JPS5919953B2 - Method for producing 8,9-dehydrotheaspirone - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides 2,6,10,10-tetramethyl-1-oxaspiro[4,5]deca-2,6-dien-8-one (common name 8,9-dehydroteaspirone, hereinafter ""Thiscompound".

). In recent years, many 4-oxotrimethylcyclohexene derivatives, which are considered to be carotenoid decomposition products in plants, have been discovered in various aromatic plants.

Among these derivative compounds, the present compound has been isolated from tobacco plants in recent years and has a flower-like aroma including a book-like aroma.
It is said to be an extremely useful compound as a tobacco flavor improver.
Although not reported to date, brumenol B (described in Journal of the Chemical Society, Chemical Communication, 1975, p. 567) and pyridinium chlorochromate (described in Tetrahedron Letters, 1975, p. 2647) ) to cause a cyclization reaction. However, this method is quite expensive because its raw material, Blumenol B, not only requires many manufacturing steps, but also the yield in these steps is not high. The object of the present invention is to provide a manufacturing method that does not have the drawbacks associated with conventionally assumed manufacturing methods of the present compound and can be easily and inexpensively mass-produced.

That is, the present invention provides 2,6,6-trimethyl-4,4-
Ethylenedioxy-2-cyclohexen-1-one (hereinafter simply referred to as "ketoketal") and 4-chloro-2-
Ptanone ethylene acetal (hereinafter simply referred to as "1-hydroxy-1" obtained by reacting chloroketano U and (U) in tetrahydrofuran in the presence of metallic lithium)
-(3,3-ethylenedioxybutyl)-2,6,6-
The gist is to obtain the present compound by treating trimethyl-4,4-ethylenedioxy-2-cyclohexene with an acid. The manufacturing method of the present invention will be explained in detail below based on the manufacturing process described below. First, a known ketoketal, which is one of the raw material compounds of the present invention, is produced by the following method. That is, oxophorone (■) is obtained by air oxidizing isoborone (I) according to a known method (Japanese Patent Application Publication No. 531-28907), and then the obtained oxophorone () is mixed with ethylene glycol in a catalytic amount. The ketoketal () is obtained by ketalization using an acid or a salt thereof by a known method.

On the other hand, chloroketal (
V) can be obtained by adding hydrogen chloride to methyl vinyl ketone () and then ketalizing it in the same manner as described above.

(Refer to Tetrahedron Magazine, Vol. 31, p. 1251) Next, under a flow of an inert gas such as nitrogen or argon, add 1 to 4 times the mole of the above-mentioned ketoketal, preferably 2 times the mole of the metal. Lithium is added to an appropriate amount of dehydrated tetrahydrofuran (hereinafter simply referred to as "THF"). Next, 20 to 60%, preferably 40% T of a 1:1 (mole ratio) of ketoketal () and chloroketal (V) is added to this mixed solution while stirring vigorously.
Add the HF mixed solution dropwise to react. In addition, since this reaction is an exothermic reaction, it is necessary to carry out the reaction under water cooling. This reaction is completed in about 4 hours.

After the reaction is complete, the reaction mixture is poured into ice water to convert excess metallic lithium into lithium hydroxide, and then ether, benzene,
Organic solvents such as dichloromethane to ketoketals,
Extraction is performed using 5 to 20 times the amount (weight ratio), preferably 10 times the amount. Next, after washing the organic solvent layer with water, it is dried using a drying agent such as anhydrous sodium sulfate, anhydrous calcium chloride, anhydrous magnesium sulfate, etc., and the solvent is evaporated under reduced pressure to obtain a pale yellow oily substance containing white crystals. is obtained. This mixture is dissolved in 2 to 3 times (by weight) ether, and then 20 to 30 times (by weight) petroleum ether is added, and by standing at a low temperature, approximately With a yield of 82%, 1-hydroxy-1
-(3,3-ethylenedioxybutyl)-2,6,6-
White needle-like crystals of trimethyl-4,4-ethylenedioxy-2-cyclohexene (hereinafter simply referred to as "diketal") are obtained. Next, this diketal []
Dissolve in an organic solvent such as dichloromethane, THF', or acetone, and add 0.05 to 1 N, preferably 0.1
A specified mineral acid, preferably hydrochloric acid, is added dropwise at room temperature for 10~
Allow to stir for 30 hours, preferably 20 hours.

After the reaction is completed, the same method as above, i.e., ether,
When extracted with an organic solvent such as benzene or dichloromethane, and the organic solvent layer is washed with water, dried, and the solvent is removed, 1-
Hydroxy-1-(3-oxobutyl)-2,6,6-
Trimethyl-2-cyclohexen-4-one (hereinafter simply referred to as [keto alcohol]). Together with [], the present compound [], in which the hemiacetalization and dehydration reactions of this compound have further progressed, is obtained as a mixture with the keto alcohol []. This mixture is dissolved in an organic solvent such as dichloromethane or chloroform, and a mineral acid of 0.05 to 1N, preferably 0.1N, preferably sulfuric acid, is added thereto and suspended. The hemiacetalization and dehydration reactions are completed in minutes. After the reaction is complete, the organic solvent layer is separated, washed with water, dried, and the solvent removed in the same manner as described above.
By distilling at 4 mmHg), the present compound can be obtained as a fraction at 99 to 100° C. with a yield of about 93%.

) As explained in detail above, the manufacturing method according to the present invention includes:
It has the advantage that it can be easily manufactured from inexpensive and easily obtained compounds such as isoborone and methyl vinyl ketone, the manufacturing process is short, and the yield in each process is relatively good. .

Furthermore, except for steps involving metallic lithium, the process proceeds in air under mild conditions and is easy to operate, making it extremely effective for industrial implementation. Example Oxophorone 307 obtained by air oxidation of isoborone
(197mm01) was dissolved in 200ml of pensery,
Ethylene glycol 25f (403 mm01) and paratoluenesulfonic acid pyridine salt 0.57 were added therein, and the mixture was refluxed for 30 hours using an azeotropic dehydrator to react.

After the reaction is completed, the organic solvent layer is washed with an appropriate amount of saturated aqueous sodium bicarbonate solution, then the organic solvent layer is dried with anhydrous sodium sulfate, and the solvent is removed under reduced pressure to obtain a crude ketoketal product containing oxophorone. I got it.
By distilling this under reduced pressure (16 ml tHg), the ketoketal []
27-27 (yield 72% from oxophorone) was obtained.
On the other hand, chloroketal [ ] was synthesized as follows.

That is, 14 ml of methyl vinyl ketone in 50 ml of benzene.
7 (200 mm 01) was dissolved, and anhydrous hydrogen chloride gas was blown into the solution while cooling with ice salt. After 1.5 times the amount of hydrogen chloride based on methyl vinyl ketone was consumed, the blowing was stopped and the mixture was stirred for an additional 30 minutes. After the reaction was completed, it was washed twice with a saturated aqueous sodium bicarbonate solution (and dried over sodium sulfate. Then, the polymer and highly polar substances were removed by passing it through a Florisil column (20f7) using benzene as a developing solvent. Ethylene glycol 257 (403 mm01) and 0.1 t of para-toluenesulfonic acid pyridine salt were added to this solution, and the mixture was refluxed for 2 hours using an azeotropic dehydrator.

After the reaction was completed, it was washed with a saturated aqueous sodium bicarbonate solution and dried over sodium sulfate. Next, the mixture was passed through a Florisil column (207) using benzene as a developing solvent, and the solvent was removed to obtain a light brown oily substance. By careful distillation under reduced pressure (511 Hg), the colorless chloroketal 23 was obtained as a fraction with a boiling point of 40-42 °C.
f7 (yield 76% from methyl vinyl ketone) was obtained.
Next, 1 V (143 mm) of metallic lithium was cut into small pieces and placed in a 50 ml T-box under an argon stream and stirred.

Then, using a dropwise load, the ketoketal 10
7 (51mm01) [] and chloroketanol 87 (5
30 ml of a THF solution of 3 mm01) [V] was added dropwise. The reaction system was all carried out under an argon stream, and the reaction vessel was kept under water cooling to remove heat generated by the reaction. The reaction mixture immediately turned yellow and then turned black, and the reaction was completed in about 4 hours.

This reaction mixture was poured into ice water 507, and excess metallic lithium was converted into lithium hydroxide. Then ether 100m
Extract 3 times using each sample, wash with water in the same manner as above,
Drying and removal of the solvent gave a pale yellow oil. White crystals will eventually form from this oily substance. After dissolving these in 20ml of ether, adding 100ml of petroleum ether and leaving it at low temperature,
137 white crystals of diketal [] (yield 8 from []
2%).

This diketal [] crystal was dissolved in THFlOOml, and 10ml of 0.1N hydrochloric acid was added dropwise.

After stirring at room temperature for 20 hours, the mixture was extracted three times with 100a of ether each. Next, the organic solvent layer was washed with water, dried, and the solvent was removed using the same method as described above to obtain a mixture of the present compound [] and the keto alcohol []. This mixture was dissolved in 50 ml of dichloromethane, and 1 ml of 0.1N sulfuric acid was added dropwise to suspend it. After reacting for 30 minutes, the dichloromethane layer was separated, washed with water, dried, and the solvent removed using the same method as above, and then distilled under reduced pressure (4 mmHg) to 99-100 °C. The present compound 81 (yield 93% from []) was obtained as a fraction of .

The compound was identified by comparing its mass spectrum, infrared absorption spectrum, and nuclear magnetic resonance spectrum with a standard sample of 8,9-dehydrotheaspican, and was confirmed to be the same compound as the standard sample.

Claims (1)

[Claims] 1 2,6,6-trimethyl-4,4-ethylenedioxy-2-cyclohexen-1-one and 4-chloro-2
- obtained by reacting butanone ethylene acetal in tetrahydrofuran in the presence of metallic lithium, 1
-Hydroxy-1-(3,3-ethylenedioxybutyl)-2,6,6-trimethyl-4,4-ethylenedioxy-2-cyclohexane is treated with an acid, 8.9 - A method for producing dehydrotheaspirone.