KR850000756B1 - Process for preparing benzoisothiazoline derivatives - Google Patents

Abstract

The title compds. I (R = ethyl, isopropyl) were prepared. Thus, 2.01g 2-cyanobenzenesulfonicchloride was reacted with 1.5g 2,6- diethylaniline in 6 mL pyridine and the resultant solution was refluxed for 1 hr. with stirring, then washed with methanol, to give 1.1g 2-(2,6'-diethylphenyl)-3-imino-1,2-benzoisothiazoline1,1- dioxide. Antibacterial data from I was reported.

Description

Manufacturing method of plant disease releasing agent compound

The present invention relates to a method for producing a novel plant disease prevention compound.

More specifically, the present invention is achieved by a ring closure reaction of 2-cyano-N- (2 ', 6'-dialkylphenyl) -benzenesulfonate amide of the following general formula [IV] I] relates to a method for producing a plant disease releasing agent compound.

Wherein R is an ethyl group or an isopropyl group, respectively.

At present, antibiotics, which are widely used as pharmaceuticals for paperback disease, are beginning to feel a great concern for their continued use, including the emergence of resistant bacteria from various places and the lack of slogans. .

On the other hand, asodine, a non-aqueous agent, is also used as a morbidity control agent, but since the active ingredient contains heavy metal compounds, there are many difficulties in existing control drugs, such as the trend of use regulation in terms of toxicity and environmental pollution to human beings. There is a strong demand for development of new types of pharmaceuticals. Therefore, the present invention is to solve the above-mentioned point by providing a novel compound having plant disease releasing agent activity.

The novel compounds according to the present invention generally exhibit control against a wide range of agro-horticultural diseases, but have excellent control effects against rice paddy disease and cutting diseases of tomato and cucumber. .

This new compound is a very low-toxic synthetic compound that does not contain heavy metals and has no practical toxicity to livestock and fish, and no weakness to crops. Therefore, this compound is considered to have sufficient functionality to compensate for the shortcomings of the conventional medicine.

Next, the present invention will be described in detail.

1. Compound

The compound according to the present invention is represented by the general formula [I], and the following compounds (1) and (2) are representative.

Compound (1)

2- (2 ', 6'-diethylphenyl) -3-imino-1,2-benzoisothiazolyl-1,1-dioxide

Compound (2)

2- (2 ', 6'-diisopropylphenyl) -3-imino-1,2-benzoisothiazolyl-1,1-dioxide

2. Preparation of Compound

The compound of the present invention can be synthesized by any method suitable for the purpose of introducing or forming a desired substitution or bond in formula [I].

Formation of compounds

One suitable synthesis method is by reaction represented by the following reaction formula (A), and reactive derivatives related to the hydroxyl group of 2-cyanobenzenesulfonic acid, for example, halogenides, in particular chloride [II] and 2,6-di It is a method of obtaining target object [I] by making alkylaniline [III] react. Intermediate [IV] may or may not be made consciously of purpose.

Since the reaction between the compounds [II] and [III] involves the generation of hydrogen halides, it is preferable to carry out in the presence of an acid trapping agent of various organic bases to inorganic bases. The reaction can dissolve or disperse at least one of the compounds [I] to [III] and the acid trapping agent to be used, if desired, and furthermore, the presence of a solvent or dispersion medium that does not substantially inhibit the reaction. Can be carried out. In that case, excess compound [III] can be used as an acid trapping agent, a solvent, or a dispersion medium.

Specific reaction conditions when carrying out this reaction, etc. are described in later experimental examples and J. Am. Chem. Soc. 82. 1594 (1960) (Document 1) or Khim. Geterosikl. Soedin. What is necessary is just to select suitably according to the method of No. 12, 1632 (1978) (document 2). Moreover, compound [II] which is one of a raw material can be synthesize | combined according to the method of Beilstein Handuch der Organischem Chemie XI, 376 (document 3), for example.

Another suitable synthesis method is by a reaction represented by the following reaction formula (B), and the ring closure of 2-cyano-N- (2 ', 6'-dialkylphenyl) -benzenesulfonate amide of formula [IV] Iii) A method of obtaining the target product [I] by reaction.

This ring-closure reaction can be performed by heating, and can also be performed by using an acid and a base as a catalyst of reaction. As in the case of reaction (A), a suitable solvent or dispersion medium can be used.

What is necessary is just to select the specific reaction conditions etc. at the time of performing these reaction suitably according to description of a later experiment example and the method of the said document.

Next, the usefulness of the compound and the control of plant diseases will be discussed.

The plant disease control agent according to the present invention can take any form or use mode that can be employed as an agricultural or horticultural agent, in particular, a bactericide, provided that the active ingredient is the compound [I].

Specifically, for example, the compound of the present invention can be diluted as it is, or using a solid powder or other suitable carrier, and added with an adjuvant such as an electrodeposition agent, if necessary, or used in the preparation of pesticides. Various liquids or solid carriers are mixed by a method generally used, and if necessary, additives such as a humectant, an electrodeposition agent, a dispersant, an emulsifier, and a fixing agent are used to add a hydrating agent and a liquid agent. (I), an emulsion, powder, granules, etc. It can be used as a formulation form.

In the preparation of these preparations, as the liquid carrier, ones that can be dispersed or dissolved by a solvent or an adjuvant with respect to the compound of the present invention are used. For example, clay, kaolin, tark, diatomaceous earth, silica, calcium carbonate, calcium bicarbonate and the like are used as solid carriers such as carrosine, dioxane, acetone, dimethyl sulfooxide, animal and vegetable oils and surfactants.

The content of the active ingredient in the formulation thus obtained can be changed in a wide range. For example, when used as a liquid, the concentration in the liquid is preferably about 10 ppm to 500 ppm, and in the case of powder or granules, it is preferable to contain the compound of the present invention in the range of about 1% to 20%. It goes without saying that it can be formulated to a higher concentration than such a concentration and diluted at the time of use. In addition, if the circumstances permit, other compatible horticultural agents or fertilizers may be mixed in the formulation.

The control agent according to the present invention can be used by spraying on the foliage of crops, and can also be used on the surface of water, water, soil surface or soil. In this case, compatible agrohorticultural agents or fertilizers can be mixed. Such agricultural and horticultural agents include, for example, fungicides, insecticides, herbicides, plant growth regulators and the like.

The dosage varies depending on the type and extent of the disease, the type of crop, the type of application, etc. However, when applied to soil, the dosage of about 0.1 kg to 10 kg per 10 are usually appropriate. .

The following experimental example is described.

Synthesis Example 1 Synthesis of Compound (1)

2.01 g of 2-cyanobenzenesulfonic acid chloride and 1.5 g of 2,6-diethylaniline were added to 6 ml of pyridine, and the mixture was stirred and heated to reflux for 1 hour. To the residue obtained by distilling off pyridine under reduced pressure, methanol was added to the residue under ice cooling, and the precipitated white crystals were filtered off, washed with a small amount of methanol, and then washed with a small amount of methanol to obtain 2- (2,6'-diethylphenyl) -3-imino-1,2-. 1.1 g (yield 35%) of benzoisothiazoline-1,1-dioxide was obtained.

(1) Melting point 136 ° ~ 137 ° C (Recrystallized solvent methanol)

(2) Infrared absorption spectrum (Nujo) (cm ^-1 )

3230 (NH), 1651 (C≡N), 1348, 1328, 1270, 1249, 1216, 1170, 1122, 1074, 967, 860, 808, 776, 758, 747

(3) NMR spectrum (DMSO-d6-TMS) δ

8.48-6.98 (7H, multiple and wide signal, aromatic protons), 2.51 (4H, quadruple, J = 7.5 Hz, -CH ₂ -CH ₃ × 2), 1.08 (6H, triplet, J = 7.5 Hz , -CH ₂ -CH ₃ × 2)

(4) Elemental analysis value (%) C ₁₇ H ₁₈ N ₂ O ₂ S (314.4)

Calculated Value: C 64.95, H 5.77, N 8.91

Analytical Value: C 64.56, H 5.63, N 8.92

(5) Mass spectrum m / e

314 (M ⁺ ), 285 (MC ₂ H ₅ ), 235.91

Synthesis Example 2 Synthesis of Compound (1)

2.01 g of 2-cyanobenzene sulfonic acid chlorides and 3.0 g of 2,6-diethylaniline were mixed, and it heated at 150 degreeC, stirring. It reacts with exotherm and the clear solution solidifies soon. Immediately, heating was stopped, allowed to cool, methanol was added to precipitate, and the precipitated crystals were filtered off, washed with a small amount of methanol, and 2-cyano-N- (2 ', 6'-diethylphenyl) -benzene as an intermediate of compound (1). 1.3 g of sulfonamides (compound of R = ethyl group in general formula [IV]) were obtained.

(1) Melting point 131.5 ~ 133 ° C. (Recrystallized solvent methanol)

(2) Infrared absorption spectrum (Nujo1) (cm ^-1 )

3230 (NH), 2260 (C≡N), 1660, 1586, 1406, 1334, 1264, 1192, 1158, 1132, 1068, 1038, 971, 684, 606

(2) NMR spectrum (DMSO-d6-TMS) δ

8.05 ~ 6.78 (7H, multiplet, aromatic ring proton), 2.30 (4H, quadruple, J = 7Hz, -CH ₂ -CH ₃ × 2), 0.93 (6H, triplet, J = 7Hz, -CH _2- CH ₃ × 2)

(4) Mass spectrum m / e 314 (M ⁺ )

(5) Elemental analysis value (%) C ₁₇ H ₁₈ N ₂ O ₂ S (314.4)

Calculated Value: C 64.95, H 5.77, N 8.91

Analytical Value: C 64.87, H 5.80, N 8.88

200 mg of the obtained intermediate was dissolved in 3 ml of dioxane, 0.1 ml of triethylamine was added, and the mixture was heated to reflux for 1 hour. The oily substance obtained by distilling off the solvent soon crystallized. This crystal coincided with Compound (1) obtained in Synthesis Example 1 first. Quantity 200 mg.

Synthesis Example 3 Synthesis of Compound (1)

10 g of 2-cyanobenzenesulfonic acid chloride and 7.5 g of 2,6-diethylaniline were dissolved in 40 ml of dioxane, 6 g of triethylamine was added, and the mixture was heated and refluxed for 3 hours. The mixture was washed several times with a brown oily product obtained by distilling off the solvent, and finally, 30 ml of methanol was added to crystallize, and this was filtered and washed with a small amount of methanol to obtain 8 g of crude Compound (1). 1 g of the crude compound (1) obtained here was taken and dissolved in 30 ml of methanol. The insolubles were heated, filtered to remove, and ice crystals were precipitated and white crystals precipitated. The filtrate was concentrated to dryness and the solid obtained was recrystallized from hydrous methanol to obtain 560 mg of the target substance. This substance was consistent with compound (1) obtained in Synthesis Examples 1 and 2.

Synthesis Example 4 Synthesis of Compound (2)

2.1 g of 2-cyanobenzenesulfonic acid chloride and 1.77 g of 2,6-diisopropylaniline were dissolved in 30 ml of pyridine, and heated to reflux at a bath temperature of 180 ° C. for 2 hours. 15 ml of methanol was added to the brown oil obtained by distilling pyridine, and the mixture was stirred under ice cooling, and the precipitated white crystals were filtered off and washed with a small amount of methanol. 2- (2 ', 6'-diisopropylphenyl) -3-amino- 1.5 g of 1,2-benzoisothiazoline-1,1-dioxide was obtained.

(1) Melting Point 195-196 ° C (Recrystallized Solvent Methanol)

(2) Infrared Absorption Spectrum (Nujo1) (cm ^-1 )

3320 (NH), 1651 (C≡N), 1467, 1368, 1353, 1332, 1320, 1270, 1187, 1160, 1110, 1063, 927, 862, 842, 806, 773, 753, 651, 608, 588, 553

(2) NMR spectrum (DMSO-d6-TMS) δ

8.44 to 7.08 (7H, multiplet, aromatic ring proton), 2.90 (2H, multiplet, J = 7Hz, -CH (CH ₃ ) ₂ 2), 1.16 (6H, doublet, J = 7Hz, -CH (CH ₃ ) ₂ ), 1.02 (6H, doublet, J = 7Hz, -CH (CH ₃ ) ₂ )

(4) Mass spectrum m / e

342 (M ⁺ ), 299 (M-CH (CH ₃ ) ₂ ), 235

(5) Elemental Analysis Value (%)

Calculated Value: C 66.63, H 6.48, N 8.18

Analytical Value: C 66.67, H 6.48, N 8.18

Synthesis Example 5 Synthesis of Compound (2)

6.48 g of 2,6-diisopropylaniline and 4.2 g of 2-cyano-benzenesulfonic acid chloride were mixed, and the bath was stirred and heated to 140 ° C. The clear solution gradually solidified. When the internal temperature reached 120 ° C and the contents were completely solidified, the heating was stopped, allowed to cool, 30 ml of methanol was added to form a slurry, and the precipitated colorless crystals were filtered and washed with cold methanol to obtain 2.8 g of 2-cyano. Crystals of -N- (2 ', 6'-diisopropylphenyl) -benzenesulfonamide were obtained.

(1) Melting point 175-176.5 ° C. (decomposition) (recrystallized solvent methanol)

(2) Infrared Absorption Spectrum (Nujo1) (cm ^-1 )

3240 (NH), 2260 (C≡N), 1589, 1408, 1339, 1260, 1185, 1161, 1131, 1104, 1066, 928, 804, 773, 756, 703, 688, 625, 600, 571

(3) NMR spectrum (DMSO-d6-TMS) δ

8.05 ~ 6.82 (7H, multiplet, aromatic ring proton), 2.97 (2H, quintet, J = 6.5Hz, -CH (CH ₃ ) ₂ × 2), 0.91 (12H, doublet, J = 6.5Hz,- CH ( CH ₃ ) × 2)

(4) Elemental Analysis Value (%) C ₁₉ H ₂₂ N ₂ O ₂ S (342.46)

Calculated Value: C 66.63, H 6.48, N 8.18

Analytical Value: C 66.56, H 6.52, N 8.13

(5) Mass spectrum m / e

342 (M ⁺ ), 299 (M-CH (CH ₃ ) ₂ ), 176

500 mg of 2-cyano-N- (2 ', 6'-diisopropylphenyl) -benzenesulfonamide obtained here was dissolved in 10 ml of dioxane, 0.3 ml of triethylamine was added and heated and refluxed for 1 hour. The oily product obtained by distilling off the solvent soon crystallized. This crystal was consistent with Compound (2) obtained in Synthesis Example 4. Quantity 500mg.

Formulation

Preparation Example 1 Hydration

The ingredients are uniformly mixed and ground to form a hydrating composition and sparged at 100-150 liters per 10 liters at a predetermined concentration.

Preparation Example 2 Powder

The powder composition obtained by mixing and milling the above components is sparged with 4 kg per 10 ares.

[Example 3] Preparation

The ingredient materials are mixed, added by adding an appropriate amount of water, shaping, and then dried to spread 3 kg of granule composition per 10 ares.

Drug test

Example 1 Control effect test of rice paddy disease

Pharmaceutical spraying device spray gun (3kg / cm) in which the hydration agent prepared according to Formulation Example 1 was adjusted to the spraying liquid of a predetermined concentration in rice (breast stone) immediately before the ear cultivated with a wagner pot of 1/5000 ar ² ) was used to spray at a rate of 70 ml / 3 pot.

The inoculation incubation port contains the mycelia obtained from a cope bowl with a 0.5 cm diameter of the paperback bacterium obtained by planar culture for 48 hours in agar medium containing the decoction of potato with peptone immediately after air drying. The agar operation was inoculated by inserting 15 cm from the surface of the rice plant in the center of rice dumplings. In addition, the inoculation port on the seventh day after spraying to prevent the invasion was allowed to stand in the glass greenhouse for seven days after spraying the chemical liquid, and then inoculated by the method according to the inoculation port on the same day.

After inoculation, both inoculation holes on the day and 7 days after inoculation are covered with a plastic cylinder for each port to promote the invasion of paperback bacteria. After 10 days of treatment, the lesion length of the stem in which the disease occurred was measured and the control value was calculated according to the following equation. In addition, the occurrence of weak damage was carried out by observation at the same time.

The results were as shown in the following table.

Test Example 2 Seedling Disease Control Test

Seedling disease (Lyconia bacteria type IIIA) was incubated on agar plate containing potato decoction and mixed with three times of rice bran to inoculate. Sprouted seeds of 20 grains / port in 1 / 5000-are Wagner pot containing soil sterilized using tomato (breed, Hikari) and cucumber (breed, Satsuki Midori) as starting materials The seedlings were sown, the soil was covered, and the same amount of the inoculator and the sterilized soil was mixed in an equal amount to inoculate the same. After inoculation, it is placed in a constant temperature room at 28 ° C for 48 hours, and then the formulation is used as a liquid to adjust the compound of the present invention to a predetermined concentration, and 100 ml of this chemical solution per pot is uniformly applied to the surface of the pipette. Sprinkled Thereafter, in order to facilitate the invasion and invasion of the inoculation bacteria, they were brought into a glass greenhouse at 30 ° C.-28 ° C., and the disease was caused by passing the soil temperature in the pot slightly dry. Investigations were conducted to investigate the number of germination and healthy seedlings up to 3 weeks after sowing, and to calculate the germination rate for the number of sowing seeds and the incidence of healthy seedlings for germination.

The results were as shown in the following table.

Claims (1)

By the ring-closure reaction of 2-cyano-N- (2 ', 6'-dialkylphenyl) -benzenesulfonic acid imide of the following general formula [IV] Preparation of Plant Disease Control Compounds

In formula, R is an ethyl group or an isopro, respectively.