KR100470382B1 - Process for preparing 3-(1-hydroxyphenyl-1-alkoximinomethyl)dioxazines) - Google Patents

Abstract

The present invention provides a number of novel preparations for preparing 3- (1-hydroxyphenyl-1-alcoximinomethyl) dioxazine known as intermediates for the preparation of compounds with fungicidal properties (see WO 95-04728). To methods and novel intermediates.

Description

Process for preparing 3- (1-hydroxyphenyl-1-alkoximinomethyl) dioxazines}

The present invention provides a number of novel preparations for preparing 3- (1-hydroxyphenyl-1-alcoximinomethyl) dioxazine known as intermediates for the preparation of compounds with fungicidal properties (see WO 95-04728). To methods and novel intermediates.

It is already known that certain 3- (1-hydroxyphenyl-1-alkoxyminomethyl) dioxazine can be prepared from the corresponding hydroxyphenyl acetates (WO 95-04728). Thus, for example, (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxyphenyl) methanone 0-methyloxime (1) is methyl hydroxyphenylacetate ( a) is reacted with dihydropyran and the obtained dihydropyranyl ether (b) is converted to methyl 2- [2- (tetrahydropyran-2-yloxy) phenyl] -2-hydroxy with t-butyl nitrite. After conversion to minoacetate (c), the compound was alkylated with iodomethane to give methyl 2- [2- (tetrahydropyran-2-yloxy) phenyl] -2-methoximinoacetate (d) The obtained compound (d) is reacted with hydroxylamine to give 2- [2- (tetrahydropyran-2-yloxy) phenyl-2-methoximino-N-hydroxyacetate (e), This was closed with dibromoethane to yield 3- {1- [2- (tetrahydropyran-2-yloxy) phenyl] -2-methoximinomethyl} -5,6-dihydro-1,2,4- Dioxazine (f) was obtained and finally Obtained by removing tetrahydropyranyl groups using an acid catalyst. This synthesis can be illustrated by the following scheme:

The main disadvantage of the method is that it requires a number of steps, some of which proceed in low yields, which severely affects the overall yield.

According to the present invention, 3- (1-hydroxyphenyl-1-alkoxyiminomethyl) dioxazine of the following general formula (I)

a) Rearranged 0-hydroxyethyl-0'-methyl-benzofurandione dioxime of the general formula (II) in the presence of a diluent and optionally in the presence of a base or an acid Or

b) reacting the hydroxybenzoyldioxazine of the general formula (III) with an alkoxyamine of the general formula (IV) or an acid addition complex thereof, optionally in the presence of a diluent and optionally in the presence of an acid acceptor ,

c) obtained by reacting hydroxyphenyl-hydroxyiminomethyl-dioxazine of the general formula (V) with an alkylating agent of the following general formula (VI) in the presence of a diluent and optionally in the presence of a base: This turned out to be:

In the above formula,

A represents alkyl,

R ¹ , R ² , R ³ and R ⁴ are the same or different and each independently of each other hydrogen, halogen, cyano, nitro, or in each case optionally halogen-substituted alkyl, alkoxy, alkylthio, alkylsulfinyl or Alkylsulfonyl,

Z ¹ , Z ² , Z ³ and Z ⁴ are the same or different and each independently represent hydrogen, alkyl, halogenoalkyl or hydroxyalkyl, or

Z ¹ and Z ² , or Z ¹ and Z ³ , or Z ³ and Z ⁴ together with each carbon atom to which they are attached form an alicyclic ring,

X represents halogen, alkylsulfonyloxy, alkoxysulfonyloxy or arylsulfonyloxy.

In the definition, saturated or unsaturated hydrocarbon chains such as alkyl, in combination with heteroatoms such as alkoxy or alkylthio, are in each case straight or branched chains.

Process a-c) according to the invention is preferably

A represents methyl, ethyl, or n- or i-propyl,

R ¹ , R ² , R ³ and R ⁴ are the same or different and each independently of one another are hydrogen, halogen, cyano, nitro, or each having 1 to 6 carbon atoms and each optionally being selected by 1 to 5 halogen atoms Substituted alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl,

Z ¹ , Z ² , Z ³ and Z ⁴ are the same or different and each independently of each other hydrogen, alkyl or hydroxyalkyl having 1 to 4 carbon atoms in the case of R, or 1 to 4 carbon atoms and 1 Or to halogenoalkyl having from 5 to 5 identical or different halogen atoms, or

Z ¹ and Z ² , or Z ¹ and Z ³ , or Z ³ and Z ⁴ together with the respective carbon atoms to which they are attached form compounds of general formula (I) which form an alicyclic ring of 5, 6 or 7 carbon atoms; Used to make

Particularly preferably

A represents methyl or ethyl,

R ¹ , R ² , R ³ and R ⁴ are the same or different and each independently represent hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n- or i-propyl, n-, i- , s- or t-butyl, methoxy, ethoxy, n- or i-propoxy, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, tri Fluoroethyl, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, difluorochloromethylthio, trifluoromethylthio, trifluoromethyl Sulfinyl or trifluoromethylsulfonyl,

Z ¹ , Z ² , Z ³ and Z ⁴ are the same or different and are each independently hydrogen, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, hydroxy Methyl, trifluoromethyl or trifluoroethyl, or

Z ¹ and Z ² , or Z ¹ and Z ³ , or Z ³ and Z ⁴ together with the respective carbon atoms to which they are attached form compounds of general formula (I) which form an alicyclic ring of 5, 6 or 7 carbon atoms; Used to make

The 0-hydroxyethyl-0'-methyl-benzofurandion dioxime required as starting material for carrying out process a) according to the invention is defined in the general manner by the general formula (II). In this general formula (II), A, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are each preferably, or in particular can be prepared according to the invention Regarding the description of compounds of general formula (I), the meanings mentioned as being preferred or particularly preferred for these A, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are indicated. .

The starting materials of formula (II) are not previously known and form part of the material of interest in the present application as novel compounds.

0-hydroxyethyl-0'-methyl-benzofurandione dioxime of Formula (II)

Method d) alkoxyamine derivatives of the general formula (IV) with 0-hydroxyethyl-benzofurandone monooxime of the general formula (VII), optionally in the presence of a diluent and optionally in the presence of an acid acceptor, or React with acid addition complexes thereof

Process e)-reacting 0-alkyl-benzofurandione dioxime of the general formula (VIII) with the ethane derivative of the general formula (IX) below, optionally in the presence of a diluent and optionally in the presence of a base: ,

Process f)-reacting the 0-hydroxyethyl-benzofurandione dioxime of the general formula (X) with the alkylating agent of the general formula (VI) in the presence of a diluent and optionally in the presence of a base, or ,

Method m)-reaction of 0-oxyethyl-0'-methyl-benzofurandione dioxime of the general formula (VIII) with water or an alcohol, optionally in the presence of a diluent and optionally in the presence of an acid or a base Obtained by:

In the above formula,

A, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are each as mentioned above,

Y ¹ represents halogen, alkylsulfonyloxy, arylsulfonyloxy or alkanoyloxy,

G represents hydrogen, or

Y ¹ and G are connected to each other by a single bond,

From here,

Y ¹ represents oxygen,

G is , Or

Y ¹ and G together represent a single bond,

E represents an acyl group or a ketal protecting group.

The 0-hydroxyethyl-benzofurandione monooxime required as starting material for carrying out process d) according to the invention is defined in the general manner by the general formula (VII). In this general formula (VII), R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are preferably, or in particular general formulas that can be prepared according to the invention ( Regarding the description of the compounds of I), the meanings mentioned as preferred or particularly preferred for these R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are indicated.

The starting material of formula (VII) is not previously known and forms part of the material of interest in the present application as a novel compound.

0-hydroxyethyl-benzofurandone monooxime of formula (VII)

Process g)-reacting the benzofurandone monooxime of the general formula (XI) with an ethane derivative of the general formula (IX), optionally in the presence of a diluent and optionally in the presence of a base,

Process n)-obtained by reacting 0-oxyethyl-benzofurandione monooxime of the general formula (XIV) with water or an alcohol, optionally in the presence of a diluent and optionally in the presence of an acid or a base:

In the above formula,

E, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are as mentioned above, respectively.

The benzofurandone monooxime required as starting material for carrying out process g) according to the invention is defined in a general manner by the general formula (XI). In this general formula (XI), R ¹ , R ² , R ³ and R ⁴ are preferably, or in particular, these R ^{1 in} connection with the description of the compounds of general formula (I) which can be prepared according to the invention. , R ² , R ³ and R ⁴ denote the meanings mentioned as being preferred or particularly preferred.

Benzofurandone monooximes of formula (XI) are known and can be prepared by known methods (see Beilstein, E (II) 17, 462; Mameli, G. 56, 768; Chem. Ber. 35 ( 1902), 1640-1646; Proc. Indian Acad. Sci. Sect.A (1976) 83A (6), 238-242).

The O-oxyethyl-benzofurandione monooxime required as starting material for carrying out process n) according to the invention is defined in a general manner by the general formula (XIV). In this general formula (XIV), R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are preferably, or in particular general formulas which can be prepared according to the invention ( Regarding the description of the compounds of I), the meanings mentioned as preferred or particularly preferred for these R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are indicated. E preferably denotes the meanings mentioned as preferred or particularly preferred for this E in connection with the description of the compounds of the general formula (XIII) according to the invention.

Starting materials of general formula (XIV) were previously unknown and form part of the target material of the present application as novel compounds.

0-oxyethyl-benzofurandone monooxime of formula (XIV)

Method o)-obtained by reacting a benzofurandione monooxime of general formula (XI) with an ethanol derivative of general formula (XV) in the presence of a diluent and, optionally, in the presence of an acid acceptor:

In the above formula,

E, Z ¹ , Z ² , Z ³ and Z ⁴ are each as mentioned above,

Y ² represents halogen, alkylsulfonyloxy, arylsulfonyloxy or alkanoyloxy.

The benzofurandione monooxime of general formula (XI) necessary as starting material for carrying out process o) according to the invention is described in the description of process g) according to the invention.

The 0-alkyl-benzofurandion dioxime required as starting material for carrying out process e) according to the invention is defined in the general manner by the general formula (VIII). In this general formula (VIII), R ¹ , R ² , R ³ and R ⁴ are preferably, or in particular, these R ^{1 in} connection with the description of the compounds of general formula (I) which can be prepared according to the invention. , R ² , R ³ and R ⁴ denote the meanings mentioned as being preferred or particularly preferred.

The starting materials of formula (VIII) are not previously known and form part of the target material of the present application as novel compounds.

0-hydroxy-benzofurandone monooxime of formula (VIII)

Method h)-reacting the benzofurandion monooxime of formula (XI) with an alkoxyamine of formula (IV), optionally in the presence of a diluent and optionally in the presence of an acid acceptor,

Process p)-obtained by reacting the benzofuranded dioxime of the general formula (XII) with an alkylating agent of the general formula (VI) in the presence of a diluent and optionally in the presence of a base:

In the above formula,

R ¹ , R ² , R ³ and R ⁴ are each as mentioned above.

The benzofurandione monooxime of general formula (XI) which is required as starting material for carrying out process h) according to the invention is described in the description of process g) according to the invention.

The benzofurandion dioxime required as starting material for carrying out process p) according to the invention is defined in a general manner by the general formula (XII). In this general formula (XII), R ¹ , R ² , R ³ and R ⁴ are preferably, or in particular, these R ^{1 in} connection with the description of the compounds of general formula (I) which can be prepared according to the invention. , R ² , R ³ and R ⁴ denote the meanings mentioned as being preferred or particularly preferred.

Benzofurandion dioximes of formula (VII) are known and can be prepared by known methods (Chem. Ber. 42 (1909), 202).

The 0-hydroxyethyl-benzofurandion dioxime required as starting material for carrying out process f) according to the invention is defined in the general manner by the general formula (X). In this general formula (X), R ¹ , R ² , R ³ and R ⁴ are preferably, or in particular, these R ^{1 in} connection with the description of the compounds of general formula (I) which can be prepared according to the invention. , R ² , R ³ and R ⁴ denote the meanings mentioned as being preferred or particularly preferred.

Starting materials of general formula (X) were previously unknown and form part of the target material of the present application as novel compounds.

0-hydroxyethyl-benzofurandion dioxime of general formula (X)

Method i)-Reacting 0-hydroxyethyl-benzofurandione monooxime of general formula (VII) with hydroxylamine or an acid addition complex thereof in the presence of a diluent and optionally in the presence of an acid acceptor Or

Method q)-obtained by reacting 0-oxyethyl-benzofurandione dioxime of the general formula (XVI) with water or an alcohol, optionally in the presence of a diluent and optionally in the presence of an acid or a base:

In the above formula,

E, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are as mentioned above, respectively.

The 0-hydroxyethyl-benzofurandione monooxime of general formula (VII) necessary as starting material for carrying out process i) according to the invention is described in the description of process d) according to the invention.

The 0-oxyethyl-benzofurandion dioxime required as starting material for carrying out process q) according to the invention is defined in a general manner by the general formula (XVI). In this general formula (XVI), R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are preferably, or in particular general formulas which can be prepared according to the invention ( Regarding the description of the compounds of I), the meanings mentioned as preferred or particularly preferred for these R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are indicated. E preferably denotes the meanings mentioned as preferred or particularly preferred for this E in connection with the description of the compounds of the general formula (XIII) according to the invention.

Starting materials of general formula (XVI) were previously unknown and form part of the target material of the present application as novel compounds.

0-oxyethyl-benzofurandion dioxime of formula (XVI)

Method r)-obtained by reacting 0-oxyethyl-benzofurandone monooxime of general formula (XIV) with hydroxylamine or an acid addition complex thereof in the presence of a diluent and optionally in the presence of an acid acceptor do.

The 0-oxyethyl-benzofurandione monooxime of the general formula (XIV) required as starting material for carrying out the process r) according to the invention is described in the description of the method n) according to the invention.

The 0-oxyethyl-0'-methyl-benzofurandion dioxime required as starting material for carrying out process m) according to the invention is defined in the general manner by the general formula (XIII). In this general formula (XIII), A, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are preferably, or in particular, general which can be prepared according to the invention. Regarding the description of the compounds of the formula (I), the meanings mentioned as preferred or particularly preferred for these A, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are indicated. E is an acyl group, preferably formyl, acetyl or benzoyl, or a ketal protecting group, preferably 2-tetrahydropyranyl, 1-methoxy-1-ethyl, 1-ethoxy-1-ethyl, methoxy Methyl or ethoxymethyl.

Starting materials of general formula (XIII) were previously unknown and form part of the target material of the present application as novel compounds.

0-oxyethyl-0'-methyl-benzofurandion dioxime of formula (XIII)

Method s)-Addition of the alkoxyamine of the general formula (IV) or the acid thereof to the 0-oxyethyl-benzofurandione monooxime of the general formula (XIV), optionally in the presence of a diluent and optionally in the presence of an acid acceptor React with the complex,

Method t)-reacting 0-oxyethyl-benzofurandion dioxim of general formula (XVI) with an alkylating agent of general formula (VI) in the presence of a diluent and optionally in the presence of a base, or

Method u)-obtained by reacting a 0-alkyl-benzofurandion dioxime of general formula (VIII) with an ethanol derivative of general formula (XV) in the presence of a diluent and optionally in the presence of an acid acceptor do.

The 0-oxyethyl-benzofurandione monooxime of the general formula (XIV) required as starting material for carrying out the method s) according to the invention is described in the description of the method n) according to the invention.

The 0-oxyethyl-benzofurandion dioxime of the general formula (XVI) necessary as starting material for carrying out process t) according to the invention is described in the description of process q) according to the invention.

The 0-alkyl-benzofurandione dioximes of the general formula (VIII) which are necessary as starting materials for carrying out the process u) according to the invention are described in the description of the process e) according to the invention.

The hydroxybenzoyldioxazine required as starting material for carrying out process b) according to the invention is defined in a general manner by the general formula (III). In this general formula (III), R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are preferably, or in particular general formulas that can be prepared according to the invention ( Regarding the description of the compounds of I), the meanings mentioned as preferred or particularly preferred for these R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are indicated.

The starting materials of general formula (III) are not previously known and form part of the target material of the present application as novel compounds.

The hydroxybenzoyl dioxazine of general formula (III)

Method k)-obtained by reacting 0-hydroxyethyl-benzofurandione monooxime of general formula (VII), optionally in the presence of a diluent and optionally in the presence of an acid or a base.

The 0-hydroxyethyl-benzofurandione monooxime of general formula (VII) necessary as starting material for carrying out process k) according to the invention is described in the description of process d) according to the invention.

The hydroxyphenylhydroxyminomethyldioxazine required as starting material for carrying out process c) according to the invention is defined in the general manner by the general formula (V). In this general formula (V), R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are preferably, or in particular general formulas that can be prepared according to the invention ( Regarding the description of the compounds of I), the meanings mentioned as preferred or particularly preferred for these R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are indicated.

The starting materials of general formula (V) were previously unknown and form part of the material of interest in the present application as novel compounds.

The hydroxyphenyl hydroxide iminomethyl dioxazine of general formula (V)

Method l)-reacting hydroxybenzoyldioxazine of general formula (III) with a hydroxylamine or acid addition thereof, optionally in the presence of a diluent and optionally in the presence of an acid acceptor, or

Method v)-obtained by rearranging 0-hydroxyethyl-benzofurandione dioxime of general formula (X), optionally in the presence of a diluent and optionally in the presence of an acid or a base.

The hydroxybenzoyldioxazines of general formula (III) which are necessary as starting materials for carrying out the process l) according to the invention are described in the description of the method b) according to the invention.

The 0-hydroxyethyl-benzofurandione monooxime of general formula (X) which is necessary as a starting material for carrying out the process v) according to the invention is described in the description of the process f) according to the invention.

The alkoxyamines necessary as starting materials for carrying out the processes b), d), h) and s) according to the invention are defined in a general manner by the general formula (IV). In this general formula (IV), A preferably refers to the meanings mentioned as preferred or particularly preferred for this A in connection with the description of the compounds of the general formula (I) which may be prepared in particular or in particular according to the invention. Indicates. Preferred acid addition complexes of alkoxyamines of the general formula (IV) are their hydrochlorides, sulfates and hydrogensulfates.

Alkoxyamines of formula (IV) and acid addition complexes thereof are known chemicals in the synthesis.

The alkylating agents required as starting materials for carrying out the processes c), f), p) and t) according to the invention are defined in a general manner by the general formula (VI). In this general formula (VI), A preferably refers to the meanings mentioned as preferred or particularly preferred for this A in connection with the description of the compounds of general formula (I), which may be prepared in particular or in particular according to the invention. Indicates. X is halogen, preferably chlorine, bromine, iodine, alkylsulfonyloxy, preferably methylsulfonyloxy, alkoxysulfonyloxy, preferably methoxysulfonyloxy, or arylsulfonyloxy, preferably 4- Tolylsulfonyloxy.

Alkylating agents of formula (VI) are known chemicals in the synthesis.

The ethane derivatives which are further needed as starting materials for carrying out the processes e) and g) according to the invention are defined in a general manner by the general formula (IX). In this general formula (IX), Z ¹ , Z ² , Z ³ and Z ⁴ are preferably, or in particular, these Z ^{1 in} connection with the description of the compounds of the general formula (I) which can be prepared according to the invention. , Z ² , Z ³ and Z ⁴ represent the meanings mentioned as being preferred or particularly preferred. Y ¹ is halogen, preferably chlorine, bromine or iodine, alkylsulfonyloxy, preferably methylsulfonyloxy, arylsulfonyloxy, preferably 4-tolylsulfonyloxy, or alkanoyloxy, preferably Acetyloxy. G represents hydrogen or is connected to Y ¹ by a single bond, in which case Y ¹ represents oxygen, G represents carbonyl, or G and Y ¹ together represent a single bond.

Ethane derivatives of general formula (IX) are chemicals known in the synthesis.

The hydroxylamines or acid addition complexes thereof, which are additionally required as starting materials for carrying out the processes i), l) and r) according to the invention, preferably their hydrochlorides, sulfates and hydrogensulfates are chemicals known in the synthesis. to be.

Derivatives of ethane which are additionally necessary as starting materials for carrying out the processes o) and u) according to the invention are defined in a general manner by the general formula (XV). In this general formula (XV), Z ¹ , Z ² , Z ³ and Z ⁴ are preferably, or in particular, these Z ¹ with reference to the description of the compounds of general formula (I) which can be prepared according to the invention. , Z ² , Z ³ and Z ⁴ represent the meanings mentioned as being preferred or particularly preferred. E preferably denotes the meanings mentioned as preferred or particularly preferred for this E in connection with the description of the compounds of the general formula (XIII) according to the invention. Y ² is halogen, preferably chlorine, bromine or iodine, alkylsulfonyloxy, preferably methylsulfonyloxy, arylsulfonyloxy, preferably 4-tolylsulfonyloxy, or alkanoyloxy, preferably Acetyloxy.

Ethanol derivatives of general formula (XV) are known and can be prepared by known methods (see, eg, Newkome, George R .; Marston, Charles R., J. Org. Chem., 50, 22, 1985, 4238). 4245; Henry, Chem. Ber., 7 1874, 70).

When the processes a), k) and v) according to the invention are carried out in the presence of an acid, suitable diluents are all inert organic solvents. These are preferably aliphatic, cycloaliphatic or aromatic hydrocarbons such as petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; Halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; Ethers such as diethyl ether, diisopropyl ether, dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; Esters such as methyl acetate or ethyl acetate, or sulfones such as sulfolane and mixtures of these mentioned diluents. Particularly preferred diluents are ethers such as diethyl ether, 1,2-diethoxyethane or anisole; And aromatic hydrocarbons such as benzene, toluene or xylene.

When the processes a), k) and v) according to the invention are carried out in the presence of a base, suitable diluents are water and all organic solvents. These are preferably aliphatic, cycloaliphatic or aromatic hydrocarbons such as petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; Halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; Ethers such as diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or an brush; Nitriles such as acetonitrile, propionitrile, n- or i-butyronitrile, or benzonitrile; Amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphate triamide; Esters such as methyl acetate or ethyl acetate; Sulfoxides such as dimethyl sulfoxide; Sulfones such as sulfolane; Alcohols such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or t-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene Glycol monomethyl ether, diethylene glycol monoethyl ether, and mixtures thereof with water.

Preferred diluents are water, alcohols such as methanol, ethanol, n- or i-propane, n-, i-, sec- or t-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, Methoxyethanol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, and mixtures thereof with water. Particularly preferred diluents are water or alcohols such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or t-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, Methoxyethanol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, and mixtures thereof with water.

Suitable diluents for carrying out the processes b), d), h), i), l), r) and s) according to the invention are all inert organic solvents. These preferably include aromatic hydrocarbons such as benzene, toluene or xylene; Halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; Ethers such as diethyl ether, diisopropyl ether, methyl t-butylether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or an brush; Amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphate triamide; Organic acids such as acetic acid; Esters such as methyl acetate or ethyl acetate; Sulfoxides such as dimethyl sulfoxide; Sulfones such as sulfolane; Alcohols such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or t-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene Glycol monomethyl ether, diethylene glycol monoethyl ether, and mixtures thereof with water or pure water. Particularly preferred diluents are amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphate triamide; Alcohols such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or t-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene Glycol monomethyl ether, diethylene glycol monoethyl ether, acids such as acetic acid; And mixtures thereof with water or pure water. It is also mentioned that two phase-mixtures such as, for example, water / toluene are particularly preferred.

Suitable diluents for carrying out the processes c), e), f), g), o), p), t) and u) according to the invention are all inert organic solvents. These are preferably aliphatic, cycloaliphatic or aromatic hydrocarbons such as petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; Halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; Ethers such as diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or an brush; Ketones such as acetone, butanone, methylisobutyl ketone or cyclohexanone; Nitriles such as acetonitrile, propionitrile, n- or i-butyronitrile, or benzonitrile; Amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphate triamide; Esters such as methyl acetate or ethyl acetate; Sulfoxides such as dimethyl sulfoxide; Sulfones such as sulfolane; Alcohols such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or t-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene Glycol monomethyl ether, diethylene glycol monoethyl ether, and mixtures thereof with water or pure water. Particularly preferred diluents are ketones such as acetone, butanone, methylisobutyl ketone or cyclohexanone; Nitriles such as acetonitrile, propionitrile, n- or i-butyronitrile, or benzonitrile; Amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphate triamide; Alcohols such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or t-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene Glycol monomethyl ether or diethylene glycol monoethyl ether. It is also mentioned that two phase-mixtures such as, for example, water / toluene are particularly preferred. Suitable diluents for carrying out the processes m), n) and q) according to the invention are water and all organic solvents. These are preferably ethers, for example diethyl ether, diisopropyl ether, methyl t-buryl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2 Diethoxyethane or anisole; Ketones such as acetone, butanone, methylisobutyl ketone or cyclohexanone; Nitriles such as acetonitrile, propionitrile, n- or i-butyronitrile, or benzonitrile; Amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphate triamide; Esters such as methyl acetate or ethyl acetate; Sulfoxides such as dimethyl sulfoxide; Sulfones such as sulfolane; Alcohols such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or t-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene Glycol monomethyl ether, diethylene glycol monoethyl ether, and mixtures thereof with water or pure water.

Processes a), k) and v) according to the invention are optionally carried out in the presence of an acid or a base. Suitable acids are all inorganic or organic protic acids and Lewis acids, and also all polymeric acids. These include, for example, hydrogen chloride, hydrogen bromide, sulfuric acid, formic acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, toluenesulfonic acid, boron trifluoride (also as etherate), boron tribromide , Aluminum trichloride, zinc chloride, iron (III) chloride, antimony pentachloride, acid ion exchangers, acid clays and acid silica gels. Hydrogen chloride or hydrogen bromide are preferred. Suitable bases include all customary inorganic or organic bases. These are preferably hydrides, hydroxides, amides, alkoxides, acetates, carbonates or bicarbonates of alkaline earth metals or alkali metals, for example sodium hydride, sodium amide, sodium methoxide, sodium ethoxide, potassium t-butoxide Sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate or ammonium carbonate, and also trimethylamine, triethylamine, tributylamine, N, N-dimethylaniline, N, N-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N, N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene Tertiary amines such as (DBN) or diazabicycloundecene (DBU). Particularly preferred bases are sodium methoxide, sodium ethoxide, potassium t-butoxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide and trimethylamine, triethylamine, tributylamine, N, N-dimethylaniline, N, N- Dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N, N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU Tertiary amines, such as

If desired, the processes b), d), h), i), l), r) and s) according to the invention are carried out in the presence of a suitable acid acceptor. These include all customary inorganic or organic bases. These are preferably hydroxides, alkoxides, acetates, carbonates or bicarbonates of alkaline earth metals or alkali metals, for example sodium methoxide, sodium ethoxide, potassium t-butoxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium Acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate or ammonium carbonate, and also trimethylamine, triethylamine, tributylamine, N, N-dimethylaniline, N, N-dimethyl Benzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N, N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU) Tertiary amines such as;

If desired, the methods c), e), f), g), o), p), t) and u) according to the invention are carried out in the presence of a suitable acid acceptor. These include all common inorganic or organic bases. These are preferably hydrides, hydroxides, amides, alkoxides, carbonates or bicarbonates of alkaline earth metals or alkali metals, for example sodium hydride, sodium amide, sodium methoxide, sodium ethoxide, potassium t-butoxide, hydroxide Sodium, potassium hydroxide, sodium carbonate, potassium carbonate, potassium bicarbonate or sodium bicarbonate, and also trimethylamine, triethylamine, tributylamine, N, N-dimethylaniline, N, N-dimethylbenzylamine, pyridine, N-methylpi Tertiary amines such as ferridine, N-methylmorpholine, N, N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU).

In the case of carrying out the processes a), k) and v) according to the invention, the reaction temperature can vary within a relatively wide range. The reaction is generally carried out at a temperature of -20 ° C to 100 ° C, preferably -10 ° C to 80 ° C.

In the case of carrying out the processes b), d), h), i), l), r) and s) according to the invention, the reaction temperature can vary within a relatively wide range. The reaction is generally carried out at a temperature of 0 ° C to 200 ° C, preferably 20 ° C to 150 ° C.

In the case of carrying out the processes c), e), f), g), o), p), t) and u) according to the invention, the reaction temperature can vary within a relatively wide range. The reaction is generally carried out at a temperature of -20 ° C to 100 ° C, preferably 0 ° C to 80 ° C.

Processes a) to v) according to the invention are generally carried out under atmospheric pressure. However, it is also possible to carry out the process at elevated or reduced pressure, generally from 0.1 bar to 10 bar.

In a preferred process (A), the benzofurandone monooxime of general formula (XI) is first reacted with an ethane derivative of general formula (IX) as described in method g) to form a 0-hydride of general formula (VII). Convert to oxyethyl-benzofurandione monooxime. Thereafter, without further purification, 0-hydroxyethyl-benzofurandone monooxime of general formula (VII) is optionally subjected to general operation in the presence of a buffer system, for example sodium acetate / acetic acid, as described in process d). The alkoxyamine of formula (IV) or its acid addition reacts with the complex to give 0-hydroxyethyl-0'-methyl-benzofurandione dioxime of formula (II), which is reacted with acid or base by method a). Treatment affords the desired 3- (1-hydroxyphenyl-1-alcoximinomethyl) dioxazine of general formula (I) without further purification.

In another preferred method (B), the benzofurandone monooxime of general formula (XI) is first reacted with an ethane derivative of general formula (IX), as described in method g), to give 0- Convert to hydroxyethyl-benzofurandione monooxime. This was treated with an acid or a base to obtain hydroxybenzoyldioxazine of general formula (III), and then an alkoxyamine of general formula (IV) or an acid addition thereof reacted with a complex to give 3- ( Obtain 1-hydroxyphenyl-1-alcoximinomethyl) dioxazine.

In a third preferred method (C), the benzofurandone monooxime of general formula (XI) is first reacted with an alkoxyamine of general formula (IV) or an acid addition thereof to the 0-alkyl-benzo of general formula (VII) Convert to Furandion Dioxime. Thereafter, it is reacted with an ethane derivative of general formula (IX) to obtain 0-hydroxyethyl-0'-methyl-benzofurandion dioxime of general formula (II), and treated with an acid or a base to give a desired general formula 3- (1-hydroxyphenyl-1-alcoximinomethyl) dioxazine of (I) is obtained.

Very surprisingly, the process according to the invention provides a high yield of products of high purity, especially when performed in combination. Chem. Ber. 1902, 1640 describe methods for obtaining salicylic acid derivatives or hydroxyphenylglyoxylic acid derivatives, for example, by digesting the benzofurandone monooxime of general formula (XI) with acid and base. Thus, it was unexpected that 3- (1-hydroxyphenyl-1-alkoxyminomethyl) dioxazine could be prepared without serious side reactions in a reaction involving only three steps.

The method according to the invention has many advantages. For example, the process according to the invention provides large amounts of 3- (1-hydroxyphenyl-1-alkoxyminomethyl) dioxazine in high yield and high purity. The process according to the invention also has the advantage of obtaining in a simple manner large amounts of the benzofurandione monooxime required as starting material (Beilstein, E (II) 17, 462; Mameli, G. 56, 768).

Methods and Preparation Examples:

Example 1

Method (A)

Step 1

Compound (VII-1)

Method g)

11.8 g (0.0725 mol) of benzofuran-2,3-dione-2-oxime (XI-1) (Stoermer, Kahlert, B. 35, 1644) was dissolved in 75 ml of dimethylformamide. While cooling, 3 g (0.075 mol) of 60% sodium hydrogen hydride (mineral oil suspension) was added little at a time, and stirring was continued until gas evolution stopped at a temperature of 25 ° C. for about 1 hour. The mixture was then cooled to 0 ° C., at which point 9.3 g (0.0744 moles) of 2-bromoethanol were added dropwise, followed by stirring at 25 ° C. for 24 hours. The reaction mixture was poured into water, the resulting mixture was extracted with ethyl acetate, the organic phase was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was recrystallized from a mixture of 150 ml of toluene and 100 ml of cyclohexane to give 11.5 g of benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] (VII-1) (64 of theory). %) (Content according to HPLC analysis: 83.5%). The sample recrystallized from toluene had a melting point of 110-111 ° C.

Step 2

Compound (II-1)

Method d)

11.5 g of crude benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] (VII-1) and 5.15 g (0.0616 mol) of 0-methylhydroxylamine hydrochloride were added to dimethylformamide 60 Dissolve in mL and stir at 80 ° C. for 30 min. The reaction mixture was poured into water and the resulting mixture was extracted with ethyl acetate. The organic phase is dried over sodium sulfate, and then the solvent is distilled off under reduced pressure. Benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] 3- (0-methyloxime) (II-1) 40.5% and (5,6-dihydro-1,4, 14.1 g of an oil containing 14% of 2-dioxazin-3-yl)-(2-hydroxyphenyl) methanone 0-methyloxime (1) was obtained.

Step 3

Compound (1)

Method a)

14.1 g of the oil containing compound (II-1) and (1) obtained from step 2 of method A) was dissolved in 200 ml of diethyl ether which was previously saturated with hydrogen chloride gas at 0 ° C. The mixture was stirred for 30 minutes without further cooling and then poured into sodium bicarbonate solution cooled to 0 ° C. The organic phase was separated and the aqueous phase was extracted repeatedly with diethyl ether. The combined organic phases were dried over sodium sulfate and then concentrated at reduced pressure. The residue was stirred with t-butylmethyl ether and the product crystallized. Crystallinity (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxyphenyl) methanone 0-methyloxime (1) 5.4 g (benzofuran-2,3- 64% of theory based on Dion 2-oxime) was obtained (content according to HPLC analysis: 88.8%).

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 4.10 (3H); 4.19 / 4.20 / 4.21 / 4.22 (2H); 4.47 / 4.48 / 4.49 / 4.50 (2H); 6.26 (1 H); 6.95-7.0 (2H); 7.21 / 7.23 (1 H); 7.31-7.36 (2H) ppm.

Example 2

Method (B)

Step 1

Compound (VII-1)

This step has already been described as method g) in step 1 of method (A).

Step 2

Compound (III-1)

Method k)

At 20 ° C., anhydrous hydrogen chloride gas was passed through a mixture of 19 g (0.0917 mol) of benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] (VII-1) and 439 ml of diethyl ether. Wherein the mixture is warmed to 35 ° C. After 7 hours, the mixture was decanted from the material at no cost and the solvent was distilled off under reduced pressure. The residue was dissolved in ethyl acetate and washed first with 50 ml of water and then with 20 ml of saturated aqueous sodium bicarbonate solution. The organic phase was separated and dried over sodium sulfate and the solvent was distilled off under reduced pressure. 17 g of crude product were obtained. This product was chromatographed on silica gel with dichloromethane. 10 g of (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxyphenyl) methanone (III-1) (theoretical based on compound (VII-1) 51.9%) was obtained with a purity of 98.7% (HPLC).

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 4.28 / 4.29 / 4.30 / 4.31 (2H); 4.55 / 4.56 / 4.57 / 4.58 (2H); 6.90 / 6.92 / 6.93 / 6.95 / 6.99 / 7.02 (2H); 7.50 / 7.51 / 7.53 / 7.54 / 7.55 / 7.56 (1H); 8.27 / 8.29 / 8.30 (1 H); 11.52 (1 H) ppm.

Step 3

 Compound (1)

Method b)

1.87 g (0.022 mol) of 0-methylhydroxylamine hydrochloride in 22 ml of dimethylformamide and (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxyphenyl) 4.4 g (0.021 mol) of methanone (III-1) were heated at 100 ° C. for 2 hours. The reaction mixture was poured into water, the resulting mixture was extracted with ethyl acetate, and then the organic phase was dried over sodium sulfate and the solvent was distilled off under reduced pressure. Crude (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxyphenyl) methanone found by HPLC to contain 17.5% E isomer and 38% Z isomer 5.7 g of 0-methyloxime (1) was obtained. This crude product was chromatographed on silica gel using a mixture of petroleum ether / t-butylmethyl ether (1: 1) to give Z- (5,6-dihydro-1,4,2- with a purity of 91.5% (HPLC). 1.55 g (28.27% of theory) of dioxazin-3-yl)-(2-hydroxyphenyl) methanone 0-methyloxime (1) were obtained.

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 4.08 (3H); 4.30 / 4.32 / 4.33 (2H); 4.53 / 4.54 / 4.55 (2H); 6.89 / 6.92 / 6.94 / 6.98 / 7.01 (2H); 7.28 / 7.31 / 7.33 / 7.34 / 7,35 / 7.37 (2H); 10.11 (1H) ppm.

In addition, E- (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxyphenyl) methanone 0-methyloxime (1) 0.9 having a purity of 93.7% (HPLC) g (16.8% of theory) was obtained.

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 4.09 (3H); 4.18 / 4.19 / 4.20 / 4.21 (2H); 4.47 / 4.48 / 4.50 (2H); 6.28 (1H; OH); 6.94 / 6.95 / 6.97 (2H); 7.20-7.36 (2H) ppm.

Example 3

Method (C)

Step 1

Compound (VIII-1)

Method h)

3.36 g (0.04 mol) of 0-methylhydroxylamine hydrochloride and 3.26 g (0.02 mol) of benzofuran-2,3-dione 2-oxime (XI-1) in 20 ml of dimethylformamide were added at 20 DEG C for 20 minutes. After stirring, the mixture was stirred at 80 ° C. for 45 minutes. The reaction mixture was poured into a mixture of aqueous sodium bicarbonate solution and ethyl acetate. The organic phase was separated and dried over sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was stirred with diethyl ether. 1.4 g of crystalline benzofuran-2,3-dione 3- (0-methyloxime) 2-oxime (VIII-1) was found to contain 70.7% A stereoisomer and 8.5% B stereoisomer by HPLC analysis. Obtained.

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 4.09 (3H, Isomer B); 4.11 (3H, isomer A); 7.21-7.35 (2H); 7.51-7.65 (1H, isomers A and 2H, isomers B); 8.02 / 8.04 / 8.05 (1H isomer A); 11.35 (1H, isomer A); 11.74 (1H, isomer B) ppm.

Step 2

Compound (II-1)

Method e)

4.49 g (0.0234 mol) of benzofuran-2,3-dione 3- (0-methyloxime) 2-oxime (VIII-1) was dissolved in 25 ml of dimethylformamide. 1 g (0.025 mol) of 60% strength sodium hydride was added to the solution, followed by stirring at room temperature for 1 hour. 3.1 g (0.0248 mol) of 2-bromoethanol was added and the mixture was stirred at 25 ° C. for 12 h. 0.5 g sodium methoxide and 1.22 g 2-bromoethanol were added, and then the mixture was stirred at room temperature for 2 hours. Further 0.5 g sodium methoxide and 1.22 g 2-bromoethanol were added, and then the mixture was further stirred at room temperature for 2 hours. The reaction mixture was poured into water, the resulting mixture was extracted with ethyl acetate and the organic phase was washed three times with 20 mL of 2N aqueous sodium hydroxide solution. The solvent was distilled off under reduced pressure and the residue was chromatographed on silica gel using diethyl ether / petroleum ether (1: 1). The eluent was distilled under high pressure to yield benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] 3- (0 containing 84.29% of A stereoisomer and 12.58% of B stereoisomer according to HPLC. 2.26 g (39.6% of theory) of methyl oxime) (II-1) were obtained.

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 3.95-4.03 (2H); 4.20 (3H, Isomer B); 4.21 (3H, isomer A); 4.37-4.40 (2H); 7.14-7.21 (2H); 7.40-7.49 (1 H); 7.63 / 7.64 / 7.66 (1H, Isomer B); 8.04 / 8.06 / 8.07 (1H, Isomer A) ppm.

Step 3

Compound (1)

Method a)

2 g of benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] 3- (0-methyloxime) (II-1) prepared by method e) (content according to HPLC analysis) 96.88%, 0.0082 mole) was dissolved in 50 ml of diethyl ether which was previously saturated with hydrogen chloride gas at 0 ° C. After the mixture was stirred for 30 minutes without further cooling, the solvent was distilled off under reduced pressure and the residue was once again dissolved in diethyl ether. A portion of the product was precipitated and filtered. The mother liquor was concentrated under reduced pressure and the residue was dissolved in 25 ml of diethyl ether saturated with hydrogen chloride gas at 0 ° C. After stirring the solution for 30 minutes without further cooling, the solvent was distilled off under reduced pressure and the residue was once again dissolved in diethyl ether. Another fraction of the product was precipitated and filtered as above. In total, 1.37 g (69% of theory) of (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxyphenyl) methanone 0-methyloxime (1) Obtained (content according to HPLC analysis: 97.59%).

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 4.09 (3H); 4.18 / 4.l9 / 4.20 / 4.21 (2H); 4.47 / 4.48 / 4.50 (2H); 6.94 / 6/95/6/97 (2H); 7.20-7.36 (2H) ppm.

Example 4

Method (D)

Step 1

Compound (XIV-1)

Method o)

1.63 g (0.01 mol) of benzofuran-2,3-dione 2-oxime (XI-1) in 5 ml of N-methyl-2-pyrrolidinone was stirred with 1.14 g (0.0108 mol) of sodium carbonate at 20 ° C. for 30 minutes. It was. 1.7 g (0.0102 mol) of 2-bromoethyl acetate was added and stirring continued at 70 ° C. for 2 hours. The mixture was poured into 30 ml of water and the product was filtered off. The product was dried to give 1.57 g (63% of theory) of crystalline 2- (3-oxo-3H-benzofuran-2-ylideneaminooxy) -ethylacetate (XIV-1).

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 2.11 (3H); 4.43 / 4.44 / 4.45 / 4.46 / 4.47 (2H); 4.52 / 4.54 / 4.55 / 4.57 (2H); 7.28 / 7.30 / 7.33 (2H); 7.72 / 7.74 / 7.76 / 7.78 / 7.80 (2H) ppm.

Step 2

Compound (XIII-1)

Method s)

10 g (0.04 mol) of 2- (3-oxo-3H-benzofuran-2-ylideneaminooxy) ethyl acetate (XIV-1) and 4.18 g (0.05 mol) of 0-methylhydroxylamine hydrochloride were added to N- It was dissolved in 40 ml of methyl-2-pyrrolidinone and stirred at 80 ° C. for 1 hour. The reaction mixture was poured into water and the resulting mixture was extracted with ethyl acetate. The organic phase was dried over sodium sulphate and the solvent was distilled off under reduced pressure. 10.6 g of crude product were obtained and chromatographed on silica gel using t-butylmethyl ether / petroleum ether (1: 1). 6.9 g (5-9.1% of theory) of 2- (3-methoxyimino-3H-benzofuran-2-ylideneaminooxy) ethylacetate (XIII-1) with 82.15% of A isomer and 13.38% of B isomer (HPLC) Obtained.

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 2.10 (3H); 4.21 (3H, isomer B); 4.22 (3H, isomer A); 4.41-4.48 (4H); 7.15 / 7.17 / 7.20 (2H); 7.44-7.50 (1 H); 7.63-7.66 (1H, Isomer B); 8.05-8.09 (IH, Isomer A) ppm.

Step 3

Compound (II-1)

Method m)

2 g (0.00718 mol) of 2- (3-methoxyimino-3H-benzofuran-2-ylideneaminooxy) ethylacetate (XIII-1) in 8 ml of dimethylformamide was added to 7.2 ml of a 2N aqueous sodium hydroxide solution at 20 ° C. (0.0144 mol) and stirred at 20 ° C for 16 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase is dried over sodium sulfate and the solvent is distilled off under reduced pressure. Benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] 3- (0-methyloxime) (identified by HPLC as having 56.8% A stereoisomer and 10.7% B stereoisomer) II-1) 1.7 g (67.6% of theory) were obtained.

GC / MS analytical data (pre-analysis material was silylated with N-methyl-N-trimethylsilyl trifluoroacetamide).

Stereoisomer A:

Retention index = 2062

M ⁺ = 309, 308, 293, 249, 233, 192, 176, 145, 132, 89, 73, 45, 26.

Stereoisomer B:

Holding Index = 2000

M ⁺ = 309, 308, 293, 249, 218, 192, 176, 145, 132, 90, 73, 45.

Step 4

Compound (1)

This step has already been described as method a) in step 3 of method (A) and step 3 of method (C).

Additional Examples of Individual Methods

Example 5

Compound (1)

Method c)

1.2 g (0.0054 mol) of Z- (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxyphenyl) methanone oxime (V-1) in 5 ml of dimethylformamide ) Was first stirred at 20 ° C. with 0.66 g (0.0062 mol) of sodium carbonate for 30 minutes. Then 0.83 g (0.00658 mol) of dimethylsulfate was added and stirring was continued at 20 ° C. for 16 hours. The reaction mixture was adjusted to slightly acidic with 2N aqueous hydrochloric acid and extracted with ethyl acetate. The organic phase is dried over sodium sulfate and the solvent is distilled off under reduced pressure. 10.8 g of Z- (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxyphenyl) methanone 0-methyloxime (1) with 80.3% purity (HPLC) 50.35% of theory).

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 4.08 (3H); 4.30 / 4.32 / 4.33 (2H); 4.53 / 4.54 / 4.55 (2H); 6.89 / 6.92 / 6.94 / 6.98 / 7.01 (2H); 7.28 / 7.31 / 7.33 / 7.34 / 7.35 / 7.37 (2H); 10.11 (1H) ppm.

Example 6

Compound (II-1)

Method e)

3.19 g (0.0166 mol) of benzofuran-2,3-dione 3- (0-methyloxime) 2-oxime (VIII-1) (a mixture of two stereoisomers A: B = 13:86) was suspended in 20 ml of methanol It was added dropwise to 8.3 g of 2 mol sodium methoxide solution at 20 ° C. Once the mixture became homogeneous the methanol was distilled off under reduced pressure and the crystalline residue was dried in a desiccator for 12 hours. 3.55 g of sodium salt of benzofuran-2,3-dione 3- (0-methyloxime) 2-oxime (VIII-1) were obtained. This salt was suspended in 16 ml of N-methyl-2-pyrrolidinone at 20 ° C. and then 2.1 g (0.0168 mol) of 2-bromoethanol was added. The mixture was stirred at 20 ° C for 48 h. The reaction mixture was poured into water, the resulting mixture was extracted with ethyl acetate and the organic phase was washed three times with 20 mL of 2N aqueous sodium hydroxide solution. The solvent was distilled off under reduced pressure and the residue was chromatographed on silica gel using diethyl ether / petroleum ether (1: 1). The eluent was distilled off under reduced pressure to yield benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime containing 88.6% B stereoisomer, 7.7% A stereoisomer and 3.2% C isomer (HPLC). 2.91 g (73.8% of theory) of 3- (0-methyloxime) (II-1) were obtained.

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 3.43 (1H, broad); 4.0-4.03 (2H); 4.20 (3 H); 4.38-4.41 (2H); 7.14-7.21 (2H); 7.40 / 7.42 / 7.43 / 7.445 (1H); 7.63 / 7.67 / 7.66 (1H) ppm.

Example 7

Compound (II-1)

Method f)

60% strength of 0.44 g (0.002 mol) of benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] 3-oxime in 20 ml of dimethylformamide Stir for 20 minutes with 0.08 g (0.002 mol) of sodium hydride. After gas evolution had ceased, 0.28 g (0.002 mol) of methyl iodide was added and the mixture was stirred at 20 ° C. for 16 h. The reaction mixture was poured into water, the resulting mixture was extracted with ethyl acetate, the organic phase was dried over sodium sulfate, and the solvent was distilled off under reduced pressure to give 0.5 g (35% of theory) of the crude product. According to HPLC analysis, the crude product comprises 10.1% of B stereoisomer of benzofuran-2,3-dione2- [0- (2-hydroxyethyl) oxime] 3- (0-methyloxime) (II-1) and 23% of A stereoisomers.

GC / MS analytical data (pre-analysis material was silylated with N-methyl-N-trimethylsilyl trifluoroacetamide).

Retention Index = 2053 (Isomer A)

M ⁺ = 309, 308, 293, 249, 233, 192, 176, 145, 132, 89, 73, 45, 26.

Retention Index = 1997 (Isomer B)

M ⁺ = 309, 308, 293, 249, 218, 192, 176, 145, 132, 90, 73, 45.

The crude product also contains 20.5% (HPLC) of N- [2- (2-hydroxyethoxyimino) benzofuran-3-ylidene] -N-methylamine N-oxide.

CC / MS analysis data (silylated samples).

Holding Index = 2234

M ⁺ = 310, 308, 233, 192, 175, 159, 132, 102, 73, 45, 26.

Example 8

Compound (VII-1)

Method i)

At 80 ° C., 10.1 g (0.05 mol) of benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] (VII-1) in 50 ml of N-methyl-2-pyrrolidinone was added. Stir for 2 h with 3.5 g of hydroxylamine hydrochloride. The reaction mixture is poured into water and the resulting mixture is extracted with ethyl acetate, then the organic phase is dried over sodium sulfate and the solvent is distilled off under reduced pressure. The residue was then chromatographed on silica gel using t-butylmethyl ether / petroleum ether (1: 1). The eluent was distilled off under reduced pressure to yield 4.2 g of benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] 3-oxime containing 15.8% of B isomer and 62.4% of A isomer (HPLC). 29.6% of theory).

^' H NMR Spectrum (DMSOd ₆ / TMS): δ = 3.64-3.71 (2H); 4.10-4. 26 (2H); 4.78-4.87 (1 H); 7.2-7.3 (1 H); 7.3-7.4 (1 H); 7.5-7.7 (1 H); 8.11-8.14 (1 H); 12.82 (1H, isomer A); 12.91 (1H, Isomer B) ppm.

Example 9

Compound (V-1)

Method ℓ)

4.14 g (0.02) of (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxyphenyl) methanone (III-1) in 20 ml of dimethylformamide at 80 ° C Mole) was stirred with 2.1 g (0.03 mole) of hydroxylamine hydrochloride for 2 hours. The reaction mixture was poured into water, the resulting mixture was extracted with ethyl acetate, and then the organic phase was dried over sodium sulfate and concentrated under reduced pressure. 4.7 g of crude product containing 15% E isomer and 57.5% Z isomer (HPLC) were obtained. The crude product was chromatographed on silica gel using a mixture of diethyl ether and petroleum ether (1: 1). 2.7 g (60.8% of theory) of (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxyphenyl) methanone oxime (V-1) were obtained (HPLC) Content according to analysis: 93.4%).

^' H NMR Spectrum (DMSOd ₆ / TMS): δ = 4.19 / 4.20 / 4.21 (2H); 4.45 / 4.46 / 4.47 (2H); 6.89-6.92 (2H); 7.22-7.32 (1 H); 7.33-7.40 (1 H); 10.30 (1 H); 12.16 (1 H) ppm.

Example 10

Compound (VII-1)

Method n)

2.07 g (0.01 mol) of benzofuran-2,3-dione 2- {0- [2- (tetrahydrofuran-2-yloxy) ethyl] oxime} (XIV-2) is dissolved in 12 ml of methanol and room temperature Was stirred with 100 mg of acidic ion exchanger resin for 16 h. 40 ml of methanol was added to the reaction mixture, which was then warmed until the crystals dissolved. The acidic ion exchanger resin was filtered to concentrate the filtrate and the residue was recrystallized from 10 ml of toluene. 1.69 g (81.5% of theory) of crystalline benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] (VII-1) having a melting point of 110 to 111 ° C were obtained.

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 2.33 (1H, broad); 4.00-4.02 (2H); 4.47-4.50 (2H); 7.27-7.32 (2H); 7.70-7.78 (2H) ppm.

Example 11

Compound (XIV-2)

Method o)

5 g (0.03 mol) of benzofuran-2,3-dione 2-oxime (XI-1) was dissolved in 30 ml of methanol, and 15 ml of a 2-mol solution of sodium methoxide in methanol was added dropwise at 20 占 폚. The solvent was distilled off under reduced pressure. The crystalline residue was dissolved in 30 mL of N-methyl-2-pyrrolidinone and treated with 6.27 g (0.03 mol) of 2- (2-bromoethoxy) tetrahydropyran at 20 ° C. The reaction mixture was stirred at 20 ° C. for 16 hours and poured into 100 mL of water, and the resulting mixture was extracted twice with 100 mL of dichloromethane each. The solvent was distilled off under reduced pressure and the residue was chromatographed on silica gel using a mixture of diethyl ether / dichloromethane / petroleum ether (1: 1: 2). 5.55 g (62.1% of theory) of benzofuran-2,3-dione 2- {0- [2- (tetrahydropyran-2-yloxy) ethyl] oxime} (XIV-2) were obtained.

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 1.50-1.86 (6H); 3.49-3.53 (1 H); 3.81-3.88 (2H); 4.02-4.09 (IH); 4.52-4.55 (2H); 4.66-4.69 (1 H); 7.26-7.31 (2H); 7.69-7.80 (2H) ppm.

Example 12

Compound (VIII-1)

Method p)

A solution of 11 g (0.0617 mol) of benzofuran-2,3-dione dioxime in 50 ml of dimethylformamide was added dropwise to a suspension of 2.4 g (0.06 mol) of 60% strength sodium hydride in 25 ml of dimethylformamide and Stirred for 1 h. 7.55 g (0.06 mol) of dimethylsulfate were added dropwise and stirring was continued at 20 ° C. for 16 hours. The reaction mixture was poured into water, the resulting mixture was extracted with ethyl acetate, and then the organic phase was dried over sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on silica gel using hexanes / acetone (7: 3). The residue was stirred with diethyl ether to give benzofuran-2,3-dione-3- (0-methyloxime) 2-oxime (a mixture of stereoisomers containing 90.6% A and 9% B isomers (HPLC). VIII-1) 0.7 g were obtained.

Example 13

Compound (X-1)

Method q)

45% strength of 5,28 g (0.02 mol) of 2- (3-hydroxyimino-3H-benzofuran-2-ylideneaminooxy) ethyl acetate (XVI-1) in 20 ml of dimethylformamide at 20 ° C It was stirred with 4.24 g (0.048 mol) of an aqueous sodium hydroxide solution for 3 hours. The mixture was acidified with 2N hydrochloric acid and extracted with ethyl acetate, then the organic phase was dried over sodium sulfate and the solvent was distilled off under reduced pressure. According to HPLC analysis the crude product was subjected to 23.4% A stereoisomer and 4.1% B stereoisomer of benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] 3-oxime (X-1). It contains. The crude product was stirred with diethyl ether to form crystalline benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime 3 containing 84.7% A stereoisomer and 6% B stereoisomer (HPLC). 1.4 g (28.5% of theory) of oxime (X-1) were obtained.

^' H NMR Spectrum (DMSOd ₆ / TMS): δ = 3.64-3.71 (2H); 4.10-4. 26 (2H); 4.78-4.87 (1 H); 7.2-7.3 (1 H); 7.3-7.4 (1 H); 7.5-7.7 (1 H); 8.11-8.14 (1 H); 12.82 (1H, stereoisomer A); 12.91 (1H, stereoisomer B) ppm.

Example 14

Method (XVI-1)

Method r)

5 g (0.02 mol) of 2- (3-oxo-3H-benzofuran-2-ylideneaminooxy) ethyl acetate (XIV-1) and 1.74 g (0.025 mol) of hydroxylamine hydrochloride 20 ml of dimethylformamide Dissolved in and stirred at 100 ° C. for 2 h. The reaction mixture was poured into water and the resulting mixture was extracted with ethyl acetate. The organic phase is dried over sodium sulfate and the solvent is distilled off under reduced pressure. The residue was chromatographed on silica gel using t-butylmethyl ether / petroleum ether (1: 1). 2.7 g of 2- (3-hydroxyimino-3H-benzofuran-2-ylideneaminooxy) ethylacetate (XVI-1) containing 64.23% A stereoisomer and 14.9% B stereoisomer (HPLC) 38.5%).

^' H NMR Spectrum (CDCl ₃ -d ₆ / TMS): δ = 2.11 (3H, stereoisomer A); 2.12 (3H, stereoisomer B); 4.43-4, 46 (4H); 7.19-7. 23 (2H); 7.46-7.52 (1 H); 7.65-7.8 (1H, stereoisomer B); 8.16 / 8.17 / 8.19 (1H, stereoisomer A); 8.9 (1H) ppm.

Example 15

Compound (XIII-1)

Method s)

10 g (0.04 mol) of 2- (3-oxo-3H-benzofuran-2-ylideneinooxy) ethyl acetate (XIV-1) and 4.18 g (0.05 mol) of 0-methylhydroxylamine hydrochloride were added to N Dissolve in 40 ml of methyl-2-pyrrolidinone and stir at 80 ° C. for 1 hour. The reaction mixture was poured into water and the resulting mixture was extracted with ethyl acetate. The organic phase was dried over sodium sulfate and the solvent was distilled off under reduced pressure. 10.6 g of crude 2- (3-methoxyimino-3H-benzofuran-2-ylideneaminooxy) ethylacetate (XIII-1) was obtained to give a mixture of t-butylmethyl ether and petroleum ether (1: 1). Chromatography on silica gel using 2- (3-methoxyimino-3H-benzofuran-2-ylideneaminooxy) ethylacetate (XIII-) containing 82.15% A stereoisomer and 13.38% B stereoisomer (HPLC) 1) 6.9 g (59.1% of theory) were obtained.

^' H NMR Spectrum (CDCl ₃ / TMS): δ = 2.10 (3H); 4.21 (3H, stereoisomer B); 4.22 (3H, stereoisomer A); 4.41-4.48 (4H); 7.15 / 7.17 / 7.20 (2H); 7.44-7.50 (1 H); 8.05-8.09 (1 H) ppm.

Example 16

Compound (XIII-1)

Method t)

0.26 g (0.001 mol) of 2- (3-hydroxyimino-3H-benzofuran-2-ylideneaminooxy) ethyl acetate (XVI-1) was dissolved in 2 ml of dimethylformamide. At 20 ° C., 0.04 g (0.001 mol) of 60% strength sodium hydride was added and the mixture was stirred until gas evolution ceased. 0.05 g (0.0005 mol) of sodium carbonate and 0.13 g (0.001 mol) of dimethylsulfate were added to the reaction mixture, and then left at 20 ° C. for 2 hours. The reaction mixture was poured into water and the resulting mixture was extracted with ethyl acetate. The organic phase is dried over sodium sulfate and the solvent is distilled off under reduced pressure. 0.24 g of crude 2- (3-methoxyimino-3H-benzofuran-2-ylideneaminooxy) ethylacetate (XIII-1) found to contain 33.9% A stereoisomer and 15.4% B isomer according to HPLC (42.5% of theory) was obtained.

GC / MS Analysis Data:

Retention Index = 2097 (stereoisomer A)

M ⁺ = 279, 278, 218, 187, 160, 144, 130, 87, 75, 43, 26.

Retention Index = 2097 (stereoisomer B)

M ⁺ = 279, 278, 218, 187, 160, 144, 130, 87, 63, 43, 26.

Example 17

Compound (XIII-1)

Method u)

At 20 ° C., 1.92 g (0.01 mol) of benzofuran-2,3-dione 3- (0-methyloxime) 2-oxime (VIII-1) was dissolved in 10 ml of dimethylformamide. 0.4 g (0.01 mol) of 60% strength sodium hydride was added to the solution, and the mixture was stirred at 20 ° C. for 1 hour. Thereafter, 1.67 g (0.01 mol) of 2-bromoethyl acetate was added, and stirring was continued at 20 ° C. for 16 hours. The reaction mixture was poured into water and the resulting mixture was extracted with ethyl acetate. The organic phase was dried over sodium sulphate and concentrated under reduced pressure. 2.3 g of 2- (3-methoxyimino-3H-benzofuran-2-ylideneaminooxy) ethylacetate (XIII-1) containing 51.17% A stereoisomer and 12.49% B isomer (HPLC) (52.6 of theory) %) Was obtained.

GC / MS analytical data (pre-analysis material was silylated with N-methyl-N-trimethylsilyl trifluoroacetamide).

Retention Index = 2097 (stereoisomer A)

M ⁺ = 279, 278, 218, 187, 160, 144, 130, 87, 75, 43, 26.

Retention Index = 2035 (stereoisomer B)

M ⁺ = 279, 278, 218, 187, 160, 144, 130, 87, 75, 43, 26.

Example 18

Compound (V-1)

Method v)

Benzofuran-2,3-dione 2- [0- (2-hydroxyethyl) oxime] diethyl ether pre-saturated with 1.11 g (0.005 mol) of 3-oxime (X-1) at 0 ° C. with cine hydrogen gas Dissolved in 20 ml. The mixture was stirred for 3 hours without further cooling and then poured into sodium bicarbonate solution cooled to 0 ° C. The organic phase was separated and the aqueous phase was extracted repeatedly with diethyl ether. The combined organic phases were dried over sodium sulfate and then concentrated at reduced pressure. Crude (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxyphenyl) methanone oxime containing 19.7% E isomer and 21.8% Z isomer (HPLC) 0.8 g (29.9% of theory) were obtained.

GC / MS analytical data (pre-analysis material was silylated with N-methyl-N-trimethylsilyl trifluoroacetamide).

Retention Index = 1980 (E Isomers)

M ⁺ = 368, 351, 307, 292, 250, 235, 203, 176, 147, 117, 100, 73, 45.

Retention Index = 2036 (Z isomers)

M ⁺ = 367, 351, 306, 292, 250, 235, 203, 176, 147, 117, 100, 73, 45.

Claims (16)

0-hydroxyethyl-0'-methyl-benzofurandione dioxime of the general formula (II) is rearranged in the presence of a diluent and optionally in the presence of a base acid. To prepare a compound of formula (I): In the above formula, A represents methyl, ethyl, or n- or i-propyl, R ¹ , R ² , R ³ and R ⁴ are the same or different and each independently of one another are hydrogen, halogen, cyano, nitro, or each having 1 to 6 carbon atoms and each optionally being selected by 1 to 5 halogen atoms Substituted alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl, Z ¹ , Z ² , Z ³ and Z ⁴ are the same or different and each independently of each other hydrogen, or alkyl or hydroxyalkyl having from 1 to 4 carbon atoms in each case, or 1 to 4 carbon atoms and 1 Or to halogenoalkyl having from 5 to 5 identical or different halogen atoms, or Z ¹ and Z ² , or Z ¹ and Z ³ , or Z ³ and Z ⁴ together with the respective carbon atoms to which they are attached form an alicyclic ring of 5, 6 or 7 carbon atoms. A compound according to claim 1 in general formula (I) A represents methyl or ethyl, R ¹ , R ² , R ³ and R ⁴ are the same or different and each independently represent hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n- or i-propyl, n-, i- , s- or t-butyl, methoxy, ethoxy, n- or i-propoxy, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, tri Fluoroethyl, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, difluorofluoromethylthio, trifluoromethylthio, trifluoro Methylsulfinyl or trifluoromethylsulfonyl, Z ¹ , Z ² , Z ³ and Z ⁴ are the same or different and each independently represent hydrogen, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, hydroxymethyl , Trifluoromethyl or trifluoroethyl, or Z ¹ and Z ² , or Z ¹ and Z ³ , or Z ³ and Z ⁴ together with the respective carbon atom to which they are attached form a cycloaliphatic ring of 5, 6 or 7 carbon atoms. Compound of formula (II): In the above formula, A, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are each as defined in claim 1. d) an alkoxyamine derivative of the following general formula (IV) or a 0-hydroxyethyl-benzofurandone monooxime of the general formula (VII), optionally in the presence of a diluent and optionally in the presence of an acid acceptor React with acid addition complexes, e) reacting the 0-alkyl-benzofurandion dioxime of the general formula (VIII) with the ethane derivative of the general formula (IX) below, optionally in the presence of a diluent and optionally in the presence of a base, f) reacting the 0-hydroxyethyl-benzofurandione dioxime of formula (X) with the alkylating agent of formula (VI), optionally in the presence of a diluent and optionally in the presence of a base, or m) reacting 0-oxyethyl-0'-methyl-benzofurandione dioxime of the general formula (XIII) with water or an alcohol, optionally in the presence of a diluent and optionally in the presence of an acid or a base; A process for the preparation of a compound of formula (II) as defined in claim 3: A-0-NH ₂ (IV) A-X (Ⅵ) In the above formula, A, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are each as defined in claim 1, Y ¹ represents halogen, methylsulfonyloxy, 4-tolylsulphonicoxy or acetyloxy, G represents hydrogen, or Y ¹ and G are connected to each other by a single bond, From here, Y ¹ represents oxygen, G is , Or Y ¹ and G together represent a single bond, X represents halogen, methylsulfonyloxy, methoxysulfonyloxy or 4-tolylsulfonyloxy, E represents an acyl group or a ketal protecting group. Compound of formula (VII): In the above formula, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are each as defined in claim 1. g) reacting the benzofurandion monooxime of the general formula (XI) with the ethane derivative of the general formula (IX) below, optionally in the presence of a diluent and optionally in the presence of a base, n) reacting 0-oxyethyl-benzofurandone monooxime of the general formula (XIV) with water or an alcohol, optionally in the presence of a diluent and, optionally, in the presence of an acid or a base. Process for preparing a compound of formula (VII) as defined in claim: In the above formula, EG, Y ¹ , R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are each as defined in claim 4. Compound of Formula (XIV): In the above formula, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are each as defined in claim 1, E represents an acyl group or a ketal protecting group. o) reacting a benzofurandone monooxime of the general formula (XI) with an ethanol derivative of the general formula (XV) below in the presence of a diluent and optionally in the presence of an acid acceptor Process for preparing compounds of general formula (XIV) as defined in claim 7: In the above formula, E, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are each as defined in claim 7, Y ² represents halogen, methylsulfonyloxy, 4-tolylsulfonyloxy or acetyloxy. Compound of formula (VIII): In the above formula, A, R ¹ , R ² , R ³ and R ⁴ are each as defined in claim 1. h) reacting the benzofurandone monooxime of the general formula (XI) with an alkoxyamine of the general formula (IV), optionally in the presence of a diluent and optionally in the presence of an acid acceptor, p) reacting the benzofurandion dioxime of the general formula (XII) with the alkylating agent of the general formula (VI) in the presence of a diluent and optionally in the presence of a base, Process for preparing a compound of defined general formula (VIII): A-0-NH ₂ (IV) In the above formula, A, R ¹ , R ² , R ³ and R ⁴ are each as defined in claim 1, X represents halogen, methylsulfonyloxy, methoxysulfonyloxy or 4-tolylsulfonyloxy. Compound of Formula (X): In the above formula, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are each as defined in claim 1. i) Hydroxylamine or acid addition thereof, 0-hydroxyethyl-benzofurandione monooxime of formula (VIII) as defined in claim 5, optionally in the presence of a diluent and optionally in the presence of an acid acceptor React with the complex, q) reacting 0-oxyethyl-benzofurandion dioxime of the general formula (XVI) with water or an alcohol, optionally in the presence of a diluent and, optionally, in the presence of an acid or a base. A process for preparing the compound of formula (X) as defined in claim: In the above formula, E, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are each as defined in claim 4. Compound of general formula (XVI): In the above formula, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are each as defined in claim 1, E represents an acyl group or a ketal protecting group. Reacting 0-oxyethyl-benzofurandione monooxime of formula (XIV) as defined in claim 7 with hydroxylamine or an acid addition complex thereof, optionally in the presence of a diluent and optionally in the presence of an acid acceptor To prepare a compound of formula (XVI) as defined in claim 13. Compound of general formula (XIII): In the above formula, A, R ¹ , R ² , R ³ , R ⁴ , Z ¹ , Z ² , Z ³ and Z ⁴ are each as defined in claim 1, E represents an acyl group or a ketal protecting group. 0-oxyethyl-benzofurandione monooxime of the general formula (XIV) as defined in claim 7 is optionally alkoxyamine of the general formula (IV) in the presence of a diluent and optionally in the presence of an acid acceptor or React with acid addition complexes thereof t) 0-oxyethyl-benzofurandione dioxime of general formula (XVI) as defined in claim 13, in the presence of a diluent and optionally in the presence of a base, with an alkylating agent of the general formula (VI) React, u) Ethanol derivatives of the general formula (XV) having the 0-alkyl-benzofurandione dioxime of general formula (VIII) as defined in claim 9, optionally in the presence of a diluent and optionally in the presence of an acid acceptor A process for preparing a compound of formula (XIII) as defined in claim 15 characterized by reacting with: A-0-NH ₂ (IV) A-X (Ⅵ) Where A, Z ¹ , Z ² , Z ³ and Z ⁴ are each as defined in claim 1, X represents halogen, methylsulfonyloxy, methoxysulfonyloxy or 4-tolylsulfonyloxy, E represents an acyl group or a ketal protecting group, Y ² represents halogen, methylsulfonyloxy, 4-tolylsulfonyloxy or acytyloxy.