JPS60142940A - Separation of z-9-hexadecenoic acid from e-9-hexadecenoic acid - Google Patents

Abstract

PURPOSE:To separate Z-9-hexadecenoic acid from E-9-hexadecenoic acid by a simple operation in high purity in high yield, by treating a mixtue containing E- and Z-9-hexadecenoic acid with an alkali metal compound, collecting selectively an alkali metal salt of E-9-hexadecenoic acid or an alkali metal salt of Z-9-hexadecenoic acid from the prepared mixture of alkali metal salts by crystallization method. CONSTITUTION:A mixture containing E-9-hexadecenoic acid and Z-9-hexadecenoic acid is reacted with an alkali metal compound (e.g., lithium compound such as preferably lithium hydroxide, etc.) in a solvent at 0-150 deg.C, preferably at room temperature -100 deg.C, so that they are converted to alkali metal salts. Z-9-Hexadecenoic acid or E-9-hexadecenoic acid useful as a nutrient for promoting yeast growth or a raw material for drugs are separated from the prepared mixture of alkali metal salts by crystallization method. The crystallization is carried out by adding standard alkali metal salts of E-9-hexadecenoic acid or Z-9-hexadecenoic acid as seed crystal to a solution of the mixture of the metal salts in a solvent.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method for obtaining E-9-hexadecenoic acid or Z-9-hexadecenoic acid from a mixture containing E-9-hexadecenoic acid and Z-9-hexadecenoic acid. Regarding.

Z-9-hexadecenoic acid is used as a nutrient in various fields, such as by adding it to a culture medium to promote the growth of yeast, and is also used as a nutrient in drugs, paints, lubricants, surfactants, It is a useful compound that is widely used as a raw material for cosmetics, etc.

However, the Z-9-hexadecenoic acid is conventionally produced by extracting it from animal fats and fats such as mink oil, vegetable fats and fats such as palm oil and coconut oil, or by chemical synthesis. , J.

Bus tmann', W, Stran*ky, O
, Vostrowsky, p., Hange;
Chem, Bet, , 108, 858! -85
95 (1975) and D.

Bergatson, y, A, yaver, y, yu
, xovtun, L, B, 5enya-vina,
MlM, 9henyakken; zh, □bsh,
Khim, , 82, 1785-1789 (1
962) :].

However, in the above extraction method from fats and oils, the amount of Z-9-hexadecenoic acid contained in the fats and oils used as raw materials is small (usually 4 to 18% by weight for animal fats, and 2% by weight or less for vegetable fats). The raw material itself contains 5 to 8 similar fatty acids in addition to the target Z-9-hexadecenoic acid, which are also extracted at the same time and are extremely difficult to separate, making it highly purified and available in large quantities. However, it has the disadvantage of being malty. Also, E-9-hexadecenoic acid cannot be obtained by the above extraction method.

On the other hand, the chemical synthesis method is carried out according to the reaction shown in the following reaction scheme-1.

[Reaction scheme-1] “(7H1B-PcPh)8 X” +1-C6H12
CHO (21141 thousand ten Rogc-(cH2)7-cHo Rogc-(cii
g) sJ'(ph)s-x"'131, 151 n-C6H12CH=CH(CHg)7CO2R(6) n-CsHx2ca-cH(cixg)ycoon(1
) [In each formula, X represents a halogen atom, R represents a lower alkyl group, and Ph represents a phenyl group] As shown in the reaction scheme-1 above, the chemical synthesis method produces 2- and E-9-hexadecene. Acid (1) is produced in a mixed state, and it is not possible to selectively synthesize only one of them. It is very difficult to separate the above mixture, and a separation method has not yet been established.

In view of the above-mentioned current situation, the present inventors have attempted to obtain each of the above-mentioned two-body and E-one-body compounds obtained by chemical synthesis methods with a simple operation, industrially advantageous, and with high purity and high yield. I have conducted extensive research with this purpose in mind. As a result, when the above mixture is treated with an alkali metal compound to form an alkali metal salt and the resulting alkali metal salt mixture is subjected to a crystallization method, each alkali metal salt is separated, thereby achieving the above purpose. I discovered that.

The present invention was completed based on this new knowledge, and its gist is that E-9-hexadecenoic acid and Z-
A mixture containing 9-hexadecenoic acid is reacted with an alkali metal compound to form a chilkali metal salt, and the resulting alkali metal salt mixture is crystallized to form E-9 dihexadecenoic acid alkali metal salt or Z-9-. The present invention relates to a method for separating 2- and E-9-hexadecenoic acid, which is characterized by obtaining an alkali metal salt of xadecenoic acid.

According to the present invention, from a mixture of E-9-hexadecenoic acid and 2-9-hexadecenoic acid, it is possible to efficiently produce
Either one of them can be selectively separated and obtained as an alkali metal salt with high purity and high yield, and the desired free acid can be easily obtained from this salt according to a conventional method.

Therefore, the method of the present invention uses Z-9-hexadecenoic acid or E-9
- As a new production method or purification method for hexadecenoic acid,
It is extremely advantageous for industrial implementation.・The mixture containing E-9-hexadenoic acid and Z-9-hexadenoic acid to be treated in the method of the present invention 5 can be prepared according to a conventional chemical synthesis method as shown in reaction scheme-1 above, for example. It will be done. There is no particular restriction on the mixing ratio of the E-unit and the 2-unit, but when it is desired to separate and obtain a compound, for example, the E-unit, it is preferable to use the E-unit as the main component.

In the method of the present invention, an alkali-metal compound is first applied to the mixture to be treated to form an alkali metal salt mixture. As the alkali metal compound, any of various compounds that can convert 9-hexadecenoic acid into its alkali metal salts such as lithium salt, sodium salt, potassium salt, etc. can be used.

Specific examples thereof include alkali metals themselves such as lithium, sodium, potassium, etc. and hydroxides of the alkaline genus such as lithium hydroxide, sodium hydroxide, potassium hydroxide, etc.; carbonates, etc. Examples include lithium carbonate, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, and the like. Among these, compounds that can provide lithium salts, such as lithium compounds such as lithium hydroxide, are particularly preferred. The reaction of converting the mixture to be treated into an alkali metal salt mixture is carried out in a suitable solvent. Examples of solvents include water, alcohols such as methanol, ethanol, and impropatol, ethers such as dioxane, tetrahydrofuran, and diethyl ether,
Ketones such as methyl ethyl ketone and acetone, polar solvents such as dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, hexamethylphosphoric acid triamide, etc., and mixed solvents of two or more of these can be used. The above reaction is usually carried out at a temperature of about θ to 150°C, preferably room temperature to about 100°C, and takes about several minutes to about 8 hours. There is no particular restriction on the amount of alkali metal compound used, but it is usually at least an equimolar amount, preferably about an equimolar to 1.6 times the molar amount, relative to the total amount of E- and Z-9-hexadenoic acid in the object to be treated. It is better to do so.

In the present invention, each alkali metal salt (E monolithic or divalent) is then crystallized from the alkali metal salt mixture obtained as described above.
separate). This crystallization method is carried out in more detail as follows. That is, this is advantageously carried out by adding a standard alkali metal salt of F, -9-hexadecenoic acid or Z-9-++fcephic acid as crystal seeds to a solution of the alkali metal salt mixture in a suitable solvent. As the solvent, for example, water, lower alcohols such as methanol, ethanol, and impropatul, ketones such as acetone and methyl ethyl ketone, and mixed solvents thereof can be used.

Among these, acetone-water mixed solvent and impropanol-water mixed solvent are particularly suitable. In addition, the standard product as the above crystal seed is E-9-hexadenoic acid or Z-9-
Hexadecenoic acid converted into an alkali metal salt by the method described above can be used. As the standard product, the same salt as the compound to be separated and obtained by crystallization is also used. The above crystallization method is usually performed at room temperature to 150°C, preferably about 60 to 10°C.
When the alkali metal salt mixture is dissolved in a solvent at a temperature around 0°C, and then allowed to cool naturally, the reaction liquid begins to turn white (usually when the reaction liquid temperature reaches about 80 to 60°C). The desired Z-9
The alkali metal salt of -hexadecene acid or the alkali metal salt of E-9-hexadecene acid can be separated and obtained as crystals. Although it is possible to obtain crystals of fairly high purity by carrying out the above operation only once, it is usually preferable to repeat the operation several times, whereby substantially pure target crystals can be obtained.

The obtained salt crystals can be converted into the desired free form of the product by treating them in a suitable solvent in the presence of an acid catalyst according to a conventional method. In this case, water is used as a solvent,
Alcohols such as methanol, ethanol and isopropanol, ethers such as dioxane, tetrahydrofuran and diethyl ether, ketones such as acetone and methyl ethyl ketone, aliphatic hydrocarbons such as n-hexane and cyclohexane, dimethylformamide, dimethyl sulfoxide, Polar solvents such as N-methylpyrrolidone, hexamethylphosphoric triamide, etc. or mixed solvents thereof can be used. As acid catalysts, mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid can be advantageously used. Further, the treatment is usually carried out at 0 to 100°C, preferably around room temperature, for about several minutes to about 1 hour.

Reference examples and examples are shown below. The ratio and purity of E-unit and 2-unit on each side were determined by high performance liquid chromatography analysis under the following conditions.

Equipment used: Shimabara liquid chromatography LC-8A (
(manufactured by Shimabara) Column: 3pherimorb 50DS
(4.0mm ID-29cm) Eluate = 70% CH3CN, 196-phosphoric acid test
Output: 205im (room temperature) Reference example 1 n-heptyltriphenylphosphonium bromide lK
F and sodium methyl) 1225' with dimethylformamide 10I! , and stirred at room temperature for 1 hour under a nitrogen stream to dissolve. Under external water cooling, methyl 8-formyl octanony 1-5147 was added dropwise thereto, and after the addition was completed, the mixture was stirred for 1 hour. The reaction solution was slowly poured into a 496 hydrochloric acid aqueous solution under water cooling, and after confirming that the pH was below 8P1, hexane ioI! Extract using. The extract was dried and concentrated to methyl hexadecenoate 49B,
Get 5S'.

Boiling point 118-151℃ 10.5mm 1l Reference example 2 Methyl hexadecenoate 1.24 K9 was dissolved in methanol 12.4j', and sodium hydroxide 2
78 g of 2.21 aqueous solution are added dropwise. The internal temperature of the dripping machine is 40
Maintain the temperature at ~50°C and heat and stir for about 6 hours.

After distilling off methanol under reduced pressure, 6.21 g of water was added to the residue to dissolve it, and 6.21 g of ethyl acetate was added to the residue. Clean 'fG twice with . After adjusting the pH to about 8 by adding concentrated hydrochloric acid, it is extracted with hexane 12.41. The extract is dried and concentrated to obtain a mixture of E- and Z-9-hexadecenoic acids 647y.

The ratio of E integrated and 2 integrated (Z integrated/E integrated) is 81
．． The weight ratio was 7/9.8 (the same applies hereinafter).

Example I E- and Z-9-hexadecenoic acid mixture (2 units/E unit = 81.7/9.8) 429 7-k) 7
Dissolve in 210 m7 and heat and stir. The internal temperature was maintained at 55°C, and 69 m of 6.9 y of lithium hydroxide hydrate was added to this.
Gradually add the J aqueous solution dropwise. After dropping, the reaction solution was gradually allowed to cool, cooled to room temperature, and the precipitated crystals were removed with F and dried.
- and Z-9-hexadecenic acid lithium salt mixture 84.
Get 6f. E unitary and 2 in this lithium salt mixture
Ratio to integral (2 integral/E integral) Ha87.7 / 7
．． 6'T! A). Mata Its melting point is 209.7-21
The temperature was 2.7°C.

Next, a mixed solvent 82 of isopropyl alcohol and water = 4:1 (volume ratio) was added to the lithium salt mixture 82y obtained above.
Add 0 ml and heat to reflux to dissolve E- and Z-9-hexadecenic acid lithium salts. The solution is gradually cooled with external hot water, and when the internal temperature reaches 42° C., 8 mV of Z-9-hexadecenoic acid lithium salt (standard product) is added as a crystal seed. Furthermore, it is cooled to room temperature using external ηl cooling.
Thereafter, it is cooled with water to about -10°C, and the precipitated crystals are collected, washed with acetone, and then dried. The above operation is repeated twice to obtain z-9-hexadecenic acid lithium salt 21.89. Purity 96.5%, melting point 218.6-215.6℃
.

The Z integral/K 4: of this product was 98/2.

Add 150 ml of 5% hydrochloric acid to 15 g of Z-9-hexadecenic acid lithium salt obtained above! and 150 ml of hexane were added and stirred at room temperature to completely dissolve Z-9-hexadecenic acid lithium salt. Then, the hexane layer was separated, washed with water, dried, and concentrated to give 14.85% of 2-9-hexadecenoic acid.
get '.

Boiling point 155-156°C/0.05 mm1 (P Example 2 E- and Z-9-hexadecenoic acid mixture (E-1/z-1 = 87/1B) 2 Dissolved in 710mf of 7cell and heated Stir. Keeping the internal temperature at 50°C, gradually add 8.8 ml of an aqueous solution of 0.889 lithium hydroxide hydrate to the ζ
Drip. After the dropwise addition, the reaction solution was stirred for about 10 minutes, and the reaction solution was gradually cooled and returned to room temperature. E in this lithium salt mixture is obtained.
The ratio of one piece to two pieces (E one piece/two pieces) was 98/7.

Next, to 1.0 y of the lithium salt mixture obtained above, a mixed solvent of 4 parts of inpropyl alcohol to water (volume ratio) was added to 10 y of the lithium salt mixture obtained above.
tnI! Add E- and Z-9 with rapid heating and stirring.
- Dissolve the hexadecene il IJ thium salt. The solution was allowed to cool slowly, and when the internal temperature reached 54° C., E-9-hexadecenic acid lithium salt (supported product) smy was added as a crystal seed, and the mixture was further allowed to cool.

After cooling to room temperature, it is cooled with water to -5°C, and the precipitated crystals are collected. After drying this, E-9 ~ 0.8f of lithium hexadecenate salt! get. Purity 95.496, melting point 206
．． 5-208.5℃.

The Z one piece/E one piece of this one was 8/97.

The above lithium salt was treated with hydrochloric acid as in Example 1 to obtain the free form of E-9-hexadecenoic acid.

(that's all) Agent: Patent Attorney Eiji Sanae ・、-2g

Claims (1)

[Claims] ■ A mixture containing E-9-hexadenoic acid and Z-9-hexadenoic acid is treated with an alkali metal compound to form an alkali metal salt, and the resulting alkali metal salt mixture is crystallized to produce E-9-hexadecene. A method for separating 2- and E-9-hexadecenoic acid, characterized by obtaining an acid alkali metal salt or a z-9-hexadecenoic acid alkali metal salt.