JPH03264557A - 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 substituting group other than halogen, substitutable 2-6C alkenyl or alkinyl, hydrazino, R<2>NHNH, R<3>NH, R<4>ONH, CN, imidazolyl, triazolyl, azide, R<2>OCONH or R<2>N(COOR<3>)NH; R<2> and R<3> are substitutable alkyl, phenyl or benzyl, R<4> is substitutable alkyl]. EXAMPLE:A compound expressed by formula III. USE:Agricultural chemical, medical drug or an intermediate of said drugs. PREPARATION:An imidoyl halide expressed by formula II (x is halogen) is reacted with a nucleophilic reagent in the presence of an inorganic base or organic base, or the compound expressed by formula II is reacted with an organic metallic compound to afford the compound expressed by formula I in high yield.

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.

[Conventional technology]

The following are known as known techniques 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.

C6■sN = C(CF3)z (compound A)■
Chemical Ab
structs), Volume 90, 121702 (19
79) and Vol. 91, 74669 (1979), Compound B and its analogs are disclosed, but the amino group bonded to the carbon atom of the imino group is limited to dialkylamino groups.

5 C6H5N = C-N H3 (Compound B) F3 (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.

F3 ■ Chemical Afstruction (Chemical
8BSTRA toTS), Volume 109, 148974
('1988) discloses compound E and its analogs, but the bonding position of the imino group is different.

■ Chemical A
bstructs), Volume 109, 230466 (
Compound C was disclosed in 1988), but
The group bonded to the imino carbon is a methyl group.

■ Chemical A
bstructs), Volume 109, 55185 (1
988), the imino CH3 compound of the present invention differs in its chemical structure from the compounds disclosed in the above-mentioned prior art.

[Means for solving problems]

The present invention is based on the general formula [I]: Ch C=NR(1) 1 [In the above formula, R represents an optionally substituted phenyl group, benzyl group, alkoxycarbonyl group, or alkylcarbonyl group, and R1 is 02-CIO alkyl group,
Cl-C6 alkyl group having a substituent (however, excluding an alkyl group substituted with a halogen atom), an optionally substituted 02 to CG alkenyl group or alkynyl group, hydrazino group, R''NHNH group, R3NH group, R'
ONH group, cyano group, imidazolyl group, triazolyl group, azide group, l? 20cONl(group or R”N(CO
OR'')N)I, R2 and R3 represent an optionally substituted alkyl group, phenyl group or benzyl group, and R4 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 general formula (I), when R, R'' and R3 represent an optionally substituted phenyl group or benzyl group, the types of 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.

[In the formula, R and R1 have the same meanings as above, and X represents a halogen atom. ] In the reaction shown by the above reaction formula, the imidoyl halide represented by the general formula [11] and a nucleophile are combined with an inorganic base (e.g., sodium hydride, sodium amide, etc.) or an organic base (e.g., pyridine, lutidine, etc.). The compound (1) of the present invention can be synthesized in good yield by reacting in the presence of dimethylaminopyridine, triethylamine, etc.).

In addition, the compound CI) of the present invention is an imidoyl halide [■]
It can also be synthesized in good yield by reacting with an organometallic compound (for example, a Grignard reagent, an organolithium compound, a silyl compound, etc.).

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

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

The solvent used is preferably a solvent that does not participate in the reaction, such as hydrocarbons (e.g., hexane, pentane, benzene, toluene, etc.), ethers (e.g., diethyl ether, monoglyme, isopropyl ether, tetrahydrofuran, 1,4-dioxane, etc.). ), halogenated hydrocarbons (eg, 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 have (rail, general formula [111): (:1 ([[) [wherein, R6 represents an alkylcarbonyl group or an alkoxycarbonyl group, and R7 represents an alkyl group]. The present invention also includes the tautomer [1] of the compound [1] of the present invention.

When R is a benzyl derivative in imidoyl halide (I[a), (Ila) the compound of the present invention [1b] 10CF3-CH-N = C-R' RI R8 (IV) [wherein X and R1 has the same meaning as above, and RI
+ represents a hydrogen atom or an alkyl group, and R9 represents an optionally substituted phenyl group. ] As shown in the above reaction formula, with the production of the compound (Ib) of the present invention, the general formula (T
The isomer represented by V) may be produced as a by-product.

When purifying the compound [1] of the present invention, conventional purification methods (recrystallization, column chromatography, vacuum distillation, etc.)
It can be separated and purified by

Imidoyl halide (II) as a starting material can be synthesized by the following formula.

CF3C0N) IR-111→ CF*C= N-R(
II)(V)X [wherein R and X represent the same meanings as above. ] It can be easily synthesized by reacting the amide compound represented by the general formula (V) with a halogenating reagent (for example, phosphorus pentachloride, boron trichloride, etc.). The imidoyl halide used (
Certain types of II) 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.

On-machine 'H-NMR (60MB2.CDC13); δ1.
18 (t, J = 7.2 Hz, 311), 2.49 (q
, J=7.2,2H), 3.80(s, 3)1), 6.
60-6.99 (m, 4H) 11 forceps ΔC) 12cH.

Synthesis of (Present Invention Compound No. 1) Imidoyl chloride (CF+C(
CI2) -NC6H4(OCH3)-4) (10
After weighing out 0mg, 0.42ml) and replacing with nitrogen,
Add ether (1.5 mI!) and stir. Next, ethyl Grignard reagent (0,8
4nl) 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. Wash the extract twice with saturated saline,
Dry over anhydrous sodium sulfate, and remove the solvent under reduced pressure.

The crude product was subjected to silica gel column chromatography (n-
When purified with hexane:ethyl acetate-50:1), 80.3 mg (yield: 83%) of the compound Nα1 of the present invention was obtained as an oil.
)was gotten.

Synthesis of (Present Invention Compound No. 6) Sodium hydride (41 mg 1
, 68 mmol) was washed three times with hexane, dried, and purged with nitrogen. Then, dehydrated and purified tetrahydrofuran (2n+1!) was added and stirred at room temperature.

Next, ethyl acetoacetate (0.21mj2.0.68mm
ol) was added dropwise with a syringe, and then imidoyl chloride (CF2O(Cffi)=NC6■4(OCH3
)-4) Drop (100 mg, 0°42 mmol) with a syringe. After 3 hours, the reaction is stopped by adding 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.

When the crude product was purified by silica gel chromatography (n-hexane; ethyl acetate - 40:1), 90.4 mg (yield 65%) of an oily substance of the present compound No. 6 was obtained.
was gotten.

'H-NMR (200MB2.CDC13); δ1.2
3 (q, J = 7.1 Hz + 3H9), 1.67 (s,
3H), 3.73 (s, 3H), 4.18 (dq, J=
10.8 Hz, IH), 4.27 (dq, J=10
．． 8 Hz, IH), 6.79 (m, 411) (hereinafter, blank) 2 Synthesis of (inventive compound 25) Sodium hydride, methylurethane (H2NCOOCH3) and imidoyl chloride (CF2O(CI2)- NC6H, CH3-4
) were mixed, stirred at room temperature for 5 hours, and then isolated and purified to obtain Compound No. 25 of the present invention in 93% yield.

3 (Present Compound No. 27) Synthesis Sodium azide (NaN3) and imidoyl chloride (CF2O(Cf)=NC6H4CH3) were added to a mixed solvent of acetone and water.
-4) at room temperature, inventive compound Nα27 is produced, but inventive compound No. 27 is thermally unstable;
It changed to the following tetrazole compound.

Table 1 CF3C=N represented by R in compounds Compound side.

NMR (delta direct, CDCj2+) yield of tetrazole compound 87%. "Oil" F-NMR (CDCl
3, δ value from C6F6): 101', 73M5
: m/e=228 (M", 10), 199 (1
00) 105 (85).

Table 1 shows the compounds of the present invention synthesized according to Production Examples 1 to 4.

(Hereafter, blank space) 4-CICbHs E tOcOcH2 4-o2NC61 (4 5 Compound surface RR' NMR l 0 3-CFiCJn 4-CI!, CJJ
Ill 1 4-MeCJnCHz t! t1
2 2-CF3-4-CIC6H+ In.

13 2.44-Cff1zCJ131゜14 2
．． 4-Cj2gC6H3Tr.

15 2.6-EhC6H+ HOCOCH2
ONH164-MeC&MeNHNHl
7 2.6-Cj! zc611+ MeNHl
8 MeOCOMeOCOCHz19
MeCOCN (δ emer cocpr) compound plane, R234-MeC5H.

hNHNH Physical property value nm boiled μg 4-MeC,H4 4-MeC6H4 4-MeC6■4 MeOCONH (2-EtOCO)CJJ■ Oily substance (hereinafter referred to as the margin) Imidoyl halide (I [) The specific synthesis method is shown in the following reference example.

CF3C0NHC6H4 (OC11
3) Weigh out -4 (2 g, 9.12 mmol) and phosphorus pentachloride (2.47 g, 11.9 mmol),
Stir thoroughly and heat to 100°C. The reaction mixture becomes liquid and then solidifies again.

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■, 33%).
bp 100-110°C/20 mmHg 0'H
-NMR (500MH2, CDCl5); 3.84 (
s, 3H), 6.95 (d, J=9.0Hz, 2H),
7.30 (d, J=9.0Ilz, 2H), 19F-N
MR (470MH2, CDC13); 90.4(s)
Reference 4■ Hikikime Cf CF+C0NHCHHzC6tls in a 30mff reactor
(2.03 g, 10 mmol) and phosphorus pentachloride (2.03 g, 10 mmol)
, 70g, 13 mmol), stir thoroughly, and heat to 100°C. After the mixture becomes liquid, it is refluxed for 4 hours.

After completion of the reaction, the produced phosphoryl trichloride is distilled off under reduced pressure, and the product is simultaneously distilled under reduced pressure to obtain the title compound (1.22 g, 58χ).

bp 90-95°C/25 mmHg0'H-NM
R (500MH2, CDC13); 4.83 (s, 2
)1), 7.25-7.38 (m, 58) 19F-NMR (470MH2, CDCl5); δ
90.3(s) (hereinafter, blank) 9 The compound of the present invention is useful as an intermediate for the synthesis of physiologically active heterocyclic compounds, and is shown below as a reference example.

Synthesis of Keiko Ni 1 nt+ (Reference Compound No. 1) Compound No. 20 (100■) of the present invention was mixed with cumene (0,3
mI! , ) was refluxed for 5 hours at 200°C using a glass tube oven. After cooling, the reaction mixture was recrystallized to obtain the title compound (Reference Compound No.
, 56 mg of white crystals of 1) were obtained.

'H-NMR (200MHz, CDCff1.)
;2.59 (s, 3H), 4.06 (s, 3H)
, 7.71 (dd, J+=8.6Hz, Jz=2.
01(z, III), 8.00(d, J=8.6Hz,
LH), 8.13 (bs, IH), 12.7 (m
, LH) 0 Reference ■ Synthesis of I'1M (Reference Compound No. 2) Compound No. 21 of the present invention was reacted in the same manner as in Reference Example 3,
The title compound (Reference Compound No. 2) was obtained in a yield of 70%.

'II-NMR (500MHz, DMSO-d6)
; 2.47 (s, 3H), 2.52 (s.

3H), 7.59(dd, J+=8.6Hz, J
z=1.8Hz, 11()+7.79(d, J=8.6
Hz, LH), 7.96 (s, LH), 12.5 (
bs, IH) Reference compounds No. 1 and No. 2 are useful as active ingredients of agricultural chemicals. In particular, as a herbicide, it can kill broad-leaved weeds (for example, cyperus japonica, cyperus japonica, cyperus japonica, japonica, and so on) with a dosage of 50 to 10 (Lg/a) by soil treatment and foliage treatment.

Synthesis of Moxibustion n■ (Reference Compound No. 3) Reference compound No. 1 (50■) was mixed with 10% aqueous sodium hydroxide solution (2mff) and heated at 80°C for 1 hour. Heated. After cooling, the reaction solution was extracted with ethyl acetate, and after post-treatment, it was purified to obtain the title compound (Reference Compound No. 3) 39
mg (82% yield).

'H-NMR (200MHz, DMSO-d6);
2.5Hs, 3)l), 7.52(dd, J+=8
．． 5Hz, Jz=2.0Hz, LH), 7.74(d
, J=8.5Hz.

Synthesis of IH) 8.04(s, 18) (hereinafter, blank) (Reference compound No. 4) By heating the present compound No. 25 at 250°C for 30 minutes, the yield of reference compound No. 4 was determined. Obtained at 71%. White crystal; melting point 235-240° CICl9F-N
(CDCI!, 3 δ value from C6F6): 9
3.27m/e=228 (M”, 100), 159
(30).

104 (25).

Synthesis of the Compound No. 5 (Reference Compound No. 5) Reference Compound No. 5 was obtained in a yield of 65% by heating the compound No. 26 of the present invention at 200° C. for 3 hours. White crystal; melting point 142-143°C" F-NMR (
CDCj23, δ value from CbFb): 97.
663 m/e=304 (M”, 100), 23
5 (50).

9 1 (30).

Synthesis of Reference Compound No. 4 (Reference Compound No. 6) By heating the present compound No. 24 at 200° C. for 20 minutes, reference compound No. 6 was obtained in a yield of 84%. White crystal; melting point 127-128°C1C19F-N
(CD(,!!,, , δ value from C6F6)
:93.33m/e=319 (M”85),
186(10).

91 (100).

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 C2 to C10 alkyl group, a C1 to C6 alkyl group having a substituent. (However, excluding alkyl groups substituted with halogen atoms), optionally substituted C2 to C6 alkenyl groups or alkynyl groups, hydrazino groups, R^2NHNH groups, R^3NH groups, R^4ONH groups, cyano groups , imidazolyl group, triazolyl group, azide group, R^2OCONH group or R^2
N(COOR^3)NH, R^2 and R^3 represent an optionally substituted alkyl group, phenyl group or benzyl group, and R^4 represents an optionally substituted alkyl group. ]