JPH0142268B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel method for producing compound () by directly introducing a sulfur source into compound (), as shown in the reaction formula below. In the above formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are the same or different and represent hydrogen, alkyl, aryl (phenyl, tolyl, methoxyphenyl, chlorophenyl, etc.), but R ⁴ and R ⁵ may be combined to form a benzene ring. The nitrogen-containing aromatic 2-mercapto-N-oxide provided by the present invention, such as 2-mercaptopyridine-N-oxide, is an important compound in disinfectant raw materials, cosmetics, and the like. Conventionally, methods for producing 2-mercaptopyridine-N-oxide include a method via 2-chloropyridine, a method using a strong base such as butyllithium or lithium hydride, and a method using a metal salt of α-carboxylpyridine-N-oxide. Examples include reactions by decarboxylation. However, the method involves long steps, the production of the raw material 2-chloropyridine requires high temperatures and isomers are produced, the method is complicated and expensive, and requires a strong base that cannot be reused; There are drawbacks such as the need for α-picolinic acid. In the present invention, in the presence of a phase transfer catalyst and a metal hydroxide, in water, an organic solvent, or a water-organic solvent,
This invention consists of reacting a nitrogen-containing aromatic N-oxide with a sulfur source such as elemental sulfur, a sulfur-containing metal salt, a mercapto group-containing compound, or a mercapto group-forming compound. The effects of the present invention are that the process can be shortened, the operation is simple and mild reaction conditions can be performed, inexpensive metal hydroxides can be used, and the phase transfer catalyst used can be recovered and reused. I can give points such as: The nitrogen-containing aromatic N-oxide used in the present invention includes, for example, pyridine N-oxide, α-picoline N-oxide, 2-ethylpyridine N-oxide, 2-propylpyridine N-oxide,
-Butylpyridine N-oxide, 2-pentylpyridine N-oxide, 2-hexylpyridine N-
oxide, 2-nonylpyridine N-oxide, 2
-vinylpyridine N-oxide, 2-phenylpyridine N-oxide, 2-(1-naphthyl)pyridine N-oxide, 2-(4-biphenylyl)pyridine N-oxide, 2-methoxypyridine N-
oxide, 2-ethoxypyridine N-oxide and their 3-substituted, 4-substituted, 2,3-,
Each disubstituted product of 2,4-, 2,5-, 3,4-, 3,5-, trisubstituted product of 2,3,4-, 3,4,5-, 2,3,4,5 Examples include pyridine N-oxide derivatives such as tetrasubstituted -, quinoline N-oxide, and the like. A phase transfer catalyst is a compound that induces reactions such as heterophase reactions, for example, by complexing or forming ion pairs with inorganic salts that are insoluble in organic solvents and reaction reagents that do not come into contact with each other (for example, double ．P. Weber (WP
Weber), G. Double you. Gokel (GW
Gokel) co-author “Phase transfer catalysts in organic synthesis”
(Phase Transfer Catalysis in Organic
Synthesis), published by Springer Verlag, 1977). Typical examples include cryptate (crown ether, cryptand), quaternary ammonium salt, quaternary phosphonium salt, sulfonium salt,
Tertiary amine, Calixarene.
(see Journal of the American Chemical Society 103 , 3782, 1981), polyethers of polybutadiene derivatives, polyethylene glycol derivatives, hexasubstituted benzenes, etc.
molecule or "octopus molecule", (Area of Chemistry 31 , (4),
74, 1977), but more specifically, 14-crown-4, 15-crown-5, 18-
Crown-6,21-crown-7,22-crown-6,24-crown-6, benzo-15-crown-6, jinzo-18-crown-6, dicyclohexyl-18-crown-6, furano-18- Crown-6, insoluble 18- supported on polystyrene, etc.
Crown-6, macrocyclic oxo crown ether, diaza 15-crown, diaza 18-crown, [2.1.1]-cryptand, [2.2.1]-cryptand, [2.2.2]-cryptand, [2,2,
2]-decylcryptant, [2,2,2]-benzocryptand, and compounds in which oxygen atoms in these compounds are partially or completely replaced by nitrogen, sulfur, or phosphorus atoms may be used. Also included are calixuarenes and spheranands represented by formulas (2) and (3). Formula (2) n=1,3,5, R: methyl, t-butyl, phenyl, methoxy,
Carbomethoxy formula (3) A polybutadiene derivative represented by formula (4). Polyethylene glycol with a molecular weight of 600 or 1000 and its diethers such as diethyl, dibutyl, dimethyl ether, “octopus molecules” shown by formula (5), formula (4)

[Formula] R: ethylene, pro Pirene Formula (5)

[Formula] R=-S(-CH ₂ CH ₂ O-) ₃ C ₄ H ₉ (CH ₃ ) ₄ NBr, (C ₃ H ₇ ) ₄ NBr, (C ₄ H ₉ ) ₄ NBr,
(C ₄ H ₉ ) ₄ NI, C ₆ H ₅ CH ₂ N (C ₂ H ₅ ) ₃ Br, C ₁₂ H ₂₅ N
( _CH3 )Cl, _{C16H33N ( CH3} ) _3Br ,
(C ₆ H ₅ ) ₃ PCH ₃ I, (C ₆ H ₅ ) ₄ PCl, (C ₄ H ₉ ) ₄ PCl,
(C ₆ H ₅ ) ₄ AsCl, (the counter ion may be Br, Cl, I, or other anions), tributylamine, tetramethylethylenediamine, N-methylproline, etc., but these The present invention is not limited to these, and even substances other than those described above can be used as long as they have the function of functioning as a phase transfer catalyst. Metal hydroxides include, for example, LiOH, NaOH,
KOH, Ca(OH) ₂ , CsOH, RbOH, Be(OH) ₂ ,
Mg(OH) ₂ , Sr(OH) ₂ , Ba(OH) ₂ , Mn(OH) ₂ ,
Examples include Zn(OH) ₂ or hydroxides of iron, copper, nickel, cobalt, etc. Sulfur sources include elemental sulfur, alkali metal sulfides, alkaline earth metal sulfides, alkali metal hydrosulfides, other metal sulfides, ammonium sulfide, nitrogen sulfide, and sulfur-containing compounds such as P(S)X ₃ and RP. (S)X ₂ , R ₂ P
(S)X, R(RO)P(O)SX, [(RO) ₂ P(S)] ₂
,
[ _R2P (S)CH2 _{] -2} (R is alkyl, aryl,
is a halogen), organic isothiocyanates such as methylisothiocyanate, organic diisothiocyanates such as methylene diisoocyanate, inorganic isothiocyanates, thioepoxides such as 1,2-diphenylethylenethioeposide, ethylenethiocarbonate, thiourea and Examples include thioketone compounds such as carbon disulfide, and organic polysulfides such as dimethyltorsulfide, but preferable examples include elemental sulfur, Na ₂ S _x , K ₂ S _x , MaSH, and KSH.
(x is an integer). The present invention is carried out in water, an organic solvent, or a water-organic solvent, and the organic solvents used include aromatic hydrocarbons such as benzene, toluene, xylene, mesitylene, and tetralin, dichloromethylene, chloroform, bromoform, carbon tetrachloride, and trichloroethane. , halogenated hydrocarbons such as tetrachloroethane, chlorobenzene, bromobenzene, dichlorobenzene, dibromobenzene, trichlorobenzene, diethyl ether, dipropyl ether, dibutyl ether, ethylpropyl ether, ethyl butyl ether, diphenyl ether, anisole, tetrahydro Furan, dioxane, ethylene glycol dimethyl ether,
Ethers such as ethylene glycol diethyl ether, ethylene glycol dibutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, triethylene glycol dimethyl ether, triethylene glycol diethyl ether, triethylene glycol dibutyl ether, methanol, ethanol, propanol, butanol, Alcohols such as heptanol, hexanol, ethylene glycol monoalkyl ether, diethylene glycol monoalkyl ether, triethylene glycol monoalkyl ether, ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, nitrobenzene, acetonitrile, DMF, DMSO, HMPA, etc. However, it is not particularly limited to this solvent. Next, the phase transfer catalyst may be used in excess of 0.0001 mole or more and several moles per mole of the nitrogen-containing aromatic N-oxide used in carrying out the present invention, and the sulfur source may be used in excess of at least an equivalent amount. It's okay to do that. The metal hydroxide is used in an amount ranging from an equivalent to several tens of times the equivalent, and the reaction is carried out at a temperature of 30°C to 250°C.
It is preferable to carry out the reaction at a temperature of 0.5 hours or more for 10 hours. The examples will be specifically described above. Example 1 9.5 g of pyridine N-oxide,
4.0 g of sodium hydroxide, 1.3 g of 18-crown-6, 3.2 g of elemental sulfur, and 150 ml of toluene were charged at the same time. The reaction solution was heated and stirred (for 3 hours) while being refluxed and dehydrated. The amount of water dehydrated is 1.2ml
It was hot. After the reaction solution was cooled to room temperature, water was added to separate the aqueous layer from the organic layer. The aqueous layer was made acidic with an aqueous hydrochloric acid solution and cooled with ice water. The crystallized product was filtered off with suction. Product: 2-mercaptopyridine-N-oxide, yield 1.8 g (melting point 66-68°C).
The melting point of the crystal obtained by repeating the separation and crystallization operation was 68 to 69°C. Collect the separated toluene layer and aqueous layer and 18-crown-6
was collected by column chromatography. Example 2 Using the reaction equipment used in Example 1, 9.5 g of pyridine N-oxide, 8 g of sodium hydroxide,
3.6 g of dibenzo-18-crown-6, 6.4 g of elemental sulfur, and 150 ml of toluene were charged at the same time.
The operations were the same as in Example 1. Product: 2-mercaptopyridine N-oxide, yield
5.5g (melting point 66-68℃) Example 3 In a 300ml round bottom flask equipped with a stirrer and condenser
9.5 g of pyridine N-oxide, 8 g of sodium hydroxide, 13 g of 18-crown-6, 3.2 g of elemental sulfur, 150 ml of toluene, and 50 ml of pure water were charged at the same time. The reaction solution was heated and stirred at reflux temperature for 10 hours. After the reaction solution was cooled to room temperature, the aqueous layer was separated from the organic layer. The aqueous layer was made acidic with an aqueous hydrochloric acid solution and cooled with ice water. The crystallized product was filtered off with suction. Product: 2-mercaptopyridine N-oxide, yield 9.4 g (melting point 67-68°C) Example 4 In the reaction apparatus used in Example 1, 9.5 g pyridine N-oxide, 4 g sodium hydroxide, 2.6 g
18-crown-6, 7.3 g of methyl isothiocyanate, and 150 ml of toluene were charged at the same time.
The operations were the same as in Example 1. Product: 2-mercaptopyridine N-oxide, yield
5.2 g (melting point 68°C) Example 5 In the reaction apparatus used in Example 3, 9.5 g of pyridine N-oxide, 8 g of sodium hydroxide, 3.2
g of tetra-n-butylammonium bromide, 3.2 g of elemental sulfur, 150 ml of toluene, 50
ml of pure water was added at the same time. The reaction solution was heated and stirred for 10 hours. After the reaction solution was cooled to room temperature, the aqueous layer was separated from the organic layer. The aqueous layer was made acidic with an aqueous hydrochloric acid solution and cooled with ice water. The crystallized product was separated by suction, and the separation and crystallization operation was repeated. Product: 2-
Mercaptopyridine N-oxide, yield 8.2g
(Melting point 68°C) Example 6 Into the reaction apparatus used in Example 1, 10.9 g of γ-picoline N-oxide, 4.0 g of sodium hydroxide,
1.3g of 18-crown-6, 3.2g of elemental sulfur,
150ml of toluene was added at the same time. The operations were the same as in Example 1. Product: 2-mercapto-4-methylpyridine N-oxide, yield
11.7g (melting point 59-60℃)

Claims (1)

[Claims] 1. In the presence of a phase transfer catalyst and a metal hydroxide,
In water, an organic solvent or a water-organic solvent, the general formula characterized by reacting the compound represented by with elemental sulfur, a sulfur-containing metal salt, a mercapto group-containing compound, or a mercapto group-forming compound,
general formula Nitrogen-containing aromatic 2-mercapto-N-
Method for producing oxide. In the above formula, R ¹ , R ² , R ³ , R ⁴ , and R ⁵ are the same or different and represent hydrogen, alkyl, or aryl,
R ⁴ and R ⁵ may be combined to form a benzene ring.