DE859620C - Process for the separation of cholesterol from wool wax alcohols - Google Patents

Description

Process for the separation of cholesterol from wool wax alcohols Die Invention relates to a new or improved method for the extraction of Cholesterol, which is an important raw material for the production of sex hormones is off. the unsaponifiable portion of wool fat, known as wool wax alcohol.

A method has already been proposed in which, after separation of the unwanted isocholesterol by known means, the separation of the cholesterol is brought about, either by selective crystallization of the Oholesterirns or by selective solution: the wax-like impurities, in any case in the presence of acetic acid or another simple fatty acid. This method gave a better yield of high purity cholesterol than it used to be was possible; but there was some loss of cholesterol due to reluctance in the isocholesterol extract, which consists mainly of agnosterol and lanosterol. This was due to the fact that the starting material was made from large sizes in the usual process Amounts of methanol recrystallized at elevated temperature, and beyond that required this method working with relatively large amounts of liquid, what often led to difficulties in the equipment used.

The aim of the present invention is to develop a process for the separation of the cholesterol from the wool wax alcohols, because of the even higher _- "embed in cholesterol can be achieved with a high degree of severity, where also the _ @@ separation of considerable lengths Isocholesterol in high levels is possible. -_ According to the present invention @@ v ird -the isochole- sterol with a mixture of benzene or his All of the lolriologists and methanol from the wool -., - achsali @ ohr @ lcn al: separated and then the. Chole- sterol of tvaclisä <ililiclien impurities through selective crystallization from a Niederinol @ el: ular # eri Fatty acid, e.g. B. acetic acid, or by selective tive loosening of the contamination ° n by a low- molecular fatty acid, in each case under careful carefully regulated complexion conditions divorced. At d;: r implementation of the present invention the @ -4'oll% vaclisallcoliole at approx. 60 ° geschinolzeii and in the -2 @: '@ fiiclien volume of a Mixture of benzene or one of its lower-- molecular @lolnologists, ;; they toluene or -'- ylol, and Methanolel @@ st. Then let cool hen the isocholesterol is collected in fine needles part. Dir '_nreil des enzƒls in cjer-. -Benzäl-- Methanal mixture can be between 20 and 6o vol- lum percent, if the crystallization temperature d ° m The high yield of cholesterol and isochole- sterol is achieved by a mixture that contains about 209lo benzene, where the iso- cholesterol lcristallisierii leaves and at about 30l filtered off. If the benzene content is -5ö to 6o Vo @ lum percent is increased, the temperature should be at of crystallization and filtering on approx 2o to 25 @ 'with the same, constant practical Leadership reduced @@ - crden, although in diesels Fall the I-tight of @ soclr, @ le @ -er ins somewhat reduced will. It may be muzzled for the application of -ilet # iaiioi in this way a significant advantage part is because the J @ OCliQle @ ter quickly turns into a crystalline is brought into a form, while when using of other alcohols, amorphous masses divorce. The Isocliolest @ rü @@ the 5 to io% -der originally-, a'-Ölhrä @ hsäil> ohol :: forms, then becomes filtered off and the filtrate concentrated to dryness. If the erliaitene arrears from a ni ..der = .- molecular fatty acids, such as acetic acid or pro- pionic acid, crystallized at 3o to 35 ', so separates the cholesterol easily. When paint it lieohol; - e.g. B.- teaiüiscli # -lü. .llethallol to @ sristalli- if desired, rnan receives a pure product in an Atish ° üt- from 18 to 2ö0 / 0. Alternately you can also use the acetic or propionic acid solution to Zilnnrertemp;: ratur abldililen- and the wax- similar i @ Iaterial- ° by laiijsame heating Selectively dissolve 3o to .33 @ ' while stirring. From- booty is the same as above .-- The temperature is of the different - # leligen ratio of the iso- cholesterol dependent on the mass treated. the Experience has shown that the working temperature in most cases zt =, isclien 3o and 32 '. In addition, the _ «- acl @ sülmlicliell itnreinigungeli a; #probably in the form of an over- 'saturate = -. soldering -before: and- be. Then -crystalline- If the solution cools down gradually, it is best to reduce the cholesterol after inoculation. At 3o to 3r ° the crystallization is almost complete, below that the impurities separate out. This last temperature will vary slightly from time to time. In fact, crystallization begins at around 50 degrees. If you accept a lower yield of the desired cholesterol, you can also use a higher final temperature. Likewise, the waxy residue 1) 2i of the selective dissolution is dissolved when the temperature is raised to about 30 to 30 °, while the cholesterol remains almost undissolved. The temperature could actually be increased to 45 °, if a smaller yield is accepted. It may be stated, however, that an economically more favorable yield is achieved when the temperature is within the range of 30 to 35 °, which is suitable both for the selective crystallization of the desired cholesterol and for the selective dissolution of the impurities. The yield is higher than any other known method, and the cholesterol has a high degree of purity. This method also has the advantage that the solutions only take up a volume of a little more than a third compared to that of the earlier methods and thus makes it possible to process larger quantities.

The following examples serve to illustrate. Example i 200 kg of wool wax alcohols are refluxed (57 °) in 500 l of a mixture of 60 percent by volume benzene and 40 percent by volume methanol until the wax has dissolved. The solution is cooled to 50 ° with shaking, then seed crystals of isocholesterol are added. Then leave them in place and cool to a temperature of 30 to 30 ° for the next 2 days: By inoculating with isocholesterol and cooling for 2 days, larger crystals are formed which facilitate filtering. On the third day, the mixture is filtered under vacuum, expediently at a temperature of over 30 °, since the waxy impurities then do not separate out of the solution. However, when the temperature exceeds 35 °, cholesterol is lost. The filtrate is distilled at atmospheric pressure - until the Teniperätür - reaches ung-ef-ähr irö °. The collecting vessel_söllt # hold approximately - 45o to 5oo 1 solvent, which is re-used in the further processing of the starting material. The solid distillation residue is removed from the last traces in a vacuum. freed of the solvent. The yield of residue is 36o. In the further treatment, 36o 1 glacial acetic acid with 36o kg of residue are heated to about -60 ° with stirring in order to maintain a homogeneous solution. The temperature is lowered to -5 °, and Cliolesterirl-Im fleristalle = are added. With occasional stirring, the mixture never lets it cool: within 2 days to -32 °. At this temperature the crystal wets are filtered off in order to prevent the deposition of the wax impurities. The purified cholesterol is washed with .15o ll acetic acid -from 32 ° -and dried in vacuo-et.-The yield is 60 to 80 kg. . _ If desired, another. Purification can be carried out by recrystallization from technical grade methyl alcohol. The above-mentioned 69 to 80 kg of cholesterol are refluxed with 2q.01 technical grade methyl alcohol for 1/2 hour ..- and cooled overnight to crystallize: The 'crystallized cholesterol-. is filtered off,: rt and washed with technical methyl alcohol. -Yield: 6o to 70 kg, melting point: z48 - bis_149 °, -specific rotation in chloroform: -39 °: Example: 2 i kg wool wax alcohols were in 2.5 l of a boiling methanol-benzene mixture, the 411 / o contains methanol, dissolved. After cooling to 20 ° overnight, the isocholesterol (72 g) was filtered off and washed with 100 cc of the methanol-benzene mixture. The filtrate was distilled to dryness and the residue was dissolved in 1 liter of propionic acid. The solution is allowed to cool slowly to 30 ° over the course of 1 to 5 hours, stirring occasionally. The crystallized cholesterol was filtered off, washed with a little propionic acid and then with water and dried. Yield: 185 g, melting point: 146 to 147o. Example 3 1 kg of wool wax alcohols were treated as in Example 2 in order to remove the isocholesterol, and then dissolved in 1 liter of propionic acid. It is allowed to cool to room temperature overnight. The solid mass was then slowly heated to 32 ° with stirring until the wax dissolved and the crystalline cholesterol remained undissolved. The cholesterol was filtered off, washed with warm propionic acid and then with water and dried. Yield: 180 g, melting point: 146.5 to 147.5 °. Example 4 51o g of wool wax alcohols were dissolved in 1 liter of a mixture of methanol-benzene which contained 811 per cent of methanol. The solution was slowly cooled to 30 ° and held at this temperature for 2 hours. The crystalline isocholesterol was then filtered off and washed with 100 cc of the same methanol-benzene mixture at 30 °. The yield of isocholesterol was 57 g. The filtrate leaves a waxy substance on cooling to 15 ° which can be filtered off if the wax is needed, but filtration is difficult. The filtrate, which contained the wax, was distilled to dryness, the residue was dissolved in 51o cc of glacial acetic acid and cooled to 30 °. After the liquid had been kept at this temperature for 2 hours, the cholesterol was filtered off, washed at 30 ° with a little glacial acetic acid and then with water and dried. Yield: 98.g, melting point: 147 to 148 °.

EXAMPLE 5 1 kg of wool wax alcohols were dissolved in 2 liters of a boiling benzene-methanol mixture containing 0.1/0 methanol. The solution was slowly cooled to 20 ° and held at 20 ° for a further 12 hours. The isocholesterol (60 g) was then filtered off and the filtrate was distilled to dryness. The residue was dissolved in 1 glacial acetic acid. The solution would be inoculated with finite cholesterol and slowly, with stirring, cooled to room temperature. After 24 hours, the mass was carefully warmed to 32 ° with stirring, until. had dissolved all of the wax-like material. The undissolved cholesterol crystals were filtered off, then washed at 32 ° with glacial acetic acid and with water. After drying, the yield was igi g. Melting point: 147 to i48.5 °. Recrystallization from technical grade methyl alcohol gave 183 g. Melting point: 149 to 14g, 5 °. Example 6 5009 wool wax alcohols were dissolved in a boiling mixture of 55o cc of toluene and 450 cc of methanol. The isocholesterol (39 g) was, after the liquid had cooled to 20 ° overnight, filtered off and dried. The filtrate was distilled to dryness under reduced pressure and the residue was dissolved in 51o cc of glacial acetic acid. The solution is allowed to cool slowly to 30 ° and is kept at this temperature for 2 to 3 hours: the crystalline cholesterol is filtered off, washed with warm acetic acid and then with water and dried. Yield: 96 g, melting point: 147 to 148o. Example ? 5009 wool wax alcohols were dissolved in a boiling mixture of 51o cc xylene and 51o cc methanol. After the liquid had been allowed to cool slowly to 20 ° overnight, the isocholesterol (4i, 5 g) was filtered off and the filtrate was distilled to dryness. The residue was dissolved in 51o cc of glacial acetic acid and the cholesterol was separated off as in Example 6. Yield: g3 g, melting point: 146.5 to 1q.7.5 °.

As indicated above, the invention is not limited to temperature ranges particularly related to crystallization from acetic or propionic acid, or limited to selective dissolution in the same solvent, although the yield is somewhat lower at higher temperature. The following example characterizes the yield obtained. Example 8 Four portions of wool wax, 3009 each, were freed from isochromatic ester and treated in a similar manner to the crystallization from acetic acid in Example i. These four portions were crystallized at 32 °, 35 °, 4.0 ° and 4.5 °, respectively. Filtration temperature 1 Yield in g 32 57.7 17.3 35 # 41.9 12.6 40'- 38.0 11.4 .15 26.9 8.1

Claims (3)

PATENT CLAIMS: i. Process for separating the cholesterol from wool wax alcohols, characterized in that the isocholesterol is first deposited by crystallization at a temperature of about 20 to 30 ° from a solution of the wool wax alcohols in a mixture of benzene or its low molecular weight homologues and methanol, the remaining solution evaporated to dryness and thereafter the cholesterol is separated from woolly waxy impurities by selective crystallization from a low molecular weight fatty acid such as acetic acid or by selectively dissolving the impurities in this fatty acid at a temperature of about 30 to 35 °. 2. Process according to Claim i, characterized in that the wool wax alcohols in a mixture of 2o to 6o% benzene, toluene or xylene and 80 to 4.0% methanol solves. 3. The method according to claim i and 2, characterized in that the crystallization the isocholesterol is relieved by inoculation and by gradual cooling, to allow the formation of relatively large crystals.