heated under reflux for 2 hours (44
° C). The reaction solution was cooled to room temperature and quantified by liquid chromatography internal standard method.
1.80 g of-(1-fluoroethyl) pyrimidine was produced (yield 92.3%). The organic layer was concentrated under reduced pressure and distilled under reduced pressure to obtain 4,5-dichloro-6- (1
0.76 g of (-fluoroethyl) pyrimidine was obtained. Boiling point: 84 to 88 ° C. / 5 mmHg · Mass analysis: CI-MS m / e = 195 (m + 1) · 1 H-NMR (CDCl 3) δ (ppm) 1.66~
1.78 (3H, dd), 5.89-6.14 (1H,
dq), 8.92 (1H, s)

Example 2 [4,5-dichloro-6- (1-
Synthesis of fluoroethyl) pyrimidine] 6- (1-Fluoroethyl) -4-pyrimidone 1.42
g, in a solution of N, N-
After adding 2.19 g of dimethylformamide, the mixture was heated to reflux (4.
At 37 ° C., 3.37 g of sulfuryl chloride was added dropwise over 20 minutes, and the mixture was further heated under reflux (44 ° C.) for 2 hours. The reaction solution was cooled to room temperature and quantified by liquid chromatography internal standard method. As a result, 1.74 g of 4,5-dichloro-6- (1-fluoroethyl) pyrimidine was produced (yield: 89.2%).

Example 3 [4,5-dichloro-6- (1-
Synthesis of fluoroethyl) pyrimidine] 6- (1-Fluoroethyl) -4-pyrimidone 1.42
g was suspended in 7.5 ml of chlorobenzene, and 1.35 g of sulfuryl chloride was added. After stirring at 60 ° C. for 30 minutes, 2.92 g of N, N-dimethylformamide was added.
Further, 2.02 g of sulfuryl chloride was added and reacted at 60 ° C. for 1 hour. The reaction solution was cooled to room temperature and quantified by liquid chromatography internal standard method to give 1.76 g of 4,5-dichloro-6- (1-fluoroethyl) pyrimidine.
Was produced (yield 90.5%).

Example 4 [4,5-dichloro-6- (1-
Synthesis of fluoroethyl) pyrimidine] 6- (1-Fluoroethyl) -4-pyrimidone 1.42
g of sulfuryl chloride in 7.5 ml of chlorobenzene were added to the solution, and stirred at 80 ° C. for 30 minutes. The internal temperature was lowered to 40 ° C., and N, N-dimethylformamide (2.92 g) and sulfuryl chloride 2 Add 15g and add 4
The reaction was performed at 0 ° C. for 2 hours. The reaction solution was cooled to room temperature and quantified by liquid chromatography internal standard method.
1.78 g of -dichloro-6- (1-fluoroethyl) pyrimidine was produced (yield 91.1%).

Example 5 [4,5-dichloro-6- (2-
Synthesis of fluoro-2-propyl) pyrimidine] N, N-dimethylformamide (5.85 g) was added to a solution of 3.12 g of 6- (2-fluoro-2-propyl) -4-pyrimidone suspended in 15 ml of dichloromethane, followed by cooling. Then, 6.75 g of sulfuryl chloride was added dropwise at 1 to 5 ° C, and the mixture was reacted at 1 to 5 ° C for 2 hours, and further heated under reflux (44 ° C) for 2 hours. The reaction solution was cooled to room temperature and quantified by a liquid chromatography internal standard method. As a result, 3.75 g of 4,5-dichloro-6- (2-fluoro-2-propyl) pyrimidine was produced (yield: 89.5). %). The organic layer was concentrated under reduced pressure and then distilled under reduced pressure to give 4,5-dichloro-6- (1-fluoroethyl) pyrimidine as 3.1.
4 g were obtained. Boiling point: 56-57 ° C. / 2 mmHg · Mass analysis: CI-MS m / e = 209 (m + 1) · 1 H-NMR (CDCl 3) δ (ppm) 1.79
(6H, dd), 8.81 (1H, s)

Example 6 [4,5-dichloro-6- (1-
Synthesis of Fluoro-1-pentyl) pyrimidine] 4.39 g of N, N-dimethylformamide was added to a solution of 2.76 g of 6- (1-fluoro-1-pentyl) -4-pyrimidone suspended in 15 ml of dichloromethane, followed by cooling. Then, 5.06 g of sulfuryl chloride was added dropwise at 0 to 5 ° C, and the mixture was reacted at 1 to 5 ° C for 2 hours, and further heated under reflux (44 ° C) for 2 hours. The reaction solution was cooled to room temperature, and determined by liquid chromatography internal standard method, 3.13 g of 4,5-dichloro-6- (1-fluoro-1-pentyl) pyrimidine was produced (yield: 88.0). %). The organic layer was concentrated under reduced pressure and distilled under reduced pressure to obtain 2.65 g of 4,5-dichloro-6- (1-fluoro-1-pentyl) pyrimidine. Boiling point: 81-82 ° C. / 1.5 mm Hg · Mass analysis: CI-MS m / e = 237 (m + 1) · 1 H-NMR (CDCl 3) δ (ppm) 0.94
(3H, t), 1.35 to 1.62 (4H, m), 1.
85 to 2.12 (2H, m), 5.77 to 5.92 (1
H, dq), 8.92 (1H, s)

Reference Example 1 [Synthesis of methyl 4-fluoro-3-oxopentanoate] 2.00 g of methyl 2-fluoropropionate was added to a solution of 1.31 g of 62.8% sodium hydride in 10 ml of tetrahydrofuran. And a mixed solution of 2.10 g of methyl acetate was dropped in 10 minutes, and then heated at 30 to 35 ° C. for 4 hours. After completion of the reaction, the mixture was cooled to room temperature, neutralized with 1N-hydrochloric acid, separated, and the organic layer was quantified by a gas chromatography internal standard method to yield 2.57 g of methyl 4-fluoro-3-oxopentanoate. (Yield 92
%). The organic layer was concentrated under reduced pressure and distilled under reduced pressure to obtain 2.03 g of methyl 4-fluoro-3-oxopentanoate. Boiling point: 80~81 ℃ / 24~25mmHg · Mass analysis: CI-MS m / e = 149 (m + 1) · 1 H-NMR (CDCl 3) δ (ppm) 1.47~
1.60 (3H, m), 3.66-3.67 (1.7
H, d), 3.76 to 3.77 (3H, d), 4.87
~ 5.12 (1H, m), 5.33 (0.15H,
s), 11.80-12.00 (0.15H, bs) ¹ H-NMR analysis reveals keto-enol foam.

Reference Example 2 [6- (1-fluoroethyl)-
Synthesis of 4-pyrimidone] To a solution of 9.33 g of methyl 4-fluoro-3-oxopentanoate in 115 ml of methanol was added 2
36.5 g of 8% sodium methylate / methanol solution
And 9.84 g of formamidine acetate were sequentially added at room temperature, followed by heating and stirring at 40 ° C. for 12 hours. Further, 0.66 g of formamidine acetate was added, and the mixture was heated and stirred at 50 ° C. for 2 hours, cooled to 10 ° C. or lower, and a mixture of 9.51 g of concentrated sulfuric acid and 8.5 g of water was added. After stirring at 50 ° C. for 30 minutes, insolubles were separated by filtration, and the filtrate was quantified by a liquid chromatography internal standard method to give 6- (1-fluoroethyl)-.
7.99 g of 4-pyrimidone was produced (yield: 89.
2%). After the filtrate was concentrated under reduced pressure, the concentrated solution was diluted with 40 ml of 2
The crystals were recrystallized from -propanol to obtain 5.82 g of 6- (1-fluoroethyl) -4-pyrimidone. Melting point: 170 to 171.5 ° C. Mass spectrometry: CI-MS m / e = 143 (m + 1) ¹ H-NMR (CDCl ₃ ) δ (ppm) 1.60 to
1.67 (3H, dd), 5.34-5.47 (1H,
dq), 6.62 to 6.63 (1H, t), 8.13
(1H, s), 13.3 (1H, bs)

[0026]

According to the present invention, 4,5-dihalo-1- (α-haloalkyl) pyrimidine, which is important as an intermediate for the synthesis of insecticides, can be reacted with 6- (α-haloalkyl) -4-pyrimidone in one step. Thus, it can be industrially manufactured at low cost and with high yield.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Kazuhiro Morita 5 in Ube Research Institute, Ube City, Ube-shi, Yamaguchi 5 Ube Research Institute Co., Ltd. Ube Laboratory Co., Ltd.

Claims (1)

[Claims] 1. The following formula (1): Wherein R ¹ represents an alkyl group and R ² represents a hydrogen atom or an alkyl group. 6- (α-fluoroalkyl) -4-pyrimidone is reacted with sulfuryl chloride in the presence of a catalyst. The following formula (2): (Wherein, R ¹ and R ² have the same meanings as described above.) A method for producing 4,5-dichloro-6- (α-fluoroalkyl) pyrimidine represented by the formula: