JPH01215994A - Production of benzenecarboxyimidamido derivative by electrolytic reaction - Google Patents

Abstract

PURPOSE:To produce a benzenecarboxyimidamido deriv. by putting amidoximes represented by a specified formula and a halocarboxylic acid deriv. represented by a specified formula in a cathode chamber and by supplying electric current to bring them into a reaction. CONSTITUTION:Amidoximes represented by formula I (where each of X and Y is halogen, lower alkyl, etc., and each of (m) and (n) is an integer of 0-3) and a halocarboxylic acid deriv. represented by formula II [where B is halogen, etc., A is methylene which may have a lower alkyl substituent, etc., and R is Ra-Z (Ra is H, etc., and Z is 0, etc.)] are put in a cathode chamber and electric current is supplied to bring them into a reaction. A benzenecarboxyimidamido deriv. represented by formula III is advantageously produced by electrolytic reduction and is useful as a sterilizer for agriculture and horticulture.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention is useful as a fungicide for gardening and relates to a novel method for producing a novel benzenecarboximidamide derivative using electrolytic reaction. More specifically, the general formula (m
) and a helocarboxylic acid derivative, an alkylsulfonyloxycarboxylic acid derivative, or an arylsulfonyloxycarboxylic acid derivative represented by the general formula (II) are placed in a cathode chamber, and electricity is applied to cause the reaction to occur, or the general formula Put (II[) into the cathode chamber and after energizing,
Provided is a method for advantageously producing a benzenecarboximidamide derivative represented by general formula (I) by reacting the generated anion species of amidoximes represented by general formula (■') with general formula (II). It's about doing.

Therefore, the present invention is useful in the chemical industry field.

(Prior Art) The benzenecarboximitamide derivative represented by the general formula (I) is a new compound and is useful as a fungicide for agricultural and horticultural purposes. To obtain these derivatives, it is conceivable to use ordinary organic synthesis reactions, but to date, there is no known method for producing the compounds of the present invention.

On the other hand, in recent years, attempts have been made to utilize active anion species generated at the cathode through electrolytic reduction in organic synthesis. For example, regarding active oxygen anion species, Chemistry Letters, p. 371 (1985) states that carboxylade anions generated by electrolytic reduction of carboxylic acids in the presence of a quaternary ammonium salt supporting electrolyte and alkyl halides or tosyloxyalkyl Synthesis of esters by reaction with
(986) describes the synthesis of diaryl ethers by reacting phenolate anions and benzenethiolate anions generated at the cathode with halonitrobenzenes in addition to similar esterification of carboxylic acids. However, as seen in the present invention, a novel benzenecarboxylic compound is produced by reacting an anion species generated by electrolytic reduction of amidoximes with a helocarboxylic acid derivative, an alkylsulfonyloxycarboxylic acid derivative, or an arylsulfonyloxycarboxylic acid derivative. There is no known method for producing Mitamito derivatives.

(Problems to be Solved by the Invention) The present invention provides a novel and industrially advantageous method for producing benzenecarboximitamide derivatives useful as agricultural and horticultural fungicides by electrolytic reduction, rather than by conventional organic synthesis methods. The purpose is to provide a method.

(Means for Solving the Problems) In order to solve the above problems, the present inventors have intensively studied numerous industrial manufacturing methods. As a result, in the electrolytic cell, the cathode chamber has the general formula (m) (wherein, , a nitro group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group or a lower alkoxycarbonyl group, m and n are integers of 0 to 3] and the compound represented by the general formula (I
I) B-A-COR(H) [wherein, B/ represents a halogen atom, an alkylsulfonyloxy group, or an arylsulfonyloxy group, and A
represents a methylene group or ethylene group that may have a lower alkyl substituent or a phenyl substituent, a polymethylene group or a lower alkenylene group that may contain a double bond, and R
is Ra Z -(Tatashi, Ra is a hydrogen atom, lower alkyl group, lower alkenyl group, lower alkynyl group, C3-
6 cycloalkyl group, lower alkoxy lower alkyl group,
Lower alkoxycarbonyl represents a lower alkyl group, phenyl group, pencil group, or an inorganic or organic base cation, and 2 represents an oxygen atom or a sulfur atom), or 〉N-(Tatashi, Rc Rb and Rc are a hydrogen atom, a lower alkyl group,
Lower alkenyl group, lower alkynyl group.

C3-6 cycloalkyl group, lower alkoxy group, phenyl group or pencil group), or both Rb and Rc together with the adjacent nitrogen atom may further contain one oxygen, sulfur or nitrogen atom as a heteroatom. or a six-membered heterocycle (in the case of an additional heteroatom or nitrogen atom, one valency shall be filled by a hydrogen atom or a lower alkyl group)) A compound of the general formula (III) (in the formula, X, Y, m
, n have the same meanings as above), and after applying electricity, the resulting general formula (■') [wherein, X, Y, m, and n have the same meanings as above] The compound represented by the general formula (n)B-A-COR(n) is reacted with the compound represented by the general formula (1) [wherein X and Y may be the same or different from each other. may represent a halogen atom, a lower alkyl group, a lower haloalkyl group, a lower alkoxy group, a nitro group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group or a lower alkoxycarbonyl group, and m and n are 0 to 3. is an integer, A represents a methylene group or an ethylene group having a lower alkyl substituent or a phenyl substituent, a polymethylene group or a lower alkenylene group which may contain a double bond, and R is a RaZ-
(However, Ra is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a C3-6 cycloalkyl group, a lower alkoxy lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a phenyl group, a pencil group, or an inorganic or Represents an organic cation, Z is an oxygen source N
- (Rh and Rc are each hydrogen atom, lower alkyl group, lower alkenyl group, lower alkynyl group, C
3-6 cycloalkyl group, lower alkoxy group, phenyl group or benzyl group), or Rb and R
Both of c are 5- or 6-membered heterocycles which may further contain one oxygen, sulfur or nitrogen atom as a heteroatom together with the adjacent nitrogen atom (if the additional heteroatom is a nitrogen atom) , one valence of which is filled with a hydrogen atom or a lower alkyl group) has been found to be industrially advantageous to produce.

Representative examples of compounds of formula (I) obtained by the production method of the present invention are shown in Table 1. In the table, the symbol "-" in the Xm and Yn columns indicates m and n, respectively, or 0, that is,
This refers to the case where the benzene nucleus does not have substituents X and Y.

Note that the compound numbers in Table 1 are also referred to in Examples and Reference Test Examples. Furthermore, in the present specification, compounds of formulas (I), (II), and (m) may contain two or more isomers based on double bonds, asymmetric carbon atoms, etc., unless specifically mentioned. It goes without saying that the compounds according to the present invention may include not only one type of isomer but also any mixture of two or more isomers.

The present invention can be broadly divided into the following first method and second method, but it can be carried out by a combination of these two methods or by a continuous method thereof.

The first method is to place a compound of formula (II), a compound of formula (m), a solvent, and a supporting electrolyte in a cathode chamber separated by a membrane,
A solvent and a supporting electrolyte are placed in the anode chamber, and a direct current is passed through the electrode.

As the solvent, aprotic polar solvents are preferred, and dimethylformamide, dimethylsulfoxide, hexamethylphosphonamide, sulfolane, acetonitrile and methanol can be used.

As the supporting electrolyte, quaternary ammonium is preferable,
Examples of cations include tetramethylammonium, trimethylpensylammonium, tetraethylammonium, triethylammonium, tetrapropylammonium, tetraisopropylammonium, tetramethylammonium, and tetrahexylammonium.
Examples of anions used include chloride ions, bromide ions, iodine ions, paratoluenesulfonate ions, benzenesulfonate ions, perchlorate ions, sulfate ions, nitrate ions, and borofluoride ions. Frequently used are sodium paratoluene sulfonate, tetraethylammonium perchlorate, and tetramethylammonium perchlorate.

Glass filters, unglazed cylinders and ion exchange membranes can be used as diaphragms.

As electrodes, metal electrodes such as platinum, mercury, lead, and copper, as well as those commonly used in electrolytic reactions such as carbon, can be used in various shapes depending on the reaction apparatus. Particularly preferable electrode materials include platinum and carbon. It is carbon.

Since the electrolytic reaction is small enough to avoid reduction of the compound of formula (II), even if electrolysis is carried out with a constant current of an appropriate magnitude, the yield is often low (the desired product may be obtained). Can the temperature of the electrolytic reaction be set arbitrarily within the range from room temperature to the boiling point of the solvent?
Usually, the temperature is between room temperature and 80°C. It is a raw material (m
Although the molar ratio of the compound of formula ) and the compound of formula (II) can be set arbitrarily, it is preferably set around 1:1. Further, it is preferable to perform stirring in order to perform the electrolytic reaction smoothly. After the reaction is completed, water and benzene,
The target product can be obtained by adding an organic solvent such as toluene, tetrahydrofuran, or chloroform to extract the target product, and then distilling off the solvent.

In the second method, the compound of formula (m), a solvent, and a supporting electrolyte are placed in a cathode chamber separated by a diaphragm, and the solvent and supporting electrolyte are placed in an anode chamber. Then, a direct current necessary to convert the compound of formula (m) into an anion is passed through the electrode. After energizing,
The generated anion species of the compound of formula (m) and the compound of formula (II) are reacted. The solvent, supporting electrolyte, diaphragm and electrode used here are exactly the same as in the first method.
The reaction temperature and post-treatment are also similar to the first method.

Is the second method applicable to all compounds of the invention?
This is particularly advantageous when the compound of formula (II) is easily reduced. In addition, carbonic acid derivatives in which R is a hydroxyl group in compounds of formula (IT) are usually reduced more easily than compounds of formula (m). Side reactions may occur due to the reaction of the carboxy anion of the compound. In this case, the desired product can be obtained without side reactions by the second method using 2 equivalents of the compound of formula (m) relative to the compound of formula (II).

Production examples of the present invention are shown in Examples 1 to 5.

Next, the method of the present invention will be described with specific examples. However, the present invention is not limited to these examples.

Example 1 6.0 g of 4-chloro-N-hydroxy-N'-shiimitamide was placed in the cathode chamber of a reaction vessel equipped with a 4-chloro-N-(1-carbomethoxy) unglazed cylindrical diaphragm and a platinum electrode.
(0.02 mol), α-bromopropionic acid methyl ester 3.3 g (0.02 mol) and tetraethylammonium perchlorate in DMF solution (0.5 molar concentration)
60rnlL, and in the anode chamber, a DMF solution of tetraethylammonium perchlorate (0.75 molar concentration) 2
0 m statement, the current density of both poles was set to 1.5 Adm-2, the amount of electricity was set to 1.0 FmoJl-', and after stirring at room temperature,
It was poured into a mixture of tetrahydrofuran, toluene and water in the cathode chamber. The organic layer was washed with IN hydrochloric acid, then IN sodium hydroxide, washed with water, and dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography to obtain 7.2 g of the title compound as a colorless transparent oil (yield 93%, current efficiency 93%).
) obtained, n3'=1. '4964 was shown.

2 in the cathode chamber of the reaction vessel equipped with an unglazed cylindrical diaphragm and a platinum electrode.
-trifluoromethyl-N-hydroxy-N'-(2,
6-diethyl)phenylbenzenecarboximitamite 6.7 g (0.02 mol), chloroacetic acid ethyl ester 2.5 g (0.02 mol) and tetraphthylammonium perchlorate in DMSO solution (0.75 mol). Concentration) 60mM, and in the anode chamber, a DMF solution of tetraphthylammonium perchlorate (0.75 molar concentration) 2
The current density at both electrodes was set to 1-51-5Ad, the amount of electricity was set to 1.05F+5ou-', and the current was applied for 84 minutes while stirring at 60°C. After energization, it was cooled and the liquid in the cathode chamber was poured into a mixture of toluene and water. IN organic layer
It was washed with hydrochloric acid, then with IN sodium hydroxide, and after washing with water, it was dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel chromatography to obtain 7.8 g (yield 92%, current efficiency 88%) of the title compound as a colorless transparent oil, nP-1,5440.
showed that.

2 in the cathode chamber of the reaction vessel equipped with an unglazed cylindrical diaphragm and a platinum electrode.
-Methyl-N-hydroxy-N'-(2,6-diethyl)phenylbenzenecarboxymitamito 5.6g
(0.02 mol), 5.4 g (0.02 mol) of α-para-toluenesulfonyloxypropionic acid ethyl ester, and 60 m of a DMF solution (0.5 mol concentration) of tetraethylammonium para-toluene sulfonate were added to the anode. The chamber contains 20 ml of DMF solution (0.75 molar concentration) of tetraethylammonium paratoluene sulfonate.
The current density at both poles was set to 1.5Adm-2, the amount of electricity was set to 1.0Ffflou-', and the temperature was 80°C while stirring at room temperature.
Power was applied for 00 minutes. After electricity was applied and the mixture was stirred 3 times, the liquid in the cathode chamber was poured into a mixture of toluene and water. When treated in the same manner as in Example 1, the title compound was obtained as a colorless transparent oil.
．． 0 g (yield 92%, current efficiency 92%) was obtained, n,
1ff=1.

4493 was shown.

Production of carboxyimitamite (compound No. 168) [Second method] In the cathode chamber of a reaction vessel equipped with an unglazed cylindrical diaphragm and a platinum electrode,
-Chlor-N-hydroxy-N'-(2,6-ethyl)phenylbenzenecarboximitamito 6.0g
(0.02 mol) and a DMF solution of tetraethylammonium perchlorate < o, y 1 molar concentration) 60 m is placed in the anode chamber, and the DMF mol-' of tetraethylammonium perchlorate is placed in the anode chamber and kept at room temperature without stirring. Electricity was applied for 80 minutes. After electricity was applied, 3.9 g (0.02 mol) of α-furomoisoacetic acid ethyl ester was added dropwise to the cathode chamber and stirred for 30 minutes. After the reaction was completed, the same treatment as in Example 2 yielded 7.6 g of the title compound as white crystals (yield 91%,
The current efficiency was 91%) and the melting point was 90-92°C.

Production of (Compound No. 37) [Second method] In a cathode chamber of a reaction vessel equipped with an unglazed cylindrical diaphragm and a platinum electrode, two
-Methyl-N-hydroxy-N'-(3-isopropoxy)phenylbenzenecarboxymitamito 5.7g
(0.02 mol) and tetraethylammonium para-toluene sulfonate in DMF aqueous solution (0.5 mol)
In the anode chamber, a DMF aqueous solution of tetraethylammonium para-toluene sulfonate (0.75
molarity), and the current density at both poles was set to 1.9A.
dm-2, the amount of electricity is 1. The temperature was set to OF+5oJL-', and electricity was applied for 80 minutes while stirring at room temperature. After energizing, add 0.95 g (0.0 fmol) of chloroacetic acid to the cathode chamber in a small amount of DMF.
and added dropwise. After dropping and stirring for 30°, the liquid in the cathode chamber was poured into a mixture of tetrahydrofuran, toluene and IN hydrochloric acid, and the organic layer was separated. The organic layer is extracted with a 10% aqueous sodium bioxide solution, and half of 2-methyl-N-hydroxy-N'-(3-impropoxy)phenylbenzenecarboximidamide is recovered from the organic layer. The aqueous layer is acidified with concentrated hydrochloric acid and extracted with chloroform. After washing with water, drying with anhydrous sodium sulfate, and distilling off the solvent under reduced pressure.
The residual solid was recrystallized from a mixed solvent of cyclohexane-acetone to obtain 3.0 g of the title compound as white crystals (yield 88%, current efficiency 88%), melting point 110.5-1.
It showed 13°C.

The compound of formula (m), which is a raw material, is known or can be produced by a known production method, for example, the method described in Chemical Assembles, Vol. 56, p. 7304 (1962). Moreover, the compound of formula (II) is a known compound.

(Effects of the Invention) According to the method of the present invention, it is possible to industrially advantageously produce the compound of formula (I) which is extremely useful as an agricultural and horticultural fungicide. That is, firstly, it is possible to obtain the target product with high purity, high yield, high electrical efficiency, and simple operation.

Secondly, especially the second method is advantageous when the compound of formula (m) is easily reduced, and it is possible to obtain the desired product without side reactions.

Third, due to electrical operations, the manufacturing site is clean.

Fourthly, both the first method and the second method basically proceed according to the same reaction mechanism, and can obtain the target compound at approximately the same level of high yield. Therefore, it is possible to carry out a combination of the first method and the second method, and it is also possible to carry out a continuous reaction of the method by combining the first method, the second method, and the two methods. It is.

Next, for reference, a bactericidal test of the compound of formula (I) is shown below.

Reference test example Chinese cabbage clubroot disease control effect test Chinese cabbage clubroot fungus (Plasmodeiophora thurasicae)
Soil contaminated with Vodiophora brassicae) is placed on a 5 mm wall, 1 kg of this is placed in a plastic bag, and mixed well with a designated powder powder prepared in a conventional manner. This chemically treated soil was placed in a square pot (20cm
1-Ocm x 10 cm), and sow Chinese cabbage (variety: Sakumidori) seeds in 5 locations. After that, Chinese cabbage will be cultivated and managed in a glass greenhouse. Then, when the cotyledons of Chinese cabbage are in the stage of development, leave 5 plants per pot and pull out the rest.

To investigate the onset of disease, all the plants from each pot were pulled out 10 days after sowing, and the roots were examined according to the degree of disease, and the degree of disease was determined. From this, the control value (%) was calculated in comparison with the disease severity in the untreated area, as shown by the following formula.

N: Total number of plants investigated a: Large galls or epiphytes on the base of the taproot, and growth is severely suppressed.b: galls or galls are epiphytic on the tips of the taproots and lateral roots, or the galls are small. Type C: Slight galls are attached to the lateral roots, and growth is almost normal. D: Healthy. On the other hand, for chemical damage, the degree of growth and deterioration of leaves are examined with the naked eye, and the following criteria are used: Displayed by.

0: No chemical damage, 1: Little 2: Medium 3: High 4-Severe 5: Withering This test was conducted in triplicate for each chemical treatment.

The results are shown in Table 2.

As is clear from the results in Table 2 and above, the compound of formula (I) obtained by the production method of the present invention is effective as a fungicide for agriculture and horticulture, and is particularly effective against clubroot disease of cruciferous vegetables, which is a difficult-to-control disease. In contrast, it is a new drug that can replace the conventional pentachlornitrobenzene.

Patent applicant: Hokuko Chemical Industry Co., Ltd.

Claims (1)

[Claims] In the electrolytic cell, the cathode chamber contains the general formula (III) ▲mathematical formula, chemical formula, table, etc.▼(III) [In the formula, X and Y may be the same or different from each other. , represents a halogen atom, lower alkyl group, lower haloalkyl group, lower alkoxy group, nitro group, lower alkylthio group, lower alkylsulfinyl group, lower alkylsulfonyl group or lower alkoxycarbonyl group, m and n are integers of 0 to 3. [In the formula, B represents a halogen atom, an alkylsulfonyloxy group, or an arylsulfonyloxy group, and A represents a lower alkyl substituent or Represents a methylene group or ethylene group that may have a phenyl substituent, a polymethylene group that may contain a double bond, or a lower alkenylene group; Alkynyl group, C_3_-_
6 cycloalkyl group, lower alkoxy lower alkyl group,
Lower alkoxycarbonyl represents a lower alkyl group, phenyl group, benzyl group, or an inorganic or organic base cation; , Rb and Rc are each a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, C_3_-_
6 cycloalkyl group, lower alkoxy group, phenyl group or benzyl group) or 5-membered or A compound represented by a 6-membered heterocyclic ring (provided that if the additional heteroatom is a nitrogen atom, one valence thereof shall be filled with a hydrogen atom or a lower alkyl group) is added, and electricity is applied. It is expressed by the general formula (III) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (III) [In the formula, X, Y, m, and n have the same meanings as above] After adding the compound and applying electricity, the general formula (III
') ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III') Compounds represented by [In the formula, X, Y, m, and n have the same meanings as above] and general formula (II) B-A- COR (II) [In the formula, B, A, and R have the same meanings as above] By reacting with a compound represented by the general formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [Formula In the middle, X and Y may be the same or different from each other, and each may be a halogen atom, a lower alkyl group, a lower haloalkyl group, a lower alkoxy group, a nitro group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, or Represents a lower alkoxycarbonyl group, m and n are integers of 0 to 3, and A is a methylene group or ethylene group that may have a lower alkyl substituent or a phenyl substituent, a polymethylene group or lower alkenylene that may contain a double bond. represents a group, R is RaZ
- (However, Ra is a hydrogen atom, lower alkyl group, lower alkenyl group, lower alkynyl group, C_3_-_6 cycloalkyl group, lower alkoxy lower alkyl group, lower alkoxycarbonyl lower alkyl group, phenyl group, benzyl group, or inorganic or organic (represents a cation of
each represents a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a C_3_-_6 cycloalkyl group, a lower alkoxy group, a phenyl group or a benzyl group), or both Rb and Rc represent an adjacent nitrogen A 5- or 6-membered heterocycle which, together with the atoms, may contain an additional oxygen, sulfur or nitrogen atom as a heteroatom (provided that if the additional heteroatom is a nitrogen atom, one valence of the hydrogen atom or A method for producing a benzenecarboximidamide derivative represented by: