JP3317309B2 - Method for producing 3-substituted amino-4,4,4-trifluorocrotonate - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

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

2. Description of the Related Art Conventionally, 3-substituted amino-4,4,4-trifluorocrotonates having an amino group substituted at the 3-position have been disclosed in Journal of Organic Chemistry, Vol. 1358 pages (Madel
eine M.E. Joullie, et al., J. Mol. O
rg. Chem., 21 , 1358 (1956)).
-Ethyl butylamino-4,4,4-trifluorocrotonate, Journal of Heterocyclic Chemistry, vol. 9, p. 513 (Albert W. Lu)
tz, et al., J. Mol. 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, 3-substituted amino-4,4,4-trifluorocrotonates are obtained by subjecting the corresponding salts of trifluoroacetoacetate and amine to thermal rearrangement in a sealed tube at a high temperature. In addition to these, an amide compound reacted with an ester is by-produced, so that a more excellent production method is desired (see Reference Examples 2 and 3 described later).

Means for Solving the Problems The present inventors have obtained the formula (1)

Embedded image Wherein R ¹ represents a C _1-6 alkyl group. And a trifluoroacetoacetic ester represented by the formula (2):

Embedded image 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,
Represents a _3-6 alkynyl group, a benzyl group or a C _1-4 alkoxycarbonyl 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.

Embedded image [In the formula, R ¹ and R ² represent the same meaning as described above. And a method for producing a 3-substituted amino-4,4,4-trifluorocrotonate represented by the formula (4):

Embedded image Wherein R ¹ represents a C _1-6 alkyl group, and R ² represents a C _1-6
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. That the 3-substituted amino-4,4,4-trifluorocrotonate represented by the formula (3) can be produced even when the salt represented by the formula (3) is dehydrated in a solvent in the presence of a C _1-4 fatty acid. Heading, the present invention has been completed. Among the 3-amino-4,4,4-trifluorocrotonates represented by the formula (3), a compound represented by the formula (5)

Embedded image Wherein R ¹⁰ represents a C _1-6 alkyl group, and R ²⁰ represents a C _1-6
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. However, compounds of the following combinations are excluded.
^{(R 10, R 20) :(} CH 3, CH 3), (CH 3, C 2
_{H 5), (C 2 H} 5, CH 3 CH 2 CH 2 CH 2),
_{(C 2 H 5, (CH} 3) 2 CH), 3- substituted amino-4,4,4-trifluoro-crotonate ester represented by] are novel compounds. Hereinafter, the present production method will be described in detail. 1 equivalent of trifluoroacetoacetic acid ester represented by the formula (1) and 0.5 equivalent of the substituted amine represented by the formula (2)
To 2.0 equivalents, preferably 1.0 to 1.2 equivalents,
0.5 to 24 hours, preferably 1 to 10 hours, 0 to 200 ° C. in a solvent in the presence of 0.001 to 2.0 equivalents, preferably 0.01 to 1.2 equivalents of C _1-4 fatty acid.
The reaction is preferably carried out at 20 to 160 ° C. or at the boiling point of the solvent, and the 3-substituted amino-4,4,4
-Trifluorocrotonates can be obtained. At this time, instead of the trifluoroacetoacetic acid ester represented by the formula (1) and the substituted amine represented by the formula (2),
The salt represented by the formula (4) can be used. C _1-4 fatty acids include formic acid, acetic acid, propionic acid and butyric acid, preferably acetic acid. Examples of the solvent include 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 and the like. Ketones or mixtures thereof are mentioned. After completion of the reaction, distillation is performed after distilling off or appropriately concentrating the solvent, or distilling off the C _1-4 fatty acid in the system beforehand with an aqueous alkali solution such as a sodium hydrogen carbonate solution, followed by distillation to obtain the formula (3)
To obtain a 3-substituted amino-4,4,4-trifluorocrotonate represented by the following formula: The trifluoroacetoacetic ester represented by the formula (1) has the following equilibrium, and is therefore also represented by the formula (1 ′).

Embedded image Hereinafter, the present invention will be described in detail with reference to Examples and Reference Examples. [Example 1] Production of ethyl trifluoroacetoacetate methylamine salt

Embedded image60 g of ethyl trifluoroacetoacetate and methylene chloride
500 ml of the mixed solution in a dry ice-acetone bath -2
Cool to 0 ° C. and add 13 g of methylamine into
I blew it over 0 minutes. After stirring for another hour,
The salt was filtered off. Wash the salt with a small amount of hexane on the funnel
After purification, drying under reduced pressure gave 68 g of the target product as white crystals.
Was. The filtrate was distilled off to further obtain 2 g of the target substance as a white solid.
I got it. Yield = 99.8%¹ H-NMR (60 MHz, CDCl_Three+ D₆ -DMS
O), δ (TMS): 1.19 (t,J= 7Hz, 3H, CO
OCH_TwoCH _Three), 2.44 (s, 3H, NC)H _Three), 3.
97 (q,J= 7Hz, 2H, COOCH _TwoCH_Three), 4.83
(S, 1H, C = CHCOO), 7.05 (brs, 3H,H
_ThreeNCH_ThreeExample 2 3-Methylamino-4,4,4-trifluorocroton
Of ethyl acetate

Embedded image 21. Ethyl trifluoroacetoacetate methylamine salt
6 g of acetic acid was added to a mixture of 5 g and 100 ml of ethanol and refluxed for 2 hours. After distilling off ethanol at normal pressure, a rectification tube was attached, and acetic acid was further distilled off. Distillation was performed under reduced pressure to obtain 12.4 g (yield = 63%) of the target product as a colorless transparent liquid. Boiling point: 80.5-81.0 ° C / 25 mmHg. The purity by gas chromatography was 98.2%. Example 3 Production of ethyl 3-benzylamino-4,4,4-trifluorocrotonate

Embedded image Ethyl trifluoroacetoacetate / benzylamine salt 50
10.3 g of acetic acid was added to a mixture of g and 200 ml of ethanol, and the mixture was refluxed for 8 hours. After distilling off ethanol under reduced pressure, the residue was extracted with ethyl acetate, washed with a saturated aqueous solution of sodium hydrogencarbonate and brine, and then dried over anhydrous sodium sulfate. After distilling off the solvent, a rectification tube packed with 5 cm of glass beads was attached and distilled under reduced pressure to obtain 26.9 g of the desired product (yield = 5%).
7%) as a clear, colorless liquid. Boiling point 98.5-9
The purity by gas chromatography at 9.5 ° C / 0.20 mmHg was 99%. [Reference Example 1] Production of ethyl 3-amino-4,4,4-trifluorocrotonate

Embedded image A mixed solution of 200 g of ethyl trifluoroacetoacetate and 1090 ml of methylene chloride was mixed with dry ice-acetone.
After cooling to 10 to 0 ° C., an equimolar amount of ammonia gas was blown. 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 the ethanol was distilled off, ethyl acetate was added, and the mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off. A rectification tube packed with 5 cm of glass beads was attached and distilled under reduced pressure.
6 g (Yield from ethyl trifluoroacetoacetate = 73)
%) Was obtained as a colorless transparent liquid. Boiling point 66.5-67.
The purity by gas chromatography at 5 ° C / 20 mmHg was 99%. [Reference Example 2] Production of ethyl 3-methylamino-4,4,4-trifluorocrotonate

Embedded image Ethyl trifluoroacetoacetate / methylamine salt 10g
In an autoclave (1.3 × 10 ⁶ Pa)
Heat at 60 ° C. for 3 hours. After cooling, insolubles were removed by decantation, and the resulting brown liquid was distilled under reduced pressure. The fraction having a boiling point of 50 to 70 ° C./100 mmHg was subjected to GC-M
When analyzed by S, it was found that the target substance was contained at about 5%. [Reference Example 3] Synthesis of ethyl 3-methylamino-4,4,4-trifluorocrotonate

Embedded image 1 g of ethyl trifluoroacetoacetate / methylamine salt,
10 ml of ethanol and 0.4 g of acetic acid were heated in an autoclave (6 × 10 ⁵ Pa) at 150 to 160 ° C. for 2 hours with stirring. After standing to cool, the solvent was distilled off, and 690 mg of the obtained brown-red oil was purified by preparative thin-layer chromatography (developing solvent: chloroform) to give an _Rf value of 0.85 to 0.9.
The fraction 0 was collected and extracted with ethyl acetate, and the solvent was distilled off to obtain 100 mg of the desired product (yield = 11%) as a pale yellow liquid. The purity by gas chromatography is 94.4.
%Met. 3-Substituted amino-produced in Examples 1-3
Table 1 shows the structure, physical properties and yield of 4,4,4-trifluorocrotonates and the compounds produced according to them, ¹ H-NMR is shown in Table 2, and ¹⁹ F-NMR is shown in Table 3.
In the table, ¹³ C-NMR is shown in Table 4 and MS is shown in Table 5. [Table 1]

Embedded image

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

[Table 2] [Table 2 continued]

[Table 3] [Table 3]

[Table 4] [Table 4]

[Table 5] [Table 4 continued]

[Table 6] [Table 4 continued]

[Table 7] [Table 5]

[Table 8] Example 4 36.8 g of ethyl trifluoroacetoacetate
6.20 g (0.200 mol) of methylamine gas was blown into the ethanol solution containing (0.200 mol), acetic acid was added, and for Nos. 1 to 3, 1.24 g (0.040 mol) of methylamine gas was further added. Mol). Heat reflux 3
After an hour, a Vigreux tube was attached, and ethanol was distilled off until the liquid temperature reached 110 ° C. Evaporated ethanol and the residue were subjected to internal standard determination by liquid chromatography to determine the yield of ethyl 3-methylamino-4,4,4-trifluorocrotonate. Table 6 shows the reaction conditions, and Table 7 shows the results. [Table 6]

[Table 9]

[Table 7]

[Table 10]

Continuing on the front page (72) Inventor Hiroshi Kita 722-1, Tsuboi-cho, Funabashi-shi, Chiba Pref. Nissan Chemical Industry Co., Ltd. (72) Inventor Yoshihiro Iwasawa 722-1, Tsuboi-cho, Funabashi-shi, Chiba Nissan Chemical Co., Ltd. Inside the laboratory (72) Inventor Norio Tanaka 722-1, Tsuboi-cho, Funabashi-shi, Chiba Nissan Chemical Industry Co., Ltd. (72) Inventor Masafumi Nomura 722-1, Tsuboi-cho, Funabashi-shi, Chiba Nissan Chemical Industry Co., Ltd. In-house examiner Naoki Kono (56) References JP-A-64-25764 (JP, A) Org. Chem. , 1971, Vol. 36, No. 1, pages 37-43 (58) Fields investigated (Int. Cl. ⁷ , DB name) C07C 229/00 C07C 227/00 CA (STN) REGISTRY (STN)

Claims (3)

(57) [Claims] (1) Formula (1) Wherein R ¹ represents a C _1-6 alkyl group. Trifluoroacetic acetoacetic ester of formula (2) ## STR2 ## wherein represented by], R ² is C _1-6 alkyl, 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. Wherein the substituted amine of formula (3) is dehydrated in a solvent in the presence of a C _1-4 fatty acid. [In the formula, R ¹ and R ² represent the same meaning as described above. The method for producing a 3-substituted amino-4,4,4-trifluorocrotonate represented by the formula: 2. Formula (4) Wherein R ¹ represents a C _1-6 alkyl group, and R ² represents a C _1-6
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. Wherein the salt represented by the formula (3) is dehydrated in a solvent in the presence of a C _1-4 fatty acid. [In the formula, R ¹ and R ² represent the same meaning as described above. The method for producing a 3-substituted amino-4,4,4-trifluorocrotonate represented by the formula: 3. Formula (5) Wherein R ¹⁰ represents a C _1-6 alkyl group, and R ²⁰ represents methyl
Represents a group. Represented by 3-substituted amino with] 4,4,4
Trifluorocrotonate.