Title of Invention

A NOVEL TRIMETHYLCYCLODODECATRIENE COMPOUND AND A PROCESS FOR PREPARING THE SAME

Abstract The invention relates to a compound of general formula (I) wherein: A) a) R4, R5, and R2 each represent a hydrogen atom and R3, R6 and R8 each represent a methyl radical, or b) R4, R6, and R2 each represent a hydrogen atom and R3, R5, and R8 each represent a methyl radical, or c) R3, R6, and R7 each represent a hydrogen atom and R4, R5, and R8 each represent a methyl radical, and the dotted lines are present and represent cis-double bonds or trans-double bonds, and R1 represents a hydrogen atom and R2 represents on OH, OCH3 or OC2H5 group, or the dotted lines are absent and R1 represents a hydrogen atom and R2 represents an OCH3 group or an OC2H5 group; or B) R1, R4 and R6 each represent a hydrogen atom and R2, R3 and R5 each represent a methyl radical, and the dotted lines are present and represent cis-double bonds or trans- double bonds, and R7 represents a hydrogen atom and R8 represents an OH1 OCH3 or OC2H5 bond, or the dotted lines are absent and R7 represents a hydrogen atom and R8 represents an OCH3 group or an OC2H5 group. The inventive compound is an alcoholic derivative or an other derivative. The inventive also relates to the use of at least one compound of formula (I) as an odorant agent.
Full Text NOVEL TRIMETHYLCYCLODODECATRIENE DERIVATIVES, USE
THEREOF AND PERFUMED PRODUCTS CONTAINING THE SAME
The present invention relates in general to novel
fragrant compounds that may be used in perfumery. The
invention relates especially to novel alcohols and
macrocyclic ethers, to a process for synthesizing them
and to their use in perfumery as a result of their
fragrancing properties.
The term "perfumery" is used herein to denote not only
perfumery in the usual sense of the term, but also
other fields in which the odor of products is
important. They may be perfumery compositions in the
usual sense of the term, such as fragrancing bases and
concentrates, eaux de Cologne, eaux de toilette,
perfumes and similar products; topical compositions -
in particular cosmetic compositions - such as face and
body creams, talcum powders, hair oils, shampoos, hair
lotions, bath salts and oils, shower and bath gels,
toiletry soaps, antiperspirants and body deodorants,
shaving lotions and creams, soaps, creams, toothpastes,
mouthwashes, pomades, and similar products; and
maintenance products, such as laundry softeners,
detergents, laundry washing products, ambient
deodorants, and similar products.
The term "fragrant" is used herein to denote a compound
that gives off an odor.
Macrocycles are already used in perfumery. In
particular, the trimerization of isoprene results in a
mixture of macrocyclic alkenes, which mainly contains
two stereoisomers in varied ratios, especially 1,5,10-
trimethylcyclododeca-1,5,9-triene and 1,5,9-trimethyl-
cyclododeca-1,5,9-triene. This mixture of macrocycles
provides the perfumery industry with a low-cost raw
material. Certain derivatives, such as Cedroxyde™

(trimethyl-13-oxabicyclo[10.1.0]trideca-4,8-diene from
Firmenich), Boisanol from Symrise or Trimofix™ 0
(2,5, 10-trimethyl-2,5,9-cyclododecatrien-l-yl methyl
ketone) from IFF, to name but a few, are commonly used.
Moreover, patent US 3 723 478 from Firmenich describes
the oxidation of certain trimethylcyclododecatrienes to
ketone derivatives. The trimethylcyclododecadienones
are obtained via an epoxidation, followed by opening of
the epoxide and then oxidation. However, the yields for
the steps of this synthetic route are low and the
conversions are not very selective.
Consequently, there is still a need for novel fragrant
macrocycles, and for a synthetic process whose yield
and selectivity are improved.
The inventors have discovered, surprisingly, a novel
process for synthesizing novel macrocycles, which have
fragrant properties and which may thus be used in
perfumery.
One subject of the present invention is thus a novel
family of cyclic macromolecules represented by formula
(I) below:

in which:
A)
a) R4, R5 and R7 each represent a hydrogen atom and
R3, R5 and R8 each represent a methyl radical,
or

b) R4, R6 and R7 each represent a hydrogen atom and
R3, R5 and R8 each represent a methyl radical,
or
c) R3, R6 and R7 each represent a hydrogen atom and
R4, R5 and R8 each represent a methyl radical,
and
the dashed linos are present and represent cis or
trans double bonds and R1 represents a hydrogen
atom and R2 represents an -OH, -OCH3 or -OC2H5
group,
or
the dashed lines are absent and R1 represents a
hydrogen atom and R2 represents an -OCH3 or -OC2H5
group,
or
B)
R1, R4 and R6 each represent a hydrogen atom and
R2, R3 and R5 each represent a methyl radical,
and
the dashed lines are present and represent cis or
trans double bonds and R7 represents a hydrogen
atom and R8 represents an -OH, -OCH3 or -OC2H5
group,
or
the dashed lines are absent and R7 represents a
hydrogen atom and R8 represents an -OCH3 or -OC2H5
group.
In particular, a subject of the invention is the novel
compounds of formulae (5a-d), (6a-d) and (6a'-d')
below,


in which R is hydrogen atom (compounds 5a, 5b, 5c, 5d)
or a methyl group (compounds 6a, 6b, 6c, 6d) or an
ethyl group (compounds 6a', 6b', 6c', 6d').
Compounds 5a, 6a and 6a' are compounds of formula (I)
in which
R1 represents a hydrogen atom,
R2 represents a group -OH (compound 5a), -OCH3 (compound
6a) or -OC2H5 (compound 6a'),
R3 is a methyl group,
R4 is a hydrogen atom,
R5 is a hydrogen atom,
R6 is a methyl group,
R7 is a hydrogen atom,
R8 is a methyl group, and
the double bonds are present.
Compounds 5b, 6b and 6b' are compounds of formula (I)
in which
R1 represents a hydrogen atom,
R2 represents a group -OH (compound 5b), -OCH3 (compound
6b) or -OC2H5 (compound 6b'),
R3 is a methyl group,
R4 is a hydrogen atom,
R5 is a methyl group,
R6 is a hydrogen atom,
R7 is a hydrogen atom,
R8 is a methyl group, and

the double bonds are present.
Compounds 5c, 6c and 6c' are compounds of formula (I)
in which
R1 represents a hydrogen atom,
R2 represents a group -OH (compound 5c), -OCH3 (compound
6c) or -OC2H5 (compound 6c' ) ,
R3 i s a hydrogen atom,
R4 is a methyl group,
R5 is a methyl group,
R6 is a hydrogen atom,
R7 is a hydrogen atom,
R8 is a methyl group, and
the double bonds are present.
Compounds 5d, 6d and 6d' are compounds of formula (I)
in which
R1 represents a hydrogen atom,
R2 is a methyl group,
R3 is a methyl group,
R4 is a hydrogen atom,
R5 is a methyl group,
R6 is a hydrogen atom,
R7 is a hydrogen atom,
R8 represents a group -OH (compound 5d), -OCH3 (compound
6d) or -OC2H5 (compound 6d'), and
the double bonds are present.
In particular, a subject of the invention is also the
novel compounds of formulae (7a-d) and (7a'-d') below:


in which R is a methyl group (compounds 7a, 7b, 7c, 7d)
or an ethyl group (compounds 7a' , 7b' , 7c' , 7d' ) .
Compounds 7a and '7a' are compounds of formula (I) in
which
R1 represents a hydrogen atom,
R2 represents a group -OCH3 (compound 7a) or -OC2H5
(compound 7a'),
R3 is a methyl group,
R4 is a hydrogen atom,
R5 is a hydrogen atom,
R6 is a methyl group,
R7 is a hydrogen atom,
R8 is a methyl group, and
the double bonds are absent.
Compounds 7b and 7b' are compounds of formula (I) in
which
R1 represents a hydrogen atom,
R2 represents a group -OCH3 (compound 7b) or -OC2H5
(compound 7b'),
R3 is a methyl group,
R4 is a hydrogen atom,
R5 is a methyl group,
R6 is a hydrogen atom,
R7 is a hydrogen atom,
R8 is a methyl group, and
the double bonds are absent.

Compounds 7c and 7c' are compounds of formula (T) in
which
R1 represents a hydrogen atom,
R2 represents a group -OCH3 (compound 7c) or -OC2H5
(compound 7c' ) ,
R3 is a hydrogen atom,
R4 is a methyl group,
R5 is a methyl group,
R6 is a hydrogen atom,
R7 is a hydrogen atom,
R8 is a methyl group, and
the double bonds are absent.
Compounds 7d and 7d' are compounds of formula (I) in
wh Ich
R1 represents a hydrogen atom,
R2 is a methyl group,
R3 is a methyl group,
R4 is a hydrogen atom,
R5 is a methyl group,
R6, is a hydrogen atom,
R7 is a hydrogen atom,
R8 represents a group -OCH3 (compound 7d) or -OC2H5
(compound 7d') and
the double bonds are absent.
The compounds of formula (I) may be present in the form
of an isomer or a mixture of isomers, in particular of
an enantiomer and a mixtures of enantiomers, or of a
racemic mixture, or of a diastereoisomer or mixture of
diastereoisomers .
The compounds of formula (I) all have fragrant
properties. Compounds (5a-d) have an amber, musk odor.
Compounds (6a-d) and (6a'-d') have woody, camphor notes
with a vetiver register. Compounds (7a-d) have fruity,
green notes. As a result of these fragrant properties,
these various products, most particularly the methyl

ethers (6a-d), find very varied use, especially in
perfumery.
A subject of the invention is thus also the use of
these compounds as fragrant agents.
A subject of the present invention is also the process
for synthesizing the compounds of formula (I).
Each of the compounds (5a-d), (6a-d), (6a'-d'), (7a-d)
and (7a'-d') may be synthesized directly or indirectly
from compounds (4a-d) below:

which themselves may be synthesized starting with
trimethylcyclododecatrienes. The present invention also
provides a novel process for preparing the macrocyclic
ketones 4a-d, described below.
The scheme that follows shows a process for
synthesizing the compounds according to the invention.


In general, the process according to the invention
comprises the following steps:
- formation of chloro-nitroso derivatives from
1,5, 10-trimethylcyclododeca-1 ,5,9-triene (la)
and from 1,5,9-trimethylcyclododeca-1,5,9-
triene (1b),
conversion of these derivatives into oximes,
reductive conversion of the oximes into ketones
in the presence of Raney nickel, acetone and
boric acid,
reduction of the ketones to alcohols,
etherification to ethers,
optionally, hydrogenation to saturated ethers.

In a first stage, the chloro-nitroso derivatives (2a-d)
of 1,5,10-trimethylcyclododecatriene (la) and 1,5,9-
trimethylcyclododecatriene (lb) are formed. A large
number of reagents, known to those skilled in the art,
are available for this reaction and allow the expected
result to be achieved. Among these reagents, sodium
nitrite is advantageous for economic reasons. The
trimethylcyciododecatrienes (1a-b) are cooled, in a
solvent such as sec-butanol, to a temperature of about
-10°C to -20°C, since the reaction is highly
exothermic. Sodium nitrite (the reagent used in this
embodiment) is then added portionwise, while
hydrochloric acid is added dropwise in parallel. White
crystals form. After the end of addition of the
reagents, the reaction medium is stirred for a further
16 hours while allowing the bulk temperature to return
to room temperature. Next, the solution is neutralized
with cooling, such that the bulk temperature does not
exceed 25°C, with sodium hydroxide or another suitable
base. The chloro-nitroso derivatives (2a-d) are
obtained in the form of crystals, which are washed,
filtered and dried, and may be used directly in the
following step.
Next, the chloro-nitroso derivatives (2a-d) are
converted into oximes (3a-d), under suitable conditions
that a person skilled in the art can determine given
his general knowledge. The conversion into oximes is
preferably performed in an aqueous medium in the
presence of a base. The use of several bases may be
envisaged, but. a good yield is obtained in the presence
of triethyl amine. The crystals (2a-d) are suspended in
a mixture of water, toluene and triethylamine. The
suspension is refluxed for about four to six hours.
Total disappearance of the crystals indicates total
conversion. After cooling, the phases are separated and
the organic phase is washed until neutral with brine,
then with sulfuric acid and again with brine. After
concentrating the solvent, the oximes (3a-d) are

obtained in the form of a brown mass, which may be used
directly in the following reaction, since purification
is possible but difficult given the molecular mass and
the complexity of the crude product.
There is a wide variety of oxidizing and reducing
methods for converting an oxime into a ketone, which
are known to those skilled in the art, and several
reagents may be used to obtain ketones, for instance
sodium bisulfite, copper sulfate, sodium nitrite,
levulinic acid and cxcne, to name but a few. In the
present case, all these attempts failed. Only the
reductive conversion in the presence of Raney nickel,
acetone/ethanol and boric acid made it possible to
obtain ketones (4a-d). To do this, the oximes (3a-d)
were partially dissolved in a mixture of ethanol and
acetone and were placed in an autoclave in the presence
of Raney nickel and boric acid. The reaction medium is
then stirred for about 14 hours at a temperature of
about 25°C to 60°C and a hydrogen pressure of about
1 x 104 HPa to b x 104 HPa, which makes it possible to
obtain the ketones (4a-d); i.e. 4,9,12-trimethylcyclo-
dodeca-4,8-dienone (4a); 4,8,12-trimethylcyclo-
dodeca-4,8-dienone (4b), 5,8,12-trimethylcyclo-
dodeca-4,8-dienone (4c); 5,9,12-trimethylcyclo-
dodeca-4,8-dienone (4d).
The solution is then cooled to room temperature,
quenched in water and extracted with a solvent, for
instance toluene. The combined organic phases are
washed until neutral, dried, concentrated and then
distilled. The mixture of ketones (4a-d) has a musk,
flowery and slightly woody odor.
Reduction of the ketones (4a-d) to alcohols (ba-d) may
be performed under suitable conditions that a person
skilled in the art can determine. In particular, the
reduction in ethanol may be performed using sodium
borohydride, which is preferred to other suitable

reagents for its ease of use and its reasonable price.
The sodium borohydride is added to the alcoholic
solution over a period of about 36 hours at a
temperature of about 5°C to 15°C. The excess hydride is
destroyed with acetone. After acidification with
hydrochloric acid, the solution is quenched with water
and then extracted. The combined organic phases are
washed until neutral, dried, filtered and concentrated.
After distillation, alcohols (5a-d) are obtained.
These alcohols have an amber, musk odor, which is
relatively faint but definite.
The alcohols may then be etherified under suitable
conditions known to those skilled in the art. Two
classes of reagents are generally used for the
etherification of alcohols: alkyl halides and alkyl
sulfates. The two classes of reagents may be used to
obtain the ethers (6a-d and 6a'-d'). For economic
reasons, dimethyl sulfate and diethyl sulfate are
preferred. In order to facilitate the formation of the
alkoxides, isoprene is added dropwise to the solution
of the trimethylcyclododecadienols (5a-d) in
tetranydrofuran, in which pieces of sodium are
suspended. The sodium reacts first with the isoprene,
forming a cation that then reacts rapidly with the
alcohols present. This reaction is performed at a
temperature of about 10°C to 20°C. Once all the sodium
has reacted, the etherification reagent (for example
dimethyl or diethyl suLfate) is added. The reaction
medium is refluxed for about six hours. The reaction is
complete once the solution has become colorless.
Aqueous ammonia solution is added with cooling (10°C to
20°C) to destroy the excess sulfate. The aqueous phase
is extracted with a solvent such as t-butyl methyl
ether. The combined organic phases are washed until
neulral, dried, filtered and concentrated. Distillation
gives the methyl ethers (6a-d) or the ethyl ethers
(6a'-d'), which are novel compounds. The methyl ethers

(6a-d) have woody, camphor notes with a vetiver
register, which are highly appreciated by perfumers.
The ethyl ethers (6a'-d') have more or less the same
notes as the methyl ethers (6a-d), while at the same
time being much less volatile.
The ethers (6a-d) may then be hydrogenated to obtain
the corresponding saturated ethers (7a-d), under
conditions that may be determined by a person skilled
in the art. In particular, the hydrogenation may be
performed in the presence of palladium-on-charcoal, for
example, at a temperature of about 20°C to 80°C, under
a pressure of about 2 × 104 HPa to 8 × 104 HPa of
hydrogen. The ethers obtained are novel compounds. They
have fleeting fruity, green notes.
The process described above makes it possible to obtain
each group of compounds 4,5, 6 and 7 in the form of a
mixture a-d or a' -d' . It is difficult but possible to
separate the compounds of a mixture, via suitable
techniques known to those skilled in the art, in
particular via separation on a chiral column or
preparative chromatography. Given these difficulties,
it is not absolutely necessary to separate Lhem, and
the compounds may also be used as a mixture, since each
mixture itself has fragrant properties.
A subject of the invention is also the use of at least
one compound of formula (I) according to the invention
as a fragrant agent, as an odor-masking agent or as an
odor-neutralizing agent, alone or as a mixture with one
or more other fragrant compounds known to those skilled
in the art, which a person skilled in the art is
capable of selecting as a function of the desired
effect. The additional fragrant agent (s) may be
compounds of formula (I) or other fragrant agents known
to those skilled in the art.

A subject of the invention is also compositions
comprising a base product and an effective amount of
one or more compounds of formula (I) according to the
invention.
It may be a composition that is itself fragrant, or a
composition in which the fragrant agent is used to mask
or neutralize certain odors.
The base product will readily be determined by a person
skilled in the art as a function of the intended
composition and thus of the intended use, for which the
usual components, such as solvent(s) and/or
adjuvant(s), are well known.
The effective amount of the compounds of formula (I)
according to the invention incorporated into the
composition will vary according to the nature of the
composition, the desired fragrancing effect, and the
nature of the other fragrant or non-fragrant compounds
that may be present, and may be readily determined by a
person skilled in the art, given that it may vary
within a very wide range, from 0.1% to 99% by weight,
in particular 0.1% to 50% by weight and especially 0.1%
to 30% by weight.
The compounds of formuia (I) according to the invention
may be used in unmodified form or may be incorporated
into or onto a support material that is inert or that
may contain other active ingredients of the finished
composition. A wide variety of support materials may be
used, including, for example, polar solvents, oils,
greases, finely divided solids, cyclodextrins,
maltodextrins, gums, resins and any other support
material known for such compositions.
A subject of the invention is thus also the use of the
compounds of formula (I) for the preparation of a
fragrant composition or of a fragrant article in the

applications described above, in particular in
perfumery, in cosmetics, for example for shampoos or
soaps, or for maintenance products, such as laundry
softeners or laundry washing products.
The invention relates in particular to a perfumery
composition, especially a fragrant base or concentrate,
an eau de Cologne, an eau de toilette or a fragrance,
comprising at least one compound of formula (I) or a
compound comprising at least one compound of formula
(T) .
The invention also relates in particular to a cosmetic
composition, especially face or body cream, talcum
powder, hair or body oil, shampoo, hair lotion, bath
salt, bath oil, shower gel, bath gel, toiletry soap,
body antiperspirant, body deodorant, lotions, shaving
cream, shaving soap, cream, toothpaste, mouthwash or
pomade comprising at least one compound of formula (I)
or at least one composition comprising at least one
compound of formula (I) . Another subject of the
invention is a preventive or non-preventive cosmetic
treatment or care method, using at least one compound
of formula (I) or at least one composition comprising
at least one compound of formula (I).
The invention also relates to a maintenance product,
especially laundry softener, detergent, laundry washing
product or ambiance deodorizer, comprising at least one
compound of formula (I) or at least one composition
comprising at least one compound of formula (I).
The compounds according to the invention may be used,
alone or in combination, in unmodified form or may be
incorporated into or onto a support material that is
inert or that may contain other active ingredients of
the finished composition. A wide variety of support
materials may be used, including, for example, polar
solvents, oils, greases, finely divided solids,

cyclodextrins, maltodextrins, gums, resins and any
other support material known for such compositions.
A subject of the invention is thus also the use of the
novel compounds for the preparation of a fragrant
composition or of a fragrant article in the
applications described above, in particular in
perfumery, in cosmetics, for example for shampoos or
soaps, and for maintenance products, such as softeners
or laundry washing products.
The invention relates in particular to a perfumery
composition, especially a fragrant base or concentrate,
an eau de Cologne, an eau de toilette or a fragrance,
comprising at least one compound of formula (I) or a
composition comprising at least one compound of formula
(I) .
The invention also relates in particular to a cosmetic
composition, especially face or body cream, talcum
powder, hair or body oil, shampoo, hair lotion, bath
salt, bath oil, shower gel, bath gel, toiletry soap,
body antiperspirant, body deodorant, lotions, shaving
cream, shaving soap, cream, toothpaste, mouthwash or
pomade, comprising at least one compound of formula (I)
or a composition comprising at least one compound of
formula (I) . Another subject of the invention is a
preventive or non-preventive cosmetic treatment or care
method, using at least one compound of formula (I) or
at least one composition comprising at least one
compound of formula (I).
The examples that follow further illustrate the various
processes for manufacturing the already-known or novel
molecules according to the invention, and also the use
and value thereof. These examples are given for purely
illustrative purposes and should not be considered as
limiting the invention.

Example 1: Synthesis of the chlorotrimethylnitroso-
cyclododecadienes (2a-d)
408.0 g (2.00 mol) of trimethylcyclododecatrienes (la
and b) and 700.0 g of sec-butanol are placed in a four-
liter round-bottomed flask equipped with a side tube
with a powder funnel, a dropping funnel and a
thermometer. The solution is cooled to between -10 °C
and -15°C. 640.0 g (6.00 mol) of 34% hydrochloric acid
are added dropwise over a period of about six hours,
with simultaneous portionwise addition of 160.0 g
(2.32 mol) of sodium nitrite. The reaction is highly
exothermic. Efficient cooling is recommended so as not
to exceed 0oC in the bulk. The reaction medium is
stirred for a further sixteen hours while allowing the
bulk temperature to return to room temperature. Gray-
white crystals form and the reaction medium becomes
pasty. Next, 1000.0 g of water are added to facilitate
the stirring. The mixture is cooled again and 300.0 g
(3.53 mol) of 47% sodium hydroxide are added dropwise
without exceeding 25°C in the bulk. The crystals are
filtered off, rinsed with 325.0 g of hexane and
screened (1.25 screen). The crystals are dried under
vacuum (first at 40 HPa and then at 0.7 HPa). 419.7 g
(max. 1.56 mol) of chlorotrimethylnitrosocyclodo-
decadienes (2a-d) are obtained, which contain traces of
starting material and which are virtually insoluble in
all the solvents tried. The yield is maximal at 78.0%.
The crystals are used directly in the following step.
Example 2 : Synthesis of the trimethylcyclododeca-
trienone oximes (3a-d)
270.0 g (1.00 mol) of chlorotrimethylnitrosocyclo-
dodccadienes (2a-d), 301.0 g of toluene and 121.5 g
(1.20 mol) of trimethylanine are placed in a two-liter
round-bottomed flask equipped with a condenser, a
dropping funnel and a thermometer, and the mixture is
brought to 60°C. 350.0 ml of water are added dropwise

at this temperature and the reaction medium is then
refluxed (at about 80°C) with vigorous stirring for
four hours. The reaction medium is cooled to 60°C and
the aqueous phase is separated out. The organic phase
is then washed twice with 2 00 mi of brine, once with
250 ml of 10% sulfuric acid and then once again with
200 ml of brine. The solvent is concentrated under
reduced pressure (about 40 HPa), without exceeding 50°C
in the bulk. 228.00 g of a pasty brown mass are
obtained, and are used directly in the following step.
Example 3: Synthesis of the
trimethylcyclododecadienones (4a-d)
78.0 g of ethanol, 158.0 g (2.72 mol) of acetone, 2.3 g
(0.04 mol) of boric acid, 30.0 g (1.67 mol) of water,
4.0 g of Raney nickel and 228.0 g of crude
trimethylcyclododecatrienone oximes (3a-d) are placed
in an 800 ml autoclave. The apparatus is flushed three
times with hydrogen. The mixture is stirred for 24
hours at 50oC and a hydrogen pressure of 3 × 104 HPa.
The apparatus is cooled to room temperature and the
reaction medium is recovered. 500 ml of toluene and
then 300 ml of brine are added. The phases are
separated and the aqueous phase is extracted once with
100 ml of toluene. The combined organic phases are
washed six times with 100 ml of 10% hydrochloric acid
to neutral pH. The resulting organic phase is washed
once more with 100 ml of brine and then dried, filtered
and concentrated under vacuum (40 HPa) without
exceeding 50°C in the bulk. After distillation, 124.8 g
(0.57 mol) of trimethylcyclododecadienones (4a-d) are
obtained (b.p.: 94-97°C/0.3 HPa). The yield for the two
steps is 57%. The infrared, NMR and mass spectrum
analyses correspond to the structures of the expected
compounds.

Example _4: Synthesis of _ trimethylcyclododecadienols
(ba-d)
124.8 g (0.57 mol) of trimethylcyclododecadienones (4a-
d) and 390.0 g of ethanol are placed in a two-liter
round-bottomed flask equipped with a thermometer. The
mixture is cooled to 5°C and 10.7 g of sodium
borohydride are added portionwise without exceeding
10°C in the bulk. The mixture is stirred at this
temperature for 42 hours. Additional amounts of sodium
borohydride are added during this period (5.3 g after
six hours, 10.1 g after 24 hours and 5.3 g after 36
hours; total amount of sodium borohydride used: 31.4 g
(0.863 mol)). 79.0 g (1.36 mol) of acetone are added
dropwise to destroy the excess reducing agent, without
exceeding 10°C in the bulk. The reaction mixture is
acidified with 500.0 g of 10% hydrochloric acid,
without exceeding 10°C in the bulk. A further 800 g of
water and then 344 g of toluene are added with vigorous
stirring. The phases are separated and the organic
phase is washed three times with 200 g of water and
once with 200 g of brine. The resulting organic phase
is dried and filtered, and the toluene is evaporated
off under reduced pressure (40 HPa) without exceeding
50°C in the bulk. After distillation, 69.6 g (0.31 mol)
of trimethylcyclodoaecadienes (5a-d) are obtained
(b.p.: 98-100°C/0.2 HPa). The yield is 55.3%. The
infrared, NMR and mass spectrum analyses correspond to
the structures of the expected compounds.
Example 5: Synthesis of the methoxytrimethylcyclo-
dodecadienes (6a-d)
360.0 g of tetrahydrofuran, 69.6 g (0.31 mol) of
trimethylcyclododecadienols (5a-d) and 8.2 g (0.36 mol)
of sodium, chopped into small pieces, are placed in a
two-liter round-bottomed flask equipped with a
condenser, a thermometer and a dropping funnel. The
reaction medium is cooled to 15°C and 41.6 ml (28.3 g,

0.42 mol) of isoprene are added dropwise, without
exceeding 15°C in the bulk. Stirring is continued until
the sodium has completely dissolved. The mixture is
cooled to 10°C and 33.8 ml (45.0 g, 0.357 mol) of
dimethyl sulfate are added dropwise at this
temperature. The reaction medium is refluxed for 6
hours until the solution has totally decolorized. The
resulting solution is cooled to 10°C and 300 ml of
aqueous 10% ammonia solution are added dropwise,
without exceeding 15°C in the bulk. The phases are
separated and the aqueous phase is extracted twice with
150 ml of t-butyl methyl ether. The combined organic
phases are washed once with 150 g of 10% hydrochloric
acid, twice with 150 g of water and then once with
150 g of brine. The resulting organic phase is dried
and filtered, and the solvents are evaporated off under
vacuum (40 HPa), without exceeding 50°C in the bulk.
After distillation, 33.5 g (0.14 mol) of methoxy-
trimethylcyclododecadienes (6a-c) are obtained
(b.p.: 68-72°C/0.2 HPa). The yield is 45.7%. The
infrared, NMR and mass spectrum analyses correspond to
the structures of the expected compounds.
Example 6:_ Synthesis of the ethoxytrimethyl-
cyclododecadienes (6a'-d')
The ethoxytrimethylcyclododecadienes (6a'-d') are
synthesized as described in Example 4, using 28.9 g
(0.12 mol) of trimethylcyclododecadienes (5a-d) and
20.4 g (0.36 mol) of diethyl sulfate. 18.2 g (0.07 mol)
of ethoxytrimethylcyclododecadienes (6a'-d') are
obtained (b.p.: 105/108°C/0.2 HPa). The yield is 62.7%.
The infrared, NMR and mass spectrum analyses correspond
to the structures of the expected compounds.
Example 7: Synthesis of the methoxytrimethyl-
cyclododecanas (7a-d)
7.6 g (32 mmol) of methoxytrimethylcyclododecadienes

(6a-d), 100 ml of ethanol and 0.5 g of palladium-on-
charcoal are placed in an autoclave. The apparatus is
closed and flushed three times with hydrogen. The
mixture is stirred for six hours at 40°C and 4 x 104
UPa of hydrogen, and then cooled to room temperature
and the reaction medium is recovered. The catalyst is
filtered off and the solvent is evaporated off under
reduced pressure (40 HPa), without exceeding 50°C in
the bulk. After micro-distillation, 5.0 g (20.8 mmol)
of methoxytrimethylcyclododecanes (7a-d) are obtained
(71-78°C/0.3 HPa). The yield is 65.0%. The infrared,
NMR and mass spectrum analyses correspond to the
structures of the expected compounds.
Example 8: Olfactory evaluation
In a first stage, the fragrance characteristics of the
pure methoxytrimethylcyclododecadienes (6a-d) were
evaluated by a panel at the same time as the fragrance
characteristics of known, commercially available
compounds. The evaluation panel is composed of several
professionals, who evaluate each compound qualitatively
and quantitatively. The mixture of compounds was
described as woody, camphoric, in the vetiver register
and very strong. Analogies were found with certain
commercially available products, for instance
Spirambrene™ (2,2,3',7',7-pentamethylspiro-1,3-dioxane-
5,2'-norcarane) from Givaudan, Karanal™ (5-sec-butyl-2-
(2,4-dimethylcyclohex-3-enyl)-5-methyl[1,3]dioxane)
from Quest international, Cedramber™ (6-methoxy-
3,6,8,8-tetramethyloctahydro-3a,7-methanoazuiene) from
International Flavours and Fragrances, or Boisambrene™
(ethoxymethoxycyclododecane) from Henkel.
Next, two alcoholic compositions were produced, in
which the mixture of methoxytrimethyicyclododecadienes
(6a-d) was compared with commercial products. In each
case, the evaluations of the olfactory impact were made
at t0, t+48h and t+168h to evaluate the head, core and

base notes, in comparison with known compounds.


2.. 3a, 6, 6, 9a-Tetramethyldodecahydronaphtho [2,1-b]-
furan; origin: V. Mane Fils, France.
3. 1,1,2,3,3-Pentamethyl-1,2,3,5,6,7-hexahydroinden-
4-one; origin: International Flavours and
Fragrances, USA.
4. 1,1,2,3,3,8-Hexamethyl-1,2,3,5,7,8-hexahydro-6-
oxacyclopenta[b]naphthalene; origin: International
Flavours and Fragrances, USA.
5. [3-Oxo-2-((E)-pentyl)cyclopentyl]acetic acid
methyl ester; origin: Firmenich, Switzerland.
6. 1-(2,3,8,8-Tetramethyl-l,2,3,4,5,6,7,8-octahydro-
naphthaien-2-yl)ethanone; origin: International
Flavours and Fragrances, USA.
7. Dipropylene glycol.
8. 6-Methoxy-3,6,8,8-tetramethyloctahydro-3a,7-
methanoazulene; origin: International Flavours and
Fragrances, USA.
9. Ethoxymethoxycyclododecane; origin: Henkel,
Germany



1. (E)-Undeca-1,3-dien-5-yne; origin: Firmenich,
Switzerland
2. 3a, 6, 6,9a-Tetramethyldodecahydronaphtho[2,1-b]-
furan; origin: V. Mane Fils, France.
3. 7-Methylbenzo[b][1,4]dioxepin-3-one; origin;
Symrise, Germany
4. 2,4-Dihydroxy-3,6-dimethylbenzoic acid methyl
ester; origin: International Flavours and
Fragrances, USA.
5. Origin: Givaudan, Switzerland.
6. 2-l3obutyl-4-methyltetrahydropyran-4-ol; origin:
Firmenich, Switzerland.
7. [3-Oxo-2-{(E)-pentyl)cyclopentyl]acetic acid
methyl ester; origin: Firmenich, Switzerland.
8. 3-Benzo[1,3]dioxol-5-yl-2-methylpropionaldehyde;
origin: International Flavours and Fragrances,
USA.
9. 1-(2,3,8,8-Tetramethyl-l,2,3,4, 5,6,7,8-octahydro-
naphtha.i en-2-yl) ethanone; origin: International
Flavours and Fragrances, USA.
10. 3-(4-tert-Butylphenyl)-2-methylpropionaldehyde:
origin: Givaudan, Switzerland.
11. 2,6-Dimethylhept-5-enal; origin: Guivaudan
Switzerland.

12. (E)-3-Methyl-4-(2,6,6-trimethylcyclohex-2-enyl)-
but-3-en-2-one; origin; Firmenich, Switzerland.
13. Origin: V. Mane Fils, France.
14. 10% in dipropylene glycol.
15. Origin: Firmenich, Switzerland.
16. Carbonic acid (E)-hex-3-enyl ester methyl ester;
origin: International Flavours and Fragrances,
USA.
17. 2-4-Dimethylcyclohex-3-enecarbaldehyde; origin:
International Flavours and Fragrances, USA.
18. Ethoxymethoxycyclododecane; origin: Henkel,
Germany.
The tests of composition 1 showed that the methoxy-
trimethylcyclododecadienes (6a-d) are free of the amber
note of Boisambrene™ but are, on the other hand, more
powerful than Boisambrene™ in their woody notes and as
a result have a similar impact to that of Cedramber™.
The tests of composition 2 confirmed that the methoxy-
trimcthyicyclododecadienes (6a-d) are less ambery and
less rising than Boisambrene™, but, on the other hand,
are deeper in the base notes and give cedar wood, honey
and waxy hints.
Furthermore, the loss of intensity over time appears
relatively linear in all cases, without revealing a
substantial change in fragrance characteristic.
The results of these evaluations show without the
slightest doubt that the mixture of compounds described
above has advantageous fragrance characteristics, which
will find an application in particular in perfumery.

WE CLAIM:
1. A compound of general formula (I) below:

in which:
A)
a) R4, R5 and R7 each represent a hydrogen atom and R3, R6 and R8
each represent a methyl radical,
or
b) R4, R6, and R7 each represent a hydrogen atom and R3, R5 and R8
each represent a methyl radical,
or
c) R3, R6 and R7 each represent a hydrogen atom and R4, R5 and R8
each represent a methyl radical,
and
the dashed lines are present and represent cis or trans double
bonds and R1 represents a hydrogen atom and R2 represents an -
OH, -OCH3 or OC2H5 group,
or
the dashed lines are absent and R1 represents a hydrogen atom
and R2 represents an -OCH3 or -OC2H5 group,
or
B) R1, R4 and R6 each represent a hydrogen atom and R2, R3 and R5
each represent a methyl radical,
and

the dashed lines are present and represent cis or trans double bonds and
R7 represents a hydrogen atom and R8 represents an -OH, -OCH3 or -
OC2H5 group,
or
the dashed lines are absent and R7 represents a hydrogen atom and R8
represents an -OCH3 or -OC2H5 group,
said compound being an alcohol or ether derivative.
2. The compound as claimed in claim 1, corresponding to one of the
following formulae:

in which R is a hydrogen atom, a methyl group or an ethyl group.
3. The compound as claimed in claim 1, corresponding to one of the
following formulae:


in which R is a methyl group or an ethyl group.
4. A process for preparing the ketones 4a-d below

and/ or a compound of formulae (I) as defined in claims 1 to 3,
comprising the steps of:
formation of chloro-nitroso, derivatives from 1, 5, 10-
trimethylcyclododeca-1, 5,9-triene (1a) and from 1,5,9-
trimethycyclododeca-1,5,9-triene (1b) as defined in the description.
conversion of these derivaties into oximes as defined in the
description.
reductive conversion of the oximes into ketones in the presence of
Raney nickel, acetone and boric acid, as defined in the description.

5. The preparation process as claimed in claim 4, characterized in
that it also comprises an additional steps of reducing the ketones to
alcohols, as defined in the description.
6. The preparation process as claimed in either or claims 4 and 5,
characterized in that it also comprises an additional step of etherification,
in order to obtain ethers, as defined in the description.
7. The preparation process as claimed in any one of claims 4 to 6,
characterized in that it also comprises an additional hydrogenation step,
in order to obtain saturated ethers, as defined in the description.
8. A process for preparing compounds (5a-d), (6a-d), (6a'-d') and/or
(7a-d) (7a'-d') from compounds (4a-d) below:

by reducing the ketones (4a-d) to alcohols (5a-d) as defined in the
description.


and then, if desired, etherification of said alcohols to ethers (6a-d) or
(6a'-d') as defined in the description.

and, if desired, hydrogenation of said ethers to the corresponding
saturated ethers (7a-d) or (7a'-d') as defined in the description.

9. A composition, characterized in that it contains at least one
compound of formula (I), as define in any one of claims 1 to 3, in the form
of an isomer or a mixture of isomers, in particular or an enantiomer or a
mixture of enantiomers, or of a racemic mixture, or of a diastereoisomer or
mixture of diastereoisomers.
10. The composition as claimed in claim 9, characterized in that it
contains a mixture of at least two compounds chosen from compounds 5a,
5b, 5c and/or 5d, preferentially a mixture of the four compounds 5a, 5b,
5c and 5d below:


11. The composition as claimed in claim 9, characterized in that it
contains a mixture of at least two compounds chosen from compounds
6a, 6b, 6c and/or 6d, and preferentially a mixture of the four compounds
6a, 6b, 6c and 6d:

in which R is a methyl group.
12. The composition as claimed in claim 9, characterized in that it
contains a mixture of at least two compounds chosen from compounds
6a', 6b', 6c' and/or 6a', and preferentially a mixture of the four
compounds 6a', 6b', 6c' and 6d':


in which R is an ethyl group.
13. The composition as claimed in claim 9, characterized in that it
contains a mixture of at least two compounds chosen from compounds
7a, 7b, 7c and/or 7d, and preferentially a mixture of the four compounds
7a, 7b, 7c and 7d:

in which R is a methyl group.
14. The composition as claimed in claim 9, characterized in that it
contains a mixture of at least two compounds chosen from compounds
7a', 7b', 7c' and/or 7d', and preferentially a mixture of the four
compounds 7a', 7b', 7c' and 7d':

in which R is an ethyl group.
15. The composition as claimed in any one of claims 9 , 5 to 14,
characterized in that said compound(s) of formula (I) is (are) incorporated
into or onto a support material that is inert or that may contain other
active ingredients, said support especially being chosen from polar
solvents, oils, greases, finely divided solids, cyclodextrins, maltodextrins,
gums and resins.
16. A perfumery composition, especially a fragrant base or
concentrate, eau de Cologne, eau de toilette or fragrance, characterized
in that it comprises at least one compound as defined in any one of
claims 1 to 3 or a composition as claimed in any one of claims 9 to 14.
17. The perfumery composition as claimed in claim 16, characterized
in that it comprises at least one composition as defined in claim 11.
18. A cosmetic composition, especially a face or body cream, talcum
powder, hair or body oil, shampoo, hair lotion, bath salt, bath oil, shower
gel, bath gel, toiletry soap, body antiperspirant, body deodorant, lotions,
shaving cream, shaving soap, cream, toothpaste, mouthwash or pomade,
characterized in that it comprises at least one compound as defined in
any

one of claims 1 to 3 or a composition as claimed in any one of claims 9 to
14.
19. A household cleaning product, especially laundry softener,
detergent, laundry washing product or ambiance deodorant,
characterized in that it comprises at least one compound as defined in
any one of claims 1 to 3 or a composition as claimed in any one of claims
9 to 18.
20. A composition comprising a compound of formula (I) as defined in
any one of claims 1 to 3, or a composition as claimed in any one of
claims 9 to 18, for use as a fragrant agent or as an odor-masking agent
or as an odor-neutralizing agent.
21. The composition as claimed in claim 20, in which said composition
further comprises other fragrant agents.


The invention relates to a compound of general formula (I) wherein: A) a) R4, R5,
and R2 each represent a hydrogen atom and R3, R6 and R8 each represent a
methyl radical, or b) R4, R6, and R2 each represent a hydrogen atom and R3, R5,
and R8 each represent a methyl radical, or c) R3, R6, and R7 each represent a
hydrogen atom and R4, R5, and R8 each represent a methyl radical, and the
dotted lines are present and represent cis-double bonds or trans-double bonds,
and R1 represents a hydrogen atom and R2 represents on OH, OCH3 or OC2H5
group, or the dotted lines are absent and R1 represents a hydrogen atom and
R2 represents an OCH3 group or an OC2H5 group; or B) R1, R4 and R6 each
represent a hydrogen atom and R2, R3 and R5 each represent a methyl radical,
and the dotted lines are present and represent cis-double bonds or trans-
double bonds, and R7 represents a hydrogen atom and R8 represents an OH1
OCH3 or OC2H5 bond, or the dotted lines are absent and R7 represents a
hydrogen atom and R8 represents an OCH3 group or an OC2H5 group. The
inventive compound is an alcoholic derivative or an other derivative. The
inventive also relates to the use of at least one compound of formula (I) as an
odorant agent.

Documents:

02679-kolnp-2007-abstract.pdf

02679-kolnp-2007-claims.pdf

02679-kolnp-2007-correspondence others 1.1.pdf

02679-kolnp-2007-correspondence others 1.2.pdf

02679-kolnp-2007-correspondence others.pdf

02679-kolnp-2007-description complete.pdf

02679-kolnp-2007-form 1.pdf

02679-kolnp-2007-form 2.pdf

02679-kolnp-2007-form 3.pdf

02679-kolnp-2007-form 5.pdf

02679-kolnp-2007-gpa.pdf

02679-kolnp-2007-international exm report.pdf

02679-kolnp-2007-international publication.pdf

02679-kolnp-2007-international search report.pdf

02679-kolnp-2007-pct request form.pdf

2679-KOLNP-2007-ABSTRACT 1.1.pdf

2679-KOLNP-2007-AMANDED CLAIMS.pdf

2679-KOLNP-2007-CORRESPONDENCE-1.3.pdf

2679-kolnp-2007-correspondence.pdf

2679-KOLNP-2007-DESCRIPTION (COMPLETE) 1.1.pdf

2679-KOLNP-2007-ENGLISH TRANSLATION.pdf

2679-kolnp-2007-examination report.pdf

2679-KOLNP-2007-FORM 1 1.1.pdf

2679-kolnp-2007-form 18.1.pdf

2679-kolnp-2007-form 18.pdf

2679-KOLNP-2007-FORM 2 1.1.pdf

2679-kolnp-2007-form 26.pdf

2679-KOLNP-2007-FORM 3 1.1.pdf

2679-kolnp-2007-form 3.pdf

2679-kolnp-2007-form 5.pdf

2679-KOLNP-2007-FORM-27.pdf

2679-kolnp-2007-granted-abstract.pdf

2679-kolnp-2007-granted-claims.pdf

2679-kolnp-2007-granted-description (complete).pdf

2679-kolnp-2007-granted-form 1.pdf

2679-kolnp-2007-granted-form 2.pdf

2679-kolnp-2007-granted-specification.pdf

2679-KOLNP-2007-IPRB.pdf

2679-KOLNP-2007-OTHERS 1.1.pdf

2679-kolnp-2007-others.pdf

2679-KOLNP-2007-PETITION UNDER RULR 137.pdf

2679-KOLNP-2007-REPLY TO EXAMINATION REPORT.pdf

2679-kolnp-2007-reply to examination report1.1.pdf

abstract-02679-kolnp-2007.jpg


Patent Number 249660
Indian Patent Application Number 2679/KOLNP/2007
PG Journal Number 44/2011
Publication Date 04-Nov-2011
Grant Date 01-Nov-2011
Date of Filing 18-Jul-2007
Name of Patentee V. MANE FILS
Applicant Address 620, ROUTE DE GRASSE 06620 BAR SUR LOUP
Inventors:
# Inventor's Name Inventor's Address
1 CHANOT JEAN-JACQUES 21 BIS RUE DES ORANGERS 06530 SPERACEDES
2 SCHROEDER MARTIN 47 REEDMACE CLOSE ASHFORD TN 235GE
3 MANE JEAN DOMAINE SAINT MATHIEU 290 ROUTE DE DE SAINT MATHIEU 06130 GRASSE
PCT International Classification Number C07C 49/607
PCT International Application Number PCT/FR2006/000081
PCT International Filing date 2006-01-13
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 05/00,550 2005-01-19 France