JPH0414663B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention is based on the general formula () (In the formula, R represents an aryl group, an aralkyl group, a pyridyl group, a 2-thiazolyl group, a 2-benzothiazolyl group, a 2-benzimidazolyl group, a 2-benzooxazolyl group, or a 6-purinyl group, and n is 0
or represents an integer of 1. ) and a method for producing the same. Allyl sulfide represented by the general formula () provided by the present invention is useful as a synthetic intermediate for terpene compounds such as vitamin A used as medicines and feed additives, as described below. [Prior Art] Conventionally, it is known that vitamin A is produced by the following method. [In the formula, Ac represents an acetyl group; Helvetica
See Chemica Acta, 30 , 1911 (1947)] [In the formula, Ph represents a phenyl group, X represents a halogen atom, and Ac represents an acetyl group;
See Chemie Ingeniuor Technik, 45 , 646 (1973)] [In the formula, Ph represents a phenyl group, Ac represents an acetyl group, and _tBu represents a t-butyl group;
Refer to Bull.Soc.Chim.Fi.746 (1973) No. 2] [Problems to be solved by the invention] The above method () requires a large number of steps, especially the catalyst used in the step of partial hydrogenation of acetylene bonds. In order to prevent the poisoning of vitamin A, it is necessary to purify the raw material acetylene diol, and in order to obtain highly pure vitamin A, the product C ₂₀ of the partial hydrogenation reaction must be purified.
It is not necessarily a simple method, as it involves extremely complicated steps such as the necessity of purifying the diol, and requires highly skilled techniques for the partial hydrogenation reaction itself. In addition, method () and method () use expensive reactants such as triphenylphosphine and alkali metal salts of phenylsulfinic acid, respectively, and it is complicated to recover and reuse these reactants. Regeneration, separation and recovery operations are required. Therefore, one object of the present invention is to provide a novel compound that can be easily produced in good yield from inexpensive and easily available industrial raw materials, and that is easily derived from vitamin A and the like. Another object of the invention is to provide a method for producing the new compounds. [Means for solving the problems] According to the present invention, the above object is achieved by providing an allyl sulfide represented by the general formula (), and also by providing an allyl sulfide represented by the general formula (). (wherein, n is as defined above) and a thiol of the general formula () RSH () (wherein, R is as defined above) in the presence of an acid. This is achieved by providing a method for producing allyl sulfide represented by the general formula (), which is characterized by reacting with. R in the above general formula will be explained in detail. R
is an aryl group such as phenyl group, biphenyl group, naphthyl group, anthryl group, phenanthryl group;
Aralkyl groups such as benzyl group and phenethyl group;
Represents a pyridyl group, 2-thiazolyl group, 2-benzothiazolyl group, 2-benzimidazolyl group, 2-benzooxazolyl group or 6-purinyl group.
Among these groups, groups having a benzene ring include those in which the benzene ring is methyl, ethyl, i-propyl,
Lower alkyl groups such as n-propyl, i-butyl, n-butyl; halogen atoms such as fluorine, chlorine, bromine, iodine; or methoxy, ethoxy, i-
propoxy, n-propoxy, i-butoxy, n
It may be substituted with one or more lower alkoxy groups such as -ptoxy. The acid to be present in the reaction system in the reaction of the allyl alcohol represented by the general formula () and the thiol represented by the general formula () according to the present invention is an acid having the ability to protonate the allyl alcohol, and representative examples thereof Examples include organic carboxylic acids such as formic acid, acetic acid and propionic acid; mineral acids such as hydrochloric acid and sulfuric acid. The amount of acid used may generally be a catalytic amount. For example, when the reaction is carried out at room temperature using sulfuric acid, the reaction proceeds by using about 1 mol % of sulfuric acid with respect to the allyl alcohol represented by the general formula (). The amount of the thiol represented by the general formula () is determined in order to improve the conversion rate of the allyl alcohol represented by the general formula () and to increase the yield of the target allyl sulfide represented by the general formula (). It is preferable that the amount is equal to or more than the molar amount relative to the alcohol. The reaction is usually about -
It is carried out within a temperature range of 50℃ to 150℃, and nitrogen,
It is advantageous to carry out under an inert gas atmosphere such as helium or argon. This reaction also reacts with hydrocarbons such as hexane, heptane, benzene, and toluene; alcohols such as methanol and ethanol;
Ethers such as ethyl ether, tetrahydrofuran, dioxane; methyl acetate, ethyl acetate,
dimethylformamide, N-methylpyrrolidone,
It can also be carried out in organic solvents such as hexamethylphosphoryltriamide. The reaction time varies depending on the raw materials used, the acid, the reaction temperature, etc., but for example, when using β-vinylonol and 2-mercaptopyridine as the raw materials and acetic acid as the acid and carrying out the reaction at room temperature, the reaction time is approximately 50%. It's time. The allyl sulfide represented by the general formula () obtained by the above reaction can be separated and recovered by a conventional method. For example, if the reaction mixture is water,
After pouring into an aqueous solution of sodium carbonate, etc., extract with benzene, hexane, ethyl acetate, diethyl ether, etc., wash the extract with water, and dry with anhydrous sodium sulfate. Next, low-boiling substances were distilled off from the extract under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain the general formula ().
The allyl sulfide represented by can be isolated. The allyl alcohol represented by the general formula () used as a raw material can be easily produced in good yield from the ketone represented by the general formula () represented by β-ionone, which is an industrial raw material. (In the formula, n is as defined above.) That is, by reacting a ketone represented by the general formula () with vinyl magnesium chloride prepared from vinyl chloride and metal magnesium in a tetrahydrofuran solvent, the general formula ( )
Allyl alcohol represented by is produced. In addition, when using a ketone in which n is 0 in the general formula (), that is, β-ionone, as a raw material in the above reaction, the yield is 91% and n in the general formula () is used.
Allyl alcohol having 0 is obtained. [Bull.
Chem.Soc.Japan, 37 , 207 (1964) and Rec.
Trav.Chim., 95 (5), 316 (1979)] Of the allyl sulfides represented by the general formula (), the allyl sulfide in which n is 0 can be produced in good yield and by the following method, for example. Easily induced by vitamin A. (In the formula, R is as defined above.) Each step in this method will be explained next. Step A: Allyl sulfide represented by general formula (') is dissolved in tetrahydrofuran and cooled to about -30°C or lower in a dry ice-acetone bath.
Next, a hexane solution of n-butyllithium, for example, is added to this solution to generate a carbanion at the α-position of the -SR group in the allyl sulfide, and then 1-chloro-4-(2-tetrahydropyranyloxy )-2-methyl-2
- A solution of butene (1) in tetrahydrofuran is added at the same temperature and allowed to react. After the reaction is completed, the compound represented by the general formula () is separated from the reaction mixture by a conventional method. Step B: Dissolve the compound represented by the general formula () in a solvent such as toluene, add an alkali such as potassium t-butyrate to this solution, and heat from room temperature to
Stir at a temperature of approximately 100°C. After the reaction is completed, vitamin A tetrahydropyranyl ether (2) is separated from the reaction mixture by a conventional method. Step C: Tetrahydropyranyl ether (2) of vitamin A is dissolved in a solvent such as tetrahydrofuran, and a dilute aqueous solution such as sulfuric acid is added to this solution to perform hydrolysis. After the reaction is completed, vitamin A(3) is separated from the reaction mixture by a conventional method. [Examples] The present invention will be explained below with reference to Examples, but the present invention is not limited to these Examples. Example 1 11.0 g of β-vinylonol, 5.6 g of 2-mercaptopyridine and 50 ml of acetic acid were placed in a 200 ml flask and stirred at room temperature under a nitrogen gas atmosphere for 5 hours. After the reaction is complete, pour the reaction solution into a large amount of water and add n-
Extracted with hexane. The hexane extract was washed with a 10% aqueous sodium carbonate solution, further washed with water, and then dried over anhydrous magnesium sulfate. After removing hexane from this extract using an evaporator, the remaining oil was subjected to silica gel column chromatography (developing solution: a mixture of ethyl acetate and n-hexane) to obtain 14.9 g of a product. Yield 95%. This product was confirmed to be β-ionylidene ethyl-2-pyridyl sulfide based on the following instrumental analysis data. NMR ( _CDCl3 , ppm): 0.93 (s, 6H,

【formula】); 1.59, 1.64 (each s, 3H,

【formula】); 1.81(s, 3H,

[Formula]); 3.91 (d, 2H, -CH ₂ -S-); 5.55 (t, 1H,

【formula】); 5.99, 6.21 (each s, 2H,

【formula】; 6.7~7.6 (m, 3H,

【formula】); 8.3~8.6 (m, 1H,

[Formula]) IR (cm ^-1 ): 2930, 2860, 1580, 1550, 1450,
1410, 1130, 970, 750 Example 2 β-vinylonol 1.10g, thiophenol
Put 0.55g and 5ml of acetic acid into a 25ml flask,
The mixture was stirred at room temperature for 8 hours under a nitrogen gas atmosphere. After the reaction was completed, the reaction solution was extracted in the same manner as in Example 1,
Then, 1.27 g of product was obtained by subjecting it to similar silica gel column chromatography. yield
81%. This item is based on the following instrumental analysis data.
It was confirmed that it was β-ionylidene ethyl phenyl sulfide. NMR ( _CDCl3 , ppm): 0.95 (s, 6H,

【formula】); 1.61(s, 3H,

[Formula] or

【formula】); 1.63(s, 3H,

[Formula] or

【formula】); 3.60(d, 2H,

【formula】); 5.68(t, 1H,

【formula】); 5.96, 6.18 (each s, 2H,

[Formula]); 7.0 to 7.5 (m, 5H, -SC ₆ H ₅ ) IR (cm ^-1 ): 2930, 2860, 1580, 1480, 1440,
1360, 1020, 960, 780, 730 Examples 3 to 19 Reactions were carried out under the same conditions as in Example 1 using various allyl alcohols represented by the general formula () and thiols represented by the general formula (), and the resulting reaction solution was extracted in the same manner, and then silica gel Allyl sulfide represented by the general formula () was obtained by subjecting it to column chromatography.
The results are shown in the table below.

【table】

〔Effect of the invention〕

According to the method of the present invention, as is clear from the above examples, allyl sulfide represented by the general formula () can be produced almost quantitatively and easily depending on the type from inexpensive and easily available industrial raw materials. I can do it. Furthermore, as is clear from the above reference examples, many of the allyl sulfides represented by the general formula () of the present invention can be easily converted into vitamin A
be guided by.

Claims (1)

[Claims] 1. General formula (In the formula, R represents an aryl group, an aralkyl group, a pyridyl group, a 2-thiazolyl group, a 2-benzothiazolyl group, a 2-benzimidazolyl group, a 2-benzooxazolyl group, or a 6-purinyl group, and n is 0
or represents an integer of 1. ) Allyl sulfide. 2 General formula (In the formula, n represents an integer of 0 or 1.) Allyl alcohol represented by the general formula RSH (In the formula, R is an aryl group, an aralkyl group, a pyridyl group, a 2-thiazolyl group, a 2-benzothiazolyl group, -represents a benzimidazolyl group, 2-benzoxazolyl group or 6-purinyl group.) A general formula characterized by reacting a thiol represented by the following in the presence of an acid: (In the formula, R and n are as defined above.) A method for producing allyl sulfide represented by: