JPS5948821B2 - Production method of sulfoximine - Google Patents

Description

[Detailed description of the invention] The present invention relates to a method for producing sulfoximine.

More specifically, the present invention relates to a method for producing sulfoximine, which comprises oxidizing sulfuimine with permanganic acid or a salt thereof in the presence of a metal sulfate. When sulfoylimine is oxidized, for example, when hydrogen peroxide, benzoyl peroxide, etc. are used as the oxidizing agent, a large number of by-products such as sulfone and sulfoxide are produced.When nitric acid is used, sulfoximine is not obtained, but only sulfoxide is produced. .

Also, when potassium permanganate is used as an oxidizing agent,
There are many by-products such as sulfide, sulfoxide, and sulfone, making separation of sulfoximine very difficult, and in some cases, the desired sulfyl imine cannot be obtained at all.
Sulfoximine has excellent uses as, for example, medicines, agricultural chemicals, surfactants, various polymer additives, various synthetic intermediates, solvents, etc., and a good method for producing sulfoximine is desired.

As a result of extensive research into the oxidation of sulfuimine, the present inventors surprisingly found that upon permanganate acidification,
The present invention was completed by discovering that sulfoximine can be easily obtained in high yield by coexisting a metal sulfate.

Although the effects of metal sulfates are not necessarily clear, there is no doubt that they have some effect in suppressing deimination reactions. That is, the present invention provides the following formula: [In the formula, Rl and R2 optionally represent a lower alkyl group, a phenyl group, an alkyl-substituted phenyl group, an alkoxy-substituted phenyl group, or a nitro-substituted phenyl group, and R3 is hydrogen or a phenylsulfonyl group. , represents an alkyl-substituted phenylsulfonyl group.

] is characterized by oxidizing the sulfuimine represented by the following with permanganic acid or a salt thereof in the presence of a metal sulfate.

formula: [In the formula, Rl, R2, and R3 are the same as above.

] This is a method for producing sulfoximine. In the present invention, oxidation with permanganic acid or a salt thereof must be carried out in the presence of a metal sulfate. When a metal sulfate is not used in combination, a reductive deimination reaction mainly occurs at the same time, and a large amount of sulfide, sulfoxide, sulfone, etc. are produced as by-products. In particular, in the case of diarylsulfilimine having a substituent at the ortho position, only sulfide, sulfoxide, sulfone, etc. are obtained, and the desired sulfoximine is not obtained at all. However, according to the present invention, if a metal sulfate is used in conjunction with the oxidation of sulfuimine with permanganic acid or its salt, the conventional method cannot be obtained at all, or the yield is low, separation is not easy, and the operation is complicated. Hot sulfoximine can be easily obtained in good yield. The sulfuimine according to the present invention can be obtained, for example, by treating N-tosylsulfuimine produced by a reaction between sulfide and chloramine T with sulfuric acid, followed by alkali treatment.

In the present invention, R1 and/or R2 of the compounds represented by general formulas [1] and [] include, for example, a methyl group,
Saturated alkyl groups such as ethyl group, propyl group, butyl group, tert-butyl group, hexyl group, 2-ethylhexyl group, dodecyl group, vinyl group, 1-propedyl group, 4-hexenyl group, 9-pentadecenyl group, etc. Examples include unsaturated alkyl groups, cycloalkyl groups such as cyclopropyl groups and cyclohexyl groups, unsaturated cycloalkyl groups such as cyclohexenyl groups, and aryl groups such as phenyl groups and naphthyl groups.

Further, R1 and R2 may form a ring, and examples of the skeleton of the sulfur-containing cyclic compound in which R1 and R2 form a ring include thiolane,
Examples include thian, oxathian, 1,2-dihydrothionaphthene, benzothian, thiabicycloheptane, phenoxathin, phenothiazine, thioxanthene penicillin, cephalosporin, isothiazole, tetrahydroisothiazole, benzisothiazole, and the like.

R1 or/and R of compound [1] and [] according to the present invention
2 may be a substituted alkyl group, a substituted aryl group, or a substituted sulfuric acid-containing yellow cyclic compound, and examples of these substituents include:
In addition to hydrocarbon groups such as alkyl groups and aryl groups, examples include halogen, alkoxy groups, aryloxy groups, alkylthio groups, arylthio groups, nitro groups, cyano groups, acyl groups, and sulfonyl groups.

Examples of metal sulfates according to the present invention include alkali metal sulfates such as sodium sulfate and potassium sulfate, and alkaline earth metal sulfates such as calcium sulfate, magnesium sulfate, and barium sulfate.

Examples of permanganic acid or its salts include permanganic acid, alkali metal permanganates such as sodium permanganate and potassium permanganate, and permanganese such as calcium permanganate, magnesium permanganate and barium permanganate. Examples include acid alkaline earth metal salts.

The present invention can be easily implemented, for example, as follows.

Sulfuilimine, permanganic acid or its salt, and metal sulfate are mixed and reacted, for example, by heating and cooling or at room temperature. Permanganic acid or a salt thereof is usually preferably used in a stoichiometric amount or more relative to sulfuilimine, and metal sulfate is usually used in an equimolar amount relative to permanganic acid or a salt thereof. Examples of solvents that may be used if necessary include, for example, water, acetone, methanol, ethanol,
Tert-butanol, pyridine, chloroform, isooctane, benzene, petroleum ether, methylcyclohexane, etc. can be used without any problem, and may be used alone or in combination.

The reaction system may be a homogeneous system or a suspension system. After the reaction, it is optional to separate and purify according to conventional methods.

Some examples of sulfoximines obtained by the present invention are S,S-dimethylsulfoximine, S-methyl-S-propylsulfoximine, S-methyl-S-
Phenylsulfoximine, S-cyclopropyl-S-
Phenylsulfoximine, S-ethyl-S-cyclohexylsulfoximine, S-0-methoxyphenyl-S-ethylsulfoximine, S-ethyl-S-p-ethoxyphenylsulfoximine, S,S -diphenylsulfoximine, S-0-methylthiophenyl-S-
Phenylsulfoximine, S-0-methoxyphenyl-S-p-tolylsulfoximine, S-phenyl-S
-0-promophenylsulfoximine, S-phenyl-S-2,6-dichlorophenylsulfoximine, S
-Phenyl-S-p-cyanophenylsulfoximine, N-β-cyanoethyl-S-methyl-S-phenylsulfoximine, N-propyl-S,S-diphenylsulfoximis, N-β -methylsulfonylethyl-S
, S-diphenylsulfoximine, N-phenyl-S
-Methyl-S-phenylsulfoximine, S-methyl-S-benzylsulfoximine, ,N-methyl-S-
Phenyl-S-benzylsulfoximine, S-imino-S-oxythiane, S-imino-S-oxythionaphthene, S-imino-S-oxy-4,4-dimethylbenzo[b]thiane, 7-imino-J [oxy-J me[thiabicyclo[2,2,1]heptane, S-imino-S-oxy-4-chlorophenoxat, S-ethylimino-S
-Oxyphenothiazine, S-propylimino-S-oxythioxanthene, S-imino-S-oxypenicillin, S-imino-S-oxycephalosporin, S-oxyisoxazole, S-oxybenzo Isoxazole N-tosyl-S,S-dimethylsulfoximine, N
monotosyl-S,S-diphenylsulfoximine, N-
p-Bromobenzenesulfonyl-S-methyl-S-phenylsulfoximine, N-methylsulfonyl-S-ethyl-S-phenylsulfoximine, N-cyclohexylsulfonyl-S-methyl-S-p-chlorophenylsulfonyl xymine, N-acetyl-S,S-diphenylsulfoximine, N-chloroacetyl-S,S-diphenylsulfoximine, N-benzoyl-S-methyl-S-phenylsulfoximine, N- Benzoyl-S
-p-tosyl-S-phenylsulfoximine, S-p
-tosylimino-S-oxythiane, S-benzoylimino-S-oxytetrahydrothiophene, S-benzenesulfonylimino-S-oxyphenothiazine, S-
Examples include benzoylimino-S-oxythioxanthene.

As mentioned above, in the oxidation of sulfoylimine, sulfoximine, which conventionally produced many by-products, was not easy to separate, and the operation was complicated, and the yield was low or not obtained at all, can be easily and highly purified by the present invention. It is a major contribution to this industry, as it provides high yields and facilitates industrial implementation. EXAMPLES The present invention will be explained in more detail by referring to Examples and Comparative Examples below.

Example 1 Potassium permanganate 50f! in a solution of 209 diphenylsulfylimine/11 methanol! A solution of 500 ml of water and magnesium sulfate 409 was added, and the mixture was refluxed for 1 hour.

Separate the insoluble matter, pour into a line, extract with chloroform,
After washing and drying, chloroform is distilled off to obtain diphenylsulfoximine 219 (yield 100%). Recrystallize from benzene. MplO 4°C Comparative Example 1 A solution of 50 g of potassium permanganate/500 ml of water is added to a solution of 209 diphenylsulfilimine/11 methanol and refluxed for 1 hour.

After filtering out the insoluble matter, the solvent was distilled off to obtain diphenylsulfoximine 99 (yield 42.9%). Recrystallize from benzene. MplO4°C. R, elemental analysis was consistent with Example 1. Example 2 S-phenyl-S-p-tolylsulfoylimine 21.
59/methanol 11 solution, potassium permanganate 50f! and 500TfL of water with magnesium sulfate 409
Add 1 solution and reflux for 1 hour.

Separate the insoluble matter, pour into water, extract with chloroform,
After washing and drying, chloroform was distilled off and S-phenyl-
S-p-tolylsulfoximine 23. lfl (yield 1
00%). Benzene. more recrystallized. mplO
2°C Example 3 In a solution of 24.69 S-phenyl-S-p-nitrophenylsulfylimine/1 liter of methanol, 509% of potassium permanganate and 409% of magnesium sulfate were added to 509% of water.
Add Wll solution and reflux for 1 hour.

After removing the insoluble matter, pour it into water, extract with chloroform, wash, dry, and distill off the chloroform to obtain S-phenyl-S-p-nitrophenylsulfoximine 26.2
g (yield 95%). Recrystallize from benzene. mpl44℃ Example 4 Potassium permanganate 47 fl and magnesium sulfate 36
9 and dissolved in 1 liter of acetone-aqueous solution (3:1), (f)-S-0-methoxyphenyl-S-phenylsulfyl imine ([α]D-19C (C = 1.07; CHCI
,))239/acetone lOOd was added dropwise over 30 minutes and stirred at room temperature for 4 hours.

Add 1.5 liters of chloroform, filter out insoluble matter, and extract with 4H monohydrochloric acid aqueous solution. Ice and 50% caustic soda aqueous solution are added to the aqueous solution, and the mixture is made alkaline and extracted with chloroform. After washing with water and drying, the solvent was distilled off, and (4)-S-0
-methoxyphenyl-S-phenylsulfoximine 1
8.19 (yield 73%, [α]D+2.C (C=2.0
5:CHC23)) is obtained. Recrystallize from benzene-hexane. Comparative Example 2 A reaction was carried out in the same manner as in Example 4 without adding magnesium sulfate.

According to thin layer chromatography (silica gel, developing solvent: CHC23) of this reaction solution, S-phenyl-S-0-
Methoxyphenyl sulfide, S-phenyl-S-0-
Methoxyphenyl sulfoxide, S-phenyl-S-0
-AuthenticSa of methoxyphenyl sulfone
A spot appears at the position that matches the Rf value of mple,
No spot appeared at the position corresponding to the AuthenticSample0Rf value of S-phenyl-S-0-methoxyphenylsulfoquimine. Example 5 N-tosyl-S-methyl-S-p-tolylsulfoylimine 30.79 and magnesium sulfate 24f! and potassium permanganate 319 in an acetone-water mixed solution (3:l
) and reflux for 2 hours.

After removing insoluble matter, the reaction solution was poured into ice water and extracted with chloroform. After drying, the solvent was distilled off and N-tosyl-S
-Methyl-S-p-tolylsulfoximine 32.39
(100% yield). Recrystallize from ethanol.
mp140-141.5℃ without using magnesium sulfate,
When reacting similarly, N-tosyl-S-methyl-S-p
-The yield of tolylsulfoximine was 55%.

Example 6 32.39 N-tosyl-S-methyl-S-p-methoxyphenylsulfimine and 24 fl of magnesium sulfate
and potassium permanganate 319 were added to 500 ml of acetone-water mixed solution (3:l), and in the same manner as in Example 5, N-tosyl-S-methyl-S-p-methoxyphenylsulfoximine 33.99 ( 100% yield).

Recrystallize from ethanol. When the reaction was carried out in the same manner without using magnesium sulfate, the yield of N-tosyl-S-methyl-S-p-methoxyphenylsulfoximine was 5507).

Example 7 N-tosyl-S-ethyl-S-tolylsulfoylimine 32.19 and magnesium sulfate 24f! and potassium permanganate 319 in an acetone/water mixed solution (3:l
) and reacted in the same manner as in Example 5,
N-tosyl-S-ethyl-S-p-tolylsulfoximine 32.6S (yield 95 (:fl)) is obtained.

Recrystallize from acetone-n-hexane. Mp77
．． 5~78″CIR(KBr);v=1220,1
095,1110,1050CTrL-1 When the reaction was performed without using magnesium sulfate, the yield of N-tosyl-S-ethyl-S-p-tolylsulfoximine was 35%.

Example 8 N-tosyl-S,S-diphenylsulfuimine 35
．． 59 and magnesium sulfate 24f! and potassium permanganate 31f! and an acetone-water mixed solution (3:l) 5
00ml, and in the same manner as in Example 5, 35.3y of N-tosyl-S,S-diphenylsulfoximine (
A yield of 9501)) is obtained.

Recrystallize from acetone-n-hexane. Mpl3
5~136 CIR (KBr);・V=1245,11
15,1095,1070CTrL-1 When the reaction is performed without using magnesium sulfate, the yield of N-tosyl-S,S-diphenylsulfoximine is 35
It was %.

Claims (1)

[Claims] 1 Formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼[I][In the formula, R
^1 and R^2 optionally represent a lower alkyl group, phenyl group, alkyl-substituted phenyl group, alkoxy-substituted phenyl group, or nitro-substituted phenyl group, and R^3 represents hydrogen, a phenylsulfonyl group, or an alkyl-substituted phenylsulfonyl group. . ] A formula characterized by oxidizing a sulfuimine represented by the formula with permanganic acid or its salt in the presence of a metal sulfate: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [II] [In the formula, R^
1, R^2, and R^3 are the same as above. ] A method for producing sulfokiimine.