JPS63264448A - Novel beta-ketonitrile - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I (R is alkyl having plural F atoms; R<1> is H or alkyl). EXAMPLE:Trifluoroacetoacetonitrile. USE:A synthetic raw material for agricultural chemicals and medicines, such as weeding agent, germicide and antifungal agent, having isoxazolyl groups. PREPARATION:A carboxylic acid ester expressed by the formula RCO2R<3> (R<3> is alkyl) is subjected to condensation reaction with a compound expressed by the formula R<1>CH2CN in a solvent, such as tetrahydrofuran, in the presence of lithium diisopropylamide at -78-0 deg.C to afford the aimed compound expressed by the formula. Although the resultant beta-ketonitrile is unstable, it can be stably handled by coexistence of a trace amount of toluenesulfonic acid or a mineral acid.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel β-ketonitrile having an isoxasilyl group and useful as a synthetic raw material for agricultural chemicals and medicines such as herbicides, fungicides, and antifungal agents.

Various herbicides, fungicides, antifungal agents, etc. having an isoxacylyl group have been provided in the past, and their synthetic intermediates include, for example, U.S. Pat. JP-A-57-31672, JP-A-57-53484 and JP-A-57-81467
No. 1 discloses various isoxasilylamines. However, no literature has been found that specifically discloses isoxasilylamines having an alkyl group substituted with a plurality of fluorine atoms.

The present invention provides a β-ketonitrile of the formula: [wherein R is alkyl having multiple fluorines, and R1 means hydrogen or alkyl] which is useful as a raw material for the synthesis of such novel isoxasilylamines. This is what we provide.

Corresponding compounds in which R' is phenyl or substituted phenyl are known (Chemical Abstracts 70 (21)
): 96286s, 95(21):186755q
, 102(9): 78829w, etc.), for example, W. R. Ness and A. Berger, Journal of the American Chemical Society (
Get, R, Nes and A, Barger.

J, Am, Chem, Soc, ), 72. 540
9 (1950). However, the compound of formula [I] has not been reported so far, and is a new compound produced by a different method from compounds in which R1 is phenyl or substituted phenyl.

The alkyl having multiple fluorine atoms represented by R includes groups having 1 to 9 fluorine atoms and 1 to 4 carbon atoms, for example,
Examples include trifluoromethyl, pentafluoroethyl, heptafluoropropyl, 2-(trifluoromethyl)propyl, and the like.

Alkyl represented by R1 includes groups having 1 to 5 carbon atoms, such as methyl, ethyl, isopropyl, ter
Examples include t-butyl.

The compound of formula [1] is prepared in tetrahydrofuran in the presence of lithium diisopropylamide with a carboxylic acid ester represented by the formula: % [wherein R is the same as above and R3 means alkyl]; Formula: %Formula %[ ] EIn the formula, R1 is the same as above] It is obtained by condensation with a compound represented by the following formula. The condensation reaction is preferably carried out at -78 to 0°C in a solvent such as tetrahydrofuran or ethyl ether. The obtained β-ketonitrile is not purified by distillation,
Since it is partially decomposed, it is preferable to use the obtained β-ketonitrile in its crude form in the next step.

The compounds of formulas [1] and [I[I] are known or can be produced according to known methods.

The compound of formula [I] of the present invention is useful as a new synthetic intermediate for agricultural chemicals and medicines having an isoxasilyl group. ] Polyfluoroalkyl isoxasilylamines or salts thereof, such as hydrochloride, nitrate, acetate, p
-Useful for the production of toluenesulfonate, methanesulfonate, etc.

The compound of formula [IV] is β represented by formula [1] of the present invention.
- Obtained by reacting ketonitrile with hydroxylamine, hydroxylamine hydrochloride, hydroxylamine sulfate, hydroxyurea, etc.

This reaction is carried out in a solvent such as water, methanol, ethanol, or ethylene glycol at 60-120°C, optionally neutralized with an alkali such as sodium bicarbonate, sodium carbonate, or sodium hydroxide. , 5-36
It is preferable to add 1 to 2 times the mole of % hydrochloric acid and conduct the reaction at 60 to 120°C.

The compound of formula [IV] is useful as a synthetic intermediate for agricultural chemicals and medicines such as herbicides, fungicides, and antifungal agents, especially herbicides and fungicides.

Next, the present invention will be explained in more detail with reference to Examples and Reference Examples, but the present invention is not limited thereto.

Example 1 - Production of trifluoroacetoacetonitrile Dry diisopropylamine (64xQC0,46 mol) dissolved in 400ytQ of dry tetrahydrofuran is kept at 0°C or below while n-butyllithium/n-hexane solution 280xQ
(0.44 mol) was added.

After stirring at 0°C for 30 minutes, the mixture was cooled to -72°C. While maintaining this temperature, methyl trifluoroacetate 25°61 (0,2
A mixture of 16.429 (0.40 mol) acetonitrile (0.40 mol) and dry tetrahydrofuran 200112 was added dropwise thereto, and the mixture was kept at -75°C for an additional 45 minutes, and then returned to room temperature over 1 hour.

Add 700 tQ of ice water, add tetrahydrofuran and n-
Hexane was distilled off under reduced pressure at a bath temperature of 40°C. The residue was extracted with ethyl ether to remove neutral and basic components, then 36% hydrochloric acid was added to obtain I)) (1), and extracted with methylene chloride to remove by-products such as acetoacetonitrile.

After extraction with ethyl ether and drying the extract over anhydrous sodium sulfate, p-toluenesulfonic acid 40+9 (0,000
2 mol) was added and distilled under normal pressure, and then distilled under reduced pressure to remove the solvent to obtain crude product 26.829 (crude yield 97.8%). This product was further subjected to vacuum distillation to obtain the title compound 16.789 (yield 61.2%) as a colorless liquid. boiling point 37
°C/2,4 mxHg~43°C/2,5 m
xHg, the resulting compound was dissolved in d8-acetone,
According to NMR measurement, the ratio of keto type/enol type is 17/8.
It turned out to be 3.

Example 2 Preparation of pentafluoropropionylacetonitrile 4.1 g (0.10 mol) of acetonitrile, 9.619 (0.05 mol) of ethyl pentafluoropropionate and 70 i (!) of n-butylridium/n-hexane solution.
(0.11 mol) was used to prepare the compound 7 according to Example 1.
．． 289 (yield 77.8%) was obtained. When the obtained compound was dissolved in deuterated chloroform and subjected to NMR measurement, the ratio of keto type/enol type was 26/74. Deliquescent. Melting point 4
7-54°C6 boiling point 69-7 piC/18ixHg.

Elemental analysis, C3HffiNOF, 1/7H, O, calculated value (%): C, 3t, ee; H, 1,22°N, 7.39 Actual value (%): C, 31,65; H, 1,59;N
, 7.23 Example 3 Preparation of 2-(trifluoroaceto)propionitrile a) Propionitrile 19.81? (0.36 mol),
Methyl trifluoroacetate 23.059 (0.18 mol)
and n-butyllithium/n-hexane solution 2521
112 (0,396 mol) according to Example 1 to obtain the title compound 27.729C (yield: 100%). When the obtained compound was dissolved in deuterated chloroform and subjected to NMR measurement, the keto form/enol form ratio was 49,151.

Boiling point 52-57°C/2.7% HLb) Change methyl trifluoroacetate to trifluoroacetic acid (-butyl) and perform the same operation as a) to obtain the title compound 14.709 (yield 54.1
%) was obtained.

Example 4 Preparation of 2-(pentafluoropropionyl)propionitrile Propionitrile 13.29 (0.24 mol), ethyl pentafluoropropionate 23.059 (0° 12 mol) and n-butyllithium/n- Hexane solution 16
According to Example 1, 22.72 g (crude yield 94.1%) of the title compound was obtained as a crude product using 8xC (0,264 mol). The yield in terms of purity was 8461%. When the obtained compound was dissolved in deuterated chloroform and subjected to NMR measurement, the ratio of keto type/enol type was 71/29. Boiling point 63~
65°C/28! SuHg.

Elemental analysis, C, H, NOF, calculated value (%): C, 35,83; H, 2,01:N
, 6.97 Actual value (%): C, 35, 10: H, 2, 52°N
, 7.21 Reference Example 1 Production of 5-trifluoromethyl-4-methyl-3-aminoisoxazole 96% hydroxylamine hydrochloride 19.549 (0,2
7 mol, 1.5 times mol) was dissolved in 180 iQ of water. 8% aqueous sodium hydrogen carbonate solution 28 at below 10°C under stirring
After adding 8J112 (0.27 mol, 15 times the mol) to form free hydroxylamine, Example 3 was added to the mixture.
Upon addition of the crude 2-(trifluoroaceto)propionitrile obtained in (a) (27.729<0.18 mol), the pH of the reaction mixture became 6.2. ) After heating under reflux for 8 hours, 36% hydrochloric acid 15°3112 (0,178 mol, 1.
0 times mole) was added thereto, and the mixture was further heated under reflux for 1 hour to react. (To perform ring closure of the oxime compound.) After the reaction was completed, a 48% aqueous sodium hydroxide solution was added dropwise to the reaction mixture while it was cold. After drying the extract over anhydrous sodium sulfate, methylene chloride was distilled off and the residue was subjected to silica gel column chromatography (Rover Column) to obtain the title compound 9.499 (9.499) as colorless crystals.
A yield of 3157% was obtained. Melting point 3465-36.0°C
0 boiling point 67-70°C 10,78imHg.

Elemental analysis, CsHsN to P, calculated value (
%): C, 36,15; H, 3,04; N, 16.
87 Actual measurement value (%): C, 36, 20, H, 3, 10°N,
16.84 Structural confirmation was also performed by IR, NMR and UV.

At the same time, 0.799 of 3-trifluoromethyl-4-methyl-5-aminoisoxazole (yield 2.6%) was obtained. Boiling point 85-87 °C/l 2 miHg.

Reference Example 2 Production of 5-trifluoromethyl-3-aminoisoxazole 96% hydroxylamine hydrochloride 1.63Li (0°0
225 mol, 1.5 times mol) was dissolved in 15zρ of water.

8% aqueous sodium hydrogen carbonate solution 2 at below 10°C under stirring
4J112 (0,0225 mol, 1.5 times mol) was added to form free hydroxylamine, and 2.169 (0,0 mol) of crude trifluoroacetoacetonitrile was added to the mixture.
After adding 15 mol) and heating under reflux for 2.5 hours, 36%
5.7 mQ of hydrochloric acid was added and the mixture was further heated under reflux for [times] to react. After the reaction was completed, a 48% aqueous sodium hydroxide solution was added dropwise to the reaction mixture while it was cooled to adjust the pH to 10 or higher, and the mixture was extracted with methylene chloride.

After drying the extract over anhydrous sodium sulfate, methylene chloride was distilled off and the residue was subjected to silica gel column chromatography (Roper column) to obtain a mixture of the title compound and 3-trifluoromethyl-5-aminoisoxazole (NM
The ratio of both by R measurement is 4.4:95.6)0.609
(yield 26.0%).

Reference Example 3 Production of 5-pentafluoroethyl-3-aminoisoxazole Crude pentafluoropropionylacetonitrile 2.20
9 (0,010 mol), 10 J of water! 12, according to Reference Example 1, the title compound 0.01049 (yield 0°5%)
I got it. At the same time, 0.0259 (yield: 1.2%) of 3-pentafluoroethyl-5-aminoisoxazole was obtained.

Reference Example 4 Production of 5-pentafluoroethyl-4-methyl-3-aminoisoxazole 25.11 g (0.12 mol) of 2-(pentafluoropropionyl)propionitrile, 120R12 of water and 10.2 mg of 36% hydrochloric acid. According to Reference Example 1, the title compound 9.049 (yield 34.9%) was obtained as colorless crystals. Melting point 32=34°C. Boiling point 86-87'C/2,7
miHg.

Elemental analysis, calculated value (%) as Ce Hs N t OF s: C, 33, 34: H, 2, 34: N, 1
2.96 Actual value (%): C, 33,09: H, 2,54; N
12.06 At the same time, 0.969 of 3-pentafluoroethyl-4-methyl-5-aminoisoxazole (yield: 3.7%) was obtained.

Reference Example 5 Production of 3-trifluoromethyl-5-aminoisoxazole Trifluoroacetoacetonitrile 16.789 (0,
122 mol) in dry methanol 220xQ and 96%
11.52 g (0,159 mol) of hydroxylamine hydrochloride was added, and the mixture was heated under reflux for 68 hours with stirring. Next, methanol was distilled off under reduced pressure, and water 24 (JnQ) was added to the residue, followed by a 48% aqueous sodium hydroxide solution to adjust the pH to 11 or higher. Extracted with methylene chloride, dried over anhydrous sodium sulfate, and then distilled off the solvent under reduced pressure to approximately Colorless crystals of the title compound to,
309 (yield 55.2%) was obtained. Melting point 57-58°C.

Boiling point 66-67°C/0,8 mxHg0 Reference Example 6 Production of 3-pentafluoroethyl-5-aminoisoxazole Pentafluoropropionylacetonitrile 2°85g
(0,015 mol) according to Reference Example 5 to obtain the title compound 2.319 (yield 76.2%) as colorless plate-like crystals. Melting point: 86-87°C. Boiling point 89-90°C/3πxHg.

Reference Example 7 Production of 3(5)-)-lifluoromethyl-5(3)-aminopyrazole Trifluoroacetoacetonitrile 9.958(0,
0.075 mol) to 75 iL of benzene and 6.31 g of acetic acid (0.075 mol).
105 mol) and 90% hydrazine hydrate 5.4
4 g (0,0975 mol) was added and heated under reflux for 3 hours. After the reaction was completed, 25 rQ of water was added, the pH was adjusted to 9 to 10 with a 48% aqueous solution of caustic soda, and the mixture was separated. The aqueous layer was extracted with methylene chloride, combined with the benzene layer, and the solvent was distilled off at normal pressure. The residue was subjected to silica gel column chromatography to obtain 3.33 g of crystals of the title compound (yield 2964
%) was obtained. Boiling point 96.0-98.5℃/0,13
xxHg, melting point 94.0-95.0°C.

Claims (5)

[Claims] (1) Formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, R is alkyl having multiple fluorines, R^1
means hydrogen or alkyl] β-ketonitrile represented by (2) The compound of item (1) above, wherein R is trifluoromethyl. (3) The compound of item (1) above, wherein R is pentafluoroethyl. (4) The compound according to item (1) above, wherein R^1 is hydrogen. (5) The compound according to item (1) above, wherein R^1 is methyl.