JPS631941B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing N-substituted quinoneimine compounds. N-substituted quinone imine compounds are useful as pharmaceuticals, pharmaceutical intermediates, organic synthesis intermediates, and the like. The inventors have previously observed that both alkylthionitrite or alkylthionitrate react readily with various arylamines in the presence of copper halides, respectively, to give the corresponding aryl halides in good yields. Initially, a patent application was filed (Japanese Patent Application No. 120594-1983). The invention of this application was completed based on the discovery that when the arylamine is hydroxyarylamine, the reaction does not proceed as described above and an N-substituted quinone imine compound []a or []b is obtained. It is something that Note that when alkylthionitrite is used, an N-substituted quinone imine compound cannot be obtained. Regarding N-substituted quinone imine compounds, only a few examples have been reported so far, and only a method for producing them using N-chloro-p-benzoquinone imine and thiol has been reported. The method for producing an N-substituted quinoneimine compound of the present invention is a simple process for producing from an aminophenol compound, and is particularly excellent in that it is a basic method for producing N-alkanesulfenyl derivatives. ing. That is, the present invention provides thionitrate represented by the general formula R ¹ -SNO ₂ [] (in the formula [], R ¹ represents an alkyl group or an aryl group) and a thionitrate represented by the general formula (In the formula [], R ² and R ³ each represent hydrogen, halogen, or an alkyl group, and R ₂ and R ₃ may be linked to each other to form an aromatic ring.) The general formula is characterized by reacting with and in the presence of copper halide. or general formula (In formula [a] to b, R ¹ represents an alkyl group or an aryl group, R ² and R ³ each represent hydrogen, halogen, or an alkyl group, and R ² and R ³ are connected to each other to form an aromatic ring. )
This is a method for producing a substituted quinone imine compound []. The present invention can be easily implemented, for example, as follows. That is, thionitrate and copper halide are suspended in a solvent, and an aminophenol compound is added thereto. Thionitrates can be obtained by treating the corresponding thiol with dinitrogen tetroxide; examples include tertiary butylthionitrate, tertiary amylthionitrate, and tertiary nonitrogen tetroxide. Examples include tertiary alkylthionitrates such as ruthionitrate, alkylthionitrates such as secondary butylthionitrate, and arylthionitrates such as p-tolylthionitrate.Tertiary alkylthionitrates are stable. It is excellent because it has good characteristics. When using a solvent, it is preferable to use alkyl cyanide or ether as the reaction solvent. Examples of alkyl cyanide include acetonitrile, propionitrile, etc. Ether is an organic compound that contains at least Examples include isopropyl ether, tetrahydrofuran, dioxane, etc. as long as it has one ether bond. Examples of aminophenol compounds include:
Aminophenols such as o-aminophenol and p-aminophenol; aminoalkylphenols such as 4-amino-3-methylphenol and 4-amino-2,6-dimethylphenol; and 4-amino-2,6-dichlorophenol. Examples thereof include aminohalophenols such as, aminonaphthols such as 4-amino-1-naphthol, and the like. The reaction is preferably carried out under anhydrous conditions,
The reaction temperature is usually room temperature, which is sufficient, and in this case, the reaction is completed within a short time, usually within about 1 hour. After the reaction, according to or according to a method known per se,
Separation, purification, etc. are optional. Examples are shown below. Examples 1 to 10 546 mg (5 mmol) of p-aminophenol,
Add to a suspension of 810 mg (6 mmol) of anhydrous cupric chloride and 1020 mg (7.5 mmol) of tertiary-butylthionitrate in 15 ml of anhydrous acetonitrile under stirring for 5 minutes. After stirring for 1 hour at room temperature, 20% hydrochloric acid 100%
ml and extract with ether. Dry the ether layer (MgSO ₄ ) and concentrate. The concentrated residue was subjected to silica gel thin layer chromatography (hexane:ether=
10:1) to obtain 390 mg of yellow crystals of N-(t-butanesulfenyl)-p-benzoquinoneimine. Yield 40%. The same treatment was performed using the aminophenol compound and thionitrate shown in Table 1 to obtain the crystals shown in Table 1. The thionitrate used was obtained as follows. (1) t-Butylthionitrate Dinitrogen tetroxide (1.5 mol) carbon tetrachloride 135 ml
Add the solution to 55.3 g of t-butyl mercaptan.
(0.6 mol) was added dropwise to a solution of 500 ml of dry ether under stirring over 30 minutes at such a rate that the ether slowly refluxed. After the addition is complete, stir for an additional 30 minutes. Wash with cold water, dry (MgSO ₄ ), concentrate, and distill (molecular sieve) to obtain 67.8 g of oil (colorless). Yield 84%. bp40−41
℃/6mmHg (literature value: 55℃/13mmHg). (2) T-Amylthionitrate Obtained by the same treatment as (1). pb36−38℃/3
mmHg. (3) T-nonylthionitrate Obtained by the same treatment as (1). pb78−81℃/2
mmHg. All of these tertiary alkylthionitrates are stable and can be isolated, but other thionitrates, such as secondary butylthionitrate and p-tolylthionitrate, are unstable and cannot be isolated. was processed as follows to obtain the desired product. Next, the case where secondary butylthionitrate is used will be shown, but the same applies to the case where p-tolylthionitrate is used. A solution of 3 ml of dinitrogen tetroxide (30 mmol) in carbon tetrachloride was added to 1.35 g (15 ml) of secondary butyl mercaptan.
mol) under stirring at 0°C. The solution is

【table】

[Table] a) Hydrochloride was used as the starting material. b) Since these thionitrates are unstable and cannot be isolated in pure form at room temperature, an oxidation reaction mixture of thiol and 2 equivalents of N ₂ O ₄ was used.
The color immediately changes to red, indicating the formation of thionitrite, and the red color soon disappears, which is clearly due to further oxidation of secondary butylthionitrite to form secondary butylthionitrate. It shows that it will be generated. 1.78 g (10 mmol) of 4-amino-2,6-dichlorophenol is added over 2 to 3 minutes and stirred for an additional 1.5 hours. The brown precipitate was removed by filtration, the liquid was diluted with ether, washed with an aqueous sodium bicarbonate solution, dried (MgSO ₄ ), concentrated, and separated by thin layer chromatography (hexane:ether = 7:1) in a conventional manner. , 256 mg of N-(s-butanesulfenyl)-2,6-dichloro-p-benzoquinoneimine are obtained. Yield 10%. All of the obtained N-substituted quinone imine compounds have good stability and strong absorption near 400 nm (εmax>
10 ⁴ ) shows yellow color. The structure of the target N-substituted quinone imine compound can be determined by IR, NMR, UV,
Identified by MS spectrum. All elemental analyzes of the target product supported the structure of an N-substituted quinoneimine compound.

Claims (1)

[Scope of Claims] 1 Thionitrate represented by the general formula R ¹ −SNO ₂ [] (R ¹ in the formula [ ] represents an alkyl group or an aryl group) and the general formula (In the formula [], R ² and R ³ each represent a hydrogen atom, a halogen atom, or an alkyl group, and R ² and R ³ may be linked to each other to form an aromatic ring.) A general formula characterized by reacting a compound with a compound in the presence of a copper halide. or general formula (Formula [] In _{a to b} , R ¹ represents an alkyl group or an aryl group, R ² and R ³ each represent a hydrogen atom, a halogen atom, or an alkyl group, and R ² and R ³ are connected to form an aromatic ring. A method for producing an N-substituted quinone imine compound []. 2 Alkyl cyanide R ⁴ −CN as reaction solvent
(In the formula, R ⁴ represents an alkyl group having 1 to 10 carbon atoms.)
A method for producing an N-substituted quinone imine compound according to claim 1, which uses the following. 3. The method for producing an N-substituted quinone imine compound according to claim 1, which uses an ether compound as a reaction solvent. 4 Claim 1 where the reaction is carried out under anhydrous conditions
A method for producing an N-substituted quinone imine compound according to item 1, 2 or 3.