CN100366596C - Preparation method of 2- (L-menthoxy) ethanol compound - Google Patents

Abstract

The present invention provides a method for producing a 2- (L-menthoxy) ethanol compound having a cool and refreshing feeling in foods, drinks, tobaccos, cosmetics and the like, using inexpensive raw materials, through a simple process step, and at a low cost. A process for producing 2- (L-menthoxy) ethanol compounds represented by the following general formula comprises reacting L-menthol with 1, 2-alkylene oxide hydrocarbon compounds in the presence of a catalyst composed of a Lewis acid. R in the formula represents a hydrogen atom, an alkyl group or a 1-hydroxyalkyl group.

Description

The preparation method of 2-(L-menthoxy)ethanol compound

technical field

The invention relates to a preparation method of 2-(L-menthoxy)ethanol compounds. More specifically, the present invention provides a kind of 2-(L-menthoxy)ethanols with cooling effect and refreshing feeling prepared by simple process steps and at a lower cost compound method.

Background technique

It is known that there are many substances that can produce a cooling sensation (cooling sensation) or refreshing sensation (cooling sensation) on human skin and mucous membranes, especially the oral cavity, nasal cavity, throat, and eyes (hereinafter collectively referred to as "cooling and refreshing sensation"). An example of a representative substance is L-menthol, a main component of peppermint oil, which is widely used in chewing gum, toothpaste, shampoo and the like. Although L-menthol has a strong cooling and refreshing feeling, its effect cannot last for a long time, and its use and dosage are often limited due to its strong mint-type aroma.

Therefore, for the purpose of improving persistence and flavor, compounds having cooling and refreshing effect similar to L-menthol have been continuously developed. As this type of compound, there are, for example, 3-substituted-p-menthane compounds (see JP-A-47-16647 Gazette; JP-A-47-16449 Gazette; and British Patent GB 1,315,626 specification), N- Substituted-p-menthane-3-carboxamides (see JP-A-47-16648), p-menthanediols (see JP-A-47-16650), 3-(L- Menthyloxy)-1,2-propanediol (refer to JP-A-61-48813, and USP 4,459,425 specification), (2S)-3-{(1R,2S,5R)-[5-methyl -2-(1-methylethyl)cyclohexyl]oxy}-1,2-propanediol (refer to Japanese Patent Laid-Open No. 7-82200), (1'R, 2'S, 5'R)-3-L- Menthoxyalkan-1-ol compounds (see JP-A-2001-294546 specification) and the like. These compounds are very useful because they do not have a strong minty smell like L-menthol, and the cooling and refreshing effect lasts for a relatively long time.

Among the above-mentioned compounds, although the (1'R, 2'S, 5'R)-3-L-menthoxyalkan-1-ol compounds described in JP-A-2001-294546 have a good cooling and refreshing feeling effect, but so far cannot be prepared in a simple and inexpensive way. According to Japanese Patent Application Laid-Open No. 2001-294546, the compound is prepared by reducing an ether compound obtained from L-menthol and chloroacetic acid with lithium aluminum hydride, and the procedures are cumbersome and costly.

Contents of the invention

The object of the present invention is to provide a kind of (1'R, 2'S, 5'R)-3 which can use cheap raw materials, through simple process, and can prepare at a lower cost with good cooling agent and refreshing agent function - A method for 2-(L-menthoxy)ethanol and its analogues of L-menthoxyalkan-1-ols.

The inventors of the present invention conducted repeated studies to achieve the above object. It was found that if Lewis acid is used as a catalyst to react L-menthol with 1,2-alkylene oxide, it is possible to use expensive raw materials, expensive catalysts, and sodium hydride that need to be careful when handling, and without complicated procedures. The step, through one-step reaction, prepares described target compound 2-(L-menthoxy)ethanol compound extremely simply and with lower cost, and complete the present invention based on this understanding.

That is, the present invention is: (1) a method for preparing 2-(L-menthoxy)ethanol compounds, characterized in that: in the presence of a catalyst composed of a Lewis acid, L represented by the following general formula (I) is -Menthol:

React with the 1,2-epoxy alkylene compounds represented by the following general formula (II),

(wherein, R represents a hydrogen atom, an alkyl group or a 1-hydroxyalkyl group),

Preparation of 2-(L-menthyloxy)ethanol compounds represented by the following general formula (III):

(wherein, R represents the same group as above).

And, the present invention also includes:

(2) The preparation method as described in (1) above, wherein the catalyst composed of Lewis acid is selected from the group consisting of aluminum chloride, zinc chloride, zinc bromide, iron (III) chloride and boron trifluoride One or more compounds in ether complexes; and

(3) The preparation method as described in the above (1) or (2), wherein the catalyst composed of Lewis acid is one or both of aluminum chloride and zinc chloride;

(4) The preparation method as described in any one of (1) to (3) above, wherein the 1,2-alkylene oxide compound is ethylene oxide.

BEST MODE FOR CARRYING OUT THE INVENTION

Next, the present invention will be described in detail.

As mentioned above, the present invention uses cheap L-menthol and 1,2-epoxyalkylene compound (hereinafter referred to as "1,2-epoxyalkylene compound (II)" represented by the above-mentioned general formula (II) ) as a raw material compound to produce 2-(L-menthyloxy)ethanol compounds (hereinafter referred to as "2-(L-menthoxyl)ethanol compounds (III) represented by the above general formula (III) through one-step reaction ").

L-menthol as a raw material compound is a known compound, and the other raw material compound 1,2-alkylene oxide compound (II) may be a commercially available product, or a compound synthesized by a conventional method may be used.

In the above general formula (II) and general formula (III), R represents a hydrogen atom, an alkyl group or a 1-hydroxyalkyl group.

When R is an alkyl group, it may be either a straight-chain alkyl group or a branched-chain alkyl group, preferably a straight-chain or branched chain alkyl group having 1 to 5 carbon atoms. Specific examples of preferred alkyl groups having 1 to 5 carbon atoms include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl , n-pentyl, isopentyl, neopentyl, tert-pentyl, etc.

In addition, when R is a 1-hydroxyalkyl group, it may be a linear 1-hydroxyalkyl group or a branched 1-hydroxyalkyl group. In this case, R is preferably a linear or branched 1-hydroxyalkyl group having 1 to 5 carbon atoms. Specific examples of preferred 1-hydroxyalkyl groups include hydroxymethyl, 1-hydroxyethyl, 1-hydroxy-n-propyl, 1-hydroxy-1-methylethyl, 1-hydroxy-n-butyl and 1 -Hydroxy n-pentyl etc.

The use ratio of L-menthol and 1,2-epoxyalkane compound (II) is relative to 1 mol of L-menthol, preferably 0.1-5.0 mol, more preferably 0.5-2.5 mol of 1,2-epoxyalkane Class compound (II). When the ratio of the two is outside the above range, it is difficult to produce the target compound 2-(L-menthoxy)ethanol compound (III) smoothly.

The Lewis acid used as catalyst can be any Lewis acid in which, due to (anhydrous) aluminum chloride, (anhydrous) zinc chloride, zinc bromide, iron (III) chloride and boron trifluoride diethyl ether One or more of the complexes can obtain the target compound 2-(L-menthyloxy)ethanol compound (III) with high selectivity and high yield, so it is preferably used. Wherein, from the selectivity of reaction and the productive rate of target compound 2-(L-menthyloxy)ethanol compound (III), it is more preferable to use (anhydrous) aluminum chloride and (anhydrous) zinc chloride alone Either or a combination of both.

The amount of Lewis acid used is preferably 0.01 to 3.0 mol, more preferably 0.1 to 1.0 mol, based on 1 mol of the raw material compound (substrate) L-menthol. If the usage amount of Lewis acid is less than the above-mentioned 0.01mol, then it is difficult to generate the target compound 2-(L-menthyloxy)ethanol compound (III) smoothly, on the other hand, even if the usage amount exceeds 1.0mol, the yield and productivity cannot be improved. conversion rate and is therefore uneconomical.

From the viewpoints of smooth progress of the reaction and operability, it is preferable to carry out the reaction of L-menthol and the 1,2-epoxyalkylene compound (II) in an organic solvent. The kind of organic solvent is not particularly limited, can enumerate for example hydrocarbon solvents such as hexane, heptane, toluene; Halogenated hydrocarbon solvents such as methylene chloride; Tetrahydrofuran, dioxane, diethyl ether, diisopropyl base ether, methyl tert-butyl ether, ethylene glycol dimethyl ether and other ether solvents. Among these, hydrocarbon solvents such as hexane, pentane, and toluene are preferably used from the viewpoints of price and workability during post-treatment.

Usually at -50°C to 100°C, preferably at a temperature of -30°C to 40°C, L-menthol is reacted with 1,2-alkylene oxide compound (II) for 0.5 to 15 hours, preferably 1.0 to 5.0 hours, The target compound 2-(L-menthyloxy)ethanol compound (III) can be obtained extremely simply and with high selectivity through one-step reaction.

The 2-(L-menthyloxy)ethanol compound (III) thus obtained can be purified by one or more of the common purification methods such as various chromatography, distillation and recrystallization.

In addition, the full text of the contents described in the specification of Japanese Patent Application (Japanese Patent Application) No. 2003-111597 is included in this specification.

Example

Hereinafter, the present invention will be specifically described by citing examples, but the present invention is not limited to the following examples.

Example 1: Preparation of 2-(L-menthyloxy)ethanol using anhydrous aluminum chloride

(1) In a 1000ml four-neck flask, add 100.0g (641mmol) of L-menthol and 42.7g (320mmol) of anhydrous aluminum chloride, replace with nitrogen, add 500ml of toluene while ice-cooling and start stirring. After confirming that the temperature of the reaction liquid had dropped to about 5°C, 57 g of ethylene oxide was added while maintaining the liquid temperature at 5 to 10°C. After the feed was complete, further stirring was carried out at room temperature for 1 hour to complete the reaction.

(2) Next, the reaction solution was cooled again and washed with 150 ml of 10% hydrochloric acid while keeping the temperature below 20°C. Next, wash with 50 ml of saturated sodium bicarbonate and 100 ml of saturated brine, remove water with sodium sulfate, and recover the solvent under reduced pressure to obtain 123.1 g of crude 2-(L-menthoxy)ethanol. Carry out Vigoreux distillation (Vigoureux distillation) (Vigoureux distillation) to it, reclaim unreacted raw material and separate and refine target compound, obtain 2-(L-menthyloxy)ethanol 60.8g (theoretical yield based on L-menthol) Rate is 47.4%), and reclaim unreacted L-menthol 45.7g.

Comparative Example 1: Preparation of 2-(L-menthyloxy)ethanol using sodium hydride

With respect to the L-menthol of 1mol, use the sodium hydride of 1.1mol, the liquid temperature during reaction is about 95 ℃, and total reaction time is 1.0 hour, other conditions are the same as embodiment 1, make L-menthol and epoxy Ethane reacts to produce 2-(L-menthoxy)ethanol.

The results of Example 1 and Comparative Example 1 are shown in Table 1 below, including the conversion rate of L-menthol, the selectivity of 2-(L-menthoxy)ethanol and the selectivity of 2-(L-menthoxyl)ethanol. Yield.

Table 1

Catalyst (Reagent) Reaction temperature (°C) Response time (hr) Conversion rate(%) selectivity (%) Yield(%) type Usage¹⁾ Example 1 Anhydrous AlCl₃ 0.5mol 5～10 2.0 54.5 88.6 47.4 Comparative example 1 NaH 1.1mol 95 1.0 68.8 61.6 42.4

1) Relative to the usage amount of 1molL-menthol

As can be seen from the results in Table 1 above, compared with Example 1 using Lewis acid catalyst anhydrous aluminum chloride, in Comparative Example 1 using alkaline catalyst sodium hydride, the necessary amount of catalyst used is more, and the target product The selectivity and yield of 2-(L-menthoxy)ethanol were low.

Example 2: Preparation of 2-(L-menthoxy)ethanol using various Lewis acid catalysts

With respect to the L-menthol of 1mol, respectively use the Lewis acid catalyst shown in table 2 below 0.2mol, adopt the reaction temperature and the reaction time as shown in table 2, other conditions are the same as embodiment 1, make L-menthol and Ethylene oxide reacts to produce 2-(L-menthoxy)ethanol. The results are shown in Table 2 below, and the conversion, selectivity and yield have the same meanings as in Table 1.

Table 2

experiment number Catalyst (Reagent) Reaction temperature (°C) Response time (hr) Conversion rate(%) Selectivity (%) Yield(%) type Usage ¹⁾ 1 Anhydrous AlCl₃ 0.2mol 40 2.0 38.8 86.2 33.5 2 ZnCl₂ 0.2mol 40 3.0 27.4 91.2 25.0 3 BF₃ OEt₂ 0.2mol 40 2.0 49.7 48.7 24.2

1) Relative to the usage amount of 1molL-menthol

From the results in Table 2 above, it can be seen that when using anhydrous aluminum chloride and zinc chloride as a catalyst composed of Lewis acids, the target product 2-(L-menthyloxy)ethanol can be obtained with high selectivity and high yield.

Industrial Applicability

2-(L-menthyloxy)ethanol compound (III) has good cooling effect and refreshing effect, but because there is no preparation method suitable for practical application, it has not been widely used so far. By the method of the present invention, it can be used Commonly used cheap compounds such as L-menthol and 1,2-epoxyalkane compound (II) are used as raw materials, and 2-(L-menthyloxy) is prepared simply, at low cost and with high yield through a one-step reaction process Ethanol compound (III).

By adding the 2-(L-menthoxy)ethanol compound prepared by the present invention to various commodities such as food and drink, cosmetics, tobacco, etc., it can have mild fragrance and long-lasting good cooling and refreshing feeling , thereby increasing the value of these commodities.

Claims (4)

The preparation method of 1.2-(L-menthoxy group) ethanol compound is characterized in that: in the presence of a catalyst formed by Lewis acid, the L-menthol represented by the following general formula (I) is made:

React with the 1,2-epoxy alkylene compounds represented by the following general formula (II), In the formula, R represents a hydrogen atom, an alkyl group or a 1-hydroxyalkyl group, Prepare the 2-(L-menthyloxy)ethanol compound represented by the following general formula (III):

In the formula, R represents the same group as above. 2. The preparation method as claimed in claim 1, wherein the catalyst composed of Lewis acid is selected from the group consisting of aluminum chloride, zinc chloride, zinc bromide, iron(III) chloride and boron trifluoride diethyl ether complex One or two or more compounds of substances. 3. The preparation method according to claim 1 or 2, wherein the catalyst composed of Lewis acid is one or both of aluminum chloride and zinc chloride. 4. The preparation method according to any one of claims 1-3, wherein said 1,2-alkylene oxide compound is ethylene oxide.