Title of Invention

PROCESS FOR PRODUCING 2-(L-MENTHOXY)ETHANOL COMPOUND

Abstract

A process for production of a 2-(L -methoxy) ethanol- compound represented by the general formula (III) (R is a hydrogen atom, an alkyl group or a l-hydroxyalkyl group), comprising reacting L -menthol represented by the general formula (I) 1 with 1,2-epoxyalkanes represented by the general formula (II) (R is the same group as described above), in the presence of 0.1. to 1.0 mol of catalyst comprising a Lewis acid per 1 mol of L-menthol represented by the general formula (I).

Full Text

■ DESCRIPTION PROCESS FOR PRODUCING 2-(L-MENTHOXY)ETHANOL COMPOUND Technical Field The present invention relates to a process for producing 2-(L-menthoxy)ethanol compound. More specifically the present invention provides a process for producing 2-(L-menthoxy)ethanol compound which can give effect of cool feeling and refreshing feeling to food and beverage, cigarettes, cosmetics and the like, through a simple step and at low cost. Background Art Various substances which give cool feeling or refreshing feeling (hereinafter, these may wholly called as "cool and refreshing feeling") to human epidermis or mucous membrane, particularly to oral cavity, nasal cavity, throat, or eye parts, are already known. A representative example is L-menthol, which is a main component of peppermint oil and widely used in chewing gum, dentifrice, shampoo, and the like. However, L-menthol indeed has strong cooi and refreshing feeling, but the effect does not last for a long time, and uses or amount of formula thereof are often limited due to its strong mint-like odor. Therefore, in order to improve the continuousness and odor, compounds having behavior of cool and refreshing feeling such as L-menthol have been developed. Such compounds include, for example, 3-substituted-p-menthanes (see JP-A-47-16647, JP;:;^_-47-16449, and the specification of UK Patent No. 1,315,626), N-substituted-p-menthane-3-carboxamides (see JP-A-47-16648), p-menthane diols (see JP-A-47-16650), 3-(L-menthoxy)-propane-l, 2-diols (see JP-A-61-488I3, and the specification of US Patent No. 4,459,425), (2S)-3-{(lR, > ^ 2S, 5R)-[5-methyl-2-(l-methylethyl)cyclohexyl]oxy}-l, 2-propanediol (see JP-A-7-82200), (I'R, 2'S, 5'R)-3-L-menthoxyaIkane-l-ols (see JP-A-2001-294546), and the like. These compounds do not have strong mint-like smell as L-menthol, and have the behavior of cool and refreshing feeling lasting for a comparatively long period, and therefore extremely useful. Among the above-described compounds, (I'R, 2'S, 5'R)-3-L-menthoxyalkane-l-ols as described in JP-A-2001-294546 have excellent behavior of cool and refreshing feeling, but up to now, a simple and inexpensive production process thereof has not been established. A process for producing said compound adopted in JP-A-2001-294546 is a process wherein reducing an ether compound obtained from L-menthol and a chloroacetic acid by using lithium aluminum hydryde, which is a complexed and costly process. Disclosure of the Invention The purpose of the present invention is to provide a process for producing 2-(L-menthoxy)ethanol and relative compounds thereof which belong to (I'R, 2'S, 5'R)-3-L-menthoxyalkane-l-ols having excellent behavior as an agent for providing cool and refreshing feeling, using an inexpensive raw material and a simple step, furthermore, at low cost. The present inventors have intensively studied a way to accomplish the above-described purpose and have found that when L-menthol and 1, 2-epoxyalkanes are reacted using a Lewis acid as a catalyst, the objective 2-(L-menthoxy)ethanols can be produced extremely simply in a single step process, and at low cost using an inexpensive raw material compound and a catalyst, or without using sodium hydride which necessitates cautious handling, and further without taking complicated processes. Based on such finding, the > :i the catalyst comprising of the Lewis acid is one kind or at least two kinds of compounds selected from a group consisting of aluminum chloride, zinc chloride, zinc bromide, ferric chloride (III), and a boron trifluoride diethyl etherate. (3) The process for the production according to the above aspect (1) or (2), wherein the catalyst comprising of the Lewis acid is one or both of aluminum chloride and zinc chloride. (4) The process for the production according to any one of the above aspects (1) to (3), wherein the 1, 2-epoxyalkanes are ethylene oxide. Best Mode for Carrying Out the Invention Hereinafter, the present invention is explained in detail. As is clear from the above description, the present invention produces, in a single step reaction process, 2-(L-menthoxy)ethanols represented by the above-described general formula (III) [hereinafter called as "2-(L-menthoxy)ethanoIs (III)"] using L-menthol and 1, 2-epoxyalkanes represented by the above described general Formula (II) [hereinafter called as "1, 2-epoxyalkanes (II)"] as an inexpensive raw material compound. L-menthol is a well-known raw material compound, and the other raw material compound 1, 2-epoxyalkanes (II) may be those of commercially available ones or synthesized by a usual method. In the above described general formula (II), further in the above described 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 linear alkyl group or a ^b branched alkyl group, and it is preferably a linear or branched alkyl group having 1 to 5 carbon atom(s). Specific examples of a preferable alkyl group having 1 to 5 carbon atom(s) include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isopentyl group, a neopentyl group, a tert-pentyl group, and the like. When R is a 1-hydroxyalkyl group, it may be either a linear 1-hydroxyalkyl group or a branched 1-hydroxyalkyl group. In that case, R is preferably a linear or branched 1-hydroxyalkyl group having 1 to 5 carbon atom(s). Specific examples of a preferable 1-hydroxyalkyl group include a hydroxymethyl group, a 1-hydroxyethyl group, a l-hydroxy-n-propyl group, a 1-hydroxy-I-methylethyl group, a I-hydroxy-n-butyl group, a 1-hydroxy-n-pentyl group, and the like. As for use ratio of L-menthol and I, 2-epoxyalkanes (II), to 1 mol of L-menthol, 0.1 to 5.0 mol of 1, 2-epoxyalkanes (II) is preferable, and 0.5 to 2.5 mol thereof is more preferable. When the use ratio of the both compounds falls outside the above described range, the objective 2-(L-menthoxy)ethanols (III) cannot be obtaiaed smoothly. As for a Lewis acid used as a catalyst, any one may be used so long as it is a Lewis acid, but among them, one kind or at least two kinds among aluminum chloride (anhydride), zinc chloride (anhydride), zinc bromide, ferric chloride (III), and a boron trifluoride diethyl ether complex are preferably used, since the objective 2-(L-menthoxy)ethanols (III) can be obtained in high selectivity and yield. Among them, a single use of either one of aluminum chloride (anhydride) and zinc chloride (anhydride) or a combined use of the both is preferable from the points of reaction selectivity and yield of the objective 2-(L-menthoxy)ethanols ^-6 (III). Usage of a Lewis acid is preferably 0.01 to 3.0 mol, more preferably 0.1 to 1.0 mol, based on 1 mol of L-menthol which is a compound of a raw material (a substrate). When the usage of a Lewis acid is less than the above-described 0.01 mol, the objective 2-(L-menthoxy)ethanols (III) cannot be generated smoothly, and on the other hand, even when it exceeds 1.0 mol, there is no improvement in yield or conversion, and thus it is not economical. A reaction of L-menthol with 1, 2-epoxyalkanes (II) is preferably conducted in an organic solvent from the points of smooth proceeding and operationality of the reaction. Kinds of the organic solvent is not especially limited, and includes, for example, a hydrocarbon type solvent such as hexane, heptane, and toluene, a halogenated hydrocarbon type solvent such as dichloromethane, an ether type solvent such as tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, methyl tertiary-butyl ether, and ethylene glycol dimethyl ether, and the like. Among them, a hydrocarbon type solvent such as hexane, heptane, and toluene, is preferably used from the points of price, operationality in post treatment, and the like. A reaction of L-menthol with 1, 2-epox:yalkanes (II) is usually conducted within the range of -50°C to lOO^C, preferably between -30°C to 40°C, and by reacting them for 0,5 to 15 hours, preferably 1.0 to 5.0 hours at the above described temperature, the objective 2-(L-menthoxy)ethanols (HI) can be obtained in a single step process, extremely simply, and in high selectivity. Thus obtained 2-(L-menthoxy)ethanols (III) can be purified by adopting one kind or at least two kinds of purification methods usually used such as various types of chromatography, distillation, recrystallization, and the like. Meanwhile, the whole content described in the specification of Patent Sf V Application No. 2003-lU597 is incorporated in the present specification. Examples Hereinafter the present invention is specifically explained by way of Examples, but the present invention should not in the least be limited by Examples below as reference. Example 1 [Production of 2-(L-menthoxy)ethanol using aluminum chloride anhydride] (1) To a 1000 ml four-necked flask, 100.0 g (641 mmol) of L-menthol and 42.7 g (320 mmol) of aluminum chloride anhydride were added, and after purging with nitrogen and the addition of 500 ml of toluene, stirring was started under ice cooling. After confirming temperature of a reaction solution to be lowered to about 5°C, 57 g of ethylene oxide was provided while retaining the solution temperature at 5 to 10°C. After the end of the provision, stirring was further conducted at room temperature for one hour to complete the reaction. (2) Next, the reaction solution was cooled again and washed with a ISO ml of a 10% of hydrochloric acid while retaining at temperature not higher than 20°C. Then, after consecutive washing with 50 ml of water saturated with sodium bicarbonate and 100 ml of saturated salt water, water was removed with sodium sulfate, and a solvent was recovered under reduced pressure to obtain 123.1 g of crude 2-(L-menthoxy)ethanol. Vigoureux distillation thereof was conducted, followed by recovery of an unreacted raw material, isolation and purification of the objective substance to obtain 60.8 g of purified 2-(L-menthoxy)ethanol (theoretical yield based on L-menthol: 47.4%) and recover 45.7 g of unreacted L-menthol. ^6 Comparative Example 1 [Production of 2-(L-menthoxy)6thanol using sodium hydride instead of aluminum chloride anhydride] In the same way as in Example 1 except that 1.1 mol of sodium hydride was used based on I moi of L-menthol, solution temperature on reaction is about 95°C, and total reaction time is 1.0 hour, 2-(L-menthoxy)ethanol was produced by reacting L-menthol and ethylene oxide. Results of Example 1 and Comparative Example 1 are shown in Table 1 below, together with conversion of L-menthol, selectivity to 2-(L-menthoxy)ethanol, and yield of 2-(L-menthoxy)ethanol. sodium hydride was used as a basic catalyst, usage of catalyst was more and selectivity and yield of objective 2-(L-menthoxy)ethanol were lower, as compared with Example 1 wherein aluminum chloride anhydride was used as a Lewis acid catalyst. Example 2 [Production of 2-(L-menthoxy)ethanol using various Lewis acids] In the same way as in Example ] except that 0.2 mol of each of Lewis acids shown in Table 2 below was used based on 1 mol of L-menthol, and reaction temperatures and reaction times shown in Table 2 were adopted, 2-(L-menthoxy)ethanol was produced by reacting L-menthol and ethylene oxide. The results are shown in Table 2 below. In addition, conversion, selectivity and yield have the same meanings as in Table 1. As seen from the result in Table 2, when aluminum chloride anhydride and zinc chloride were used as catalysts comprising of a Lewis acid catalyst, the objective 2-(L-menthoxy)ethanols could be obtained in high selectivity and high yield. Industrial Applicability According to the method of the present invention, 2-(L-menthoxy)ethanols (III), with excellent behavior of cool and refreshing feeling, which have not very much used up to now since practical production method was not available, can be produced in a single step process, simply and at low cost, and additionally in high yield, using commonly used inexpensive compounds such as L-nienthol and 1,2-epoxyalkanes (II) as raw materials. By adding 2-(L-menthoxy)ethanols produced by the present invention to various kinds of commodities such as various food and beverage, cosmetics, cigarettes and the like, it enables to give them excellent cool and refreshing feeling with miid aroma and further continuousness, and thus, can enhance the values of those commodities. We Claim, 1. A process for production of a 2-(L-rTiethoxy) ethanol- compound represented by the general formula (III) (R is the same group as described above), in the presence of 0.1 to 1.0 mol of catalyst comprising a Lewis acid per 1 mol of L-menthol represented by the general formula (I). 2. The process as claimed in claim 1, wlierein the catalyst comprising of a Lewis acid is one kind or at least two l consisting of aluminum chloride, zinc chloride, zinc bromide, ferric chloride (III), and a boron trifluoride diettiyl etherate. 3. The process as claimed in claims 1 or 2, wherein the catalyst comprising of a Lewis acid is one or both of aluminum chloride and zinc chloride. 4. The process as claimed in any one of claims 1 to 3, wherein 1,2-epoxyalkanes are ethylene oxide. 1^

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