JPS58183667A - Preparation of methylthiomethyl aryl sulfone - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a reaction reagent in high yield, by reacting a fatty acid anhydride with dimethyl sulfoxide, and reacting the resultant reaction product with a sulfinate in the presence of a fatty acid. CONSTITUTION:A fatty acid anhydride of formula I (R<1> is lower alkyl) is reacted with dimethyl sulfoxide at 25-150 deg.C to give an acyloxymethyl sulfide of formula II, which is then reacted with a sulfinate of formula III (R<2> is aryl; M is alkali metal or alkaline earth metal) in the presence of a fatty acid, e.g. acetic acid, propionic acid or butyric acid, at 25-150 deg.C, preferably 80-150 deg.C, to afford the aimed substance of formula IV. The compound of formula III and the fatty acid are respectively used in amounts of one equivalent - excess based on the compound of formula II.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing methylthiomethylarylsulfone. More specifically, the present invention provides (1) a compound of the general formula r(R'co)orz) by reacting a fatty acid anhydride represented by the general formula (R'co)orz) [in which R1 represents a lower alkyl group] with dimethyl sulfoxide; [Additionally, 0H, 5CH2000Rrn] [In the formula, R1 represents a lower alkyl group]. OH,5OH2So2R2[Ml [In the formula, R2 is A method for producing methylthiomethylarylsulfone represented by general formula (3) [in which R1 represents a lower alkyl group] General formula (8) % Formula % (8) [In the formula, R2 represents an aryl group and M represents an alkali metal or alkaline earth metal] is reacted with a sulfinate salt represented by the formula (8) in the presence of a fatty acid. The present invention relates to a method for producing methylthiomethylarylsulfone represented by the general formula OH, 5OH2So2R2 [wherein R2 represents an aryl group] characterized by the following.

Methylthiomethyl 71J-rusulfone (hereinafter referred to as the present compound) represented by the above general formula (2) is useful as a reaction reagent in organic synthesis. It can be synthesized by reacting an ester with this compound.

Conventionally, the method for producing this compound is a method in which arylsulfonylacetone and S-methyl toluenethiosulfonate are reacted under basic conditions [Journal of the Chemical Society (J, Ohem, SoC, )]
1952, p. 1819], Substitution reaction of halomethylsulfone with methanethiolate anion [Journal Op the Chemica/L/-Society 4 (J, Ohem,
8oc, ) 0.1968, p. 2180], and the method of oxidizing a sulfone having a methylthio group at the α-position with potassium permanganate or alkaline hydrogen peroxide [Pulte/Of the Chemical Society's Nyabano (Bull, Chew Soc, Ja
p., vol. 55, p. 1414 (1980)] are known. However, when using these methods to produce the present compound, it may be difficult to obtain starting materials, or
This method was not industrially advantageous because it required many steps to synthesize the starting materials.

As a result of intensive research into an excellent new method for producing this compound, the present inventor obtained acyloxymethyl sulfide by reacting a fatty acid anhydride with dimethyl sulfoxide, and then combined this compound with a sulfinate and a fatty acid or its salt. The present invention was completed by discovering a method for producing methylthiomethylarylsulfone easily and in good yield by reacting it in the coexistence of .

In the present invention, the general formula [Eng] (R' 00) 20 (
Examples of R1 in the fatty acid anhydride represented by i') include lower alkyl groups such as methyl, ethyl, propyl and isopropyl groups, with methyl being preferred. In the reaction between fatty acid anhydride and dimethyl sulfoxide, the molar ratio is not limited, but an equivalent amount or an excess of either of them may be used. Although a solvent is not particularly required, an aprotic solvent such as benzene, toluene, xylene, chlorobenzene, chloroform, dioxane, tetrahydrofuran, etc. may be used.

The reaction temperature and time are not particularly limited and vary depending on the type of raw materials and solvent used; the reaction is slow at room temperature and can be accelerated by heating. The reaction temperature range is preferably 25 to 150°C. General formula Qrl OH,5OH2000R' which is a reaction product of a fatty acid anhydride of general formula rI) and dimethyl sulfoxide
(3) The acyloxymethyl sulfide represented by [in the formula, R1 represents a lower alkyl group] may be isolated by an operation such as distillation and then subjected to the next reaction, or it may be subjected to the next reaction without being isolated. You can continue until the next reaction.

General formula (2) R2SO2M [flO
R1 of the sulfinate salt represented by is an aryl group such as phenyl group, o-1-lyl group, m-tolyl group,
p-tolyl group, 0-ethylphenyl group, m-ethylphenyl group, p-ethylphenyl group, xylyl group (the position of the R substituent may be any), O-chlorophenyl group, m-
Examples include chlorophenyl group, p-chlorophenyl group, α-naphthyl group, β-naphthyl group, and M includes alkali metals or alkaline earth metals, such as potassium, sodium, calcium, and the like. Examples of fatty acids coexisting in the reaction between acyloxymethyl sulfide and sulfinate include acetic acid, propionic acid, and butyric acid, but acetic acid is preferred because of its high reaction yield and availability at low cost. preferable. The molar ratio when reacting in the presence of acyloxymethyl sulfide, sulfinate, and all fatty acids is not particularly limited, and the sulfinate and fatty acid are each used in an amount of 1 equivalent or in excess relative to the acyloxymethyl sulfide. Good.

Although the reaction temperature and time are not limited, the reaction temperature is preferably 25 to 150°C, particularly 80 to 150°C. In this reaction, the yield can be improved by adding an alkali metal salt or an alkaline earth metal salt of a fatty acid.

The compound according to the present invention has the general formula [0HSSOH2130]
In order to isolate the methylthiomethylarylsulfone represented by 2R2(t) [wherein R2 represents an aryl group] from the reaction product, conventional separation and purification operations such as extraction, washing, drying, concentration, and column chromatography are performed. The manufacturing method according to the present invention will be explained in more detail by way of all examples below, but the present invention is not limited thereto.

Example 1 Dimethyl sulfoxide 6.808 f (87,14 m
A mixture of m1) and acetic anhydride 1 t 942 f (117, O plate o1) was heated and stirred at 80° C. for 24 hours. After that, the temperature was returned to room temperature, and acetic acid 80- was added, followed by sodium p-toluenesulfinate 2300f (129,2
mmol) f was added, and the mixture was heated and stirred at 100°C for 26 hours. After the reaction is complete, add 50rnt of dichloromethane and 10rnt of water.
0+nl'z added. Dichloromethane (50rntX4
), the organic layer was washed with water (200me x 6),
It was dried with anhydrous sodium sulfate. After filtration, it was concentrated under reduced pressure, and the residue was recrystallized from 95% ethanol. 40517 (18.75 mmol) of colorless needle-like crystals were obtained. The mother liquor was again concentrated under reduced pressure and separated by column chromatography (silica gel, 1: hexane, 2: benzene) to give methylthiomethyl p-) IJ sulfone at 6,715
S' (51.04 mmol) was obtained.

The total yield was 57.

o mp 82-83°C ONMR (CDOl, ): δ 2.29 (5H,S
, -Careful, )2.46(5H,S, -5o4cdi)0
Engineering R (KBr): 1295.1160.1117.10
80.740. '542°507(B''-' Example 2 Dimethyl sulfoxide 8.7621i'(112,1m
mol ) and anhydrous vinegar fil 17.92 f (175
, 5 mnol) at 80°C for 5 h followed by 1 at room temperature.
The mixture was stirred for 2 hours, and further stirred for 4 hours at 90°C on an oil bath. Then, under water cooling, p-) Sodium luenesulfinate 52
．． 0 Of (179,8 mmol) i added, 80
The mixture was stirred at 90°C for 19 hours and then at 90°C for 48 hours. After the reaction was completed, dichloromethane IGO mg and 100 mg of water were added, extracted with dichloromethane (5o+ntx4), and the organic layer was washed with water (200dx5) and dried over anhydrous sodium sulfate. After passing through the mouth, it was concentrated under reduced pressure and recrystallized with 95% ethanol to give 5.2245' (24.15 mmol
) crystals were obtained. The mother liquor was again concentrated under reduced pressure and separated by column chromatography (silica gel, 1: hexane, 2: benzene, 6: ethyl acetate), and 5.812 f (17, 62 mmo
l) Obtained. The total yield was 67.

Example 3 Dimethyl sulfoxide 9.247 f (0,1184
A mixture of 15.60 f (0,1528 mol) of acetic anhydride and 15.60 f (0,1528 mol) of acetic anhydride was heated and stirred at 80° C. for 24 hours.

After that, return to room temperature and add 90 n1t of acetic acid, 9.7 mol of IJ [109 (0,1182 mol) and p-)
51.60 f (0°11-1775 moles) of sodium luenesulfinate were added. The mixture was heated and stirred on an oil bath at 100°C for 26 hours.

After the reaction was completed, dichlorometh/70rn1. and water 150m
ef added. Extraction was performed with dichloromethane (70 d×4), and the organic layer was washed with water (150 d×4) and dried over anhydrous sodium sulfate. Concentrate under reduced pressure to obtain pale milky yellow crystals 27.
20 f was obtained. Recrystallization was performed with 95% ethanol (approximately 200ml) to obtain 13.507f of colorless needle-like crystals.

The mother liquor was again concentrated under reduced pressure and separated by column chromatography (silica gel, 1:hexane, 2:benzene 7.3:6 ethyl acetate) to give methylthiomethyl p-)lylsulfo/
4.8854 S' (0,02258 mol) was obtained.

The total yield was 71 cm.

Example 4 Dimethyl sulfoxide t D 63 ? (1s, 6
1 mmol) and acetic anhydride 2.580 ? (18, 29
The mixture of mm01) and 12- was heated and stirred at 80°C for 24 hours.

After that, the temperature was returned to room temperature, 20 ml of acetic acid was added, and then 5.550 f (20,4
1 mmol) was added thereto, and the mixture was heated and stirred at 100° C. for 48 hours. After the reaction was completed, 2Qmt of dichloromethane and 50g of water were added. The organic layer was extracted with dichloromethane (40 dX4), washed with gold water (100 dXl), and dried with anhydrous sodium sulfate. After filtration, the mixture was concentrated under reduced pressure and separated using Kara"P40 mudgraphy (silica gel, 1:hexane, 2:benzene) to obtain 0.685 rtl" of white crystals. 9 of these crystals
Recrystallization was performed using 5-diethanol to obtain colorless needle-like crystals.

The yield was 0.685 f (3!186 mmol) and the yield was 25 g.

0 colorless needle crystals o mp 86.5-87.5°C ONMR (CDC13): δ 2.52 (i
, S, -8 animals, ) 7.48-8.09 (5H, m,
06H-EI02- )o IR(KBr) 1
292,1160. (1116), 1080,741°544, 520U''-1 Example 5 Dimethyl sulfoxide 1.275 r (16,29m
nn1) and propionic anhydride 2.840 y (21,8
A mixture of 2 mmol) was heated and stirred on an oil bath at 80° C. for 24 hours. After that, the temperature was returned to room temperature, and 20-propionic acid was added, followed by 4.5% p-) sodium luenesulfinate.
50? (24.44 mmol) and put it on an oil bath.
The mixture was heated and stirred at 00°C for 48 hours. After the reaction was completed, 40 g of dichloromethane and 40 me of water were added. Dichloromethane (40mtX4)? Extract and wash the organic layer with water (15
0-X3)t.

It was dried with anhydrous sulfuric acid (IJum). After filtration, it was concentrated under reduced pressure and separated by column chromatography (silica gel, 1: hexane, 2: benzene) to give white crystals of 0.51%.
I got 8ft. The yield was 0518y (2395 mmol), which was 15%.

Example 6 Acetoxymethyl methyl sulfide 2.2 to 20 m acetic acid
749 (18,92 mmol) and p-tol x sodium sulfinate 5.061? (28,45mm
ol)k was added at room temperature, and the mixture was heated and stirred at 100°C for 2 days. After the reaction is complete, add 40d of dichloromethane and 40r of water.
nt'i added. The organic layer was extracted with dichloromethane (40 mg x 4), washed with gold water (150 d x 3), and dried over anhydrous sodium sulfate.

After filtration, it was concentrated under reduced pressure and separated using column chromatography 15- (silica gel, 1: hexane, 2: benzene, 3: ethyl acetate) to give methylthiomethyl p-tolylsulfo/2.665? (12,51 mmol) was obtained. The yield was 65 cm.

0 colorless needle crystals mp82-85°C Patent applicant: Nissan Chemical Industries, Ltd. 16-

Claims (2)

[Claims] (1) A fatty acid anhydride represented by the general formula (x) (R'(10)20 rI) [wherein R1 represents a lower alkyl group], dimethyl sulfoxide, and t
The siloxymethyl sulfide represented by the general formula 0H8S 0H7OOOR (TfJ [in the formula, R1 represents a lower alkyl group] is obtained by crushing the ashes, and then the compound and the general formula (6) % formula % [ [in the formula, R2 is aryl] group, M represents an alkali metal or alkaline earth metal] with a sulfinate represented by the following in the presence of a fatty acid: Method for producing methylthiomethylarylsulfone represented by (2) General formula (4) % formula % [ [In the formula, R1 represents a lower alkyl group] Acyloxymethyl sulfite represented by the general formula (2
) A general method characterized by reacting a sulfinate salt represented by the formula % [110 [in the formula, R2 represents a ryoyl group and M represents an alkali metal or alkaline earth metal] in the coexistence of a fatty acid. Method for producing methylthiomethylarylsulfone represented by the formula (g) OH,5OH2802R2rrv) [wherein R2 represents an aryl group]