JPH05140060A - Production of 3-substituted amino-4,4,4-trifluorocrotonic acid ester - Google Patents

Abstract

PURPOSE:To obtain the subject compound useful as an intermediate of agricultural chemicals, medicinal drugs, etc., by putting a trifluoroacetoacetic acid ester and a substituted amine to dehydration in a solvent in the presence of a specific aliphatic acid. CONSTITUTION:A trifluoroacetoacetic acid ester of formula I (R is C1-6 alkyl) and a substituted amine of formula H2NR<2> (R<2> is C1-6 alkyl, C2-6 alkenyl, etc.) (e.g. methyl amine, etc.) are subjected to dehydration in a solvent (e.g. methanol, THF, etc.) in the presence of C1-4 aliphatic acid (preferably acetic acid) to obtain the objective compound of formula II. The reaction is preferably done by using 1-1.2 equivalents substituted amine and 0.01-1.2 equivalents C1-4 aliphatic acid to 1 equivalent compound of formula I at 20-160 deg.C for 1-10 hours. Here, the objective compounds of formula II will be new compounds when R<1> is C1-6 alkyl and R<2> is C1-6 haloalkyl, benzyl, etc.

Description

Detailed Description of the Invention

[0001]

The present invention relates to 3-substituted amino-4, which is useful as an intermediate for agricultural chemicals, pharmaceuticals, dyes, photographic materials, etc.
The present invention relates to 4,4-trifluorocrotonic acid ester and a method for producing the compound. These compounds are particularly important as raw materials for the herbicides described in JP-A-3-204865.

[0002]

PRIOR ART AND PROBLEMS Conventionally, 3-substituted amino-4,4,4-trifluorocrotonate having an amino group substituted at the 3-position has been reported in Journal of Organic Chemistry, Vol. P. 1358 (Madel
eine M. Joullie, et al., J. O
rg. Chem., 21 , 1358 (1956)) 3
-Ethyl butylamino-4,4,4-trifluorocrotonate, Journal of Heterocyclic Chemistry, vol. 9, p. 513 (Albert W. Lu
tz, et al., J. Am. Heterocycl. Ch
em., 9 , 513 (1972)), ethyl 3-isopropylamino-4,4,4-trifluorocrotonate, Russian literature (Fomin, AN et al.,
Zh. Org. Khim. , 22 , 1603 (198
6)) to 3-methylamino and 3-ethylamino-4,
Only methyl 4,4-trifluorocrotonate has been reported.

In these documents, the corresponding trifluoroacetoacetate and amine salt are thermally rearranged at high temperature in a sealed tube to obtain a 3-substituted amino-4,4,4-trifluorocrotonate ester. However, since a amide compound that has reacted with an ester is produced as a by-product in addition to the desired product, a more excellent production method is desired (see Reference Examples 2 and 3 below).

[0004]

The inventors of the present invention have shown that the formula (1)

[0005]

[Chemical 7]

[In the formula, R ¹ represents a C _1-6 alkyl group. ] A trifluoroacetoacetic acid ester represented by the formula (2)

[0007]

[Chemical 8]

[Wherein R ² is a C _1-6 alkyl group, C _1-6
Haloalkyl group, C _3-6 cycloalkyl group, C _2-6 alkenyl group, C _3-6 alkynyl group, benzyl group or C
_1-4 alkoxycarbonyl represents a C _1-4 alkyl group. ]
Wherein the substituted amine represented by the formula (3) is dehydrated in a solvent in the presence of a C _1-4 fatty acid.

[0009]

[Chemical 9]

[In the formula, R ¹ and R ² have the same meanings as described above. ] The production method of 3-substituted amino-4,4,4-trifluorocrotonic acid ester represented by

[0011]

[Chemical 10]

[Wherein R ¹ represents a C _1-6 alkyl group,
R ² is a C _1-6 alkyl group, a C _1-6 haloalkyl group, C
_3-6 cycloalkyl group, C _2-6 alkenyl group, C _3-6 alkynyl group, benzyl group or C _1-4 alkoxycarbonyl C _1-4 alkyl group. C _1-4 a salt represented by]
The present invention has been completed by finding that the 3-substituted amino-4,4,4-trifluorocrotonic acid ester represented by the formula (3) can be produced even when dehydrated in a solvent in the presence of a fatty acid.

3-amino-4,4 represented by the formula (3)
Among the 4-trifluorocrotonic acid esters, the formula (5)

[0014]

[Chemical 11]

[Wherein R^TenIs C_1-6Represents an alkyl group,
R²⁰Is C_1-6Alkyl group, C_1-6Haloalkyl group, C
_3-6Cycloalkyl group, C_2-6Alkenyl group, C_3-6A
Rukinyl group, benzyl group or C_1-4Alkoxy carbo
Nil C_1-4Represents an alkyl group. However, the combination of the following
Excluding compound. (R^Ten, R²⁰): (CH₃, CH₃),
(C ₂H_Five, CH₃), (C₂H_Five, CH₃CH₂CH
₂CH₂), (C₂H_Five, (CH₃)₂CH),]
3-substituted amino-4,4,4-trifluorochloro
Tonic ester is a novel compound.

The manufacturing method will be described in detail below. 1 equivalent of trifluoroacetoacetic acid ester represented by formula (1) and 0.5 to 2.0 substituted amine represented by formula (2)
Equivalent, preferably 1.0 to 1.2 equivalent, 0.001
To 2.0 equivalents, preferably 0.01 to 1.2 equivalents of C _1-4 fatty acid in the solvent, for 0.5 to 24 hours, preferably 1 to 10 hours, 0 to 200 ° C., preferably 2
The 3-substituted amino-4,4,4-trifluorocrotonic acid ester represented by the formula (3) can be obtained by reacting at 0 to 160 ° C. or at the boiling point of the solvent.

At this time, the salt represented by the formula (4) can be used in place of the trifluoroacetoacetic acid ester represented by the formula (1) and the substituted amine represented by the formula (2). C _1-4 fatty acids include formic acid, acetic acid, propionic acid and butyric acid, preferably acetic acid. As a solvent, alcohols such as methanol and ethanol, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as ethyl ether and THF, halogenated hydrocarbons such as chloroform and methylene chloride, acetone, methyl ethyl ketone, etc. Examples thereof include ketones and mixtures thereof.

After completion of the reaction, the solvent is distilled off or the solvent is appropriately concentrated and then distilled, or the C _1-4 fatty acid in the system is previously removed with an alkaline aqueous solution such as a sodium hydrogen carbonate solution, and then distilled to obtain the compound represented by the formula (3 The 3-substituted amino-4,4,4-trifluoro crotonic acid ester represented by these can be obtained. Since the trifluoroacetoacetic acid ester represented by the formula (1) has the following equilibrium, it is also represented by the formula (1 ′).

[0019]

[Chemical 12]

The present invention will be described in detail below with reference to examples and reference examples. Example 1 Production of ethyl trifluoroacetoacetate methylamine salt

[0021]

[Chemical 13]

60 g of ethyl trifluoroacetoacetate and
A mixed solution of 500 ml of methylene chloride was mixed with dry ice-acetate.
In a ton bath, cool to -20 to 0 ° C, and then add 13g of methyl.
Luamine was blown in for 30 minutes. Stir for another hour
After that, the produced salt was collected by filtration. A little salt on the funnel
After washing with hexane and drying under reduced pressure, 68 g of the target product is white
Obtained as crystals. When the filtrate is distilled off, 2 g of the target product is added.
Obtained as a white solid. Yield = 99.8%¹ H-NMR (60MHz, CDCl₃+ D₆ -DMS
O), δ (TMS): 1.19 (t,J= 7Hz, 3H, CO
OCH₂CH ₃), 2.44 (s, 3H, NC)H ₃), 3.
97 (q,J= 7Hz, 2H, COOCH ₂CH₃), 4.83
(S, 1H, C = CHCOO), 7.05 (br s, 3H,H
₃NCH₃) [Example 2] 3-methylamino-4,4,4-triflu
Production of ethyl orocrotonate

[0023]

[Chemical 14]

To a mixture of 21.5 g of ethyl trifluoroacetoacetate methylamine and 100 ml of ethanol 6
g of acetic acid was added and refluxed for 2 hours. After distilling off ethanol at atmospheric pressure, a rectification tube was attached and acetic acid was further distilled off. Distillation under reduced pressure gave 12.4 g of the desired product (yield = 63%) as a colorless transparent liquid. Boiling point 80.5-81.0 ℃ / 25mmH
g. The purity by gas chromatography was 98.2%.

[Example 3] 3-benzylamino-4,
Production of ethyl 4,4-trifluorocrotonate

[0026]

[Chemical 15]

To a mixture of 50 g of ethyl trifluoroacetoacetate / benzylamine salt and 200 ml of ethanol 1
0.3 g of acetic acid was added and refluxed for 8 hours. After ethanol was distilled off under reduced pressure, the mixture was extracted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate solution and saturated saline, and then dehydrated with anhydrous sodium sulfate. After distilling off the solvent, a rectification tube filled with 5 cm of glass beads was attached and distilled under reduced pressure to obtain the desired product 26.9.
g (rate = 57%) was obtained as a colorless transparent liquid. Boiling point 9
8.5-99.5 ° C / 0.20 mmHg, purity by gas chromatography was 99%. ． [Reference Example 1] Production of ethyl 3-amino-4,4,4-trifluorocrotonate

[0028]

[Chemical 16]

A mixed solution of 200 g of ethyl trifluoroacetoacetate and 1090 ml of methylene chloride was mixed with dry ice.
It was cooled to −10 to 0 ° C. with acetone, and an equimolar amount of ammonia gas was blown thereinto. Methylene chloride was distilled off, 1180 ml of ethanol and 32.6 g of acetic acid were added to the obtained salt, and the mixture was refluxed for 3 hours. After ethanol was distilled off, ethyl acetate was added, and the mixture was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. A rectification tube filled with 5 cm of glass beads was attached and distilled under reduced pressure to obtain 144.6 g of the target product (yield rate from ethyl trifluoroacetoacetate = 73%) as a colorless transparent liquid. Boiling point 6
It was 6.5 to 67.5 ° C / 20 mmHg, and the purity by gas chromatography was 99%.

Reference Example 2 3-Methylamino-4,4
Production of ethyl 4-trifluorocrotonate

[0031]

[Chemical 17]

10 g of ethyl trifluoroacetoacetate / methylamine salt was autoclaved (1.3 × 10 ⁶ Pa).
Heated at 150-160 ° C. for 3 hours. After cooling, insoluble matter was removed by decantation, and the obtained brown liquid was distilled under reduced pressure. When a fraction having a boiling point of 50 to 70 ° C./100 mmHg was analyzed by GC-MS, it was found that the target product was contained in about 5%.

Reference Example 3 3-Methylamino-4,4
Synthesis of ethyl 4-trifluorocrotonate

[0034]

[Chemical 18]

150 g of ethyl trifluoroacetoacetate / methylamine salt, 10 g of ethanol and 0.4 g of acetic acid were stirred in an autoclave (6 × 10 ⁵ Pa) under stirring.
Heated at 0 ° C. for 2 hours. After cooling, the solvent was distilled off, and 690 mg of the obtained brown red oily matter was purified by preparative thin layer chromatography (developing solvent: chloroform) to give an R _f value of 0.85.
A portion of ˜0.90 was separated, extracted with ethyl acetate, and the solvent was evaporated to obtain 100 mg of the desired product (yield = 11%) as a pale yellow liquid. The purity by gas chromatography is 9
It was 4.4%.

3-Substituted amino-prepared in Examples 1-3
The structures, physical properties and yields of 4,4,4-trifluorocrotonic acid esters and the compounds produced according to them are shown in Table ¹ , ¹ H-NMR is shown in Table 2 and ¹⁹ F-NMR is shown in Table 3.
¹³ C-NMR is shown in Table 4, and MS is shown in Table 5. [Table 1]

[0037]

[Chemical 19]

[0038]

[Table 1]

In the table, n, i and c mean normal, iso and cyclo, respectively. ^* 2f has a yield of 42%, and 16% contains ethyl 3-cyclopropylimino-4,4,4-trifluorobutyrate. The ratio of isomers was calculated from the proton ratio of ¹ H-NMR. [Table 2]

[0040]

[Table 2]

[Table 2 Continuation]

[0042]

[Table 3]

[Table 3]

[0044]

[Table 4]

[Table 4]

[0046]

[Table 5]

[Continued Table 4]

[0048]

[Table 6]

[Continued Table 4]

[0050]

[Table 7]

[Table 5]

[0052]

[Table 8]

Front Page Continuation (72) Inventor Kaoru Ito 1 722 Tsuboi-cho, Funabashi-shi, Chiba Central Research Laboratory, Nissan Chemical Industry Co., Ltd. (72) Inventor Hiroshi Kita 1 722 Tsuboi-cho, Funabashi, Chiba Pref. Company Central Research Institute

Claims (3)

[Claims] 1. Formula (1): [In the formula, R ¹ represents a C _1-6 alkyl group. ] And a trifluoroacetoacetic acid ester represented by the formula (2): [Wherein R ² is a C _1-6 alkyl group, a C _1-6 haloalkyl group, a C _3-6 cycloalkyl group, a C _2-6 alkenyl group, C
_{3-6 represents an} alkynyl group, a benzyl group or a C _1-4 alkoxycarbonyl C _1-4 alkyl group. ] The substituted amine represented by the formula is dehydrated in a solvent in the presence of a C _1-4 fatty acid, and is represented by the formula (3): [In the formula, R ¹ and R ² have the same meanings as described above. ] The manufacturing method of 3-substituted amino-4,4,4-trifluoro crotonic acid ester represented by these. 2. Formula (4): [In the formula, R ¹ represents a C _1-6 alkyl group, and R ² represents C _1-6.
It represents an alkyl group, a C _1-6 haloalkyl group, a C _3-6 cycloalkyl group, a C _2-6 alkenyl group, a C _3-6 alkynyl group, a benzyl group or a C _1-4 alkoxycarbonyl C _1-4 alkyl group. ] The salt represented by the formula] is dehydrated in a solvent in the presence of a C _1-4 fatty acid, and is represented by the formula (3): [In the formula, R ¹ and R ² have the same meanings as described above. ] The manufacturing method of 3-substituted amino-4,4,4-trifluoro crotonic acid ester represented by these. 3. Formula (5):[In the formula, R^TenIs C_1-6Represents an alkyl group, R²⁰Is C_1-6
Alkyl group, C_1-6Haloalkyl group, C_3-6Cycloal
Kill group, C_2-6Alkenyl group, C_3-6Alkynyl group,
Group or C_1-4Alkoxycarbonyl C_1-4Al
Represents a kill group. However, the compounds of the following combinations are excluded.
(R^Ten, R²⁰): (CH₃, CH₃), (C ₂H_Five, C
H₃), (C₂H_Five, CH₃CH₂CH₂CH₂),
(C₂H_Five, (CH₃)₂CH)]
Amino-4,4,4-trifluorocrotonate ester
Le.