JPH02229147A - Fluorine-containing compound - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I [R is substitutable phenyl, benzyl, alkoxycarbonyl or alkylcarbonyl; R<1> is 2-10C alkyl, 1-6C alkyl having substituted group (with a proviso that alkyl substituted with halogen is omitted), substitutable 2-6C alkenyl or alkinyl or R<2>NHNH (R<2> is substitutable alkyl or phenyl, etc.), etc.]. USE:Synthetic intermediate of agricultural agent and medicine. Further, also useful as active component of agricultural agent and medicine. PREPARATION:Imidoyl halide expressed by formula II (X is halogen) is reacted with nucleophilic reagent in the presence of base or the compound expressed by formula II is reacted with organic metallic compound (e.g. Grignard reagent) to afford the compound expressed by formula I. Reaction is performed in a solvent such as hexane at a temperature from -20 deg.C to boiling point of solvent.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to a novel fluorine-containing compound, which is useful as an intermediate for the synthesis of active ingredients of agricultural chemicals and medicines, and which is useful as an intermediate for the synthesis of active ingredients of agricultural chemicals and medicines. It is also useful as an active ingredient in agricultural chemicals and medicines.

[Prior Art] The following are known as publicly known technologies related to the fluorine-containing compound of the present invention (hereinafter referred to as the compound of the present invention).

■ Bulletin Chemical Society of Japan
ety of Japan) Volume 46, page 3260 (19
Compound A and its analogs are disclosed in 1973), but the alkyl group bonded to the carbon atom of the imino group is only a perfluoroalkyl group.

C6H3N = C(CF:l)2 (Compound A)
■ Chemical A
bstructs), Volume 90, 121702 (1
979) and Volume 91, 74669 (1979)
discloses Compound B and its analogs, but the amino group bonded to the imino carbon atom is limited to dialkyl and ruamino groups.

C, H6N = C-N H3 (Compound B) CF3 (In the formula, R5 represents a methyl group or an alkyl group having a substituent.) The group bonded to the carbon group is a methoxycarbonyl group.

■ Chemical Abstracts, (Chemical^
bs tracts), Volume 109, 148974
(1988) discloses compound E and its analogues, but the bonding position of the imino group is different.

■Chemical Afstruction (Chemtcal)
Abstracts), Volume 109, 230466
(1988) discloses compound C, in which the group bonded to the imino carbon is a methyl group.

■ Chemical Abstracts (Chemical A
bstructs), Volume 109, 55185 (1
No. 988) discloses a compound, but the imino compound of the present invention differs in its chemical structure from the compound disclosed in the above-mentioned prior art.

[Means for Solving the Problems] The present invention provides - ritual [I]: CF3C=NR(Il+ [In the above formula, R is an optionally substituted phenyl group, benzyl group, alkoxycarbonyl group moiety or represents an alkylcarbonyl group, R1 is a C2 to C10 alkyl group,
01-C6 alkyl group having a substituent (however, excluding alkyl groups substituted with halogen atoms), optionally substituted 02-C6 alkenyl group or alkynyl group, hydrazino group, R2NIIN) 1 group, R' NH group,
R'ONH group, cyano group, imidazolyl group or triazolyl group; R2 and R3 represent an optionally substituted alkyl group, phenyl group or benzyl group;
4 represents an optionally substituted alkyl group. ], the compound is useful as a synthetic intermediate for fluorine-containing amino acids, fluorine-containing heterocyclic compounds, active ingredients of agricultural chemicals, and active ingredients of medicines, and the compound is The present invention was completed by discovering that the compound itself is useful as an active ingredient in agricultural chemicals and medicines.

In the above-mentioned ritual (1), when R, R'' and R3 represent an optionally substituted phenyl group or benzyl group, the types of those substituents include, for example:
Alkyl group, alkoxy group, alkylthio group, halogen atom, cyano group, nitro group, haloalkyl group, haloalkoxy group, amino group, alkylamino group, phenyl group,
Phenyl group, alkylcarbonyl group, phenylcarbonyl group, alkoxycarbonyl group, alkylaminocarbonyl group, alkylcarbonyloxy group having a substituent,
Examples include hydroxyl group.

Further, when R, R', R2, R' and R4 represent an optionally substituted alkoxycarbonyl group, alkylcarbonyl group, alkyl group, alkenyl group or alkynyl group, the types of those substituents include, for example. , alkoxy group, alkylthio group, cyano group, nitro group, haloalkoxy group, alkylamino group, phenyl group, phenyl group having a substituent, alkylcarbonyl group,
Examples include phenylcarbonyl group, alkoxycarbonyl group, alkylaminocarbonyl group, alkylcarbonyloxy group, and carboxylic acid group.

Next, the method for producing the compound of the present invention will be explained by citing a reaction formula.

CF, -C= N-R---→ CF3 - C=
N-1? X
R' [■] Compound (1) of the present invention [
In the formula, P and R1 have the same meanings as above, and X represents a halogen atom. ] In the reaction shown by the above reaction formula, an imidoyl halide represented by general 2[TI] and a nucleophilic reagent are combined with an inorganic base (e.g., sodium hydride, sodium amide, etc.) or an organic base (e.g., pyridine, lutidine, etc.). dimethylaminopyridine, triethylamine, etc.], the compound (1) of the present invention can be synthesized in a good yield.

Moreover, the compound [I] of the present invention is imidoyl halide (Tl
) and an organometallic compound (for example, a Grignard reagent, an organolidium compound, a silyl compound, etc.) can also be synthesized in good yield.

Although the molarization of the raw materials can be set arbitrarily, it is advantageous to carry out the reaction at equimolar or nearly equimolar ratios.

The reaction temperature is not particularly limited, but the reaction can be carried out usually in a range from -20'C to the boiling point of the solvent used.

The solvent used is preferably a solvent that does not participate in the reaction, such as hydrocarbons M (e.g., hexane, pentane, henzene, toluene, etc.), ethers (e.g., diethyl ether, monoglyme, isopropyl ether, tetrahydrofuran, 1,4-dioxane, etc.). ), halogenated hydrocarbons (for example, dichloroethane, carbon tetrachloride, etc.), etc. can be used.

The compound of the present invention has the following syn-type and anti-type structural isomers, and the present invention includes both isomers.

Further, certain compounds of the present invention are (Ia), general II (III) and (ra) [■] [wherein R6 represents an alkylcarbonyl group or an alkoxycarbonyl group, and R7 represents an alkyl group. ] The present invention also includes the tautomer (I) of the present compound [1].

When R is a Hensyl derivative in imidoyl halide (ITa), (Ila: 1 compound of the present invention (I b: 1 + CF3-CI-N = C-R9[IV) [wherein, X and RJ, Represents the same meaning as above, R8
represents a hydrogen atom or an alkyl group, and R9 represents an optionally substituted phenyl group. ] As shown in reaction 2 above, with the production of the compound of the present invention [:I b), -ritual [
Isomers represented by [2] may be produced as by-products.

When purifying the compound [I] of the present invention, conventional purification methods (recrystallization, column chromatography, vacuum distillation, etc.)
It can be separated and purified by

The starting material imidoyl halide CI+) can be synthesized by the following formula.

CF3C0NHR−□−−→ CF3C= N−R(
ff)[:V)X [In the formula, R and X represent the same meanings as above. It can be easily synthesized by reacting the amide compound represented by [General formula V] with a halogenating reagent (for example, phosphorus pentachloride, boron trichloride, etc.). The imidoyl halide used (
Certain types of n) are known.

Next, the method for producing the compound of the present invention will be specifically described with reference to Examples, but the present invention is not limited to these.

Manufacture world'H-NMR (60MB2.CDCl5); δ1.
18(t, J=7.21(z, 3H), 2.49(q,
J=7.2, 2H), 3.80 (s, 3H), 6.60
-6.99(111,411) Cleft M% Synthesis of H2CHi (Inventive Compound No. 1) 10mi! Imidoyl chloride (CF3C
(CI) = NC6H4(OC113)-43(10
After weighing out 0mg, '0.42111J2) and purging with nitrogen, add ether (1.5mff1) and stir.

Next, prepare the ethyl Grignard reagent in a separate container (
0.84m! ! ) with a syringe. After 30 minutes, the reaction is quenched with ice-cold saturated aqueous ammonium chloride solution and the product is extracted with ether. The extract was washed twice with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The crude product was purified by silica gel column chromatography (n-hexane:ethyl acetate = 50:1) to obtain 3 mg (yield: 83%) of the present compound No. 1 as an oil.

Synthesis of (Present Compound No. 6) Sodium hydride (41 mg1,
68 mmol) was weighed out, washed three times with hexane, dried, and purged with nitrogen. Then, dehydrated and purified tetrahydrofuran (2 mI!) was added and stirred at room temperature.

Next, ethyl acetoacetate (0.21mj2.0.68mm
Imidoyl chloride l:cF3c(Cffi)=NC6)+4(OCI) dissolved in dehydrated and purified tetrahydrofuran (1mj2) was added dropwise with a syringe.
(3)-4) (100 g, 0.42 mmol
) with a syringe. After 3 hours, the reaction is quenched by adding ice-cold saturated aqueous ammonium chloride solution and the product is extracted with ether. Wash the extract twice with saturated saline,
Dry over anhydrous sodium sulfate, and remove the solvent under reduced pressure.

When the crude product was purified by silica gel chromatography (n-hexane; ethyl acetate - 40:1), the present compound N
90.4 ll1 g (yield 65%) of an oily substance of 0.6 was obtained.

'H-NMR (200M+12.CDCl5); δ1.
23 (q, J = 7.1 H2, 31L), 1.67 (s
, 3H), 3.73 (s, 3H), 4.18 (dq, J
=IO, 8Hz', IH), 4.27(dq, J=1
0.8 H2, IH), 6.79 (m, 4H) The compound of the present invention synthesized according to Production Examples 1 and 2 was
Shown in the table.

(Hereinafter, blank space) Table 1 R1 expressed as CF3-C=N-R
Compound No., R NMR (δIiii, CDCf1z)4-CI!
, C61(4 4-0□NC61(4 E tOcOcH2 N R 3-CFffC6H.

4-MeC611aCHz :2-CFz-4-Cj2C6)L+ 2.4-Cffi 2C, N3 2.4-Cffi2C6H3 2,6-EtzCJb 4-1’1ecJI4 2.6-Cff zcJL+ eOCO eCO 4-Ce　CJ4NH t In.

In Tr.

110cOcI (2ONH eNHNH eNII MeOCOCHz N NMR (δia CD(J!:+)) A specific synthesis method of imidoyl halide [■] which is a starting material is shown in the following reference example.

Based on reference CI! .

30 "! CF3CON11C6114 (OC
Weigh out 1+3)-4 (2 g, 9.12 mmol) and phosphorus pentachloride (2.47 g, 1.1.9 mmol), stir thoroughly, and heat to 100"C. The reaction mixture becomes a liquid. It will solidify again later.

When this substance is heated to 150°C, it becomes a dark liquid.
This is refluxed for 4 hours. After the reaction is complete, the produced phosphoryl trichloride is distilled off under reduced pressure, and the product is simultaneously distilled under reduced pressure to obtain the title compound (715 mg, 33%).
. bp 100410°C/20 mm41g 0')
l-IJMR (50 Kano H2, CDCl5); 3.8
4 (s, 3H), 6.95 (d, J=9.0Hz, 2H
), 7.30 (d, J=9.0IIz, 2H), 9F-
NMR (470MH2, CDCl:l); 90.4 (
s) For reference (procedural corrector (spontaneous) ChCONHCHzC6■s (
2,03g, 10 mmol) and phosphorus pentachloride (2,7
Weigh out 0 g, 13 mmol), stir thoroughly, and heat to 100°C. Once the mixture is liquid, reflux for 4 hours.

After the reaction is complete, the phosphoryl trichloride formed is distilled off under reduced pressure, and the product is simultaneously distilled under reduced pressure to obtain the title compound (1.22 g, 58%).

bp 90-95°C/25 mm) IgoH-N
MR (500MH2, CDCl5); 4.83 (S,
2H), 7.25-7.38 (m, 5H)

Claims (1)

[Claims] (1) General formula [I]: ▲There are mathematical formulas, chemical formulas, tables, etc.▼A fluorine-containing compound represented by [I]. [In the above formula, R represents an optionally substituted phenyl group, benzyl group, alkoxycarbonyl group, or alkylcarbonyl group, and R^1 is a C_2 to C_1_0 alkyl group, a C_1 to C_6 alkyl group having a substituent. (
However, alkyl groups substituted with halogen atoms are excluded),
Represents an optionally substituted C_2 to C_6 alkenyl group or alkynyl group, hydrazino group, R^2NHNH group, R^3NH group, R^4ONH group, cyano group, imidazolyl group or triazolyl group, and R^2 and R ^
3 represents an optionally substituted alkyl group, phenyl group or benzyl group, and R^4 represents an optionally substituted alkyl group. ]