KR19990004221A - 3,4-Substituted Butanoic Acid Derivatives, Process for Producing the Same, and Fungicide Composition - Google Patents

Abstract

The present invention relates to a 3,4-diphenylbutanoic acid derivative having the following formula (1), a process for producing the same, and a fungicide composition containing the same as an active ingredient,

[Chemical Formula 1]

Wherein X is selected from the group consisting of a halogen atom, an alkyl group of 1 to 4 carbon atoms, a methoxy group, a phenoxy group or a bromophenyl group, Y is an alkyl group of 1 to 4 carbon atoms, (Phenyl, chlorine, bromine and iodine) substituted phenyl group substituted by an alkyl group of 4 or substituted by a halogen element (fluorine, chlorine, bromine and iodine).

Description

3,4-Substituted Butanoic Acid Derivatives, Process for Producing the Same, and Fungicide Composition

The present invention relates to a novel alkanoic acid derivative, more specifically to a 3,4-substituted butanoic acid derivative (I) represented by the following general formula (I), a process for producing the same and a fungicide composition containing the same as an active ingredient.

[Chemical Formula 1]

Wherein X represents a halogen atom, an alkyl group of 1 to 4 carbon atoms, a methoxy group, a phenoxy group or a bromophenyl group, Y represents an alkyl group of 1 to 4 carbon atoms directly substituted with an alkyl group of 1 to 4 carbon atoms Represents a substituted phenyl group or a phenyl group substituted with a halogen atom.

Many alkanoic acids have been reported to exhibit biological activities such as antibacterial and anticancer chemotherapy [Chem. Pharm. Bull., 40 (1993), 381-384, DE 2,635,664 (1978)]. More specifically, alkanoic acids have been developed as herbicides which can be used under conditions such as previous works, marquis or rice fields, and in addition, several compounds have been developed and commercialized as growth regulators, insecticides and the like. For example, the following alkanoic acid derivatives have been commercialized.

Among them, Chlorfenac (GBP 860,310) is a herbicide used in the previous works (2.8 to 3.4 kg / ㏊), 2,4-DB is an effective herbicide for light leaf weeds, Daminozide (USP 3, 240799) discloses a growth regulator, 4-Indol-3-yl-butyric acid (Van Overbeek, Encylopedia of Plant Physiology, 1996,14,1145) Chlorambucil is used as an insecticide. However, 3,4-substituted butanoic acid derivatives are not known.

Many kinds of fungicides, insecticides, growth regulators and herbicides have been developed for the protection of crops and are now being used. However, due to the resistance of the strain to the long-term use of such drugs, the efficacy thereof decreases over time, and thus many studies have been conducted to discover new lead compounds exhibiting biological activity.

As a result of research for solving these problems, it has been found that a novel compound which is not disclosed in patents or papers so far can be easily synthesized, can be easily changed into various forms and can be synthesized at a high yield, A novel 3,4-substituted butanoic acid derivative (I) having a fungicidal activity could be synthesized.

[Reaction Scheme 1]

The compound (I) can be synthesized by an intermediate step of synthesizing the compound (III) and the compound (IV) starting from an acetyl chloride derivative and X-substituted benzene (II) do. This will be described in more detail as follows.

a) X-substituted benzene (II) is dissolved in a solvent such as dichloromethane or 1,2-dichloroethane, and Lewis acid such as anhydrous aluminum chloride is slowly added. The Y-substituted acetyl chloride derivative is added to the mixture at a temperature of 0-5 ° C. The reaction mixture is stirred at room temperature for 5 to 10 hours, then added with a 5 to 10% sulfuric acid or hydrochloric acid solution, and then extracted with a solvent such as dichloromethane or 1,2-dichloroethane. The solvent is distilled off and recrystallized in ethanol to prepare the ketone compound (III) as the primary intermediate.

b) reacting the primary intermediate (III) and ethyl bromoacetate in benzene, ligroin or a mixed solvent thereof at a temperature of 80 to 100 ° C for 5 to 8 hours in the presence of zinc powder and an iodine catalyst, Or a hydrochloric acid solution is added at room temperature to terminate the reaction. The organic layer is separated, the solvent is removed, and the residue is recrystallized to obtain a high-yield secondary intermediate (IV).

C) After dissolving the secondary intermediate compound (IV) in dichloromethane, an equivalent amount or a slight excess of triethylsilane and anhydrous magnesium sulfate is added. BF ₃揃 Et ₂ O dissolved in trifluoroacetic acid The reaction solution is added slowly to the above reaction solution while maintaining the reaction temperature at 0 to 5 ° C, and the reaction temperature is maintained at 0 to 5 ° C and stirred for 4 to 8 hours. After the magnesium sulfate was removed by filtration, the solvent and trifluoroacetic acid were distilled off under reduced pressure (about 30 mmHg). The residue is dissolved in ethyl alcohol and heated under reflux for about 4 to 6 hours in the presence of about 20 to 30% of caustic soda or parasitic base. The reaction mixture is cooled to room temperature, acidified with hydrochloric acid or sulfuric acid, and then extracted with chloroform or dichloromethane. The extracted organic layer is dried over anhydrous magnesium sulfate, and then the solvent is distilled off. The residue was recrystallized in hexane to give the final compound 3,4-substituted butanoic acid derivative (I). In the test in vitro, the 3.4-substituted butanoic acid derivative (I) according to the present invention showed excellent hyphal inhibition rate against rice blast fungus, and it was confirmed that the anthrax anthracnose, apple spoilage, apple spotted fungus and cucumber powdery mildew High activity. In addition, the compound (I) of the above formula (1) showed high activity against rice blast fungus and cucumber powdery mildew in in vivo test.

In the following examples, methods for producing the compound (III), the compound (IV) and the compound (I) and the activity test method are described in more detail. This embodiment is intended to illustrate the present invention and does not limit the scope of the present invention.

(Example)

A. Preparation of Compound (III)

Example 1. Preparation of 4-fluorophenylbenzyl ketone

To a mixture of 23.5 g of anhydrous aluminum chloride and 300 mL of dichloromethane, 15 mL of 4-fluorobenzene was slowly added while maintaining the temperature at 5 ° C, and then 29.3 mL of phenylacetyl chloride was added dropwise over 2 hours. The reaction mixture was stirred at room temperature for 10 hours, and then 500 mL of a 10% hydrochloric acid aqueous solution was added to separate the organic layer. The separated organic layer was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized in ethyl alcohol to give 26 g of 4-fluorophenylbenzyl ketone as a white solid.

Yield: 78%, recrystallized from ethanol, melting ^{point: 79 ~ 80 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 4.22 (s, 2H), 7.08 (t, J = 8.31 Hz, 2H), 7.28 (m, 5H), 8.01 (dd, J = 8.31 Hz, 2H); ^{13 C NMR (300 MHz, CDC1} 3) δ 45.53, 115.77 (d, J = 21.8 HZ, C 2 -F), 127.17, 128.79, 130.54, 131.32, 133.10, 134.45, 165.66 (d, J = 225.11 Hz C 1 -F), 196.53; IR (KBr) 1688 cm ^-1 .

Example 2. 4-Bromophenyl benzyl ketone

4-bromobenzene and phenylacetyl chloride in the same manner as in Example 1,

Yield: 50%, recrystallized from ethanol, melting ^{point: 111 ~ 112 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 4.22 (s, 2H), 7.26 (m, 5H), 7.56 (d, J = 8.52 Hz, 2H), 7.84 (d, J = 8.52 Hz, 2H); ¹³ C NMR (300 MHz, CDCl ₃ ) 隆 45.57, 127.09, 128.38, 128.81, 129.43, 130.16, 130.25, 132.01, 134.24, 135.39, 196.58

Example 3. Synthesis of 4- (4-bromophenylphenyl) benzyl ketone

Was prepared from 4-bromobiphenyl and phenylacetyl chloride in the same manner as in Example 1,

Yield: 85%, recrystallized from ethanol, melting ^{point: 154 ~ 155 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 4.32 (s, 2H), 7.33 (m, 4H), 7.50 (m, 3H), 7.65 ( m, 4H), 8.10 (d, J = 8.51 Hz, 2H); ¹³ C NMR (300 MHz, CDCl ₃ ) δ 45.66, 122.75, 126.88, 127.11, 128.30, 128.67, 128.78, 129.01, 129.34, 132.16, 134.57, 135.65, 144.55, 197.13; IR (KBr) 1608 (CO) cm ^-1 .

Example 4. 4-Methoxyphenyl benzyl ketone

Pyrimidin-2-one, anisole and phenylacetyl chloride.

Yield: 66%, recrystallized from ethanol, melting ^{point: 72 ~ 73 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 3.86 (s, 2H), 4.25 (s, 3H), 6.94 (d, J = 8.79 Hz, 2H), 7.30 (m, 5H), 8.02 (d, J = 8.94 Hz, 2H); ¹³ C NMR (300 MHz, CDCl ₃ ) 隆 45.28, 55.43, 113.91, 126.86, 128.72, 129.56, 129.71, 131.03, 163.64, 196.25; IR (KBr) 1690 (CO) cm ^-1 .

Example 5. 4-phenoxyphenyl benzyl ketone

Prepared by the same method as in Example 1, from phenyl ether and phenylacetyl chloride.

Yield: 89%, recrystallized from ethanol, melting ^{point: 92 ~ 93 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 4.16 (s, 2H), 6.92 (d, J = 8.67 Hz, 2H), 7.00 (d, J = 7.74 Hz, 2H), 7.23 (m, 7H), 7.94 (d, J = 8.58 Hz, 2H); ¹³ C NMR (300 MHz, CDCl ₃ ) 隆 45.48, 117.54, 120.40, 124.87, 127.01, 128.84, 129.63, 130.00, 130.56, 130.95, 131.33, 135.02, 155.56, 162.17, 196.19; IR (KBr) 1681 (CO) cm ^-1 .

Example 6. Synthesis of phenyl ethyl ketone

Benzene and propionyl chloride in the same manner as in Example 1,

Yield: 99%, melting point: ^{liquid, 1 H NMR (300 MHz,} CDC1 3) δ 1.02 (t, J = 6.96 Hz, 3H), 2.84 (s, 3H), 7.24 ~ 7.43 (m, 2H), 7.87 ( d, J = 7.2 Hz, 2H).

Example 7. 3- (4-Chlorophenyl) ethyl ketone

Was prepared from 4-chlorobenzene and propionyl chloride in the same manner as in Example 1,

Yield: 90%, melting ^{point: 33 ~ 33.5 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 1.21 (t, J = 7.32 Hz, 3H), 2.97 (q, J = 7.32 Hz, 2H), 7.40 (d , J = 4.41 Hz, 2H), 7.88 (d, J = 4.29 Hz, 2H).

Example 8. Synthesis of 3- (4-methylphenyl) ethyl ketone

Was prepared from toluene and propionyl chloride in the same manner as in Example 1,

Yield: 50.3%, melting point: liquid (72 ~ 80 ℃ / 1.2 torr ), 1 H NMR (300 MHz, CDC1 3) δ 1.02 (t, J = 7.08 Hz, 3H), 2.18 (s, 3H), 2.73 ( q, J = 7.08 Hz, 2H), 7.03 (d, J = 7.92 Hz, 2H), 7.67 (d, J = 8.52 Hz 2H).

Example 9. Preparation of 3- (4-methoxyphenyl) ethyl ketone

Pyridin-2-yl-anisole and propionyl chloride.

Yield: 72%, melting ^{point: 23 ~ 23.5 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 1.23 (t, J = 7.32 Hz, 3H), 2.99 (q, J = 7.32 Hz, 2H), 3.86 (s , 3H), 6.94 (d, J = 8.67 Hz, 2H), 7.96 (d, J = 8.79 Hz, 2H).

Example 10. 3- (4-bromophenyl) ethyl ketone

Was prepared from 4-bromobenzene and propionyl chloride in the same manner as in Example 1,

Yield: 172%; melting point: liquid (100 ~ 120 ℃ / 1.25torr) , 1 H NMR (300 MHz, CDC1 3) δ 1.16 (t, J = 7.2 Hz, 3H), 2.92 (q, J = 7.2 Hz, 2H), 7.54 (d, J = 8.19 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H).

Example 11 1- (4-phenoxyphenyl) -2 (2-fluorophenyl) ethanone

Phenyl ether and 2-fluorophenylacetyl chloride in the same manner as in Example 1,

Yield: 88%, recrystallization: ethanol, melting point: 99-99.5 캜, ¹ H NMR (300 MHz, CDCl ₃ ) δ 4.2 (s, 2H), 6.88-7.98 (m, 13H).

Example 12. Preparation of 1- (4-phenoxyphenyl) -2- (3-fluorophenyl) ethanone

Phenylethanol and 3-fluorophenylacetyl chloride in the same manner as in Example 1,

Yield: 80%, recrystallization: ethanol, melting point: 56-56.5 캜, ¹ H NMR (300 MHz, CDCl ₃ ) 隆 4.20 (s, 2H), 6.92-7.40 (m, 11H), 7.98 (d, 2H).

Example 13. Preparation of 1- (4-phenoxyphenyl) -2- (4-fluorophenyl) ethanone

Phenyl ether and 4-fluorophenylacetyl chloride by the same method as in Example 1, supra.

Yield: 80%, recrystallized from ethanol, melting ^{point: 85 ~ 85.5 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 4.15 (s, 2H), 6.92 ~ 7.37 (m, 11H), 7,95 (d, 2H ).

B. Preparation of compound (IV)

Example 14 Ethyl 3- (4-fluorophenyl) -3-hydroxy-4-phenylbutanoate

To 500 mL of a mixed solvent of benzene or ligroin benzene (1: 1), an iodine catalyst and 19.4 g of zinc powder were added and refluxed for about 1 hour and then cooled to room temperature to obtain 25.4 g of 4-fluorophenylbenzyl ketone (Example 1) 10 mL of ethyl bromoacetate was added to the reaction mixture. The reaction was initiated with gentle refluxing of the reaction mixture followed by the slow addition of 22.8 mL of the remaining ethyl bromoacetate. The reaction mixture was refluxed for 8 hours, then cooled to room temperature and 10-15% sulfuric acid or hydrochloric acid solution was added. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was recrystallized in n-hexane to obtain ethyl 3- (4-fluorophenyl) -3-hydroxy- The neat was obtained as 25 g of a white solid.

Yield: 70%, recrystallization: n- hexane, melting ^{point: 57 ~ 58 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 1.11 (t, J = 7.14 Hz, 3H), 2.79 (d, J = 15.93 Hz, J = 13.59 Hz, 1 H), 3.03 (d, J = 13.59 Hz, 1 H), 3.05 (d, J = 15.93 Hz, ), 4.54 (s, 1H), 7.01 (m, 4H), 7.24 (m, 3H), 7.35 (m, 2H); ^{13 C NMR (300 MHz, CDC1} 3) δ 14.02, 43.92, 50.07, 60.82, 75.17, 114.80 (d, J = 20.84 Hz), 126.70, 127.31, 127.93, 130.97, 136.38, 141.54, 161.94 (d, J = 245.22 Hz), 172.75; IR (KBr) 3474 (OH), 1700 (CO) cm ^-1 .

Example 15 Ethyl 3- (4-bromophenyl) -3-hydroxy-4-phenylbutaate

Prepared by the same method as in Example 14 using 4-bromophenylbenzyl ketone (Example 2) as a starting material.

Yield: 76%, recrystallization: n- hexane, melting ^{point: 65 ~ 66 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 1.13 (t, J = 7.13 Hz, 3H), 2.77 (d, J = 16.03 Hz, J = 12.3 Hz, 1H), 3.00 (d, J = 12.60 Hz, 1H), 3.02 ), 4.53 (s, IH), 7.04 (m, 2H), 7.23 (m, 5H), 7.30 (m, 2H); ¹³ C NMR (300 MHz, CDCl ₃ ) δ 14.07, 43.68, 49.85, 60.93, 75.18, 121.09, 126.76, 127.35, 127.96, 130.87, 130.95, 144.75, 172.65.

Example 16. Preparation of ethyl 3-4- (4-bromophenyl) phenyl) -3-hydroxy-4-phenylbutanoate

Was prepared in the same manner as in Example 14, starting from 4- (4-bromophenylphenyl) benzyl ketone (Example 3) as a starting material.

Yield: 85%, recrystallization: n- hexane, melting ^{point: 88 ~ 89 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 1.09 (t, J = 7.14 Hz, 3H), 2.80 (d, J = 15.95 Hz, J = 13.47 Hz, 1H), 3.01 (d, J = 13.47 Hz, 1H), 3.05 (d, J = 15.95 Hz, ), 4.47 (s, IH), 7.05 (m, 2H), 7.21 (m, 2H), 7.53 (m, 8H); ¹³ C NMR (300 MHz, CDCl ₃ ) 隆 14.02, 43.78, 49.97, 60.75, 75.03, 121.51, 125.53, 126.53, 127.54, 128.54, 131.01, 132.01, 136.28, 138.04, 139.55, 145.03, 173.02; IR (KBr) 3445 (OH), 1720 (CO) cm- ¹ .

Example 17. Preparation of ethyl 3- (4-methoxyphenyl) -3-hydroxy-4-phenylbutanoate

4-methoxyphenylbenzyl ketone (Example 4) as a starting material.

Yield: 94%, recrystallization: n- hexane, melting ^{point: 58 ~ 59 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 1.06 (t, J = 7.14 Hz, 3H), 2.75 (d, J = 15.81 Hz, 1H), 3.00 (d, J = 14.94 Hz, 1H), 3.02 (d, J = 15.81 Hz, 1H), 3.03 , J = 7.14 Hz, 2H) , 4.39 (s, 1H), 6.82 (d, J = 8.79 Hz, 2H), 7.00 (m, 2H), 7.23 (m, 5H; 13 C NMR (300 MHz, CDC1 3 IR (KBr) 3434 (OH), 1702 (CO), < RTI ID = 0.0 > ) Cm ^-1 .

Example 18 Ethyl 3- (4-phenoxyphenyl) -3-hydroxy-4-phenylbutanoate

Prepared by the same method as in Example 14 using 4-phenoxyphenylbenzyl ketone (Example 5) as a starting material.

Yield: 90%, recrystallization: n- hexane, melting ^{point: 78 ~ 79 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 1.13 (t, J = 7.14 Hz, 3H), 2.77 (d, J = 15.90 Hz, J = 13.47 Hz, 2H), 3.01 (d, J = 13.47 Hz, 1H), 3.01 ), 4.47 (s, 1 H), 6.91-7.44 (m, 14H); ¹³ C NMR (300 MHz, CDCl ₃ ) δ 14.07, 43.81, 50.10, 60.78, 75.16, 118.37, 118.68, 123.18, 126.70, 126.84, 127.83, 12972, 130.84, 136.37, 140.43, 154.78, 172.79; IR (KBr) 3455 (OH), 1710 (CO) cm ^-1 .

Example 19. 3-Ethyl-3-hydroxypentanoic acid

The title compound was prepared by the same method as in Example 14, using phenylethylketone (Example 6) as a starting material.

Yield: 29%, melting ^{point: 1 H NMR (300 MHz,} CDC1 3) δ 0.74 (t, J = 7.44 Hz, 3H), 1.01 (t, J = 7.08 Hz, 3H), 1.77 (m, 2H), 2.78 (d, J = 25.93 Hz, 1H), 2.95, (d, J = 15.93 Hz, 1H), 3.94 (q, J = 7.08 Hz, 2H), 4.30 .

Example 20. Preparation of 3- (4-chlorophenyl) -3-hydroxypentanoic acid

Prepared by the same method as in Example 14 using 3- (4-chlorophenyl) ethyl ketone (Example 7) as a starting material.

Yield: 70%, melting point: ^{liquid, 1 H NMR (300 MHz,} CDC1 3) δ 0.73 (t, J = 7.2 Hz, 3H), 1.08 (t, J = 7.14 Hz, 3H), 1.76 (m, 2H) , 2.78 (d, J = 15.93 Hz, 1 H), 2.93 (s, J = 15.93 Hz, 1 H), 4.01 = 8.52 Hz, 2H), 7.34 (d, J = 8.79 Hz, 2H).

Example 21. Synthesis of 3- (4-methylphenyl) -3-hydroxypentanoic acid

Prepared by the same method as in Example 14 using 3- (4-methylphenyl) ethyl ketone (Example 8) as a starting material.

Yield: 71%, melting point: ^{liquid, 1 H NMR (300 MHz,} CDC1 3) δ 0.74 (t, J = 7.52 Hz, 3H), 1.06 (t, J = 7.08 Hz, 3H), 1.75 (m, 2H) (S, 3H), 2.76 (d, J = 15.99 Hz, 1H), 2.94 (d, J = 15.99 Hz, 1H), 3.97 , 7.10 (d, J = 8.07 Hz, 2H), 7.27 (d, J = 8.55 Hz, 2H).

Example 22. Preparation of 3- (4-methoxyphenyl) -3-hydroxypentanoic acid

Was prepared in the same manner as in Example 14, using 3- (4-methoxyphenyl) ethyl ketone (Example 9) as a starting material.

Yield: 43%, melting point: ^{liquid, 1 H NMR (300 MHz,} CDC1 3) δ 0.75 (t, J = 7.44 Hz, 3H), 1.08 (t, J = 7.32 Hz, 3H), 1.76 (m, 2H) , 2.76 (d, J = 15.57 Hz, 1 H), 2.93 (d, J = 15.57 Hz, 1 H), 3.76 , 6.84 (d, J = 8.67 Hz, 2H), 7.32 (d, J = 8.67 Hz, 2H).

Example 23. Preparation of 3- (4-bromophenyl) -3-hydroxypentanoic acid

Was prepared in the same manner as in Example 14, using 3- (4-bromophenyl) ethyl ketone (Example 10) as a starting material.

Yield: 84%, melting point: ^{liquid, 1 H NMR (300 MHz,} CDC1 3) δ 0.68 (t, J = 7.44 Hz, 3H), 1.02 (t, J = 7.2 Hz, 3H), 1.71 (m, 2H) , 2.73 (d, J = 15.69 Hz, 1H), 2.87 (d, J = 15.69 Hz, 1H), 3.95 (q, J = 7.2 Hz 2H), 4.36 4H).

Example 24. Preparation of ethyl 3- (4-phenoxyphenyl) -3-hydroxy-4- (2-fluorophenyl) butanoate

Prepared by the same method as in Example 14, starting with 1- (4-phenoxyphenyl) - (2-fluorophenyl) ethanone (Example 11) as a starting material.

^{Yield: 90%, 1 H NMR (} 300 MHz, CDC1 3) δ 1.11 (t, J = 7.44 Hz, 3H), 2.76 (t, J = 15.7 Hz, 1H), 3.00 (d, J = 13.00 Hz, 2H 1H), 3.03 (d, J = 15.7 Hz, 1H), 3.09 (d, J = 13.00 Hz, 1H), 4.00 14H).

Example 25. Preparation of ethyl 3- (4-phenoxyphenyl) -3-hydroxy-4- (3-fluorophenyl) butanoate

Was prepared in the same manner as in Example 14, starting from 1- (4-phenoxyphenyl) -2- (3-fluorophenyl) ethanone (Example 12) as a starting material.

Yield: 95%, ¹ H NMR (300 MHz, CDCl ₃ )? 1.10 (t, J = 7.2 Hz, 3H), 2.76 1H), 3.02 (d, J = 15.8 Hz, 1H), 3.07 (d, J = 14H).

Example 26. Ethyl 3- (4-phenoxyphenyl) -3-hydroxy-4- (4-fluorophenyl) butanoate

Was prepared in the same manner as in Example 14, starting from 1- (4-phenoxyphenyl) -2- (4-fluorophenyl) ethanone (Example 13) as a starting material.

^{Yield: 91%, 1 H NMR (} 300 MHz, CDC1 3) δ 1.11 (t, J = 7.2 Hz, 3H), 2.75 (d, J = 15.5 Hz, 1H), 3.03 (d, J = 12.88 Hz, 2H 1H), 3.05 (d, J = 15.6 Hz, 1H), 3.10 (d, J = 14H).

C. Synthesis of Compound (I)

Example 27. 3- (4-Fluorophenyl) -4-phenylbutanoic acid (1)

1.8 g of anhydrous magnesium sulfate, 5.1 mL of triethylsilane and 8 g of ethyl 3- (4-fluorophenyl) -3-hydroxy-4-nonoate (Example 14) were added to 70 mL of dichloromethane, A mixed solution of 16.1 mL of fluoroacetic acid and 0.34 mL of BF ₃ .Et ₂ O was added slowly and reacted for 4 hours at a temperature of 5 ° C or lower while stirring. After completion of the reaction, anhydrous sodium sulfate was filtered out, and the solvent and trifluoroacetic acid were distilled off under reduced pressure. The residue was dissolved in 20 mL of ethanol, 20 mL of a 30% aqueous solution of KOH or NaOH was added, and the mixture was refluxed for 5 hours. After the reaction was completed, the ethanol was removed under reduced pressure and acidified with a 10% aqueous hydrochloric acid solution. And extracted. The organic layer was dried over anhydrous sodium sulfate, and the organic solvent was removed under reduced pressure. The residue was recrystallized from n-hexane to obtain 4.5 g of 3- (4-fluorophenyl) -4-butanoic acid.

Yield: 66%, recrystallization: n- hexane, melting ^{point: 110 ~ 111 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 2.60 (m, 2H), 2.85 (m, 2H), 3.40 (m, 1H), 6.96-7.42 (m, 9H), 10.93 (s, 1 H); ¹³ C NMR (300 MHz, CDCl ₃ ) δ 40.13, 43.02, 43.13, 115.32 (d, J = 20.76 Hz), 126.44,127.57,128.65,139.14,158.78,161.69 (d, J = 244.54 Hz), 178.54. IR (KBr) 3028 (OH), 1704 (CO) cm ^-1 .

Example 28. 3- (4-bromophenyl) -4-phenylbutanoic acid (2)

Prepared by the same method as in Example 27 from ethyl 3- (4-bromophenyl) -3-hydroxy-4-phenylbutanoate (Example 15).

Yield: 85%, recrystallization: n- hexane, melting ^{point: 139 ~ 140 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 2.65 (m, 2H), 2.87 (m, 2H), 3.36 (tt, J = 7.44 , 7.44 Hz, 1 H), 6.91-7.44 (m, 9H); ¹³ C NMR (300 MHz, CDCl ₃ ) 隆 39.40, 42.82, 43.17, 120.49, 126.40, 128.34, 129.22, 131.55, 138.86, 142.08, 176.60; IR (KBr) 3010 (OH), 1700 (CO) cm ^-1 .

Example 29. 3- (4- (4-bromophenyl) phenyl) -4-4 phenylbutanoic acid (3)

4-phenylbutanoate (Example 16) was prepared in the same manner as in Example 27, from ethyl 3- (4- (4-bromophenyl) phenyl)

Yield: 86%, recrystallization: n- hexane, melting ^{point: 115 ~ 116 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 2.62 (m, 2H), 2.92 (m, 2H), 3.43 (m, 1H), 7.01-7.63 (m, 13H); ¹³ C NMR (300 MHz, CDCl ₃ ) δ 40.12, 42.92, 43.34, 126.32, 126.87, 127.07, 128.00, 128.11, 128.32, 128.57, 129.26, 139.30, 142.90, 178.45; IR (KBr) 3027 (OH), 1706 (CO) cm ^-1 .

Example 30. 3- (4-methoxyphenyl) -4-phenylbutanoic acid (4)

Was prepared in the same manner as in Example 27 from ethyl 3- (4-methoxyphenyl) -3-hygioxy-4-phenylbutanoate (Example 17).

Yield: 92%, recrystallized from ethanol, melting ^{point: 125 ~ 126 ℃, 1 H} NMR (300 MHz, CDC1 3) δ 2.63 (m, 2H), 2.87 (d, J = 5.49 Hz, 2H), 3.35 (m, 1H), 3.77 (s, 3H), 7.04 (m, 2H), 7.10 (m, 7H), 10.80 (s, 1H); ¹³ C NMR (300 MHz, CDCl ₃ ) 隆 39.96, 42.88, 43.21, 55.16, 113.96, 126.29, 128.32, 128.49, 129.33, 135.28, 139.55, 158.32, 178.89; IR (KBr) 3027 (OH), 1711 (CO) cm ^-1 .

Example 31. 3- (4-methoxyphenyl) -4-phenylbutanoic acid (5)

Was prepared in the same manner as in Example 27 from ethyl 3- (4-methoxyphenyl) -3-hygioxy-4-phenylbutanoate (Example 18).

Yield: 71%, recrystallization: mixed solvent of n-hexane and benzene; Melting point: 110-111 DEG C; ^{1 H NMR (300 MHz, CDC1} 3) δ 2.67 (m, 2H), 2.95 (d, J = 7.44 Hz, 2H), 3.43 (tt, J = 7.40, 7.40 Hz, 1H), 6.93 ~ 7.40 (m, 14H); ¹³ C NMR (300 MHz, CDCl ₃ ) 隆 39.92, 43.12, 118.72, 118.89, 123.13, 126.33, 128.75, 129.30, 129.83, 138.04, 139.28, 155.82; IR (KBr) 3046 (OH), 1701 (CO) cm ^-1 .

Example 32. 3-Phenylpentanoic acid (6)

Was prepared from 3-phenyl-3-hydroxypentanoic acid (Example 19) in the same manner as in Example 27.

Yield: 91%, recrystallization: liquid; ^{1 H NMR (300 MHz, CDC1} 3) δ 0.75 (t, J = 7.2 Hz, 3H), 1.62 (m, 2H), 1.71 (m, 1H), 2.60 (m, 2H), 2.96 (m, 1H) , 7.12-7.34 (m, 5H), 10.68 (s, 1H).

Example 33. 3- (4-Chlorophenyl) pentanoic acid (7)

Prepared by the same method as in Example 27 from 3- (4-chlorophenyl) -3-hydroxypentanoic acid (Example 20).

Yield: 90%, melting point: 66-66.5 캜; ^{1 H NMR (300 MHz, CDC1} 3) δ 0.75 (t, J = 7.58 Hz, 3H), 1.62 (m, 1H), 1.71 (m, 1H), 2.62 (m, 2H), 2.96 (m, 1H) , 7.06 (d, 2H), 7.25 (d, 2H).

Example 34. 3- (4-Methylphenyl) pentanoic acid (8)

Prepared by the same method as in Example 27 from 3- (4-methylphenyl) -3-hydroxypentanoic acid (Example 21).

Yield: 88%, melting point: 49-49.5 캜; ^{1 H NMR (300 MHz, CDC1} 3) δ 0.77 (t, J = 7.32 Hz, 3H), 1.54 (m, 1H), 1.72 (m, 1H), 2.30 (s, 3H), 2.57 (m, 2H) , 2.94 (m, 1 H), 7.10 (m, 5 H).

Example 35. 3- (4-Methoxyphenyl) pentanoic acid (9)

Prepared by the same method as in Example 27 from 3- (4-methoxyphenyl) -3-hydroxypentanoic acid (Example 22).

Yield: 86%, melting point: 79-79.5 DEG C; ^{1 H NMR (300 MHz, CDC1} 3) δ 0.77 (t, J = 7.20 Hz, 3H), 1.58 (m, 1H), 1.69 (m, 1H), 2.64 (m, 2H), 2.93 (m, 1H) , 3.76 (s, 3H), 6.84 (d, 2H), 7.09 (d, 2H), 11.20 (s, 1H).

Example 36. 3- (4-Bromophenyl) pentanoic acid (10)

Prepared by the same method as in Example 27 from 3- (4-bromophenyl) -3-hydroxypentanoic acid (Example 23).

Yield: 82%; Melting point: 69-69.5 DEG C; ^{1 H NMR (300 MHz, CDC1} 3) δ 0.75 (t, J = 7.38 Hz, 3H), 1.57 (m, 1H), 1.69 (m, 1H), 2.55 (s, 2H), 2.93 (m, 1H) , 7.04 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 11.50 (s, 1H).

Example 37. 3- (4-phenoxyphenyl) -4- (2-fluorophenyl) butanoic acid (11)

Was prepared from 3- (4-phenoxyphenyl) -3-hydroxy-4-2 (2-fluorophenyl) butanoic acid (Example 24) in the same manner as in Example 27.

^{Yield: 77%, 1 H NMR (} 300 MHz, CDC1 3) δ 2.51 (d, J = 9.57 Hz, 2H), 2.92 (m, 2H), 3.45 (m, 1H), 6.72 ~ 7.42 (m, 13H) , 10.22 (s, 1 H).

Example 38. 3- (4-phenoxyphenyl) -4- (3-fluorophenyl) butanoic acid (12)

Was prepared in the same manner as in Example 27 from 3- (4-phenoxyphenyl) -3-hydroxy-4- (3-fluorophenyl) butanoate (Example 25).

^{Yield: 80%, 1 H NMR (} 300 MHz, CDC1 3) δ 2.65 (m, 2H), 2.94 (m, 2H), 3.35 (m, 1H), 6.68 ~ 8.03 (m, 13H), 10.78 (s, 1H).

Example 39. 3- (4-phenoxyphenyl) -4- (4-fluorophenyl) butanoic acid (13)

Prepared by the same method as in Example 27 from ethyl 3- (4-phenoxyphenyl) -3-hydroxy-4- (4-fluorophenyl) butanoate (Example 26).

^{Yield: 85%, 1 H NMR (} 300 MHz, CDC1 3) δ 2.58 (m, 2H), 2.91 (m, 2H), 3.37 (m, 1H), 6.78 ~ 7.35 (m, 13H), 11.19 (s, 1H).

D. Antimicrobial activity test

Example 40. In vitro testing

Compounds of formula 1 of the present invention were mixed with batches of potato agar at concentrations of 50 and 200 ppm, respectively, by agar plate dilution method to prepare plate media. For each concentration, 10 kinds of mycorrhizal fungi were inoculated and cultured in a thermostat at 27 ° C for 72 hours. Mycelial growth inhibition rate (%) on the medium containing the drug solution was examined. The bioactivity of the drug solution is shown in Table 1 below in comparison with the untreated solution.

In-vitro test results

[Table 1]

Example 41. In vivo test

- rice blast test

The seeds were seeded in a square pot (16 × 7 × 7 cm) and seeded with rice seeds (variety: Chusong) for 21 days (four leaves). The compound of formula (1) was diluted in water for each test concentration and a small amount of surfactant Rice were sprayed. One day after the medicament treatment, a spore suspension of rice blast fungus was prepared, and an appropriate amount of the spore suspension was inoculated to the medicinally treated crops and allowed to stand for 48 hours in an inoculation phase (temperature: 29 ° C, humidity: RH 100% It caused blast disease. Seven days after inoculation, the number of lesions on the leaf was noted, and the activity was evaluated by calculating the control value by comparing with the untreated control.

- rice paperback test

10 seedlings were seeded in square pots (16 x 7 x 7 cm), and hair growth was carried out for 21 days (four leaves). The compound of formula (1) was diluted in water by the test concentration to prepare a small amount After the addition, rice was sprayed. One day after the chemical treatment, the inoculum of the rice paperback disease was placed on the central part of the plant where the host plants were raised, lightly wound and placed in the inoculation phase (temperature: 29 ° C, humidity: RH 100%) for 72 hours, transferred to the greenhouse, . After 5 days of inoculation, leaf damage was calculated, and the activity was evaluated by calculating the control value by comparing with the untreated control.

- Cucumber white powder bottle test

Two seedlings of cucumber seeds were sown on square pots (16 × 7 × 7 cm) and seedlings were grown for 15 days (2 to 4 leafy days). The compound of formula (1) was diluted in water for each test concentration and a small amount of surfactant was added And sprayed on the leaf surface of cucumber. One day after the chemical solution treatment, cucumber white flour disease was inoculated and allowed to stand for 10 days in a greenhouse (temperature: 29 ° C). After 10 days of inoculation, the disease severity was calculated, and the activity was evaluated by calculating the control value by comparing with the untreated control.

- tomato root bacillus

After seeding two ripos of tomatoes in a square pot (16 × 7 × 7 cm), the seedlings were cultivated for 25 days (2-4 days), and the compound of formula (1) was diluted with water according to the test concentration. The leaves were sprayed. One day after the chemical solution treatment, tomato rot fungus was inoculated and allowed to stand for 5 days in a greenhouse (temperature: 21 ° C). After 5 days of inoculation, the degree of disease was calculated, and the activity was evaluated by calculating the control value by comparing with the untreated control.

The in vivo test results are shown in Table 2 below.

In vivo test results

[Table 2]

The novel 3, 4-substituted butanoic acid derivative (I) according to the present invention has a high bactericidal activity, in particular, a high bactericidal activity against rice blast fungus, cucumber powdery mildew, apple decay bacteria and the like, Therefore, it is expected that it is easy to synthesize a new derivative, so that it is expected that a derivative having more excellent fungicidal activity can be easily produced.

Claims (3)

A 3,4-diphenylbutanoic acid derivative having the following formula (1): < EMI ID = Formula 1 Wherein X is selected from the group consisting of a halogen atom, an alkyl group of 1 to 4 carbon atoms, a methoxy group, a phenoxy group or a bromophenyl group, Y is an alkyl group of 1 to 4 carbon atoms, A phenyl group substituted with an alkyl group having 4 or a phenyl group substituted with a halogen atom. (a) dissolving an acetyl chloride derivative and substituted benzene in a solvent of dichloromethane or 1,2-dichloroethane and adding aluminum chloride to react to prepare a primary intermediate or ketone compound having the following formula, Wherein X is selected from the group consisting of a halogen atom, an alkyl group of 1 to 4 carbon atoms, a methoxy group, a phenoxy group or a bromophenyl group, Y is an alkyl group of 1 to 4 carbon atoms, A phenyl group substituted with an alkyl group having 1 to 4 carbon atoms or a phenyl group substituted with a halogen atom, (b) reacting the ketone compound with ethyl bromoacetate in benzene, ligroin or a mixed solvent thereof at a temperature of 80 to 100 ° C for 5 to 8 hours in the presence of a zinc powder and an iodine catalyst to obtain a secondary intermediate ester chemical And, (c) dissolving the secondary intermediate or ester compound in a dichloromethane solvent, adding triethylsilane and anhydrous magnesium sulfate in an equivalent amount or a slight excess, adding BF ₃揃 Et ₂ O dissolved in trifluoroacetic acid to 0 - Diphenyl butanoic acid derivative having the following chemical formula 1, which is obtained by slowly adding water while keeping the temperature at 5 ° C, and maintaining the mixture at 0 to 5 ° C for 4 to 8 hours with stirring. Formula 1 Wherein X and Y are as defined above. Disinfectant composition comprising a 3,4-diphenylbutanoic acid derivative having the following formula (1) as an active ingredient: Formula 1 Wherein X is selected from the group consisting of a halogen atom, an alkyl group of 1 to 4 carbon atoms, a methoxy group, a phenoxy group or a bromophenyl group, Y is an alkyl group of 1 to 4 carbon atoms, A phenyl group substituted with an alkyl group having 4 or a phenyl group substituted with a halogen atom.