JPH053872B2 - - Google Patents

Description

[Detailed description of the invention]

[Field of Application of the Invention] The present invention relates to a novel method for producing sulfinate salts useful as pharmaceuticals, agricultural chemicals, and other synthetic raw materials or synthetic intermediates. [Background of the Invention] Many attempts have been made to synthesize sulfinic acid. For example, oxidation of thiol, reduction of sulfochloride with zinc powder or sodium amalgam, sulfite, sodium sulfide, potassium hydrosulfide, etc. (Schiller and Otto, Ber., 9 ,
1586 (1876); Otto, Ann., 142 , 93 (1867);
Blomstrand, Ber., 3 , 965 (1870); Meister,
Lucius, and Bruning, Ger.patent.224, 019;
Fromm and Erfurt, Ber., 42 , 3821 (1909)
etc.), a method of reacting aromatic compounds with sulfite in the presence of aluminum chloride (E. Knoevenagel, J.
Kenner, Chem. Ber., 41 , 3315 (1908)), method by reaction of Grignard reagent with dry sulfur dioxide (HG Houlton and HVTartar, J. Am. Chem.
Soc., 60 , 544 (1938)), a method of reacting diazonium salt with sulfite in the presence of copper powder (L.
Gatterman, Chem. Ber., 32 , 1136 (1899)), but there are few examples of synthesis of alkylsulfinic acids, and the yield is not good. In addition, the present inventors have recently discovered that the sulfonyl group in 2-alkyl and 2-arylsulfonylpyridines can be quantitatively substituted with various nucleophiles, and in this reaction, They also discovered that the leaving group sulfonyl group can be obtained as a sulfinate. However, when using 2-substituted sulfonylpyridine as the reaction substrate, as shown in Table 1,
When 3 equivalents of alkoxide were reacted with the substrate, the reaction was completed in 15 minutes, but when 1 equivalent was reacted, when R = ph, the reaction required 19 hours under reflux to complete. .

[Purpose of the invention]

The present invention was made in view of the above-mentioned current situation, and aims to provide a novel and extremely useful method for producing organic sulfinates, which can yield sulfinates quantitatively in a short period of time. purpose. [Structure of the invention] The present invention is based on the general formula

【formula】 (I) or

〔Example〕

Reference Example 1 500 ml of ethanol was added to 50 g (0.336 mol) of 2-sodiumsulfenylpyridine N-oxide and dissolved under heating. This is benzyl bromide
40 ml (0.337 mol) was added, and the mixture was stirred and reacted under reflux for 10 minutes. After the reaction was completed, ethanol was distilled off, extracted with methylene chloride, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. By recrystallizing the residue from ethanol, 70.0 g of 2-benzylsulfenylpyridine N-oxide (yield 96.2
%) was obtained. mp173-174℃. The following compound was obtained by the same experimental procedure.

【table】

[Table] Reference example 2 1.6g of metallic sodium in 100ml of ethanol
(69.3 mmol) was added and dissolved with stirring. This is t-
After adding 9.4 ml (83.2 mmol) of butylthiol and stirring for 10 minutes, 10 g (57.8 mmol) of 2-methylsulfonylpyridine N-oxide was added, and the mixture was stirred and reacted under reflux for 15 minutes. After the reaction was completed, the solvent was distilled off, extracted with methylene chloride, and dried over magnesium sulfate.
The solvent was distilled off under reduced pressure. The residue was purified by column chromatography [activated alumina (200mesh) manufactured by Wako Pure Chemical Industries, Ltd., eluent benzene → ethanol] to obtain 9.034 g of 2-t-butylsulfenylpyridine N-oxide ( yield 85.4%)
I got it. Reference Example 3 20.37 g (81.3 mmol) of 2-benzylsulfenylpyridine N-oxide was dissolved in 50 ml of methylene chloride. To this, 23.5 g (82 mmol) of mCPBA dissolved in 1 liter of methylene chloride was added dropwise with stirring. After stirring for 1 hour, add the same amount of mCPBA and K ₂
11.2g (81mmol) of CO ₃ was added and stirred for 1 hour (this oxidation reaction was carried out from the beginning without dividing into two stages).
mCPBA 47g (164mmol), _{K2CO3 11.2g} (81mmol)
The same result can be obtained even if the reaction is carried out with stirring for 2 hours. ). After the reaction is complete, the precipitated m-chlorobenzoic acid (mCBA) is removed by suction, and the liquid is added with _NH3.
After neutralizing by blowing gas, it was filtered again to remove impurities. After drying the liquid with magnesium sulfate,
The solvent was distilled off under reduced pressure to obtain 23 g of a crude product. Add this to a shoot column [activated alumina (200mesh) manufactured by Wako Pure Chemical Industries, Ltd., eluent methylene chloride → ethanol]
2-benzylsulfonylpyridine-N oxide (yield: 18 g).
77.2%). mp131.5~132.5℃. The following compound was obtained by the same experimental procedure.

[Table] Example 1 23 g (1 mol) of sodium metal was dissolved in 1 liter of ethanol to prepare an ethanol solution of sodium ethoxide (concentration 1 mol/l). 2-Phenylsulfonylpyridine N-oxide 10.94g (47mmol)
Add 200ml of ethanol to the above EtONa/EtOH
47 ml of the solution was added, and the mixture was stirred and reacted under reflux for 15 minutes.
The solvent was distilled off, and methylene chloride was slowly added to this while cooling to crystallize it, and this was collected to obtain 6.8 g of phenylsulfinate sodium salt (yield: 88%).
I got it. ^1H -NMR of the obtained sulfinate
No ethyl group peak appears in the spectrum.
I confirmed that it was not a mixture. IR (KBr): ν1020, 970cm ^-1 . In addition, from the methylene chloride solution which is the filtrate, 2
-Ethoxypyridine N-oxide was obtained quantitatively. In addition, for further confirmation, the following alkylation experiment of the obtained sulfinate was carried out. That is, the obtained sulfinic acid was dissolved in ethanol.
It was dissolved in a mixed solvent of 100 ml and water, 50 ml of methyl iodide was added, and the mixture was stirred overnight. The organic layer was extracted with methylene chloride and washed with 0.5N _{aqueous Na2S2O3} and _water . After drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was recrystallized from ethanol to obtain phenylmethylsulfone (yield 68%). mp88.5~89.5℃. The following compound was obtained by the same experimental procedure. In each case, 2-ethoxypyridine N-oxide was quantitatively obtained from the liquid.

[Table] phCH ₂ SO ₂ Na NMR (D ₂ O): δ 7.36, 4.68, 3.63 ppm. IR (KBr): ν 1030, 1000~990cm ^-1 . ( _CH3 ) _2CHSO2Na NMR ( _D2O ): δ 4.71, 1.10, _0.99ppm . IR (KBr): ν 1010, 975cm ^-1 . _CH3 ( _CH2 ) _7SO2Na NMR ( _D2O ): δ 4.69, 1.30 _, 0.85ppm. IR (KBr): ν 1015cm ^-1 . ( _CH3 ) _{3CSO2Na NMR} ( _D2O ): δ 4.69, 0.98ppm. IR (KBr): ν 1025cm ^-1 . Example 2 Instead of 10.94 g (47 mmol) of 2-phenylsulfonylpyridine N-oxide in Example 1,
2-allylsulfonylpyridine N-oxide
Using 9.36g (47mmol), the reaction and post-treatment were carried out in the same manner as in Example 1, and CH ₂ =CHCH ₂ SO ₂ Na
3.19 g (yield 53%) and this rearrangement product CH ₃
-CH= _CHSO2Na2.11g (yield 35%) was obtained. Example 3 2-Phenylsulfonylpyridine N-oxide
Dissolve 11.64g (50mmol) in 200ml of ethanol,
2 g of sodium hydroxide powder was added to this, and the mixture was stirred and reacted under reflux for 15 minutes. The solvent was distilled off, and methylene chloride was slowly added to this while cooling to cause crystallization, and the mixture was taken to obtain 7.47 g (yield: 91%) of phenylsulfinate sodium salt. Furthermore, 2-ethoxypyridine N-oxide was quantitatively obtained from the methylene chloride solution which was the filtrate. Example 4 2-Phenylsulfonylpyridine N-oxide
200 ml of acetonitrile was added to 11.63 g (50 mmol), 2 g of potassium hydroxide powder was added thereto, and the mixture was stirred and reacted under reflux for 15 minutes. The solvent was distilled off, and while cooling, methylene chloride was slowly added to crystallize the product, which was collected to obtain 8.65 g (yield: 96%) of phenylsulfinate potassium salt. Similar results were also obtained when the above experiment was conducted in methylene chloride instead of acetonitrile. Example 5 Instead of the ethanol solution of sodium ethoxide (concentration 1 mol/l) in Example 1, an ethanol solution of sodium thiomethoxide (concentration 1 mol/l) was used.
The reaction and post-treatment were carried out in the same manner as in Example 1, and the following results were obtained.

〔Effect of the invention〕

As described above, the present invention provides pharmaceuticals, agricultural chemicals,
The present invention provides a new and extremely useful method for producing organic sulfinates useful as synthetic raw materials or synthetic intermediates for various other organic compounds, and 2-
(or 6-) or 4-substituted sulfonylpyridine N
- An invention that has a remarkable effect in that the desired sulfinate can be obtained easily, quantitatively, and in an extremely short time by reacting an oxide and a nucleophile under anhydrous conditions. This is an extremely significant invention that contributes to this industry. In addition, the N-oxide derivative obtained as a by-product of sulfinate in the method of the present invention can be easily reduced to a pyridine derivative, so it is very useful for introducing substituents onto the pyridine ring. Therefore, the present invention is also interesting as a new method for producing pyridine derivatives.

Claims (1)

[Claims] 1 General formula [Formula] (I) or [Formula] (wherein R ¹ and R ² are an alkyl group, a cycloalkyl group, a substituted cycloalkyl group, a vinyl group, an allyl group, a substituted vinyl group) , substituted allyl group, aryl group,
Indicates a substituted aryl group, aralkyl group, substituted aralkyl group, heterocyclic group, and substituted heterocyclic group. Also, X ¹
~X ⁴ and Y ¹ to ^{Y 4} are each hydrogen, an alkyl group, an aryl group, an alkoxy group, an aryloxy group, a thioalkoxy group, a thioaryloxy group,
It represents an amino group, a cyano group, a hydroxyl group, a carbonyl group, a sulfone group, or a halogen, and furthermore, X ¹ , X ³ , and Y ² , Y ³ may be a sulfonyl group or a sulfinyl group. 2-(or 6-) or 4-substituted sulfonylpyridine N-oxide derivative represented by (represents a thiocyano group; M represents an ^alkali metal ion), characterized in that it is reacted with a _nucleophile represented by ^the following _formula :
() (In the formula, R ¹ , R ² and M are the same as above.) A method for producing an organic sulfinate salt represented by the following formula.