JPS6257172B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing a 3-oxocyclopentene compound, and more particularly, to a method for producing a 3-oxocyclopentene compound, more specifically, a method for producing a 3-oxocyclopentene compound, and more specifically, [In the formula, R ₁ is an alkyl group with up to 6 carbon atoms, an alkenyl group with up to 6 carbon atoms that does not have an unsaturated bond at the bond end, an alkynyl group, or a general formula

Represents a group represented by [Formula]. R ₂ here represents a hydrogen atom, a methyl group or a halogen atom. ] It is related with the new manufacturing method of the 3-oxocyclopentene compound shown by these. The compound represented by the above general formula () is a useful intermediate for agricultural chemicals and can also be an intermediate for pharmaceuticals such as prostaglandins, and is extremely important as an intermediate. The conventional method for producing the compound represented by the general formula () is (R: allyl, n-butyl, cyclohexyl,
A method using the phenyl, 2-thienyl, p-tolyl) route is known (G. Piancatelli
et al., Tetrahedron, 34 volumes,
2775-2778 (1978). However, with this method, Table 1 on page 2776 of the same document
When R represents a phenyl group, 2-thienyl group or p-tolyl group, that is, for an aromatic or heterocyclic compound as described in
Although the target compound (2) can be obtained in a short time and in a relatively high yield, in the case of a furan carbinol compound in which R is a substituent that does not have an unsaturated bond at its bond end like the target compound of the present invention, However, the reaction is difficult to proceed, the yield is extremely low, and it takes a long time, making it difficult to put it to practical use. Under these circumstances, the present inventors conducted various studies and found that the general formula () [In the formula, R ₁ has the same meaning as above. ] The present invention was completed by discovering a method for obtaining a 3-oxocyclopentene compound represented by the general formula () from a furancarbinol compound represented by the following. That is, the present invention relates to the production of a 3-oxocyclopentene compound represented by the general formula (), which is characterized by treating a furancarbinol compound represented by the general formula () in an aqueous solvent in the presence of an inorganic salt of magnesium. The present invention provides a method. The present invention will be explained in detail below. A feature of the present invention is that the reaction is carried out in an aqueous solvent and in the presence of an inorganic salt of magnesium. The aqueous solvent referred to here may include water alone or a small amount of organic solvents such as toluene, xylene, diisopropyl ether, benzene, acetone, tetrahydrofuran, and dioxane. It has been discovered that the object compound of the present invention represented by the general formula () can be conveniently obtained only by carrying out the reaction in the presence of a salt. That is, according to the above-mentioned known literature, using a furan carbinol compound in which R is a substituent having no unsaturated bond at the bond end, as in the target compound of the present invention, zinc chloride is added in an acetone solvent containing a small amount of water. When reacted in the presence of , the desired 3-
The yield of the oxocyclopentene compound is extremely low and the reaction requires a long time. Furthermore, it is truly remarkable that according to the present invention, the reaction proceeds in a short time and in high yield even when using magnesium bromide, which the inventor of the above-mentioned known document claims has no catalytic ability. . In the present invention, specific examples of R ₁ in the compound represented by the general formula () include a methyl group, a propyl group,
hexyl group, cyclohexyl group, allyl group, 4-
pentenyl group, propargyl group, benzyl group, p
-methylbenzyl group, p-chlorobenzyl group, etc. Examples of inorganic salts of magnesium used in the present invention include magnesium chloride,
Examples include magnesium bromide, magnesium nitrate, magnesium sulfate, etc., and the amount used is 0.01 to 100% of the compound represented by the general formula ().
The amount is in the range of twice the mole, preferably 0.1 to 10 times the mole, and more preferably 0.5 to 2 times the mole. In the present invention, the pH during the reaction is important, and the pH is 3~
7, preferably 3 to 6, more preferably
It ranges from 3.5 to 5.8. Further, at this time, if the reaction is carried out on a more acidic side, the amount of by-products increases, and if the reaction is carried out on an alkaline side, the reaction rate becomes extremely slow. In addition, if the reaction is continued for a long time, the compound represented by the general formula () will become the general formula () [In the formula, R ₁ has the same meaning as above. ] Because it changes to cyclopentenolones shown by
Unless the purpose is to ultimately produce the cyclopentenolone, the reaction should be followed by analysis by gas chromatography, etc.
It is desirable to complete the reaction at a time when the production of the compound represented by the general formula () is maximized. In the present invention, a wide variety of known acids and bases can be used for pH control.Specifically, acids include inorganic acids such as sulfuric acid, hydrochloric acid, and nitric acid, organic acids such as acetic acid and p-toluenesulfonic acid, and phosphoric acids. Examples include acidic metal salts such as sodium dihydrogen acid and sodium hydrogensulfite, and acidic ion exchange resins. Specific examples of the base include hydroxides of alkali metals such as sodium and potassium, alkaline earth metals such as calcium and barium, basic salts such as carbonates, bicarbonates, and acetates, triethylamine, Examples include amines such as pyridine, basic ion exchange resins, and the like. It is also possible to use buffer solutions of acids and bases using these. Furthermore, the amount of water solvent used in the present invention is 0.5 times to 100 times the amount of the compound represented by the general formula (),
It is preferable to use 5 to 40 times the weight. The reaction temperature is usually 20℃ to 200℃, preferably 80℃
~150℃. Specifically, the present invention involves dissolving or suspending a compound represented by the general formula () in an aqueous solvent in which a metal salt is dissolved, raising the temperature, and then reacting while adjusting the pH between 3 and 7. ) is carried out by terminating the reaction at a time when the production of the compound represented by is at its maximum. In addition, the compound represented by the general formula () which is _the starting material of the present invention has the general formula () R ₁ Represents an iodine atom. ] The general formula () R ₁ MX () obtained by reacting Mg, Zn or Al metal with the compound represented by [where R ₁ and X have the same meanings as above and M is Mg, Zn or Al2 /3 represents an atom. ] It can be obtained by reacting the compound represented by 5-methylfurfural with 5-methylfurfural. The present invention will be specifically explained below using Examples. Example 1 Pour 750 ml of water, raise the temperature to 100°C and reflux. Next, a solution prepared by dissolving 24 g of 5-methyl-2-furyl-allyl-carbinol and 1.5 g of MgCl ₂ .6H ₂ O in 160 ml of water was added dropwise over 2.5 hours and 3.5 hours, respectively. At that time, the pH of the reaction solution was controlled to be between 5.7 and 5.3 using a 10% monopotassium phosphoric acid aqueous solution and 1N aqueous sodium hydroxide. The pH stopped changing around 1.5 hours after the start of the reaction. After the dropwise addition of the MgCl ₂ aqueous solution was completed, the mixture was stirred under reflux at 100° C. for 4.5 hours at pH 5.5. After cooling this to 40℃, neutralize it with 1N sodium hydroxide solution, add 320g of common salt, and then add 250ml of toluene.
Extracted 4 times. After drying the extract over anhydrous magnesium sulfate, toluene was distilled off under reduced pressure at 60°C.
21.6 g of oil was obtained. Next, this was distilled at 0.5 mmHg and 88 to 90℃ to obtain a 20.4
g of 4-hydroxy-4-methyl-5-allyl-2-cyclopentenone was obtained. Yield 85
% Example 2 Charge 200 ml of water, dissolve 17 g of MgCl ₂ .6H ₂ O therein, and then add 13.0 g of 5-methyl-2-furyl-allyl-carbinol. This was heated to 100℃, refluxed, and mixed with 2N-hydrochloric acid and 1N.
The mixture was stirred under reflux for 8 hours while maintaining the pH at 5.0 to 5.2 with -NaOH water. Next, after cooling to 40°C, neutralize with 1N NaOH water, add 70g of common salt, and extract 4 times with 70ml of toluene. After drying the extract over anhydrous magnesium sulfate, toluene was distilled off under reduced pressure at 60°C to obtain 11.9 g of an oily substance. Next, this was distilled at 0.5 mmHg at 88 to 90°C to obtain 9.5 g of 4-hydroxy-4-methyl-5-allyl-
2-cyclopentenone was obtained. Yield: 73% Example 3 Charge 100 ml of water, dissolve 6.8 g of MgCl ₂ .6H ₂ O therein, and then add 5 g of 5-methyl-2-furyl-propargyl-carbinol. Raise the temperature to 100℃ and reflux it with 1N-hydrochloric acid water and 1N-
The mixture was stirred under reflux for 8 hours while keeping the pH at 3.8 to 4.1 with NaOH water. This was cooled to 40°C, neutralized with 1N NaOH water, added with 35 g of common salt, and extracted four times with 50 ml of toluene. After drying the extract with anhydrous magnesium sulfate,
Toluene was distilled off under reduced pressure at °C to obtain 4.7 g of oil. This was then developed with ethyl acetate-n-hexane (1 volume to 2 volumes) using 60 g of silica gel. First the high boilers flow out, then a small amount of unreacted 5-methyl-2-furyl-propargyl-carbinol, and much later the desired 4
-Hydroxy-4-methyl-5-propargyl-2-cyclopentenone flows out and this fraction is concentrated and 4-hydroxy-4-methyl-5-
3.6 g of propargyl-2-cyclopentenone was obtained. Yield: 72% Examples 4 to 11 Using 5 g of the following furancarbinol compound,
The same operation as in Example 3 was carried out under the following conditions to obtain each 3-oxocyclopentene compound.

[Table] Example 12 Prepare 10 g of 5-methyl-2-furyl-allyl-carbinol, then add 400 ml of 19 g of MgBr ₂ 6H ₂ O.
A solution dissolved in water was added thereto, the temperature was raised to 100°C, the mixture was refluxed, the pH was adjusted to 5.8 with 1N NaOH water, and the mixture was stirred under reflux for 5.5 hours. The pH at that time was 3.6. After cooling, 120 g of common salt was added, and the mixture was extracted four times with 300 ml of toluene. After drying the extract with anhydrous magnesium sulfate,
Toluene was distilled off under reduced pressure at 60℃, and then 0.5mmHg88~
Distilled at 90°C to yield 6.1 g of 4-hydroxy-4
-Methyl-5-allyl-2cyclopentenone was obtained. Yield: 61% Reference Example 1 Charge 7.4 g of magnesium scraps and 40 ml of ether. Then add a small amount of iodine. At around 20°C, about 10 drops of a solution of 21.4 g of allyl chloride dissolved in 40 ml of ether were added and stirred until the pale yellow color of iodine disappeared. After cooling, the remaining ether solution of allyl chloride was added dropwise over 4 hours while maintaining the temperature at 0 to 5°C, and the mixture was stirred while keeping it warm for 1 hour. Next, a solution prepared by dissolving 22 g of 5-methylfurfural in 100 ml of ether was added dropwise over 2 hours while keeping the temperature at 0 to 5°C, and the mixture was stirred for 1 hour while keeping it warm. An aqueous solution in which 30 g of NH ₄ Cl was dissolved was added over 20 minutes under ice cooling, and the mixture was stirred for 1 hour. Unreacted magnesium was removed through celite, and 100 g of common salt was added to the solution to separate the ether layer. The aqueous layer was extracted three times with 200 ml of ether, and the ether layers were combined to make 30 ml of saturated
After washing with _NaHCO3 water and drying with 50g of _{anhydrous Na2SO4} ,
The mixture was then concentrated at 40° C. under reduced pressure to obtain 27.9 g of oil. This was rectified at 9mmHg and 92℃, and 21.9g of 5
-Methyl-2-furyl-allylcarbinol was obtained. Yield 72.1% Reference example 2 39.3g of magnesium scraps and 400ml of ether
Add a small amount of iodine and stir. Around room temperature, about 10 in 167.8g of allyl bromide
Add dropwise and stir until the pale yellow color of iodine disappears. After cooling, the remaining allyl bromide was added dropwise over 4 hours while maintaining the temperature at 0 to 5°C, and the mixture was stirred for 30 minutes. Next, a solution prepared by dissolving 84.5 g of 5-methylfurfural in 200 ml of ether was added dropwise over 1.5 hours while maintaining the temperature at 0 to 5°C, and the mixture was stirred for an additional 1 hour while keeping it warm. 500 ml of 20% NH ₄ Cl water was ice-cooled to 10°C, and the ether solution of the metal complex was poured down over 20 minutes while maintaining the temperature at 10 to 20°C. After stirring at room temperature for 1 hour, the ether layer was separated, the aqueous layer was extracted twice with 200 ml of ether, the ether layers were combined, washed with 30 ml of saturated NaHCO ₃ water, dried over anhydrous MgSO ₄ and concentrated under reduced pressure at 40°C. As a result, 124.3 g of oil was obtained. This was rectified at 4mmHg60~61℃, and 106.7g of 5
-Methyl-2-furyl-allyl-carbinol was obtained. Yield: 91% Reference Example 3 0.77 g of aluminum powder, 17.8 mg of HgCl ₂ and a small amount of iodine are charged and heated at 150°C for 10 minutes. After cooling, 10 ml of tetrahydrofuran was charged, and 4.8 g of propargyl bromide was added dropwise at 30° C. over 4 hours, followed by stirring while keeping it warm for 1 hour. After cooling in an acetone-dry ice bath, a solution prepared by dissolving 4.6 g of 5-methylfurfural in 10 ml of tetrahydrofuran was added dropwise over 3 hours while maintaining the temperature at -10°C or lower. Next, raise the temperature to 30℃ and
After stirring for 30 minutes, cool to 0℃, add a solution of 5.3 g of NH ₄ Cl in 20 ml of water over 20 minutes, and stir for 30 minutes, then reduce to 30%.
50 ml of NaCl water was added and extracted three times with 200 ml of ether. After washing the ether layer with 30 ml of saturated _NaHCO3 water,
Dry with anhydrous MgSO ₄ and concentrate under reduced pressure at 50 °C to 4.4
g of oil was obtained. Next, 60 g of silica gel was developed with ethyl acetate-n-hexane (2 volumes to 5 volumes), and 4.1 g
5-methyl-2-furyl-propargyl-carbinol was obtained. Yield: 65% Reference Example 4 7.3 g of magnesium scraps and 30 ml of ether are charged, a small amount of iodine is added, and the mixture is stirred at room temperature. About 10 drops of a solution of 21.3 g of methyl iodide dissolved in 40 ml of ether were added to this, and the mixture was stirred until the pale yellow color of iodine disappeared. Next, the methyl iodide solution was heated between 22°C and 35°C at 1.5°C.
The mixture was added dropwise over a period of time and stirred at room temperature for 1 hour. Then 5-
A solution of 15.4 g of methylfurfural dissolved in 60 ml of ether was added dropwise over 30 minutes, and the mixture was stirred for 1 hour at room temperature.
60 ml of saturated NH ₄ Cl water was added to this over 20 minutes, and after stirring for 30 minutes, unreacted magnesium was removed through celite, the ether layer was separated, and the aqueous layer was diluted with 100 ml of ether.
Extract twice and combine the ether layers with 20 ml of saturated NaHCO ₃ solution.
After washing with , it was dried over anhydrous MgSO ₄ , and the solvent was distilled off under reduced pressure at 40° C. to obtain 13.5 g of an oily substance. This is 10mm
Hg, rectified at 67-69°C, 11.8 g of 5-methyl-2
-furyl-methyl-carbinol was obtained. Yield: 67% Reference Example 5 2.8 g of magnesium scraps and 12 ml of ether are charged, a small amount of iodine is added, and the mixture is stirred at room temperature. Approximately 10 drops of a solution of 8.6 g of propyl chloride dissolved in 20 ml of ether were added and stirred until the pale yellow color of iodine disappeared. Next, this propyl chloride solution was added dropwise over 2 hours.
Stirred at room temperature for 1 hour. Next, a solution prepared by dissolving 10 g of 5-methylfurfural in 50 ml of ether was added dropwise to the mixture over 1 hour, and the mixture was stirred at room temperature for 1 hour. Further, 50 ml of saturated NH ₄ Cl water was added to this over 20 minutes, stirred for 30 minutes, filtered through Celite to remove unreacted magnesium, the ether layer was separated, the aqueous layer was extracted twice with 100 ml of ether, and the ether layers were combined to achieve saturation. After washing with 20 ml of NaHCO ₃ solution, it was dried over anhydrous MgSO ₄ and the solvent was distilled off under reduced pressure at 40° C. to obtain 12.8 g of oil. Add this to silica gel
Ethyl acetate-n-hexane (2
11.3 g of 5-methyl-2-furyl-propyl-carbinol was obtained. Yield: 81% Reference Examples 6 to 8 The same operations as in Reference Example 5 were performed using the following halogen compounds to obtain furancarbinol compounds represented by the general formula (). The results are shown below.

[Table] Contents Reference Example 9 5.5 g of shavings of magnesium, 5.5 g of powdered magnesium, and 100 ml of ether are charged, a small amount of iodine is added, and the mixture is stirred under reflux. About 10 g of p-chlorobenzyl chloride dissolved in 120 ml of ether
It was added dropwise and stirred until the pale yellow color of iodine disappeared. Next, the remaining p-chlorobenzyl chloride solution was added dropwise over 5 hours, and the mixture was stirred for 1 hour. A solution prepared by dissolving 10 g of 5-methylfurfural in 50 ml of ether was then added dropwise over 2 hours, and the mixture was stirred for 1 hour. This was then added with saturated NH ₄ Cl
Add 50ml of water over 20 minutes, stir for 30 minutes, remove unreacted magnesium through Celite, and separate the ether layer.
The aqueous layer was extracted twice with 100 ml of ether, the ether layers were combined, washed with 20 ml of saturated NaHCO ₃ , and then anhydrous.
Dry with MgSO ₄ and evaporate the solvent under reduced pressure at 40°C.
g of oil was obtained. Using 300g of silica gel, add ethyl acetate-n-hexane (2 volumes to 5 volumes).
and 21.6 g of 5-methyl-2-furyl-p-
Chlorbenzyl-carbinol was obtained. Yield: 83% Reference Examples 10-11 Using the following halogen compounds, the same operation as in Reference Example 9 was carried out to obtain each furan carbinol compound represented by the general formula (). The results are shown below.

[Table] Contents

Claims (1)

[Claims] 1. General formula [In the formula, R ₁ represents an alkyl group having up to 6 carbon atoms, an alkenyl group having up to 6 carbon atoms having no unsaturated bond at the bond end, an alkynyl group, or a group represented by the general formula [Formula]. R ₂ here represents a hydrogen atom, a methyl group or a halogen atom. ] A general formula characterized in that a furancarbinol compound represented by is treated in an aqueous solvent in the presence of an inorganic salt of magnesium. [In the formula, R ₁ has the same meaning as above. ] A method for producing a 3-oxocyclopentene compound. 2. The method according to claim 1, wherein the treatment is carried out at 20 to 200°C.