Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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
1 3 1 3
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)
011 OH
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:
CH3 1 3
, 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 `
~',
-- 3
.
.. , , : . . .
. . , ~ .
~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;
-- 7 --
~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 ;
- 8 -
'' ~,' :
.. , , :. -, , ~ . . ~ : : . ; .
~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
-- 1 0 --
.: .: : . . . ..
~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. ~
- 12 - -
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
- 14 -
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.
- 15
. ~ .. ..
7SQ2
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 -
. ~
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-
- 19 -
.. . . ........ . . .
,. ~. . . . .. . .. . .
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.
20 -
~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
' ' ''
- 21 -
, - ~ :
- .~ : ,. .. - .
- 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 - ~
