CA1037502A - Process for preparing squalane - Google Patents
Process for preparing squalaneInfo
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- CA1037502A CA1037502A CA283,747A CA283747A CA1037502A CA 1037502 A CA1037502 A CA 1037502A CA 283747 A CA283747 A CA 283747A CA 1037502 A CA1037502 A CA 1037502A
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- hydrogenolysis
- squalane
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Abstract
DIACETYLENE DIOL DERIVATIVES AND PROCESS
FOR PREPARING THE SAME
Abstract of the Disclosure The present invention relates to a process for preparing squalane which consists of (a) submitting a compound of the general formula:
(I) wherein R and R' are the same or different and each represent a saturated or unsaturated hydrocarbon residue having 11 carbon atoms and possessing the following carbon atom skeleton:
each said residue being optionally substituted by a radical capable of being replaced by a hydrogen atom upon hydrogenolysis;
to hydrogenolysis in the presence of an acidic substance; or (b) submitting a compound of the general formula:
FOR PREPARING THE SAME
Abstract of the Disclosure The present invention relates to a process for preparing squalane which consists of (a) submitting a compound of the general formula:
(I) wherein R and R' are the same or different and each represent a saturated or unsaturated hydrocarbon residue having 11 carbon atoms and possessing the following carbon atom skeleton:
each said residue being optionally substituted by a radical capable of being replaced by a hydrogen atom upon hydrogenolysis;
to hydrogenolysis in the presence of an acidic substance; or (b) submitting a compound of the general formula:
Description
375Cl'~
Illis Illvcntloll relat~s to novc1 in~el-~e~iates for preparing squa1ane ~In~ to new metl~ods o~ preparing the inter-mediates and sq-lalane.
Squala~e, i.e. 2,6,10,15,19,23-hexamethyltetracosane, is used as ad~itive or base in several cosmetlcs because of its characteristics of exhibiting cleansing action and penetrating action with respect to skin. It is also useful as a lubricant for precision machines. It has previously been prepared by hydrogenation of the squalene portion obtained from shark's liver oil. Its preparation using industrial products as starting materials has virtually never been tried. A method for preparing hydrocarbons having about 30 carbon atoms from a low polymer product of isoprene has been proposed; but this method gives several isomers having different carbon skeletons and a mixture of products having different molecular weights. Thus, even if this mixture contains squalane, it is impossible to separate the squalane from it.
According to the invention there is provided a process for preparing squalane which comprises (a) submitting a compound of the general formula:
CH CH
R - 7 - C - C - C - C - C - R' (I) -~
OH OH
wherein R and R' are the same or different and each represent a saturated or unsaturated hydrocarbon residue having ll carbon atoms and possessing the following carbon atom skeleton:
Cl C ' C -- C -- C -- C -- C ~ C -- C -- C -- C --each said residue being optionally substituted by a radical capable of being replaced by a hydrogen atom upon hydrogenolysis;
to hydrogenolysis in the presence of an acidic substance; or :: , ~ - : : . .
~, . ~ .:
~75~
(b) submittlng a compound of the general formula:
~ 3 ~ 3 R - f c - c c - c c R' (I) wherein R and R' are as defined above; to partial hydrogenation to obtain a corresponding intermediate compound with triple bonds converted to double bonds, and then sub;ecting the intermediate compound to hydrogenolysis.
Other aspects of the apparatus disclosed herein are claimed in patent application Serial No. l95,lO6 filed on March 15, l974 of which the present application is a division.
lC As mentioned above, the intermediates (I`) have the followlng formula:
C1ll3 1 3 R - f - C ~ C - C - C - C - R' (I) OH OH
wherein R and R' are as defined above.
Among the radicals capable of being replaced by hydrogen atoms upon hydrogenolysis, R and R' may be substituted by, for
Illis Illvcntloll relat~s to novc1 in~el-~e~iates for preparing squa1ane ~In~ to new metl~ods o~ preparing the inter-mediates and sq-lalane.
Squala~e, i.e. 2,6,10,15,19,23-hexamethyltetracosane, is used as ad~itive or base in several cosmetlcs because of its characteristics of exhibiting cleansing action and penetrating action with respect to skin. It is also useful as a lubricant for precision machines. It has previously been prepared by hydrogenation of the squalene portion obtained from shark's liver oil. Its preparation using industrial products as starting materials has virtually never been tried. A method for preparing hydrocarbons having about 30 carbon atoms from a low polymer product of isoprene has been proposed; but this method gives several isomers having different carbon skeletons and a mixture of products having different molecular weights. Thus, even if this mixture contains squalane, it is impossible to separate the squalane from it.
According to the invention there is provided a process for preparing squalane which comprises (a) submitting a compound of the general formula:
CH CH
R - 7 - C - C - C - C - C - R' (I) -~
OH OH
wherein R and R' are the same or different and each represent a saturated or unsaturated hydrocarbon residue having ll carbon atoms and possessing the following carbon atom skeleton:
Cl C ' C -- C -- C -- C -- C ~ C -- C -- C -- C --each said residue being optionally substituted by a radical capable of being replaced by a hydrogen atom upon hydrogenolysis;
to hydrogenolysis in the presence of an acidic substance; or :: , ~ - : : . .
~, . ~ .:
~75~
(b) submittlng a compound of the general formula:
~ 3 ~ 3 R - f c - c c - c c R' (I) wherein R and R' are as defined above; to partial hydrogenation to obtain a corresponding intermediate compound with triple bonds converted to double bonds, and then sub;ecting the intermediate compound to hydrogenolysis.
Other aspects of the apparatus disclosed herein are claimed in patent application Serial No. l95,lO6 filed on March 15, l974 of which the present application is a division.
lC As mentioned above, the intermediates (I`) have the followlng formula:
C1ll3 1 3 R - f - C ~ C - C - C - C - R' (I) OH OH
wherein R and R' are as defined above.
Among the radicals capable of being replaced by hydrogen atoms upon hydrogenolysis, R and R' may be substituted by, for
- 2 ~ ~
:
:
3~5~2 exnml) le, n llyd roxy r nLI Lc.l 1, .1 Ik~xy r~ld icn I, oxygcn aLom (~ = ()), llalogcn a~om (clllorine aCom, bromine atom et al), amino radical, imino radical, hydrazino radical, nitro radical, thionyl radical, sulfinyl radLcal or sulEonyl radlcal. For the purpose of lndustri~l prep~r~Lioll, avail~bllity nnd co.st of starting materials, easlness of preparation oE the compounds (I) or their mixtures and e~sy transformation of the compounds (I) into squalene, R and R' having no such substituent as above mentioned may be preferred.
The intermediate (I), can be prepared: (a) bv reacting a C13 ketone (II) having the formula R - C - CH or R' - C - CH (II) O
wherein R and R' are as defin~d above, with acetylene; or (b) by coupling a monoacetylenic alcohol (III) or a mixture thereof having the formula:
, R - C - C - CH or R' - C - C CH (III) OH OH
C13 ketones (II) which may be used on an industrial scale include, for example, geranyl acetone, hexalhydroseudoionone, 6,10-dimethylundeca-5,11-diene-2-one, pseudoionone, citronellidene acetone and dihydrocitronellidene acetone. These ketones can be prepared on an industrial scale and at a comparative low price by the following method. For example, geranyl acetone can be prepared industrially by Carroll rearrangement reaction of linallol with acetoacetic acid ester. Hexahydropseudoionone can be easily obtained by hydrogenation of geranyl acetone or pseudoionone.
6,10-Dimethylundeca-5,10-diene-2-one can be easily prepared by partial hydrogenation of 3,7-dimethylocta-7-en~l-in-3-ol obtained by the method of W. Hoffmann et al. (Ann. 747 60 (1971)) to 3,7-dimethylocta-1,7-dien-3-ol and then by a Carroll rearrangement reaction of the resultant product with acetoacetic acid ester in the same manner as with linallol. Pseudoionone, citronellidene `
~', .
.. , , : . . .
. . , ~ .
~l~37~
aC(!tOIl~! ilnll ~lilly~lrOCi~rOllC~ CllC` ilCetOllC can I)C prcparcd, resp~ctlvely, by .ll-lol condellsatLon of citral, cltronellal and tetrahydrocitral with acetone.
~ ldol condensation of hydroxycitronellal or alkoxy-cltronelInl wi~h acetolle ln placc of ci~ronellal ~ives corres-ponding compoun~s (II). In general, the hydroxy- or alkoxy-citronellal can be prepared from citronellal itself, but these com-poun~s are notpreferred to citronellal; since they result only in an increase in reaction steps.
Diacetylene which is reacted with the C13-ketone (II) has never been used commercially and has hitherto been discarded as a by-product in acetylene preparation; so it can be available at a low price.
The monoacetylenic alcohols (III) can also be prepared by the reaction of the compounds (II) with acetylene by the same method for preparing the compounds (I), which comprises reacting the compounds (II) with diacetylene, as will be described in detail hereinafter. By ethynylation of several compounds (II) with acetylene, the corresponding compounds (III~ can be prepared. Compounds (III) having various substituents can be prepared from the compounds (II) having equivalent substituents.
But as above mentioned, usin~ industrially available compounds (II) is preferred. For example, 3,7,11-trimethyldodeca-6,10-dien-1-in-3-ol, 3,7,11-trimethyldodeca-6,11-dien-1-in-3-ol and 3,7,11-trimethyldodeca-1-in-3-ol can be easily prepared by ethynylation of geranyl acetone, and 6,10-dimethylundeca-5,10- ~ ;
dien-2-on respectively with acetylene. These compounds are preferred compounds among the compounds (III) according to this invention.
Upon reaction of the compound (II) with diacetylene, known methods for preparing acetylenic alcohols can be applied broadly. The preferred methods according to this invention are as follows~
1~375~
(I) rca(~LIoll or Lhe coml)ound (Il) wltll a (;rignard conll)ound of diaccLyl~lle in a solvent such as diethyl ether whîch is used in the general Crignard reaction;
(2) reaction of the compound (II) wlth diacetylide made by passlng diacetylene into a liguid ammonia solution made by dissolving an alkali metal or al~aline earth ~etal such as lithium, sodium, potassium or calcium in liquid ammonia;
(3) reaction of the compound (II) Witil diacetylene in the presence of an alkali metal in liquid ammonia or in an organic solvent (for example, the reaction of compound (II) with diacetylene in the presence of potassium hydroxide or sodium amide in a solvent such as ether or tetrahydrofuran).
In an oxidative coupling reaction of compounds (III), the principles of known oxidative coupling reactions can be applied broadly. The preferred methods according to this invention are as follows:
(1) adding a solution of the compound (III) in a solvent soluble in water, such as ethanol, acetone or tetrahydrofuran, to an aqueous solution of a monovalent copper salt, such as cuprous chlorlde, and ammonium chloride and effecting oxidative coupling of the compound (III) in an oxygen atmosphere;
(2) adding the compound (III) to a solution of a monovalent copper salt, such as cuprous chloride, in a solvent, such as pyridine or picoline, and effecting oxidative coupling of the compound in an oxygen atmosphere;
(3) adding the compound (III) to a solution of a bivalent copper salt, such as cupric acetate, in a solvent such as pyridine or picoline.
In the above coupling method ~1), a small amount of hydrochloric acid, cupric chloride or ammonia may be added to the ~ 5 -.
9.~);~75~
~;yst~m for l)romo~lol~ ol~ tl~c r~.lcLio~ So in tlle ~bove coupling metho~ (3), a rc~cti~n promotln~ agent, such as tetramethyl-ethylenedi~mine, may be added and a mixture of pyridine ~ith met~anol, ~ther or acetone may be use~.
Repr~sentativ~ co~poun~s of tlle inv~ntion ~f f~rmula (I) are a~ follows:
(1) 2,6,10,15,19,23-hexa~ethyltetracosa-2,6,18,22-tetraene-11,13-diin-:lO,15-diol (2) 2,6,10,15,19,23-hexamethyltetrAcosa-18,22-diene-11,13-diin-10,15-diol (3) 2,6,10,15,19,23-hexamethyltetracosa-1,6,18,22-tetraene-11,13-diin-10,15-diol
The intermediate (I), can be prepared: (a) bv reacting a C13 ketone (II) having the formula R - C - CH or R' - C - CH (II) O
wherein R and R' are as defin~d above, with acetylene; or (b) by coupling a monoacetylenic alcohol (III) or a mixture thereof having the formula:
, R - C - C - CH or R' - C - C CH (III) OH OH
C13 ketones (II) which may be used on an industrial scale include, for example, geranyl acetone, hexalhydroseudoionone, 6,10-dimethylundeca-5,11-diene-2-one, pseudoionone, citronellidene acetone and dihydrocitronellidene acetone. These ketones can be prepared on an industrial scale and at a comparative low price by the following method. For example, geranyl acetone can be prepared industrially by Carroll rearrangement reaction of linallol with acetoacetic acid ester. Hexahydropseudoionone can be easily obtained by hydrogenation of geranyl acetone or pseudoionone.
6,10-Dimethylundeca-5,10-diene-2-one can be easily prepared by partial hydrogenation of 3,7-dimethylocta-7-en~l-in-3-ol obtained by the method of W. Hoffmann et al. (Ann. 747 60 (1971)) to 3,7-dimethylocta-1,7-dien-3-ol and then by a Carroll rearrangement reaction of the resultant product with acetoacetic acid ester in the same manner as with linallol. Pseudoionone, citronellidene `
~', .
.. , , : . . .
. . , ~ .
~l~37~
aC(!tOIl~! ilnll ~lilly~lrOCi~rOllC~ CllC` ilCetOllC can I)C prcparcd, resp~ctlvely, by .ll-lol condellsatLon of citral, cltronellal and tetrahydrocitral with acetone.
~ ldol condensation of hydroxycitronellal or alkoxy-cltronelInl wi~h acetolle ln placc of ci~ronellal ~ives corres-ponding compoun~s (II). In general, the hydroxy- or alkoxy-citronellal can be prepared from citronellal itself, but these com-poun~s are notpreferred to citronellal; since they result only in an increase in reaction steps.
Diacetylene which is reacted with the C13-ketone (II) has never been used commercially and has hitherto been discarded as a by-product in acetylene preparation; so it can be available at a low price.
The monoacetylenic alcohols (III) can also be prepared by the reaction of the compounds (II) with acetylene by the same method for preparing the compounds (I), which comprises reacting the compounds (II) with diacetylene, as will be described in detail hereinafter. By ethynylation of several compounds (II) with acetylene, the corresponding compounds (III~ can be prepared. Compounds (III) having various substituents can be prepared from the compounds (II) having equivalent substituents.
But as above mentioned, usin~ industrially available compounds (II) is preferred. For example, 3,7,11-trimethyldodeca-6,10-dien-1-in-3-ol, 3,7,11-trimethyldodeca-6,11-dien-1-in-3-ol and 3,7,11-trimethyldodeca-1-in-3-ol can be easily prepared by ethynylation of geranyl acetone, and 6,10-dimethylundeca-5,10- ~ ;
dien-2-on respectively with acetylene. These compounds are preferred compounds among the compounds (III) according to this invention.
Upon reaction of the compound (II) with diacetylene, known methods for preparing acetylenic alcohols can be applied broadly. The preferred methods according to this invention are as follows~
1~375~
(I) rca(~LIoll or Lhe coml)ound (Il) wltll a (;rignard conll)ound of diaccLyl~lle in a solvent such as diethyl ether whîch is used in the general Crignard reaction;
(2) reaction of the compound (II) wlth diacetylide made by passlng diacetylene into a liguid ammonia solution made by dissolving an alkali metal or al~aline earth ~etal such as lithium, sodium, potassium or calcium in liquid ammonia;
(3) reaction of the compound (II) Witil diacetylene in the presence of an alkali metal in liquid ammonia or in an organic solvent (for example, the reaction of compound (II) with diacetylene in the presence of potassium hydroxide or sodium amide in a solvent such as ether or tetrahydrofuran).
In an oxidative coupling reaction of compounds (III), the principles of known oxidative coupling reactions can be applied broadly. The preferred methods according to this invention are as follows:
(1) adding a solution of the compound (III) in a solvent soluble in water, such as ethanol, acetone or tetrahydrofuran, to an aqueous solution of a monovalent copper salt, such as cuprous chlorlde, and ammonium chloride and effecting oxidative coupling of the compound (III) in an oxygen atmosphere;
(2) adding the compound (III) to a solution of a monovalent copper salt, such as cuprous chloride, in a solvent, such as pyridine or picoline, and effecting oxidative coupling of the compound in an oxygen atmosphere;
(3) adding the compound (III) to a solution of a bivalent copper salt, such as cupric acetate, in a solvent such as pyridine or picoline.
In the above coupling method ~1), a small amount of hydrochloric acid, cupric chloride or ammonia may be added to the ~ 5 -.
9.~);~75~
~;yst~m for l)romo~lol~ ol~ tl~c r~.lcLio~ So in tlle ~bove coupling metho~ (3), a rc~cti~n promotln~ agent, such as tetramethyl-ethylenedi~mine, may be added and a mixture of pyridine ~ith met~anol, ~ther or acetone may be use~.
Repr~sentativ~ co~poun~s of tlle inv~ntion ~f f~rmula (I) are a~ follows:
(1) 2,6,10,15,19,23-hexa~ethyltetracosa-2,6,18,22-tetraene-11,13-diin-:lO,15-diol (2) 2,6,10,15,19,23-hexamethyltetrAcosa-18,22-diene-11,13-diin-10,15-diol (3) 2,6,10,15,19,23-hexamethyltetracosa-1,6,18,22-tetraene-11,13-diin-10,15-diol
(4) 2,6,10,15,19,23-hexamethyltetracosa-2,6,8,18,22-pentaene-11,13-diin-10,15 diol
(5) 2,6,10,15,19,23-hexamethyltetracosa-2,8,18,22-tetraene-11,13-diin-10,15-diol ~
~6) 2,6,10,15,19,23-hexameth~ltetracosa-8,18,22- ~ -triene-11,13-diin-10,15-diol ~7) 2,6,10,15,19,23-hexamethyltetracosa-11,13-diin-10,15-diol ~ . .
(~) 2,6,10,15,19,23-hexamethyltetracosa-1,6-diene-11,13- ;~ -diin-10,15-diol (9) 2,6$10,15,19,23-hexamethyltetracosa-2,6,8-triene-11,13-diin-10,15-diol : ~
(10) 2,6,10,15,19,~3-hexamethyltetracosa-2,8-diene-11,13- ' ,~ . -diin-10,15-diol ~:
(11) 2,6,10,15,19,23-hexamethyltetracosa-8-ene-11,13-diin-10,15-diol (12) 2,5,10,15,19l23-hexamethyltetraco6a-1,6,18,23-tetraene-11,13-diin-10,15-diol ~ .
(13) ~,6,10,15,19,23-hexamethyltetr~cosa-?,6,8,18,2~
penta~ne-11,13-diin-10,15-diol ~ ~ :
.
2,6,1C),l5119,;?3-hex~met;h;~ltetr~osa-2,~3,18,2~-tetrr~ene-ll,l~-diin-10,15-d.iol (15) 2,G,10,15,1~ -hexa~ethyltetr~cosa-8,18,23-triene-11,13-diin-10,15 ~liol (16) ~,lO,t5,19,~3-hex~me-thyltetrc~co~-2$6,8,16,18,~2-h~x~ene-ll,l',-diin-10,15-diol (17) " 6,10,19,23-hexamethyltetracos~-2,~,18,~2-tetr~ene-11,17-diin-10,15-diol (18) 2,~,10,15,19,23-hexam2thyltet~acos~-8,18,22-triene-11,13-diin-10,15-diol (19) 2,6,10,15,19,23-hexamethyltetracos~-~,8,16,22-tetraene-11,13-diin-10,15-diol (20~ 2,6,10,15,19,~3-hexamethyltetracosa-8,16,~2-triene-11,13-diin-10,15-diol (21) 2,6,10,15,19,~3-hexamethyltetracosa-8,16-die~e-11,13-diin-10,1~-diol Squalane can be prepared by hydrogenolysis of the compounds (I) obtained by the above methods. Hydrogenolysis can be carried out at higher temperatures by addlng an acldic material to the usual hydrogenation system.
The catalysts used to effect hydrogenolysis are pre-ferably metal catalysts such asnickel, palladium or platinum or compounds of these metals or catalysts in which these catalyst components are supported on a suitable carrier. The hydrogenolysis using such catalysts can be carried out, for example, by the following methods:
(1) catalysis carried out in an organic carboxylic acid.
Organic carboxylic acids used for this method are preferably acetic acid, propionic acld, lactic acid or isolactic acid- These acids can be used in combination with a higher acld such as an.~-halogenated fatty acid or -hydroxy fatty acid;
~37S132 (~) c.lL;llysis c~rri~(l ouL in an lnert or~allic solvent in tl~e pre~qcncc oE an aci(lic substance. Preferre~ or~anic solvents used for this method are saturated hydrocarbons such as hexalle, heptane, cyclohexane, ethylcyclohexane, decaline, hexa~ecaline and squalane. Tlle use of aromatic hydrocarbons, cycllc ethers, esters, ketones and alcohols (especially tertiary alcohols) is preferably avoided in view of the conditions of the reaction, because such solvents could cause hydrogenation, ring-opening, hydrolysis, dehydration and the like, depending upon the reaction conditions.
Preferred acidic substances are Br~sted acids such as sulfuric acid, hydrochloric acid, phosphoric acid, perchloric acid and boric acid; Lewis acids such as zinc chloride, and boron trifluoride; hydrogen salts of strong acids and strong bases, such as sodium hydrogen sulfate, sodium hydrogen phosphate and potassium hydrogen phosphate; salts of strong acids and strong bases such as magnesium sulfate, zinc sulfate, calcium sulfate, copper sulfate, and magnesium chloride; solid acids such as silica alumina, alumina, and solid phosphoric acid; and organic acids such as acetic acid, formic acid, monochloroacetic acid and lactic acids.
Upon hydrogenolysis of the compounds (I) by the above method,combination of a catalyst with an acidic substance or ~ ;
combination of catalyst with acidic substance and solYent is preferably such that the catalyst is not poisoned in part by the acidic substance and/or solvent. The hydrogenolysis methods `
especlally recommended for this reason and from the point of view of using industrially economic catalysts are as follows~
(1) catalysis carried out in the presence of a nickel or palladium catalyst supported on a carrier (for example, a ., .
nickel catalyst supported on diatomaceous earth, or a ~ ~
palladium catalyst supported on active carbon) or in the ;
'' ~,' :
.. , , :. -, , ~ . . ~ : : . ; .
~3~S~2 pre~(ml~e Of a s.ll~ or a strollg aci(l an(l ., strong base or a solLd ncLd in tllc absence of a solvent or ln an inert solvent;
(2) catal~sis carrie~ Ollt in the presence of a palladium catalyst supported on a carrLer SUCII as active carbon in an organic ~cid or in a mixture of an organic acid and an inert organic solvent stable in the said organic acid.
Hydrogenolysis of compounds (I~ by means oE the above methods is generally carried out in liquid phase at elevated temperatures. The reaction temperature is preferably over about 100C, especially from 150 to 300C. This reaction can be carried out at atmospheric pressure but it is preferably carried out under elevated hydrogen pressure, usually a hydrogen pressure of about 10 to 100 kg/cm (G). The amount of catalyst used varies with the nature of the catalyst, but is generally in the broad range of about 0.1 to 10%/w based on the weight of compound (I).
~ ccording to another aspect of this invention, as mentioned above, squalane can also be prepared by another method.
This method comprises a two-step reaction,one step consisting of ;
mild partial hydrogenation of a compound (I) resulting in a compound having double bonds but no triple bonds that is, it ~-consists of selective partial hydrogenation of only the triple bonds contained in the compound (I). The second step consists ~
of hydrogenolysis of the partially-hydrogenated product resulting - --in squalane. That is, the second step comprises replacing hydroxy radicals or other substituents as mentioned above by hydrogen and completing hydrogenation of the remaining unsaturated ~
bonds. ~ ; -The above method consisting of dlrect hydrogenolysis of the compounds ~I) to squalane is liable to produce by-products which may be considered as skeletal isomers of squalane, because -~ ~-- the compounds (I) tend to rearrange under rigorous reaction _ g _ ,:
1~375~32 coodLti()ll~ nwin~- to the triple bollcls colltnined in tlle compounds (I). Tllc by-prod~lcts are dlfflcult to separate from squalane, so that this method is ineffective for obtaining pure squalane.
~lowever, the two-step reaction method does not produce by-products and can be used to prepare purer squalane in a good yield.
With respect to the partial hydrogenation, metal catalysts such as nickel, cobalt, palladium, platinum, rhodium, and iridium or their compounds optionally supported on a suitable carrier may be used as hydrogenation catalysts. Preferred catalysts which have strong hydrogenating activity and are preferred from the aspect of economy are Raney nickel, Raney cobalt or palladium on active carbon, barium sulfate or calcium carbonate. The hydrogen pressure in the reaction is adequate below 100 kg/cm2 and the hydrogenation may be carried out at atmospheric pressure. The hydrogenation reaction is preferably carried out in a suitable solvent because of the high viscosity of the compounds (I). Any organic solvent which does not hinder hydrogenation may be used. Suitable solvents are, for example, aliphatic hydrocarbons, aromatic hydrocarbons, ethers, esters, alcohols and organic carboxylic acids, but amines and compounds containing sulfur are not preferred. A suitable amount of solvent is at least the same amount as that of the compound (I) although a lesser amount is preferred, provided the catalyst used .:
is satisfactorily dispersed.
Thus, squalane can be obtained by submitting the above `~
partial hydrogenation products of the compounds (I) to hydro~
genolysis. The conditions of this hydrogenolysis may be almost ;~
the same as those of the above direct hydrogenation; and their details will not be repeated. `~
In addition to the methods according to this invention, for preparing squalane, a method comprising hydrogenation of the compounds (I), dehydration and hydrogenation, or a method comprising transformation of the compounds (I) to saturated diol .: .: : . . . ..
~C~37S~2 coml)oun(ls, aud l)y(lrogcllolysis can ho col~siderc(l. Ilowcvcr, accordlng to tl~e presellt inventors' expcriments, squalane can be prepared in better yield by the methods o~ this invention.
Tlle following Examples are given to further illustrate the presellt invention.
Example 1 Into a 5 liter three-necked, round-bottomed flask were placed 114.7 g of 3,7,11-trimethyldodeca-6,10-dien-1-in-3-ol, 305.9 g of ammonium chloride, 765 ml of water and 76.5 ml oE
ethyl alcohol and the mixture was stirred at room temperature by passing oxygen for 18 hours. After completion of the reaction, no starting material remained. The reaction mixture was centrifuged and was extracted with benzene. The organic layer was distllled off to remove bPnzene and ethyl alcohol. The residue was dissolved in benzene and washed with water. The benzene solution was dried over anhydrous calcium sulfate and the solid material was filtered off. The benzene solution thus obtained was distilled off to give 107.8 g of 2,6,10,15,19,23-hexamethyltetracosa-2,6,18,22-tetraene-11,13-diin-10,15-diol as a viscous liquid. 3 g of this substance was further dissolved in 10 ml of benzene, treated with active carbon and purified by ;~
distilling off the benzene. ~ -Elementary analysis for C30H4602 t%)~
Calculated: C; 82.14, H; 10.57, 0; 7.29. `
Found: C; 81.86, H; 10.33, 0; 7.58. ~
Confirmation that this compound is 296,10,15,19,23- ~ ;
hexamethyltetracosa-2,6,18,22-tetraene-11,13-diin-10,15-diol was obtained by means of the following method: -~
2 g of this compound was dissolved in 20 ml of acetic acid and 0.2 ml of 3N HCl and 0.2 g of 5 % palladium on active carbon were added thereto. The mixture was hydrogenated in a ~
hydrogen atmosphere at atmospheric pressure for 18 hours. Gas - -chromatography, NMR spectra and mass spectra of the main product lL
1~37S~2 sll0wc~1 il lo l~o i~lcllL~c<ll Wi~ vail..ll)le s(lu.~ nc. 'l'llc theoretical amourlt or ily~rogen ab~sorption was 1021 ml but thc actual amount Eound was 1040 ml.
Examele 2 10.5 ~ of 3,7,11-trimetllyldodeca-1-in-3-ol, 5.0 ~ of ammonium cllloride, 12.0 g of tetrametilylenediamine and 675 ml of pyridine were placed in a 1 liter three-necked, round-bottomed flask. The mixture was reacted at a temperature of 50 to 55C
for 6 hours under an oxygen atmosphere. ~fter completion of the reaction, the alcohol starting material was not detectable. After distillation of pyridine from the reaction mixture, 300 ml of ben~ene and 200 ml of water were added to the residue and, after ~`
decanting, the organic layer was washed with 3N H2S04 and then with water and dried. The benzene solution was distilled off to give 8.55 g of 2,6,10,15,19,23-llexamethyltetracosa-11,13-diin- " `
10,15-diol as a viscous liquid. This compound was treated with active carbon and purified in the same manner as described in Example 1.
. ~ , ., Elementary analysis for C30H5402 of this purified ``
compound (%):
Calculated: C; 80.65, H; 12.18, 0; 7.16.
Found: C; 80.46, H; 12.05, 0; 7.21.
Confirmation that this compound is the object compound was obtained by the fact that mass analysis of this compound showed ~I+ to be 446 and that this compound gave squalane upon hydro-genolysis in the same manner as in Example 1.
' Example 3 This Example was carried out in the same manner as in Example 2 except that 10.1 g of 3,7,11-trimethyldodeca-6,11-dien-1-in-3-ol was used in place of the 3,7,11-trimethyldodeca-l-in-3-ol. 8.34 g of 2,6,10,15,19,23-hexamethyltetracosa- ;~
1,6,18,23-tetraene-11,13-diin-10,15-diol was thus obtained. ~
1(~375C~2 n~ t;~rY ~ <~lysi~5 ~or ~:30ll46(12 (~) Calculatc(l: C; 82.14, ~I; 10.57, o; 7.29.
Found: C; 82.04, H; 10.35, 0; 7.59.
Confirmation that this compound is tl-e ob~ect compound was obtained from the fact that it gave squalane on hydrogenolysis ln the same manner as in Example 1.
Example 4 220 g of 3,7,11-trimethyl-6,10-dien-1-in-3-ol, 1 g of copper acetate, 20.2 ml of pyridine and 440 ml of n-heptane were placed in a 2 liter three-necked, round-bottomed flask. The mixture was stirred at a temperature of 60 to 70C for 5 hours by passing oxygen. The reaction mixture was washed with a 3N
H2S04 solution and then with a 10 % aqueous sodium chloride solution, respectively, three times and the n-heptane was distilled off to give 348 g of a crude product. A 100 g portion of this crude product was placed in a 500 ml autoclave and 200 ml of n-heptane, 1.8 g of nickel catalyst supported on diatomaceous earth (in an amount which is roughly the same as that of the nickel) and 3.6 g oE silica-alumina t28 to 30 7~ alumina) were added thereto. The mixture was subjected to hydrogenolysis at a temperature of 200C under a hydrogen pressure of 100 to 20 kg/cm with stirring for 16 hours. After filtering off the -catalyst and distilling off the n-heptane, the residue was -. . . -. . .
distilled off at 202 to 208C under a reduced pressure of 0.3 . .. . . .
to 0.4 mmHg to give 45.0 g of squalane.
Example 5 40 g of 6,10-dimethylundeca-2-one, 30 g of a 10 7 solution of diacetylene in N-methyl-pyrrolidone and 200 ml of liquid ammonia were placed in a 500 ml ~autoclave and the m~xture was reacted at 20C for one hour. After purging the `~
ammonia, 200 ml of n-heptane was added to the residue and the mixture was washed with water and a crude product was obtained by distilling off the n-heptane. Confirmation that the main - 13 ~
, :" . : -75C~2 c o m l~ o ~ ; o r L l ~ p r o (l ~l c t .I r ~ 6, l 0 ~ n ~ t ll y l ~ c .~ o starting m~terlaI ~nd 2,6,10,15,19,23-hexamethyltetracosa-11,13-diin-10,l5-diol o~ Example 2 was obtained by means of gel permeatioll chromatography (for the compounds of low molecular weight).
The crudc product obtalned by the above ethynylation was placed in a 300 ml shaking type ~lastelloy autoclave (Hastelloy is the trademark of a nickel alloy manufactured by ~;~
- Haynes Stellite Co.) and 100 ml of acetic acid, and 0.6 g of 5 %
palladium on active carbon were added thereto. The mixture was shaken at 200C under a hydrogen pressure of 100 to 50 kg/cm for 16 hours. Gas chromatography showed that the reaction mixture contained 19.4 g of squalane.
Example 6 : . .:, 20.0 g of 2,6,10,15,19,23-hexamethyltetracosa-2,6,18,22-tetraene-11,13-diin-10,15-diol obtained by the method of Example 1, 40 ml of benzene and 1.0 g of 5 % palladium on carbon were placed in a 300 ml shaking type Hastelloy autoclave, and the mixture was sub~ected to hydrogenolysis at 200C under a hydrogen pressure of 100 kg/cm2 for 16 hours. Gas chromatography . .: .
and NMR analysis showed that there remainet no compound having unsaturated bonds and hydroxy radicals and the starting `~
material was almost all transformed into squalane. ;;~
Example 7 10.0 g of 2,6,10,15,19,23-hexamethyltetracosa-2,6,18j22-tetraene-11,13-diin-10,15-diol obtained as described in Example 1, 100 ml of acetic acid and 1.0 g of 5 % palladium on active carbon were placed in a 500 ml shaking type glass autoclave, and the mixture was subjected to hydrogenolysis at 150C under a hydrogen pressure of 5 kg/cm for 16 lIours. Analysis of the crude product thus obtained showed that there remained no unsaturated compound ;~
and that the main components consist of squalane and . - : ~
2,6,10,15,19,23-hexamethyltetracosa-10-ol as well as some lower 3~3~5~3~
hoil~n~ sul~sl;lnles, Ll~o area ri)tio of the former to thu latter beln~ 93 : 7 by rneiJns of gas chromatography.
Example 8 ~ 1. of liquid ammonia and 7 g of lithium were placed in a 2-litcr autoclave and 25 g of diacetylene was added thereto.
To tl~is .solution 192 g of pseudoionone was added dropwise and reacted at 15C for 5 hours. After completion of the reaction, the reaction mixture was cooled and neutrali~ed by adding ammonium chloride. After purging liquid ammonia, the residue was dissolved in 1 l.of n-hexane and 1 l.of water. After ~ -decanting, the organic layer was washed with water several times and then tlle n-hexane was distilled off to give 200 g of crude ~--product.
A 100 g portion of the crude product, 100 ml of acetic acid and 1.0 g of 5 % palladium on active caroon were placed in a 500 ml shaking type glass autoclave. The mixture was subjected to hydrogenolysis at 150C under a hydrogen pressure of 5 kg/cm2 for 16 hours. Analysis of the crude product showed that there remained no unsaturated compound and that the crude .
product consists of mainly squalane and 2,6,10,15,19,23-hexamethyltetracosa-10-ol.
Example 9 About 2 l.of liquid ammonia was placed in a 3 liter ~;
round-bottomed flask and by adding 7 g of lithium and then passing - .
acet~lene gas therethrough, lithium acetylide was prepared. To this solution 192 g of pseudoionone was added and the reaction .:`:: ::
mixture was subJected to reaction under reflux of ammonia for 8 hours by passing a small amount of acetylene. After completion ;~
of tlle reaction, ammonium chloride was added to neutralize the `reaction mixture and after purging the liquid ammonia, the residue was dissolved in 1 1. of n-hexane and 1 1. of water and decanted~
,., ~: :: .:
The organic layer obtained was washed with water several times and the n-hexane was distilled off to give 265 g of crude product.
. ~ .. ..
Ille cr~ld( prodll(~L w;ms sul)jcct:e(l to an oxidativ~ couplin~
reactlon to ~ive 426 g oE product in the same manner as Ln Example 4 except that the crude product was used in place of the 3,7,11-trimetllyldotleca-6,10-dien-1-in-3-ol.
rhe product thus obtained was subjected to hydrogenolysis In the same manncr as in Example 8 to give a mixture of squalane ~
and 2,6,10,15,19,23-llexamethyltetracosa-10-ol. ~ ; -Exam~le 10 Ethynylation of 194 g of citronellidene acetone with diacetylene was carried out in the same manner as in Example 8 except that citronellidene acetone was used in place of the pseudoionone. 268 g of a crude product was thus obtained.
A 10 g portion of the crude product, 100 ml of acetic acid and 1.0 g of 5 % palladium on active carbon were placed ;~
in a S00-ml shaking type glass autoclave and the mixture was sub;ected to reaction at 150C under a hydrogen pressure of 5 kg/cm for 16 hours. An analysis o~ the product obtained showed that there remained no unsaturated compounds and that the crude product consists of main~y squalane and 2,6,10,15,19,23--hexamethyltetracoSa-10-ol, plus lower boiling compounds.
Example 11 Ethynylation of 194 g of citronellidene acetone with aceeylene was carried out in the same manner as in Example 9 except that citronellidene acetone was used in place of the pseudoionone. 278 g of a crude product was obtained. Th~s product was sub~ected to oxidative coupling and hydrogenolysis in the same manner as in Example 9 and squalane was obtained thereby.
Example 12 ~thynylation of 212 g of 6,10-dimethylundeca-3-en-2-on-10-ol (obtained by aldol condensation of hydroxycitronellal and acetone) with acetylene was carried out in the same manner as in Example 9 except that hydroxycitronellal was used in place . ~
16~3r75 l3~2 of the p~ doiollollc. 269 g oE ;I cru~c producL W<IS Lhus obtained.
~ e cru(le product was subJected to oxidative coupling in the same way a9 in Example 4 except tllat it was used in place of tl~e 3,7,11-trimethyldocleca-6,10-dien-1-in-3-ol. 442 g of product wa~ thus obtained.
20 ~ of tlliS crude prodllct, 0.2 ~ of nickel on diatomaceous earth (nickel content: about 50 %), 0.4 g of silica-alumina catalyst and 90 ml of n-heptane were placed in a 300 ml autoclave, and the mixture was sub~ected to reaction at 230C under a hydrogen pressure of 80 to 100 kg/cm for 16 hours to give squalane. ~-Example 13 10.1 g of 3,7,11-trimethyldodeca-6,11-dien-1-in-3-ol, 5.0 g of cuprous chloride, 12.0 g of tetramethyletllylenediamine and 675 ml of pyridine were placed in a 1 liter three-necked and round-bottomed flask, and the mixture ~as subjected to reaction at a temperature of 50 to 55C under an oxygen atmosphere for
~6) 2,6,10,15,19,23-hexameth~ltetracosa-8,18,22- ~ -triene-11,13-diin-10,15-diol ~7) 2,6,10,15,19,23-hexamethyltetracosa-11,13-diin-10,15-diol ~ . .
(~) 2,6,10,15,19,23-hexamethyltetracosa-1,6-diene-11,13- ;~ -diin-10,15-diol (9) 2,6$10,15,19,23-hexamethyltetracosa-2,6,8-triene-11,13-diin-10,15-diol : ~
(10) 2,6,10,15,19,~3-hexamethyltetracosa-2,8-diene-11,13- ' ,~ . -diin-10,15-diol ~:
(11) 2,6,10,15,19,23-hexamethyltetracosa-8-ene-11,13-diin-10,15-diol (12) 2,5,10,15,19l23-hexamethyltetraco6a-1,6,18,23-tetraene-11,13-diin-10,15-diol ~ .
(13) ~,6,10,15,19,23-hexamethyltetr~cosa-?,6,8,18,2~
penta~ne-11,13-diin-10,15-diol ~ ~ :
.
2,6,1C),l5119,;?3-hex~met;h;~ltetr~osa-2,~3,18,2~-tetrr~ene-ll,l~-diin-10,15-d.iol (15) 2,G,10,15,1~ -hexa~ethyltetr~cosa-8,18,23-triene-11,13-diin-10,15 ~liol (16) ~,lO,t5,19,~3-hex~me-thyltetrc~co~-2$6,8,16,18,~2-h~x~ene-ll,l',-diin-10,15-diol (17) " 6,10,19,23-hexamethyltetracos~-2,~,18,~2-tetr~ene-11,17-diin-10,15-diol (18) 2,~,10,15,19,23-hexam2thyltet~acos~-8,18,22-triene-11,13-diin-10,15-diol (19) 2,6,10,15,19,23-hexamethyltetracos~-~,8,16,22-tetraene-11,13-diin-10,15-diol (20~ 2,6,10,15,19,~3-hexamethyltetracosa-8,16,~2-triene-11,13-diin-10,15-diol (21) 2,6,10,15,19,~3-hexamethyltetracosa-8,16-die~e-11,13-diin-10,1~-diol Squalane can be prepared by hydrogenolysis of the compounds (I) obtained by the above methods. Hydrogenolysis can be carried out at higher temperatures by addlng an acldic material to the usual hydrogenation system.
The catalysts used to effect hydrogenolysis are pre-ferably metal catalysts such asnickel, palladium or platinum or compounds of these metals or catalysts in which these catalyst components are supported on a suitable carrier. The hydrogenolysis using such catalysts can be carried out, for example, by the following methods:
(1) catalysis carried out in an organic carboxylic acid.
Organic carboxylic acids used for this method are preferably acetic acid, propionic acld, lactic acid or isolactic acid- These acids can be used in combination with a higher acld such as an.~-halogenated fatty acid or -hydroxy fatty acid;
~37S132 (~) c.lL;llysis c~rri~(l ouL in an lnert or~allic solvent in tl~e pre~qcncc oE an aci(lic substance. Preferre~ or~anic solvents used for this method are saturated hydrocarbons such as hexalle, heptane, cyclohexane, ethylcyclohexane, decaline, hexa~ecaline and squalane. Tlle use of aromatic hydrocarbons, cycllc ethers, esters, ketones and alcohols (especially tertiary alcohols) is preferably avoided in view of the conditions of the reaction, because such solvents could cause hydrogenation, ring-opening, hydrolysis, dehydration and the like, depending upon the reaction conditions.
Preferred acidic substances are Br~sted acids such as sulfuric acid, hydrochloric acid, phosphoric acid, perchloric acid and boric acid; Lewis acids such as zinc chloride, and boron trifluoride; hydrogen salts of strong acids and strong bases, such as sodium hydrogen sulfate, sodium hydrogen phosphate and potassium hydrogen phosphate; salts of strong acids and strong bases such as magnesium sulfate, zinc sulfate, calcium sulfate, copper sulfate, and magnesium chloride; solid acids such as silica alumina, alumina, and solid phosphoric acid; and organic acids such as acetic acid, formic acid, monochloroacetic acid and lactic acids.
Upon hydrogenolysis of the compounds (I) by the above method,combination of a catalyst with an acidic substance or ~ ;
combination of catalyst with acidic substance and solYent is preferably such that the catalyst is not poisoned in part by the acidic substance and/or solvent. The hydrogenolysis methods `
especlally recommended for this reason and from the point of view of using industrially economic catalysts are as follows~
(1) catalysis carried out in the presence of a nickel or palladium catalyst supported on a carrier (for example, a ., .
nickel catalyst supported on diatomaceous earth, or a ~ ~
palladium catalyst supported on active carbon) or in the ;
'' ~,' :
.. , , :. -, , ~ . . ~ : : . ; .
~3~S~2 pre~(ml~e Of a s.ll~ or a strollg aci(l an(l ., strong base or a solLd ncLd in tllc absence of a solvent or ln an inert solvent;
(2) catal~sis carrie~ Ollt in the presence of a palladium catalyst supported on a carrLer SUCII as active carbon in an organic ~cid or in a mixture of an organic acid and an inert organic solvent stable in the said organic acid.
Hydrogenolysis of compounds (I~ by means oE the above methods is generally carried out in liquid phase at elevated temperatures. The reaction temperature is preferably over about 100C, especially from 150 to 300C. This reaction can be carried out at atmospheric pressure but it is preferably carried out under elevated hydrogen pressure, usually a hydrogen pressure of about 10 to 100 kg/cm (G). The amount of catalyst used varies with the nature of the catalyst, but is generally in the broad range of about 0.1 to 10%/w based on the weight of compound (I).
~ ccording to another aspect of this invention, as mentioned above, squalane can also be prepared by another method.
This method comprises a two-step reaction,one step consisting of ;
mild partial hydrogenation of a compound (I) resulting in a compound having double bonds but no triple bonds that is, it ~-consists of selective partial hydrogenation of only the triple bonds contained in the compound (I). The second step consists ~
of hydrogenolysis of the partially-hydrogenated product resulting - --in squalane. That is, the second step comprises replacing hydroxy radicals or other substituents as mentioned above by hydrogen and completing hydrogenation of the remaining unsaturated ~
bonds. ~ ; -The above method consisting of dlrect hydrogenolysis of the compounds ~I) to squalane is liable to produce by-products which may be considered as skeletal isomers of squalane, because -~ ~-- the compounds (I) tend to rearrange under rigorous reaction _ g _ ,:
1~375~32 coodLti()ll~ nwin~- to the triple bollcls colltnined in tlle compounds (I). Tllc by-prod~lcts are dlfflcult to separate from squalane, so that this method is ineffective for obtaining pure squalane.
~lowever, the two-step reaction method does not produce by-products and can be used to prepare purer squalane in a good yield.
With respect to the partial hydrogenation, metal catalysts such as nickel, cobalt, palladium, platinum, rhodium, and iridium or their compounds optionally supported on a suitable carrier may be used as hydrogenation catalysts. Preferred catalysts which have strong hydrogenating activity and are preferred from the aspect of economy are Raney nickel, Raney cobalt or palladium on active carbon, barium sulfate or calcium carbonate. The hydrogen pressure in the reaction is adequate below 100 kg/cm2 and the hydrogenation may be carried out at atmospheric pressure. The hydrogenation reaction is preferably carried out in a suitable solvent because of the high viscosity of the compounds (I). Any organic solvent which does not hinder hydrogenation may be used. Suitable solvents are, for example, aliphatic hydrocarbons, aromatic hydrocarbons, ethers, esters, alcohols and organic carboxylic acids, but amines and compounds containing sulfur are not preferred. A suitable amount of solvent is at least the same amount as that of the compound (I) although a lesser amount is preferred, provided the catalyst used .:
is satisfactorily dispersed.
Thus, squalane can be obtained by submitting the above `~
partial hydrogenation products of the compounds (I) to hydro~
genolysis. The conditions of this hydrogenolysis may be almost ;~
the same as those of the above direct hydrogenation; and their details will not be repeated. `~
In addition to the methods according to this invention, for preparing squalane, a method comprising hydrogenation of the compounds (I), dehydration and hydrogenation, or a method comprising transformation of the compounds (I) to saturated diol .: .: : . . . ..
~C~37S~2 coml)oun(ls, aud l)y(lrogcllolysis can ho col~siderc(l. Ilowcvcr, accordlng to tl~e presellt inventors' expcriments, squalane can be prepared in better yield by the methods o~ this invention.
Tlle following Examples are given to further illustrate the presellt invention.
Example 1 Into a 5 liter three-necked, round-bottomed flask were placed 114.7 g of 3,7,11-trimethyldodeca-6,10-dien-1-in-3-ol, 305.9 g of ammonium chloride, 765 ml of water and 76.5 ml oE
ethyl alcohol and the mixture was stirred at room temperature by passing oxygen for 18 hours. After completion of the reaction, no starting material remained. The reaction mixture was centrifuged and was extracted with benzene. The organic layer was distllled off to remove bPnzene and ethyl alcohol. The residue was dissolved in benzene and washed with water. The benzene solution was dried over anhydrous calcium sulfate and the solid material was filtered off. The benzene solution thus obtained was distilled off to give 107.8 g of 2,6,10,15,19,23-hexamethyltetracosa-2,6,18,22-tetraene-11,13-diin-10,15-diol as a viscous liquid. 3 g of this substance was further dissolved in 10 ml of benzene, treated with active carbon and purified by ;~
distilling off the benzene. ~ -Elementary analysis for C30H4602 t%)~
Calculated: C; 82.14, H; 10.57, 0; 7.29. `
Found: C; 81.86, H; 10.33, 0; 7.58. ~
Confirmation that this compound is 296,10,15,19,23- ~ ;
hexamethyltetracosa-2,6,18,22-tetraene-11,13-diin-10,15-diol was obtained by means of the following method: -~
2 g of this compound was dissolved in 20 ml of acetic acid and 0.2 ml of 3N HCl and 0.2 g of 5 % palladium on active carbon were added thereto. The mixture was hydrogenated in a ~
hydrogen atmosphere at atmospheric pressure for 18 hours. Gas - -chromatography, NMR spectra and mass spectra of the main product lL
1~37S~2 sll0wc~1 il lo l~o i~lcllL~c<ll Wi~ vail..ll)le s(lu.~ nc. 'l'llc theoretical amourlt or ily~rogen ab~sorption was 1021 ml but thc actual amount Eound was 1040 ml.
Examele 2 10.5 ~ of 3,7,11-trimetllyldodeca-1-in-3-ol, 5.0 ~ of ammonium cllloride, 12.0 g of tetrametilylenediamine and 675 ml of pyridine were placed in a 1 liter three-necked, round-bottomed flask. The mixture was reacted at a temperature of 50 to 55C
for 6 hours under an oxygen atmosphere. ~fter completion of the reaction, the alcohol starting material was not detectable. After distillation of pyridine from the reaction mixture, 300 ml of ben~ene and 200 ml of water were added to the residue and, after ~`
decanting, the organic layer was washed with 3N H2S04 and then with water and dried. The benzene solution was distilled off to give 8.55 g of 2,6,10,15,19,23-llexamethyltetracosa-11,13-diin- " `
10,15-diol as a viscous liquid. This compound was treated with active carbon and purified in the same manner as described in Example 1.
. ~ , ., Elementary analysis for C30H5402 of this purified ``
compound (%):
Calculated: C; 80.65, H; 12.18, 0; 7.16.
Found: C; 80.46, H; 12.05, 0; 7.21.
Confirmation that this compound is the object compound was obtained by the fact that mass analysis of this compound showed ~I+ to be 446 and that this compound gave squalane upon hydro-genolysis in the same manner as in Example 1.
' Example 3 This Example was carried out in the same manner as in Example 2 except that 10.1 g of 3,7,11-trimethyldodeca-6,11-dien-1-in-3-ol was used in place of the 3,7,11-trimethyldodeca-l-in-3-ol. 8.34 g of 2,6,10,15,19,23-hexamethyltetracosa- ;~
1,6,18,23-tetraene-11,13-diin-10,15-diol was thus obtained. ~
1(~375C~2 n~ t;~rY ~ <~lysi~5 ~or ~:30ll46(12 (~) Calculatc(l: C; 82.14, ~I; 10.57, o; 7.29.
Found: C; 82.04, H; 10.35, 0; 7.59.
Confirmation that this compound is tl-e ob~ect compound was obtained from the fact that it gave squalane on hydrogenolysis ln the same manner as in Example 1.
Example 4 220 g of 3,7,11-trimethyl-6,10-dien-1-in-3-ol, 1 g of copper acetate, 20.2 ml of pyridine and 440 ml of n-heptane were placed in a 2 liter three-necked, round-bottomed flask. The mixture was stirred at a temperature of 60 to 70C for 5 hours by passing oxygen. The reaction mixture was washed with a 3N
H2S04 solution and then with a 10 % aqueous sodium chloride solution, respectively, three times and the n-heptane was distilled off to give 348 g of a crude product. A 100 g portion of this crude product was placed in a 500 ml autoclave and 200 ml of n-heptane, 1.8 g of nickel catalyst supported on diatomaceous earth (in an amount which is roughly the same as that of the nickel) and 3.6 g oE silica-alumina t28 to 30 7~ alumina) were added thereto. The mixture was subjected to hydrogenolysis at a temperature of 200C under a hydrogen pressure of 100 to 20 kg/cm with stirring for 16 hours. After filtering off the -catalyst and distilling off the n-heptane, the residue was -. . . -. . .
distilled off at 202 to 208C under a reduced pressure of 0.3 . .. . . .
to 0.4 mmHg to give 45.0 g of squalane.
Example 5 40 g of 6,10-dimethylundeca-2-one, 30 g of a 10 7 solution of diacetylene in N-methyl-pyrrolidone and 200 ml of liquid ammonia were placed in a 500 ml ~autoclave and the m~xture was reacted at 20C for one hour. After purging the `~
ammonia, 200 ml of n-heptane was added to the residue and the mixture was washed with water and a crude product was obtained by distilling off the n-heptane. Confirmation that the main - 13 ~
, :" . : -75C~2 c o m l~ o ~ ; o r L l ~ p r o (l ~l c t .I r ~ 6, l 0 ~ n ~ t ll y l ~ c .~ o starting m~terlaI ~nd 2,6,10,15,19,23-hexamethyltetracosa-11,13-diin-10,l5-diol o~ Example 2 was obtained by means of gel permeatioll chromatography (for the compounds of low molecular weight).
The crudc product obtalned by the above ethynylation was placed in a 300 ml shaking type ~lastelloy autoclave (Hastelloy is the trademark of a nickel alloy manufactured by ~;~
- Haynes Stellite Co.) and 100 ml of acetic acid, and 0.6 g of 5 %
palladium on active carbon were added thereto. The mixture was shaken at 200C under a hydrogen pressure of 100 to 50 kg/cm for 16 hours. Gas chromatography showed that the reaction mixture contained 19.4 g of squalane.
Example 6 : . .:, 20.0 g of 2,6,10,15,19,23-hexamethyltetracosa-2,6,18,22-tetraene-11,13-diin-10,15-diol obtained by the method of Example 1, 40 ml of benzene and 1.0 g of 5 % palladium on carbon were placed in a 300 ml shaking type Hastelloy autoclave, and the mixture was sub~ected to hydrogenolysis at 200C under a hydrogen pressure of 100 kg/cm2 for 16 hours. Gas chromatography . .: .
and NMR analysis showed that there remainet no compound having unsaturated bonds and hydroxy radicals and the starting `~
material was almost all transformed into squalane. ;;~
Example 7 10.0 g of 2,6,10,15,19,23-hexamethyltetracosa-2,6,18j22-tetraene-11,13-diin-10,15-diol obtained as described in Example 1, 100 ml of acetic acid and 1.0 g of 5 % palladium on active carbon were placed in a 500 ml shaking type glass autoclave, and the mixture was subjected to hydrogenolysis at 150C under a hydrogen pressure of 5 kg/cm for 16 lIours. Analysis of the crude product thus obtained showed that there remained no unsaturated compound ;~
and that the main components consist of squalane and . - : ~
2,6,10,15,19,23-hexamethyltetracosa-10-ol as well as some lower 3~3~5~3~
hoil~n~ sul~sl;lnles, Ll~o area ri)tio of the former to thu latter beln~ 93 : 7 by rneiJns of gas chromatography.
Example 8 ~ 1. of liquid ammonia and 7 g of lithium were placed in a 2-litcr autoclave and 25 g of diacetylene was added thereto.
To tl~is .solution 192 g of pseudoionone was added dropwise and reacted at 15C for 5 hours. After completion of the reaction, the reaction mixture was cooled and neutrali~ed by adding ammonium chloride. After purging liquid ammonia, the residue was dissolved in 1 l.of n-hexane and 1 l.of water. After ~ -decanting, the organic layer was washed with water several times and then tlle n-hexane was distilled off to give 200 g of crude ~--product.
A 100 g portion of the crude product, 100 ml of acetic acid and 1.0 g of 5 % palladium on active caroon were placed in a 500 ml shaking type glass autoclave. The mixture was subjected to hydrogenolysis at 150C under a hydrogen pressure of 5 kg/cm2 for 16 hours. Analysis of the crude product showed that there remained no unsaturated compound and that the crude .
product consists of mainly squalane and 2,6,10,15,19,23-hexamethyltetracosa-10-ol.
Example 9 About 2 l.of liquid ammonia was placed in a 3 liter ~;
round-bottomed flask and by adding 7 g of lithium and then passing - .
acet~lene gas therethrough, lithium acetylide was prepared. To this solution 192 g of pseudoionone was added and the reaction .:`:: ::
mixture was subJected to reaction under reflux of ammonia for 8 hours by passing a small amount of acetylene. After completion ;~
of tlle reaction, ammonium chloride was added to neutralize the `reaction mixture and after purging the liquid ammonia, the residue was dissolved in 1 1. of n-hexane and 1 1. of water and decanted~
,., ~: :: .:
The organic layer obtained was washed with water several times and the n-hexane was distilled off to give 265 g of crude product.
. ~ .. ..
Ille cr~ld( prodll(~L w;ms sul)jcct:e(l to an oxidativ~ couplin~
reactlon to ~ive 426 g oE product in the same manner as Ln Example 4 except that the crude product was used in place of the 3,7,11-trimetllyldotleca-6,10-dien-1-in-3-ol.
rhe product thus obtained was subjected to hydrogenolysis In the same manncr as in Example 8 to give a mixture of squalane ~
and 2,6,10,15,19,23-llexamethyltetracosa-10-ol. ~ ; -Exam~le 10 Ethynylation of 194 g of citronellidene acetone with diacetylene was carried out in the same manner as in Example 8 except that citronellidene acetone was used in place of the pseudoionone. 268 g of a crude product was thus obtained.
A 10 g portion of the crude product, 100 ml of acetic acid and 1.0 g of 5 % palladium on active carbon were placed ;~
in a S00-ml shaking type glass autoclave and the mixture was sub;ected to reaction at 150C under a hydrogen pressure of 5 kg/cm for 16 hours. An analysis o~ the product obtained showed that there remained no unsaturated compounds and that the crude product consists of main~y squalane and 2,6,10,15,19,23--hexamethyltetracoSa-10-ol, plus lower boiling compounds.
Example 11 Ethynylation of 194 g of citronellidene acetone with aceeylene was carried out in the same manner as in Example 9 except that citronellidene acetone was used in place of the pseudoionone. 278 g of a crude product was obtained. Th~s product was sub~ected to oxidative coupling and hydrogenolysis in the same manner as in Example 9 and squalane was obtained thereby.
Example 12 ~thynylation of 212 g of 6,10-dimethylundeca-3-en-2-on-10-ol (obtained by aldol condensation of hydroxycitronellal and acetone) with acetylene was carried out in the same manner as in Example 9 except that hydroxycitronellal was used in place . ~
16~3r75 l3~2 of the p~ doiollollc. 269 g oE ;I cru~c producL W<IS Lhus obtained.
~ e cru(le product was subJected to oxidative coupling in the same way a9 in Example 4 except tllat it was used in place of tl~e 3,7,11-trimethyldocleca-6,10-dien-1-in-3-ol. 442 g of product wa~ thus obtained.
20 ~ of tlliS crude prodllct, 0.2 ~ of nickel on diatomaceous earth (nickel content: about 50 %), 0.4 g of silica-alumina catalyst and 90 ml of n-heptane were placed in a 300 ml autoclave, and the mixture was sub~ected to reaction at 230C under a hydrogen pressure of 80 to 100 kg/cm for 16 hours to give squalane. ~-Example 13 10.1 g of 3,7,11-trimethyldodeca-6,11-dien-1-in-3-ol, 5.0 g of cuprous chloride, 12.0 g of tetramethyletllylenediamine and 675 ml of pyridine were placed in a 1 liter three-necked and round-bottomed flask, and the mixture ~as subjected to reaction at a temperature of 50 to 55C under an oxygen atmosphere for
6 hours. ~fter completion of the reaction there remained no starting alcohol. The pyridine was distilled off fro~ the reaction mixture and the residue was dissolved in 300 ml of benzene and 200 ml of water and, after decanting the organic layer was washed with a solution of 3N H3S04 and then with water and dried.
The ben~ene solution was distilled off to give 8.34 g of 2~,6,10, `~
15,19,23-hexamethyltetracosa-1,6,18,23-tetraene-11,13-diin~
10,15-diol. This product was purified with active carbon treatment and analyzed.
Elementary analysis for C30H4602 (%)~
Calculated: C; 82.14, H; 10.57, 0; 7.29.
Found: C; 82.04, H; 10.35, 0; 7.59. ;~
Example 14 220 g Or 3,7,11-trimPthyldodeca-6,11-dien-1-in-3-ol, ;~
9.1 g of copper acetate, 20.2 ml of pyridine and 440 ml of ~`
n-heptane were placed in a 2 liter three-necked and round-bottomed ~`
:
- 17 - ~;
.
7S~02 flask, al~(l the mixtllrC WilS sub jecLo(l Lo reaction <~L a ~eml)erature o~ 60 to 7()C for 5 hours by passlll~ oxygen and was w~shed with a 3N ll2S04 solution and with a lO % aqueous solution of sodium chloride, respectively, tllree times. The n-heptane was distilled off to give 348 g of crude product.
A 100 g portion of this crude product, 3.6 ml of Raney nickel (about 2.5 g) and lO0 ml of n-heptane were placed in a 300 ml autoclave, and the mixture was hydrogenated at room temperatures under a hydrogen pressure of 100 to 50 kgtcm for 16 hours. The reaction temperature rose to a maximum temperature of about 55C owing to the heat of the reaction. After the reaction, the Raney nickel was filtered off and the n-heptane was distilled off from the mixture to give 70.8 g of a viscous -brown liquid. Investigation with C -NMR spectra confirmed qualitatively that thls liquid was free from triple bonds and that some of the double bonds were hydrogenated, but that a considerable amount of the double bonds remained.
This liquid was dissolved in lO0 ml of isolatic acid and l.5 g oE 5 X palladium on active carbon was added thereto.
The mixture was placed in a 300 ml Hastelloy autoclave and caused to react at 200C under a hydrogen pressure of lO0 to 50 kg/cm for 16 hours. The catalyst was filtered off and the reaction mixture was distilled under reduced pressure to give 33 g of squalane.
A lO0 g portion of the above oxidative coupling product was caused to react in lO0 ml of acetic acid in the same manner as above-mentioned and 41.2 g of squalane was obtained by distillation. ~ ;~
Investigation ~f this squalane by gas chromatography (column:
~ Diasolidfl~ Carbowax~20~1 2 cm, ~emperature of measurement:
240C~ a substance having a sharp shoulder peak next to that of squalene. The structure of the substance showing this peak is not clear but the conclusion that this substance is a saturated hydrocarbon is reached by means of measurement of iodine number, ~ - .
- 18 - ~
~.~3'75U;~
In~rare(l sl)ectra alld C: -NM~ spectr.l. T~lercrorc this substance seems to be a by-l~roduct which llas a cyclized structure related to squal~ne.
In contrast, the above-mcntioned product in which the triple bonds were first removed by partial hydrogenation does not exhibit such a shoulder peak.
Examplc 15 40 g of 6,10-dimethylundeca-5,10-dien-2-on, 30 g of a 10% diacetylene solutlon ln N-metllyl-pyrrolidone, 1.5 g of potassium hydroxide and 200 ml of liquid ammonia were placed in a 200 ml autoclave, and the reaction was caused to react at 20C for one hour. ~fter removal of ammonia by purging, 200 ml of n-heptane was added to the residue and washed with water.
The n-heptane was distllled off to afford a crude product.
Confirmation that the prlncipal components of the crude product are 6,10-dimethylundeca~5,10-dien-2-on starting materlal and 2,6,10,15,19,23-hexamethyltetracosa-1,6,18,23-tetraene-11,13-diln-10,15-dlol obtained by Example 13 was obtained by means of gel permeation chromatography tColumn for low-molecular co~pounds). The crude product obtained by the above ethynylation was placed in a 300 ml shaking type autoclave and 40 ml of n-heptane and 0.8 g o~ 5 ~ palladium on active carbon were added thereto. The mixture was caused to react at a temperature from room temperature to 60C under a hydrogen pressure of 50 to 100 kg/cm for 16 hours. The product obtained had no triple bond but some double bonds. By adding a further 20 ml of acetic acid to the above reaction system, the mixture was caused to react at 200C under a hydrogen pressure of 50 to 100 kg/cm for 10 hours. Confirmation that 20.5 g of squalane was obtained having no shoulder peak as described ln Example 14 was reached by means of gas chromatography.
Example 16 13.2 g of 2,6,10,15,19,23-hexamethyltetracosa-2,6,18,22-.. . . ........ . . .
,. ~. . . . .. . .. . .
1~)375~
~ctracrle-ll,l3-~liin--l0,15-(llol obL;Iine(l in thc same manner as in Example 1, about 0.65 g of 5 % palladium on active carbon, and 100 ml of benzene in a 500 ml autoclave, were placed and the mixture was caused to react at 50C at a hydrogen pressure of 4 to 6 kg¦cm for 6 hours. The catalyst was filtered off and the benzene was distilled off. Confirmation that the crude product obtained had no triple bond but some double bonds were made. To this crude product, 100 ml of n-heptane, 0.40 g oE
nickel on an equal amount of diatomaceous earth, and 0.80 g of silica-alumina catalyst (28 to 30 % alumina) were added, and the mixture was caused to react at 220C under a hydrogen pressure of 50 to 100 kg/cm for 2 hours. Investigation by means of gas chromatography showed that there was obtained 11.0 g of squalane, which did not exhibit a shoulder peak as described in Example 14.
Example 17 87.8 g of 2,6,10,15,19,23-hexamethyltetracosa- ~ ~
.:
2,6,18,22-tetraene-11,13-diin-10,15-diol obtained as in Example 1, 2.6 g oE Raney nickel and 200 ml of n-heptane were placed in a 500 ml autoclave. The mixture was caused to react at a temperature from room temperature to 60C under a hydrogen pressure of S0 ;
to 100 kg/cm for 3 hours. After removal of the catalyst, the n-heptane was distilled off to afford 10.4 g of a crude product having double bonds but no triple bonds.
10.2 g of the crude product, 40 ml of n-heptane, 0.2 g of nickel on diatomaceous earth and 1.0 g of zinc sulfate were placed in a 100 ml autoclave. The mixture was caused to react ~ ~ ~
:
at 200C at a hydrogen pressure of 90 to 100 kg/cm for 16 hours to afford 2.3 g of squalane.
Example 18 This example was carried out in the same manner as Example l7, except that 1.0 g of calcined gypsum was used in place of the zinc sulfate. 7.4 g of squalane was obtained.
~75~;)2 I._ ~le 19 l liLcr oE llqllld ammonia, 17 g o~ lithium and 25 g of diacetylene were placed in a 2 liter autoclave. To this solution 192 g of pseudoionone was added dropwise witll stirring and caused to re~ct at 15C for 5 hours. After completion of the reaction, the mixture was coole~ and neutralized by adding ammonium chloride. After purgin~ the ammonia, the residue was -~
dissolved in 1 1. of n-hexane and 1 1. of water. After decanting the organic layer was washed with water several times and the hexane was distilled off to afford 200 g of crude product.
A lO0 g portion of the crude product, 3.6 ml of Raney nickel (about 2.5 g) and 100 ml of n-heptane were placed in a 300 ml autoclave. The mixture was caused to react at room temperature under a hydrogen pressure of 50 to 100 kg~cm2.
The reaction temperature in the reaction system rose to a maximum temperature of about 58C owing to the heat of the reaction.
After shaking for 16 hours, the Raney nickel was filtered oEf and the heptane was distilled off from the mixture to afford ~ -108 g of crude product free from triple bonds.
10.2 g of the above crude product, 40 ml of n-heptane, 0.2 g of nickel on diatomaceous earth, and 1.0 g of zinc sulfate were placed in a 100 ml autoclave and the mixture was caused to react at 200C at a hydrogen pressure of 80 to 90 kg/cm for 16 hours. 2.5 g of squalane (2,6,10,15,19,23 hexamethyltetracosane) was thus obtained. -~
Example 20 About 2 l. of liquid ammonia was placed in a 3 liter round-bottomed flask, and by passing acetylene therethrough after the addition Or lithium, litl-ium acetylide was prepared. After the addition of 192 g of pseudoionone, the solution was caused ;
to react under reflux of liquid ammonia for 8 hours by passing in a little amount of acetylene. After the reaction, the solution was neutralized by adding ammonium chloride and, after purging ' ' '' , - ~ :
- .~ : ,. .. - .
- 1~375~2 ammonla, tl~e resi(llle was ~issolved in 1 1. Or n-l)exane and 1 1.
of waLer. ~ftcr dec;llltaLLoll, the organic layer was washcd with water several times and 265 g of a crude product was thus obtained.
The crude product was subjected to oxidative-coupling in the same manner as in Example 14 except that it was used in place of the 3,7,11-trimethyldodeca-6,10-dien-1-in-3-ol. 426 g of product was thus obtained. ~ 100 g portion of the product was placed in-i~ 500 ml autoclave and subjected to hydrogenation and hydrogenolysis in the same manner as in Example 14 to give 21 g of squalane.
Example 21 Ethynylation of 194 g of citronellidene acetone with ~ ~ ;
diacetylene was carried out in the same manner as in Example 19, except that citronellidene acetone was used in place of the pseudoionone. 268 g of a crude product was thus obtained.
100 g of the ~rude product, 3.6 ml (about 2.5 g) of Raney nickel and 100 ml of n-heptane were placed in a 300 ml autoclave, and the mixture was caused to react at room temperature under a hydrogen pressure of 50 to 100 kg/cm2. The reaction ~0 temperature rose to a maximum temperature of about 56C. After shaking for 18 hours, the Raney nickel was filtered off and the heptane was distilled off to afford 112 g of a crude product having double bonds but no triple bonds. ;~
10.2 g of the crude product, 40 ml of n-heptane, 0.2 g of nickel on diatomaceous earth and 1.0 g of zinc sulfate were placed in a 100 ml autoclave, and the mixture was caused to react at 200C under a hydrogen pressure of 30 to 90 kg/cm for 10 hours to give 3.2 g of squalane (2,6,10,15,19,23-hexamethyltetracosane).
Example 22 Ethynylation of 194 g of citronellidene acetone was carried out with acetylene in the same manner as in Example 20 except that citronellidene acetone was used in place of the ~ 22 ~
:,,: : : :
, .
- :1133~5~)~
)Sell~lOiOl~OII-'. 27~ E of cru(le product was thus obta~ned. This ~rodllct w;lL; slll)jocLccl to oxid.ltive-coupllllg, hy~lrogcnation and hydrogenolysis in sequcllce in the same manner as in Example 20 and squalalle was thus obtained in a yleld of 36.3 ~ based on the citronellldene acetone.
Example 23 Ethynylatlon of 212 g of 6,10-~imethylundeca-3-en-2-on-10-ol obtained by aldol condensation of hydroxycitronellal and acetone was carried out ln the same manner as in Example 20 except that llydrexycitronellal was used in place of the pseudoionone 269 g of a crude product was thus obtained.
The crude product was subjected to an oxidative-coupling reaction in the same manner as in Example 14 except that it was used in place of the 3,7,11-trimethyldodeca-6,10-dien-1-in-3-ol. 442 g of a crude product was thus obtained. ~ -A 50 g portion of the product, 50 ml of n-heptane and 5 g of 5 % Lindlar catalyst were placed in a 300 ml round-bottomed flask, and the mixture was caused to react at 50C under normal atmospheric pressure for 8 hours. Confirmation that the 2(~ product thus obtained contained almost no triple bond but only double bonds was confirmed by means of its C -NMR spectra.
After filtering off the Lindlar catalyst, the product was placed in a 300 ml autoclave and the hydrogenolysis catalysts used in ;~
Example 16, namely 1.5 g of nickel on diatomaceous earth and 3 g of silica-alumina catalyst, were added thereto. The mixture was `;
caused to react at 230C under a hydrogen pressure of 80 to 100 kg/cm2 for 5 hours. Con~irmation that the product thus obtained ~ `
contained 14.2 g of squalene was achieved by means of gas chromatography.
'' ~
- 23 - ~
The ben~ene solution was distilled off to give 8.34 g of 2~,6,10, `~
15,19,23-hexamethyltetracosa-1,6,18,23-tetraene-11,13-diin~
10,15-diol. This product was purified with active carbon treatment and analyzed.
Elementary analysis for C30H4602 (%)~
Calculated: C; 82.14, H; 10.57, 0; 7.29.
Found: C; 82.04, H; 10.35, 0; 7.59. ;~
Example 14 220 g Or 3,7,11-trimPthyldodeca-6,11-dien-1-in-3-ol, ;~
9.1 g of copper acetate, 20.2 ml of pyridine and 440 ml of ~`
n-heptane were placed in a 2 liter three-necked and round-bottomed ~`
:
- 17 - ~;
.
7S~02 flask, al~(l the mixtllrC WilS sub jecLo(l Lo reaction <~L a ~eml)erature o~ 60 to 7()C for 5 hours by passlll~ oxygen and was w~shed with a 3N ll2S04 solution and with a lO % aqueous solution of sodium chloride, respectively, tllree times. The n-heptane was distilled off to give 348 g of crude product.
A 100 g portion of this crude product, 3.6 ml of Raney nickel (about 2.5 g) and lO0 ml of n-heptane were placed in a 300 ml autoclave, and the mixture was hydrogenated at room temperatures under a hydrogen pressure of 100 to 50 kgtcm for 16 hours. The reaction temperature rose to a maximum temperature of about 55C owing to the heat of the reaction. After the reaction, the Raney nickel was filtered off and the n-heptane was distilled off from the mixture to give 70.8 g of a viscous -brown liquid. Investigation with C -NMR spectra confirmed qualitatively that thls liquid was free from triple bonds and that some of the double bonds were hydrogenated, but that a considerable amount of the double bonds remained.
This liquid was dissolved in lO0 ml of isolatic acid and l.5 g oE 5 X palladium on active carbon was added thereto.
The mixture was placed in a 300 ml Hastelloy autoclave and caused to react at 200C under a hydrogen pressure of lO0 to 50 kg/cm for 16 hours. The catalyst was filtered off and the reaction mixture was distilled under reduced pressure to give 33 g of squalane.
A lO0 g portion of the above oxidative coupling product was caused to react in lO0 ml of acetic acid in the same manner as above-mentioned and 41.2 g of squalane was obtained by distillation. ~ ;~
Investigation ~f this squalane by gas chromatography (column:
~ Diasolidfl~ Carbowax~20~1 2 cm, ~emperature of measurement:
240C~ a substance having a sharp shoulder peak next to that of squalene. The structure of the substance showing this peak is not clear but the conclusion that this substance is a saturated hydrocarbon is reached by means of measurement of iodine number, ~ - .
- 18 - ~
~.~3'75U;~
In~rare(l sl)ectra alld C: -NM~ spectr.l. T~lercrorc this substance seems to be a by-l~roduct which llas a cyclized structure related to squal~ne.
In contrast, the above-mcntioned product in which the triple bonds were first removed by partial hydrogenation does not exhibit such a shoulder peak.
Examplc 15 40 g of 6,10-dimethylundeca-5,10-dien-2-on, 30 g of a 10% diacetylene solutlon ln N-metllyl-pyrrolidone, 1.5 g of potassium hydroxide and 200 ml of liquid ammonia were placed in a 200 ml autoclave, and the reaction was caused to react at 20C for one hour. ~fter removal of ammonia by purging, 200 ml of n-heptane was added to the residue and washed with water.
The n-heptane was distllled off to afford a crude product.
Confirmation that the prlncipal components of the crude product are 6,10-dimethylundeca~5,10-dien-2-on starting materlal and 2,6,10,15,19,23-hexamethyltetracosa-1,6,18,23-tetraene-11,13-diln-10,15-dlol obtained by Example 13 was obtained by means of gel permeation chromatography tColumn for low-molecular co~pounds). The crude product obtained by the above ethynylation was placed in a 300 ml shaking type autoclave and 40 ml of n-heptane and 0.8 g o~ 5 ~ palladium on active carbon were added thereto. The mixture was caused to react at a temperature from room temperature to 60C under a hydrogen pressure of 50 to 100 kg/cm for 16 hours. The product obtained had no triple bond but some double bonds. By adding a further 20 ml of acetic acid to the above reaction system, the mixture was caused to react at 200C under a hydrogen pressure of 50 to 100 kg/cm for 10 hours. Confirmation that 20.5 g of squalane was obtained having no shoulder peak as described ln Example 14 was reached by means of gas chromatography.
Example 16 13.2 g of 2,6,10,15,19,23-hexamethyltetracosa-2,6,18,22-.. . . ........ . . .
,. ~. . . . .. . .. . .
1~)375~
~ctracrle-ll,l3-~liin--l0,15-(llol obL;Iine(l in thc same manner as in Example 1, about 0.65 g of 5 % palladium on active carbon, and 100 ml of benzene in a 500 ml autoclave, were placed and the mixture was caused to react at 50C at a hydrogen pressure of 4 to 6 kg¦cm for 6 hours. The catalyst was filtered off and the benzene was distilled off. Confirmation that the crude product obtained had no triple bond but some double bonds were made. To this crude product, 100 ml of n-heptane, 0.40 g oE
nickel on an equal amount of diatomaceous earth, and 0.80 g of silica-alumina catalyst (28 to 30 % alumina) were added, and the mixture was caused to react at 220C under a hydrogen pressure of 50 to 100 kg/cm for 2 hours. Investigation by means of gas chromatography showed that there was obtained 11.0 g of squalane, which did not exhibit a shoulder peak as described in Example 14.
Example 17 87.8 g of 2,6,10,15,19,23-hexamethyltetracosa- ~ ~
.:
2,6,18,22-tetraene-11,13-diin-10,15-diol obtained as in Example 1, 2.6 g oE Raney nickel and 200 ml of n-heptane were placed in a 500 ml autoclave. The mixture was caused to react at a temperature from room temperature to 60C under a hydrogen pressure of S0 ;
to 100 kg/cm for 3 hours. After removal of the catalyst, the n-heptane was distilled off to afford 10.4 g of a crude product having double bonds but no triple bonds.
10.2 g of the crude product, 40 ml of n-heptane, 0.2 g of nickel on diatomaceous earth and 1.0 g of zinc sulfate were placed in a 100 ml autoclave. The mixture was caused to react ~ ~ ~
:
at 200C at a hydrogen pressure of 90 to 100 kg/cm for 16 hours to afford 2.3 g of squalane.
Example 18 This example was carried out in the same manner as Example l7, except that 1.0 g of calcined gypsum was used in place of the zinc sulfate. 7.4 g of squalane was obtained.
~75~;)2 I._ ~le 19 l liLcr oE llqllld ammonia, 17 g o~ lithium and 25 g of diacetylene were placed in a 2 liter autoclave. To this solution 192 g of pseudoionone was added dropwise witll stirring and caused to re~ct at 15C for 5 hours. After completion of the reaction, the mixture was coole~ and neutralized by adding ammonium chloride. After purgin~ the ammonia, the residue was -~
dissolved in 1 1. of n-hexane and 1 1. of water. After decanting the organic layer was washed with water several times and the hexane was distilled off to afford 200 g of crude product.
A lO0 g portion of the crude product, 3.6 ml of Raney nickel (about 2.5 g) and 100 ml of n-heptane were placed in a 300 ml autoclave. The mixture was caused to react at room temperature under a hydrogen pressure of 50 to 100 kg~cm2.
The reaction temperature in the reaction system rose to a maximum temperature of about 58C owing to the heat of the reaction.
After shaking for 16 hours, the Raney nickel was filtered oEf and the heptane was distilled off from the mixture to afford ~ -108 g of crude product free from triple bonds.
10.2 g of the above crude product, 40 ml of n-heptane, 0.2 g of nickel on diatomaceous earth, and 1.0 g of zinc sulfate were placed in a 100 ml autoclave and the mixture was caused to react at 200C at a hydrogen pressure of 80 to 90 kg/cm for 16 hours. 2.5 g of squalane (2,6,10,15,19,23 hexamethyltetracosane) was thus obtained. -~
Example 20 About 2 l. of liquid ammonia was placed in a 3 liter round-bottomed flask, and by passing acetylene therethrough after the addition Or lithium, litl-ium acetylide was prepared. After the addition of 192 g of pseudoionone, the solution was caused ;
to react under reflux of liquid ammonia for 8 hours by passing in a little amount of acetylene. After the reaction, the solution was neutralized by adding ammonium chloride and, after purging ' ' '' , - ~ :
- .~ : ,. .. - .
- 1~375~2 ammonla, tl~e resi(llle was ~issolved in 1 1. Or n-l)exane and 1 1.
of waLer. ~ftcr dec;llltaLLoll, the organic layer was washcd with water several times and 265 g of a crude product was thus obtained.
The crude product was subjected to oxidative-coupling in the same manner as in Example 14 except that it was used in place of the 3,7,11-trimethyldodeca-6,10-dien-1-in-3-ol. 426 g of product was thus obtained. ~ 100 g portion of the product was placed in-i~ 500 ml autoclave and subjected to hydrogenation and hydrogenolysis in the same manner as in Example 14 to give 21 g of squalane.
Example 21 Ethynylation of 194 g of citronellidene acetone with ~ ~ ;
diacetylene was carried out in the same manner as in Example 19, except that citronellidene acetone was used in place of the pseudoionone. 268 g of a crude product was thus obtained.
100 g of the ~rude product, 3.6 ml (about 2.5 g) of Raney nickel and 100 ml of n-heptane were placed in a 300 ml autoclave, and the mixture was caused to react at room temperature under a hydrogen pressure of 50 to 100 kg/cm2. The reaction ~0 temperature rose to a maximum temperature of about 56C. After shaking for 18 hours, the Raney nickel was filtered off and the heptane was distilled off to afford 112 g of a crude product having double bonds but no triple bonds. ;~
10.2 g of the crude product, 40 ml of n-heptane, 0.2 g of nickel on diatomaceous earth and 1.0 g of zinc sulfate were placed in a 100 ml autoclave, and the mixture was caused to react at 200C under a hydrogen pressure of 30 to 90 kg/cm for 10 hours to give 3.2 g of squalane (2,6,10,15,19,23-hexamethyltetracosane).
Example 22 Ethynylation of 194 g of citronellidene acetone was carried out with acetylene in the same manner as in Example 20 except that citronellidene acetone was used in place of the ~ 22 ~
:,,: : : :
, .
- :1133~5~)~
)Sell~lOiOl~OII-'. 27~ E of cru(le product was thus obta~ned. This ~rodllct w;lL; slll)jocLccl to oxid.ltive-coupllllg, hy~lrogcnation and hydrogenolysis in sequcllce in the same manner as in Example 20 and squalalle was thus obtained in a yleld of 36.3 ~ based on the citronellldene acetone.
Example 23 Ethynylatlon of 212 g of 6,10-~imethylundeca-3-en-2-on-10-ol obtained by aldol condensation of hydroxycitronellal and acetone was carried out ln the same manner as in Example 20 except that llydrexycitronellal was used in place of the pseudoionone 269 g of a crude product was thus obtained.
The crude product was subjected to an oxidative-coupling reaction in the same manner as in Example 14 except that it was used in place of the 3,7,11-trimethyldodeca-6,10-dien-1-in-3-ol. 442 g of a crude product was thus obtained. ~ -A 50 g portion of the product, 50 ml of n-heptane and 5 g of 5 % Lindlar catalyst were placed in a 300 ml round-bottomed flask, and the mixture was caused to react at 50C under normal atmospheric pressure for 8 hours. Confirmation that the 2(~ product thus obtained contained almost no triple bond but only double bonds was confirmed by means of its C -NMR spectra.
After filtering off the Lindlar catalyst, the product was placed in a 300 ml autoclave and the hydrogenolysis catalysts used in ;~
Example 16, namely 1.5 g of nickel on diatomaceous earth and 3 g of silica-alumina catalyst, were added thereto. The mixture was `;
caused to react at 230C under a hydrogen pressure of 80 to 100 kg/cm2 for 5 hours. Con~irmation that the product thus obtained ~ `
contained 14.2 g of squalene was achieved by means of gas chromatography.
'' ~
- 23 - ~
Claims (11)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for preparing squalane which comprises (a) submitting a compound of the general formula:
(I) wherein R and R' are the same or different and each represent a saturated or unsaturated hydrocarbon residue having 11 carbon atoms and possessing the following carbon atom skeleton:
each said residue being optionally substituted by a radical capable of being replaced by a hydrogen atom upon hydrogenolysis;
to hydrogenolysis in the presence of an acidic substance;
or (b) submitting a compound of the general formula:
(I) wherein R and R' are as defined above; to partial hydrogenation to obtain a corresponding intermediate compound with triple bonds converted to double bonds, and then subjecting the intermediate compound to hydrogenolysis.
(I) wherein R and R' are the same or different and each represent a saturated or unsaturated hydrocarbon residue having 11 carbon atoms and possessing the following carbon atom skeleton:
each said residue being optionally substituted by a radical capable of being replaced by a hydrogen atom upon hydrogenolysis;
to hydrogenolysis in the presence of an acidic substance;
or (b) submitting a compound of the general formula:
(I) wherein R and R' are as defined above; to partial hydrogenation to obtain a corresponding intermediate compound with triple bonds converted to double bonds, and then subjecting the intermediate compound to hydrogenolysis.
2. A process as claimed in claim 1, in which the hydrogenolysis is carried out at a temperature from 100 to 300°C
under a hydrogen pressure of 10 to 100 kg/cm2.
under a hydrogen pressure of 10 to 100 kg/cm2.
3. A process as claimed in claim 1, in which a metal catalyst is employed selected from nickel, palladium, platinum, rhodium and iridium and compounds thereof optionally supported on a suitable carrier.
4. A process as claimed in claim 1, in which the hydrogenolysis is carried out in an organic acid.
5. A process as claimed in claim 4, in which the organic acid is a carboxylic acid selected from acetic acid, propionic acid, lactic acid and isolactic acid and combinations of one of said acids and a fatty acid having higher acidity.
6. A process as claimed in claim 5, wherein the fatty acid having higher acidity is an .alpha.-halogenofatty acid or .alpha.-hydroxyfatty acid.
7. A process as claimed in claim 1, in which the hydrogenolysis is carried out in an inert organic solvent in the presence of an acidic substance.
8. A process as claimed in claim 7, in which the acidic substance is selected from Bronsted acids, Lewis acids, hydrogen salts of a strong acid and a weak base, strong acids salts of a strong acid and a weak base, and solid acids.
9. A process as claimed in claim 1, in which the partial hydrogenation is carried out at a temperature from room temperature to about 60°C under a hydrogen pressure of 10 to 100 kg/cm2 in the presence of Raney nickel, Raney cobalt or palladium on active carbon, or barium or calcium carbonate.
10. A process as claimed in claim 1, in which the hydrogenolysis of method (b) is carried out using a metal catalyst selected from nickel, palladium, platinum, rhodium or iridium and compounds thereof, optionally supported on a suitable carrier, and in the presence of an acidic substance.
11. A process as claimed in claim 1 or 10, in which the hydrogenolysis of method (b) is carried out in an organic carboxylic acid selected from acetic acid, propionic acid, lactic acid and isolactic acid or in a combination of the said acid and a higher acidic carboxylic acid selected from .alpha.-halogenofatty acid and .alpha.-hydroxyfatty acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA283,747A CA1037502A (en) | 1973-03-19 | 1977-07-29 | Process for preparing squalane |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3227473A JPS547765B2 (en) | 1973-03-19 | 1973-03-19 | |
| JP726974A JPS577132B2 (en) | 1974-01-14 | 1974-01-14 | |
| JP726874A JPS55365B2 (en) | 1974-01-14 | 1974-01-14 | |
| CA283,747A CA1037502A (en) | 1973-03-19 | 1977-07-29 | Process for preparing squalane |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1037502A true CA1037502A (en) | 1978-08-29 |
Family
ID=27426006
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA283,747A Expired CA1037502A (en) | 1973-03-19 | 1977-07-29 | Process for preparing squalane |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1037502A (en) |
-
1977
- 1977-07-29 CA CA283,747A patent/CA1037502A/en not_active Expired
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