KR20060098428A - Process for production of o-substituted hydroxylamines - Google Patents

Abstract

Provided is a process by which O-substituted hydroxyl- amines can be produced from industrially available raw materials in high yield, namely, a process for the production of O-substituted hydroxylamines which comprises the step of reacting an alkali metal salt of hydroxylaminedisulfonic acid with a halide such as an alkylating agent (RX) to form an alkali metal salt of an O-substituted hydroxylaminedisulfonic acid and the step of hydrolyzing the alkali metal salt obtained in the preceding step.

Description

Production method of hydroxylamine O-substituent {PROCESS FOR PRODUCTION OF O-SUBSTITUTED HYDROXYLAMINES}

The present invention relates to a process for the preparation of hydroxylamine O-substituents.

The hydroxylamine O-substituent represented by the O-methyl substituent of the hydroxylamine is a compound used as an intermediate for the preparation of various pharmaceutical ingredient compounds or agrochemical ingredient compounds, and until now hydroxylamine oxime as a raw material of hydroxylamine The method via via or the method via via hydroxyphthalimide etc. has been known and used. However, since a hydroxylamine which requires careful handling as a raw material should be used, and neither of these methods proceeds with the reaction of leaving ketone or phthalic acid completely by hydrolysis performed after the introduction of the O-substituent, There existed a problem that it was difficult to obtain the target hydroxylamine O-substituent in high yield, and a purification operation was easy to become complicated. For example, the yield is 66-72% in the example of synthesizing aminooxyacetic acid via the acetoxime described in Volume 3 of the Organic Synthesis Collective.

An object of the present invention is to provide a method for producing a hydroxylamine O-substituent in high yield using an industrially available raw material.

MEANS TO SOLVE THE PROBLEM As a result of studying the method of manufacturing a hydroxylamine O-substituent in high yield, this inventor discovered the new method using the hydroxylamine disulfonic acid alkali metal salt which is industrially available as a manufacturing raw material.

That is, the present invention provides a process for obtaining an O-substituted hydroxylamine disulfonic acid alkali metal salt by a reaction represented by the following reaction formula (1) between a hydroxylamine disulfonic acid alkali metal salt and a halide:

(1) (MSO ₃ ) ₂ NOH + RX → (MSO ₃ ) ₂ NOR + HX

[Wherein M represents an alkali metal atom, R represents an alkyl group, alkenyl group, alkynyl group, aryl group, aralkyl group, carboxyl group, ester group or ether group which may each have a substituent, and X represents a halogen atom] And a method for producing a hydroxylamine O-substituent including a step of hydrolyzing the obtained O-substituted hydroxylamine disulfonic acid alkali metal salt.

Embodiment of the invention

The present invention uses a hydroxyl amine disulfonic acid alkali metal salt as a raw material to react a halogen compound represented by an alkylating agent to it, converts it to an O-substituted hydroxyl amine disulfonic acid alkali metal salt, and then hydrolyzes the metal salt. It relates to a process for preparing amine O-substituents.

The hydroxylamine disulfonic acid alkali metal salt used as a raw material for the reaction used in the production method of the present invention is a compound represented by the hydroxylamine sodium sulfonate salt. For example, known hydroxylamine salts (NH ₂ 0H · A, A are Sodium bisulfite and sodium sulfite used in the production of an acid such as H ₂ SO ₄ , H ₂ PO ₄ , HCl and the like can be easily obtained by a method of reacting in an aqueous solution. Therefore, the compound produced at the time of manufacture of hydroxylamine can be used as a raw material of this invention as it is. In addition, although the said product may be used after isolate | separating the said product from the aqueous solution of the hydroxylamine disulfonic acid alkali metal salt obtained by this reaction once, this aqueous solution of the hydroxylamine disulfonic acid alkali metal salt may be used for the reaction of this invention as it is. Although sodium salt is typical as an alkali metal salt, potassium salt, a lithium salt, etc. can also be used.

In the reaction used in the production method of the present invention, a halogen compound represented by RX such as an alkylating agent in the presence of an aqueous medium is used for the above-described hydroxylamine disulfonic acid alkali metal salt.

Preferred examples of R in the above formula of RX include alkyl groups having 1 to 6 carbon atoms such as methyl, ethyl, propyl, butyl, pentyl and hexyl groups, each of which may have a substituent; Alkenyl groups having 1 to 6 carbon atoms such as allyl group, propenyl group, butenyl group, etc .; An alkynyl group having 1 to 6 carbon atoms such as an acetylene group, propynyl group, butynyl group and the like; Aryl groups such as phenyl group, naphthyl group, anthranyl group and the like; Aralkyl groups such as benzyl and phenethyl; Carboxyl groups; Ester groups such as ethoxycarbonyl groups; And ether groups such as ethoxyethyl group. Especially preferred are alkyl groups and carboxyl groups having 1 to 6 carbon atoms. Examples of the substituent which may be attached to R include an alkyl group, an alkoxy group, an aryl group, an aralkyl group, a halogen atom and a halogen-containing alkyl group.

X represents a halogen atom such as chlorine, bromine, fluorine or iodine, but chlorine is preferable.

The reaction of the reaction formula (1) is not particularly limited with respect to the reaction temperature and the reaction time, but is usually performed at a temperature of about 0 to 100 ° C, preferably about 10 to 80 ° C for about 1 to 20 hours. However, the reaction time is appropriately adjusted in consideration of the amount of the reaction raw material. In addition, when the halogen compound represented by RX is gas at reaction temperature, it is preferable to carry out reaction using pressure-resistant vessels, such as an autoclave, as a reaction vessel.

The O-substituted hydroxylamine disulfonic acid alkali metal salt produced by the reaction of Scheme (1) can be converted into the desired hydroxylamine O-substituent by hydrolyzing it. This hydrolysis can be carried out by first heating the O-substituted hydroxylamine disulfonic acid alkali metal salt in an aqueous medium in the presence of a strong acid such as sulfuric acid to hydrolyze it, and then neutralizing it with an alkaline agent such as sodium hydroxide. This hydrolysis reaction is realized by, for example, a reaction represented by the following reaction formula (2) and reaction formula (3).

(2) (MSO ₃ ) ₂ NOR + H ₂ O →

_{(H 2 NOR) 2 · H} 2 SO 4 + H 2 SO 4

_{(3) (H 2 NOR)} 2 · H 2 SO 4 + H 2 SO 4 + NaOH →

H ₂ NOR + Na ₂ SO ₄

The resulting hydroxylamine O-substituents can also be extracted as hydrochloride, for example by contact with hydrochloric acid.

Example 1

500 mL of aqueous sodium amine disulfonate solution (2 mol / L) and 80 g of 50% aqueous sodium hydroxide solution were placed in a pressure-resistant vessel. Next, 50.5 g of methyl chloride was put into a separately prepared pressure vessel, and the pressure vessels were connected so that the contents in each pressure vessel could flow with each other, and the contents were mixed and contacted. The contents were stirred and mixed for 2 hours while maintaining the temperature in the pressure resistant vessel at 50 ° C. After the pressure in the pressure resistant vessel was lowered (meaning the end of the reaction), the pressure vessel was opened to extract the reaction liquid therein (an aqueous solution of the produced O-methylhydroxylamine disulfonate salt).

9.8 g of concentrated sulfuric acid was added to the reaction solution, and the sulfonic acid group was removed from the reaction product by hydrolysis under heating at about 90 ° C for 24 hours. Subsequently, 330 g of a 50% aqueous sodium hydroxide solution was added to the hydrolyzate and neutralized, and then 66 g (yield: 80%) were removed by using a strip column to remove nonvolatile matters such as salts in the neutralization solution and distilling off the column. ) O-methylhydroxylamine (boiling point: about 49 ℃) was obtained.

A 30% aqueous solution of O-methylhydroxylamine hydrochloride was obtained by dissolving 171.7 g of 15% base in 33 g of the obtained O-methylhydroxylamine.

Example 2

500 mL of aqueous sodium amine disulfonates (2 mol / L) and 80 g of 50% aqueous sodium hydroxide solution were placed in a beaker, and then 94.5 g of chloroacetic acid was added and stirred at 50 ° C for 24 hours. When the pH of the reaction solution was lowered to 9 or less and the completion of the reaction could be confirmed, 9.8 g of concentrated sulfuric acid was added to the reaction solution, and the reaction product was heated at about 90 ° C for 24 hours at atmospheric pressure. Amine disulfonic acid salt) was hydrolyzed and the sulfonic acid group was released. Subsequently, 50% sodium hydroxide aqueous solution was gradually added to this hydrolysis solution until it became pH7, and it neutralized, and the produced aminooxy acetic acid was extracted using 700 mL of ethyl acetate.

Ethyl acetate was removed from the extract under liquid pressure, and then 104 g of 37% hydrochloric acid was added to the residue. This hydrochloric acid addition liquid was heated to 70 degreeC, and the residue was dissolved. Subsequently, recrystallization at room temperature yielded a crystal in which one molecule of hydrochloric acid was bound to two molecules of aminooxyacetic acid (amount 107 g, yield 98%).

According to the production method of the present invention, hydroxyamine O-substituents can be produced in high yield by using an industrially available hydroxylamine disulfonic acid alkali metal salt as a production raw material.

Claims (3)

A process for obtaining an O-substituted hydroxylamine disulfonic acid alkali metal salt by the following reaction between a hydroxylamine disulfonic acid alkali metal salt and a halide: (MSO ₃ ) ₂ NOH + RX → (MSO ₃ ) ₂ NOR + HX [Wherein M represents an alkali metal atom, R represents an alkyl group, alkenyl group, alkynyl group, aryl group, aralkyl group, carboxyl group, ester group or ether group which may each have a substituent, and X represents a halogen atom] , And Step of hydrolyzing the obtained O-substituted hydroxylamine disulfonic acid alkali metal salt Method for producing a hydroxylamine O-substituent comprising a. The method for producing a hydroxylamine O-substituent according to claim 1, wherein M is a sodium atom. The method for producing a hydroxylamine O-substituent according to claim 1 or 2, wherein R is an alkyl or carboxyl group having 1 to 6 carbon atoms.