JPH0421659B2 - - Google Patents

Description

[Detailed description of the invention]

TECHNICAL FIELD The present invention relates to novel sulfonium derivatives. Object and Structure of the Invention The sulfonium derivative of the present invention is represented by the following general formula (). [In the formula, R ₁ and R ₂ are the same or different and represent a lower alkyl group. _R3 is

[Formula] (Fueni ruthio group),

[Formula] (Phenyl sulfonylamino group),

[Formula] enylsulfinyl group),

[Formula] (phenylsulfonyl group),

[Formula] (benzoylamino group),

[Formula] (carboxyben zoylamino group),

[Formula] (phthalimide group), (Rx represents a lower alkoxy group) (lower dialkoxycinnamoylamino group) or

[Manufacturing method A]

General formula R ₁ S(CH ₂ ) _o −R ₃ () [In the formula, R ₁ , R ₃ and n are the same as above. ] A sulfide compound represented by the general formula R ₂ Y ( ) [wherein R ₂ and Y are the same as above. ] React with the compound represented by. This method is preferred, and the above reaction is carried out in a solvent or without a solvent at -30 to 150°C, preferably at 0.
The reaction time is about 0.5 to 72 hours at ~100°C.
Although the compound () may be used in an excess amount relative to the sulfide compound (), it is preferably used in an amount of about 1 to 4 times the theoretical amount. Examples of solvents include alcohols such as methanol, ethanol, and propanol; polar solvents such as acetonitrile, nitromethane, dimethylformamide, and dimethyl sulfoxide; halogenated hydrocarbons such as methylene chloride and chloroform; benzene, toluene,
Aromatic hydrocarbons such as xylene, ethers such as ethyl ether and propyl ether, acetone, petroleum ether, ethyl acetate, water, and mixed solvents of these solvents can be used. The reaction can be carried out in a closed container if necessary. In the above reaction, the sulfide compound ( ) used as a raw material has, for example, the general formula Hal-(CH ₂ ) _o -R ₃ ( ) [wherein R ₃ and n are the same as above. Hal indicates a halogen atom. ] A compound represented by the general formula R ₁ SH ( ) [wherein R ₁ is the same as above. ] It is synthesized by reacting the compound represented by the following in a solventless or appropriate solvent at a temperature of about 0 to 200°C. The synthesis reaction is preferably carried out in the presence of a basic compound, such as an alkali metal such as sodium or potassium, a hydride thereof, or a hydroxide thereof. Details of the synthesis of the above sulfide compound () will be described in Reference Examples below. [Manufacturing method B] General formula [In the formula, R ₁ , R ₂ , R ₃ and n are the same as above. X represents a halogen atom. ] A sulfonium halide represented by the general formula ZY ₁ ( ) [wherein Z represents a silver atom or an alkali metal atom. Y ₁ represents an acid residue other than the halogen atom represented by X above. ] React with the compound represented by. This method is also preferred, and utilizes the salt exchange reaction of sulfonium halide () (in the compound represented by the general formula () of the present invention, Y represents a hydrohalic acid residue). be. The raw material compound () is produced according to the above production method A. The sulfonium halide () can be used in this reaction in the form of a reaction mixture without being isolated from the reaction system shown in Production Method A. Of course, it can also be used after being isolated and purified from the reaction system. The compound () to be reacted with the above sulfonium halide () is Y in the general formula () of the present invention.
Silver salts or alkali metal salts of each acid capable of providing acid residues corresponding to, for example, sodium salts, potassium salts,
Lithium salt etc. can be used. Examples of the above acids include hydrogen chloride, hydrogen bromide, hydrogen iodide, perchloric acid,
Inorganic acids such as tetrafluoroboric acid, maleic acid, malonic acid, lactic acid, camphorsulfonic acid, methanesulfonic acid, tosylic acid, picrylsulfonic acid, 1,5-
Examples include organic acids such as naphthalene disulfonic acid. This salt exchange reaction is carried out in a solvent at about -30 to 150°C, preferably about 0 to 100°C. Compound()
is preferably used in an amount of about 1 to 4 times the theoretical amount based on the sulfonium halide (). As the solvent, any of the same various solvents used in the reaction of production method A above can be used. [Production method C] The same sulfonium halide () as shown in the above production method B, silver oxide and the general formula HY ₁ () [in the formula, Y ₁ is the same as above. ] React with the compound (acid) represented by: This method also utilizes the salt exchange reaction of sulfonium halide (), and the compound () is a free form capable of providing the acid residue represented by Y in the compound represented by the general formula () of the present invention. Use organic or inorganic acids. Specific examples of these acids are as shown in Production Method B above. In this reaction, silver oxide can be used in a molar ratio of usually at least equimolar, preferably about 1 to 4 times, relative to the sulfonium halide () used as a raw material. The proportion of the compound () to be used is at least equimolar to the sulfonium halide (), preferably about 1 to 1.
A 4-fold molar ratio is preferable. This reaction is usually carried out in a solvent at about -30 to 150°C, preferably about 0 to 100°C. The solvent may be the same as that used in Production Method A above. The sulfonium compound () of the present invention obtained according to the above production methods A to C can be isolated according to a conventional separation method after the reaction is completed. As the separation method, for example, a recrystallization method, an extraction method, a concentration method, a column chromatography, etc. can be adopted. EXAMPLES Next, in order to further explain the present invention, a production example of a sulfide compound () used as a raw material will be given as a reference example, and then a production example of the compound of the present invention will be given as an example. Reference example 1 Synthesis of methyl-2-phenylthioethyl sulfide 90% ethanol 200ml and sodium hydroxide
4.00g absorbs 4.81g of methyl mercaptan. 2-phenylthioethyl chloride under ice cooling
After dropping 17.3g, reflux for 30 minutes. The reaction solution was concentrated, and the residue was extracted with ether. After washing the ether layer with water, it is dehydrated and concentrated. The residue was distilled under reduced pressure to obtain 17.0 g (yield 92.4%) of methyl-2-phenylthioethyl sulfide. b _p ． 112℃/2mmHg Reference Example 2 Synthesis of 2-(4-carboxybenzoylamino)ethylmethylsulfide 300ml of 50% ethanol and sodium hydroxide
Absorb 4.81 g of methyl mercaptan in 8.00 g. After adding 27.2 g of 2-(4-carboxybenzoylamino)ethyl bromide, the mixture was refluxed for 2 hours. Concentrate the reaction solution and bring the residue to pH=1. The precipitated crystals were collected and recrystallized from acetonitrile to give 2-(4-carboxybenzoylamino).
Ethyl methyl sulfide 2.10g (yield 87.9%)
get. mp237～240℃ Reference example 3 2-(3,4-dimethoxycinnamoylamino)
Synthesis of ethyl methyl sulfade 4.81 g of methyl mercaptan is absorbed into 200 ml of ethanol and 5.61 g of potassium hydroxide. 2-
After adding 27.0 g of (3,4-dimethoxycinnamoylamino)ethyl chloride, the mixture was refluxed for 3 hours. The reaction solution was concentrated, and the residue was extracted with ethyl acetate. After washing the ethyl acetate with water, dehydrate the sodium sulfate and concentrate. Recrystallized from ethanol to obtain 2-(3,4-
27.0 g (yield 96.1%) of dimethoxycinnamoylamino)ethylmethylsulfide is obtained. Example 1 Synthesis of dimethyl-2-phenylthioethylsulfonium p-toluenesulfonate (compound 1) Methyl-2-phenylthioethylsulfide
Methyl p-toluenesulfonate 5.58 in 1.84g
g and react at room temperature for 48 hours. Ether is added to the reaction mixture, and the insoluble portion is separated and recrystallized from ethanol-ether to obtain 3.50 g (yield: 94.3%) of dimethyl-2-phenylthioethylsulfonium p-toluenesulfonate (Compound 1).
mp118-119℃ Example 2 Tables 1 and 2 below were obtained by the same operation as in Example 1.
Compounds 2, 3, 5, 6, 7 and 9 shown in were synthesized. Example 3 2-(3,4-dimethoxycinnamoylamino)
Synthesis of ethyldimethylsulfonium p-toluenesulfonate (compound 8) Dissolve 2.81g of 2-(3,4-dimethoxycinnamoylamino)ethylmethylsulfide in 30ml of dichloromethane, add 7.00g of methyl p-toluenesulfonate, and heat at room temperature. Incubate for 48 hours. After adding ether to the reaction solution, the same procedure as in Example 1 was carried out to obtain 4.25 g of 2-(3,4-dimethoxycinnamoylamino)ethyldimethylsulfonium p-toluenesulfonate (Compound 8) (yield 90.8).
%). Example 4 Synthesis of dimethyl-2-phenylsulfonylethylsulfonium p-toluenesulfonate (compound 4) 2.16 g of methyl-2-phenylsulfonylethylsulfide and 50 ml of acetonitrile were mixed with 4.26 g of methyl iodide, then p-toluenesulfone. Add 2.79 g of silver acid and stir at room temperature for 12 hours. The reaction solution is filtered, and hydrogen sulfide and activated carbon are added to the solution. The liquid was concentrated and recrystallized from ethanol-ether to obtain 3.85 g (yield 95.5%) of dimethyl-2-phenylsulfonylethylsulfonium p-toluenesulfonate (compound 4).
mp147-148℃ Compounds obtained in each of the above examples (compounds 1 to 1)
The structure of 9) is shown in Table 1, and the yield (%), mp (°C), elemental analysis value, and nuclear magnetic resonance spectrum (NMR) analysis result (δ value, ppm) of each compound are shown in Table 1. Shown in 2. In Table 2, the values shown in parentheses in the elemental analysis values are calculated values (%), and the values shown without parentheses are actually measured values (%). Also, NMR
This is a value measured in DMSO- _d6 using TMS as an internal standard.

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Claims (1)

[Claims] 1. General formula [In the formula, R ₁ and R ₂ are the same or different and represent a lower alkyl group. _R3 is (Rx represents a lower alkoxy group.) Or represents [Formula]. n represents an integer of 1 to 3. Moreover, Y represents an acid residue. ] A sulfonium derivative represented by.