JPH02235874A - Production of dioxazine derivative - Google Patents

Abstract

NEW MATERIAL:The dioxazine derivative of formula IV (R1 is H, alkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, alkylthioalkyl, aryl, arylalkyl, aryloxyalkyl, etc.; R2 is H, lower alkyl, aryl or arylalkyl; R3 is OH, lower alkoxy, lower alkylthio or NR4R5; R4 and R5 are H, alkyl, cycloalkyl, alkoxyalkyl, aryl, arylalkyl, etc.). EXAMPLE:3-tert-Butyl-5-(2,6-diethylphenylaminocarbonyl)1,4,2-dioxazine. USE:A herbicide and an intermediate for agricultural chemicals, pharmaceuticals, etc. PREPARATION:The objective compound of formula IV can be produced by reducing a compound of formula I by electrolytic reduction and reacting the produced anion with a compound of formula II-III (X-Z are halogen).

Description

DETAILED DESCRIPTION OF THE INVENTION [Above] The present invention relates to a method for producing a novel dioxazine derivative. More specifically, it relates to a method for producing a dioxazine derivative by electrolytically reducing a hydroxylamine compound and reacting the generated anion species with an α,β-diyakuchi carboxylic acid derivative or an α-diyakuchi acrylic acid derivative. It is. The dioxazine derivatives produced by the method of the present invention are useful as herbicides, and are also useful as intermediates for the synthesis of physiological substances such as agricultural chemicals and medicines. Therefore, the production method of the present invention can be used in the chemical industry, particularly in the agricultural and pharmaceutical manufacturing fields. Until now, there have been some literature descriptions of compounds having a 5,6-dihydro-1,4,2-dioxazine skeleton, and there have also been reports of their synthesis by conventional organic synthesis methods. It is stated. According to it, the Journal of
Organic Chemistry Volume 36 No. 2 No. 284
(1971), penzhydroxamic acid, l,
By reaction with 2-dibromoethane, 3-phenyl-5
．． It is stated that 6-dihydro-1,4,2-dioxazine was obtained. Also, the Journal of the Chemical Society of Japan, 1975, No. 6
Vol. 1041 describes that by reacting long-chain hydroxamic acid with 1,2-dibromoethane, 3-long-chain alkyl-substituted -
A 5,6-dihythro-1,4,2-dioxazine derivative has been obtained. On the other hand, as an example of application to physiologically active substances, 3-substituted -
A method for producing 5,6-dihydro-1,4,2-dioxazine is described in JP-A-47-42685, and specific examples of substituents at the 31-position include, for example, 3-benzyl compound, 3-benzyl compound,
- Derivatives such as orthochlorphenyl derivatives and 3-methachlorophenyl derivatives have been disclosed. Applications as agricultural chemicals are limited to those with special structures that are modified versions of known agricultural chemicals that have carboxylic acid derivatives as substituents. These are described in JP-A-57-154181 and German Patent No. 3220525, and are also known to have herbicidal activity. However, to date, there is no literature description of a compound having a carboxylic acid derivative as a substituent at the 5-position. Conventionally, 5, which has a carboxylic acid derivative as a substituent at the 5-position,
There is no known method for producing 6-dihydro 1.4.2-dioxazine. ↓ The purpose of the present invention is to provide a method for producing novel dioxazine derivatives at extremely high yields by applying electrolytic reactions. The present inventors have tried various synthetic methods to achieve the above objective. As a result, the anion species produced by electrolytically reducing the compound of the general formula (I) below as a raw material,
We have now discovered that by reacting a compound of general formula (]r) or general formula (m), it is possible to obtain a new dioxazine derivative useful as a herbicide. Therefore, the gist of the present invention is that the general formula (I) R. -C-
NHOH (I) I O (wherein R. is a hydrogen atom, an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an alkoxyalkyl group, an alkylthioalkyl group, an aryl group, an arylalkyl group, an aryloxyalkyl group, ruthioalkyl group, arylalkyl group, oxyalkyl group, or arylalkylthioalkyl group (however, alkyl may be saturated or unsaturated, and aryl is
It means a benzene nucleus, a pyridine nucleus, a thiophene nucleus or a furan nucleus, and these nuclei can contain up to two identical or different octarogen atoms, a lower alkyl group, a lower haloalkyl group,
A hydroxylamine compound (which may be substituted with a hydroxy group, a lower alkoxy group, a lower alkylthio group, a cyano group, a nitro group, a phenoxy group, or a phenylthio group)) is electrolytically reduced, and the anion species generated are A method for producing a dioxazine derivative represented by general formula (17) (wherein R,,R...R, are the same as above), which is characterized by reacting with an acrylic acid derivative of general formula (n). Consists of. R t . used in the production method of the present invention. R *, R
．． ．． X. 'l; and zcvsm, and the physical properties of the obtained compound of formula (IV) are shown in Table 1. (In the formula, R2 and R are the same as above, and X and Y represent the same or different halogen atoms.)
General formula (m) R * - C H - C - C O R s
(m) (in the formula, R and R are the same as above, and 2 represents a halogen atom),
α18 mouth To carry out the present invention, s1
It can be roughly divided into the first method and the second method, but it can be carried out by a combination of these two methods or by a continuous method using them. The first method is to put the compound represented by the general formula (1), (II) or (m), a solvent and a supporting electrolyte into the cathode chamber of the electrolyte layer separated by a diaphragm, and put the molten butter and the anode chamber into the anode chamber. Add a supporting electrolyte and pass a direct current through the electrodes as a quantity of electricity (■)
For the compound 2FmoJl-'. In the case of the compound (III), current is applied before and after IFmojL-''. As the solvent, an aprotic polar solvent is preferable. Dimethylformamide, dimethylsulfoxide, hexamethylphosphonamide, sulfolane, acetonitrile S and methanol can be used as the supporting electrolyte. is preferably a quaternary ammonium salt, and the cations include tetramethylammonium, trimethylbenzylammonium, tetraethylammonium, triethylammonium, triethylammonium,
Tetrabrobylammonicum, tetraisobroammonium, tetrabutylammonium, and tetrahexylammonium, etc., and anions include chloride ion, bromine ion, iodide ion, valatoluenesulfonate ion, benzenesulfonate ion, perchloride ion, and sulfuric acid. ion, nitrate ion and borofluoride ion, among others, tetraethylammonium,
Balatoluene sulfonate. Tetraethylammonium perchlorate and tetrabutylammonium perchlorate are often used. Glass filters, unglazed cylinders, and ion exchange membranes can be used as diaphragms. As electrodes, metal electrodes such as platinum, mercury, lead, and copper, and those commonly used in electrolytic reactions such as carbon can be used in various shapes depending on the reaction apparatus, but particularly preferred electrodes are platinum and carbon. ．． Electrolytic reactions require electrolysis at a constant potential lower than these reduction potentials in order to avoid reduction of compounds of formulas (■) and (m), but generally the reduction potential of compounds of formula (I) is lower, Even if electrolysis is performed at an appropriate constant current, the desired product can often be obtained in good yield. The temperature of the electrolytic reduction reaction can be set arbitrarily within the range from room temperature to the boiling point of the solvent, but it is usually carried out between room temperature and 80°C. Formula (I) compound, formula (n) compound and formula (
m) The molar ratio of the compounds can be set arbitrarily, but it is preferably set around 1:1. In addition, it is preferable to perform stirring to ensure a smooth electrolytic reaction. After the reaction is complete, the target product can be obtained by adding water and an organic solvent such as benzene, toluene, tetrahydrofuran, or chloroform, and then distilling off the solvent, as in a normal organic reaction. can. In the second method, the compound represented by the general formula (r), 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 around IFmof-' is passed through the electrode as the amount of electricity necessary to convert the compound of formula (I) into an anion. After electricity is applied, the anion species of the formula (I) compound produced in the cathode chamber is reacted with half a mole of the formula (II) compound or with an equivalent mole of the formula (m) compound. The solvent, supporting electrolyte, separation WXS, and electrode used here are exactly the same as the W4l method, and the reaction temperature and post-treatment also follow the first method. Second
Although the method can be applied to all compounds of the present invention, it is particularly advantageous when compounds of formulas (II) and (m) are easily reduced. The starting materials, compounds of formulas (I), (n) and (m), can be easily produced using known compounds or known synthetic methods. Next, the method of the present invention will be specifically explained in Examples 1 to 4. However, the present invention is not limited to these examples. Tertiarybutylcarbonylhydroxylamine was added to the cathode chamber of a reaction vessel equipped with an unglazed cylindrical diaphragm and a platinum electrode.1.
17g (0.01 mol), N-(2.6-diethylphenyl)-2.3-dichloro11! DMF solution of lyuyu 3-phenyl-5-α,α-di (0.5 molar concentration) 6
0 mjL, and 20 ml of a DMF solution (0.75 molar concentration) of tetraethylammonium perchlorate in the anode chamber.
, and a current with a current density of 1.5Adm" at both poles is applied to 2
．． 0FmoJ1-', was heated at 50°C with stirring for 80 minutes, cooled, and the liquid in the cathode chamber was poured into a mixture of toluene and water. The organic layer was washed with IN hydrochloric acid and then with IN sodium hydroxide. After washing with water, it was dried with anhydrous sodium sulfate. When the solvent was distilled off under reduced pressure, the title compound was obtained as pale brown crystals (yield 90%, current efficiency 90%).
Recrystallization from a hexane-acetone mixed solvent gave white crystals with a melting point of 125-127°C. 1.37 g (0.01 mol) of penzhydroxamic acid was placed in the cathode chamber of a reaction vessel equipped with an unglazed cylindrical diaphragm and a platinum electrode.
Amyl N-(α,α-dimethylbenzyl)-2-promocrotonate (2.82 g (0.01 mol) and tetraethylammonium valatoluenesulfonate in DMF
Add 30 m of solution (0.5 molar concentration) and add D of tetraethylammonium valatoluene sulfonate to the anode chamber.
Add 10 ml of MF solution (0.75 molar concentration) and apply a current with a current density of 1.5 Adm-' at both poles to l.OFmoi-'
Electricity was applied for 80 minutes while stirring at 60°C. After energization, the cathode chamber was cooled, and the liquid in the cathode chamber was poured into a mixture of toluene and water, and treated in the same manner as in Example 1 to obtain a brown oil. When purified by silica gel column chromatography using a mixed solvent of toluene and ethyl acetate, 2.97 g (yield 88%, current efficiency 88%) of the title compound was obtained as a colorless oil, showing n:' = 1.5036. Ta. }C3.63g
(0.1 mol) was added and stirred at room temperature for 2 hours. After the reaction was completed, the treatment was carried out according to Example 1, and 3.66 g of the title compound was obtained as light brown crystals (yield: 89%, current efficiency: 89%).
), which was recrystallized from a hexane-ethyl acetate mixed solvent to give white crystals with a melting point of 153-56°C. Method Q: 2 in the cathode chamber of a reaction vessel equipped with an unglazed cylindrical diaphragm and a platinum electrode.
- Put 4.31 g (0.02 mol) of parachlorophenoxyethylcarbonylhydroxylamine and 60 mM of a DMF solution (0.5 molar concentration) of tetraethylammonium perchlorate into the anode chamber. DMF solution (0.75 molar concentration) 2
0 ml of N-(2.6-diethylphenyl)-2. 1.21 g (0.1 mol) of methylthiocarbonylhydroxylamine was placed in the electrode chamber of a reaction vessel equipped with a 3-dibromoprobionic acid amine clay cylindrical diaphragm and a platinum electrode.
and 30 ml of DMF solution (0.5 molar concentration) of tetraethylammonium valatoluene sulfonate,
10 ml of a DMF solution (0.75 molar concentration) of tetraethylammonium valatoluene sulfonate was placed in the anode chamber, and a current of 1.5 Adm-'' was applied to both electrodes.
FmoR-'Electricity was applied for 80 minutes while stirring at room temperature. After energization, 2.40 g (0.1 mol) of N-methyl-N-phenyl-2-bromoacrylic acid amide was added to the cathode chamber, and 50
The mixture was stirred at ℃ for 1 hour. After cooling, a light brown oil was obtained by processing according to Example 1. Purification by silica gel column chromatography using a toluene-acetone mixed solvent yielded 2.44 g of the title compound as a colorless oil.
(yield 87%, current efficiency 87%) was obtained, nll1=
It showed 1.5114. According to the method of the present invention, compounds of formula (IT), which are highly useful as herbicides and intermediates for pharmaceuticals and agricultural chemicals, can be industrially advantageously produced. Firstly, the desired product can be obtained with high purity, high yield, high electrical efficiency, and simple operation. In particular, the yield of the method of the present invention is 80% or more. Second, and especially the second method, the formula (n
) It is advantageous when the compound is easily reduced, and the desired product can be obtained without side reactions. Third, both the first method and the second method basically proceed with the same reaction mechanism, and can obtain the desired product at almost the same high yield. Therefore, it is also possible to perform a combination of the first and second methods or a continuous reaction. Fourth, since it uses electrical energy, it can be operated cleanly. The compound of general formula (ff) produced as described above has herbicidal activity. This herbicide is formulated and used according to conventional methods as shown in the following reference production example. l Compound? b. 30 parts of the compound No. 152, 3 parts of calcium alkylbenzenesulfonate, 5 parts of polyoxyethylene nonyl phenyl ether, and 62 parts of clay are uniformly mixed and pulverized to obtain an irrigation agent containing 30% of the active ingredient. 2 (agent) Compound decomposition. 30 parts of compound 48, methyl ethyl ketone 4
By mixing and dissolving 0 parts of polyoxyethylene nonylphenyl ether and 30 parts of polyoxyethylene nonylphenyl ether, an emulsion containing 30% of the active ingredient is obtained. Compound no. 5 parts of the compound No. 130, 1.5 parts of lauryl sulfate, 1.5 parts of calcium lignin sulfonate, 25 parts of bentonite and 67 parts of white carbon were uniformly mixed, water was added thereto, and the mixture was kneaded using a mixer to form granules. and dried in a fluidized fluid dryer to obtain granules containing 5% of the active ingredient. A Wagner pot with a size of 175,000 are was filled with rice paddy soil (alluvial loam), and 50 seeds each of Japanese barnyard grass, firefly, Japanese cypress, Japanese azalea, azalea, and cypress grass were uniformly sown on the surface layer. One day after sowing, the plants were flooded and the water depth was maintained at 2 cm.
Three days after sowing, two 2.5Ii seedlings of paddy rice were planted, and three plants were transplanted per pot. One day after transplanting paddy rice, an emulsion prepared according to Reference Formulation Example 2 was diluted with water, and 10 mJL of the treatment chemical solution per pot (equivalent to 50 g per 1O are in terms of application amount of active ingredient) was added dropwise. This test was conducted in duplicate per 1 drug solution concentration section, and
After a few days, the herbicidal effect and the degree of chemical damage to rice were investigated based on the evaluation indicators shown below. The results are shown in Table 2. Weeding rate (%) 100% Less than 80~lOO% 6 0~ 80ll 4 0~ BOn 2 0~ 4011 'l, Qn Degree of chemical damage Blight Killing chemical damage Large II Medium I Small H Very small 11 None Table 2 (Germany) Compound described in Japanese Patent No. 3220525)
Test Example 2 Weeding against weeds in field crops Fruits and crops 1) Test of herbicidal effect against weeds Field soil (
Alluvial loam) was packed, and an emulsion prepared according to the soil of 1 cm of the surface layer was diluted with water, and an emulsion was prepared according to the method for the soil of 1 cm of the surface layer. (equivalent to 100 g per 10 are) was sprayed onto the soil surface. This test was conducted in two consecutive plots, and 30 days after the chemical treatment, the herbicidal effect was investigated based on the same evaluation index as in Test Example 1. 2) Test for phytotoxicity on crops Pour field soil (alluvial loam) into a clay pot with a size of 1/10,000 are, and add seeds of each crop (5 soybean grains, 5 corn grains, 10 beet grains, rapeseed 10 grains). and 10 grains of wheat) were diluted and sprayed onto the soil surface with 100 grams of treatment solution per 10 ares (equivalent to 100 g of active ingredient per 10 ares). This test was conducted in two consecutive plots, and 30 days after the chemical treatment, the chemical damage to each crop was investigated based on the same evaluation index as in Test Example 1. The results are shown in Table 3.

Claims (1)

[Claims] 1) General formula (I) ▲ Numerical formula, chemical formula, table, etc. ▼ (I) [In the formula, R_1 is a hydrogen atom, an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, or an alkoxyalkyl group. group, alkylthioalkyl group, aryl group, arylalkyl group, aryloxyalkyl group, arylthioalkyl group, arylalkyloxyalkyl group or arylalkylthioalkyl group (however, alkyl may be saturated or unsaturated, and aryl means a benzene nucleus, a pyridine nucleus, a thiophene nucleus or a furan nucleus, which can contain up to two identical or different halogen atoms, a lower alkyl group, a lower haloalkyl group, a hydroxy group, a lower alkoxy group, a lower alkylthio group. A hydroxylamine compound represented by the following formula (which may be substituted with a group, a cyano group, a nitro group, a phenoxy group or a phenylthio group) is electrolytically reduced, and the generated anion species is converted to the general formula (II) ▲Mathematical formula, chemical formula, There are tables, etc.▼(II) [In the formula, R_2 represents a hydrogen atom, a lower alkyl group, an aryl group, or an arylalkyl group, and R_3 represents a hydroxy group, a lower alkoxy group, a lower alkylthio group, or a group▲Mathematical formula, chemical formula , tables, etc. ▼ (However, R
_4 and R_5 are the same or different hydrogen atoms, alkyl groups, cycloalkyl groups, alkoxyalkyl groups,
is an aryl group, an arylalkyl group, an arylalkyloxy group, or is bonded to each other to form a nitrogen-containing 5- to 7-membered ring, in which case the ring may further contain another heteroatom) . (wherein, R_2 and R_3 are the same as above, and Z represents a halogen atom), the general formula (IV) is characterized by reacting with an α-haloacrylic acid derivative ▲Mathematical formula, chemical formula, table etc.▼(IV) (In the formula, R_1, R_2, R_3 are the same as above)
A method for producing a dioxazine derivative represented by