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Description  |
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FIELD OF THE INVENTION
This invention relates to novel components useful as fragrances,
particularly those possessing a sandalwood aroma. The invention also
provides an economical process for preparing these compounds.
BACKGROUND OF THE INVENTION
Certain chemicals possessing a sandalwood odor have enjoyed wide usage in
fragrance compositions. The component of East Indian sandalwood oil (See
E. J. Brunke and E. Klein, "Chemistry of Sandalwood Fragrance" in
Fragrance Chemistry, E. T. Theimer, ed, Academic Press, p. 397,1982),
obtained from Santalum album (Linn.), responsible for its sandalwood odor
has been identified as (-)-.beta.-santalol having the structure
##STR3##
Other components of East Indian sandalwood oil that also possess the
sandalwood odor, but not as intensely as (-)-.beta.-santalol, are
(+)-.alpha.-santalol and lanceal shown respectively below as structures
##STR4##
Various laboratory syntheses of these naturally occurring sandalwood
chemicals have been reported (see U.S. Pat. No. 4,223,167). In addition,
non-naturally occurring chemicals possessing the sandalwood odor have been
synthesized. The dihydro-.beta.-santalol (See Fanta and Erman, J. Org.
Chem., 37, 1624 (1972)) having the structure
##STR5##
possesses a strong sandalwood note. The 3-desmethyl-.beta.-santalols (See
U.S. Pat. No. 3,673,261 issued 1972, and Fanta and Erman, 1972) having the
structure
##STR6##
also possess a sandalwood note.
Certain monocyclic chemicals possessing the sandalwood odor have also been
prepared in the laboratory. A chemical (See U.S. Pat. No. 4,046,716,
issued 1977) having the structure
##STR7##
is reported as having a mild sandalwood odor.
The monocyclic alcohols (See U.S. Pat. No. 4,052,341, issued 1976, and Ger.
Off. 1,922,391, issued 1970) shown respectively as structures
##STR8##
also possess the sandalwood aroma.
Certain acyclic chemicals possessing the sandalwood note have also been
prepared in the laboratory. An example is the chemical (See Ger. Off.
2,244,199, issued 1973) having the structure
##STR9##
Certain non-naturally occurring substituted cyclohexanols possessing the
sandalwood odor have been synthesized. U.S. Pat. No. 4,188,310, issued
1980, described the synthesis of a fragrance material having the structure
##STR10##
wherein the dashed line may be either a carbon-carbon single bond or a
carbon-carbon double bond. A mixture of geometrical and optical isomers
having the above structure is said to exhibit soft, warm woody notes
rendering it useful as a fragrance material.
U.S. Pat. No. 4,104,203, issued 1978, describes another substituted
cyclohexanol mixture having the structures
##STR11##
where R is
##STR12##
which were also reported to possess a strong sandalwood-type odor.
These known materials, however, have complex bicyclic structures and/or are
difficult to synthesize. Therefore, it is an object of the invention to
prepare a cyclohexanol compound that is devoid of a complex bicyclic
structure yet has a sandalwood odor. Yet another object is to develop a
compound that is synthetically easy to prepare.
SUMMARY OF THE INVENTION
These and other objects are achieved by the present invention which is
directed to novel substituted cyclohexanol compounds possessing a strong
sandalwood aroma. These compounds have the formula:
##STR13##
wherein A is
##STR14##
and where R.sub.1 is methyl or ethyl, R.sub.2 -R.sub.7 are independently
hydrogen or methyl with the proviso that a maximum of two of the
substituents R.sub.2 -R.sub.7 are methyl, and R.sub.8 is hydrogen, lower
alkyl (C.sub.1 to C.sub.5) or acyl. It will be recognized that the
compounds of the invention can exist in several stereoisomeric forms. The
foregoing structural formulae are intended to embrace the individual
stereoisomers, as well as mixtures of the various stereoisomers of the
substituted cyclohexanols of this invention.
The present invention also provides efficient and economical processes for
preparing these compounds. Thus, for example, the compound having the
structure
##STR15##
where the dotted line represents either a carbon-carbon single bond or a
carbon-carbon double bond, may be prepared by condensation of an
acetoacetic ester having the structure
##STR16##
wherein R is a lower alkyl, and 4-methyl-4-methoxypentanal having the
structure
##STR17##
in the presence of a suitable base. The 4-methyl-4-methoxypentanal may be
synthesized by hydroformylation of readily available
3-methoxy-3-methylbut-1-ene having the structure
##STR18##
Condensation of the acetoacetic ester iii and 4-methyl-4-methoxypentanal iv
forms a carboalkoxycyclohexenone having the structure
##STR19##
Compound vi is then decarboxylated by conventional procedures such as
treatment with alkali, to yield a compound having the structure
##STR20##
which upon reduction yields
##STR21##
wherein the dashed line represents either a carbon-carbon single bond or a
carbon-carbon double bond depending upon the conditions used for the
reduction.
It has been found that the above compounds (formula i) and diastereoisomers
either separately or as mixtures are useful as fragrance materials. Useful
fragrance compositions have been prepared by incorporating these compounds
or as admixtures.
DETAILED DESCRIPTION OF THE INVENTION
The novel substituted cyclohexanol compounds of the present invention
possess a strong sandalwood aroma. They exhibit woody, musky nuances
rendering them useful as fragrance materials. These compounds exhibit
similar odor characteristics and may be used individually or as mixtures
in fragrance applications. Geometrical and optical isomers of these
compounds may be separated by techniques known to the art. However, such
separations are not necessary, since these mixtures can be employed
directly without further separations.
The following reaction schemes illustrate processes of the present
invention for conveniently and efficiently preparing novel aldehyde
intermediates, cyclohexanone intermediates and cyclohexanols and
derivatives useful in the preparation of fragrance materials.
##STR22##
Four different processes are depicted in Scheme I for the formation of a
novel aldehyde intermediate. In Process 1, 2-methylprop-2-en-1-ol (2) is
heated in the range of 150.degree. to 250.degree. C. in the presence of a
vinyl ether 1, wherein R.sub.1 is ethyl and an acid catalyst such as
phosphoric acid, toluenesulfonic acid or, preferably, mercuric acetate.
This reaction is proposed to proceed through the intermediate enol ether 3
to generate the unsaturated aldehyde 4. The aldehyde 4 is then heated with
methanol and an acid catalyst such as Dowex-50 acidic resin to provide the
dimethylacetal compound 5 (R.sub.2 is methyl). Hydrolysis of compound 5
using an acid catalyst such as formic acid, acetic acid, benzoic acid,
hydrochloric acid, phosphoric acid or, preferably, oxalic acid, under
aqueous conditions with heating provides the novel aldehyde 6. Compound 6
is a useful and novel intermediate for the synthesis of fragrance
materials.
Process 2 in Scheme I depicts another method for producing the novel
aldehyde compound 6. A starting compound 7, wherein R.sub.3 is hydrogen or
a lower alkyl group such as methyl, is treated with an organo-metallic
reagent such as methylmagnesium iodide, methylmagnesium chloride or
methyllithium under aprotic conditions to form, after an acidic workup,
compound 8.
Compound 8 is etherified by treatment with a strong base such as sodium
hydride, sodium metal, n-butyllithium or lithium hydride in an aprotic
solvent such as THF or diethyl ether followed by addition of an alkylating
agent such as dimethyl sulfate or methyl iodide to yield compound 9 where
R.sub.2 is methyl.
Ozonolysis of 9 is performed in the temperature range of -70.degree. to
-20.degree. C. in a mixture of a chlorocarbon such as methylene chloride
or dichloroethane and a low molecular weight alcohol solvent such as
ethanol, 1-butanol, 2-propanol, 1-propanol or, preferably, methanol. The
ratio of methylene chloride to methanol may range from 1:0 to 0:1,
preferably 1:1. The intermediate ozonide is reduced with an appropriate
reducing agent such as triphenylphosphine, sodium bisulfite or dimethyl
sulfide, to form 6 (R.sub.2 is methyl).
In Process 3 of Scheme I, 2-methoxy-2-methylbut-3-ene 10, prepared by the
method of Tzeng and Weber (J. Org. Chem., 46, 265 (1981)), incorporated
herein by reference, from 2-methyl-3-buten-2-ol, is hydroformylated in a
hydrocarbon solvent such as benzene, pentane, cyclohexane, heptane,
octane, or, preferably, hexane, in the presence of a catalyst such as
dicobaltoctacarbonyl or tris(triphenylphosphine)rhodium(I) chloride at
temperatures of from 125.degree. to 200.degree. C. and pressures in the
range of 1000 to 2000 psi to form a mixture of ethers 6 and 11 (R.sub.2 is
methyl).
In Process 4 of Scheme I the cyclic acetal 12 obtained by the procedure of
U.S. Pat. No. 4,123,444, incorporated herein by reference, is converted
into the ether acetal 5 by heating compound 12 in the presence of
methanol, a mineral acid such as sulfuric acid, phosphoric acid, nitric
acid, hydrochloric acid, hydrobromic acid or hydroiodic acid, a solid
support such as Montmorillonite clay, DOWEX-50.TM. acidic resin,
NAFION.TM. or silica and an orthoformate ester such as trimethyl
orthoformate for a time period of 1 hour to 3 days. Preferred conditions
are 2 eq. of methanol, sulfuric acid catalyst, Montmorillonite clay and
trimethyl orthoformate for 16 hours. Compound 5 is converted to aldehyde 6
using the method described in Process 1.
In addition, the side products of the hydroformylation of
3-methylbut-1-en-3-ol such as the dimeric ether 13 and enol ether 14 may
also be subject to the above conditions to generate the acetal ether 5.
The aldehyde compound 6 (R.sub.2 is methyl) is a unique and necessary
intermediate toward the generation of novel and useful fragrance materials
according to the invention.
##STR23##
Scheme II depicts a pathway to the formation of intermediate cyclohexenones
such as 17. Compound 17 represents the branch point for a variety of novel
and useful fragrance materials. Aldehyde 6 is treated with an excess of
the acetoacetate ester 14 (R.sub.4 is a lower alkyl such as ethyl) in the
presence of a suitable secondary amine base such as pyrrolidine, diethyl
amine, morpholine or, preferably, piperidine, to form proposed unisolated
intermediates 15 and 16 as per the procedure of U.S. Pat. No. 4,188,310.
Compound 16 is decarbalkoxylated in the presence of a hydroxide base such
as sodium hydroxide to yield cyclohexenone 17.
Scheme II can also be used to produce compounds of formula 17a:
##STR24##
wherein A is
##STR25##
and where R.sub.1 is methyl or ethyl, R.sub.2 -R.sub.6 are independently
hydrogen or methyl with the proviso that a maximum of two of the
substituents R.sub.2 -R.sub.6 are methyl. Compound 15 can be mildly
condensed to form the corresponding cyclohexenone followed by protection
of the ketone as a ketal and reduction of the carboxyl groups to methyl.
In the same fashion, compound 16 can be converted to a ketal and the
carboxyl group reduced to form a methyl.
Alternatively, compound 17 can be alkylated by condensing the enol base
with methyl iodide. A mixture will result which can be separated to
provide the desired products.
These compounds can be converted to compounds of formula i by the methods
described in Scheme III.
##STR26##
Scheme III depicts pathways to the formation of fragrance materials of this
invention. Treatment of cyclohexenone 17 with a suitable reducing agent
such as sodium borohydride, diisobutylaluminum hydride, lithium
tri-tert-butoxyaluminum hydride, lithium borohydride,
tri-sec-butylborohydride, sodium cyanoborohydride or, preferably, lithium
aluminum hydride, generates the allylic alcohol 18 whose odor exhibits
green, woody notes.
Hydrogenation of cyclohexenone 17 in the presence of a suitable catalyst
such as Raney nickel, platinum oxide, iridium on carbon, rhodium on carbon
or, preferably, 5% palladium on carbon provides the saturated ketone 19 as
a mixture of two diastereoisomers. The depicted isomer is the major isomer
in the palladium catalyzed reduction.
Reduction of ketone 19 with a suitable reducing agent such as lithium
aluminum hydride, sodium borohydride, diisobutylaluminum hydride, lithium
tri-tert-butoxyaluminum hydride, lithium borohydride, sodium
bis(2-metyhoxyethoxy)-aluminum hydride, sodium cyanoborohydride or,
preferably, lithium tri-sec-butylborohydride, provides the alcohol 20 as a
mixture of four diastereoisomers. The depicted isomer 20 is the major
component. This mixture is determined to possess strong, tenacious,
sandalwoody, musky notes making it valuable as a fragrance material.
A variety of methods are examined to effect the reduction of the
unsaturated ketone 17 or saturated ketone 19 to alcohol 20. These are
tabulated in Table I.
The alcohol 20 yields ester 21 in the presence of a suitable acylating
agent such as acetic anhydride, acetyl chloride, acetyl bromide or ketene
in an aprotic solvent such as toluene, hexane, THF, or dimethoxyethane
with heating. Compound 21 is evaluated as having a weak, woody odor.
Treatment of unsaturated ketone 17 with a methyl organocuprate reagent such
a lithium dimethylcuprate generated saturated ketone 22. Reduction of
compound 22 with a suitable reducing agent such as lithium
tri-sec-butylborohydride provided alcohol 23 as a mixture of two
diastereoisomers with the depicted isomer as the principal component which
has been determined to possess a woody odor.
Treatment of saturated ketone 19 with a methyl organometallic reagent such
as methylmagnesium iodide, methylmagnesium chloride or methyllithium in an
aprotic solvent such as toluene, hexane, THF, dimethoxyethane with heating
yields the tertiary alcohol 24 which has been evaluated as having a woody
odor.
TABLE 1
__________________________________________________________________________
##STR27##
X - Dotted line is a carbon-carbon single bond
Y - Dotted line is a carbon-carbon double bond
Starting Isomer Ratio
Material
Conditions A B* C D (% Yield)
__________________________________________________________________________
X Sodium borohydride,
-- 26.0
72.7
1.3 (93)
2-propanol, room
temperature.
X Lithium aluminum
2.8 15.3
79.2
2.8 (79)
hydride, tetrahydro-
furan, 0.degree. C. to room
temperature.
Y Raney nickel, hydrogen,
4.7 22.6
65.4
7.4 (90)
100 psi 100.degree. C.
X Sodium borohydride,
-- 27.8
69.0
3.2
acetone (2 equiv.),
2-propanol
Y Raney nickel, 8.6 21.8
62.3
8.3 (78)
2-propanol, hydrogen,
room temperature
X Lithium tri-t-butoxy-
-- 14.3
78.2
7.6 (70)
aluminum hydride, 0.degree. C.
to room temperature,
tetrahydrofuran
X Aluminum iso-propoxide,
-- 42.2
54.0
3.8 (74)
2-propanol
X Rhodium on carbon (5%),
-- 45.0
52.5
2.4
ethanol, hydrogen
X Lithium tri-sec-butyl-
-- 87.3
5.5 4.6 (86)
borohydride, -65.degree. C.,
tetrahydrofuran
__________________________________________________________________________
*Diastereoisomer having the strongest woody, musky notes.
TABLE II
______________________________________
Structure and Odor Characteristics of Claimed Odorants
______________________________________
##STR28## woody, green
##STR29## musky, sandalwood
##STR30## warm, woody,
##STR31## warm, woody
##STR32## sandalwood
______________________________________
##STR33##
Scheme IV depicts the pathway to the monosubstituted cyclohexanol 29, the
parent compound of the invention.
Aldehyde 6 is reacted with the anion of triethylphosphono acetate,
generated by a suitable base such as methyllithium, sodium hydride,
lithium hydride or phenyllithium in the temperature range of -20.degree.
to 20.degree. C., to form the unsaturated ester 25.
The unsaturated ester 25 and 3-hydroxypyrone 26 are dissolved in a suitable
solvent such as toluene, ethyl acetate, or hexane and heated in the
temperature range of 15.degree. to 25.degree. C. for 3 to 16 hours. The
resulting mixture is reduced using a suitable catalyst such as palladium
on carbon, platinum on carbon, platinum oxide, Raney nickel or rhodium on
carbon in an alcoholic solvent such as ethanol for 6 to 20 hours to yield
the ketoester 27.
The ketoester 27 is decarboxylated to ketone 28 under aqueous basic
conditions e.g. a hydroxide base such as sodium hydroxide, potassium
hydroxide or barium hydroxide with a lower alcohol such as methanol or
ethanol as a co-solvent at reflux.
Reduction of ketone 28 with a suitable reducing agent such as lithium
aluminum hydride, sodium borohydride, diisobutylaluminum hydride, lithium
tri-tert-butoxyaluminum hydride, or lithium borohydride, or hydrogenation
catalysts such as palladium on carbon, Raney nickel or platinum oxide,
yielded cyclohexanol 29 as a mixture of diastereoisomers. Lithium
tri-sec-butylborohydride reduction yields the highest ratio of trans to
cis diastereoisomers. This mixture of diastereomers was determined to
possess warm, sandalwoody nuances.
Additional methylated analogues of the parent compound 29 which may exhibit
desirable woody odors are as follows:
##STR34##
It is expected that the above compounds would possess a strong sandalwood
odor. These compounds may be prepared from the aldehyde 6 shown below:
##STR35##
by methods known to those skilled in the art. For example, compounds I, II
and III may be prepared by the alkylation of the ketone followed by
reduction.
##STR36##
Similarly, compounds IV and V may be prepared by alkylation of the ketone
followed by reduction.
##STR37##
Using published methods (see B. A. McAndrew, J. Soc. Cosmet. Chem., 28, pp.
629-639 (1977)), alcohol VI may be formed in the following manner
##STR38##
The following examples serve to illustrate the preparation of specific
fragrance materials and their intermediates in accordance with the
invention, but are not meant to limit the scope thereof.
The compounds of Examples 5, 6, 8, 9 and 19 may be employed in a number of
consumable products where sandalwood aroma may be desirable, for example,
colognes, detergent and soap compositions, liquid detergents,
pre-fragranced coatings for textiles, among others.
The fragrance properties attributed to the compounds of Examples 5, 6, 8, 9
and 19 were determined by submitting each to a panel of expert perfumers.
Their evaluations are included in each appropriate Example.
The fragrance compounds produced according to the invention are
incorporated into colognes at concentrations of about 1.5% to 5.0% in 95%
aqueous ethanol. The use of these compounds provides a cologne having a
sandalwood character.
An air freshener produced from an accord containing compound 20 is mixed
with ethanol and water to obtain a concentration range of 0.5% to 20% by
weight to obtain a substantially homogeneous composition. The air
freshener manifests a characteristic sandalwood fragrance.
The invention in its broader aspects is described with respect to the
following examples which are intended only to illustrate the preferred
embodiments of the invention and are not in any way intended to limit the
scope thereof.
EXAMPLE 1
Preparation of 2, 6-Dimethyl-2-methoxyhept-5-ene
##STR39##
To sodium hydride (93.5 g, 3.9 mol) suspended in tetrahydrofuran (300 mL)
was added 2,6-dimethylhept-5-en-2-ol (500 g, 3.5 mol) in tetrahydrofuran
(1000 mL). The mixture was heated at reflux until gas evolution was
complete. Dimethylsulfate (274 mL, 2.9 mol) in tetrahydrofuran (226 mL)
was added to the cold (0.degree. C.) mixture. After standing for 16 h, the
mixture was heated at reflux for 7 hours. Aqueous workup yielded
2,6-dimethyl-2-methoxyhept-5-ene, bp.sub.40 65.degree.-68.degree. C.
(461.5 g); NMR(CDCl.sub.3).delta.1.2(s,6H), 1.4-1.6(m,2H), 1.6(s,3H),
1.7(s,3H), 1.9-2.1(m,2H), 3.2(s,3H), 5.1-5.2(m,1H); IR(neat) 2970, 2932,
1462, 1442, 1373, 1357, 1195, 1072 cm.sup.-1 ; MS(m/e) 41, 67, 73, 109,
124, 142.
EXAMPLE 2
Preparation of 4-Methoxy-4-methylpentanal
##STR40##
Method A
A stirred, cooled (-65.degree. C.) mixture of
2,6-dimethyl-2-methoxyhept-5-ene (125 g, 1.25 mol), methylene chloride
(500 mL) and methanol (500 mL) was treated with a gas stream enriched with
ozone. Upon the appearance of a blue color pure oxygen was passed through
the mixture followed by nitrogen. Dimethyl sulfide (88 mL, 1.4 mol) was
added and the mixture was allowed to stand 16 hours at 25.degree. C. Upon
workup 4-methoxy-4-methylpentanal was obtained, bp.sub.30
85.degree.-87.degree. C. (64.4 g); NMR(CDCl.sub.3).delta.1.2(s,6H),
1.9(t,2H), 2.5(m,2H), 3.2(s,3H), 9.8(t,1H); IR(neat) 2975, 2825, 2725,
1730, 1470, 1370, 1090 cm.sup.-1 ; MS(m/e) 43, 73, 83, 115.
Method B
##STR41##
A mixture of 1,1,4-trimethoxy-4-methylpentane (3.2 g, 0.018 mol),
tetrahydrofuran (100 mL), water (10 mL) and oxalic acid (1.0 g, 0.022 mol)
was heated at reflux for 40 hours. Workup provided
4-methoxy-4-methylpentanal (2.0 g).
Method C
##STR42##
Dicobaltoctacarbonyl (1.6 g, 0.0047 mol), tri-n-butylphosphine (41.0 mL),
2-methoxy-2-methyl3-butene (30 g, 0.30 mol) and hexane (93 mL) were
combined and placed under an atmosphere of 1:1 hydrogen:carbon monoxide
and stirred at 195.degree. C., pressure 1200 psi. The resulting mixture
was distilled to yield 2.8 g 4-methoxy-4-methylpentanal.
EXAMPLE 3
Preparation of 3-(3-methoxy-3-methylbut-1-yl)-5-methylcyclohex-5-en-1-one
##STR43##
To a stirred mixture of 4-methoxy-4-methylpentanal (60 g, 0.46 mol) and
ethyl acetoacetate (156 g, 1.2 mol) at 5.degree. C. was added a 21%
solution of piperidine in ethanol (4.1 mL). Further additions (4.times.18
mL) of the piperidine solution were made at about 24 hour intervals. The
mixture was heated at reflux for 7 hours and concentrated to about 200 mL
volume. Methanol (420 mL), water (420 mL) and sodium hydroxide (24 g) were
added and the resulting mixture was heated at reflux 16 hours. Workup gave
3-(3-methoxy-3-methylbut-1-yl)-5-methylcyclohex-5-en-1-one bp.sub.0.1
135.degree.-140.degree. C. (69.2 g); NMR(CDCl.sub.3).delta.1.2(s,6H),
0.9-1.6(m,5H), 1.9(s,3H), 5.9(brs,1H); IR(neat) 2975, 2930, 1675, 1640,
1380, 1080 cm.sup.-1 ; MS(m/e) 43, 73, 81, 109, 122, 163, 196.
EXAMPLE 4
Preparation of 3-(3-Methoxy-3-methylbut-1-yl)-5-methylcyclohexan-1-one
##STR44##
A solution of 3-(3-methoxy-3-methylbut-1-yl)-5-methylcyclohex-5-en-1-one
(30.0 g, 0.14 mol) in methanol (150 mL) was placed in a thick walled
bottle. Palladium on charcoal (5%, 2.0 g) was added and the mixture was
shaken under 53.5 psi of hydrogen. When the theoretical amount of hydrogen
had been consumed, workup yielded
3-(3-methoxy-3-methylbut-1-yl)-5-methylcyclohexan-1-one as a mixture of
two diastereoisomers bp.sub.0.5 104.degree.-107.degree. C. (27.6 g, ratio
69:93.1); NMR(CDCl.sub.3).delta.1.0(d,3H), 1.1(s,6H), 1.3-1.5(m,6H),
1.6-2.0(m,4H), 2.2-2.4(m,2H),3.1(s,3H). IR(neat) 2970, 2925, 1720, 1360,
1090 cm.sup.-1 ; MS(m/e) 41, 73, 124, 147, 165, 180, 197.
EXAMPLE 5
Preparation of 3-(3-Methoxy-3-methylbut-1-yl)-5-methylcyclohex-5-en-1-ol
##STR45##
To a suspension of lithium aluminum hydride (0.1 g, 0.0024 mol) in
tetrahydrofuran (5 mL) cooled to 0.degree. C. was added
3-(3-methoxy-3-methylbut-1-yl)-5-methylcyclohex-5-en-1-one (1.0 g, 0.0048
mol) in tetrahydrofuran (5 mL). The mixture warmed on standing 16 hours
and was treated with 10% sodium hydroxide solution. Subsequent workup
yielded 3-(3-methoxy-3-methylbut-1-yl)-5-methylcyclohex-5-en-1-ol as a
mixture of two diastereoisomers (ratio: 6.5:93.5, 0.853 g). This material
was determined to possess green, woody notes.
NMR(CDCl.sub.3).delta.0.8-1.1(m,2H), 1.2(s,6H), 1.3-1.6(m,5H), 1.7(s,1H),
1.9-2.2(m,5H), 3.2(s,3H), 4.2(brs,1H), 5.4(s,1H); IR(neat) 3400, 2975,
2925, 1670, 1380, 1360, 1090 cm.sup.-1 ; MS(m/e) 43, 73, 91, 106, 124,
147, 162, 180, 194.
EXAMPLE 6
Preparation of 3-(3-Methoxy-3-methylbut-1-yl)-5-methylcyclohexan-1-ol
##STR46##
Method A
A solution of lithium tri-sec-butylborohydride (267 mL of a 1M solution in
tetrahydrofuran, 0.27 mol) was added to a cooled (-65.degree. C.) solution
of 3-(3-methoxy-3-methlybut-1-yl)-5-methylcyclohexan-1-one (48.6 g, 0.22
mol) dissolved in tetrahydrofuran (350 mL). The solution was stirred at
25.degree. C. for 16 hours and was quenched by addition of sodium
hydroxide (10% aqueous, 165 mL) followed by hydrogen peroxide (30%
aqueous, 170 mL). Workup yielded 3-(3-methoxy-3-methylbutyl)-5-methyl
cyclohexan-1-ol as a mixture of diastereoisomers (ratio 90.1:7.2:2.7),
bp.sub.0.75 120.degree.-122.degree. C. (40.7 g). This compound and
mixtures of diastereomers possess strong, tenacious, sandalwoody, musky
notes. NMR(CDCl.sub.3).delta.0.6 (q,1H), 0.9(d,3H), 1.0-1.1(m,2H),
1.1(s,6H), 1.2-1.3 (m,2H), 1.4-1.6(m,2H), 1.6-1.9(m,5H), 2.2 (brs,1H),
3.2(s,3H), 4.1(m,1H). IR(neat) 3400, 2975, 2925, 1460, 1385, 1365, 1210,
1090, 1015 cm.sup.-1 ; MS(m/e) 43, 73, 93, 111, 149, 167, 182, 199, 200.
Method B
A mixture of 3-(3-methoxy-3-methylbut-1-yl)-5-methylcyclohex-5-en-1-one
(1.0 g, 0.0048 mol) in 2-propanol (40 mL) and Raney nickel (about 0.1 g)
was shaken under hydrogen (37 psi) at 25.degree. C. for 16 hours.
Subsequent workup yielded
3-(3-methoxy-3-methylbut-1-yl)-5-methylcyclohexan-1-ol (0.78 g) as a
mixture of four diastereoisomers (ratio 8.1:20.6:57.8:7.8).
Method C
A solution of 3-(3-methoxy-3-methylbut-1-yl)-5-methylcyclohexan-1-one (0.50
g, 0.0024 mol) in tetrahydrofuran (1 mL) was added to a suspension of
lithium aluminum hydride (0.10 g, 0.0027 mol) in tetrahydrofuran (1 mL)
cooled to 0.degree. C. The mixture was stirred at 20.degree. C. for 16 h.
Subsequent workup yielded 3-(3-methoxy-3-methylbutyl)-5-methylcyclohexanol
(0.40 g) as a mixture of four diastereoisomers (ratio 2.8:15.3:79.2:2.8).
EXAMPLE 7
Preparation of 3-(3-Methoxy-3-methylbut-1-yl)-5,5-dimethylcyclohexan-1-one
##STR47##
To a suspension of copper(I) iodide (6.0 g, 0.032 mol) in tetrahydrofuran
(120 mL) cooled to 0.degree. C. was added a methyllithium solution (45 mL
of a 1.4M solution in diethyl ether, 0.063 mol). After stirring 0.5 hour,
3-(3-methoxy-3-methylbutyl)-5-methylcyclohex-5-en-1-one (2.0 g, 0.0095 mL)
in tetrahydrofuran (80 mL) was slowly added. After stirring 2.5 hours, the
mixture was added to ice cold dilute hydrochloric acid. Subsequent workup
yielded 3-(3-methoxy-3-methylbutyl)-5,5-dimethylcyclohexan-1-one,
bp.sub.0.5 125.degree.-130.degree. C. (1.3 g); NMR
(CDCl.sub.3).delta.0.9(s,3H), 1.1(s,3H), 1.1(s,6H), 1.2-1.6(m,6H),
1.6-2.5(m,5H), 3.2(s,3H); IR(neat) 2960, 1715, 1365, 1085 cm.sup.-1.
MS(m/e) 41, 55, 73, 138, 161, 211, 212.
EXAMPLE 8
Preparation of 3-(3-Methoxy-3-methylbut-1-yl)-5,5-dimethylcyclohexan-1-ol
##STR48##
To lithium tri-sec-butylborohydride (2.7 mL of a 1.0M solution in
tetrahydrofuran, 0.0027 mol) cooled to -65.degree. C. was added
3-(3-methoxy-3-methylbutyl)-5,5-dimethylcyclohexan-1-one (0.5 g, 0.0022
mol) dissolved in tetrahydrofuran (3.5 mL). The mixture was allowed to
stir at 25.degree. C. for 16 hours. Workup yielded
3-(3-methoxy-3-methylbut-1-yl)-5,5-dimethylcyclohexan-1-ol, bp.sub.1.0
210.degree.-212.degree. C. (0.31 g). This compound was determined to
possess a warm woody note. NMR(CDCl.sub.3).delta.0.9(s,3H), 1.1 (s,3H),
1.2(s,6H), 1.2-1.4(m,4H), 1.4-1.7(m,6H), 1.7-1.9(m,2H), 3.2(s,3H),
4.2(m,1H); IR(neat) 3425, 2970, 2940, 1470, 1365, 1080 cm.sup.-1 ; MS(m/e)
43, 55, 73, 125, 163, 213, 214.
EXAMPLE 9
Preparation of 3-(3-methoxy-3-methylbutyl)-1,5-dimethylcylohexan-1-ol
##STR49##
3-(3-Methoxy-3-methylbut-1-yl)-5-methylcyclohexan-1-one (5.0 g, 0.025 mol)
dissolved in diethyl ether (5.0 mL) was added to a cooled (5.degree. C.)
solution of methylmagensium iodide formed by treating magnesium turnings
(0.70 g, 0.028 mol) in diethyl ether (20 mL) with iodomethane (1.6 mL,
0.026 mol). After stirring 16 hours at 25.degree. C., a saturated aqueous
ammonium chloride solution (ca. 2 mL) was added and subsequent workup
yielded 3-(3-methoxy-3-methylbutyl)-1,5-dimethylcyclohexan-1-ol as a
mixture of diastereoisomers in a ratio of 2.9:65.6:1.9:29.6, bp.sub.0.5
147.degree.-149.degree. C. This compound was determined to possess a warm
woody note. NMR(CDCl.sub.3).delta.0.5(m,1H), 0.9(d,3H), 1.0-1.1(m,1H),
1.2(s,6H), 1.3(s,3H), 1.3-1.9(m,10H), 1.9-2.0(brs,1H), 3.2(s,3H); IR(neat)
3400, 2925, 1460, 1370, 1220, 1080 cm.sup.-1 ; MS(m/e) 43, 55, 73, 107,
122, 163, 181, 213, 214.
EXAMPLE 10
Preparation of 2-Methoxy-2-methylhex-5-ene
##STR50##
To a stirred suspension of sodium hydride (46.8 g of a 60% oil dispersion,
1.15 mol) in tetrahydrofuran (240 mL) was added 2-methylhex-5-en-2-ol (120
g, 1.05 mol) in tetrahydrofuran (240 mL). Dimethylsulfate (75 mL, 0.79
mol) in tetrahydrofuran (120 mL) was added to the cooled (0.degree. C.)
mixture. The mixture was heated at reflux for 6 hours. Workup yielded
2-methoxy-2-methylhex-5-ene, bp.sub.40 53.degree.-58.degree. C. (51.36 g);
NMR(CDCl.sub.3).delta.1.1(s,6H), 1.5-1.6(m,2H), 2.0-2.2(m,2H), 3.2(s,3H),
4.8-5.1(m,2H), 5.7-6.0(m,1H); IR(neat) 2960, 2925, 1640, 1460, 1360, 1300,
1085 cm.sup.-1 ; MS(m/e) 43, 55, 73, 81, 95, 97, 113, 114.
EXAMPLE 11
Preparation of 4-Methylpent-4-enal
##STR51##
Methallyl alcohol (15 g, 0.21 mol), ethyl vinyl ether (120 mL, 1.26 mol)
and mercuric acetate (4.2 g, 0.013 mol) were combined and heated at
200.degree. C. in a sealed container for 2 h. Distillation yielded
4-methylpent-4-enal, bp 110.degree.-112.degree. C. (14.5 g);
NMR(CDCl.sub.3).delta.1.8(s,3H), 2.3(m,2H), 2.6(m,2H), 5.7(brs,2H),
9.8(t,1H); IR(neat) 2950, 2900, 2700, 1725, 1650, 1440, 1370, 885
cm.sup.-1 ; MS(m/e) 41, 55, 56, 70, 83, 98, 115.
EXAMPLE 12
Preparation of 2-Methylhex-5-en-2-ol
##STR52##
Methyllithium (800 mL of a 1.4M solution of diethyl ether, 1.1 mol) was
added to mixture of hex-5-en-2-one (100 g, 1.0 mol) in tetrahydrofuran
(800 mL) cooled to -78.degree. C. The mixture was allowed to warm to
25.degree. C. over the course of 1 hour, after which saturated aqueous
ammonium chloride solution was added. Workup yielded
2-methylhex-5-en-2-ol, bp.sub.30 63.degree.-66.degree. C. (140 g);
NMR(CDCl.sub.3).delta.1.2(s,6H), 1.5-1.6(m,2H), 2.1-2.2(m,2H), 2.5(s,1H),
4.9-5.1(m,2H), 5.7-5.9(m,1H); IR(neat) 3350, 2945, 2905, 1635, 1370, 1140,
985, 900 cm.sup.-1 ; MS(m/e) 43, 58, 81, 99, 114.
EXAMPLE 13
Preparation of 1,1,4-Trimethoxy-4-methylpentane
##STR53##
Method A:
A mixture of methanol (30 mL), Dowex 50 acidic resin (1.0 g) and
4-methylpent-4-enal (3.9 g, 0.0031 mol) was heated at reflux for 16 h.
Workup yielded 1,1,4-trimethoxy-4-methylpentane, bp.sub.125
86.degree.-88.degree. C. (3.3 g). NMR(CDCl.sub.3).delta.1.2(s,6H),
1.5-1.8(m,4H), 3.2(s,3H), 3.3(s,6H), 4.4(t,1H). IR(neat) 2975, 2930, 1470,
1385, 1365, 1160, 1090, 1055 cm.sup.-1. MS(m/e) 43, 55, 73, 81, 83, 97,
115.
##STR54##
Method B:
A mixture of 2-methoxy-5,5-dimethyltetrahydrofuran (10 g, 0.077 mol),
methanol (7.9 g, 0.25 mol), concentrated sulfuric acid (1.0 mL),
Montmorillonite clay (1.0 g) and trimethyl orthoformate (29 g, 0.27 mol)
was heated at reflux 16 hours. After cooling the mixture was filtered and
diluted with water and 10% NaOH (aq.) and extracted with hexanes. The
extracts were dried (sodium sulfate) and distilled to yield the desired
product, 9.0 g.
The above procedure may also be carried out on the other products of the
hydroformylation of 3-methylbut-1-en-3-ol such as the dimeric ether and
the enol ether shown below.
##STR55##
EXAMPLE 14
Preparation of 1-Acetoxy-3-(3-methoxy-3-methylbut-1-yl)-5-methylcyclhexane
##STR56##
Acetic anhydride (1.4 mL, 0.014 mol),
3-(3-methoxy-3-methylbut-1-yl)-5-methylcyclohexan-1-ol (2.0 g, 0.0093
mol), toluene (3.0 mL) and sodium acetate (0.05 g) were combined and
heated at reflux for 16 hours. Workup provided
1-acetoxy-3-(3-methoxy-3-methylbut-1-yl)-5-methylcyclohexane, bp.sub.0.5
175.degree.-177.degree. C. (1.61 g) as a mixture of diasteroisomers (ratio
92.3:3.2:4.5); NMR(CDCl.sub.3).delta.0.6(q,1H), 0.9(d,3H), 1.0-1.3(m,3H),
1.2(s,6H), 1.4-1.6(m,4H), 1.6-2.0(m,4H), 2.1(s,3H), 3.2(s,3H), 5.1(m,1H);
IR(neat) 2960, 2925, 1740, 1460, 1380, 1250, 1085, 1015 cm.sup.-1 ;
MS(m/e) 43, 73, 93, 108, 149, 164, 181, 241, 242.
EXAMPLE 15
Preparation of 2,6-Dimethylhept-5-en-2-ol
##STR57##
To a cooled (0.degree. C.) solution of methylmagnesium chloride formed by
exhaustive treatment of magnesium turnings (121.5 g, 5.0 mol) in
tetrahydrofuran (1500 mL) with chloromethane was added with stirring
6-methylhept-5-en-2-one (600 g, 4.8 mol) in tetrahydrofuran (1500 mL).
Stirring was continued for 16 hours at 25.degree. C. After treatment with
saturated aqueous ammonium chloride solution (about 200 mL) workup yielded
2,6-dimethylhept-5-en-2-ol, bp.sub.40 83.degree.-85.degree. C., (538 g);
NMR (CDCl.sub.3).delta.1.2(s,6H), 1.3-1.5(m,2H), 1.8(s,3H), 1.9(s,3H),
2.1(m,2H), 2.9(s,1H), 5.3(m,1H); IR(neat) 3375, 2975, 2940, 1470, 1450,
1385, 1200, 1155, 1135, 930, 910 cm.sup.-1. MS(m/e) 41, 59, 69, 81, 109,
124, 142.
EXAMPLE 16
Preparation of Ethyl 6-methoxy-6-methoxy 6-methyl-2-heptenoate
##STR58##
Sodium hydride (5.5 g, 0.27 mol) was suspended in tetrahydrofuran (95 mL)
under a nitrogen atmosphere. A solution of triethylphosphonoacetate (57 g,
0.25 mol) in tetrahydrofuran (95 mL) was added dropwise to the suspension
with stirring at 29.degree. C. The mixture was cooled to 5.degree. C. and
4-methoxy-4-methylpentanal (30 g, 0.23 mol) in tetrahydrofuran (75 mL) was
added in a single portion. After 2 hours the mixture was added to water
and extracted with diethyl ether. The extracts were dried (MgSO.sub.4) and
concentrated to an oil which was distilled, bp.sub.0.5
95.degree.-97.degree. C. (34.8 g); NMR(CDCl.sub.3).delta.1.2(s,6H),
1.3(t,3H), 1.6(m,2H), 2.3(m,2H), 3.2(s,3H), 4.2(q,2H), 5.8(d,1H),
7.0(m,1H); IR(neat) 2975, 2940, 2820, 1730, 1660, 1365, 1265, 1220, 1180,
1135, 1080 cm.sup.-1 ; MS(m/e) 43, 55, 73, 95, 123, 139, 155, 185, 187.
EXAMPLE 17
Preparation of 2-Carbethoxy-3-(3-methoxy-3-methylbut-1-yl)cyclohexanone
##STR59##
A mixture of 3-Hydroxypyrone (obtained by the procedure of R. H. Wiley and
C. H. Jorboe, J. Am. Chem. Soc., 78, 2398, (1956), 5.0 g, 0.045 mol) and
ethyl 6-methoxy-6-methyl-2-heptenoate (8.9 g, 0.045 mol) were dissolved in
toluene (15 mL) and heated in a sealed vessel for 7 hours at 200.degree.
C. After cooling 5% Pd/C (1.0 g) and methanol (50 mL) were added and the
vessel was pressurized with hydrogen gas (200 psi). After stirring 20
hours the mixture was filtered and concentrated to the residue. The crude
product decomposed on distillation. No further purification was attempted.
NMR of crude material (CDCl.sub.3).delta.1.2(s,6H), 1.3(t,3H), 3.2(s,3H),
3.7(m,1H), 4.2(m,2H); IR(neat) 2600-3800, (broad band), 2990, 2950, 1740,
1720, 1680, 1650, 1620, 1470, 1390, 1370, 1220, 1090 cm.sup.-1.
EXAMPLE 18
Preparation of 3-(3-Methoxy-3-methylbut-1-yl)cyclohexanone
##STR60##
Crude 2-carbethoxy-3-(3-methoxy-3-methylbut-1-yl)cyclohexanone (7.0 g) of
example 17 was added to a mixture of potassium hydroxide (3.0 g), methanol
(50 mL) and water (50 mL) and heated at reflux 4.5 hours. The cooled
mixture was extracted with hexane, the extracts were dried (Na.sub.2
SO.sub.4) and concentrated to an oil which was purified by bulb to bulb
distillation, airbath temperature 175.degree. C., 0.1 mm Hg to yield
3-(3-methoxy-3-methylbut-1-yl)cyclohexanone (1.0 g);
NMR(CDCl.sub.3).delta.1.2(s,6H), 1.2-1.5(m,5H), 1.6-1.8(m,2H),
1.9-2.1(m,3H), 2.2-2.4(m,3H), 3.2(s,3H); IR(neat) 2970, 2950, 1720, 1460,
1370, 1230, 1090 cm.sup.-1 ; MS(m/e) 41, 55, 73, 110, 133, 151, 183, 184.
EXAMPLE 19
Preparation of 3-(3-Methoxy-3-methylbut-1-yl)cyclohexanol
##STR61##
3-(3-methoxy-3-methylbut-1-yl)cyclohexanone (1.4 g, 0.0051 mol) was
dissolved in tetrahydrofuran (10 mL) and cooled to -78.degree. C. under a
nitrogen atmosphere with stirring. A solution of lithium
tri-sec-butylborohydride (6.1 mL of a 1M solution of tetrahydrofuran,
0.0061 mol) was added. The mixture was allowed to come to 20.degree. C.
over 16 hours and 10% NaOH (aq, 4.0 mL) was added, followed by 30%
hydrogen peroxide (aq, 4.0 mL). The mixture was extracted with hexane. The
extracts were dried (Na.sub.2 SO.sub.4) and concentrated to the residue
which was purified by bulb to bulb distillation (air bath temp 175.degree.
C., 0.1 mm Hg) to yield 3-(3-methoxy-methylbut-1-yl)cyclohexanol as a
mixture of diastereoisomers in the ratio of 94:6 (0.7 g).
NMR(CDCl.sub.3).delta.1.1(s,6H), 1.2-1.8(m,13H), 3.2(s,3H), 4.1(brs,1H).
IR(neat) 3410, 2990, 2960, 2870, 1460, 1370, 1110, 1090, 980 cm.sup.-1.
MS(m/e) 43, 73, 109, 124, 143, 181, 201, 214.
EXAMPLE 20
FLORAL BOUQUET FORMULATION
A floral bouquet composition was prepared using the following formulation:
______________________________________
Material %
______________________________________
Oil Lemon Rectified 1.0
Linalool FCC Synthetic
2.0
Phenylethyl Alcohol FCC
11.0
Benzyl Acetate FCC Extra
1.5
Styrolyl Alcohol 1.5
Citronellol R BASF 5.5
Hydroxycitonellal FCC Extra
4.0
Eugenol FCC extra 0.5
Lillial 1.0
Hedione 2.0
Lyral 1.5
Hexyl cinnamic aldehyde FCC
2.0
Benzyl salicylate 5.5
Methyl ionone gamma pure
3.0
Musk ether 2.0
Aldehyde C-12 FCC lauric
0.1
Diethyl phthalate 45.9
3-(3-methoxy-3-methylbut-1-yl)-5-
methylcyclohexanol of Example 6
10.00
100.00
______________________________________
EXAMPLE 21
WOODY PERFUME FORMULATION
A woody perfume composition was prepared by mixing the following
formulation:
______________________________________
Material %
______________________________________
Heliotropin extra FCC
1.0
Musk ether 2.5
Coumarin 7.0
Benzyl acetate FCC extra
10.0
Hydroxycitronellal FCC extra
3.0
Terpinyl acetate FCC 2.0
Oil Bergamot Rectified
10.0
Methyl Ionone Gamma Pure
5.0
Cedrol Recrystallized
5.0
Oil Cedarwood Terpeneless
3.0
Cedryl Acetate 4.0
Oil Amyris FCC 12.0
Dipropylene Glycol 25.5
3-(3-methoxy-3-methylbut-1-yl)-5-
methylcyclohexanol of Example 6
10.0
100.00
______________________________________
EXAMPLE 22
FLORAL AIR FRESHNER FORMULATION
A floral composition was prepared using the following formulation:
______________________________________
Material %
______________________________________
Oil Lemon Rectified 1.0
Linalool FCC Synthetic
2.0
Phenylethyl Alcohol FCC
11.0
Benzyl Acetate FCC Extra
1.5
Styrolyl Alcohol 1.5
Citronellol R BASF 5.5
Hydroxycitonellal FCC Extra
4.0
Eugenol FCC Extra 0.5
Lillial 1.0
Hedione 2.0
Lyral 1.5
Hexyl Cinnamic Aldehyde FCC
2.0
Benzyl Salicylate 5.5
Methyl Ionone Gamma Pure
3.0
Musk ether 2.0
Aldehyde C-12 FCC Lauric
0.1
Diethyl Phthalate 45.9
3-(3-methoxy-methylbut-1-yl)-5-
methylcyclohexanol of Example 6
10.00
100.00
______________________________________
The above formulation was diluted to 5% concentration with 95% Ethanol and
distilled water was added with stirring until the solution turned cloudy.
The mixture was backtitrated to clarity with more 95% Ethanol. This was
used in a wick-type room air freshner.
EXAMPLE 23
______________________________________
Chypre Formulation
A chypre fragrance composition was
prepared using the following formulation:
Material %
______________________________________
Oil Bergamot 26.0
Oil Orange Sweet 13.0
Methyl Ionone 20.0
Oil Rose 2.0
Jasmine Absolute 5.0
Oil Basil Sweet 0.5
Oil Estragon 0.5
Benzyl Salicylate 0.3
Oil Ylang Extra 0.3
Cinnamic Alcohol 0.6
Eugenol 1.8
Aldehyde C-14 0.3
10% Sol. Aldehyde C-12 NMA in DEP Odorless
0.2
10% Sol. Aldehyde C-11 Undecylenic in Phthalate
Odorless 1.0
Civet Absolute 1.0
Coumarin 4.0
Labdanum Resinoid 3.5
Musk Ketone 3.0
Oakmoss Absolute 3.5
Oil Patchouly 3.5
Vanillin 0.5
Oil Vetiver Reunion 5.5
3-(3-Methoxy-3-methylbut-1-yl)cyclohexanol
of Example 19 10.0
100.0
______________________________________
EXAMPLE 24
______________________________________
Preparation of Sandalwood Base
A sandalwood fragrance base was
prepared using the following formulation:
Material %
______________________________________
Oil Balsam Gurgon 2.0
Oil Amyris 8.0
Osyrol BBA 10.0
3-(3-methoxy-3-methylbut-1-yl)cyclohexanol of
Example 19 80.0
100.0
______________________________________
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