JPS588063A - 5-trifluoromethylpyridin-2-yloxyphenylalkane- carboxylic acid derivative - Google Patents

Abstract

NEW MATERIAL:The 5-trifluoromethylpyridin-2-yloxyphenylalkanecarboxylic acid derivative of formulaI(X is H or halogen; Y is H, nitro or amino; Z is H, cation, or alkyl; R is H or methyl). EXAMPLE:3-(3-Chloro-5-trifluoromethylpyridin-2-yloxy) phenylacetic acid. USE:Herbicide, antiphlogistic agent, analgesic agent, antipyretic agent, blood lipid level lowering agent, and their intermediate. PROCESS:The compound of formulaIis prepared by reacting the compound of formula II with the compound of formula III in the presence of an acid acceptor such as sodium hydroxide and a solvent such as dimethylsulfoxide.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to 5-trifluoromethylpyridin-2-yloxyphenylalkane carboxylic acid derivatives useful as agricultural chemicals, such as weight removal agents, medicines, or intermediates thereof.

More specifically, the present invention relates to the general formula (where X is a hydrogen atom or a halogen atom, Y is a hydrogen atom, a nitro group or an amine group, 2 is a hydrogen atom, a cation or an alkyl group, and R is It relates to a 5-trifluoromethylpyridin-2-yloxyphenylalkane carboxylic acid derivative represented by a hydrogen atom or a methyl group.

In the definition of the above general formula, halogen atoms include fluorine, chlorine, bromine, and iodine, and alkyl groups include methyl, ethyl, n-propyl, inglovil, n-butyl, isobutyl, aec-butyl, and tert-butyl. Cations include alkali metal ions such as sodium and potassium, alkaline earth metal ions such as calcium and magnesium, ammonium ions, organic ammonium ions such as dimethylammonium, and diethanolammonium, and are used as agricultural chemicals. Alternatively, those that are acceptable as pharmaceuticals may be mentioned.

The 5-trifluoromethylpyridin-2-yloxyphenylalkane carboxylic acid derivative of the present invention is usually produced, for example, by the following method, and in the above reaction formula, X, Y, Z and Ri are as described above, and H
It is an ALi-logen atom.

Examples of deoxidizers used include sodium oxide, potassium hydroxide, sodium carbonate, potassium carbonate, etc.
Examples of the solvent include aprotic polar solvents such as dimethyl sulfoxide, dimethylformamide, hexamethylphosphoramide, and sulfolane. In addition, a quaternary ammonium salt type phase transfer catalyst can be used in the reaction, which is effective because it can proceed efficiently in some cases.

Furthermore, the compound of the present invention obtained by the above reaction formula can be converted into Y or 2 by applying various reactions such as nitration, amination, hydrolysis, and esterification, and converted into other compounds of the present invention. You can also do that.

Next, the synthetic sidetones of the compounds of the present invention will be described.

Synthesis Example 1 3-(3-chloro-5-trifluoromethylpyridin-2-yloxy) phenylacetic acid 2.3-dichloro-5-trifluoromethylpyridine 1
Al? , m-Hydroxyphenylacetic acid 10t1 Anhydrous potassium carbonate 289 and dimethyl sulfoxide 70%t2 Pour into the fourth flask [1. Under stirring [Immersed in a 120°C oil bath and reacted for 2.5 hours] After the completion of the reaction, the product was The mixture was poured into water, made acidic with concentrated hydrochloric acid, and then extracted with methylene chloride. The extracted layer was washed with water, dried, concentrated under reduced pressure to obtain a solid, washed with hexane, and air-dried to obtain a solid with a melting point of 108-114.
Objective material 17 was obtained at ℃.

Synthesis Example 22-Nitro-5-(3-chloro-5-trifluoromethylpyridin-2-yloxy)phenylacetic acid 3-(3-chloro-5-trifluoromethylpyridin-2- obtained in Synthesis Example 1 above) yloxy)phenylacetic acid 15
61 was dissolved in concentrated sulfuric acid 70- and cooled to 3°C. There, 4.6 tons of concentrated nitric acid and 2 grams of concentrated sulfuric acid. A mixed acid was added dropwise to the cooled base coat, and the mixture was left to stand for 4.5 hours after the dropwise addition was completed. After the mixture was left at room temperature for a while, the product was poured into water and extracted with methylene chloride. The extraction layer was post-processed in the same manner as in Synthesis Example 1, and the target substance lh'bt with a melting point of 123-127°C was obtained.
I got it.

+fa Example 3 2-nitro-5-(3-chloro-5-trifluoromethylpyridin-2-yloxy)phenylacetic acid ethyl ester Synthesis Example 2T"
5-Trifluoromethylpyridin-2-yloxy)phenyl acetic acid was dissolved in 9 km of water and ethyl 4Q, and after adding 5.15% of the ether complex salt of boron trifluoride,
The mixture was heated and refluxed for 50 minutes at C. After the reaction was completed, a small amount of water was added to the product, concentrated under reduced pressure, and extracted with methylene chloride. After complete post-treatment, the target product a has a melting point of 94-96°C.

Got #.

Synthesis Example 4 2-(3-chloro-5-trifluoromethylpyridin-2-yloxy) phenylacetic acid In the same manner as in Synthesis Example 1 above, 2,3-dichloro-5-trifluoromethylpyridine L"/l, 0 -Hydroxyphenylacetic acid @Log, anhydrous potassium carbonate L8) and dimethyl sulfoxide 20.1 were reacted at 70-80°C for 200 hours and post-treated to obtain the desired product 1IPt- with a melting point of L37-143°C. Table 1 shows the compounds of the present invention synthesized according to the general production method or the synthesis example described above.

E. 1 Table The compounds of the present invention include, for example, agricultural chemicals, as shown in the test examples below.
As an active ingredient of a medicine, it has herbicidal activity, anti-inflammatory effect, analgesic effect, antipyretic effect, or blood lipid-lowering effect,
It is also useful as an intermediate for agricultural chemicals and medicines.

Next, various test examples showing the chemical properties of the compounds of the present invention will be described; however, of course, the uses of the compounds of the present invention are not limited to those described here.

Test Example 1 ``/4ooo After putting paddy soil in a Rbot and allowing it to become saturated with water, feed Bini seeds, Hotarui seeds, and Urikawa tubers were sown or planted in separate bottles, and lightly piled as needed. It was soil.

When each weed germinates, the depth of the water is set to about 3 degrees, and each test compound is diluted with water and the required amount is dropped. After 3 weeks of chemical treatment, the growth condition was observed with the naked eye, and the following criteria (1 to 1) were evaluated.
Based on the 5-point method of 5), the degree of growth inhibition was expressed as 7, and the results in Table 2 were obtained. 78 parts by weight of Nizikrite,
A mixture of 15 parts by weight of White Carbon, 211 parts by weight of Labelin S (trade name: O Kogyo Seiyaku Co., Ltd.), and 5 parts by weight of Tsurupol 5039 (trade name: Toho Chemical Industries Co., Ltd.) is uniformly mixed in a ratio of 1=4 as an irrigation agent. .

Table 2 Table Test Example 2 1/muooo Weed seeds of Japanese barnyard grass, blueberry, red-spotted deer, and polygonum were sown and grown in a greenhouse in a field condition. Barnyard grass is in the two-leaf stage,
Aobiyu is 35! When the golden deer reached the 2-leaf stage and the knotweed reached the 2.5-leaf stage, the Qinqi product used in Test Example 1 was added to the
It was diluted with L/a of water and sprayed. 20 days after chemical treatment
On day 0, the growth state of the weeds was visually observed, and results 1 in Table 3 were obtained. The numerical value 0 in the table indicates that the growth was completely suppressed, and the numerical value 1 indicates that the growth was not suppressed as in the untreated area. 3 Table Test Example 3 All tests, observations, and evaluations were carried out in the same manner as in Test Example 2, except that the amount of active ingredient was changed. I got 1.

Table 4 Test Seven-week-old rats with side number SD Itoo were kept in a fasted state for 16 hours and tested in groups of 10 rats. Compounds 3 and 7 were forcibly administered orally once at a rate of 10 mt per IEIKF (active ingredient equivalent: 50 WLt, 7 Kg) suspended in an aqueous solution containing carboxymethyl cellulose α5, and a control Group carboxymethyl cellulose 05%
A predetermined amount of aqueous solution was similarly administered. Rats were kept in a fasted state throughout the study period and were given only drinking water ad libitum. Eight hours after administration, the rats in each group were anesthetized with bentoparbital, blood was collected from the right ventricle, and serum total cholesterol was measured using a conventional method. A decrease in cholesterol was observed. In addition, the compounds of the present invention, which are categorized as 3, are usually anti-inflammatory,
Carrageenin limb edema test conducted as an analgesic and antipyretic test, ultraviolet erythema test by Winder et al. test, Haffner test,
As a result of conducting analgesic tests using phenylquinone, favorable test results were obtained in all tests.

Patent applicant: Ishihara Sangyo Co., Ltd.

Claims (1)

[Claims] (In the formula, X is a hydrogen atom or a halogen atom, Y is a hydrogen atom, a nitro group or an amino group, zB is a water atom, a cation or an alkyl group, and R is a hydrogen atom or a methyl group) 5-trifluoromethylpyridin-2-yloxyphenylalkanecarboxylic acid derivative represented by: