JPH0643362B2 - Process for producing optically active 2-fluoroalkanoic acid - Google Patents

Description

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

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

[Prior Art] Optically active 2-fluoroalkanoic acid is particularly useful when used as an optically active group of a ferroelectric liquid crystal to obtain a liquid crystal excellent in high-speed response. -
A method has been proposed in which fluoro-1-alkanol is converted to acetic acid ester and then oxidized with nitric acid [Nohira et al., 13th Liquid Crystal Conference 1Z02 (1987)].

This method consists of a two-step reaction process, and since acetic acid is used as a solvent in the second step of the oxidation reaction of acetic acid ester with nitric acid, a large amount of water for dilution and the accompanying extraction water are used. It was not preferable because it required a large amount of ether, and required heating and stirring for 25 hours to complete the oxidation reaction, which was complicated and complicated in the reaction operation [Dean et al.
al.), Organic Synthesis (Org.Synth.), Coll.V
ol.V, p.580 (1973)].

[Problems to be Solved by the Invention] An object of the present invention is to solve the above-mentioned drawbacks. The reaction is carried out in one step, the reaction time is short, and the post-treatment is easy and simple. -To provide a method for producing a fluoroalkanoic acid.

[Means for Solving the Problems] As a result of intensive research to solve the above problems, the present inventors have found that potassium permanganate is used as an oxidant for optically active 2-fluoro-1-alkanols. Surprisingly, it was found that, when used for oxidation, racemization did not occur at all, and only the hydroxymethyl group was oxidized to the optically active 2-fluoroalkanoic acid while maintaining the optical activity.

The present invention was made based on the above findings, and the present invention is
It consists of oxidizing an optically active 2-fluoro-1-alkanol with potassium permanganate.

The optically active 2-fluoro-1-alkanol used as a starting material in the present invention should have an optical purity of 70% ee or more in order to obtain a good ferroelectric liquid crystal or a physiologically active substance. preferable. This 2-fluoro-1-alkanol preferably has 3 to 18 carbon atoms for the same reason, and includes (-)-2-fluoro-1-propanol, (-)-2-fluoro-1-butanol, ( -)-2-fluoro-1-pentanol,
(-)-2-Fluoro-1-hexanol, (-)-2-Fluoro-1-heptanol, (-)-2-Fluoro-1-octanol, (-)-2-
Fluoro-1-nonanol, (-)-2-fluoro-1-decanol, (-)-2-fluoro-1-undecanol, (-)-2-fluoro-1-dodecanol, (-)-2-fluoro- 1-tridecanol, (-)-2-fluoro-1-tetradecanol, (-)-2-fluoro-1-pentadecanol, (-)-2-fluoro-1-hexadecanol, (-)- 2-fluoro-1-heptadecanol and (-)
-2-Fluoro-1-octadecanol, etc., and (+) above 2
Examples thereof include -fluoro-1-alkanols. Incidentally, these 2-fluoro-1-alkanols can be easily obtained by reacting an optically active 1,2-epoxyalkane with an amine-hydrogen fluoride complex. The epoxides can be prepared by oxidizing α-olefin using a microorganism (see Japanese Patent Publication No. 56-40).

The above-mentioned 2-fluoro-1-alkanol is oxidized with potassium permanganate, and this oxidation is preferable because the reaction proceeds rapidly because it is carried out under acidic conditions, especially under acidic conditions with sulfuric acid. That is, 2-fluoro-1-alkanol is suspended in a 2 to 40% sulfuric acid aqueous solution, and 1 to 3 times the molar amount of potassium permanganate is added and reacted. This reaction is preferably carried out near room temperature, that is, at a temperature of 10 to 40 ° C. Incidentally, at this temperature, the solid 2-fluoro-1-alkanol, the reaction progresses slowly as it is, so the solvent that dissolves the 2-fluoro-1-alkanol, for example, acetone, t-butyl alcohol, Pre-dissolved in chloroform, benzene, petroleum ether, etc., or use this solvent for 5 ~ 2
About 0% is preferably added to the reaction system. This reaction is completed relatively quickly, and the obtained reaction mixture is transferred to an aqueous sodium hydrogensulfate solution to dissolve and remove unreacted potassium permanganate and manganese dioxide in an aqueous layer, and an organic solvent such as ether. The 2-fluoro-1-alkanoic acid can be easily obtained by extracting with a known means such as distillation or column chromatography.

As described above, the present invention is a one-step reaction and the reaction solvent is an acidic aqueous solution, so that the operation for the reaction and isolation is extremely simple.

Next, the present invention will be specifically described based on examples, but the present invention is not limited to these examples.

[Examples] (-)-2-Fluoro-1-with a specific optical power ▲ [α] ²⁵ _D ▼ of -13.6 °
2.40 g (16.2 mmol) of octanol and 4.5 ml of acetone were mixed and stirred to homogenize them, and then 45 ml of 11% strength aqueous sulfuric acid solution was added thereto to obtain a suspension. 6.0 g (38.0 mmol) of potassium permanganate was added to this suspension over 50 minutes while cooling this with a water bath and maintaining the liquid temperature at 22 to 25 ° C. After the addition was complete, the reaction mixture was transferred to 50 ml ice water,
Sodium bisulfite was added, and hydrochloric acid was added,
After adjusting the pH to 1 or less, the mixture was extracted with ether. The extract was extracted with a 10% aqueous sodium hydroxide solution. Next, while adding ice to this aqueous solution and cooling, concentrated hydrochloric acid was added to adjust the pH to 1 or less, and the mixture was extracted with chloroform.
The extract was washed with water and dried over magnesium sulfate. After separation, the solution is concentrated and distilled under reduced pressure to 110-110.
1.70 g of a fraction of 130 ° C./0.7 mmHg was collected. As a result of measuring the physical properties of this, it is as follows, (-)-2-fluoro-1-
It was found to be octanoic acid. The yield was 65%. ¹ H-NMR (in CDCl ₃ , TMS standard, ppm): 8.65 (s, 1 H), 4.93 (d
t, 1H, J HF = 50Hz, J CH-CH ₂ = 6Hz), 2.1 to 1.0 (10H), 0.9
(t, 3H) IR (cm ^-1 ): 2920, 1720 ▲ [α] ²⁵ _D ▼: -8.5 ° [Effect of the Invention] The present invention provides an optically active 2-fluoroalkanoic acid in one step and in a With the reaction of time, the post-treatment and the like are extremely easy, and the special effect of being able to be produced easily is exhibited.

Continuation of front page (72) Inventor Mitsuru Fukumasa, 3-17-35, Shinzonan, Toda City, Saitama Prefecture, Japan Mining Co., Ltd. (56) Reference JP-A-63-243058 (JP, A)

Claims (1)

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