JPS6270344A - Production of nitrophenoxyamine - Google Patents

Abstract

PURPOSE:To industrially and advantageously obtain the titled compound useful for synthesizing medicines and agricultural chemicals in high yield, by reacting an N-aryloxyimide derivative with hydroxylamine. CONSTITUTION:An N-aryloxyimide derivative expressed by formula I (n is an integer 1-3; X is H, halogen or alkyl; -A-B- is formula II-IV; R<1> is Cl or alkyl; R<2>-R<5> are H, alkyl, alkenyl, etc.) is reacted with hydroxylamine to afford a nitrophenoxyamine expressed by formula V. This method is industrially advantageous since not only the aimed compound expressed by formula V is obtained in high yield by simple operation in a few steps but also N- hydroxyimides, expressed by formula VI and formed as a by-product can be readily led to the compound expressed by formula I for reuse. The reaction temperature is normally -40-+150 deg.C, preferably -10-+80 deg.C.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention provides compounds of the general formula (V) and C, which are useful compounds in the synthesis of pharmaceuticals and agricultural chemicals, where n is an integer of 1 to 6, and X is an integer of 1 to 6. It represents a hydrogen atom, a halogen atom, an alkyl group, or an alkyl group substituted with a halogen atom, and the plurality of Xs may be the same or different from each other. ) The present invention relates to a method for producing nitrophenoxyamines represented by: More specifically, N-amino form, S-amino form,
It can be widely used as an aminating reagent in the synthesis of P-amino or C-amine. As described above, this method can also be applied to the synthesis of 0-amine compounds.

[Conventional technology]

-ff There have been several reports on methods for producing some of the nitrophenoxyamine compounds represented by the formula fV). For example, Journal of Heterocyclic Chemistry (Tourna, la
fHeterocyclic Ohemist, ry
) Volume 4, page 415 (1967), N-
A method using hydroxycarbamine f'#t-butyl ester has been proposed.

However, this method requires the use of expensive N-hydroxycarbamic acid monobutyl ester or trifluoroacetic acid, and cannot be said to be an industrially practical method.

In addition, the Societe de France
France)
On page 855 (1976), the following method of reacting N-hydroxyphthalimide and hydrazine is proposed.

However, this method also has the drawback that phthalhydrazide, which has little utility value, is produced as a by-product, and this method cannot be said to be an industrially advantageous method for producing nitrophenoxyamines.

Therefore, it has hitherto been difficult to industrially produce nitrophenoxyamines represented by general formula (V) at low cost.

[Purpose of the invention]

The present inventors have conducted various studies with the aim of developing an industrially advantageous method for producing nitrophenoxyamines represented by the general formula F%'). the result.

In the general formula easily obtained by reacting N-hydroxyimides and halogenated nitrobenzenes, n is 1.
X represents a hydrogen atom, a halogen atom, an alkyl group, or an alkyl group substituted with a halogen atom; in the formula C, R1 is a chlorine atom or an alkyl group; Including those in which 1 to 4 benzene nuclei are substituted.

R2, R', and R4-R5 are each a hydrogen atom, an argyl group, or an alkenyl group, or [R2 and R6 and R4 and R5 are bonded to each other to form a ring, and there are double bonds and 7 years old or may contain oxygen atoms). ] It has been discovered that by reacting the N-aryl ogiciimide derivative represented by hydroxylamine with hydroxylamine, the desired nitrophenoxyamines represented by the general formula fV) can be obtained, and the N-hydroxyimides can be regenerated. This led to the present invention.

[Structure of the invention]

That is, in the sixth aspect of the present invention, in the general formula (I) A/C, n, X and 1 are the same as described above. )
Nitrophenoxy represented by the general formula (in the LC formula, n and The gist is a method for producing amines.

The reaction formula for the production method of the present invention is shown in formula (1).

(V) (4) N-hydroxyimide obtained here (■ can be easily led to (1) as shown in formula (2).

=7-〇(I> That is, according to the method of the present invention, not only can nitrophenoxyamines (V) be obtained in good yield with a small number of steps and simple operation, but also reusable N-hydroxy It can be said that this method is industrially extremely advantageous since it can produce imide sulfur as a by-product.

The method for producing nitrophenoxyamines according to the present invention will be explained in detail below.

In the compound of general formula (■) used as a raw material in the present invention, examples of the halogen atom of X include fluorine, chlorine, and bromine, and preferably fluorine and chlorine. X is also a linear or branched alkyl group, preferably a lower alkyl group. Examples of such lower alkyl groups include methyl group, ethyl group, n-propyl group, and isopropyl group.

Carbon W such as n-butyl group, isobutyl group - t-butyl group
Examples include straight-chain or branched alkyl groups having 1 to 4 tj, particularly preferably a methyl group or a methyl group. The same thing can be said about the alkyl group of R1 to 1°R5, which will be described later, as the alkyl group of X. The alkyl group substituted with a halogen atom of X is one in which the above-mentioned alkyl group is substituted with an arbitrary number of halogens, and among them, those in which a lower alkyl group is substituted with a halogen are preferable. '/A Evadifluoromethyl group, trifluoromethyl group, urorodifluoromethyl group, pentafluoroethyl group, dichlorodifluoroethyl group with 1 to 2 carbon atoms, fluorine and 7 or chlorine, 2 to 5
Among them, trifluoromethyl group is particularly preferred. More specifically, the general formula (
xn of D, (NO2)n and monolophenyl groups, dinitrophenyl groups, trinitrophenyl groups, fluoronitrophenyl groups, chloronitrophenyl groups m,)lifluoromethylnitrophenyl groups, fluorodinitrophenyl groups, Preferred examples include fluoromethyldinitrophenyl groups, methylnitrophenyl groups, methyldinitrophenyl groups, and chlorodinitrophenyl groups. Further preferred for the weight of general formula (I) are phenin groups,
Examples of the compound represented by the above general formula (D) include, for example, methylphenylene groups, methylphenylene groups, and methylphenylene groups.

HalvettcaOh
l, mi, ca, Acta) vol. 46, p. 2009 (1965).

Bllllfitin de la 6 oaiete
In the presence of a base, according to the method described in Ohimiqueda France), p.
It can be easily synthesized by the reaction of formula (2) above.

In the present invention, the target compound, nitrophenoxyamines represented by general 2
- Obtained by reacting an aryloxyimide derivative with hydroxylamine. Hydroxylamine used here and C, hydroxylamine hydrochloride,
It refers to salts such as sulfates and oxalates, or hydroxylamine in a free state obtained by neutralizing the salts with an alkali.

Preferably it is free hydroxylamine.

As the alkali, hydroxides, alkoxides, carbonaceous salts or bicarbonates of alkali metals such as sodium and potassium, or ammonia can be used. The amount of these alkalis to be used is 1 y o.9 to 2.0 times the equivalent of the above-mentioned hydroxylamine salt, preferably 1
．． The prize is 0 to 1.5 times.

The amount of hydroxylamine used is m = D, 9tJ to 2 times the molar amount of the compound represented by the general formula (1>).

Preferably it is 1.0 to 1.5 times the molar amount. The solvent used in the present invention is preferably water, alcohols such as methanol and ethanol, and ethers such as diethyl ether, tetrahydrofuran, dioxane and diglyme, and the above solvents can be used alone or in combination. The amount of these solvents used is usually 1 to 100 parts by weight, preferably 2 to 50 parts by weight, per 1 part by weight of the compound of general formula (I). The reaction temperature is usually -40 to 150°C.

Preferably it is -10 to 80°C. The reaction time is usually 0.1 to 50 hours, preferably 5 to 20 hours.
It's time. After the reaction - To obtain the target product (V), commonly used separation means such as filtration or solvent extraction can be employed. Furthermore, high purity (V> can be obtained by recrystallizing if necessary or dissolving it in an organic solvent that is immiscible with water and washing with alkaline water. N-hydroxyimides represented by the formula (■,
If (b) precipitates as the reaction progresses, it can be separated by filtration, or it can be acidified with mineral acid and liberated (■) by filtration or solvent extraction before or after separation of (■). Obtainable.

〔Effect of the invention〕

As described above, according to the present invention, in the reaction of the N-aryloxyimide derivative represented by the general formula (1) with hydroxylamine, the desired nitrophenoxyamines represented by the general formula (■) can be produced in high yield. Not only can N-hydroxyimides be obtained at high yields, but also reusable N-hydroxyimides can be produced as a by-product, and therefore the present invention is extremely useful industrially.

〔Example〕

The method of the present invention will be specifically explained below using examples.

Example 1 N-(2,4-dinitrophenoxy)phthalimide4.
94 g (15 mmol) and 1.15 gr (16.5 mmol) of hydroxylamine hydrochloride in 50 ml of methanol.
β, suspended in a mixed solvent of 6 J of water, and in it an aqueous solution of 0.66 q (16.5 mmol) of sodium hydroxide 6
rn (l was added dropwise. After stirring at 25°C for 2 hours, the reaction mixture was poured into 200 J of ethyl acetate and 100 m/? of water, and the liquids were separated after shaking. The ethyl acetate layer was oxidized with 5 hydroxides) I
After washing with an aqueous Jumium solution and then with a saturated saline solution, it was dried over anhydrous magnesium sulfate. Ethyl acetate is distilled off. ! =O
-(2,4-dinitrophenyl)hydroxyamine is 2
．． 60 g (C yield 87%), the aqueous layer and the sodium hydroxide washing solution were combined, and the pH was adjusted with concentrated hydrochloric acid.
After adjusting the amount to 2, the precipitated crystals were washed with water after P was removed and dried, resulting in 2.08 g of N-hydroxyphthalimide.
(yield 85%).

Examples 2 to 7 The reaction was carried out in the same manner as in Example 1, except that the imide derivatives shown in Table 1 were used in place of N-(2,,!l-dinitrophenoxy)phthalimide. Example 1
When treated in the same manner as above, -0-(2,4-dinitrophenyl)hydroxyamine and H-N-hydroxyimide derivatives were obtained in the yields shown in Table 1.

Examples 8 to 10 In Example 1, N-(2,4-dinitrophenoxy)
The reaction was carried out in the same manner as in Example 1, except that the imide derivatives shown in Table 2 were used instead of phthalimide. When treated in the same manner as in Example 1, nitrophenoxyamine and N-
Hydroxyimide derivatives were obtained in the yields shown in Table 2.

Claims (1)

[Claims] (1) General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, n is an integer from 1 to 3, and X is a hydrogen atom, a halogen atom, an alkyl group, or a halogen atom. Represents a substituted alkyl group, multiple Xs may be the same or different from each other, ▲There are mathematical formulas, chemical formulas, tables, etc.▼
There are general formulas (II) to (IV), ▲ mathematical formulas, chemical formulas, tables, etc. ▼ (II), ▲ there are mathematical formulas, chemical formulas, tables, etc. ▼
(III), ▲There are mathematical formulas, chemical formulas, tables, etc.▼(IV)
In the formula, R^1 is a chlorine atom or an alkyl group, and R^1 is a chlorine atom or an alkyl group;
2, R^3, R^4, and R^5 are each a hydrogen atom, an alkyl group, or an alkenyl group, or R^2 and R
^3 and R^4 and R^5 may be bonded to each other to form a ring, and the ring may contain a double bond and/or an oxygen atom. ) is shown. General formula (V), which is characterized by reacting an N-aryloxyimide derivative represented by A method for producing nitrophenoxyamines represented by