JPH01316341A - Production of omega-hydroxy fatty acid - Google Patents

Abstract

PURPOSE:To obtain the title compound useful as a raw material for synthesizing macrocyclic lactone suitable as a raw material for drugs, perfume, etc., from inexpensive raw materials simply and advantageously by directly reducing an alkali metallic salt of long-chain diacid monoester with a boron hydride compound. CONSTITUTION:An alkali metallic salt or an alkaline earth metallic salt of long-chain diacid monoester is reacted with preferably 0.5-1mol based on 1mol of the salt of long-chain diacid monoester of a boron hydride compound in an organic solvent such as diethylene glycol dimethyl ether, etc., at 0-100 deg.C to give the aimed compound. The alkali metallic salt or the alkaline earth metallic salt of the monoester is obtained by diesterifying an alkanediacid with an alcohol, adding an alkali metal hydroxide or an alkaline earth metal hydroxide to the esterified substance and subjecting to solid-liquid separation. Lithium boron hydride is preferable as the boron hydride compound.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing ω-hydroxy fatty acids. ω-Hydroxy fatty acids are useful as raw materials for the synthesis of macrocyclic lactones used as raw materials for pharmaceuticals or fragrances.

Furthermore, it has a wide range of uses as a polymer raw material.

[Prior Art] Conventionally, as a method for producing ω-hydroxy fatty acids, ω-
Hydroxy- or ω-acyloxy-alkyl-γ
- A method of catalytically reacting butyrolactone in the presence of a hydrogen cracking catalyst and in the coexistence of hydrogen gas (Japanese Patent Publication No. 61-37
76) or 13-oxa-bicyclo[10,
A method has been proposed in which 4゜0]-hexadecene [1(12)] is converted into a lactone and the lactone ring is opened by the Wolffukisiner method or the van-minolone method (Japanese Patent Publication No. 61-21474). has been done. All of these methods use complex compounds as starting materials, resulting in the use of expensive raw materials, and as a result, 'I5
The problem was that the manufacturing cost was high.

In contrast, the present inventor uses a relatively inexpensive long-chain diacid as a starting material, converts this diacid into a diester, and then adds, for example, barium hydroxide to this to obtain a monosalt of barium. Next, we proposed a method for producing ω-hydroxy fatty acids by substituting the barium with an acid to monoesterify the monoester and reducing the monoester in the presence of a copper-chromium oxide catalyst (Japanese Patent Application No. 61-231253). issue).

[Problems to be Solved by the Invention] As a result of conducting research to make the above method a simpler process, the present inventor discovered that the alkali metal salt of the long chain diacid monoester or Alkaline earth metal salts can be reduced with borohydride compounds, and in particular, when lithium borohydride, calcium borohydride, magnesium borohydride, zinc borohydride, etc. are used as reducing agents, high selectivity can be achieved. We found that only the ester group was reduced.

The present invention was made in view of the above findings, and an object of the present invention is to propose a method for producing ω-hydroxy fatty acids at low cost and efficiently using inexpensive raw materials and a relatively simple process. It's about doing.

[Means for solving the problems] The present invention is a method for producing ω-hydroxy fatty acids, which comprises reducing an alkali metal salt or alkaline earth metal salt of a long-chain diacid monoester with a borohydride compound. .

The long-chain diacid monoester mentioned above is preferably a monoester of alkanniic acid having 9 to 18 carbon atoms when obtaining a lactone for pharmaceutical raw materials or fragrances, but it is limited to those having such a carbon number. isn't it.

The alkali metal salt or alkaline earth metal salt of this monoester is obtained by diesterizing an alkanioic acid with an alcohol,
When an alkali metal or alkaline earth metal hydroxide is added to this, one of the ester groups becomes a monoester salt and precipitates out of the reaction system as a solid, which is obtained by solid-liquid separation. In this case, the alkali metals or alkaline earth metals include lithium, sodium, potassium, rubidium, beryllium, magnesium, calcium, and strontium.

Examples include barium, but barium is preferred because it can increase the yield of the monoester salt.

Moreover, it is preferable to use a lower alcohol having 1 to 4 carbon atoms as the alcohol for the above-mentioned diesterification, since the esterified product can be easily separated and purified.

Incidentally, alkaniic acid is produced relatively inexpensively by oxidizing an alkane having a corresponding number of carbon atoms in the presence of microorganisms.

A borohydride compound is allowed to act as a reducing agent on the alkali metal salt or alkaline earth metal salt of the long-chain diacid monoester mentioned above. In this case, the amount used is per mole of the diacid monoester in the salt. , it is economically preferable to set the amount to about 0.5 to 1 mol. In addition, this borohydride compound is
Lithium borohydride, calcium borohydride, zinc borohydride, magnesium borohydride, potassium borohydride, beryllium borohydride, barium borohydride, etc. can be used, but especially those with high selectivity for reduction can be used. Lithium borohydride, calcium borohydride, magnesium borohydride, and zinc borohydride are preferred. Furthermore, the borohydride compound can be used in mixture with other compounds1, for example,
When sodium borohydride is used as a mixture with aluminum chloride, the rate of the reduction reaction becomes faster. Also,
The above-mentioned borohydride compounds can be obtained by reacting borohydride, sodium borohydride, and the corresponding halide; for example, lithium borohydride can be obtained by reacting sodium borohydride with lithium chloride. In this case, the activity and selectivity vary depending not only on the type of borohydride compound but also on the method of preparing the borohydride compound. Zinc has extremely high selectivity and reactivity,
This is particularly preferred. Note that these borohydride compounds may be prepared in advance and added when performing the reduction reaction, or they may be prepared in the reaction vessel for the reduction reaction and used as they are in the reaction.

In this reduction reaction, the above-mentioned borohydride compound is treated with an organic solvent,
For example, diethylene glycol dimethyl ether, diethyl ether, tetrahydrofuran, dioxane, N,
It is suspended in N-dimethylformamide, dimethyl sulfoxide, etc. at a concentration of 1 to 10% by weight, and a solution prepared by suspending the above monoester salt in the same solvent at a concentration of 10 to 30% by weight is added dropwise to the suspension, and the mixture is heated at 0 to 100°C. The reaction can be carried out by stirring the reaction at a temperature of 1 to 30 hours.

After the reaction is complete, add the reaction solution to an aqueous acid solution such as hydrochloric acid, sulfuric acid, nitric acid, or acetic acid to crush the unreacted borohydride compound.
Next, the barium salt of the ω-hydroxy fatty acid is acidified, and the precipitated organic matter is removed by filtration to obtain the ω-hydroxy fatty acid.

[Example] (Example 1) Sodium borohydride 0.76g (20n+mol)
was suspended in 20 ml of diethylene glycol dimethyl ether, and 0.85 g of lithium chloride (20 s mo
1) was added and stirred at room temperature for 30 minutes.

Next, a suspension of 7.18 g (20 mmol of barium salt of pentadecanedioic acid monomethyl ester) in 30 ml of diethylene glycol dimethyl ether was added dropwise to this, and the reaction was subsequently stirred at a temperature of 80° C. for 22 hours. After that, the reaction solution was added to 120 ml of ion-exchanged water containing 11 ml of concentrated hydrochloric acid, and stirred at room temperature for 30 minutes.
ω-hydroxypentadecanoic acid was precipitated. This was filtered to obtain ω-hydroxypentadecanoic acid.

As a result of analysis by gas chromatography, the purity was 84.
%, yield was 76%.

(Example 2) Instead of pentadecanedioic acid monomethyl ester, 7.36 g of pentadecanedioic acid monoethyl ester (2
ω-hydroxypentadecanoic acid was obtained in the same manner as in Example 1 except that ω-hydroxypentadecanoic acid was used. The yield in this case was 70%.

(Example 3) 6.24 g of dodecanedioic acid monomethyl ester (20 r as the second floor) was used instead of pentadecanedioic acid monomethyl ester.
ω-
Hydroxydodecanoic acid was obtained. The yield in this case is 70%
Met.

(Example 4) Sodium borohydride 0.76g (20+mmol)
was suspended in 20ml of diethylene glycol dimethyl ether, and 2.22g of calcium chloride (20n
mol) and stirred at room temperature for 30 minutes.

Next, a suspension of 7.18 g (20 mmol of barium salt of pentadecanedioic acid monomethyl ester) in 30 ml of diethylene glycol dimethyl ether was added dropwise thereto, followed by stirring at a temperature of 80° C. for 9 hours. After the reaction is completed, the same operation as in Example 1 is performed, and ω
-Hydroxypentadecanoic acid was obtained with a yield of 76%.

(Example 5) In Example 4, 1.90 g (20 mmol) of magnesium chloride was used instead of calcium chloride.

The same operation as in Example 4 was performed except that stirring was performed at 100°C for 6 hours instead of at 80°C for 9 hours to obtain ω-hydroxypentadecanoic acid. The yield in this case was 88%.

(Example 6) In Example 4, zinc chloride 2 was used instead of calcium chloride.
．． 73 g (20 mmol) was used at 80°C.

The same operation as in Example 4 was performed except that stirring was performed at 80° C. for 3 hours instead of 9 hours to obtain ω-hydroxypentadecanoic acid. The yield in this case was 84%.

(Example 7) In Example 6, 3.1% of zinc iodide was used instead of zinc chloride.
Except for adding 9 g (10 mmol), the same operation as in Example 6 was performed to obtain ω-hydroxypentadecanoic acid. The yield in this case was 94%.

(Example 8) In Example 6, 2.25% of zinc bromide was used instead of zinc chloride.
The same operation as in Example 6 was performed except that g (10 mmol) was added to obtain ω-hydroxypentadecanoic acid. The yield in this case was 46%.

(Actually, stream side 9) Sodium borohydride 0.76 g (20 m mol
) was suspended in 50 ml of dioxane, and 5 ml of zinc chloride was added to it.
．． Add 45 g (40+++ mol) and leave at room temperature for 30
Stir for a minute. Next, 7.18 g of barium salt of pentadecanedioic acid monomethyl ester (20 g as a second layer) was added to this.
n mol) in 50 ml of dioxane was added dropwise at a temperature of 80°C.

Stirred for 9 hours. After the reaction was completed, the same operation as in Example 1 was performed to obtain ω-hydroxypentadecanoic acid in a yield of 82%.

(Example 10) 0.76 g (20 mmol) of sodium borohydride was suspended in 20 ml of dimethoxyethane, 2.73 g (20 mmol) of zinc chloride was added thereto, and the mixture was stirred at room temperature for 30 minutes. Next, add to this 7.18 g of barium salt of pentadecanedioic acid monomethyl ester (20n as a second layer).
mol) in 30 ml of dimethoxyethane was added dropwise, followed by stirring at a temperature of 80° C. for 9 hours.

After the reaction was completed, the same operation as in Example 1 was performed to obtain ω-hydroxypentadecanoic acid in a yield of 35%.

[Effects of the invention] In the present invention, the alkali metal salt or alkaline earth metal salt of a long-chain second-order monoester is directly reduced with a borohydride compound, so the process is relatively simple and the manufacturing cost is low. Moreover, it has the special effect of being able to efficiently produce ω-hydroxy fatty acids.

Claims (1)

[Claims] A method for producing ω-hydroxy fatty acids, which comprises reducing an alkali metal salt or alkaline earth metal salt of a long-chain diacid monoester with a borohydride compound.