JPH0643363B2 - Process for producing optically active 2-fluoro-2-methylalkanoic acid - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing optically active 2-fluoro-2-methylalkanoic acid.

This optically active 2-fluoro-2-methylalkanoic acid is useful as a synthetic intermediate for functional materials such as ferroelectric liquid crystal substances capable of taking a chiral smectic C phase and physiologically active substances such as pharmaceuticals and agricultural chemicals. Is.

[Conventional technology]

The optically active 2-fluoro-2-methylalkanoic acid is
It is known that a liquid crystal excellent in high-speed response can be obtained by using it as an optically active group of a ferroelectric liquid crystal. As a method for synthesizing this compound, the carboxyl group of optically active 2-fluoro-2-methylmalonic acid monoethyl ester was selectively reduced to an alcohol, tosylated and then alkylated, and then the ester was decomposed. Has been proposed [Kitazume et al., J. Org. Chem., 51, 1003 (1986)].

In this method, the reaction step is composed of 4 steps, and each step except for tosylation is not preferable because it is complicated in reaction operation such as temperature adjustment and reaction time.

[Problems to be Solved by the Invention]

The present inventor, as a result of intensive research to solve the above problems, was found to be surprising when optically active 2-fluoro-2-methyl-1-alkanol was oxidized with potassium permanganate as an oxidizing agent. In particular, it has been found that only hydroxymethyl group is oxidized without any ceramilation and the optically active 2-fluoro-2-methylalkanoic acid can be obtained while maintaining the optical activity.

The present invention has been made on the basis of such findings, and an object of the present invention is to carry out a reaction in one step, a reaction time is short, and post-treatment and the like are easy and simple, and optically active 2-fluoro-2-
It is to provide a method for producing methylalkanoic acid.

[Means for Solving the Problems]

The present invention is a method for producing an optically active 2-fluoro-2-methylalkanoic acid, which comprises oxidizing an optically active 2-fluoro-2-methyl-1-alkanol with potassium permanganate.

The optically active 2-fluoro-2-methyl-1-alkanol used as a starting material in the present invention has an optical purity of 8 to obtain a good ferroelectric liquid crystal or a physiologically active substance.
It is preferable to use one having 0% ee or more. This 2-fluoro-2-methyl-1-alkanol preferably has 4 to 18 carbon atoms for the same reason, and (-)-2-fluoro-2-methyl-1-butanol, (-)-2 -Fluoro-2-methyl-1-pentanol, (-)-2-fluoro-2-methyl-1-hexanol,
(-)-2-Fluoro-2-methyl-1-heptanol, (-)-2-Fluoro-2-methyl-1-octanol, (-)-2-Fluoro-2-methyl-1-nonanol, (- ) -2-Fluoro-2-methyl-1-decanol, (-)-2-fluoro-2-methyl-1-undecanol,
(-)-2-Fluoro-2-methyl-1-dodecanol, (-)-2-fluoro-2-methyl-1-tridecanol, (-)-2-fluoro-2-
Methyl-1-tetradecanol, (-)-2-fluoro-2-methyl
-1-pentadecanol, (-)-2-fluoro-2-methyl-1-hexadecanol, (-)-2-fluoro-2-methyl-1-heptadecanol, (-)-2-fluoro Examples thereof include -2-methyl-1-octadecanol and the like, as well as the (+) alkanols. Incidentally, these 2-fluoro-2-methyl-1-alkanols can be easily obtained by reacting an optically active 2-methyl-1,2-epoxyalkane with an amine-hydrogen fluoride complex or silicon tetrafluoride. Can be obtained (Japanese Patent Application No. 64-56058)
issue). In addition, this epoxide uses α
-It can be prepared by oxidizing an olefin (see Japanese Patent Publication No. 56-40).

The present invention is to oxidize the above-mentioned 2-fluoro-2-methyl-1-alkanol with potassium permanganate, but this oxidation accelerates the reaction if carried out under acidic conditions, especially under acidic conditions of sulfuric acid. preferable. That is, 2-fluoro-2-methyl-1-alkanol is suspended in a 2-40% sulfuric acid aqueous solution, and 1-5 mol of permanganese is mixed with 1 mol of the 2-fluoro-2-methyl-1-alkanol. Add potassium acid and react. This reaction is preferably carried out near room temperature, that is, at a temperature of 10 to 40 ° C. At this temperature, 2-fluoro-2-methyl-
If the 1-alkanol is solid, the reaction proceeds slowly as it is, so a solvent that dissolves the 2-fluoro-2-methyl-1-alkanol, such as acetone, t-butyl alcohol, chloroform, benzene, petroleum ether, etc. It is preferable that the solvent is dissolved in advance before use, or about 5 to 20% of this solvent is added to the reaction system. This reaction proceeds relatively quickly, and the obtained reaction product is transferred to an aqueous sodium hydrogen sulfite solution, and unreacted potassium permanganate and manganese dioxide are dissolved and removed in an aqueous layer to remove an organic solvent such as ether. The 2-fluoro-2-methylalkanoic acid can be easily obtained by extracting with a known means such as distillation or column chromatography.

〔Example〕

Example 1 2.5 g (-)-2-fluoro-2-methyl-1-heptanol (0.02 mo
To l), 100 ml of a 10% strength sulfuric acid aqueous solution was added to give a suspension. While cooling this in a water bath and maintaining the liquid temperature at 21 to 28 ° C, 9.7 g (0.06 mol) of kalim permanganate was added over 4 hours. After the addition was completed, the reaction mixture was ice-cooled, sodium bisulfite (7.3 g, 0.07 mol) was added, and hydrochloric acid was further added to adjust the pH to 1 or less, followed by extraction with ether. The extract was extracted with a 10% aqueous sodium hydroxide solution. Next, while cooling this aqueous solution with ice, hydrochloric acid was added to adjust the pH to 1 or less and the mixture was extracted with methylene chloride. The extract was washed with water and dried over magnesium sulfate.
After separation, the solution is concentrated and distilled under reduced pressure to 85.5 ℃ -87.0 ℃ / 2
1.80 g of mmHg fraction was collected. As a result of measuring the physical properties of this, it was as follows and was found to be (-)-2-fluoro-2-methylheptanoic acid. The yield was 56%. ¹ H-NMR (CDCl ₃ , TMS standard, ppm) 8.40 (S, 1H), 0.70 to 2.70 (m, 14H) ▲ [α] ²⁵ _D ▼ = -3.67 ° (d = 0.1, c6.54) Example 5.0 g (0.04mo) of 2 (-)-2-fluoro-2-methyl-1-hexanol
To l), 200 ml of 10% sulfuric acid aqueous solution was added to give a suspension. While this was cooled in a water bath and the liquid temperature was maintained at 21 to 28 ° C, 19.0 g (0.12 mol) of potassium permanganate was added over 4 hours. Thereafter, the same treatment as in Example 1 was carried out to collect 3.6 g of a fraction at 100 ° C to 101.0 ° C / 12 mmHg. As a result of measuring the physical properties of it, it is as follows, (-)-
It was found to be 2-fluoro-2-methylhexanoic acid. The yield was 60%. ¹ H-NMR (CDCl ₃ , TMS standard, ppm) 8.40 (S, lH), 0.70 to 2.70 (m, 12H) ▲ [α] ²⁵ _D ▼ = -3.55 ° (d = 0.1, c5.35) Example 5.0 g (0.04mo) of 3 (-)-2-fluoro-2-methyl-1-pentanol
l) and 19.0 g (0.12 mol) of potassium permanganate were reacted and treated in the same manner as in Example 2, 99.0 ° C to 100.0 ° C / 1
2.9 g of a 9 mmHg fraction was collected. As a result of measuring the physical properties of this, it was as follows and was found to be (-)-2-fluoro-2-methylpentanoic acid. The yield was 54%. ¹ H-NMR (CDCl ₃ , TMS standard, ppm) 8.10 (S, 1H), 0.70 to 2.70 (m, 10H) ▲ [α] ²⁵ _D ▼ = -1.58 ° (d = 0.1, c6.98) [Invention Effect] The present invention has a special effect that an optically active 2-fluoro-2-methylalkanoic acid can be produced in one step, in a short reaction time, and after-treatment is extremely easy and can be simply produced. Is.

Claims (1)

[Claims] 1. A method for producing an optically active 2-fluoro-2-methylalkanoic acid, which comprises oxidizing an optically active 2-fluoro-2-methyl-1-alkanol with potassium permanganate.