JPS6013732A - Production of ketal derivative - Google Patents

Abstract

PURPOSE:To produce the titled compound useful as a raw material of carotinoid, perfumery component, etc., easily, in high yield, by converting 2,6,6-trimethyl-2- cyclohexene-1,4-dione to monoketal, and catalytically reducing the product. CONSTITUTION:The 2,6,6-trimethyl-2-cyclohexene-1,4-dione of formula 2 is converted to monoketal to obtain the enone ketal derivative of formula 6 (R<1> and R<2> are 1-3C alkyl; the dotted line represents that R<1> and R<2> form separate groups or together form a covalent bond between the carbon atoms of R<1> and R<2>). The catalytic reduction of the derivative gives the ketal derivative of formula I , especially the compound of formula I wherein -R<1>-R<2>- is -CH2-CH2-, i.e. 4-ethylenedioxy-2,2,6-trimethyl-1-cyclohexanone. EFFECT:The catalyst for the catalytic reduction can be recovered by a simple method such as filtration, etc., and can be reused.

Description

Detailed Description of the Invention The present invention provides an alicyclic ketal of general formula 1 (in the formula, R1, B+'' represents an alkyl group having 1 to 3 carbon atoms, and the broken line indicates that R1 and R1 each form an independent group). Or,
(indicates that R1 and R1 are covalently bonded via carbon atoms).

Ketal derivatives of general formula 1, especially -R1-R''- is -C
Compounds that are H, -CH, - are known as certain compounds such as rotinoids [e.g., J, Chem, 8oc, (C)b4
04 (1971): He, 1. v s Ch 1m
% Human Cta, 59b454 (1956) L or fragrance ingredients [e.g. Agrlc, Biol, Che
m, 45% 515 (1981); He1v, C
him, Acta, 51. .

It is a compound useful as a starting material when synthesizing 1sos(t97g)).

Conventionally, a 10-ketal derivative with the general formula, %K.

R1,,,R,! The following method has been proposed for the production of compounds that are -10H, -OH, -0(1)
He1v, Chlm, Acta, 59.454
(1956) This method uses s2*6.6) dimethyl-2
-Cyclohexene-1,4-dione 2 was reduced with zinc-acetic acid to give 2,2,6-drimethyl-1,4-Schiff-affected hexanedione 6, which was then siketalized with ethylene glycol to form 4-ethylene dione. Oxy-2,2,6
-) 4% dimethyl-1-cyclohexanone, that is, a compound of general formula 1 where -X-Y- is -CH, -CH, - is obtained. However, this synthetic route has a relatively low yield of 69% in the zinc reduction process, and uses a large excess of zinc, a heavy metal, so a large amount of wastewater treatment must be done to avoid environmental pollution. It requires a lot of effort and is not suitable for implementation on an industrial scale. In addition, since there is no detailed description of the yield in the literature regarding the ketalization process, we repeated the literature method several times and found that the desired 4-ethylenedioxy-2,2,6-)dimethyl- It was confirmed that in addition to 1-cyclohexanone 4, diketal 5 was always produced as a by-product. Their production ratio is typically 85:27=4:5. Therefore, the produced 4-ethylenedioxy-2,2
, 6-) Even if dimethyl-1-cyclohexanone 4 could be ideally separated, the yield would never exceed 85%. In reality, since a relatively large amount of diketal 5 is produced as a by-product, separation from 4-ethylenedioxy-2,2,6-drimethyl-1-cyclohexanone 4 is laborious, and the yield drop due to purification is large. There is.

The present inventors conducted research to overcome the drawbacks of such conventional methods, and as a result, they arrived at the present invention. After converting 2 into a monoketal to obtain an enone ketal derivative of the general formula 6 (in which R1, R1 and the broken line have the same meanings as defined in the general formula 1), ketal derivative 1 is obtained by catalytic reduction. In the method of the present invention, in the general formula 1, -X-Y- is -OH -
OH, - compound, i.e. 4-ethylenedioxy-
It also includes a method for producing 2,2,6-)dimethyl-1-fuclohexanone 4.

According to the method of the present invention, the production of diketals in the ketalization reaction in the first step is hardly recognized, and for example, the general formula 6
The yield of the compound where -X-Y- is -CH, -CH, - is 9
It reaches 5%. This is in contrast to the conventional method 2.2.6-)rifthyl-1,4-cyclohexadiene 30 ketalization described above.

In addition, the second step of catalytic reduction has a high yield of 90% or more, and also has the advantage that the catalyst for catalytic reduction can be recovered by a simple method such as filtration. In some cases, it can be reused and has better operability than the reed and zinc reduction methods. Therefore 1
According to the method of the present invention, a 1-ketal derivative of the general formula which also contains 4-ethylenedioxy-2,2,6-)dimethyl-1-cyclohexanone 4 can be obtained easily and in high yield.

Ketalization, which is the first step of the method of the present invention, is carried out by reacting a diol compound in the presence of an acid catalyst.

Usually, benzene, toluene, xylene, etc. are used as the reaction solvent, and the reaction is carried out under conditions such that the water produced during the reaction is azeotropically dehydrated by heating to the reflux temperature of the solvent. As the diol compound, ethylene glycol, 1,3-p4-panediol, etc. are preferably used.

Acid catalysts include sulfuric acid and benzenesulfonic acid.

Toluenesulfonic acid, naphthalenesulfonic acid or the salts of these acids with pyridine are preferably used. In addition to the above method, ketalization can also be carried out using a combination system of an orthoformate ester and the above acid, or a combination system in which the above diol compound is added in addition to the orthoformate ester and the above acid. As the acid ester, methyl orthoformate and ethyl orthoformate are preferably used. These systems do not particularly require an additional solvent, but ketalization can also be carried out by adding a solvent. Examples of solvents include aliphatic hydrocarbons such as hexane and cyclohexane, aromatic hydrocarbons such as benzene, toluene, and xylene, diethyl ether, dipropyl ether, dibutyl ether, tetrahydro-7rane, dioxane, and 1,2-dimethoxyethane. Examples include ether solvents, dichloromethane, polyproform, and halogenated hydrocarbon solvents such as carbon tetrachloride. Reaction temperature is 0-80℃
.

Preferably it is 20-50°C.

The second step of catalytic reduction is carried out by reacting the compound of general formula 6 with hydrogen in the presence of a reduction catalyst. Palladium and Raney nickel are preferably used as catalysts. The catalyst can also be used in the form of being supported on a carrier such as activated carbon. The amount of catalyst used is 1 to 5 of the compound of general formula 6.
0 wt%, preferably 2 to 50 wt%. The reaction temperature is 0 to 100°C, preferably 20 to 60°C. Hydrogen is supplied at normal pressure and under pressure. Although a solvent is not particularly required, reduction can also be carried out by adding a solvent. As a solvent, methanol, ethanol, gropanol,
Alcohol solvents such as butanol, ether solvents such as diethyl ether, dipropyl ether, dibutyl ether, tetrahydro7ran, dioxane, 1,2-dimethoxyethane, aromatic hydrocarbon solvents such as benzene, toluene, and xylene, acetone Examples include ketone solvents such as methyl ethyl ketone, ester solvents such as methyl acetate and ethyl acetate, and aliphatic hydrocarbon solvents such as hexane and cyclohexane.

Next, the present invention will be specifically explained with reference to Examples.Example 1 2.6.6-)dimethyl-2-cyclohexene-1,4
- Dione 2 (519,2f, 2.10 mot) with ethylene glycol (782,1?, 12.6 mot
) and paratoluenesulfonic acid aquarium (1289) t-7
7I + Methyl orthoformate C555,9 while stirring
f%l i 5 mot) was added dropwise in 5 minutes. During this time, the temperature inside the reaction system decreased from 21°C to 12°C.After the completion of the dropwise addition, the temperature was raised to 42-45°C, and the mixture was heated and stirred for 4 hours. Thereafter, at the same temperature, the temperature is suctioned to 250 to 60 Torr, and the low-boiling portion is distilled off.The residue is poured into an aqueous solution of IJ and extracted with ethyl acetate. After washing the organic layer with water, the solvent is distilled off. The residue was subjected to simple distillation (bp 86-87℃/
CL I Torr ) and the main fraction 391b75 f
Gas chromatography analysis of this product revealed that 4-ethylenedioxy-2,6,6-)dimethyl-2-cyclohexen-1-one 6 (-X-Y-=-
The purity of OHs-CH") is 962%, the yield is 92.7%
It turned out to be. The main distillate is the McMahon rectifier (1
m) 4-ethylenedioxy-2,6,6-drimethyl-2-cyclohexene with a purity of 99.7% after rectification.
54 [L7f (yield 82.8%) of 1-one was obtained. This item has a standard IH-NMJ IR spectrum (J, N,
Marx and F., Sondheimer.

Tetrahedron 8upp1. : ■, Part
1 (1966)).

Example 2 Raney nickel (280■) stored in ethanol
Methanol (4d) and 4-ethylenedioxy-
2,6,6-)dimethyl-2-cyclohexene-1-oy(toor.

5, 10 mmol). This mixture was heated at 20°C.
The reaction was followed by gas chromatography by passing hydrogen under normal pressure while stirring, and when the raw materials disappeared, the catalyst, which had stopped the reaction, was removed by filtration.

Wash with methanol. The filtrate and methanol wash were combined, and the solvent was distilled off to obtain a residue of Th t074. As a result of analyzing this product by gas chromatography, the purity of 4-ethylenedioxy-2,2,6-)samethyl-1-cyclohexanone 4 was 93.2% (yield 9a7%).

Example 3 5% pd-C (4aElv), 4-ethylenedioxy-2,6,6-)dimethyl-2-cyclohexene-
1-Oy (i, o o tls, 1 mmot) and methanol (4d) were added, and catalytic reduction was carried out by passing hydrogen through at normal pressure while stirring at 25°C.

Post-treatment was carried out in the same manner as in Example 2, and 4 was obtained with a yield of 913%.
-ethylenedioxy-2,2,6-)samethyl-1-cyclohexanone 4 was obtained.

Reference example 1 2.2.6-) dimethyl-1,4-cyclohexanedione 3 (24,45 fs j 59 mmot), benzene (100 sl) b ethylene glycol (15 41.21
6 mmol) and hibaradruenesulfonic acid (15
The mixture of 0■) was heated under reflux for 6 hours.

The water distilled out during this time is separated and removed. When the crude product was analyzed by gas chromatography, almost no raw material was detected, and 4-ethylenedioxy-2 was found in an area ratio of 85%.
,2,6-)samethyl-1-cyclohexanone 4 and 27
% diketal was produced. The reaction mixture was poured into an aqueous sodium hydrogen carbonate solution and extracted with benzene.

After washing the organic layer with water, the solvent is distilled off. The remaining oil was rectified in a spinning band rectifier (6 m + 18 inches height) to give 4-z ethylene dioxy-2,2,6-drimethyl-1. 22.01F of -cyclohexanone 4 (purity 9a 9%, yield 70%) was obtained.

Take some of the residue from rectification.

Pure sidiketal 5 was obtained by silica gel column chromatography (ethyl acetate-hexane 1:10). The spectral data of this substance is given in the following passage.

IR (liquid film) 1570Th 11511100, 1045゜965偲-1 IH-NMR (CDC2s) δ (185 (d, J = 7Hz% 5H), a85 (Bs
5H)s tl 4 (as 5H')h t32.0
(rns 4H)% 2.1-2.5 (m%IH)
.

170 3.95 (1'sB*s 4H) s
3.954, 15 (AvB* *4H) Patent applicant Toshi Co., Ltd.

Claims (2)

[Claims] (1) 2.6.6-) General formula 1 characterized by converting riftyl-2-cyclohexene-1,4-dione into a monoketal and then catalytically reducing it (wherein R1, B+" is a carbon number of 1 ~5 alkyl groups are shown, and the dashed line represents l(,1 and R
Method for producing a ketal derivative represented by Bt (indicates that each group forms an independent group or is covalently bonded to Bt through the carbon of R3) (2) In general formula 1, -KL-R snow- is -OH, -CH, -
A method for producing a ketal derivative according to claim (1), which is a ketal derivative.