JPH0469362A - Preparation of acetoacetic acid l-menthyl ester - Google Patents

Abstract

PURPOSE:To prepare the subject compound useful as a raw material for optically active compounds in a greatly high yield by adding diketene to l-menthol containing a catalyst in a solvent-free state while the reaction system is maintained at a specific temperature. CONSTITUTION:When a diketene is made to react with l-menthol to prepare an acetoacetic acid l-menthol ester, the diketene is added to l-menthol containing a catalyst (e.g. triethylamine) in a solvent-free state while the reaction temperature is maintained at 75 deg.C, thereby providing the acetoacetic acid l-men thol ester in a high yield. The mol. ratio of the diketene with l-menthol is preferably 0.9:1 to 1:0.85. The method is a simple and industrially highly useful process. The product is a greatly basic and valuable compound as a raw mate rial for the preparation of optically active chemical compounds.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing acetoic acid 1[-menthyl ester.

Acetoacetic acid 2-menthyl ester is an optically active ester, and is an extremely basic and highly useful compound that is used as a raw material for the production of optically active chemicals. [Prior art] Conventional acetoacetic acid 2-menthyl ester As a manufacturing method, the easily available methyl or ethyl ester of acetoacetate and! - A well-known method is transesterification with menthol.

For example, Journal of Organism, Fever Science (D, F, Taber et al., J', 'C1rg, Che
316B-3169 (1985), ), 4
-(Dimethylamino)pyridine is used as a catalyst to react l menthol and methyl acetoacetate in a toluene solvent.
a et al., Tetrahedron Lett, 27.2
383-2386 (1986), describes a method of reacting 2-menthol and ethyl acetoacetate using an organotin compound as a catalyst, which allows transesterification under neutral conditions. There is.

A well-known method for producing acetoacetate is to react a C-nidiketene with an alcohol to form the corresponding acetoacetate.

For example, Anna-Len Hemy (0, Mauz, Ju
stusLiebigs Annalen Chemi
e, 13ha, 345. ) describes a method of reacting diketene with various alcohols to produce the corresponding acetoacetic esters using triethylamine as a catalyst. or,
Organink Synthesis (Org, 5ynth,,
42.28-29. ) discloses a method for synthesizing the corresponding acetoacetate by reacting diketene and tert-butyl alcohol using sodium acetate as a catalyst. The above method is a solvent-free method, but with diketene! - Regarding the method of reacting with menthol, see the Journal of Organic Chemistry (D, p.

Taber et al., J.Org.Chem., 45.4
699-4102. (1980), ), a solvent is used to dilute and control the reaction.

[Problem to be Solved by the Invention 1] An object of the present invention is to produce 2-menthyl ester of acetoacetic acid by an industrially advantageous method.

In the conventional transesterification method, toluene, etc. (in each section) is reacted under reflux conditions for 24 or 42 hours to obtain a satisfactory reaction rate, which requires an extremely long reaction time and reduces productivity. Very low.

Moreover, this reaction is an equilibrium reaction, and in order to avoid this problem, relatively inexpensive acetoacetate is used in large excess relative to 2-menthol, and unreacted It is necessary to collect and recycle acetoacetate and solvent. Therefore, energy costs are high and the separation process becomes complicated, which is undesirable. Therefore, without solvent! - A method can be considered in which menthol and methyl acetoacetic acid are reacted in stoichiometric amounts, and the reaction is carried out under normal pressure or reduced pressure while expelling the generated methanol from the system. However, although the present inventors have conducted intensive studies on this method, it has been found that a large number of by-products are produced even under conditions of both acid catalysts and weakly basic catalysts. Well then! - Considerable amounts of menthol dehydrated to become olefins and further rearranged menthol were detected, making it impossible to obtain a product that could be industrially viable and easily partitioned.

On the other hand, it is well known that the corresponding acetoacetate ester can be easily obtained by reacting diketene with various alcohols, but! - There is no known example of the production of acetoacetate by the reaction of menthol and diketene using a solvent-free method, and when the present inventors carried out the reaction with reference to the cited solvent-free method, the target compound was obtained only slightly. However, the yield was so low that it could not be used as an industrial method.

The cause is not clear, but the basic problem is! - The reactivity of menthol was extremely low (it was immediately observed that only diketene self-reacted, producing a large amount of diketene dimer).

[Means for Solving the Problems] Therefore, the present inventors have developed a method for obtaining 2-menthyl ester of acetoacetic acid in high yield by reacting diketene with p-menthol, which is easy to purify. We have been conducting intensive research on a method of conducting the reaction at a raw material ratio close to the stoichiometric amount, and we have found that we can add p-menthol-modiketene containing a catalyst without a solvent while maintaining a specific reaction temperature. The present inventors discovered that the desired product could be obtained in a very high yield through the reaction, leading to the completion of the present invention.

That is, the present invention uses diketene! - In a method for producing l-menthyl ester of acetoacetic acid by reacting it with menthol, the reaction temperature is maintained at 75°C or less in the absence of a solvent, and a catalyst is added. -Acetoacetic acid characterized by adding diketene to menthol and reacting it! - A method for producing menthyl ester, more specifically, the molar ratio of diketene and e-menthol to be reacted is 09
This is a manufacturing method characterized in that the ratio is 1 to 1.0.85.6 Hereinafter, the features of the present invention will be explained in more detail.

The diketene used in the present invention is industrially produced and commercially available and can be used as is.

However, diketene easily undergoes condensation and deterioration when stored for a long period of time, so it may be necessary to re-purify it by distillation or the like before using it in the reaction.

! -Menthol is manufactured industrially with high purity and can be used as is.

As the catalyst, various known catalysts that are commonly used when synthesizing the corresponding acetoacetic esters by reaction of diketene and alcohol can be used. For example, alkali metal salts of acetic acid such as sodium acetate and potassium acetate, triethylamine, triethanolamine,
Examples include amines such as pyridine.

In this reaction, the main purpose is to simplify the purification and separation process, and no solvents used in boat fishing to proceed mildly are used. The key point of the present invention is to include the catalyst while maintaining the reaction temperature below 75°C! - consists in slowly adding diketene to the menthol reaction phase. This reaction is an exothermic reaction, and it is necessary to conduct the reaction while sufficiently removing the heat generated by the reaction. If this is not done, only a large amount of diketene monomer will be produced, and most of the target product will not be obtained. do not have. The addition rate of diketene is generally not determined depending on the reaction volume or the heat removal efficiency of the reactor, but is generally about 10 minutes to 5 hours. Further, according to the present invention, the reaction time after addition of a predetermined amount of diketene is about 2 hours at most. The total reaction time required is relatively short, and varies depending on other reaction conditions, but is approximately 1 to 8 hours. Heating to a reaction temperature exceeding 75°C and rapid addition of diketene should be avoided. The lower limit of the reaction temperature varies depending on the type and amount of the catalyst and cannot be generally determined, but if the reaction temperature is too low, the reaction rate will decrease. It is recommended that the reaction be carried out desirably at a temperature of about 50°C or higher.

With Jiketen! - The reaction molar ratio with menthol may basically be stoichiometric, and is carried out in the range of 09:l to i:o, 85. The obtained reaction solution can be subjected to column chromatography purification or distillation, if necessary, to isolate a highly pure target compound. In the present invention, there is almost no need for special treatment for separating and recovering unreacted raw materials. That is, the present manufacturing process provides a simple and industrially very useful process.

[Example] Hereinafter, the present invention will be explained in more detail with reference to Examples.

Example 1 A 100 d tube flask equipped with a visual stirrer, a thermometer, and a dropping funnel contained 15.6 g! - Menthol and 0.1 g of sodium acetate were added and heated to 70° C. with stirring, and then 9.2 g of diketene was added dropwise from the dropping funnel. Immediately after the start of dripping, heat generation occurs, so be careful not to let the internal temperature exceed 75℃.
The dropping was completed in about 90 minutes while adjusting the dropping speed and heating. After the dropwise addition was completed, the mixture was heated and stirred for an additional hour while maintaining the reaction temperature at 70° C., followed by cooling.

When the obtained reaction solution was analyzed by gas chromatography (column: silicon 5E-521m, 150'C, constant temperature), the conversion rate of P-menthol was 98%, and the yield of menthyl acetoacetate was 91%. there were.

The reaction solution was diluted with 150 d of ethyl ether,
After washing twice with saturated brine, it was dried over anhydrous magnesium sulfate to remove ether. The obtained residue was purified by column chromatography on Nlicagel (3% ethyl acetate/petroleum ether) to give 20.4 g (yield: 85%).
) was obtained as a colorless transparent oil.

Elemental analysis Ca1cd for C+ a H2403: C69
,95; H10,07Found: C70,0
8: H10,22 Example 2 The procedure was carried out in exactly the same manner as in Example 1 except that 0.1 g of pyridine was used as a catalyst instead of sodium acetate, and the isolated yield after column chromatography was 83% and colorless. A clear oil was obtained.

Comparative Example 1 The same procedure as in Example 1 was carried out except that diketene was added dropwise at 80°C and the reaction temperature after the addition was 80°C. Gas chromatography analysis revealed that diketene dimer was About 60% of the amount was generated.

[Effects of the Invention] As described above, according to the present invention, diketene! -Acetoacetic acid 2-menthyl ester can be obtained in high yield by reacting with menthol in almost stoichiometric amounts, and it can be carried out without solvent, so the separation process is extremely simple and the target compound of high purity can be obtained. This provides an industrially extremely advantageous process.

Patent applicant: Mitsui Toatsu Chemical Co., Ltd.

Claims (2)

[Claims] (1) In a method for producing l-menthyl ester of acetoacetic acid by reacting diketene and l-menthol, the reaction temperature is maintained at 75°C or less in the absence of a solvent, and l containing a catalyst is used. - A method for producing l-menthyl acetoacetate, which comprises adding diketene to menthol and causing the reaction. (2) The molar ratio of diketene and l-menthol is 0.9:
The method according to claim 1, wherein the ratio is 1 to 1:0.85.