WO2004092104A1

WO2004092104A1 - Process for producing 2-(l-menthoxy)ethanol compound

Info

Publication number: WO2004092104A1
Application number: PCT/JP2004/003058
Authority: WO
Inventors: Kenichiro Adachi; Kenya Ishida; Hiroyuki Matsuda
Original assignee: Takasago International Corporation
Priority date: 2003-04-16
Filing date: 2004-03-10
Publication date: 2004-10-28
Also published as: JP4179916B2; ES2267408B1; JP2004315427A; KR20050114238A; CN1764622A; CN100366596C; ES2267408A1

Abstract

A process by which a 2-(L-menthoxy)ethanol compound which can enable foods or beverages, cigarettes, cosmetics, etc. to give a refreshing cool feeling can be produced from inexpensive materials through a simple step at low cost. The process, which is for producing a 2-(L-menthoxy)ethanol compound represented by the general formula (1) (wherein R represents hydrogen, alkyl, or 1-hydroxyalkyl), comprises reacting L-menthol with a 1,2-epoxyalkane in the presence of a catalyst comprising a Lewis acid.

Description

Specification

2-(L-menthoxy) Method for producing ethanol

The present invention relates to a method for producing 2- (L-menthoxy) ethanols. More specifically, the present invention provides 2- (L-menthoxy) ethanols that can impart a refreshing cooling sensation effect and a refreshing sensation to foods, drinks, tobacco, cosmetics, and the like in a simple process and at a very low level. It is intended to provide a cost-effective manufacturing method. Background art

Cold sensation (cold sensation) in the epidermis and mucous membranes of humans, especially in the oral cavity, nasal cavity, throat, and eyes ゃ Refreshing sensation (cool sensation) Various substances have already been known. A typical substance is L-menthol, the main component of peppermint oil, which is widely used in chewing gum, dentifrice, shampoos and the like. However, although L-menthol has a strong cooling and refreshing sensation, its effect does not last for a long time, and its intense mint-like aroma often limits its use and formulation.

Therefore, compounds having a cooling / cooling effect similar to L-menthol have been developed for the purpose of improving persistence and aroma. Examples of such compounds include tri-substituted mono-p-menthanes (JP-A-47-16647; JP-A-47-167).

No. 449, and British Patent No. 1,315,626), and N-substituted-p-menthane-13-hexolpoxamides (JP-A-47-16648) Gazette), P-Mendiol (see JP-A-47-16650), 3- (L-menthoxy) -propane-1,2-diol (JP-A-61-160) No. 4,881,13 and U.S. Pat. Nos. 4,459,425), (2S) —3 — {(1R, 2S _:

5R)-[5-Methyl-2- (1-methylethyl) cyclohexyl] oxy} 1-1,2-propanediol (see Japanese Patent Application Laid-Open No. 7-822000), (l'R, 2, S, 5'R) -1-L-menthoxyalkane-1-ols (JP-A 2001- No. 2,945,464). These compounds are extremely useful because they do not have a strong mint odor like L-menthol and have a long-lasting cooling / cooling effect.

Among the above-mentioned compounds, it is described in Japanese Unexamined Patent Application Publication No. 2000-2949546 (1'R, 2'S, 5 ')-13-L-menthoxyalkane-1 —Alls have excellent cooling / cooling effects, but no simple yet inexpensive manufacturing method has been established. According to Japanese Patent Application Laid-Open No. 2000-294654, 'The compound is produced by a method of reducing an etherified product obtained from L-menthol and chloroacetic acid using lithium hydride aluminum. And other labor-intensive and costly methods are adopted. Disclosure of the Invention.

An object of the present invention is to provide a cooling sensation agent that has an excellent function as a cooling agent (1′R, 2 ′S, 5′.R) —3—L -Mentoxy) It is an object of the present invention to provide a method capable of producing ethanol and its analogous compounds using inexpensive raw materials in a simple process and at low cost. The present inventors have been studying to achieve the above object. As a result, when L-menthol is reacted with 1,2-epoxy alkanes using Lewis acid as a catalyst, expensive raw material compounds, expensive catalysts, and hydrogenated sodium hydride requiring careful handling are used. Without the use of a system, etc., and without going through complicated processes.

(L-menthoxy) It has been found that ethanol can be produced very easily and at low cost in a single-step reaction, and the present invention has been completed based on such findings.

That is, the present invention

(1) The following formula (I);

(I)

L-menthol represented by the following general formula (II);

(Wherein, R represents a hydrogen atom, an alkyl group or a 1-hydroxyalkyl group.) 1,2-epoxyalkane represented by the following formula: The following general formula (III):

(In the formula, R represents the same group as described above.)

This is a method for producing 2- (L-menthoxy) ethanols, characterized by the production of 2- (L-menthoxy) ethano one-swords.

• And the present invention

(2) The catalyst comprising a Lewis acid is one or more compounds selected from the group consisting of aluminum chloride, zinc chloride, zinc bromide, iron (III) chloride, and boron trifluoride getyl ether complex. (1) The production method according to the above (1);

(3) The method of (1) or (2) above, wherein the 'catalyst comprising a Lewis acid' is one or both of aluminum chloride and zinc chloride;

(4) The method according to any one of the above (1) to (3), wherein the 1,2-epoxyalkane is ethylene oxide;

It is. Best mode for carrying out the invention.

Hereinafter, the present invention will be described in detail. As is clear from the above, the present invention provides, as raw material compounds, inexpensive L-menthols and 1,2-epoxyalkanes [hereinafter referred to as “1,2-epoxyalkanes” represented by the above general formula (II). Alkanes (II) ”], 2- (L-menthoxy) ethanols [hereinafter referred to as“ 2- (L-menthoxy) ethanols (III) ”represented by the above general formula (III) Is produced in a single-stage reaction process.

The raw material compound L-menthol is a well-known compound, and the other raw material compound 1,2-epoxyalkanes (II) may be commercially available ones or synthesized by a conventional method. May be used.

In the general formula (II) and the 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 any of a linear alkyl group and a branched alkyl group, and is preferably a linear or branched alkyl group having 1 to 5 carbon atoms. Specific examples of the preferred alkyl group having 1 to 5 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, and n-pentyl. Group, isopentyl group, neopentyl group, tert-pentyl group and the like.

When R is a 1-hydroxyalkyl group, it may be a linear 1-hydroxyalkyl group or a branched 1-hydroxyloxyalkyl group. In this case, R is a linear or branched 1-hydroxy group having 1 to 5 carbon atoms.

It is preferably an alkyl group. Specific examples of preferred 1-hydroxyalkyl groups include a hydroxymethyl group, a 1-hydroxyl group, a 1-hydroxyl-n-propyl group, a 1-hydroxyl-l-methylethyl group, and a 1-hydroxyl-n-butyl group. Examples thereof include a tyl group and a 1-hydroxy_n-pentyl group.

The proportion of L-menthol and 1,2-epoxyalkanes (II) used is from 0.1 to 5.0 mol of 1,2-epoxyalkanes (II) per mole of L-menthol. Preferably, it is 0.5 to 2.5 moles. If the use ratio of both is out of the above range, it becomes difficult to obtain the desired 2- (L-menthoxy) ethanol (III) smoothly. As the Lewis acid used as the catalyst, any Lewis acid may be used. Among them, (anhydrous) aluminum chloride, (anhydrous) zinc chloride, zinc bromide, iron chloride

(III) and one or more of the boron trifluoride getyl ether complexes are capable of producing the desired 2- (L-menthoxy) ethanols (ΠΙ) in high selectivity and yield. It is preferably used. Among them, the use of either (anhydrous) aluminum chloride or (anhydrous) zinc chloride alone or in combination is critical for the selectivity of the reaction and the desired 2- (L-menthoxy) ethanol. It is more preferable in view of the yield of the compound (III).

The amount of the Lewis acid used is preferably from 0.01 to 3.0 mol, more preferably from 0.1 to 1.0 mol, per mol of L-menthol, which is the starting compound (substrate). preferable. If the amount of the Lewis acid used is less than 0.01 mol, the desired 2- (L-menthoxy) ethanols (III) will not be produced smoothly, whereas 1. Even if it exceeds 0 mol, the yield and the conversion are not improved, and it is not economical.

The reaction between L-menthol and 1,2-epoxyalkanes (II) is preferably carried out in an organic solvent in terms of the smooth progress of the reaction and operability. The type of organic solvent is not particularly limited, and examples thereof include hydrocarbon solvents such as hexane, heptane, and toluene, halogenated hydrocarbon solvents such as dichloromethane, tetrahydrofuran, dioxane, dimethyl ether, diisopropyl ether, and the like. Methyl tertiary esters include ether solvents such as ethylene glycol dimethyl ether. Among them, hydrocarbon solvents such as hexane, heptane, and toluene are preferably used from the viewpoint of price and operability in post-treatment.

The reaction of L-menthol with 1,2-epoxyalkanes (II) is usually carried out at −50 ° C. to 100 t, preferably at 130: to 40 ° C. After reacting for up to 15 hours, preferably for 1.0 to 5.0 hours,

(L-menthoxy) Ethanols (III) can be obtained very easily and with high selectivity in a single step.

The 2- (L-menthoxy) ethanols (III) thus obtained can be obtained by employing one or more of the commonly used purification methods such as chromatography, distillation, and recrystallization. It can be purified. The contents described in the specification of Japanese Patent Application No. 2003-111115 are incorporated herein in their entirety. Example

Hereinafter, the present invention will be described specifically with reference to examples. However, the present invention is not limited to the following examples. Example 1 [Production of 2- (L-menthoxy) ethanol using anhydrous aluminum chloride]

(1) To a 100 ml four-necked flask, add L-menthol 100.0.0 g (64 1 mmo 1) and anhydrous aluminum chloride 42.7 g (320 mmo 1). After nitrogen replacement, 500 ml of toluene was added while cooling with ice, and stirring was started. After confirming that the temperature of the reaction solution had dropped to about 5 ° C, 57 g of oxidized titanium was supplied while maintaining the solution temperature at 5 to 10 ° C. After the completion of the supply, the mixture was further stirred at room temperature for 1 hour to complete the reaction.

(2) Then, the reaction solution was cooled again and washed with 150 ml of 10% hydrochloric acid while maintaining the temperature at 20 ° C. or lower. Then, the mixture was washed successively with 50 ml of saturated aqueous sodium bicarbonate and 100 ml of saturated saline, then water was removed with sodium sulfate, and the solvent was recovered under reduced pressure to obtain crude 2- (L-menthoxy). 1) 23.1 g of ethanol were obtained. This was subjected to a single-vig distillation to recover the unreacted raw material and to isolate and purify the target substance.Purification 2- (L-menthoxy) ethanol 60.8 g (theoretical yield based on L-menthol 47. 4%) and 45.7 g of unreacted L-menthol were recovered. Comparative Example 1 [Production of 2- (L-menthoxy) ethanol using sodium hydride]

Using 1.1 mol of sodium hydride per 1 mol of L-menthol, the reaction temperature was about 95, the total reaction time was 1.0 hour, and the other conditions were the same as in Example 1. 1-menthol reacts with ethylene oxide to give 2- (L-menthoxy) ethanol Manufactured. The results of Example 1 and Comparative Example 1 are shown in Table 1 below, together with the conversion of L-menthol, the selectivity to 2- (L-menthoxy) ethanol, and the yield of 2 (L-menthoxy) 'ethanol. .

1) Amount used per mole of L-menthol As shown in the results in Table 1 above, in Comparative Example 1 using sodium hydride as a basic catalyst, anhydrous aluminum chloride as a Lewis acid catalyst was used. Compared to Example 1, the required amount of the catalyst is large, and the selectivity and the yield of the target product, 2- (L'-menthoxy) ethanol, are low. Example 2 [Production of 2- (L-menthoxy) ethanol using various Lewis acid catalysts]

With respect to 1 mol of L-menthol, each of the Louis' acid catalysts shown in Table 2 below was used in a ratio of 0.2 mol, and the reaction temperature and reaction time shown in Table 2 were used. Otherwise, in the same manner as in Example 1, L-menthol was reacted with ethylene oxide to produce 2- (L-menthoxy) ethanol. The results are shown in Table 2 below. The conversion, selectivity and yield have the same meanings as in Table 1. Table 2

1) Amount used per mole of L-menthol As shown in the results in Table 2 above, when anhydrous aluminum chloride and zinc chloride are used as the catalyst comprising the Lewis acid, the target substance is 2- ( L-menthoxy) Ethanols were obtained with high selectivity and high yield. Industrial applicability

According to the method of the present invention, there is no practical manufacturing method while having an excellent cooling sensation effect and a cooling effect, and thus it has not been used so far.

(L-menthoxy) Ethanols (III) can be prepared easily and in a single step using L-menthol and 1,2-epoxyalkanes (II) as general-purpose inexpensive compounds as raw materials. It can be manufactured at low cost and high yield.

The 2- (L-menthoxy) ethanols produced according to the present invention can be added to various foods, cosmetics, tobacco, and other various products to provide a mild, long-lasting and excellent cooling sensation. It is possible to give a refreshing feeling and increase their commercial value.

Claims

Iff Equation (I) below;

Request

L-menthol represented by the following general formula (I I)

of

(Wherein R represents a hydrogen atom, an alkyl group or a 1-hydroxyalkyl group). The 1,2-epoxyalkane represented by the following formula is reacted in the presence of a Lewis acid catalyst to obtain the following. One

(In the formula, R represents the same group as described above.)

A method for producing 2- (L-menthoxy) ethanols, characterized by producing 2- (L-menthoxy) ethanols represented by the formula:

2. The catalyst comprising a Lewis acid is one or more compounds selected from the group consisting of aluminum chloride, zinc chloride, zinc bromide ', iron (III) chloride and trifluoro boron getyl ether complex. The production method according to claim 1.

3. The production method according to claim 1, wherein the catalyst comprising a Lewis acid is one or both of aluminum chloride: aluminum and zinc chloride.

4. The method according to any one of claims 1 to 3, wherein the 1,2-epoxyalkane is ethylene oxide.