PL177171B1 - Derivatives of 3-phenyl-5-methylisoxzaole and 4,5-dihydroisoxasole - Google Patents

Abstract

3-phenyl-5-methylisoxazole and 4,5-dihydroisoxazole derivatives of the formula in which X is -OCH3 or NO2, when Y is a hydrogen atom or X = Y = Cl or -OCH3, Z is a Cl, Br or -OH group, n = 1 for 4,5-di derivatives, hydroisoxazole or n = 0 for isoxazole derivatives.

Description

The invention relates to new compounds from the group of isoxazole and 4,5-dihydroisoxazole derivatives of the general formula shown in the figure, having one or two substituents in the phenyl group and a substituted methyl group in the 5-position.

There are known from the German patent description No. 2723688 derivatives of 3-phenylisoxazole substituted in the 4-position of the phenyl ring with halogen atoms or a trifluoromethyl group and containing in the 5-position a methyl group substituted with halogen, or with NH2COOH, COOR, CONH2, CONHR, NHCOOR, SCN, NHCSNHR groups, characterized by or as drugs such as - anelgesics, antipyretics and others, depending on the type and position of substituents on the phenyl ring and the methyl group. Thus, 5-bromomethyl, 3-phenylisoxazole substituted in the 4-position of the phenyl ring shows a fungicidal effect, while 3- (4-chlorophenyl) isoxazole substituted in the 5-position with an aminomethyl group shows a pharmacological effect.

The subject of the invention are new compounds, 3-phenyl-5-methylisoxazole and 4,5-dihydroisoxazole derivatives of the general formula shown in the figure, in which X is a group -OCH3 or -NO2 when Y is a hydrogen atom or X = Y = -Cl or = -OCH3, Z is a -Cl, Br or an -OH group, n = 1 for 4,5-dihydroisoxazole derivatives or n = 0 for isoxazole derivatives.

The compounds according to the invention included in the general formula shown in the figure exhibit fungicidal activity.

The preparation of the derivatives according to the invention is shown in the examples.

EXAMPLE 1 A solution of 45.3 g (0.3 mol) of 4-methoxybenzaldehyde oxime in 250 ml of dimethylformamide (DMF) was placed in a 0.5 liter three-neck flask equipped with a thermometer and a mechanical stirrer. The contents of the flask were heated to 40 ° C and dosing of solid N-chlorosuccinimide (NCS) was started. The entire amount of NCS (40.1 g - 0.3 mol) was added over 20 minutes while the reaction was highly exothermic. The temperature in the flask was controlled by the NCS dosing rate so that it did not exceed 50 ° C. After the dispensing was completed, the contents of the flask were stirred until it had cooled down to ambient temperature, and then poured into 1 liter of ice water. The precipitated solid was filtered off, the filtrate was extracted twice (2 x 0.4 liters) with ethyl ether. The ether extracts were combined, dissolved therein before chlorooksym filtered and washed with water (2 x 0.5 dm3) and brine (2 x 0.5 dm ^3). The ether layer was dried over anhydrous MgSO4 and the solvent was chased on a rotary evaporator. The obtained chlorooxime was converted directly after the synthesis to the isoxazole derivative (4,5-dihydroisoxazole).

In a three-necked flask volume of 1 dm3 equipped with a dropping funnel, a thermometer and a stirrer and dissolved in 0.3 dm ³ of ethyl ether 56 g (0.3 mol) of aldehyde chlorooksymu 4-methoxybenzoic acid obtained above and 19.6 (0.35 mol) propargyl alcohol. The solution was cooled to 0 ° C and 35 g (0.35 mol) of triethylamine was added dropwise over 1 hour so that the temperature did not exceed 5 ° C. Stirring was carried out at this temperature for an additional hour after the addition was complete, and for a further 1.5 hours at room temperature. The precipitated triethylamine hydrochloride was dissolved by adding 0.3 dm ^{3 of} water to the flask. The layers were separated, the ether layer was washed with 0.2 liters of water, dried over anhydrous MgSO4, and then the ether was stripped off on a rotary evaporator. 35 g (57%) of 3- (4-methoxyphenyl) -5-hydroxymethylisoxazole with mp. 95-97 ° C.

1 H-NMR spectrum (TESLA BS-587A spectrometer, 80 MHz, CDCb, δ ppm): 2.90 bs; 1H; -OH; 3.78, s; 3H, O-CH3; 4.80, s, 2H; HO-CH ₂ ; 6.52, s, 1H, HC-; 6.81 - 7.61, m, 4H, Phenyl protons.

The NMR spectrum fully confirms the structure of the compound.

Example II. Proceeding as in Example 1, from 45.3 g (0.3 mole) of 4-methoxybenzaldehyde oxime, its chloroxime was prepared and this was cycloadditioned, as in Example 1, to 41 g (0.35 mole) of propargyl bromide. 64 g (80%) of 3- (4-methoxyphenyl) -5-bromomethylisoxazole with mp. 69-72 ° C.

The 1 H-NMR spectrum confirms the product structure (CDCl 2, δ ppm): 3.36 - 3.50, m, 2H, Br-CH _r ; 3.82. s, 3H, -O-CH3; 4.75-5.25, m, 1H, HC-; 6.89-7.59, m, 4H, Phenyl protons.

Example III. Proceeding as in Example 1, from 45.3 g of 4-methoxybenzaldehyde oxime, through its chloroxime and 27 g of alkyl chloride, there were obtained 45.3 g (67%) of 3- (4-methoxyphenyl) -5-chloromethyl-4.5-dihydroisoxazohi. at mp. 62-63 ° C.

1 H-NMR Spectrum, (CDCbSppm): 3.12 - 3.40, m, 2H, -CH ₂ - (isoxazole ring); 3.49 - 3.72, m, 2H, Cl-CH _2; 3.78, s, 3H, -OCH3; 4.71 - 5.07, m, 1H, -CH- (isoxazole ring), 6.81 - 7.61, m, 4H, phenyl protons.

Examples of compounds according to the invention with physicochemical data are presented in the table.

Table

Properties of compounds covered by the general formula shown in the figure

No. X y with n mp temp. 1 4-OCH3 H. Br 0 69-72 2 4-OCH3 H. Br 1 115-119 3 4-OCH3 H. Cl 0 48-50 4 4-OCH3 H. Cl 1 62-63 5 4-OCH3 H. -OH 0 95-97 6 2-NO2 H. -OH 0 102-104 7 3-NO ₂ H. -Br 0 60-62 8 3-NO ₂ H. -Cl 0 54-57 9 3-NO ₂ H. -Br 1 76-78 10 3-NO ₂ H. -Cl 1 86-87 11 2-C1 4-C1 Br ABOUT 33-36 12 2-C1 4-C1 Cl 0 45-48 13 2-C1 4-Cl Br 1 42-44 14 2-Cl 4-Cl Cl 1 59-61 15 3-Cl 4-Cl Br 0 89-93 16 3-Cl 4-Cl Cl 0 103 - 107 17 3-Cl 4-Cl Br 1 65-70 18 3-Cl 4-Cl Cl 1 92-96 19 2-OCH3 4-OCH3 Br 0 91-95 twenty 2-OCH3 4-OCH3 Cl 0 67-71 21 2-OCH3 4-OCH3 Br 1 75-80 22 2-OCH3 4-OCH3 Cl 1 99-102

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Claims (1)

Patent claim 3-phenyl-5-methylisoxazole and 4,5-dihydroisoxazole derivatives of the formula, where X is -OCH3 or NO2, when Y is hydrogen or X = Y = Cl or -OCH3, Z is Cl , Br or -OH group, n = 1 for 4,5-dihydroisoxazole derivatives or n = 0 for isoxazole derivatives. * * *