JPS582213B2 - Trans↓-method for producing sabinene hydrate - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing trans-zabinene hydrate, which is useful as a flavoring ingredient for toothpastes, foods and drinks, and particularly as an accentuator for peppermint and spearmint peppermint.

Conventionally, the method for synthesizing zabinen hydrate is as follows:
As shown in the reaction formula (a) below, 5-isopropylbicyclo[3.1.0]hexane-2-one represented by the chemical structural formula (1) is reacted with a methyl Grignard reagent such as methylmagnesium bromide or a methyl lithium. A method is known in which a methyl metallide is added and reacted (US Pat. No. 3,591,643).

However, in this method, cis-zabinene hydrate [chemical structural formula (2)] is mainly produced, and trans-zabinene hydrate [chemical structural formula (3)] is produced only in a very small amount (both cis form and The production ratio with trans isomer is usually 8.
5:1).

Therefore, when synthesizing trans-zabinene hydrate, photosensitization is carried out in the presence of rose bengal using α-thuene represented by chemical structural formula (4) as a sensitizer, as shown in formula (b). Oxygen-sensitive oxidation is performed to synthesize a peroxide (trans-4-hydroperoxy-β-tzene) shown by the chemical structural formula (5), and then sodium sulfite is added to this to synthesize the peroxide shown by the chemical structural formula (6). trans-4-hydroxy-
A method has been proposed in which trans-zabinene hydrate is obtained by reducing it to β-tzene and then hydrogenating it with a metal catalyst (Erich Klein
and Willi Rojahn, Chem. B
er. , 98(9), 3045-9(1965
) ;G. Ohloff et al. , T etr
ahedron, 22, 309 (1966)]
However, in this method, when the peroxide of formula (5) is reacted with sodium sulfite, a large amount of sodium sulfite is required, which must be added over a long period of time, and the reaction is carried out at a low temperature. In addition, the resulting product (trans-4-hydroxy-β-tzene) must be subjected to solvent extraction, solvent distillation, and purification, and many other extremely complicated operations. Moreover, it is necessary to purify the intermediate product trans-4-hydroxy-β-tzene, etc.
There is a problem that the overall yield is considerably reduced.

Furthermore, after synthesizing the peroxide, the solvent must be distilled off, and since peroxide is dangerous, this operation must be performed at low temperature and low pressure, which is cumbersome. Furthermore, there is a problem in that it is not suitable for mass synthesis, and therefore, a method for synthesizing trans-zabinene hydrate simply and with good yield has been desired.

As a result of intensive research in response to the above-mentioned needs, the present inventors have found that a new compound trans- In addition to obtaining 3,4-epoxy-thyan, this compound is an important synthetic intermediate for trans-zabinene hydrate, and by treating this compound with a reducing agent such as lithium aluminum hydride, it can be easily synthesized. The present inventors have discovered that trans-zabinene hydrate can be obtained in a relatively high yield, and have completed the present invention.

That is, the present invention provides a method for producing trans-zabinene hydrate, which is characterized by reacting the novel compound trans-3,4-epoxy-thyan with a reducing agent.

The present invention will be explained in detail below.

In the method for producing trans-vinene hydrate according to the present invention, trans-3/4 used as a starting material
-Epoxy-Tsuyan is represented by the chemical structural formula (7) below, is a colorless liquid at room temperature, and is 33-36
It has a boiling point of 72 mmHg.

In order to produce this trans-3,4-epoxy-thuane, α-thuene is used as a sensitizer as shown in formula (e).
- Photosensitized oxygen oxidation in the presence of diketones.

In this case, the α-diketones used as sensitizers include benzyl (PhCOCOPh), diacetyl (CH
3COCOCH3), 1-phenyl-1,2-propanedione (PhCOCOCH3), and the like are preferably used.

The amount of these sensitizers is usually 0.
The range is about 5 to 10 times the molar amount, but equimolar amounts are preferred.

In addition, as a light source used for photosensitized oxygen oxidation of α-thuene, a tungsten halogen lamp, a low-pressure, medium-pressure, or high-pressure mercury lamp, etc. are used, and the irradiation method is an internal irradiation method,
Any method of external irradiation can be employed.

Furthermore, in the photosensitized oxygen oxidation of α-tzene, although the reaction can occur without a solvent, it is preferable to use a solvent, and the use of a solvent improves the yield.

Aprotic solvents are suitable as solvents, such as pentane, hexane, petroleum ether, licroine, benzene, toluene, xylene, monochlorobenzene, dichlorobenzene,
One or more types of dichloromethane, dichloroethane, etc. can be used.

In addition, these solvents have a ratio of 1 to 100 relative to the weight of α-tzene.
Can be used up to double.

After the photosensitized oxygen oxidation of α-thuene, the sensitizer and solvent are distilled off according to the conventional method, followed by distillation under reduced pressure, and if necessary, purification is performed to collect trans-3,4-epoxy-thuane. do.

When producing trans-zabinene hydrate from this new compound, the product after vacuum distillation is used as it is or is further purified, and a reducing agent is added to it as shown in formula (d). Let it work.

Reducing agents used in this case include metal hydride complexes such as aluminum hydride, lithium trialkoxyaluminum hydride, lithium trialkyl aluminum hydride, metal hydrides such as sodium hydride, lithium, sodium, sodium- Examples include metals such as potassium alloys, hydrazine, alkyl borane, etc., but lithium aluminum hydride, lithium trialkoxyaluminum hydride, lithium trialkyl aluminum hydride, lithium, sodium, and potassium-sodium alloys are particularly preferred.

The amount of these reducing agents used is about 5 times the stoichiometric molar equivalent to that of trans-3,4-epoxy-thyan, and good results are obtained by using the reducing agent in a slight excess.

In addition, in this reduction reaction, a wide range of solvents used in ordinary chemical reactions can be used, but when using metal hydride complexes and metal hydrides as reducing agents, ethyl ether, tetrahydrofuran, bis(2-methoxyethyl )
It is preferable to use ether, dimethoxyethane, etc. alone or in appropriate combinations. When metals are used, liquid ammonia, lower amines such as ethylamine and ethylenediamine, mixed solvents of these and alcohols, and hexamethylphosphorus are preferred. It is preferable to use a mixed solvent of folic triamide and tertiary butyl alcohol.

Furthermore, when using hydrazine, it is preferable to use diethylene glycol or triethylene glycol, and when using diborane or alkylborane, it is preferable to use bis(2-methoxyethyl) ether or tetrahydrofuran.

In addition, in this reduction reaction, the reaction temperature is -80℃
-100°C, preferably 0-80°C; performing the reaction at a low temperature can prevent side reactions, while heating can accelerate the reaction.

Further, the reaction time varies depending on the reaction temperature, the amount of reducing agent used, etc., but is from several tens of minutes to one day.

After the reduction reaction, a crude product is collected by performing appropriate post-treatment depending on the reducing agent used, and is further purified if necessary to obtain trans-zabinene hydrate.

Note that this crude product contains almost no cis-zabinene hydrate, and almost no cis-zabinene hydrate is produced in this reduction reaction.

Further, the trans-zabinene hydrate thus obtained is used as a fragrance component or for other purposes, either as it is contained in the crude product or after being purified.

Thus, according to the method of the present invention, trans-3・4-
By applying a reducing agent to the epoxy gloss,
Trans-zabinene hydrate can be easily synthesized, and the yield is as high as around 90%.

Therefore, when producing trans-zabinene hydrate from α-thuene, conventionally, three steps are required as shown in formula (b), and the operation is also troublesome and complicated due to the use of peroxide, etc. However, transformer-3/4-
By using epoxy resin, trans-zabinene hydrate can be easily synthesized with relatively high yield by simplifying the process. Thus, the method of the present invention is advantageous for industrial production, and Mass production of hydrate is also easy.

Hereinafter, the present invention will be specifically explained with reference to Examples.

Example Preparation of trans-3,4-epoxy-thuane α-thuene 10. Add 6.3 g of diacetyl as a sensitizer to O g (73.4 mm), dissolve it by adding 100 ml of petroleum ether, and stir for 10 minutes under oxygen bubbling.
The interior was irradiated with light from a 0W high-pressure mercury lamp for 10 hours.

After the reaction, the sensitizer and solvent were distilled off at room temperature under reduced pressure after washing with a saturated sodium carbonate solution and drying over anhydrous magnesium sulfate. Obtained with a yield of 3%.

The properties of this compound are shown below.

Colorless liquid boiling point: 33-36℃/2mmHg GC (PEG20M10%, 2m, 130℃): RT3
．． 5m IR (NaCl plate): 1250cm-1, 840cm-1, 800cm-1M
S (m/e value): M+152 (MW152.23) NM
R: See formula (7') below, [(CCl4, TMS)δ]
0.2 2 (1H, q, 6 -Ha), 0.5
0(1H, q, 6-Hb), 0.78(3H, d
18-CH3or9-CH3), 0.83(3H, d
, 8-CH3or9-CH3), 1.32(3H,S
, 10-CH3), 2-63(1H, broad
-S13-H) Production of trans-zabinene hydrate Next, the trans-3,4-epoxy-thyan obtained by the above method was dissolved in 10 ml of ethyl ether, and 1.50 g of lithium aluminum hydride (39 ．．
5 mM) in 40 ml of ethyl ether at 0°C.
It was added dropwise for 0 minutes, stirred at room temperature for 2.5 hours, and then heated to 0°C.
Saturated sodium sulfate solution was added to the reaction solution, and then ethyl ether was added and the mixture was decanted.

Next, the ether layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure, the residue was fractionated under reduced pressure, and the results were determined by gas chromatography [gas chromatography conditions PEG-20M
10%, 2m, column temperature 130°C (inlet 150°C)
], trans-zabinene hydrate was obtained in a yield of 92-1% (overall yield from α-thuene 39.0%).

In addition, as a result of isolating this by preparative gas chromatography and identifying it by mass spectrum and NMR spectrum, it was confirmed that the obtained product corresponded to the standard product (natural trans-zabinene hydrate).

Furthermore, this method hardly produced cis-zabinene hydrate.

Example 2 15.4 g of benzyl was added to 10.0 g of α-tzene, 100 ml of benzene was added thereto and dissolved, and the light of a 100 W high-pressure mercury lamp was irradiated for 10 hours while stirring under oxygen blowing.
Internally irradiated for hours.

Thereafter, the same procedure as in Example 1 was carried out to obtain trans-3,4-epoxy-tyan in a yield of 32.9%.

Next, add 20 m of this trans-3/4-epoxy yarn.
12.3 g of hydrogenated triterallybutoxyaluminum lithium
The mixture was added dropwise to 80 ml of tetrahydrofuran at 0° C. over 20 minutes, and stirred at room temperature for 3 hours.

Thereafter, the same procedure as in Example 1 was carried out to obtain trans-zabinene hydrate in a yield of 89.5% (total yield from α-tzene 29.4%).

Example 3 10.4 g of 1-phenyl-1,2-propanedione was added to 10.0 g of α-thuene, and 10.4 g of dichloroethane was added to this.
0 ml was added and dissolved, and the mixture was internally irradiated with light from a 100 W high-pressure mercury lamp for 10 hours while stirring under oxygen blowing.

Thereafter, the same procedure as in Example 1 was carried out to obtain trans-3,4-epoxy-thyan in a yield of 40.5%.

Further, this material was dissolved in 180 ml of ethylenediamine, 0.7 g of metallic lithium was added thereto, and the mixture was heated for 35 hours for 4 hours.
After stirring vigorously at ℃, the mixture was cooled to room temperature.

Next, ice water was added to the reaction solution, extracted with tetrahydrofuran, and the extract was dried over magnesium sulfate, and then the solvent was distilled off.

Thereafter, the same procedure as in Example 1 was carried out to obtain trans-zabinene hydrate in a yield of 92.3% (total yield from α-tzene 37.4%).

Example 4 0.06 g of diacetyl was added to 0.1 g of α-tzene, 10 rIL of benzene was added thereto, and the mixture was dissolved. The mixture was externally irradiated with light from a 30 W low-pressure mercury lamp for 5 hours while stirring under oxygen blowing.

Thereafter, the same procedure as in Example 1 was carried out to obtain trans-3,4-epoxy-thyan in a yield of 34.5%.

Next, 0.01 g of metallic sodium was dissolved in 10 ml of liquid ammonia under cooling, and a solution of the above reactant (trans-3,4-epoxy-tyan) dissolved in 2 ml of tetrahydrofuran was added to this with stirring. .

After stirring for 1 hour, aqueous ethanol was added to vaporize ammonia, and water was further added to perform ether extraction.

The following procedure was carried out in the same manner as in Example 1, and trans-zabinene hydrate was obtained in a yield of 90.2% (total yield from α-tzene 31.1%).

Claims (1)

[Scope of Claims] 1. A method for producing trans-zabinene hydrate, which comprises reacting trans-3,4-epoxy-tyan and a reducing agent. 2. The transusabinene according to claim 1, wherein the reducing agent is selected from lithium aluminum hydride, lithium trialkoxyaluminum hydride, lithium trialkylaluminum hydride, lithium, sodium, and sodium-potassium alloy.・Production method of idrate.